A pilot investigation of enteric pathogens and stunting and malnutrition using a combination of hospital surveillance and a birth cohort of children in Dili, Timor-Leste

Background Enteric pathogens contribute to child malnutrition in low-to-middle-income countries. In Timor-Leste, there has been limited study of this relationship. Methodology/Principal findings We investigated enteric disease, stunting, and malnutrition in children in Dili, Timor-Leste (July 2019 – October 2020). Sixty infants received up to four home visits. We collected faecal samples, demographics, anthropometrics, food and water sources, feeding practices, and animal husbandry details. For 160 children admitted to Hospital Nacional Guido Valadares with clinical diagnosis of severe diarrhoea or severe acute malnutrition (SAM), we collected faecal samples, diagnostics, and anthropometrics. Faeces were tested by polymerase chain reaction (PCR) using the BioFire® FilmArray® Gastrointestinal Panel. Descriptive analyses and regression analyses were conducted using R. We detected enteric pathogens in 68.8% (95% confidence interval [CI] 60.4–76.2%) of infants, 88.6% of children with SAM (95% CI 81.7–93.3%), and 93.8% of children with severe diarrhoea (95% CI 67.7– 99.7%). Diarrhoeagenic Escherichia coli and Campylobacter spp. were most frequently detected. A median weight-for-height Z-score (WHZ) of -1.1 (interquartile range [IQR] -2.0 to -0.1) for infants across all home visits, -3.9 (IQR -4.7 to -3.0) for children with SAM and -2.6 (IQR -4.2 to -1.1) for children with severe diarrhoea was observed. The most common admission diagnosis was SAM (88.1%, 95% CI 81.7–92.5%). Hospitalised children had increased odds of Shigella /enteroinvasive E. coli (OR 11.4, 95% CI 2.8–47.3) and Giardia lamblia detection (OR 31.7, 95% CI 3.6–280) compared with infants. For home visits, bottle feeding was associated with increased odds of pathogen detection (OR 8.2, 95% CI 1.1–59.7). Conclusions/Significance We detected high prevalence of enteric pathogens and signs of malnutrition in children in Dili. Our pilot is proof of concept for a study to fully explore the risk factors and associations between enteric pathogens and malnutrition in Timor-Leste. Author summary Enteric pathogens are a contributing factor to child malnutrition in low-to-middle-income countries. This study investigated the relationship between enteric disease, malnutrition, and stunting in children in Dili, Timor-Leste. Sixty infants received up to four home visits and 160 children were admitted to the hospital with a clinical diagnosis of severe diarrhoea or severe acute malnutrition. Faecal samples were collected and tested for enteric pathogens and risk factors were explored. The study found that enteric pathogens were detected in most infants and children with malnutrition and diarrhea. The most commonly detected pathogens were diarrheagenic Escherichia coli and Campylobacter spp. Most children exhibited signs of malnutrition from infancy, and hospitalised children had a higher likelihood of having certain enteric pathogens. Feeding practices, water use, and animal cohabitation may pose risks for enteric pathogen infection. The results suggest that enteric pathogens are a significant problem in Dili, Timor-Leste, and further research is needed to explore the complexity of risk factors. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Australian Centre for International Agricultural Research (project number LS/2018/184v1). DMC is funded by an Australian Government Research Training Program (AGRTP) Scholarship. MDK is supported by a National Health and Medical Research Council fellowship (GNT1145997). The funder (ACIAR) did not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Timor-Leste National Institute of Health-Research Ethics & Technical Committee (reference 462/MS-INS/GDE/IV/2019) for the Timor-Leste Instituto Nacional de Saúde (INS), and the Australian National University Ethics Committee (reference 2019/221) provided ethical approval. 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. Not Applicable 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). Not Applicable 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. Not Applicable All relevant data are within the manuscript and its Supporting Information files.