CRYPTOSPORIDIOSIS: GUARDED PROGRESS

Some quiet developments may be breaking the miasma of
research to find an effective treatment for Cryptosporidium
parvum infection, which causes severe diarrhea. For
background reports on various antibiotics and other approaches,
see AIDS TREATMENT NEWS #95 and #107. Following is
additional information on some of the drugs discussed in those
articles.


Diclazuril, Related Developments

Diclazuril is a veterinary drug used to treat parasites in
chickens, and over a year ago was found to help some people
with cryptosporidiosis. Contrary to what we implied in our
previous articles, diclazuril is not marketed to U.S.
veterinarians, although a number of people have acquired
personal supplies from other countries.

A version redesigned by the manufacturer, Janssen
Pharmaceutica, for human use was tested in recent clinical trials
in New York. Rosemary Soave, M.D., reported the results thus
far at the Sixth International Conference on AIDS in June. She
tested daily doses from 200 mg to 600 mg, and saw the best
responses at the higher doses.

Even though cryptosporidiosis is usually not a problem
outside the gastrointestinal tract, Dr. Soave said that those
people who experienced the best response to diclazuril also
showed higher levels of the drug in their bloodstream. So
Janssen is again reformulating diclazuril to improve
absorbability. Trials of the improved compounds are planned,
but details have not been released. Meanwhile, Janssen has
applied to the Food and Drug Administration for permission to
provide compassionate use access to diclazuril.

On a speculative note, a pharmacist told us that a close
chemical relative of diclazuril, called toltrazuril, is also used
for treating parasites in animals. Toltrazuril, a product of
Bayer (under the trade name Baycox), is a broad-spectrum
anti-protozoal used to treat sheep, poultry, and fish. Like
diclazuril (trade name Clinicox), it is marketed in some Latin
American countries for veterinary use. We were told that in
animal studies, toltrazuril was as safe as diclazuril, and that
it is formulated in a liquid more concentrated than the
diclazuril powder mixed with poultry feed. However, we know of
no human experience with toltrazuril nor of any laboratory data
testing it against Cryptosporidium. A veterinarian friend of
ours is looking further into toltrazuril, as well as other
veterinary drugs which might be able to treat infections in
humans.

Humatin Success?

One of the studies of cryptosporidiosis presented at the
Sixth International Conference was a hospital chart review of
patients treated with the common anti-parasite drug paromomycin
(brand name Humatin); the study found good results (see AIDS
TREATMENT NEWS #107, July 20, 1990, page 5). Surprised that
an ordinary, available medicine was found useful after years of
research into numerous possibilities, we contacted the author of
the abstract, Joseph Gathe, M.D., at Park Plaza Hospital in
Houston. Dr. Gathe said that he continues to see very good
responses to paromomycin in about 90% of his patients with
cryptosporidiosis. The improvements include a substantial
decrease in the quantity and frequency of diarrhea, and often a
decrease in stool counts of the parasite's cysts.

This drug is an intraluminal agent, which means it passes
through the gastrointestinal tract with little absorption into the
bloodstream. Dr. Gathe explained that this characteristic is an
advantage for controlling toxicity (none was seen in his
patients), but would make the drug useless for treating
infections which have disseminated to other body systems.
However, drug handbooks caution that if this drug should reach
the bloodstream, such as through intestinal ulcers or blockage, it
could lead to hearing loss or kidney toxicity or other side effects
attributed to large or extended doses of aminoglycoside
antibiotics.

We consulted three other physicians who have tried
paromomycin in the past to treat cryptosporidiosis: two of them
had not seen any response. One of the two pointed out that
chart reviews can be unreliable methods of drawing conclusions
about a treatment because they analyze data retrospectively,
without control over variables which a prospective clinical
study would eliminate or at least manage.

The third was Paula Sparti, M.D., a respected HIV physician
in Miami. She has tried paromomycin with her patients diagnosed
with cryptosporidiosis, sometimes without any results. But one
of her patients responded dramatically within 36 hours after
starting paromomycin, at 500 mg given four times daily. His
profuse diarrhea completely cleared, and related abdominal
pain subsided. Shortly after, a patient treated by an associate of
Dr. Sparti's responded similarly to the drug.

Dr. Sparti's assessment is that some people, not all, may
benefit from paromomycin. She feels that since it is available
and safe, people with cryptosporidiosis should be offered a trial.
If there is no improvement within 7 to 10 days, the drug can be
discontinued.

It is possible that some of the differences in response to
the drug may result from the difficulty in diagnosing intestinal
infections. In the search for a cause of diarrhea or
malabsorption, several organisms capable of causing illness
might be identified in stool specimens. Other microbes may not
be readily found in the specimens, yet be present and causing
problems in the intestinal tract. Given these uncertainties, the
treatment for diarrhea and resulting weight loss can be hit and
miss. If symptoms begin to clear up during the administration
of a given drug, such as paromomycin, it might not always be
possible to know which organism the drug acted upon, if any.

Macrolide Antibiotics?

Two other drugs tried so far to treat this infection are
spiramycin and clindamycin; there have been positive, but
limited, results. Clindamycin is already approved to treat
certain infections; spiramycin is an investigational macrolide
antibiotic, available through compassionate use. A related drug
called azithromycin, approved in Yugoslavia, has strong
laboratory activity against another protozoal infection,
toxoplasmosis. Human trials to test azithromycin against
toxoplasmosis are long overdue. A pilot study testing the drug
in MAI infections is already in progress. The manufacturer,
Pfizer, Inc., is now working toward FDA approval as a treatment
for certain respiratory infections and chlamydia. We have heard
that some buyer's clubs are investigating how to increase access
to azithromycin in this country.

Given azithromycin's broad potential, we wondered about
trying it for cryptosporidial infections. We spoke to Shelley
Gordon, M.D., an infectious disease specialist in San Francisco
who usually tries clindamycin with primaquine to treat
cryptosporidiosis, with some success. She noted that her
patients with higher helper cells tend to have the best results.
We asked her about the logic of trying azithromycin, and she
agreed that it is worth considering. A spokesperson for Pfizer
told us that they were not aware of any studies suggesting that
azithromycin has activity against Cryptosporidium.

The safety and availability of paromomycin suggest that it
is worth trying for cryptosporidiosis. Diclazuril and its future
analogs appear promising, and speedy development could spare
many people from resorting to veterinary versions.
Azithromycin is a speculative possibility, but it warrants
research attention. These drugs, like clindamycin, spiramycin,
and hyperimmune milk, may work for some people some of the
time. Until one is proven consistently effective, we support
aggressive experiments with the reasonable choices at hand.