Cryptosporidiosis: Scattered Success, Research Delays

Several antibiotics and antidiarrheals were among the
treatments discussed at the International AIDS Conference last
month for use against AIDS-related infections of Cryptosporidium
parvum. Rosemary Soave, M. D., has been investigating new
therapies for cryptosporidiosis at Cornell University. She
presented results of her studies of diclazuril and spiramycin, as
well as data on other agents under investigation.

The results regarding diclazuril were approximately the same
as those reported in our last update on treatment for
cryptosporidiosis (see AIDS TREATMENT NEWS #95, Jan. 19, 1990).
Various responses of symptom improvement and decreases in counts
of the parasite's oocysts were seen using doses ranging from 200
mg to 600 mg a day, with stronger responses at the higher doses.

Dr. Soave noted that serum (blood) levels of diclazuril were
measurably higher in participants who had the strongest response.
The drug used in these studies was hastily prepared for human
consumption after a veterinary version for treating parasites in
poultry, under the trade name Clinicox, was also discovered
recently to be useful in some people. Ironically, the original
compound formulated for chickens was apparently better absorbed
than the newer "human" version. We have not heard of any ill
effects in people who tried the veterinary product.

Dr. Soave is eager to continue studies of diclazuril, but
the manufacturer claims there are limited supplies of the drug
for humans. We spoke to Mr. Bob Lagendre, spokesperson for
Janssen Pharmaceutica in the U. S., who said that they are now
revising the formulation to improve absorption and that within a
few months the manufacturing headquarters in Belgium hopes to
make available two new analogs, dubbed "clazuril" and
"letrazuril." These will be studied in six new trials around the
U. S.

In the past, oral spiramycin did not appear to affect
cryptosporidiosis significantly. But administered intravenously,
spiramycin is now obtaining some good results. Of fifteen
patients who completed a regimen of IV spiramycin, four
experienced a complete response in symptom improvements and a
decrease in cyst counts. Two of the four exhibited a complete
absence of parasites in stool specimens after the treatment.

Other therapies presented at the Conference included
hyperimmune bovine colostrum, transfer factor, paromomycin,
loperamide oxide, and two analogs of the drug somatostatin, SMS
201-995 and Vapreotide.

Hyperimmune colostrum has been discussed now for several
years as a potential therapy for cryptosporidiosis. The
particular study presented at the Conference was authored by
several Danish institutions and offered mildly positive results.
Another study of colostrum was recently reported in AIDS (volume
4, number 6) by researchers at St. Vincent's Hospital in New
York. A very small study of five patients produced results which
warrant larger, more carefully-designed trials of colostrum.

The transfer factor discussed by Dr. Soave was an extract of
lymphocytes derived from infected cows. Fourteen people who
received this transfer factor demonstrated both improved symptoms
and decreased cyst counts. Neither hyperimmune colostrum nor
transfer factor are widely accessible now to people diagnosed
with cryptosporidiosis.

Paromomycin, a prescription drug available under the brand
name Humatin, is used for treating intestinal parasites. Park
Plaza Hospital in Houston presented a 24-month chart review of 23
episodes of gastrointestinal cryptosporidiosis in 12 patients who
were treated with paromomycin. All the patients showed some
degree of symptom improvement after receiving the antibiotic, and
in seven patients' stools the organism became undetectable.
Minimal toxicity was reported. The dosing ranged from 1500 to
2000 mg daily, for a median duration of two weeks.

Loperamide, marketed as an antidiarrheal under the trade
name Imodium, and the investigational somatostatin analogs were
discussed as attempts to control AIDS-related diarrhea, and not
as a cryptosporidia treatment per se. Managing the debilitating
symptoms of diarrhea and weight loss of cryptosporidiosis is a
critical measure, though only a stop-gap one.

Meanwhile, a truly effective treatment for eradicating this
infection is urgently needed.

References

The Conference tape of Dr. Soave's presentation is tape #90ICA-
63. (For information on ordering Conference tapes or abstracts,
see "Obtaining Conference Information," below.)

The following references are to the three-volume set of abstracts
of the Sixth International Conference on AIDS:

Gathe, J and others. Treatment of gastrointestinal
cryptosporidiosis with paromomycin. Park Plaza Hospital,
Houston, Texas. Abstract #2121.

Girard, PM and others. Preliminary results of Vapreotide (a new
somatostatin analog) in AIDS related diarrhea. Hopitaux Bichat-
C Bernard, Necker, St Antoine, Paris, France. Abstract #Th.B365.

Hojlyng, N and others. Cryptosporidium diarrhoea in AIDS
patients treated with hyperimmune bovine colostrum. Statens
Seruminstitut, Copenhagen, Denmark. Abstract #Th.B. 521.

Mallolas, J and others. Efficacy and tolerance of SMS 201-995 (a
somatostatin analog) in HIV infected patients with diarrhea.
Hospital Clinic, Barcelona, Spain. Abstract #Th.B. 364.

Mukololo, P and others. Efficacy of loperamide oxide in HIV-
related diarrhoea. University Teaching Hospital, Lusaka, Zambia.
Abstract #2025.

Soave, R and others. Oral diclazuril therapy for
cryptosporidiosis. Cornell Medical Center, New York University
and St. Luke's/Roosevelt, New York. Abstract #Th.B. 520.