Angelle Desiree LaBeaud

All Publications

• Molecular epidemiology and evolutionary characteristics of dengue virus 2 in East Africa. Nature communications Nyathi, S., Rezende, I. M., Walter, K. S., Thongsripong, P., Mutuku, F., Ndenga, B., Mbakaya, J. O., Aswani, P., Musunzaji, P. S., Chebii, P. K., Maina, P. W., Mutuku, P. S., Ng'ang'a, C. M., Malumbo, S. L., Jembe, Z., Vu, D. M., Mordecai, E. A., Bennett, S., Andrews, J. R., LaBeaud, A. D. 2024; 15 (1): 7832

  Abstract

  Despite the increasing burden of dengue, the regional emergence of the virus in Kenya has not been examined. This study investigates the genetic structure and regional spread of dengue virus-2 in Kenya. Viral RNA from acutely ill patients in Kenya was enriched and sequenced. Six new dengue-2 genomes were combined with 349 publicly available genomes and phylogenies used to infer gene flow between Kenya and other countries. Analyses indicate two dengue-2 Cosmopolitan genotype lineages circulating in Kenya, linked to recent outbreaks in coastal Kenya and Burkina Faso. Lineages circulating in Western, Southern, and Eastern Africa exhibiting similar evolutionary features are also reported. Phylogeography suggests importation of dengue-2 into Kenya from East and Southeast Asia and bidirectional geneflow. Additional lineages circulating in Africa are also imported from East and Southeast Asia. These findings underscore how intermittent importations from East and Southeast Asia drive dengue-2 circulation in Kenya and Africa more broadly.

  View details for DOI 10.1038/s41467-024-51018-0

  View details for PubMedID 39244569

  View details for PubMedCentralID 3651993

• HIV in Eswatini: Climate Change Impacts and Adaptation Strategies CURRENT TROPICAL MEDICINE REPORTS Mkhatshwa, N. P., Dlamini, W., LaBeaud, A., Mandalakas, A. M., Lanza, K. 2024

  View details for DOI 10.1007/s40475-024-00325-z

  View details for Web of Science ID 001263436000001

• Expanding Understanding of Urban Rift Valley Fever Risk and Associated Vector Ecology at Slaughterhouses in Kisumu, Kenya. Pathogens (Basel, Switzerland) Gerken, K. N., Owuor, K. O., Ndenga, B., Wambua, S., Winter, C., Chemutai, S., Omukuti, R., Arabu, D., Miring'u, I., Wilson, W. C., Mutuku, F., Waggoner, J. J., Pinsky, B., Bosire, C., LaBeaud, A. D. 2024; 13 (6)

  Abstract

  Rift Valley fever virus (RVFV) is an adaptable arbovirus that can be transmitted by a wide variety of arthropods. Widespread urban transmission of RVFV has not yet occurred, but peri-urban outbreaks of RVFV have recently been documented in East Africa. We previously reported low-level exposure in urban communities and highlighted the risk of introduction via live animal influx. We deployed a slaughtered animal testing framework in response to an early warning system at two urban slaughterhouses and tested animals entering the meat value chain for anti-RVFV IgG and IgM antibodies. We simultaneously trapped mosquitoes for RVFV and bloodmeal testing. Out of 923 animals tested, an 8.5% IgG seroprevalence was identified but no evidence of recent livestock exposure was detected. Mosquito species abundance varied greatly by slaughterhouse site, which explained 52% of the variance in blood meals. We captured many Culex spp., a known RVFV amplifying vector, at one of the sites (p < 0.001), and this species had the most diverse blood meals. No mosquito pools tested positive for RVFV antigen using a rapid VecTOR test. These results expand understanding of potential RVF urban disease ecology, and highlight that slaughterhouses are key locations for future surveillance, modelling, and monitoring efforts.

  View details for DOI 10.3390/pathogens13060488

  View details for PubMedID 38921786

• Development of a trash classification system to map potential Aedes aegypti breeding grounds using unmanned aerial vehicle imaging. Environmental science and pollution research international Rosser, J. I., Tarpenning, M. S., Bramante, J. T., Tamhane, A., Chamberlin, A. J., Mutuku, P. S., De Leo, G. A., Ndenga, B., Mutuku, F., LaBeaud, A. D. 2024

  Abstract

  Aedes aegypti mosquitos are the primary vector for dengue, chikungunya, and Zika viruses and tend to breed in small containers of water, with a propensity to breed in small piles of trash and abandoned tires. This study piloted the use of aerial imaging to map and classify potential Ae. aegypti breeding sites with a specific focus on trash, including discarded tires. Aerial images of coastal and inland sites in Kenya were obtained using an unmanned aerial vehicle. Aerial images were reviewed for identification of trash and suspected trash mimics, followed by extensive community walk-throughs to identify trash types and mimics by description and ground photography. An expert panel reviewed aerial images and ground photos to develop a classification scheme and evaluate the advantages and disadvantages of aerial imaging versus walk-through trash mapping. A trash classification scheme was created based on trash density, surface area, potential for frequent disturbance, and overall likelihood of being a productive Ae. aegypti breeding site. Aerial imaging offers a novel strategy to characterize, map, and quantify trash at risk of promoting Ae. aegypti proliferation, generating opportunities for further research on trash associations with disease and trash interventions.

  View details for DOI 10.1007/s11356-024-33801-0

  View details for PubMedID 38842780

• Sofosbuvir Off-label Treatment of Yellow Fever Patients During an Outbreak in Brazil, 2018: A Cohort Study. Open forum infectious diseases Rezende, I. M., Mendonça, D. C., Costa, T. A., de Oliveria, G. F., Arruda, M. S., Gonçalves, A. P., Alves, P. A., Calzavara-Silva, C. E., Martins-Filho, O. A., Teixeira-Carvalho, A., Bonjardim, C. A., Monath, T. P., LaBeaud, A. D., Drumond, B. P., Pascoal-Xavier, M. A., Pereira, L. S., Ramalho, D. B. 2024; 11 (6): ofae312

  Abstract

  We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post-symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post-symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.

  View details for DOI 10.1093/ofid/ofae312

  View details for PubMedID 38933737

  View details for PubMedCentralID PMC11204906

• Evaluation of humoral immune response after yellow fever infection: an observational study on patients from the 2017-2018 sylvatic outbreak in Brazil. Microbiology spectrum Gonçalves, A. P., Almeida, L. T., Rezende, I. M., Fradico, J. R., Pereira, L. S., Ramalho, D. B., Pascoal Xavier, M. A., Calzavara Silva, C. E., Monath, T. P., LaBeaud, A. D., Drumond, B. P., Campi-Azevedo, A. C., Martins-Filho, O. A., Teixeira-Carvalho, A., Alves, P. A. 2024: e0370323

  Abstract

  Between 2016 and 2018, Brazil experienced major sylvatic yellow fever (YF) outbreaks that caused hundreds of casualties, with Minas Gerais (MG) being the most affected state. These outbreaks provided a unique opportunity to assess the immune response triggered by the wild-type (WT) yellow fever virus (YFV) in humans. The plaque reduction neutralization test (PRNT) is currently the standard method to assess the humoral immune response to YFV by measuring neutralizing antibodies (nAbs). The present study aimed to evaluate the humoral immune response of patients from the 2017-2018 sylvatic YF outbreak in MG with different disease outcomes by using PRNTs with a WT YFV strain, isolated from the 2017-2018 outbreak, and a vaccine YFV strain. Samples from naturally infected YF patients were tested, in comparison with healthy vaccinees. Results showed that both groups presented different levels of nAb against the WT and vaccine strains, and the levels of neutralization against the strains varied homotypically and heterotypically. Results based on the geometric mean titers (GMTs) suggest that the humoral immune response after a natural infection of YFV can reach higher levels than that induced by vaccination (GMT of patients against WT YFV compared to GMT of vaccinees, P < 0.0001). These findings suggest that the humoral immune responses triggered by the vaccine and WT strains of YFV are different, possibly due to genetic and antigenic differences between these viruses. Therefore, current means of assessing the immune response in naturally infected YF individuals and immunological surveillance methods in areas with intense viral circulation may need to be updated.IMPORTANCEYellow fever is a deadly febrile disease caused by the YFV. Despite the existence of effective vaccines, this disease still represents a public health concern worldwide. Much is known about the immune response against the vaccine strains of the YFV, but recent studies have shown that it differs from that induced by WT strains. The extent of this difference and the mechanisms behind it are still unclear. Thus, studies aimed to better understand the immune response against this virus are relevant and necessary. The present study evaluated levels of neutralizing antibodies of yellow fever patients from recent outbreaks in Brazil, in comparison with healthy vaccinees, using plaque reduction neutralization tests with WT and vaccine YFV strains. Results showed that the humoral immune response in naturally infected patients was higher than that induced by vaccination, thus providing new insights into the immune response triggered against these viruses.

  View details for DOI 10.1128/spectrum.03703-23

  View details for PubMedID 38511952

• Short Report: Low Rate of Asymptomatic Dengue Infection Detected in Coastal Kenya Using Pooled Polymerase Chain Reaction Testing. The American journal of tropical medicine and hygiene Kiener, M., Shayegh, N., Nyathi, S. V., Ndenga, B. A., Mutuku, F. M., LaBeaud, A. D. 2024

  Abstract

  Asymptomatic dengue virus (DENV) infections have important public health implications but are challenging to identify. We performed a cross-sectional study of reverse transcription quantitative polymerase chain reaction on pooled sera of asymptomatic individuals from the south coast of Kenya at two time periods to identify cases of asymptomatic viremia. Among 2,460 samples tested in pools of 9 or 10, we found only one positive case (0.04% incidence). Although pooling of samples has the potential to be a cost-effective and time-efficient method for asymptomatic DENV detection, mass cross-sectional pooled testing may not provide accurate data on rates of asymptomatic infection, likely owing to a decrease in the sensitivity with pooling of samples, a short period of viremia, or testing in the absence of an outbreak.

  View details for DOI 10.4269/ajtmh.23-0650

  View details for PubMedID 38471167

• Yellow fever virus infection in human hepatocyte cells triggers an imbalance in redox homeostasis with increased reactive oxygen species production, oxidative stress, and decreased antioxidant enzymes FREE RADICAL BIOLOGY AND MEDICINE Ferraz, A., Menegatto, M., Lima, R., Ola-Olub, O., Costa, D., de Magalhaes, J., Rezende, I., LaBeaud, A., Monath, T. P., Alves, P., de Carvalho, A., Martins-Filho, O., Drumond, B. P., Magalhaes, C. 2024; 213: 266-273

  Abstract

  Yellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes cells, could trigger an imbalance in redox homeostasis, culminating in oxidative stress. YFV infection resulted in a significant increase in reactive oxygen species (ROS) levels from 2 to 4 days post infection (dpi). When measuring oxidative parameters at 4 dpi, YFV infection caused oxidative damage to lipids, proteins, and DNA, evidenced by an increase in lipid peroxidation/8-isoprostane, carbonyl protein, and 8-hydroxy-2'-deoxyguanosine, respectively. Furthermore, there was a significant reduction in the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), in addition to a reduction in the ratio of reduced to oxidized glutathione (GSH/GSSG), indicating a pro-oxidant environment. However, no changes were observed in the enzymatic activity of the enzyme catalase (CAT) or in the gene expression of SOD isoforms (1/2/3), CAT, or GPx. Therefore, our results show that YFV infection generates an imbalance in redox homeostasis, with the overproduction of ROS and depletion of antioxidant enzymes, which induces oxidative damage to cellular constituents. Moreover, as it has been demonstrated that oxidative stress is a conspicuous event in YFV infection, therapeutic strategies based on antioxidant biopharmaceuticals may be new targets for the treatment of YF.

  View details for DOI 10.1016/j.freeradbiomed.2024.01.042

  View details for Web of Science ID 001178333200001

  View details for PubMedID 38278309

  View details for PubMedCentralID PMC10911966

• Top 5 Things Health Professions Students Should Know About Ecology and Waste Management. AMA journal of ethics Rosser, J. I., Lavery, O. X., Christofferson, R. C., Nasoro, J., Mutuku, F. M., LaBeaud, A. D. 2024; 26 (2): E132-141

  Abstract

  The environments in which we live affect individual and community risk for disease transmission and illness severity. Communities' and neighborhoods' waste stream management designs and health care organizations' spatial and structural architecture also influence individuals' and communities' pathogenic vulnerabilities and how well health sector industrial hygiene practices support them. This article describes a One Health approach to planetary environmental health and suggests strategies for implementing a One Health or Planetary Health approach in the context of climate change.

  View details for DOI 10.1001/amajethics.2024.132

  View details for PubMedID 38306203

• Non-household environments make a major contribution to dengue transmission: Implications for vector control. medRxiv : the preprint server for health sciences Peña-García, V. H., Desiree LaBeaud, A., Ndenga, B. A., Mutuku, F. M., Bisanzio, D. A., Mordecai, E. A., Andrews, J. R. 2024

  Abstract

  Aedes-borne pathogens have been increasing in incidence in recent decades despite vector control activities implemented in endemic settings. Vector control for Aedes-transmitted arboviruses typically focuses on households because vectors breed in household containers and bite indoors. Yet, our recent work shows a high abundance of Aedes spp. vectors in public spaces. To investigate the impact of non-household environments on dengue transmission and control, we used field data on the number of water containers and abundance of Aedes mosquitoes in Household (HH) and Non-Household (NH) environments in two Kenyan cities, Kisumu and Ukunda, from 2019-2022. Incorporating information on human activity space, we developed an agent-based model to simulate city-wide conditions considering HH and five types of NH environments in which people move and interact with other humans and vectors during peak biting times. We additionally evaluated the outcome of vector control activities implemented in different environments in preventive (before an epidemic) and reactive (after an epidemic commences) scenarios. We estimated that over half of infections take place in NH environments, where the main spaces for transmission are workplaces, markets, and recreational locations. Accordingly, results highlight the important role of vector control activities at NH locations to reduce dengue. A greater reduction of cases is expected as control activities are implemented earlier, at higher levels of coverage, with greater effectiveness when targeting only NH as opposed to when targeting only HH. Further, local ecological factors such as the differential abundance of water containers within cities are also influential factors to consider for control. This work provides insight into the importance of vector control in both household and non-household environments in endemic settings. It highlights a specific approach to inform evidence-based decision making to target limited vector control resources for optimal control.

  View details for DOI 10.1101/2024.01.08.24301016

  View details for PubMedID 38260355

  View details for PubMedCentralID PMC10802645

• Yellow Jack's Potential Return to the American South. The New England journal of medicine Hotez, P. J., LaBeaud, A. D. 2023

  View details for DOI 10.1056/NEJMp2308420

  View details for PubMedID 37843124

• The Importance of Including Non-Household Environments in Dengue Vector Control Activities. Viruses Peña-García, V. H., Mutuku, F. M., Ndenga, B. A., Mbakaya, J. O., Ndire, S. O., Agola, G. A., Mutuku, P. S., Malumbo, S. L., Ng'ang'a, C. M., Andrews, J. R., Mordecai, E. A., LaBeaud, A. D. 2023; 15 (7)

  Abstract

  Most vector control activities in urban areas are focused on household environments; however, information relating to infection risks in spaces other than households is poor, and the relative risk that these spaces represent has not yet been fully understood. We used data-driven simulations to investigate the importance of household and non-household environments for dengue entomological risk in two Kenyan cities where dengue circulation has been reported. Fieldwork was performed using four strategies that targeted different stages of mosquitoes: ovitraps, larval collections, Prokopack aspiration, and BG-sentinel traps. Data were analyzed separately between household and non-household environments to assess mosquito presence, the number of vectors collected, and the risk factors for vector presence. With these data, we simulated vector and human populations to estimate the parameter m and mosquito-to-human density in both household and non-household environments. Among the analyzed variables, the main difference was found in mosquito abundance, which was consistently higher in non-household environments in Kisumu but was similar in Ukunda. Risk factor analysis suggests that small, clean water-related containers serve as mosquito breeding places in households as opposed to the trash- and rainfall-related containers found in non-household structures. We found that the density of vectors (m) was higher in non-household than household environments in Kisumu and was also similar or slightly lower between both environments in Ukunda. These results suggest that because vectors are abundant, there is a potential risk of transmission in non-household environments; hence, vector control activities should take these spaces into account.

  View details for DOI 10.3390/v15071550

  View details for PubMedID 37515236

• OVIPOSITION PREFERENCES OF AEDES AEGYPTI IN MSAMBWENI, KWALE COUNTY, KENYA JOURNAL OF THE AMERICAN MOSQUITO CONTROL ASSOCIATION Musunzaji, P., Ndenga, B. A., Mzee, S., Abubakar, L. U., Kitron, U. D., Labeaud, A. D., Mutuku, F. 2023; 39 (2): 85-95

  Abstract

  Aedes aegypti is the primary vector of dengue fever virus (DENV) worldwide. Infusions made from organic materials have been shown to act as oviposition attractants for Ae. aegypti; however, studies on locally suitable infusion materials are lacking. The current study assessed the suitability of 4 locally available materials as oviposition infusions for use in surveillance and control of Ae. aegypti in Kwale County, Kenya. Oviposition infusion preferences were assessed in laboratory, semifield, and field conditions, using 4 infusions made from banana, grass, neem, and coconut. In addition, ovitrapping in wall, grass, bush, and banana microhabitats was done in 10 houses each in urban and rural coastal households to determine suitable oviposition microhabitats. Overall, the highest oviposition responses were observed for banana infusion, followed by neem and grass infusions, which were comparable. Coconut infusion resulted in the lowest oviposition response. Although female Ae. aegypti did not show preference for any microhabitat, the oviposition activity across all the microhabitats was highly enhanced by use of the organic infusions. Banana, neem, and grass infusions could be used to attract gravid mosquitoes to oviposition sites laced with insecticide to kill eggs. Additionally, banana plantings could be important targets for integrated vector control programs.

  View details for Web of Science ID 001032006400003

  View details for PubMedID 37270926

• Does Intra-Uterine Exposure to the Zika Virus Increase Risks of Cognitive Delay at Preschool Ages? Findings from a Zika-Exposed Cohort from Grenada, West Indies. Viruses Fernandes, M., Evans, R., Cheng, M., Landon, B., Noël, T., Macpherson, C., Cudjoe, N., Burgen, K. S., Waechter, R., LaBeaud, A. D., Blackmon, K. 2023; 15 (6)

  Abstract

  Maternal infection with Zika virus (ZIKV) is associated with a distinct pattern of birth defects, known as congenital Zika syndrome (CZS). In ZIKV-exposed children without CZS, it is often unclear whether they were protected from in utero infection and neurotropism. Early neurodevelopmental assessment is essential for detecting neurodevelopmental delays (NDDs) and prioritizing at-risk children for early intervention. We compared neurodevelopmental outcomes between ZIKV-exposed and unexposed children at 1, 3 and 4 years to assess exposure-associated NDD risk. A total of 384 mother-child dyads were enrolled during a period of active ZIKV transmission (2016-2017) in Grenada, West Indies. Exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. Neurodevelopment was assessed using the Oxford Neurodevelopment Assessment, the NEPSY® Second Edition and Cardiff Vision Tests, at 12 (n = 66), 36 (n = 58) and 48 (n = 59) months, respectively. There were no differences in NDD rates or vision scores between ZIKV-exposed and unexposed children. Rates of microcephaly at birth (0.88% vs. 0.83%, p = 0.81), and childhood stunting and wasting did not differ between groups. Our results show that Grenadian ZIKV-exposed children, the majority of whom were without microcephaly, had similar neurodevelopmental outcomes to unexposed controls up to at least an age of 4 years.

  View details for DOI 10.3390/v15061290

  View details for PubMedID 37376590

  View details for PubMedCentralID PMC10304152

• Factors Associated with Chikungunya Infection among Pregnant Women in Grenada, West Indies. The American journal of tropical medicine and hygiene Kiener, M., Cudjoe, N., Evans, R., Mapp-Alexander, V., Tariq, A., Macpherson, C., Noel, T., Gerardin, P., Waechter, R., LaBeaud, A. D. 2023

  Abstract

  Neonates are vulnerable to vector-borne diseases given the potential for mother-to-child congenital transmission. To determine factors associated with chikungunya virus (CHIKV) infection among pregnant women in Grenada, West Indies, a retrospective cohort study enrolled women who were pregnant during the 2014 CHIKV epidemic. In all, 520/688 women (75.5%) were CHIKV IgG positive. Low incomes, use of pit latrines, lack of home window screens, and subjective reporting of frequent mosquito bites were associated with increased risk of CHIKV infection in bivariate analyses. In the multivariate modified Poisson regression model, low income (adjusted relative risk [aRR]: 1.05 [95% CI: 1.01-1.10]) and frequent mosquito bites (aRR: 1.05 [95% CI: 1.01-1.10]) were linked to increased infection risk. In Grenada, markers of low socioeconomic status are associated with CHIKV infection among pregnant women. Given that Grenada will continue to face vector-borne outbreaks, interventions dedicated to improving living conditions of the most disadvantaged will help reduce the incidence of arboviral infections.

  View details for DOI 10.4269/ajtmh.23-0157

  View details for PubMedID 37253436

• Author Correction: Chikungunya fever. Nature reviews. Disease primers Bartholomeeusen, K., Daniel, M., LaBeaud, D. A., Gasque, P., Peeling, R. W., Stephenson, K. E., Ng, L. F., Ariën, K. K. 2023; 9 (1): 26

  View details for DOI 10.1038/s41572-023-00442-5

  View details for PubMedID 37208376

• Characterization and investigation of risk factors for Late-relapsing hepatitis after yellow fever. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America de Rezende, I. M., McClure, M. A., Pereira, L. S., Fradico, J. R., Cenachi, A. R., Moura, A. S., Paladino, L. L., Dutra, M. R., Alves, P. A., Xavier, M. A., Said, R. F., Ramalho, D. B., Gama, T. D., Martins-Filho, O. A., Monath, T. P., Teixeira-Carvalho, A., Drumond, B. P., LaBeaud, A. D., Yellow Fever Collaborative Group, Castro Bragato, A. M., Araujo, A. L., de Almeida Faria, F. A., Penido, I., Menezes, L., Rabelo, L. F., Pamplona, L., da Cunha Melo, L. F., Fonte Boa, L. S., Dos Santos, L. Z., de Paula, L., Marcal, M. C., Albuquerque, N. S., Macedo, R., Araujo, T. 2023

  Abstract

  BACKGROUND: Late relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by the rebound in liver enzymes and non-specific clinical manifestations around 30-60 days after YF symptom onset.METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais, and were followed-up at 30-, 45- and 60- days post symptom onset (dps).RESULTS: From 46 up to 60 dps, 16% of YF patients (n=36/221) exhibited a rebound of transaminases (AST or ALT >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF.CONCLUSIONS: These findings provide new data on the clinical course of late relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

  View details for DOI 10.1093/cid/ciad249

  View details for PubMedID 37099356

• Chikungunya fever. Nature reviews. Disease primers Bartholomeeusen, K., Daniel, M., LaBeaud, D. A., Gasque, P., Peeling, R. W., Stephenson, K. E., Ng, L. F., Ariën, K. K. 2023; 9 (1): 17

  Abstract

  Chikungunya virus is widespread throughout the tropics, where it causes recurrent outbreaks of chikungunya fever. In recent years, outbreaks have afflicted populations in East and Central Africa, South America and Southeast Asia. The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Chikungunya fever is characterized by severe arthralgia and myalgia that can persist for years and have considerable detrimental effects on health, quality of life and economic productivity. The effects of climate change as well as increased globalization of commerce and travel have led to growth of the habitat of Aedes mosquitoes. As a result, increasing numbers of people will be at risk of chikungunya fever in the coming years. In the absence of specific antiviral treatments and with vaccines still in development, surveillance and vector control are essential to suppress re-emergence and epidemics.

  View details for DOI 10.1038/s41572-023-00429-2

  View details for PubMedID 37024497

  View details for PubMedCentralID 9860750

• Serum soluble mediators as prognostic biomarkers for morbidity, disease outcome, and late-relapsing hepatitis in yellow fever patients. Clinical immunology (Orlando, Fla.) Fradico, J. R., Campi-Azevedo, A. C., Speziali, E., do Valle Antonelli, L. R., Peruhype-Magalhães, V., de Rezende, I. M., Alves, P. A., Pascoal-Xavier, M. A., Pereira, L. S., Dutra, M. R., Ramalho, D. B., Cenachi, A., de Paula, L., Santos, T. A., do Carmo Said, R. F., Calzavara-Silva, C. E., Coelho-Dos-Reis, J. G., de Magalhães, C. R., Rabelo, L. L., Valim, V., Brito-de-Sousa, J. P., da Costa-Rocha, I. A., de Souza Gomes, M., Amaral, L. R., de Lima, S. M., Trindade, G. F., Santos, R. T., da Silva, J. F., Monath, T., LaBeaud, A. D., Drumond, B. P., Martins-Filho, O. A., Teixeira-Carvalho, A. 2023: 109321

  Abstract

  This study described a soluble mediator storm in acute Yellow Fever/YF infection along the kinetic timeline towards convalescent disease. The analyses of the YF Viral RNAnemia, chemokines, cytokines, and growth factors were performed in YF patients at acute/(D1-15) and convalescent/(D16-315) phases. Patients with acute YF infection displayed a trimodal viremia profile spreading along D3, D6, and D8-14. A massive storm of mediators was observed in acute YF. Higher levels of mediators were observed in YF with higher morbidity scores, patients under intensive care, and those progressing to death than in YF patients who progress to late-relapsing hepatitis/L-Hep. A unimodal peak of biomarkers around D4-6 with a progressive decrease towards D181-315 was observed in non-L-Hep patients, while a bimodal pattern with a second peak around D61-90 was associated with L-Hep. This study provided a comprehensive landscape of evidence that distinct immune responses drive pathogenesis, disease progression, and L-Hep in YF patients.

  View details for DOI 10.1016/j.clim.2023.109321

  View details for PubMedID 37019421

• Spatiotemporal overlapping of dengue, chikungunya, and malaria infections in children in Kenya. BMC infectious diseases Khan, A., Bisanzio, D., Mutuku, F., Ndenga, B., Grossi-Soyster, E. N., Jembe, Z., Maina, P. W., Chebii, P. K., Ronga, C. O., Okuta, V., LaBeaud, A. D. 2023; 23 (1): 183

  Abstract

  Malaria, chikungunya virus (CHIKV), and dengue virus (DENV) are endemic causes of fever among children in Kenya. The risks of infection are multifactorial and may be influenced by built and social environments. The high resolution overlapping of these diseases and factors affecting their spatial heterogeneity has not been investigated in Kenya. From 2014-2018, we prospectively followed a cohort of children from four communities in both coastal and western Kenya. Overall, 9.8% were CHIKV seropositive, 5.5% were DENV seropositive, and 39.1% were malaria positive (3521 children tested). The spatial analysis identified hot-spots for all three diseases in each site and in multiple years. The results of the model showed that the risk of exposure was linked to demographics with common factors for the three diseases including the presence of litter, crowded households, and higher wealth in these communities. These insights are of high importance to improve surveillance and targeted control of mosquito-borne diseases in Kenya.

  View details for DOI 10.1186/s12879-023-08157-4

  View details for PubMedID 36991340

  View details for PubMedCentralID 6881070

• Pupal productivity of larval habitats of Aedes aegypti in Msambweni, Kwale County, Kenya. Parasitology research Mwakutwaa, A. S., Ngugi, H. N., Ndenga, B. A., Krystosik, A., Ngari, M., Abubakar, L. U., Yonge, S., Kitron, U., LaBeaud, A. D., Mutuku, F. M. 2023

  Abstract

  Aedes aegypti is an important vector of several arboviruses including dengue and chikungunya viruses. Accurate identification of larval habitats of Ae. aegypti is considered an essential step in targeted control. This study determined Ae. aegypti productivity in selected larval habitats in Msambweni, Kwale County, Kenya. Three sequential larval habitat surveys were conducted. The first survey was habitat census (baseline) through which 83 representative larval habitats were identified and selected. The second and third surveys involved estimating daily productivity of the 83 selected larval habitats for 30 consecutive days during a wet and a dry season, respectively. Of 664 larval habitats examined at baseline, 144 larval habitats (21.7%) were found to be infested with Ae. aegypti larvae. At baseline, majority (71%) of the pupae were collected from two (2/6) larval habitat types, tires and pots. Multivariate analysis identified habitat type and the habitat being movable as the predictors for pupal abundance. During the 30-day daily pupal production surveys, only a few of the habitats harbored pupae persistently. Pupae were found in 28% and 12% of the larval habitats during the wet and dry seasons, respectively. In the wet season, drums, tires, and pots were identified as the key habitat types accounting for 85% of all pupae sampled. Three habitats (all drums) accounted for 80% of all the pupae collected in the dry season. Predictors for pupal productivity in the wet season were habitat type, place (whether the habitat is located at the back or front of the house), habitat purpose (use of the water in the habitat), and source of water. Although the multivariate model for habitat type did not converge, habitat type and habitat size were the only significant predictors during the dry season. Drums, pots, and tires were sources of more than 85% of Ae. aegypti pupae, reinforcing the "key container concept." Targeting these three types of habitats makes epidemiological sense, especially during the dry season.

