Multidrug-resistant tuberculosis in Central Asia

Emerging Infectious Diseases, May, 2004 by Helen Suzanne Cox, Juan Daniel Orozco, Roy Male, Sabine Ruesch-Gerdes, Dennis Falzon, Ian Small, Darebay Doshetov, Yared Kebede, Mohammed Aziz

These declines in healthcare spending in both countries have resulted in intermittent shortages of most first-line anti-TB drugs. Local TB physicians in Karakalpakstan (Uzbekistan) estimate that before the DOTS program started, nearly 50% of patients had their treatment interrupted because of problems with drug supply. Additionally, because of the lack of drugs, patients were often requested to purchase drugs themselves after they left the hospital for the continuation phase at home. Many patients likely could not afford all drugs and therefore purchased what they could, resulting again in treatment interruptions. High streptomycin resistance attests to the widespread use of this popular injectable antimicrobial agent, often as a short monotherapy course. Although drug shortages have been reported over the last decade in Turkmenistan, they likely affected an overall lower percentage of patients, which explains the lower rate of drug resistance seen in Dashoguz.

The extent to which drug resistance existed before the collapse of the Soviet Union is unknown. The Soviet system hospitalized TB patients for long periods, with consequently high levels of interruption and default. In addition, treatment regimens using combinations of all first-line and some second-line drugs were not standardized (1). These conditions may have contributed to a baseline level of resistance from which the notable level of MDR-TB shown here has emerged. Most retreatment patients were not previously treated under DOTS; thus, our results cannot be attributed to the implementation of DOTS.

Elsewhere in the former Soviet Union, high rates of MDR-TB have been seen among prisoner populations (15). Although a high proportion of patients in our study reported previous imprisonment, no greater level of MDR-TB was seen among these patients. This finding suggests that MDR-TB is not confined to specific sectors of the population, such as prisoners, but is a problem affecting the general community. Of particular concern in this area is the high rate of out-migration attributable to worsening environmental and socioeconomic conditions (16; unpub. data, Medecins Sans Frontieres, 2002), which can lead to international transmission of MDR-TB.

The finding of a greater risk for MDR-TB among women, independent of previous TB treatment status, is important and confirms similar findings in Archangels Oblast in Russia (17) and Estonia (18). In the Aral Sea area, women make up slightly less than 50% of all patients with positive smears registered in the DOTS program. This statistic suggests a greater susceptibility to drug-resistant TB and warrants further research.

Clearly, such high rates of MDR-TB as seen in both Karakalpakstan, Uzbekistan, and Dashoguz, Turkmenistan, are a substantial threat to TB control. Standardized treatment with first-line, through drugs implementing the DOTS strategy, would be expected to result in poor outcomes for more than one fourth of patients with positive smears in Karakalpakstan (19) and would render the WHO target of 85% success unattainable. These patients will remain infectious for long periods, with the resultant risk of transmitting drug-resistant strains. WHO suggests that high levels of MDR-TB (>3% among new cases) warrant the direct management of MDR-TB to contain transmission and reduce the high incidence and costs of this disease (20).

DOTS treatment on its own may well stop the production of more MDR-TB, but it is unlikely to reduce high levels of existing drug resistance (21). Effective treatment of all cases of TB is required to prevent transmission. MDR-TB treatment is expensive and lengthy, and the pool of those with expertise treating MDR-TB is limited. A simpler, more affordable, and more effective treatment strategy is required; however, until this exists, patients require treatment with existing strategies. As a result of this survey, Medecins Sans Frontieres has decided to launch a pilot DOTS-Plus MDR-TB treatment project in Karakalpakstan because the cost of inaction will be high.