Tuberculosis (TB) is the leading cause of death associated with infectious diseases globally. The incidence of TB is expected to increase substantially worldwide during the next 10 years because of the interaction between the TB and human immunodeficiency virus (HIV) epidemics. This report uses TB notification data (i.e., cases reported to the ministries of health and collected by the World Health Organization {WHO}) to estimate the future global public health impact of TB and assesses the present and future contribution of HIV infection to TB. Morbidity

The incidence of TB in 1990 was calculated for each WHO region by first estimating the incidence in some of the most populated countries in each region for which notification data were considered reliable (i.e., the data were provided by programs with established surveillance systems) (1). For countries without reliable notification data, annual risk of infection was used to estimate incidence (2). Incidence estimates were then applied to the populations in subregions and then used in calculating regional totals. For projections of future TB incidence, regional age-specific incidence rates for 1990 were first derived by applying regional data on the age distribution of reported cases to the estimated crude incidence rates. Based on the assumption that future age-specific trends will remain stable, trends in regional reporting rates during 1985-1990 were applied to the 1990 regional age-specific incidence rates to derive such rates for 1995, 2000, and 2005. These rates were subsequently applied to regional age-specific population projections (3,4).

During 1990, an estimated 7.5 million incident cases of TB occurred worldwide (Table_1). Approximately 4.9 million cases (66%) occurred in the Southeast Asian and Western Pacific regions; India (2.1 million), China (1.3 million), and Indonesia (0.4 million) accounted for the largest number of cases. By 2005, the incidence of TB may increase to 11.9 million cases per year -- an increase of 58% over 1990. Demographic factors (e.g., population growth and changes in the age structure of populations) will account for 77% of the predicted increase in incidence; epidemiologic factors (e.g., changes in incidence rates associated with the HIV epidemic) will account for 23%. For example, incidence rates for Africa may increase by 10 additional cases per 100,000 population per year during 1990-2005, primarily because of the HIV epidemic. In the Southeast Asian, Western Pacific, Eastern Mediterranean, and American regions, age-specific incidence rates are expected to decline during 1990-2005; in comparison, age-specific rates in Eastern Europe, Western Europe, and other industrialized countries may remain stable. However, because of population growth, the total number of new cases in these regions will continue to increase. HIV Infection

The estimated impact of HIV infection on TB incidence was based on reported HIV seroprevalence data among patients with TB (5), assumed changes in HIV seroprevalence by region through 2000, and the estimation that 95% of HIV-associated TB cases are attributable to HIV infection (4). For 1990, an estimated 4.2% of all incident TB cases were attributable to HIV infection. This proportion may increase to 8.4% in 1995 and to 13.8% by 2000, when more than 1.4 million cases will be attributable to HIV infection (4). During 1990-1999, an estimated 88.2 million persons will develop TB; 8 million of those cases will be attributable to HIV infection (4). Mortality

Estimates of TB deaths for 1990 were derived using 1) published case-fatality rates of 7% for industrialized countries (6), 2) estimated case-fatality rates of 15% for Eastern Europe, 3) an estimated case-fatality rate of 20% for Central and South America, and 4) the assumption that all cases reported to WHO were treated and that 5% of treated cases were not reported for other regions. Based on these considerations, an estimated 40%-50% of new cases were treated in 1990; assuming a case-fatality rate of 55% for persons not receiving treatment and 15% for those receiving treatment, the overall case-fatality rates for other regions ranged from 35% to 40%. In estimating future mortality, the proportion of persons with cases treated was assumed to remain at the 1990 level. The number of TB deaths associated with HIV infection were estimated by applying these same case-fatality rates to the estimates of HIV-attributable cases.

For 1990, an estimated 2.5 million deaths occurred from TB, of which 116,000 were associated with HIV infection (Table_2). In 2000, an estimated 3.5 million TB deaths will occur (39% more than in 1990), and approximately 0.5 million will be associated with HIV infection. Almost half of these HIV-associated deaths will occur in sub-Saharan Africa. During 1990-1999, an estimated 30 million persons will die from TB; approximately 3 million of those deaths will be associated with HIV infection. In Southeast Asia, 12.3 million deaths from TB will occur during the decade, of which approximately 1 million will be associated with HIV infection. Nearly 6 million TB deaths are projected in sub-Saharan Africa, of which approximately 1.5 million will be associated with HIV infection. Reported by: PJ Dolin, PhD, Imperial Cancer Research Fund, Cancer Epidemiology Unit, Radcliffe Infirmary, Univ of Oxford, Oxford, United Kingdom. MC Raviglione, MD, A Kochi, MD, Tuberculosis Program, World Health Organization, Geneva.

Editorial Note

Editorial Note: The estimates of current TB incidence in this report, which are based primarily on notification data, are similar to those produced by other methods and document the substantial public health burden of TB in developing countries (7,8). Moreover, because TB cases are generally underreported, estimates of incidence based on notification data are likely conservative. Similarly, estimates of TB mortality should be considered to be conservative (8): earlier estimates used a case-fatality rate of 50% for HIV-associated cases, while the current estimate did not assume that mortality was different between HIV-positive and HIV-negative persons. Because TB mortality is highly related to case finding and treatment, projections beyond 2000 were not made.