  View details for DOI 10.1007/s00436-022-07777-0

  View details for PubMedID 36683088

• Exploring potential risk pathways with high risk groups for urban Rift Valley fever virus introduction, transmission, and persistence in two urban centers of Kenya. PLoS neglected tropical diseases Gerken, K. N., Maluni, J., Mutuku, F. M., Ndenga, B. A., Mwashee, L., Ichura, C., Shaita, K., Mwaniki, M., Orwa, S., Seetah, K., LaBeaud, A. D. 2023; 17 (1): e0010460

  Abstract

  Rift Valley fever virus (RVFV) is a zoonotic arbovirus that has profound impact on domestic ruminants and can also be transmitted to humans via infected animal secretions. Urban areas in endemic regions across Africa have susceptible animal and human hosts, dense vector distributions, and source livestock (often from high risk locations to meet the demand for animal protein). Yet, there has never been a documented urban outbreak of RVF. To understand the likely risk of RVFV introduction to urban communities from their perspective and guide future initiatives, we conducted focus group discussions with slaughterhouse workers, slaughterhouse animal product traders, and livestock owners in Kisumu City and Ukunda Town in Kenya. For added perspective and data triangulation, in-depth interviews were conducted one-on-one with meat inspector veterinarians from selected slaughterhouses. A theoretical framework relevant to introduction, transmission, and potential persistence of RVF in urban areas is presented here. Urban livestock were primarily mentioned as business opportunities, but also had personal sentiment. In addition to slaughtering risks, perceived risk factors including consumption of fresh milk. High risk groups' knowledge and experience with RVFV and other zoonotic diseases impacted their consideration personal risk, with consensus towards lower risk in the urban setting compared to rural areas as determination of health risk was said to primarily rely on hygiene practices rather than the slaughtering process. Groups relied heavily on veterinarians to confirm animal health and meat safety, yet veterinarians reported difficulty in accessing RVFV diagnostics. We also identified vulnerable public health regulations including corruption in meat certification outside of the slaughterhouse system, and blood collected during slaughter being used for food and medicine, which could provide a means for direct RVFV community transmission. These factors, when compounded by diverse urban vector breeding habitats and dense human and animal populations, could create suitable conditions for RVFV to arrive an urban center via a viremic imported animal, transmit to locally owned animals and humans, and potentially adapt to secondary vectors and persist in the urban setting. This explorative qualitative study proposes risk pathways and provides initial insight towards determining how urban areas could adapt control measures and plan future initiatives to better understand urban RVF potential.

  View details for DOI 10.1371/journal.pntd.0010460

  View details for PubMedID 36634153

• Detection of acute dengue virus infection, with and without concurrent malaria infection, in a cohort of febrile children in Kenya, 2014-2019, by clinicians or machine learning algorithms. PLOS global public health Vu, D. M., Krystosik, A. R., Ndenga, B. A., Mutuku, F. M., Ripp, K., Liu, E., Bosire, C. M., Heath, C., Chebii, P., Maina, P. W., Jembe, Z., Malumbo, S. L., Amugongo, J. S., Ronga, C., Okuta, V., Mutai, N., Makenzi, N. G., Litunda, K. A., Mukoko, D., King, C. H., LaBeaud, A. D. 2023; 3 (7): e0001950

  Abstract

  Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naive Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance.

  View details for DOI 10.1371/journal.pgph.0001950

  View details for PubMedID 37494331

• Leveraging livestock movements to urban slaughterhouses for wide-spread Rift Valley fever virus surveillance in Western Kenya ONE HEALTH Gerken, K., Ndenga, B., Owuor, K., Winter, C., Seetah, K., LaBeaud, A. 2022; 15: 100457

  Abstract

  Rift Valley fever virus (RVFV) is an economically devastating, zoonotic arbovirus endemic across Africa with potential to cause severe disease in livestock and humans. Viral spread is primarily driven by movement of domestic ruminants and there is a high potential for transboundary spread. Despite influx of livestock to urban areas in response to the high demand for meat and animal products, RVFV has not been detected in any urban center. The objectives of this study were to determine the feasibility of assessing risk of RVFV introduction to urban Kisumu, Kenya, by testing slaughtered livestock for RVFV exposure and mapping livestock origins. Blood was collected from cattle, sheep, and goats directly after slaughter and tested for anti-RVFV IgG antibodies. Slaughterhouse businessmen responded to a questionnaire on their individual animals' origin, marketplace, and transport means. Thereafter, we mapped livestock flow from origin to slaughterhouse using participatory methods in focus group discussions with stakeholders. Qualitative data on route choice and deviations were spatially integrated into the map. A total of 304 blood samples were collected from slaughtered livestock in October and November 2021. Most (99%) of animals were purchased from 28 different markets across eight counties in Western Kenya. The overall RVFV seroprevalence was 9% (19% cattle, 3% in sheep, and 7% in goats). Migori County bordering Tanzania had the highest county-level seroprevalence (34%) and 80% of all seropositive cattle were purchased at the Suba Kuria market in Migori County. Road quality and animal health influenced stakeholders' decisions for choice of transport means. Overall, this proof-of-concept study offers a sampling framework for RVFV that can be locally implemented and rapidly deployed in response to regional risk. This system can be used in conjunction with participatory maps to improve active livestock surveillance and monitoring of RVFV in Western Kenya, and these methods could be extrapolated to other urban centers or livestock diseases.

  View details for DOI 10.1016/j.onehlt.2022.100457

  View details for Web of Science ID 000890330700002

  View details for PubMedID 36532672

  View details for PubMedCentralID PMC9754961

• Characterization and regulation of microplastic pollution for protecting planetary and human health. Environmental pollution (Barking, Essex : 1987) Jung, Y. S., Sampath, V., Prunicki, M., Aguilera, J., Allen, H., LaBeaud, D., Veidis, E., Barry, M., Erny, B., Patel, L., Akdis, C., Akdis, M., Nadeau, K. 2022: 120442

  Abstract

  Microplastics are plastic particles <5 mm in diameter. Since the 1950s, there has been an exponential increase in the production of plastics. As of 2015, it is estimated that approximately 6300 million metric tons of plastic waste had been generated of which 79% has accumulated in landfills or the natural environment. Further, it is estimated that if current trends continue, roughly 12,000 million metric tons of plastic waste will accumulate by 2050. Plastics and microplastics are now found ubiquitously-in the air, water, and soil. Microplastics are small enough to enter the tissues of plants and animals and have been detected in human lungs, stools, placentas, and blood. Their presence in human tissues and the food chain is a cause for concern. While direct clinical evidence or epidemiological studies on the adverse effects of microplastic on human health are lacking, in vitro cellular and tissue studies and in vivo animal studies suggest potential adverse effects. With the ever-increasing presence of plastic waste in our environment, it is critical to understand their effects on our environment and on human health. The use of plastic additives, many of which have known toxic effects are also of concern. This review provides a brief overview of microplastics and the extent of the microplastic problem. There have been a few inroads in regulating plastics but currently these are insufficient to adequately mitigate plastic pollution. We also review recent advances in microplastic testing methodologies, which should support management and regulation of plastic wastes. Significant efforts to reduce, reuse, and recycle plastics are needed at the individual, community, national, and international levels to meet the challenge. In particular, significant reductions in plastic production must occur to curb the impacts of plastic on human and worldwide health, given the fact that plastic is not truly recyclable.

  View details for DOI 10.1016/j.envpol.2022.120442

  View details for PubMedID 36272609

• How Should US Health Care Lead Global Change in Plastic Waste Disposal? AMA journal of ethics Jain, N., LaBeaud, D. 2022; 24 (10): E986-993

  Abstract

  Disposal of health care waste is one of the biggest threats to global sustainable health care. Current practices of dumping domestic and international health care waste into the earth's terra firma and oceans also undermine global health equity by adversely affecting the health of vulnerable communities. While the United Kingdom works toward circular health care economy streams that produce minimal waste, the United States continues to amplify downstream environmental and health effects of health care organizational waste management decisions. This article suggests how to reframe social and ethical responsibility for health care waste production and management by assigning strict accountability to health care organizational leaders, incentivizing circular supply chain implementation and maintenance, and encouraging strong collaborations across medical, plastic, and waste industries.

  View details for DOI 10.1001/amajethics.2022.986

  View details for PubMedID 36215191

• Yellow Fever Molecular Diagnosis Using Urine Specimens during Acute and Convalescent Phases of the Disease. Journal of clinical microbiology de Rezende, I. M., Oliveira, G. F., Costa, T. A., Khan, A., Pereira, L. S., Santos, T. A., Alves, P. A., Calzavara-Silva, C. E., Martins-Filho, O. A., Teixeira-Carvalho, A., LaBeaud, A. D., Drumond, B. P. 2022: e0025422

  Abstract

  Prior studies have demonstrated prolonged presence of yellow fever virus (YFV) RNA in saliva and urine as an alternative to serum. To investigate the presence of YFV RNA in urine, we used RT-PCR for YFV screening in 60 urine samples collected from a large cohort of naturally infected yellow fever (YF) patients during acute and convalescent phases of YF infection from recent YF outbreaks in Brazil (2017 to 2018). Fifteen urine samples from acute phase infection (up to 15days post-symptom onset) and four urine samples from convalescent phase infection (up to 69days post-symptom onset), were YFV PCR-positive. We genotyped YFV detected in seven urine samples (five collected during the acute phase and two collected during the YF convalescent phase). Genotyping indicated the presence of YFV South American I genotype in these samples. To our knowledge, this is the first report of wild-type YFV RNA detection in the urine this far out from symptom onset (up to 69 DPS), including YFV RNA detection during the convalescent phase of YF infection. The detection of YFV RNA in urine is an indicative of YFV infection; however, the results of RT-PCR using urine as sample should be interpreted with care, since a negative result does not exclude the possibility of YFV infection. With a possible prolonged period of detection beyond the viremic phase, the use of urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory YF diagnosis.

  View details for DOI 10.1128/jcm.00254-22

  View details for PubMedID 35916519

• Why Climate Action Is Global Health Action. The American journal of tropical medicine and hygiene 2022

  Abstract

  The impacts of climate change on global health and populations are far-reaching, yet they disproportionately affect vulnerable groups, thereby exacerbating disparities. As humanity reckons with the emergency of climate change, our global health community needs to contend with our own contributions to greenhouse gas emissions. We know that transformation is possible and that climate action is the antidote to the existential challenge. As a global health community, we have an immense opportunity, responsibility, and commitment to lead, support, inspire, and empower climate action, research, and innovation that align deeply with our mission and core values.

  View details for DOI 10.4269/ajtmh.22-0189

  View details for PubMedID 35895350

• Urban risk factors for human Rift Valley fever virus exposure in Kenya. PLOS global public health Gerken, K. N., Mutuku, F. M., Ndenga, B. A., Agola, G. A., Migliore, E., Fabre, E. P., Malumbo, S., Shaita, K. N., Rezende, I. M., LaBeaud, A. D. 2022; 2 (7): e0000505

  Abstract

  The Rift Valley fever virus (RVFV) is a zoonotic arbovirus that can also transmit directly to humans from livestock. Previous studies have shown consumption of sick animal products are risk factors for RVFV infection, but it is difficult to disentangle those risk factors from other livestock rearing activities. Urban areas have an increased demand for animal source foods, different vector distributions, and various arboviruses are understood to establish localized urban transmission cycles. Thus far, RVFV is an unevaluated public health risk in urban areas within endemic regions. We tested participants in our ongoing urban cohort study on dengue (DENV) and chikungunya (CHIKV) virus for RVFV exposure and found 1.6% (57/3,560) of individuals in two urban areas of Kenya had anti-RVFV IgG antibodies. 88% (50/57) of RVFV exposed participants also had antibodies to DENV, CHIKV, or both. Although livestock ownership was very low in urban study sites, RVFV exposure was overall significantly associated with seeing goats around the homestead (OR = 2.34 (CI 95%: 1.18-4.69, p = 0.02) and in Kisumu, RVFV exposure was associated with consumption of raw milk (OR = 6.28 (CI 95%: 0.94-25.21, p = 0.02). In addition, lack of piped water and use of small jugs (15-20 liters) for water was associated with a higher risk of RVFV exposure (OR = 5.36 (CI 95%: 1.23-16.44, p = 0.01) and this may contribute to interepidemic vector-borne maintenance of RVFV. We also investigated perception towards human vaccination for RVFV and identified high acceptance (91% (97/105) at our study sites. This study provides baseline evidence to guide future studies investigating the urban potential of RVFV and highlights the unexplored role of animal products in continued spread of RVFV.

  View details for DOI 10.1371/journal.pgph.0000505

  View details for PubMedID 36962424

  View details for PubMedCentralID PMC10021321

• A Retrospective Study of the Seroprevalence of Dengue Virus and Chikungunya Virus Exposures in Nigeria, 2010-2018. Pathogens (Basel, Switzerland) Ekong, P. S., Aworh, M. K., Grossi-Soyster, E. N., Wungak, Y. S., Maurice, N. A., Altamirano, J., Ekong, M. J., Olugasa, B. O., Nwosuh, C. I., Shamaki, D., Faburay, B., LaBeaud, D. A. 2022; 11 (7)

  Abstract

  Arboviruses are important public health threats in many regions of the world. Nigeria has experienced outbreaks of arboviruses over the past decades, leading to concerns of widespread endemicity, which are frequently misdiagnosed. This study aimed to determine the seroprevalence of dengue virus (DENV) (a flavivirus) and chikungunya virus (CHIKV) (an alphavirus) infections in three major population centers of Nigeria. A convenience sample of 701 sera was collected from both healthy and febrile participants between August 2010 and March 2018. Sera were tested for prior exposure to CHIKV virus and DENV using indirect IgG ELISA. Results showed that 54.1% (379/701) of participants were seropositive for anti-DENV antibodies, 41.3% (290/701) were seropositive for anti-CHIKV antibodies, and 20.1% (141/701) had previous exposure to both. The seropositivity for prior CHIKV exposure and prior exposure to DENV and CHIKV was significantly associated with age (CHIKV: OR = 2.7 (95% CI: 1.7-4.3); DENV and CHIKV: OR = 2.2 (95% CI: 1.2-4.0) for adults compared to participants under 18 years old). Overall, the high seropositivity across all age groups suggests that arboviral infections are prevalent in Nigeria and indicates that surveillance and further epidemiological studies are required to determine the true burden of these infections and the spectrum of diseases associated with these exposures.

  View details for DOI 10.3390/pathogens11070762

  View details for PubMedID 35890007

• Night Time Extension of Aedes aegypti Human Blood Seeking Activity. The American journal of tropical medicine and hygiene Ndenga, B. A., Mutuku, F. M., Ngugi, H. N., Mbakaya, J. O., Mukoko, D., Kitron, U., LaBeaud, A. D. 2022

  Abstract

  This study examined whether Aedes aegypti extends its human blood seeking activity into night hours. Human landing catches (HLC) were conducted hourly from early morning (04:30) to late evening (21:30) in urban and rural sites in Kisumu County in western Kenya, and in Kwale County at the coast. Out of 842 female Ae. aegypti mosquitoes, 71 (8.5%) were collected at night (nocturnal), 151 (17.9%) at twilight (crepuscular), and 620 (73.6%) during the day (diurnal). Three-fold and significantly more Ae. aegypti female mosquitoes were collected during the twilight (crepuscular) hours than night (nocturnal) hours. Significantly more Ae. aegypti female mosquitoes were collected during daytime (diurnal) than night time (nocturnal). In general, the number of mosquitoes collected reduced as darkness increased. Extended time into the night to seek for blood meals enhances chances for Ae. aegypti to contact humans and transmit arboviruses diseases.

  View details for DOI 10.4269/ajtmh.21-0309

  View details for PubMedID 35640647

• Characterizing the Severity of SARS-CoV-2 Variants at a Single Pediatric Center FRONTIERS IN MEDICINE Khan, A., Ichura, C., Wang, H., Rezende, I., Sahoo, M. K., Huang, C., Solis, D., Sibai, M., Yamamoto, F., Nyathi, S., Bayrau, B., Pinsky, B. A., LaBeaud, A. 2022; 9: 896352

  Abstract

  Since March 2020, SARS-CoV-2 has plagued the world with COVID-19 and individuals of all ages have experienced varying symptoms of disease. Older adults were experiencing more severe disease compared to children and were prioritized by vaccination efforts. While biologic therapies and vaccinations were implemented, there were changes in public health restrictions with subsequent surges resulting in more infected children. During these surges there was a rise of different SARS-CoV-2 variants with the dominant variant initially alpha (B.1.1.7 and other Pango lineages) and epsilon (B.1.427/B.1.429) in early 2021 and a dramatic shift to delta (B.1.617.2 and other Pango lineages) by mid-summer 2021. In this study we aimed to characterize the clinical severity and host factors associated with disease by SARS-CoV-2 variant and evaluate if there are differences in disease severity by circulating variant. We retrospectively included all individuals 0-25 years of age who presented to our center and had a positive SARS-CoV-2 RT-PCR, SARS-CoV-2 variant mutation testing, and documented clinical notes from 1 January 2021 through 31 December 2021. We identified 745 individuals who met inclusion criteria and found the delta variant was associated with severe/critical disease compared to the other variants studied. The results of the model showed that underlying respiratory disease and diabetes were risk factors for progression to severe disease. These insights are important when evaluating public health measures and treatment options for children as more variants arise.

  View details for DOI 10.3389/fmed.2022.896352

  View details for Web of Science ID 000807127000001

  View details for PubMedID 35677819

  View details for PubMedCentralID PMC9168367

• Majority of pediatric dengue virus infections in Kenya do not meet 2009 WHO criteria for dengue diagnosis. PLOS global public health Khan, A., Ndenga, B., Mutuku, F., Bosire, C. M., Okuta, V., Ronga, C. O., Mutai, N. K., Musaki, S. K., Chebii, P. K., Maina, P. W., Jembe, Z., Amugongo, J. S., Malumbo, S. L., Ng'ang'a, C. M., LaBeaud, D. 2022; 2 (4): e0000175

  Abstract

  From 1975-2009, the WHO guidelines classified symptomatic dengue virus infections as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. In 2009 the case definition was changed to a clinical classification after concern the original criteria was challenging to apply in resource-limited settings and not inclusive of a substantial proportion of severe dengue cases. Our goal was to examine how well the current WHO definition identified new dengue cases at our febrile surveillance sites in Kenya. Between 2014 and 2019 as part of a child cohort study of febrile illness in our four clinical study sites (Ukunda, Kisumu, Msambweni, Chulaimbo) we identified 369 dengue PCR positive symptomatic cases and characterized whether they met the 2009 revised WHO diagnostic criteria for dengue with and without warning signs and severe dengue. We found 62% of our PCR-confirmed dengue cases did not meet criteria per the guidelines. Our findings also correlate with our experience that dengue disease in children in Kenya is less severe as reported in other parts of the world. Although the 2009 clinical classification has recently been criticized for being overly inclusive and non-specific, our findings suggest the 2009 WHO dengue case definition may miss more than 50% of symptomatic infections in Kenya and may require further modification to include the African experience.

  View details for DOI 10.1371/journal.pgph.0000175

  View details for PubMedID 36962138

• Larval source reduction with a purpose: Designing and evaluating a household- and school-based intervention in coastal Kenya. PLoS neglected tropical diseases Forsyth, J. E., Kempinsky, A., Pitchik, H. O., Alberts, C. J., Mutuku, F. M., Kibe, L., Ardoin, N. M., LaBeaud, A. D. 2022; 16 (4): e0010199

  Abstract

  BACKGROUND: Since Aedes aegypti mosquitoes preferentially breed in domestic containers, control efforts focus on larval source reduction. Our objectives were to design and test the effectiveness of a source reduction intervention to improve caregiver knowledge and behaviors in coastal Kenya.METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster-randomized controlled trial with 261 households from 5 control villages and 259 households from 5 intervention villages. From each household, one child (10-16 years old) and his or her primary caregiver participated in the intervention. We assessed caregiver knowledge and behavior at baseline, as well as 3 and 12 months after the intervention. We assessed household entomological indices at baseline and 12 months after the intervention to avoid seasonal interference. We conducted qualitative interviews with 34 caregivers to understand barriers and facilitators to change. We counted and weighed containers collected by children and parents during a community container clean-up and recycling event. After 12 months, caregiver knowledge about and self-reported behavior related to at least one source reduction technique was more than 50 percentage points higher in the intervention compared to control arm (adjusted risk differences for knowledge: 0.69, 95% CI [0.56 to 0.82], and behavior: 0.58 [0.43 to 0.73]). Respondents stated that other family members' actions were the primary barriers to proper container management. The number of containers at households did not differ significantly across arms even though children and parents collected 17,200 containers (1 ton of plastics) which were used to planted 4,000 native trees as part of the community event.CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that source reduction interventions can be effective if designed with an understanding of the social and entomological context. Further, source reduction is not an individual issue, but rather a social/communal issue, requiring the participation of other household and community members to be sustained.

  View details for DOI 10.1371/journal.pntd.0010199

  View details for PubMedID 35363780

• Uncovering the Burden of Dengue in Africa: Considerations on Magnitude, Misdiagnosis, and Ancestry. Viruses Gainor, E. M., Harris, E., LaBeaud, A. D. 2022; 14 (2)

  Abstract

  Dengue is a re-emerging neglected disease of major public health importance. This review highlights important considerations for dengue disease in Africa, including epidemiology and underestimation of disease burden in African countries, issues with malaria misdiagnosis and co-infections, and potential evidence of genetic protection from severe dengue disease in populations of African descent. The findings indicate that dengue virus prevalence in African countries and populations may be more widespread than reported data suggests, and that the Aedes mosquito vectors appear to be increasing in dissemination and number. Changes in climate, population, and plastic pollution are expected to worsen the dengue situation in Africa. Dengue misdiagnosis is also a problem in Africa, especially due to the typical non-specific clinical presentation of dengue leading to misdiagnosis as malaria. Finally, research suggests that a protective genetic component against severe dengue exists in African descent populations, but further studies should be conducted to strengthen this association in various populations, taking into consideration socioeconomic factors that may contribute to these findings. The main takeaway is that Africa should not be overlooked when it comes to dengue, and more attention and resources should be devoted to this disease in Africa.

  View details for DOI 10.3390/v14020233

  View details for PubMedID 35215827

• Climate Change and Global Health: A Call to more Research and more Action. Allergy Agache, I., Sampath, V., Aguilera, J., Akdis, C., Akdis, M., Barry, M., Bouagnon, A., Chinthrajah, S., Collins, W., Dulitzki, C., Erny, B., Gomez, J., Goshua, A., Jutel, M., Kizer, K. W., Kline, O., LaBeaud, A. D., Pali-Scholl, I., Perrett, K. P., Peters, R. L., Plaza, M. P., Prunicki, M., Sack, T., Salas, R. N., Sindher, S. B., Sokolow, S. H., Thiel, C., Veidis, E., Wray, B. D., Traidl-Hoffmann, C., Witt, C., Nadeau, K. C. 1800

  Abstract

  There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

  View details for DOI 10.1111/all.15229

  View details for PubMedID 35073410

• Paving the way for human vaccination against Rift Valley fever virus: A systematic literature review of RVFV epidemiology from 1999 to 2021. PLoS neglected tropical diseases Gerken, K. N., LaBeaud, A. D., Mandi, H., L'Azou Jackson, M., Breugelmans, J. G., King, C. H. 1800; 16 (1): e0009852

  Abstract

  BACKGROUND: Rift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review's objective was to consolidate understanding of RVFV epidemiology during 1999-2021 and highlight knowledge gaps relevant to plans for human vaccine trials.METHODOLOGY/PRINCIPAL FINDINGS: The review is registered with PROSPERO (CRD42020221622). Reports of RVFV infection or exposure among humans, animals, and/or vectors in Africa, the Arabian Peninsula, and the Indian Ocean during the period January 1999 to June 2021 were eligible for inclusion. Online databases were searched for publications, and supplemental materials were recovered from official reports and research colleagues. Exposures were classified into five groups: 1) acute human RVF cases, 2) acute animal cases, 3) human RVFV sero-surveys, 4) animal sero-surveys, and 5) arthropod infections. Human risk factors, circulating RVFV lineages, and surveillance methods were also tabulated. In meta-analysis of risks, summary odds ratios were computed using random-effects modeling. 1104 unique human or animal RVFV transmission events were reported in 39 countries during 1999-2021. Outbreaks among humans or animals occurred at rates of 5.8/year and 12.4/year, respectively, with Mauritania, Madagascar, Kenya, South Africa, and Sudan having the most human outbreak years. Men had greater odds of RVFV infection than women, and animal contact, butchering, milking, and handling aborted material were significantly associated with greater odds of exposure. Animal infection risk was linked to location, proximity to water, and exposure to other herds or wildlife. RVFV was detected in a variety of mosquito vectors during interepidemic periods, confirming ongoing transmission.CONCLUSIONS/SIGNIFICANCE: With broad variability in surveillance, case finding, survey design, and RVFV case confirmation, combined with uncertainty about populations-at-risk, there were inconsistent results from location to location. However, it was evident that RVFV transmission is expanding its range and frequency. Gaps assessment indicated the need to harmonize human and animal surveillance and improve diagnostics and genotyping. Given the frequency of RVFV outbreaks, human vaccination has strong potential to mitigate the impact of this now widely endemic disease.

  View details for DOI 10.1371/journal.pntd.0009852

  View details for PubMedID 35073355

• Dietary Intake and Pneumococcal Vaccine Response Among Children (5-7 Years) in Msambweni Division, Kwale County, Kenya. Frontiers in nutrition Migliore, E., Amaitsa, V. K., Mutuku, F. M., Malhotra, I. J., Mukoko, D., Sharma, A., Kalva, P., Kang, A. S., King, C. H., LaBeaud, A. D. 2022; 9: 830294

  Abstract

  Background: Vaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.Methods: In this study, the 10-valent pneumococcal conjugate vaccine (Synflorix or PCV10) was administered to a child cohort (5-7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4-8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay.Findings: Chronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5-7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p < 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p < 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p < 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p < 0.03).Interpretation: Overall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.

  View details for DOI 10.3389/fnut.2022.830294

  View details for PubMedID 35677545

• Wild-type Yellow fever virus in cerebrospinal fluid from fatal cases in Brazil, 2018. Frontiers in virology (Lausanne, Switzerland) de Rezende, I. M., Cenachi, A. R., Costa, T. A., Oliveira, G. F., Rabelo, L., Menezes, L. M., Penido, I., Pereira, L. S., Arruda, M. S., Gonc Alves, A. P., Alves, P. A., Kroon, E. G., Calzavara-Silva, C. E., Ramalho, D. B., Martins-Filho, O. A., Teixeira-Carvalho, A., LaBeaud, A. D., Drumond, B. P. 2022; 2

  Abstract

  Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a hemorrhagic and viscerotropic acute disease. Severe YF has been described in approximately 15-25% of YF patients, with 20-50% of severe YF cases being fatal. Here we analyzed cerebrospinal fluid (CSF) samples collected during the YF outbreak in Brazil in 2018, aiming to investigate CNS neuroinvasion in fatal YFV cases. YFV RNA was screened by RT-qPCR targeting the 3'UTR region of the YFV genome in CSF. CSF samples were tested for the presence of anti-YFV IgM and neutralizing antibodies, coupled with routine laboratory examinations. Among the 13 patients studied, we detected anti-YFV IgM in CSF from eight patients and YFV RNA in CSF from five patients. YFV RNA genomic load in CSF samples ranged from 1.75*103 to 5.42*103 RNA copies/mL. We genotyped YFV from three CSF samples that grouped with other YFV samples from the 2018 outbreak in Brazil within the South-American I genotype. Even though descriptions of neurologic manifestations due to wild type YFV (WT-YFV) infection are rare, since the last YF outbreak in Brazil in 2017-2018, a few studies have demonstrated WT-YFV RNA in CSF samples from YF fatal cases. Serological tests indicated the presence of IgM and neutralizing antibodies against YFV in CSF samples from two patients. Although the presence of viral RNA, IgM and neutralizing antibodies in CSF samples could indicate neuroinvasiveness, further studies are needed to better elucidate the role of YFV neuroinvasion and possible impacts in disease pathogenesis.

