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TREATMENT OF PARASITIC DISEASES 447
persons sleeping in adobe dwellings in rural,
endemic areas in Latin America. The incidence
of new infections has decreased in
Brazil and other countries due to urbanization
and improved living conditions, but millions
of persons remain infected. Trypanosoma
cruzi can also be transmitted via blood transfusion,
which is a major concern in endemic
countries in Latin America as well as in North
America, where a substantial number of
chronically infected immigrants now live. Less
commonly, infection occurs across the placenta
or following a laboratory accident.
Acute Chagas’ disease can be life threatening,
but it is usually a non-specific febrile illness in
children and others living in endemic areas that
resolves spontaneously without diagnosis or
therapy. After the resolution of acute symptoms,
infected persons enter a prolonged, asymptomatic,
indeterminate phase. Some of those
chronically infected have no further evidence of
disease, while others develop chronic Chagasic
cardiomyopathy or mega-disease of the esophagus
or intestines decades later. The cardiomyopathy
is associated with histopathological
changes of chronic inflammation of the heart.
Mega-disease is associated with destruction of
the myenteric plexus in the gastrointestinal
tract. These late manifestations of infection are
thought to be due at least in part to toxic effects
of the host immune response.
In the treatment of acute Chagas’ disease,
anti-parasitic chemotherapy is effective in
shortening the duration of symptoms and
decreasing the likelihood of death. Until
recently, chemotherapy was not thought to
have a role in the treatment of persons with
indeterminate or chronic Chagas’ disease. Data
from Latin America now suggest that treatment
of young persons in the indeterminate phase
of infection cures more than half and may
reduce the likelihood of chronic Chagas’ disease
developing later in life. Once symptoms
of cardiomyopathy or mega-disease develop,
anti-parasitic chemotherapy is thought to have
minimal value in reversing the chronic pathological
changes. Unfortunately, the only drugs
now available for Chagas’ disease, nifurtimox
and benznidazole, are relatively toxic and
require prolonged administration.
Nifurtimox
Nifurtimox has been the mainstay of therapy
for Chagas’ disease in the United States.
Although it is currently out of production,
remaining supplies are available through the
Centers for Disease Control and Prevention.
Treatment with nifurtimox reduces the duration
of symptoms and the likelihood of death
from acute Chagas’ disease. Treatment failures
occur, and there is geographic variation in
responsiveness. Therapy for 90 days is recommended,
but treatment must often be terminated
prematurely because of drug toxicity.
Nifurtimox is well absorbed orally. The
mechanism of action is uncertain, but it may
be related to free radical formation and oxidative
damage to the parasite. Its effects are not
specific to the parasite, and as a result, nifurtimox
is associated with multiple side-effects
including nausea, vomiting, weight loss, severe
neuritis, weakness, paresthesias and sleep
disturbances.
Benznidazole
Benznidazole is used for the treatment of
Chagas’ disease in Latin America. It is well
absorbed orally and is administered for periods
of 30 to 90 days. The mechanism of action is
not known, but it, too, is a nitroimidazole and
may act by free radical formation. Benznidazole
causes dose-dependent polyneuropathy, gastrointestinal
side-effects, psychological disturbances
and allergic skin rashes.
MEDICAL APPLICATIONS