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TB OR NOT TB
GENEVA- The discovery in 1944 of streptomycin, a drug
which effectively cured tuberculosis, was greeted with tremendous
enthusiasm and hope that the disease could be eradicated. Now 50
years later, public health authorities are pessimistic about the
growing increase in tuberculosis cases throughout the world.
Ninety million new cases of TB will be diagnosed and 30
million people will die of the disease in this decade, according
to the latest projections from the World Health Organization. The
two main factors contributing to the increasing rise in
tuberculosis cases are AIDS and the rise of drug-resistant forms
of the disease. Homelessness and declining public health
services are also believed to be factors in the U.S.
The number of cases of tuberculosis declined steadily in the
US after WWII until the trend reversed course in the mid-1980's.
The number of cases of TB has increased in U.S. from two per
100,000 to more than 10 per 100,000 now. The increase in TB
correlates closely with the spread of the AIDS epidemic. In
Europe, the highest TB rates are found in Portugal, while Denmark
has the lowest.
Tuberculosis has also reached epidemic proportions in many
parts of the developing world. Central Africa, Southeast Asia and
parts of the Western Pacific have been severely affected. HIV
infection is considered the primary cause of the TB explosion in
these areas.
The problem in the US is not just more cases of TB, but more
cases of the most difficult to treat form of the disease,
multi-drug resistant (MDR) TB. This form of the disease is caused
by variants of M. tuberculosis (the organism that causes TB)
which are resistant to standard treatments including isoniazid,
rifampin and ethambutol.
Patients most likely to develop MDR-TB are those who have
been treated for TB in past but who failed to complete
conventional treatment regimens. Nearly half of TB patients seen
in some New York hospitals present with MDR-TB. Patients with
AIDS and MDR-TB have poor prognoses, with mortality rates as high
as 89% within 16 weeks of diagnosis.
MDR-TB is also a threat to US healthcare workers, having
killed several in recent years. Factors associated with hospital
related infection include delayed diagnosis and treatment, poor
infection control and inadequate ventilation.
The treatment and prevention of MDR-TB is based on
susceptibility testing of isolates, and may require the use of
seven or more drugs. However, appropriate therapy for MDR-TB is
often delayed because of the length of time required for
conducting drug susceptibility tests, up to six months.
Conventional TB and MDR-TB both require aggressive drug
therapy. It can cost up to $250,000 to cure a single case of
MDR-TB, almost 100 times as much as treating conventional TB. In
both forms of the disease, treatment may be required for six
months or longer. Premature cessation of treatment not only leads
to treatment failure, but to development of more resistant
strains.
The necessity of long term treatment has led to the
controversial use of almost forgotten laws allowing public health
authorities to detain patients against their will, making sure
they take every pill prescribed over a six to twelve month
period. Such treatment, called 'directly observed therapy', has
been used to treat patients not considered capable of following
the recommended regimens.
The CDC has initiated an action plan which involves
strategies to improve detection and treatment of active cases of
TB across the country. The CDC plan also calls for earlier
identification of patients with latent TB who are at risk for
developing TB, such as AIDS patients.
The American Medical Association has proposed routine HIV testing
for all TB patients, as well as routine TB tests for all HIV
patients. The AMA also advocates more aggressive contact tracing.
Public health authorities have expressed frustration over
the medical world's inability to eradicate TB. The rise of MDR-TB
is largely attributed to sloppy treatment practices throughout
the world with drug regimens which otherwise would have been
effective. Moreover, a vaccine has been available for many years,
but is underutilized.
"We are not using existing tuberculosis drugs effectively,
and we are not developing the new drugs we need. Anti-TB drugs
discovered decades ago are sitting on the shelf, even though they
are nearly 100 percent effective and cost as little as $13 for
six months worth of treatment,'' said Dr. Arata Kochi, manager,
WHO TB program.
TB is caused by exposure to Mycobacterium tuberculosis, a
species of rod-shaped bacteria. Transmission occurs via exposure
to airborne particles produced in the sneezes and coughs of
infected patients. The most common site of infection is the
lungs. Nearly 90 percent of TB cases are the result of a dormant
infection becoming active when the host immune system weakens. TB
has become one of the leading causes of death among people with
AIDS.
On the research front, French and British researchers have
identified a gene associated with drug resistance. This discovery
could offer potential new strategies for drug development, and
may also speed development of a much need rapid test for
determining drug resistant strains of TB.
SOURCES: Journal of the American Medical Association,
1/18/95, v.273, No.3, 220-226. Heart Lung, 1993;22:365-369. FDA
Online documents.
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