TY - JOUR
T1 - A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases
T2 - a prospective derivation and external validation cohort study
AU - Saunders, Matthew J.
AU - Wingfield, Tom
AU - Tovar, Marco A.
AU - Baldwin, Matthew R.
AU - Datta, Sumona
AU - Zevallos, Karine
AU - Montoya, Rosario
AU - Valencia, Teresa R.
AU - Friedland, Jon S.
AU - Moulton, Lawrence Hale
AU - Gilman, Robert H.
AU - Evans, Carlton A.
N1 - Publisher Copyright:
© 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2017/11
Y1 - 2017/11
N2 - Background Contacts 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. Methods In 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. Findings In 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). Interpretation Our 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. Funding Wellcome 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.
AB - Background Contacts 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. Methods In 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. Findings In 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). Interpretation Our 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. Funding Wellcome 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.
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U2 - 10.1016/S1473-3099(17)30447-4
DO - 10.1016/S1473-3099(17)30447-4
M3 - Article
C2 - 28827142
AN - SCOPUS:85027718009
SN - 1473-3099
VL - 17
SP - 1190
EP - 1199
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 11
ER -