  View details for DOI 10.3389/fviro.2022.936191

  View details for PubMedID 37461745

• COLLECTING TRASH FOR PROFIT TO REDUCE VECTOR BREEDING SITES IN SOUTH COAST KENYA Mutuku, F. M., Kibe, L., Krystosik, A., Dzoga, M., Ratanya, S., Njoroge, G., Forsyth, J., Forsyth, J., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 320

  View details for Web of Science ID 000778105603092

• ABUNDANCE OF AEDES AEGYPTI FEMALE MOSQUITOES IN SPACES SURROUNDING RESIDENTIAL AND NON-RESIDENTIAL STRUCTURES IN WESTERN AND COASTAL KENYA Ndenga, B. A., Mutuku, F., Agola, G., Mbakaya, J., Ndire, S., Malumbo, S., Mutuku, P., LaBeaud, A. D. AMER SOC TROP MED & HYGIENE. 2021: 322

  View details for Web of Science ID 000778105603098

• SPATIOTEMPORAL OVERLAPPING OF DENGUE, CHIKUNGUNYA, AND MALARIA INFECTIONS IN CHILDREN IN KENYA Khan, A., Bisanzio, D., Mutuku, F., Ndenga, B., Jembe, Z., Maina, P., Chebii, P., Ronga, C., Mwambingu, L., Okuta, V., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2021: 44-45

  View details for Web of Science ID 000778105601139

• USING MHEALTH SMS SURVEYS FOR ACTIVE SURVEILLANCE OF FEBRILE ILLNESS IN KENYA Ivory, J., Khan, A., Mutuku, F., Ndenga, B., Ronga, C., Godana, O., Mwangosho, K., Wanjala, L., Okuta, V., Jembe, Z., Agola, G., Kang, A., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 31

  View details for Web of Science ID 000778105601094

• MAJORITY OF PEDIATRIC DENGUE VIRUS INFECTIONS IN KENYA DO NOT MEET THE 2009 WHO CRITERIA FOR DENGUE DIAGNOSIS Khan, A., Ndenga, B., Mutuku, F., Ronga, C., Mwambingu, L., Okuta, V., Jembe, Z., Maina, P., Chebii, P., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2021: 185

  View details for Web of Science ID 000778105602270

• EFFECT OF COVID-19 ON TREATMENT-SEEKING AMONG PEOPLE LIVING IN A MALARIA-ENDEMIC AREA OF COASTAL KENYA Bisanzio, D., Mutuku, F., Ndenga, B., N'ang'a, C., Malumbo, S., Agola, G., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 65-66

  View details for Web of Science ID 000778105601206

• SEROPREVALENCE OF RIFT VALLEY FEVER VIRUS IN URBAN KENYA: A POTENTIAL PUBLIC HEALTH BURDEN HIDING IN PLAIN SIGHT Gerken, K. N., Migliore, E., Malumbo, S., Shaita, K. N., Agola, G., Fabre, E., Mutuku, F., Ndenga, B., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 57-58

  View details for Web of Science ID 000778105601180

• DENGUE AND CHIKUNGUNYA VIRUS EXPOSURE AMONG URBAN POPULATIONS IN WESTERN AND COASTAL KENYA Migliore, E., Mutuku, F. M., Ndenga, B. A., Agola, G., Sagina, J., Jembe, Z., Ng'ang'a, C., Godana, O., Kalva, P., Puntasecca, C. J., Sharma, A., Kang, A. S., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 46

  View details for Web of Science ID 000778105601143

• DIETARY INTAKE AND PNEUMOCOCCAL VACCINE RESPONSE AMONG CHILDREN (5-7 YEARS) IN MSAMBWENI DIVISION, KWALE COUNTY, KENYA Migliore, E., Amaitsa, V. K., Mutuku, F. M., Malhotra, I., Mukoko, D., Sharma, A., Kalva, P., Kang, A. S., King, C. H., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 429-430

  View details for Web of Science ID 000778105603435

• DESCRIBING PREDICTOR RISK FACTORS FOR LATE-RELAPSING HEPATITIS AFTER YELLOW FEVER Rezende, I. M., McClure, M., Pereira, L. S., Fradico, J. B., Kang, A. S., Goncalves, A. P., Oliveira, G. G., Alkifeles, T., Alves, P. A., Xavier, M. P., Martins-Filho, O. A., Teixeira-Carvalho, A., Drumond, B. P., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 270-271

  View details for Web of Science ID 000778105602535

• URINE AS A POSSIBLE RESOURCE FOR YELLOW FEVER DIAGNOSIS Rezende, I. M., Pereira, L. S., Khan, A., Oliveira, G. G., Alkifeles, T., Goncalves, A. P., Alves, P. A., Martins-Filho, O. A., Teixeira-Carvalho, A., LaBeaud, A., Drumond, B. P. AMER SOC TROP MED & HYGIENE. 2021: 187

  View details for Web of Science ID 000778105602276

• EVOLUTION AND GENOMIC EPIDEMIOLOGY OF DENGUE VIRUSIN RURAL AND URBAN COMMUNITIES IN KENYA Nyathi, S., Mutuku, F., Ndenga, B., Walter, K., Andrews, J., Bennett, S., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 328

  View details for Web of Science ID 000778105603119

• DENGUE VIRUS INFECTION LOWERED THE PERCENTAGE OF ATYPICAL MEMORY B CELLS IN KENYAN CHILDREN Vu, D. M., Kowli, S., Mutuku, F. M., Krystosik, A. R., Amugongo, J. S., Malumbo, S. L., Chebii, P. K., Maina, P. W., Maecker, H. T., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 327-328

  View details for Web of Science ID 000778105603117

• Neurodevelopment in normocephalic children with and without prenatal Zika virus exposure. Archives of disease in childhood Blackmon, K., Evans, R., Fernandes, M., Landon, B., Noel, T., Macpherson, C., Cudjoe, N., Burgen, K. S., Punch, B., Krystosik, A., Gross-Soyster, E. N., LaBeaud, A. D., Waechter, R. 2021

  Abstract

  OBJECTIVE: Zika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls.DESIGN: Cohort study.SETTING: Public health centres in Grenada, West Indies.PATIENTS: 384 mother-child pairs were enrolled during a period of active ZIKV transmission (April 2016-March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum.MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child's exposure status.RESULTS: A total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays.CONCLUSIONS: Overall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.

  View details for DOI 10.1136/archdischild-2020-321031

  View details for PubMedID 34479857

• Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition. Proceedings of the National Academy of Sciences of the United States of America Chapman, N. S., Zhao, H., Kose, N., Westover, J. B., Kalveram, B., Bombardi, R., Rodriguez, J., Sutton, R., Genualdi, J., LaBeaud, A. D., Mutuku, F. M., Pittman, P. R., Freiberg, A. N., Gowen, B. B., Fremont, D. H., Crowe, J. E. 2021; 118 (14)

  Abstract

  Rift Valley fever virus (RVFV), an emerging arboviral and zoonotic bunyavirus, causes severe disease in livestock and humans. Here, we report the isolation of a panel of monoclonal antibodies (mAbs) from the B cells of immune individuals following natural infection in Kenya or immunization with MP-12 vaccine. The B cell responses of individuals who were vaccinated or naturally infected recognized similar epitopes on both Gc and Gn proteins. The Gn-specific mAbs and two mAbs that do not recognize either monomeric Gc or Gn alone but recognized the hetero-oligomer glycoprotein complex (Gc+Gn) when Gc and Gn were coexpressed exhibited potent neutralizing activities in vitro, while Gc-specific mAbs exhibited relatively lower neutralizing capacity. The two Gc+Gn-specific mAbs and the Gn domain A-specific mAbs inhibited RVFV fusion to cells, suggesting that mAbs can inhibit the exposure of the fusion loop in Gc, a class II fusion protein, and thus prevent fusion by an indirect mechanism without direct fusion loop contact. Competition-binding analysis with coexpressed Gc/Gn and mutagenesis library screening indicated that these mAbs recognize four major antigenic sites, with two sites of vulnerability for neutralization on Gn. In experimental models of infection in mice, representative mAbs recognizing three of the antigenic sites reduced morbidity and mortality when used at a low dose in both prophylactic and therapeutic settings. This study identifies multiple candidate mAbs that may be suitable for use in humans against RVFV infection and highlights fusion inhibition against bunyaviruses as a potential contributor to potent antibody-mediated neutralization.

  View details for DOI 10.1073/pnas.2025642118

  View details for PubMedID 33782133

• COVID-19 Cliff Notes-A COVID-19 Multi-disciplinary Care Compendium: COVID-19 Cliff Notes. Transplantation and cellular therapy Williams, K. M., Wilson, P. T., Silva-Palacios, F., Kebbe, J., LaBeaud, A. D., Agudelo, H. N., Sidonio, R. F., Stowell, S. R., Josephson, C., Beth, A. T., Holter, C. J., Agwu, A. L. 2021

  Abstract

  As we pass the nearly 9 month mark of the coronavirus virus disease 2019 (COVID-19) pandemic in the United States, we sought to compile a brief multi-disciplinary compendium of COVID-19 information learned to date. COVID-19 is an active viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confers high morbidity and mortality. COVID-19 has been associated with: pulmonary compromise and acute respiratory distress syndrome, thrombotic events, inflammation and cytokine, and post-infectious syndromes. Mitigation of these complications and expeditious therapy are a global urgency; this is brief summary of current data and management approaches synthesized from publications, experience, cross-disciplinary expertise (Figure 1).

  View details for DOI 10.1016/j.jtct.2021.02.036

  View details for PubMedID 33686384

• Impact of recent climate extremes on mosquito-borne disease transmission in Kenya. PLoS neglected tropical diseases Nosrat, C., Altamirano, J., Anyamba, A., Caldwell, J. M., Damoah, R., Mutuku, F., Ndenga, B., LaBeaud, A. D. 2021; 15 (3): e0009182

  Abstract

  Climate change and variability influence temperature and rainfall, which impact vector abundance and the dynamics of vector-borne disease transmission. Climate change is projected to increase the frequency and intensity of extreme climate events. Mosquito-borne diseases, such as dengue fever, are primarily transmitted by Aedes aegypti mosquitoes. Freshwater availability and temperature affect dengue vector populations via a variety of biological processes and thus influence the ability of mosquitoes to effectively transmit disease. However, the effect of droughts, floods, heat waves, and cold waves is not well understood. Using vector, climate, and dengue disease data collected between 2013 and 2019 in Kenya, this retrospective cohort study aims to elucidate the impact of extreme rainfall and temperature on mosquito abundance and the risk of arboviral infections. To define extreme periods of rainfall and land surface temperature (LST), we calculated monthly anomalies as deviations from long-term means (1983-2019 for rainfall, 2000-2019 for LST) across four study locations in Kenya. We classified extreme climate events as the upper and lower 10% of these calculated LST or rainfall deviations. Monthly Ae. aegypti abundance was recorded in Kenya using four trapping methods. Blood samples were also collected from children with febrile illness presenting to four field sites and tested for dengue virus using an IgG enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). We found that mosquito eggs and adults were significantly more abundant one month following an abnormally wet month. The relationship between mosquito abundance and dengue risk follows a non-linear association. Our findings suggest that early warnings and targeted interventions during periods of abnormal rainfall and temperature, especially flooding, can potentially contribute to reductions in risk of viral transmission.

  View details for DOI 10.1371/journal.pntd.0009182

  View details for PubMedID 33735293

• No Evidence of O'nyong-Nyong Viremia among Children with Febrile Illness in Kenya (2015-2018). The American journal of tropical medicine and hygiene Shah, M. M., Ndenga, B. A., Mutuku, F. M., Okuta, V., Ronga, C. O., Chebii, P. K., Maina, P., Jembe, Z., Sahoo, M. K., Huang, C., Weber, J., Pinsky, B. A., LaBeaud, A. D. 2021

  Abstract

  O'nyong-nyong virus (ONNV) is a little-known arbovirus causing intermittent, yet explosive, outbreaks in Africa. It is closely related to chikungunya virus, an emerging infectious disease. O'nyong-nyong virus causes a self-limited illness characterized by bilateral polyarthritis, rash, low-grade fever, and lymphadenopathy. In 1959, an extensive outbreak of ONNV occurred in East Africa, and decades later, another large outbreak was documented in Uganda in 1996. Limited evidence for interepidemic transmission is available, although serologic studies indicate a high prevalence of exposure; 1,045 febrile child participants in western and coastal Kenya were tested for the presence of ONNV using a multiplexed real-time reverse transcriptase-PCR assay. More than half of the participants had malaria parasitemia, and there was no evidence of active ONNV viremia in these participants. Further work is required to better understand the interepidemic circulation of ONNV and to reconcile evidence of high serologic exposure to ONNV among individuals in East Africa.

  View details for DOI 10.4269/ajtmh.20-0580

  View details for PubMedID 33617476

• Measuring the global burden of chikungunya and Zika viruses: A systematic review. PLoS neglected tropical diseases Puntasecca, C. J., King, C. H., LaBeaud, A. D. 2021; 15 (3): e0009055

  Abstract

  Throughout the last decade, chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have spread globally, causing a spectrum of disease that ranges from self-limited febrile illness to permanent severe disability, congenital anomalies, and early death. Nevertheless, estimates of their aggregate health impact are absent from the literature and are currently omitted from the Global Burden of Disease (GBD) reports. We systematically reviewed published literature and surveillance records to evaluate the global burden caused by CHIKV and ZIKV between 2010 and 2019, to calculate estimates of their disability-adjusted life year (DALY) impact. Extracted data on acute, chronic, and perinatal outcomes were used to create annualized DALY estimates, following techniques outlined in the GBD framework. This study is registered with PROSPERO (CRD42020192502). Of 7,877 studies identified, 916 were screened in detail, and 21 were selected for inclusion. Available data indicate that CHIKV and ZIKV caused the average yearly loss of over 106,000 and 44,000 DALYs, respectively, between 2010 and 2019. Both viruses caused substantially more burden in the Americas than in any other World Health Organization (WHO) region. This unequal distribution is likely due to a combination of limited active surveillance reporting in other regions and the lack of immunity that left the previously unexposed populations of the Americas susceptible to severe outbreaks during the last decade. Long-term rheumatic sequelae provided the largest DALY component for CHIKV, whereas congenital Zika syndrome (CZS) contributed most significantly for ZIKV. Acute symptoms and early mortality accounted for relatively less of the overall burden. Suboptimal reporting and inconsistent diagnostics limit precision when determining arbovirus incidence and frequency of complications. Despite these limitations, it is clear from our assessment that CHIKV and ZIKV represent a significant cause of morbidity that is not included in current disease burden reports. These results suggest that transmission-blocking strategies, including vector control and vaccine development, remain crucial priorities in reducing global disease burden through prevention of potentially devastating arboviral outbreaks.

  View details for DOI 10.1371/journal.pntd.0009055

  View details for PubMedID 33661908

• Tackling the Ubiquity of Plastic Waste for Human and Planetary Health. The American journal of tropical medicine and hygiene Veidis, E. M., LaBeaud, A. D., Phillips, A. A., Barry, M. 2021

  View details for DOI 10.4269/ajtmh.21-0968

  View details for PubMedID 34749307

• Climate predicts geographic and temporal variation in mosquito-borne disease dynamics on two continents. Nature communications Caldwell, J. M., LaBeaud, A. D., Lambin, E. F., Stewart-Ibarra, A. M., Ndenga, B. A., Mutuku, F. M., Krystosik, A. R., Ayala, E. B., Anyamba, A., Borbor-Cordova, M. J., Damoah, R., Grossi-Soyster, E. N., Heras, F. H., Ngugi, H. N., Ryan, S. J., Shah, M. M., Sippy, R., Mordecai, E. A. 2021; 12 (1): 1233

  Abstract

  Climate drives population dynamics through multiple mechanisms, which can lead to seemingly context-dependent effects of climate on natural populations. For climate-sensitive diseases, such as dengue, chikungunya, and Zika, climate appears to have opposing effects in different contexts. Here we show that a model, parameterized with laboratory measured climate-driven mosquito physiology, captures three key epidemic characteristics across ecologically and culturally distinct settings in Ecuador and Kenya: the number, timing, and duration of outbreaks. The model generates a range of disease dynamics consistent with observed Aedes aegypti abundances and laboratory-confirmed arboviral incidence with variable accuracy (28-85% for vectors, 44-88% for incidence). The model predicted vector dynamics better in sites with a smaller proportion of young children in the population, lower mean temperature, and homes with piped water and made of cement. Models with limited calibration that robustly capture climate-virus relationships can help guide intervention efforts and climate change disease projections.

  View details for DOI 10.1038/s41467-021-21496-7

  View details for PubMedID 33623008

• The Zika Virus Individual Participant Data Consortium: A Global Initiative to Estimate the Effects of Exposure to Zika Virus during Pregnancy on Adverse Fetal, Infant, and Child Health Outcomes TROPICAL MEDICINE AND INFECTIOUS DISEASE Alger, J., de Alencar Ximenes, R., Avelino-Silva, V., Bardaji, A., Becerra Mojica, C., Benedetti, A., Benamor Teixeira, M., Bethencourt, S., Borja Aburto, V., Brant, F., Brasil, P., Brickley, E. B., Broutet, N., Buekens, P., Luisa Cafferata, M., Calvet, G., Campbell, H., Carabali, M., Chan, D., Costa, F., Ferreira, O., Coutinho, C., Cunha, A., Cure, C., Damen, J. A., de Jong, V. T., Debray, T. P., DeBiasi, R. L., Alfonso Diaz-Martinez, L., Duarte, G., Maria Ferriol, D., Ganz, J. S., Gerardin, P., Gilboa, S. M., Gonzalez, M., Grajales Muniz, C., Gustafson, P., Gutierrez Sanchez, L., Guzman, M. G., Hofer, C., Holband, N., Inwani, I., Jaenisch, T., Joao, E., Juliana, A., Kara, E., Kim, C., Ko, A., Koopmans, M., LaBeaud, A., Lash, M., Lee, E. H., Leo, Y., Levis, B., Low, N., Macpherson, C. L., Marban-Castro, E., Mattar, S., Maxwell, L., Mayaud, P., Melo, A., Menendez, C., Mercado Reyes, M., Miranda Montoya, M., Miranda-Filho, D., Moons, K. M., Morales, I., Moreira, M., Mulkey, S. B., Munoz Medina, J., Mussi-Pinhata, M., Natrajan, M. S., Njenga, M., Noel, T. P., Nogueira, M., Osoro, E., Ospina Martinez, M., Paladini, M., Passos, S., Perez, F., Pomar, L., Prata-Barbosa, A., Reis, M., Reveiz, L., Rodo, C., Pela Rosado, L., Rosenberger, K. D., Clemente, N., Sayers, J. L., Silva, A. A., de Siqueira, I. C., Sohan, K., Soria-Segarra, C., Soriano-Arandes, A., Sousa, P., Souza, J., Suy Franch, A., Tami, A., Teixeira, M., Thwin, S., Tong, V. T., Turchi, M., Turchi Martelli, C., Valencia, D., Van Kerkhove, M. D., Barreto de Araujo, T., Angel Villar, L., Vinuela Beneitez, C., Wei, Y., Widdowson, M., Wilder-Smith, A., Zika Virus Individual Participant 2020; 5 (4)

  Abstract

  This commentary describes the creation of the Zika Virus Individual Participant Data Consortium, a global collaboration to address outstanding questions in Zika virus (ZIKV) epidemiology through conducting an individual participant data meta-analysis (IPD-MA). The aims of the IPD-MA are to (1) estimate the absolute and relative risks of miscarriage, fetal loss, and short- and long-term sequelae of fetal exposure; (2) identify and quantify the relative importance of different sources of heterogeneity (e.g., immune profiles, concurrent flavivirus infection) for the risk of adverse fetal, infant, and child outcomes among infants exposed to ZIKV in utero; and (3) develop and validate a prognostic model for the early identification of high-risk pregnancies and inform communication between health care providers and their patients and public health interventions (e.g., vector control strategies, antenatal care, and family planning programs). By leveraging data from a diversity of populations across the world, the IPD-MA will provide a more precise estimate of the risk of adverse ZIKV-related outcomes within clinically relevant subgroups and a quantitative assessment of the generalizability of these estimates across populations and settings. The ZIKV IPD Consortium effort is indicative of the growing recognition that data sharing is a central component of global health security and outbreak response.

  View details for DOI 10.3390/tropicalmed5040152

  View details for Web of Science ID 000602276200001

  View details for PubMedID 33007828

  View details for PubMedCentralID PMC7709585

• Zika Syndrome: Assessing the fatality rate since the 2015 Zika outbreak Mendes Neto, N. N., Maia, J., Zacarkim, M., Queiroz, I. T., Labeaud, A. D., Aronoff, D. ELSEVIER SCI LTD. 2020: 351

  View details for DOI 10.1016/j.ijid.2020.09.921

  View details for Web of Science ID 000612135101122

• How radiological findings and neurological disorders are related in congenital zika syndrome: A cohort study Neto, N., Maia, J., Zacarkim, M., Labeaud, A. D., Aronoff, D. ELSEVIER SCI LTD. 2020: 241

  View details for DOI 10.1016/j.ijid.2020.11.065

  View details for Web of Science ID 000612135100533

• Epilepsy surveillance in normocephalic children with and without prenatal Zika virus exposure. PLoS neglected tropical diseases Blackmon, K., Waechter, R., Landon, B., Noel, T., Macpherson, C., Donald, T., Cudjoe, N., Evans, R., Burgen, K. S., Jayatilake, P., Oyegunle, V., Pedraza, O., Abdel Baki, S., Thesen, T., Dlugos, D., Chari, G., Patel, A. A., Grossi-Soyster, E. N., Krystosik, A. R., LaBeaud, A. D. 2020; 14 (11): e0008874

  Abstract

  Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003-0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings.

  View details for DOI 10.1371/journal.pntd.0008874

  View details for PubMedID 33253174

• Addressing Climate Change and Its Effects on Human Health: A Call to Action for Medical Schools. Academic medicine : journal of the Association of American Medical Colleges Goshua, A., Gomez, J., Erny, B., Burke, M., Luby, S., Sokolow, S., LaBeaud, A. D., Auerbach, P., Gisondi, M. A., Nadeau, K. 2020

  Abstract

  Human health is increasingly threatened by rapid and widespread changes in the environment and climate, including rising temperatures, air and water pollution, disease vector migration, floods, and droughts. In the United States, many medical schools, the American Medical Association, and the National Academy of Sciences have published calls for physicians and physicians-in-training to develop a basic knowledge of the science of climate change and an awareness of the associated health risks. The authors--all medical students and educators--argue for the expeditious redesign of medical school curricula to teach students to recognize, diagnose, and treat the many health conditions exacerbated by climate change as well as understanding public health issues. In this Invited Commentary, the authors briefly review the health impacts of climate change, examine current climate change course offerings and proposals, and describe the rationale for promptly and comprehensively including climate science education in medical school curricula. Efforts in training physicians now will benefit those physicians' communities, whose health will be impacted by a period of remarkable climate change. The bottom line is that the health effects of climate reality cannot be ignored, and people everywhere must adapt as quickly as possible.

  View details for DOI 10.1097/ACM.0000000000003861

  View details for PubMedID 33239537

• High Dengue Burden and Circulation of 4 Virus Serotypes among Children with Undifferentiated Fever Kenya, 2014-2017 EMERGING INFECTIOUS DISEASES Shah, M. M., Ndenga, B. A., Mutuku, F. M., Vu, D. M., Grossi-Soyster, E. N., Okuta, V., Ronga, C. O., Chebii, P. K., Maina, P., Jembe, Z., Bosire, C. M., Amugongo, J. S., Sahoo, M. K., Huang, C., Weber, J., Edgerton, S., Hortion, J., Bennett, S. N., Pinsky, B. A., LaBeaud, A. 2020; 26 (11): 2638–50

  Abstract

  Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014-2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014-2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya.

  View details for DOI 10.3201/eid2611.200960

  View details for Web of Science ID 000596803200012

  View details for PubMedID 33079035

  View details for PubMedCentralID PMC7588514

• Re-Emergence of Yellow Fever in Brazil during 2016-2019: Challenges, Lessons Learned, and Perspectives VIRUSES-BASEL de Oliveira Figueiredo, P., Stoffella-Dutra, A., Barbosa Costa, G., Silva de Oliveira, J., Dourado Amaral, C., Duarte Santos, J., Soares Rocha, K., Araujo Junior, J., Lacerda Nogueira, M., Zaza Borges, M., Pereira Paglia, A., Desiree LaBeaud, A., Santos Abrahao, J., Geessien Kroon, E., Bretas de Oliveira, D., Paiva Drumond, B., de Souza Trindade, G. 2020; 12 (11)

  Abstract

  Yellow fever (YF) is a re-emerging viral zoonosis caused by the Yellow Fever virus (YFV), affecting humans and non-human primates (NHP). YF is endemic in South America and Africa, being considered a burden for public health worldwide despite the availability of an effective vaccine. Acute infectious disease can progress to severe hemorrhagic conditions and has high rates of morbidity and mortality in endemic countries. In 2016, Brazil started experiencing one of the most significant YF epidemics in its history, with lots of deaths being reported in regions that were previously considered free of the disease. Here, we reviewed the historical aspects of YF in Brazil, the epidemiology of the disease, the challenges that remain in Brazil's public health context, the main lessons learned from the recent outbreaks, and our perspective for facing future YF epidemics.

  View details for DOI 10.3390/v12111233

  View details for Web of Science ID 000594354900001

  View details for PubMedID 33143114

  View details for PubMedCentralID PMC7692154

• Risk factors for Aedes aegypti household pupal persistence in longitudinal entomological household surveys in urban and rural Kenya. Parasites & vectors Ngugi, H. N., Nyathi, S., Krystosik, A., Ndenga, B., Mbakaya, J. O., Aswani, P., Musunzaji, P. S., Irungu, L. W., Bisanzio, D., Kitron, U., Desiree LaBeaud, A., Mutuku, F. 2020; 13 (1): 499

  Abstract

  BACKGROUND: Aedes aegypti is an efficient vector of several arboviruses of public health importance, including Zika and dengue. Currently vector management is the only available avenue for disease control. Development of efficient vector control strategies requires a thorough understanding of vector ecology. In this study, we identified households that are consistently productive for Ae. aegypti pupae and determined the ecological and socio-demographic factors associated with the persistence and abundance of pupae in households in rural and urban Kenya.METHODS: We collected socio-demographic, environmental and entomological data monthly from July 2014 to June 2018 from 80 households across four sites in Kenya. Pupae count data were collected via entomological surveillance of households and paired with socio-demographic and environmental data. We calculated pupal persistence within a household as the number of months of pupal presence within a year. We used spatially explicit generalized additive mixed models (GAMMs) to identify the risk factors for pupal abundance, and a logistic regression to identify the risk factors for pupal persistence in households.RESULTS: The median number of months of pupal presence observed in households was 4 and ranged from 0 to 35 months. We identified pupal persistence in 85 house-years. The strongest risk factors for high pupal abundance were the presence of bushes or tall grass in the peri-domicile area (OR: 1.60, 95% CI: 1.13-2.28), open eaves (OR: 2.57, 95% CI: 1.33-4.95) and high habitat counts (OR: 1.42, 95% CI: 1.21-1.66). The main risk factors for pupal persistence were the presence of bushes or tall grass in the peri-domicile (OR: 4.20, 95% CI: 1.42-12.46) and high number of breeding sites (OR: 2.17, 95% CI: 1.03-4.58).CONCLUSIONS: We observed Ae. aegypti pupal persistence at the household level in urban and rural and in coastal and inland Kenya. High counts of potential breeding containers, vegetation in the peri-domicile area and the presence of eaves were strongly associated with increased risk of pupal persistence and abundance. Targeting households that exhibit pupal persistence alongside the risk factors for pupal abundance in vector control interventions may result in more efficient use of limited resources.

  View details for DOI 10.1186/s13071-020-04378-7

  View details for PubMedID 33004074

• Absence of YF-neutralizing antibodies in vulnerable populations of Brazil: A warning for epidemiological surveillance and the potential risks for future outbreaks VACCINE Stoffella-Dutra, A., de Oliveira, J., Costa, G., Kroon, E., Abrahao, J., LaBeaud, A., Drumond, B., de Oliveira, D., Trindade, G. 2020; 38 (42): 6592–99

  Abstract

  Yellow Fever (YF) is an acute febrile illness caused by yellow fever virus (YFV), a mosquito-borne flavivirus transmitted to humans and non-human primates. In Brazil, YF is a public health threat and may cause recurrent epidemics, even with the availability of a vaccine. We evaluated the sero-status for YFV in 581 individuals living in a risk area for YF in Brazil. The area presents history of cases and is located in the southeast region of country where outbreaks of YF have been reported since 2016. Through, a PRNT assay, we found 25.8% of individuals lacking YF-neutralizing antibodies. Furthermore, neutralizing antibodies were not detected in 10 individuals with proven vaccination. Our findings reinforce the importance of surveillance systems and the need of an urgent intensification of immunization programs in regions with YFV circulation. Monitoring susceptible individuals that could act as potential disseminators for YFV in risk areas should also be considered.

  View details for DOI 10.1016/j.vaccine.2020.07.077

  View details for Web of Science ID 000573425200015

  View details for PubMedID 32788140

• High frequency of antibiotic prescription in children with undifferentiated febrile illness in Kenya. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Hooft, A. M., Ndenga, B., Mutuku, F., Otuka, V., Ronga, C., Chebii, P. K., Maina, P. W., Jembe, Z., Lee, J., Vu, D. M., Mukoko, D., LaBeaud, A. D. 2020

  Abstract

  BACKGROUND: In low-resource, malaria-endemic settings, accurate diagnosis of febrile illness in children is challenging. The World Health Organization (WHO) currently recommends laboratory-confirmed diagnosis of malaria prior to starting treatment in stable children. Factors guiding management of children with undifferentiated febrile illness outside of malaria are not well understood.METHODS: This study examined clinical presentation and management of a cohort of febrile Kenyan children at five hospital/clinic sites from January 2014 to December 2017. Chi-squared and multivariate regression analyses were used to compare frequencies and correlate demographic, environmental, and clinical factors with patient diagnosis and prescription of antibiotics.RESULTS: Of 5735 total participants, 68% were prescribed antibiotic treatment (n = 3902), despite only 28% given a diagnosis of bacterial illness (n = 1589). Factors associated with prescription of antibiotic therapy included: negative malaria testing, reporting head, ears, eyes, nose and throat (HEENT) symptoms (i.e., cough, runny nose), HEENT findings on exam (i.e., nasal discharge, red throat), and having a flush toilet in the home (likely a surrogate for higher socioeconomic status).CONCLUSION: In a cohort of acutely ill Kenyan children, prescription of antimalarial therapy and malaria test results were well correlated, whereas antibiotic treatment was prescribed empirically to most of those who tested malaria negative. Clinical management of febrile children in these settings is difficult given the lack of diagnostic testing. Providers may benefit from improved clinical education and implementation of enhanced guidelines in this era of malaria testing, as their management strategies must rely primarily on critical thinking and decision-making skills.

