To treat or not to treat? Implementation of DOTS in Central Asia

Uzbekistan's failing tuberculosis system is undoubtedly contributing to some of the highest rates of multidrugresistant tuberculosis yet recorded in the world; 13% of new patients presenting to Médecins Sans Frontières clinics in the Karakalpakstan region have multidrugresistant tuberculosis.

A high incidence of tuberculosis (new case notification rate 261/100,000 per year) exacts a heavy toll on a population already suffering the economic and environmental effects of one of the worst man-made disasters of the twentieth century: the desiccation of the Aral Sea.1

Médecins Sans Frontières arrived in the region in 1997, and began a DOTS (directly observed treatment, short course) treatment programme in collaboration with local tuberculosis services.

However, in Uzbekistan only the lucky get DOTS. Only 7% of Uzbekistan's population are covered by the DOTS strategy.2

Indeed, globally, WHO has recently acknowledged that the pace of DOTS expansion has fallen below expectation. The 70% case-detection target will now not be reached until 2013, not 2000 as originally planned.3

The unlucky in Uzbekistan, and much of Central Asia, still receive treatment under the pre-DOTS Soviet-style treatment system. Once a strong system, the break-up of the former Soviet Union in 1991 sent the health services of the Central Asian states into rapid decline.4 Treatment now involves widely varying and often inadequate drug regimens, and an intermittent drug supply that forces many to purchase drugs at unregulated local bazaars: exactly the conditions under which multidrug-resistant tuberculosis is created.5 Nowhere is the need to rapidly expand the DOTS programme more evident than in this part of the world.

However, implementation of DOTS is far from straightforward. In the field, expert opinion is conflicting and clear guidance is lacking about how to provide the most appropriate treatment with maximum benefits. Two of the five key pillars of the DOTS strategy—directly observed therapy and diagnosis by smear microscopy— are tricky to implement in the face of a dispersed population and poorly paid, poorly motivated staff with continued allegiance to a deteriorating Soviet system.

Discussion about the pace of DOTS expansion in such a context is fundamental. Many argue that these problems are impediments to expansion; that expansion should only happen when all the conditions are exactly right, assessed by reaching the WHO target of 85% success for new smear-positive cases.6 However, this argument is invalid in Central Asia, where high rates of multidrugresistant tuberculosis render reaching this target impossible7 and the alternative to DOTS is dangerously inappropriate.

Uzbekistan's failing tuberculosis system is undoubtedly contributing to some of the highest rates of multidrugresistant tuberculosis yet recorded in the world; 13% of new patients presenting to Médecins Sans Frontières clinics in the Karakalpakstan region have multidrugresistant tuberculosis. In this context, the introduction of DOTS, with an assured drug supply, standardised regimens, and its effect on the priority given to tuberculosis, is a vast improvement; even with its attendant constraints. Given the constraints, DOTS will prevent the continued large-scale emergence of multidrugresistant tuberculosis.

In addition to drug resistance, the deteriorating Soviet system has created a large pool of patients who have previously received more than a month of tuberculosis treatment, so-called retreatment cases. These cases make up around half of the smear-positive cases seen in the Médecins Sans Frontières programme and currently less than 10% have received DOTS in the past.

Over 40% of these retreatment cases in Karakalpakstan have multidrug-resistant tuberculosis. Of course, over time these cases will gradually be reduced, but the dilemma remains about how to treat them. The WHO manual focuses on treating new cases of tuberculosis and failures of DOTS treatment.6

There is no guidance about treating infectious patients previously treated with a non-DOTS regimen. Indeed many experts advocate that this group not be included in DOTS at all; at least in the early stages of programmes. The non-inclusion argument is based on the view that to control tuberculosis the priority should be new smear-positive cases, as these cases represent recent transmission. Additionally, by only including new cases, programme success can be used to convince the still sceptical medical community of the effectiveness of DOTS.

