Bio


Jade Benjamin-Chung, PhD MPH, is an Assistant Professor at Stanford University in the Department of Epidemiology and Population Health and Chan Zuckerberg Biohub Investigator. Her group conducts research to identify interventions to control, eliminate, or eradicate environmentally-transmitted infectious diseases, including malaria, diarrhea, soil-transmitted helminths, and influenza. We use a variety of epidemiologic, computational, and statistical methods, including causal inference and machine learning methods and focus on vulnerable populations from low-resource settings, both domestically and internationally.

Honors & Awards


  • Rosenkranz Prize, Stanford University (2023)
  • Stanford Program on Research Rigor and Reproducibility Award, Stanford University (2023)
  • Investigator, Chan Zuckerberg Biohub (2022-2027)

Boards, Advisory Committees, Professional Organizations


  • Faculty Fellow, Stanford Center for Innovation in Global Health (2021 - Present)

Professional Education


  • PhD, UC Berkeley, Epidemiology (2014)
  • MA, UC Berkeley, Biostatistics (2013)
  • MPH, UC Berkeley, Epidemiology & Biostatistics (2008)

Current Research and Scholarly Interests


Our research aims to improve population health by creating high quality evidence about what health interventions work in whom and where, when, and how to implement them. Most of our research is focused on environmentally-mediated infectious diseases, including malaria, diarrhea, soil-transmitted helminths, and influenza. Our focus is on improving the health of vulnerable populations from low-resource settings, both domestically and internationally. We use a variety of epidemiologic, computational, and statistical methods, including causal inference and machine learning methods.

Clinical Trials


  • Cement flooRs AnD chiLd hEalth (CRADLE) Recruiting

    This randomized trial in rural Bangladesh will measure whether installing concrete floors in households with soil floors reduces child enteric infection. The trial will randomize eligible households to receive concrete household floors or to no intervention and measure effects on child soil-transmitted helminth infection, diarrhea, and other enteric infections. The study will collect longitudinal follow-up measurements at birth and when children are ages 3, 6, 12, 18, and 24 months.

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2023-24 Courses


Stanford Advisees


  • Doctoral Dissertation Reader (AC)
    Jason Hernandez
  • Doctoral Dissertation Advisor (AC)
    Luke Caddell, Anna Nguyen
  • Doctoral (Program)
    Luke Caddell

All Publications


  • Causes and consequences of child growth faltering in low-resource settings. Nature Mertens, A., Benjamin-Chung, J., Colford, J. M., Coyle, J., van der Laan, M. J., Hubbard, A. E., Rosete, S., Malenica, I., Hejazi, N., Sofrygin, O., Cai, W., Li, H., Nguyen, A., Pokpongkiat, N. N., Djajadi, S., Seth, A., Jung, E., Chung, E. O., Jilek, W., Subramoney, V., Hafen, R., Häggström, J., Norman, T., Brown, K. H., Christian, P., Arnold, B. F. 2023

    Abstract

    Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

    View details for DOI 10.1038/s41586-023-06501-x

    View details for PubMedID 37704722

    View details for PubMedCentralID 2270351

  • Early-childhood linear growth faltering in low- and middle-income countries. Nature Benjamin-Chung, J., Mertens, A., Colford, J. M., Hubbard, A. E., van der Laan, M. J., Coyle, J., Sofrygin, O., Cai, W., Nguyen, A., Pokpongkiat, N. N., Djajadi, S., Seth, A., Jilek, W., Jung, E., Chung, E. O., Rosete, S., Hejazi, N., Malenica, I., Li, H., Hafen, R., Subramoney, V., Häggström, J., Norman, T., Brown, K. H., Christian, P., Arnold, B. F. 2023

    Abstract

    Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards)1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering-a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n = 32 cohorts, 52,640 children, ages 0-24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children's linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

    View details for DOI 10.1038/s41586-023-06418-5

    View details for PubMedID 37704719

    View details for PubMedCentralID 5084763

  • Child wasting and concurrent stunting in low- and middle-income countries. Nature Mertens, A., Benjamin-Chung, J., Colford, J. M., Hubbard, A. E., van der Laan, M. J., Coyle, J., Sofrygin, O., Cai, W., Jilek, W., Rosete, S., Nguyen, A., Pokpongkiat, N. N., Djajadi, S., Seth, A., Jung, E., Chung, E. O., Malenica, I., Hejazi, N., Li, H., Hafen, R., Subramoney, V., Häggström, J., Norman, T., Christian, P., Brown, K. H., Arnold, B. F. 2023

    Abstract

    Sustainable Development Goal 2.2-to end malnutrition by 2030-includes the elimination of child wasting, defined as a weight-for-length z-score that is more than two standard deviations below the median of the World Health Organization standards for child growth1. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence-key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z-score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z-score varied substantially (more than 0.5 z in some cohorts), with the lowest mean z-scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6-59 months.

    View details for DOI 10.1038/s41586-023-06480-z

    View details for PubMedID 37704720

    View details for PubMedCentralID 4143239

  • Household finished flooring and soil-transmitted helminth and Giardia infections among children in rural Bangladesh and Kenya: a prospective cohort study. The Lancet. Global health Benjamin-Chung, J. n., Crider, Y. S., Mertens, A. n., Ercumen, A. n., Pickering, A. J., Lin, A. n., Steinbaum, L. n., Swarthout, J. n., Rahman, M. n., Parvez, S. M., Haque, R. n., Njenga, S. M., Kihara, J. n., Null, C. n., Luby, S. P., Colford, J. M., Arnold, B. F. 2021; 9 (3): e301–e308

    Abstract

    Soil-transmitted helminths and Giardia duodenalis are responsible for a large burden of disease globally. In low-resource settings, household finished floors (eg, concrete floors) might reduce transmission of soil-transmitted helminths and G duodenalis.In a prospective cohort of children nested within two randomised trials in rural Bangladesh and Kenya, we estimated associations between household finished flooring and soil-transmitted helminths and G duodenalis prevalence. In 2015-16, we collected stool samples from children aged 2-16 years in rural Bangladesh and Kenya. We detected soil-transmitted helminth infection using quantitative PCR (qPCR; Bangladesh n=2800; Kenya n=3094), and G duodenalis using qPCR in Bangladesh (n=6894) and ELISA in Kenya (n=8899). We estimated adjusted prevalence ratios (aPRs) using log-linear models adjusted for potential confounders.7187 (92·2%) of 7795 children in Bangladesh and 9077 (93·7%) of 9686 children in Kenya provided stool specimens that were analysed by qPCR. At enrolment, 691 (10%) households in Bangladesh and 471 (5%) households in Kenya had finished floors. In both countries, household finished flooring was associated with lower Ascaris lumbricoides prevalence (Bangladesh aPR 0·33, 95% CI 0·14-0·78; Kenya 0·62, 0·39-0·98) and any soil-transmitted helminths (Bangladesh 0·73, 0·52-1·01; Kenya 0·57, 0·37-0·88). Household finished floors were also associated with lower Necator americanus prevalence in Bangladesh (0·52, 0·29-0·94) and G duodenalis prevalence in both countries (Bangladesh 0·78, 0·64-0·95; Kenya 0·82, 0·70-0·97).In low-resource settings, living in households with finished floors over a 2-year period was associated with lower prevalence of G duodenalis and some soil-transmitted helminths in children.Bill & Melinda Gates Foundation and Task Force for Global Health.

    View details for DOI 10.1016/S2214-109X(20)30523-4

    View details for PubMedID 33607029

  • Evaluation of a city-wide school-located influenza vaccination program in Oakland, California, with respect to vaccination coverage, school absences, and laboratory-confirmed influenza: A matched cohort study PLOS MEDICINE Benjamin-Chung, J., Arnold, B. F., Kennedy, C. J., Mishra, K., Pokpongkiat, N., Nguyen, A., Jilek, W., Holbrook, K., Pan, E., Kirley, P. D., Libby, T., Hubbard, A. E., Reingold, A., Colford, J. M. 2020; 17 (8): e1003238

    Abstract

    It is estimated that vaccinating 50%-70% of school-aged children for influenza can produce population-wide indirect effects. We evaluated a city-wide school-located influenza vaccination (SLIV) intervention that aimed to increase influenza vaccination coverage. The intervention was implemented in ≥95 preschools and elementary schools in northern California from 2014 to 2018. Using a matched cohort design, we estimated intervention impacts on student influenza vaccination coverage, school absenteeism, and community-wide indirect effects on laboratory-confirmed influenza hospitalizations.We used a multivariate matching algorithm to identify a nearby comparison school district with pre-intervention characteristics similar to those of the intervention school district and matched schools in each district. To measure student influenza vaccination, we conducted cross-sectional surveys of student caregivers in 22 school pairs (2017 survey, N = 6,070; 2018 survey, N = 6,507). We estimated the incidence of laboratory-confirmed influenza hospitalization from 2011 to 2018 using surveillance data from school district zip codes. We analyzed student absenteeism data from 2011 to 2018 from each district (N = 42,487,816 student-days). To account for pre-intervention differences between districts, we estimated difference-in-differences (DID) in influenza hospitalization incidence and absenteeism rates using generalized linear and log-linear models with a population offset for incidence outcomes. Prior to the SLIV intervention, the median household income was $51,849 in the intervention site and $61,596 in the comparison site. The population in each site was predominately white (41% in the intervention site, 48% in the comparison site) and/or of Hispanic or Latino ethnicity (26% in the intervention site, 33% in the comparison site). The number of students vaccinated by the SLIV intervention ranged from 7,502 to 10,106 (22%-28% of eligible students) each year. During the intervention, influenza vaccination coverage among elementary students was 53%-66% in the comparison district. Coverage was similar between the intervention and comparison districts in influenza seasons 2014-2015 and 2015-2016 and was significantly higher in the intervention site in seasons 2016-2017 (7%; 95% CI 4, 11; p < 0.001) and 2017-2018 (11%; 95% CI 7, 15; p < 0.001). During seasons when vaccination coverage was higher among intervention schools and the vaccine was moderately effective, there was evidence of statistically significant indirect effects: The DID in the incidence of influenza hospitalization per 100,000 in the intervention versus comparison site was -17 (95% CI -30, -4; p = 0.008) in 2016-2017 and -37 (95% CI -54, -19; p < 0.001) in 2017-2018 among non-elementary-school-aged individuals and -73 (95% CI -147, 1; p = 0.054) in 2016-2017 and -160 (95% CI -267, -53; p = 0.004) in 2017-2018 among adults 65 years or older. The DID in illness-related school absences per 100 school days during the influenza season was -0.63 (95% CI -1.14, -0.13; p = 0.014) in 2016-2017 and -0.80 (95% CI -1.28, -0.31; p = 0.001) in 2017-2018. Limitations of this study include the use of an observational design, which may be subject to unmeasured confounding, and caregiver-reported vaccination status, which is subject to poor recall and low response rates.A city-wide SLIV intervention in a large, diverse urban population was associated with a decrease in the incidence of laboratory-confirmed influenza hospitalization in all age groups and a decrease in illness-specific school absence rate among students in 2016-2017 and 2017-2018, seasons when the vaccine was moderately effective, suggesting that the intervention produced indirect effects. Our findings suggest that in populations with moderately high background levels of influenza vaccination coverage, SLIV programs are associated with further increases in coverage and reduced influenza across the community.

