Honors & Awards

  • ASTMH Travel Award, American Society of Tropical Medicine and Hygiene (ASTMH) (2023)
  • Oral presentation, IV FAMERP-UTMB: Emerging infections in the Americas (2019)
  • Travel Grant: 16th International Course on Dengue, Zika, and other Emergent Arboviruses., Institute of Tropical Medicine Pedro Kourí. La Havana, Cuba. Scholarship: OPAS (2019)
  • Travel grant for oral abstract presentation, 6th Pan-American Dengue Research Network Meeting (2018)
  • Travel Grant for arboviruses course participation, São Paulo School of Advanced Science (2017)
  • Travel grant: Molecular Epidemiology in Infectious Diseases of Global Significance, ICOPHAI and Centre for Genetic Engineering and Biotechnology (ICGEB) (2013)

Boards, Advisory Committees, Professional Organizations

  • Editor-in-Chief, Revista Docência do Ensino Superior (UFMG - Brazil) https://periodicos.ufmg.br/index.php/rdes (2020 - 2020)
  • Member, American Society of Tropical Medicine and Hygiene (2020 - Present)
  • Member, Brazilian Society of Virology (2012 - Present)

Stanford Advisors

Lab Affiliations

All Publications

  • 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


    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

  • 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


    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

  • Late-Relapsing Hepatitis after Yellow Fever VIRUSES-BASEL Rezende, I., Pereira, L., Fradico, J., Xavier, M., Alves, P., Campi-Azevedo, A., Speziali, E., dos Santos, L., Albuquerque, N., Penido, I., Santos, T., Bom, A., da Silva, A., Fernandes, C., Calzavara, C., Kroon, E., Martins-Filho, O., Teixeira-Carvalho, A., Drumond, B. 2020; 12 (2)


    One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.

    View details for DOI 10.3390/v12020222

    View details for Web of Science ID 000521256600063

    View details for PubMedID 32079143

    View details for PubMedCentralID PMC7077229

  • 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


    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

  • Persistence of Yellow fever virus outside the Amazon Basin, causing epidemics in Southeast Brazil, from 2016 to 2018 PLOS NEGLECTED TROPICAL DISEASES de Rezende, I., Sacchetto, L., de Mello, E., Alves, P., de Melo Iani, F., Ribeiro Adelino, T., Duarte, M., Furtado Cury, A., Leal Bernardes, A., Santos, T., Pereira, L., Teixeira Dutra, M., Ramalho, D., de Thoisy, B., Kroon, E., Trindade, G., Drumond, B. 2018; 12 (6): e0006538


    Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group.Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017-2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage BR-YFV_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014-2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil.The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.

    View details for DOI 10.1371/journal.pntd.0006538

    View details for Web of Science ID 000437442000027

    View details for PubMedID 29864115

    View details for PubMedCentralID PMC6002110

  • 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


    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

  • 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


    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

  • Genomic characterization of SARS-CoV-2 from an indigenous reserve in Mato Grosso do Sul, Brazil. Frontiers in public health de Oliveira, L. A., de Rezende, I. M., Navarini, V. J., Marchioro, S. B., Torres, A. J., Croda, J., Croda, M. G., Gonçalves, C. C., Xavier, J., de Castro, E., Lima, M., Iani, F., Adelino, T., Aburjaile, F., Ferraz Demarchi, L. H., Taira, D. L., Zardin, M. C., Fonseca, V., Giovanetti, M., Andrews, J., Alcantara, L. C., Simionatto, S. 2023; 11: 1195779


