Potential therapies for Cryptosporidium parvum
some in vivo results

Updated: 18 February 2008
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At the present, there is no totally effective therapy for eliminating Cryptosporidium parvum other than a healthy, intact immune system. Hundreds of compounds have been tested both in vitro and in animal models, but clinical trials in humans have yielded disappointing results. Saying that, however, it appears that effective intervention can sometimes be achieved using combinational nucleoside analogs and protease inhibitors (cocktails), which are currently used for inhibiting propagation of HIV. Several antimicrobials, for instance paromomycin and nitazoxanide, also have some effect on the parasite and can occasionally eliminate the disease. Finally, there is also some evidence that a couple of the antibody based therapies may, under some circumstances, reduce or eliminate the parasite. Below I have listed in vivo results of some select, potentially effective, and commercially available compounds pertaining to chronic cryptosporidiosis. I have avoided citing studies where the treatment regime was poorly defined, the paper confusing, or additional drugs were being given to the patient and it was unclear what might have actually been acting on the parasite. Some effective compounds, such as the ionophores, have been totally ignored because of their known toxicity to humans and I have not listed the bovine milk products since I have a bibliography on that topic here.


Antiretrovial therapies

  1. Indinavir at 800 mg three times a day for 24 weeks eliminated the parasite in two AIDS patients with chronic cryptosporidiosis (1998, AIDS 12: 35-41)
  2. Three AIDS patients given antiretrovial therapy for chronic cryptosporidiosis had resolution of diarrhea (4-8 weeks) and elimination of the parasite from the intestinal tract (when examined at the end of the treatment). The treatment for one patient was ritonavir at 600 mg twice daily, saquinavir at 600 mg three times daily, and stavudine at 40 mg twice daily for 22 weeks; the treatment for a second patient was indinavir at 800 mg three times a day and stavudine at 40 mg twice daily for 12 weeks; and the treatment for the third patient was indinavir at 800 mg three times a day, stavudine at 40 mg twice daily, and lamivudine at 150 mg twice daily for (apparently) 12 weeks (1998, Lancet 351: 256-261)
  3. Indinavir at 800 mg three times per day, and zidovudine at 200 mg three times per day, were administered for an unspecified length of time to an AIDS patient with chronic diarrhea due to cryptosporidiosis. Within 3 months the patient had gained 23 pounds and 3 different stool examinations failed to reveal oocysts (1997, Am J Gastroent 92: 726)
  4. Zidovudine at 100 mg IV every 4 hours, and acyclovir at 500 mg three times a day, were administered for 4 weeks to an AIDS patient with chronic cryptosporidiosis. At the end of this treatment, no oocysts were found in the stools although the patient eventually died of cardiac failure (1989, Gastroenterology 97: 1327-1330)
  5. A statistical survey revealed a decrease in the prevalence of cryptosporidiosis in AIDS patients in France between January 1995 and December 1996. This was directly correlated with the introduction and use of protease inhibitors (1998, AIDS 12: 1395-1397).
  6. Six month courses of combinational antiretroviral therapy (3-4 different anti-retrovirals were administered per individual) were found to eliminate infections in two patients (1999, AIDS 13: 734-735). A third patient receiving only a one month treatment relapsed once the drugs were withdrawn.
  7. A wide variety of combinations and dosages of protease inhibitors and/or nucleoside analogs, along with paromomycin, spiramycin, or azithromycin, were examined in 40 HIV+ patients with chronic cryptosporidiosis (2000, Eur J Clin Microbiol Infect Dis 19: 213-217). Prolonged combinational therapy resulted in most patients clearing infections and only two relapses were noted. Antiviral drugs used were azidothymidine, zalcitabine, stavudine, indinavir, ritonavir, saquinavir, and lamivudine.


Azithromycin

  1. Two HIV-positive teenagers with chronic cryptosporidiosis were given 250 mg azithromycin for 1 day, and then 125 mg per day for 9 additional days. No oocysts were detected in the stools after that time. A third teenager was given 500 mg on day 1, and 250 mg per day for 4 weeks before he became negative for the parasite. A three-year old HIV positive child also had chronic cryptosporidiosis and was given 10 mg/kg on day 1 and 5 mg/kg per day for 9 additional days. The child was negative for the parasite thereafter (1996, J Pediatr 129: 297-300)
  2. 40 mg/kg body weight administered for 3 weeks to a 14 month old child with chronic cryptosporidiosis due to chemotherapy. Numbers of parasites was significantly reduced, but not eliminated. Four days after completing the treatment, diarrhea with oocysts in the feces resumed. An additional 2 week course of the drug resulted in no detectable oocysts in the feces (1993, J Pediatr 123: 154-156)
  3. 200 mg/kg per day for 9 days in immunosuppressed rats with chronic cryptosporidiosis revealed the compound to reduce parasite levels dramatically, but not to eliminate it entirely as infections reoccurred after the drug was withdrawn (1991, J Inf Dis 163: 1293-1296)
  4. 1000 g given on day one, followed by 500 mg 2x per day for 2 weeks, failed to eliminate the parasite in most AIDS patients as revealed by intestinal biopsy and by the presence of oocysts in the feces (1997, Intern J. STD and AIDS 8: 124-129)