    View details for DOI 10.1371/journal.pmed.1003238

    View details for Web of Science ID 000563452200004

    View details for PubMedID 32810149

    View details for PubMedCentralID PMC7433855

  • Substantial underestimation of SARS-CoV-2 infection in the United States. Nature communications Wu, S. L., Mertens, A. N., Crider, Y. S., Nguyen, A. n., Pokpongkiat, N. N., Djajadi, S. n., Seth, A. n., Hsiang, M. S., Colford, J. M., Reingold, A. n., Arnold, B. F., Hubbard, A. n., Benjamin-Chung, J. n. 2020; 11 (1): 4507

    Abstract

    Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Here, we use a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy. We estimate 6,454,951 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) in the United States as of April 18, 2020. Accounting for uncertainty, the number of infections during this period was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference is due to incomplete testing, while 14% (0.3-36%) is due to imperfect test accuracy. The approach can readily be applied in future studies in other locations or at finer spatial scale to correct for biased testing and imperfect diagnostic accuracy to provide a more realistic assessment of COVID-19 burden.

    View details for DOI 10.1038/s41467-020-18272-4

    View details for PubMedID 32908126

    View details for PubMedCentralID PMC7481226

  • A Randomized Controlled Trial to Measure Spillover Effects of a Combined Water, Sanitation, and Handwashing Intervention in Rural Bangladesh AMERICAN JOURNAL OF EPIDEMIOLOGY Benjamin-Chung, J., Amin, N., Ercumen, A., Arnold, B. F., Hubbard, A. E., Unicomb, L., Rahman, M., Luby, S. P., Colford, J. M. 2018; 187 (8): 1733–44

    Abstract

    Water, sanitation, and handwashing interventions may confer spillover effects on neighbors of intervention recipients by interrupting pathogen transmission. We measured geographically local spillovers in WASH Benefits, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention vs. control participants. WASH Benefits randomly allocated geographically-defined clusters to a compound-level intervention (chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control. From January to August 2015, in 180 clusters, we enrolled 1,799 neighboring children age-matched to trial participants that would have been eligible for WASH Benefits had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples, measured soil-transmitted helminth infections, and recorded caregiver-reported diarrhea and respiratory illness. Neighbors' characteristics were balanced across arms. The prevalence of detectable E. coli in tubewell samples was lower for neighbors of intervention vs. control trial participants (prevalence ratio = 0.83; 0.73, 0.95). There was no difference in fecal indicator bacteria prevalence between arms for other environmental samples. Prevalence was similar in neighbors of intervention vs. control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors' tubewell water contamination but did not impact neighboring children's health.

    View details for PubMedID 29596644

    View details for PubMedCentralID PMC6070113

  • Spillover effects in epidemiology: parameters, study designs and methodological considerations INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Benjamin-Chung, J., Arnold, B. F., Berger, D., Luby, S. P., Miguel, E., Colford, J. M., Hubbard, A. E. 2018; 47 (1): 332–47

    Abstract

    Many public health interventions provide benefits that extend beyond their direct recipients and impact people in close physical or social proximity who did not directly receive the intervention themselves. A classic example of this phenomenon is the herd protection provided by many vaccines. If these 'spillover effects' (i.e. 'herd effects') are present in the same direction as the effects on the intended recipients, studies that only estimate direct effects on recipients will likely underestimate the full public health benefits of the intervention. Causal inference assumptions for spillover parameters have been articulated in the vaccine literature, but many studies measuring spillovers of other types of public health interventions have not drawn upon that literature. In conjunction with a systematic review we conducted of spillovers of public health interventions delivered in low- and middle-income countries, we classified the most widely used spillover parameters reported in the empirical literature into a standard notation. General classes of spillover parameters include: cluster-level spillovers; spillovers conditional on treatment or outcome density, distance or the number of treated social network links; and vaccine efficacy parameters related to spillovers. We draw on high quality empirical examples to illustrate each of these parameters. We describe study designs to estimate spillovers and assumptions required to make causal inferences about spillovers. We aim to advance and encourage methods for spillover estimation and reporting by standardizing spillover parameter nomenclature and articulating the causal inference assumptions required to estimate spillovers.

    View details for PubMedID 29106568

    View details for PubMedCentralID PMC5837695

  • Scaling Up a Water, Sanitation, and Hygiene Program in Rural Bangladesh: The Role of Program Implementation. American journal of public health Benjamin-Chung, J., Sultana, S., Halder, A. K., Ahsan, M. A., Arnold, B. F., Hubbard, A. E., Unicomb, L., Luby, S. P., Colford, J. M. 2017; 107 (5): 694-701

    Abstract

    To evaluate whether the quality of implementation of a water, sanitation, and hygiene program called SHEWA-B and delivered by UNICEF to 20 million people in rural Bangladesh was associated with health behaviors and sanitation infrastructure access.We surveyed 33 027 households targeted by SHEWA-B and 1110 SHEWA-B hygiene promoters in 2011 and 2012. We developed an implementation quality index and compared the probability of health behaviors and sanitation infrastructure access in counterfactual scenarios over the range of implementation quality.Forty-seven percent of households (n = 14 622) had met a SHEWA-B hygiene promoter, and 47% of hygiene promoters (n = 527) could recall all key program messages. The frequency of hygiene promoter visits was not associated with improved outcomes. Higher implementation quality was not associated with better health behaviors or infrastructure access. Outcomes differed by only 1% to 3% in scenarios in which all clusters received low versus high implementation quality.SHEWA-B did not meet UNICEF's ideal implementation quality in any area. Improved implementation quality would have resulted in marginal changes in health behaviors or infrastructure access. This suggests that SHEWA-B's design was suboptimal for improving these outcomes.

    View details for DOI 10.2105/AJPH.2017.303686

    View details for PubMedID 28323462

  • Spillover effects on health outcomes in low- and middle-income countries: a systematic review. International journal of epidemiology Benjamin-Chung, J., Abedin, J., Berger, D., Clark, A., Jimenez, V., Konagaya, E., Tran, D., Arnold, B. F., Hubbard, A. E., Luby, S. P., Miguel, E., Colford, J. M. 2017

    Abstract

    Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity. Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects.We searched 19 electronic databases for articles published before 2014 and hand-searched titles from 2010 to 2013 in five relevant journals. We adapted the Cochrane Collaboration's quality grading tool for spillover estimation and rated the quality of evidence.A total of 54 studies met inclusion criteria. We found a wide range of terminology used to describe spillovers, a lack of standardization among spillover methods and poor reporting of spillovers in many studies. We identified three primary mechanisms of spillovers: reduced disease transmission, social proximity and substitution of resources within households. We found the strongest evidence for spillovers through reduced disease transmission, particularly vaccines and mass drug administration. In general, the proportion of a population receiving an intervention was associated with improved health. Most studies were of moderate or low quality. We found evidence of publication bias for certain spillover estimates but not for total or direct effects. To facilitate improved reporting and standardization in future studies, we developed a reporting checklist adapted from the CONSORT framework specific to reporting spillover effects.We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease. There was little high quality evidence of spillovers for other interventions.

    View details for DOI 10.1093/ije/dyx039

    View details for PubMedID 28449030

  • Improved Child Feces Management Mediates Reductions in Childhood Diarrhea from an On-Site Sanitation Intervention: Causal Mediation Analysis of a Cluster-Randomized Trial in Rural Bangladesh. Journal of epidemiology and global health Contreras, J. D., Islam, M., Mertens, A., Pickering, A. J., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Rahman, M., Unicomb, L., Luby, S. P., Colford, J. M., Ercumen, A. 2024

    Abstract

    The WASH benefits Bangladesh trial multi-component sanitation intervention reduced diarrheal disease among children < 5 years. Intervention components included latrine upgrades, child feces management tools, and behavioral promotion. It remains unclear which components most impacted diarrhea.We conducted mediation analysis within a subset of households (n = 720) from the sanitation and control arms. Potential mediators were categorized into indicators of latrine quality, latrine use practices, and feces management practices. We estimated average causal mediation effects (ACME) as prevalence differences (PD), defined as the intervention's effect on diarrhea through its effect on the mediator.The intervention improved all indicators compared to controls. We found significant mediation through multiple latrine use and feces management practice indicators. The strongest mediators during monsoon seasons were reduced open defecation among children aged < 3 and 3-8 years, and increased disposal of child feces into latrines. The strongest mediators during dry seasons were access to a flush/pour-flush latrine, reduced open defecation among children aged 3-8 years, and increased disposal of child feces into latrines. Individual mediation effects were small (PD = 0.5-2 percentage points) compared to the overall intervention effect but collectively describe significant mediation pathways.The effect of the WASH Benefits Bangladesh sanitation intervention on diarrheal disease was mediated through improved child feces management and reduced child open defecation. Although the intervention significantly improved latrine quality, relatively high latrine quality at baseline may have limited benefits from additional improvements. Targeting safe child feces management may increase the health benefits of rural sanitation interventions.

