# Factors Involved in Tuberculosis Recurrence in a Low-incidence Setting; Reactivation Predominates Over Reinfection in a 30-year Surveillance Study

## TL;DR

This study finds that tuberculosis recurrence in a low-incidence region is mostly due to reactivation of old infections, not new ones, and identifies risk factors like HIV and mobility.

## Contribution

The study provides long-term molecular surveillance data showing reactivation dominates TB recurrence in low-incidence settings.

## Key findings

- Only 2.30% of TB cases in Aragón were recurrent, with reactivation being 1.93% and reinfection 0.42%.
- Reinfection was linked to factors like residence change, HIV, cancer, and multimorbidity.
- Reactivation recurred faster (median 2 years) than reinfection (median 7 years).

## Abstract

Tuberculosis (TB) recurrence remains a significant public health concern, even in regions with low incidence. Recurrent TB may result from endogenous reactivation of a previous infection or from exogenous reinfection with a new strain. Distinguishing between these mechanisms is crucial for understanding TB dynamics and optimizing control strategies. This study aims to determine the frequency of TB recurrence in Aragón, Spain, a region with low TB incidence, and to identify factors associated with reactivation and reinfection over a 30-year period.

A retrospective, descriptive study including all genotyped Mycobacterium tuberculosis isolates from 1993 to 2022 was conducted in Aragón. IS6110-RFLP was the method used to genotype strains. Recurrences were classified as reactivation or reinfection based on molecular profiles. Clinical and epidemiological data were retrieved from medical records. Appropriate statistical tests were applied to compare groups.

Among 3510 genotyped TB cases, 81 (2.30%) were recurrent: 68 reactivations (1.93%) and 15 reinfections (0.42%). Reinfection was significantly associated with change of residence, HIV infection, cancer diagnosis in the second episode, and multimorbidity. Time to recurrence was significantly longer in reinfections (median 7.0 years) compared to reactivations (2.0 years). Most isolates belonged to Lineage 4 , and reinfection strains were more often linked to clustered strains circulating in the community.

In this low-incidence setting, TB recurrence is rare and mainly the result of reactivation. Reinfections, though less frequent, are linked to mobility, HIV co-infection, neoplasm, and compromised health status. These findings underscore the importance of long-term molecular surveillance and targeted follow-up for high-risk patients.

Tuberculosis recurrence in Aragón (1993–2022) was rare (2.30%). Reactivation predominated over reinfection, which was associated with mobility, HIV, cancer status, and multimorbidity. Molecular surveillance and targeted follow-up are essential to address recurrence dynamics in low-incidence settings.