Antibiotics for Children With Severe Diarrhoea

Summary

Although the current World Health Organization (WHO) recommended management package for acute diarrhoea (ORS, zinc and feeding advice) has contributed to significant reductions in diarrhoea associated mortality, over half a million children continue to die annually as a result of acute diarrhoeal episodes. In addition, rates of mortality in young children in the 90 days following an episode of acute diarrhoea appear at least as high as mortality that occurs during the acute episode. The long-term benefits of antibiotic administration may result from direct antimicrobial effects on pathogens or from other incompletely understood mechanisms including improved nutrition, alterations in immune tolerance or improved enteric function. Optimizing antibiotic treatment of acute diarrhoea episodes in very young children with severe disease may offer the opportunity to significantly reduce diarrhoea associated deaths in the 180 days following presentation for acute diarrhoea and may also improve growth. The investigators propose to evaluate the efficacy of an antibiotic (azithromycin) delivered in a specific, targeted fashion to young children (\< 2 years of age) at high risk of diarrhoea associated mortality in a multi-site randomized, double-blind, placebo-controlled trial. The study will evaluate the ability of the intervention to reduce mortality within 180 days of the acute diarrhoeal episode, and improve nutritional status over the first 90 days.

Timeline

Start

2017-05-13

Primary completion

2020-01-15

Completion

2020-01-15

Publications

• Somji S, Ashorn P, Manji K, Ahmed T, Chisti M, Dhingra U, Sazawal S, Singa B, Walson JL, Pavlinac P, Bar-Zeev N, Houpt E, Dube Q, Kotloff K, Sow S, Yousafzai MT, Qamar F, Bahl R, De Costa A, Simon J, Sudfeld CR, Duggan CP; ABCD Study Group. Clinical and nutritional correlates of bacterial diarrhoea aetiology in young children: a secondary cross-sectional analysis of the ABCD trial. BMJ Paediatr Open. 2024 Apr 11;8(1):e002448. doi: 10.1136/bmjpo-2023-002448.
• Pavlinac PB, Platts-Mills JA, Liu J, Atlas HE, Gratz J, Operario D, Rogawski McQuade ET, Ahmed D, Ahmed T, Alam T, Ashorn P, Badji H, Bahl R, Bar-Zeev N, Chisti MJ, Cornick J, Chauhan A, De Costa A, Deb S, Dhingra U, Dube Q, Duggan CP, Freyne B, Gumbi W, Hotwani A, Kabir M, Islam O, Kabir F, Kasumba I, Kibwana U, Kotloff KL, Khan SS, Maiden V, Manji K, Mehta A, Ndeketa L, Praharaj I, Qamar FN, Sazawal S, Simon J, Singa BO, Somji S, Sow SO, Tapia MD, Tigoi C, Toure A, Walson JL, Yousafzai MT, Houpt ER; AntiBiotics for Children with severe Diarrhea (ABCD) Study Group. Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics. J Infect Dis. 2024 Apr 12;229(4):988-998. doi: 10.1093/infdis/jiad252.
• Antibiotics for Children With Diarrhea (ABCD) Study Group; Ahmed T, Chisti MJ, Rahman MW, Alam T, Ahmed D, Parvin I, Kabir MF, Sazawal S, Dhingra P, Dutta A, Deb S, Chouhan A, Sharma AK, Jaiswal VK, Dhingra U, Walson JL, Singa BO, Pavlinac PB, McGrath CJ, Nyabinda C, Deichsel EL, Anyango M, Kariuki KM, Rwigi D, Tornberg-Belanger SN, Kotloff KL, Sow SO, Tapia MD, Haidara FC, Mehta A, Coulibaly F, Badji H, Permala-Booth J, Tennant SM, Malle D, Bar-Zeev N, Dube Q, Freyne B, Cunliffe N, Ndeketa L, Witte D, Ndamala C, Cornick J, Qamar FN, Yousafzai MT, Qureshi S, Shakoor S, Thobani R, Hotwani A, Kabir F, Mohammed J, Manji K, Duggan CP, Kisenge R, Sudfeld CR, Kibwana U, Somji S, Bakari M, Msemwa C, Samma A, Bahl R, De Costa A, Simon J, Ashorn P. Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial. JAMA Netw Open. 2021 Dec 1;4(12):e2136726. doi: 10.1001/jamanetworkopen.2021.36726.
• ABCD study team. A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol. Trials. 2020 Jan 13;21(1):71. doi: 10.1186/s13063-019-3829-y.

Drugs

Indications