    View details for DOI 10.1007/s44197-024-00210-y

    View details for PubMedID 38507184

    View details for PubMedCentralID 7579056

  • Is detection of enteropathogens and human or animal faecal markers in the environment associated with subsequent child enteric infections and growth: an individual participant data meta-analysis. The Lancet. Global health Mertens, A., Arnold, B. F., Benjamin-Chung, J., Boehm, A. B., Brown, J., Capone, D., Clasen, T., Fuhrmeister, E. R., Grembi, J. A., Holcomb, D., Knee, J., Kwong, L. H., Lin, A., Luby, S. P., Nala, R., Nelson, K., Njenga, S. M., Null, C., Pickering, A. J., Rahman, M., Reese, H. E., Steinbaum, L., Stewart, J. R., Thilakaratne, R., Cumming, O., Colford, J. M., Ercumen, A. 2024; 12 (3): e433-e444

    Abstract

    Quantifying contributions of environmental faecal contamination to child diarrhoea and growth faltering can illuminate causal mechanisms behind modest health benefits in recent water, sanitation, and hygiene (WASH) trials. We aimed to assess associations between environmental detection of enteropathogens and human or animal microbial source tracking markers (MSTM) and subsequent child health outcomes.In this individual participant data meta-analysis we searched we searched PubMed, Embase, CAB Direct Global Health, Agricultural and Environmental Science Database, Web of Science, and Scopus for WASH intervention studies with a prospective design and concurrent control that measured enteropathogens or MSTM in environmental samples, or both, and subsequently measured enteric infections, diarrhoea, or height-for-age Z-scores (HAZ) in children younger than 5 years. We excluded studies that only measured faecal indicator bacteria. The initial search was done on Jan 19, 2021, and updated on March 22, 2023. One reviewer (AM) screened abstracts, and two independent reviewers (AM and RT) examined the full texts of short-listed articles. All included studies include at least one author that also contributed as an author to the present Article. Our primary outcomes were the 7-day prevalence of caregiver-reported diarrhoea and HAZ in children. For specific enteropathogens in the environment, primary outcomes also included subsequent child infection with the same pathogen ascertained by stool testing. We estimated associations using covariate-adjusted regressions and pooled estimates across studies.Data from nine published reports from five interventions studies, which included 8603 children (4302 girls and 4301 boys), were included in the meta-analysis. Environmental pathogen detection was associated with increased infection prevalence with the same pathogen and lower HAZ (ΔHAZ -0·09 [95% CI -0·17 to -0·01]) but not diarrhoea (prevalence ratio 1·22 [95% CI 0·95 to 1·58]), except during wet seasons. Detection of MSTM was not associated with diarrhoea (no pooled estimate) or HAZ (ΔHAZ -0·01 [-0·13 to 0·11] for human markers and ΔHAZ -0·02 [-0·24 to 0·21] for animal markers). Soil, children's hands, and stored drinking water were major transmission pathways.Our findings support a causal chain from pathogens in the environment to infection to growth faltering, indicating that the lack of WASH intervention effects on child growth might stem from insufficient reductions in environmental pathogen prevalence. Studies measuring enteropathogens in the environment should subsequently measure the same pathogens in stool to further examine theories of change between WASH, faecal contamination, and health. Given that environmental pathogen detection was predictive of infection, programmes targeting specific pathogens (eg, vaccinations and elimination efforts) can environmentally monitor the pathogens of interest for population-level surveillance instead of collecting individual biospecimens.The Bill & Melinda Gates Foundation and the UK Foreign and Commonwealth Development Office.

    View details for DOI 10.1016/S2214-109X(23)00563-6

    View details for PubMedID 38365415

  • WASH interventions and child diarrhea at the interface of climate and socioeconomic position in Bangladesh. Nature communications Ante-Testard, P. A., Rerolle, F., Nguyen, A. T., Ashraf, S., Parvez, S. M., Naser, A. M., Benmarhnia, T., Rahman, M., Luby, S. P., Benjamin-Chung, J., Arnold, B. F. 2024; 15 (1): 1556

    Abstract

    Many diarrhea-causing pathogens are climate-sensitive, and populations with the lowest socioeconomic position (SEP) are often most vulnerable to climate-related transmission. Household Water, Sanitation, and Handwashing (WASH) interventions constitute one potential effective strategy to reduce child diarrhea, especially among low-income households. Capitalizing on a cluster randomized trial population (360 clusters, 4941 children with 8440 measurements) in rural Bangladesh, one of the world's most climate-sensitive regions, we show that improved WASH substantially reduces diarrhea risk with largest benefits among children with lowest SEP and during the monsoon season. We extrapolated trial results to rural Bangladesh regions using high-resolution geospatial layers to identify areas most likely to benefit. Scaling up a similar intervention could prevent an estimated 734 (95% CI 385, 1085) cases per 1000 children per month during the seasonal monsoon, with marked regional heterogeneities. Here, we show how to extend large-scale trials to inform WASH strategies among climate-sensitive and low-income populations.

    View details for DOI 10.1038/s41467-024-45624-1

    View details for PubMedID 38378704

    View details for PubMedCentralID 10118100

  • Geographic pair matching in large-scale cluster randomized trials. Nature communications Arnold, B. F., Rerolle, F., Tedijanto, C., Njenga, S. M., Rahman, M., Ercumen, A., Mertens, A., Pickering, A. J., Lin, A., Arnold, C. D., Das, K., Stewart, C. P., Null, C., Luby, S. P., Colford, J. M., Hubbard, A. E., Benjamin-Chung, J. 2024; 15 (1): 1069

    Abstract

    Cluster randomized trials are often used to study large-scale public health interventions. In large trials, even small improvements in statistical efficiency can have profound impacts on the required sample size and cost. Location integrates many socio-demographic and environmental characteristics into a single, readily available feature. Here we show that pair matching by geographic location leads to substantial gains in statistical efficiency for 14 child health outcomes that span growth, development, and infectious disease through a re-analysis of two large-scale trials of nutritional and environmental interventions in Bangladesh and Kenya. Relative efficiencies from pair matching are ≥1.1 for all outcomes and regularly exceed 2.0, meaning an unmatched trial would need to enroll at least twice as many clusters to achieve the same level of precision as the geographically pair matched design. We also show that geographically pair matched designs enable estimation of fine-scale, spatially varying effect heterogeneity under minimal assumptions. Our results demonstrate broad, substantial benefits of geographic pair matching in large-scale, cluster randomized trials.

    View details for DOI 10.1038/s41467-024-45152-y

    View details for PubMedID 38316755

    View details for PubMedCentralID 1448268

  • Child wasting and concurrent stunting in low- and middle-income countries NATURE Mertens, A., Benjamin-Chung, J., Colford Jr, J. M., Hubbard, A. E., van der Laan, M. J., Coyle, J., Sofrygin, O., Cai, W., Jilek, W., Rosete, S., Nguyen, A., Pokpongkiat, N. N., Djajadi, S., Seth, A., Jung, E., Chung, E. O., Malenica, I., Hejazi, N., Li, H., Hafen, R., Subramoney, V., Haggstrom, J., Norman, T., Christian, P., Brown, K. H., Arnold, B. F. 2023
  • Causes and consequences of child growth faltering in low-resource settings NATURE Mertens, A., Benjamin-Chung, J., Jr, J., Coyle, J., Van der Laan, M. J., Hubbard, A. E., Rosete, S., Malenica, I., Hejazi, N., Sofrygin, O., Cai, W., Li, H., Nguyen, A., Pokpongkiat, N. N., Djajadi, S., Seth, A., Jung, E., Chung, E. O., Jilek, W., Subramoney, V., Hafen, R., Haggstrom, J., Norman, T., Brown, K. H., Christian, P., Arnold, B. F., Ki Child Growth Consortium 2023
  • Rigour and reproducibility in perinatal and paediatric epidemiologic research using big data. Paediatric and perinatal epidemiology Nguyen, A., Benjamin-Chung, J. 2023

    View details for DOI 10.1111/ppe.12971

    View details for PubMedID 36959100

  • Assessing sustained uptake of latrine and child feces management interventions: Extended follow-up of a cluster-randomized controlled trial in rural Bangladesh 1-3.5 years after intervention initiation. International journal of hygiene and environmental health Islam, M., Rahman, M., Kafi, M. A., Unicomb, L., Rahman, M., Mertens, A., Benjamin-Chung, J., Arnold, B. F., Colford, J. M., Luby, S. P., Ercumen, A. 2023; 250: 114149

    Abstract

    BACKGROUND: Sanitation interventions typically result in modest increases in latrine access, and any gains in latrine access and use are often not sustained over time. Sanitation programs also rarely include child-focused interventions such as potties. We aimed to assess the sustained effect of a multi-component sanitation intervention on access to and use of latrines and child feces management tools in rural Bangladesh.METHODS: We conducted a longitudinal substudy nested within the WASH Benefits randomized controlled trial. The trial provided latrine upgrades, child potties and sani-scoops for feces removal, along with behavior change promotion to encourage use of the delivered hardware. Promotion visits to intervention recipients were frequent during the first 2 years after intervention initiation, decreased in frequency between years 2-3, and ceased after 3 years. We enrolled a random subset of 720 households from the sanitation and control arms of the trial in a substudy and visited them quarterly between 1 and 3.5 years after intervention initiation. At each visit, field staff recorded sanitation-related behaviors through spot-check observations and structured questionnaires. We assessed intervention effects on observed indicators of hygienic latrine access, potty use and sani-scoop use and investigated whether these effects were modified by duration of follow-up, ongoing behavior change promotion and household characteristics.RESULTS: The intervention increased hygienic latrine access from 37% among controls to 94% in the sanitation arm (p<0.001). Access among intervention recipients remained high 3.5 years after intervention initiation, including periods with no active promotion. Gains in access were higher among households with less education, less wealth and larger number of residents. The intervention increased availability of child potties from 29% among controls to 98% in the sanitation arm (p<0.001). However, fewer than 25% of intervention households reported exclusive child defecation in a potty or had observed indicators of potty and sani-scoop use, and gains in potty use declined over the follow-up period, even with ongoing promotion.CONCLUSION: Our findings from an intervention that provided free products and intensive initial behavior change promotion suggest a sustained increase in hygienic latrine access up to 3.5 years after intervention initiation but infrequent use of child feces management tools. Studies should investigate strategies to ensure sustained adoption of safe child feces management practices.

    View details for DOI 10.1016/j.ijheh.2023.114149

    View details for PubMedID 36913791

  • Effects of water, sanitation, and hygiene interventions on detection of enteropathogens and host-specific faecal markers in the environment: a systematic review and individual participant data meta-analysis. The Lancet. Planetary health Mertens, A., Arnold, B. F., Benjamin-Chung, J., Boehm, A. B., Brown, J., Capone, D., Clasen, T., Fuhrmeister, E., Grembi, J. A., Holcomb, D., Knee, J., Kwong, L. H., Lin, A., Luby, S. P., Nala, R., Nelson, K., Njenga, S. M., Null, C., Pickering, A. J., Rahman, M., Reese, H. E., Steinbaum, L., Stewart, J., Thilakaratne, R., Cumming, O., Colford, J. M., Ercumen, A. 2023; 7 (3): e197-e208

    Abstract

    Water, sanitation, and hygiene (WASH) improvements are promoted to reduce diarrhoea in low-income countries. However, trials from the past 5 years have found mixed effects of household-level and community-level WASH interventions on child health. Measuring pathogens and host-specific faecal markers in the environment can help investigate causal pathways between WASH and health by quantifying whether and by how much interventions reduce environmental exposure to enteric pathogens and faecal contamination from human and different animal sources. We aimed to assess the effects of WASH interventions on enteropathogens and microbial source tracking (MST) markers in environmental samples.We did a systematic review and individual participant data meta-analysis, which included searches from Jan 1, 2000, to Jan 5, 2023, from PubMed, Embase, CAB Direct Global Health, Agricultural and Environmental Science Database, Web of Science, and Scopus, of prospective studies with water, sanitation, or hygiene interventions and concurrent control group that measured pathogens or MST markers in environmental samples and measured child anthropometry, diarrhoea, or pathogen-specific infections. We used covariate-adjusted regression models with robust standard errors to estimate study-specific intervention effects and pooled effect estimates across studies using random-effects models.Few trials have measured the effect of sanitation interventions on pathogens and MST markers in the environment and they mostly focused on onsite sanitation. We extracted individual participant data on nine environmental assessments from five eligible trials. Environmental sampling included drinking water, hand rinses, soil, and flies. Interventions were consistently associated with reduced pathogen detection in the environment but effect estimates in most individual studies could not be distinguished from chance. Pooled across studies, we found a small reduction in the prevalence of any pathogen in any sample type (pooled prevalence ratio [PR] 0·94 [95% CI 0·90-0·99]). Interventions had no effect on the prevalence of MST markers from humans (pooled PR 1·00 [95% CI 0·88-1·13]) or animals (pooled PR 1·00 [95% CI 0·97-1·03]).The small effect of these sanitation interventions on pathogen detection and absence of effects on human or animal faecal markers are consistent with the small or null health effects previously reported in these trials. Our findings suggest that the basic sanitation interventions implemented in these studies did not contain human waste and did not adequately reduce exposure to enteropathogens in the environment.Bill and Melinda Gates Foundation and the UK Foreign and Commonwealth Development Office.

