Academic journal article Bulletin of the World Health Organization

Controlling Multidrug-Resistant Tuberculosis and Access to Expensive Drugs: A Rational Framework. (Round Table)

Academic journal article Bulletin of the World Health Organization

Controlling Multidrug-Resistant Tuberculosis and Access to Expensive Drugs: A Rational Framework. (Round Table)

Article excerpt

Voir page 493 le resume en francais. En la pagina 493 figura un resumen en espanol.

Introduction

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) could threaten global TB control. The treatment of patients with MDR-TB is prolonged, expensive and often unsuccessful (1,2). Many experts assert that standard TB control prevents the emergence of MDR-TB in a cost-effective way (3). Others argue that it is unethical to abandon patients with MDRTB and maintain that, if untreated, MDR-TB strains will become dominant and undermine TB control in future generations (4). These arguments are of particular consequence in settings where resources are scarce. While additional evidence would help to define the right point between efficiency and equity, we propose a preliminary rational framework for addressing the problem of MDR-TB in various circumstances.

Genesis and magnitude of multidrug-resistant TB

Treatment with only one effective drug, because of inappropriate prescription or poor adherence, suppresses the growth of organisms susceptible to it but permits the multiplication of isolated strains with spontaneous drug-resistance mutations. This phenomenon is called acquired drug resistance. Subsequent transmission leads to TB disease in new patients which is drug-resistant at the outset, a phenomenon known as primary resistance (5). Independent, cumulative events result in MDR-TB, defined as resistance to at least isoniazid and rifampicin. Both the creation and the transmission of drug resistance contribute to its incidence.

Resistance to TB drugs emerged soon after their introduction 50 years ago (6). A survey conducted by the International Union Against Tuberculosis and Lung Disease in 17 countries during the late 1950s found primary resistance of 3.7% for streptomycin, 3% for isoniazid, and 1% for both drugs together (7). Clinical outcomes were poorer with dual resistance (analogous to MDR-TB today), but the problem was deemed unimportant because it accounted for only a small proportion of treatment failures (8). Furthermore, clinical trials demonstrated that standard treatment without routine baseline testing for drug susceptibility produced outcomes similar to those obtained where such testing was applied and individualized treatment was given (9). The introduction of rifampicin in the early 1970s brought about ambulatory short-course chemotherapy, a regimen of three or four drugs including rifampicin for at least the first two months, given over six to nine months (10). This reinforced hopes for the elimination of TB.

By the early 1990s the incidence of TB had increased in the USA (11), following reductions in control programmes associated with the HIV epidemic, growing poverty, and homelessness (12). Poor adherence to recommended treatment regimens by doctors and patients fostered high levels of MDRTB (13). MDR-TB came to widespread attention with the occurrence of nosocomial and prison outbreaks (14). High case-fatality rates (15) and cases of MDR-TB among health care workers and others (16) led to an increase in public concern (17). WHO declared TB a global emergency in 1993, focusing on developing countries where 95% of cases occurred (18).

Although MDR-TB was one of many concerns in global TB control, there were no data on the magnitude of the problem. For this reason, WHO and the International Union Against Tuberculosis and Lung Disease began the Global Project on Anti-tuberculosis Drug Resistance Surveillance in 1994. A network of supranational reference laboratories provided quality control for drug susceptibility-testing (19). It emerged that the prevalence of multidrug resistance among new patients was generally low, the median value being 1%, especially in Africa. However, several hot spots, i.e. countries or regions where the prevalence of multidrug resistance among new TB patients exceeded 3%, were identified, particularly in the former Soviet Union (20). …

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