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International Notes Tuberculosis and Leprosy Control in Developing Countries
Recent information indicates that the epidemiologic behavior of tuberculosis in some tropical areas may be substantially different from its well-known pattern in developed countries. Wide gaps in knowledge necessitate a revision of present research priorities. The epidemiology of leprosy is even less well understood, primarily
Tuberculosis and Leprosy Control in Developing Countries Recent information indicates that the epidemiologic behavior of tuberculosis in some tropical areas may be substantially different from its well-known pattern in developed countries. Wide gaps in knowledge necessitate a revision of present research priorities. The epidemiology of leprosy is even less well understood, primarily because no appropriate method exists to measure the prevalence and risk of infection.
In November 1982, a consulting group of epidemiologists met in Geneva to identify the most important and immediate problems in tuberculosis and leprosy control and to indicate areas for research. The group reviewed present knowledge of the epidemiology of tuberculosis and leprosy in developing countries and selected problems that are most relevant to control policies and can be explored with limited resources.
At present, several centers in developing countries appear to have useful epidemiologic information on tuberculosis and leprosy available and easily retrievable. All such data bases, especially those involving longitudinal follow-up of large populations (e.g., in Chingleput district in South India, described below) should be used for epidemiologic studies of tuberculosis and leprosy, particularly for testing hypotheses that might explain epidemiologic differences between areas. CHINGLEPUT TRIAL
To verify and possibly quantify previous contradictory results* on the protective effect of BCG vaccination, a new trial (organized by the Indian Council for Medical Research in cooperation with the World Health Organization (WHO) and the United States Public Health Service) was started in 1968 in Chingleput District near Madras, South India. Sensitization with environmental mycobacteria was highly prevalent in this area.
Two vaccines, prepared in accordance with the best available knowledge, and a placebo were randomly administered to over 270,000 persons of all ages. After 7 1/2 years of follow-up, the number of pulmonary tuberculosis cases in the different groups was approximately the same, indicating that BCG vaccination had given no protection against this form of disease.
To assess the protective effect of BCG vaccination against leprosy, a baseline survey was carried out approximately 5 years after the vaccinations, with follow-up every 2 1/2 years. Results of the two follow-up rounds completed so far will be published in the near future. TUBERCULOSIS
Prevalence of bacteriologically confirmed tuberculosis: Patients who excrete tubercle bacilli (seen on direct smear examination) are primarily responsible for transmitting the infection and disease in a community. Thus, a prevalence survey in a developing country can provide reliable information on the magnitude of the infectious sources pool in the community and form the basis for planning an appropriate control strategy. In the last 20 years, a number of countries in the Southeast Asian and Western Pacific regions have conducted periodic prevalence surveys. The collected data should be analyzed to determine the value of such surveys, not only in epidemiologic terms but also for planning and evaluating the control programs.
Assessment of the annual risk of tuberculosis infection: The tuberculin test has proven a powerful epidemiologic tool for measuring transmission of tuberculosis infection. It is of particular value for assessing change (or the absence of change) in the infection level in an area and provides the best single epidemiologic index of the trend of the tuberculosis problem in a developing country. It is relatively inexpensive, but the interpretation of test results is often complicated by sensitivity induced by mycobacteria other than M. tuberculosis, including sensitivity caused by BCG vaccination in some members of the population. Special survey and analysis methods will be needed to overcome these problems, and these require further investigation.
Further studies of the epidemiologic pattern of tuberculosis: The results now emerging from the Chingleput trial will contribute greatly to understanding the epidemiology of tuberculosis. Various hypotheses have been proposed for further examination in relation to these data, including:
South Indian variant of M. tuberculosis may be radically different from that following virulent infection with the normal strain, i.e., a low risk of progressive primary tuberculosis development and a high risk of endogenous reactivation.
2. Sensitivity from other mycobacterial infections in the adult population may provide good protection against tuberculosis in early adult life, but host immunity may wane with increasing age, leaving older adults susceptible to both endogenous and exogenous disease.
3. A substantial proportion of tuberculosis cases among adults is nevertheless likely to result from exogenous reinfection, because risk of infection is high.
Despite intervention by BCG and treatment, the (presumably) stable epidemiologic pattern of the disease in this community is probably little disturbed. A study of the infection risks, the incidence and prevalence of tuberculosis, and the outcome of disease in terms of continued infectivity and death, at different ages in both sexes, should help in understanding the pathogenesis of tuberculosis in the area.
Data from other developing areas should be examined similarly to decide whether the Chingleput experience is unique or can be regarded as typical of tuberculosis in a developing country. Virulence of the organisms isolated in the Chingleput trial should be determined experimentally and, if possible, in vitro to enable the pathogenesis of tuberculosis in the area to be studied further. In addition, current assessment could be made of the risk of tuberculous infection among unvaccinated children in the area population.
Comparisons of the outcome of different case-finding and treatment policies for bacillary cases and assessment of their epidemiologic impact: The poor outcome of treatment among bacillary cases detected in the Chingleput trial illustrates a number of problems. Smear-positive cases are the principal sources of infection in the community, and their rapid and lasting cure by effective and inexpensive forms of short-course chemotherapy will contribute not only to a better outcome for those patients, but also to some reduction in the risk of infection, by cutting short the duration of smear-positivity.
Thus, studies are needed of 1) better approaches to the treatment of bacillary cases of tuberculosis in developing countries and 2) approaches to the more comprehensive detection of smear-positive and, where possible, culture-positive tuberculosis. (The outcome of treatment should be monitored, in terms of both bacillary excretion and survival, and prognostic factors should be studied. In parallel, the risk of tuberculosis infections should be assessed, to detect whether improvements in case-finding and treatment policies are having the desired epidemiologic impact.)
The epidemiologic impact of treating smear-positive cases, relative to that of treating culture-positive cases, is of some importance in tuberculosis control in developing countries. Treatment of smear-positive cases will shorten the duration of their positivity, whereas treatment of culture-positive cases will prevent a proportion of them from becoming smear-positive and perhaps remaining positive for a considerable period. Analyses of the Chingleput trial data and a tuberculosis survey in Bangalore may help resolve this question, or special studies may be needed.
Surveillance of primary drug resistance: Where possible, arrangements should be made to periodically survey primary drug resistance in developing countries (i.e., drug resistance in newly diagnosed and previously untreated patients). Sputum specimens should be examined in regional reference laboratories. A continued low level special studies may be needed.
Surveillance of primary drug resistance: Where possible, arrangements should be made to periodically survey primary drug resistance in developing countries (i.e., drug resistance in newly diagnosed and previously untreated patients). Sputum specimens should be examined in regional reference laboratories. A continued low level of primary drug resistance would be a good indication that satisfactory policies were being maintained.
Use of BCG in the prevention of tuberculosis: The most recent results from the Chingleput trial show some BCG protection from 5 to 10 years after vaccination among children initially aged 0-14 years. The lack of protection during the first 5 years remains unexplained.
It will be important to follow the trial subjects further to see whether protection continues from 10 to 15 years after vaccination. Further studies on the efficacy of BCG in very young children in
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