Jason Andrews is an Assistant Professor in the Division of Infectious Diseases and Geographic Medicine and a practicing infectious diseases physician.
- Infectious Disease
Honors & Awards
NIH Director's New Innovator Award, NIH (2016)
George Rosenkranz Prize for Healthcare Research In Developing Countries, Rosenkranz Prize (2015)
The Union Young Investigator Prize, International Union Against Tuberculosis and Lung Disease (2015)
Young Physician-Scientist Award, American Society of Clinical Investigation (2014)
Dean’s Community Service Award, Harvard Medical School (2012)
David Brudnoy Scholar Award, Massachusetts General Hospital (2011)
David Brudnoy Scholar Award, Massachusetts General Hospital (2010)
Award for Best International Health Thesis, Yale School of Medicine Award (2007)
Merck Book Award for Academic Excellence, Yale School of Medicine (2007)
Boards, Advisory Committees, Professional Organizations
Faculty Fellow, Stanford Center for Innovation in Global Health (2015 - Present)
Center for Latin American Studies
Board Certification, American Board of Internal Medicine, Infectious Diseases (2012)
Fellowship, Harvard Combined Program in Infectious Diseases (Massachusetts General and Brigham and Women's Hospitals), Infectious Diseases (2012)
DTM&H, Gorgas Memorial Institute of Tropical & Preventive Medicine (2012)
Board Certification, American Board of Internal Medicine, Internal Medicine (2010)
SM, Harvard School of Public Health (2012)
Residency, University of California, San Francisco (2009)
Internship, University of California, San Francisco (2008)
MD, Yale University (2007)
BA, Yale University (2002)
Current Research and Scholarly Interests
Our laboratory aims to develop and test innovative approaches to the diagnosis, treatment and control of infectious diseases in resource-limited settings. We draw upon multiple fields including mathematical modeling, microbial genetics, field epidemiology, and statistical inference to work on challenging problems in infectious diseases, with an emphasis on tuberculosis and tropical diseases. Our current field research sites are in Brazil, South Africa, Nepal and India.
Etiologies of acute febrile illness in rural Nepal, Stanford University
Strategies for tuberculosis control in Brazilian prisons, Stanford University and Federal University of Grande Dourados
Congregate Air Sampling for Population-Based Detection of Tuberculosis, Stanford University and University of Cape Town
Cape Town, South Africa
Evaluating effectiveness of typhoid conjugate vaccine introduction in Navi Mumbai, India, Stanford
Navi Mumbai, India
Surveillance for Enteric Fever in Asia Project (SEAP)
Evaluating novel diagnostic approaches for tuberculosis
Campo Grande, Brazil
- Epidemiology of Infectious Diseases
HRP 231 (Spr)
Independent Studies (7)
- Directed Reading in Health Research and Policy
HRP 299 (Aut, Win, Spr, Sum)
- Directed Reading in Medicine
MED 299 (Win, Spr)
- Early Clinical Experience in Medicine
MED 280 (Win, Spr)
- Graduate Research
HRP 399 (Aut, Win, Spr, Sum)
- Graduate Research
MED 399 (Win, Spr)
- Medical Scholars Research
MED 370 (Aut, Win, Spr, Sum)
- Undergraduate Research
MED 199 (Win, Spr)
- Directed Reading in Health Research and Policy
Med Scholar Project Advisor
Postdoctoral Faculty Sponsor
Shama Cash-Goldwasser, Leonardo Martinez Pantoja, Renu Verma, Katharine Walter
Doctoral Dissertation Advisor (AC)
Master's Program Advisor
Postdoctoral Research Mentor
Shama Cash-Goldwasser, Leonardo Martinez Pantoja, Renu Verma
Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study.
The Lancet. Respiratory medicine
The value of quantitative interferon-γ release assay results for predicting progression from Mycobacterium tuberculosis infection to active disease is unknown. We aimed to investigate the relation between QuantiFERON-TB Gold In-Tube (QFT) conversion interferon-γ values and risk of subsequent active tuberculosis disease and of QFT reversion.We analysed data from a reported vaccine efficacy trial of the tuberculosis vaccine MVA85A in South Africa. QFT negative, HIV uninfected young children aged 18-24 weeks were enrolled. We stratified participants by quantitative QFT result (interferon-γ <0·35 IU/mL, 0·35-4·00 IU/mL, and >4·00 IU/mL) at the intermediate study visit (day 336) and determined risk of progression to active tuberculosis disease over the subsequent 6-24 months. No QFT differences were observed between placebo and MVA85A groups at day 336 or end of study; therefore, both groups were included in analyses. Study clinicians were not masked to QFT values, but strict case definitions were used that excluded QFT results. We used generalised additive models to evaluate the quantitative relation between day 336 QFT value and subsequent disease risk, and we compared disease rates between QFT strata using a two-sample Poisson test.Among 2512 young children with QFT tests done at day 336, 172 (7%) were positive; 87 (7%) of 1267 in placebo group and 85 (7%) of 1245 in the MVA85A group (p=1·00). Compared with QFT non-converters (tuberculosis disease incidence 0·7 per 100 person-years [95% CI 0·4-1·1]), children with QFT conversion at interferon-γ values between 0·35-4·00 IU/mL did not have significantly increased risk of disease (2·5 per 100 person-years [95% CI 0·4-9·4]; incidence rate ratio (IRR) 3·7 (95% CI 0·4-15·8; p=0·23). However, QFT conversion at interferon-γ values higher than 4·00 IU/mL was associated with substantially increased disease incidence (28·0 per 100 person-years [95% CI 14·9-45·7]) compared with non-converters (IRR 42·5 [95% CI 17·2-99·7]; p<0·0001), and compared with children with interferon-γ values between 0·35-4·00 IU/mL (IRR 11·4 [95% CI 2·4-107·2]; p=0·00047). Among 91 QFT converters who were given a repeat test, 53 (58%) reverted from positive to negative. QFT reversion risk was inversely associated with interferon-γ value at QFT conversion and was highest with interferon-γ values less than 4·00 IU/mL (47 [77%] of 61).In young children, tuberculosis disease risk was not significantly increased, and QFT reversion was common, following QFT conversion at interferon-γ values up to 10 times the recommended test threshold (0·35 IU/mL). By contrast, QFT conversion at very high interferon-γ values (>4·00 IU/mL) warrants intensified diagnostic and preventive intervention because of the extremely high risk of tuberculosis disease in these young children.Aeras, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium (OETC) were the funders of the MVA85A 020 Trial. National Institute of Allergy and Infectious Diseases supported this analysis.
View details for DOI 10.1016/S2213-2600(17)30060-7
View details for PubMedID 28215501
Assessment of global guidelines for preventive chemotherapy against schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study
LANCET INFECTIOUS DISEASES
2016; 16 (9): 1065-1075
WHO guidelines recommend annual treatment for schistosomiasis or soil-transmitted helminthiasis when prevalence in school-aged children is at or above a threshold of 50% and 20%, respectively. Separate treatment guidelines are used for these two helminthiases, and integrated community-wide treatment is not recommended. We assessed the cost-effectiveness of changing prevalence thresholds and treatment guidelines under an integrated delivery framework.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulates integrated preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis. We assessed a 5-year treatment programme with praziquantel (40 mg/kg per treatment) against schistosomiasis and albendazole (400 mg per treatment) against soil-transmitted helminthiasis at 75% coverage. We defined strategies as highly cost-effective if the incremental cost-effectiveness ratio was less than the World Bank classification for a low-income country (gross domestic product of US$1045 per capita). We calculated the prevalence thresholds for cost-effective preventive chemotherapy of various strategies, and estimated treatment needs for sub-Saharan Africa.Annual preventive chemotherapy against schistosomiasis was highly cost-effective in treatment of school-aged children at a prevalence threshold of 5% (95% uncertainty interval [UI] 1·7-5·2; current guidelines recommend treatment at 50% prevalence) and for community-wide treatment at a prevalence of 15% (7·3-18·5; current recommendation is unclear, some community treatment recommended at 50% prevalence). Annual preventive chemotherapy against soil-transmitted helminthiasis was highly cost-effective in treatment of school-aged children at a prevalence of 20% (95% UI 5·4-30·5; current guidelines recommend treatment at 20% prevalence) and the entire community at 60% (35·3-85·1; no guidelines available). When both helminthiases were co-endemic, prevalence thresholds using integrated delivery were lower. Using this revised treatment framework, we estimated that treatment needs would be six times higher than WHO guidelines for praziquantel and two times higher for albendazole. An additional 21·3% (95% Bayesian credible interval 20·4-22·2) of the population changed from receiving non-integrated treatment under WHO guidelines to integrated treatment (both praziquantel and albendazole). Country-specific economic differences resulted in heterogeneity around these prevalence thresholds.Annual preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis are likely to be highly cost-effective at prevalences lower than WHO recommendations. These findings support substantial treatment scale-up, community-wide coverage, integrated treatment in co-endemic settings that yield substantial cost synergies, and country-specific treatment guidelines.Doris Duke Charitable Foundation, Mount Sinai Hospital-University Health Network AMO Innovation Fund, and Stanford University Medical Scholars Programme.
View details for DOI 10.1016/S1473-3099(16)30073-1
View details for Web of Science ID 000381655200036
View details for PubMedID 27286968
Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study.
The Lancet. Global health
2015; 3 (10): e629-38
More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire.We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted.Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities.Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment.Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.
View details for DOI 10.1016/S2214-109X(15)00047-9
View details for PubMedID 26385302
Integrating Social Contact and Environmental Data in Evaluating Tuberculosis Transmission in a South African Township
JOURNAL OF INFECTIOUS DISEASES
2014; 210 (4): 597-603
Background. Population models of tuberculosis transmission have not accounted for social contact structure and the role of the environment in which tuberculosis is transmitted.Methods. We utilized extensions to the Wells-Riley model of tuberculosis transmission, using exhaled carbon dioxide as a tracer gas, to describe transmission patterns in an endemic community. Drawing upon social interaction data and carbon dioxide measurements from a South African township, we created an age-structured model of tuberculosis transmission in households, public transit, schools and workplaces. We fit the model to local data on latent tuberculosis prevalence by age.Results. Most tuberculosis infections (84%) were estimated to occur outside of one's own household. 50% of infections among young adults (ages 15-19) occurred in schools, due to high contact rates and poor ventilation. Despite lower numbers of contacts in workplaces, assortative mixing among adults with high rates of smear-positive tuberculosis contributed to transmission in this environment. Households and public transit were important sites of transmission between age groups.Conclusions. Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission.
View details for DOI 10.1093/infdis/jiu138
View details for Web of Science ID 000340243500013
View details for PubMedID 24610874
Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting
PLOS NEGLECTED TROPICAL DISEASES
2013; 7 (6)
In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella.Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months.A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.
View details for DOI 10.1371/journal.pntd.0002292
View details for Web of Science ID 000321201300043
View details for PubMedID 23853696
Projecting the Benefits of Antiretroviral Therapy for HIV Prevention: The Impact of Population Mobility and Linkage to Care
JOURNAL OF INFECTIOUS DISEASES
2012; 206 (4): 543-551
Recent mathematical models suggested that frequent human immunodeficiency virus (HIV) testing with immediate initiation of antiretroviral therapy (ART) to individuals with a positive test result could profoundly curb transmission. The debate about ART as prevention has focused largely on parameter values. We aimed to evaluate structural assumptions regarding linkage to care and population mobility, which have received less attention.We modified the linkage structure of published models of ART as prevention, such that individuals who decline initial testing or treatment do not link to care until late-stage HIV infection. We then added population mobility to the models. We populated the models with demographic, clinical, immigration, emigration, and linkage data from a South African township.In the refined linkage model, elimination of HIV transmission (defined as an incidence of <0.1%) did not occur by 30 years, even with optimistic assumptions about the linkage rate. Across a wide range of estimates, models were more sensitive to structural assumptions about linkage than to parameter values. Incorporating population mobility further attenuated the reduction in incidence conferred by ART as prevention.Linkage to care and population mobility are critical features of ART-as-prevention models. Clinical trials should incorporate relevant data on linkage to care and migration to evaluate the impact of this strategy.
View details for DOI 10.1093/infdis/jis401
View details for Web of Science ID 000306667000012
View details for PubMedID 22711905
Risk of Progression to Active Tuberculosis Following Reinfection With Mycobacterium tuberculosis
CLINICAL INFECTIOUS DISEASES
2012; 54 (6): 784-791
The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable.We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study.We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0-26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6-87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14-.30).Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models.
