A recent study led by Harvard Medical School scientists has found that the chances of someone getting infected with tuberculosis (TB) depend on whether the person and the bacterium share the same hometown. This study highlights the unique interaction between the pathogen, place, and human host, which affects infection risk and susceptibility.
The research supports a long-standing hypothesis that specific bacteria and their human hosts have likely coevolved over hundreds or thousands of years. These findings could help inform new prevention and treatment approaches for TB, a disease that affects over 10 million people and causes more than a million deaths worldwide each year, according to the World Health Organization.
Key Findings
The study is the first controlled comparison of TB strains’ infectivity in populations of mixed geographic origins. Researchers created a study cohort by combining TB case files from patients in New York City, Amsterdam, and Hamburg, providing enough data to power their models.
The analysis showed that close household contacts of people diagnosed with a geographically restricted strain of TB had a 14% lower infection rate and a 45% lower rate of developing active TB disease compared to those exposed to a widespread strain. Strains with narrow geographic ranges were more likely to infect people with roots in the bacteria’s native region than those from outside the region.
Specifically, the odds of infection dropped by 38% when a person was exposed to a restricted pathogen from a different geographic region than their own background. This was true for people who had lived in the region and for those whose parents could trace their heritage to the region.
Evolutionary Connection
This pathogen-host affinity suggests a shared evolution between humans and microbes, with certain biological features making both more compatible, thus increasing infection risk. “The size of the effect is surprisingly large,” said Maha Farhat, a professor at Harvard Medical School, indicating a substantial public health impact.
With the increasing use of genetic sequencing, researchers have noticed that not all TB strains are created equal. Some lineages are widespread, while others are limited to specific areas. The study found that whether a person has ancestors from where the strain is common was a bigger predictor of infection risk than bacterial load in the sputum.
Implications for Public Health
The findings highlight the importance of understanding the wide variation between different TB lineages and how they interact with different host populations. Previous studies have shown that some TB genetic groups are more prone to drug resistance and that TB vaccines work better in some places than others. There is also evidence that some treatment regimens might be more effective for specific strains of TB.
Experimental Insights
In addition to analyzing clinical, genomic, and public health data, researchers tested different TB strains’ ability to infect human immune cells called macrophages. They grew cells from donors from different regions and found that cell lines from people with ancestry matching the native habitat of a restricted TB strain were more susceptible to infection than those from outside the area.
Future Research and Collaboration
While the experiment was not designed to understand the mechanism behind this affinity, it underscores the importance of using multiple TB strains and cells from diverse populations to inform treatment and prevention. More basic research is needed to understand the genomic and structural differences in how bacterial and host cells interact.
“This study shows the importance of understanding the diversity of human and TB genetics and how they impact drug and vaccine responses,” said Farhat. “We are just beginning to appreciate this diversity’s significance.”
By collaborating with public health departments and research teams from the U.S., the Netherlands, and Germany, the researchers were able to assemble a large database integrating TB case reports, pathogen genetic profiles, and public health records. The study included 5,256 TB cases and 28,889 close contacts.
“This collaboration allowed us to answer a complicated question with important implications for public health and evolutionary biology,” said Matthias Groeschel, the study’s first author.
Conclusion
The study’s findings highlight the need to consider the diverse genetic interactions between humans and TB when developing prevention and treatment strategies. This research could lead to better-targeted treatments and vaccines, ultimately improving TB control worldwide.