  View details for DOI 10.1093/cid/ciaa1305

  View details for PubMedID 32882032

• Climate change could shift disease burden from malaria to arboviruses in Africa LANCET PLANETARY HEALTH Mordecai, E. A., Ryan, S. J., Caldwell, J. M., Shah, M. M., LaBeaud, A. 2020; 4 (9): E416–E423

  View details for Web of Science ID 000569270300013

• Theoretical risk of genetic reassortment should not impede development of live, attenuated Rift Valley fever (RVF) vaccines commentary on the draft WHO RVF Target Product Profile VACCINE: X Monath, T. P., Kortekaas, J., Watts, D. M., Christofferson, R. C., LaBeaud, A., Gowen, B. B., Peters, C. J., Smith, D. R., Swanepoel, R., Morrill, J. C., Ksiazek, T. G., Pittman, P. R., Bird, B. H., Bettinger, G. 2020; 5: 100060

  Abstract

  In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during field use, that such a reassortment event if it occurred would have no untoward consequence, and that the TPPs should be revised to provide a more balanced assessment of the benefits versus the theoretical risks of reassortment.

  View details for DOI 10.1016/j.jvacx.2020.100060

  View details for Web of Science ID 000608620000001

  View details for PubMedID 32337506

  View details for PubMedCentralID PMC7176985

• High Seroprevalence of Dengue Virus Infection in Sudan: Systematic Review and Meta-Analysis. Tropical medicine and infectious disease Elduma, A. H., LaBeaud, A. D., A Plante, J., Plante, K. S., Ahmed, A. 2020; 5 (3)

  Abstract

  The goal of this study was to systematically review the published data on dengue virus (DENV) seroprevalence in Sudan and to estimate disease burden through meta-analysis. We searched, reviewed, and extracted online available reports on DENV in Sudan. Among 168 identified records, 19 were selected. Dengue infections were documented in 11/18 states. The overall seroprevalence of DENV in Sudan was estimated to be 27%, while the prevalence of dengue IgM was 22% and IgG was 38%. The prevalence of dengue estimated from community and hospital-based cross-sectional studies were 26% and 30% respectively. Additionally, one cohort study and a single PCR-based study reported a prevalence of 1% and 4%, respectively. Regional analysis revealed that the variation in seroprevalence in East, North, West, and Central Sudan was 23%, 24%, 36% and 43%, respectively. Interestingly, we found that DENV is circulating countrywide with a significant spatiotemporal variation in the disease seroprevalence. Furthermore, publications on dengue prevalence are temporally and geographically fragmented, perhaps due to limited resources. However, this gap in data and knowledge highlights the urgent need for a country-wide surveillance system and continued study of dengue burden in Sudan to accurately estimate the disease prevalence and determine the associated risk factors.

  View details for DOI 10.3390/tropicalmed5030120

  View details for PubMedID 32708492

• Rift Valley Fever: Important Considerations for Risk Mitigation and Future Outbreaks. Tropical medicine and infectious disease Grossi-Soyster, E. N., LaBeaud, A. D. 2020; 5 (2)

  Abstract

  Rift Valley fever virus (RVFV) is a zoonotic phlebovirus of the Phenuiviridae family with great opportunity for emergence in previously unaffected regions, despite its current geographical limits. Outbreaks of RVFV often infect humans or domesticated animals, such as livestock, concurrently and occur sporadically, ranging from localized outbreaks in villages to multi-country events that spread rapidly. The true burden of Rift Valley fever (RVF) is not well defined due to underreporting, misdiagnosis caused by the broad spectrum of disease presentation, and minimal access for rapid and accurate laboratory confirmation. Severe symptoms may include hemorrhagic fever, loss of vision, psychological impairment or disturbances, and organ failure. Those living in endemic areas and travelers should be aware of the potential for exposure to ongoing outbreaks or interepidemic transmission, and engage in behaviors to minimize exposure risks, as vaccinations in humans are currently unavailable and animal vaccinations are not used routinely or ubiquitously. The lack of vaccines approved for use in humans is concerning, as RVFV has proven to be highly pathogenic in naive populations, causing severe disease in a large percent of confirmed cases, which could have considerable impact on human health.

  View details for DOI 10.3390/tropicalmed5020089

  View details for PubMedID 32498264

• Prevalence of pfdhfr and pfdhps mutations in Plasmodium falciparum associated with drug resistance among pregnant women receiving IPTp-SP at Msambweni County Referral Hospital, Kwale County, Kenya. Malaria journal Gikunju, S. W., Agola, E. L., Ondondo, R. O., Kinyua, J., Kimani, F., LaBeaud, A. D., Malhotra, I., King, C., Thiong'o, K., Mutuku, F. 2020; 19 (1): 190

  Abstract

  BACKGROUND: Prevention and treatment of malaria during pregnancy is crucial in dealing with maternal mortality and adverse fetal outcomes. The World Health Organization recommendation to treat all pregnant women with sulfadoxine-pyrimethamine (SP) through antenatal care structures was implemented in Kenya in the year 1998, but concerns about its effectiveness in preventing malaria in pregnancy has arisen due to the spread of SP resistant parasites. This study aimed to determine the prevalence of SP resistance markers in Plasmodium falciparum parasites isolated from pregnant women seeking antenatal care at Msambweni County Referral Hospital, located in coastal Kenya, between the year 2013 and 2015.METHODS: This hospital-based study included 106 malaria positive whole blood samples for analysis of SP resistance markers within the Pfdhfr gene (codons 51, 59 and 108) and Pfdhps gene (codons 437 and 540). The venous blood collected from all pregnant women was tested for malaria via light microscopy, then the malaria positive samples were separated into plasma and red cells and stored in a -86° freezer for further studies. Archived red blood cells were processed for molecular characterization of SP resistance markers within the Pfdhfr and Pfdhps genes using real time PCR platform and Sanger sequencing.RESULTS: All samples had at least one mutation in the genes associated with drug resistance; polymorphism prevalence of Pfdhfr51I, 59R and 108N was at 88.7%, 78.3% and 93.4%, respectively, while Pfdhps polymorphism accounted for 94.3% and 91.5% at 437G and 540E, respectively. Quintuple mutations (at all the five codons) conferring total SP resistance had the highest prevalence of 85.8%. Quadruple mutations were observed at a frequency of 10.4%, and 24.5% had a mixed outcome of both wildtype and mutant genotypes in the genes of interest.CONCLUSION: The data suggest a high prevalence of P. falciparum genetic variations conferring resistance to SP among pregnant women, which may explain reduced efficacy of IPTp treatment in Kenya. There is need for extensive SP resistance profiling in Kenya to inform IPTp drug choices for successful malaria prevention during pregnancy.

  View details for DOI 10.1186/s12936-020-03263-z

  View details for PubMedID 32448228

• Factors associated with early childhood stunted growth in a 2012-2015 birth cohort monitored in the rural Msambweni area of coastal Kenya: a cross-sectional study. BMC pediatrics Martin, S., Mutuku, F., Sessions, J., Lee, J., Mukoko, D., Malhotra, I., King, C. H., LaBeaud, A. D. 2020; 20 (1): 208

  Abstract

  BACKGROUND: Chronic malnutrition, often measured as stunted growth, is an understudied global health problem. Though poor nutritional intake has been linked to stunted growth, there is evidence suggesting environmental exposures may have a significant role in its occurrence. Here, we characterize the non-nutritional prenatal and postnatal factors that contribute to early childhood stunted growth in rural coastal Kenya.METHODS: Overall, 232 women and 244 children from a 2012-2015 maternal-child cohort in Msambweni, Kenya were included. Women were tested for parasitic infections during the prenatal period and at the time of delivery. Children were tested for parasitic infections and assessed for stunted growth using height-for-age Z-scores (HAZ) at 6-month intervals after birth. Socioeconomic status (SES) was evaluated using both a simplified water, asset, maternal education, and income (WAMI) index and a principal component analysis (PCA) asset score. Multivariate logistic regression analysis was used to determine the relative influence of prenatal and postnatal factors on the occurrence of stunted growth.RESULTS: Of the 244 children (ages 6-37months), 60 (25%) were stunted at the study endpoint. 179 mothers (77%) had at least one parasitic infection during pregnancy and 94 children (38%) had at least one parasitic infection during the study period. There was no significant association between maternal parasitic infection and child stunted growth (p=1.00). SES as determined using the WAMI index was not associated with HAZ in linear regression analysis (p=0.307), however, the PCA asset score was (p=0.048). Multivariate logistic regression analysis identified low birth weight (AOR: 3.24, 95% CI: [1.38, 7.57]) and child parasitic infectious disease burden (AOR: 1.41, 95% CI: [1.05, 1.95]) as independent predictors of stunted growth, though no significant association was identified with PCA asset score (AOR: 0.98, 95% CI: [0.88, 1.10]).CONCLUSIONS: Stunted growth remains highly prevalent in rural Kenya, with low birth weight and child parasitic infectious disease burden demonstrated to be significantly associated with this indicator of chronic malnutrition. These results emphasize the multifaceted nature of stunted growth and the need to address both the prenatal and postnatal environmental factors that contribute to this problem.

  View details for DOI 10.1186/s12887-020-02110-z

  View details for PubMedID 32398049

• Archaeology and contemporary emerging zoonosis: A framework for predicting future Rift Valley fever virus outbreaks INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY Seetah, K., LaBeaud, D., Kumm, J., Grossi-Soyster, E., Anangwe, A., Barry, M. 2020

  View details for DOI 10.1002/oa.2862

  View details for Web of Science ID 000512278200001

• GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 5: Entomological aspects ANTIVIRAL RESEARCH Pezzi, L., Diallo, M., Rosa-Freitas, M. G., Vega-Rua, A., Ng, L. P., Boyer, S., Drexler, J. F., Vasilakis, N., Lourenco-de-Oliveira, R., Weaver, S. C., Kohl, A., de Lamballerie, X., Failloux, A., Brasil, P., Busch, M., Diamond, M. S., Drebot, M. A., Gallian, P., Jaenisch, T., LaBeaud, A. D., Lecui, M., Neyts, J., Reusken, C. B., Ribeiro, G. S., Rios, M., Rodriguez-Morales, A. J., Sall, A., Simmons, G., Simon, F., Siqueira, A. M., GloPID-R Chikungunya Onyong-nyong 2020; 174: 104670

  Abstract

  The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through an enzootic cycle that has not been characterized yet, with Anopheles species as main vectors and humans as amplification hosts during epidemics. MAYV is transmitted by Haemagogus species in an enzootic cycle using non-human primates as the main amplification and maintenance hosts, and humans becoming sporadically infected when venturing in or nearby forest habitats. Here, we focused on the transmission cycle and natural vectors that sustain circulation of these viruses in their respective locations. The knowledge of the natural ecology of transmission and the capacity of different vectors to transmit these viruses is crucial to understand CHIKV emergence, and to assess the risk that MAYV and ONNV will expand on wide scale using anthropophilic mosquito species not normally considered primary vectors. Finally, the experts identified knowledge gaps and provided adapted recommendations, in order to address future entomological investigations in the right direction.

  View details for DOI 10.1016/j.antiviral.2019.104670

  View details for Web of Science ID 000523596900024

  View details for PubMedID 31812638

• Risks and Challenges of Arboviral Diseases in Sudan: The Urgent Need for Actions. Viruses Ahmed, A., Dietrich, I., LaBeaud, A. D., Lindsay, S. W., Musa, A., Weaver, S. C. 2020; 12 (1)

  Abstract

  The risk of emergence and/or re-emergence of arthropod-borne viral (arboviral) infections is rapidly growing worldwide, particularly in Africa. The burden of arboviral infections and diseases is not well scrutinized because of the inefficient surveillance systems in endemic countries. Furthermore, the health systems are fully occupied by the burden of other co-existing febrile illnesses, especially malaria. In this review we summarize the epidemiology and risk factors associated with the major human arboviral diseases and highlight the gap in knowledge, research, and control in Sudan. Published data in English up to March 2019 were reviewed and are discussed to identify the risks and challenges for the control of arboviruses in the country. In addition, the lack of suitable diagnostic tools such as viral genome sequencing, and the urgent need for establishing a genomic database of the circulating viruses and potential sources of entry are discussed. Moreover, the research and healthcare gaps and global health threats are analyzed, and suggestions for developing strategic health policy for the prevention and control of arboviruses with focus on building the local diagnostic and research capacity and establishing an early warning surveillance system for the early detection and containment of arboviral epidemics are offered.

  View details for DOI 10.3390/v12010081

  View details for PubMedID 31936607

• Recent sylvatic yellow fever virus transmission in Brazil: the news from an old disease. Virology journal Silva, N. I., Sacchetto, L. n., de Rezende, I. M., Trindade, G. d., LaBeaud, A. D., de Thoisy, B. n., Drumond, B. P. 2020; 17 (1): 9

  Abstract

  Yellow fever (YF) is an acute viral disease, affecting humans and non-human primates (NHP), caused by the yellow fever virus (YFV). Despite the existence of a safe vaccine, YF continues to cause morbidity and mortality in thousands of people in Africa and South America. Since 2016, massive YF outbreaks have taken place in Brazil, reaching YF-free zones, causing thousands of deaths of humans and NHP. Here we reviewed the main epidemiological aspects, new clinical findings in humans, and issues regarding YFV infection in vectors and NHP in Brazil. The 2016-2019 YF epidemics have been considered the most significant outbreaks of the last 70 years in the country, and the number of human cases was 2.8 times higher than total cases in the previous 36 years. A new YFV lineage was associated with the recent outbreaks, with persistent circulation in Southeast Brazil until 2019. Due to the high number of infected patients, it was possible to evaluate severity and death predictors and new clinical features of YF. Haemagogus janthinomys and Haemagogus leucocelaenus were considered the primary vectors during the outbreaks, and no human case suggested the occurrence of the urban transmission cycle. YFV was detected in a variety of NHP specimens presenting viscerotropic disease, similar to that described experimentally. Further studies regarding NHP sensitivity to YFV, YF pathogenesis, and the duration of the immune response in NHP could contribute to YF surveillance, control, and future strategies for NHP conservation.

  View details for DOI 10.1186/s12985-019-1277-7

  View details for PubMedID 31973727

• Iron Deficiency Anemia at Time of Vaccination Predicts Decreased Vaccine Response and Iron Supplementation at Time of Vaccination Increases Humoral Vaccine Response: A Birth Cohort Study and a Randomized Trial Follow-Up Study in Kenyan Infants. Frontiers in immunology Stoffel, N. U., Uyoga, M. A., Mutuku, F. M., Frost, J. N., Mwasi, E., Paganini, D., van der Klis, F. R., Malhotra, I. J., LaBeaud, A. D., Ricci, C., Karanja, S., Drakesmith, H., King, C. H., Zimmermann, M. B. 2020; 11: 1313

  Abstract

  Background: Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain. Methods: We performed two studies in southern coastal Kenya. In a birth cohort study, we followed infants to age 18 mo and assessed whether anemia or iron deficiency at time of vaccination predicted vaccine response to three-valent oral polio, diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine, ten-valent pneumococcal-conjugate vaccine and measles vaccine. Primary outcomes were anti-vaccine-IgG and seroconversion at age 24 wk and 18 mo. In a randomized trial cohort follow-up, children received a micronutrient powder (MNP) with 5 mg iron daily or a MNP without iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were anti-measles IgG, seroconversion and avidity at age 11.5 mo and 4.5 y. Findings: In the birth cohort study, 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometric indices and maternal antibodies, hemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis-IgG at 24 wk (p = 0.0071, p = 0.0339) and 18 mo (p = 0.0182, p = 0.0360); (B) anti-pertussis filamentous hemagglutinin-IgG at 24 wk (p = 0.0423); and (C) anti-pneumococcus 19 IgG at 18 mo (p = 0.0129). Anemia and serum transferrin receptor at time of vaccination were the strongest predictors of seroconversion against diphtheria (p = 0.0484, p = 0.0439) and pneumococcus 19 at 18 mo (p = 0.0199, p = 0.0327). In the randomized trial, 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5 y. Compared to infants that did not receive iron, those who received iron at time of vaccination had higher anti-measles-IgG (p = 0.0415), seroconversion (p = 0.0531) and IgG avidity (p = 0.0425) at 11.5 mo. Interpretation: In Kenyan infants, anemia and iron deficiency at time of vaccination predict decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine may be increased by iron supplementation at time of vaccination. These findings argue that correction of iron deficiency during early infancy may improve vaccine response.

  View details for DOI 10.3389/fimmu.2020.01313

  View details for PubMedID 32754150

• Source reduction with a purpose: Mosquito ecology and community perspectives offer insights for improving household mosquito management in coastal Kenya. PLoS neglected tropical diseases Forsyth, J. E., Mutuku, F. M., Kibe, L. n., Mwashee, L. n., Bongo, J. n., Egemba, C. n., Ardoin, N. M., LaBeaud, A. D. 2020; 14 (5): e0008239

  Abstract

  Understanding mosquito breeding behavior as well as human perspectives and practices are crucial for designing interventions to control Aedes aegypti mosquito-borne diseases as these mosquitoes primarily breed in water-holding containers around people's homes. The objectives of this study were to identify productive mosquito breeding habitats in coastal Kenya and to understand household mosquito management behaviors and their behavioral determinants. The field team conducted entomological surveys in 444 households and semi-structured interviews with 35 female caregivers and 37 children in Kwale County, coastal Kenya, between May and December 2016. All potential mosquito habitats with or without water were located, abundances of mosquito immatures measured and their characteristics recorded. Interviews explored household mosquito management behaviors and their behavioral determinants. 2,452 container mosquito habitats were counted containing 1,077 larvae and 390 pupae, predominantly Aedes species. More than one-third of the positive containers were found outside houses in 1 of the 10 villages. Containers holding water with no intended purpose contained 55.2% of all immature mosquitoes. Containers filled with rainwater held 95.8% of all immature mosquitoes. Interviews indicated that households prioritize sleeping under bednets as a primary protection against mosquito-borne disease because of concern about night-time biting, malaria-transmitting Anopheles mosquitoes. Respondents had limited knowledge about the mosquito life cycle, especially with respect to day-time biting, container-breeding Aedes mosquitoes. Therefore, respondents did not prioritize source reduction. Most mosquitoes breed in containers that have no direct or immediate purpose ("no-purpose containers"). These containers may be left unattended for several days allowing rainwater to collect, and creating ideal conditions for mosquito breeding. An intervention that requires little effort and targets only the most productive containers could effectively reduce mosquito indices and, relatedly, mosquito-borne disease risk.

  View details for DOI 10.1371/journal.pntd.0008239

  View details for PubMedID 32392226

• Focal epilepsy features in a child with Congenital Zika Syndrome EPILEPSY & BEHAVIOR REPORTS Jayatilake, P., Oyegunle, V., Waechter, R., Landon, B., Fernandes, M., Cudjoe, N., Evans, R., Noel, T., Macpherson, C., Donald, T., Abdelbaki, S. G., Mandalaneni, K., Dlugos, D., Chari, G., Patel, A. A., Grossi-Soyster, E. N., LaBeaud, A., Blackmon, K. 2020; 14: 100411

  Abstract

  Zika virus (ZIKV) is a mosquito-borne, single-stranded DNA flavivirus that is teratogenic and neurotropic. Similar to the teratogenic effects of other TORCH infections, ZIKV infection during pregnancy can have an adverse impact on fetal and neonatal development. Epilepsy is detected in 48-96% of children with Congenital Zika Syndrome (CZS) and microcephaly. Early epilepsy surveillance is needed in children with prenatal ZIKV exposure; yet, most ZIKV-endemic regions do not have specialist epilepsy care. Here, we describe the demographic, clinical, imaging, and EEG characteristics of a 2-year-old child with CZS and microcephaly who presented with focal epileptiform activity, suboptimal growth, and severe neurodevelopmental delays. Administration of a brief seizure questionnaire by allied health professionals to the patient's caregiver helped to characterize the child's seizure semiology and differentiate focal from generalized seizure features. A telemedicine EEG interpretation platform provided valuable diagnostic information for the patient's local pediatrician to integrate into her treatment plan. This case illustrates that CZS can present with focal epilepsy features and that a telemedicine approach can be used to bridge the gap between epilepsy specialists and local care providers in resource limited ZIKV-endemic regions to achieve better seizure control in children with CZS.

  View details for DOI 10.1016/j.ebr.2020.100411

  View details for Web of Science ID 000610548000003

  View details for PubMedID 33313503

  View details for PubMedCentralID PMC7720018

• Climate change could shift disease burden from malaria to arboviruses in Africa. The Lancet. Planetary health Mordecai, E. A., Ryan, S. J., Caldwell, J. M., Shah, M. M., LaBeaud, A. D. 2020; 4 (9): e416–e423

  Abstract

  Malaria is a long-standing public health problem in sub-Saharan Africa, whereas arthropod-borne viruses (arboviruses) such as dengue and chikungunya cause an under-recognised burden of disease. Many human and environmental drivers affect the dynamics of vector-borne diseases. In this Personal View, we argue that the direct effects of warming temperatures are likely to promote greater environmental suitability for dengue and other arbovirus transmission by Aedes aegypti and reduce suitability for malaria transmission by Anopheles gambiae. Environmentally driven changes in disease dynamics will be complex and multifaceted, but given that current public efforts are targeted to malaria control, we highlight Ae aegypti and dengue, chikungunya, and other arboviruses as potential emerging public health threats in sub-Saharan Africa.

  View details for DOI 10.1016/S2542-5196(20)30178-9

  View details for PubMedID 32918887

• Chikungunya Infection in Pregnancy- Reassuring Maternal and Perinatal Outcomes: A Retrospective Observational Study. BJOG : an international journal of obstetrics and gynaecology Foeller, M. E., Nosrat, C. n., Krystosik, A. n., Noel, T. n., Gérardin, P. n., Cudjoe, N. n., Mapp-Alexander, V. n., Mitchell, G. n., Macpherson, C. n., Waechter, R. n., LaBeaud, A. D. 2020

  Abstract

  To evaluate pregnancy and neonatal outcomes, disease severity, and mother-to-child transmission of pregnant women with Chikungunya infection (CHIKV).Retrospective observational study.Grenada.Women who gave birth during a Chikungunya outbreak between January 2014 to September 2015 were eligible.This descriptive study investigated 731 mother-infant pairs who gave birth during a CHIKV outbreak. Women and infants underwent serologic testing for CHIKV by ELISA.Primary outcomes: composite pregnancy complication (abruption, vaginal bleeding, preterm labor/cervical incompetence, cesarean delivery for fetal distress/abruption/placental abnormality or delivery for fetal distress) and composite neonatal morbidity.Of 416 mother-infant pairs, 150 (36%) had CHIKV during pregnancy, 135 (33%) had never had CHIKV, and 131 (31%) had CHIKV outside of pregnancy. Mean duration of joint pain was shorter among women infected during pregnancy (μ = 898 days, σ = 277 days) compared to infections outside of pregnancy (μ = 1,064 days, σ = 244 days) (P<0.0001). Rates of pregnancy complications (RR = 0.76, p = 0.599), intrapartum complications (RR = 1.50, p = 0.633), and neonatal outcomes were otherwise similar. Possible mother-to-child transmission occurred in two (1.3%) mother-infant pairs and two of eight intrapartum infections (25%).CHIKV infection during pregnancy may be protective against long-term joint pain sequelae that is often associated with acute CHIKV infection. Infection during pregnancy did not appear to pose a risk for pregnancy complications nor neonatal health, but maternal infection just prior to delivery might have increased risk of mother-to-child transmission of CHIKV.

  View details for DOI 10.1111/1471-0528.16562

  View details for PubMedID 33040457

• Pre and postnatal exposure to Chikungunya virus does not affect child neurodevelopmental outcomes at two years of age. PLoS neglected tropical diseases Waechter, R. n., Ingraham, E. n., Evans, R. n., Cudjoe, N. n., Krystosik, A. n., Isaac, R. n., Watts, A. n., Noël, T. n., Landon, B. n., Fernandes, M. n., Mapp-Alexander, V. n., Suresh, P. n., Mitchell, G. n., Macpherson, C. n., Gérardin, P. n., LaBeaud, A. D. 2020; 14 (10): e0008546

  Abstract

  The 2005-06 chikungunya virus (CHIKV) outbreak in La Réunion suggested that mothers could transmit CHIKV to their neonates while viremic during the intrapartum period, and more than half of the infected neonates showed impaired neurodevelopment at two years of age. However, data sparsity precluded an overview of the developmental impact of vertical infection within the whole prenatal period.The current study assessed two-year old children born to mothers who were infected during the 2014 CHIKV outbreak in Grenada to determine the neurodevelopmental impact of perinatal CHIKV infection throughout gestation. Mother and child infection status were confirmed by serologic testing (IgG and IgM) for CHIKV. Cognitive, fine motor, gross motor, language and behavioral outcomes were assessed at two years of age on the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA).No differences in neurodevelopmental outcomes were observed between two-year-old children born to mothers infected with CHIKV during gestation (n = 149) and those born to mothers not infected with CHIKV (n = 161). No differences were found in INTER-NDA scores between children infected with CHIKV (n = 47) and children not infected with CHIKV (n = 592). Likewise, there were no differences between children infected with CHIKV post-partum (n = 19) versus children not infected with CHIKV (n = 592).Our findings suggest that children exposed and/or infected with CHIKV outside of the intrapartum period experience no significant neurodevelopmental delay at two years of age, as measured by the INTER-NDA, compared to their unexposed and/or uninfected peers. These results complement those of previous studies which showed a neurodevelopmental risk only for children infected during the intrapartum period, while the mother was highly viremic. These results might be reassuring for women of childbearing age and public health officials in CHIKV-endemic regions.

  View details for DOI 10.1371/journal.pntd.0008546

  View details for PubMedID 33017393

• Evidence of transovarial transmission of Chikungunya and Dengue viruses in field-caught mosquitoes in Kenya. PLoS neglected tropical diseases Heath, C. J., Grossi-Soyster, E. N., Ndenga, B. A., Mutuku, F. M., Sahoo, M. K., Ngugi, H. N., Nbakaya, J. O., Siema, P. n., Kitron, U. n., Zahiri, N. n., Hortion, J. n., Waggoner, J. J., King, C. H., Pinsky, B. A., LaBeaud, A. D. 2020; 14 (6): e0008362

  Abstract

  Arboviruses are among the most important emerging pathogens due to their increasing public health impact. In Kenya, continued population growth and associated urbanization are conducive to vector spread in both urban and rural environments, yet mechanisms of viral amplification in vector populations is often overlooked when assessing risks for outbreaks. Thus, the characterization of local arbovirus circulation in mosquito populations is imperative to better inform risk assessments and vector control practices. Aedes species mosquitoes were captured at varying stages of their life cycle during different seasons between January 2014 and May 2016 at four distinct sites in Kenya, and tested for chikungunya (CHIKV), dengue (DENV) and Zika (ZIKV) viruses by RT-PCR. CHIKV was detected in 45 (5.9%) and DENV in 3 (0.4%) mosquito pools. No ZIKV was detected. Significant regional variation in prevalence was observed, with greater frequency of CHIKV on the coast. DENV was detected exclusively on the coast. Both viruses were detected in immature mosquitoes of both sexes, providing evidence of transovarial transmission of these arboviruses in local mosquitoes. This phenomenon may be driving underlying viral maintenance that may largely contribute to periodic re-emergence among humans in Kenya.