View details for DOI 10.1093/cid/cir951
View details for Web of Science ID 000300790900009
View details for PubMedID 22267721
Transmission dynamics and control of cholera in Haiti: an epidemic model
2011; 377 (9773): 1248-1255
Official projections of the cholera epidemic in Haiti have not incorporated existing disease trends or patterns of transmission, and proposed interventions have been debated without comparative estimates of their effect. We used a mathematical model of the epidemic to provide projections of future morbidity and mortality, and to produce comparative estimates of the effects of proposed interventions.We designed mathematical models of cholera transmission based on existing models and fitted them to incidence data reported in Haiti for each province from Oct 31, 2010, to Jan 24, 2011. We then simulated future epidemic trajectories from March 1 to Nov 30, 2011, to estimate the effect of clean water, vaccination, and enhanced antibiotic distribution programmes.We project 779,000 cases of cholera in Haiti (95% CI 599,000-914,000) and 11,100 deaths (7300-17,400) between March 1 and Nov 30, 2011. We expect that a 1% per week reduction in consumption of contaminated water would avert 105,000 cases (88,000-116,000) and 1500 deaths (1100-2300). We predict that the vaccination of 10% of the population, from March 1, will avert 63,000 cases (48,000-78,000) and 900 deaths (600-1500). The proposed extension of the use of antibiotics to all patients with severe dehydration and half of patients with moderate dehydration is expected to avert 9000 cases (8000-10,000) and 1300 deaths (900-2000).A decline in cholera prevalence in early 2011 is part of the natural course of the epidemic, and should not be interpreted as indicative of successful intervention. Substantially more cases of cholera are expected than official estimates used for resource allocation. Combined, clean water provision, vaccination, and expanded access to antibiotics might avert thousands of deaths.National Institutes of Health.
View details for DOI 10.1016/S0140-6736(11)60273-0
View details for Web of Science ID 000289597300031
View details for PubMedID 21414658
- Exogenous reinfection as a cause of multidrug-resistant and extensively drug-resistant tuberculosis in rural South Africa. Journal of Infectious Diseases 2008; 198 (11): 1582-9
Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.
Proceedings of the National Academy of Sciences of the United States of America
Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.
View details for DOI 10.1073/pnas.1708729114
View details for PubMedID 29301964
Plasma IgA responses against two Salmonella Typhi antigens identify patients with typhoid fever.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
There is a need for a reliable, simple diagnostic assay for typhoid fever. Available commercial serologic assays for typhoid fever have limited sensitivity and specificity. Using high-throughput immuno-screening technologies, we previously identified several immuno-reactive Salmonella Typhi antigens that appear promising for possible inclusion in a new diagnostic assay: hemolysin E (HlyE); cytolethal distending toxin (CdtB), S. Typhi LPS, and S. Typhi membrane preparation (MP).We assessed plasma antibody responses (IgM, IgA, and IgG) to these antigens via ELISA in patients with suspected enteric fever, controls with other febrile illnesses, and healthy controls in Dhaka, Bangladesh and performed Tubex, Typhidot, Widal and the Typhoid/Paratyphoid test (TPTest) on each patient. Using machine learning methods, we identified a parsimonious serology signature to distinguish acute typhoid cases from controls and then validated our findings in an independent test cohort from Nepal of culture-confirmed S. Typhi patients and controls with other bacteremic illnesses.We identified anti-MP IgG and IgA plasma responses to HlyE, LPS, and MP as important predictors of acute typhoid in the Bangladesh cohort. Using our Nepalese validation cohort, we demonstrated that the use of two antigens (HlyE and LPS) with one antibody isotype (IgA) could distinguish typhoid from other invasive bacterial infections (AUC 0.95; sensitivity 90%, specificity 92%). Use of a single antigen (HlyE) and isotype (IgA) had an AUC of 0.93.Our results suggest that development of a diagnostic assay for acute typhoid fever focused on detecting IgA responses against HlyE, with or without LPS, is warranted.
View details for DOI 10.1093/cid/ciy578
View details for PubMedID 30020426
Suicide in Brazilian indigenous communities: clustering of cases in children and adolescents by household.
Revista de saude publica
2018; 52: 56
OBJECTIVE To estimate age and sex-specific suicide rates, compare suicide rates between indigenous communities, and quantify the frequency of intrafamilial suicide clustering. METHODS We performed a retrospective cohort study involving 14,666 indigenous individuals in reservations in Dourados, state of Mato Grosso do Sul, Brazil, from 2003 through 2013 using national and local census. RESULTS The overall suicide rate was 73.4 per 100,000 person-years. Adolescent males aged 15-19 and girls aged 10-14 had the highest rates for each sex at 289.3 (95%CI 187.5-391.2) and 85.3 (95%CI 34.9-135.7), respectively. Comparing the largest reservations, Bororo had a higher suicide rate than Jaguapiru (RR = 4.83, 95%CI 2.85-8.16) and had significantly lower socioeconomic indicators including income and access to electricity. Nine of 19 suicides among children under 15 occurred in household clusters. Compared with adult suicides, a greater proportion of child (OR = 5.12, 95%CI 1.89-13.86, p = 0.001) and adolescent (OR = 3.48, 95%CI 1.29-9.44, p = 0.017) suicides occurred within household clusters. CONCLUSIONS High rates of suicide occur among children and adolescents in these indigenous reservations, particularly in poor communities. Nearly half of child suicides occur within household clusters. These findings underscore the need for broad public health interventions and focused mental health interventions in households following a suicide.
View details for DOI 10.11606/s1518-8787.2018052000541
View details for PubMedID 29791676
Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis and tuberculin skin test conversion among prisoners.
2018; 8 (1): 997
Poor vitamin D status has been associated with tuberculosis (TB); whether poor status is cause or consequence of disease is uncertain. We conducted a case-control study and two nested case-control studies to determine whether vitamin D levels were associated with active TB, tuberculin skin test (TST) conversion, and risk of progression to the active TB in prisoners in Brazil. In multivariable conditional logistic regression, subnormal vitamin D levels (OR, 3.77; 95% CI, 1.04-13.64) were more likely in prisoners with active TB. In contrast, vitamin D was not found to be a risk factor for either TST conversion (OR, 2.49; 95% CI, 0.64-9.66) or progression to active disease (OR, 0.59; 95% CI, 0.13-2.62). Black race (OR, 11.52; 95% CI, 2.01-63.36), less than 4 years of schooling (OR, 2.70; 95% CI, 0.90-8.16), cigarette smoking (OR, 0.23; 95% CI, 0.06-0.79) were identified as risk factors for TST conversion. Risk of progression to active TB was found to be associated with cigarette smoking (OR, 7.42; 95% CI, 1.23-44.70). Our findings in the prison population show that poor vitamin D status is more common in individuals with active TB, but is not a risk factor for acquisition of latent TB or progression to active TB.
View details for DOI 10.1038/s41598-018-19589-3
View details for PubMedID 29343733
What is the best immunization strategy for protecting African children against invasive Salmonella disease?
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
The WHO recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons aged ≥6 months to 45 years residing in typhoid fever (TF)-endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations in Africa.The Typhoid Fever Surveillance in Africa Program (TSAP) in 10 sub-Saharan African countries included blood culture-based surveillance in febrile people presenting at healthcare-facilities originating from defined catchment areas. The TF/invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0-10 year-old children in yearly increments.Salmonella Typhi and iNTS were the most frequently isolated pathogens, 135 and 94 cases were identified, respectively. Isolates (12 and 4, respectively) from Ethiopia, Senegal and South Africa were excluded due to person-years of observation (PYO) data absence. 37/123 (30.1%) TF and 71/90 (78.9%) iNTS disease cases occurred among individuals aged <5 years. No TF and 8/90 (8.9%) iNTS-infections were observed in children aged <9 months. The TF incidences (/100,000 PYO) for children aged <1 year and 1-<2 years were 5 and 39, respectively; the highest incidence was 304/100,000 PYO in 4-<5 year-old children. The iNTS incidence in the defined age groups ranged between 81 and 233/100,000 PYO, with the highest incidence in 1-<2 year-old children. Higher TF/iNTS disease incidences were observed in West Africa.The high TF burden observed in TSAP merits TCV introductions. Considering the additional iNTS disease burden, a trivalent vaccine targeting S. Typhi, S. Typhimurium, and S. Enteritidis may be a future solution.
View details for DOI 10.1093/cid/ciy386
View details for PubMedID 29746615
Drivers of seasonal variation in tuberculosis incidence: insights from a systematic review and mathematical model.
Epidemiology (Cambridge, Mass.)
Seasonality in tuberculosis incidence has been widely observed across countries and populations; however, its drivers are poorly understood. We conducted a systematic review of studies reporting seasonal patterns in tuberculosis to identify demographic and ecologic factors associated with timing and magnitude of seasonal variation.We identified studies reporting seasonal variation in tuberculosis incidence through PubMed and EMBASE and extracted incidence data and population metadata. We described key factors relating to seasonality and, when data permitted, quantified seasonal variation and its association with metadata. We developed a dynamic tuberculosis natural history and transmission model incorporating seasonal differences in disease progression and/or transmission rates to examine magnitude of variation required to produce observed seasonality in incidence.Fifty-seven studies met inclusion criteria. In the majority of studies (n=49), tuberculosis incidence peaked in spring or summer and reached a trough in late fall or winter. A standardized seasonal amplitude was calculated for 34 of the studies, resulting in a mean of 17.1% (range: 2.7-85.5%) after weighting by sample size. Across multiple studies, stronger seasonality was associated with younger patients, extrapulmonary disease, and latitudes farther from the Equator. The mathematical model was generally able to reproduce observed levels of seasonal case variation; however, substantial variation in transmission and/or disease progression risk was required to replicate several extreme values.We observed seasonal variation in tuberculosis, with consistent peaks occurring in spring, across countries with varying tuberculosis burden. Future research is needed to explore and quantify potential gains from strategically conducting mass screening interventions in the spring.
View details for DOI 10.1097/EDE.0000000000000877
View details for PubMedID 29870427
Development of a new dipstick (Cholkit) for rapid detection of Vibrio cholerae O1 in acute watery diarrheal stools.
PLoS neglected tropical diseases
2018; 12 (3): e0006286
Recognizing cholera cases early, especially in the initial phase of an outbreak and in areas where cholera has not previously circulated, is a high public health priority. Laboratory capacity in such settings is often limited. To address this, we have developed a rapid diagnostic test (RDT) termed Cholkit that is based on an immunochromatographic lateral flow assay for the diagnosis of cholera cases using stool. Cholkit contains a monoclonal antibody (ICL-33) to the O-specific polysaccharide (OSP) component of V. cholerae O1 lipopolysaccharide, and recognizes both Inaba and Ogawa serotypes. We tested the Cholkit dipstick using fresh stool specimens of 76 adults and children presenting with acute watery diarrhea at the icddr,b hospital in Dhaka, Bangladesh. We compared Cholkit's performance with those of microbial culture, PCR (targeting the rfb and ctxA genes of V. cholerae) and the commercially available RDT, Crystal VC (Span Diagnostics; Surat, India). We found that all stool specimens with a positive culture for V. cholerae O1 (n = 19) were positive by Cholkit as well as Crystal VC. We then used Bayesian latent class modeling to estimate the sensitivity and specificity of each diagnostic assay. The sensitivity of Cholkit, microbiological culture, PCR and Crystal VC was 98% (95% CI: 88-100), 71% (95% CI: 59-81), 74% (95% CI: 59-86) and 98% (95% CI: 88-100), respectively. The specificity for V. cholerae O1 was 97% (95% CI: 89-100), 100%, 97% (95% CI: 93-99) and 98% (95% CI: 92-100), respectively. Of note, two Crystal VC dipsticks were positive for V. cholerae O139 but negative by culture and PCR in this area without known circulating epidemic V. cholerae O139. In conclusion, the Cholkit dipstick is simple to use, requires no dedicated laboratory capacity, and has a sensitivity and specificity for V. cholerae O1 of 98% and 97%, respectively. Cholkit warrants further evaluation in other settings.
View details for DOI 10.1371/journal.pntd.0006286
View details for PubMedID 29538377
Deworming in pre-school age children: A global empirical analysis of health outcomes.
PLoS neglected tropical diseases
2018; 12 (5): e0006500
There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and generalizability. However, programmatic deworming continues throughout low and middle-income countries.We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1-4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005-2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI [-1.9, -0.5%]; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI [-2.1, -0.2%]; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI [-2.8, -0.7%]; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings.Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children.
View details for DOI 10.1371/journal.pntd.0006500
View details for PubMedID 29852012
Invasive Pomacea snails as important intermediate hosts of Angiostrongylus cantonensis in Laos, Cambodia and Vietnam: implications for outbreaks of eosinophilic meningitis.
