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BackgroundAssessments of disease burden are important to inform national, regional, and global strategies and to guide investment. We aimed to estimate the drinking water, sanitation, and hygiene (WASH)-attributable burden of disease for diarrhoea, acute respiratory infections, undernutrition, and soil-transmitted helminthiasis, using the WASH service levels used to monitor the UN Sustainable Development Goals (SDGs) as counterfactual minimum risk-exposure levels.MethodsWe assessed the WASH-attributable disease burden of the four health outcomes overall and disaggregated by region, age, and sex for the year 2019. We calculated WASH-attributable fractions of diarrhoea and acute respiratory infections by country using modelled WASH exposures and exposure-response relationships from two updated meta-analyses. We used the WHO and UNICEF Joint Monitoring Programme for Water Supply, Sanitation and Hygiene public database to estimate population exposure to different WASH service levels. WASH-attributable undernutrition was estimated by combining the population attributable fractions (PAF) of diarrhoea caused by unsafe WASH and the PAF of undernutrition caused by diarrhoea. Soil-transmitted helminthiasis was fully attributed to unsafe WASH.FindingsWe estimate that 1·4 (95% CI 1·3-1·5) million deaths and 74 (68-80) million disability-adjusted life-years (DALYs) could have been prevented by safe WASH in 2019 across the four designated outcomes, representing 2·5% of global deaths and 2·9% of global DALYs from all causes. The proportion of diarrhoea that is attributable to unsafe WASH is 0·69 (0·65-0·72), 0·14 (0·13-0·17) for acute respiratory infections, and 0·10 (0·09-0·10) for undernutrition, and we assume that the entire disease burden from soil-transmitted helminthiasis was attributable to unsafe WASH.InterpretationWASH-attributable burden of disease estimates based on the levels of service established under the SDG framework show that progress towards the internationally agreed goal of safely managed WASH services for all would yield major public-health returns.FundingWHO and Foreign, Commonwealth & Development Office.

The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 16 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group's insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.

BackgroundBiannual mass azithromycin administration reduces all-cause childhood mortality in some sub-Saharan African settings, with the largest effects in children aged 1-5 months. Azithromycin has not been distributed to children

PurposeTo identify if noninfectious uveitis (NIU) is associated with a greater risk of Coronavirus Disease 2019 (COVID-19) infection, hospitalization, and death.DesignA retrospective cohort study from January 20, 2020 to December 31, 2020, using a national claims-based database.ParticipantsEnrollees who had continuous enrollment with both medical and pharmacy coverage for 3 years before January 20, 2020. Patients with an NIU diagnosis within 3 years of the start of the study were included in the NIU cohort. Those with infectious uveitis codes or new NIU diagnoses during the risk period were excluded.MethodsCox proportional hazard models were used to identify unadjusted hazard ratios (HRs) and adjusted HRs for all covariates for each outcome measure. Adjusted models accounted for patient demographics, health status, and immunosuppressive medication use during the risk period.Main outcome measuresRates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death identified with International Classification of Disease 10th revision codes.ResultsThis study included 5 806 227 patients, of whom 29 869 (0.5%) had a diagnosis of NIU. On unadjusted analysis, patients with NIU had a higher rate of COVID-19 infection (5.7% vs. 4.5%, P < 0.001), COVID-19-related hospitalization (1.2% vs. 0.6%, P < 0.001), and COVID-19-related death (0.3% vs. 0.1%, P < 0.001). However, in adjusted models, NIU was not associated with a greater risk of COVID-19 infection (HR, 1.05; 95% confidence interval [CI], 1.00-1.10; P= 0.04), hospitalization (HR, 0.98; 95% CI, 0.88-1.09; P= 0.67), or death (HR, 0.90, 95% CI, 0.72-1.13, P= 0.37). Use of systemic corticosteroids was significantly associated with a higher risk of COVID-19 infection, hospitalization, and death.ConclusionsPatients with NIU were significantly more likely to be infected with COVID-19 and experience severe disease outcomes. However, this association was due to the demographics, comorbidities, and medications of patients with NIU, rather than NIU alone. Patients using systemic corticosteroids were significantly more likely to be infected with COVID-19 and were at greater risk of hospitalization and in-hospital death. Additional investigation is necessary to identify the impact of corticosteroid exposure on COVID-19-related outcomes.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 16 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group's insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.