    View details for DOI 10.1016/S2542-5196(23)00028-1

    View details for PubMedID 36889861

  • Effects of water, sanitation, and hygiene interventions on detection of enteropathogens and host-specific faecal markers in the environment: a systematic review and individual participant data meta-analysis LANCET PLANETARY HEALTH Mertens, A., Arnold, B. F., Benjamin-Chung, J., Boehm, A. B., Brown, J., Capone, D., Clasen, T., Fuhrmeister, E., Grembi, J. A., Holcomb, D., Knee, J., Kwong, L. H., Lin, A., Luby, S. P., Nala, R., Nelson, K., Njenga, S. M., Null, C., Pickering, A. J., Rahman, M., Reese, H. E., Steinbaum, L., Stewart, J., Thilakaratne, R., Cumming, O., Colford, J. M., Ercumen, A. 2023; 7 (3): E197-E208
  • The effect of a large-scale water, sanitation and hygiene intervention in Bangladesh on knowledge, behaviour and health: Findings from an endline programme evaluation TROPICAL MEDICINE & INTERNATIONAL HEALTH Aluri, K., Halder, A. K., Islam, M., Benjamin-Chung, J., Alam, M., Shoab, A., Rahman, M., Unicomb, L., Luby, S. P. 2022

    Abstract

    The Sanitation, Hygiene Education and Water Supply in Bangladesh Programme (SHEWA-B) was a 5-year intervention aiming to improve water, sanitation and hygiene (WASH) practices among 20 million rural residents through community hygiene promoters. This analysis evaluates the impact of SHEWA-B on knowledge, behaviour and childhood diarrhoea outcomes.The evaluation included repeated cross-sectional surveys and health surveillance in matched cohorts in intervention and control clusters. Cross-sectional surveys and structured observations at baseline, midline, and endline assessed the availability of WASH technology, caregiver knowledge and behaviour. Fieldworkers collected monthly health data in a subset of control and intervention households to determine the prevalence of diarrhoea.Of 5091 households surveyed, participants residing in intervention clusters showed minimal improvements in knowledge, reported behaviour, or use of WASH technology compared to the control clusters. During structured observations, intervention households increased more than control households at handwashing before preparing food and after cleaning a baby's anus when comparing endline to baseline, but these changes were not seen when comparing endline to the midline. The prevalence of childhood diarrhoea remained similar in both groups before (10.2% in intervention, 10.0% in control) and after (8.8% in intervention, 11.7% in control) midline changes were made to improve the intervention. Intervention clusters showed no improvement in diarrhoea over time compared to control clusters.SHEWA-B's community-based WASH promotion did not yield the intended impact on knowledge, behaviour or health. Greater priority should be given to approaches that have demonstrated effectiveness. Including rigorous evaluations would broaden the evidence base to support and improve large-scale programmes.

    View details for DOI 10.1111/tmi.13813

    View details for Web of Science ID 000852794600001

    View details for PubMedID 36096154

  • Influence of community-level sanitation coverage and population density on environmental fecal contamination and child health in a longitudinal cohort in rural Bangladesh. International journal of hygiene and environmental health Contreras, J. D., Islam, M., Mertens, A., Pickering, A. J., Kwong, L. H., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Alam, M., Sen, D., Islam, S., Rahman, M., Unicomb, L., Luby, S. P., Colford, J. M., Ercumen, A. 2022; 245: 114031

    Abstract

    BACKGROUND: Household-level sanitation interventions have had limited effects on child health or environmental contamination, potentially due to low community coverage. Higher community-level coverage with safely managed sanitation can reduce opportunities for disease transmission.METHODS: We estimated associations between community sanitation coverage, environmental fecal contamination, and child health among 360 compounds in the control arm of the WASH Benefits trial in rural Bangladesh (NCT01590095). In each compound, we enumerated E. coli in environmental samples and recorded the 7-day prevalence of caregiver-reported diarrheal disease and acute respiratory infections (ARI) in children under five. We observed indicators of latrine access and quality among all neighboring compounds within 100m of study compounds. We defined community coverage as the proportion of neighboring compounds with (1) at least one latrine, and (2) exclusively hygienic latrines (improved facility observed to safely contain feces), within both 50m and 100m of study compounds. We assessed effect modification by population density and season.RESULTS: Adjusted for confounders, study compounds surrounded by 100% coverage of at least one latrine per compound within 50m had slightly lower log10E. coli counts in stored water (Deltalog=-0.13, 95% CI -0.26, -0.01), child hand rinses (Deltalog=-0.13, 95% CI -0.24, -0.02), and caregiver hand rinses (Deltalog=-0.16, 95% CI -0.29, -0.03) and marginally lower prevalence of diarrheal disease (prevalence ratio [PR]=0.82, 95% CI 0.64, 1.04) and ARI (PR=0.84, 95% CI 0.69, 1.03) compared to compounds surrounded by <100% coverage. Effects were similar but less pronounced at 100m. At higher population densities, community latrine coverage was associated with larger reductions in E. coli on child and caregiver hands and prevalence of diarrheal disease. Coverage with exclusively hygienic latrines was not associated with any outcome.CONCLUSION: Higher community sanitation coverage was associated with reduced fecal contamination and improved child health, with stronger effects at highly local scales (50m) and at high population densities. Our findings indicate that the relationship between community sanitation coverage, environmental contamination, and child health varies by definition of coverage, distance, and population density. This work highlights significant uncertainty around how to best measure sanitation coverage and the expected health effects of increasing sanitation coverage using a specific metric. Better understanding of community-level sanitation access is needed to inform policy for implementing sanitation systems that effectively protect community health.

    View details for DOI 10.1016/j.ijheh.2022.114031

    View details for PubMedID 36058111

  • Evaluation of an on-site sanitation intervention against childhood diarrhea and acute respiratory infection 1 to 3.5 years after implementation: Extended follow-up of a cluster-randomized controlled trial in rural Bangladesh. PLoS medicine Contreras, J. D., Islam, M., Mertens, A., Pickering, A. J., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Rahman, M., Unicomb, L., Luby, S. P., Colford, J. M., Ercumen, A. 2022; 19 (8): e1004041

    Abstract

    BACKGROUND: Diarrhea and acute respiratory infection (ARI) are leading causes of death in children. The WASH Benefits Bangladesh trial implemented a multicomponent sanitation intervention that led to a 39% reduction in the prevalence of diarrhea among children and a 25% reduction for ARI, measured 1 to 2 years after intervention implementation. We measured longer-term intervention effects on these outcomes between 1 to 3.5 years after intervention implementation, including periods with differing intensity of behavioral promotion.METHODS AND FINDINGS: WASH Benefits Bangladesh was a cluster-randomized controlled trial of water, sanitation, hygiene, and nutrition interventions (NCT01590095). The sanitation intervention included provision of or upgrades to improved latrines, sani-scoops for feces removal, children's potties, and in-person behavioral promotion. Promotion was intensive up to 2 years after intervention initiation, decreased in intensity between years 2 to 3, and stopped after 3 years. Access to and reported use of latrines was high in both arms, and latrine quality was significantly improved by the intervention, while use of child feces management tools was low. We enrolled a random subset of households from the sanitation and control arms into a longitudinal substudy, which measured child health with quarterly visits between 1 to 3.5 years after intervention implementation. The study period therefore included approximately 1 year of high-intensity promotion, 1 year of low-intensity promotion, and 6 months with no promotion. We assessed intervention effects on diarrhea and ARI prevalence among children <5 years through intention-to-treat analysis using generalized linear models with robust standard errors. Masking was not possible during data collection, but data analysis was masked. We enrolled 720 households (360 per arm) from the parent trial and made 9,800 child observations between June 2014 and December 2016. Over the entire study period, diarrheal prevalence was lower among children in the sanitation arm (11.9%) compared to the control arm (14.5%) (prevalence ratio [PR] = 0.81, 95% CI 0.66, 1.00, p = 0.05; prevalence difference [PD] = -0.027, 95% CI -0.053, 0, p = 0.05). ARI prevalence did not differ between sanitation (21.3%) and control (22.7%) arms (PR = 0.93, 95% CI 0.82, 1.05, p = 0.23; PD = -0.016, 95% CI -0.043, 0.010, p = 0.23). There were no significant differences in intervention effects between periods with high-intensity versus low-intensity/no promotion. Study limitations include use of caregiver-reported symptoms to define health outcomes and limited data collected after promotion ceased.CONCLUSIONS: The observed effect of the WASH Benefits Bangladesh sanitation intervention on diarrhea in children appeared to be sustained for at least 3.5 years after implementation, including 1.5 years after heavy promotion ceased. Existing latrine access was high in the study setting, suggesting that improving on-site latrine quality can deliver health benefits when latrine use practices are in place. Further work is needed to understand how latrine adoption can be achieved and sustained in settings with low existing access and how sanitation programs can adopt transformative approaches of excreta management, including safe disposal of child and animal feces, to generate a hygienic home environment.TRIAL REGISTRATION: ClinicalTrials.gov; NCT01590095; https://clinicaltrials.gov/ct2/show/NCT01590095.