The rat lungworm Angiostrongylus cantonensis causes human eosinophilic meningitis and it is endemic in Southeast Asia, but little is known about its distribution in Laos, Cambodia and Vietnam. We conducted a multi-country survey for A. cantonensis in these countries to estimate its prevalence in snails along the Mekong River and the east coast of Vietnam. We identified Angiostrongylus species by morphological and molecular analysis. We found A. cantonensis in the invasive snail, Pomacea spp. The wide accessibility of Pomacea snails, along with their infection by A. cantonensis, indicates that this snail species could be used in surveillance for preventing outbreaks of eosinophilic meningitis.
View details for DOI 10.1016/j.actatropica.2018.03.021
View details for PubMedID 29574000
Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study.
The Journal of infectious diseases
Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year.Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness.Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.
View details for DOI 10.1093/infdis/jix598
View details for PubMedID 29444257
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
2017; 372 (1722)
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 Web of Science ID 000399956400009
View details for PubMedID 28438917
Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh.
PLoS neglected tropical diseases
2017; 11 (4)
To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings.We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993-2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41-5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4-12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30-1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens.There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset.
View details for DOI 10.1371/journal.pntd.0005512
View details for PubMedID 28448489
A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now.
The Lancet. Infectious diseases
2017; 17 (2): e64-e69
In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.
View details for DOI 10.1016/S1473-3099(16)30535-7
View details for PubMedID 27914852
View details for PubMedCentralID PMC5280090
Increase in Tuberculosis Cases among Prisoners, Brazil, 2009-2014(1).
Emerging infectious diseases
2017; 23 (3): 496–99
During 2009-2014, incarceration rates in Brazil rose 34%, and tuberculosis (TB) cases among prisoners rose 28.8%. The proportion of national TB cases that occurred among prisoners increased from 6.2% to 8.4% overall and from 19.3% to 25.6% among men 20-29 years of age.
View details for DOI 10.3201/eid2303.161006
View details for PubMedID 28221118
High Rates of Enteric Fever Diagnosis and Lower Burden of Culture-Confirmed Disease in Peri-urban and Rural Nepal.
The Journal of infectious diseases
In South Asia, data on enteric fever are sparse outside of urban areas. We characterized enteric fever diagnosis patterns and the burden of culture-confirmed cases in peri-urban and rural Nepal.We used national reports to estimate enteric fever diagnosis rates over 20 years (1994-2014) and conducted a prospective study of patients presenting with a >72-hour history of fever to 4 peri-urban and rural healthcare facilities (during August 2013-June 2016). We compared clinical characteristics of patients with culture-confirmed Salmonella Typhi or Paratyphi infection to those of patients without enteric fever. We used generalized additive models with logistic link functions to evaluate associations of age and population density with culture positivity.National rates of enteric fever diagnosis were high, reaching 18.8 cases per 1000 during 2009-2014. We enrolled 4309 participants with acute febrile illness. Among those with a provisional clinical diagnosis, 55% (1334 of 2412) received a diagnosis of enteric fever; however, only 4.1% of these had culture-confirmed typhoidal Salmonella infection. Culture positivity was highest among young adults and was strongly associated with higher population density (P < .001).Enteric fever diagnosis rates were very high throughout Nepal, but in rural settings, few patients had culture-confirmed disease. Expanded surveillance may inform local enteric fever treatment and prevention strategies.
View details for DOI 10.1093/infdis/jix221
View details for PubMedID 28961918
Drivers of Tuberculosis Transmission.
The Journal of infectious diseases
2017; 216 (suppl_6): S644–S653
Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed.
View details for DOI 10.1093/infdis/jix354
View details for PubMedID 29112745
Identification of Novel Serodiagnostic Signatures of Typhoid Fever Using a Salmonella Proteome Array.
Frontiers in microbiology
2017; 8: 1794
Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterogeneous antibody responses with increasing IgM/IgA signals at diagnosis. In down-selected 250-antigen arrays we validated responses in a second challenge cohort (n = 30), and selected diagnostic signatures using machine learning and multivariable modeling. In four models containing responses to antigens including flagellin, OmpA, HlyE, sipC, and LPS, multi-antigen signatures discriminated typhoid (n = 100) from other febrile bacteremia (n = 52) in Nepal. These models contained combinatorial IgM, IgA, and IgG responses to 5 antigens (ROC AUC, 0.67 and 0.71) or 3 antigens (0.87), although IgA responses to LPS also performed well (0.88). Using a novel systematic approach we have identified and validated optimal serological diagnostic signatures of typhoid fever.
View details for DOI 10.3389/fmicb.2017.01794
View details for PubMedID 28970824
View details for PubMedCentralID PMC5609549
Genetic Clustering of Tuberculosis in an Indigenous Community of Brazil.
The American journal of tropical medicine and hygiene
We conducted a population-based study of tuberculosis (TB) from 2009 to 2015 in an indigenous community of Brazil, the largest in the country, to investigate risk factors associated with recent TB transmission. The clinical isolates of Mycobacterium tuberculosis were genotyped by IS6110-RFLP (restriction fragment length polymorphism) and spoligotyping analysis. Among 67 isolates typed by RFLP, 69% fell into fifteen clusters, and 91% of TB cases with shared IS6110-RFLP pattern were diagnosed within 2 years of another case in the cluster. Individual risk factors associated with genetic clustering were domestic overcrowding (odds ratio [OR]: 6.10; 95% confidence interval [CI]: 1.50-24.88) and low social class (OR: 3.72; 95% CI: 1.00-13.98). Most reported contacts (76%) were identified within the household of the index TB case, but most of the genetic clustering of M. tuberculosis occurred outside of household (79%). Expanded contacts investigation and prophylaxis outside of household should be considered as a priority for TB control programs in this population.
View details for DOI 10.4269/ajtmh.17-0480
View details for PubMedID 29210353
Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of M. tuberculosis Infection.
American journal of respiratory and critical care medicine
Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (M.tb) infection, which predisposes to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability.To improve consistency of serial QuantiFERON-TB testing algorithms and provide a data-driven definition of conversion.Sources of QuantiFERON-TB variability were assessed and optimal procedures identified. Distributions of IFNγ response levels were analysed in healthy adolescents, M.tb-unexposed controls, and pulmonary tuberculosis patients.Individuals with no known M.tb exposure had IFNγ values <0.2 IU/mL. Among individuals with IFNγ values <0.2, 0.2-0.34, 0.35-0.7, and >0.7 IU/mL, tuberculin skin test positivity was 15%, 53%, 66% and 91% (p<0.005), respectively. Together, these findings suggest that values <0.2 IU/mL were true negatives. In short-term serial testing, "uncertain" conversions, with at least one value within the uncertainty zone (0.2-0.7 IU/mL), were partly explained by technical assay variability. Individuals who had a change in QuantiFERON-TB IFNγ values from <0.2 to >0.7 IU/mL had 10-fold higher tuberculosis incidence rates than those who maintained values <0.2 IU/mL over 2 years (p=0.0003). By contrast, "uncertain" converters were not at higher risk than non-converters (p=0.229). Eighty-seven percent of active TB patients had IFNγ values >0.7 IU/mL, suggesting that these values are consistent with established M.tb infection.Implementation of optimized procedures and a more rigorous QuantiFERON-TB conversion definition, an increase from IFNγ <0.2 to >0.7 IU/mL, would allow more definitive detection of recent M.tb infection and potentially improve identification of those more likely to develop disease.
View details for DOI 10.1164/rccm.201704-0817OC
View details for PubMedID 28737960
Evaluation of a Mobile Phone-Based Microscope for Screening of Schistosoma haematobium Infection in Rural Ghana.
The American journal of tropical medicine and hygiene
2017; 96 (6): 1468–71
AbstractSchistosomiasis affects over 170 million people in Africa. Here we compare a novel, low-cost mobile phone microscope to a conventional light microscope for the label-free diagnosis of Schistosoma haematobium infections in a rural Ghanaian school setting. We tested the performance of our handheld microscope using 60 slides that were randomly chosen from an ongoing epidemiologic study in school-aged children. The mobile phone microscope had a sensitivity of 72.1% (95% confidence interval [CI]: 56.1-84.2), specificity of 100% (95% CI: 75.9-100), positive predictive value of 100% (95% CI: 86.3-100), and a negative predictive value of 57.1% (95% CI: 37.4-75.0). With its modest sensitivity and high specificity, this handheld and cost-effective mobile phone-based microscope is a stepping-stone toward developing a powerful tool in clinical and public health settings where there is limited access to conventional laboratory diagnostic support.
View details for DOI 10.4269/ajtmh.16-0912
View details for PubMedID 28719262
Eosinophilic Meningitis Caused by Angiostrongylus cantonensis.
ACS chemical neuroscience
Rat lungworm, Angiostrongylus cantonensis, is one major cause of human eosinophilic meningitis. This helminth is endemic in Southeast Asia, Pacific Islands, and the Caribbean and has recently expanded to South America. The infection is characterized by an elevated eosinophil count in cerebrospinal fluid. Common symptoms and signs include headache, neck stiffness, paresthesia and nausea/vomiting. The unique history of eating freshwater and land snails or slugs within 2 weeks before onset is helpful for diagnosis. Antihelminthic agents have not shown efficacy in human infection; treatment involves supportive care with management of inflammation and intracranial pressure.
View details for DOI 10.1021/acschemneuro.7b00233
View details for PubMedID 28704038
Poor Validity of Noninvasive Hemoglobin Measurements by Pulse Oximetry Compared with Conventional Absorptiometry in Children in Cote d'Ivoire
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2017; 96 (1): 217-220
Anemia remains a major public health issue in many African communities. We compared a novel, commercially available noninvasive hemoglobin (Hb)-measuring device to direct Hb measurements by finger-prick samples in a pediatric cohort in rural Côte d'Ivoire. Noninvasive Hb measurements were attempted in 191 children 2-15 years of age and obtained in 102 (53.5%) children. The median Hb for the 102 children was 12.0 g/dL (interquartile range [IQR] = 11.3-12.7 g/dL) for conventional absorptiometry and 13.3 g/dL (IQR = 12.1-14.2 g/dL) for noninvasive measurements. A Bland-Altman analysis demonstrated a median bias of +1.1 g/dL (IQR = 0.4-2.0 g/dL), with greater overestimation of Hb by noninvasive testing occurring at low Hb values. This overestimation of the noninvasive Hb-measuring device to direct Hb measurements persisted across preschool- and school-aged children, and both sexes. The Pearson correlation coefficient was 0.50 for children 4-9 years of age, and 0.33 for children 10-15 years of age. Further study and development of noninvasive Hb devices is necessary prior to implementation in African pediatric populations.
View details for DOI 10.4269/ajtmh.16-0505
View details for Web of Science ID 000397822900040
View details for PubMedID 28077748
- The benefits of mass deworming on health outcomes: new evidence synthesis, the debate persists. The Lancet. Global health 2017; 5 (1): e4-e5
Mobile phone and handheld microscopes for public health applications
Lancet Public Health
2017; 2 (8): e355
View details for DOI 10.1016/S2468-2667(17)30120-2
The global burden of tuberculosis: results from the Global Burden of Disease Study 2015.
The Lancet. Infectious diseases
An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories.We analysed 10 691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates. We analysed all available age-specific and sex-specific data sources, including annual case notifications, prevalence surveys, and estimated cause-specific mortality, to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how observed tuberculosis incidence, prevalence, and mortality differed from expected trends as predicted by the Socio-demographic Index (SDI), a composite indicator based on income per capita, average years of schooling, and total fertility rate. We also estimated tuberculosis mortality and disability-adjusted life-years attributable to the independent effects of risk factors including smoking, alcohol use, and diabetes.Globally, in 2015, the number of tuberculosis incident cases (including new and relapse cases) was 10·2 million (95% uncertainty interval 9·2 million to 11·5 million), the number of prevalent cases was 10·1 million (9·2 million to 11·1 million), and the number of deaths was 1·3 million (1·1 million to 1·6 million). Among individuals who were HIV negative, the number of incident cases was 8·8 million (8·0 million to 9·9 million), the number of prevalent cases was 8·9 million (8·1 million to 9·7 million), and the number of deaths was 1·1 million (0·9 million to 1·4 million). Annualised rates of change from 2005 to 2015 showed a faster decline in mortality (-4·1% [-5·0 to -3·4]) than in incidence (-1·6% [-1·9 to -1·2]) and prevalence (-0·7% [-1·0 to -0·5]) among HIV-negative individuals. The SDI was inversely associated with HIV-negative mortality rates but did not show a clear gradient for incidence and prevalence. Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV-negative tuberculosis burden than expected given their SDI. Alcohol use accounted for 11·4% (9·3-13·0) of global tuberculosis deaths among HIV-negative individuals in 2015, diabetes accounted for 10·6% (6·8-14·8), and smoking accounted for 7·8% (3·8-12·0).Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes could also substantially reduce the burden of tuberculosis.Bill & Melinda Gates Foundation.
View details for DOI 10.1016/S1473-3099(17)30703-X
View details for PubMedID 29223583
Schistosoma haematobium Egg Excretion does not Increase after Exercise: Implications for Diagnostic Testing.
The American journal of tropical medicine and hygiene
Children are frequently invited to exercise before micturition, as it is believed that this will result in higher Schistosoma haematobium egg excretion, and hence, increases sensitivity of microscopic diagnoses. However, the evidence of this recommendation is scant. In the study presented here, 257 children, aged 2-15 years from south Côte d'Ivoire, provided urine samples for microscopy on consecutive days; one sample without prior exercise and one sample after exercise. Comparing the same individuals without and with prior exercise, sample positivity for S. haematobium (25.7% versus 23.0%, P = 0.31) and mean egg counts (10.2 eggs/10 mL versus 8.5 eggs/10 mL, P = 0.45) did not differ. Exercise before urine collection does not appear to increase S. haematobium egg excretion.
View details for DOI 10.4269/ajtmh.17-0728
View details for PubMedID 29260647
- Mobile-phone and handheld microscopy for neglected tropical diseases. PLoS neglected tropical diseases 2017; 11 (7): e0005550
Evaluation of a Smartphone Decision-Support Tool for Diarrheal Disease Management in a Resource-Limited Setting.
PLoS neglected tropical diseases
2017; 11 (1)
The emergence of mobile technology offers new opportunities to improve clinical guideline adherence in resource-limited settings. We conducted a clinical pilot study in rural Bangladesh to evaluate the impact of a smartphone adaptation of the World Health Organization (WHO) diarrheal disease management guidelines, including a modality for age-based weight estimation. Software development was guided by end-user input and evaluated in a resource-limited district and sub-district hospital during the fall 2015 cholera season; both hospitals lacked scales which necessitated weight estimation. The study consisted of a 6 week pre-intervention and 6 week intervention period with a 10-day post-discharge follow-up. Standard of care was maintained throughout the study with the exception that admitting clinicians used the tool during the intervention. Inclusion criteria were patients two months of age and older with uncomplicated diarrheal disease. The primary outcome was adherence to guidelines for prescriptions of intravenous (IV) fluids, antibiotics and zinc. A total of 841 patients were enrolled (325 pre-intervention; 516 intervention). During the intervention, the proportion of prescriptions for IV fluids decreased at the district and sub-district hospitals (both p < 0.001) with risk ratios (RRs) of 0.5 and 0.2, respectively. However, when IV fluids were prescribed, the volume better adhered to recommendations. The proportion of prescriptions for the recommended antibiotic azithromycin increased (p < 0.001 district; p = 0.035 sub-district) with RRs of 6.9 (district) and 1.6 (sub-district) while prescriptions for other antibiotics decreased; zinc adherence increased. Limitations included an absence of a concurrent control group and no independent dehydration assessment during the pre-intervention. Despite limitations, opportunities were identified to improve clinical care, including better assessment, weight estimation, and fluid/ antibiotic selection. These findings demonstrate that a smartphone-based tool can improve guideline adherence. This study should serve as a catalyst for a randomized controlled trial to expand on the findings and address limitations.
View details for DOI 10.1371/journal.pntd.0005290
View details for PubMedID 28103233
Advances in diagnosis, treatment, and prevention of invasive Salmonella infections.
Current opinion in infectious diseases
2016; 29 (5): 453-458
Typhoidal and nontyphoidal Salmonella enterica serotypes are among the most common bacterial causes of acute febrile illnesses in the developing world. In this review, we discuss new advances in understanding of the burden, diagnostic approaches, treatment and vaccines for invasive Salmonella infections.Recent estimates of the global burden of typhoidal and nontyphoidal Salmonella not only affirm the importance of these infections but also highlight the paucity of systematic incidence data from many regions. New data from Africa indicate that typhoidal Salmonella may be more common than previously considered. Novel diagnostic techniques for Salmonella include new serologic, molecular and metabolomic approaches, but blood culture - although slow and insensitive - remains the primary means of establishing a diagnosis. Antibiotic resistance, particularly to fluoroquinolones, continues to emerge and threatens to undermine treatment success for these infections. New vaccines for typhoid, including conjugate vaccines with longer duration of immunity than prior vaccines, represent a promising tool for prevention of enteric fever.Invasive Salmonella infections are a major cause of morbidity and mortality worldwide. Increasing antibiotic resistance in Salmonella is concerning, and empiric oral options are being rapidly eroded. Where new effective antimicrobials are lacking, developments in vaccines offer hope for reducing the burden of Salmonella infections globally.
View details for DOI 10.1097/QCO.0000000000000302
View details for PubMedID 27479027
Evaluation of Malaria Diagnoses Using a Handheld Light Microscope in a Community-Based Setting in Rural Cote d'Ivoire
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2016; 95 (4): 831-834
Portable microscopy may facilitate quality diagnostic care in resource-constrained settings. We compared a handheld light microscope (Newton Nm1) with a mobile phone attachment to conventional light microscopy for the detection of Plasmodium falciparum in a cross-sectional study in rural Côte d'Ivoire. Single Giemsa-stained thick blood film from 223 individuals were prepared and read by local laboratory technicians on both microscopes under 1,000× magnification with oil. Of the 223 samples, 162 (72.6%) were P. falciparum positive, and the overall mean parasite count was 1,392/μL of blood. Sensitivity and specificity of the handheld microscope was 80.2% (95% confidence interval [CI]: 73.1-85.9%) and 100.0% (95% CI: 92.6-100.0%), respectively, with a positive and negative predictive value of 100.0% (95% CI: 96.4-100.0%) and 65.6% (95% CI: 54.9-74.9%), respectively. If sensitivity can be improved, handheld light microscopy may become a valuable public health tool for P. falciparum diagnosis.
View details for DOI 10.4269/ajtmh.16-0328
View details for Web of Science ID 000400206500021
View details for PubMedID 27527637
Risk of self-reported symptoms or diagnosis of active tuberculosis in relationship to low body mass index, diabetes and their co-occurrence.
Tropical medicine & international health
2016; 21 (10): 1272-1281
Globally, tuberculosis prevalence has declined, but its risk factors have varied across place and time - low body mass index (BMI) has persisted while diabetes has increased. Using India's National Family Health Survey (NFHS), wave 3 and World Health Survey (WHS) data, we examined their relationships to support projection of future trends and targeted control efforts.Multivariate logistic regressions at the individual level with and without diabetes/BMI interactions assessed the relationship between tuberculosis, diabetes and low BMI and the importance of risk factor co-occurrence. Population-level analyses examined how tuberculosis incidence and prevalence varied with diabetes/low BMI co-occurrence.In NFHS, diabetic individuals had higher predicted tuberculosis risks (diabetic vs. non-diabetic: 2.50% vs. 0.63% at low BMI; 0.81% vs. 0.20% at normal BMI; 0.37% vs. 0.09% at high BMI), which were not significantly different when modelled independently or allowing for risk modification with diabetes/low BMI co-occurrence. WHS findings were generally consistent. Population-level analysis found that diabetes/low BMI co-occurrence may be associated with elevated tuberculosis risk, although its predicted effect on tuberculosis incidence/prevalence was generally ≤0.2 percentage points and not robustly statistically significant.Concerns about the additional elevation of tuberculosis risk from diabetes/low BMI co-occurrence and hence the need to coordinate tuberculosis control efforts around the nexus of co-occurring diabetes and low BMI may be premature. However, study findings robustly support the importance of individually targeting low BMI and diabetes as part of ongoing tuberculosis control efforts.
View details for DOI 10.1111/tmi.12763
View details for PubMedID 27495971
Evaluation of a Urine Pooling Strategy for the Rapid and Cost-Efficient Prevalence Classification of Schistosomiasis.
PLoS neglected tropical diseases
2016; 10 (8)
A key epidemiologic feature of schistosomiasis is its focal distribution, which has important implications for the spatial targeting of preventive chemotherapy programs. We evaluated the diagnostic accuracy of a urine pooling strategy using a point-of-care circulating cathodic antigen (POC-CCA) cassette test for detection of Schistosoma mansoni, and employed simulation modeling to test the classification accuracy and efficiency of this strategy in determining where preventive chemotherapy is needed in low-endemicity settings.We performed a cross-sectional study involving 114 children aged 6-15 years in six neighborhoods in Azaguié Ahoua, south Côte d'Ivoire to characterize the sensitivity and specificity of the POC-CCA cassette test with urine samples that were tested individually and in pools of 4, 8, and 12. We used a Bayesian latent class model to estimate test characteristics for individual POC-CCA and quadruplicate Kato-Katz thick smears on stool samples. We then developed a microsimulation model and used lot quality assurance sampling to test the performance, number of tests, and total cost per school for each pooled testing strategy to predict the binary need for school-based preventive chemotherapy using a 10% prevalence threshold for treatment.The sensitivity of the urine pooling strategy for S. mansoni diagnosis using pool sizes of 4, 8, and 12 was 85.9%, 79.5%, and 65.4%, respectively, when POC-CCA trace results were considered positive, and 61.5%, 47.4%, and 30.8% when POC-CCA trace results were considered negative. The modeled specificity ranged from 94.0-97.7% for the urine pooling strategies (when POC-CCA trace results were considered negative). The urine pooling strategy, regardless of the pool size, gave comparable and often superior classification performance to stool microscopy for the same number of tests. The urine pooling strategy with a pool size of 4 reduced the number of tests and total cost compared to classical stool microscopy.This study introduces a method for rapid and efficient S. mansoni prevalence estimation through examining pooled urine samples with POC-CCA as an alternative to widely used stool microscopy.
View details for DOI 10.1371/journal.pntd.0004894
View details for PubMedID 27504954
View details for PubMedCentralID PMC4978437
Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Cote d'Ivoire
PLOS NEGLECTED TROPICAL DISEASES
2016; 10 (6)
Handheld light microscopy using compact optics and mobile phones may improve the quality of health care in resource-constrained settings by enabling access to prompt and accurate diagnosis.Laboratory technicians were trained to operate two handheld diagnostic devices (Newton Nm1 microscope and a clip-on version of the mobile phone-based CellScope). The accuracy of these devices was compared to conventional light microscopy for the diagnosis of Schistosoma haematobium, S. mansoni, and intestinal protozoa infection in a community-based survey in rural Côte d'Ivoire. One slide of 10 ml filtered urine and a single Kato-Katz thick smear from 226 individuals were subjected to the Newton Nm1 microscope and CellScope for detection of Schistosoma eggs and compared to conventional microscopy. Additionally, 121 sodium acetate-acetic acid-formalin (SAF)-fixed stool samples were examined by the Newton Nm1 microscope and compared to conventional microscopy for the diagnosis of intestinal protozoa.The prevalence of S. haematobium, S. mansoni, Giardia intestinalis, and Entamoeba histolytica/E. dispar, as determined by conventional microscopy, was 39.8%, 5.3%, 20.7%, and 4.9%, respectively. The Newton Nm1 microscope had diagnostic sensitivities for S. mansoni and S. haematobium infection of 91.7% (95% confidence interval (CI) 59.8-99.6%) and 81.1% (95% CI 71.2-88.3%), respectively, and specificities of 99.5% (95% CI 97.0-100%) and 97.1% (95% CI 92.2-99.1%), respectively. The CellScope demonstrated sensitivities for S. mansoni and S. haematobium of 50.0% (95% CI 25.4-74.6%) and 35.6% (95% CI 25.9-46.4%), respectively, and specificities of 99.5% (95% CI 97.0-100%) and 100% (95% CI 86.7-100%), respectively. For G. intestinalis and E. histolytica/E. dispar, the Newton Nm1 microscope had sensitivity of 84.0% (95% CI 63.1-94.7%) and 83.3% (95% CI 36.5-99.1%), respectively, and 100% specificity.Handheld diagnostic devices can be employed in community-based surveys in resource-constrained settings after minimal training of laboratory technicians to diagnose intestinal parasites.
View details for DOI 10.1371/journal.pntd.0004768
View details for Web of Science ID 000379346200031
View details for PubMedID 27348755
Diagnosis of Opisthorchis viverrini Infection with Handheld Microscopy in Lao People's Democratic Republic.
American journal of tropical medicine and hygiene
2016; 94 (1): 158-160
Opisthorchis viverrini infection is a neglected tropical disease, yet it is of considerable public health importance in southeast Asia given the predilection for chronically infected persons to develop cholangiocarcinoma. We evaluated a handheld microscope for the diagnosis of O. viverrini in a community-based setting in Lao People's Democratic Republic compared with conventional light microscopy. In stool samples collected from 104 individuals, handheld microscopy revealed a sensitivity of 70.6% and a specificity of 89.5% for O. viverrini infection. Pearson's correlation for quantitative fecal egg counts between the two devices was 0.98 (95% confidence interval: 0.98-0.99). With small adjustments to further increase diagnostic sensitivity, a handheld microscope may become a helpful tool to screen for O. viverrini and other helminth infections in public health settings.