PurposeTo identify if non-infectious uveitis (NIU) is associated with a greater risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death.DesignA retrospective cohort study from January 20, 2020 to December 31, 2020 using a national claims-based database.ParticipantsEnrollees who had continuous enrollment with both medical and pharmacy coverage for three years prior to January 20, 2020. Patients with an NIU diagnosis within three years of the start of the study were included in the NIU cohort. Those with infectious uveitis codes or new NIU diagnoses during the risk period were excluded.MethodsCox proportional hazards models were used to identify unadjusted hazard ratios as well as adjusted hazard ratios for all covariates for each outcome measure. Adjusted models accounted for patient demographics, health status, and immunosuppressive medication use during the risk period.Main outcome measuresRates of COVID-19 infection, COVID-19-related hospitalization, and COVID-19-related in-hospital death identified with International Classification of Disease 10th revision codes.ResultsThis study included 5,806,227 patients of which 29,869 (0.5%) had a diagnosis of NIU. On unadjusted analysis, patients with NIU had a higher rate of COVID-19 infection (5.7% vs. 4.2%, p

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify.

Additional file 2: Supplemental Table S1. Baseline demographic and anthropometric characteristics among children lost and not lost to follow-up at 14 days and 6 months. (PDF 2577 kb)

Additional file 1.

Additional file 1: Supplemental Table 1. Association between number of antenatal care visits and birthweight among urban- (N = 17,736) and rural-dwelling (N = 3487) newborns in 5 regions of Burkina Faso. Supplemental Table 2. Association between number of antenatal care visits and low birthweight (

Additional file 1.

Biannual mass azithromycin distribution reduces all-cause child mortality in some settings in sub-Saharan Africa; however, adverse events and short-term infectious outcomes following treatment have not been well characterized. Children aged 0-59 months were recruited in Nouna Town, Burkina Faso, and randomized 1:1 to a single directly observed oral 20 mg/kg dose of azithromycin or placebo. At 14 days after treatment, caregivers were interviewed about adverse event symptoms their child experienced since treatment and if they had sought health care for their child. All children had tympanic temperature measured at the 14-day visit. We compared adverse events and clinic visits using logistic regression models between azithromycin- and placebo-controlled children. Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. On average, children were aged 28 months, and 50.9% were female. Caregivers of 20% of children reported that their child experienced at least one adverse event, with no significant difference between study arms (19.9% azithromycin; 20.0% placebo, logistic regression P = 0.96). Vomiting was more often reported by caregivers of azithromycin-treated children than by those of placebo-treated children (7.2% azithromycin, 1.9% placebo, logistic regression P = 0.01). There were no significant differences in other adverse events or clinic visits. Adverse events following a single oral dose of azithromycin in preschool children were rare and mild. Azithromycin administration appears safe in this population.

PurposeThe usefulness of topical antibiotic prophylaxis for routine oculofacial plastic surgery is not well established. Given concerns such as contact dermatitis, antibiotic resistance, and healthcare costs in conjunction with a low baseline rate of surgical site infections, the investigators sought to determine the frequency of infection with and without the use of topical antibiotic prophylaxis.DesignRandomized, controlled, unmasked clinical trial.ParticipantsAdult patients undergoing routine periocular surgery without prior history of periocular surgical site infection, need for perioperative oral or parenteral antibiotics, or allergy to all study medications.MethodsParticipants were randomized before surgery to receive either antibiotic or placebo (mineral oil and petrolatum-based) ointment after surgery. Outcomes were measured at the first postoperative visit. The 2-tailed Fisher exact test was used to compare outcomes between groups.Main outcome measuresThe primary outcome was the incidence of surgical site infections. The secondary outcomes included stratification of infections by patient risk characteristics, incidence of allergic contact dermatitis, and incidence of wound complications.ResultsFour hundred one participants were enrolled and randomized, and 13 participants did not proceed with surgery or were lost to follow-up. High-risk features for infection were identified in 24% of the placebo group and 21% of the antibiotic group. Surgical site infections were more common in the placebo group (2.7% vs. 0.0%; P= 0.025). The rate of contact dermatitis was similar (0.5% vs. 0.5%; P= 1.00), as was the rate of wound dehiscence (2.7% vs. 3.5%; P= 0.77). Among the placebo group, the incidence of infections in the low- and high-risk participants was 2.9% and 2.2%, respectively. Infections were treated with oral or topical antibiotics and resolved without complication, except in 1 patient who required 2 subsequent surgeries to address the sequelae.ConclusionsAfter routine oculofacial plastic surgery, patients treated with a topical antibiotic ointment showed a lower risk of surgical site infection compared with patients treated with a nonantibiotic ointment.

