Association between tuberculosis in men and social network structure in Kampala, Uganda.

BACKGROUND: Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men's contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. METHODS: We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). RESULTS: The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. CONCLUSIONS: This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.

Effects of single and integrated water, sanitation, handwashing, and nutrition interventions on child soil-transmitted helminth and Giardia infections: A cluster-randomized controlled trial in rural Kenya.

BACKGROUND: Helminth and protozoan infections affect more than 1 billion children globally. Improving water quality, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration, while providing other quality of life benefits. METHODS AND FINDINGS: We enrolled geographic clusters of pregnant women in rural western Kenya into a cluster-randomized controlled trial (ClinicalTrials.gov NCT01704105) that tested 6 interventions: water treatment, improved sanitation, handwashing with soap, combined water treatment, sanitation, and handwashing (WSH), improved nutrition, and combined WSH and nutrition (WSHN). We assessed intervention effects on parasite infections by measuring Ascaris lumbricoides, Trichuris trichiura, hookworm, and Giardia duodenalis among children born to the enrolled pregnant women (index children) and their older siblings. After 2 years of intervention exposure, we collected stool specimens from 9,077 total children aged 2 to 15 years in 622 clusters, including 2,346 children in an active control group (received household visits but no interventions), 1,117 in the water treatment arm, 1,160 in the sanitation arm, 1,141 in the handwashing arm, 1,064 in the WSH arm, 1,072 in the nutrition arm, and 1,177 in the WSHN arm. In the control group, 23% of children were infected with A. lumbricoides, 1% with T. trichiura, 2% with hookworm, and 39% with G. duodenalis. The analysis included 4,928 index children (median age in years: 2) and 4,149 older siblings (median age in years: 5); study households had an average of 5 people, <10% had electricity access, and >90% had dirt floors. Compared to the control group, Ascaris infection prevalence was lower in the water treatment arm (prevalence ratio [PR]: 0.82 [95% CI 0.67, 1.00], p = 0.056), the WSH arm (PR: 0.78 [95% CI 0.63, 0.96], p = 0.021), and the WSHN arm (PR: 0.78 [95% CI 0.64, 0.96], p = 0.017). We did not observe differences in Ascaris infection prevalence between the control group and the arms with the individual interventions sanitation (PR: 0.89 [95% CI 0.73, 1.08], p = 0.228), handwashing (PR: 0.89 [95% CI 0.73, 1.09], p = 0.277), or nutrition (PR: 86 [95% CI 0.71, 1.05], p = 0.148). Integrating nutrition with WSH did not provide additional benefit. Trichuris and hookworm were rarely detected, resulting in imprecise effect estimates. No intervention reduced Giardia. Reanalysis of stool samples by quantitative polymerase chain reaction confirmed the reductions in Ascaris infections measured by microscopy in the WSH and WSHN groups. Trial limitations included imperfect uptake of targeted intervention behaviors, limited power to detect effects on rare parasite infections, and that it was not feasible to blind participants and sample collectors to treatment status. However, lab technicians and data analysts were blinded to treatment status. The trial was funded by the Bill & Melinda Gates Foundation and the United States Agency for International Development. CONCLUSIONS: Integration of improved water quality, sanitation, and handwashing could contribute to sustainable control strategies for Ascaris infections, particularly in similar settings with recent or ongoing deworming programs. Combining nutrition with WSH did not provide further benefits, and water treatment alone was similarly effective to integrated WSH. Our findings provide new evidence that drinking water should be given increased attention as a transmission pathway for Ascaris. TRIAL REGISTRATION: ClinicalTrials.gov NCT01704105.

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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: The Bill & Melinda Gates Foundation and the UK Foreign and Commonwealth Development Office.

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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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]). INTERPRETATION: 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. FUNDING: Bill and Melinda Gates Foundation and the UK Foreign and Commonwealth Development Office.

Household finished flooring and soil-transmitted helminth and Giardia infections among children in rural Bangladesh and Kenya: a prospective cohort study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Bill & Melinda Gates Foundation and Task Force for Global Health.

Effect of a sanitation intervention on soil-transmitted helminth prevalence and concentration in household soil: A cluster-randomized controlled trial and risk factor analysis.

