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
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 - https://doi.org/10.1016/j.meegid.2015.08.028
DO - https://doi.org/10.1016/j.meegid.2015.08.028
M3 - Article
C2 - 26319998
SN - 1567-1348
VL - 36
SP - 517
EP - 523
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
ER -