Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys

• Published in: eLife 2023-12, Vol.12
• Main Authors: Emery, Jon C, Dodd, Peter J, Banu, Sayera, Frascella, Beatrice, Garden, Frances L, Horton, Katherine C, Hossain, Shahed, Law, Irwin, van Leth, Frank, Marks, Guy B, Nguyen, Hoa Binh, Nguyen, Hai Viet, Onozaki, Ikushi, Quelapio, Maria Imelda D, Richards, Alexandra S, Shaikh, Nabila, Tiemersma, Edine W, White, Richard G, Zaman, Khalequ, Cobelens, Frank, Houben, Rein M G J
• Format: Article
• Language: English
• Subjects: Aerosols; Asia; asymptomatic transmission; asymptomatic tuberculosis; Data analysis; Disease transmission; Epidemiology and Global Health; Health aspects; household Mtb infection surveys; Households; Humans; Infections; Lung diseases; mathematical modelling; Medical research; Medicine, Experimental; Microbiology and Infectious Disease; Mtb transmission; Mycobacterium tuberculosis; Prevalence; Prevalence studies (Epidemiology); Sputum; subclinical transmission; Surveys; Tuberculosis; Tuberculosis - epidemiology; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - epidemiology
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.82469

Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to ( ) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. We reviewed the literature to identify studies where surveys of infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global transmission. We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the Euro