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Phylogeography and transmission of Mycobacterium tuberculosis spanning prisons and surrounding communities in Paraguay

Recent rises in incident tuberculosis (TB) cases in Paraguay and the increasing concentration of TB within prisons highlight the urgency of targeting strategies to interrupt transmission and prevent new infections. However, whether specific cities or carceral institutions play a disproportionate role in transmission remains unknown. We conducted prospective genomic surveillance, sequencing 471 Mycobacterium tuberculosis complex genomes, from inside and outside prisons in Paraguay’s two largest urban areas, Asunción and Ciudad del Este, from 2016 to 2021. We found genomic evidence of frequent recent transmission within prisons and transmission linkages spanning prisons and surrounding populations. We identified a signal of frequent M. tuberculosis spread between urban areas and marked recent population size expansion of the three largest genomic transmission clusters. Together, our findings highlight the urgency of strengthening TB control programs to reduce transmission risk within prisons in Paraguay, where incidence was 70 times that outside prisons in 2021.

Despite significant tuberculosis (TB) control efforts, the incidence rate of TB has declined only slowly in the World Health Organization Region of the Americas, and, alarmingly, has stagnated since 20141. The COVID-19 pandemic disrupted access to healthcare—including critical TB diagnostic and treatment programs—compounding the burden of TB and reversing decades of progress in TB control1.

New approaches to limit transmission are urgently needed in Paraguay, where TB control is chronically underfunded1 and where TB incidence was 48 (41–56) per 100,000 people in 2020, higher than the mean incidence rate across the region1. More than a quarter of the country’s population lives below the national poverty line2 and are at heightened risk of TB infection and mortality. Further, recent dramatic increases in incarceration3,4 put a rapidly growing population at high risk of infection and disease5,6,7. To guide interventions in Paraguay, there is a critical need to identify the populations at greatest risk of infection and locations and institutions where transmission most frequently occurs8.

Whole genome sequencing of the Mycobacterium tuberculosis complex has been powerfully applied to characterize recent transmission dynamics. Genomic approaches have dated introductions of M. tuberculosis and reconstructed patterns of historic spread across Central and South America9,10, estimated the contribution of recent transmission to incident TB cases11, reconstructed the emergence of resistance-associated mutations12, and inferred likely individual-level transmission events13. In Brazil14 and Georgia13, for example, genomic approaches identified frequent transmission within prisons as well as evidence of spillover from prisons to surrounding communities. A single M. tuberculosis molecular study from Paraguay15 on strains collected in 2003 reported that M. tuberculosis families found across South America, including the Latin-American (LAM; sub-lineage 4.3) and Haarlem (4.1.2.1) were also common in Paraguay15,16.

Genomic approaches have not been applied to address major gaps in our understanding of TB transmission in Paraguay. First, the conditions of incarceration put people at high risk of many infectious diseases, and globally, over the past twenty years, the incarcerated population in Central and South America has grown by 206%, the greatest increase in the world4. Escalating incarceration rates have been paralleled by an increasing concentration of notified TB among incarcerated individuals6. Yet the role of prison environments on TB transmission both inside and beyond prisons, as sources of broader infection, has not yet been described in Paraguay. Second, while incidence of TB is heterogeneous across the country15, it remains unknown whether specific cities or regions function as hotspots, fueling transmission elsewhere. Finally, due to limited surveillance infrastructure, the prevalence of drug-resistance and multi-drug-resistance has not yet been systematically measured17,18,19. Only 56% of bacteriologically confirmed new cases of pulmonary TB were tested for rifampicin resistance in 20201. Read More…

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