Chest
Volume 149, Issue 2, February 2016, Pages 516-525
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Original Research: Chest Infections
Risk of Active Tuberculosis in the Five Years Following Infection . . . 15%?

https://doi.org/10.1016/j.chest.2015.11.017Get rights and content

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.

Section snippets

Materials and Methods

The full methods are described in e-Appendix 1 and are summarized as follows.

Results

Of the 15,094 contacts identified over the study period, 613 met the study criteria for infection at the time of exposure, and the characteristics of these cases are presented in Table 2. Results differed markedly according to age, with 29 of 81 (35.8%) aged < 5 years, 27 of 136 (17.4%) aged 5 to 14 years, and 11 of 396 (2.8%) aged ≥ 15 years developing TB. Of the 67 cases of active TB, 64 met the full case definition,18 and three were classified as presumptive cases; all cases were treated

Discussion

We estimated the 4½-year risk of active TB following an index infection at 14.5% by using a realistic reconstruction of a true survival analysis of contacts who could confidently determine that they had been infected at the time of their exposure. Moreover, even with less specific definitions for infection at time of exposure, our point estimates of risk remained > 11%. These values are considerably higher than the widely accepted estimates of 5% to 10% lifetime risk, with one-half occurring

Conclusions

The 5-year risk of active TB after infection was estimated at 11% to 18%, and this value is more likely to be an underestimate than an overestimate. Although this value is approximately twofold to sevenfold the traditionally accepted rate, our estimates are consistent with much of the previous research. Because the risk of developing active TB is likely to be higher in developing countries,3 as well as in populations with a high prevalence of comorbidities, even higher levels of risk may be

Acknowledgments

Author contributions: J. M. T. affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. J. M. T. conceived the study, developed the analysis approach, performed the analysis, and drafted the manuscript. N. M. and E.-L. T. compiled the broader database from which the subjects were

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      These findings are of great concern because the greatest focus of screening and tracing of TB contacts should be placed on children during their first 5 years of life, as this is a period of high risk of progression from TBI to active disease. Indeed, the risk of TB incidence among exposed infants and children is very high, reaching 20% within 2 years of exposure.7,8 Many previous studies have described the investigation of contacts in children and adults for TBI and TPT,8,19,22,23 however we have previously demonstrated that the use of the TBI cascade of care can provide a greater depth of understanding of the dynamics of TBI care and follow-up of contacts of TB index cases.12,13,17

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    FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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