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BackgroundSafely managed drinking water is critical to prevent diarrhoeal diseases, including cholera, but evidence on the effectiveness of piped water supply in reducing these diseases in low-income and complex emergency settings remains scarce.MethodsWe conducted a trial of water supply infrastructure improvements in Uvira (DRC). Our primary objective was to estimate the relationship between a composite index of water service quality and the monthly number of suspected cholera cases admitted to treatment facilities and, as a secondary analysis, the number of cases confirmed by rapid diagnostic tests. Other exposures included the quantity of supplied water and service continuity. We used Poisson generalised linear models with generalised estimating equations to estimate incidence rate ratios.FindingsAssociations between suspected cholera incidence and water service quality (RR 0·86, 95% CI 0·73-1·01), quantity (RR 0·80, 95% CI 0·62-1·02) and continuity (RR 0·81, 95% CI 0·77-0·86) were estimated. The magnitudes of the associations were similar between confirmed cholera incidence and water service quality (RR 0·84, 95% CI 0·73-0·97), quantity (RR 0·76, 95% CI 0·61-0·94) and continuity (RR 0·75, 95% CI 0·69-0·81). These results suggest that an additional 5 L/user/day or 1.2 hour per day of water production could reduce confirmed cholera by 24% (95% CI 6-39%) and 25% (95% CI 19-31%), respectively.InterpretationEnsuring a sufficient and continuous piped water supply may substantially reduce the burden of endemic cholera and diarrhoeal diseases but evaluating this rigorously is challenging. Pragmatic strategies are needed for public health research on complex interventions in protracted emergency settings.Trial registrationThe trial is registered in ClinicalTrials.gov ID NCT02928341. https://classic.clinicaltrials.gov/ct2/show/NCT02928341.

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood. Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity. Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment. Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable). Results: Of n = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad. Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.

Introduction Increasing handwashing with soap (HWWS) among older children in emergency settings can have a large public health impact, however, evidence on what works is limited. One promising approach is the ‘Surprise Soap’ intervention in which a novel soap with an embedded toy is delivered to children in a short, participatory household session that includes a glitter game and HWWS practice. Here, we evaluate this intervention against a standard intervention in a complex emergency setting.Methods A cluster-randomised controlled equivalence trial was conducted in Naivasha refugee settlement, Sudan. Blinding was not possible. 203 randomly selected households, with at least one child aged 5–12, were randomised to receive the Surprise Soap intervention (n=101) or a standard intervention comprising a short household session with health messaging and plain soap distribution (n=102). The primary outcome was the proportion of prespecified potential HWWS events observed for children aged 5–12, accompanied by HWWS, at baseline, 4, 12 and 16 weeks post intervention delivery.Results 200 households were included in the analyses: 101 intervention and 99 control. No difference in intervention effectiveness was observed at any follow-up (4 weeks: adjusted rate ratio (RR) 1.2, 95% CI 0.8 to 1.7; 12 weeks: RR 0.8, 95% CI 0.5 to 1.1; 16 weeks: RR 1.1, 95% CI 0.8 to 1.5). However, we observed increased HWWS in both arms at 4 weeks (27 and 23 percentage point increase in the intervention and control arm, respectively) that was sustained at 16 weeks.Conclusions We find that the Surprise Soap intervention is no more effective at increasing older children’s HWWS than a standard, household-level, health-based intervention in this complex humanitarian emergency. There appears to be no marginal benefit in terms of HWWS that would justify the additional cost of implementing the Surprise Soap intervention. Further trials that include a passive control arm are needed to determine the independent effects of each intervention and guide future intervention design.

Abstract Consumption of unhealthy commercial foods and beverages (UCFB) is common among infants and young children living in low‐ and middle‐income countries. Such foods can displace other nutritious foods, however, there is limited evidence on how this consumption tracks across time. This study assessed and tracked UCFB consumption of children living in rural/peri‐urban Cambodia during the complementary feeding period, identified UCFB consumption patterns of these children, and explored the association between UCFB consumption and growth. A 6‐month longitudinal cohort study was implemented among 567 caregivers of children aged 10–14 months at recruitment. UCFB consumption was estimated each month via a telephone‐administered 7‐day food frequency questionnaire, and UCFB consumption patterns were identified based on changes in this frequency of consumption over time. The majority of children either maintained (45.7%, n = 246) or developed (43.5%, n = 234) an unhealthy consumption pattern and only 10.8% (n = 58) of children maintained/transitioned into a healthy consumption pattern. High consumers of UCFB at 10–14 months had a 4.7 (CI: 4.7 [3.1–7.2]) times odds of being high consumers of UCFB at 15–19 months (p

