Time Since Infection and Risks of Future Disease for Individuals with Mycobacterium tuberculosis Infection in the United States

Abstract

Background: Risk of tuberculosis (TB) declines over time since Mycobacterium tuberculosis infection, but progression to clinical disease is still possible decades later. In the United States, most TB cases result from the progression of latent TB infection acquired over 2 years ago.

Methods: We synthesized evidence on TB natural history and incidence trends using a transmission-dynamic model. For the 2020 US population, we estimated average time since infection and annual, cumulative, and remaining lifetime risks of progression to TB, by nativity and age.

Results: For a newly infected adult with no other risk factors for progression to TB, estimated rates of progression declined from 38 (95% uncertainty interval: 33, 46) to 0.38 (0.32, 0.45) per 1000 person-years between the first and 25th year since infection. Cumulative risk over 25 years from new infection was 7.9% (7.0, 8.9). In 2020, an estimated average age of individuals with prevalent infection was 62 (61, 63) for the US-born population, 55 (54, 55) for non-US-born, and 57 (56, 58) overall. Average risks of developing TB over the remaining lifetime were 1.2% (1.0, 1.4) for US-born, 2.2% (1.8, 2.6) for non-US-born, and 1.9% (1.6, 2.2) for the general population. Risk estimates were higher for younger age groups.

Conclusions: Our analysis suggests that, although newly infected individuals face appreciable lifetime TB risks, most US individuals with latent TB infection were infected long ago, and face low future risks of developing TB. Better approaches are needed for identifying recently infected individuals and those with elevated progression risks.

FIGURE 1.

Estimated risks of progression to TB as a function of time since infection, for an individual infected at age 20. A, Model estimates for annual rate of progression to TB as a function of time since infection, for an individual infected at 20 years of age with no other risk factors for progression to TB. B, Model estimates for cumulative risk of progression to TB as a function of time since infection, for an individual infected at 20 years of age with no other risk factors for progression to TB. C, Model estimates for remaining lifetime risk of progression to TB as a function of time since infection, for an individual infected at 20 years of age with no other risk factors for progression to TB, and who has not yet developed TB. Estimates assume no reinfection or treatment of Mtb infection. Difference between year 1 risk in (C) and final year risk in (B) represents additional risk accruing after 25 years following infection.

FIGURE 2.

Average time since infection for US-born individuals with prevalent Mtb infection and incident TB in 2020, by current age. A, Average number of years since infection and distribution of number of years since infection for US-born individuals with prevalent Mtb infection in 2020, by age. B, Average number of years since infection and distribution of number of years since infection for US-born individuals developing TB disease in 2020, by age.

FIGURE 3.

Remaining lifetime risk of progression to TB for individuals with prevalent Mtb infection, by age and population group. “Pop. Mean” represents the population-average value for each population group. Estimates not stratified by age include all individuals with prevalent Mtb infection, with average age 62 (61, 63), 55 (54, 55), and 57 (56, 58) for US-born, non-US-born, and total population, respectively. Lower risk estimates among non-US-born children reflect longer average time since infection, related to infections acquired prior to entry.