tuberculosis infantil y desnutricion jid 2012

M A J O R A R T I C L E

Childhood Tuberculosis and Malnutrition

Devan Jaganath1,3 and Ezekiel Mupere2,3

1David Geffen School of Medicine at the University of California, Los Angeles; 2Makerere University, Kampala, Uganda; and 3Tuberculosis ResearchUnit (TBRU), Case Western Reserve University, Cleveland, Ohio

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on themechanisms that underlie this relationship. From available research, it appears that malnutrition is a predic-tor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines ofevidence, including the role of vitamin D receptor genotypes, malnutritions effects on immune development,respiratory infections among malnourished children, and limited work specically on pediatric tuberculosisand malnutrition. Nutritional supplementation has yet to suggest signicant benets on the course of tuber-culosis in children. There is a critical need for research on childhood tuberculosis, specically on how nutri-tional status affects the risk and progression of tuberculosis and whether nutritional supplementationimproves clinical outcomes or prevents disease.

Tuberculosis remains a signicant source of morbidityand mortality among children in resource-limited set-tings. Of the 9 million new tuberculosis infectionseach year, 11% are in children [1]. Malnutrition is alsohighly prevalent in children living in tuberculosisendemic countries and contributes to 2.2 milliondeaths in children under 5 years of age globally [2].Poverty, overcrowding, food insecurity, and humanimmunodeciency virus (HIV) further set the stagefor both malnutrition and poor infection control.

Although the World Health Organization (WHO)states that malnutrition is a signicant risk factor forchildhood tuberculosis [1], there are limited studies toexplain the mechanisms underlying this association.This may be due to the challenges in diagnosing pedi-atric tuberculosis, difculty in establishing a causalrole of malnutrition on tuberculosis, and an overalllow research priority because of the limited infectivityof children. We will review 4 lines of support thatserve as the foundation of our understanding of the

interaction between pediatric tuberculosis and nutri-tional status, namely, (1) gene polymorphisms relatingvitamin metabolism to risk of tuberculosis, (2) studiesinvestigating immune development among malnour-ished children, (3) associations between malnutritionand respiratory tract infections in children, and (4) as-sociations between nutritional status and tuberculosisin both animal models and children. Taken together,the evidence suggests that malnutrition affects geneticexpression and immune function that predisposeschildren to tuberculosis progression, and the resultingdisease and inammatory response further worsensthe nutritional state. Because of this devastating cycle,understanding the mechanisms that contribute to thisprecise interaction in children is essential to address-ing both epidemics and ascertaining whether nutri-tional interventions will be of benet.

METHODS

References were identied through searches onPubMed, Cochrane, Web of Knowledge, and GoogleScholar. Inclusion criteria were articles in Englishrelated to risk factors, etiology, and management oftuberculosis in relation to nutritional status. PubMedsearches included the terms tuberculosis, malnutri-tion [MeSH], nutritional status [MeSH], infec-tion, pulmonary infection, respiratory tractinfections [MeSH], milk, human/immunology, andmicronutrient. Searches were completed with and

Received 10 April 2012; accepted 13 July 2012; electronically published 2October 2012.

Correspondence: Ezekiel Mupere, MBChB, PhD, School of Medicine, College ofHealth Sciences, Makerere University, Dept of Pediatrics and Child Health, ClinicalResearch Bldg, Gr Fl Rm 9, Kampala, Uganda (mupez@yahoo.com).

The Journal of Infectious Diseases 2012;206:180915 The Author 2012. Published by Oxford University Press on behalf of the InfectiousDiseases Society of America. All rights reserved. For Permissions, please e-mail:journals.permissions@oup.com.DOI: 10.1093/infdis/jis608

Childhood Tuberculosis and Malnutrition JID 2012:206 (15 December) 1809