Helminth infection and the risk of tuberculosis in children

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DESCRIPTION (provided by applicant): In the year 2000, an estimated 884,019 children less than 15 years of age became ill with tuberculosis. Despite the existence of curative therapy, the World Health Organization (WHO) has estimated that approximately one third of TB cases among children in this age group result in death. The paucity of data describing TB risk factors in children poses a challenge to the design of interventions that could decrease TB disease progression in this group. The identification of modifiable risk factors might lead to interventions that could substantially decrease TB-related morbidity and mortality in children. Helminth infection, including round worm and hookworm infection, may be one such risk factor. Recent case-control studies in adults and adolescents demonstrate that TB disease is associated with both helminth infection and immunological responses consistent with helminth infection. To date, however, no studies have examined the association between TB endpoints and helminth infection in children, the group most vulnerable to helminth infection and about which the least is known regarding risk factors for progression to active TB disease. The general objective of this study is to examine whether helminth infection increases susceptibility to TB infection and TB disease in children. We will pursue the following specific aims: (1) To determine whether helminth infection among children is associated with an increased risk of TB infection and disease; (2) To examine whether there is a dose-response relationship between the total burden of helminths and/or the number of helminth species with which a child is infected and progression to active TB disease and infection; (3) To compare the immune response to TB disease in children with and without helminths. We will conduct two matched case-control studies in Lima, Peru. To examine whether helminth infection is a risk factor for active TB disease, we will compare the prevalence of helminth infection among children with and without TB disease. To examine whether helminth infection is a risk factor for TB infection, we will compare the prevalence of helminth infection among children with and without TB infection. In both studies we will measure parasite burden and compare serum IgE levels in these two groups. Cases will be matched to controls by age, neighborhood, and TB contact history.