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In this Commentary, the article by Rosenfeld et al. "Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses" is put into context of the historic poliovirus epidemics and resultant vaccination success story as it compares to the current state of acute flaccid myelitis; the relationship to nonpoliovirus enteroviruses (EVs), in particular EV-D68 and EV-A71; and the potential for successful vaccination strategies. The discovery of cross-protective antibody neutralization among polio and nonpolio enteroviruses, specifically EV-D68, opens future questions about EV-D68 vaccination strategies, circulation patterns of nonpolio enteroviruses, and the interpretation of EV-D68 serostudies.

Background: It is estimated that 1.5 billion people are infected with soil-transmitted helminths (STHs) worldwide. Re-infection occurs rapidly following deworming, and interruption of transmission is unlikely without complementary control efforts such as improvements in water, sanitation, and hygiene (WASH) access and behaviours., Objectives: To assess the effectiveness of WASH interventions to prevent STH infection., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 19 October 2021., Selection Criteria: We included interventions to improve WASH access or practices in communities where STHs are endemic. We included randomized controlled trials (RCTs), as well as trials with an external control group where participants (or clusters) were allocated to different interventions using a non-random method (non-RCTs). We did not include observational study designs. Our primary outcome was prevalence of any STH infection. Prevalence of individual worms was a secondary outcome, including for Ascaris lumbricoides, Trichuris trichiura, hookworm (Ancylostoma duodenale or Necator americanus), or Strongyloides stercoralis. Intensity of infection, measured as a count of eggs per gram of faeces for each species, was another secondary outcome., Data Collection and Analysis: Two review authors independently reviewed titles and abstracts and full-text records for eligibility, performed data extraction, and assessed risk of bias using the Cochrane risk of bias assessment tool for RCTs and the EPOC tool for non-RCTs. We used a random-effects meta-analysis to pool study estimates. We used Moran's I² statistic to assess heterogeneity and conducted subgroup analyses to explore sources of heterogeneity. We assessed the certainty of the evidence using the GRADE approach., Main Results: We included 32 studies (16 RCTs and 16 non-RCTs) involving a total of 52,944 participants in the review. Twenty-two studies (14 RCTs (16 estimates) and eight non-RCTs (11 estimates)) reported on our primary outcome, prevalence of infection with at least one STH species. Twenty-one studies reported on the prevalence of A lumbricoides (12 RCTs and 9 non-RCTs); 17 on the prevalence of T trichiura (9 RCTs and 8 non-RCTs); 18 on the prevalence of hookworm (10 RCTs and 8 non-RCTs); and one on the prevalence of S stercoralis (1 non-RCT). Sixteen studies measured the intensity of infection for an individual STH type. Ten RCTs and five non-RCTs reported on the intensity of infection of A lumbricoides; eight RCTs and five non-RCTs measured the intensity of infection of T trichiura; and eight RCTs and five non-RCTs measured the intensity of hookworm infection. No studies reported on the intensity of infection of S stercoralis. The overall pooled effect estimates showed that the WASH interventions under study may result in a slight reduction of any STH infection, with an odds ratio (OR) of 0.86 amongst RCTs (95% confidence interval (CI) 0.74 to 1.01; moderate-certainty evidence) and an OR of 0.71 amongst non-RCTs (95% CI 0.54 to 0.94; low-certainty evidence). All six of the meta-analyses assessing individual worm infection amongst both RCTs and non-RCTs had pooled estimates in the preventive direction, although all CIs encapsulated the null, leaving the possibility of the null or even harmful effects; the certainty of the evidence ranged from very low to moderate. Individual studies assessing intensity of infection showed mixed evidence supporting WASH. Subgroup analyses focusing on narrow specific subsets of water, sanitation, and hygiene interventions did very little to elucidate which interventions might be better than others. Data on intensity of infection (e.g. faecal egg count) were reported in a variety of ways across studies, precluding the pooling of results for this outcome. We did not find any studies reporting adverse events resulting from the WASH interventions under study or from mass drug administration (MDA)., Authors' Conclusions: Whilst the available evidence suggests that the WASH interventions under study may slightly protect against STH infection, WASH also serves as a broad preventive measure for many other diseases that have a faecal oral transmission route of transmission. As many of the studies were done in addition to MDA/deworming (i.e. MDA was ongoing in both the intervention and control arm), our data support WHO recommendations for implementation of improvements to basic sanitation and adequate access to safe water alongside MDA. The biological plausibility for improved access to WASH to interrupt transmission of STHs is clear, but WASH interventions as currently delivered have shown impacts that were lower than expected. There is a need for more rigorous and targeted implementation research and process evaluations in order that future WASH interventions can better provide benefit to users. Inconsistent reporting of the intensity of infection underscores the need to define the minimal, standard data that should be collected globally on STHs to enable pooled analyses and comparisons., (Copyright © 2022 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Interventions aimed at improving dietary intake and feeding practices have alone proven insufficient for combatting stunting resulting from poor nutrition and repeated infections., Objectives: To support the development of an integrated water, sanitation, and hygiene (WASH) and nutrition, social, and behavior change strategy aimed at reducing stunting, formative research was conducted in 2 program sites in western Kenya., Methods: Twenty-nine key informant interviews were conducted with community leaders, health workers, and project staff, and 24 focus group discussions with caregivers of children under 2 y on topics related to feeding, sanitation, and hygiene behaviors. Three frameworks informed the study design and analysis of our formative research: the Capabilities, Opportunities, and Motivations model for behavior change, which identifies what needs to change in order for behavior change interventions to be effective; the Grandmother Project's Change Through Culture Approach, which values the important role of influential household and community members in producing household health; and Starr and Fornoff's approach to Theory of Change development., Results: Caregivers exhibited sufficient psychological capabilities (knowledge and skills) for many of the key maternal and infant nutrition behaviors. However, reflective motivation to perform optimal behaviors was undermined by limitations in physical and social opportunities, including limited time and competing priorities for mothers, limited accessibility and availability of diverse foods, low self-efficacy for exclusive breastfeeding, and fears of negative consequences related to specific foods and recommended practices., Conclusions: Interventions that aim to improve maternal and child diets should address the underlying social, cultural, and environmental determinants that contribute to motivations and opportunities to perform recommended practices., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Safe water, sanitation, and hygiene (WaSH) is important for health, livelihoods, and economic development, but WaSH programs have often underdelivered on expected health benefits. Underperformance has been attributed partly to poor ability to retain effectiveness following adaptation to facilitate WaSH programs' implementation in diverse contexts. Adaptation of WaSH interventions is common but often not done systematically, leading to poor outcomes. Models and frameworks from the adaptation literature have potential to improve WaSH adaptation to facilitate implementation and retain effectiveness. However, these models and frameworks were designed in a healthcare context, and WaSH interventions are typically implemented outside traditional health system channels. The purpose of our work was to develop an adaptation model tailored specifically to the context of WaSH interventions., Methods: We conducted a scoping review to identify key adaptation steps and identify tools to support systematic adaptation. To identify relevant literature, we conducted a citation search based on three recently published reviews on adaptation. We also conducted a systematic database search for examples of WaSH adaptation. We developed a preliminary model based on steps commonly identified across models in adaptation literature, and then tailored the model to the WaSH context using studies yielded by our systematic search. We compiled a list of tools to support systematic data collection and decision-making throughout adaptation from all included studies., Results and Conclusions: Our model presents adaptation steps in five phases: intervention selection, assessment, preparation, implementation, and sustainment. Phases for assessment through sustainment are depicted as iterative, reflecting that once an intervention is selected, adaptation is a continual process. Our model reflects the specific context of WaSH by including steps to engage non-health and lay implementers and to build consensus among diverse stakeholders with potentially competing priorities. We build on prior adaptation literature by compiling tools to support systematic data collection and decision-making, and we describe how they can be used throughout adaptation steps. Our model is intended to improve program outcomes by systematizing adaptation processes and provides an example of how systematic adaptation can occur for interventions with health goals but that are implemented outside conventional health system channels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Anderson, Birken, Bartram and Freeman.)

Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies prove effective at driving coverage is not well-established. To address this gap, we identified critical success factors associated with advancing key policies and programs that may have led to the substantial changes in routine childhood immunization coverage in Zambia between 2000 and 2018., Methods: We identified Zambia as an exemplar in the delivery of childhood vaccines through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national and subnational levels, we investigated factors that contributed to high and sustained vaccination coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data., Results: The following success factors emerged: 1) the Inter-agency Coordinating Committee was strengthened for long-term engagement which, complemented by the Zambia Immunization Technical Advisory Group, is valued by the government and integrated into national-level decision-making; 2) the Ministry of Health improved the coordination of data collection and review for informed decision-making across all levels; 3) Regional multi-actor committees identified development priorities, strategies, and funding, and iteratively adjusted policies to account for facilitators, barriers, and lessons learned; 4) Vaccine messaging was disseminated through multiple channels, including the media and community leaders, increasing trust in the government by community members; 5) The Zambia Ministry of Health and Churches Health Association of Zambia formalized a long-term organizational relationship to leverage the strengths of faith-based organizations; and 6) Neighborhood Health Committees spearheaded community-driven strategies via community action planning and ultimately strengthened the link between communities and health facilities., Conclusion: Broader health systems strengthening and strong partnerships between various levels of the government, communities, and external organizations were critical factors that accelerated vaccine coverage in Zambia. These partnerships were leveraged to strengthen the overall health system and healthcare governance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction: Increases in global childhood vaccine delivery have led to decreases in morbidity from vaccine-preventable diseases. However, these improvements in vaccination have been heterogeneous, with some countries demonstrating greater levels of change and sustainability. Understanding what these high-performing countries have done differently and how their decision-making processes will support targeted improvements in childhood vaccine delivery., Methods and Analysis: We studied three countries-Nepal, Senegal, Zambia-with exemplary improvements in coverage between 2000 and 2018 as part of the Exemplars in Global Health Programme. We apply established implementation science frameworks to understand the 'how' and 'why' underlying improvements in vaccine delivery and coverage. Through mixed-methods research, we will identify drivers of catalytic change in vaccine coverage and the decision-making process supporting these interventions and activities. Methods include quantitative analysis of available datasets and in-depth interviews and focus groups with key stakeholders in the global, national and subnational government and non-governmental organisation space, as well as community members and local health delivery system personnel., Ethics and Dissemination: Working as a multinational and multidisciplinary team, and under oversight from all partner and national-level (where applicable) institutional review boards, we collect data from participants who provided informed consent. Findings are disseminated through a variety of forms, including peer-reviewed manuscripts related to country-specific case studies and vaccine system domain-specific analyses, presentations to key stakeholders in the global vaccine delivery space and narrative dissemination on the Exemplars.Health website., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Adaptations are modifications made to programming to improve effectiveness or contextual fit, and are important for program improvement. However, adaptations can be detrimental if they do not preserve an intervention's underlying theory of change. We present a case study of 45 adaptations made to rural WaSH programming in Nepal, identified through qualitative interviews with implementers conducted in June through August 2019. For each adaptation, we characterized its target outcomes and implementers' motivations for making the adaptation, and we assessed the adaptation's intended and unintended effects on program quality. Participants described adaptations to both interventions (e.g., changes to hygiene promotion messages) and implementation strategies (e.g., sanctions to enforce toilet construction, such as denying work permits to households without a toilet). Adoption was the most common target outcome, specifically increasing toilet construction. Other target outcomes included feasibility of program delivery, acceptability of messages or WaSH products, reach of program activities in the community, and sustainability. Implementers were commonly motivated by intense pressure to meet national open defecation free targets. Most adaptations achieved their target outcomes. However, sanctions adaptations had substantial unintended negative effects. Implementers reported that sanctions were unpopular with communities and had poor sustainability. In contrast, non-sanctions adaptations that targeted outcomes of feasibility, acceptability, and sustainability had few unintended negative consequences. Our findings suggest that adaptations to promote rapid adoption of toilet construction do not consistently achieve sustained behavior change. Furthermore, adaptations to improve feasibility of program delivery or cost and acceptability of WaSH products can indirectly improve adoption even when it is not an explicit target outcome., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Behaviors related to water, sanitation, and hygiene (WASH) are key drivers of infectious disease transmission, and experiences of WASH are potential influencers of mental well-being. Important knowledge gaps exist related to the content and delivery of effective WASH programs and their associated health impacts, particularly within the contexts of government programs implemented at scale. We developed and tested a demand-side intervention called Andilaye, which aimed to change behaviors related to sanitation, personal hygiene, and household environmental sanitation. This theory-informed intervention was delivered through the existing Ethiopian Health Extension Programme (HEP). It was a multilevel intervention with a catalyzing event at the community level and behavior change activities at group and household levels. We randomly selected and assigned 50 kebeles (sub-districts) from three woredas (districts), half to receive the Andilaye intervention, and half the standard of care sanitation and hygiene programming (i.e., community-led total sanitation and hygiene [CLTSH]). We collected data on WASH access, behavioral outcomes, and mental well-being. A total of 1,589 households were enrolled into the study at baseline; 1,472 households (94%) participated in an endline assessment two years after baseline, and approximately 14 months after the initiation of a multi-level intervention. The intervention did not improve construction of latrines (prevalence ratio [PR]: 0.99; 95% CI: 0.82, 1.21) or handwashing stations with water (PR: 0.96; 95% CI: 0.72, 1.26), or the removal of animal feces from the compound (PR: 1.10; 95% CI: 0.95, 1.28). Nor did it impact anxiety (PR: 0.90; 95% CI: 0.72, 1.11), depression (PR: 0.83; 95% CI: 0.64, 1.07), emotional distress (PR: 0.86; 95% CI: 0.67, 1.09) or well-being (PR: 0.90; 95% CI: 0.74, 1.10) scores. We report limited impact of the intervention, as delivered, on changes in behavior and mental well-being. The effectiveness of the intervention was limited by poor intervention fidelity. While sanitation and hygiene improvements have been documented in Ethiopia, behavioral slippage, or regression to unimproved practices, in communities previously declared open defecation free is widespread. Evidence from this trial may help address knowledge gaps related to challenges associated with scalable alternatives to CLTSH and inform sanitation and hygiene programming and policy in Ethiopia and beyond. Trial registration: This trial was registered with clinicaltrials.gov (NCT03075436) on March 9, 2017., Competing Interests: The authors declare no competing interests., (Copyright: © 2022 Freeman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: WHO promotes the SAFE strategy for the elimination of trachoma as a public health programme, which promotes surgery for trichiasis (ie, the S component), antibiotics to clear the ocular strains of chlamydia that cause trachoma (the A component), facial cleanliness to prevent transmission of secretions (the F component), and environmental improvements to provide water for washing and sanitation facilities (the E component). However, little evidence is available from randomised trials to support the efficacy of interventions targeting the F and E components of the strategy. We aimed to determine whether an integrated water, sanitation, and hygiene (WASH) intervention prevents the transmission of trachoma., Methods: The WASH Upgrades for Health in Amhara (WUHA) was a two-arm, parallel-group, cluster-randomised trial in 40 rural communities in Wag Hemra Zone (Amhara Region, Ethiopia) that had been treated with 7 years of annual mass azithromycin distributions. The randomisation unit was the school catchment area. All households within a 1·5 km radius of a potential water point within the catchment area (as determined by the investigators) were eligible for inclusion. Clusters were randomly assigned (at a 1:1 ratio) to receive a WASH intervention either immediately (intervention) or delayed until the conclusion of the trial (control), in the absence of concurrent antibiotic distributions. Given the nature of the intervention, participants and field workers could not be masked, but laboratory personnel were masked to treatment allocation. The WASH intervention consisted of both hygiene infrastructure improvements (namely, construction of a community water point) and hygiene promotion by government, school, and community leaders, which were implemented at the household, school, and community levels. Hygiene promotion focused on two simple messages: to use soap and water to wash your or your child's face, and to always use a latrine for defecation. The primary outcome was the cluster-level prevalence of ocular chlamydia, measured annually using conjunctival swabs in a random sample of children aged 0-5 years from each cluster at 12, 24, and 36 month timepoints. Analyses were done in an intention-to-treat manner. This trial is ongoing and is registered at ClinicalTrials.gov, NCT02754583., Findings: Between Nov 9, 2015, and March 5, 2019, 40 of 44 clusters assessed for eligibility were enrolled and randomly allocated to the trial groups (20 clusters each, with 7636 people from 1751 households in the intervention group and 9821 people from 2211 households in the control group at baseline). At baseline, ocular chlamydia prevalence among children aged 0-5 years was 11% (95% CI 6 to 16) in the WASH group and 11% (5 to 18) in the control group. At month 36, ocular chlamydia prevalence had increased in both groups, to 32% (24 to 41) in the WASH group and 31% (21 to 41) in the control group (risk difference across three annual monitoring visits, after adjustment for prevalence at baseline: 3·7 percentage points; 95% CI -4·9 to 12·4; p=0·40). No adverse events were reported in either group., Interpretation: An integrated WASH intervention addressing the F and E components of the SAFE strategy did not prevent an increase in prevalence of ocular chlamydia following cessation of antibiotics in an area with hyperendemic trachoma. The impact of WASH in the presence of annual mass azithromycin distributions is currently being studied in a follow-up trial of the 40 study clusters. Continued antibiotic distributions will probably be important in areas with persistent trachoma., Funding: National Institutes of Health-National Eye Institute., Translation: For the Amharic translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests BA reports financial support to attend global health meetings from the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Most pediatric studies of asthma and COVID-19 to date have been ecological, which offer limited insight. We evaluated the association between asthma and COVID-19 at an individual level., Methods: Using data from prospective clinical registries, we conducted a nested case-control study comparing three groups: children with COVID-19 and underlying asthma ("A+C" cases); children with COVID-19 without underlying disease ("C+" controls); and children with asthma without COVID-19 ("A+" controls)., Results: The cohort included 142 A+C cases, 1110 C+ controls, and 140 A+ controls. A+C cases were more likely than C+ controls to present with dyspnea and wheezing, to receive pharmacologic treatment including systemic steroids (all p < .01), and to be hospitalized (4.9% vs. 1.7%, p = .01). In the adjusted analysis, A+C cases were nearly 4 times more likely to be hospitalized than C+ controls (adjusted OR = 3.95 [95%CI = 1.4-10.9]); however, length of stay and respiratory support level did not differ between groups. Among A+C cases, 8.5% presented with an asthma exacerbation and another 6.3% developed acute exacerbation symptoms shortly after testing positive for SARS-CoV-2. Compared to historic A+ controls, A+C cases had less severe asthma, were less likely to be on controller medications, and had better asthma symptom control (all p < .01)., Conclusions: In our cohort, asthma was a risk factor for hospitalization in children with COVID-19, but not for worse COVID-19 outcomes. SARS-CoV-2 does not seem to be a strong trigger for pediatric asthma exacerbations. Asthma severity was not associated with higher risk of COVID-19., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Rapid urbanization, resulting in population growth within informal settlements, has worsened exclusion and inequality in access to water and sanitation (WASH) services in the poorest and most marginalized communities. In this study, we describe the heterogeneity in water service satisfaction and WASH access in low-income, peri-urban neighborhoods of Beira, Mozambique, and examine whether this heterogeneity can be explained by distance to water distribution mains. Using spatial statistics and regression analyses, we identify spatial heterogeneity in household WASH access, as well as consumer-reported satisfaction with water services (services, pressure, quality, and sufficient quantity). We find that as distance from the water main increased, both access to an improved water source at the household and satisfaction with water pressure decreases, and water supply intermittency increases, controlling for household density and socioeconomic status. The odds of a household having access to a water source at the household or on the compound decreases with every 100-meter increase in distance from a water main pipe (odds ratio [OR] 0.87, 95% confidence interval [CI]: 0.82, 0.92). Satisfaction with water services also decreases with every 100-meter increase in distance from a water main pipe (OR: 0.80; 95% CI: 0.69, 0.94). Days of availability in the past week decreases by a factor of 0.22 for every 100-meter increase in distance from the water main (95% CI: -0.29, -0.15). Findings from this study highlight the unequal household access to water and sanitation in urban informal settlements, even within low-income neighborhoods. Describing this heterogeneity of access to water services, sanitation, and satisfaction-and the factors influencing them-can inform stakeholders and guide the development of infrastructural solutions to reduce water access inequities within urban settings., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Objective: To determine whether a water, sanitation and hygiene intervention could change hygiene behaviours thought to be important for trachoma control., Methods: We conducted a cluster-randomized trial in rural Ethiopia from 9 November 2015 to 5 March 2019. We randomized 20 clusters to an intervention consisting of water and sanitation infrastructure and hygiene promotion and 20 clusters to no intervention. All intervention clusters received a primary-school hygiene curriculum, community water point, household wash station, household soap and home visits from hygiene promotion workers. We assessed intervention fidelity through annual household surveys., Findings: Over the 3 years, more wash stations, soap and latrines were seen at households in the intervention clusters than the control clusters: risk difference 47 percentage points (95% confidence interval, CI: 41-53) for wash stations, 18 percentage points (95% CI: 12-24) for soap and 12 percentage points (95% CI: 5-19) for latrines. A greater proportion of people in intervention clusters reported washing their faces with soap (e.g. risk difference 21 percentage points; 95% CI: 15-27 for 0-5 year-old children) and using a latrine (e.g. risk difference 9 percentage points; 95% CI: 2-15 for 6-9 year-old children). Differences between the intervention and control arms were not statistically significant for many indicators until the programme had been implemented for at least a year; they did not decline during later study visits., Conclusion: The community- and school-based intervention was associated with improved hygiene access and behaviours, although changes in behaviour were slow and required several years of the intervention., ((c) 2021 The authors; licensee World Health Organization.)

