Lactoferrin and Lysozyme Supplementation for Long-term Diarrhea Sequelae

Summary

Children in low- and middle-income countries who are hospitalized for diarrhea and also have malnutrition are at high risk for illness and death in the 6 months period following treatment for diarrhoea despite receiving current guideline recommended diarrhea management (such as oral rehydration solution, or "ORS"). This study will test whether nutritional supplements made from milk (lactoferrin or lysozyme) or a combination of the two (lactoferrin and lysozyme) will prevent children from having repeated diarrhea episodes and help improve their nutrition by improving their stomach health or preventing new disease during this 6-month period. The study is taking place at 7 hospitals in Western Kenya. Six hundred participants will be enrolled if they provide informed consent to participate, are aged 6-24 months, were hospitalized with diarrhea and malnutrition and have been managed by the facility nutritionists and ready to return home. Participation in the study will entail providing information on the child's health history, collection of stool samples, blood, and potentially urine. The caregiver will be provided sachets of the investigational product to take home and mix daily with their child's porridge or other complimentary food, and asked to return to the clinic 4 times in the subsequent 6 months, and also consent to having a community health worker visit their home every two weeks for a follow up visit. The risks to the participant and their caregiver are minimal. The information gained in this study will help us create new treatments and develop new strategies to treat sick children to prevent death and illness.

Timeline

Start

2023-03-10

Primary completion

2026-07

Completion

2026-12

Publications

• Background Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013 Aug 3;382(9890):427-451. doi: 10.1016/S0140-6736(13)60937-X. Epub 2013 Jun 6.
• Background Tickell KD, Pavlinac PB, John-Stewart GC, Denno DM, Richardson BA, Naulikha JM, Kirera RK, Swierczewski BE, Singa BO, Walson JL. Impact of Childhood Nutritional Status on Pathogen Prevalence and Severity of Acute Diarrhea. Am J Trop Med Hyg. 2017 Nov;97(5):1337-1344. doi: 10.4269/ajtmh.17-0139.
• Background Talbert A, Ngari M, Bauni E, Mwangome M, Mturi N, Otiende M, Maitland K, Walson J, Berkley JA. Mortality after inpatient treatment for diarrhea in children: a cohort study. BMC Med. 2019 Jan 28;17(1):20. doi: 10.1186/s12916-019-1258-0.
• Background Tickell KD, Sharmin R, Deichsel EL, Lamberti LM, Walson JL, Faruque ASG, Pavlinac PB, Kotloff KL, Chisti MJ. The effect of acute malnutrition on enteric pathogens, moderate-to-severe diarrhoea, and associated mortality in the Global Enteric Multicenter Study cohort: a post-hoc analysis. Lancet Glob Health. 2020 Feb;8(2):e215-e224. doi: 10.1016/S2214-109X(19)30498-X.
• Background Brander RL, Pavlinac PB, Walson JL, John-Stewart GC, Weaver MR, Faruque ASG, Zaidi AKM, Sur D, Sow SO, Hossain MJ, Alonso PL, Breiman RF, Nasrin D, Nataro JP, Levine MM, Kotloff KL. Determinants of linear growth faltering among children with moderate-to-severe diarrhea in the Global Enteric Multicenter Study. BMC Med. 2019 Nov 25;17(1):214. doi: 10.1186/s12916-019-1441-3.
• Background Cheng WD, Wold KJ, Bollinger LB, Ordiz MI, Shulman RJ, Maleta KM, Manary MJ, Trehan I. Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial. Am J Gastroenterol. 2019 Apr;114(4):671-678. doi: 10.14309/ajg.0000000000000170.
• Background Ochoa TJ, Chea-Woo E, Baiocchi N, Pecho I, Campos M, Prada A, Valdiviezo G, Lluque A, Lai D, Cleary TG. Randomized double-blind controlled trial of bovine lactoferrin for prevention of diarrhea in children. J Pediatr. 2013 Feb;162(2):349-56. doi: 10.1016/j.jpeds.2012.07.043. Epub 2012 Aug 30.
• Background Zavaleta N, Figueroa D, Rivera J, Sanchez J, Alfaro S, Lonnerdal B. Efficacy of rice-based oral rehydration solution containing recombinant human lactoferrin and lysozyme in Peruvian children with acute diarrhea. J Pediatr Gastroenterol Nutr. 2007 Feb;44(2):258-64. doi: 10.1097/MPG.0b013e31802c41b7.
• Tiwari R, Tickell KD, Yoshioka E, Otieno J, Shah A, Richardson BA, Keter L, Okello M, Nyabinda C, Trehan I, McGrath CJ, Means AR, Houpt ER, Liu J, Platts-Mills JA, Njunge JM, Rwigi D, Diakhate MM, Nyaoke J, Ochola E, John-Stewart G, Walson JL, Pavlinac PB, Singa BO. Lactoferrin and lysozyme to promote nutritional, clinical and enteric recovery: a protocol for a factorial, blinded, placebo-controlled randomised trial among children with diarrhoea and malnutrition (the Boresha Afya trial). BMJ Open. 2024 Aug 9;14(8):e079448. doi: 10.1136/bmjopen-2023-079448.

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