What types of tuberculosis are most contagious and why the differences are important

The shared geographic origin between the tuberculosis (TB) strain and its human host may increase the risk of infection, a new study suggests.

For some formats shamethe chances of an exposed person becoming infected depends on whether the individual and the bacteria come from the same geographic area, according to a new study that compares how different strains moving through mixed populations in cosmopolitan cities.

The results of the research, led by scientists from Harvard Medical School (HMS) and published on August 1 in Nature microbiologyprovides the first hard evidence of long-term observations that have led scientists to suspect that the pathogen, the site, and the human host collide in a unique interaction that affects the risk of infection and which promote differences in the risk of infection.

The researchers said the study strengthens a long-held hypothesis in the field that some bacteria and their human hosts likely evolved at the same time. over hundreds or thousands of years.

The findings could also help develop new prevention and treatment methods for tuberculosis, a virulent pathogen that sickens more than 10 million people and causes more than a million deaths worldwide each year. according to the World Health Organization (WHO).

In the recent analysis, which is believed to be the first controlled comparison of tuberculosis infection in populations of diverse geographic origins, researchers created an existing study group by combining patient records. with tuberculosis in New York City, Amsterdam and Hamburg. So, they got enough data to feed their models.

According to the analysis, close family contacts of people diagnosed with TB from a geographically restricted lineage had a 14% lower rate of infection and a 45% lower rate of active TB disease, compared to those who was exposed to a strain belonging to a wide range of diseases. offspring

The study also showed that strains with a wide geographic range are far more likely to infect people with roots in the geographic region of origin of the bacteria than people outside the region.

The researchers found that the chance of infection decreased by 38% when a contact was exposed to a pathogen restricted from a geographical area unrelated to the person’s origin, compared to when a person was exposed to a microbe restricted to geographically from an area that was the same as the country of origin.

This was true for people who lived in that area and for people whose both parents could trace their descent (genetic inheritance) to that area.

This pathogen-host relationship reflects a shared evolution between humans and pathogens, with specific biological characteristics that make them more adaptable and promote the risk of infection, the researchers said.

“The magnitude of the effect is surprisingly large,” said Dr. Maha Farhat, professor of biomedical informatics at the Blavatnik Institute at HMS, in a statement.

“This is a good sign that the impact on public health is significant,” he said.

Why the differences are important

Due to the increasing use of genetic sequencing, researchers have noticed that not all types of circuits are created equal.

Some strains are widespread and are responsible for a large proportion of consumption worldwide, while others are distributed in only a few limited areas.

Because of the complexity of TB transmission in high-incidence settings, where people are often exposed to multiple types, researchers were unable to compare strains under similar conditions and were have to consider possible explanations for differences between series.

Many factors increase the risk of contracting tuberculosis through close contact.

One of the best predictors of whether a person will suffer from a close contact is the bacterial load, measured by a test called sputum smear microscopy, which shows the amount of bacteria carried in the t -their respiratory system.

But the new study showed that for geographically limited strains, whether or not a person had ancestors who lived where the common strain was an even greater predictor of infection risk than the bacterial load the sputum.

In the cases analyzed in the study, this common ancestral risk was even higher than the risk that comes from diabetes and other chronic diseases that have previously been shown to make people more susceptible to disease.

The findings add to a growing body of evidence about the importance of paying particular attention to the differentiation between different TB lineages and the details of how they interact with different host numbers.

Previous studies have shown that certain genetic groups of TB are more likely to develop drug resistance and that TB vaccines seem to work better in some areas than others.

There is also evidence that some treatment methods may be more suitable for certain types of TB than others.

“These findings underline the importance of understanding what makes different types of tuberculosis behave so differently from each other and why some types have such a strong relationship with specific groups of people,” said the first author of the study, Matthias Groeschel. researcher in biomedical informatics in the HMS laboratory and resident physician at Charité, a university hospital in Berlin.

As well as analyzing clinical, genomic and public health data, the researchers also tested the ability of different strains of TB to infect human macrophages, a type of immune cell that TB takes over to cause disease and illness.

The researchers made cells from donors in different regions. Again, cell lines from people with ancestry that matched the native habitat of a restricted species of tuberculosis bacteria were more susceptible to the germs than cells from people outside the area, mirroring the results of their epidemiological study.

Until now, most experiments on the interaction between human immune cells and TB have not compared how TB interacts with host cells from different populations or sites, the researchers said. research.

Although this experiment was not designed to capture information about the mechanism underlying the relationship between human and TB populations that share geographic environments, it highlights the importance of using multiple TB type and cells from different populations to inform treatment and prevention.

The findings also emphasize the need for more basic research to understand the genomic and structural differences in how bacteria and host cells interact.

“It’s so important to understand that the great diversity in human genetics and TB can have a big impact on how people and microbes react to each other and to things like drugs and vaccines,” Farhat said. “We need to incorporate this into the way we think about the disease. “

“We are at the beginning of understanding the importance of this diversity,” Groeschel said. “There is still so much to learn about how this could affect the effectiveness of drugs, vaccines and disease progression in different strains.”

Advances in gene sequencing reveal other unknowns

While the closely related but distinct genetic clusters of tuberculosis have been discovered through more traditional genotyping methods, the widespread use of whole-genome sequencing by public health departments around the world has allowed doctors and researchers to establish the profile of tuberculosis germs and to genetically trace outbreaks and drug resistance.

Realizing that highly localized outbreaks do not spread well to other regions led researchers to speculate that regionally limited strains were less infectious than widespread strains. Because the restricted strains persisted within their narrow boundaries, some researchers speculated that local populations of the bacteria might have interbred with their human hosts, producing different populations. human more susceptible to different types of TB.

The researchers thought that this could also mean that different types of TB would have different sensitivities to different treatments and vaccines.

For example, structural differences in the shape of bacteria could prevent some drugs from binding effectively to bacteria from different strains.

Until recently, it was almost impossible to test these hypotheses, given the differences in cultural and environmental conditions that could affect disease rates in different communities and in other parts of the world.

Furthermore, because the limited spots moved so rarely away from home it was difficult to collect enough data to measure differences between lines.

Multidisciplinary science solved the problem

To overcome these obstacles, the research team collaborated with public health departments and research teams in the United States, the Netherlands, and Germany to compile a large database including TB case reports, genetic profiles of the pathogens and public health records on infection rates among intimates. seers.

The analysis also included demographic details about the social networks of people with the disease to assess how the different genetic forms of tuberculosis spread to other populations.

In total, the study included 5,256 tuberculosis cases and 28,889 close contacts.

“This study is a great example of why it is so important for researchers to collaborate with many different types of partners,” said Groeschel.

“We were able to bring together public health data from three major cities and use the powerful computational biology tools we have in academic medicine to answer a complex question that has important implications for public health and evolutionary biology, vaccine development and research drugs”, pointed out the researcher.