Building the Evidence Base for Appropriate Care of the Sick, Undernourished Child in Limited Resource Settings

Despite an overall reduction of child mortality in LMICs, acutely-ill undernourished children continue to have a greatly elevated risk of death, both during hospitalisation and following discharge. However, we currently lack robust evidence for their management. Factors underlying the risks of mortality may relate to the acute illness itself, to children's longer term health trajectories, or to the home nutritional and care environment. The ultimate goal of the CHAIN Network is to identify and prioritize actionable intervention targets to reduce mortality among acutely ill undernourished children.

CHAIN's initial aim is to better understand the characteristics that determine increased risk of mortality in this vulnerable population, whether biological (related to infection, immunity and metabolism), nutritional (intake and anthropometry), health system factors (affecting management and discharge) or behavioural (community/caregiver interactions). CHAIN brings clinicians and scientists together from a variety of high-burden settings in Africa and South Asia. CHAIN will establish prospective cohorts of acutely ill young children across different geographies with differing population, social and environmental characteristics (stunted vs. wasting, rural vs. urban and presence of risk factors such as malaria and HIV).

Eight sites will be involved, including three hospitals in Kenya (Kilifi County, Migori County and Mbagathi District), two in Bangladesh (Matlab and the icddr,b Dhaka), and one in each of Uganda (Mulago), Malawi (Queen Elizabeth Community Hospital), Pakistan (Civil Hospital Karachi) and in West Africa (TBA). Site will enroll children at admission to hospital, and assess their clinical, social and economic status at admission, during hospitalisation, at discharge and during follow up for 180 days after discharge. The sites will also enrol children from the community to determine community norms (where ill and undernourished children would be expected to typically recover to). Protocols and procedures will be carefully harmonised across sites.

Children aged 2 months to 2 years admitted to hospital will be considered for inclusion and enrolment stratified by nutritional status. Following informed consent, baseline data of prognostic importance, including demographic and social information, a detailed clinical examination, anthropometry and measurement of vital signs, including pulse oximetry, will be collected using a standard proforma. A research blood sample will be collected together with the routine clinical blood draw to minimize the patient's discomfort. Rectal swabs and faecal sample will also be obtained from all children.

During admission, care will be provided according to WHO and national guidelines. Children will be reviewed daily and clinical features, progress and treatment received recorded on a structured case report form. In the event of death in hospital, a standard audit questionnaire will be completed. During admission, primary caregivers, usually the mother, will be interviewed screened for mental health problems. At discharge, anthropometry, a clinical assessment and blood, rectal swab and whole stool collected. Families will be linked with chronic care services where needed.