Summary Growth faltering (low length-for-age or weight-for length) in the first 1000 days — from conception to two years of age — influences both short and long-term health and survival. Evidence for interventions to prevent growth faltering such as nutritional supplementation during pregnancy and the postnatal period has increasingly accumulated, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. In addition, there is need to better understand age-windows and population subgroups in which to focus future preventive efforts. Here, we show using a population intervention effects analysis of 33 longitudinal cohorts (83,671 children) and 30 separate exposures that improving maternal anthropometry and child condition at birth, in particular child length-at-birth, accounted for population increases by age 24 months in length-for-age Z of 0.04 to 0.40 and weight-for-length Z by 0.02 to 0.15. Boys had consistently higher risk of all forms of growth faltering than girls, and early growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits had higher mortality rates from birth to two years than those without 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 key opportunities for new preventive interventions.

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and abundance 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 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 relative egg count reductions (ECR) to compare the prevalence of any STH eggs and arithmetic and geometric mean egg counts for any STH per gram of soil between 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. 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 environmental reservoirs of STH eggs. In order to effectively reduce the prevalence and abundance 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.Author summaryImproved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and abundance 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 STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the control and sanitation 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 found no effect of the sanitation intervention on STH eggs in soil. In order to effectively reduce the prevalence and abundance 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.

BackgroundAnemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene.ObjectiveWe evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh.DesignWe nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y. These substudies included 4 groups: water, sanitation, and handwashing (WSH); nutrition (N), including lipid-based nutrient supplements (LNSs; ages 6-24 mo) and infant and young child feeding (IYCF) counseling; WSH+N; and control. Hemoglobin and micronutrient biomarkers were measured after 2 y of intervention and compared between groups using generalized linear models with robust SEs.ResultsIn Kenya, 699 children were assessed at a mean±SD age of 22.1±1.8 mo, and in Bangladesh 1470 participants were measured at a mean±SD age of 28.0±1.9 mo. The control group anemia prevalences were 48.8% in Kenya and 17.4% in Bangladesh. There was a lower prevalence of anemia in the 2 N intervention groups in both Kenya [N: 36.2%; prevalence ratio (PR): 0.74; 95% CI: 0.58, 0.94; WSH+N: 27.3%; PR: 0.56; 95% CI: 0.42, 0.75] and Bangladesh (N: 8.7%; PR: 0.50; 95% CI: 0.32, 0.78; WSH+N: 7.9%, PR: 0.46; 95% CI: 0.29, 0.73). In both trials, the 2 N groups also had significantly lower prevalences of iron deficiency, iron deficiency anemia, and low vitamin B-12 and, in Kenya, a lower prevalence of folate and vitamin A deficiencies. In Bangladesh, the WSH group had a lower prevalence of anemia (12.8%; PR: 0.74; 95% CI: 0.54, 1.00) than the control group, whereas in Kenya, the WSH+N group had a lower prevalence of anemia than did the N group (PR: 0.75; 95% CI: 0.53, 1.07), but this was not significant (P=0.102).ConclusionsIYCF counseling with LNSs reduced the risks of anemia, iron deficiency, and low vitamin B-12. Effects on folate and vitamin A varied between studies. Improvements in WSH also reduced the risk of anemia in Bangladesh but did not provide added benefit over the nutrition-specific intervention. These trials were registered at clinicaltrials.gov as NCT01590095 (Bangladesh) and NCT01704105 (Kenya).

