bioRxiv ScienceSearch

Biology subjects

Hubbard, A. E.

Publications and source records attributed to Hubbard, A. E..

2 recordsLinked to original sources

Spillover effects of a combined water, sanitation, and handwashing intervention in rural Bangladesh: a randomized controlled trial

BackgroundWater, sanitation, and handwashing (WSH) interventions may confer indirect benefits (\"spillovers\") on neighbors of 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.\n\nMethodsWASH Benefits had randomly allocated geographically-defined clusters to a compound-level intervention (chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control and followed children for two years. We enrolled 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. Neither fieldworkers nor participants were masked. Analysis was intention-to-treat.\n\nResultsWe enrolled neighbors of WASH Benefits participants in 90 control (N=900) and 90 intervention clusters (N=899). Neighbors characteristics were balanced across arms. The prevalence of any detectable E. coli in tubewell samples was lower for neighbors of intervention vs. control (prevalence ratio=0.83; 0.73, 0.95). There was no difference in E. coli and coliform prevalence between arms for other environmental samples. Disease prevalence was similar in neighbors of intervention vs. control participants: Ascaris (prevalence difference [PD]=0.00; -0.07, 0.08), hookworm (PD=0.01; -0.01, 0.04), Trichuris (PD=0.02; -0.02, 0.05), diarrhea (PD=0.00; -0.02,0.03), respiratory illness (PD=-0.01; -0.04, 0.03).\n\nConclusionsWe found spillover effects of a compound-level combined WSH intervention for tubewell water contamination but not for child health outcomes.\n\nKey MessagesO_LIWater, sanitation, and handwashing (WSH) interventions may confer indirect benefits (\"spillovers\") on neighbors of recipients by interrupting pathogen transmission, reducing environmental contamination, or spurring the adoption of health behaviors.\nC_LIO_LIWe conducted a randomized trial in rural Bangladesh to measure whether neighbors of a compound-level WSH intervention improved hygiene behaviors and had lower prevalence environmental contamination, soil-transmitted helminth infection, diarrhea, and respiratory illness among children under 5 years after two years of intervention.\nC_LIO_LIWe did not find evidence of intervention adoption or improved hygiene behavior among neighbors of a WSH intervention delivered for 2 years.\nC_LIO_LIThe WSH intervention reduced fecal contamination of neighbors tubewell water but did not lead to spillovers for other proximal measures of contamination in the domestic environment or for child health outcomes. For proximal spillover effects to translate to distal spillover effects, improvements in neighbors health behaviors may have been necessary.\nC_LI

epidemiology

Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels

BackgroundSerologicalantibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels in low transmission settings. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays.\n\nMethods/Principal FindingsWe developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearmans rho=0.75). Seroprevalence estimates recapitulated patterns observed in quantitative antibody levels, albeit with lower resolution.\n\nConclusions/SignificanceAge-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, and scales to surveillance activities that require high spatiotemporal resolution. The approach represents a new opportunity to conduct integrated serological surveillance for neglected tropical diseases, malaria, and other infectious diseases with well-defined antigen targets.\n\nAuthor SummaryGlobal elimination strategies for infectious diseases like neglected tropical diseases and malaria rely on accurate estimates of pathogen transmission to target and evaluate control programs. Circulating antibody levels can be a sensitive measure of recent pathogen exposure, but no broadly applicable method exists to measure changes in transmission directly from quantitative antibody levels. We developed a novel method that applies recent advances in machine learning and data science to flexibly fit age-dependent antibody curves. Shifts in age-dependent antibody curves provided remarkably consistent, sensitive measures of transmission changes when evaluated across many globally important pathogens (filarial worms, malaria, enteric infections). The methods generality and performance in diverse applications demonstrate its broad potential for integrated serological surveillance of infectious diseases.

epidemiology