Independent and combined effects of nutrition and sanitation interventions on enteric pathogen carriage and child growth in rural Cambodia: a factorial cluster-randomised controlled trial

Background Childhood exposure to enteric pathogens associated with poor sanitation contributes to undernutrition, associated with adverse effects later in life. This trial assessed the independent and combined effects of nutrition and sanitation interventions on child growth outcomes and enteric pathogen infection in rural Cambodia, where the prevalence of childhood stunting remains high. Methods We conducted a factorial cluster-randomised controlled trial of 4,015 households with 4,124 children (1-28 months of age at endline) across three rural provinces in Cambodia. Fifty-five communes (clusters) were randomly assigned to a control arm or one of three treatments: a nutrition-only arm, a sanitation-only arm, and a combined nutrition and sanitation arm receiving both treatments. The primary outcome was length-for-age Z-score (LAZ); other outcomes included weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), stunting, wasting, underweight, and caregiver-reported diarrhoea. We assayed stool specimens from a subset of all children (n = 1,620) for 27 enteric pathogens (14 bacteria, 6 viruses, 3 protozoa, and 4 soil-transmitted helminths) and estimated effects of interventions on enteric pathogen detection and density. Analysis was by intention-to-treat. The trial was pre-registered with ISRCTN Registry (ISRCTN77820875). Findings Self-reported adherence was high for the nutrition intervention but uptake was low for sanitation. Compared with a mean LAZ of -1.04 (SD 1.2) in the control arm, children in the nutrition-only arm (LAZ +0.08, 95% CI -0.01-0.18) and combined nutrition and sanitation arm (LAZ +0.10, 95% CI 0.01-0.20) experienced greater linear growth; there were no measurable differences in LAZ in the sanitation-only arm (LAZ -0.05, 95% CI -0.16-0.05). We found no effect of any intervention (delivered independently or combined) on either enteric pathogen frequency or pathogen load in stool. Compared with a mean WAZ of -1.05 (SD 1.1) in the control arm, children in the nutrition-only arm (WAZ +0.10, 95% CI 0.00-0.19) and combined intervention arm (WAZ +0.11, 95% CI 0.03-0.20) were heavier for their age; there was no difference in WAZ in the sanitation-only arm. There were no differences between arms in prevalence of stunting, wasting, underweight status, one-week period prevalence of diarrhoea, pathogen prevalence, or pathogen density in stool. Interpretation Improvements in child growth in nutrition and combined nutrition and sanitation arms are consistent with previous efficacy trials of combined nutrition and sanitation interventions. We found no evidence that the sanitation intervention alone improved child growth or reduced enteric pathogen detection, having achieved only modest changes in access and use. Funding United States Agency for International Development (USAID), contracts AID-OAA-M-13-00017 and AID-OAA-TO-16-00016. The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN77820875 ### Clinical Protocols ### Funding Statement United States Agency for International Development (USAID), contracts AID-OAA-M-13-00017 and AID-OAA-TO-16-00016. The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study received approval from the National Ethics Committee for Health Research in the Cambodian Ministry of Health, Georgia Institute of Technology, and New England Institutional Review Board. Prior to any data collection, the trial was explained to participants in the Khmer language. Written and verbal consent were obtained prior to administering the surveys and anthropometry measurements. The trial was pre-registered with ISRCTN Registry, reference number [ISRCTN77820875][1] and available at . I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data that support the findings of this study are openly available in OSF at DOI 10.17605/OSF.IO/PNU4A. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN77820875