Dataset Information

Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study.

ABSTRACT: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), causes 9 million new cases worldwide and 2 million deaths annually. Genetic linkage and association analyses have suggested several chromosomal regions and candidate genes involved in TB susceptibility. This study examines the association of TB disease susceptibility with a selection of biologically relevant genes on regions on chromosomes 7 (IL6 and CARD11) and 20 (CTSZ and MC3R) and fine mapping of the chromosome 7p22-p21 region identified through our genome scan. We analyzed 565 individuals from Kampala, Uganda, who were previously included in our genome-wide linkage scan. Association analyses were conducted for 1,417 single-nucleotide polymorphisms (SNP) that passed quality control. None of the candidate gene or fine mapping SNPs was significantly associated with TB susceptibility (p > 0.10). When we restricted the analysis to HIV-negative individuals, 2 SNPs on chromosome 7 were significantly associated with TB susceptibility (p < 0.05). Haplotype analyses identified a significant risk haplotype in cathepsin X (CTSZ; p = 0.0281, odds ratio = 1.5493, 95% confidence interval [1.039, 2.320]).

SUBMITTER: Baker AR

PROVIDER: S-EPMC3078986 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study.

Baker Allison R AR Zalwango Sarah S Malone LaShaunda L LL Igo Robert P RP Qiu Feiyou F Nsereko Mary M Adams Mark D MD Supelak Pamela P Mayanja-Kizza Harriet H Boom W Henry WH Stein Catherine M CM

Human immunology 20110225 5

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), causes 9 million new cases worldwide and 2 million deaths annually. Genetic linkage and association analyses have suggested several chromosomal regions and candidate genes involved in TB susceptibility. This study examines the association of TB disease susceptibility with a selection of biologically relevant genes on regions on chromosomes 7 (IL6 and CARD11) and 20 (CTSZ and MC3R) and fine mapping of the chromosome 7p22-p21 region id ...[more]

PMID: 21354459

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Project description:BackgroundTuberculosis is recognised as a major cause of morbidity and mortality in children, with most cases in children going undiagnosed and resulting in poor outcomes. Household contact management, which aims to identify children with active tuberculosis and to provide preventive therapy for those with HIV or those younger than 5 years, has long been recommended but has very poor coverage globally. New guidelines include widespread provision of preventive therapy to children with a positive tuberculin skin test (TST) who are older than 5 years.MethodsIn this mathematical modelling study, we provide the first global and national estimates of the impact of moving from zero to full coverage of household contact management (with and without preventive therapy for TST-positive children older than 5 years). We assembled data on tuberculosis notifications, household structure, household contact co-prevalence of tuberculosis disease and infection, the efficacy of preventive therapy, and the natural history of childhood tuberculosis. We used a model to estimate households visited, children screened, and treatment courses given for active and latent tuberculosis. We calculated the numbers of tuberculosis cases, deaths, and life-years lost because of tuberculosis for each intervention scenario and country.FindingsWe estimated that full implementation of household contact management would prevent 159 500 (75% uncertainty interval [UI] 147 000-170 900) cases of tuberculosis and 108 400 (75% UI 98 800-116 700) deaths in children younger than 15 years (representing the loss of 7 305 000 [75% UI 6 663 000-7 874 000] life-years). We estimated that preventing one child death from tuberculosis would require visiting 48 households, screening 77 children, giving 48 preventive therapy courses, and giving two tuberculosis treatments versus no household contact management.InterpretationHousehold contact management could substantially reduce childhood disease and death caused by tuberculosis globally. Funding and research to optimise its implementation should be prioritised.FundingUK Medical Research Council, US National Institutes of Health, Fulbright Commission, Janssen Global Public Health.

Project description:BACKGROUND:The World Health Organization (WHO) recommends household contact investigation for tuberculosis (TB) in high-burden countries. However, household contacts who complete evaluation for TB during contact investigation may have difficulty accessing their test results. Use of automated short-messaging services (SMS) to deliver test results could improve TB status awareness and linkage to care. We sought to explore how household contacts experience test results delivered via SMS, and how these experiences influence follow-up intentions. METHODS:We conducted semi-structured interviews with household contacts who participated in a randomized controlled trial evaluating home sputum collection and delivery of TB results via SMS (Pan-African Clinical Trials Registry #201509000877140). We asked about feelings, beliefs, decisions, and behaviors in response to the SMS results. We analyzed the content and emerging themes in relation to the Theory of Planned Behavior. RESULTS:We interviewed and achieved thematic saturation with ten household contacts. Nine received TB-negative results and one a TB-positive result. Household contacts reported relief upon receiving SMS confirming their TB status, but also said they lacked confidence in the results delivered by SMS. Some worried that negative results were incorrect until they spoke to a lay health worker (LHW). Household contacts said their long-term intentions to request help or seek care were influenced by perceived consequences of not observing the LHW's instructions related to the SMS and follow-up procedures; beliefs about the curability of TB; anticipated support from LHWs; and perceived barriers to responding to an SMS request for further evaluation. CONCLUSION:Household contacts experienced relief when they received results. However, they were less confident about results delivered via SMS than results delivered by LHWs. Delivery of results by SMS should complement continued interaction with LHWs, not replace them.

Dataset Information

Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study.

Publications

Genetic susceptibility to tuberculosis associated with cathepsin Z haplotype in a Ugandan household contact study.

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