Within-household transmission risk of pulmonary tuberculosis in the era of universal antiretroviral therapy

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Abstract
Background: Tuberculosis remains the leading infectious cause of death worldwide. In the WHO African region, declining incidence has coincided with antiretroviral therapy (ART) scale-up, though whether this reflects reduced progression to disease or reduced transmission is unclear. We evaluated how ART and symptom status influence within-household Mycobacterium tuberculosis complex (MTBC) transmission risk. Methods: We conducted a case-contact household study in rural South Africa, enrolling index adults with bacteriologically-confirmed pulmonary tuberculosis. MTBC immunoreactivity was measured in all child household contacts (aged 2-14 years) as a proxy measure of within-household transmission. We assessed the influence of index person ART status and symptom status and explored effect-measure modification of the association between index person HIV status and transmission risk by sex. Results: Among 755 child contacts of 296 index persons, effective ART was not associated with within-household MTBC transmission risk (risk ratio [RR], 1.07; 95% CI, 0.66–1.74). Among PLHIV engaged in ART care, WHO TB four-symptom screen (WHO4SS) status was not associated with transmission risk (RR, 0.80; 95% CI, 0.43–1.47), although absence of reported cough reduced risk (RR, 0.61; 95% CI, 0.38–0.96). A pronounced interaction between sex and HIV status was observed: HIV-negative women had the highest within-household MTBC transmission risk (30.5% vs. 14.3% in women with HIV) whereas risks were similar between HIV-positive and HIV-negative men. Conclusions: We found no evidence that effective ART or WHO4SS status influenced within-household MTBC transmission risk, though confidence intervals were wide. Absence of reported cough was associated with lower risk, and transmission risk was highest among child contacts of HIV-negative women. These findings suggest reported cough is a useful marker of transmission risk and that routine tuberculosis screening within ART care may reduce transmission from PLHIV; intensified efforts are nonetheless needed to achieve earlier tuberculosis detection in HIV-negative individuals.
Funding Information
  • National Institute of Allergy and Infectious Diseases of the National Institutes of Health (1R01AI147321-01)

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