Cryptosporidiosis, and Treatment Leads: Preliminary Report

Cryptosporidiosis is a serious, sometimes fatal opportunistic infection which causes severe diarrhea. Persons
with a normal immune system can get the disease, which seems to be responsible for many cases of ordinary diarrhea, but they recover in a few days or at most about two weeks. Persons with a serious immune deficiency may not recover, however; and at least 20 drugs expected to be effective against this organism have been tried but they largely failed to work. No one knows why the parasite which causes the illness is so resistant to available antibiotics.
Some people with AIDS do recover spontaneously from cryptosporidiosis, however, and at least one drug does seem to cure or control the disease in some people.
This article cannot offer a complete or authoritative coverage of cryptosporidiosis. Instead, we called physicians,
alternative practitioners, and persons with AIDS, to collect leads about treatments they may have found helpful or have
reason to believe might offer promise. We didn't find confirmed cures, of course, but several treatments are clearly
worth more investigation. These are listed after the "background" section below.
Readers should be warned that we have not been able to check out these treatments--their dangers or supporting
evidence--as much as we usually do. The leads presented here are only options to consider and explore with one's physician. We hope this article will help researchers by highlighting a wide range of treatment options worthy of investigation.

Background

An authoritative review of the published literature, covering what was known about cryptosporidiosis as of July
1987, appears in "Cryptosporidiosis: Overview, Epidemiology, Microbiology and Pathogenesis" by Constance Wofsy, M.D. This article was published on AIDS Knowledge Base, a computerized collection of AIDS articles written mainly for physicians. We summarize some of the information here; our comments are in parenthesis:
* The organism cryptosporidium, a protozoan (single-cell animal), was first discovered in animals in 1907, and in humans in 1975. It is an intestinal parasite which later was found to cause many cases of ordinary diarrhea. (Presumably it has long been a common infection in humans, but was not recognized until recently because it was hard to diagnose.)
The organism is related to the protozoan which causes toxoplasmosis.
* Infection can be diagnosed by bowel biopsy, or by examination of stools, but special techniques must be used for
the stool examination, since otherwise the protozoan looks like yeast and can easily be missed.
* The disease can spread from person to person or from animals to persons, probably by feces to mouth transmission. The incubation period is five to 14 days.
* Even in severe cases, cryptosporidiosis causes little structural damage to the intestines. This finding suggests
that the organism may cause the diarrhea by secreting a t oxin, as cholera does. (It also suggests that full recovery should be possible even after severe illness, if the organism could be eliminated or if the effect of the toxin could be blocked.)
* Cryptosporidiosis usually appears late in AIDS, when other infections are present. But this disease alone, if it
lasts more than a month in a person not know to have any other immune deficiency, is now officially part of the definition of AIDS. About four percent of AIDS cases are diagnosed this way, with cryptosporidiosis as the presenting infection.
(The disease seems less common than we had feared. Many physicians and other practitioners we spoke to who treat AIDS patients had seen few or no cases.)
* Cryptosporidium can sometimes spread outside the digestive tract, to infect the gall bladder or respiratory
system, but it has not been found to infect other organs.
* In an animal study, 25 drugs which were tried failed to treat cryptosporidiosis effectively. In humans only one drug,
spiramycin, seemed to cure or control the disease in some cases.
Spiramycin, an antibiotic with little toxicity, is manufactured by Rhone Poulenc and used in Canada and Europe to
treat a number of infections, including toxoplasmosis. In 1982, the U.S. Centers for Disease Control reported that the
drug showed benefit in some cases of cryptosporidiosis. But today (over five years later) the drug is still available in
the U.S. only for investigational use.
(Today at least one placebo-controlled trial being conducted in the U.S., apparently required as part of the FDA
approval process. Meanwhile we don't know how many U.S. patients are or are not able to get spiramycin when medically indicated.)
* Besides spiramycin, most medical treatment for cryptosporidiosis has been supportive, such as fluid and
electrolyte replacement, antidiarrheals, and sometimes total parenteral nutrition (intravenous feeding) if the patient
cannot absorb food.

