Abstract
SummaryBackgroundContacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases.MethodsIn 2002–06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014–15.FindingsIn the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5–11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80–1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7–4·4), 6·2% (4·8–8·1), and 20·6% (17·3–24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4–2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7–2·8), 3·9% (2·5–5·9), and 8·6%· (5·9–12·6).InterpretationOur externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit.FundingWellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.
Highlights
Contacts of people with tuberculosis are at high risk of developing tuberculosis.[1]
We found several reviews of tuberculosis contact investigation and preventive therapy that highlighted the low attention given to such interventions worldwide and emphasised the urgent need for scale-up if the objectives of WHO’s End TB Strategy are to be achieved
We found many studies and reviews characterising risk factors for tuberculosis, only one attempted to define a method to predict tuberculosis risk in adults with assessment of a blood RNA signature
Summary
Contacts of people with tuberculosis are at high risk of developing tuberculosis.[1]. The tests for latent tuberculosis infection that are commonly used to guide prescription of preventive therapy, such as the tuberculin skin test (TST) and interferon-γ-release assays, are technically and logistically complicated.[4,5] These factors lead to difficulties in assessing who has latent tuberculosis or, when infection is confirmed, who is at high risk of progression to disease and, most likely to benefit from preventive therapy
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