According to a recent study evaluating how various strains migrate across mixed populations in cosmopolitan cities, the likelihood of an exposed person contracting TB varies depending on whether the individual and the bacterium share a common geographical origin.
Unique Interaction Between Pathogen, Place, and Host
The study, led by Harvard Medical School scientists, provides evidence that the interaction between pathogens, place, and human hosts uniquely affects infection risk and susceptibility. This research strengthens the long-standing hypothesis that specific bacteria and their human hosts likely coevolved over hundreds or thousands of years.
Potential Impact on TB Prevention and Treatment
The findings may also inform new prevention and treatment approaches for tuberculosis, a persistent pathogen that annually affects more than 10 million people and causes over a million deaths worldwide, according to the World Health Organization.
Methodology and Data Analysis
In this analysis, considered to be the first controlled comparison of TB strains’ infectivity in mixed geographic populations, researchers created a custom study cohort by combining case files from patients with TB in New York City, Amsterdam, and Hamburg. This provided sufficient data to power their models.
Key Findings: Strain Specificity and Infection Risk
The analysis revealed that close household contacts of individuals diagnosed with a TB strain from a geographically restricted lineage had a 14 percent lower rate of infection and a 45 percent lower rate of developing active TB disease compared to those exposed to a strain from a widespread lineage.
Geographic Affinity Influences Infection Rates
The study also indicated that strains with narrow geographic ranges are much more likely to infect people with origins in the bacteria’s native region than those from outside it. Specifically, the odds of infection dropped by 38 percent when a contact was exposed to a restricted pathogen from a region different from their background, compared to exposure to a strain from their own region. This was true for people who had lived in the region and for those whose parents traced their heritage to that region.
Implications for Public Health and Evolutionary Biology
This pathogen-host affinity suggests a shared evolutionary history between humans and microbes, making both more compatible and increasing infection risk. “The size of the effect is surprisingly large,” said Maha Farhat, Gilbert S. Omenn, MD ’65, PhD Associate Professor of Biomedical Informatics in the Blavatnik Institute at HMS. “That’s a good indicator that the impact on public health is substantial.”
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Diverse Strains and Their Impact
With advances in genetic sequencing, researchers have found that not all circulating TB strains are equal. Some lineages are widespread and contribute significantly to global TB rates, while others are restricted to specific areas. The complexity of TB transmission, particularly in high-incidence settings with multiple strain exposures, has previously hindered direct comparisons of strains under similar conditions.
Risk Factors Beyond Bacterial Load
Many factors influence the risk of contracting tuberculosis from close contact. One key predictor is bacterial load, measured by sputum smear microscopy, which assesses the number of bacteria in a person’s respiratory system. However, the new study found that for geographically restricted strains, having ancestry from the strain’s native region was a more significant predictor of infection risk than bacterial load. This risk of common ancestry even outweighed the risk associated with chronic diseases like diabetes.
Importance of Strain-Specific Research
The findings highlight the need to consider the wide variation between TB strains and their interactions with different host populations. Previous research has shown that some TB genetic groups are more prone to drug resistance and that vaccines may be more effective in certain regions. There is also evidence suggesting that some treatment regimens might be better suited to specific strains of TB.
Future Directions for Research
“These findings emphasize how important it is to understand what makes different strains of TB behave so differently from one another, and why some strains have such a close affinity for specific, related groups of people,” said Matthias Groeschel, research fellow in biomedical informatics in Farhat’s lab at HMS and the study’s first author.
Experimental Insights and Further Research
In addition to analyzing clinical, genomic, and public health data, the researchers tested different TB strains’ ability to infect human macrophages, immune cells that TB exploits to cause infection. They found that cell lines from people with ancestry matching the bacteria’s native region were more susceptible to infection, reflecting the epidemiological study results.
Conclusion: Incorporating Diversity into TB Research
The experiment underscores the importance of using multiple TB strains and diverse host cells to inform treatment and prevention. It also points to the need for further research into the genomic and structural differences in bacterial and host cell interactions.
“It’s crucial to appreciate that the great diversity of human and tuberculosis genetics can significantly impact responses to drugs and vaccines,” Farhat said. “We need to incorporate this understanding into our approach to the disease.”
“We’re at the very beginning of appreciating the importance of that diversity,” Groeschel added. “There’s much more to learn about its impact on drug efficacy, vaccine effectiveness, and disease progression in different strains.”
Collaboration and Data Integration
The use of whole genome sequencing has enhanced the profiling of TB germs, tracking outbreaks, and drug resistance. Researchers speculated that highly localized strains were less infectious and might have coevolved with their human hosts, making certain populations more susceptible to specific TB strains. This could imply that different strains might respond differently to treatments and vaccines due to structural differences.
To overcome the challenges of studying such localized strains, the research team collaborated with public health departments and research teams from the U.S., the Netherlands, and Germany. They assembled a comprehensive database integrating TB case reports, pathogen genetic profiles, and public health records, including demographic details about infected individuals’ social networks. This study included 5,256 TB cases and 28,889 close contacts.
“This study exemplifies the importance of collaborating with diverse partners,” Groeschel said. “We merged data from three major cities and utilized advanced computational biology tools to address a complex question with significant implications for public health, evolutionary biology, vaccine development, and drug research.”
(Except for the headline, this story has not been edited by Newsx staff and is published from a syndicated feed.)
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