But if this argument is followed, half the infectious cases diagnosed do not fall into the category that entitles them to DOTS. Elsewhere in the world, this pool of retreatment cases is smaller, closer to 10% of infectious cases in Benin, for example,8 and much of Africa. This difference undoubtedly fuels the general confusion and conflicting opinions as to what to do with retreatment patients.

In practical terms, to not include retreatment cases would translate on the tuberculosis ward to half the patients receiving a full course of free DOTS and a promise of full recovery but the other half being offered whatever drugs are currently available (including even second-line tuberculosis drugs) in the government system or privately, with a regimen that may or may not work, and which does not enable treatment and outcomes for these patients to be monitored. In effect, such treatment exposes patients to a significant risk of developing multidrug-resistant tuberculosis.

Additionally, the numbers of patients in this category are contributing substantially to tuberculosis transmission. Although 40% of retreatment cases in Karakalpakstan will have multidrug-resistant tuberculosis, for which there is no treatment available at this time, the remaining 60% have a good chance of cure under DOTS, thereby lessening further transmission.

Added to this, there is an obligation to treat patients when there is an effective treatment available.

Limiting DOTS expansion and restricting DOTS to only new cases does not offer hope for a rapid and longlasting solution to the ongoing tuberculosis epidemic in this region. There is an urgent need for context-specific discussion around these issues, a need already acknowledged by WHO,3 leading to an improved strategy to tackle tuberculosis in areas with high levels of multidrug-resistant disease. This strategy should include appropriate individualised treatment regimens for retreatment cases in this context.

Conflicting opinions from experts, a lack of clarity in many areas of the DOTS protocol, and limited international discussion over the practical considerations of treating a disease that is set to kill 30 million people in the next decade9 leaves those working on the ground unsure of the best way to assist the populations at risk.

We thank Gabit Ismailov, Roy Male, and Yared Kebede for substantial input into this Commentary.

*Helen Cox, Sally Hargreaves Médecins Sans Frontières, Uzbekistan and Turkmenistan, PO Box 333, 700000 Tashkent, Uzbekistan (e-mail: hom@msfh-tashkent.uz)

FOOTNOTES:

1 Small I, van der Meer J, Upshur REG. Acting on an environmental disaster: the case of the Aral Sea. Environ Health Persp 2001; 109: 547-49.

2 WHO. Global tuberculosis control: surveillance, planning, financing.

WHO/CDS/TB/2002.295. Geneva: World Health Organization, 2002. http://www.who.int/gtb/publications/globrep02/index.html (accessed Nov 28, 2002).

3 Raviglione MC. Global DOTS expansion: will we reach the targets? Presentation to 33rd IUATLD World Conference on Lung Health, Montreal, Canada, Oct 6-10, 2002. http://www.who.int/gtb/ whats-new/montreal_oct02/iuatld/raviglione.ppt (accessed Jan 8, 2003).

4 Ilkhamov FA, Jakubowski E. European observatory on health care systems: health care systems in transition. In: McKee M, Healy J, Falkingham J, eds. The European Observatory on Health Care Systems: health care in Central Asia. Buckhingham: Open University, 2001: 179-93.

5 Espinall MA, Laserson K, Camacho M, et al. Determinants of drug resistant tuberculosis: analysis of 11 countries. Int J Tuberc Lung Dis 2001; 5: 887-93.

6 WHO. Tuberculosis handbook. WHO/TB/98.253. Geneva: World Health Organization, 1998. http://www.who.int/gtb/ publications/tbhandbook/index.htm (accessed Nov 28, 2002).

7 Conninx R, Mathieu C, Debacher M, et al. First-line tuberculosis therapy and drug-resistant Mycobacterium tuberculosis in prisons.

Lancet 1999; 353: 969-73.

8 Trébucq A, Anagonou S, Gninafon M, Lambregts K, Boulahbal F.

Prevalence of primary and acquired resistance of mycobacterium tuberculosis to antituberculosis drugs in Benin after 12 years of short course chemotherapy. Int J Tuberc Lung Dis 1999; 3: 466-70.

9 WHO report on the tuberculosis epidemic, 1996. Geneva: World Health Organization, 1996.