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Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area.

Guerra-Assunção JA, Crampin AC, Houben RM, Mzembe T, Mallard K, Coll F, Khan P, Banda L, Chiwaya A, Pereira RP, McNerney R, Fine PE, Parkhill J, Clark TG, Glynn JR - Elife (2015)

Bottom Line: 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).Transmissions resulting in disease decreased markedly over time.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.

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Relationship between number of SNPs and the number of days betweendates of disease onset for transmissions identified from the network, bylineage.(Random noise has been introduced to allow multiple similar results to bevisualized.) The slopes are given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.011
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fig4s2: Relationship between number of SNPs and the number of days betweendates of disease onset for transmissions identified from the network, bylineage.(Random noise has been introduced to allow multiple similar results to bevisualized.) The slopes are given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.011

Mentions: Figure 4D shows the number of SNPs in thelikely transmissions identified from the network, by lineage. Lineage-2 had thelowest number of SNPs per transmission, and lineage 1 the highest. The medianmutation rates per year for the different lineages were lineage-1, 0.58 (IQR0.11–1.9); lineage-2, 0.11 (0–0.66); lineage-3, 0.35 (0–1.1);lineage-4, 0.40 (0–1.2) (p = 0.004, equality-of-medians test). Theregression of number of SNPs by number of days showed no clear differences betweenlineages (Figure 4—figure supplement2).


Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area.

Guerra-Assunção JA, Crampin AC, Houben RM, Mzembe T, Mallard K, Coll F, Khan P, Banda L, Chiwaya A, Pereira RP, McNerney R, Fine PE, Parkhill J, Clark TG, Glynn JR - Elife (2015)

Relationship between number of SNPs and the number of days betweendates of disease onset for transmissions identified from the network, bylineage.(Random noise has been introduced to allow multiple similar results to bevisualized.) The slopes are given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.011
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384740&req=5

fig4s2: Relationship between number of SNPs and the number of days betweendates of disease onset for transmissions identified from the network, bylineage.(Random noise has been introduced to allow multiple similar results to bevisualized.) The slopes are given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.011
Mentions: Figure 4D shows the number of SNPs in thelikely transmissions identified from the network, by lineage. Lineage-2 had thelowest number of SNPs per transmission, and lineage 1 the highest. The medianmutation rates per year for the different lineages were lineage-1, 0.58 (IQR0.11–1.9); lineage-2, 0.11 (0–0.66); lineage-3, 0.35 (0–1.1);lineage-4, 0.40 (0–1.2) (p = 0.004, equality-of-medians test). Theregression of number of SNPs by number of days showed no clear differences betweenlineages (Figure 4—figure supplement2).

Bottom Line: 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).Transmissions resulting in disease decreased markedly over time.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus