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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).

Swimming and recreating in lakes, oceans, and rivers is common, yet the literature suggests children may be at greater risk of illness following such exposures. These effects might be due to differences in immunity or differing behavioral factors such as poorer hygiene, longer exposures to, and greater ingestion of potentially contaminated water and sand. We pooled data from 12 prospective cohorts (n=68,685) to examine exposures to potentially contaminated media such as beach water and sand among children compared with adults, and conducted a simulation using self-reported time spent in the water and volume of water swallowed per minute by age to estimate the total volume of water swallowed per swimming event by age category. Children aged 4-7 and 8-12 years had the highest exposures to water, sand, and algae compared with other age groups. Based on our simulation, we found that children (6-12 years) swallow a median of 36 ml (90th percentile=150 ml), whereas adults aged ≥35 years swallow 9 ml (90th percentile=64 ml) per swimming event, with male children swallowing a greater amount of water compared with females. These estimates may help to reduce uncertainty surrounding routes and durations of recreational exposures and can support the development of chemical and microbial risk assessments.

BACKGROUND: Diarrheal disease is a leading cause of childhood morbidity and mortality globally. Household water, sanitation, and handwashing (WASH) interventions can reduce exposure to diarrhea-causing pathogens, but meteorological factors may impact their effectiveness. Information about effect heterogeneity under different weather conditions is critical to refining these targeted interventions. OBJECTIVES: We aimed to determine whether temperature and precipitation modified the effect of low-cost, point-of-use WASH interventions on child diarrhea. METHODS: We analyzed data from a trial in rural Bangladesh that compared child diarrhea prevalence between clusters (푁 = 720) that were randomized to different WASH interventions between 2012 and 2016 (NCT01590095). We matched temperature and precipitation measurements to diarrhea outcomes (푁 = 12,440 measurements, 6,921 children) by geographic coordinates and date. We estimated prevalence ratios (PRs) using generative additive models and targeted maximum likelihood estimation to assess the effectiveness of each WASH intervention under different weather conditions. RESULTS: Generally, WASH interventions most effectively prevented diarrhea during monsoon season, particularly following weeks with heavy rain or high temperatures. The PR for diarrhea in the WASH interventions group compared with the control group was 0.49 (95% CI: 0.35, 0.68) after 1 d of heavy rainfall, with a less-protective effect [PR = 0:87 (95% CI: 0.60, 1.25)] when there were no days with heavy rainfall. Similarly, the PR for diarrhea in the WASH intervention group compared with the control group was 0.60 (95% CI: 0.48, 0.75) following above-median temperatures vs. 0.91 (95% CI: 0.61, 1.35) following below-median temperatures. The influence of precipitation and temperature varied by intervention type; for precipitation, the largest differences in effectiveness were for the sanitation and combined WASH interventions. DISCUSSION: WASH intervention effectiveness was strongly influenced by precipitation and temperature, and nearly all protective effects were observed during the rainy season. Future implementation of these interventions should consider local environmental conditions to maximize effectiveness, including targeted efforts to maintain latrines and promote community adoption ahead of monsoon seasons. [ABSTRACT FROM AUTHOR]

Background Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting. Objectives We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < −3) and severe stunting (length-for-age z score < −3). Methods We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. Results SQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n  = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n  = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n  = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n  = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. Conclusions Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592. [ABSTRACT FROM AUTHOR]

