[Emerging Infectious Diseases]                                                         
[Volume 4 No. 3 / July - September 1998]

Special Issue

Global Tuberculosis Challenges

Kenneth G. Castro
Centers for Disease Control and Prevention, Atlanta, Georgia, USA

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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 Calmette-Guerin (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
culture-filtrate proteins have been protective. Auxotrophic mutants may
also prove useful in immuno-compromised patients, as may recombinant BCG
vaccines that secrete host-specific cytokines. Clearly, a major national
effort is required for TB vaccine development, recommendations on policies
and priorities, and cooperation between the government and private sector
in these efforts.

Christopher Murray, Harvard School of Public Health, described a
mathematical model developed to forecast the future impact of improvements
in TB prevention and control. Specifically, this model projected the number
of TB cases and deaths averted through the year 2050. Different scenarios
were simulated to project the effect of adding TB vaccines to existing
interventions. Six specific scenarios assessed the effect of vaccines (with
efficacy levels of 20%, 50%, and 80%) to protect from M. tuberculosis
infection, as well as the effect of vaccines of the same levels of efficacy
to protect latently infected persons from "breakdown" to active TB.
Although a TB infection vaccine with 20% efficacy would prevent more than
30 million TB cases, the best protection is obtained from a TB breakdown
vaccine with 80% efficacy, which would prevent almost 130 million TB cases.
The breakdown vaccine could be used in the large number of persons with
latent M. tuberculosis infection, now estimated at almost one third of the
world's population. Such anticipated gains justify the effort to develop
better TB vaccines.

Denise Garrett, Centers for Disease Control and Prevention, presented the
findings of recent tuberculin skin test studies regarding the risk for TB
among health-care workers in Thailand and Brazil. In Thailand, 35% of 911
health-care workers had a positive test at the 15-mm cutoff, while 69% were
positive at the 10-mm cutoff. BCG scar was associated with positive skin
test reaction at the lower cutoff value, but not at the 15-mm cutoff.
Additionally, tuberculin skin test reactivity correlated with more than 1
year's employment as a health-care worker, and with occasional or frequent
patient contact. In Brazil, 48% of 524 health-care workers had a reaction
of 10 mm, while 26% had a reaction of 15 mm. As in Thailand, BCG scar
correlated only with 10-mm skin test reactivity but not with 15-mm. Workers
with occasional or frequent patient contact were also more likely to have a
positive tuberculin test. Factors that appear to contribute to the risk for
TB in these workers include delays in the diagnosis of TB, inadequate
isolation practices, and lack of personal protection during high-risk
procedures. Important measures to reduce the risk for TB in these settings
include increasing the awareness and training of health-care workers about
the risk for TB, improving the ability to establish the diagnosis of TB by
smear microscopy, reducing the need for hospitalization of TB patients,
considering the establishment of chest clinics at separate times or in
separate areas, and improving ventilation by keeping windows open.
Laboratories should contain all needed safety features.


Emerging Infectious Diseases
National Center for Infectious Diseases
Centers for Disease Control and Prevention
Atlanta, GA

URL: ftp://ftp.cdc.gov/pub/EID/vol4no3/ascii/cast.txt

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