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August 2, 2024 – A groundbreaking study led by scientists at Harvard Medical School and published in Nature Microbiology has unveiled that the infectivity of certain tuberculosis (TB) strains is closely linked to the geographic background of both the pathogen and the exposed individual. This research, the first of its kind, highlights the complex interplay between pathogen, place, and human host that affects infection risk and susceptibility.
The study analyzed TB cases in cosmopolitan cities with diverse populations, including New York City, Amsterdam, and Hamburg. Researchers constructed a cohort from these cities to investigate how different TB strains move through mixed populations. The findings reveal that individuals exposed to a geographically restricted strain of TB—one that is common in a specific region—are less likely to develop active TB if their ancestry aligns with the strain’s native geographic area. Specifically, close household contacts of individuals with geographically restricted strains had a 14% lower rate of infection and a 45% lower rate of developing active TB disease compared to those exposed to widespread strains.
Notably, the study found that individuals with ancestry from the TB strain’s native region had a 38% lower risk of infection when exposed to a strain from an unrelated geographic area. This suggests a significant pathogen-host affinity, indicating that certain TB strains have evolved to be more compatible with specific human populations.
“This finding underscores the substantial public health impact of geographic and genetic factors on TB infection,” said Maha Farhat, Associate Professor of Biomedical Informatics at Harvard Medical School and the study’s senior author. “The size of the effect is surprisingly large, which indicates that these factors are crucial in shaping TB epidemiology.”
The study also demonstrated that the ancestry of individuals was a stronger predictor of infection risk than bacterial load, which is typically measured by sputum smear microscopy. In fact, ancestry-related risk outweighed other known risk factors such as diabetes and chronic diseases.
These insights contribute to a deeper understanding of TB’s complex behavior and its interaction with different host populations. The researchers emphasize the need for tailored prevention and treatment approaches, as certain strains of TB may respond differently to drugs and vaccines based on their geographic origins and the genetic backgrounds of those infected.
In addition to analyzing clinical and public health data, the study involved testing TB strains on human macrophages—immune cells that the bacteria target. This analysis revealed that cells from individuals with ancestry matching the strain’s native region were more susceptible to infection, reinforcing the epidemiological findings.
The research highlights the importance of considering genetic diversity in TB research and treatment strategies. “The diversity of human and bacterial genetics significantly impacts responses to treatments and vaccines,” Farhat added. “We need to incorporate this diversity into our disease management strategies.”
This study represents a significant advancement in understanding the epidemiology of TB and underscores the importance of multidisciplinary collaboration in addressing complex public health challenges. Future research will need to delve deeper into the genomic and structural differences influencing pathogen-host interactions to refine treatment and prevention strategies.
For more detailed information, see the study: “Differential rates of Mycobacterium tuberculosis transmission associate with host–pathogen sympatry,” published in Nature Microbiology. DOI: 10.1038/s41564-024-01758-y.
