James M Trauer1, Nompilo Moyo2, Ee-Laine Tay3, Katie Dale2, Romain Ragonnet4, Emma S McBryde5, Justin T Denholm6. 1. Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, Australia; Centre for Population Health, the Burnet Insitute, Melbourne, Australia. Electronic address: james.trauer@mh.org.au. 2. Victorian Tuberculosis Program at the Peter Doherty Institute, Melbourne, Australia. 3. Victorian Department of Health and Human Services, Melbourne, Australia. 4. Centre for Population Health, the Burnet Insitute, Melbourne, Australia. 5. Victorian Infectious Diseases Service at the Peter Doherty Institute, Melbourne, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Australia. 6. Victorian Infectious Diseases Service at the Peter Doherty Institute, Melbourne, Australia; Department of Microbiology and Immunology, the University of Melbourne at the Peter Doherty Institute, Melbourne, Australia.
Abstract
BACKGROUND: It is often stated that the lifetime risk of developing active TB after an index infection is 5% to 10%, one-half of which accrues in the 2 to 5 years following infection. The goal of this study was to determine whether such estimates are consistent with local programmatic data. METHODS: This study included close contacts of individuals with active pulmonary TB notified in the Australian state of Victoria from January 1, 2005, to December 31, 2013, who we deemed to have been infected as a result of their exposure. Survival analysis was first performed on the assumption of complete follow-up through to the end of the study period. The analysis was then repeated with imputation of censorship for migration, death, and preventive treatment, using local mortality and migration data combined with programmatic data on the administration of preventive therapy. RESULTS: Of 613 infected close contacts, 67 (10.9%) developed active TB during the study period. Assuming complete follow-up, the 1,650-day cumulative hazard was 11.5% (95% CI, 8.9-14.1). With imputation of censorship for death, migration, and preventive therapy, the median 1,650-day cumulative hazard over 10,000 simulations was 14.5% (95% CI, 11.1-17.9). Most risk accrued in the first 5 months after infection, and risk was greatest in the group aged < 5 years, reaching 56.0% with imputation, but it was also elevated in older children (27.6% in the group aged 5-14 years). CONCLUSIONS: The risk of active TB following infection is several-fold higher than traditionally accepted estimates, and it is particularly high immediately following infection and in children.
BACKGROUND: It is often stated that the lifetime risk of developing active TB after an index infection is 5% to 10%, one-half of which accrues in the 2 to 5 years following infection. The goal of this study was to determine whether such estimates are consistent with local programmatic data. METHODS: This study included close contacts of individuals with active pulmonary TB notified in the Australian state of Victoria from January 1, 2005, to December 31, 2013, who we deemed to have been infected as a result of their exposure. Survival analysis was first performed on the assumption of complete follow-up through to the end of the study period. The analysis was then repeated with imputation of censorship for migration, death, and preventive treatment, using local mortality and migration data combined with programmatic data on the administration of preventive therapy. RESULTS: Of 613 infected close contacts, 67 (10.9%) developed active TB during the study period. Assuming complete follow-up, the 1,650-day cumulative hazard was 11.5% (95% CI, 8.9-14.1). With imputation of censorship for death, migration, and preventive therapy, the median 1,650-day cumulative hazard over 10,000 simulations was 14.5% (95% CI, 11.1-17.9). Most risk accrued in the first 5 months after infection, and risk was greatest in the group aged < 5 years, reaching 56.0% with imputation, but it was also elevated in older children (27.6% in the group aged 5-14 years). CONCLUSIONS: The risk of active TB following infection is several-fold higher than traditionally accepted estimates, and it is particularly high immediately following infection and in children.
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