Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients

Yanina Balabanova, Vladyslav Nikolayevskyy, Olga Ignatyeva, Irina Kontsevaya, Svetlana Mironova, Alexander Kovalyov, Andrey Kritsky, Yulia Rodionova, Ivan Fedorin, Nicola Casali, Richard Hooper, Rolf D Horstmann, Sergey Nejentsev, Sven Hoffner, Peter Nuernberg, Francis Drobniewski

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

We conducted a prospective study to establish factors associated with survival in tuberculosis patients in Russia including social, clinical and pathogen-related genetic parameters. Specifically we wished to determine whether different strains/clades of the Beijing lineage exerted a differential effect of survival. HIV-negative culture-confirmed cases were recruited during 2008-2010 across Samara Oblast and censored in December 2011. Molecular characterization was performed by a combination of spoligotyping, multilocus VNTR typing and whole genome sequencing (WGS). We analyzed 2602 strains and detected a high prevalence of Beijing family (n=1933; 74%) represented largely by two highly homogenous dominant clades A (n=794) and B (n=402) and non-A/non-B (n=737). Multivariable analysis of 1366 patients with full clinical and genotyping data showed that multi- and extensive drug resistance (HR=1.86; 95%CI: 1.52, 2.28 and HR=2.19; 95%CI: 1.55, 3.11) had the largest impact on survival. In addition older age, extensive lung damage, shortness of breath, treatment in the past and alcohol abuse reduced survival time. After adjustment for clinical and demographic predictors there was evidence that clades A and B combined were associated with poorer survival than other Beijing strains (HR=0.48; 95%CI 0.34, 0.67). All other pathogen-related factors (polymorphisms in genes plcA, plcB, plcC, lipR, dosT and pks15/1) had no effect on survival. In conclusion, drug resistance exerted the greatest effect on survival of TB patients. Nevertheless we provide evidence for the independent biological effect on survival of different Beijing family strains even within the same defined geographical population. Better understanding of the role of different strain factors in active disease and their influence on outcome is essential.

Original languageEnglish
Pages (from-to)517-523
Number of pages7
JournalInfection, Genetics and Evolution
Volume36
DOIs
Publication statusPublished - Dec 2015

Cite this

Balabanova, Y., Nikolayevskyy, V., Ignatyeva, O., Kontsevaya, I., Mironova, S., Kovalyov, A., ... Drobniewski, F. (2015). Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients. Infection, Genetics and Evolution, 36, 517-523. https://doi.org/10.1016/j.meegid.2015.08.028
Balabanova, Yanina ; Nikolayevskyy, Vladyslav ; Ignatyeva, Olga ; Kontsevaya, Irina ; Mironova, Svetlana ; Kovalyov, Alexander ; Kritsky, Andrey ; Rodionova, Yulia ; Fedorin, Ivan ; Casali, Nicola ; Hooper, Richard ; Horstmann, Rolf D ; Nejentsev, Sergey ; Hoffner, Sven ; Nuernberg, Peter ; Drobniewski, Francis. / Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients. In: Infection, Genetics and Evolution. 2015 ; Vol. 36. pp. 517-523.
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abstract = "We conducted a prospective study to establish factors associated with survival in tuberculosis patients in Russia including social, clinical and pathogen-related genetic parameters. Specifically we wished to determine whether different strains/clades of the Beijing lineage exerted a differential effect of survival. HIV-negative culture-confirmed cases were recruited during 2008-2010 across Samara Oblast and censored in December 2011. Molecular characterization was performed by a combination of spoligotyping, multilocus VNTR typing and whole genome sequencing (WGS). We analyzed 2602 strains and detected a high prevalence of Beijing family (n=1933; 74{\%}) represented largely by two highly homogenous dominant clades A (n=794) and B (n=402) and non-A/non-B (n=737). Multivariable analysis of 1366 patients with full clinical and genotyping data showed that multi- and extensive drug resistance (HR=1.86; 95{\%}CI: 1.52, 2.28 and HR=2.19; 95{\%}CI: 1.55, 3.11) had the largest impact on survival. In addition older age, extensive lung damage, shortness of breath, treatment in the past and alcohol abuse reduced survival time. After adjustment for clinical and demographic predictors there was evidence that clades A and B combined were associated with poorer survival than other Beijing strains (HR=0.48; 95{\%}CI 0.34, 0.67). All other pathogen-related factors (polymorphisms in genes plcA, plcB, plcC, lipR, dosT and pks15/1) had no effect on survival. In conclusion, drug resistance exerted the greatest effect on survival of TB patients. Nevertheless we provide evidence for the independent biological effect on survival of different Beijing family strains even within the same defined geographical population. Better understanding of the role of different strain factors in active disease and their influence on outcome is essential.",
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author = "Yanina Balabanova and Vladyslav Nikolayevskyy and Olga Ignatyeva and Irina Kontsevaya and Svetlana Mironova and Alexander Kovalyov and Andrey Kritsky and Yulia Rodionova and Ivan Fedorin and Nicola Casali and Richard Hooper and Horstmann, {Rolf D} and Sergey Nejentsev and Sven Hoffner and Peter Nuernberg and Francis Drobniewski",
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Balabanova, Y, Nikolayevskyy, V, Ignatyeva, O, Kontsevaya, I, Mironova, S, Kovalyov, A, Kritsky, A, Rodionova, Y, Fedorin, I, Casali, N, Hooper, R, Horstmann, RD, Nejentsev, S, Hoffner, S, Nuernberg, P & Drobniewski, F 2015, 'Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients' Infection, Genetics and Evolution, vol. 36, pp. 517-523. https://doi.org/10.1016/j.meegid.2015.08.028

Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients. / Balabanova, Yanina; Nikolayevskyy, Vladyslav; Ignatyeva, Olga; Kontsevaya, Irina; Mironova, Svetlana; Kovalyov, Alexander; Kritsky, Andrey; Rodionova, Yulia; Fedorin, Ivan; Casali, Nicola; Hooper, Richard; Horstmann, Rolf D; Nejentsev, Sergey; Hoffner, Sven; Nuernberg, Peter; Drobniewski, Francis.

In: Infection, Genetics and Evolution, Vol. 36, 12.2015, p. 517-523.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Beijing clades of Mycobacterium tuberculosis are associated with differential survival in HIV-negative Russian patients

AU - Balabanova, Yanina

AU - Nikolayevskyy, Vladyslav

AU - Ignatyeva, Olga

AU - Kontsevaya, Irina

AU - Mironova, Svetlana

AU - Kovalyov, Alexander

AU - Kritsky, Andrey

AU - Rodionova, Yulia

AU - Fedorin, Ivan

AU - Casali, Nicola

AU - Hooper, Richard

AU - Horstmann, Rolf D

AU - Nejentsev, Sergey

AU - Hoffner, Sven

AU - Nuernberg, Peter

AU - Drobniewski, Francis

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015/12

Y1 - 2015/12

N2 - We conducted a prospective study to establish factors associated with survival in tuberculosis patients in Russia including social, clinical and pathogen-related genetic parameters. Specifically we wished to determine whether different strains/clades of the Beijing lineage exerted a differential effect of survival. HIV-negative culture-confirmed cases were recruited during 2008-2010 across Samara Oblast and censored in December 2011. Molecular characterization was performed by a combination of spoligotyping, multilocus VNTR typing and whole genome sequencing (WGS). We analyzed 2602 strains and detected a high prevalence of Beijing family (n=1933; 74%) represented largely by two highly homogenous dominant clades A (n=794) and B (n=402) and non-A/non-B (n=737). Multivariable analysis of 1366 patients with full clinical and genotyping data showed that multi- and extensive drug resistance (HR=1.86; 95%CI: 1.52, 2.28 and HR=2.19; 95%CI: 1.55, 3.11) had the largest impact on survival. In addition older age, extensive lung damage, shortness of breath, treatment in the past and alcohol abuse reduced survival time. After adjustment for clinical and demographic predictors there was evidence that clades A and B combined were associated with poorer survival than other Beijing strains (HR=0.48; 95%CI 0.34, 0.67). All other pathogen-related factors (polymorphisms in genes plcA, plcB, plcC, lipR, dosT and pks15/1) had no effect on survival. In conclusion, drug resistance exerted the greatest effect on survival of TB patients. Nevertheless we provide evidence for the independent biological effect on survival of different Beijing family strains even within the same defined geographical population. Better understanding of the role of different strain factors in active disease and their influence on outcome is essential.

AB - We conducted a prospective study to establish factors associated with survival in tuberculosis patients in Russia including social, clinical and pathogen-related genetic parameters. Specifically we wished to determine whether different strains/clades of the Beijing lineage exerted a differential effect of survival. HIV-negative culture-confirmed cases were recruited during 2008-2010 across Samara Oblast and censored in December 2011. Molecular characterization was performed by a combination of spoligotyping, multilocus VNTR typing and whole genome sequencing (WGS). We analyzed 2602 strains and detected a high prevalence of Beijing family (n=1933; 74%) represented largely by two highly homogenous dominant clades A (n=794) and B (n=402) and non-A/non-B (n=737). Multivariable analysis of 1366 patients with full clinical and genotyping data showed that multi- and extensive drug resistance (HR=1.86; 95%CI: 1.52, 2.28 and HR=2.19; 95%CI: 1.55, 3.11) had the largest impact on survival. In addition older age, extensive lung damage, shortness of breath, treatment in the past and alcohol abuse reduced survival time. After adjustment for clinical and demographic predictors there was evidence that clades A and B combined were associated with poorer survival than other Beijing strains (HR=0.48; 95%CI 0.34, 0.67). All other pathogen-related factors (polymorphisms in genes plcA, plcB, plcC, lipR, dosT and pks15/1) had no effect on survival. In conclusion, drug resistance exerted the greatest effect on survival of TB patients. Nevertheless we provide evidence for the independent biological effect on survival of different Beijing family strains even within the same defined geographical population. Better understanding of the role of different strain factors in active disease and their influence on outcome is essential.

KW - Female

KW - Genetic Linkage

KW - Genome, Bacterial

KW - Genotype

KW - HIV Seronegativity

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Mycobacterium tuberculosis/classification

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Factors

KW - Russia/epidemiology

KW - Tuberculosis/epidemiology

U2 - 10.1016/j.meegid.2015.08.028

DO - 10.1016/j.meegid.2015.08.028

M3 - Article

VL - 36

SP - 517

EP - 523

JO - Infection, Genetics and Evolution

JF - Infection, Genetics and Evolution

SN - 1567-1348

ER -