Understanding TB Transmission with Whole Genome Sequencing

K. Bjorn-Mortensen, B. Soborg, A. Koch, K. Ladefoged, M. Merker et al. Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland. Scientific Reports 6, Article number: 33180 (2016) doi:10.1038/srep33180

Genotyping of TB, which has been available since 2004, first gave us a peek into better understanding of TB transmission as well as relapse vs reinfection. If the TB bacteria obtained from two patients have the same genotype, one may have reason to believe that the bacteria that caused disease in each are related (they may have gotten it from each other or a common person, or something to that effect). Similarly, if a patient had TB, got cured then had TB again, if the bacteria from the two instances match in genotype, one may be led to believe that it was the same disease that relapsed. Whereas, if the bacteria from the two instances do not match, the second episode may be due to reinfection rather than relapse. Genotyping targets genetic material that are mostly stable over time. However, it only represents <1% of the TB genome.

2012 brought forth whole genome sequencing (WGS) of TB. Now we are talking about approximately 90% or more of the TB genome. With this, even just one nucleotide change can be noted. This is called a single nucleotide polymorphism (SNP). TB genome changes very slowly such that it accumulates only 0.5SNP/year. Therefore, when the TB bacteria obtained from different patients have only few SNPs differences, that means these bacteria are closely related and signal recent transmission. Here in Austin, we have several cases that share identical WGS, meaning no SNP were identified. With common epidemiological links as well, this is highly suggestive of recent relationship between these cases. Science has afforded us this knowledge. Hopefully we can act on it.

Image above is from: K. Bjorn-Mortensen, B. Soborg, A. Koch, K. Ladefoged, M. Merker et al. Tracing Mycobacterium tuberculosis transmission by whole genome sequencing in a high incidence setting: a retrospective population-based study in East Greenland. Scientific Reports 6, Article number: 33180 (2016) doi:10.1038/srep33180.