Summary Background Poor nutrition and hygiene make children vulnerable to delays in growth and development. We aimed to assess the effects of water quality, sanitation, handwashing, and nutritional interventions individually or in combination on the cognitive, motor, and language development of children in rural Bangladesh. Methods In this cluster-randomised controlled trial, we enrolled pregnant women in their first or second trimester from rural villages of Gazipur, Kishoreganj, Mymensingh, and Tangail districts of central Bangladesh, with an average of eight women per cluster. Groups of eight geographically adjacent clusters were block-randomised, using a random number generator, into six intervention groups (all of which received weekly visits from a community health promoter for the first 6 months and every 2 weeks for the next 18 months) and a double-sized control group (no intervention or health promoter visit). The six intervention groups were: chlorinated drinking water; improved sanitation; handwashing with soap; combined water, sanitation, and handwashing; improved nutrition through counselling and provision of lipid-based nutrient supplements; and combined water, sanitation, handwashing, and nutrition. Here, we report on the prespecified secondary child development outcomes: gross motor milestone achievement assessed with the WHO module at age 1 year, and communication, gross motor, personal social, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at age 2 years. Masking of participants was not possible. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01590095. Findings Between May 31, 2012, and July 7, 2013, 5551 pregnant women residing in 720 clusters were enrolled. Index children of 928 (17%) enrolled women were lost to follow-up in year 1 and an additional 201 (3%) in year 2. 4757 children were assessed at 1 year and 4403 at 2 years. At year 1, compared with the control group, the combined water, sanitation, handwashing, and nutrition group had a higher rate of attaining the standing alone milestone (hazard ratio 1·19, 95% CI 1·01–1 ·40), and the nutrition group had a higher rate of attaining the walking alone milestone (1·32, 95% CI 1·07–1·62). The combined water, sanitation, handwashing, and nutrition group had a higher rate of attaining the walking alone milestone than those in the water, sanitation, and handwashing group (1·29, 1·01–1·65). At 2 years, we noted beneficial effects in the combined EASQ score in all intervention groups, with effect sizes smallest in the water treatment group (difference 0·15, 95% CI 0·04 to 0·26 vs control) and largest in the combined water, sanitation, handwashing, and nutrition treatment group (0·37, 0·27–0·46). Interpretation Improvements in water quality, handwashing, sanitation, or nutrition supported by intensive interpersonal communication, when delivered either individually or in combination, contributed to improvements in child development. A crucial next step is to establish whether similar effects can be achieved with reduced intensity of promoter contacts that could be supported in large-scale interventions. Funding Bill & Melinda Gates Foundation.

BackgroundPoor nutrition and infectious diseases can prevent children from reaching their developmental potential. We aimed to assess the effects of improvements in water, sanitation, handwashing, and nutrition on early child development in rural Kenya.MethodsIn this cluster-randomised controlled trial, we enrolled pregnant women in their second or third trimester from three counties (Kakamega, Bungoma, and Vihiga) in Kenya's western region, with an average of 12 households per cluster. Groups of nine geographically adjacent clusters were block-randomised, using a random number generator, into the six intervention groups (including monthly visits to promote target behaviours), a passive control group (no visits), or a double-sized active control group (monthly household visits to measure child mid-upper arm circumference). The six intervention groups were: chlorinated drinking water; improved sanitation; handwashing with soap; combined water, sanitation, and handwashing; improved nutrition through counselling and provision of lipid-based nutrient supplements; and combined water, sanitation, handwashing, and nutrition. Here we report on the prespecified secondary child development outcomes: gross motor milestone achievement assessed with the WHO module at year 1, and communication, gross motor, personal social, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at year 2. Masking of participants was not possible, but data assessors were masked. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.FindingsBetween Nov 27, 2012, and May 21, 2014, 8246 women residing in 702 clusters were enrolled. No clusters were lost to follow-up, but 2212 households with 2279 children were lost to follow-up by year 2. 5791 (69%) children were measured at year 1 and 6107 (73%) at year 2. At year 1, compared with the active control group, the combined water, sanitation, handwashing, and nutrition group had greater rates of attaining the standing with assistance milestone (hazard ratio 1·23, 95% CI 1·09-1·40) and the walking with assistance milestone (1·32, 1·17-1·50), and the handwashing group had a greater rate of attaining the standing alone milestone (1·15, 1·01-1·31). There were no differences when comparing the other intervention groups with the active control group on any of the motor milestone measures at year 1. At year 2, there were no differences among groups for the communication, gross motor, personal social, or combined EASQ scores.InterpretationThe handwashing and combined water, sanitation, handwashing, and nutrition interventions might have improved child motor development after 1 year, although after 2 years there were no other differences between groups. Future research should examine ways to make community health and nutrition programmes more effective at supporting child development.FundingBill & Melinda Gates Foundation.

