Tuberculosis in Developing Countries

Since 1988, The World Bank has supported a series of studies ("Health Sector Priorities Review") on the public health importance of clusters of certain diseases in the developing world and on the costs and effectiveness of technologies for prevention and management of these diseases. Since the 1940s, the number of cases and deaths from tuberculosis (TB) has been decreasing in most developed countries; in developing countries, however, TB remains a major problem. This report summarizes findings of The World Bank's evaluation of TB in developing countries (1).

Because reporting of cases and deaths in developing countries is incomplete, for this analysis the burden of TB was estimated indirectly using data on the average annual risk of TB infection (ARI)* (i.e., the probability that any person will be infected or reinfected with Mycobacterium tuberculosis in 1 year), the incidence of sputum smear-positive pulmonary TB, the proportion of all cases of TB that are smear-positive, and case-fatality rates for smear-positive TB and other TB. The ARI is highest in sub-Saharan Africa (1.5%-2.5%) and Asia (1.0%-2.0%) (2). In comparison, the ARI in the Netherlands in 1985 was estimated at 0.012% (3). Incidence

A regression analysis of data from several countries in which both ARI and the incidence of sputum smear-positive pulmonary TB were known indicated 49 cases of smear-positive TB per 100,000 population for every 1% ARI (1) (95% confidence interval: 39-59). Based on these estimates and the observed ARIs from different regions of the world, greater than 3,000,000 new cases of smear-positive TB occur annually in developing countries (Table 1, page 567). Because an estimated 1.2 cases of smear-negative pulmonary TB and extrapulmonary TB occur for every case of smear-positive pulmonary TB (1), the total number of new TB cases occurring annually in developing countries is greater than 7,000,000 (Table 2, page 567). Mortality

Without appropriate chemotherapy, the death rate from TB is approximately 50% (4). For persons enrolled in a typical national treatment program and treated with isoniazid, thiacetazone, and/or streptomycin, the death rate is approximately 20% (1). Based on these rates and estimates of the number of cases that remain undetected and untreated and the number that are detected and treated with standard chemotherapy regimens (World Health Organization (WHO), unpublished data), the estimated annual number of deaths from TB in the developing world is greater than 2,500,000 (Table 3), or approximately 6.7% of all deaths (5) and, among persons 15-59 years of age, 18.5% of deaths and 26% of preventable deaths (6). Prevention and Control

Three major strategies for controlling TB are BCG vaccination of children, chemoprophylaxis, and case-finding/treatment.

Total coverage with BCG can prevent 40%-70% of deaths from TB among children and reduce total TB mortality by approximately 6% (1). However, because the effect of BCG on TB mortality is limited in older age groups, expanded BCG coverage cannot be the sole means employed to control TB.

Although clinical TB can be secondarily prevented by treating persons with latent tuberculous infection, mass chemoprophylaxis of all such persons cannot be efficiently or economically accomplished. However, selective treatment of high-risk groups (e.g., close family contacts of smear-positive sources) may be feasible. If proven effective in clinical trials, chemoprophylaxis might also play an important role in preventing clinical TB in persons with dual human immunodeficiency virus (HIV) and tuberculous infections. Treatment

The most effective means of reducing transmission of tuberculous infection, and thus the number of TB cases, is to treat and cure patients with smear-positive TB. Each person with undiagnosed and untreated smear-positive TB will cause 10-14 infections per year. Of these, 0.6-1.2 eventually will become new cases of TB (1).

