Rifampin- and Multidrug-Resistant Tuberculosis in Russian Civilians and Prison Inmates: Dominance of the Beijing Strain Family

Francis Drobniewski, Yanina Balabanova, Michael Ruddy, Laura Weldon, Katya Jeltkova, Timothy Brown, Nadezdna Malomanova, Elvira Elizarova, Alexander Melentyey, Ebgeny Mutovkin, Svetlana Zhakharova, Ivan Fedorin


Emerging Infectious Diseases. 2002;8(11) 

In This Article

Abstract and Introduction

Consecutive patient cultures (140) of Mycobacteriium tuberculosis were collected from five Russian civilian and prison tuberculosis laboratories and analyzed for rifampin (rpoB) and isoniazid resistance (inhA, katG, ahpC); transmission of Beijing family isolates; and the importance of prison and previous therapy in drug resistance. Rifampin, isoniazid, and multidrug resistance occurred in 58.2%, 51.6%, and 44.7% of cultures, respectively; 80% of prison cultures were rifampin resistant. Spoligotyping and variable number tandem repeat (VNTR) fingerprinting divided the isolates into 43 groups. Spoligotyping demonstrated that a high proportion (68.1%) of patients were infected with Beijing family strains and that most (69.1%) were rifampin resistant; the highest proportion (81.6%) occurred in prison. One VNTR subgroup (42435) comprised 68 (72.3%) of the Beijing isolates with a small number of IS6110 types; 50 (73.5%) were rifampin resistant. Rifampin-resistant Beijing isolates are dominant within the patient population, especially among prisoners, and threaten treatment programs.

The true extent of drug-resistant tuberculosis (TB) globally is unknown. Few national surveys are representative and validated by external laboratories[1,2]. Accurate drug-susceptibility testing is difficult to do well. The quality of results can be further compromised if bacterial cultures originate from a selected population from which key groups, such as prisoners, have been omitted. Only limited susceptibility-testing data are available in those countries with the highest rates of TB such as India, Pakistan, Indonesia, China, and[3,4,5,6] Russia.

The spread of resistant isolates, especially multidrug-resistant strains that are resistant to at least isoniazid and rifampin, compromises both clinical efficacy and public health control measures. Patients with infectious multidrug-resistant cases continue to expectorate smear-positive sputum longer than patients with drug-sensitive cases, increasing the probability of spread of infection. The transmission of highly drug-resistant strains has been documented within health-care institutions and prisons, and the spread of one highly resistant strain, W, has been documented from New York City to other U.S. states and Puerto Rico[7].

In Russia, TB incidence rates declined from the 1950s to the 1990s; the lowest incidence and mortality rates were recorded in 1991 (34.0/100 000 and 8.1/100 000, respectively). By 1999, these rates had risen to 85.2/100 000 and 20.0/100 000, respectively[8,9,10]. The average age of TB patients has declined, reflecting high levels of recent transmission. Data on drug resistance for the whole of the Russian Federation are scarce; information comparable with international data have been reported by the World Health Organization from only 2 of the 89 oblasts (regions). In Ivanavo and Tomsk Oblasts, the prevalence of multidrug-resistant TB was 9.0% and 6.5%, respectively, in 1998-1999[1,2].

We initiated a pilot study in Samara, Russia, 1 of 89 oblasts to determine the following: the value of genotypic methods for identifying rifampin resistance and multidrug-resistant TB; the extent of rifampin and multiple-drug resistance within the civilian and prison systems; the extent to which this drug resistance was associated with dominant strains, such as those of the Beijing family, by using molecular DNA fingerprinting techniques; and whether drug resistance was associated with being a prisoner or with previous TB treatment.

DNA fingerprinting that uses techniques such as restriction fragment length polymorphism (RFLP) based on IS6110 is the international standard for documenting transmission at the molecular level[11,12,13,14]. Rapid techniques that use polymerase chain reaction (PCR) amplification such as spacer-oligonucleotide typing (spoligotyping)[13,14,15] are usually less discriminating but may provide greater information on evolutionary origins and can be used when cultures are contaminated or nonviable.

Spoligotyping is particularly valuable in defining strains belonging to the Beijing family as well as subspeciating strains of the Mycobacteriium tuberculosis complex and does not require viable organisms. The Beijing family of isolates was first reported at a high rate in the Beijing area in 1995[16] and less frequently in other parts of Asia such as Vietnam[17]. These isolates may be associated with a higher occurrence of drug resistance; for instance, the highly drug-resistant W strain, first identified in New York, is a member of the Beijing family[7,18]. They These isolates have previously been frequently seen in convenience samples taken in the Russian Federation[18,19]. In our study, isolates were collected from both the prison and civilian sectors at the same time in one region of the Russian Federation. These isolates were analyzed with molecular epidemiologic techniques (spoligotyping, variable number tandem repeat [VNTR], rapid epidemiological typing [RAPET], IS6110) to characterize the role of Beijing isolates and molecular genotypic methods to determine rifampin, isoniazid, and multidrug resistance.