Background: Antigen testing offers rapid and inexpensive testing for SARS-CoV-2 but concerns regarding performance, especially sensitivity, remain. Limited data exists for use of antigen testing in asymptomatic patients; thus, performance and reliability of antigen testing remains unclear., Methods: 148 symptomatic and 144 asymptomatic adults were included. A nasal swab was collected for testing by Quidel Sofia SARS IFA (Sofia) as point of care. A nasopharyngeal swab was also collected and transported to the laboratory for testing by Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV RT-PCR (Cepheid)., Results: Overall, Sofia had good agreement with Cepheid (> 95%) in adults, however was less sensitive. Sofia had a sensitivity of 87.8% and 33.3% for symptomatic and asymptomatic patients, respectively. Among symptomatic patients, testing > 5 days post symptom onset resulted in lower sensitivity (82%) when compared with testing within 5 days of symptom onset (90%). Of the four Sofia false-negative results in the asymptomatic cohort, 50% went on to develop COVID-19 disease within 5 days of testing. Specificity in both symptomatic and asymptomatic cohorts was 100%., Conclusions: Sofia has acceptable performance in symptomatic adults when tested < 5 days of symptom onset. Caution should be taken when testing patients with ≥ 5 days of symptoms. The combination of low prevalence and reduced sensitivity results in relatively poor performance of in asymptomatic patients. NAAT-based diagnostic assays should be considered in when antigen testing is unreliable, particularly in symptomatic patients with > 5 days of symptom onset and asymptomatic patients., (© 2021. The Author(s).)