Mid‐upper arm circumference (MUAC) < 11.5 cm and weight‐for‐height Z‐score (WHZ) < −3 are used for screening for severe acute malnutrition (SAM). Underweight and concurrent wasting and stunting may better target those at the highest risk of mortality. We compared anthropometric outcomes in children enrolled in a trial of antibiotics for SAM based on categories of baseline anthropometry, including indicators for programme admission (WHZ < −3, MUAC < 11.5) and alternative indicators (weight‐for‐age Z‐score [WAZ] < −3, concurrent wasting and stunting [WHZ < −3 and height‐for‐age Z‐score < −3]). Participants were followed weekly until nutritional recovery and at 8 weeks. We evaluated changes in weight gain (g/kg/day), MUAC, and WHZ in children admitted by admissions criteria (MUAC only, WHZ only, or MUAC and WHZ) and by underweight or concurrent wasting and stunting. Of 301 admitted children, 100 (33%) were admitted based on MUAC only, 41 (14%) WHZ only, and 160 (53%) both MUAC and WHZ, 210 (68%) were underweight and 67 (22%) were concurrently wasted/stunted. Low MUAC and low WHZ children had the lowest probability of nutritional recovery (17% vs. 50% for MUAC‐only and 34% for WHZ‐only). There was no difference in weight gain velocity or WHZ by admissions criteria (WHZ and/or MUAC). Underweight and concurrently wasted/stunted children had lower MUAC and WHZ at 8 weeks compared with those who were not underweight or concurrently wasted and stunted. Children with both low MUAC and low WHZ had the worst outcomes. Relying on MUAC alone may miss children who have poor outcomes. Other indicators, such as WAZ, may be useful for identifying vulnerable children. Key messages: Mid‐upper arm circumference (MUAC) and weight‐for‐height Z‐score (WHZ) are currently used for severe acute malnutrition (SAM) screening, but alternative indicators such as weight‐for‐age Z‐score (WAZ) may be additional options.Children admitted to the nutritional program based on both low MUAC and low WHZ had the worst outcomes, including the lowest probability of nutritional recovery and the worst anthropometric outcomes.While MUAC identified most children with SAM, WHZ may provide additional information about poor outcomes beyond MUAC alone.WAZ may be a useful alternative indicator to identify children who would benefit from a therapeutic feeding program without requiring height measurement. [ABSTRACT FROM AUTHOR]

We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs. Clinical trials registration NCT02047981 [ABSTRACT FROM AUTHOR]

Of 61 355 visits by children <5 years old to 48 government-run primary healthcare facilities in Nouna District, Burkina Faso, 30 975 had an antibiotic prescribed (58% for pneumonia diagnoses). A minority of prescriptions were for diagnoses not requiring antibiotics, including malaria, nonbloody diarrhea, and cough without pneumonia. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend community-wide mass azithromycin for trachoma, but a targeted treatment strategy could reduce the volume of antibiotics required. Methods In total, 48 Ethiopian communities were randomized to mass, targeted, or delayed azithromycin distributions. In the targeted arm, only children aged 6 months to 5 years with evidence of ocular chlamydia received azithromycin, distributed thrice over the following year. The primary outcome was ocular chlamydia at months 12 and 24, comparing the targeted and delayed arms (0–5 year-olds, superiority analysis) and the targeted and mass azithromycin arms (8–12 year-olds, noninferiority analysis, 10% noninferiority margin). Results At baseline, the mean prevalence of ocular chlamydia in the 3 arms ranged from 7% to 9% among 0–5 year-olds and from 3% to 9% among 8–12 year-olds. Averaged across months 12–24, the mean prevalence of ocular chlamydia among 0–5 year-olds was 16.7% (95% confidence interval [CI]: 9.0%–24.4%) in the targeted arm and 22.3% (95% CI: 11.1%–33.6%) in the delayed arm (P  = .61). The final mean prevalence of ocular chlamydia among 8–12 year-olds was 13.5% (95% CI: 7.9%–19.1%) in the targeted arm and 5.5% (95% CI: 0.3%–10.7%) in the mass treatment arm (adjusted risk difference 8.5 percentage points [pp] higher in the targeted arm, 95% CI: 0.9 pp–16.1 pp higher). Conclusions Antibiotic treatments targeted to infected preschool children did not result in significantly less ocular chlamydia infections compared with untreated communities and did not meet noninferiority criteria relative to mass azithromycin distributions. Targeted approaches may require treatment of a broader segment of the population in areas with hyperendemic trachoma. [ABSTRACT FROM AUTHOR]

Background We hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting. Methods Within a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1β) at median ages 3, 14, and 28 months. Analysis was intention-to-treat. Results We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (–0.21 log nmol/L; 95% confidence interval [CI], –.37, –.05) and N+WSH (–0.20 log nmol/L; 95% CI, –.34, –.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (–0.60 to –0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23–0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI,.07,.53). Conclusions Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health. Clinical Trials Registration NCT01590095. [ABSTRACT FROM AUTHOR]