Improved sanitation has been associated with a reduced prevalence of soil-transmitted helminth (STH) infection and has been hypothesized to prevent fecal contamination from spreading throughout the household environment. We evaluated the effect of providing households with a pit latrine with a plastic slab and drophole cover, child feces management tools, and associated behavioral messaging on reducing STH eggs in household soil. We collected soil samples from 2107 households (898 control and 1209 improved sanitation intervention households) that were enrolled in the WASH Benefits cluster randomized controlled trial in rural Kenya and performed a post-intervention analysis after two years of intervention exposure. Following a pre-specified analysis plan, we combined all households that received the sanitation intervention into one group for comparison to control households. The prevalence of STH eggs in soil was 18.9% in control households and 17.0% in intervention households. The unadjusted prevalence ratio of total STH eggs in the intervention groups compared to the control group was 0.94 (95% CI: 0.78-1.13). The geometric mean concentration was 0.05 eggs/g dry soil in control households and intervention households. Unadjusted and adjusted models gave similar results. We found use of a shared latrine, presence of a roof over the sampling area, and the number of dogs owned at baseline was associated with an increased prevalence of STH eggs in soil; the presence of a latrine that was at least 2 years old and a latrine with a covered drophole was associated with a reduction in the prevalence of STH eggs in soil. Soil moisture content was also associated with an increased prevalence of STH eggs in soil. Our results indicate that an intervention designed to increase access to improved latrines and child feces management tools may not be enough to impact environmental occurrence of STH in endemic areas where latrine coverage is already high.

Following the Worms: Detection of Soil-Transmitted Helminth Eggs on Mothers' Hands and Household Produce in Rural Kenya.

Approximately one-quarter of the world's population is infected with at least one species of soil-transmitted helminth (STH). The role of produce and hands in STH transmission is not well understood. We collected and processed mother hand rinse and garden-grown produce rinse samples from 116 rural households in Kakamega, Kenya, in an area previously identified to have high STH egg contamination in household soil. Ascaris was the only STH species detected; 0.9% of hand rinse, 3.5% of leafy produce, and 1.8% of root produce samples had Ascaris eggs. Our results indicate produce and hands can carry Ascaris eggs. However, due to the low detected prevalence of eggs on hands and produce, and a high prevalence of cooking the produce items tested, these pathways might have a minor contribution to STH exposure in this setting.

Detecting and enumerating soil-transmitted helminth eggs in soil: New method development and results from field testing in Kenya and Bangladesh.

Globally, about 1.5 billion people are infected with at least one species of soil-transmitted helminth (STH). Soil is a critical environmental reservoir of STH, yet there is no standard method for detecting STH eggs in soil. We developed a field method for enumerating STH eggs in soil and tested the method in Bangladesh and Kenya. The US Environmental Protection Agency (EPA) method for enumerating Ascaris eggs in biosolids was modified through a series of recovery efficiency experiments; we seeded soil samples with a known number of Ascaris suum eggs and assessed the effect of protocol modifications on egg recovery. We found the use of 1% 7X as a surfactant compared to 0.1% Tween 80 significantly improved recovery efficiency (two-sided t-test, t = 5.03, p = 0.007) while other protocol modifications-including different agitation and flotation methods-did not have a significant impact. Soil texture affected the egg recovery efficiency; sandy samples resulted in higher recovery compared to loamy samples processed using the same method (two-sided t-test, t = 2.56, p = 0.083). We documented a recovery efficiency of 73% for the final improved method using loamy soil in the lab. To field test the improved method, we processed soil samples from 100 households in Bangladesh and 100 households in Kenya from June to November 2015. The prevalence of any STH (Ascaris, Trichuris or hookworm) egg in soil was 78% in Bangladesh and 37% in Kenya. The median concentration of STH eggs in soil in positive samples was 0.59 eggs/g dry soil in Bangladesh and 0.15 eggs/g dry soil in Kenya. The prevalence of STH eggs in soil was significantly higher in Bangladesh than Kenya (chi-square, χ2 = 34.39, p < 0.001) as was the concentration (Mann-Whitney, z = 7.10, p < 0.001). This new method allows for detecting STH eggs in soil in low-resource settings and could be used for standardizing soil STH detection globally.

Soil-Transmitted Helminth Eggs Are Present in Soil at Multiple Locations within Households in Rural Kenya.

Almost one-quarter of the world's population is infected with soil-transmitted helminths (STH). We conducted a study to determine the prevalence and location of STH-Ascaris, Trichuris, and hookworm spp.-egg contamination in soil within rural household plots in Kenya. Field staff collected soil samples from July to September 2014 from the house entrance and the latrine entrance of households in Kakamega County; additional spatial sampling was conducted at a subset of households (N = 22 samples from 3 households). We analyzed soil samples using a modified version of the US Environmental Protection Agency (EPA) method for enumerating Ascaris in biosolids. We found 26.8% of households had one or more species of STH eggs present in the soil in at least one household location (n = 18 out of 67 households), and Ascaris was the most commonly detected STH (19.4%, n = 13 out of 67 households). Prevalence of STH eggs in soil was equally likely at the house entrance (19.4%, N = 67) as at the latrine entrance (11.3%, N = 62) (p = 0.41). We also detected STH eggs at bathing and food preparation areas in the three houses revisited for additional spatial sampling, indicating STH exposure can occur at multiple sites within a household plot, not just near the latrine. The highest concentration of eggs in one house occurred in the child's play area. Our findings suggest interventions to limit child exposure to household soil could complement other STH control strategies.