  View details for DOI 10.1371/journal.pntd.0008362

  View details for PubMedID 32559197

• GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 3: Epidemiological distribution of Mayaro virus. Antiviral research Pezzi, L., Rodriguez-Morales, A. J., Reusken, C. B., Ribeiro, G. S., LaBeaud, A. D., Lourenco-de-Oliveira, R., Brasil, P., Lecuit, M., Failloux, A. B., Gallian, P., Jaenisch, T., Simon, F., Siqueira, A. M., Rosa-Freitas, M. G., Vega Rua, A., Weaver, S. C., Drexler, J. F., Vasilakis, N., de Lamballerie X, GloPID-R chikungunya, o. a., Boyer, S., Busch, M., Diallo, M., Diamond, M. S., Drebot, M. A., Kohl, A., Neyts, J., Ng, L. F., Rios, M., Sall, A., Simmons, G. 2019: 104610

  View details for DOI 10.1016/j.antiviral.2019.104610

  View details for PubMedID 31545981

• GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 2: Epidemiological distribution of o'nyong-nyong virus. Antiviral research Pezzi, L., LaBeaud, A. D., Reusken, C. B., Drexler, J. F., Vasilakis, N., Diallo, M., Simon, F., Jaenisch, T., Gallian, P., Sall, A., Failloux, A. B., Weaver, S. C., de Lamballerie, X., GloPID-R chikungunya, o. a., Boyer, S., Brasil, P., Busch, M., Diamond, M. S., Drebot, M. A., Kohl, A., Lecuit, M., Lourenco-de-Oliveira, R., Neyts, J., Lfp, N., Ribeiro, G. S., Rios, M., Rodriguez-Morales, A. J., Rosa-Freitas, M. G., Simmons, G., Siqueira, A. M., Vega Rua, A. 2019: 104611

  View details for DOI 10.1016/j.antiviral.2019.104611

  View details for PubMedID 31545982

• Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species SYSTEMATIC BIOLOGY Calisher, C. H., Briese, T., Brister, J., Charrel, R. N., Duerrwald, R., Ebihara, H., Fulhorst, C. F., Gao, G., Groschup, M. H., Haddow, A. D., Hyndman, T. H., Junglen, S., Klempa, B., Klingstroem, J., Kropinski, A. M., Krupovic, M., LaBeaud, A., Maes, P., Nowotny, N., Teixeira Nunes, M., Payne, S. L., Radoshitzky, S. R., Rubbenstroth, D., Sabanadzovic, S., Sasaya, T., Stenglein, M. D., Varsani, A., Wahl, V., Weaver, S. C., Zerbini, F., Vasilakis, N., Kuhn, J. H. 2019; 68 (5): 828–39

  View details for DOI 10.1093/sysbio/syy087

  View details for Web of Science ID 000489700900011

• Making Pastoralists Count: Geospatial Methods for the Health Surveillance of Nomadic Populations. The American journal of tropical medicine and hygiene Wild, H., Glowacki, L., Maples, S., Mejia-Guevara, I., Krystosik, A., Bonds, M. H., Hiruy, A., LaBeaud, A. D., Barry, M. 2019

  Abstract

  Nomadic pastoralists are among the world's hardest-to-reach and least served populations. Pastoralist communities are difficult to capture in household surveys because of factors including their high degree of mobility over remote terrain, fluid domestic arrangements, and cultural barriers. Most surveys use census-based sampling frames which do not accurately capture the demographic and health parameters of nomadic populations. As a result, pastoralists are "invisible" in population data such as the Demographic and Health Surveys (DHS). By combining remote sensing and geospatial analysis, we developed a sampling strategy designed to capture the current distribution of nomadic populations. We then implemented this sampling frame to survey a population of mobile pastoralists in southwest Ethiopia, focusing on maternal and child health (MCH) indicators. Using standardized instruments from DHS questionnaires, we draw comparisons with regional and national data finding disparities with DHS data in core MCH indicators, including vaccination coverage, skilled birth attendance, and nutritional status. Our field validation demonstrates that this method is a logistically feasible alternative to conventional sampling frames and may be used at the population level. Geospatial sampling methods provide cost-affordable and logistically feasible strategies for sampling mobile populations, a crucial first step toward reaching these groups with health services.

  View details for DOI 10.4269/ajtmh.18-1009

  View details for PubMedID 31436151

• Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children. BMJ open Wilder-Smith, A., Wei, Y., Araujo, T. V., VanKerkhove, M., Turchi Martelli, C. M., Turchi, M. D., Teixeira, M., Tami, A., Souza, J., Sousa, P., Soriano-Arandes, A., Soria-Segarra, C., Sanchez Clemente, N., Rosenberger, K. D., Reveiz, L., Prata-Barbosa, A., Pomar, L., Pela Rosado, L. E., Perez, F., Passos, S. D., Nogueira, M., Noel, T. P., Moura da Silva, A., Moreira, M. E., Morales, I., Miranda Montoya, M. C., Miranda-Filho, D. d., Maxwell, L., Macpherson, C. N., Low, N., Lan, Z., LaBeaud, A. D., Koopmans, M., Kim, C., Joao, E., Jaenisch, T., Hofer, C. B., Gustafson, P., Gerardin, P., Ganz, J. S., Dias, A. C., Elias, V., Duarte, G., Debray, T. P., Cafferata, M. L., Buekens, P., Broutet, N., Brickley, E. B., Brasil, P., Brant, F., Bethencourt, S., Benedetti, A., Avelino-Silva, V. L., Ximenes, R. A., Alves da Cunha, A., Alger, J., Zika Virus Individual Participant Data Consortium, Abreu de Carvalho, L. M., Batista, R., Bertozzi, A. P., Carles, G., Cotrim, D., Damasceno, L., Dimitrakis, L., Duarte Rodrigues, M. M., Estofolete, C. F., Fragoso da Silveira Gouvea, M. I., Fumado-Perez, V., Gazeta, R. E., Kaydos-Daniels, N., Gilboa, S., Krystosik, A., Lambert, V., Lopez-Hortelano, M. G., Mussi-Pinhata, M. M., Nelson, C., Nielsen, K., Oliani, D. M., Rabello, R., Ribeiro, M., Rockx, B., Rodrigues, L. C., Salgado, S., Silveira, K., Sulleiro, E., Tong, V., Valencia, D., De Souza, W. V., Villar Centeno, L. A., Zin, A. 2019; 9 (6): e026092

  Abstract

  INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

  View details for DOI 10.1136/bmjopen-2018-026092

  View details for PubMedID 31217315

• GloPID-R report on Chikungunya, O'nyong-nyong and Mayaro virus, part I: Biological diagnostics ANTIVIRAL RESEARCH Pezzi, L., Reusken, C. B., Weaver, S. C., Drexler, J. F., Busch, M., LaBeaud, A. D., Diamond, M. S., Vasilakis, N., Drebot, M. A., Siqueira, A. M., Ribeiro, G. S., Kohl, A., Lecuit, M., Ng, L. P., Gallian, P., de Lamballerie, X., Boyer, S., Brasil, P., Diallo, M., Failloux, A. B., Jaenisch, T., Lourenco-de-Oliveira, R., Neyts, J., Rios, M., Rodriguez-Morales, A. J., Rosa-Freitas, M. G., Sall, A., Simmons, G., Simon, F., Rua, A., GloPID-R Chikungunya O'nyong-n 2019; 166: 66–81

  View details for DOI 10.1016/j.antiviral.2019.03.009

  View details for Web of Science ID 000469522900007

• Pediatric tropical medicine: The neglected diseases of children PLOS NEGLECTED TROPICAL DISEASES Hotez, P. J., John, A., LaBeaud, A. 2019; 13 (5)

  View details for DOI 10.1371/journal.pntd.0007008

  View details for Web of Science ID 000470188100003

• The influence of raw milk exposures on Rift Valley fever virus transmission. PLoS neglected tropical diseases Grossi-Soyster, E. N., Lee, J., King, C. H., LaBeaud, A. D. 2019; 13 (3): e0007258

  Abstract

  Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that can be transmitted to humans or livestock by mosquitoes or through direct contact with contaminated bodily fluids and tissues. Exposure to bodily fluids and tissues varies by types of behaviors engaged for occupational tasks, homestead responsibilities, or use in dietary or therapeutic capacities. While previous studies have included milk exposures in their analyses, their primary focus on livestock exposures has been on animal handling, breeding, and slaughter. We analyzed data from multiple field surveys in Kenya with the aim of associating RVFV infection to raw milk exposures from common animal species. Of those with evidence of prior RVFV infection by serology (n = 267), 77.2% engaged in milking livestock compared to 32.0% for 3,956 co-local seronegative individuals (p < 0.001), and 86.5% of seropositive individuals consumed raw milk compared to 33.4% seronegative individuals (p < 0.001). Individuals who milked and also consumed raw milk had greater odds of RVFV exposure than individuals whose only contact to raw milk was through milking. Increased risks were associated with exposure to milk sourced from cows (p < 0.001), sheep (p < 0.001), and goats (p < 0.001), but not camels (p = 0.98 for consuming, p = 0.21 for milking). Our data suggest that exposure to raw milk may contribute to a significant number of cases of RVFV, especially during outbreaks and in endemic areas, and that some animal species may be associated with a higher risk for RVFV exposure. Livestock trade is regulated to limit RVFV spread from endemic areas, yet further interventions designed to fully understand the risk of RVFV exposure from raw milk are imperative.

  View details for PubMedID 30893298

• The influence of raw milk exposures on Rift Valley fever virus transmission PLOS NEGLECTED TROPICAL DISEASES Grossi-Soyster, E. N., Lee, J., King, C. H., LaBeaud, A. 2019; 13 (3)

  View details for DOI 10.1371/journal.pntd.0007258

  View details for Web of Science ID 000463799300050

• Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B. PLoS neglected tropical diseases McKittrick, N. D., Malhotra, I. J., Vu, D. M., Boothroyd, D. B., Lee, J., Krystosik, A. R., Mutuku, F. M., King, C. H., LaBeaud, A. D. 2019; 13 (2): e0007172

  Abstract

  BACKGROUND: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy.METHODOLOGY/PRINCIPAL FINDINGS: From 2013-2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups.CONCLUSIONS/SIGNIFICANCE: These findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.

  View details for PubMedID 30818339

• Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B PLOS NEGLECTED TROPICAL DISEASES McKittrick, N. D., Malhotra, I. J., Vu, D. M., Boothroyd, D. B., Lee, J., Krystosik, A. R., Mutuku, F. M., King, C. H., LaBeaud, A. 2019; 13 (2)

  View details for DOI 10.1371/journal.pntd.0007172

  View details for Web of Science ID 000459970700056

• Solid Wastes Provide Breeding Sites, Burrows, and Food for Biological Disease Vectors, and Urban Zoonotic Reservoirs: A Call to Action for Solutions-Based Research. Frontiers in public health Krystosik, A., Njoroge, G., Odhiambo, L., Forsyth, J. E., Mutuku, F., LaBeaud, A. D. 2019; 7: 405

  Abstract

  Background: Infectious disease epidemiology and planetary health literature often cite solid waste and plastic pollution as risk factors for vector-borne diseases and urban zoonoses; however, no rigorous reviews of the risks to human health have been published since 1994. This paper aims to identify research gaps and outline potential solutions to interrupt the vicious cycle of solid wastes; disease vectors and reservoirs; infection and disease; and poverty. Methods: We searched peer-reviewed publications from PubMed, Google Scholar, and Stanford Searchworks, and references from relevant articles using the search terms ("disease" OR "epidemiology") AND ("plastic pollution," "garbage," and "trash," "rubbish," "refuse," OR "solid waste"). Abstracts and reports from meetings were included only when they related directly to previously published work. Only articles published in English, Spanish, or Portuguese through 2018 were included, with a focus on post-1994, after the last comprehensive review was published. Cancer, diabetes, and food chain-specific articles were outside the scope and excluded. After completing the literature review, we further limited the literature to "urban zoonotic and biological vector-borne diseases" or to "zoonotic and biological vector-borne diseases of the urban environment." Results: Urban biological vector-borne diseases, especially Aedes-borne diseases, are associated with solid waste accumulation but vector preferences vary over season and region. Urban zoonosis, especially rodent and canine disease reservoirs, are associated with solid waste in urban settings, especially when garbage accumulates over time, creating burrowing sites and food for reservoirs. Although evidence suggests the link between plastic pollution/solid waste and human disease, measurements are not standardized, confounders are not rigorously controlled, and the quality of evidence varies. Here we propose a framework for solutions-based research in three areas: innovation, education, and policy. Conclusions: Disease epidemics are increasing in scope and scale with urban populations growing, climate change providing newly suitable vector climates, and immunologically naive populations becoming newly exposed. Sustainable solid waste management is crucial to prevention, specifically in urban environments that favor urban vectors such as Aedes species. We propose that next steps should include more robust epidemiological measurements and propose a framework for solutions-based research.

  View details for DOI 10.3389/fpubh.2019.00405

  View details for PubMedID 32010659

• Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Kao, J., Mutuku, F., Martin, S., Lee, J., Mwandi, J., Mukoko, D., Malhotra, I., King, C. H., LaBeaud, A. 2019; 101 (1): 242–52

  View details for DOI 10.4269/ajtmh.17-0688

  View details for Web of Science ID 000476680300039

• Acute flavivirus and alphavirus infections among childdren in two different areas of Kenya, 2015 Am J Trop Med Hyg Hortion, L., Mutuku, F., Eyherabide, F., Vu, D., Boothroyd, D., Grossi-Soyster, E., King, C., Ndenga, B., LaBeaud, A. 2019; 100 (1): 170-173
• Acute Flavivirus and Alphavirus Infections among Children in Two Different Areas of Kenya, 2015 AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Hortion, J., Mutuku, F. M., Eyherabide, A. L., Vu, D. M., Boothroyd, D. B., Grossi-Soyster, E. N., King, C. H., Ndenga, B. A., Desiree LaBeaud, A. 2019; 100 (1): 170–73

  View details for DOI 10.4269/ajtmh.18-0297

  View details for Web of Science ID 000455207700036

• Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition. The American journal of tropical medicine and hygiene Kao, J. n., Mutuku, F. n., Martin, S. n., Lee, J. n., Muinde, J. n., Mukoko, D. n., Malhotra, I. n., King, C. H., LaBeaud, A. D. 2019

  Abstract

  Anemia is known to impact a child's growth and development, but not all anemias are caused by iron deficiency, and the CDC and WHO have emphasized investigating other contributors to anemia. This cross-sectional sub-study of a 2012-2016 maternal-child cohort in coastal Kenya evaluated 244 children and found 185 (76%) to have been anemic on at least one time point since birth. At the time of assessment in 2016, evaluation included a complete blood count, nutritional assessment, and testing for parasitic infections, focusing on the primary outcome of anemia, defined as hemoglobin (Hb) < 11 g/dL. The average age at assessment was 20.5 ± 7 months. Ninety-five percent had a lifetime average Hb in the anemic range. Adjusting for age and gender, prior or current malaria infection (prior: Hb β = -0.99, 95% CI: -1.49 to -0.49, P = 0.01), or having any current infection with hookworm, Trichuris, Strongyloides, Ascaris, and/or malaria (β = -0.84, 95% CI: -1.36 to -0.33, P = 0.01) was associated with decreased current Hb. Nutritional evaluation revealed that children with a declining Hb ate fewer vitamin-A-rich vegetables per week (P = 0.01) or eggs (P = 0.01), drank more milk (P = 0.07), and ate more bread (P = 0.01), and were more likely to live in a household that experienced food shortage (P = 0.05). The high prevalence of anemia, polyparasitism, and dietary insufficiency among children in rural coastal Kenya suggests that remedial interventions will need to address both diet and parasitic infections to effectively combat this significant health threat.

  View details for PubMedID 31074407

• Pediatric tropical medicine: The neglected diseases of children. PLoS neglected tropical diseases Hotez, P. J., Odom John, A. R., LaBeaud, A. D. 2019; 13 (5): e0007008

  View details for PubMedID 31071087

• Malaria smear positivity among Kenyan children peaks at intermediate temperatures as predicted by ecological models. Parasites & vectors Shah, M. M., Krystosik, A. R., Ndenga, B. A., Mutuku, F. M., Caldwell, J. M., Otuka, V. n., Chebii, P. K., Maina, P. W., Jembe, Z. n., Ronga, C. n., Bisanzio, D. n., Anyamba, A. n., Damoah, R. n., Ripp, K. n., Jagannathan, P. n., Mordecai, E. A., LaBeaud, A. D. 2019; 12 (1): 288

  Abstract

  Ambient temperature is an important determinant of malaria transmission and suitability, affecting the life-cycle of the Plasmodium parasite and Anopheles vector. Early models predicted a thermal malaria transmission optimum of 31 °C, later revised to 25 °C using experimental data from mosquito and parasite biology. However, the link between ambient temperature and human malaria incidence remains poorly resolved.To evaluate the relationship between ambient temperature and malaria risk, 5833 febrile children (<18 years-old) with an acute, non-localizing febrile illness were enrolled from four heterogenous outpatient clinic sites in Kenya (Chulaimbo, Kisumu, Msambweni and Ukunda). Thick and thin blood smears were evaluated for the presence of malaria parasites. Daily temperature estimates were obtained from land logger data, and rainfall from National Oceanic and Atmospheric Administration (NOAA)'s Africa Rainfall Climatology (ARC) data. Thirty-day mean temperature and 30-day cumulative rainfall were estimated and each lagged by 30 days, relative to the febrile visit. A generalized linear mixed model was used to assess relationships between malaria smear positivity and predictors including temperature, rainfall, age, sex, mosquito exposure and socioeconomic status.Malaria smear positivity varied between 42-83% across four clinic sites in western and coastal Kenya, with highest smear positivity in the rural, western site. The temperature ranges were cooler in the western sites and warmer in the coastal sites. In multivariate analysis controlling for socioeconomic status, age, sex, rainfall and bednet use, malaria smear positivity peaked near 25 °C at all four sites, as predicted a priori from an ecological model.This study provides direct field evidence of a unimodal relationship between ambient temperature and human malaria incidence with a peak in malaria transmission occurring at lower temperatures than previously recognized clinically. This nonlinear relationship with an intermediate optimal temperature implies that future climate warming could expand malaria incidence in cooler, highland regions while decreasing incidence in already warm regions with average temperatures above 25 °C. These findings support efforts to further understand the nonlinear association between ambient temperature and vector-borne diseases to better allocate resources and respond to disease threats in a future, warmer world.

  View details for DOI 10.1186/s13071-019-3547-z

  View details for PubMedID 31171037

• CHIKUNGUNYA AND DENGUE VIRUS SEROPREVALENCE AMONG CHILDREN IN COASTAL AND WESTERN KENYA AND RISK FACTORS FOR EXPOSURE Cash-Goldwasser, S., Altamirano, J., Ndenga, B., Ng'ang'a, C., Malumbo, S., Amugongo, J., Lwamba, L., Denga, F., Musaki, S., Mutuku, F., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2019: 243–44

  View details for Web of Science ID 000507364503150

• SEROPREVALENCE OF MOSQUITO-BORNE VIRUSES AMONG RESIDENTS FROM DIFFERENT CITIES OF NIGERIA Suner, G. S., Grossi-Soyster, E. N., Ekong, P. S., Aworh, M. K., Wungak, Y. S., Maurice, N. A., Ekong, M. J., Faburay, B., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2019: 67–68

  View details for Web of Science ID 000507364502223

• Unmeasured Risk Factors Impacting Arboviral Transmission, Outbreaks and Prevention Krystosik, A. R., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2019: 244

  View details for Web of Science ID 000507364501005

• THE USE OF SPATIAL VIDEO GEONARRATIVES TO DESCRIBE LOCALIZED ENVIRONMENTAL RISK PATTERNS FOR ARBOVIRAL TRANSMISSION IN URBAN KENYA Krystosik, A. R., Curtis, A., Mutuku, P., Bempah, S., Ajayakumar, J., Odhiambo, L., Bisanzio, D., Forsyth, J., Mwashee, L., Adamz, B., Mutuku, F., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2019: 243

  View details for Web of Science ID 000507364503148

• FIELD TEST OF MINIATURIZED AUTOMATED WHOLE BLOOD CELLULAR ANALYSIS SYSTEM TO ASSESS IMMUNITY TO ARBOVIRUSES IN MSAMBWENI, KENYA Krystosik, A. R., Hale, M., Mutuku, F., Kowli, S., Sagina, J., Lipi, S., Chebii, P. K., Maina, P. W., Grossi-Soyster, E. N., Maecker, H., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2019: 51

  View details for Web of Science ID 000507364502167

• ENVIRONMENTAL AND DEMOGRAPHIC RISK FACTORS FOR AEDES AEGYPTI VECTOR PERSISTENCE IN URBAN AND RURAL KENYA Nyathi, S., Ngugi, H. N., Krystosik, A., Ndenga, B., Bisanzio, D., Kitron, U., Mordecai, E., LaBeaud, D., Mutuku, F. AMER SOC TROP MED & HYGIENE. 2019: 445

  View details for Web of Science ID 000507364504159

• ENGAGING YOUNG PEOPLE AS AGENTS OF CHANGE: A SCHOOL-BASED INTERVENTION TO REDUCE ARBOVIRUS TRANSMISSION - ONE YEAR FOLLOW-UP INTERVIEWS Kempinsky, A. M., Forsyth, J. E., Ling, E. J., Alberts, C. J., Mutuku, F., Kibe, L., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2019: 31–32

  View details for Web of Science ID 000507364502100

• Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species. Systematic biology Calisher, C. H., Briese, T., Rodney Brister, J., Charrel, R. N., Durrwald, R., Ebihara, H., Fulhorst, C. F., Fu Gao, G., Groschup, M. H., Haddow, A. D., Hyndman, T. H., Junglen, S., Klempa, B., Klingstrom, J., Kropinski, A. M., Krupovic, M., LaBeaud, A. D., Maes, P., Nowotny, N., Roberto Teixeira Nunes, M., Payne, S. L., Radoshitzky, S. R., Rubbenstroth, D., Sabanadzovic, S., Sasaya, T., Stenglein, M. D., Varsani, A., Wahl, V., Weaver, S. C., Zerbini, F. M., Vasilakis, N., Kuhn, J. H. 2018

  Abstract

  The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (orders to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV's official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world and therefore have limited use for ICTV-devised taxa. Instead, these professionals look to the ICTV as an expert point source that provides the most current taxonomic affiliations of viruses of interests to facilitate document writing. These needs are currently unmet as an ICTV-supported, easily-searchable database that includes all published virus names and abbreviations linked to their taxa is not available. In addition, in stark contrast to other biological taxonomic frameworks, virus taxonomy currently permits individual species to have several members. Consequently, confusion emerges among those who are not aware of the difference between taxa and viruses, and because certain well-known viruses cannot be located in ICTV publications or be linked to their species. In addition, the number of duplicate names and abbreviations has increased dramatically in the literature. To solve this conundrum, the ICTV could mandate listing all viruses of established species and all reported unclassified viruses in forthcoming online ICTV Reports and create a searchable webpage using this information. The International Union of Microbiology Societies could also consider changing the mandate of the ICTV to include the nomenclature of all viruses in addition to taxon considerations. With such a mandate expansion, official virus names and name abbreviations could be catalogued and virus nomenclature could be standardized. As a result, the ICTV would become an even more useful resource for all stakeholders in virology.

  View details for PubMedID 30597118

• Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of Cali, Colombia from 2014 to 2016 INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH Krystosik, A. R., Curtis, A., LaBeaud, A., Davalos, D. M., Pacheco, R., Buritica, P., Alvarez, A. A., Bhatta, M. P., Rojas Palacios, J., James, M. A. 2018; 15 (10)

  View details for DOI 10.3390/ijerph15102144

  View details for Web of Science ID 000448818100086

• Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of Cali, Colombia from 2014 to 2016. International journal of environmental research and public health Krystosik, A. R., Curtis, A., LaBeaud, A. D., Davalos, D. M., Pacheco, R., Buritica, P., Alvarez, A. A., Bhatta, M. P., Rojas Palacios, J. H., James, M. A. 2018; 15 (10)

  Abstract

  Arboviruses are responsible for a large burden of disease globally and are thus subject to intense epidemiological scrutiny. However, a variable notably absent from most epidemiological analyses has been the impact of violence on arboviral transmission and surveillance. Violence impedes surveillance and delivery of health and preventative services and affects an individual's health-related behaviors when survival takes priority. Moreover, low and middle-income countries bear a disproportionately high burden of violence and related health outcomes, including vector borne diseases. To better understand the epidemiology of arboviral outbreaks in Cali, Colombia, we georeferenced chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viral cases from The National System of Surveillance in Public Health between October 2014 and April 2016. We extracted homicide data from the municipal monthly reports and kernel density of homicide distribution from IdeasPaz. Crucially, an overall higher risk of homicide is associated with increased risk of reported DENV, lower rates of acute testing, and higher rates of lab versus clinical discordance. In the context of high violence as a potential barrier to access to preventive health services, a community approach to improve health and peace should be considered.

  View details for PubMedID 30274270

• Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis. PLoS neglected tropical diseases Contopoulos-Ioannidis, D., Newman-Lindsay, S., Chow, C., LaBeaud, A. D. 2018; 12 (6): e0006510

  Abstract

  BACKGROUND: Chikungunya virus (CHIKV) is an emerging arboviral infection with a global distribution and may cause fetal and neonatal infections after maternal CHIKV-infections during gestation.METHODOLOGY: We performed a systematic review to evaluate the risk for: a) mother-to-child transmission (MTCT), b) antepartum fetal deaths (APFD), c) symptomatic neonatal disease, and d) neonatal deaths from maternal CHIKV-infections during gestation. We also recorded the neonatal clinical manifestations after such maternal infections (qualitative data synthesis). We searched PubMed (last search 3/2017) for articles, of any study design, with any of the above outcomes. We calculated the overall risk of MTCT, APFDs and risk of symptomatic neonatal disease by simple pooling. For endpoints with ≥5 events in more than one study, we also synthesized the data by random-effect-model (REM) meta-analysis.PRINCIPAL FINDINGS: Among 563 identified articles, 13 articles from 8 cohorts were included in the quantitative data synthesis and 33 articles in the qualitative data synthesis. Most cohorts reported data only on symptomatic rather than on all neonatal infections. By extrapolation also of these data, the overall pooled-MTCT-risk across cohorts was at least 15.5% (206/1331), (12.6% by REMs). The pooled APFD-risk was 1.7% (20/1203); while the risk of CHIKV-confirmed-APFDs was 0.3% (3/1203). Overall, the pooled-risk of symptomatic neonatal disease was 15.3% (203/1331), (11.9% by REMs). The pooled risk of symptomatic disease was 50.0% (23/46) among intrapartum vs 0% (0/712) among antepartum/peripartum maternal infections. Infected newborns, from maternal infections during gestation were either asymptomatic or presented within their first week of life, but not at birth, with fever, irritability, hyperalgesia, diffuse limb edema, rashes and occasionally sepsis-like illness and meningoencephalitis. The pooled-risk of neonatal death was 0.6% (5/832) among maternal infections and 2.8% (5/182) among neonatal infections; long-term neurodevelopmental delays occurred in 50% of symptomatic neonatal infections.CONCLUSIONS/SIGNIFICANCE: Published cohorts with data on the risk to the fetus and/or newborn from maternal CHIKV-infections during gestation were sparse compared to the number of recently reported CHIKV-infection outbreaks worldwide; however perinatal infections do occur, at high rates during intrapartum period, and can be related to neonatal death and long-term disabilities.

  View details for PubMedID 29897898

• Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis PLOS NEGLECTED TROPICAL DISEASES Contopoulos-Ioannidis, D., Newman-Lindsay, S., Chow, C., LaBeaud, A. 2018; 12 (6)

  View details for DOI 10.1371/journal.pntd.0006510

  View details for Web of Science ID 000437442000019

• Cord Blood Antiparasite Interleukin 10 as a Risk Marker for Compromised Vaccine Immunogenicity in Early Childhood JOURNAL OF INFECTIOUS DISEASES Malhotra, I., Labeaud, A., Morris, N., Mckibben, M., Mungai, P., Muchiri, E., King, C. L., King, C. H. 2018; 217 (9): 1426–34

  Abstract

  Antenatal exposure to parasites can affect infants' subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns' antiparasite cytokine profiles relate to immunoglobulin G (IgG) responses to standard vaccination during infancy.A total of 450 Kenyan women were tested for parasitic infections during pregnancy. Their newborns' responses to Plasmodium falciparum, schistosome, and filaria antigens were assessed in cord blood lymphocytes. Following standard neonatal vaccination, this infant cohort was followed biannually to age 30 months for measurement of circulating IgG levels against Haemophilus influenzae b (Hib), diphtheria toxoid (DT), hepatitis B virus (HBV), and tetanus toxoid.Trajectories of postvaccination IgG levels were classified by functional principal component (PC) analysis to assess each child's response profile. Two main components, PC1, reflecting height of response over time, and PC2, reflecting crossover from high to low responses or from low to high responses, were identified. Cord blood cytokine responses to schistosome and filarial antigens showed a significant association between augmented antihelminth interleukin 10 and reduced antibody levels, particularly to DT and HBV, and a more rapid postvaccination decline in circulating IgG levels against Hib.Antenatal sensitization to schistosomiasis or filariasis and related production of antiparasite interleukin 10 at birth are associated with reduced antivaccine IgG levels in infancy, with possibly impaired protection.

  View details for DOI 10.1093/infdis/jiy047

  View details for Web of Science ID 000430729300014

  View details for PubMedID 29390149

  View details for PubMedCentralID PMC5894090

• Perinatal Case Fatality Rate in Cases of Congenital Zika Syndrome: a Cross-Sectional Study da Maia, J. S., Alves Vidal, S., Mendes, T., Lins, M., Zacarkim, M., Rolim, D., Aronoff, D. M., LaBeaud, A., Mendes Neto, N. N. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000453090804009

• Radiological Findings and Neurological Disorders in Microcephaly Cases Related to Zika Virus: A Cohort Study De Alcantara, T., da Silva Maia, J., Aronoff, D., Rolim, D., Zacarkim, M., LaBeaud, A., Fernandes, K. E., Neto, N. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000453090801286

• CT Scan Findings in Microcephaly Cases During 2015-2016 Zika Outbreak: A Cohort Study De Alcantara, T., LaBeaud, A., Aronoff, D., Zacarkim, M., da Silva Maia, J., Fernandes, K. E., Neto, N. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000453090801282

• Perinatal Case Fatality Rate Related to Congenital Zika Syndrome in Brazil: A Cross-Sectional Study PEDIATRIC NEUROLOGY Mendes Neto, N. N., da Silva Maia, J., Zacarkim, M., Queiroz, I., Labeaud, A., Aronoff, D. M. 2018; 81: 47–48

  View details for PubMedID 29526344

• Nasopharyngeal Carriage of Streptococcus pneumoniae in Children in Coastal Kenya. The American journal of tropical medicine and hygiene Heath, C. J., Nayakwadi-Singer, M., King, C. H., Malhotra, I., Mutuku, F., Mukoko, D., LaBeaud, A. D. 2018; 98 (4): 1046–50

  Abstract

  Streptococcus pneumoniae (SP) is a leading cause of child mortality globally, killing around half a million children aged 5 years and less per year. Nasopharyngeal carriage of SP is a prerequisite to disease, and the prevalence of colonization reaches 100% within the first few years of life. Serotype prevalence varies geographically, impacting the serotype coverage of pneumococcal vaccines, and serotype prevalence data are limited from large regions of the world, including sub-Saharan Africa. We enrolled 323 unvaccinated children, aged 4-7 years from coastal Kenya and obtained nasopharyngeal swab samples before and after vaccination with the 10-valent pneumococcal vaccine. Vaccination did not reduce the overall prevalence of pneumococcal carriage in our cohort, with 65 (20%) children colonized before vaccination and 63 (19.4%) colonized postvaccination. However, the prevalence of vaccine-included serotypes (vaccine strains) declined from 43% to 19% of positive swabs, whereas non-vaccine serotypes increased from 46% to 73%. This study contributes to the few data available regarding pneumococcal carriage and serotype prevalence in Kenya and is in concordance with reports of dynamic serotype replacement, driven by vaccine pressure.