    View details for DOI 10.1371/journal.pmed.1004041

    View details for PubMedID 35939520

  • A Review of the Ring Trial Design for Evaluating Ring Interventions for Infectious Diseases. Epidemiologic reviews Butzin-Dozier, Z., Athni, T. S., Benjamin-Chung, J. 2022

    Abstract

    In trials of infectious disease interventions, rare outcomes and unpredictable spatiotemporal variation can introduce bias, reduce statistical power, and prevent conclusive inferences. Spillover effects can complicate inference if individual randomization is used to gain efficiency. Ring trials are a type of cluster-randomized trial that may increase efficiency and minimize bias, particularly in emergency and elimination settings with strong clustering of infection. They can be used to evaluate ring interventions, which are delivered to individuals in proximity to or contact with index cases. Here we review ring trials, compare them to other trial designs for evaluating ring interventions, and describe strengths and weaknesses of each design. We conducted a systematic review to identify trials and trial protocols evaluating ring interventions. Of 849 articles and 322 protocols screened, we identified 26 ring trials, 15 cluster-randomized trials, five trials that randomized households or individuals within rings, and one individually randomized trial. The most common interventions were post-exposure prophylaxis (n = 23) and focal mass drug administration and screening and treatment (n = 7). Ring trials require robust surveillance systems and contact tracing for directly transmitted diseases. For rare diseases with strong spatiotemporal clustering, they may have higher efficiency and internal validity than cluster-randomized designs in part because they ensure that no clusters are excluded from analysis due to zero cluster incidence. Though further research is needed to compare them to other types of trials, ring trials hold promise as a design that can increase trial speed and efficiency while reducing bias.

    View details for DOI 10.1093/epirev/mxac003

    View details for PubMedID 35593400

  • Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh SCIENCE Abaluck, J., Kwong, L. H., Styczynski, A., Haque, A., Kabir, M., Bates-Jefferys, E., Crawford, E., Benjamin-Chung, J., Raihan, S., Rahman, S., Benhachmi, S., Bintee, N., Winch, P. J., Hossain, M., Reza, H., Jaber, A., Momen, S., Rahman, A., Banti, F., Huq, T., Luby, S. P., Mobarak, A. 2022; 375 (6577): 160-+
  • Evaluating the robustness of targeted maximum likelihood estimators via realistic simulations in nutrition intervention trials. Statistics in medicine Li, H., Rosete, S., Coyle, J., Phillips, R. V., Hejazi, N. S., Malenica, I., Arnold, B. F., Benjamin-Chung, J., Mertens, A., Colford, J. M., van der Laan, M. J., Hubbard, A. E. 2022

    Abstract

    Several recently developed methods have the potential to harness machine learning in the pursuit of target quantities inspired by causal inference, including inverse weighting, doubly robust estimating equations and substitution estimators like targeted maximum likelihood estimation. There are even more recent augmentations of these procedures that can increase robustness, by adding a layer of cross-validation (cross-validated targeted maximum likelihood estimation and double machine learning, as applied to substitution and estimating equation approaches, respectively). While these methods have been evaluated individually on simulated and experimental data sets, a comprehensive analysis of their performance across real data based simulations have yet to be conducted. In this work, we benchmark multiple widely used methods for estimation of the average treatment effect using ten different nutrition intervention studies data. A nonparametric regression method, undersmoothed highly adaptive lasso, is used to generate the simulated distribution which preserves important features from the observed data and reproduces a set of true target parameters. For each simulated data, we apply the methods above to estimate the average treatment effects as well as their standard errors and resulting confidence intervals. Based on the analytic results, a general recommendation is put forth for use of the cross-validated variants of both substitution and estimating equation estimators. We conclude that the additional layer of cross-validation helps in avoiding unintentional over-fitting of nuisance parameter functionals and leads to more robust inferences.

    View details for DOI 10.1002/sim.9348

    View details for PubMedID 35172378

  • Evaluation of a city-wide school-located influenza vaccination program in Oakland, California with respect to race and ethnicity: A matched cohort study. Vaccine Nguyen, A. T., Arnold, B. F., Kennedy, C. J., Mishra, K., Pokpongkiat, N. N., Seth, A., Djajadi, S., Holbrook, K., Pan, E., Kirley, P. D., Libby, T., Hubbard, A. E., Reingold, A., Colford, J. M., Benjamin-Chung, J. 2021

    Abstract

    BACKGROUND: Increasing influenza vaccination coverage in school-aged children may substantially reduce community transmission. School-located influenza vaccinations (SLIV) aim to promote vaccinations by increasing accessibility, which may be especially beneficial to race/ethnicity groups that face high barriers to preventative care. Here, we evaluate the effectiveness of a city-wide SLIV program by race/ethnicity from 2014 to 2018.METHODS: We used multivariate matching to pair schools in the intervention district in Oakland, CA with schools in a comparison district in West Contra Costa County, CA. We distributed cross-sectional surveys to measure caregiver-reported student vaccination status and estimated differences in vaccination coverage levels and reasons for non-vaccination between districts stratifying by race/ethnicity. We estimated difference-in-differences (DID) of laboratory confirmed influenza hospitalization incidence between districts stratified by race/ethnicity using surveillance data.RESULTS: Differences in influenza vaccination coverage in the intervention vs. comparison district were larger among White (2017-18: 21.0% difference [95% CI: 9.7%, 32.3%]) and Hispanic/Latino (13.4% [8.8%, 18.0%]) students than Asian/Pacific Islander (API) (8.9% [1.3%, 16.5%]), Black (5.9% [-2.2%, 14.0%]), and multiracial (6.3% [-1.8%, 14.3%)) students. Concerns about vaccine effectiveness or safety were more common among Black and multiracial caregivers. Logistical barriers were less common in the intervention vs. comparison district, with the largest difference among White students. In both districts, hospitalizations in 2017-18 were higher in Blacks (Intervention: 111.5 hospitalizations per 100,00; Comparison: 134.1 per 100,000) vs. other races/ethnicities. All-age influenza hospitalization incidence was lower in the intervention site vs. comparison site among White/API individuals in 2016-17 (DID -25.14 per 100,000 [95% CI: -40.14, -10.14]) and 2017-18 (-36.6 per 100,000 [-52.7, -20.5]) and Black older adults in 2017-18 (-282.2 per 100,000 (-508.4, -56.1]), but not in other groups.CONCLUSIONS: SLIV was associated with higher vaccination coverage and lower influenza hospitalization, but associations varied by race/ethnicity. SLIV alone may be insufficient to ensure equitable influenza outcomes.

    View details for DOI 10.1016/j.vaccine.2021.11.073

    View details for PubMedID 34872797

  • Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh. Science (New York, N.Y.) Abaluck, J., Kwong, L. H., Styczynski, A., Haque, A., Kabir, M. A., Bates-Jefferys, E., Crawford, E., Benjamin-Chung, J., Raihan, S., Rahman, S., Benhachmi, S., Bintee, N. Z., Winch, P. J., Hossain, M., Reza, H. M., Jaber, A. A., Momen, S. G., Rahman, A., Banti, F. L., Huq, T. S., Luby, S. P., Mobarak, A. M. 2021: eabi9069

    Abstract

    [Figure: see text].

    View details for PubMedID 34855513

  • LONGITUDINAL EFFECTS OF A SANITATION INTERVENTION ON ENVIRONMENTAL FECAL CONTAMINATION IN A CLUSTER-RANDOMIZED CONTROLLED TRIAL IN RURAL BANGLADESH Contreras, J. D., Islam, M., Mertens, A., Pickering, A. J., Kwong, L. H., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Alam, M., Sen, D., Islam, S., Rahman, M., Unicomb, L., Luby, S. P., Colford, J. M., Ercumen, A. AMER SOC TROP MED & HYGIENE. 2021: 287-288
  • City-wide school-located influenza vaccination: A retrospective cohort study. Vaccine Benjamin-Chung, J., Arnold, B. F., Mishra, K., Kennedy, C. J., Nguyen, A., Pokpongkiat, N. N., Djajadi, S., Seth, A., Klein, N. P., Hubbard, A. E., Reingold, A., Colford, J. M. 2021

    Abstract

    BACKGROUND: We measured the effectiveness of a city-wide school-located influenza vaccination (SLIV) program implemented in over 102 elementary schools in Oakland, California.METHODS: We conducted a retrospective cohort study among Kaiser Permanente Northern California (KPNC) members of all ages residing in either the intervention or a multivariate-matched comparison site from September 2011 - August 2017. Outcomes included medically attended acute respiratory illness (MAARI), influenza hospitalization, and Oseltamivir prescriptions. We estimated difference-in-differences (DIDs) in 2014-15, 2015-16, and 2016-17 using generalized linear models and adjusted for race, ethnicity, age, sex, health plan, and language.RESULTS: Pre-intervention member characteristics were similar between sites. The proportion of KPNC members vaccinated for influenza by KPNC or the SLIV program was 8-11% higher in the intervention site than the comparison site during the intervention period. Among school-aged children, SLIV was associated with lower Oseltamivir prescriptions per 1,000 (DIDs: -3.5 (95% CI -5.5, -1.5) in 2015-16; -4.0 (95% CI -6.5, -1.6) in 2016-17) but not with other outcomes. SLIV was associated with lower MAARI per 1,000 in adults 65+years (2014-15: -13.2, 95% CI -23.2, -3.2; 2015-16: -21.5, 95% CI -31.1, -11.9; 2016-17: -13.0, 95% CI -23.2, -2.9). There were few significant associations with other outcomes among adults.CONCLUSIONS: A city-wide SLIV intervention was associated with higher influenza vaccination coverage, lower Oseltamivir prescriptions in school-aged children, and lower MAARI among people over 65years, suggesting possible indirect effects of SLIV among older adults.

    View details for DOI 10.1016/j.vaccine.2021.08.099

    View details for PubMedID 34535312

  • Telomere length is associated with growth in children in rural Bangladesh ELIFE Lin, A., Mertens, A. N., Arnold, B. F., Tan, S., Lin, J., Stewart, C. P., Hubbard, A. E., Ali, S., Benjamin-Chung, J., Shoab, A. K., Rahman, M., Famida, S. L., Hossen, M., Mutsuddi, P., Akther, S., Rahman, M., Unicomb, L., Naved, R., Al Mamun, M., Parvin, K., Dhabhar, F. S., Kariger, P., Fernald, L. H., Luby, S. P., Colford, J. M. 2021; 10
  • Telomere length is associated with growth in children in rural Bangladesh. eLife Lin, A., Mertens, A. N., Arnold, B. F., Tan, S., Lin, J., Stewart, C. P., Hubbard, A. E., Ali, S., Benjamin-Chung, J., Shoab, A. K., Rahman, M. Z., Famida, S. L., Hossen, M. S., Mutsuddi, P., Akther, S., Rahman, M., Unicomb, L., Naved, R. T., Mamun, M. M., Parvin, K., Dhabhar, F. S., Kariger, P., Fernald, L. C., Luby, S. P., Colford, J. M. 2021; 10

    Abstract

    Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score (95% CI 0.05, 0.42; FDR-corrected p-value = 0.01)). TL was not associated with other outcomes.Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first two years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.Funding: Funded by the Bill and Melinda Gates Foundation.