Objectives The aim of this study was to test whether household environmental hygiene and behavioural conditions moderated associations between diarrhoea and enteric pathogen detection in infants 5 months of age in Kenya and pathogen sources, including latrine access, domestic animal co-habitation and public food sources.Design Cross-sectional study utilising enrolment survey data of households participating in the Safe Start cluster-randomised controlled trial .Setting Kisumu, Kenya.Participants A total of 898 caregivers with 5-month (22 week ± 1 week) aged infants were enrolled in the study and completed the enrolment survey.Primary and secondary outcome measures Outcomes were (1) caregiver-reported 7-day diarrhoea prevalence and (2) count of types of enteric viruses, bacteria and parasites in infant stool. Exposures and effect modifiers included water access and treatment, cohabitation with domestic animals, sanitation access, handwashing practices, supplemental feeding, access to refrigeration and flooring.Results Reported handwashing after handling animals (adjusted odds ratio (aOR)=0.20; 95% CI=0.06 to 0.50) and before eating (aOR=0.44; 95% CI=0.26 to 0.73) were strongly associated with lower risk of caregiver-reported diarrhoea, while cohabitation with animals (aOR=1.54; 95% CI=1.01 to 2.34) living in a household with vinyl-covered dirt floors (aOR=0.60; 95% CI=0.45 to 0.87) were strongly associated with pathogen codetection in infants. Caregiver handwashing after child (p=0.02) or self-defecation (p=0.03) moderated the relationship between shared sanitation access and infant exposure to pathogens, specifically private latrine access was protective against pathogen exposure of infants in households, where caregivers washed hands after defecation. In the absence of handwashing, access to private sanitation posed no benefits over shared latrines for protecting infants from exposure.Conclusion Our evidence highlights eliminating animal cohabitation and improving flooring, postdefecation and food-related handwashing, and safety and use of cow milk sources as interventions to prevent enteric pathogen exposure of young infants in Kenya.Trial registration number NCT03468114

Resume (version française) Please note this translation has been generated by the authors and has not been checked against the original, peer-reviewed English version by the Journal. Any discrepancies between the two versions should be raised with the authors. Cette traduction a été préparée par les auteurs et sa conformité avec la version anglaise revue par les pairs n’a pas été vérifiée par le journal. Toute différence entre les deux versions doit être signalée aux auteurs. Introduction Les maladies diarrhéiques restent une cause majeure de mortalité et morbidité dans le monde. Le choléra seul cause environ 95’000 morts par an, dont la plupart dans des contextes endémiques où l’accès à l’eau est inadéquat. Tandis qu’une stratégie globale pour l’élimination du choléra d’ici à 2030 appelle des investissements dans l’amélioration des services d’approvisionnement en eau, il y a peu de données probantes et rigoureuses sur l’impact d’un approvisionnement en eau amélioré sur la transmission endémique du choléra dans les contextes urbains à faibles ressources. Notre protocole d’étude est conçu pour livrer une évaluation d’impact épidémiologique pragmatique d’une intervention d’approvisionnement en eau à large échelle à Uvira, République Démocratique du Congo, un point focal de transmission du choléra. Méthodes/Conception Un essai randomisé par grappes par échelons (stepped-wedge cluster randomised trial, SW-CRT) a été conçu pour évaluer l’impact d’une intervention d’approvisionnement en eau potable à large échelle sur l’incidence du choléra parmi les 280'000 habitants d’Uvira. La ville a été divisée en 16 grappes, dans lesquelles de nouvelles bornes fontaines et branchements individuels seront installés suivant une séquence randomisée sur une période allant jusqu’à 8 semaines par grappe. Le principal résultat de l’essai sera l’incidence mensuelle des cas de choléra « confirmés » (patients positifs par tests de détection rapide) et des cas « suspects » (patients admis au centre de traitement du choléra). Des évaluations de processus et économique menées en parallèle fourniront des informations complémentaires sur le contexte, les coûts et l’efficience de l’intervention. Discussion Dans ce protocole, nous présentons une approche pragmatique pour effectuer une recherche rigoureuse visant à évaluer les impacts d’une intervention complexe d’approvisionnement en eau sur la diarrhée sévère et le choléra dans un contexte instable et à faibles ressources, représentatif des zones affectées par le choléra. En particulier, nous considérons une série de risques pré-identifiés et les stratégies de mitigation associées ainsi que la valeur de combiner différentes méthodes de collecte de données et de préparer de multiples scénarios d’analyse pour tenir compte d’éventuelles déviations du protocole. L’étude présentée ici a le potentiel de fournir des évidences scientifiques robustes pour soutenir des stratégies de contrôle du choléra plus efficientes dans les contextes difficiles qui sont fortement affectés. Enregistrement de l’essai Cet essai est enregistré sur clinicaltrials.gov ( NCT02928341 , 10 octobre 2016) et a reçu les approbations éthiques de la London School of Hygiene and Tropical Medicine (8913, 10603) ainsi que de l’Ecole de Santé Publique de l’Université de Kinshasa, République Démocratique du Congo (ESP/CE/088/2015).

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak ® ) in multiple sclerosis (MS) patients. Methods: Litak ® was offered to MS-patients irrespective of disease course. Litak ® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak ® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

We conducted a controlled before-and-after trial to evaluate the impact of an onsite urban sanitation intervention on the prevalence of enteric infection, soil transmitted helminth re-infection, and diarrhea among children in Maputo, Mozambique. A non-governmental organization replaced existing poor-quality latrines with pour-flush toilets with septic tanks serving household clusters. We enrolled children aged 1–48 months at baseline and measured outcomes before and 12 and 24 months after the intervention, with concurrent measurement among children in a comparable control arm. Despite nearly exclusive use, we found no evidence that intervention affected the prevalence of any measured outcome after 12 or 24 months of exposure. Among children born into study sites after intervention, we observed a reduced prevalence of Trichuris and Shigella infection relative to the same age group at baseline (