The use of short-course therapy in well-managed national TB programs has reduced TB-associated morbidity, even under the most adverse circumstances (e.g., in countries with high prevalences of HIV infection) (9). The use of this intervention for persons with smear-positive TB is also among the most cost-effective health interventions available (10). The potential benefits of these and other strategies for TB control should be evaluated by those countries most severely affected by TB and by donor countries and organizations that invest in health-care programs in countries with high rates of TB.

References

1. World Health Organization. Tuberculosis notification update,

July 1992. Geneva: World Health Organization, Division of Communicable Diseases, Tuberculosis Program, 1992; publication no. WHO/TB/92.169.

2. Cauthen GM, Pio A, Ten Dam HG. Annual risk of tuberculosis infection. Geneva: World Health Organization, Tuberculosis Program, 1988; publication no. WHO/TB/88.154.

3. United Nations. Global estimates and projections of population by sex and age, 1988 revision. New York: United Nations, 1989; publication no. ST/ESA/SER.R/93.

4. Dolin PJ, Raviglione MC, Kochi A. A review of current epidemiological data and estimations of current and future incidence and mortality from tuberculosis. Geneva: World Health Organization, Tuberculosis Program, 1993 (in press).

5. Narain JP, Raviglione MC, Kochi A. HIV-associated tuberculosis in developing countries: epidemiology and strategies for prevention. Tuber Lung Dis 1992;3:311-21.

6. Raviglione MC, Sudre P, Rieder HL, Spinaci S, Kochi A. Secular trends of tuberculosis in Western Europe. Bull World Health Organ 1993;71:297-306.

7. Murray CJ. Health sector priorities review: tuberculosis. In: Jamison DT, Mosley WH, eds. Disease control priorities in developing countries. New York: Oxford University Press, 1993.

8. Sudre P, Ten Dam G, Kochi A. Tuberculosis: a global overview of the situation today. Bull World Health Organ 1992;70:149-59.

9. Styblo K. The impact of HIV infection on the global epidemiology of tuberculosis. Bull Int Union Tuberc Lung Dis 1991;66:27-32. 10. Murray CJL, DeJonghe E, Chum HJ, Nyangulu DS, Salomao A, Styblo K. Cost effectiveness of chemotherapy for pulmonary tuberculosis in three sub-Saharan African countries. Lancet 1991;338:1305-8.
Table_1
Note: To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.

TABLE 1. Estimated number of tuberculosis cases * and rates + -- worldwide, 1990,
1995, 2000, and 2005
===========================================================================================
                           1990           1995           2000           2005
                       ------------   ------------   ------------   ------------
Region                 Cases   Rate   Cases   Rate   Cases   Rate   Cases   Rate
--------------------------------------------------------------------------------
Southeast Asia         3,106   237    3,499   241    3,952   247    4,454   256
Western Pacific &      1,839   136    2,045   140    2,255   144    2,469   151
Africa                   992   191    1,467   242    2,079   293    2,849   345
Eastern Mediterranean    641   165      745   168      870   168      987   170
Americas @               569   127      606   123      645   120      681   114
Eastern Europe **        194    47      202    47      210    48      218    49
Western Europe
  and others ++          196    23      204    23      211    24      217    24

All regions            7,537   143    8,768   152   10,222   163   11,875   176

Percentage increase
  since 1990                              16.3%          35.6%          57.6%
--------------------------------------------------------------------------------
 * In thousands.
 + Crude incidence rate per 100,000 population.
 & Includes all countries of the World Health Organization's (WHO) Western Pacific region
   except Japan, Australia, and New Zealand.
 @ Includes all countries of WHO's American region except the United States and Canada.
** Includes all independent states of the former Union of Soviet Socialist Republics.
++ Western Europe and the United States, Canada, Japan, Australia, and New Zealand.
===========================================================================================

TABLE 2. Estimated HIV-attributable and total tuberculosis deaths, assuming regional
treatment coverage rates remain at the 1990 level -- worldwide, 1990, 1995, and 2000
========================================================================================================
                                    1990                      1995                      2000
                           -----------------------   -----------------------   -----------------------
                               HIV-                      HIV-                      HIV-
Region                     attributable    Total     attributable    Total     attributable    Total
------------------------------------------------------------------------------------------------------
Southeast Asia                23,000     1,087,000      88,000     1,225,000     200,000     1,383,000
Western Pacific *              7,000       644,000      11,000       716,000      24,000       789,000
Africa                        77,000       393,000     150,000       581,000     239,000       823,000
Eastern Mediterranean          4,000       249,000       6,000       290,000      15,000       338,000
Americas +                     4,000       114,000       9,000       121,000      19,000       129,000
Eastern Europe &                <200        29,000        <600        30,000        <900        32,000
Western Europe
  and others @                  <500        14,000       1,000        14,000       2,000        15,000

All regions                  116,000     2,530,000     266,000     2,977,000     500,000     3,509,000

Percentage
  HIV-attributable                  4.6%                     8.9%                     14.2%

Percentage increase
  since 1990                                                17.7%                     38.7%
------------------------------------------------------------------------------------------------------
* Includes all countries of the World Health Organization's (WHO) Western Pacific region except
  Japan, Australia, and New Zealand.
+ Includes all countries of WHO's American region except the United States and Canada.
& Includes all independent states of the former Union of Soviet Socialist Republics.
@ Western Europe and the United States, Canada, Japan, Australia, and New Zealand.
========================================================================================================

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