It is expected that 62 percent of all new multidrug-resistant tuberculosis (MDR-TB) cases will be concentrated in Russia, China, and India, warned Dr. Salmaan Keshavjee, instructor at the Brigham and Woman's Hospital and Harvard Medical School. Speaking at a July 24, 2007 discussion co-sponsored by the Global Health Initiative and the Kennan Institute, Dr. Keshavjee said that although people have known for a number of years that mycobacterium tuberculosis (TB) is prone to resistance when treated ineffectively, overall, the number of antibiotic-resistant strains of TB continues to rise. Some experts worry that a ‘perfect storm' of HIV, very high TB rates, and a programmatic infrastructure that lacks the ability to adequately address complex health interventions is brewing in the former Soviet republics, he continued. Murray Feshbach, senior scholar at the Woodrow Wilson Center, highlighted the lethargy in addressing TB in Russia by mentioning that, until quite recently, political will and funding were not available in substantial levels to address the health crisis facing the Russian population. Based on his research and first-hand experience, Russian officials have been extremely slow to address TB at the national level, and are just now beginning to acknowledge the existence of extensively drug-resistant tuberculosis (XDR-TB) within the Russian population.
The substantial success in controlling TB during the Soviet years has been lost, and TB deaths have skyrocketed in Russia over the past 18 years, particularly among working-age men. Much of this increase is due to overcrowding in urban centers, and in prison populations especially, explained Dr. Keshavjee. Globally, TB strains—including MDR- and XDR-TB strains—kill approximately 1.8 million people per year, he said, disproportionally affecting the poor and immunocompromised.
Worldwide each year there are approximately 400,000 cases of MDR-TB tuberculosis, strains that are resistant to the first-line and most effective TB drugs, and often select second-line drugs. Due to the relative weakness of second- and third-line drugs, effective treatment of MDR-TB often requires an 18-24 month course of rigorously managed, directly observed therapy. XDR-TB strains are only susceptible to questionably effective third-line drugs. Because of this, XDR-TB requires a longer course of drugs and often times surgery if treatment is effective at all. Russia has a 14 percent prevalence of XDR-TB among TB positive patients, one of the highest rates in the world. Particularly frightening, said Dr. Keshavjee, is the increase in person-to-person spread of drug-resistant TB: "At least 10 percent of new cases of TB in the [former Soviet Union] are MDR [strains] and 50 percent of re-treated cases are MDR."
Tomsk Oblast: A Case Study of Drug-Resistant TB in Russia
In 1998 Dr. Keshavjee and his collaborators from Harvard Medical School, Brigham and Women's Hospital, and Partners in Health, were invited to Tomsk oblast in Western Siberia to investigate why current TB treatment protocols were not effective in curing TB in the prison populations. Tomsk oblast is an area the size of Poland with a population of 1,073,600 and a particularly high prevalence of MDR-TB. Of all the smear-positive and re-treatment cases, 40.6 percent were MDR-TB strains, and 5.1 percent were XDR-TB strains. The situation in Tomsk oblast, explained Dr. Keshavjee, represents the structural breakdown in the social and medical systems in Russia that have played a part in the development and high prevalence of MDR-TB and XDR-TB. Dr. Keshavjee continued by stating that unreliable drug supplies, unsupervised therapy, poor management, and a lack of political will have plagued treatment programs in Tomsk and throughout Russia. TB transmission rates have been increasing due to excessive incarceration, rising HIV rates, and the increasing prevalence of drug resistance resulting in a much lower cure rate.
Dr. Keshavjee and his team initiated a program which began in the prisons and moved to the civilian sector in Tomsk. The initial Tomsk cohort of TB cases, including both prisoners and civilians, showed 100 percent resistance to first-line drugs and high resistance to several second-line drugs. Dr. Keshavjee found that the low cure rates they were investigating in Tomsk were due to the high rate of drug-resistant TB and ineffective treatment strategies, which utilized first-line drugs without the internationally recommended TB control strategy, DOTS. Dr. Keshavjee reported, that with an increase in the variety and reliability of drug supplies, and through the implementation of DOTS, his team was able to achieve a 77 percent cure rate in the prison and civilian populations among MDR-TB patients, and a 55 percent cure rate among XDR-TB patients. "This was actually very good," explained Dr. Keshavjee, noting that expected cure rates for MDR-TB are 60-70 percent.
However, the second cohort showed a dip in the effectiveness of treatment in the civilian sector, with a drop in the cure rate from 77 percent to 65 percent. Cure rates among prison populations remained the same. This drop was partly attributed to the structural and social challenges faced by the program implementers, explained Dr. Keshavjee, which were amplified in the civilian sector compared to the prisons. The cohorts faced problems with drug and alcohol abuse (60 percent of enrollees were considered alcoholics), poverty, adverse events, the long duration of TB treatment, debilitating side effects, and difficult terrain for patients and staff to cover to and from the treatment sites. These factors combined to decrease adherence to treatment directives, and to increase the risk of transmission of drug-resistant strains of TB.
