1. Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area
- Author
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Francesc Coll, Themba Mzembe, José Afonso Guerra-Assunção, Louis Banda, Julian Parkhill, Rui P. A. Pereira, Paul E. M. Fine, Palwasha Khan, Judith R. Glynn, Taane G. Clark, Kim Mallard, A. Chiwaya, Rein M G J Houben, Amelia C. Crampin, and Ruth McNerney
- Subjects
Malawi ,Mutation rate ,medicine.medical_specialty ,Tuberculosis ,QH301-705.5 ,Science ,Single-nucleotide polymorphism ,Disease ,Drug resistance ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Mycobacterium tuberculosis ,03 medical and health sciences ,Epidemiology ,Prevalence ,medicine ,Humans ,Biology (General) ,Pathogen ,Phylogeny ,030304 developmental biology ,Genetics ,0303 health sciences ,General Immunology and Microbiology ,biology ,030306 microbiology ,General Neuroscience ,transmission ,General Medicine ,biology.organism_classification ,medicine.disease ,Virology ,3. Good health ,Epidemiology and Global Health ,Mutation ,Medicine ,Other ,Genome, Bacterial ,Research Article - Abstract
To improve understanding of the factors influencing tuberculosis transmission and the role of pathogen variation, we sequenced all available specimens from patients diagnosed over 15 years in a whole district in Malawi. Mycobacterium tuberculosis lineages were assigned and transmission networks constructed, allowing ≤10 single nucleotide polymorphisms (SNPs) difference. We defined disease as due to recent infection if the network-determined source was within 5 years, and assessed transmissibility from forward transmissions resulting in disease. High-quality sequences were available for 1687 disease episodes (72% of all culture-positive episodes): 66% of patients linked to at least one other patient. The between-patient mutation rate was 0.26 SNPs/year (95% CI 0.21–0.31). We showed striking differences by lineage in the proportion of disease due to recent transmission and in transmissibility (highest for lineage-2 and lowest for lineage-1) that were not confounded by immigration, HIV status or drug resistance. Transmissions resulting in disease decreased markedly over time. DOI: http://dx.doi.org/10.7554/eLife.05166.001, eLife digest Tuberculosis is an important public health threat around the globe and is particularly common in developing countries. It is difficult to control the spread of the disease because the bacteria that cause it can spread when an infected individual coughs or sneezes. It may take years for an infected individual to develop symptoms of tuberculosis so it can be hard to trace the source of an outbreak, and people infected with HIV are particularly susceptible to the disease. The bacterium that causes the majority of cases of tuberculosis is called Mycobacterium tuberculosis. There are several different varieties or ‘lineages’ of M. tuberculosis, and it is thought that they may vary in their ability to spread and cause disease. However, the results of previous studies have been inconsistent and there also seems to be a lot of variation between strains within the same lineage. In this study, Guerra-Assunção et al. used an approach called whole genome sequencing alongside more traditional methods to study the spread of tuberculosis in Malawi. They sequenced the genomes of every available sample of M. tuberculosis collected from patients in the Karonga district of Malawi over a 15-year period. This produced high-quality DNA sequence data about the bacteria responsible for almost 1700 cases of disease. Using this massive amount of data, Guerra-Assunção et al. constructed networks that showed how the bacteria had spread in the community. This revealed that there were differences between the ability of the various M. tuberculosis lineages to cause disease and to spread in communities. For example, lineage 1 was less likely than the other lineages to cause disease soon after infecting an individual and was less able to spread. The data also show that the proportion of cases of disease due to recent infection declined substantially during the 15-year period. This indicates that the tuberculosis and HIV control programmes in the area have been successful. Guerra-Assunção et al.'s findings show that it is possible to understand how tuberculosis is transmitted on a large scale. The next challenge is to understand why the lineages differ in their ability to cause disease and spread between individuals. DOI: http://dx.doi.org/10.7554/eLife.05166.002
- Published
- 2015