  View details for PubMedID 29488456

• MAKING PASTORALISTS COUNT: HEALTH SURVEILLANCE OF A NOMADIC POPULATION USING A GEOSPATIALLY DERIVED SAMPLING FRAME Wild, H., Glowacki, L., Maples, S., Mejia-Guevara, I., Hiruy, A., Krystosik, A., Bonds, M., LaBeaud, A., Barry, M. AMER SOC TROP MED & HYGIENE. 2018: 659–60

  View details for Web of Science ID 000461386605149

• PUPAL PRODUCTIVITY OF LARVAL HABITATS OF <it>AEDES AEGYPTI</it> IN MSAMBWENI, KWALE COUNTY KENYA Mutuku, F., Mwakutwaa, A., Ngugi, H., Ndenga, B., Kitron, U., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 51

  View details for Web of Science ID 000461386602163

• GOT MILK? DEFINING THE LINK BETWEEN MILK AND RIFT VALLEY FEVER Grossi-Soyster, E., Lee, J., Muiruri, S., King, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 424

  View details for Web of Science ID 000461386604049

• PREVALENCE OF CHIKUNGUNYA AND DENGUE VIRUS EXPOSURE AMONG CHILDREN IN WESTERN KENYA Musaki, S., Grossi-Soyster, E., Ndenga, B., Mutuku, F., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2018: 282

  View details for Web of Science ID 000461386603233

• RISK FACTORS FOR MALARIA POSITIVITY AMONG FEBRILE CHILDREN AT FOUR HETEROGENEOUS KENYAN CLINICS Shah, M., Krystosik, A., Caldwell, J., Mutuku, F., Ndenga, B., Otuka, V., Ronga, C., Chebii, P., Maina, P., Jembe, Z., Ripp, K., Vora, R., Jagannathan, P., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2018: 553–54

  View details for Web of Science ID 000461386604460

• DECREASED INCIDENCE OF DENGUE, CHIKUNGUNYA, AND ZIKA INFECTIONS IN CHILDREN THROUGHOUT BELO HORIZONTE, BRAZIL: SURPRISING FINDINGS FROM A PILOT PROJECT IN A REFERRAL EMERGENCY DEPARTMENT IN 2017 Maurer, M., Ferreira, J., Grossi-Soyster, E., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2018: 57

  View details for Web of Science ID 000461386602182

• MALARIA IN PREGNANCY: IMPACT OF MICROSCOPIC AND SUB-MICROSCOPIC INFECTIONS ON NEWBORN CHILDREN'S CORD BLOOD IMMUNE RESPONSES Ottichilo, R., Nyakundi, R., Mukuko, D., Mutuku, F., LaBeaud, D., King, C., Malhotra, I. AMER SOC TROP MED & HYGIENE. 2018: 113

  View details for Web of Science ID 000461386602365

• EARLY AND LATE NIGHT HUMAN LANDING PERIODICITY OF <it>AEDES AEGYPTI</it> FEMALES IN URBAN AND RURAL SITES IN KENYA Ndenga, B., Mutuku, F., Ngugi, H., Mbakaya, J., Aswani, P., Musunzaji, P., Mukoko, D., Kitron, U., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2018: 51

  View details for Web of Science ID 000461386602164

• IMPAIRED EXPRESSIVE LANGUAGE IN 24-MONTH-OLD INFANTS EXPOSED TO THE CHIKUNGUNYA VIRUS IN EARLY CHILDHOOD Waechter, R., Cudjoe, N., Noel, T., Krystosik, A., Watts, A., Punch, B., Crandell, H., Isaac, R., Murray, T., Andrew, E., Mapp-Alexander, V., Baptiste, S., Suresh, P., Mitchell, G., Landon, B., Fernandes, M., Gerardin, P., Macpherson, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 203–4

  View details for Web of Science ID 000461386602657

• SUSCEPTIBILITY OF FIELD-COLLECTED <it>AEDES AEGYPTI</it> (L.) TO CONVENTIONAL INSECTICIDES IN COASTAL KENYA Ngugi, H., Mutuku, F., Ndenga, B., Irungu, L., Krystosic, A., Kitron, U., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 44

  View details for Web of Science ID 000461386602140

• NEED FOR REAL TIME ARBOVIRAL SURVEILLANCE DATA TO PREVENT OUTBREAKS. A RETROSPECTIVE STUDY OF ZIKA, CHIKUNGUNYA, AND DENGUE OUTBREAKS IN CALI COLOMBIA 2014 TO 2016 Krystosik, A., LaBeaud, A., Davalos, D., Bhatta, M., Curtis, A., Pacheco, R., Buritica, P., Alvarez, A., Palacios, J., James, M. AMER SOC TROP MED & HYGIENE. 2018: 74–75

  View details for Web of Science ID 000461386602240

• DISTRIBUTION OF DENGUE CASES IN KISUMU CITY AND ENVIRONS Ombewa, E., Mutai, N., Kitron, U., LaBeaud, A., Ndenga, B. AMER SOC TROP MED & HYGIENE. 2018: 60–61

  View details for Web of Science ID 000461386602194

• BUILDING ECOLOGY INTO MODELS TO PREDICT ARBOVIRUS DYNAMICS Caldwell, J., Mutuku, F., Ndenga, B., Mordecai, E., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2018: 63

  View details for Web of Science ID 000461386602203

• THE CHIKUNGUNYA VIRUS OUTBREAK IN GRENADA 2013-EVOLUTION, EPIDEMIC ACTIVITY, AND PHYLODYNAMICS Edgerton, S., Ohashi, S., Lane, K., Heath, C., Noel, T., Macpherson, C., Mitchell, G., Morrison, T., LaBeaud, A., Bennett, S. AMER SOC TROP MED & HYGIENE. 2018: 504–5

  View details for Web of Science ID 000461386604303

• ZIKA AND DENGUE VIRUS INFECTIONS IN PREGNANT MOTHERS IN GRENADA Cudjoe, N., Noel, T., Krystostik, A., Waechter, R., Phillip, S., Mapp-Alexander, V., Grossi-Soyster, E., Suresh, P., Lee, J., Mitchell, G., Macpherson, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 49–50

  View details for Web of Science ID 000461386602158

• ARBOVIRUS AND MALARIA CO-INFECTIONS AMONG FEBRILE KENYAN CHILDREN Shah, M., Sahoo, M., Krystosik, A., Mutuku, F., Ndenga, B., Otuka, V., Ronga, C., Chebii, P., Maina, P., Jembe, Z., Pinsky, B., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 162–63

  View details for Web of Science ID 000461386602521

• UNRECOGNIZED DENGUE AND CHIKUNGUNYA HUMAN TRANSMISSION IN WESTERN AND COASTAL KENYA LaBeaud, A., Mutuku, F., Grossi-Soyster, E., Vu, D., Krystosik, A., Lee, J., Mukoko, D., King, C., Ndenga, B. AMER SOC TROP MED & HYGIENE. 2018: 505

  View details for Web of Science ID 000461386604305

• LARVAL SOURCE REDUCTION WITH A PURPOSE: DESIGNING AND EVALUATING A SCHOOL AND COMMUNITY INTERVENTION IN COASTAL KENYA Forsyth, J., Mutuku, F., Kibe, L., Mwashee, L., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2018: 440

  View details for Web of Science ID 000461386604097

• Nasopharyngeal Carriage of Streptococcus pneumoniae in Children in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Heath, C. J., Nayakwadi-Singer, M., King, C. H., Malhotra, I., Mutuku, F., Mukoko, D., LaBeaud, A. 2018; 98 (4): 1046–50

  View details for DOI 10.4269/ajtmh.16-0813

  View details for Web of Science ID 000430958200014

• USING COMPLEX DATA AND DEEP LEARNING TO PREDICT RIFT VALLEY FEVER OUTBREAKS Kumm, J., Grossi-Soyster, E., Seetah, K., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 301

  View details for Web of Science ID 000461386603295

• PHYLOGENETIC ANALYSES OF ALL FOUR DENGUE VIRUS SEROTYPES DETECTED IN WESTERN KENYA, 2014-2015 Hortion, J., Edgerton, S., Vu, D., Mutai, N., Ndenga, B., Bennett, S., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2018: 280

  View details for Web of Science ID 000461386603228

• Bunyavirus Taxonomy: Limitations and Misconceptions Associated with the Current ICTV Criteria Used for Species Demarcation AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Blitvich, B. J., Beaty, B. J., Blair, C. D., Brault, A. C., Dobler, G., Drebot, M. A., Haddow, A. D., Kramer, L. D., LaBeaud, A., Monath, T. P., Mossel, E. C., Plante, K., Powers, A. M., Tesh, R. B., Turell, M. J., Vasilakis, N., Weaver, S. C. 2018; 99 (1): 11–16

  Abstract

  The International Committee on Taxonomy of Viruses (ICTV) has implemented numerous changes to the taxonomic classification of bunyaviruses over the years. Whereas most changes have been justified and necessary because of the need to accommodate newly discovered and unclassified viruses, other changes are a cause of concern, especially the decision to demote scores of formerly recognized species to essentially strains of newly designated species. This practice was first described in the seventh taxonomy report of the ICTV and has continued in all subsequent reports. In some instances, viruses that share less than 75% nucleotide sequence identity across their genomes, produce vastly different clinical presentations, possess distinct vector and host associations, have different biosafety recommendations, and occur in nonoverlapping geographic regions are classified as strains of the same species. Complicating the matter is the fact that virus strains have been completely eliminated from ICTV reports; thus, critically important information on virus identities and their associated biological and epidemiological features cannot be readily related to the ICTV classification. Here, we summarize the current status of bunyavirus taxonomy and discuss the adverse consequences associated with the reclassification and resulting omission of numerous viruses of public health importance from ICTV reports. As members of the American Committee on Arthropod-borne Viruses, we encourage the ICTV Bunyavirus Study Group to reconsider their stance on bunyavirus taxonomy, to revise the criteria currently used for species demarcation, and to list additional strains of public and veterinary importance.

  View details for PubMedID 29692303

• Clinical, Serological, and Molecular Observations from a Case Series Study during the Asian Lineage Zika Virus Outbreak in Grenada during 2016 CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY Brenciaglia, M., Noel, T. P., Fields, P. J., Bidaisee, S., Myers, T. E., Nelson, W. M., Venkateswaran, N., Venkateswaran, K., Parameswaran, N., Bahadoor, A., Yearwood, K., Mapp-Alexander, V., Mitchell, G., LaBeaud, A., Macpherson, C. L. 2018: 4635647

  Abstract

  This paper describes the spatial and temporal distribution of cases, demographic characteristics of patients, and clinical manifestations of Zika virus (ZIKV) during the 2016 outbreak in Grenada. The first reported case was recorded in St. Andrew Parish in April, and the last reported case was seen in November, with peak transmission occurring in the last week of June, based on test results. Data were collected from a total of 514 patients, of whom 207 (40%) tested positive for ZIKV. No evidence was found that testing positive for ZIKV infection was related to age, gender, or pregnancy status. Clinical presentation with rash (OR = 2.4, 95% CI = 1.5 to 3.7) or with lymphadenopathy (OR = 1.7, 95% CI = 1.0 to 2.9) were the only reported symptoms consistent with testing positive for ZIKV infection. During the Zika outbreak, the infection rate was 20 clinical cases per 10,000 in the population compared to 41 cases per 10,000 during the chikungunya outbreak in Grenada in 2014 and 17 cases per 10,000 during the dengue outbreak in 2001-2002. Even though the country has employed vector control programs, with no apparent decrease in infection rates, it appears that new abatement approaches are needed to minimize morbidity in future arbovirus outbreaks.

  View details for PubMedID 29623138

• The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study OPEN FORUM INFECTIOUS DISEASES Heath, C. J., Lowther, J., Noel, T. P., Mark-George, I., Boothroyd, D. B., Mitchell, G., MacPherson, C., LaBeaud, A. 2018; 5 (1): ofx234

  Abstract

  Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics.We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded.Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk.These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

  View details for PubMedID 29308412

• Seroepidemiological Studies of Arboviruses in Africa Gudo, E., Ali, S., Antonio, V. S., Chelene, I. R., Chongo, I., Demanou, M., Falk, K., Guiliche, O. C., Heinrich, N., Monteiro, V., Muianga, A. F., Oludele, J., Mula, F., Mutuku, F., Amade, N., Alho, P., Betsem, E., Chimbuinhe, Z., Cristovam, A. J., Galano, G., Gessain, A., Harris, E., Heise, M., Inalda, F., Jala, I., Jaszi, E., King, C., Kitron, U., Kuemmerer, B. M., LaBeaud, A. D., Lagerqvist, N., Malai, G., Mazelier, M., Mendes, S., Mukoko, D., Ndenga, B., Njouom, R., Pinto, G., Tivane, A., Vu, D. M., Vulule, J., Hilgenfeld, R., Vasudevan, S. G. SPRINGER-VERLAG SINGAPORE PTE LTD. 2018: 361–71

  Abstract

  The literature on sero-epidemiological studies of flaviviral infections in the African continent is quite scarce. Much of the viral epidemiology studies have been focussing on diseases such as HIV/AIDS because of their sheer magnitude and impact on the lives of people in the various affected countries. Increasingly disease outbreaks caused by arboviruses such as the recent cases of chikungunya virus, dengue virus and yellow fever virus have prompted renewed interest in studying these viruses. International agencies from the US, several EU nations and China are starting to build collaborations to build capacity in many African countries together with established institutions to conduct these studies. The Tofo Advanced Study Week (TASW) was established to bring the best scientists from the world to the tiny seaside town of Praia do Tofo to rub shoulders with African virologists and discuss cutting-edge science and listen to the work of researchers in the field. In 2015 the 1st TASW focussed on Ebola virus. The collections of abstracts from participants at the 2nd TASW which focused on Dengue and Zika virus as well as presentations on other arboviruses are collated in this chapter.

  View details for PubMedID 29845545

• Characteristics of Aedes aegypti adult mosquitoes in rural and urban areas of western and coastal Kenya PLOS ONE Ndenga, B., Mutuku, F., Ngugi, H., Mbakaya, J., Aswani, P., Musunzaji, P., Vulule, J., Mukoko, D., Kitron, U., LaBeaud, A. 2017; 12 (12): e0189971

  Abstract

  Aedes aegypti is the main vector for yellow fever, dengue, chikungunya and Zika viruses. Recent outbreaks of dengue and chikungunya have been reported in Kenya. Presence and abundance of this vector is associated with the risk for the occurrence and transmission of these diseases. This study aimed to characterize the presence and abundance of Ae. aegypti adult mosquitoes from rural and urban sites in western and coastal regions of Kenya. Presence and abundance of Ae. aegypti adult mosquitoes were determined indoors and outdoors in two western (urban Kisumu and rural Chulaimbo) and two coastal (urban Ukunda and rural Msambweni) sites in Kenya. Sampling was performed using quarterly human landing catches, monthly Prokopack automated aspirators and monthly Biogents-sentinel traps. A total of 2,229 adult Ae. aegypti mosquitoes were collected: 785 (35.2%) by human landing catches, 459 (20.6%) by Prokopack aspiration and 985 (44.2%) by Biogents-sentinel traps. About three times as many Ae. aegypti mosquitoes were collected in urban than rural sites (1,650 versus 579). Comparable numbers were collected in western (1,196) and coastal (1,033) sites. Over 80% were collected outdoors through human landing catches and Prokopack aspiration. The probability of collecting Ae. aegypti mosquitoes by human landing catches was significantly higher in the afternoon than morning hours (P<0.001), outdoors than indoors (P<0.001) and in urban than rural sites (P = 0.008). Significantly more Ae. aegypti mosquitoes were collected using Prokopack aspiration outdoors than indoors (P<0.001) and in urban than rural areas (P<0.001). Significantly more mosquitoes were collected using Biogents-sentinel traps in urban than rural areas (P = 0.008) and in western than coastal sites (P = 0.006). The probability of exposure to Ae. aegypti bites was highest in urban areas, outdoors and in the afternoon hours. These characteristics have major implications for the possible transmission of arboviral diseases and for the planning of surveillance and control programs.

  View details for PubMedID 29261766

• IS TIMING OF IN UTERO EXPOSURE KEY IN PREVENTING FETAL PRIMING? Ottichilo, R., Nyakundi, R., Mutuku, F., LaBeaud, D., King, C., Malhotra, I. AMER SOC TROP MED & HYGIENE. 2017: 113–14

  View details for Web of Science ID 000412851501363

• COMPARISON OF ALPHAVIRUS AND FLAVIVIRUS PREVALENCE IN WESTERN KENYA Grossi-Soyster, E. N., Cooke, E. A., Fevre, E. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 222–23

  View details for Web of Science ID 000412851502228

• ADVANCING WATER TREATMENT FOR RESOURCE RECOVERY TO ENHANCE DISEASE MITIGATION Grossi-Soyster, E., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 182

  View details for Web of Science ID 000412851502105

• SEROPREVALENCE OF FLAVIVIRUSES AND ALPHAVIRUSES IN CHILDREN IN COASTAL KENYA: A 2015 SNAPSHOT Grossi-Soyster, E., Mutuku, F., Lipi, S., Ng'ang'a, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 223

  View details for Web of Science ID 000412851502229

• EFFECT OF PRENATAL EXPOSURE TO SCHISTOSOMIASIS AND CO-INFECTIONS WITH SCHISTOSOMIASIS ON FETAL IMMUNE RESPONSES Nyakundi, R. K., Ottichilo, R. K., Mutuku, F., LaBeaud, D., King, C. H., Malhotra, I. AMER SOC TROP MED & HYGIENE. 2017: 587

  View details for Web of Science ID 000412851503427

• CHIKUNGUNYA VIRUS INFECTION IS CAUSING ACUTE FEBRILE ILLNESS AMONG CHILDREN IN KENYA Hortion, J., Vu, D. M., Grossi-Soyster, E. N., Okuta, V., Jembe, Z., Maina, P., Chebii, P., Onyango, W. A., King, C. H., Ndenga, B. A., Mutuku, F. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 223

  View details for Web of Science ID 000412851502230

• PLASMODIUM FALCIPARUM CO-INFECTION MODULATES DENGUE DISEASE SEVERITY Vu, D. M., Ripp, K., Mutai, N., Ndenga, B. A., Heath, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 32

  View details for Web of Science ID 000412851501095

• CHARACTERIZATION OF LARVAL HABITATS OF AEDES AEGYPTI IN KENYA Ngugi, H. N., Mutuku, F., Ndenga, B., Siema, P., Maleka, H., Irungu, L., Mukoko, D., Vulule, J., Kitron, U., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 56–57

  View details for Web of Science ID 000412851501177

• HUMAN-DISEASE CAUSING ARBOVIRUS PREVALENCE IN KENYAN MOSQUITOES Heath, C., Sahoo, M. K., Ndenga, B., Mutuku, F., Ngugi, N., Mbakaya, J., Siema, P., Aswani, P., Macdonald, W. P., Zahiri, N., Waggoner, J. J., Pinsky, B. A., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 447

  View details for Web of Science ID 000412851502947

• SEASONAL PREVALENCE OF ALPHAVIRUSES AND FLAVIVIRUSES IN CHILDREN IN WESTERN KENYA Grossi-Soyster, E., Musaki, S., Ndenga, B., King, C. H., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 421–22

  View details for Web of Science ID 000412851502864

• Unrecognized Dengue Virus Infections in Children, Western Kenya, 2014-2015 EMERGING INFECTIOUS DISEASES Vu, D. M., Mutai, N., Heath, C. J., Vulule, J. M., Mutuku, F. M., Ndenga, B. A., LaBeaud, A. 2017; 23 (11): 1915–17

  Abstract

  We detected a cluster of dengue virus infections in children in Kenya during July 2014-June 2015. Most cases were serotype 1, but we detected all 4 serotypes, including co-infections with 2 serotypes. Our findings implicate dengue as a cause of febrile illness in this population and highlight a need for robust arbovirus surveillance.

  View details for DOI 10.3201/eid2311.170807

  View details for Web of Science ID 000413109500030

  View details for PubMedID 29048283

  View details for PubMedCentralID PMC5652413

• DENGUE VIREMIA IN KENYAN CHILDREN WITH ACUTE FEBRILE ILLNESS Vu, D. M., Mutai, N., Heath, C., Ndenga, B. A., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 429

  View details for Web of Science ID 000412851502888

• PRINCIPLES, PRACTICES, AND KNOWLEDGE OF PROVIDERS EVALUATING CHILDREN PRESENTING WITH FEVER IN KENYA Hooft, A. M., Ripp, K., Ndenga, B., Mutuku, F., Vu, D., Baltzell, K., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 332

  View details for Web of Science ID 000412851502583

• IDENTIFICATION OF FACTORS ASSOCIATED WITH CHRONIC CHIKUNGUNYA DISEASE IN PATIENTS IN GRENADA, WEST INDIES Heath, C. J., Lowther, J., Noel, T. P., Mark-George, I., Boothroyd, D. B., MacPherson, C. N., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 223–24

  View details for Web of Science ID 000412851502231

• MATERNAL PARASITIC INFECTIONS ALTER INFANT ANTIBODY RESPONSE TO PNEUMOCOCCAL IMMUNIZATION McKittrick, N. D., Vu, D. M., Boothroyd, D., Malhotra, I., King, C. H., Mutuku, F. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 29

  View details for Web of Science ID 000412851501084

• EVALUATION OF THE HEALTH-RELATED QUALITY OF LIFE OF CHILDREN WITH DENGUE AND MALARIA IN WESTERN KENYA Liu, E., Vu, D., Boothroyd, D., Ndenga, B., Onyango, W., Okuta, V., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 31–32

  View details for Web of Science ID 000412851501092

• Serological and spatial analysis of alphavirus and flavivirus prevalence and risk factors in a rural community in western Kenya PLOS NEGLECTED TROPICAL DISEASES Grossi-Soyster, E. N., Cook, E. J., de Glanville, W. A., Thomas, L. F., Krystosik, A. R., Lee, J., Wamae, C., Kariuki, S., Fevre, E. M., LaBeaud, A. 2017; 11 (10): e0005998

  Abstract

  Alphaviruses, such as chikungunya virus, and flaviviruses, such as dengue virus, are (re)-emerging arboviruses that are endemic in tropical environments. In Africa, arbovirus infections are often undiagnosed and unreported, with febrile illnesses often assumed to be malaria. This cross-sectional study aimed to characterize the seroprevalence of alphaviruses and flaviviruses among children (ages 5-14, n = 250) and adults (ages 15 ≥ 75, n = 250) in western Kenya. Risk factors for seropositivity were explored using Lasso regression. Overall, 67% of participants showed alphavirus seropositivity (CI95 63%-70%), and 1.6% of participants showed flavivirus seropositivity (CI95 0.7%-3%). Children aged 10-14 were more likely to be seropositive to an alphavirus than adults (p < 0.001), suggesting a recent transmission period. Alphavirus and flavivirus seropositivity was detected in the youngest participants (age 5-9), providing evidence of inter-epidemic transmission. Demographic variables that were significantly different amongst those with previous infection versus those without infection included age, education level, and occupation. Behavioral and environmental variables significantly different amongst those in with previous infection to those without infection included taking animals for grazing, fishing, and recent village flooding. Experience of recent fever was also found to be a significant indicator of infection (p = 0.027). These results confirm alphavirus and flavivirus exposure in western Kenya, while illustrating significantly higher alphavirus transmission compared to previous studies.

  View details for PubMedID 29040262

• Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya MALARIA JOURNAL Hooft, A. M., Ripp, K., Ndenga, B., Mutuku, F., Vu, D., Baltzell, K., Masese, L. N., Vulule, J., Mukoko, D., LaBeaud, A. 2017; 16: 381

  Abstract

  Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya.A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes.The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children.Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels.

  View details for PubMedID 28931399

• Current Status of Rift Valley Fever Vaccine Development. Vaccines Faburay, B., LaBeaud, A. D., McVey, D. S., Wilson, W. C., Richt, J. A. 2017; 5 (3)

  Abstract

  Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease.

  View details for DOI 10.3390/vaccines5030029

  View details for PubMedID 28925970

  View details for PubMedCentralID PMC5620560

• Current Status of Rift Valley Fever Vaccine Development VACCINES Faburay, B., LaBeaud, A., McVey, D., Wilson, W. C., Richt, J. A. 2017; 5 (3)

  View details for DOI 10.3390/vaccines5030029

  View details for Web of Science ID 000411994000014

• Characterization and productivity profiles of Aedes aegypti (L.) breeding habitats across rural and urban landscapes in western and coastal Kenya PARASITES & VECTORS Ngugi, H. N., Mutuku, F. M., Ndenga, B. A., Musunzaji, P. S., Mbakaya, J. O., Aswani, P., Irungu, L. W., Mukoko, D., Vulule, J., Kitron, U., LaBeaud, A. D. 2017; 10: 331

  Abstract

  Aedes aegypti, the principal vector for dengue and other emerging arboviruses, breeds preferentially in various man-made and natural container habitats. In the absence of vaccine, epidemiological surveillance and vector control remain the best practices for preventing dengue outbreaks. Effective vector control depends on a good understanding of larval and adult vector ecology of which little is known in Kenya. In the current study, we sought to characterize breeding habitats and establish container productivity profiles of Ae. aegypti in rural and urban sites in western and coastal Kenya.Twenty sentinel houses in each of four study sites (in western and coastal Kenya) were assessed for immature mosquito infestation once a month for a period of 24 months (June 2014 to May 2016). All water-holding containers in and around the households were inspected for Ae. aegypti larvae and pupae.Collections were made from a total of 22,144 container visits: Chulaimbo (7575) and Kisumu (8003) in the west, and from Msambweni (3199) and Ukunda (3367) on the coast. Of these, only 4-5.6% were positive for Ae. aegypti immatures. In all four sites, significantly more positive containers were located outdoors than indoors. A total of 17,537 Ae. aegypti immatures were sampled from 10 container types. The most important habitat types were buckets, drums, tires, and pots, which produced over 75% of all the pupae. Key outdoor containers in the coast were buckets, drums and tires, which accounted for 82% of the pupae, while pots and tires were the only key containers in the western region producing 70% of the pupae. Drums, buckets and pots were the key indoor containers, producing nearly all of the pupae in the coastal sites. No pupae were collected indoors in the western region. The coastal region produced significantly more Ae. aegypti immatures than the western region both inside and outside the sentinel houses.These results indicate that productive Ae. aegypti larval habitats are abundant outdoors and that only a few containers produce a majority of the pupae. Although the numbers were lower, productive habitats were detected within households. Targeting source reduction efforts towards these productive containers both inside and outside homes is likely to be a cost-effective way to reduce arboviral transmission in these regions.

  View details for PubMedID 28701194

• The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin of western Kenya PLOS NEGLECTED TROPICAL DISEASES Cook, E., Grossi-Soyster, E., de Glanville, W., Thomas, L., Kariuki, S., Bronsvoort, B., Wamae, C., LaBeaud, A., Fevre, E. 2017; 11 (7): e0005731

  Abstract

  Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5-1.3). The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1-1.4, p<0.001), and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0-10.5, p = 0.047). A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5-4.2). Being the slaughterman, the person who cuts the animal's throat (OR 3.5; 95% CI 1.0-12.1, p = 0.047), was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further evidence for RVFV circulation in western Kenya.

  View details for PubMedID 28686589

• Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Garchitorena, A., Sokolow, S. H., Roche, B., Ngonghala, C. N., Jocque, M., Lund, A., Barry, M., MORDECAI, E. A., Daily, G. C., Jones, J. H., Andrews, J. R., Bendavid, E., Luby, S. P., LaBeaud, A. D., Seetah, K., Guegan, J. F., Bonds, M. H., De Leo, G. A. 2017; 372 (1722)

  Abstract

  Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.

