New drugs for the treatment of tuberculosis: needs, challenges, promise, and prospects for the future.

For the first time in 40 years, a portfolio of promising new compounds for the treatment of tuberculosis is on the horizon. The introduction of new drugs in combination treatment for all forms of tuberculosis raises several issues related to patients' access to novel treatments, programmatic feasibility, cost effectiveness, and implications for monitoring and surveillance, particularly with regard to the development of drug resistance. Particular attention should be given to the identification of optimal drug combination(s) for the treatment of all forms of tuberculosis, particularly in high-risk and vulnerable groups, such as human immunodeficiency virus-coinfected persons and children, and to the rational use of new drugs. Addressing these issues adequately requires the establishment of clear guidelines to assist countries in the development of policies for the proper use of tuberculosis drugs in a way that guarantees access to best treatments for all those in need and avoids inappropriate use of new drugs. After a description of these various challenges, we present activities that will be carried out by the World Health Organization in collaboration with key stakeholders for the development of policy guidelines for optimal treatment of tuberculosis.

Resistencia inicial a drogas antituberculosas en Buenaventura, Colombia

La tasa de notificación de tuberculosis pulmonar bacilífera en 2001 en Buenaventura, Colombia, fue de 66 por 100.000 habitantes. El pobre control de la tuberculosis en este municipio durante los últimos 10 años y el uso inadecuado de medicamentos de primera línea hace sospechar una elevada resistencia a estas drogas antituberculosas. En este artículo se presentan y discuten los resultados de dos encuestas de resistencia inicial a drogas antituberculosas de primera línea en personas con tuberculosis pulmonar realizadas en Buenaventura entre el 1° de agosto de 1997 y el 31 de enero de 1998, y entre el 15 de noviembre de 2000 y el 15 de noviembre de 2001, con un intervalo de dos años y nueve meses. En las dos encuestas se utilizó el método de proporciones múltiples. Se logró aislar Mycobacterium tuberculosis en 93% y 55% de los casos nuevos de tuberculosis pulmonar diagnosticados en cada uno de los periodos estudiados. La resistencia inicial a cualquier medicamento antituberculoso fue de 25% (9/36) y 32% (23/72) en la primera y segunda encuesta, respectivamente. La multirresistencia inicial (definida como resistencia, al menos, a isoniacida y rifampicina) fue de 6% en ambas encuestas. Este porcentaje de resistencia encontrado demuestra la diseminación de cepas multirresistentes y destaca a la vigilancia epidemiológica de la resistencia a drogas antituberculosas como un componente esencial en el control de la enfermedad, por lo menos, en las zonas en las que el programa ha sido errático en el pasado. De esta manera, se podrán identificar las áreas en las que la estrategia DOTS deba ser reforzada con el uso de drogas de segunda línea (DOTS-plus).

In 2001, Buenaventura, Colombia, the rate of smear-positive pulmonary tuberculosis was of 66 per 100.000 inhabitants. The poor control of the tuberculosis in this city during the last 10 years and the inadequate use of first-line anti-tuberculosis drugs was an opportune situation for the development of high resistance to these drugs. Two surveys of initial resistance to first-line antituberculosis drugs were conducted in new cases of pulmonary TB, in the city of Buenaventura-the first from August 1, of 1997 to January 31 of 1998 and the second from November 15, of 2000 to November 15, 2001. The method of multiple proportions was used to determine drug susceptibility. Mycobacterium tuberculosis was isolated in 93% and 55% of the new cases of lung TB during each respective period. The initial resistance to at least one drug was 25% (9/ 36) and 32% (23/72), respectively. The initial multi-drug resistance (defined as resistance to at least isoniazid and rifampicin) was 6% for both surveys. This demonstrates the dissemination of multidrug-resistant bacilli and shows the need for surveillance of resistance to antituberculosis drugs in control of the disease, particularly in those areas where the TB control program has been erratically applied. In areas where multi-drug resistant TB occurs, the control strategy should be enhanced with the careful introduction of second-line drugs.