title: Tuberculosis cases caused by heterogeneous infection in Eastern Europe and their influence on outcomes.
abstract: Mycobacterium tuberculosis superinfection is known to occur in areas with high rates of tuberculosis (TB) and has a significant impact on overall clinical TB management.
  
  
  
  We aimed to estimate the superinfection rate in cohorts of drug sensitive and multi-drug resistant tuberculosis (MDR TB) patients from Eastern Europe and the potential role of a second MDR TB strain infecting a patient with active non-MDR TB in treatment outcome.
  
  
  
  The study population included 512 serial M. tuberculosis isolates obtained from 84 MDR- and 136 non-MDR TB patients recruited sequentially at sites in Lithuania, Latvia and Russia in 2011-2013. Strains were genotyped using standardized 24-loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing.
  
  
  
  Changes in two or more MIRU-VNTR loci suggesting superinfection were detected in 13 patients (5.9%). We found 4 initially non-MDR TB patients superinfected with an MDR TB strain during treatment and 3 of them had an unsuccessful outcome.
  
  
  
  An unsuccessful treatment outcome in patients initially diagnosed with drug sensitive TB might be explained by superinfection with an MDR TB strain. Bacteriological reversion could be indicative of superinfection with another strain. Archiving of all serial isolates and their genotyping in case of culture reversion could support therapeutic strategies in high MDR TB burden settings if resources are available.
authors.affiliation: Imperial College London, Du Cane Road, London W12 0NN, UK; N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: iskontsevaya@gmail.com.
authors.forename: Irina
authors.initials: I
authors.lastname: Kontsevaya
authors.affiliation: Imperial College London, Du Cane Road, London W12 0NN, UK; Public Health England National Mycobacterium Reference Laboratory, 2 Newark Street, London E1 2AT, UK; Queen Mary, University of London, Mile End Road, London E1 4NS, UK. Electronic address: v.nikolayevskyy@imperial.ac.uk.
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikolayevskyy
authors.affiliation: N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: alexferreiro@ya.ru.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kovalyov
authors.affiliation: N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: ignatyevaolga@rambler.ru.
authors.forename: Olga
authors.initials: O
authors.lastname: Ignatyeva
authors.affiliation: N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: antima2008@rambler.ru.
authors.forename: Anna
authors.initials: A
authors.lastname: Sadykhova
authors.affiliation: N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: ti-uu@rambler.ru.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Simak
authors.affiliation: N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: tiolmi29@gmail.com.
authors.forename: Olesya
authors.initials: O
authors.lastname: Tikhonova
authors.affiliation: N.V. Postnikov Samara Region Clinical Tuberculosis Dispensary, 154 Novo-Sadovaya Street, Samara 443068, Russian Federation. Electronic address: julials86@mail.ru.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Dubrovskaya
authors.affiliation: Infectious Disease and TB Hospital, P. Sirvio str. 5, 10214 Vilnius, Lithuania; Vilnius University, Department of Physiology, Biochemistry and Laboratory Medicine, Faculty of Medicine, M. K. Ciurlionio str. 21, 03101 Vilnius, Lithuania. Electronic address: edita.pimkina@yahoo.com.
authors.forename: Edita
authors.initials: E
authors.lastname: Vasiliauskiene
authors.affiliation: Infectious Disease and TB Hospital, P. Sirvio str. 5, 10214 Vilnius, Lithuania. Electronic address: edita.david@takas.lt.
authors.forename: Edita
authors.initials: E
authors.lastname: Davidaviciene
authors.affiliation: Tuberculosis and Lung Diseases Centre, Riga East University Hospital, 68 Lielvardes Street, LV-1006 Riga, Latvia. Electronic address: girts.skenders@gmail.com.
authors.forename: Girts
authors.initials: G
authors.lastname: Skenders
authors.affiliation: Samara National Research University, 1 Akademika Pavlova Street, Samara 443011, Russian Federation. Electronic address: makurina.on@mail.ru.
authors.forename: Olga
authors.initials: O
authors.lastname: Makurina
authors.affiliation: Imperial College London, Du Cane Road, London W12 0NN, UK; Robert Koch Institute, Postfach 65 02 61, Berlin D-13302, Germany. Electronic address: yanina.lenz@imperial.ac.uk.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Balabanova
authors.affiliation: Imperial College London, Du Cane Road, London W12 0NN, UK; Queen Mary, University of London, Mile End Road, London E1 4NS, UK. Electronic address: f.drobniewski@imperial.ac.uk.
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
mesh_terms: D060085:Coinfection; D005798:Genes, Bacterial; D015658:HIV Infections / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D018598:Minisatellite Repeats; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000382:microbiology
keywords: Genotyping; Multi-drug resistant tuberculosis; Superinfection; Tuberculosis