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Rationale: Policy recommendations on contact investigation of HIV-seropositive patients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa., Objectives: We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship., Methods: Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed., Measurements and Main Results: Latent tuberculosis infection was found in 577 of 878 (65.7%) and 717 of 974 (73.6%) household contacts of HIV-seropositive and -seronegative tuberculosis cases (relative risk, 0.89; 95% confidence interval, 0.82-0.97). On further stratification, cavitary lung disease (P < 0.0001 for interaction) and smear status (P = 0.02 for interaction) of tuberculosis cases modified the infectiousness of HIV-seropositive indexes. Cough duration of index cases did not display interaction (P = 0.499 for interaction)., Conclusions: This study suggests that HIV-seropositive tuberculosis cases may be less infectious than HIV-seronegative patients only when they are smear-negative or lack cavitary lung disease. These results may explain heterogeneity between prior studies and provide evidence suggesting that tuberculosis contact investigation should include HIV-seropositive index cases in high disease burden settings.

Rationale: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in response to high bacillary loads occurring during tuberculosis., Objectives: To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis., Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8(+) T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62)., Measurements and Main Results: The proportion of positive CD8(+) T-cell assays and magnitude of CD8(+) T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups., Conclusions: Among young children, M. tuberculosis-specific CD8(+) T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ-producing M. tuberculosis-specific CD8(+) T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease.