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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

Pairwise mutation rates between all pairs of samples with known RFLP(calculated as number of SNPs/number of days between dates of diseaseonset between individuals).The y axis shows the relative frequency within each subgroup: same RFLPpattern (red), different RFLP patterns (blue); same individual, same RFLP(green). (A) shows the full data set, and (B)is part of the same figure drawn at a larger scale (each bar correspondsto 0.001 SNP/day) to show the smaller distances more clearly.DOI:http://dx.doi.org/10.7554/eLife.05166.006
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fig2s1: Pairwise mutation rates between all pairs of samples with known RFLP(calculated as number of SNPs/number of days between dates of diseaseonset between individuals).The y axis shows the relative frequency within each subgroup: same RFLPpattern (red), different RFLP patterns (blue); same individual, same RFLP(green). (A) shows the full data set, and (B)is part of the same figure drawn at a larger scale (each bar correspondsto 0.001 SNP/day) to show the smaller distances more clearly.DOI:http://dx.doi.org/10.7554/eLife.05166.006

Mentions: Figure 2 shows the SNP distances between allpossible pairs of samples in the data set (including more than one per individual insome cases). Peaks corresponding to large numbers of SNPs represent comparisonsbetween lineages. On the basis of the distribution, we chose cut-offs at 5 and 10SNPs for distinguishing links. Similar figures were drawn for the mutation rate(Figure 2—figure supplement 1). Wehave previously shown that patients with relapse had up to 8 SNPs difference (Guerra-Assuncao et al., 2014), and thesecut-offs are similar to those used in other studies (Bryant et al., 2013; Walker et al.,2013).10.7554/eLife.05166.005Figure 2.Pairwise SNP distances between all pairs of samples with knownRFLP.


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)

Pairwise mutation rates between all pairs of samples with known RFLP(calculated as number of SNPs/number of days between dates of diseaseonset between individuals).The y axis shows the relative frequency within each subgroup: same RFLPpattern (red), different RFLP patterns (blue); same individual, same RFLP(green). (A) shows the full data set, and (B)is part of the same figure drawn at a larger scale (each bar correspondsto 0.001 SNP/day) to show the smaller distances more clearly.DOI:http://dx.doi.org/10.7554/eLife.05166.006
© Copyright Policy
Related In: Results  -  Collection

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

fig2s1: Pairwise mutation rates between all pairs of samples with known RFLP(calculated as number of SNPs/number of days between dates of diseaseonset between individuals).The y axis shows the relative frequency within each subgroup: same RFLPpattern (red), different RFLP patterns (blue); same individual, same RFLP(green). (A) shows the full data set, and (B)is part of the same figure drawn at a larger scale (each bar correspondsto 0.001 SNP/day) to show the smaller distances more clearly.DOI:http://dx.doi.org/10.7554/eLife.05166.006
Mentions: Figure 2 shows the SNP distances between allpossible pairs of samples in the data set (including more than one per individual insome cases). Peaks corresponding to large numbers of SNPs represent comparisonsbetween lineages. On the basis of the distribution, we chose cut-offs at 5 and 10SNPs for distinguishing links. Similar figures were drawn for the mutation rate(Figure 2—figure supplement 1). Wehave previously shown that patients with relapse had up to 8 SNPs difference (Guerra-Assuncao et al., 2014), and thesecut-offs are similar to those used in other studies (Bryant et al., 2013; Walker et al.,2013).10.7554/eLife.05166.005Figure 2.Pairwise SNP distances between all pairs of samples with knownRFLP.

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