View details for DOI 10.4269/ajtmh.15-0525
View details for PubMedID 26526923
- Improving helminth treatment access: costs and opportunities. The Lancet. Infectious diseases 2016; 16 (7): 762–64
The mass miniature chest radiography programme in Cape Town, South Africa, 1948 - 1994: The impact of active tuberculosis case finding.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
2016; 106 (12): 1263–69
Tuberculosis (TB) control programmes rely mainly on passive detection of symptomatic individuals. The resurgence of TB has rekindled interest in active case finding. Cape Town (South Africa) had a mass miniature radiography (MMR) screening programme from 1948 to 1994.To evaluate screening coverage, yield and secular trends in TB notifications during the MMR programme.We performed an ecological analysis of the MMR programme and TB notification data from the City of Cape Town Medical Officer of Health reports for 1948 - 1994.Between 1948 and 1962, MMR screening increased to 12% of the population per annum with yields of 14 cases per 1 000 X-rays performed, accounting for >20% of total annual TB notifications. Concurrent with increasing coverage (1948 - 1965), TB case notification decreased in the most heavily TB-burdened non-European population from 844/100 000 population to 415/100 000. After 1966, coverage declined and TB notifications that initially remained stable (1967 - 1978) subsequently increased to 525/100 000. MMR yields remained low in the European population but declined rapidly in the non-European population after 1966, coincidental with forced removals from District 6. An inverse relationship between screening coverage and TB notification rates was observed in the non-European adult population. Similar secular trends occurred in infants and young children who were not part of the MMR screening programme.MMR of a high-burdened population may have significantly contributed to TB control and was temporally associated with decreased transmission to infants and children. These historical findings emphasise the importance of re-exploring targeted active case finding strategies as part of population TB control.
View details for DOI 10.7196/SAMJ.2016.v106.i12.10744
View details for PubMedID 27917775
Comparison of the Performance of the TPTest, Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh, Including Using a Bayesian Latent Class Modeling Approach.
PLoS neglected tropical diseases
2016; 10 (4): e0004558
There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot.For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer ≥1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis.Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot.These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives.
View details for DOI 10.1371/journal.pntd.0004558
View details for PubMedID 27058877
Efficacy and safety of praziquantel against light infections of Opisthorchis viverrini: a randomised parallel single blind dose-ranging trial.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at single 40 mg/kg in preventive chemotherapy programs and 3 x 25 mg/kg for individual treatment is the drug of choice, yet information on the nature of the dose-response relationship is lacking.We performed a randomized, parallel, single blind dose-ranging Phase 2 trial in Lao PDR in O. viverrini-infected adults. Patients were randomly assigned to 30, 40, 50, 3 x 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 and 24 hours post-treatment. Cure rates and egg reduction rates were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using Emax models.Two-hundred and seventeen O. viverrini-infected patients were assigned to the five treatment arms. The majority (94.3%) of patients harbored light infections. The Emax model predicted a high efficacy among the observed dose range. We observed cure rates ranging from 92.7-93.3% and egg reduction rates above 99.5% for all praziquantel-treatment groups. Adverse events were mild but higher in the standard treatment group (3x25 mg/kg) than in the single dose treatment arms.Single dose praziquantel appear to be as efficacious as the standard 3x25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections.
View details for DOI 10.1093/cid/ciw785
View details for PubMedID 27927864
Impact of mass-screening on tuberculosis incidence in a prospective cohort of Brazilian prisoners.
BMC infectious diseases
2016; 16 (1): 533
Globally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood.We performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ≥10 mm and an induration increase of at least 6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models were performed to identify risk factors associated with active TB. To evaluate the impact of screening on subsequent risk of disease, we compared TB notifications over one year among individuals randomized to screening for active TB with those not randomized to screening.Among 3,771 inmates recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %) were diagnosed with TB over the subsequent year. Cases identified through active screening were less likely to be smear-positive than passively detected cases (10.0 % vs 50.9 %; p < 0.01), suggesting early case detection. However, there was no reduction in subsequent disease among individuals actively screened versus those not screened (1.3 % vs 1.7 %; p = 0.88). Drug use during the year (AHR 3.22; 95 % CI 1.05-9.89) and knows somebody with TB were (AHR 2.86; 95 % CI 1.01-8.10) associated with active TB during one year of follow up CONCLUSIONS: Mass screening in twelve Brazilian prisons did not reduce risk of subsequent disease in twelve Brazilian prisons, likely due to an extremely high force of infection. New approaches are needed to control TB in this high-transmission setting.
View details for DOI 10.1186/s12879-016-1868-5
View details for PubMedID 27716170
Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia-an observational cohort study.
2015; 70 (12): 1181-1188
In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients.A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models.From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death.We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes.
View details for DOI 10.1136/thoraxjnl-2015-207374
View details for PubMedID 26506854
The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in Brazilian Prisons
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2015; 93 (4): 739-746
Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We used a modified Wells-Riley equation to estimate the probability of infection for inmates sharing a cell with an infectious case and projected the impact of interventions, including early diagnosis and improved ventilation. Overall, prison cells were densely populated (mean 2.1 m(2) per occupant) and poorly ventilated, with only three cells meeting World Health Organization (WHO) standards for per-person ventilation (60 L/s) applied in infection control settings. In the absence of interventions, projected median risk of infection was 78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced transmission risk by 8.3%. Improving ventilation to WHO standards decreased transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission by 64.4%. Prison environments promote high infection risk over short-time intervals. In this context, enhanced diagnostics have a limited impact on reducing transmission. Improving natural ventilation may be required to effectively control TB in prisons.
View details for DOI 10.4269/ajtmh.15-0166
View details for Web of Science ID 000362311800014
View details for PubMedID 26195459
- Changes to Initial Postexposure Prophylaxis Regimens Between the Emergency Department and Clinic. Journal of acquired immune deficiency syndromes (1999) 2015; 69 (5): e182-4
- Is a Cholera Outbreak Preventable in Post-earthquake Nepal? PLoS neglected tropical diseases 2015; 9 (8)
Diagnostics for invasive Salmonella infections: Current challenges and future directions.
2015; 33: C8-15
Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics.
View details for DOI 10.1016/j.vaccine.2015.02.030
View details for PubMedID 25937611
Towards sustainable public health surveillance for enteric fever.
2015; 33: C3-7
Enteric fever that results from infection by the typhoidal Salmonellas (Salmonella Typhi and Salmonella Paratyphi A, B and C) is a life-threatening preventable illness. Surveillance of enteric fever is important to understand current burden of disease, to track changes in human health burden from increasing antimicrobial resistance and to assess the impact of efforts to reduce disease burden. Since enteric fever occurs predominantly in low income communities, expensive surveillance is not sustainable. Traditional hospital-based surveillance does not estimate population burden and intensive community-based cohort studies do not capture the severe disease that is crucial to policy decisions. While cohort studies have been considered the gold standard for incidence estimates, the resources required to conduct them are great; as a consequence, estimates of enteric fever burden have been highly geographically and temporally restricted. A hybrid approach combining laboratory diagnosis that is already being conducted in healthcare centers with community-based surveillance of health care facility use offers a low-cost, sustainable approach to generate policy relevant data.
View details for DOI 10.1016/j.vaccine.2015.02.054
View details for PubMedID 25912287
Diagnosis of Schistosoma haematobium Infection with a Mobile Phone-Mounted Foldscope and a Reversed-Lens CellScope in Ghana
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2015; 92 (6): 1253-1256
We evaluated two novel, portable microscopes and locally acquired, single-ply, paper towels as filter paper for the diagnosis of Schistosoma haematobium infection. The mobile phone-mounted Foldscope and reversed-lens CellScope had sensitivities of 55.9% and 67.6%, and specificities of 93.3% and 100.0%, respectively, compared with conventional light microscopy for diagnosing S. haematobium infection. With conventional light microscopy, urine filtration using single-ply paper towels as filter paper showed a sensitivity of 67.6% and specificity of 80.0% compared with centrifugation for the diagnosis of S. haematobium infection. With future improvements to diagnostic sensitivity, newer generation handheld and mobile phone microscopes may be valuable tools for global health applications.
View details for DOI 10.4269/ajtmh.14-0741
View details for Web of Science ID 000355785400028
View details for PubMedID 25918211
The epidemiological advantage of preferential targeting of tuberculosis control at the poor
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
2015; 19 (4): 375-380
Tuberculosis (TB) remains disproportionately concentrated among the poor, yet known determinants of TB reactivation may fail to explain observed disparities in disease rates according to wealth. Reviewing data on TB disparities in India and the wealth distribution of known TB risk factors, we describe how social mixing patterns could be contributing to TB disparities. Wealth-assortative mixing, whereby individuals are more likely to be in contact with others from similar socio-economic backgrounds, amplifies smaller differences in risk of TB, resulting in large population-level disparities. As disparities and assortativeness increase, TB becomes more difficult to control, an effect that is obscured by looking at population averages of epidemiological parameters, such as case detection rates. We illustrate how TB control efforts may benefit from preferential targeting toward the poor. In India, an equivalent-scale intervention could have a substantially greater impact if targeted at those living below the poverty line than with a population-wide strategy. In addition to potential efficiencies in targeting higher-risk populations, TB control efforts would lead to a greater reduction in secondary TB cases per primary case diagnosed if they were preferentially targeted at the poor. We highlight the need to collect programmatic data on TB disparities and explicitly incorporate equity considerations into TB control plans.
View details for DOI 10.5588/ijtld.14.0423
View details for Web of Science ID 000351967800004
View details for PubMedID 25859990
The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents.
American journal of respiratory and critical care medicine
2015; 191 (5): 584-591
Rationale: Interferon-gamma release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described. Objectives: Assess QuantiFERON® TB Gold In-tube (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting. Methods. Adolescents aged 12-18 residing near Cape Town were recruited. Tuberculin skin testing (TST) and QFT were performed at baseline and after 2 years of follow-up; half also had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to five years. Measurements and Main Results. Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) were positive by QFT and TST at baseline. Annualized QFT and TST conversion risks were 14.0% and 13.0%, respectively; reversion risks were 5.1% and 4.1%. Concordance was excellent for conversions (κ = 0.74), but poor for reversions (κ = 0.12). Among recent QFT converters, magnitude of QFT value was strongly inversely associated with risk of reversion (p<0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters, compared with persons with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, p=0.011). Conclusions. In this tuberculosis-endemic setting, annual risk of infection was extremely high, while QFT and TST conversion concordance were higher and QFT reversion rates were lower than reported from low-burden settings.
View details for DOI 10.1164/rccm.201409-1704OC
View details for PubMedID 25562578
Prisons as Reservoir for Community Transmission of Tuberculosis, Brazil
EMERGING INFECTIOUS DISEASES
2015; 21 (3): 452-455
We conducted a population-based study of tuberculosis (TB) cases in Dourados, Brazil, to assess the relationship between incarceration and TB in the general population. Incarceration was associated with TB in an urban population; 54% of Mycobacterium tuberculosis strains were related to strains from persons in prisons. TB control in prisons is critical for reducing disease prevalence.
View details for DOI 10.3201/eid2103.140896
View details for Web of Science ID 000350269300009
View details for PubMedID 25642998
- Treating multidrug-resistant tuberculosis in community settings: a wise investment. international journal of tuberculosis and lung disease 2015; 19 (2): 127-?
Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study.
BMC infectious diseases
2015; 15: 24-?
BackgroundTuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates.MethodsWe administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI).ResultsWe recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623¿1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration.ConclusionsAlthough the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass screening for active TB, utilizing sputum culture in case-detection protocols.
View details for DOI 10.1186/s12879-015-0764-8
View details for PubMedID 25608746
A Cross-Sectional Survey of HIV Testing and Prevalence in Twelve Brazilian Correctional Facilities.