A continuous-variable Bayesian network (cBN) model is used to link watershed development and climate change to stream ecosystem indicators. A graphical model, reflecting our understanding of the connections between climate change, weather condition, loss of natural land cover, stream flow characteristics, and stream ecosystem indicators is used as the basis for selecting flow metrics for predicting macroinvertebrate-based indicators. Selected flow metrics were then linked to variables representing watershed development and climate change. We fit the model to data from two river basins in southeast US and the resulting model was used to simulate future stream ecological conditions using projected future climate and development scenarios. The three climate models predicted varying ecological condition trajectories, but similar worst-case ecological conditions. The established modeling approach couples mechanistic understanding with field data to develop predictions of management-relevant variables across a heterogeneous landscape. We discussed the transferability of the modeling approach., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Children infected with SARS-CoV-2 are often asymptomatic or have only mild symptoms, leading to underestimation of disease prevalence in symptom-based testing strategies., Objectives: This study sought to determine pediatric SARS-CoV-2 disease burden during local mitigation efforts by using antibody testing to compare seroprevalence estimates to cumulative PCR prevalence estimates., Study Design: In this cross-sectional study, we collected 1142 strict phase and 1196 relaxed phase remnant blood specimens from patients less than 19-years-old in southwestern Pennsylvania (SWPA). Patients were excluded if their residential zip code was outside the region of interest, if they were under 6-months-old, or they had recently received antibody-modifying treatments. Demographic, encounter, and laboratory electronic medical record information was extracted. Samples were tested for SARS-CoV-2 spike protein IgG using an EUA ELISA, and PCR results were recorded from county health department data. Seroprevalence and Clopper-Pearson exact 95% confidence intervals were calculated., Results: The observed seroprevalence of SARS-CoV-2 spike protein antibodies in children during strictest mitigation was 0.53% (95% CI 0.19, 1.14) and 0.92% (95% CI 0.46,1.64) during moderately relaxed. Strict and relaxed phase PCR-based prevalence were significantly higher, 2.87% (95% CI 1.95, 4.08) and 3.64 (95% CI 3.01, 4.38), respectively., Conclusions: Estimates of pediatric seroprevalence were significantly lower than cumulative PCR prevalence estimates, and less than adult seroprevalence estimates, potentially due to biological, population, or sampling differences. Biological differences in pediatric immune responses to SARS-CoV-2 may make serosurvey interpretation challenging and these differences warrant further study., Competing Interests: None of the authors have any conflicts of interest that relate to the work conducted for this manuscript., (© 2021 The Authors. Published by Elsevier Ltd.)

Enterovirus D68 (EV-D68) has been implicated in outbreaks of severe respiratory illness and is associated with acute flaccid myelitis (AFM). EV-D68 is often detected in patient respiratory samples but has also been detected in stool and wastewater, suggesting the potential for both respiratory and enteric routes of transmission. Here, we used a panel of EV-D68 isolates, including a historical pre-2014 isolate and multiple contemporary isolates from AFM outbreak years, to define the dynamics of viral replication and the host response to infection in primary human airway cells and stem cell-derived enteroids. We show that some recent EV-D68 isolates have decreased sensitivity to acid and temperature compared with earlier isolates and that the respiratory, but not intestinal, epithelium induces a robust type III interferon response that restricts infection. Our findings define the differential responses of the respiratory and intestinal epithelium to contemporary EV-D68 isolates and suggest that a subset of isolates have the potential to target both the human airway and gastrointestinal tracts., Competing Interests: MF, AW, JC, MM, LY, JK, CC No competing interests declared

Competing Interests: Competing interests: RAB, KAH and MCF are recipients of funding from the Bill & Melinda Gates Foundation. MCF is a recipient of funding from Gates Ventures and serves in an unpaid role on a Gates Ventures advisory board. NF, NG, GI and DEP are employees of Gates Ventures. NF received funding as a WHO consultant from June–September 2019. Authors declare no additional interests.

Introduction: Women's active participation is important for inclusive water, sanitation, and hygiene (WaSH) programs, yet gender roles that limit women's access to formal education and employment may reduce their skills, experience, and capacity for implementation. This paper explores differences between men and women implementers of rural WaSH programs in implementation approaches, challenges, and sources of support for implementation, and success in achieving program quality outcomes., Methods: We interviewed 18 men and 13 women in community-based implementation roles in four districts of Nepal. We identified challenges and sources of support for implementation in four domains-informational, tangible, emotional, or companionship-following social support theory. We assessed successes at achieving intermediate implementation outcomes (e.g., adoption, appropriateness, sustainability) and long-term intervention outcomes (e.g., community cleanliness, health improvements)., Results: Women used relational approaches and leveraged social ties to encourage behavior change, while men used formative research to identify behavior drivers and sanctions to drive behavior change. Women experienced stigma for working outside the home, which was perceived as a traditionally male role. Companionship and emotional support from other women and male community leaders helped mitigate stigma and lack of informational support. Women were also more likely to receive no or low financial compensation for work and had fewer opportunities for feedback and training compared to men. Despite lack of support, women were motivated to work by a desire to build their social status, gain new knowledge, and break conventional gender roles., Conclusions: Both men and women perceived that women were more effective than men at mobilizing widespread, sustained WaSH improvements, which was attributed to their successes using relational approaches and leveraging social ties to deliver acceptable and appropriate messages. Their skills for motivating collective action indicate that they can be highly effective WaSH implementers despite lack of technical experience and training, and that women's active participation is important for achieving transformative community change., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections in children worldwide and a frequent cause of hospitalization. Rapid diagnostic assays (RDAs) are available for RSV and they help guide management; however, they are underutilized in developing countries. We compared molecular diagnostics to RSV RDA in hospitalized children in Amman, Jordan., Materials and Methods: Children under 2 years of age, admitted with fever and/or respiratory symptoms were enrolled prospectively from March 2010 to 2012. Demographic and clinical data were collected through parent/guardian interviews and medical chart abstraction. RSV RDAs were performed, and nasal/throat swabs were tested for RSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR)., Results: RSV RDA and PCR were performed on specimens from 1271 subjects. RSV RDA had a sensitivity of 26% and a specificity of 99%, with positive and negative predictive values of 98.6% and 43%, respectively. RDA-positive patients had fewer days of symptoms at presentation and were more likely to have a history of prematurity, lower birth weight, require supplemental oxygen, and a longer hospitalization as compared with subjects with negative RDA. Multivariate analysis showed only lower birth weight, lack of cyanosis on examination, and lower cycle threshold to be independently associated with positive RDA (p ≤ .001)., Conclusion: RSV RDAs had high specificity, but low sensitivity as compared with qRT-PCR. Positive RDA was associated with patients with a more severe disease, as indicated by oxygen use, longer length of stay, and higher viral load. Implementation of RDAs in developing countries could be an inexpensive and expedient method for predicting RSV disease severity and guiding management., (© 2020 Wiley Periodicals LLC.)

Background: Delivery of high quality, at-scale, and sustained services is a major challenge in the water, sanitation, and hygiene (WASH) sector, made more challenging by a dearth of evidence-based models for adaption across contexts in low- and middle-income countries., Objective: We aim to describe the value of implementation science (IS) for the WASH sector and provide recommendations for its application., Methods: We review concepts from the growing field of IS-defined as the "scientific study of methods to promote the systematic uptake of research findings and other evidence-based practices into routine practice, and hence, to improve the quality and effectiveness of health services"-and we translate their relevance to WASH research, learning, and delivery., Discussion: IS provides a suite of methods and theories to systematically develop, evaluate, and scale evidence-based interventions. Though IS thinking has been applied most notably in health services delivery in high-income countries, there have been applications in low-income settings in fields such as HIV/AIDS and nutrition. Expanding the application of IS to environmental health, specifically WASH interventions, would respond to the complexity of sustainable service delivery. WASH researchers may want to consider applying IS guidelines to their work, including adapting pragmatic research models, using established IS frameworks, and cocreating knowledge with local stakeholders. https://doi.org/10.1289/EHP7762.

