Reckoned without the host: The transmission of tuberculosis depends on more than just the pathogen
Different groups of TB bacteria exist worldwide with different regional distribution: some are generalists and can be found on many continents, while others are very limited in their spread. An international research team has now been able to show for the first time that the specialist strains spread more effectively among suitable hosts from the same geographical area, whereas the generalist strains can spread in different host populations in various geographical areas. The transmissibility of tuberculosis therefore depends not only on the pathogen or the host, but also on their combination.
With over 1.4 million deaths per year, tuberculosis is still one of the most dangerous infectious diseases worldwide. There are a total of ten different genetic lines of the tuberculosis pathogen in the world, which are grouped together in the so-called Mycobacterium tuberculosis complex (Mtbc) due to their close genetic relationship. In Europe and North America, Mtbc strains of the L4 lineage are found most frequently, while strains of the L2 lineage are predominant in Asia. Africa is the only place where strains of lineages 5 and 6 are regularly found. While strains of lineages L2 and L4 are widespread and common, strains of some lineages of the African region have rarely been isolated outside the continent and have a limited geographical distribution.
It is therefore assumed that geographically restricted lineages of the Mtbc spread more effectively among sympatric (‘fitting’) hosts—i.e. those that occur in the same geographical area—and show less transmissibility to allopatric (“non-fitting”) hosts—i.e. people from other geographical regions. So far, however, this assumption could not be proven, as there were no large data sets with clinical tuberculosis data and genome sequence data of the pathogen strains.
An international team of scientists from the Research Center Borstel, Leibniz Lung Center, the German Center for Infection Research, the Charité in Berlin and Harvard Medical School in Boston has now succeeded in proving this hypothesis for the first time: using pathogen genome and contact tracing data from 2,279 tuberculosis cases linked to 12,749 social contacts from three cities with low incidence (low number of new cases of tuberculosis), the researchers were able to show that bacterial strains of geographically restricted Mtbc lineages are less transmissible than strains from lineages that have a wide global distribution. The data comes from Hamburg, New York and Amsterdam and was compiled in cooperation with the respective health authorities. The team was able to show that with allopatric pathogen-host exposure, where the pathogen and host originate from different and non-overlapping areas, the probability of infection in contact persons was 38% lower than with sympatric exposure in the same geographical area.
These epidemiological observations were supported by laboratory experiments. Using a macrophage infection model, it was shown that allopatric macrophages showed a lower uptake and growth of Mtbc strains after the first exposure. These findings support the results of the epidemiological analysis and will be expanded to include further host-strain combinations in future projects.
The researchers conclude that the long-term coexistence of Mtbc strains and humans has led to a different transmissibility of Mtbc strains to human populations depending on where both occur geographically. “These differences in transmissibility mean that strains of geographically restricted Mtbc lineages have a barrier to their ability to spread to other geographical regions,” says Dr Matthias Gröschel, first author of the study and physician at Charité’s Speciality Network Infectious Diseases and Respiratory Medicine. “In subsequent work, we now aim to understand the molecular basis of allopatric and sympatric host-pathogen interactions.”
This information may be helpful in the future to personalise environmental investigations and, for example, to track high-risk contacts such as sympatric host-pathogen contacts with higher priority. These specific virulence mechanisms could also be important in the development of drugs.
“For the first time, the work allows a more precise understanding of the host-pathogen interaction in tuberculosis on a global level,” says Prof. Stefan Niemann, head of the study at the Research Center Borstel, Leibniz Lung Center and deputy coordinator of the research area Tuberculosis in the German Center for Infection Research (DZIF). “We are working hard to elucidate the pathobiological mechanisms”.
Source: Press release of the Research Center Borstel, Leibniz Lung Center
