Genomics shows reinfection drives TB recurrence in Brazil

Tuberculosis can come back after a person has been treated, but that return can happen for different reasons. It may be a relapse, in which the original infection was never fully cleared, or a new infection caused by exposure to someone else’s disease. Knowing which is happening matters for public health: relapse suggests problems with treatment success, while reinfection points to ongoing transmission in the community. To untangle these pathways, a team led by corresponding author Késia Esther da Silva looked back at more than a decade of cases in two cities in Mato Grosso do Sul, Brazil. The researchers studied people with multiple culture-confirmed tuberculosis episodes between 2012 and 2023 in Dourados and Campo Grande. They focused on pairs of bacterial isolates taken from the same individuals at different episodes and used genetic tools to compare them. The goal was to classify each recurrence as relapse or persistent infection versus reinfection, information that can guide whether the priority should be strengthening treatment or stopping transmission.

The study reviewed 9,293 people with tuberculosis and identified 772 recurrent or retreatment episodes; paired isolates were available for 82 individuals. The team used Whole-genome sequencing to measure how genetically similar or different the paired isolates were. They relied on pairwise genetic distances measured in single-nucleotide polymorphisms [SNPs]: pairs with ≤12 SNPs were classified as relapse or persistent infection, while pairs with >12 SNPs were classified as reinfection or retreatment with reinfection. Among patients who had completed treatment, 74.1% (40 of 54) of recurrent episodes were reinfections and 25.9% (14 of 54) were relapses. For people who had non-curative outcomes and required retreatment, persistent infection occurred in 53.6% (15 of 28) and retreatment with reinfection in 46.4% (13 of 28). The study also found timing differences: relapse and persistent infection tended to occur sooner after the initial episode, while reinfection became the dominant cause after two years. A history of incarceration was strongly linked to reinfection after treatment completion (92.5%, p=0.012) and following non-curative outcomes (76.9%, p=0.016).

These findings show two complementary problems in a high-burden setting: people are being reinfected because transmission is ongoing, and some recurrences are due to incomplete cure. After successful treatment, most recurrences in this study were new infections, pointing to the need for better control of spread in the community and in high-risk places such as prisons. At the same time, relapse and persistent infection remain important, particularly for people who did not reach a curative outcome, signaling the need for stronger treatment support and follow-up to prevent treatment-related failures. The study highlights the value of genomic tools such as Whole-genome sequencing and careful measurement of single-nucleotide polymorphisms [SNPs] to tell whether a repeat episode is the same strain or a new one; that distinction can change public health priorities. Overall, the results argue for an integrated approach that combines adherence support to reduce relapse with interventions to stop transmission, guided by genomic evidence and attention to high-risk populations.