2015; 10 (10): e0139487
Prior studies have reported higher HIV prevalence among prisoners than the general population in Brazil, but data have been derived from single prisons. The aim of this study was to evaluate HIV testing practices, prevalence and linkage to care among inmates in a network of 12 prisons.We administered a questionnaire to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV and syphilis testing from January to December 2013. We evaluated factors associated with HIV testing and infection using multivariable logistic regression models. Six months after HIV testing, we assessed whether each HIV-infected prisoner was engaged in clinical care and whether they had started antiretroviral therapy.We recruited 3,362 inmates, of whom 2,843 (85%) were men from 8 prisons, and 519 (15%) were women from 4 prisons. Forty-five percent of participants reported never having been tested for HIV previously. In multivariable analysis, the variables associated with previous HIV testing were lack of a stable partner (adjusted odds ratio [AOR]: 1.38; 95% CI: 1.18-1.60), completed more than four years of schooling (AOR 1.40; 95% CI: 1.20-1.64), history of previous incarceration (AOR: 1.68; 95% CI: 1.43-1.98), history of mental illness (AOR 1.52; 95% CI: 1.31-1.78) and previous surgery (AOR 1.31; 95% CI: 1.12-1.52). Fifty-four (1.6%) of all participants tested positive for HIV; this included 44 (1.54%) men and 10 (1.92%) women. Among male inmates, HIV infection was associated with homosexuality (AOR 6.20, 95% CI: 1.73-22.22), self-report of mental illness (AOR 2.18, 95% CI: 1.13-4.18), history of sexually transmitted infections (AOR 3.28, 95% CI: 1.64-6.56), and syphilis sero-positivity (AOR 2.54, 95% CI: 1.20-5.39). Among HIV-infected individuals, 34 (63%) were unaware of their HIV status; only 23 of these 34 (68%) newly diagnosed participants could be reached at six month follow-up, and 21 of 23 (91%) were engaged in HIV care.HIV testing rates among prison inmates are low, and the majority of HIV-infected inmates were unaware of their HIV diagnosis. Incarceration can be an opportunity for diagnosis and treatment of HIV among vulnerable populations who have poor access to health services, but further work is needed on transitional HIV care for released inmates.
View details for DOI 10.1371/journal.pone.0139487
View details for PubMedID 26466312
Quantitative evaluation of a handheld light microscope for field diagnosis of soil-transmitted helminth infection.
The American journal of tropical medicine and hygiene
2014; 91 (6): 1138-1141
We evaluated the Newton Nm1, a commercially available handheld light microscope and compared it with conventional light microscopy for the diagnosis of soil-transmitted helminth infections. A total of 91 Kato-Katz thick smears were examined by experienced microscopists and helminth eggs were counted and expressed as eggs per gram of stool (EPG). Mean egg counts were significantly higher with the conventional light microscope (5,190.0 EPG versus 2,385.8 EPG for Ascaris lumbricoides; 826.3 versus 455.7 for Trichuris trichiura; both P < 0.05). Using regression coefficients and accounting for intensity of infection, we found that the agreement between the two devices was excellent for both species (κ = 0.90, 95% confidence interval = 0.82-0.99 for A. lumbricoides and κ = 0.96, 95% CI = 0.91-1.00 for T. trichiura). The Newton Nm1 microscope may be a useful tool for the detection and quantification of soil-transmitted helminth infection in clinical, epidemiologic, and public health settings.
View details for DOI 10.4269/ajtmh.14-0253
View details for PubMedID 25246697
- Isoniazid preventive therapy in medium-incidence settings: the price is right. international journal of tuberculosis and lung disease 2014; 18 (12): 1388-?
Evaluation of portable microscopic devices for the diagnosis of Schistosoma and soil-transmitted helminth infection
2014; 141 (14): 1811-1818
SUMMARY The diagnosis of parasitic worm (helminth) infections requires specialized laboratory settings, but most affected individuals reside in locations without access to such facilities. We tested two portable microscopic devices for the diagnosis of helminth infections in a cross-sectional survey in rural Côte d'Ivoire. We examined 164 stool samples under a light microscope and then re-examined with a commercial portable light microscope and an experimental mobile phone microscope for the diagnosis of Schistosoma mansoni and soil-transmitted helminths. Additionally, 180 filtered urine samples were examined by standard microscopy and compared with the portable light microscope for detection of Schistosoma haematobium eggs. Conventional microscopy was considered the diagnostic reference standard. For S. mansoni, S. haematobium and Trichuris trichiura, the portable light microscope showed sensitivities of 84·8%, 78·6% and 81·5%, respectively, and specificities of 85·7%, 91·0% and 93·0%, respectively. For S. mansoni and T. trichiura, we found sensitivities for the mobile phone microscope of 68·2% and 30·8%, respectively, and specificities of 64·3% and 71·0%, respectively. We conclude that the portable light microscope has sufficient diagnostic yield for Schistosoma and T. trichiura infections, while the mobile phone microscope has only modest sensitivity in its current experimental set-up. Development of portable diagnostic technologies that can be used at point-of-sample collection will enhance diagnostic coverage in clinical and epidemiological settings.
View details for DOI 10.1017/S0031182014000432
View details for Web of Science ID 000346740700005
View details for PubMedID 24776232
Strengthening Nepal's Female Community Health Volunteer network: a qualitative study of experiences at two years
BMC HEALTH SERVICES RESEARCH
Nepal's Female Community Health Volunteer (FCHV) program has been described as an exemplary public-sector community health worker program. However, despite its merits, the program still struggles to provide high-quality, accessible services nation-wide. Both in Nepal and globally, best practices for community health worker program implementation are not yet known: there is a dearth of empiric research, and the research that has been done has shown inconsistent results.Here we evaluate a pilot program designed to strengthen the Nepali government's FCHV network. The program was structured with five core components: 1) improve local FCHV leadership; 2) facilitate structured weekly FCHV meetings and 3) weekly FCHV trainings at the village level; 4) implement a monitoring and evaluation system for FCHV patient encounters; and 5) provide financial compensation for FCHV work. Following twenty-four months of program implementation, a retrospective programmatic evaluation was conducted, including qualitative analysis of focus group discussions and semi-structured interviews.Qualitative data analysis demonstrated that the program was well-received by program participants and community members, and suggests that the five core components of this program were valuable additions to the pre-existing FCHV network. Analysis also revealed key challenges to program implementation including geographic limitations, literacy limitations, and limitations of professional respect from healthcare workers to FCHVs. Descriptive statistics are presented for programmatic process metrics and costs throughout the first twenty four months of implementation.The five components of this pilot program were well-received as a mechanism for strengthening Nepal's FCHV program. To our knowledge, this is the first study to present such data, specifically informing programmatic design and management of the FCHV program. Despite limitations in its scope, this study offers tangible steps forward for further research and community health worker program improvement, both within Nepal and globally.
View details for DOI 10.1186/1472-6963-14-473
View details for Web of Science ID 000349638000001
View details for PubMedID 25301105
Ultra-Low-Cost Urine Filtration for Schistosoma haematobium Diagnosis: A Proof-of-Concept Study.
American journal of tropical medicine and hygiene
2014; 91 (3): 544-546
Simple, efficient, and cost-effective strategies are needed for urine sample preparation in the field diagnosis of infection with Schistosoma haematobium. In this proof-of-concept study, we evaluated inexpensive and widely available paper products (paper towels, school workbook paper, and newspaper) to gravity-filter urine containing 60 eggs/mL of Schistosoma haematobium. Eggs were reliably visualized by light microscopy by using single-ply paper towels as urine filters. This filtration method has broad applicability in clinical and public health settings in resource-constrained environments.
View details for DOI 10.4269/ajtmh.14-0221
View details for PubMedID 24980496
The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model
2014; 11 (7)
India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited.We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research.The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary.
View details for DOI 10.1371/journal.pmed.1001674
View details for Web of Science ID 000340617400007
View details for PubMedID 25025235
A User-Friendly, Open-Source Tool to Project Impact and Cost of Diagnostic Tests for Tuberculosis
Most existing models of infectious diseases, including tuberculosis (TB), do not allow end-users to customize results to local conditions. We created a dynamic transmission model to project TB incidence, TB mortality, multidrug-resistant (MDR) TB prevalence, and incremental costs over five years after scale-up of nine alternative diagnostic strategies including combinations of sputum smear microscopy, Xpert MTB/RIF, microcolony-based culture, and same-day diagnosis. We developed a corresponding web-based interface that allows users to specify local costs and epidemiology. Full model code - including the ability to change any input parameter - is also included. The impact of improved diagnostic testing was greater for mortality and MDR-TB prevalence than TB incidence, and was maximized in high-incidence, low-HIV settings. More costly interventions generally had greater impact. In settings with little capacity for up-front investment, same-day microscopy had greatest impact on TB incidence and became cost-saving within five years if feasible to deliver at $10/test. In settings where more initial investment was possible, population-level scale-up of either Xpert MTB/RIF or microcolony-based culture offered substantially greater benefits, often averting ten times more TB cases than narrowly-targeted diagnostic strategies at minimal incremental long-term cost. Where containing MDR-TB is the overriding concern, Xpert for smear-positives has reasonable impact on MDR-TB incidence, but at substantial price and little impact on overall TB incidence and mortality. This novel, user-friendly modeling framework improves decision-makers' ability to evaluate the impact of TB diagnostic strategies, accounting for local conditions.
View details for DOI 10.7554/eLife.02565
View details for Web of Science ID 000336837300004
View details for PubMedID 24898755
Patient Attrition Between the Emergency Department and Clinic Among Individuals Presenting for HIV Nonoccupational Postexposure Prophylaxis
CLINICAL INFECTIOUS DISEASES
2014; 58 (11): 1618-1624
Background. Nonoccupational postexposure prophylaxis (nPEP) is recommended after a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients frequently seek care in an emergency department (ED) after an exposure and are usually referred to an HIV clinic for further management. There have been few data on determinants of attrition after presentation to EDs for nPEP. Methods. From July 2010 to June 2011, we prospectively recorded all referrals to nPEP programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts. Data were recorded on patient demographics, nature of potential HIV exposures, referrals to and attendance at HIV clinics, and reported completion of 28 days of antiretroviral therapy (ART). Multivariable logistic regression was used to evaluate risk factors for (1) patient attrition between the ED and HIV clinic follow-up and (2) documented completion of ART. Results. Of 180 individuals who were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day course of ART. Multivariable analysis revealed older age (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI], .93-.99) and self-payment (aOR, 0.32; 95% CI, .11-.97) were significant predictors for failing to attend an initial HIV clinic appointment. Women were less likely than men to complete a 28-day ART regimen (aOR, 0.34; 95% CI, .15-.79). Conclusions. Commonly used nPEP delivery models may not be effective for all patients who present with nonoccupational exposures to HIV. Interventions are needed to improve rates of follow-up and completion of nPEP to reduce the risk of preventable HIV infections.
View details for DOI 10.1093/cid/ciu118
View details for Web of Science ID 000337031200020
View details for PubMedID 24723288
Timing of Tuberculosis Transmission and the Impact of Household Contact Tracing An Agent-based Simulation Model
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2014; 189 (7): 845-852
Rationale: Household contact tracing has recently been endorsed for global tuberculosis (TB) control, but its potential population-level impact remains uncertain. Objectives: To project the maximum impact of household contact tracing for TB in a moderate-burden setting. Methods: We developed a stochastic, agent-based simulation model of a simplified TB epidemic, calibrated to a setting of moderate TB incidence. We used data from the literature to generate "community-driven" and "household-driven" scenarios in which 22% and 50% of TB transmission occurred within the household respectively. In each scenario, we simulated an intervention in which the household members are screened and treated for TB at the time of an index patient's active TB diagnosis. Measurements and Main Results: By the time of TB diagnosis, 75-95% of initial household infections had already occurred, but only 1.5-3.0% of contacts had sufficient time to progress to active TB. With 100% sensitive tracing of all contacts for five consecutive years, TB incidence declined by 10-15%: a mean year-over-year decline of 2%/year. Effects were sustained for many years after stopping the intervention. Providing preventive therapy with contact tracing nearly doubled this impact (17-27% decline in incidence). Impact was proportional to sensitivity and coverage; thus, if 50% of contacts were screened with a 50% sensitive test, TB incidence declined by only 0.5%/year. Conclusions: Household contact tracing is unlikely to transform TB epidemiology in isolation but has the potential - especially with provision of preventive therapy - to augment a comprehensive package of interventions that could substantially reduce the population-level burden of TB.
View details for DOI 10.1164/rccm.201310-1846OC
View details for Web of Science ID 000333565600014
View details for PubMedID 24559425
Quantification of shared air: a social and environmental determinant of airborne disease transmission.
2014; 9 (9)
Tuberculosis is endemic in Cape Town, South Africa where a majority of the population become tuberculosis infected before adulthood. While social contact patterns impacting tuberculosis and other respiratory disease spread have been studied, the environmental determinants driving airborne transmission have not been quantified.Indoor carbon dioxide levels above outdoor levels reflect the balance of exhaled breath by room occupants and ventilation. We developed a portable monitor to continuously sample carbon dioxide levels, which were combined with social contact diary records to estimate daily rebreathed litres. A pilot study established the practicality of monitor use up to 48-hours. We then estimated the daily volumes of air rebreathed by adolescents living in a crowded township.One hundred eight daily records were obtained from 63 adolescents aged between 12- and 20-years. Forty-five lived in wooden shacks and 18 in brick-built homes with a median household of 4 members (range 2-9). Mean daily volume of rebreathed air was 120.6 (standard error: 8.0) litres/day, with location contributions from household (48%), school (44%), visited households (4%), transport (0.5%) and other locations (3.4%). Independent predictors of daily rebreathed volumes included household type (p = 0.002), number of household occupants (p = 0.021), number of sleeping space occupants (p = 0.022) and winter season (p<0.001).We demonstrated the practical measurement of carbon dioxide levels to which individuals are exposed in a sequence of non-steady state indoor environments. A novel metric of rebreathed air volume reflects social and environmental factors associated with airborne infection and can identify locations with high transmission potential.