Objectives: Serologic assay performance studies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-​2) in pediatric populations are lacking, and few seroprevalence studies have routinely incorporated orthogonal testing to improve accuracy., Methods: Remnant serum samples for routine bloodwork from 2,338 pediatric patients at UPMC Children's Hospital of Pittsburgh were assessed using the EUROIMMUN Anti-SARS-CoV-2 ELISA IgG (EuroIGG) assay. Reactive cases with sufficient volume were also tested using 3 additional commercial assays., Results: Eighty-five specimens were reactive according to the EuroIGG, yielding 3.64% (95% confidence interval [CI], 2.91%-4.48%) seropositivity, of which 73 specimens had sufficient remaining volume for confirmation by orthogonal testing. Overall, 19.18% (95% CI, 10.18%-28.18%) of samples were positive on a second and/or third orthogonal assay. This 80.82% false positivity rate is disproportionate to the expected false positivity rate of 50% given our pediatric population prevalence and assay performance., Conclusions: In pediatric populations, false-positive SARS-CoV-2 serology may be more common than assay and prevalence parameters would predict, and further studies are needed to establish the performance of SARS-CoV-2 serology in children., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Routine immunisation is a cost-effective way to save lives and protect people from disease. Some low-income countries (LIC) achieved remarkable success in childhood immunisation. Yet, previous studies comparing the relationship between economic growth and health spending with vaccination coverage have been limited. We investigated these relationships among LIC to understand what financial changes lead to childhood immunisation changes., Methods: We identified which financial indicators were significant predictors of vaccination coverage in LIC by fitting regression models for several vaccines, controlling for population density, land area and female years of education. We then identified LIC with high vaccination coverage (LIC+) and compared their economic and health spending trends with other LIC (LIC-) and lower-middle income countries. We used cross-country multi-year regressions with mixed-effects to test financial indicators' rate of change. We conducted statistical tests to verify if financial trends of LIC+ were significantly different from LIC-., Results: During 2014-2018, gross domestic product per capita (p=0.67-0.95, range given by tests with different vaccines), total/private health spending per capita (p=0.57-0.97, p=0.32-0.57) and aggregated development assistance for health (DAH) per capita (p=0.38-0.86) were not significant predictors of vaccination coverage in LIC. Government health spending per capita (p=0.022-0.073) and total/government spending per birth on routine immunisation vaccines (p=0.0007-0.029, p=0.016-0.052) were significant positive predictors of vaccination coverage. From 2000 to 2016, LIC+ increased government health spending per capita by US$0.30 per year, while LIC- decreased by US$0.16 (significant difference, p<0.0001). From 2006 to 2017, LIC+ increased government spending per birth on routine immunisation vaccines by US$0.22 per year, while LIC- increased by US$0.10 (p<0.0093)., Conclusion: Vaccination coverage success of some LIC was not explained by economic development, total health spending nor aggregated DAH. Vaccination coverage success of LIC+ was associated with increasing government health spending particularly in routine immunisation vaccines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

In March 2020, the World Health Organization (WHO) issued a set of public guidelines for Coronavirus Disease 2019 (COVID-19) prevention measures that highlighted handwashing, physical distancing, and household cleaning. These health behaviors are severely compromised in parts of the world that lack secure water supplies, particularly in low- and middle-income countries (LMICs). We used empirical data gathered in 2017-2018 from 8,297 households in 29 sites across 23 LMICs to address the potential implications of water insecurity for COVID-19 prevention and response. These data demonstrate how household water insecurity presents many pathways for limiting personal and environmental hygiene, impeding physical distancing and exacerbating existing social and health vulnerabilities that can lead to more severe COVID-19 outcomes. In the four weeks prior to survey implementation, 45.9% of households in our sample either were unable to wash their hands or reported borrowing water from others, which may undermine hygiene and physical distancing. Further, 70.9% of households experienced one or more water-related problems that potentially undermine COVID-19 control strategies or disease treatment, including insufficient water for bathing, laundering, or taking medication; drinking unsafe water; going to sleep thirsty; or having little-to-no drinking water. These findings help identify where water provision is most relevant to managing COVID-19 spread and outcomes., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Background: The burden of coronavirus disease 2019 (COVID-19) is poorly understood in pediatric patients due to frequent asymptomatic and mild presentations. Additionally, the disease prevalence in pediatric immunocompromised patients remains unknown., Methods: This cross-sectional study tested convenience samples from pediatric patients who had clinically indicated lab work collected and an immunocompromising condition, including oncologic diagnoses, solid organ transplant (SOT), bone marrow transplant, primary immunodeficiency, and rheumatologic conditions or inflammatory bowel disease on systemic immunosuppression, for the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Results: We tested sera from 485 children and observed SARS-CoV-2 seroprevalence of 1.0% (Confidence Interval [CI] 95%: 0.3%-2.4%). Two patients were positive by nasopharyngeal (NP) swab Reverse transcriptase polymerase chain reaction (RT-PCR), but only 1 seroconverted. Patients with oncologic diagnoses or SOT were most likely to be tested for COVID-19 when presenting with respiratory illness as compared with other groups., Conclusions: Seroprevalence of antibodies to SARS-CoV-2 in immunocompromised children was similar to that of an immunocompetent pediatric population (0.6%, CI 95%: 0.3%-1.1%), suggesting an adequate antibody response. However, none of the patients who tested positive for antibodies or via NP RT-PCR had more than a mild illness course and 2 patients did not have any reported illness, suggesting that SARS-CoV-2 may not cause a worse clinical outcome in immunosuppressed children, in contrast to immunocompromised adults., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is a syndrome first reported in Japan. Neonates develop systemic exanthema, thrombocytopenia, and fever usually during the first week of life. The disease is distinguished from frank TSS because affected infants are not severely ill and do not meet TSS criteria. Most infants are confirmed to be colonized with TSST-1 producing strains of S. aureus. Suggested diagnostic criteria for NTED include a skin rash with generalized macular erythema and one of the following symptoms: fever >38.0°C, thrombocytopenia <150 x103uL, or low positive C-reactive protein (1-5 mg/dL) in the absence of another known disease process. NTED is common in Japanese NICUs, but outside Japan, only one case has been reported in France. We describe the first case of NTED reported in North America., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Facial hygiene promotion and environmental improvements are central components of the global trachoma elimination strategy despite a lack of experimental evidence supporting the effectiveness of water, sanitation and hygiene (WASH) measures for reducing trachoma transmission. The objective of the WUHA (WASH Upgrades for Health in Amhara) trial is to evaluate if a comprehensive water improvement and hygiene education programme reduces the prevalence of ocular chlamydia infection in rural Africa., Methods and Analysis: Forty study clusters, each of which had received at least annual mass azithromycin distributions for the 7 years prior to the start of the study, are randomised in a 1:1 ratio to the WASH intervention arm or a delayed WASH arm. The WASH package includes a community water point, community-based hygiene promotion workers, household wash stations, household WASH education books, household soap distribution and a primary school hygiene curriculum. Educational activities emphasise face-washing and latrine use. Mass antibiotic distributions are not provided during the first 3 years but are provided annually over the final 4 years of the trial. Annual monitoring visits are conducted in each community. The primary outcome is PCR evidence of ocular chlamydia infection among children aged 0-5 years, measured in a separate random sample of children annually over 7 years. A secondary outcome is improvement of the clinical signs of trachoma between the baseline and final study visits as assessed by conjunctival photography. Laboratory workers and photo-graders are masked to treatment allocation., Ethics and Dissemination: Study protocols have been approved by human subjects review boards at the University of California, San Francisco, Emory University, the Ethiopian Food and Drug Authority, and the Ethiopian Ministry of Innovation and Technology. A data safety and monitoring committee oversees the trial. Results will be disseminated through peer-reviewed publications and presentations., Trial Registration Number: (http://www.clinicaltrials.gov): NCT02754583; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper introduces a framework for conducting and disseminating mixed methods research on positive outlier countries that successfully improved their health outcomes and systems. We provide guidance on identifying exemplar countries, assembling multidisciplinary teams, collecting and synthesising pre-existing evidence, undertaking qualitative and quantitative analyses, and preparing dissemination products for various target audiences. Through a range of ongoing research studies, we illustrate application of each step of the framework while highlighting key considerations and lessons learnt. We hope uptake of this comprehensive framework by diverse stakeholders will increase the availability and utilisation of rigorous and comparable insights from global health success stories., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Growth shortfalls and diarrhoeal diseases remain a major cause of morbidity and mortality in low-income settings. Due to the multifaceted causes of undernutrition and the identified limitations of siloed nutrition programmes, improving the delivery of integrated water, sanitation, hygiene (WASH) and nutrition programming could improve child health., Methods: We conducted a cluster randomised trial in western Kenya to assess the impact on household behaviours of a novel, theory-informed and integrated WASH and nutrition intervention delivered through care groups as compared with the standard care group approach. We developed an intervention targeting practices relating to food hygiene, mealtime and feeding, and compound cleanliness, each using various behavioural change techniques to influence the uptake of targeted behaviours. Prespecified behavioural outcomes were verified through direct observation, 24 hours recall, and self-reported picture-based methods., Results: Compared with control households, a greater proportion of intervention households had a hygienic food preparation area (Risk double difference (RDD) 0.81, 95% CI 0.68 to 0.96), had stored food hygienically (RDD 0.76, 95% CI 0.58 to 1.00), had a functional handwashing station (RDD 0.64, 95% CI 0.56 to 0.74), provided a safe space for their child to play (RDD 0.73, 95% CI 0.56 to 0.96), and who fed their children thickened porridge (RDD 0.56, 95% CI 0.51 to 0.63) at endline. The proportion of children 6-24 months in intervention households consuming a sufficient diversity of foods (RDD 0.81, 95% CI 0.64 to 1.04) was higher than in control households; however, there was a non-significant increase in the percentage of pregnant and lactating women receiving an adequate diversity of foods in their diets (RDD 0.86, 95% CI 0.70 to 1.05) among intervention compared with control households at endline., Conclusion: Our integrated WASH and nutrition intervention resulted in important changes in behaviours. This theory-informed intervention could be added to existing care group programmes to considerable advantage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Infections with enteric pathogens impose a heavy disease burden, especially among young children in low-income countries. Recent findings from randomized controlled trials of water, sanitation, and hygiene interventions have raised questions about current methods for assessing environmental exposure to enteric pathogens. Approaches for estimating sources and doses of exposure suffer from a number of shortcomings, including reliance on imperfect indicators of fecal contamination instead of actual pathogens and estimating exposure indirectly from imprecise measurements of pathogens in the environment and human interaction therewith. These shortcomings limit the potential for effective surveillance of exposures, identification of important sources and modes of transmission, and evaluation of the effectiveness of interventions. In this review, we summarize current and emerging approaches used to characterize enteric pathogen hazards in different environmental media as well as human interaction with those media (external measures of exposure), and review methods that measure human infection with enteric pathogens as a proxy for past exposure (internal measures of exposure). We draw from lessons learned in other areas of environmental health to highlight how external and internal measures of exposure can be used to more comprehensively assess exposure. We conclude by recommending strategies for advancing enteric pathogen exposure assessments.