  View details for DOI 10.1098/rstb.2016.0128

  View details for PubMedID 28438917

• Parasitic Infections in Pregnancy Decrease Placental Transfer of Antipneumococcus Antibodies. Clinical and vaccine immunology McKittrick, N. D., Vu, D. M., Malhotra, I., King, C. H., Mutuku, F., LaBeaud, A. D. 2017; 24 (6)

  Abstract

  Many factors can influence maternal placental antibody transfer to the fetus, which confers important immune protection to the newborn infant. However, little is known about the effect of maternal parasitic infection on placental antibody transfer. To investigate this, we selected, from a parent study of 576 pregnant Kenyan women, four groups of women with term deliveries (≥37 weeks), including uninfected women (N=30) and women with solo infections of malaria (N=30), hookworm (N=30), or schistosomiasis (N=10). Maternal plasma at delivery and infant cord blood were tested via multiplex fluorescent bead assay for IgG against ten pneumococcal serotypes (PnPs 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), diphtheria toxoid, and Haemophilus influenzae type B. Infants born to mothers with prenatal malaria, hookworm, or S. haematobium infections were associated with a significantly reduced ratio of maternal:infant cord blood antibody concentration for S. pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, and 18C compared to infants of uninfected mothers. Anti-diphtheria toxoid and anti-H. influenzae type B IgG ratios were not significantly different among infection groups. Prenatal parasitic infections decrease the transfer of maternal IgG antibodies to infants for several serotypes of S. pneumoniae.

  View details for DOI 10.1128/CVI.00039-17

  View details for PubMedID 28404574

• Chikungunya Virus. Clinics in laboratory medicine Vu, D. M., Jungkind, D., Angelle Desiree LaBeaud 2017; 37 (2): 371-382

  Abstract

  For chikungunya virus (CHIKV), the long-term sequelae from infection are yet ill-defined. The prolonged debilitating arthralgia associated with CHIKV infection has tremendous potential for impacting the global economy and should be considered when evaluating the human burden of disease and the allocation of resources. There is much still unknown about CHIKV and the illnesses that it causes. Developing a better understanding of the pathogenesis of CHIKV infection is a priority and forms the basis for developing effective strategies at infection prevention and disease control.

  View details for DOI 10.1016/j.cll.2017.01.008

  View details for PubMedID 28457355

• Malaria and Chikungunya Detected Using Molecular Diagnostics Among Febrile Kenyan Children OPEN FORUM INFECTIOUS DISEASES Waggoner, J., Brichard, J., Mutuku, F., Ndenga, B., Heath, C., Mohamed-Hadley, A., Sahoo, M. K., Vulule, J., Lefterova, M., BanaeiA, N., Mukoko, D., Pinsky, B. A., LaBeaud, A. 2017; 4 (3): ofx110

  Abstract

  In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed.Sera from 385 febrile Kenyan children, who presented to 1 of 4 clinical sites, were tested using microscopy and real-time molecular assays for dengue virus (DENV), chikungunya virus (CHIKV), malaria, and Leptospira.Malaria was the primary clinical diagnosis for 254 patients, and an arboviral infection (DENV or CHIKV) was the primary diagnosis for 93 patients. In total, 158 patients (41.0%) had malaria and 32 patients (8.3%) had CHIKV infections. Compared with real-time polymerase chain reaction, microscopy demonstrated a percent positive agreement of 49.7%. The percentage of malaria cases detected by microscopy varied significantly between clinical sites. Arboviral infections were the clinical diagnosis for patients on the Indian Ocean coast (91 of 238, 38.2%) significantly more often than patients in the Lake Victoria region (2 of 145, 1.4%; P < .001). However, detection of CHIKV infections was significantly higher in the Lake Victoria region (19 of 145 [13.1%] vs 13 of 239 [5.4%]; P = .012).The clinical diagnosis of patients with an acute febrile illness, even when aided by microscopy, remains inaccurate in malaria-endemic areas, contributing to inappropriate management decisions.

  View details for PubMedID 28702473

• MORTALITY IN NEWBORNS WITH MICROCEPHALY DUE TO MATERNAL ZIKA VIRUS INFECTION IN RIO GRANDE DO NORTE STATE - NORTHEAST BRAZIL: A CROSSSECTIONAL STUDY Mendes Neto, N., da Silva Maia, J., Zacarkim, M., Rolim, D., Linz, M., Trindade, T., Luz, K., Fulco, G., Mendes, T., Alves Vidal, S., Cortez Muniz, I., Pinheiro de Souza, S., Queiroz, I., LaBeaud, A. LIPPINCOTT WILLIAMS & WILKINS. 2017

  View details for Web of Science ID 000577381505323

• Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood PEDIATRICS Singer, M. N., Heath, C., Muinde, J., Gildengorin, V., Mutuku, F. M., Vu, D., Mukoko, D., King, C. L., Malhotra, I. J., King, C. H., LaBeaud, A. D. 2017; 139 (4)

  Abstract

  Streptococcus pneumoniae is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization.Children from a 2006 to 2010 maternal-infant cohort were eligible for the current study. Children were screened for malaria, schistosomiasis, filariasis, intestinal helminths, and protozoa. Data on in utero exposure and early life infections were linked, and baseline antipneumococcal immunoglobulin G levels and nasopharyngeal carrier status were determined. Participants received decavalent pneumococcal vaccine, and 4 weeks later, serology was repeated to assess vaccine response.A total of 281 children were included. Preimmunity was associated with greater postvaccination increments in anti-pneumococcal polysaccharide immunoglobulin G, especially serotypes 4, 7, 9, 18C, and 19. Present-day growth stunting was independently associated with weaker responses to 1, 4, 6B, 7, 9V, and 19. Previous exposure to Trichuris was associated with stronger responses to 1, 5, 6B, 7, 18C, and 23, but other parasite exposures were not consistently associated with response.In our cohort, hyporesponsiveness to pneumococcal conjugate vaccine was associated with growth stunting but not parasite exposure. Parasite-related vaccine response deficits identified before age 3 do not persist into later childhood.

  View details for DOI 10.1542/peds.2016-2781

  View details for Web of Science ID 000398602400023

  View details for PubMedID 28302673

• A novel framework to account for ecological drivers in the control and elimination of environmentally transmitted disease: a modelling study De Leo, G. A., Sokolow, S. H., Garchitorena, A., Ngonghala, C. N., Lund, A., Barry, M., Burke, K. S., Mordecai, E. A., Daily, G. C., Jones, J. H., Andrews, J. R., Bendavid, E., Luby, S. P., LaBeaud, A., Seetah, K., Guegan, J., Lafferty, K., Wood, C. L., Jones, I. J., Bonds, M. H. ELSEVIER SCIENCE INC. 2017: 5

  View details for Web of Science ID 000406739900006

• Clinical aspects of Zika virus. Current opinion in pediatrics Grossi-Soyster, E. N., LaBeaud, A. D. 2017; 29 (1): 102-106

  Abstract

  Zika virus (ZIKV) is a mosquito-borne flavivirus that has caused a sudden and explosive outbreak in South America and the Caribbean in the last year, and has been declared a public health emergency by the WHO. As ZIKV afflicts previously naive populations, more severe clinical presentations and sequelae have been observed. A specific emphasis has been placed on the neurological effects in infants resulting from viral exposure in utero.Acute onset of ZIKV disease is seen in approximately 20% of cases, whereas most individuals (80%) exposed are asymptomatic. Presentation of illness is typically mild, with disease spectrum ranging from arthralgia and rash to encephalitis, myelitis, and Guillain-Barré syndrome. Infants have been uniquely impacted by the current outbreak with significant congenital exposure resulting in permanent neurological defects and developmental complications.The current ZIKV outbreak has illustrated the emergent capabilities of mosquito-borne viruses and the teratogenic nature of ZIKV. Causality and risk factors associated with severe manifestations, as well as chronic sequelae, have yet to be determined. Extensive research is required to understand the molecular mechanisms of infection, develop improved assays for differential diagnosis, and improve overall knowledge of the spectrum of ZIKV disease in order to develop modes of prevention and treatment.

  View details for DOI 10.1097/MOP.0000000000000449

  View details for PubMedID 27870688

• Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Vu, D. M., Banda, T., Teng, C. Y., Heimbaugh, C., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Brichard, J., Gildengorin, G., Borland, E. M., Powers, A. M., Kitron, U., King, C. H., LaBeaud, A. D. 2017; 96 (1): 141-143

  Abstract

  Dengue virus (DENV) and West Nile virus (WNV) are important reemerging arboviruses that are under-recognized in many parts of Africa due to lack of surveillance. As a part of a study on flavivirus, alphavirus, and parasite exposure in coastal Kenya, we measured neutralizing antibody against DENV and, to evaluate assay specificity, WNV in serum samples that tested positive for serum anti-DENV IgG by enzyme-linked immunosorbent assay. Of 830 anti-DENV IgG-positive samples that were tested for neutralizing activity, 488 (58.8%) neutralized DENV and 94 (11.3%) neutralized WNV. Of children ≤ 10 years of age, 23% and 17% had serum neutralizing antibody to DENV and WNV, respectively, indicating that DENV and WNV transmission has occurred in this region within the past decade. The results suggest that ongoing DENV and WNV transmission continues on the coast of Kenya and supports a need for routine arboviral surveillance in the area to detect and respond to future outbreaks.

  View details for DOI 10.4269/ajtmh.16-0562

  View details for Web of Science ID 000397822900025

• ALTERED FETAL IMMUNE RESPONSES BY PRENATAL EXPOSURE TO MATERNAL CO-INFECTIONS Nyakundi, R. K., Ottichilo, R., Mutuku, F., Kariuki, T., LaBeaud, D., King, C. H., Malhotra, I. AMER SOC TROP MED & HYGIENE. 2017: 556

  View details for Web of Science ID 000423215204504

• BURDEN OF ASYMPTOMATIC MALARIA IN CHILDREN 2-17 YEARS FROM MALARIA ENDEMIC REGIONS OF KENYA Mutuku, F. M., Ndenga, B., Ng'ang'a, C., Lipi, S., Lwamba, L., Denga, F., Vulule, J., Mukoko, D., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2017: 106

  View details for Web of Science ID 000423215202343

• CORD BLOOD ANTI-PARASITE IL-10 AS RISK MARKER FOR COMPROMISED VACCINE IMMUNOGENICITY IN EARLY CHILDHOOD Malhotra, I., LaBeaud, A., Morris, N., McKibben, M., Mungai, P. L., Muchiri, E., King, C. L., King, C. H. AMER SOC TROP MED & HYGIENE. 2017: 216

  View details for Web of Science ID 000423215203063

• UNDERSTANDING THE COMMUNITY CONTEXT OF AEDES AEGYPTI MOSQUITO BREEDING IN COASTAL KENYA: IMPLICATIONS FOR CONTROL Forsyth, J., Mutuku, F., Kibe, L., Kamoni, J., Mwashee, L., Ardoin, N., LaBeaud, D. AMER SOC TROP MED & HYGIENE. 2017: 56

  View details for Web of Science ID 000423215202179

• A COMPARISON OF RAPID AND STANDARD DIAGNOSTIC ASSAY EFFICACY FOR THE DETECTION OF DENGUE VIRUS Grossi-Soyster, E. N., Krystosik, A. R., Sagina, J., Kimaru, S. G., Mutuku, F. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 37

  View details for Web of Science ID 000423215202115

• DENGUE AND CHIKUNGUNYA HUMAN TRANSMISSION IN WESTERN AND COASTAL KENYA: GEOGRAPHIC, CLIMACTIC, VECTORIAL AND SOCIODEMOGRAPHIC RISK FACTORS FOR EXPOSURE AND DISEASE LaBeaud, A., Ndenga, B. A., Grossi-Soyster, E. N., Vu, D. M., Krystosik, A. R., Ngugi, H., Anyamba, A., Damoah, R., Kiptoo, C., Vulule, J., Mukoko, D., Kitron, U., King, C. H., Mutuku, F. M. AMER SOC TROP MED & HYGIENE. 2017: 429–30

  View details for Web of Science ID 000423215204097

• CHIKUNGUNYA INFECTION DURING GESTATION: IMPACT ON PREGNANCY AND NEONATAL OUTCOMES Suresh, P., Krystosik, A., Cudjoe, N., Murray, T., Isaac, R., Mitchell, G., Noel, T., Landon, B., Waechter, R., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 1

  View details for Web of Science ID 000423215202001

• Rift Valley Fever Seroprevalence in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Grossi-Soyster, E. N., Banda, T., Teng, C. Y., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Gildengorin, G., Kitron, U., King, C. H., Labeaud, A. 2017; 97 (1): 115–20

  Abstract

  Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI95] 1.3-2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI95 3.6-9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children (P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle (P < 0.01), suggesting exposure is associated with lower socioeconomic standing (P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.

  View details for DOI 10.4269/ajtmh.17-0104

  View details for Web of Science ID 000409523900020

  View details for PubMedID 28719329

  View details for PubMedCentralID PMC5508922

• DIFFERENCES IN SYMPTOMATOLOGY OF CHILDHOOD DENGUE, CHIKUNGUNYA AND MALARIA INFECTION IN KENYA Vu, D. M., Grossi-Soyster, E. N., Krystosik, A. R., Kiptoo, C., King, C. H., Vulule, J., Mukoko, D., Ndenga, B. A., Mutuku, F. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 552

  View details for Web of Science ID 000423215204491

• CONTRIBUTING FACTORS FOR ANEMIA IN YOUNG CHILDREN IN COASTAL KENYA Kao, J., Mutuku, F., Martin, S., Lee, J., Muinde, J., Mukoko, D., Malhotra, I., King, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 210

  View details for Web of Science ID 000423215203041

• PRESENCE AND ABUNDANCE OF AEDES AEGYPTI ADULT MOSQUITOES IN RURAL AND URBAN AREAS OF WESTERN AND COASTAL KENYA: A POTENTIAL RISK FOTHE OCCURRENCE AND TRANSMISSION OF ARBOVIRAL DISEASES Ndenga, B. A., Mutuku, F. M., Ngugi, H. N., Mbakaya, J. O., Aswani, P., Musunzaji, P. S., Vulule, J., Mukoko, D., Kitron, U., LaBeaud, A. D. AMER SOC TROP MED & HYGIENE. 2017: 63

  View details for Web of Science ID 000423215202203

• MALARIA IN PREGNANCY: IMPLICATIONS OF MICROSCOPIC AND SUB-MICROSCOPIC INFECTION ON CORD BLOOD CYTOKINE RESPONSES Ottichilo, R., Nyakundi, R., Mutuku, F., Malhotra, I., LaBeaud, D., King, C. AMER SOC TROP MED & HYGIENE. 2017: 520

  View details for Web of Science ID 000423215204390

• IMPACTS OF VECTORS ABUNDANCE AND WEATHER ON RISK OF DENGUE AND CHIKUNGUNYA INCIDENCE ACROSS KENYA Krystosik, A. R., Kiptoo, C., Grossi-Soyster, E., Ngugi, N., Siema, P., Aswani, P., Mbakaya, J., Mukoko, D., Vulule, J., Kitron, U., King, C. H., Mutuku, F. M., Ndenga, B. A., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 463–64

  View details for Web of Science ID 000423215204210

• THE PREVALENCE AND CONTRIBUTING FACTORS OF EARLY CHILDHOOD STUNTING IN RURAL COASTAL KENYA Martin, S., Mutuku, F., Kao, J., Lee, J., Mukoko, D., Malhotra, I., King, C., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 71

  View details for Web of Science ID 000423215202229

• Development of a Real-Time Reverse Transcription Polymerase Chain Reaction for O'nyong-nyong Virus and Evaluation with Clinical and Mosquito Specimens from Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Waggoner, J., Heath, C., Ndenga, B., Mutuku, F., Sahoo, M. K., Mohamed-Hadley, A., Vulule, J., Mukoko, D., LaBeaud, A., Pinsky, B. A. 2017; 97 (1): 121–24

  Abstract

  O'nyong-nyong virus (ONNV), an alphavirus closely related to chikungunya virus (CHIKV), has been the documented cause of two large outbreaks in east Africa; however, little is known about the contribution of ONNV to cases of acute febrile illness during interepidemic periods. An ONNV real-time reverse transcription polymerase chain reaction (rRT-PCR) was developed and evaluated using clinical and mosquito pool samples. The ONNV rRT-PCR linear range extended from 8.0 to 2.0 log10 copies/μL, and the lower limit of 95% detection was 22.4 copies/μL. No cases of ONNV infection were identified in serum from 385 Kenyan children who presented with an acute febrile illness. Additionally, ONNV was not detected in 120 mosquito pools collected in coastal and western Kenya. The ONNV rRT-PCR demonstrated good analytical sensitivity when performed in monoplex or as a component of an ONNV-CHIKV duplex assay. This assay should provide a useful diagnostic for the detection of ONNV in surveillance studies.

  View details for PubMedID 28719301

• SATELLITE AND IN SITU CLIMATE DATA MEASUREMENTS AT CHIKUNGUNYA AND DENGUE STUDY SITES IN KENYA Anyamba, A., Damoah, R., Ndenga, B. A., Mutuku, F. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 218–19

  View details for Web of Science ID 000423215203070

• DEMOGRAPHIC AND REGIONAL RISK FACTORS FOR MALARIA-ASSOCIATED HOSPITALIZATIONS IN WESTERN AND COASTAL KENYA Suresh, P., Krystosik, A., Vu, D. M., Kiptoo, C., Vulule, J., Mukoko, D., Kitron, U., King, C. H., Ndenga, B., Mutuku, F. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2017: 321

  View details for Web of Science ID 000423215203401

• Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Vu, D. M., Banda, T., Teng, C. Y., Heimbaugh, C., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Brichard, J., Gildengorin, G., Borland, E. M., Powers, A. M., Kitron, U., King, C. H., LaBeaud, A. D. 2017; 96 (1): 141-143

  View details for DOI 10.4269/ajtmh.16-0562

  View details for Web of Science ID 000401757800025

• Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya. American journal of tropical medicine and hygiene Vu, D. M., Banda, T., Teng, C. Y., Heimbaugh, C., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Brichard, J., Gildengorin, G., Borland, E. M., Powers, A. M., Kitron, U., King, C. H., LaBeaud, A. D. 2016

  Abstract

  Dengue virus (DENV) and West Nile virus (WNV) are important reemerging arboviruses that are under-recognized in many parts of Africa due to lack of surveillance. As a part of a study on flavivirus, alphavirus, and parasite exposure in coastal Kenya, we measured neutralizing antibody against DENV and, to evaluate assay specificity, WNV in serum samples that tested positive for serum anti-DENV IgG by enzyme-linked immunosorbent assay. Of 830 anti-DENV IgG-positive samples that were tested for neutralizing activity, 488 (58.8%) neutralized DENV and 94 (11.3%) neutralized WNV. Of children ≤ 10 years of age, 23% and 17% had serum neutralizing antibody to DENV and WNV, respectively, indicating that DENV and WNV transmission has occurred in this region within the past decade. The results suggest that ongoing DENV and WNV transmission continues on the coast of Kenya and supports a need for routine arboviral surveillance in the area to detect and respond to future outbreaks.

  View details for PubMedID 27821697

• Clinical and Serological Insights from the Asian Lineage Chikungunya Outbreak in Grenada, 2014: An Observational Study. American journal of tropical medicine and hygiene Macpherson, C., Noël, T., Fields, P., Jungkind, D., Yearwood, K., Simmons, M., Widjaja, S., Mitchell, G., Noel, D., Bidaisee, S., Myers, T. E., LaBeaud, A. D. 2016; 95 (4): 890-893

  Abstract

  Chikungunya virus (CHIKV) spread rapidly throughout the Caribbean region in 2014, and the first serologically confirmed case was seen in Grenada in July. This study investigated the outbreak of CHIKV in Grenada to identify the distinguishing clinical manifestations and the symptoms that corresponded the closest with serological test results. Sera were tested by IgM enzyme-linked immunosorbent assay and polymerase chain reaction to distinguish between cases positive or negative for CHIKV. Of 493 cases, 426 (86%) tested positive for CHIKV. The diagnostic decision rule, "Define as CHIKV positive a patient presenting with joint pain and any combination of the fever, body pain, or rash," produced the closest agreement (85%) with the serological test results (Cohen's kappa, κ = 0.289, P value < 0.001). When laboratory facilities are not available for diagnostic confirmation, syndromic surveillance using these four symptoms could be useful to define cases during a CHIKV outbreak when CHIKV is the predominant circulating arbovirus.

  View details for PubMedID 27527629

• Congenital Zika syndrome: time to move from case series to case-control studies and data sharing. BMJ (Clinical research ed.) Gérardin, P. n., Randrianaivo, H. n., Schaub, B. n., Césaire, R. n., Doray, B. n., LaBeaud, A. D. 2016; 354: i4850

  View details for DOI 10.1136/bmj.i4850

  View details for PubMedID 27629599

• Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya MALARIA JOURNAL Bisanzio, D., Mutuku, F., LaBeaud, A. D., Mungai, P. L., Muinde, J., Busaidy, H., Mukoko, D., King, C. H., Kitron, U. 2015; 14

  Abstract

  Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system.Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM).Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012.The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

  View details for DOI 10.1186/s12936-015-1006-7

  View details for PubMedID 26625721

• Seroepidemiological Study of Interepidemic Rift Valley Fever Virus Infection among Persons with Intense Ruminant Exposure in Madagascar and Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Gray, G. C., Anderson, B. D., LaBeaud, A. D., Heraud, J., Fevre, E. M., Andriamandimby, S. F., Cook, E. A., Dahir, S., de Glanville, W. A., Heil, G. L., Khan, S. U., Muiruri, S., Olive, M., Thomas, L. F., Merrill, H. R., Merrill, M. L., Richt, J. A. 2015; 93 (6): 1364-1370

  Abstract

  In this cross-sectional seroepidemiological study we sought to examine the evidence for circulation of Rift Valley fever virus (RVFV) among herders in Madagascar and Kenya. From July 2010 to June 2012, we enrolled 459 herders and 98 controls (without ruminant exposures) and studied their sera (immunoglobulin G [IgG] and IgM through enzyme-linked immunosorbent assay [ELISA] and plaque reduction neutralization test [PRNT] assays) for evidence of previous RVFV infection. Overall, 59 (12.9%) of 459 herders and 7 (7.1%) of the 98 controls were positive by the IgG ELISA assay. Of the 59 ELISA-positive herders, 23 (38.9%) were confirmed by the PRNT assay (21 from eastern Kenya). Two of the 21 PRNT-positive study subjects also had elevated IgM antibodies against RVFV suggesting recent infection. Multivariate modeling in this study revealed that being seminomadic (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 2.1-15.4) was most strongly associated with antibodies against RVFV. Although we cannot know when these infections occurred, it seems likely that some interepidemic RVFV infections are occurring among herders. As there are disincentives regarding reporting RVFV outbreaks in livestock or wildlife, it may be prudent to conduct periodic, limited, active seroepidemiological surveillance for RVFV infections in herders, especially in eastern Kenya.

  View details for DOI 10.4269/ajtmh.15-0383

  View details for Web of Science ID 000366540800040

  View details for PubMedID 26458775

  View details for PubMedCentralID PMC4674260

• CHIKUNGUNYA FEVER IN THE CARIBBEAN: CLINICAL FINDINGS FROM GRENADA LaBeaud, A., Noel, T., Jungkind, D., Yearwood, K., Fields, P., Widjaja, S., Mitchell, G., Simmons, M., Noel, D., Bidaisee, S., Myers, T., Macpherson, C. AMER SOC TROP MED & HYGIENE. 2015: 322

  View details for Web of Science ID 000412844103052

• DEVELOPMENT OF A QUANTITATIVE, REAL-TIME REVERSE-TRANSCRIPTASE PCR FOR O'NYONG-NYONG VIRUS AND ABSENCE OF VIRUS DETECTION AMONG FEBRILE KENYAN CHILDREN Waggoner, J. J., Heath, C. J., Mohamed-Hadley, A., Brichard, J., Coffey, L. L., LaBeaud, A., Pinsky, B. A. AMER SOC TROP MED & HYGIENE. 2015: 224

  View details for Web of Science ID 000412844102482

• PNEUMOCOCCAL VACCINE RESPONSE IN MID-CHILDHOOD IS NOT AFFECTED BY PREVIOUS PARASITE EXPOSURE IN UTERO OR DURING THE FIRST THIRTY-SIX MONTHS OF LIFE IN COASTAL KENYA Singer, M., King, C., Vu, D. M., Heath, C. J., Malhotra, I., Mutuku, F., Mwinde, J., Mungai, P., Mukoko, D., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 343

  View details for Web of Science ID 000412844103118

• SPATIO-TEMPORAL DISTRIBUTION AND ABUNDANCE OF IMMATURE STAGES OF AEDES AEGYPTI ON THE SOUTHERN COAST OF KENYA Mutuku, F. M., Kitron, U., Ndenga, B., Ngugi, N., Siema, P., Mukoko, D., Vulule, J., King, C., LaBeaud, D. A. AMER SOC TROP MED & HYGIENE. 2015: 38

  View details for Web of Science ID 000412844101124

• COMPARISON OF RIFT VALLEY FEVER VIRUS PREVALENCE AMONG COMMUNITY MEMBERS AND SLAUGHTERHOUSE WORKERS IN WESTERN KENYA Grossi-Soyster, E. N., Cooke, E. A., de Glanville, W. A., Thomas, L. F., Wamae, N. C., Kariuki, S., Fevre, E. M., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 2

  View details for Web of Science ID 000412844101005

• STREPTOCOCCUS PNEUMONIAE CARRIAGE RATES AND SEROTYPE PREVALENCE IN COASTAL KENYA Heath, C., Singer, M., Vu, D. M., Mutuku, F., King, C. H., Malhotra, I., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 343

  View details for Web of Science ID 000412844103119

• MATERNAL PARASITIC INFECTIONS DURING PREGNANCY AND SPECIFIC ANTI-PARASITE CYTOKINE RESPONSES IN CORD BLOOD ARE ASSOCIATED WITH IMPAIRED VACCINE EFFICACY IN KENYAN INFANTS Malhotra, I., Mungai, P., McKibben, M., Sutherland, L. J., Muchiri, E., Morris, N., King, C. H., King, C. L., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 379

  View details for Web of Science ID 000412844103237

• COMPARISON OF BLOOD SMEAR WITH SERUM MOLECULAR TESTING FOR THE DIAGNOSIS OF MALARIA AMONG FEBRILE KENYAN CHILDREN Waggoner, J. J., Brichard, J., Mutuku, F., Ndenga, B., Vulule, J., Mukoko, D., Pinsky, B. A., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 460–61

  View details for Web of Science ID 000412844103504

• ACUTE FEBRILE ILLNESS DUE TO DENGUE VIRUS INFECTIONS AMONG CHILDREN IN WESTERN KENYA Ndenga, B. A., Mutai, N., Heath, C., Vu, D., Mutuku, F., Mukoko, D., Vulule, J., King, C., LaBeaud, A. D. AMER SOC TROP MED & HYGIENE. 2015: 46

  View details for Web of Science ID 000412844101151

• DISCREPANCIES BETWEEN TEST RESULTS, DIAGNOSIS, AND TREATMENT OF FEBRILE ILLNESS IN KENYAN CHILDREN Hooft, A. M., Ndenga, B., Mutuku, F., Mukoko, D., Vulule, J., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 196

  View details for Web of Science ID 000412844102392

• EVIDENCE OF TRANSMISSION OF DENGUE AND CHIKUNGUNYA VIRUSES IN WESTERN KENYA Vu, D. M., Musaki, S., Ndenga, B. A., Mutuku, F. M., Harris, E., Heise, M. T., Mukoko, D., Vulule, J., Kitron, U., King, C. H., LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2015: 47

  View details for Web of Science ID 000412844101156

• Parasitism in Children Aged Three Years and Under: Relationship between Infection and Growth in Rural Coastal Kenya PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Singer, M. N., McKibben, M., Mungai, P., Muchiri, E. M., McKibben, E., Gildengorin, G., Sutherland, L. J., King, C. H., King, C. L., Malhotra, I. 2015; 9 (5)

  Abstract

  Parasitic infections, which are among the most common infections worldwide, disproportionately affect children; however, little is known about the impact of parasitic disease on growth in very early childhood. Our objective was to document the prevalence of parasitic infections and examine their association with growth during the first three years of life among children in coastal Kenya.Children enrolled in a maternal-child cohort were tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm, Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia), filaria, and Schistosoma infection every six months from birth until age three years. Anthropometrics were measured at each visit. We used generalized estimating equation (GEE) models to examine the relationship between parasitic infections experienced in the first three years of life and growth outcomes (weight, length and head circumference). Of 545 children, STHs were the most common infection with 106 infections (19%) by age three years. Malaria followed in period prevalence with 68 infections (12%) by three years of age. Filaria and Schistosoma infection occurred in 26 (4.8%) and 16 (2.9%) children, respectively. Seven percent were infected with multiple parasites by three years of age. Each infection type (when all STHs were combined) was documented by six months of age. Decreases in growth of weight, length and head circumference during the first 36 months of life were associated with hookworm, Ascaris, E. histolytica, malaria and Schistosoma infection. In a subset analysis of 180 children who followed up at every visit through 24 months, infection with any parasite was associated with decelerations in weight, length and head circumference growth velocity. Multiple infections were associated with greater impairment of linear growth.Our results demonstrate an under-recognized burden of parasitism in the first three years of childhood in rural Kenya. Parasitic infection and polyparasitism were common, and were associated with a range of significant growth impairment in terms of weight, length and/or head circumference.

