Drug-resistant TB not
cured by current tactics in developing countries
BY MITCH LESLIE
Drug-resistant
tuberculosis in developing countries is more deadly than
doctors previously recognized. One-third to one-half of
patients suffering from drug-resistant tuberculosis are
not cured despite treatment with standard antibiotics
administered by an efficient tuberculosis control
program, a team of Mexican and Stanford researchers has
discovered. The findings, published in the March 13 issue
of Archives of Internal Medicine, show the limitations of
a TB control strategy widely applied in developing
countries, said Peter M. Small, MD, assistant professor
of medicine at Stanford University Medical Center and
senior author on the paper.
"This is extremely
bad news for resource-poor countries," Small said.
"Although affordable, increasingly available and
effective for most patients, the standard approach is
inadequate for treating patients with drug-resistant
tuberculosis. To confront this disease, new tactics are
urgently needed in countries with high rates of
drug-resistant tuberculosis."
Unfortunately,
drug-resistant TB is common. A recent World Health
Organization survey found drug-resistant TB in every
country studied and in more than half of patients in some
areas. Drug resistance emerges when patients are
inadequately treated, clearing the way for the
proliferation of resistant bacteria. To ensure completion
of the full course of drugs, public health officials
devised a strategy of testing, treatment and follow-up
called DOTS, which stands for Direct Observed Therapy,
Short-course. As the name implies, one of the
requirements of DOTS is that patients take their
medications in the presence of a health care worker.
In the United States and
other developed countries, therapy goes one step further.
All TB patients are tested to determine if the strain of
bacteria they carry is resistant to antibiotics. With
that information, the patient's doctor can tailor a
treatment best suited to eradicating the bacteria.
Costing tens of thousands
to hundreds of thousands of dollars per patient, such a
strategy is too expensive for most developing countries,
Small said. As an alternative, the World Health
Organization recommends treating every patient with a
standard, affordable regimen of drugs. Administration of
these drugs under direct observation has been hailed as
one of the most important recent public health
interventions, and it has shown to prevent the emergence
of drug resistance, Small said.
However, there is scant
data about the effects of DOTS therapy where drug
resistant TB is already a problem. Small and 11 Mexican
colleagues set out to determine how well this strategy
worked in a TB control program in Orizaba in southern
Mexico. The team found that drug resistance among the
participants was disturbingly common. Twenty-eight
percent of the 232 patients were infected with bacteria
resistant to one or more antibiotics, while 11 percent
were infected with bacteria resistant to at least two
drugs.
Whether a patient harbored
drug-resistant strains had an important influence on the
outcome of treatment. While 2 percent of patients
infected with non-resistant bacteria weren't cured,
treatment failed for 56 percent of the patients infected
with strains resistant to multiple drugs. And though only
10 percent of the patients with antibiotic-susceptible
strains died during the study, 28 percent of those with
multi-drug-resistant strains died.
"Administering
standard regimens independent of the susceptibility of
the infecting organisms did not work," Small said.
"In settings where there are significant rates of
resistant TB, standard DOTS therapy, while essential, may
not be sufficient," he added. However, given the
financial limitations of the developing countries, it is
not clear what kind of treatment program would work
better, Small said. "International collaborations
will be essential to devising improved strategies.
Tuberculosis does not respect national borders and
neither should tuberculosis research and control
efforts."
The researchers also found
evidence to support the controversial idea that
drug-resistant strains are less likely to spread from
person to person. Using DNA fingerprinting, they sorted
the patients into 20 groups, or clusters, according to
the genetic characteristics of their bacteria. All the
people in each cluster can trace their infections to the
same ultimate source. Compared with patients infected
with non-resistant strains, patients who had
drug-resistant strains were less likely to belong to a
cluster, which suggests that they are not transmitting
the disease to as many other people. "The
observation that the most highly drug-resistant bacteria
were less transmissible is at best a very thin silver
lining in a fairly dark cloud," Small said.
"Drug-resistant tuberculosis had a profoundly
negative impact on these patients."
Small's Mexican
collaborators were from the Instituto Nacional de Salud
Publica in Cuernavaca, the Instituto National de la
Nutricion Salvador Zubiran in Mexico City and the
Instituto Nacional de Diagnostico y Referencia
Epidemiologicos in Mexico City.
A grant from the National
Institute of Allergy and Infectious Diseases, a branch of
the National Institutes of Health, supported the study.
SR
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