View details for DOI 10.1371/journal.pone.0106622
View details for PubMedID 25181526
Challenges in Evaluating the Cost-effectiveness of New Diagnostic Tests for HIV-Associated Tuberculosis
CLINICAL INFECTIOUS DISEASES
2013; 57 (7): 1021-1026
With an emerging array of rapid diagnostic tests for tuberculosis, cost-effectiveness analyses are needed to inform scale-up in various populations and settings. Human immunodeficiency virus (HIV)-associated tuberculosis poses unique challenges in estimating and interpreting the cost-effectiveness of novel diagnostic tools. First, gains in sensitivity and specificity do not directly correlate with impact on clinical outcomes. Second, the cost-effectiveness of implementing tuberculosis diagnostics in HIV-infected populations is heavily influenced by downstream costs of HIV care. As a result, tuberculosis diagnostics may appear less cost-effective in this population than among HIV-uninfected individuals, raising important ethical and policy questions about the design and interpretation of cost-effectiveness analyses in this setting. Third, conventional cost-effectiveness benchmarks may be inadequate for making decisions about whether to adopt new diagnostics. If we are to appropriately deploy novel diagnostics for tuberculosis to people living with HIV in resource-constrained settings, these challenges in measuring cost-effectiveness must be more widely recognized and addressed.
View details for DOI 10.1093/cid/cit412
View details for Web of Science ID 000326027400015
View details for PubMedID 23788239
Complexity in mathematical models of public health policies: a guide for consumers of models.
2013; 10 (10)
Sanjay Basu and colleagues explain how models are increasingly used to inform public health policy yet readers may struggle to evaluate the quality of models. All models require simplifying assumptions, and there are tradeoffs between creating models that are more "realistic" versus those that are grounded in more solid data. Indeed, complex models are not necessarily more accurate or reliable simply because they can more easily fit real-world data than simpler models can. Please see later in the article for the Editors' Summary.
View details for DOI 10.1371/journal.pmed.1001540
View details for PubMedID 24204214
Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2013; 88 (4): 626-629
We created a mobile phone microscope and assessed its accuracy for the diagnosis of soil-transmitted helminths compared with conventional microscopy. Mobile phone microscopy has a sensitivity of 69.4% for detecting any helminth egg and sensitivities of 81.0%, 54.4%, and 14.3% for the diagnosis of Ascaris lumbricoides, Trichuris trichiura and hookworm respectively.
View details for DOI 10.4269/ajtmh.12-0742
View details for Web of Science ID 000317024700005
Modeling the Role of Public Transportation in Sustaining Tuberculosis Transmission in South Africa
AMERICAN JOURNAL OF EPIDEMIOLOGY
2013; 177 (6): 556-561
Current tuberculosis notification rates in South Africa are among the highest ever recorded. Although the human immunodeficiency virus epidemic has been a critical factor, the density of respiratory contacts in high-risk environments may be an important and underappreciated driver. Using a modified Wells-Riley model for airborne disease transmission, we estimated the risk of tuberculosis transmission on 3 modes of public transit (minibus taxis, buses, and trains) in Cape Town, South Africa, using exhaled carbon dioxide as a natural tracer gas to evaluate air exchange. Carbon dioxide measurements were performed between October and December of 2011. Environmental risk, reflected in the rebreathed fraction of air, was highest in minibus taxis and lowest in trains; however, the average number of passengers sharing an indoor space was highest in trains and lowest in minibus taxis. Among daily commuters, the annual risk of tuberculosis infection was projected to be 3.5%-5.0% and was highest among minibus taxi commuters. Assuming a duration of infectiousness of 1 year, the basic reproductive number attributable to transportation was more than 1 in all 3 modes of transportation. Given its poor ventilation and high respiratory contact rates, public transportation may play a critical role in sustaining tuberculosis transmission in South African cities.
View details for DOI 10.1093/aje/kws331
View details for Web of Science ID 000316374500009
View details for PubMedID 23423215
Is Passive Diagnosis Enough? The Impact of Subclinical Disease on Diagnostic Strategies for Tuberculosis
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2013; 187 (5): 543-551
Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited.To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease.We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active").If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase.Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection.
View details for DOI 10.1164/rccm.201207-1217OC
View details for Web of Science ID 000315977200014
View details for PubMedID 23262515
Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults
2013; 14 (3): 182-186
The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral (ARV) era in a nontuberculosis endemic setting.A multicentred, retrospective cohort study of peripheral lymph node biopsies in HIV-positive adults was carried out. A total of 107 charts were identified and reviewed for clinical features, lymphadenopathy size, and ARV use and duration. Biopsy results were categorized, and multivariate logistic regression determined independent predictors of lymphadenopathy aetiology.Evaluation of 107 peripheral lymph node biopsies revealed that 42.9% of peripheral lymphadenopathy was attributable to malignancy, 49.5% to reactive changes, and 7.5% to infections, with only 2.8% of all cases secondary to tuberculosis. Fevers, weight loss, ARV use, and lower viral loads are significantly associated with nonreactive lymphadenopathy.Lymphadenopathy is likely to be reactive or malignant in nontuberculosis endemic regions. Readily available clinical features can aid clinicians in predicting the underlying aetiology, those at risk for malignancy, and who to biopsy.
View details for DOI 10.1111/j.1468-1293.2012.01035.x
View details for Web of Science ID 000314469500008
View details for PubMedID 22805116
Diagnosis of influenza from lower respiratory tract sampling after negative upper respiratory tract sampling
2013; 4 (1): 82-84
In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses of influenza were made solely by lower respiratory sampling in 6.9% of cases, as traditional upper respiratory tract tests were negative, indeterminate or not performed. Clinical features of these cases are presented. Clinicians should consider lower respiratory tract sampling in select cases of influenza-like illness for diagnosis.
View details for DOI 10.4161/viru.22466
View details for Web of Science ID 000313566000005
View details for PubMedID 23135351
Crossing the quality chasm in resource-limited settings
GLOBALIZATION AND HEALTH
Over the last decade, extensive scientific and policy innovations have begun to reduce the "quality chasm"--the gulf between best practices and actual implementation that exists in resource-rich medical settings. While limited data exist, this chasm is likely to be equally acute and deadly in resource-limited areas. While health systems have begun to be scaled up in impoverished areas, scale-up is just the foundation necessary to deliver effective healthcare to the poor. This perspective piece describes a vision for a global quality improvement movement in resource-limited areas. The following action items are a first step toward achieving this vision: 1) revise global health investment mechanisms to value quality; 2) enhance human resources for improving health systems quality; 3) scale up data capacity; 4) deepen community accountability and engagement initiatives; 5) implement evidence-based quality improvement programs; 6) develop an implementation science research agenda.
View details for DOI 10.1186/1744-8603-8-41
View details for Web of Science ID 000312600500001
View details for PubMedID 23193968
Simple questionnaire and urine reagent strips compared to microscopy for the diagnosis of Schistosoma haematobium in a community in northern Ghana
TROPICAL MEDICINE & INTERNATIONAL HEALTH
2012; 17 (10): 1217-1221
To evaluate the utility of a simple questionnaire and urine reagent strip testing for the rapid diagnosis of Schistosoma haematobium in rural northern Ghana.Cross-sectional parasitological and questionnaire survey in a community in northern Ghana. Participants provided two urine specimens that were examined under a microscope using a centrifugation method. The first urine sample was additionally subjected to reagent strip testing. A short questionnaire was administered to all participants.Microscopy of urine samples obtained from 208 individuals aged 1-77 years revealed an S. haematobium prevalence of 6.8%. The presence of any blood or protein on a urine reagent strip was 100% and 42% sensitive, and 93% and 80% specific for S. haematobium diagnosis. Questionnaires were completed by 198 individuals. Self-reported haematuria showed a sensitivity of 53% and a specificity of 85%. A dichotomous two-question panel was helpful in S. haematobium diagnosis, with working and playing near the river significantly associated with S. haematobium infection (P < 0.001).The use of urine reagent strips, coupled with questions pertaining to water contact patterns, might be considered for point-of-contact diagnosis of S. haematobium where microscopy is unavailable.
View details for DOI 10.1111/j.1365-3156.2012.03054.x
View details for Web of Science ID 000308714200007
View details for PubMedID 22863035
Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review
2012; 9 (6)
Private sector healthcare delivery in low- and middle-income countries is sometimes argued to be more efficient, accountable, and sustainable than public sector delivery. Conversely, the public sector is often regarded as providing more equitable and evidence-based care. We performed a systematic review of research studies investigating the performance of private and public sector delivery in low- and middle-income countries.Peer-reviewed studies including case studies, meta-analyses, reviews, and case-control analyses, as well as reports published by non-governmental organizations and international agencies, were systematically collected through large database searches, filtered through methodological inclusion criteria, and organized into six World Health Organization health system themes: accessibility and responsiveness; quality; outcomes; accountability, transparency, and regulation; fairness and equity; and efficiency. Of 1,178 potentially relevant unique citations, data were obtained from 102 articles describing studies conducted in low- and middle-income countries. Comparative cohort and cross-sectional studies suggested that providers in the private sector more frequently violated medical standards of practice and had poorer patient outcomes, but had greater reported timeliness and hospitality to patients. Reported efficiency tended to be lower in the private than in the public sector, resulting in part from perverse incentives for unnecessary testing and treatment. Public sector services experienced more limited availability of equipment, medications, and trained healthcare workers. When the definition of "private sector" included unlicensed and uncertified providers such as drug shop owners, most patients appeared to access care in the private sector; however, when unlicensed healthcare providers were excluded from the analysis, the majority of people accessed public sector care. "Competitive dynamics" for funding appeared between the two sectors, such that public funds and personnel were redirected to private sector development, followed by reductions in public sector service budgets and staff.Studies evaluated in this systematic review do not support the claim that the private sector is usually more efficient, accountable, or medically effective than the public sector; however, the public sector appears frequently to lack timeliness and hospitality towards patients.
View details for DOI 10.1371/journal.pmed.1001244
View details for Web of Science ID 000305946200015
View details for PubMedID 22723748
The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis
2012; 26 (8): 987-995
In settings with high tuberculosis (TB) prevalence, 15-30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity.To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART.We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities - in all patients or only symptomatic patients - for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/μl; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective.Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient.Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective.
View details for DOI 10.1097/QAD.0b013e3283522d47
View details for Web of Science ID 000303656000010
View details for PubMedID 22333751
- On partnership. Narrative inquiry in bioethics 2012; 2 (2): 101-106
Social and News Media Enable Estimation of Epidemiological Patterns Early in the 2010 Haitian Cholera Outbreak
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
2012; 86 (1): 39-45
During infectious disease outbreaks, data collected through health institutions and official reporting structures may not be available for weeks, hindering early epidemiologic assessment. By contrast, data from informal media are typically available in near real-time and could provide earlier estimates of epidemic dynamics. We assessed correlation of volume of cholera-related HealthMap news media reports, Twitter postings, and government cholera cases reported in the first 100 days of the 2010 Haitian cholera outbreak. Trends in volume of informal sources significantly correlated in time with official case data and was available up to 2 weeks earlier. Estimates of the reproductive number ranged from 1.54 to 6.89 (informal sources) and 1.27 to 3.72 (official sources) during the initial outbreak growth period, and 1.04 to 1.51 (informal) and 1.06 to 1.73 (official) when Hurricane Tomas afflicted Haiti. Informal data can be used complementarily with official data in an outbreak setting to get timely estimates of disease dynamics.
View details for DOI 10.4269/ajtmh.2012.11-0597
View details for Web of Science ID 000299065200013
View details for PubMedID 22232449
Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
2012; 16 (1): 90-97
Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates.To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa.Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB.Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count ≤ 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count ≤ 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009).Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation.
