Academic journal article Bulletin of the World Health Organization

Directly Observed Treatment, Short-Course Strategy and Multidrug-Resistant Tuberculosis: Are Any Modifications Required?(*)

Academic journal article Bulletin of the World Health Organization

Directly Observed Treatment, Short-Course Strategy and Multidrug-Resistant Tuberculosis: Are Any Modifications Required?(*)

Article excerpt


The introduction of rifampicin for therapeutic use in 1968 completed three decades of scientific innovation that provided several effective chemotherapeutic agents for the treatment of tuberculosis (TB) (1, 2). Clinical trials by the British Medical Research Council and others elucidated the optimal regimen while operational studies by Karel Styblo and the International Union against Tuberculosis and Lung Disease (IUATLD) demonstrated that short-course chemotherapy (SCC) given under direct observation could succeed in the field (3). Unfortunately, these tools for controlling TB have not been used properly. Between 1998 and 2030, 225 million new cases of TB and 79 million deaths attributable to the disease are expected (4). A recent global study detected resistance to antituberculosis drugs in all 35 countries and regions surveyed (5, 6).

Responding to this situation, WHO recommended a multifaceted strategy known as directly observed treatment, short-course (DOTS), which includes standardized supervised SCC (7). DOTS has proved effective in diverse settings but globally only 16% of all TB cases are treated in DOTS programmes (8, 9). DOTS should be made more widely accessible so that effective treatment is available to patients with drug-susceptible disease and acquired drug resistance is prevented. However, while DOTS is an integral part of the global TB control effort, additional interventions may be necessary in particular circumstances. For example, additional strategies (e.g. active case-finding, TB preventive therapy for persons infected with human immunodeficiency virus (HIV)) may be required in countries with high rates of combined TB/HIV infection (10). The term DOTS-plus for TB/HIV could be given to such modified programmes. It has also been suggested that DOTS programmes should provide additional services in areas where multidrug-resistant tuberculosis (MDRTB) is prevalent (i.e. DOTS-plus for MDRTB) (11-13).

While continuing to emphasize that implementation of the DOTS strategy is the top priority, WHO recognized that, in some places where the prevalence of MDRTB is high, it represents a special threat to effective TB control. WHO, in partnership with other agencies and institutions, therefore established the Working Group on DOTS-plus for MDRTB (14, 15). This group has developed protocols for pilot projects intended to assess the feasibility of MDRTB management in TB control programmes.

Below we discuss the rationale for and possible format of a DOTS-plus approach to MDRTB. After outlining the global distribution of MDRTB we indicate the importance of a strict definition for MDRTB, i.e. resistance to at least isoniazid and rifampicin. The potential risks of SCC in areas where MDRTB is prevalent are discussed and possible modifications of the DOTS strategy are proposed. The need for continuing research to determine the indications for and format of such DOTS-plus services is highlighted.

Distribution of MDRTB


Acquired drug resistance, involving the emergence of drug-resistant bacilli in previously treated patients, arises through faulty prescription or failure to ensure compliance, and therefore provides a short-term measure of the effectiveness of local treatment regimens and TB control programmes (6, 16). As the pool of patients excreting drug-resistant bacilli expands, there is an increasing risk of transmission of the bacilli to healthy individuals who can develop drug-resistant disease from the outset, i.e. primary resistance (6, 16). The prevalence of primary resistance in a community is therefore an excellent longterm indicator of the quality of TB treatment and control.

Unfortunately, however, it is often difficult in field conditions to make an accurate distinction between previously treated patients and those who have never been treated (6, 16). Consequently, surveillance studies have often only provided the crude (or combined) rate of drug resistance, which is of little epidemiological use (16, 17). …

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