TOXOPLASMOSIS UPDATE

Opportunistic infections of the protozoan Toxoplasma gondii
are usually controlled by the standard therapies, pyrimethamine
with sulfadiazine, or pyrimethamine with clindamycin for people
who are allergic to sulfa drugs. (The toxicity of pyrimethamine
can be countered with leucovorin). These drugs kill the mature
parasites but unfortunately not the cysts from which more
protozoa will emerge. So the treatments must be continued
indefinitely on a "chronic suppressive" basis. Even during
maintenance therapy, relapses are not uncommon.

Researchers at the University of Geneva reported last month
that doxycycline, a commonly prescribed antibiotic, worked better
than pyrimethamine for protecting mice infected with T. gondii
(Chang and others, 1990). A combination of the two worked better
than either drug alone. We could not find any physicians in this
country who had tried doxycycline to treat patients with
toxoplasmosis, even though an abstract of the Swiss work was
presented last September in Houston at the Twenty-Ninth
Interscience Conference on Antimicrobial Agents and Chemotherapy.
Doxycycline may provide an option in future situations when the
standard drugs fail.

Neither could we find anyone who had tried the other
possibilities sometimes discussed for use against toxoplasmosis:
arprinocid, azithromycin or trimetrexate. AIDS TREATMENT NEWS
#79 reported at length on these and other aspects of this
infection, and although that was over a year ago, little has
changed to improve significantly the survival rates for this
diagnosis. We hope that the upcoming International Conference
will report experience with new treatments.

Some success has been obtained with fresh applications of
the drugs at hand. Using an idea presented at the last
International Conference in Montreal, Larry Waites, M. D. of San
Francisco has improved the outlook for his patients by pulse-
dosing the treatments for toxoplasmosis, giving them two times a
week instead of daily (see Pedrol, E and others, 1989).

Another source of optimism comes from trials now under
consideration which would try low doses of pyrimethamine or
clindamycin to prevent reactivation of latent infections in
patients at risk. Fansidar has been tried as a prophylaxis, but
this drug has been associated with fatal allergic reactions in
some people. Fansidar was discussed at length in the January
issue of Treatment Issues, published by the Gay Men's Health
Crisis in New York, and again in the May issue of BETA, published
by the San Francisco AIDS Foundation.

The notion of some prophylactic measure makes sense for
people with HIV who have been exposed to T. gondii if the risk of
side effects from such therapy is outweighed by the benefit of
preventing disease. Prophylaxis is already the norm for people
at risk for Pneumocystis pneumonia (using septra, dapsone or
aerosol pentamidine), and is gaining interest for suppressing
latent infections of MAI (clofazimine or ansamycin) and
Cryptococcus (fluconazole). Incidentally, although all of these
microbes are widely present in the environment, T. gondii could
be the easiest to avoid, since many people acquire the infection
by eating undercooked meat. Also, cats are the natural hosts of
the parasite's reproductive cycle. All HIV+ people should avoid
contact with cat feces, whether or not they test positive for
past exposure. Careful hand washing is critical after handling a
pet cat and before eating or preparing food.

Toxoplasmosis usually presents itself as encephalitis, an
inflammation of the brain from lesions caused by T. gondii.
Robert Neger, M. D., reported in April to the Community
Consortium in San Francisco the less frequent but real danger of
retinal and optic nerve manifestations. This would be of obvious
interest to other ophthalmologists who are consulted by HIV+
patients reporting vision problems which ordinarily would be
approached as CMV retinitis. Dr. Neger noted that the most
complete exam of the retina must use indirect ophthalmoscopy,
after dilating the pupils.

A contrasting example of misdiagnosis was presented to the
Community Consortium last January. Martin Mass, M. D., discussed
the case of a patient who showed symptoms of neurological
problems memory loss and walking balance difficulty. An MRI scan
showed multiple brain lesions, but this scan cannot distinguish
toxoplasma infections from lesions caused by PML, herpes or
lymphoma. The patient's bloodwork tested positive for antibodies
to T. gondii, and in accordance with standard practice, he was
started presumptively on drugs to treat toxoplasmosis.
Unfortunately, his condition did not improve, and a subsequent
brain biopsy identified the lesions conclusively as lymphoma.
Dr. Mass suggested that if biopsies were performed earlier for
patients with neurologic symptoms, the resulting diagnosis would
be more accurate and treatment more timely. Other physicians
discussing the case felt that the current three-week trial of
presumptive toxo treatment is still appropriate.

We wonder why the development of new toxoplasmosis therapies
and prophylaxes appears to be so snail-paced. Perhaps the
existence of an already-approved treatment regimen translates
into a disincentive for pharmaceutical companies which are
primarily interested in first-line drugs targeted for large
"hostage" markets. If this is true, patients who cannot tolerate
the approved treatments, or who face drug- failure relapses are
casualties of the ubiquitous "health for profits" motivating
medical research today. This epidemic will be haunting the world
for decades to come unless that motivating force of research is
replaced by "health for people."

We plan to report developments, or the vacuum of
developments, in treating toxoplasmosis and other opportunistic
infections after the International Conference later this month.

References

Pedrol, E and others. Central nervous system toxoplasmosis in
AIDS patients. Efficacy of an intermittent maintenance therapy.
V International Conference on AIDS, abstract M. B. O. 37,
Montreal, June 5, 1989.

Chang, HR and others. In vitro and In vivo effects of
doxycycline on Toxoplasma gondii. Antimicrobial Agents and
Chemotherapy, volume 34, number 5, pages 775-780, May, 1990.