Changes in MIRU-VNTR profiles are associated with treatment failures in tuberculosis patients

Background: Superinfection by M. tuberculosis more frequently occurs in high drug-resistant tuberculosis (TB) areas due to a large pool of chronic patients and poor infection control. The aim of the study was to estimate the superinfection rate in a multicentre TB patient cohort from a high drug-resistant TB burden regions and whether superinfection affects disease outcome. Methods: The study population included 513 serial M. tuberculosis isolates (2 to 8 per patient) obtained from 84 multi-drug resistant (MDR) and 136 non-MDRTB patients recruited sequentially at sites in Lithuania, Latvia and Russia; treatment outcomes were available for 173 of them. Strains were genotyped using standardised 24-loci MIRU-VNTR typing. Results: Changes in two or more VNTR loci suggesting superinfection were seen in strains isolated from 13 (8 non-MDRTB; 5 MDRTB) patients (5.9%). As a whole this group had higher treatment failure rates compared to other patients (5/13, 38.5% vs 26/160, 16.2%, RR=2.4, 95% CI=1.1-5.1). Non-MDRTB patients infected with a second TB strain had higher (although not significant) treatment failure rate (2/8, 25.0% vs 10/109, 9.2%, RR=2.7, 95% CI=0.7-10.4); MDRTB patients infected with a second strain showed similar rates of treatment failure as those not superinfected. Conclusion: A proportion of patients in high drug-resistant TB burden areas get superinfected with another TB strain during anti-TB treatment; the superinfection might be associated with higher failure rates in non-MDRTB patients.