There are considerable challenges to achieving the Sustainable Development Goals' target of universal access to basic sanitation in schools. Schools require safe, clean, and sex-segregated facilities for a large number of students. Robust and affordable solutions are needed to address the economic, spatial, social, institutional, and political factors which contribute to poor sanitary conditions in informal settlements. In 2015, we undertook a randomized controlled trial to assess the feasibility of private sector sanitation delivery (PSSD) in 20 primary schools, in informal settlements of Nairobi, Kenya. Our preliminary evaluation after one year of service delivery suggested that PSSD of urine-diverting dry latrines with routine waste collection and maintenance provided a feasible, lower-cost alternative to the government standard delivery (GSD) of cistern-flush toilets or ventilated improved pit latrines. We conducted a mixed-methods follow-up study to assess sanitation delivery over 3-4 years and investigate prevailing drivers and barriers that may influence the scalability of PSSD. The conditions of newly constructed and rehabilitated GSD facilities diminished quickly, reverting to the conditions of existing facilities, indicating lower sustainability compared to sanitation delivered from the private sector. Barriers in financial aspects related to the ongoing implementation of PSSD emerged, particularly among public schools, and few were able to pay for continued service. Our study demonstrates that the engagement of the private sector may lead to improvements in affordable, safely managed sanitation for schools and their students. Yet, to reach a sustained scale, additional guidance is needed on how to develop these partnerships, streamline procurement and contracting processes, and incorporate appropriate financing mechanisms., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Competing interests: None declared.

Personal hygiene practices, including facewashing and handwashing, reduce transmission of pathogens, but are difficult to measure. Using color theory principles, we developed and tested a novel metric that generates quantitative measures of facial and hand cleanliness, proxy indicators of personal hygiene practices. In this cross-sectional study, conventional qualitative cleanliness metrics (e.g., presence or absence of nasal and ocular discharge, dirt under nails or on finger pads and palms) were also recorded. We generated Gwet's agreement coefficients to determine the inter-rater reliability of novel and conventional metrics between various rating groups, where appropriate, including two non-blinded raters, non-blinded vs. blinded raters, three blinded raters, and blinded vs. computer raters. Inter-rater reliability of the novel metric was high across all rating groups, ranging from 0.98 (95% CI: 0.97, 0.99) to 0.90 (95% CI: 0.90, 0.91) for facial cleanliness, and 0.97 (95% CI: 0.96, 0.98) to 0.92 (95% CI: 0.91, 0.93) for hand cleanliness. Our novel metric generates more nuanced data than conventional qualitative metrics, and allows for quantifiable assessments of facial and hand cleanliness., Competing Interests: Declaration of competing interest The authors declare no competing financial interests. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Exposure to fecal pathogens contributes to childhood diarrhea and stunting, causing harmful short- and long-term impacts to health. Understanding pathways of child fecal exposure and nutritional deficiencies is critical to informing interventions to reduce stunting. Our aim was to explore determinants of latrine use, disposal of child feces, and perceptions and provisions of a safe and clean child play environment among families with children under two (CU2) years to inform the design of a behavior change intervention to address water, sanitation, and hygiene (WASH), and nutrition behaviors. In 2016, we conducted a mixed-methods formative research in western Kenya. We conducted 29 key informant interviews with community leaders, health workers, and project staff; 18 focus group discussions with caregivers of CU2 years; and 24 semi-structured household observations of feeding, hygiene, and sanitation behaviors. We used the capability, opportunity, motivation, and behavior model as our theoretical framework to map caregiver behavioral determinants. Latrine use barriers were lack of latrines, affordability of lasting materials, and social acceptability of unobserved open defecation. Barriers to safe disposal of child feces were lack of latrines, time associated with safe disposal practices, beliefs that infant feces were not harmful, and not knowing where children had defecated. Primary barriers of clean play environments were associated with creating and maintaining play spaces, and shared human and animal compounds. The immediate cost to practicing behaviors was perceived as greater than the long-term potential benefits. Intervention design must address these barriers and emphasize facilitators to enable optimal WASH behaviors in this context.

