A prospective survey of social mixing patterns relevant to respiratory disease transmission by large droplets (e.g., influenza) or small droplet nuclei (e.g., tuberculosis) was performed in a South African township in 2010. A total of 571 randomly selected participants recorded the numbers, times, and locations of close contacts (physical/nonphysical) and indoor casual contacts met daily. The median number of physical contacts was 12 (interquartile range (IQR), 7-18), the median number of close contacts was 20 (IQR, 13-29), and the total number of indoor contacts was 30 (IQR, 12-54). Physical and close contacts were most frequent and age-associative in youths aged 5-19 years. Numbers of close contacts were 40% higher than in corresponding populations in industrialized countries (P < 0.001). This may put township communities at higher risk for epidemics of acute respiratory illnesses. Simulations of an acute influenza epidemic predominantly involved adolescents and young adults, indicating that control strategies should be directed toward these age groups. Of all contacts, 86.2% occurred indoors with potential exposure to respiratory droplet nuclei, of which 27.2%, 20.1%, 20.0%, and 8.0% were in transport, own household, crèche/school, and work locations, respectively. Indoor contact time was long in households and short during transport. High numbers of indoor contacts and intergenerational mixing in households and transport may contribute to exceptionally high rates of tuberculosis transmission reported in the community.

Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust and simple, PCR-based host-blood transcriptomic signature, RISK6, for multiple applications: identifying individuals at risk of incident disease, as a screening test for subclinical or clinical tuberculosis, and for monitoring tuberculosis treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly exceeded that of previous signatures discovered in the same cohort. Performance for diagnosing subclinical and clinical disease in HIV-uninfected and HIV-infected persons, assessed by area under the receiver-operating characteristic curve, exceeded 85%. As a screening test for tuberculosis, the sensitivity at 90% specificity met or approached the benchmarks set out in World Health Organization target product profiles for non-sputum-based tests. RISK6 scores correlated with lung immunopathology activity, measured by positron emission tomography, and tracked treatment response, demonstrating utility as treatment response biomarker, while predicting treatment failure prior to treatment initiation. Performance of the test in capillary blood samples collected by finger-prick was noninferior to venous blood collected in PAXgene tubes. These results support incorporation of RISK6 into rapid, capillary blood-based point-of-care PCR devices for prospective assessment in field studies.

Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission.