Localized TB strains are less infectious in big cities but more likely to infect people from their natural areas. This finding suggests that TB treatments should be tailored based on the strain and host match.
The research, led by Harvard Medical School and published in Nature Microbiology provides the first evidence that TB strains evolve with their human hosts, becoming more infectious to specific populations. The study shows that the chances of TB infection depend on whether the person and the bacteria share a hometown.
These results support that TB bacteria and humans have coevolved over time and may help develop new TB prevention and treatment methods. TB affects over 10 million people and causes over a million deaths yearly.
In this study, researchers compared TB strains’ infectivity in people from different regions by analyzing patient data from New York City, Amsterdam, and Hamburg. They found that close contacts of people with a localized TB strain had a 14% lower infection rate and a 45% lower rate of developing active TB than those exposed to widespread strains.
Localized strains were more likely to infect people from their native regions. The odds of infection dropped by 38% when exposed to a strain from a different area. This suggests a shared evolution between humans and microbes, making them more compatible and increasing infection risk. According to Maha Farhat from Harvard Medical School, the impact on public health is significant.
Researchers have found that not all TB strains are the same, thanks to genetic sequencing. Some strains are widespread, while others are limited to specific areas. In high-incidence settings, people often encounter multiple strains, making it hard to compare them directly. Many factors, like bacterial load measured by sputum smear microscopy, increase TB risk from close contact.
However, the new study shows that having ancestors from the strain’s common region is a more significant infection risk factor than bacterial load for localized strains. This risk even outweighs other known factors like diabetes. The findings highlight the importance of understanding the differences between TB strains and their interactions with various host populations.
Previous studies have shown that some tuberculosis strains are more likely to develop drug resistance and that TB vaccines work better in certain places. Some treatments may also be more effective for specific TB strains.
According to Matthias Groeschel, understanding why different TB strains behave differently and why some target particular groups is crucial. Researchers tested different TB strains’ ability to infect human immune cells. They found that cells from people with matching ancestry to the strain’s native region were more susceptible.
This study highlights the need to consider human and TB genetic diversity in treatment and prevention. More research is needed to understand TB’s and human cells’ genomic and structural differences. Farhat and Groeschel emphasize the importance of considering genetic diversity in how people and TB respond to drugs and vaccines.
Previously, TB strains were identified using traditional genotyping methods. However, whole genome sequencing now helps profile TB germs and track outbreaks better. Researchers noticed that localized TB strains didn’t spread well to other regions, leading them to speculate that these strains were less infectious.
They also thought that localized TB strains might have coevolved with human hosts, making different populations more susceptible to different TB strains. Different TB strains respond differently to treatments and vaccines. Testing these ideas took time due to cultural and environmental differences and the limited spread of localized strains, making data collection challenging.
To overcome challenges, the research team worked with public health departments and researchers from the U.S., the Netherlands, and Germany. They created an extensive database combining TB case reports, genetic profiles, and public health records of infection rates among close contacts. They also included demographic details to see how different TB strains spread in various populations.
The study covered 5,256 TB cases and 28,889 close contacts. Groeschel highlighted the importance of collaboration, noting that merging data from three big cities and using advanced computational tools helped answer a complex question with significant public health implications.
Journal reference:
- Gröschel, M.I., Pérez-Llanos, F.J., Diel, R. et al. Differential rates of Mycobacterium tuberculosis transmission associate with host–pathogen sympatry. Nature Microbiology. DOI: 10.1038/s41564-024-01758-y.