Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM): rationale and methods of a longitudinal observational study

Abstract

Introduction: Mortality among children hospitalised for complicated severe acute malnutrition (SAM) remains high despite the implementation of WHO guidelines, particularly in settings of high HIV prevalence. Children continue to be at high risk of morbidity, mortality and relapse after discharge from hospital although long-term outcomes are not well documented. Better understanding the pathogenesis of SAM and the factors associated with poor outcomes may inform new therapeutic interventions.

Methods and analysis: The Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) study is a longitudinal observational cohort that aims to evaluate the short-term and long-term clinical outcomes of HIV-positive and HIV-negative children with complicated SAM, and to identify the risk factors at admission and discharge from hospital that independently predict poor outcomes. Children aged 0-59 months hospitalised for SAM are being enrolled at three tertiary hospitals in Harare, Zimbabwe and Lusaka, Zambia. Longitudinal mortality, morbidity and nutritional data are being collected at admission, discharge and for 48 weeks post discharge. Nested laboratory substudies are exploring the role of enteropathy, gut microbiota, metabolomics and cellular immune function in the pathogenesis of SAM using stool, urine and blood collected from participants and from well-nourished controls.

Ethics and dissemination: The study is approved by the local and international institutional review boards in the participating countries (the Joint Research Ethics Committee of the University of Zimbabwe, Medical Research Council of Zimbabwe and University of Zambia Biomedical Research Ethics Committee) and the study sponsor (Queen Mary University of London). Caregivers provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings.

Keywords: Africa; HIV; enteropathy; malnutrition; microbiota; mortality.

Figure 1

Study flow chart. All hospital admissions are screened for eligibility for the observational cohort and enteropathy substudy, with procedures undertaken as shown in the flow chart during hospitalisation and post discharge. Well-nourished children from outpatient clinics and the community meeting eligibility criteria as well-nourished controls are enrolled and undergo a single baseline assessment as shown. The immunology, microbiota and metabolomics substudies enrol children as shown. All children with severe acute malnutrition (SAM), regardless of which arm of the study they are enrolled into, are followed for 48 weeks post discharge. ¹The immunology substudy started from 1 June 2017 and required children to have a blood sample >2 mL to conduct cellular assays. LM, lactulose-mannitol; WHZ, weight-for-height Z-score.