Additional Background

We interviewed a gastroenterologist who has treated a number of cases of cryptosporidiosis, and he added the
following information:
* The disease can vary greatly in severity. If the infection is in the lower bowel only, the persons can still
absorb food. The disease is worse if it also affects the small intestines and the stomach.
* In some patients, as in persons with cholera, the intestines expel water, as if a pump were turned on by a
biochemical switch. This mechanism apparently requires certain prostaglandins, and sometimes the switch can be turned off by drugs like indocin which inhibit prostaglandin synthesis. The patient still has the more usual diarrhea, however.
(Note: There are other indications that one kind of prostaglandins are involved in causing damage in AIDS. Some
physicians have used nonsteroidal anti-inflammatory drugs like indocin to mitigate this damage, but word of this treatment possibility has not spread widely among physicians. Some non- prescription drugs such as ibuprofen or even ordinary aspirin might also have a similar beneficial effect, but prescription drugs seem to be preferred by knowledgeable physicians.)
* This physician thought that somatostatin might be a valuable treatment for controlling the diarrhea in some cases.
However, it has not yet been tried for cryptosporidiosis.

Treatment Leads

We only have sketchy information about most of these treatment possibilities, and list them here as leads for
further research. We arranged this list more or less in order starting with the more conventional--not necessarily more or
less powerful, or better or worse. This list resulted from only a few days' research and is certainly incomplete. And we
have largely omitted the many routine supportive therapies.
* Spiramycin. See discussion above.
* Hyperimmune milk. This treatment, developed by Donald Kotler, M.D., of Columbia University St. Luke's/Roosevelt
Hospital Center, extracts antibodies from milk of cows exposed to cryptosporidiosis. An ongoing study will need more
volunteers; at this time, however, the project cannot get enough supplies of the milk extract. For information about the
study, call Anita in Dr. Kotler's office, at (212) 870-6154.
An Australian team is also studying this treatment, but for children with a congenital immune deficiency, not with
AIDS.
* Trimetrexate with leucovorin. This new treatment for pneumocystis looks very good theoretically. But we do not know
of any human test for cryptosporidiosis at this time. Trimetrexate, a experimental drug used in cancer treatment, is given in toxic doses for treating pneumocystis. Leucovorin is an antidote which rescues human cells from the trimetrexate. Protozoa cannot use the leucovorin, however, so the trimetrexate kills them without killing the human cells.
Physicians are interested in trying the treatment for cryptosporidiosis, which is also caused by a protozoan.
As a pneumocystis treatment, trimetrexate with leucovorin has had very few side effects (Allegra and others, 1987); it
had to be discontinued in only one of 49 pneumocystis patients in this trial, reported last October in the New England Journal of Medicine. This therapy should be available for cases when other pneumocystis treatments do not work or cannot be used, as it was found to save the lives of over two thirds of pneumocystis patients when standard drugs had failed. Laboratory studies have also suggested possible promise for toxoplasmosis.
We will continue to follow trimetrexate with leucovorin as a treatment for pneumocystis, and possibly for
cryptosporidiosis and other protozoal diseases.
* Bovine transfer factor. We don't have details of this research at this time.
* AZT. There have been reports of cryptosporidiosis improving or clearing up entirely in some persons when they
were treated with AZT. At this time we have little information. For one published report, see the letter in
American Journal of Medicine, July 1987, page 187.
* Artemisia Annua. This herb, a close relative of wormwood, is used in China to treat malaria, and appears to be clearly effective against malaria which has become resistant to antibiotics. Malaria, like cryptosporidiosis, is caused by a protozoan.
We have heard a report that at least one U.S. physician has obtained Artemisia Annua from China and used it
successfully to treat cryptosporidiosis, but we have not yet been able to contact anyone with first-hand experience.
* Garlic. Garlic appears to have some effectiveness against many microorganisms. For example, it has been used in China to treat cryptococcal meningitis.
While this disease is apparently unrelated to cryptosporidiosis, this indication that an active ingredient in
garlic crossed the blood-brain barrier led John Athey, a well- known person with AIDS in San Francisco, to try large amounts of garlic for controlling his toxoplasmosis. According to his report at a seminar organized by Tom O'Connor (the author of Living With AIDS: Reaching Out), a large amount of garlic has clearly worked every time for him--not to cure the disease, but to control it and stop the symptoms. Toxoplasmosis is caused by a protozoan related to the one which causes cryptosporidiosis.
However, we did not find anyone who had used garlic for cryptosporidiosis, or who knew anyone who had. And the
gastroenterologist we interviewed (above) doubted that it would work.
* Acidophilus. Acidophilus, commonly sold in health-food stores, consists of billions of living beneficial
microorganisms which may help crowd out the disease-causing ones. There are great variations in types of acidophilus, and in the quality of the products. We heard good reports about the Jarro-Dophilus brand, and also about a brand from West Germany called Eugalan Forte.
* Hydrogen peroxide. We talked to one person who was convinced that drinking dilute hydrogen peroxide helped him
recover from cryptosporidiosis; he was also using an aloe vera preparation and acidophilus. But there is much controversy about hydrogen peroxide. People disagree greatly about its possible benefits and dangers. We are looking for more information about this treatment, but don't have a clear picture at this time.