    The COVID-19 pandemic had a major impact on indigenous populations. Understanding the viral dynamics within this population is essential to create targeted protection measures.A total of 204 SARS-CoV-2 positive samples collected between May 2020 and November 2021 from an indigenous area in Mato Grosso do Sul (MS), Midwestern Brazil, were screened. Samples were submitted to whole genome sequencing using the Nanopore sequencing platform. Clinical, demographic, and phylogenetic data were analyzed.We found the co-circulation of six main SARS-CoV-2 lineages in the indigenous population, with the Zeta lineage being the most prevalent (27.66%), followed by B.1.1 (an ancestral strain) (20.21%), Gamma (14.36%) and Delta (13.83%). Other lineages represent 45.74% of the total. Our phylogenetic reconstruction indicates that multiple introduction events of different SARS-CoV-2 lineages occurred in the indigenous villages in MS. The estimated indigenous population mortality rate was 1.47%. Regarding the ethnicity of our cohort, 64.82% belong to the Guarani ethnicity, while 33.16% belong to the Terena ethnicity, with a slightly higher prevalence of males (53.43%) among females. Other ethnicities represent 2.01%. We also observed that almost all patients (89.55%) presented signs and symptoms related to COVID-19, being the most prevalent cough, fever, sore throat, and headache.Our results revealed that multiple independent SARS-CoV-2 introduction events had occurred through time, probably due to indigenous mobility, since the villages studied here are close to urban areas in MS. The mortality rate was slightly below of the estimation for the state in the period studied, which we believe could be related to the small number of samples evaluated, the underreporting of cases and deaths among this population, and the inconsistency of secondary data available for this study.In this study, we showed the circulation of multiple SARS-CoV-2 variants in this population, which should be isolated and protected as they belong to the most fragile group due to their socioeconomic and cultural disparities. We reinforce the need for constant genomic surveillance to monitor and prevent the spread of new emerging viruses and to better understand the viral dynamics in these populations, making it possible to direct specific actions.

    View details for DOI 10.3389/fpubh.2023.1195779

    View details for PubMedID 37965526

    View details for PubMedCentralID PMC10641392

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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
  • RISK-STRATIFYING YELLOW FEVER PATIENTS AT THE TIME OF ADMISSION McClure, M. A., Rezende, I. M., Kang, A. S., Pereira, L. S., Cenachi, A., Alves, P. A., Teixeira-Carvalho, A., Martins-Filho, O. A., Drumond, B. P., Desiree LaBeaud, A. AMER SOC TROP MED & HYGIENE. 2021: 436
  • 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
  • Neighbor danger: Yellow fever virus epizootics in urban and urban-rural transition areas of Minas Gerais state, during 2017-2018 yellow fever outbreaks in Brazil. PLoS neglected tropical diseases Sacchetto, L., Silva, N. I., Rezende, I. M., Arruda, M. S., Costa, T. A., de Mello, É. M., Oliveira, G. F., Alves, P. A., de Mendonça, V. E., Stumpp, R. G., Prado, A. I., Paglia, A. P., Perini, F. A., Lacerda Nogueira, M., Kroon, E. G., de Thoisy, B., Trindade, G. d., Drumond, B. P. 2020; 14 (10): e0008658


    From the end of 2016 until the beginning of 2019, Brazil faced a massive sylvatic yellow fever (YF) outbreak. The 2016-2019 YF epidemics affected densely populated areas, especially the Southeast region, causing thousands of deaths of humans and non-human primates (NHP).We conducted a molecular investigation of yellow fever virus (YFV) RNA in 781 NHP carcasses collected in the urban, urban-rural interface, and rural areas of Minas Gerais state, from January 2017 to December 2018. Samples were analyzed according to the period of sampling, NHP genera, sampling areas, and sampling areas/NHP genera to compare the proportions of YFV-positive carcasses and the estimated YFV genomic loads. YFV infection was confirmed in 38.1% of NHP carcasses (including specimens of the genera Alouatta, Callicebus, Callithrix, and Sapajus), from the urban, urban-rural interface, and rural areas. YFV RNA detection was positively associated with epidemic periods (especially from December to March) and the rural environment. Higher median viral genomic loads (one million times) were estimated in carcasses collected in rural areas compared to urban ones.The results showed the wide occurrence of YF in Minas Gerais in epidemic and non-epidemic periods. According to the sylvatic pattern of YF, a gradient of viral dissemination from rural towards urban areas was observed. A high YF positivity was observed for NHP carcasses collected in urban areas with a widespread occurrence in 67 municipalities of Minas Gerais, including large urban centers. Although there was no documented case of urban/Aedes YFV transmission to humans in Brazil during the 2016-2019 outbreaks, YFV-infected NHP in urban areas with high infestation by Aedes aegypti poses risks for YFV urban/Aedes transmission and urbanization.

