Background:  Approximately 90% of new M. tuberculosis (Mtb) infections are sub-clinical, resulting in latent TB infection (LTBI). Only 10% of LTBI progress to active disease over a healthy individual’s lifetime. However, over 10% of HIV-positive individuals with LTBI progress to active disease annually, making it critical to understand LTBI incidence in persons at risk for HIV. TB disease surveillance cannot provide direct estimates of Mtb infection incidence, and beyond outbreak investigations and healthcare worker monitoring, such estimates are rare. This study aimed to estimate Mtb infection incidence among injection drug users (IDU).

Methods:  From a cohort study including 1052 IDUs in Tijuana, Mexico, with a baseline prevalence of 67% for Mtb infection and 4.0% for HIV infection, Mtb negative participants were retested at an 18-month follow-up visit for incident Mtb infection. The QuantiFERON^® TB Gold In-Tube assay was used to detect Mtb infection at both visits. Univariate analyses were performed to identify risk factors for incident Mtb infection.

Results:  Of 354 IDU who were Mtb negative at baseline, 129 (36.4%) completed repeat testing at 18 months, which excludes 24 (15.7%) with indeterminate results. Baseline characteristics were similar to those without follow-up testing. Incident Mtb infection was observed among 67 (51.9%, 95%CI 43.3% to 60.5%) IDU. Compared to Mtb negative participants, seroconverters were more likely to have always lived in Tijuana (OR = 2.67, P =0.031), were ≥50 years old (OR = 10.70, P =0.017) and lived in a household with ≥3 members (OR = 2.50, P =0.011). Baseline HIV status was not associated with incident Mtb infection. Additionally, self-reported TB-like symptoms any time during follow-up were as common among seroconverters as non-seroconverters (27% vs 31%, P =0.64).

Conclusions:  This study—the largest incidence study among IDU to date—revealed that IDU in Tijuana are at very high risk for new Mtb infection. While the majority of such infections will become LTBI, IDU are at increased risk for HIV co-infection and subsequent progression to active TB. These findings indicate that active TB transmission is currently occurring in this population, highlighting the need for routine HIV and TB screening among IDU and TB chemoprophylactic treatment for co-infected IDU to prevent active TB from spreading within and beyond this population. Education to IDU is also needed to promote TB awareness and care-seeking when symptoms arise.