Distribution and transmission of M. tuberculosis in a high-HIV prevalence city in Malawi: a genomic and spatial analysis

BackgroundDelays in identifying and treating individuals with infectious tuberculosis (TB) contribute to poor health outcomes and allow ongoing community transmission of M. tuberculosis (Mtb). Current recommendations for screening for tuberculosis specify community characteristics (e.g., areas with high local tuberculosis prevalence) that can be used to target screening within the general population. However, areas of higher tuberculosis burden are not necessarily areas with higher rates of transmission. We investigated the genomic diversity and transmission of Mtb using high-resolution surveillance data in Blantyre, Malawi. Methods and FindingsWe extracted and performed whole genome sequencing on mycobacterial DNA from cultured M. tuberculosis isolates obtained from culture-positive tuberculosis cases at the time of tuberculosis (TB) notification in Blantyre, Malawi between 2015-2019. We constructed putative transmission networks identified using TransPhylo and investigated individual and pair-wise demographic, clinical, and spatial factors associated with person-to-person transmission. We found that 56% of individuals with sequenced isolates had a probable direct transmission link to at least one other individual in the study. We identified thirteen putative transmission networks that included five or more individuals. Five of these networks had a single spatial focus of transmission in the city, and each focus centered in a distinct neighborhood in the city. We also found that approximately two-thirds of inferred transmission links occurred between individuals residing in different geographic zones of the city. ConclusionWhile the majority of detected tuberculosis transmission events in Blantyre occurred between people living in different zones, there was evidence of distinct geographical concentration for five transmission networks. These findings suggest that targeted interventions in areas with evidence of localized transmission may be an effective local tactic, but will likely need to be augmented by city-wide interventions to improve case finding and to address social determinants of tuberculosis to have sustained impact. Author SummaryWhy was this study done? - Tuberculosis (TB) is a major global health threat and a leading cause of death due to infectious disease. Rapid diagnosis and treatment of individuals with TB is vital to reduce the spread of disease. - If public health programs can identify areas with ongoing TB transmission, resources might be directed toward intervening in those areas to interrupt transmission chains. However, in settings where many people have TB, it is often difficult to differentiate areas with high rates of disease from areas with high rates of local transmission. What did the researchers do and find? - We used whole genome sequencing data to infer networks of TB transmission in Blantyre, Malawi. We used individual residence data to identify whether transmission networks were concentrated in specific parts of the city and to describe the amount of transmission that occurred between vs. within distinct parts of the city. - We found that most TB transmission in Blantyre occurred between individuals who did not live near each other. We also identified five transmission networks which had strong local foci of transmission. What do these findings mean? - Because most TB transmission in Blantyre does not occur in concentrated areas, city-wide interventions, such as improving access to TB care services and addressing social determinants of TB, may be needed to improve TB control. - For areas where there is evidence of local concentrated transmission, additional resources and strategies, such as targeted active case finding, may help to more rapidly reduce transmission and TB incidence.