The Threat of Non-Adherence and How to Overcome It
In order to address the specific issues of non-adherence in the second cohort, Dr. Keshavjee and his Tomsk colleagues developed an accompaniment program called the "Sputnik Initiative" to work specifically with non-adherent patients. This program used a more patient-oriented approach, supervising daily treatments, and providing administrative and social support services to assist patients with other life issues, which may have been affecting their adherence to the treatment regimen. Additionally, the program incorporated ambulatory care, which sent health workers and staff to the patient to administer treatment if the patient was unable or unwilling to come to the treatment site. Dr. Keshavjee found the program to be effective, observing an increase in adherence from 42 percent to 83 percent. While Dr. Keshavjee admits that on the surface this program appears to be labor-intensive and unsustainable, he emphasized that "the cost of 1 patient failing treatment is between $6,000 and $10,000, and you can hire a nurse for that price who will care for 6-7 patients who would have probably failed or defaulted and potentially have spread [TB] to others."
A Vicious Cycle
Murray Feshbach addressed the demographic, social, and governmental issues affecting health and TB treatment in the Russian population. Despite recent pro-natalist policies, population rates and life expectancies have been declining steadily since the collapse of the Soviet Union, Feshbach said. For 15-19 year olds today in Russia, only 57 percent of males are expected to reach age 60-65, compared to 75-80 percent of females. "This indicates that there is something attacking the working age population," Feshbach noted. He explained that much of the demographic decline in Russia is due to social breakdowns resulting in poverty, unemployment, violence, traffic deaths, alcoholism, and drug abuse. This mix has become a prime environment for the spread of infectious diseases, particularly HIV, TB, and Hepatitis. Eighty percent of all AIDS cases are among individuals under age 30. "It is not only the quantity of birth, but the quality of life after birth," Feshbach emphasized.
Unfortunately, Feshbach does not see the situation improving in the future. Due to the dramatic declines in population, the Russian armed forces have stopped allowing deferment of mandatory service. As the population continues to decline, Feshbach predicts the formation of a detrimental cycle of mandatory conscription and lower advanced education enrollment. On the whole, this cycle could lead to a reduction in the breadth of productive skills and technical knowledge in the Russian workforce.
In addition to the extremely slow response to TB, mentioned earlier, it is also difficult to accurately determine how many people may be suffering from TB due to inadequate data collection systems within Russia. While Russian officials claim 120,000 new TB cases per year, the World Health Organization puts the number closer to 150,000-160,000, he said. MDR-TB rates are even more difficult to judge, with broad estimates for those receiving treatment ranging from 17,000 to 58,000. Feshbach emphasized the importance of remembering that Russian statistics only include first incidence of TB, so relapse and re-treatment are not included in the counting. There are also inaccuracies in counting deaths when both HIV and TB are detected. HIV deaths due to TB are counted as an AIDS death, not a TB death.
Both Feshbach and Dr. Keshavjee emphasized the need for improved laboratory capacity for diagnosis of drug-resistant TB and an immediate need to address HIV/TB co-infection in Russia. "Immunocompromised individuals are more likely to be infected with TB, and are also more prone to drug-resistant strains, although it is not clear why," explained Dr. Keshavjee. He continued, "It is staggering what HIV/TB co-infection can do to TB epidemiology. A study in Thailand showed total TB notification increasing markedly between 1985 and 1995. But if you remove the patients who are HIV positive, TB infection rates actually stay even over the [10 year span]." This pattern is particularly relevant to Russia, where HIV and TB rates continue to rise.
To increase adherence and decrease the development and spread of drug-resistant TB, Dr. Keshavjee stressed the need for ambulatory care to reach non-adherent patients and for increased access to primary care for all TB patients. His research showed hospitalized TB patients had a 12-fold increased risk of developing MDR-TB while hospitalized through transmission from other patients. However, using primary care over hospitalization is a battle in Russia because the incentive structure is such that long-hospitalization provides higher medical care payments.
Finally, socio-economic barriers to successful treatment can be overcome. Both speakers emphasized the need for coordination between government sectors in Russia, particularly the penal- and civilian-healthcare administrators in order to provide effective treatment for MDR-TB. Additionally, said Dr. Keshavjee, there remains a need for a variegated and reliable drug supply, increased healthcare worker capacity, improved facilities, and additional assistance with transportation to treatment facilities. In conjunction with building infrastructure, Dr. Keshavjee sees a significant need to build social support systems and primary and preventative care services throughout Russia. Fighting TB in Russia, Feshbach concluded, will depend on the quantity, quality, location, and integration of the healthcare system.
Drafted by Michaela Hoffman.