    View details for DOI 10.7554/eLife.60389

    View details for PubMedID 34494545

  • Measuring the Success of the US COVID-19 Vaccine Campaign-It's Time to Invest in and Strengthen Immunization Information Systems. American journal of public health Benjamin-Chung, J., Reingold, A. 2021: e1-e3

    Abstract

    With the recent US Food and Drug Administration approval of the Pfizer-BioNTech and Moderna SARS-CoV-2 vaccines, the United States has begun COVID-19 vaccine dissemination. The vaccination program is historic in its massive scope and complexity. It requires accurate, real-time estimates of vaccine coverage to assess progress toward achieving herd immunity. Under Operation Warp Speed, the US Centers for Disease Control and Prevention (CDC) has constructed a federal database, or "data lake," to monitor vaccine coverage nationwide and ensure that recipients receive both of the necessary doses. The data lake will be managed separately from existing state and local immunization information systems (IISs), which house vaccine data in all 50 states, five cities, the District of Columbia, and eight territories. In an open letter to the Director of the CDC in late 2020, four organizations representing immunization managers and public health officials expressed concerns about the plan to include vaccine recipients' personal identifier information in the data lake.1 They also urged stronger coordination with IISs. (Am J Public Health. Published online ahead of print Feburary 18, 2021: e1-e3. https://doi.org/10.2105/AJPH.2021.306177).

    View details for DOI 10.2105/AJPH.2021.306177

    View details for PubMedID 33600253

  • Effect of sanitation improvements on soil-transmitted helminth eggs in courtyard soil from rural Bangladesh: Evidence from a cluster-randomized controlled trial. PLoS neglected tropical diseases Kwong, L. H., Sen, D., Islam, S., Shahriar, S., Benjamin-Chung, J., Arnold, B. F., Hubbard, A., Parvez, S. M., Islam, M., Unicomb, L., Rahman, M., Nelson, K., Colford, J. M., Luby, S. P., Ercumen, A. 2021; 15 (7): e0008815

    Abstract

    Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and concentration of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing the prevalence and concentration of STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n = 419) and control (n = 914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and egg count ratio (ECR) to compare the prevalence of STH eggs and arithmetic and geometric mean egg counts for STH eggs per gram of soil in the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. In the control arm, the arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR = 0.98 (95% CI: 0.91, 1.05)) or mean egg counts (ECR = 0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on STH eggs in soil. In order to effectively reduce the prevalence and concentration of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces. Trial Registration: NCT01590095.

    View details for DOI 10.1371/journal.pntd.0008815

    View details for PubMedID 34319986

  • Longitudinal Effects of a Sanitation Intervention on Environmental Fecal Contamination in a Cluster-Randomized Controlled Trial in Rural Bangladesh. Environmental science & technology Contreras, J. D., Islam, M., Mertens, A., Pickering, A. J., Kwong, L. H., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Alam, M., Sen, D., Islam, S., Rahman, M., Unicomb, L., Luby, S. P., Colford, J. M., Ercumen, A. 2021

    Abstract

    Household latrine access generally is not associated with reduced fecal contamination in the environment, but its long-term effectiveness has not been measured. We conducted an environmental assessment nested within the WASH Benefits Bangladesh randomized controlled trial (NCT01590095). We quantified E. coli and fecal coliforms in samples of stored drinking water, child hands, mother hands, soil, and food among a random sample of households from the sanitation and control arms of the trial. Samples were collected during eight quarterly visits approximately 1-3.5 years after intervention initiation. Overall, there were no substantial differences in environmental fecal contamination between households enrolled in the sanitation and control arms. Statistically significant reductions were found in stored water and child hands after pooling across sampling rounds, but the effects were small and not consistent across rounds. In addition, we assessed potential effect modification of intervention effects by follow-up time, season, wealth, community-level latrine density and coverage, population density, and domestic animal ownership. While the intervention had statistically significant effects within some subgroups, there were no consistent patterns of effect modification. Our findings support a growing consensus that on-site latrines are insufficient to prevent fecal contamination in the rural household environment.

    View details for DOI 10.1021/acs.est.1c01114

    View details for PubMedID 34086447

  • Effect of water, sanitation, handwashing and nutrition interventions on enteropathogens in children 14 months old: a cluster-randomized controlled trial in rural Bangladesh. The Journal of infectious diseases Grembi, J. A., Lin, A., Karim, M. A., Islam, M. O., Miah, R., Arnold, B. F., McQuade, E. T., Ali, S., Rahman, M. Z., Hussain, Z., Shoab, A. K., Famida, S. L., Hossen, M. S., Mutsuddi, P., Rahman, M., Unicomb, L., Haque, R., Taniuchi, M., Liu, J., Platts-Mills, J. A., Holmes, S. P., Stewart, C. P., Benjamin-Chung, J., Colford, J. M., Houpt, E. R., Luby, S. P. 2020

    Abstract

    BACKGROUND: We evaluated the impact of low-cost water, sanitation, handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural Bangladesh.METHODS: We analyzed 1411 routine fecal samples from children 14±2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative PCR. Outcomes included the number of co-occurring pathogens; cumulative quantity of four stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat.RESULTS: 326 (99.1%) control children had one or more enteropathogens detected (mean 3.8±1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: -11% [95% confidence interval [CI], -5 to -17%]; sapovirus: -9% [95%CI, -3 to -15%]; and adenovirus 40/41: -9% [95%CI, -2 to - 15%]). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm.CONCLUSIONS: WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age.

    View details for DOI 10.1093/infdis/jiaa549

    View details for PubMedID 32861214

  • Internal replication of computational workflows in scientific research. Gates open research Benjamin-Chung, J., Colford, J. M., Mertens, A., Hubbard, A. E., Arnold, B. F. 2020; 4: 17

    Abstract

    Failures to reproduce research findings across scientific disciplines from psychology to physics have garnered increasing attention in recent years. External replication of published findings by outside investigators has emerged as a method to detect errors and bias in the published literature. However, some studies influence policy and practice before external replication efforts can confirm or challenge the original contributions. Uncovering and resolving errors before publication would increase the efficiency of the scientific process by increasing the accuracy of published evidence. Here we summarize the rationale and best practices for internal replication, a process in which multiple independent data analysts replicate an analysis and correct errors prior to publication. We explain how internal replication should reduce errors and bias that arise during data analyses and argue that it will be most effective when coupled with pre-specified hypotheses and analysis plans and performed with data analysts masked to experimental group assignments. By improving the reproducibility of published evidence, internal replication should contribute to more rapid scientific advances.

    View details for DOI 10.12688/gatesopenres.13108.2

    View details for PubMedID 32803129

    View details for PubMedCentralID PMC7403855

  • Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Environmental Enteric Dysfunction in Young Children: A Cluster-randomized, Controlled Trial in Rural Bangladesh CLINICAL INFECTIOUS DISEASES Lin, A., Ali, S., Arnold, B. F., Rahman, M., Alauddin, M., Grembi, J., Mertens, A. N., Famida, S. L., Akther, S., Hossen, M., Mutsuddi, P., Shoab, A. K., Hussain, Z., Rahman, M., Unicomb, L., Ashraf, S., Naser, A., Parvez, S. M., Ercumen, A., Benjamin-Chung, J., Haque, R., Ahmed, T., Hossain, M., Choudhury, N., Jannat, K., Alauddin, S. T., Minchala, S. G., Cekovic, R., Hubbard, A. E., Stewart, C. P., Dewey, K. G., Colford, J. M., Luby, S. P. 2020; 70 (5): 738–47

    View details for DOI 10.1093/cid/ciz291

    View details for Web of Science ID 000520551800008

  • Effect of Improved Water Quality, Sanitation, Hygiene and Nutrition Interventions on Respiratory Illness in Young Children in Rural Bangladesh: A Multi-Arm Cluster-Randomized Controlled Trial. The American journal of tropical medicine and hygiene Ashraf, S., Unicomb, L., Rahman, M., Winch, P. J., Arnold, B. F., Benjamin Chung, J., Ram, P. K., Colford, J. M., Luby, S. P. 2020

    Abstract

    Acute respiratory infections (ARIs) cause mortality in young children. We assessed the effects of water, sanitation, hygiene (WASH) and nutritional interventions on childhood ARI. Geographic clusters of pregnant women from rural Bangladesh were randomly assigned to receive 1) chlorinated drinking water and safe storage (W); 2) upgraded sanitation (S); 3) handwashing promotion (H); 4) combined water, sanitation, and handwashing (WSH); 5) nutrition intervention including lipid-based nutrient supplements; 6) combined WSH plus nutrition (WSHN); or 7) no intervention (control). Masking of participants was not possible. Acute respiratory infection was defined as caregiver-reported persistent cough, panting, wheezing, or difficulty breathing in the past 7 days among index children, those born to enrolled women. We assessed outcomes at 12 and 24 months of intervention using intention to treat. Compared with children in the control group (ARI prevalence, P: 8.9%), caregivers of index children reported significantly lower ARI in the water (P: 6.3%, prevalence ratio (PR): 0.71; 95% CI: 0.53, 0.96), sanitation (P: 6.4%, PR: 0.75, 95% CI: 0.58, 0.96), handwashing (P: 6.4%, PR: 0.68, 95% CI: 0.50, 0.93), and the combined WSH+N arms (P: 5.9%, PR: 0.67, 95% CI: 0.50, 0.90). Those in the nutrition (P: 7.4%, PR: 0.84, 95% CI: 0.63, 1.10) or the WSH arm (P: 8.9%, PR: 0.99, 95% CI: 0.76, 1.28) reported similar ARI prevalence compared with control children. Single targeted water, sanitation, and hygiene interventions reduced reported respiratory illness in young children. There was no apparent respiratory health benefit from combining WASH interventions.