    View details for DOI 10.1371/journal.pntd.0008658

    View details for PubMedID 33017419

  • Yellow Fever Virus Genotyping Tool and Investigation of Suspected Adverse Events Following Yellow Fever Vaccination VACCINES de Rezende, I., Alves, P., Arruda, M., Goncalves, A., Oliveira, G., Pereira, L., Dutra, M., Campi-Azevedo, A., Valim, V., Tourinho, R., de Oliveira, J., Calzavara, C., Said, R., Kroon, E., Martins-Filho, O., Teixeira-Carvalho, A., Drumond, B. 2019; 7 (4)


    The yellow fever (YF) vaccine consists of an attenuated virus, and despite its relative safety, some adverse events following YF vaccination have been described. At the end of 2016, Brazil experienced the most massive sylvatic yellow fever outbreak over the last 70 years and an intense campaign of YF vaccination occurred in Minas Gerais state in Southeast Brazil from 2016 to 2018. The present study aimed to develop a genotyping tool and investigate 21 cases of suspected adverse events following YF vaccination. Initial in silico analyses were performed using partial NS5 nucleotide sequences to verify the discriminatory potential between wild-type and vaccine viruses. Samples from patients were screened for the presence of the YFV RNA, using 5'UTR as the target, and then used for amplification of partial NS5 gene amplification, sequencing, and phylogenetic analysis. Genotyping indicated that 17 suspected cases were infected by the wild-type yellow fever virus, but four cases remained inconclusive. The genotyping tool was efficient in distinguishing the vaccine from wild-type virus, and it has the potential to be used for the differentiation of all yellow fever virus genotypes.

    View details for DOI 10.3390/vaccines7040206

    View details for Web of Science ID 000505709700001

    View details for PubMedID 31817103

    View details for PubMedCentralID PMC6963942

  • Circulation of Chikungunya virus East-Central-South Africa genotype during an outbreak in 2016-17 in Piaui State, Northeast Brazil REVISTA DO INSTITUTO DE MEDICINA TROPICAL DE SAO PAULO Cardoso, F., de Rezende, I., Teixeira Barros, E., Sacchetto, L., de Carvalho Souza Garces, T., Oliveira Silva, N., Alves, P., Soares, J., Kroon, E., Toledo da Cunha Pereira, A., Drumond, B., Ferreira, G. 2019; 61: e57


    Chikungunya virus (CHIKV) is an arbovirus that emerged in the Americas in 2013. Infection with CHIKV is symptomatic in most of the cases and patients can develop chronic arthralgia that lasts from months to years in over 40% of the cases. The East-Central-South Africa (ECSA) genotype was introduced in Brazil in 2014, in Bahia State. Here we report the circulation of the CHIKV ECSA genotype in Piaui State, Northeast Brazil, during the years 2016-2017. The phylogenetic analysis revealed a single introduction of this lineage probably in 2015 and its maintenance at least until 2017. This analysis has also demonstrated the proximity of this genotype with isolates from neighboring States, and its partial nucleotide sequence of the viral E1 gene revealed a synapomorphy synonyms. This finding highlights the spread of the ECSA genotype in Brazil and supports its circulation in the Brazilian Northeast.

    View details for DOI 10.1590/S1678-9946201961057

    View details for Web of Science ID 000489611000005

    View details for PubMedID 31618377

    View details for PubMedCentralID PMC6792355

  • Evidence of natural Zika virus infection in neotropical non-human primates in Brazil SCIENTIFIC REPORTS Terzian, A. B., Zini, N., Sacchetto, L., Rocha, R., Pereira Parra, M., Del Sarto, J., Fialho Dias, A., Coutinho, F., Rayra, J., da Silva, R., Costa, V., Couto De Azevedo Fernandes, N., Ressio, R., Diaz-Delgado, J., Guerra, J., Cunha, M. S., Catao-Dias, J., Bittar, C., Negri Reis, A., Penha dos Santos, I., Marascalchi Ferreira, A., Arao Antonio Cruz, L., Rahal, P., Ullmann, L., Malossi, C., de Araujo, J., Widen, S., de Rezende, I., Mello, E., Pacca, C., Kroon, E., Trindade, G., Drumond, B., Chiaravalloti-Neto, F., Vasilakis, N., Teixeira, M. M., Nogueira, M. 2018; 8: 16034


    In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil. We identified ZIKV-positive NHPs and sequences obtained were phylogenetically related to the American lineage of ZIKV. Additionally, we inoculated four C. penicillata with ZIKV and our results demonstrated that marmosets had a sustained viremia. The natural and experimental infection of NHPs with ZIKV, support the hypothesis that NHPs may be a vertebrate host in the maintainance of ZIKV transmission/circulation in urban tropical settings. Further studies are needed to understand the role they may play in maintaining the urban cycle of the ZIKV and how they may be a conduit in establishing an enzootic transmission cycle in tropical Latin America.

