Academic journal article Bulletin of the World Health Organization

A Random Sample Survey of Initial Drug Resistance among Tuberculosis Cases in Latin America

Academic journal article Bulletin of the World Health Organization

A Random Sample Survey of Initial Drug Resistance among Tuberculosis Cases in Latin America

Article excerpt


The widespread but often inadequate use of antituberculosis drugs in developing countries carries the risk that drug-resistant mycobacteria will gradually replace drug-sensitive strains as infecting agents. Under certain circumstances tuberculosis programmes may therefore gradually become ineffective, harming rather than improving the epidemiological situation.

The introduction of effective short-course chemotherapy regimens reduces the risk of drug resistance by making noncompliance less likely, but by its very nature the problem of resistance to common drugs is likely to increase in some developing countries (1), and is already a growing concern in developed countries (2).

The recommendation that drug susceptibility tests be used for epidemiological studies and for guiding tuberculosis treatment programmes in developing countries was made as early as 1969 (3), but has led only to sporadic drug resistance investigations in selected, easily reached populations, mainly in developed countries. In view of the practical difficulties in collecting comparable data from developing countries, WHO proposed that a global surveillance programme be set up through the WHO Collaborating Centres for Bacteriology of Tuberculosis. A survey proposal was elaborated in an informal meeting of the heads of the centres held in Geneva on 2-4 November 1983 and it was agreed to begin by undertaking a global survey (limited to developing countries) involving a representative sample of tuberculosis patients. The protocol for this survey was originally prepared by J. Grosset and H.G. ten Dam and subsequently tailored for use in Latin America.(a)

Background and rationale

The occurrence of drug resistance in tuberculosis is as old as drug treatment for the condition. For example, when streptomycin was introduced it proved life-saving for the acute manifestations of the disease, such as meningitis and miliary tuberculosis, but for the pulmonary form, after a few months' treatment, during which there would be dramatic clinical and bacteriological improvement, reversion would occur and the disease resumed its former course. The initial population of bacilli almost always contained strains that were not affected by the drug, and these gradually replaced those that were.

The problem of resistance was largely overcome when p-aminosalicylic acid and, especially, isoniazid became available. Simultaneous use of different drugs greatly diminished the risk of drug resistance because bacilli naturally resistant to one drug were eliminated by the other. Nevertheless, since the choice of drugs suitable for standard treatment remained limited, the emergence of multiple-drug resistance very much depended on the adequacy of treatment, and in practice was merely a question of time. Of particular concern in this connection were developing countries, where treatment results often appeared disappointing. This, if not the result of drug resistance, threatened to become an important cause of it, making regimens that are both effective and inexpensive unsuitable in those countries where they were needed most.

The main causes of treatment failure in developing countries are incorrect prescription of medication by doctors and patients' noncompliance. The latter does not necessarily entail a greatly increased risk of drug resistance; indeed, such patients who return at a later stage are generally found to excrete bacilli that are still susceptible to the drugs taken before. However, irregular, often prolonged, treatment and the use of inadequate regimens certainly do increase the risk of drug resistance. Until recently, efforts to improve the outcome of tuberculosis chemotherapy in developing countries were directed towards ensuring better regularity in the treatment of the patients detected. Apart from directly benefiting the patients, this practice curtailed the emergence of drug resistance and had the advantage of enabling the more powerful drugs to be reserved for the re-treatment of failures. …

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