  View details for DOI 10.1371/journal.pntd.0003721

  View details for Web of Science ID 000355303600014

  View details for PubMedID 25996157

  View details for PubMedCentralID PMC4440755

• Association of Symptoms and Severity of Rift Valley Fever with Genetic Polymorphisms in Human Innate Immune Pathways PLOS NEGLECTED TROPICAL DISEASES Hise, A. G., Traylor, Z., Hall, N. B., Sutherland, L. J., Dahir, S., Ermler, M. E., Muiruri, S., Muchiri, E. M., Kazura, J. W., LaBeaud, A. D., King, C. H., Stein, C. M. 2015; 9 (3)

  Abstract

  Multiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya.We conducted a cross-sectional survey among residents (N = 1,080; 1-85 yrs) in 6 villages in the Sangailu Division of Ijara District. Participants completed questionnaires on past symptoms and exposures, physical exam, vision testing, and blood collection. Single nucleotide polymorphism (SNP) genotyping was performed on a subset of individuals who reported past clinical symptoms consistent with RVF and unrelated subjects. Four symptom clusters were defined: meningoencephalitis, hemorrhagic fever, eye disease, and RVF-not otherwise specified. SNPs in 46 viral sensing and response genes were investigated. Association was analyzed between SNP genotype, serology and RVF symptom clusters. The meningoencephalitis symptom phenotype cluster among seropositive patients was associated with polymorphisms in DDX58/RIG-I and TLR8. Having three or more RVF-related symptoms was significantly associated with polymorphisms in TICAM1/TRIF, MAVS, IFNAR1 and DDX58/RIG-I. SNPs significantly associated with eye disease included three different polymorphisms TLR8 and hemorrhagic fever symptoms associated with TLR3, TLR7, TLR8 and MyD88.Of the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis.

  View details for DOI 10.1371/journal.pntd.0003584

  View details for PubMedID 25756647

• Factors Associated with Severe Human Rift Valley Fever in Sangailu, Garissa County, Kenya PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Pfeil, S., Muiruri, S., Dahir, S., Sutherland, L. J., Traylor, Z., Gildengorin, G., Muchiri, E. M., Morrill, J., Peters, C. J., Hise, A. G., Kazura, J. W., King, C. H. 2015; 9 (3)

  Abstract

  Mosquito-borne Rift Valley fever virus (RVFV) causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya.A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%). Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498) of adults seropositive vs. only 2% of children ≤15 years (12/583). Seroprevalence was higher among men (18%) than women (13%). Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14), and village location (P = 0.009) were independently associated with the severe disease phenotype.Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool for RVF screening during epidemics in high-risk rural settings.

  View details for DOI 10.1371/journal.pntd.0003548

  View details for PubMedID 25764399

• Cross-Sectional Survey of Rift Valley Fever Virus Exposure in Bodhei Village Located in a Transitional Coastal Forest Habitat in Lamu County, Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Muiruri, S., Kabiru, E. W., Muchiri, E. M., Hussein, H., Kagondu, F., LaBeaud, A. D., Kingt, C. H. 2015; 92 (2): 394-400

  Abstract

  Few studies have focused on Rift Valley fever virus (RVFV) transmission in less arid, transitional landscapes surrounding known high-risk regions. The objective of this study was to identify evidence of RVFV exposure in Bodhei Village in a forested area at the edge of the RVFV-epidemic Garissa region. In a household cluster-based survey conducted between epidemics in early 2006, 211 participants were enrolled. Overall seroprevalence for anti-RVFV was high (18%) and comparable with rates in the more arid, dense brush regions farther north. Seroprevalence of adults was 28%, whereas that of children was significantly lower (3%; P < 0.001); the youngest positive child was age 3 years. Males were more likely to be seropositive than females (25% versus 11%; P < 0.01), and animal husbandry activities (birthing, sheltering, and butchering) were strongly associated with seropositivity. The results confirm that significant RVFV transmission occurs outside of recognized high-risk areas and independent of known epidemic periods.

  View details for DOI 10.4269/ajtmh.14-0440

  View details for Web of Science ID 000349065400036

  View details for PubMedID 25535309

  View details for PubMedCentralID PMC4347346

• High Rates of O'Nyong Nyong and Chikungunya Virus Transmission in Coastal Kenya PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Banda, T., Brichard, J., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Borland, E., Gildengorin, G., Pfeil, S., Teng, C. Y., Long, K., Heise, M., Powers, A. M., Kitron, U., King, C. H. 2015; 9 (2)

  Abstract

  Chikungunya virus (CHIKV) and o'nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors.Demographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50-1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence.486 (26%) participants were seropositive by IgG ELISA. Of 443 PRNT confirmed positives, 25 samples (6%) were CHIKV+, 250 samples (56%) were ONNV+, and 168 samples (38%) had high titers for both. Age was significantly associated with seropositivity (OR 1.01 per year, 95% C.I. 1.00-1.01); however, younger adults were more likely to be seropositive than older adults. Males were less likely to be seropositive (p<0.05; OR 0.79, 95% C.I. 0.64-0.97). Adults who owned a bicycle (p<0.05; OR 1.37, 95% C.I. 1.00-1.85) or motor vehicle (p<0.05; OR 4.64, 95% C.I. 1.19-18.05) were more likely to be seropositive. Spatial analysis demonstrated hotspots of transmission within each village and clustering among local households in Milalani-Nganja, peaking at the 200-500m range.Alphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive. Household location may be a defining factor for the ecology of alphaviral transmission in this region.

  View details for DOI 10.1371/journal.pntd.0003436

  View details for Web of Science ID 000350992500014

  View details for PubMedID 25658762

  View details for PubMedCentralID PMC4319898

• Effect of Antenatal Parasitic Infections on Anti-vaccine IgG Levels in Children: A Prospective Birth Cohort Study in Kenya PLOS NEGLECTED TROPICAL DISEASES Malhotra, I., McKibben, M., Mungai, P., McKibben, E., Wang, X., Sutherland, L. J., Muchiri, E. M., King, C. H., King, C. L., LaBeaud, A. D. 2015; 9 (1)

  Abstract

  Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT).450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

  View details for DOI 10.1371/journal.pntd.0003466

  View details for Web of Science ID 000349318100051

  View details for PubMedID 25590337

  View details for PubMedCentralID PMC4295886

• Predicting the Mosquito Species and Vertebrate Species Involved in the Theoretical Transmission of Rift Valley Fever Virus in the United States PLOS NEGLECTED TROPICAL DISEASES Golnar, A. J., Turell, M. J., LaBeaud, A. D., Kading, R. C., Hamer, G. L. 2014; 8 (9)

  Abstract

  Rift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the vector and vertebrate amplification fraction, defined as the relative contribution of the mosquito or vertebrate host to pathogen transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge which would be necessary to complete a comprehensive analysis identifying the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S. Future research should focus on (1) the dose-dependent relationship between viremic exposure and the subsequent infectiousness of key mosquito species, (2) evaluation of vertebrate host competence for RVFV among North American mammal species, with particular emphasis on the order Artiodactyla, and (3) identification of areas with a high risk for RVFV introduction so data on local vector and host populations can help generate geographically appropriate amplification fraction estimates.

  View details for DOI 10.1371/journal.pntd.0003163

  View details for Web of Science ID 000342796600044

  View details for PubMedID 25211133

  View details for PubMedCentralID PMC4161329

• The Largest Drought in American History: Funding for Science Is Drying Up PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., McKeating, H. 2013; 7 (8)

  View details for DOI 10.1371/journal.pntd.0002351

  View details for Web of Science ID 000323941500018

  View details for PubMedID 24009785

  View details for PubMedCentralID PMC3757073

• Epidemiology, outcomes and predictors of recovery in childhood encephalitis: a hospital-based study. Pediatric infectious disease journal Dubray, K., Anglemyer, A., LaBeaud, A. D., Flori, H., Bloch, K., Joaquin, K. S., Messenger, S., Preas, C., Sheriff, H., Glaser, C. 2013; 32 (8): 839-844

  Abstract

  Pediatric encephalitis is a devastating diagnosis with little guidance regarding prognostic indicators early in the hospitalization.This is a retrospective cohort study of patients with encephalitis referred to the California Encephalitis Project from Children's Hospital & Research Center Oakland from 1998 to 2010. Demographic, clinical, laboratory and neuroimaging data were collected by California Encephalitis Project and chart review. Outcomes were classified into "recovery" or "incomplete recovery" and evaluated at discharge and other times (7-10 days postadmission, 3 and 12 months postdischarge). Using logistic regression, predictors associated with recovery were identified.Of 190 patients with outcomes available at discharge, 128 patients (67.4%) recovered, whereas 62 (32.6%) had an incomplete recovery, including 13 deaths (6.8%). Variables predictive of outcomes at discharge in the bivariate and multivariable analyses included Asian/Pacific Islander race, neuroimaging results and Glasgow Coma Score. Asian/Pacific Islander patients were less likely to recover than patients of other races (adjusted odds ratio = 0.43, P = 0.046). Patients with normal neuroimaging studies were more likely to recover than patients with abnormal neuroimaging (adjusted odds ratio = 2.54, P = 0.008). Patients with Glasgow Coma Score ≥7 were more likely to recover than patients with Glasgow Coma Score <7 (adjusted odds ratio = 5.82, P < 0.001). In a multivariable analysis, similar statistically significant findings were noted at all other analyzed times. Results were similar using a different population for validation, however, due to the small number of Asian/Pacific Islander patients; this finding could not be validated.This study is unique in identification of race/ethnicity as an independent predictor of pediatric encephalitis outcomes. Additional variables may be useful ancillary tools in determining prognosis.

  View details for DOI 10.1097/INF.0b013e318290614f

  View details for PubMedID 23518823

• Comparison Of Moderate And Severe Hospitalized Pediatric 2009 H1N1 Influenza Cases PEDIATRIC INFECTIOUS DISEASE JOURNAL LaBeaud, A. D., Wentworth, B., Gildengorin, G., Tam, K., Guardia-LaBar, L., Petru, A. 2013; 32 (2): E90-E93

  Abstract

  Since its discovery in 2009, H1N1 influenza (H1N1) has spread globally. Predictive factors for severe disease in children are not well defined. Our retrospective data collection and logistic regression analysis on 137 patients hospitalized between April 2009 and February 2010 at Children's Hospital and Research Center Oakland describe clinical and epidemiologic features of H1N1 in children and determines predictors of severe disease.

  View details for DOI 10.1097/INF.0b013e31827882f9

  View details for Web of Science ID 000313874500007

  View details for PubMedID 23080289

• Painful Arthritis and Extremity Rash in an 8-Year-Old Boy CLINICAL INFECTIOUS DISEASES Islam, S., Cooney, T., Singh, A., Petru, A. M., LaBeaud, A. D. 2012; 54 (10): 1473-?

  View details for DOI 10.1093/cid/cir1007

  View details for Web of Science ID 000304049300019

  View details for PubMedID 22527963

• Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Muiruri, S., Sutherland, L. J., Dahir, S., Gildengorin, G., Morrill, J., Muchiri, E. M., Peters, C. J., King, C. H. 2011; 5 (8)

  Abstract

  In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies.We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001).Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

  View details for DOI 10.1371/journal.pntd.0001265

  View details for Web of Science ID 000294479800020

  View details for PubMedID 21858236

  View details for PubMedCentralID PMC3156691

• Serologic evidence of arboviral infections among humans in Kenya. American journal of tropical medicine and hygiene Sutherland, L. J., Cash, A. A., Huang, Y. S., Sang, R. C., Malhotra, I., Moormann, A. M., King, C. L., Weaver, S. C., King, C. H., LaBeaud, A. D. 2011; 85 (1): 158-161

  Abstract

  Outbreaks of arthropod-borne viral infections occur periodically across Kenya. However, limited surveillance takes place during interepidemic periods. Using serum samples obtained from asymptomatic persons across Kenya in 2000-2004, we assessed (by indirect immunofluorescent assay) prevalence of IgG against yellow fever virus (YFV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), dengue virus serotypes 1-4 (DENV1-4), and chikungunya virus (CHIKV). Older persons on the Indian Ocean coast were more likely to be seropositive than children inland: YFV = 42% versus 6%, WNV = 29% versus 6%, TBEV = 16% versus 6%, DENV-1 = 63% versus 9%, DENV-2 = 67% versus 7%, DENV-3 = 55% versus 6%, DENV-4 = 44% versus 8%, and CHIKV = 37% versus 20%. Among inland samples, children in lowlands were more likely to be seropositive for CHIKV (42% versus 0%) than children in highlands. In Kenya, transmission of arboviral infection continues between known epidemics and remains common across the country.

  View details for DOI 10.4269/ajtmh.2011.10-0203

  View details for PubMedID 21734142

  View details for PubMedCentralID PMC3122361

• Rift Valley Fever Virus Infection in African Buffalo (Syncerus caffer) Herds in Rural South Africa: Evidence of Interepidemic Transmission AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LaBeaud, A. D., Cross, P. C., Getz, W. M., Glinka, A., King, C. H. 2011; 84 (4): 641-646

  Abstract

  Rift Valley fever virus (RVFV) is an emerging biodefense pathogen that poses significant threats to human and livestock health. To date, the interepidemic reservoirs of RVFV are not well defined. In a longitudinal survey of infectious diseases among African buffalo during 2000-2006, 550 buffalo were tested for antibodies against RVFV in 820 capture events in 302 georeferenced locations in Kruger National Park, South Africa. Overall, 115 buffalo (21%) were seropositive. Seroprevalence of RVFV was highest (32%) in the first study year, and decreased progressively in subsequent years, but had no detectable impact on survival. Nine (7%) of 126 resampled, initially seronegative animals seroconverted during periods outside any reported regional RVFV outbreaks. Seroconversions for RVFV were detected in significant temporal clusters during 2001-2003 and in 2004. These findings highlight the potential importance of wildlife as reservoirs for RVFV and interepidemic RVFV transmission in perpetuating regional RVFV transmission risk.

  View details for DOI 10.4269/ajtmh.2011.10-0187

  View details for Web of Science ID 000289023600024

  View details for PubMedID 21460024

  View details for PubMedCentralID PMC3062463

• Arbovirus Prevalence in Mosquitoes, Kenya EMERGING INFECTIOUS DISEASES LaBeaud, A. D., Sutherland, L. J., Muiruri, S., Muchiri, E. M., Gray, L. R., Zimmerman, P. A., Hise, A. G., King, C. H. 2011; 17 (2): 233-241

  Abstract

  Few studies have investigated the many mosquito species that harbor arboviruses in Kenya. During the 2006-2007 Rift Valley fever outbreak in North Eastern Province, Kenya, exophilic mosquitoes were collected from homesteads within 2 affected areas: Gumarey (rural) and Sogan-Godud (urban). Mosquitoes (n = 920) were pooled by trap location and tested for Rift Valley fever virus and West Nile virus. The most common mosquitoes trapped belonged to the genus Culex (75%). Of 105 mosquito pools tested, 22% were positive for Rift Valley fever virus, 18% were positive for West Nile virus, and 3% were positive for both. Estimated mosquito minimum infection rates did not differ between locations. Our data demonstrate the local abundance of mosquitoes that could propagate arboviral infections in Kenya and the high prevalence of vector arbovirus positivity during a Rift Valley fever outbreak.

  View details for DOI 10.3201/eid1702.091666

  View details for Web of Science ID 000287436400011

  View details for PubMedID 21291594

  View details for PubMedCentralID PMC3204744

• Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections POPULATION HEALTH METRICS LaBeaud, A. D., Bashir, F., King, C. H. 2011; 9

  Abstract

  Globally, arthropod-borne virus infections are increasingly common causes of severe febrile disease that can progress to long-term physical or cognitive impairment or result in early death. Because of the large populations at risk, it has been suggested that these outcomes represent a substantial health deficit not captured by current global disease burden assessments.We reviewed newly available data on disease incidence and outcomes to critically evaluate the disease burden (as measured by disability-adjusted life years, or DALYs) caused by yellow fever virus (YFV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). We searched available literature and official reports on these viruses combined with the terms "outbreak(s)," "complication(s)," "disability," "quality of life," "DALY," and "QALY," focusing on reports since 2000. We screened 210 published studies, with 38 selected for inclusion. Data on average incidence, duration, age at onset, mortality, and severity of acute and chronic outcomes were used to create DALY estimates for 2005, using the approach of the current Global Burden of Disease framework.Given the limitations of available data, nondiscounted, unweighted DALYs attributable to YFV, JEV, CHIKV, and RVFV were estimated to fall between 300,000 and 5,000,000 for 2005. YFV was the most prevalent infection of the four viruses evaluated, although a higher proportion of the world's population lives in countries at risk for CHIKV and JEV. Early mortality and long-term, related chronic conditions provided the largest DALY components for each disease. The better known, short-term viral febrile syndromes caused by these viruses contributed relatively lower proportions of the overall DALY scores.Limitations in health systems in endemic areas undoubtedly lead to underestimation of arbovirus incidence and related complications. However, improving diagnostics and better understanding of the late secondary results of infection now give a first approximation of the current disease burden from these widespread serious infections. Arbovirus control and prevention remains a high priority, both because of the current disease burden and the significant threat of the re-emergence of these viruses among much larger groups of susceptible populations.

  View details for DOI 10.1186/1478-7954-9-1

  View details for Web of Science ID 000300215200001

  View details for PubMedID 21219615

  View details for PubMedCentralID PMC3024945

• Planning for Rift Valley fever virus: use of geographical information systems to estimate the human health threat of white-tailed deer (Odocoileus virginianus)-related transmission GEOSPATIAL HEALTH Kakani, S., LaBeaud, A. D., King, C. H. 2010; 5 (1): 33-43

  Abstract

  Rift Valley fever (RVF) virus is a mosquito-borne phlebovirus of the Bunyaviridae family that causes frequent outbreaks of severe animal and human disease in sub-Saharan Africa, Egypt and the Arabian Peninsula. Based on its many known competent vectors, its potential for transmission via aerosolization, and its progressive spread from East Africa to neighbouring regions, RVF is considered a high-priority, emerging health threat for humans, livestock and wildlife in all parts of the world. Introduction of West Nile virus to North America has shown the potential for "exotic" viral pathogens to become embedded in local ecological systems. While RVF is known to infect and amplify within domestic livestock, such as taurine cattle, sheep and goats, if RVF virus is accidentally or intentionally introduced into North America, an important unknown factor will be the role of local wildlife in the maintenance or propagation of virus transmission. We examined the potential impact of RVF transmission via white-tailed deer (Odocoileus virginianus) in a typical north-eastern United States urban-suburban landscape, where livestock are rare but where these potentially susceptible, ungulate wildlife are highly abundant. Model results, based on overlap of mosquito, human and projected deer densities, indicate that a significant proportion (497/1186 km(2), i.e. 42%) of the urban and peri-urban landscape could be affected by RVF transmission during the late summer months. Deer population losses, either by intervention for herd reduction or by RVF-related mortality, would substantially reduce these likely transmission zones to 53.1 km(2), i.e. by 89%.

  View details for Web of Science ID 000284089600004

  View details for PubMedID 21080319

  View details for PubMedCentralID PMC3140430

• Neglected Funding for Vector-Borne Diseases: A Near Miss This Time, a Possible Disaster the Next Time PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Aksoy, S. 2010; 4 (10)

  View details for DOI 10.1371/journal.pntd.0000847

  View details for Web of Science ID 000283559600001

  View details for PubMedID 21049011

  View details for PubMedCentralID PMC2964300

• Advances in Rift Valley fever research: insights for disease prevention CURRENT OPINION IN INFECTIOUS DISEASES LaBeaud, A. D., Kazura, J. W., King, C. H. 2010; 23 (5): 403-408

  Abstract

  The purpose was to review recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates.RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines.RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority.

  View details for DOI 10.1097/QCO.0b013e32833c3da6

  View details for Web of Science ID 000281653400001

  View details for PubMedID 20613512

  View details for PubMedCentralID PMC3126654

• Facets of the Rift Valley fever outbreak in Northeastern Province, Kenya, 2006-2007. American journal of tropical medicine and hygiene King, C. H., Kahlon, S. S., Muiruri, S., LaBeaud, A. D. 2010; 82 (3): 363-?

  View details for DOI 10.4269/ajtmh.2010.09-0800

  View details for PubMedID 20207854

  View details for PubMedCentralID PMC2829890

• Pulmonary Tuberculosis Presenting as Fever Without Source in a Pediatric Patient With Acute Lymphoblastic Leukemia PEDIATRIC BLOOD & CANCER Lancioni, C., LaBeaud, A. D., Esper, F., Abughali, N., Auletta, J. 2009; 53 (7): 1318-1320

  Abstract

  Children who undergo treatment for malignancies are at high for infection with both typical and opportunistic pathogens. Fever in these children prompts extensive evaluation and empiric treatment with broad-spectrum antimicrobials. In the United States (US), tuberculosis is an infrequently reported cause of fever in the pediatric cancer patient and has not been well described. In this report we describe a case of primary pulmonary tuberculosis (TB) in a boy with precursor B-cell acute lymphoblastic leukemia (ALL) and review the pertinent literature.

  View details for DOI 10.1002/pbc.22155

  View details for Web of Science ID 000271363800026

  View details for PubMedID 19618457

• CANDIDA SKIN TESTING IS A POOR ADJUNCT TO TUBERCULIN SKIN TESTING IN INTERNATIONAL ADOPTEES PEDIATRIC INFECTIOUS DISEASE JOURNAL Yeo, K. T., Zhu, X., Kirchner, H. L., LaBeaud, A. D., Mandalakas, A. 2009; 28 (11): 1020-1021

  Abstract

  We conducted a prospective longitudinal study evaluating Candida skin testing among international adoptees presenting to our clinic between 2000 and 2006. Nineteen (17%) and 17 (15%) children had negative tests at presentation and at 6 months, respectively--only 3 were negative at both points. Our study suggests that Candida skin test reactivity is an unstable measure of anergy among international adoptees.

  View details for DOI 10.1097/INF.0b013e3181a909d3

  View details for Web of Science ID 000271253800018

  View details for PubMedID 19820428

  View details for PubMedCentralID PMC3133951

• School-Based Health Promotion for Mosquito-Borne Disease Prevention in Children JOURNAL OF PEDIATRICS LaBeaud, A. D., Glinka, A., Kippes, C., King, C. H. 2009; 155 (4): 590-592

  Abstract

  We enrolled 345 fourth-grade students in a classroom-randomized, controlled trial to evaluate a school-based West Nile virus health education program's impact on knowledge, attitudes, and personal protective behavior use. Immediate and sustained improvements in West Nile virus knowledge and greater frequencies of reported personal protective behaviors resulted from the educational intervention.

  View details for DOI 10.1016/j.jpeds.2009.03.009

  View details for Web of Science ID 000270497800031

  View details for PubMedID 19773005

  View details for PubMedCentralID PMC3104726

• Do Antenatal Parasite Infections Devalue Childhood Vaccination? PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Malhotra, I., King, M. J., King, C. L., King, C. H. 2009; 3 (5)

  Abstract

  On a global basis, both potent vaccine efficacy and high vaccine coverage are necessary to control and eliminate vaccine-preventable diseases. Emerging evidence from animal and human studies suggest that neglected tropical diseases (NTDs) significantly impair response to standard childhood immunizations. A review of efficacy and effectiveness studies of vaccination among individuals with chronic parasitic infections was conducted, using PUBMED database searches and analysis of data from the authors' published and unpublished studies. Both animal models and human studies suggest that chronic trematode, nematode, and protozoan infections can result in decreased vaccine efficacy. Among pregnant women, who in developing countries are often infected with multiple parasites, soluble parasite antigens have been shown to cross the placenta and prime or tolerize fetal immune responses. As a result, antenatal infections can have a significant impact on later vaccine responses. Acquired childhood parasitic infections, most commonly malaria, can also affect subsequent immune response to vaccination. Additional data suggest that antiparasite therapy can improve the effectiveness of several human vaccines. Emerging evidence demonstrates that both antenatal and childhood parasitic infections alter levels of protective immune response to routine vaccinations. Successful antiparasite treatment may prevent immunomodulation caused by parasitic antigens during pregnancy and early childhood and may improve vaccine efficacy. Future research should highlight the varied effects that different parasites (alone and in combination) can have on human vaccine-related immunity. To optimize vaccine effectiveness in developing countries, better control of chronic NTDs may prove imperative.

  View details for DOI 10.1371/journal.pntd.0000442

  View details for Web of Science ID 000267268000014

  View details for PubMedID 19478847

  View details for PubMedCentralID PMC2682196

• Interepidemic Rift Valley fever virus seropositivity, northeastern Kenya EMERGING INFECTIOUS DISEASES LaBeaud, A. D., Muchiri, E. M., Ndzovu, M., Mwanje, M. T., Muiruri, S., Peters, C. J., King, C. H. 2008; 14 (8): 1240-1246

  Abstract

  Most outbreaks of Rift Valley fever (RVF) occur in remote locations after floods. To determine environmental risk factors and long-term sequelae of human RVF, we examined rates of previous Rift Valley fever virus (RVFV) exposure by age and location during an interepidemic period in 2006. In a randomized household cluster survey in 2 areas of Ijara District, Kenya, we examined 248 residents of 2 sublocations, Gumarey (village) and Sogan-Godud (town). Overall, the RVFV seropositivity rate was 13% according to immunoglobulin G ELISA; evidence of interepidemic RVFV transmission was detected. Increased seropositivity was found among older persons, those who were male, those who lived in the rural village (Gumarey), and those who had disposed of animal abortus. Rural Gumarey reported more mosquito and animal exposure than Sogan-Godud. Seropositive persons were more likely to have visual impairment and retinal lesions; other physical findings did not differ.

  View details for DOI 10.3201/eid1408.080082

  View details for Web of Science ID 000258216900008

  View details for PubMedID 18680647

  View details for PubMedCentralID PMC2600406

• Why Arboviruses Can Be Neglected Tropical Diseases PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D. 2008; 2 (6)

  View details for DOI 10.1371/journal.pntd.0000247

  View details for Web of Science ID 000261807000001

  View details for PubMedID 18575597

  View details for PubMedCentralID PMC2427179

• Rapid GIS-based profiling of West Nile virus transmission: defining environmental factors associated with an urban-suburban outbreak in Northeast Ohio, USA GEOSPATIAL HEALTH LaBeaud, A. D., Gorman, A., Koonce, J., Kippes, C., McLeod, J., Lynch, J., Gallagher, T., King, C. H., Mandalakas, A. M. 2008; 2 (2): 215-225

  Abstract

  Human West Nile virus (WNV) infection was first detected in Cuyahoga county, Ohio, USA, in 2002. During that year's extensive epidemic/epizootic among non-immune human and bird populations, the county experienced 155 cases of severe human West Nile neurological disease (WNND, incidence = 11.1 cases/100,000), with 11 fatalities. Structured serosurveys indicated that 1.9%, or approximately 26,000 of county residents (population = 1,372,303) were infected that year. In early 2003, in order to better focus monitoring and control efforts, we used a geographical information system (GIS) approach and spatial statistical analysis to identify the association of environmental factors and human population structure with the observed local risk for WNV transmission. Within the varied range of urban/suburban/ rural habitats across the 1186 km2 county, exploratory analysis indicated significant clustering of WNND risk in inner-ring suburbs. Subsequent discriminant factor analysis based on inputs of census and land-use/land cover data was found to effectively classify sub-areas of the county having low, medium and high WNV risk. On a 1036 ha quadrat scale of resolution, higher risk of human infection was significantly associated with higher-income areas, increased fractionation of habitat and older housing, while it was negatively associated with areas of agricultural land, wetland or forest. The areal classification of WNV transmission risk has been validated over time through detection of increased local Culex spp. mosquito density (2002-2006), and increased frequency of WNV positive mosquito pools within the medium- and high-risk quadrats. This timely working identification of the transmission scale effectively focused control interventions against newly invasive WNV in a complex North American habitat.

  View details for Web of Science ID 000258662200008

  View details for PubMedID 18686270

  View details for PubMedCentralID PMC3140769

• Spectrum of rift valley fever virus transmission in Kenya: Insights from three distinct regions AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LaBeaud, A. D., Ochiai, Y., Peters, C. J., Muchiri, E. M., King, C. H. 2007; 76 (5): 795-800

  Abstract

  Rift Valley fever virus (RVFV) is an emerging pathogen that maintains high biodefense priority based on its threat to livestock, its ability to cause human hemorrhagic fever, and its potential for aerosol spread. To define the range of human transmission during inter-epidemic and epidemic periods in Kenya, we tested archived sera from defined populations (N = 1,263) for anti-RVFV IgG by ELISA and plaque reduction neutralization testing. RVFV seroprevalence was 10.8% overall and varied significantly by location, sex, and age. In NW Kenya, high seroprevalence among those born before 1980 indicates that an undetected epidemic may have occurred then. Seroconversion documented in highland areas suggests previously unsuspected inter-epidemic transmission. RVFV seroprevalence is strikingly high in certain Kenyan areas, suggesting endemic transmission patterns that may preclude accurate estimation of regional acute outbreak incidence. The extent of both epidemic and inter-epidemic RVFV transmission in Kenya is greater than previously documented.

  View details for Web of Science ID 000246326300003

  View details for PubMedID 17488893

  View details for PubMedCentralID PMC2367216

• Index of suspicion PEDIATRICS IN REVIEW Eneli, I., West, M., Sigal, Y., Martel, J. N., Lazerson, J., Halthore, S. N., LaBeaud, A. D., Leonard, E. G., McComsey, G. A. 2006; 27 (10): 389-394

  View details for Web of Science ID 000242176700005

  View details for PubMedID 17012490