References

Allegra CJ and others. Trimetrexate For the Treatment Of Pneumocystis Carinii Pneumonia In Patients With the Acquired Immunodeficiency Syndrome. New England Journal of Medicine, p. 978-985, October 15, 1987.
Klayman DL. Qinghaosu (Artemisinin): An Antimalarial Drug From China. Science p. 1049-1055, May 31 1985.
Horn, Bill. Bibliography On AIDS and Nutrition, Gastrointestinal Tract Lesions, Physiology and Organ Function.
Published by Bill Horn, Nutrition Services, 1517 San Andreas Ave., San Jose, CA 95118, (415) 266-7040.
Wofsy C. Cryptosporidiosis: Overview, Epidemiology, Microbiology and Pathogenesis. Published on AIDS Knowledge Base computer system. Access is available through BRS Colleague information-retrieval service; for information call (800) 468-0908.


***** Announcements *****

* More seminars by Tom O'Connor. Tom O'Connor, author of the excellent book Living With AIDS: Reaching Out (available in most gay bookstores) is continuing his one-day seminars in San Francisco. All seminars are 9:00 to 5:00 Saturdays at the Metropolitan Community Church, 150 Eureka St., in the Castro. * Feb. 20: Being Educated and In Control When Using Doctors and Hospitals.
* Feb. 27: Putting Into Place Quickly All the Resources Available To Persons With Low Income.
* March 5: Drugs, Nutrition, and Stress Reduction.
* March 12: Nutrition and Supplements For Building the Immune System.
Each one-day seminar costs $25. regular ($12. low income) if you register in advance by mail. At the door, prices are
$5. more.
To register, send a check to Tom O'Connor, P.O. Box 2806, San Francisco, CA 94126. You can call him at (415) 821-0853 for more information.

* Treatment Issues reviews Carrisyn, Dextran Sulfate. Treatment Issues, the Gay Men's Health Crisis newsletter of
experimental AIDS therapies, reviewed both Carrisyn/aloe juice, and dextran sulfate, in its second issue, December 31, 1987. Both received very favorable reports.
Barry Gingell, M.D., the editor of Treatment Issues, has studied Carrisyn in depth during the last several months--
including visiting physicians in Dallas and studying detailed medical records. Therefore we have waited for his article
instead of writing our own. Now his report is available.
The same issue has a short but important writeup on dextran sulfate, one of the most promising antivirals being
tested today. We will cover dextran sulfate in a future issue.
Both of these treatments are more or less available.
The issue also has an update on Fusidin (fusidic acid), which does NOT look very good at this time, although it has not been ruled out.
For more information, you can obtain Volume 1 Number 2 of Treatment Issues from: GMHC, Department of Medical Information, 132 West 24th St., Box 274, New York, NY 10011. GMHC distributes Treatment Issues at no charge; you can get on their mailing list for future issues.

* AIDS Organization and Hotline Directories. KPIX Channel 5, which together with the San Francisco Examiner co-sponsored the unveiling of The Names Project quilt in San Francisco's Moscone Center, has published AIDS Lifeline, an excellent San Francisco/Northern California annotated directory "of organizations and agencies who use volunteers in their services to people with AIDS and their loved ones". Over 50 organizations are listed. To obtain a copy of this short directory, write or call KPIX Channel 5, Public Relations Department, 855 Battery St., San Francisco, CA 94111, (415) 765-8874; ask for the AIDS Lifeline Directory.
An extensive national directory of hotlines and organizations listed by state was published in Medical Times,
p. 91-98, September 1987. And a list of PWA (People With AIDS) organizations is published by NAPWA, 2025 "I" Street NW, Suite 415, Washington, DC 20006.

* DHEA Safety Note. DHEA (covered in AIDS Treatment News number 48) is sold by a number of suppliers all over the world. But some of these products are not intended for human use and may contain toxic hormones or other harmful byproducts of the manufacturing process.
The best way to assure that a product is safe is to use pharmaceutical grade, intended for human use. Other grades
might be safe, but they might not be, and expert advice would be essential in determining their safety if pharmaceutical
grade cannot be obtained.
Unfortunately there is no simple test to tell whether a given sample of DHEA is fit for human use. DHEA can be
synthesized (or extracted from natural sources) in many different ways. A chemist testing a sample must know how that
product was manufactured, in order to know what impurities to look for.