Global tuberculosis challenges.

Mario Raviglione, World Health Organization (WHO), described the epidemiology of global tuberculosis (TB) using surveillance data available to WHO from 212 countries and data from a recent survey of antituberculosis drug resistance in 32 countries. Countries were categorized according to the degree of TB directly observed treatment strategy (DOTS) implementation. Performance of national TB programs was assessed by using treatment outcome indicators. In 1996, 3.8 million TB cases (887,731 from areas with DOTS) were reported to WHO. In developing countries, the bulk of TB cases are found in all age groups of native-born populations, while in many industrialized countries a large proportion of TB cases are in foreign-born residents. In countries of the former Soviet Union, TB cases and deaths have doubled in just a few years. Drug resistance and HIV infection related to TB are found only in limited foci. Acquired multidrug-resistant TB (MDRTB) was present in 27% to 54% of culture-positive TB cases from the Baltic countries and Russia. The effect of the HIV epidemic on TB has been major in Africa, where HIV seroprevalence among TB cases is 50% to 70% and TB case notifications have at times tripled. Countries with inadequate TB control are particularly exposed to the consequences of both epidemics. In Southeast Asia, cases are increasing, and MDRTB is common in Thailand, China, and Vietnam. One hundred eighty-one countries and territories (97% of the global population) have reported on the status of DOTS to WHO. Of these, 96 implemented DOTS (63 countrywide). Approximately 32% of the global population lives in areas where DOTS is available. Twenty countries have adopted DOTS since the 1996 survey, and an additional 9% of the global population were benefitting from it. However, most of these new countries had small populations; DOTS was only slowly implemented in countries with high TB prevalence. In areas that used DOTS, treatment outcome evaluation remains high (94%), and treatment success rose from 76% in 1994 to 78% in 1995. In areas that did not use DOTS, 45% of reported TB cases were not evaluated, and treatment success remained low (45%). Among the 22 countries with the highest TB prevalence, six showed progress in DOTS implementation, seven showed little progress, and nine did not implement DOTS. In summary, TB remains an important public health problem in many areas of the world where DOTS has not been implemented. Because treatment outcomes were better in countries where DOTS has been used, the strategy needs to be expanded rapidly and new tools to facilitate its implementation need to be developed. Barry Bloom, Howard Hughes Medical Institute, described advances in TB vaccine development. The available bacillus CalmetteGuerin (BCG) vaccine has a demonstrated efficacy ranging from no protection to 80% protection. Most recently, a meta analysis estimated that the overall efficacy of BCG is 50%. Because of case reports of disseminated BCG infection, this vaccine is contraindicated in immunocompromised persons, and safer and more efficacious vaccines are clearly needed. Identifying such new vaccines for use in humans will take several years. However, recent advances in this area provide optimism. Recent research activities have improved our understanding of the immunologic response to Mycobacterium tuberculosis and identified major protein antigens of M. tuberculosis and recombinant BCG forms that overexpress protective antigens. Additionally, avirulent auxotrophic mutants of both BCG and M. tuberculosis have been used in animal models. The recent sequencing of the M. tuberculosis genome has presented additional opportunities to identify virulence factors that could be deleted and other target sites that could be genetically engineered. DNA constituents can also be used to develop candidate vaccines. In animal studies, subunit vaccines consisting of pooled mycobacterial culturefiltrate proteins have been protective. Auxotrophic mutants may also prove useful in immunoGlobal Tuberculosis Challenges