Understanding Outcomes of Acutely Ill Undernourished Children (CHAIN Cohort; 2016-2020)

Understanding Outcomes of Acutely Ill Undernourished Children; Building the evidence base for care of acutely ill, undernourished children in limited resource settings (CHAIN 1.0; OPP1138537 & OPP1131320)

Information:

Sponsor - Bill and Melinda Gates Foundation
Principal Investigators –Ezekiel Mupere, MBChB, MMed, PhD, Uganda-CWRU Research Collaboration; Catherine Stein, PhD, CWRU; Christina Lancioni, MD, Oregon Health & Science University

Goal of Study:

Undernutrition underlies almost half of childhood deaths worldwide. Undernourished children are at markedly increased risk of death in the community, during admission to hospital because of acute illness and after discharge from hospital, despite the provision of nutritional rehabilitation and medical treatment according to current guidelines. However, current guidelines are not based on a good understanding of the metabolic problems and infections that are associated with undernutrition and that may underlie the increased risk of death. The goal of this study is to identify risk factors and mechanisms leading to an increased risk of mortality, in order to prioritize interventions to be taken forward into clinical trials to reduce mortality.

We aim to improve our understanding of underlying characteristics and processes that determine increased risk of mortality, readmission to hospital and inadequate nutritional recovery amongst young children admitted to hospital with acute illness. These include biological (e.g. infection, the immune system and metabolism), nutritional (e.g. breast-feeding and diet), health system (e.g. how children are assessed and managed) and social and behavioural factors (e.g. economic constraints, feeding and health seeking behaviour).

We aim to understand how undernutrition and acute infection impact infant neurodevelopment in the first 24 months of life.  In addition, we want to determine the burden of latent and active Tuberculosis in young children requiring hospitalization for acute illness, and the best way to diagnosis active Tuberculosis in this population.

Primary Objective:

To characterize acutely ill children and their outcomes in hospital and after discharge and treatment with current protocols in order to identify and prioritize potential interventions. 

Specific Objectives:

1. To determine factors associated with i) mortality in hospital; ii) mortality after discharge; iii) readmission to hospital; and iv) poor nutritional recovery amongst acutely ill children.
2. To describe clinical, socio-economic, behavioral, metabolic, infective and immune characteristics among children of different nutritional status (severe acute malnutrition cohort; moderate acute malnutrition cohort; non-malnourished cohort).
3. To determine the rate of normalization of factors associated with risk of mortality during recovery from illness.
4. To identify potential interventions and their practical and ethical dimensions to inform future trials.
5. To identify differences in immune phenotype between children of different nutritional status, and to determine if distinct immune phenotypes correlate with survival and growth outcomes.
6. To determine how nutritional status impacts neurodevelopment following acute illness.
7. To determine the burden of LTBI and TB disease among young children hospitalized with acute illness.
8. To determine how body composition correlates to growth and development and survival outcomes in six months of follow-up.

The results of this completed study can be found in:

Lwanga C, Aber P, Tickell KD, Ngari MM, Mukisa J, Atuhairwe M, Brown L, Mupere E, Potani I, Shahrin L, Morgan B, Singa BO, Nankabirwa V, Mugambe RK, Mukasa Z, Walson JL, Berkley JA, Lancioni CL. Impact of HIV exposure without infection on hospital course and mortality among young children in sub-Saharan Africa: a multi-site cohort study. BMC Med. 2024 Dec 3;22(1):573. doi: 10.1186/s12916-024-03790-5. PMID: 39627711; PMCID: PMC11613948.

Diallo AH, Mohammad AS, Shahid SB, Khan AF, Saleem AF, Singa BO, Gnoumou BS, Tigoi C, Otieno CA, Bourdon C, Oduol CO, Lancioni CL, Manyasi C, McGrath CJ, Maronga C, Lwanga C, Brals D, Ahmed D, Mondal D, Denno DM, Mangale DI, Chimezi E, Mbale E, Mupere E, Mamun GMS, Ouedraogo I, Githinji G, Berkley JA, Njirammadzi J, Mukisa J, Thitiri J, Haggstrom J, Carreon JD, Walson JL, Jemutai J, Tickell KD, Shahrin L, Mallewa M, Hossain MI, Chisti MJ, Timbwa M, Mburu M, Ngari MM, Ngao N, Aber P, Harawa PP, Sukhtankar P, Bandsma RH, Bamouni RM, Molyneux S, Feldman S, Mwaringa S, Shaima SN, Ali SA, Afsana SM, Banu S, Ahmed T, Voskuijl WP, Kazi Z. Childhood Acute Illness and Nutrition (CHAIN) Network. Characterising paediatric mortality during and after acute illness in Sub-Saharan Africa and South Asia: a secondary analysis of the CHAIN cohort using a machine learning approach. EClinicalMedicine. 2023 Feb 6;57:101838. doi: 10.1016/j.eclinm.2023.101838. PMID: 36825237; PMCID: PMC9941052.

Berkley JA, Walson JL, Diallo AH, Shahid A, Gwela A, Saleem A, Asad A, Tigoi CC, Bourdon C, Lancioni CL, Denno DM, Mangale DI, Mupere E, Tickell KD, Mwangome MK, Chisti MJ, Ngari MM, Ngao NM, Sukhtankar P, Bandsma R, Molyneux S, Ahmed T, Voskuijl W. Childhood Acute Illness and Nutrition Network. Childhood Acute Illness and Nutrition (CHAIN) Network: a protocol for a multi-site prospective cohort study to identify modifiable risk factors for mortality among acutely ill children in Africa and Asia. BMJ Open. 2019 May 5;9(5):e028454. doi: 10.1136/bmjopen-2018-028454. PMID: 31061058; PMCID: PMC6502050.