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, eLife digest Stress negatively affects health by causing changes in cells. As a result, excess stress may predispose people to fall ill more often or age faster. It is difficult to measure stress. Some studies suggest that measuring the ends of chromosomes, known as telomeres, may be one way to measure stress. Like the plastic tips on shoelaces, telomeres protect chromosomes from fraying. All peoples’ telomeres shorten over their lifetime with each cell division. Many studies show that telomeres shorten faster in people who experience more stress. When telomeres become too short, cells die faster without being replaced, and the body ages. Most studies on telomere length have looked at adults. Few studies have looked at children early in life or asked whether there are ways to intervene to stop or reverse stress-related telomere shortening. The first two years of life are a crucial period for the developing brain and immune system, which could set children on a lifelong course toward health or disease. Young children living in low-resource settings often encounter many sources of stress, like poor nutrition, infectious diseases or violence. Studies are needed to determine if interventions in early childhood aimed at reducing some sources of stress improve telomere length or long-term health. Now, Lin et al. show that interventions to provide safe water, sanitation, handwashing facilities, and better nutrition to children in rural Bangladesh unexpectedly shortened telomeres. As part of a larger study, pregnant women in rural Bangladesh were divided, at random, into groups. One group received a suite of interventions, which included more sanitary toilets, handwashing facilities, and nutritional supplements for their infants. Another group served as a control and did not receive this extra help. Lin et al. looked at telomere length, growth, and infections in a subset of 713 children whose mothers participated in the study. Children who got the extra help grew faster and were less likely to get diarrhea or parasitic infections than the children in the control group. Unexpectedly, children in the intervention group had shorter telomeres at 14 months of age than the children in the control group. Lin et al. suggest that the telomere shortening in the intervention group might be a consequence of rapid growth and immune system development in the first year of life rather than resulting from biological stress. More studies are needed to ask whether telomere shortening is indeed linked to faster growth and development early in life. The strong and unexpected findings highlight how little is known about how the length of telomeres can be used to predict future health or disease. Interpreting the length of telomeres over a person’s lifetime could prove more nuanced than originally thought.

Poor sanitation and open defecation are thought to be a major cause of diarrhea and intestinal parasite infections among young children. In 1999, India launched the Total Sanitation Campaign with the goal of achieving universal toilet coverage in rural India by 2012. This paper reports on a cluster-randomized, controlled trial that was conducted in 80 rural villages in Madhya Pradesh to measure the effect of the program on toilet access, sanitation behavior, and child health outcomes. The study analyzed a random sample of 3,039 households and 5,206 children under five years of age. Field staff collected baseline measures of sanitation conditions, behavior, and child health, and re-visited households 21 months later. The analysis finds that implementation of the program activities was slower than the original timeline (only 35 percent of villages were triggered more than six months before the follow-up survey). Nevertheless, the Total Sanitation Campaign successfully increased toilet coverage by 19 percent in intervention villages compared with control villages (41 percent v. 22 percent), while reported open defecation decreased by 10 percent among adults (74 percent v. 84 percent). The intervention also led to some improvements in water quality and protozoan infection, but consistent improvements were not observed across multiple child health outcomes (diarrhea, helminth infections, child growth). However, the exposure period was likely to have been too short to result in any benefit of the sanitation interventions on child health. Given the large improvements in toilet construction documented, an additional follow-up survey with a longer period of exposure would yield valuable information on the effects of improved sanitation conditions on health outcomes.