Letrazuril

  1. Fourteen AIDS patients with chronic cryptosporidiosis received escalating doses of 50-100 mg orally for 6 weeks. Seven (50%) had reduced levels of the parasite at the end of the study, and 5 (36%) apparently cleared the parasite. It was stated that some of the patients were also taking other antiprotozoal agents (1994, AIDS 8: 1109-1113)
  2. 35 patients were treated at an initial oral dose of 50 mg for 10-365 days. Less than 30% were noted to have eliminated the parasite from the feces on follow-up examinations (1995, J Acquired Immun Def Synd Human Retrovirol 10: 48-53)
  3. 50 mg once per day for one week, increasing by 50 mg weekly up to 200 mg per day, with a maximum of 4 weeks treatment, resulted in cessation of oocyst excretion in 70% of 10 AIDS patients but all remained positive for the parasite by biopsis (1997, Intern J STD and AIDS 8: 124-129)


Nitazoxanide

  1. Treatments of 500 mg 2x per day for 2 weeks, or 1000 mg 2x per day for 2 weeks, eliminated oocysts passed by most chronically infected patients in a double-blind, placebo-controlled study (1998, Trans R Soc Trop Med Hyg 92: 663-666)
  2. 100 mg/kg body weight per day in neonatal mice for 6 days reduced oocysts in the feces by 42-25% of controls (1998, Antimicrob Ag Chemother 42: 2877-2882)
  3. 150 mg/kg body weight per day of the injectable formulation in neonatal mice for 6 days reduced oocysts in the feces by greater than 95% of control animals (1998, Antimicrob Ag Chemother 42: 2877-2882)
  4. 200 mg/kg body weight per day in anti-gamma-interferon conditioned SCID mice for 10 days was ineffective at reducing parasite developmental stages in the intestinal tract when compared to controls (1998, Antimicrob Ag Chemother 42: 1959-1965)
  5. 250 mg/kg body weight per day for 11 days in gnotobiotic piglets lowered the number of intestinal development stages, but induced a drug-related diarrhea, when compared to control animals (1998, Antimicrob Ag Chemother 42: 1959-1965)
  6. 500 mg twice a day for 7 days in chronically infected stage 4 AIDS patients resulted in elimination or reduction in the numbers of oocysts by 95% in 7/12 patients, and reduction or resolution of diarrhea in 4 of the 7 (1997, Am J Trop Med Hyg 56: 637-639)
  7. A randomized double-blind, placebo-controlled study utilized 90 outpatients 12 years of age or older in Egypt. Patients received either a 500 mg tablet of nitazoxanide, 500 mg oral suspension of nitazoxanide, or a placebo 2x daily for 3 days. Patient stools were evaluated 4 days later. 27/28 (96%) patients receiving nitazoxanide tablets responded clinically with 26/28 (93%) free of oocysts in 2 post-treatment stool samples. Oral suspension results were similar to those of tablets. Patients receiving the placebo cleared infections 10/27(37%) of the time (2006, Clin Gastroent Hepatol 4: 320-324)


Paromomycin

  1. 50 mg/kg body weight per day in neonatal mice for 6 days reduced oocysts in the feces by greater than 98% when compared to control animals (1998, Antimicrob Ag Chemother 42: 2877-2882)
  2. 100 mg per kg body weight per day or more (7-17 days post-infection) was effective at reducing shedding of oocysts in immunosuppressed rats with persistent infections. 50 mg per kg body weight per day was shown to significantly reduce developmental stages of the parasite in the ileum, but 200 mg per kg body weight per day was needed to lower the number of these stages in the cecum. Once the drug was removed, all animals resumed oocyst shedding (1995, Antimicrob Ag Chemother 39: 2155-2157)
  3. 2000 mg per day for 4 weeks, followed by 1000 mg per day for an additional 4 weeks, was administered to AIDS patients with chronic cryptosporidiosis. Within the first month on the higher dose, 7 of 35 (20%) patients became parasite free as determined by cessation of diarrhea and lack of parasites in duodenal biopsis. Four of these patients continued to be parasite negative throughout the study, but 4 relapsed parasitologically either when the dose was reduced in half (2 patients) or when the drug was terminated at the end of the study (2 patients). An additional 15 patients had a partial response to the treatment regime (1994, J Inf Dis 170: 1349-1350)
  4. In a double-blind trial, patients received 500 mg 3-4 times daily for 2 weeks or a placebo. Many of the patients were concurrently taking AZT. Oocysts were quantitated daily in the feces. Results revealed oocyst numbers to be reduced in all patients receiving the drug, but never eliminated entirely (1994, J Inf Dis 170: 419-429).
  5. 500 mg orally 4 times a day for 10-14 days eliminated the parasite in 3 of 7 patients (1993, Clin Inf Dis 16: 298-300)
  6. 1500-2000 mg per day for varying lengths of time eliminated the parasite in 5 AIDS patients with chronic cryptosporidiosis (1992, Arch Intern Med 152: 2497-2499)
  7. 500 mg 4x per day for one month resulted in resolution of diarrhea in 12 of 20 (60%) AIDS patients but did not eliminate the parasite (1997, Intern J STD and AIDS 8: 124-129)


Roxithromycin

  1. 300 mg twice a day for 4 weeks in a non-controlled study employing AIDS patients with chronic cryptosporidiosis revealed the parasite to be absent from colonic biopsies in 15/22 (68%) patients, and reduced in numbers in an additional 6/22 (27%) (1998, J Antimicrob Chemother 41(B): 93-97)


Sinefungin

  1. 10 mg/kg body weight for 14 days in immunosuppressed adult rats with chronic cryptosporidiosis resulted in greater than 99% reduction in oocysts in the feces (1994, Folia Parasitol 41: 13-16)
  2. 6 mg/kg body weight for 3 weeks in immunosuppressed adult rats with chronic cryptosporidiosis resulted in greater than a 99% reduction in oocysts in the feces (1993, Antimicrob Ag Chemother 37: 889-892)


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