    View details for DOI 10.4269/ajtmh.19-0769

    View details for PubMedID 32100681

  • Comparison of multi-parallel qPCR and double-slide Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh. PLoS neglected tropical diseases Benjamin-Chung, J. n., Pilotte, N. n., Ercumen, A. n., Grant, J. R., Maasch, J. R., Gonzalez, A. M., Ester, A. C., Arnold, B. F., Rahman, M. n., Haque, R. n., Hubbard, A. E., Luby, S. P., Williams, S. A., Colford, J. M. 2020; 14 (4): e0008087

    Abstract

    There is growing interest in local elimination of soil-transmitted helminth (STH) infection in endemic settings. In such settings, highly sensitive diagnostics are needed to detect STH infection. We compared double-slide Kato-Katz, the most commonly used copromicroscopic detection method, to multi-parallel quantitative polymerase chain reaction (qPCR) in 2,799 stool samples from children aged 2-12 years in a setting in rural Bangladesh with predominantly low STH infection intensity. We estimated the sensitivity and specificity of each diagnostic using Bayesian latent class analysis. Compared to double-slide Kato-Katz, STH prevalence using qPCR was almost 3-fold higher for hookworm species and nearly 2-fold higher for Trichuris trichiura. Ascaris lumbricoides prevalence was lower using qPCR, and 26% of samples classified as A. lumbricoides positive by Kato-Katz were negative by qPCR. Amplicon sequencing of the 18S rDNA from 10 samples confirmed that A. lumbricoides was absent in samples classified as positive by Kato-Katz and negative by qPCR. The sensitivity of Kato-Katz was 49% for A. lumbricoides, 32% for hookworm, and 52% for T. trichiura; the sensitivity of qPCR was 79% for A. lumbricoides, 93% for hookworm, and 90% for T. trichiura. Specificity was ≥ 97% for both tests for all STH except for Kato-Katz for A. lumbricoides (specificity = 68%). There were moderate negative, monotonic correlations between qPCR cycle quantification values and eggs per gram quantified by Kato-Katz. While it is widely assumed that double-slide Kato-Katz has few false positives, our results indicate otherwise and highlight inherent limitations of the Kato-Katz technique. qPCR had higher sensitivity than Kato-Katz in this low intensity infection setting.

    View details for DOI 10.1371/journal.pntd.0008087

    View details for PubMedID 32330127

  • The WASH Benefits and SHINE trials: interpretation of WASH intervention effects on linear growth and diarrhoea. The Lancet. Global health Pickering, A. J., Null, C., Winch, P. J., Mangwadu, G., Arnold, B. F., Prendergast, A. J., Njenga, S. M., Rahman, M., Ntozini, R., Benjamin-Chung, J., Stewart, C. P., Huda, T. M., Moulton, L. H., Colford, J. M., Luby, S. P., Humphrey, J. H. 2019; 7 (8): e1139–e1146

    Abstract

    Child stunting is a global problem and is only modestly responsive to dietary interventions. Numerous observational studies have shown that water quality, sanitation, and handwashing (WASH) in a household are strongly associated with linear growth of children living in the same household. We have completed three randomised efficacy trials testing improved household-level WASH with and without improved infant and young child feeding (IYCF) on stunting and diarrhoea in Bangladesh, Kenya, and Zimbabwe. In all trials, improved IYCF had a statistically significant benefit, but WASH had no effect on linear growth. In observational analyses of data from the control groups of the three trials, baseline sanitation was a strong risk factor for stunting in the study populations, suggesting this frequently reported association might be confounded by unmeasured factors of household wellbeing. WASH interventions reduced diarrhoea in Bangladesh, but not in Kenya or Zimbabwe. Intervention promoters visited participants six times per month in Bangladesh compared with monthly in Kenya and Zimbabwe; a review of the literature shows that virtually all published studies that have reported an effect on diarrhoea through home-based water treatment and handwashing promotion achieved high adherence by visiting participants at daily to fortnightly intervals. Despite achieving substantial behavioural change and significant reduction in infection prevalence for some enteric pathogens, detection of enteropathogens among children in the WASH groups of the trials was typically at ten times higher prevalence compared with high-income countries. Considering these results, we recommend that future research in the WASH sector focus on developing and evaluating interventions that are radically more effective in reducing faecal contamination in the domestic environment than the interventions implemented in these trials.

    View details for DOI 10.1016/S2214-109X(19)30268-2

    View details for PubMedID 31303300

  • Effects of water, sanitation, handwashing and nutritional interventions on soil-transmitted helminth infections in young children: A cluster-randomized controlled trial in rural Bangladesh. PLoS neglected tropical diseases Ercumen, A., Benjamin-Chung, J., Arnold, B. F., Lin, A., Hubbard, A. E., Stewart, C., Rahman, Z., Parvez, S. M., Unicomb, L., Rahman, M., Haque, R., Colford, J. M., Luby, S. P. 2019; 13 (5): e0007323

    Abstract

    BACKGROUND: Soil transmitted helminths (STH) infect >1.5 billion people. Mass drug administration (MDA) effectively reduces infection; however, there is evidence for rapid reinfection and risk of potential drug resistance. We conducted a randomized controlled trial in Bangladesh (WASH Benefits, NCT01590095) to assess whether water, sanitation, hygiene and nutrition interventions, alone and combined, reduce STH in a setting with ongoing MDA.METHODOLOGY/PRINCIPAL FINDINGS: In 2012-2013, we randomized 720 clusters of 5551 pregnant women into water treatment, sanitation, handwashing, combined water+sanitation+handwashing (WSH), nutrition, nutrition+WSH (N+WSH) or control arms. In 2015-2016, we enrolled 7795 children, aged 2-12 years, of 4102 available women for STH follow-up and collected stool from 7187. We enumerated STH infections with Kato-Katz. We estimated intention-to-treat intervention effects on infection prevalence and intensity. Participants and field staff were not blinded; laboratory technicians and data analysts were blinded. Prevalence among controls was 36.8% for A. lumbricoides, 9.2% for hookworm and 7.5% for T. trichiura. Most infections were low-intensity. Compared to controls, the water intervention reduced hookworm by 31% (prevalence ratio [PR] = 0.69 (0.50,0.95), prevalence difference [PD] = -2.83 (-5.16,-0.50)) but did not affect other STH. Sanitation improvements reduced T. trichiura by 29% (PR = 0.71 (0.52,0.98), PD = -2.17 (-4.03,-0.38)), had a similar borderline effect on hookworm and no effect on A. lumbricoides. Handwashing and nutrition interventions did not reduce any STH. WSH and N+WSH reduced hookworm prevalence by 29-33% (WSH: PR = 0.71 (0.52,0.99), PD = -2.63 (-4.95,-0.31); N+WSH: PR = 0.67 (0.50,0.91), PD = -3.00 (-5.14,-0.85)) and marginally reduced A. lumbricoides. Effects on infection intensity were similar.CONCLUSIONS/SIGNIFICANCE: In a low-intensity infection setting with MDA, we found modest but sustained hookworm reduction from water treatment and combined WSH interventions. Impacts were more pronounced on STH species with short vs. long-term environmental survival. Our findings suggest possible waterborne transmission for hookworm. Water treatment and sanitation improvements can augment MDA to interrupt STH transmission.TRIAL REGISTRATION: NCT01590095.

    View details for PubMedID 31050672

  • Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Child Enteric Protozoan Infections in Rural Bangladesh: A Cluster-Randomized Controlled Trial CLINICAL INFECTIOUS DISEASES Lin, A., Ercumen, A., Benjamin-Chung, J., Arnold, B. F., Das, S., Haque, R., Ashraf, S., Parvez, S. M., Unicomb, L., Rahman, M., Hubbard, A. E., Stewart, C. P., Colford, J. M., Luby, S. P. 2018; 67 (10): 1515–22

    Abstract

    We evaluated effects of individual and combined water, sanitation, handwashing (WSH), and nutritional interventions on protozoan infections in children.We randomized geographical clusters of pregnant women in rural Bangladesh into chlorinated drinking water, hygienic sanitation, handwashing, nutrition, combined WSH, nutrition plus WSH (N+WSH), or control arms. Participants were not masked. After approximately 2.5 years of intervention, we measured Giardia, Cryptosporidium, and Entamoeba histolytica prevalence and infection intensity by multiplex real-time polymerase chain reaction of child stool. Analysis was intention-to-treat.Between May 2012 and July 2013, we randomized 5551 pregnant women. At follow-up, among 4102 available women, we enrolled 6694 children into the protozoan assessment. We analyzed stool from 5933 children (aged ~31 months) for protozoan infections. Compared with 35.5% prevalence among controls, Giardia infection prevalence was lower in the sanitation (26.5%; prevalence ratio [PR], 0.75 [95% confidence interval {CI}, .64-.88]), handwashing (28.2%; PR, 0.80 [95% CI, .66-.96]), WSH (29.7%; PR, 0.83 [95% CI, .72-.96]), and N+WSH (26.7%; PR, 0.75 [95% CI, .64-.88]) arms. Water and nutrition interventions had no effect. Low prevalence of E. histolytica and Cryptosporidium (<2%) resulted in imprecise effect estimates.Individual handwashing and hygienic sanitation interventions significantly reduced childhood Giardia infections, and there were no effects of chlorinated drinking water and nutrition improvements in this context. Combined WSH interventions provided no additional benefit. To reduce Giardia infection, individual WSH interventions may be more feasible and cost-effective than combined interventions in similar rural, low-income settings.NCT01590095.

    View details for PubMedID 29669039

    View details for PubMedCentralID PMC6206106

  • Do Sanitation Improvements Reduce Fecal Contamination of Water, Hands, Food, Soil, and Flies? Evidence from a Cluster-Randomized Controlled Trial in Rural Bangladesh ENVIRONMENTAL SCIENCE & TECHNOLOGY Ercumen, A., Pickering, A. J., Kwong, L. H., Mertens, A., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Alam, M., Sen, D., Islam, S., Rahman, M., Kullmann, C., Chase, C., Ahmed, R., Parvez, S., Unicomb, L., Rahman, M., Ram, P. K., Clasen, T., Luby, S. P., Colford, J. M. 2018; 52 (21): 12089–97

    Abstract

    Sanitation improvements have had limited effectiveness in reducing the spread of fecal pathogens into the environment. We conducted environmental measurements within a randomized controlled trial in Bangladesh that implemented individual and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). Following approximately 4 months of intervention, we enrolled households in the trial's control, sanitation and combined WSH arms to assess whether sanitation improvements, alone and coupled with water treatment and handwashing, reduce fecal contamination in the domestic environment. We quantified fecal indicator bacteria in samples of drinking and ambient waters, child hands, food given to young children, courtyard soil and flies. In the WSH arm, E. coli prevalence in stored drinking water was reduced by 62% (prevalence ratio=0.38 (0.32, 0.44)) and E. coli concentration by 1-log (log10 = -0.88 (-1.01, -0.75)). The interventions did not reduce E. coli along other sampled pathways. Ambient contamination remained high among intervention households. Potential reasons include non-community-level sanitation coverage, child open defecation, animal fecal sources or naturalized E. coli in the environment. Future studies should explore potential threshold effects of different levels of community sanitation coverage on environmental contamination.

