Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area.
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.
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
J A
JA
Guerra-Assunção
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
A C
AC
Crampin
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
R M G J
RM
Houben
Karonga Prevention Study, Malawi, Malawi.
T
T
Mzembe
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
K
K
Mallard
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
F
F
Coll
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
P
P
Khan
Karonga Prevention Study, Malawi, Malawi.
L
L
Banda
Karonga Prevention Study, Malawi, Malawi.
A
A
Chiwaya
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
R P A
RP
Pereira
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
R
R
McNerney
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
P E M
PE
Fine
Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
J
J
Parkhill
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
T G
TG
Clark
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
J R
JR
Glynn
D016680:Genome, Bacterial; D006801:Humans; D008295:Malawi / Q000453:epidemiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D014376:Tuberculosis / Q000453:epidemiology / Q000635:transmission*
Malawi; Tuberculosis; epidemiology; global health; transmission