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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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Related in: MedlinePlus

Relationship between number of SNPs and the number of days betweensamples from individuals with more than one specimen available from thesame of episode of disease or from a relapse.For each individual, we selected the first and last specimens if therewere more than two. (Random noise has been introduced to allow multiplesimilar results to be visualized.) The slope is given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.010
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fig4s1: Relationship between number of SNPs and the number of days betweensamples from individuals with more than one specimen available from thesame of episode of disease or from a relapse.For each individual, we selected the first and last specimens if therewere more than two. (Random noise has been introduced to allow multiplesimilar results to be visualized.) The slope is given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.010

Mentions: The within-patient mutation rate was calculated in 74 individuals with multiplespecimens, including 51 relapses, allowing ≤10 SNPs, and using the first andlast specimens if there were more than two. The estimated mutation rate was 0.45SNPs/year (95% CI 0.15–0.75), r2 = 11%, p = 0.004(Figure 4—figure supplement1).


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 betweensamples from individuals with more than one specimen available from thesame of episode of disease or from a relapse.For each individual, we selected the first and last specimens if therewere more than two. (Random noise has been introduced to allow multiplesimilar results to be visualized.) The slope is given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.010
© Copyright Policy
Related In: Results  -  Collection

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

fig4s1: Relationship between number of SNPs and the number of days betweensamples from individuals with more than one specimen available from thesame of episode of disease or from a relapse.For each individual, we selected the first and last specimens if therewere more than two. (Random noise has been introduced to allow multiplesimilar results to be visualized.) The slope is given in SNPs/year.DOI:http://dx.doi.org/10.7554/eLife.05166.010
Mentions: The within-patient mutation rate was calculated in 74 individuals with multiplespecimens, including 51 relapses, allowing ≤10 SNPs, and using the first andlast specimens if there were more than two. The estimated mutation rate was 0.45SNPs/year (95% CI 0.15–0.75), r2 = 11%, p = 0.004(Figure 4—figure supplement1).

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