    View details for PubMedID 30256095

    View details for PubMedCentralID PMC6222553

  • Effects of Single and Combined Water, Sanitation and Handwashing Interventions on Fecal Contamination in the Domestic Environment: A Cluster-Randomized Controlled Trial in Rural Bangladesh ENVIRONMENTAL SCIENCE & TECHNOLOGY Ercumen, A., Mertens, A., Arnold, B. F., Benjamin-Chung, J., Hubbard, A. E., Ahmed, M., Kabir, M., Khalil, M., Kumar, A., Rahman, M., Parvez, S., Unicomb, L., Rahman, M., Ram, P. K., Clasen, T., Luby, S. P., Colford, J. M. 2018; 52 (21): 12078–88

    Abstract

    Water, sanitation and hygiene interventions have varying effectiveness in reducing fecal contamination in the domestic environment; delivering them in combination could yield synergies. We conducted environmental assessments within a randomized controlled trial in Bangladesh that implemented single and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). After one and two years of intervention, we quantified fecal indicator bacteria in samples of drinking water (from source or storage), child hands, children's food and sentinel objects. In households receiving single water treatment interventions, E. coli prevalence in stored drinking water was reduced by 50% and concentration by 1-log. E. coli prevalence in food was reduced by 30% and concentration by 0.5-log in households receiving single water treatment and handwashing interventions. Combined WSH did not reduce fecal contamination more effectively than its components. Interventions did not reduce E. coli in groundwater, on child hands and on objects. These findings suggest that WSH improvements reduced contamination along the direct transmission pathways of stored water and food but not along indirect upstream pathways. Our findings support implementing water treatment and handwashing to reduce fecal exposure through water and food but provide no evidence that combining interventions further reduces exposure.

    View details for PubMedID 30256102

    View details for PubMedCentralID PMC6222549

  • Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Kenya: a cluster-randomised controlled trial LANCET GLOBAL HEALTH Null, C., Stewart, C. P., Pickering, A. J., Dentz, H. N., Arnold, B. F., Arnold, C. D., Benjamin-Chung, J., Clasen, T., Dewey, K. G., Fernald, L. H., Hubbard, A. E., Kariger, P., Lin, A., Luby, S. P., Mertens, A., Njenga, S. M., Nyambane, G., Ram, P. K., Colford, J. M. 2018; 6 (3): E316–E329

    Abstract

    Poor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering.The WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6-24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.Between Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score -1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 [95% CI 0·01-0·25] in the nutrition group; 0·16 [0·05-0·27] in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth.Behaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence.Bill & Melinda Gates Foundation, United States Agency for International Development.

    View details for PubMedID 29396219

  • Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Bangladesh: a cluster randomised controlled trial LANCET GLOBAL HEALTH Luby, S. P., Rahman, M., Arnold, B. F., Unicomb, L., Ashraf, S., Winch, P. J., Stewart, C. P., Begum, F., Hussain, F., Benjamin-Chung, J., Leontsini, E., Naser, A. M., Parvez, S. M., Hubbard, A. E., Lin, A., Nizame, F. A., Jannat, K., Ercumen, A., Ram, P. K., Das, K. K., Abedin, J., Clasen, T. F., Dewey, K. G., Fernald, L. C., Null, C., Ahmed, T., Colford, J. M. 2018; 6 (3): E302–E315

    Abstract

    Diarrhoea and growth faltering in early childhood are associated with subsequent adverse outcomes. We aimed to assess whether water quality, sanitation, and handwashing interventions alone or combined with nutrition interventions reduced diarrhoea or growth faltering.The WASH Benefits Bangladesh cluster-randomised trial enrolled pregnant women from villages in rural Bangladesh and evaluated outcomes at 1-year and 2-years' follow-up. Pregnant women in geographically adjacent clusters were block-randomised to one of seven clusters: chlorinated drinking water (water); upgraded sanitation (sanitation); promotion of handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate child nutrition plus lipid-based nutrient supplements (nutrition); combined water, sanitation, handwashing, and nutrition; and control (data collection only). Primary outcomes were caregiver-reported diarrhoea in the past 7 days among children who were in utero or younger than 3 years at enrolment and length-for-age Z score among children born to enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCC01590095.Between May 31, 2012, and July 7, 2013, 5551 pregnant women in 720 clusters were randomly allocated to one of seven groups. 1382 women were assigned to the control group; 698 to water; 696 to sanitation; 688 to handwashing; 702 to water, sanitation, and handwashing; 699 to nutrition; and 686 to water, sanitation, handwashing, and nutrition. 331 (6%) women were lost to follow-up. Data on diarrhoea at year 1 or year 2 (combined) were available for 14 425 children (7331 in year 1, 7094 in year 2) and data on length-for-age Z score in year 2 were available for 4584 children (92% of living children were measured at year 2). All interventions had high adherence. Compared with a prevalence of 5·7% (200 of 3517 child weeks) in the control group, 7-day diarrhoea prevalence was lower among index children and children under 3 years at enrolment who received sanitation (61 [3·5%] of 1760; prevalence ratio 0·61, 95% CI 0·46-0·81), handwashing (62 [3·5%] of 1795; 0·60, 0·45-0·80), combined water, sanitation, and handwashing (74 [3·9%] of 1902; 0·69, 0·53-0·90), nutrition (62 [3·5%] of 1766; 0·64, 0·49-0·85), and combined water, sanitation, handwashing, and nutrition (66 [3·5%] of 1861; 0·62, 0·47-0·81); diarrhoea prevalence was not significantly lower in children receiving water treatment (90 [4·9%] of 1824; 0·89, 0·70-1·13). Compared with control (mean length-for-age Z score -1·79), children were taller by year 2 in the nutrition group (mean difference 0·25 [95% CI 0·15-0·36]) and in the combined water, sanitation, handwashing, and nutrition group (0·13 [0·02-0·24]). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth.Nutrient supplementation and counselling modestly improved linear growth, but there was no benefit to the integration of water, sanitation, and handwashing with nutrition. Adherence was high in all groups and diarrhoea prevalence was reduced in all intervention groups except water treatment. Combined water, sanitation, and handwashing interventions provided no additive benefit over single interventions.Bill & Melinda Gates Foundation.

    View details for PubMedID 29396217

  • Effects of water, sanitation, handwashing and nutritional interventions on telomere length among children in a cluster-randomized controlled trial in rural Bangladesh ELIFE Lin, A., Arnold, B. F., Mertens, A. N., Lin, J., Benjamin-Chung, J., Ali, S., Hubbard, A. E., Stewart, C. P., Shoab, A. K., Rahman, M., Hossen, M., Mutsuddi, P., Famida, S. L., Akther, S., Rahman, M., Unicomb, L., Dhabhar, F. S., Fernald, L. H., Colford, J. M., Luby, S. P. 2017; 6

    Abstract

    Background: Shorter childhood telomere length (TL) and more rapid TL attrition are widely regarded as manifestations of stress. However, the potential effects of health interventions on child TL are unknown. We hypothesized that a water, sanitation, handwashing (WSH), and nutritional intervention would slow TL attrition during the first two years of life. Methods: In a trial in rural Bangladesh (ClinicalTrials.gov, NCT01590095), we randomized geographical clusters of pregnant women into individual water treatment, sanitation, handwashing, nutrition, combined WSH, combined nutrition plus WSH (N + WSH), or control arms. We conducted a substudy enrolling children from the control arm and the N + WSH intervention arm. Participants and outcome assessors were not masked; analyses were masked. Relative TL was measured at 1 and 2 years after intervention, and the change in relative TL was reported. Analysis was intention-to-treat. Findings: Between May 2012 and July 2013, in the overall trial, we randomized 720 geographical clusters of 5551 pregnant women to a control or an intervention arm. In this substudy, after 1 year of intervention, we assessed a total of 662 children (341 intervention and 321 control) and 713 children after 2 years of intervention (383 intervention and 330 control). Children in the intervention arm had significantly shorter relative TL compared with controls after 1 year of intervention (difference -163 base pairs (bp), p=0.001). Between years 1 and 2, TL increased in the intervention arm (+76 bp) and decreased in the controls (-23 bp) (p=0.050). After 2 years, there was no difference between the arms (p=0.305). Interpretation: Our unexpected finding of increased telomere attrition during the first year of life in the intervention group suggests that rapid telomere attrition during this critical period could reflect the improved growth in the intervention group, rather than accumulated stress. Funding: The Bill and Melinda Gates Foundation.

    View details for PubMedID 28980942

  • The Interaction of Deworming, Improved Sanitation, and Household Flooring with Soil-Transmitted Helminth Infection in Rural Bangladesh PLOS NEGLECTED TROPICAL DISEASES Benjamin-Chung, J., Nazneen, A., Halder, A. K., Haque, R., Siddique, A., Uddin, M. S., Koporc, K., Arnold, B. F., Hubbard, A. E., Unicomb, L., Luby, S. P., Addiss, D. G., Colford, J. M. 2015; 9 (12)

    Abstract

    The combination of deworming and improved sanitation or hygiene may result in greater reductions in soil-transmitted helminth (STH) infection than any single intervention on its own. We measured STH prevalence in rural Bangladesh and assessed potential interactions among deworming, hygienic latrines, and household finished floors.We conducted a cross-sectional survey (n = 1,630) in 100 villages in rural Bangladesh to measure three exposures: self-reported deworming consumption in the past 6 months, access to a hygienic latrine, and household flooring material. We collected stool samples from children 1-4 years, 5-12 years, and women 15-49 years. We performed mini-FLOTAC on preserved stool samples to detect Ascaris lumbricoides, Enterobius vermicularis, hookworm, and Trichuris trichiura ova. Approximately one-third (32%) of all individuals and 40% of school-aged children had an STH infection. Less than 2% of the sample had moderate/heavy intensity infections. Deworming was associated with lower Ascaris prevalence (adjusted prevalence ratio (PR) = 0.53; 95% CI 0.40, 0.71), but there was no significant association with hookworm (PR = 0.93, 95% CI 0.60, 1.44) or Trichuris (PR = 0.90, 95% CI 0.74, 1.08). PRs for hygienic latrine access were 0.91 (95% CI 0.67,1.24), 0.73 (95% CI 0.43,1.24), and 1.03 (95% CI 0.84,1.27) for Ascaris, hookworm, and Trichuris, respectively. Finished floors were associated with lower Ascaris prevalence (PR = 0.56, 95% CI 0.32, 0.97) but not associated with hookworm (PR = 0.48 95% CI 0.16,1.45) or Trichuris (PR = 0.98, 95% CI 0.72,1.33). Across helminths and combinations of exposures, adjusted prevalence ratios for joint exposures were consistently more protective than those for individual exposures.We found moderate STH prevalence in rural Bangladesh among children and women of childbearing age. This study is one of the first to examine independent and combined associations with deworming, sanitation, and hygiene. Our results suggest that coupling deworming with sanitation and flooring interventions may yield more sustained reductions in STH prevalence.

    View details for DOI 10.1371/journal.pntd.0004256

    View details for Web of Science ID 000368345100032

    View details for PubMedCentralID PMC4666415