Background: Hands are a route of transmission for fecal-oral pathogens. This analysis aimed to assess associations between hand E. coli contamination and child age and determine if observed hand cleanliness can serve as a proxy for E. coli contamination on young children’s hands. Methods: Trained field workers collected hand rinse samples from children aged 1–14 months in 584 households in rural Bangladesh and assessed the visual cleanliness of child hands (fingernails, finger pads and palms). Samples were analyzed using the IDEXX most probable number (MPN) methodto enumerate E. coli. We assessed if child age (immobile children aged 1–4 months vs. mobile children aged 5–14 months) is associated with log10 E. coli counts on hands using generalized estimating equations (GEE). We estimated the log10 difference in hand E. coli counts associated with the cleanliness of different hand parts using a multivariable GEE model.We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for dirty fingernails, fingerpads, palms and overall hands (the three observed parts combined) against binary E. coli presence on hands. Results: E. coli was detected on 43% of child hands. Children in the mobile age range had 0.17 log10 MPN higher E. coli on hands than those in the immobile age range (Δlog10 = 0.17, 95% CI = 0.02, 0.32, p = 0.03). Children with visible dirt particles on finger pads had 0.46 log10 MPN higher E. coli on hands than those with clean finger pads (Δlog10 = 0.46, 95% CI = 0.05, 0.87, p = 0.03). Dirty fingernails indicated binary E. coli presence with 81% sensitivity and 26% specificity while dirty fingerpads and palms indicated E. coli presence with 29% sensitivity and 75–77% specificity. The PPV was 45–48% and NPV 59–65% for all three types of observations. Conclusion: Hand contamination with E. coli was prevalent among young children in rural Bangladesh, with higher levels of contamination among mobile children. Studies should assess if strategies to remove animal feces from the courtyard, provide designated hygienic play spaces for children and deliver targeted messaging to mothers to wipe or wash children’s hands after contact with animals and animal feces reduce child hand contamination. Visible hand cleanliness was a poor predictor of E. coli presence on young children’s hands so other low-cost field measurements are needed to accurately detect fecal contamination on hands. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effects of weather on diarrhea could influence the health impacts of climate change. Children have the highest diarrhea incidence, especially in India, where many lack safe water and sanitation. OBJECTIVES: In a prospective cohort of 1,284 children under 5 y of age from 900 households across 25 villages in rural Tamil Nadu, India, we examined whether high temperature and heavy rainfall was associated with increased all-cause diarrhea and water contamination. METHODS: Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide (H2S) presence in drinking water, a fecal contamination indicator, was tested in a subset of households. We estimated associations between temperature and rainfall exposures and diarrhea and H2S using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week. RESULTS: There were 259 cases of diarrhea. The prevalence of diarrhea during the 7 d before visits was 2.95 times higher (95% CI: 1.99, 4.39) when mean temperature in the week before the 7-d recall was in the hottest versus the coolest quartile of weekly mean temperature during 1 December 2007 to 15 April 2009. Diarrhea prevalence was 1.50 times higher when the 3 weeks before the diarrhea recall period included ≥1 d (vs. 0 d) with rainfall of >16:82 mm (95% CI: 1.12, 2.02), and 2.60 times higher (95% CI: 1.55, 4.36) for heavy rain weeks following a 60-d dry period. The H2S prevalence in household water was not associated with heavy rain prior to sample collection. CONCLUSIONS: The results suggest that, in rural Tamil Nadu, heavy rainfall may wash pathogens that accumulate during dry weather into child contact. Higher temperatures were positively associated with diarrhea 1-3 weeks later. Our findings suggest that diarrhea morbidity could worsen under climate change without interventions to reduce enteric pathogen transmission through multiple pathways. [ABSTRACT FROM AUTHOR]

Background Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. Objectives We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. Methods We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6–24 mo of age (n  = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. Results SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. Conclusions SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663. [ABSTRACT FROM AUTHOR]

Background: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners.Main Body: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health.Conclusion: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden. [ABSTRACT FROM AUTHOR]