Despite the availability of anti-TB drugs, TB treatment programs in most developing countries have not succeeded because of poor patient compliance with therapy, emergence of drug-resistant organisms, and failure to carefully control drug supplies and therapy. Cure rates in developing countries are frequently less than 50%; however, cure rates of greater than 90% can be achieved when short-course chemotherapy regimens are given under supervision (7). A major obstacle to the more widespread use of these short-course treatment regimens is the higher cost of the drugs, especially rifampin and pyrazinamids. Cost-Effectiveness

The estimated cost of treatment per patient in developing countries, in 1986 U.S. dollars, is $123 for standard 12-month chemotherapy and $168 for short-course chemotherapy. However, the cost per patient cured is $368 for standard 12-month chemotherapy and $314 for short-course. For standard 12-month chemotherapy, the estimated cost per death averted is $569 for standard therapy and $514 for short-course therapy. The estimated cost per death averted, including the effect of reducing one round of transmission by sputum smear-positive cases, is $275 for standard chemotherapy and $243 for short-course chemotherapy (1). Reported by: CJL Murray, Harvard School of Public Health, Boston, Massachusetts. K Styblo, A Rouillon, International Union Against Tuberculosis and Lung Disease, Paris, France. Div of Tuberculosis Control, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: With the possible exception of measles (8), more persons in developing countries die from TB each year than from any other pathogen. Existing diagnostic technology and chemotherapeutic agents can prevent morbidity and mortality from TB in these countries. The National Tuberculosis Programs, assisted by the International Union Against Tuberculosis and Lung Disease (IUATLD), have shown that short-course chemotherapy can be applied on a national scale with excellent results (1). The analysis of the cost-effectiveness of both standard 12-month and short-course chemotherapy indicates that TB chemotherapy is as cost effective as other health interventions routinely applied in developing countries (e.g., immunizations and oral rehydration therapy) (9).

Recent findings indicate a marked increase in TB cases caused by an interaction of TB with HIV (10). The combination of the enormous public health burden, the existence of cost-effective interventions, and the demonstrated interaction between tuberculous and HIV infections make TB a high priority for action and research in international health. WHO and The World Bank, with assistance from IUATLD, CDC, and other organizations, are reassessing their approaches to the prevention and control of TB. Additionally, the International Task Force for Disease Eradication has recognized the public health burden of TB and has identified two requirements for reducing this burden: 1) improved diagnostic tests, chemotherapy, and vaccine; and 2) wider application of current therapy (11).

References

1. Murray CJL, Styblo K, Rouillon A. Tuberculosis in developing

countries: burden, intervention, and cost. Bull Int Union Tuberc Lung Dis 1990;65:6-24.

2. Cauthen GM, Pio A, ten Dam HG. Annual risk of tuberculous infection. Geneva: World Health Organization, 1988; document no. WHO/TB/88.154.

3. Styblo K. Overview and epidemiologic assessment of the current global tuberculosis situation with an emphasis on control in developing countries. Rev Infect Dis 1989;II(2):S339-S346.

4. Rutledge JA, Crouch JB. The ultimate results in 1654 cases of tuberculosis treated at the Modern Woodmen of America Sanitorium. Am Rev Tuberc 1919;2:755-63.

5. United Nations. World population prospects: estimates and projections as assessed in 1988. New York: United Nations, 1989.

6. Murray CJL, Feachem RG. Adult mortality in the developing world. Trans R Soc Trop Med 1990;84:21-2.

7. Styblo K, Chum HJ. Treatment results of smear-positive tuberculosis in the Tanzania National Tuberculosis and Leprosy Programme: standard and short-course chemotherapy. In: Proceedings of the XXVI IUAT World Conference on Tuberculosis and Respiratory Diseases. Tokyo: Professional Postgraduate Services, 1987:122-6.

8. Walsh J. Establishing health priorities in the developing world. New York: United Nations Development Programme, 1988.

9. Haag JG. Cost effectiveness and cost benefits analysis of immunization programs in developing countries: a review of the literature. Washington, DC: Pharmaceutical Manufacturers Association, 1982. 10. Styblo K. The global aspects of tuberculosis and HIV infection. Bull Int Union Tuberc Lung Dis 1990;65:28-32. 11. CDC. International Task Force for Disease Eradication. MMWR

• ARIs are calculated from tuberculin skin test surveys of

representative samples of non-BCG-vaccinated persons (e.g., if a sample of nonvaccinated 6-year-olds had a prevalence of TB infection of 6%, the annual risk of infection would be 1%). 1990;39:209-12,217.

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