    View details for DOI 10.1038/s41598-018-34423-6

    View details for Web of Science ID 000448727000004

    View details for PubMedID 30375482

    View details for PubMedCentralID PMC6207778

  • Genomic and epidemiological monitoring of yellow fever virus transmission potential SCIENCE Faria, N. R., Kraemer, M. G., Hill, S. C., de Jesus, J., Aguiar, R. S., Iani, F. M., Xavier, J., Quick, J., du Plessis, L., Dellicour, S., Theze, J., Carvalho, R. O., Baele, G., Wu, C., Silveira, P. P., Arruda, M. B., Pereira, M. A., Pereira, G. C., Lourenco, J., Obolski, U., Abade, L., Vasylyeva, T. I., Giovanetti, M., Yi, D., Weiss, D. J., Wint, G. W., Shearer, F. M., Funk, S., Nikolay, B., Fonseca, V., Adelino, T. R., Oliveira, M. A., Silva, M. F., Sacchetto, L., Figueiredo, P. O., Rezende, I. M., Mello, E. M., Said, R. C., Santos, D. A., Ferraz, M. L., Brito, M. G., Santana, L. F., Menezes, M. T., Brindeiro, R. M., Tanuri, A., dos Santos, F. P., Cunha, M. S., Nogueira, J. S., Rocco, I. M., da Costa, A. C., Komninakis, S. V., Azevedo, V., Chieppe, A. O., Araujo, E. M., Mendonca, M. L., dos Santos, C. C., dos Santos, C. D., Mares-Guia, A. M., Nogueira, R. R., Sequeira, P. C., Abreu, R. G., Garcia, M. O., Abreu, A. L., Okumoto, O., Kroon, E. G., de Albuquerque, C. C., Lewandowski, K., Pullan, S. T., Carroll, M., de Oliveira, T., Sabino, E. C., Souza, R. P., Suchard, M. A., Lemey, P., Trindade, G. S., Drumond, B. P., Filippis, A. B., Loman, N. J., Cauchemez, S., Alcantara, L. J., Pybus, O. G. 2018; 361 (6405): 894-+


    The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

    View details for DOI 10.1126/science.aat7115

    View details for Web of Science ID 000443547000033

    View details for PubMedID 30139911

    View details for PubMedCentralID PMC6874500

  • Molecular surveillance of dengue in Minas Gerais provides insights on dengue virus 1 and 4 circulation in Brazil JOURNAL OF MEDICAL VIROLOGY Dutra, K., Drumond, B., de Rezende, I., Nogueira, M., Lopes, D., Calzavara Silva, C., Siqueira Ferreira, J., dos Santos, L. 2017; 89 (6): 966–73


    Dengue, caused by any of the four types of Dengue virus (DENV) is the most important arbovirus in the world. In this study we performed a molecular surveillance of dengue during the greatest dengue outbreak that took place in Divinópolis, Minas Gerais state, Southeast Brazil, in 2013. Samples from 100 patients with clinical symptoms of dengue were studied and 26 were positive. The capsid/premembrane (CprM) and envelope gene sequences of some samples were amplified and sequenced. Molecular analyses demonstrated that two DENV-1 lineages, belonging to genotype V were introduced and co-circulated in Divinópolis. When compared to each other, those lineages presented high genetic diversity and showed unique amino acids substitutions in the envelope protein, including in domains I, II, and III. DENV-4 strains from Divinópolis clustered within genotype IIb and the most recent common ancestor was probably introduced into the city three years before the 2013 epidemic. Here we demonstrated for the first time the circulation of DENV-4 and the co-circulation of two DENV-1 lineages in Midwest region of Minas Gerais, Brazil. Moreover our analysis indicated the introduction of five DENV-1 lineages, genotype V into Brazil, in different times. J. Med. Virol. 89:966-973, 2017. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/jmv.24729

    View details for Web of Science ID 000398893900005

    View details for PubMedID 27926790