Trial Registration: clinicaltrials.gov (NCT02342860)., Competing Interests: The authors have declared that no competing interests exist.

Few rural sanitation programs have documented large increases in sanitation coverage or have assessed if interventions equitably increase sanitation coverage for vulnerable groups. We characterize the impact of the Sustainable Sanitation and Hygiene for All (SSH4A) approach on key program WASH (water, sanitation, and hygiene) indicators, and also assess if these increases in WASH coverage are equitably reaching vulnerable groups. The SSH4A approach was administered in 12 program areas in 11 countries, including Bhutan, Ethiopia, Ghana, Indonesia, Kenya, Mozambique, Nepal, South Sudan, Tanzania, Uganda, and Zambia. Repeated cross-sectional household surveys were administered over four rounds at annual follow-up rounds from 2014 to 2018. Surveys were conducted in an average of 21,411 households at each round of data collection. Overall, sanitation coverage increased by 53 percentage points between baseline and the final round of data collection (95% CI: 52%, 54%). We estimate that 4.8 million people gained access to basic sanitation in these areas during the project period. Most countries also demonstrated movement up the sanitation ladder, in addition to increases in handwashing stations and safe disposal of child feces. When assessing equity-if sanitation coverage levels were similar comparing vulnerable and non-vulnerable groups-we observed that increases in coverage over time were generally comparable between vulnerable groups and non-vulnerable groups. However, the increase in sanitation coverage was slightly higher for higher wealth households compared to lower wealth households. Results from this study revealed a successful model of rural sanitation service delivery. However, further work should be done to explore the specific mechanisms that led to success of the intervention.

Background: Child stunting, an indicator of chronic malnutrition, is a global public health problem. Malnutrition during pregnancy and the first 2 years of life undermines the survival, growth, and development of children. Exposure to fecal pathogens vis-à-vis inadequate water, sanitation, and hygiene (WASH) has been implicated in the etiology of child stunting, highlighting the need to integrate WASH with nutrition-sensitive interventions to comprehensively address this complex problem. The aim of this study was to describe a systematic, theoretically informed approach (that drew from the Starr and Fornoff approach to the Theory of Change development and the Behavior Change Wheel approach) to design a multi-component and integrated social and behavior change intervention to improve WASH and nutrition-related behaviors in western Kenya., Methods: This intervention was developed to be integrated into an existing project that utilized the care group model and aimed to create a culture of care and support for HIV/AIDS-affected children under two and their caregivers and was executed by local partners. We tested the newly created intervention packages in user-testing trials using an adapted Trials of Improved Practices approach to pilot acceptability and feasibility., Results: Using authentic stakeholder engagement and relevant theories, we conducted an 8-step process: (1) conduct mixed methods formative research, (2) prioritize target behaviors, (3) use causal analysis to create problem trees, (4) develop solution trees and articulate assumptions and rationales for change, (5) link solution trees to intervention functions, (6) develop the intervention plan, (7) create the intervention packages, and (8) test and refine the intervention packages., Conclusions: This study highlights the need to take a multi-sectorial, integrated approach that integrates contextually relevant behavior change theories with the experiential knowledge gleaned from stakeholders into the design of interventions that seek to reduce child stunting. This process resulted in the creation of intervention packages that grouped behaviors thematically to be most relevant and responsive to the population context. This work has the potential to make important contributions towards achievement of the United Nations' sustainable development goals., Competing Interests: Competing interestsThe authors declare they have no competing interests., (© The Author(s). 2020.)

Objective: To assess the efficacy of erenumab across the spectrum of response thresholds (≥50%, ≥75%, 100%) based on monthly migraine days (MMD) reduction in patients with chronic migraine from a 12-week, randomized study (NCT02066415)., Methods: Patients (n = 667) received (3:2:2) placebo or erenumab 70/140 mg once-monthly. The proportion of patients achieving a given response threshold was assessed. A post-hoc analysis was conducted to contextualize the actual treatment benefit in subgroups of patients achieving (or not) specified response thresholds. Outcome measures included MMD, acute migraine-specific medication treatment days (MSMD) and disability., Results: The proportion of patients responding to erenumab exceeded that of placebo at the ≥50% and ≥75% response thresholds. At month 3, 39.9% and 41.2% of patients on erenumab 70 and 140 mg, respectively, achieved ≥50% response versus placebo (23.5%). Similarly, at month 3, 17.0% and 20.9% of patients on erenumab 70 and 140 mg, respectively, achieved ≥75% response versus placebo (7.8%). Compared with the overall erenumab-treated population (change in MMD: -6.6 [both 70 and 140 mg]), ≥50% responders showed MMD reductions of -12.2/-12.5 for 70 mg/140 mg versus -2.6/-2.2 for those not achieving ≥50% response. ≥75% responders showed MMD reductions of -13.9/-14.8 for 70 mg/140 mg versus -5.0/-4.3 for those not achieving ≥75% response. Relative improvements in MSMD and disability were observed in responders versus overall erenumab-treated population., Conclusion: For erenumab-treated patients achieving ≥50% response, the actual reduction in MMD was almost twice that of the overall population. These findings provide context for setting realistic expectations regarding actual treatment benefit experienced by patients responding to treatment.

Background: Open defecation is widespread in rural India, and few households have piped water connections. While government and other efforts have increased toilet coverage in India, and evaluations found limited immediate impacts on health, longer-term effects have not been rigorously assessed., Methods: We conducted a matched cohort study to assess the longer-term effectiveness of a combined household-level piped water and sanitation intervention implemented by Gram Vikas (an Indian NGO) in rural Odisha, India. Forty-five intervention villages were randomly selected from a list of those where implementation was previously completed at least 5 years before, and matched to 45 control villages. We conducted surveys and collected stool samples between June 2015 and October 2016 in households with a child <5 years of age (n = 2398). Health surveillance included diarrhoea (primary outcome), acute respiratory infection (ARI), soil-transmitted helminth infection, and anthropometry., Results: Intervention villages had higher improved toilet coverage (85% vs 18%), and increased toilet use by adults (74% vs 13%) and child faeces disposal (35% vs 6%) compared with control villages. There was no intervention association with diarrhoea [adjusted OR (aOR): 0.94, 95% confidence interval (CI): 0.74-1.20] or ARI. Compared with controls, children in intervention villages had lower helminth infection (aOR: 0.44, 95% CI: 0.18, 1.00) and improved height-for-age z scores (HAZ) (+0.17, 95% CI: 0.03-0.31)., Conclusions: This combined intervention, where household water connections were contingent on community-wide household toilet construction, was associated with improved HAZ, and reduced soil-transmitted helminth (STH) infection, though not reduced diarrhoea or ARI. Further research should explore the mechanism through which these heterogenous effects on health may occur., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Acute flaccid myelitis is a debilitating illness characterized by acute onset of limb weakness, with one or more spinal segments displaying magnetic resonance imaging-confirmed gray matter lesions. Since the first outbreak in 2014, tracking by the Centers for Disease Control and Prevention has demonstrated biennial epidemics in the United States, with a current outbreak occurring in 2018. The cases of 3 children with acute flaccid myelitis who were initially thought to have common nonneurologic diagnoses are presented. Emergency physicians need to be vigilant to recognize the subtleties of acute flaccid myelitis because the illness progression is rapid and therapy is nuanced., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

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.

