Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area
JA Guerra-Assunção,
AC Crampin,
RMGJ Houben,
T Mzembe,
K Mallard,
F Coll,
P Khan,
L Banda,
A Chiwaya,
RPA Pereira,
R McNerney,
PEM Fine,
J Parkhill,
TG Clark,
JR Glynn
Affiliations
JA Guerra-Assunção
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
AC Crampin
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; Karonga Prevention Study, Malawi, Malawi
RMGJ Houben
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
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.