View details for DOI 10.5588/ijtld.11.0153
View details for Web of Science ID 000298726700017
View details for PubMedID 22236852
Implementing a systems-oriented morbidity and mortality conference in remote rural Nepal for quality improvement
BMJ QUALITY & SAFETY
2011; 20 (12): 1082-1088
In hospitals in rural, resource-limited settings, there is an acute need for simple, practical strategies to improve healthcare quality.A district hospital in remote western Nepal.To provide a mechanism for systems-level reflection so that staff can identify targets for quality improvement in healthcare delivery. Strategies for change To develop a morbidity and mortality conference (M&M) quality improvement initiative that aims to facilitate structured analysis of patient care and identify barriers to providing quality care, which can subsequently be improved.The authors designed an M&M involving clinical and non-clinical staff in conducting root-cause analyses of healthcare delivery at their hospital. Weekly conferences focus on seven domains of causal analysis: operations, supply chain, equipment, personnel, outreach, societal, and structural. Each conference focuses on assessing the care provided, and identifying ways in which services can be improved in the future.Staff reception of the M&Ms was positive. In these M&Ms, staff identified problem areas in healthcare delivery and steps for improvement. Subsequently, changes were made in hospital workflow, supply procurement, and on-site training.While widely practiced throughout the world, M&Ms typically do not involve both clinical and non-clinical staff members and do not take a systems-level approach. The authors' experience suggests that the adapted M&M conference is a simple, feasible tool for quality improvement in resource-limited settings. Senior managerial commitment is crucial to ensure successful implementation of M&Ms, given the challenging logistics of implementing these programmes in resource-limited health facilities.
View details for DOI 10.1136/bmjqs-2011-000273
View details for Web of Science ID 000297619300013
View details for PubMedID 21949441
- Pandemic H1N1 Influenza Infection in Adult Transplant Recipients TRANSPLANTATION 2011; 91 (12): E80-E81
- HIV-1 and 2009 H1N1 Influenza A in Adults JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES 2011; 56 (4): E111-E113
- Visceral Leishmaniasis in Far Western Nepal: Another Case and Concerns about a New Area of Endemicity AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE 2011; 84 (3): 508-508
Tuberculosis and HIV Co-Infection Screening and Treatment Strategies
2011; 71 (9): 1133-1152
Globally, tuberculosis (TB) and HIV interact in deadly synergy. The high burden of TB among HIV-infected individuals underlies the importance of TB diagnosis, treatment and prevention for clinicians involved in HIV care. Despite expanding access to antiretroviral therapy (ART) to treat HIV infection in resource-limited settings, many individuals in need of therapy initiate ART too late and have already developed clinically significant TB by the time they present for care. Many co-infected individuals are in need of concurrent ART and anti-TB therapy, which dramatically improves survival, but also raises several management challenges, including drug interactions, shared drug toxicities and TB immune reconstitution inflammatory syndrome (IRIS). Due to the survival benefits of promptly initiating ART among all HIV-infected individuals, including those with TB, it is recommended that co-infected individuals receive treatment for both diseases, regardless of CD4+ cell count. We review current screening and treatment strategies for TB and HIV co-infection. Recent findings and ongoing studies will assist clinicians in managing the prevention and treatment of TB and HIV co-infection, which remains a major global health challenge.
View details for Web of Science ID 000293101200003
View details for PubMedID 21711060
Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain.
AIDS research and treatment
2011; 2011: 729854-?
Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV). The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD), primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.
View details for DOI 10.1155/2011/729854
View details for PubMedID 21541215
Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community
2010; 5 (12)
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6).In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.
View details for DOI 10.1371/journal.pone.0015735
View details for Web of Science ID 000285793200047
View details for PubMedID 21209951
HIV Coinfection in Multidrug- and Extensively Drug-Resistant Tuberculosis Results in High Early Mortality
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
2010; 181 (1): 80-86
The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected.To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates.We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records.Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001).Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.
View details for DOI 10.1164/rccm.200907-0989OC
View details for Web of Science ID 000273147100015
View details for PubMedID 19833824
Turning a blind eye: the mobilization of radiology services in resource-poor regions.
Globalization and health
2010; 6: 18-?
While primary care, obstetrical, and surgical services have started to expand in the world's poorest regions, there is only sparse literature on the essential support systems that are required to make these operations function. Diagnostic imaging is critical to effective rural healthcare delivery, yet it has been severely neglected by the academic, public, and private sectors. Currently, a large portion of the world's population lacks access to any form of diagnostic imaging. In this paper we argue that two primary imaging modalities--diagnostic ultrasound and X-Ray--are ideal for rural healthcare services and should be scaled-up in a rapid and standardized manner. Such machines, if designed for resource-poor settings, should a) be robust in harsh environmental conditions, b) function reliably in environments with unstable electricity, c) minimize radiation dangers to staff and patients, d) be operable by non-specialist providers, and e) produce high-quality images required for accurate diagnosis. Few manufacturers are producing ultrasound and X-Ray machines that meet the specifications needed for rural healthcare delivery in resource-poor regions. A coordinated effort is required to create demand sufficient for manufacturers to produce the desired machines and to ensure that the programs operating them are safe, effective, and financially feasible.
View details for DOI 10.1186/1744-8603-6-18
View details for PubMedID 20946643
- Global Health Delivery 2.0: Using Open-Access Technologies for Transparency and Operations Research PLOS MEDICINE 2009; 6 (12)
Averting epidemics of extensively drug-resistant tuberculosis
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2009; 106 (18): 7672-7677
Extensively drug-resistant tuberculosis (XDR TB) has been detected in most provinces of South Africa, particularly in the KwaZulu-Natal province where several hundred cases have been reported since 2004. We analyzed the transmission dynamics of XDR TB in the region using mathematical models, and observed that nosocomial transmission clusters of XDR TB may emerge into community-based epidemics under the public health conditions of many South African communities. The effective reproductive number of XDR TB in KwaZulu-Natal may be around 2. Intensified community-based case finding and therapy appears critical to curtailing transmission. In the setting of delayed disease presentation and high system demand, improved diagnostic approaches may need to be employed in community-based programs rather than exclusively at tertiary hospitals. Using branching process mathematics, we observed that early, community-based drug-susceptibility testing and effective XDR therapy could help curtail ongoing transmission and reduce the probability of XDR TB epidemics in neighboring territories.
View details for DOI 10.1073/pnas.0812472106
View details for Web of Science ID 000265783600073
View details for PubMedID 19365076
Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis
LANCET INFECTIOUS DISEASES
2009; 9 (3): 153-161
Multidrug-resistant (MDR) tuberculosis is a growing clinical and public-health concern. To evaluate existing evidence regarding treatment regimens for MDR tuberculosis, we used a Bayesian random-effects meta-analysis of the available therapeutic studies to assess how the reported proportion of patients treated successfully is influenced by differences in treatment regimen design, study methodology, and patient population. Successful treatment outcome was defined as cure or treatment completion. 34 clinical reports with a mean of 250 patients per report met the inclusion criteria. Our analysis shows that the proportion of patients treated successfully improved when treatment duration was at least 18 months, and if patients received directly observed therapy throughout treatment. Studies that combined both factors had significantly higher pooled success proportions (69%, 95% credible interval [CI] 64-73%) than other studies of treatment outcomes (58%, 95% CI 52-64%). Individualised treatment regimens had higher treatment success (64%, 95% CI 59-68%) than standardised regimens (54%, 95% CI 43-68%), although the difference was not significant. Treatment approaches and study methodologies were heterogeneous across studies. Many important variables, including patients' HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR tuberculosis treatment programmes.
View details for Web of Science ID 000263787500014
View details for PubMedID 19246019
Multidrug-resistant and extensively drug-resistant tuberculosis: Implications for the HIV epidemic and antiretroviral therapy rollout in South Africa
JOURNAL OF INFECTIOUS DISEASES
2007; 196: S482-S490
Drug-resistant tuberculosis (TB) is emerging as a major clinical and public health challenge in areas of sub-Saharan Africa where there is a high prevalence of human immunodeficiency virus (HIV) infection. TB drug-resistance surveillance in this region has been limited by laboratory capacity and the public health infrastructure; however, with the maturation of the HIV epidemic, the burden of drug-resistant TB is increasing rapidly. The recent discovery of large numbers of cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB in South Africa likely represents an unrecognized and evolving epidemic rather than sporadic, localized outbreaks. The combination of a large population of HIV-infected susceptible hosts with poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing, and an overburdened MDR-TB treatment program provides ideal conditions for an MDR-TB and XDR-TB epidemic of unparalleled magnitude. In the present article, we review the history of drug-resistant TB in South Africa, describe its interaction with the HIV epidemic and the resultant consequences, and suggest measures necessary for controlling MDR-TB and XDR-TB in this context. A successful response to the emergence of MDR-TB and XDR-TB will necessitate increased resources for and collaboration between TB and HIV programs.
View details for DOI 10.1086/521121
View details for Web of Science ID 000251398100007
View details for PubMedID 18181698
Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study
2007; 370 (9597): 1500-1507
Extensively drug-resistant (XDR) tuberculosis has spread among hospitalised patients in South Africa, but the epidemic-level effect of hospital-based infection control strategies remains unknown. We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa.We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in the rural community of Tugela Ferry. Assessments were done with a mathematical model incorporating over 2 years of longitudinal inpatient and community-based data. The model simulated inpatient airborne tuberculosis transmission, community tuberculosis transmission, and the effect of HIV and antiretroviral therapy.If no new interventions are introduced, about 1300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012, more than half of which are likely to be nosocomially transmitted. Mask use alone would avert fewer than 10% of cases in the overall epidemic, but could prevent a large proportion of cases of XDR tuberculosis in hospital staff. The combination of mask use with reduced hospitalisation time and a shift to outpatient therapy could prevent nearly a third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. However, involuntary detention could result in an unexpected rise in incidence due to restricted isolation capacity.A synergistic combination of available nosocomial infection control strategies could prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will probably continue in the community, indicating the need to develop and implement parallel community-based programmes.
View details for Web of Science ID 000250487000027
View details for PubMedID 17964351
- XDR-TB in South Africa: Theory and practice PLOS MEDICINE 2007; 4 (4): 770-771
Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa
2006; 368 (9547): 1575-1580
The epidemics of HIV-1 and tuberculosis in South Africa are closely related. High mortality rates in co-infected patients have improved with antiretroviral therapy, but drug-resistant tuberculosis has emerged as a major cause of death. We assessed the prevalence and consequences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in a rural area in KwaZulu Natal, South Africa.We undertook enhanced surveillance for drug-resistant tuberculosis with sputum culture and drug susceptibility testing in patients with known or suspected tuberculosis. Genotyping was done for isolates resistant to first-line and second-line drugs.From January, 2005, to March, 2006, sputum was obtained from 1539 patients. We detected MDR tuberculosis in 221 patients, of whom 53 had XDR tuberculosis. Prevalence among 475 patients with culture-confirmed tuberculosis was 39% (185 patients) for MDR and 6% (30) for XDR tuberculosis. Only 55% (26 of 47) of patients with XDR tuberculosis had never been previously treated for tuberculosis; 67% (28 of 42) had a recent hospital admission. All 44 patients with XDR tuberculosis who were tested for HIV were co-infected. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis (IQR 6-37) among the 42 patients with confirmed dates of death. Genotyping of isolates showed that 39 of 46 (85%, 95% CI 74-95) patients with XDR tuberculosis had similar strains.MDR tuberculosis is more prevalent than previously realised in this setting. XDR tuberculosis has been transmitted to HIV co-infected patients and is associated with high mortality. These observations warrant urgent intervention and threaten the success of treatment programmes for tuberculosis and HIV.
View details for DOI 10.1016/S0140-6736(06)69573-1
View details for Web of Science ID 000242180900026
View details for PubMedID 17084757
- Populations who test drugs should benefit from them NATURE 2006; 440 (7084): 605-605
Research in the ranks - vulnerable subjects, coercible collaborotionl and the hepatitis E vaccine trial in Nepal
PERSPECTIVES IN BIOLOGY AND MEDICINE
2006; 49 (1): 35-51
Concern over the diminished autonomy of members of the armed forces has resulted in the classification of these groups as "vulnerable" in many international codes of research ethics, a designation that places the onus on researchers to provide special justification for the inclusion of these persons in research. This paper examines the application of these ethical requirements to a recent trial carried out by U.S. Army researchers among soldiers of the Royal Nepal Army (RNA) and concludes that the requirements to justify conducting research in this population were not met. Furthermore, noting the human rights abuses rampant in the RNA, it is appropriate to question the choice of this institution as both a partner and a subject pool for U.S. state-sponsored research. This case study raises another important ethical question about the vulnerability to coerced collaboration of groups or institutions. In response, I propose the idea of "institutional vulnerability" as an extension of the idea of individual "juridic vulnerability." The recent military and financial assistance that the RNA received from the U.S. Army, in light of their partnership in this biomedical research trial, constitutes an appropriate and revealing context in which to ground this discussion.
View details for Web of Science ID 000235107900004
View details for PubMedID 16489275
- US military sponsored vaccine trials and La resistance in Nepal AMERICAN JOURNAL OF BIOETHICS 2005; 5 (3): W1-W3
How do international trade agreements influence the promotion of public health?--An introduction to the issue.
Yale journal of health policy, law, and ethics
2004; 4 (2): 339-340
View details for PubMedID 15536915