Background: Limited data have been available on the global practice of handwashing with soap (HWWS). To better appreciate global HWWS frequency, which plays a role in disease transmission, our objectives were to: (i) quantify the presence of designated handwashing facilities; (ii) assess the association between handwashing facility presence and observed HWWS; and (iii) derive country, regional and global HWWS estimates after potential faecal contact., Methods: First, using data from national surveys, we applied multilevel linear modelling to estimate national handwashing facility presence. Second, using multilevel Poisson modelling on datasets including both handwashing facility presence and observed HWWS after potential faecal contact, we estimated HWWS prevalence conditional on handwashing facility presence by region. For high-income countries, we used meta-analysis to pool handwashing prevalence of studies identified through a systematic review. Third, from the modelled handwashing facility presence and estimated HWWS prevalence conditional on the presence of a handwashing facility, we estimated handwashing practice at country, regional and global levels., Results: First, approximately one in four persons did not have a designated handwashing facility in 2015, based on 115 data points for 77 countries. Second the prevalence ratio between HWWS when a designated facility was present compared with when it was absent was 1.99 (1.66, 2.39) P <0.001 for low- and middle-income countries, based on nine datasets. Third, we estimate that in 2015, 26.2% (23.1%, 29.6%) of potential faecal contacts were followed by HWWS., Conclusions: Many people lack a designated handwashing facility, but even among those with access, HWWS is poorly practised. People with access to designated handwashing facilities are about twice as likely to wash their hands with soap after potential faecal contact as people who lack a facility. Estimates are based on limited data., (© World Health Organization, 2018. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)

As cholera spread from Haiti to the Dominican Republic, Haitian migrants, a largely undocumented and stigmatized population in Dominican society, became a focus of public health concern. Concurrent to the epidemic, the Dominican legislature enacted new documentation requirements. This paper presents findings from an ethnographic study of anti-Haitian stigma in the Dominican Republic from June to August 2012. Eight focus group discussions (FGDs) were held with Haitian and Dominican community members. Five in-depth interviews were held with key informants in the migration policy sector. Theoretical frameworks of stigma's moral experience guided the analysis of how cholera was perceived, ways in which blame was assigned and felt and the relationship between documentation and healthcare access. In FGDs, both Haitians and Dominicans expressed fear of cholera and underscored the importance of public health messages to prevent the epidemic's spread. However, health messages also figured into experiences of stigma and rationales for blame. For Dominicans, failure to follow public health advice justified the blame of Haitians and seemed to confirm anti-Haitian sentiments. Haitians communicated a sense of powerlessness to follow public health messages given structural constraints like lack of safe water and sanitation, difficulty accessing healthcare and lack of documentation. In effect, by making documentation more difficult to obtain, the migration policy undermined cholera programs and contributed to ongoing processes of moral disqualification. Efforts to eliminate cholera from the island should consider how policy and stigma can undermine public health campaigns and further jeopardize the everyday 'being-in-the-world' of vulnerable groups.

Objective: We describe differences in linear growth as measured by height-for-age z-score (HAZ) between children from Bengali and tribal populations in the Chittagong Hill Tracts of Bangladesh and examine factors associated with HAZ in both groups., Design: We used nutritional surveillance data collected in Bangladesh from 2003 to 2006 to analyze HAZ among 12,006 children aged 6-23 months and conducted multivariate linear regression and Blinder-Oaxaca decomposition to quantify the relative contribution of independent variables to differences in HAZ between Bengali and tribal children., Results: Mean HAZ was stable for Bengali children (-1.88 in 2003 to -1.90 in 2006) but improved for tribal children (-1.87 in 2003 to -1.68 in 2006). The difference between groups was significant across the study period (p = 0.008). Among Bengali children, HAZ was positively associated with father's schooling (β = 0.221; 95% CI: 0.079-0.363). Among tribal children, HAZ was positively associated with consumption of animal source foods (β = 0.073; 95% CI: 0.051-0.096) and goat ownership (β = 0.240; 95% CI: 0.025-0.454). Results of a likelihood ratio test indicated that distance to a health center was inversely associated with HAZ among tribal children (p < 0.001). Blinder-Oaxaca decomposition demonstrated a difference in pooled coefficients between groups (p = 0.004), explained primarily by differences in coefficients for paternal education (p = 0.001) and village-level prevalence of open defecation (p = 0.004)., Conclusions: Different responses among Bengali and tribal children to village-level open defecation are an explanatory factor for the difference in HAZ between Bengali and tribal populations. Open defecation may also act a proxy for unmeasured factors such as household environmental conditions and food hygiene., Abbreviations: Chittagong Hill Tracts (CHT); height-for-age z-scores (HAZ); Nutrition Surveillance Project (NSP); World Health Organization (WHO).

Background: Unimproved water, sanitation, and hygiene (WASH) behaviors are key drivers of infectious disease transmission and influencers of mental well-being. While WASH is seen as a critical enabler of health, important knowledge gaps related to the content and delivery of effective, holistic WASH programming exist. Corresponding impacts of WASH on mental well-being are also underexplored. There is a need for more robust implementation research that yields information regarding whether and how community-based, demand-side interventions facilitate progressive and sustained adoption of improved sanitation and hygiene behaviors and downstream health impacts. The purpose of this protocol is to detail the rationale and design of a cluster-randomized trial evaluating the impact of a demand-side sanitation and hygiene intervention on sustained behavior change and mental well-being in rural and peri-urban Amhara, Ethiopia., Methods: Together with partners, we developed a theoretically-informed, evidence-based behavioral intervention called Andilaye. We randomly selected and assigned 50 sub-districts (kebeles) from three purposively selected districts (woredas); half to receive the Andilaye intervention, and half the standard of care sanitation and hygiene programming (i.e., community-led total sanitation and hygiene [CLTSH]). During baseline, midline, and endline, we will collect data on an array of behavioral factors, potential moderators (e.g., water and sanitation insecurity, collective efficacy), and our primary study outcomes: sanitation and hygiene behaviors and mental well-being. We will perform a process evaluation to assess intervention fidelity and related attributes., Discussion: While CLTSH has fostered sanitation and hygiene improvements in Ethiopia, evidence of behavioral slippage, or regression to unimproved practices in communities previously declared open defecation free exists. Other limitations of CLTSH, such as its focus on disgust, poor triggering, and over-saturation of Health Extension Workers have been documented. We employed rigorous formative research and practically applied social and behavioral theory to develop Andilaye, a scalable intervention designed to address these issues and complement existing service delivery within Ethiopia's Health Extension Program. Evidence from this trial may help address knowledge gaps related to scalable alternatives to CLTSH and inform sanitation and hygiene programming and policy in Ethiopia and beyond., Trial Registration: This trial was registered with clinicaltrials.gov ( NCT03075436 ) on March 9, 2017.

Background: To develop updated estimates in response to new exposure and exposure-response data of the burden of diarrhoea, respiratory infections, malnutrition, schistosomiasis, malaria, soil-transmitted helminth infections and trachoma from exposure to inadequate drinking-water, sanitation and hygiene behaviours (WASH) with a focus on low- and middle-income countries., Methods: For each of the analysed diseases, exposure levels with both sufficient global exposure data for 2016 and a matching exposure-response relationship were combined into population-attributable fractions. Attributable deaths and disability-adjusted life years (DALYs) were estimated for each disease and, for most of the diseases, by country, age and sex group separately for inadequate water, sanitation and hygiene behaviours and for the cluster of risk factors. Uncertainty estimates were computed on the basis of uncertainty surrounding exposure estimates and relative risks., Findings: An estimated 829,000 WASH-attributable deaths and 49.8 million DALYs occurred from diarrhoeal diseases in 2016, equivalent to 60% of all diarrhoeal deaths. In children under 5 years, 297,000 WASH-attributable diarrhoea deaths occurred, representing 5.3% of all deaths in this age group. If the global disease burden from different diseases and several counterfactual exposure distributions was combined it would amount to 1.6 million deaths, representing 2.8% of all deaths, and 104.6 million DALYs in 2016., Conclusions: Despite recent declines in attributable mortality, inadequate WASH remains an important determinant of global disease burden, especially among young children. These estimates contribute to global monitoring such as for the Sustainable Development Goal indicator on mortality from inadequate WASH., (Copyright © 2019. Published by Elsevier GmbH.)