Cryptosporidiosis

– Christian Hoffmann –

Cryptosporidiosis is a parasitic intestinal disease with fecal-oral transmission. It is mainly caused by the protozoon Cryptosporidium parvum (two genotypes exist, genotype 1 is now also known as C. hominis), and may affect both immunocompetent and immunocompromised hosts (review: Chen 2002). First described in 1976, cryptosporidia are among the most important and most frequent causes of diarrhea worldwide. Important sources of infection for this intracellular parasite include animals, contaminated water and food. The incubation period lasts approximately 10 days. While diarrhea almost always resolves within a few days in otherwise healthy hosts or in HIV infected patients with CD4 counts greater than 200 cells/µl, cryptosporidiosis is often chronic in AIDS patients. Particularly in severely immunocompromised patients (below 50 CD4 T cells/µl), diarrhea may become life threatening due to water and electrolyte losses (Colford 1996). Only chronic, and not acute, cryptosporidiosis is AIDS-defining.

Signs and symptoms

The typical watery diarrhea can be so severe that it leads to death as a result of electrolyte loss and dehydration. Up to twenty bowel movements a day are not uncommon. Tenesmus is frequent, along with nausea and vomiting. However, the symptoms are highly variable. Fever is usually absent. Additionally, the biliary ducts may occasionally be affected with the elevation of biliary enzymes. Pancreatitis is also possible.

Diagnosis

When submitting stool samples, the laboratory should be informed of the clinical suspicion. Otherwise, cryptosporidia are often overlooked. If the laboratory is experienced and receives the correct information, then usually just one stool sample is sufficient for detection. In contrast, antibodies or other diagnostic tests are not helpful. The differential diagnosis should include all diarrhea-causing pathogens.

Treatment

No specific treatment has been established to date. Diarrhea is self-limiting with a good immune status; therefore, poor immune status should always be improved with ART – and this often leads to resolution (Carr 1998, Miao 2000). To ensure absorption of antiretroviral drugs, symptomatic treatment with loperamide and/or opium tincture , a controlled drug prescription at its maximum dosage, is advised. If this is unsuccessful, then treatment with other anti-diarrheal medications, perhaps even sandostatin, can be attempted. Sufficient hydration is necessary and infusions may even be required.

Recent reviews confirmed the absence of evidence for effective agents in the management of cryptosporidiosis (Abubakar 2007, Pantenberg 2009). We have observed good results with the antihelminthic agent nitazoxanide (Cryptaz®). Nitazoxanide proved to be effective in a small, randomized study (Rossignol 2001). In 2005 it was licensed in the USA for treatment of cryptosporidia associated diarrhea in immunocompetent patients. Nitazoxanide is not approved to AIDS patients and showed no effects in a double blind randomized study in HIV infected children with cryptosporidia (Amadi 2009).

Rifaximine (Xifaxan®, 200 mg) is a nonabsorbed rifampicin derivative, already licensed in the US as an anti-diarrheal. The first data with AIDS patients are very promising (Gathe 2008).

Paromomycin (Humatin®) is a nonabsorbed aminoglycoside antibiotic and has shown favorable effects on diarrhea in small uncontrolled studies (White 2001). In one double-blind randomized study, however, there was no advantage over placebo (Hewitt 2000). Potentially, there is an effect in combination with azithromycin (Smith 1998).

Treatment/prophylaxis of cryptosporidiosis (daily doses)
Acute therapy    
Symptomatic Loperamide +

 
opium tincture

Loperamide 1 cap at 2 mg 2–6 times daily or

loperamide solution 10 ml (10 ml = 2 mg)
2–6 times daily and/or

Opium tincture 1% = 5–15 drops qid

Symptomatic Octreotide Sandostatin solution for injection 1 amp at 50 µg s.c. bid or tid (increase dose slowly)
Curative attempt Nitazoxanide Nitazoxanide1 tbl. at 500 mg bid
Curative attempt Rifaximin Rifaximin 2 tbl. at 200 mg bid
Prophylaxis   Exposure prophylaxis: no tap water

Prophylaxis

There is no generally accepted prophylaxis, although retrospective analyses have reported a protective effect of rifabutin and clarithromycin (Holmberg 1998). The importance of good hygiene and not drinking tap water should be emphasized to patients, at least in countries with limited access to clean, adequate drinking water. Contact with human and animal feces should be avoided. The tendency for patients to become ill during the summer months can often be linked to swimming in rivers or lakes. Cryptosporidia are resistant to most disinfectants. In hospitals and other medical facilities, the usual hygienic measures, such as wearing gloves, are adequate. Moreover, patients do not need to be isolated. However, they should not be put in the same room with other significantly immunocompromised patients.

References

Abubakar I, Aliyu SH, Arumugam C, Usman NK, Hunter PR. Treatment of cryptosporidiosis in immuno-compromised individuals: systematic review and meta-analysis. Br J Clin Pharmacol 2007;63:387-93.

Amadi B, Mwiya M, Musuku J, et al. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet 2002, 360:1375-1380.

Amadi B, Mwiya M, Sianongo S, et al. High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial. BMC Infect Dis 2009, 9:195.

Carr A, Marriott D, Field A, Vasak E, Cooper DA. Treatment of HIV-1 associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998, 351:256-61.

Chen XM, Keithly JS, Paya CV, LaRusso NF. Cryptosporidiosis. N Engl J Med 2002, 346: 1723-31.

Colford JM Jr, Tager IB, Hirozawa AM, et al. Cryptosporidiosis among patients infected with HIV. Factors related to symptomatic infection and survival. Am J Epidemiol 1996, 144:807-16.

Gathe JC Jr, Mayberry C, Clemmons J, Nemecek J. Resolution of severe cryptosporidial diarrhea with rifaximin in patients with AIDS. J AIDS 2008, 48:363-4.

Griffiths JK. Treatment for AIDS-associated cryptosporidiosis. J Infect Dis 1998, 178:915-6.

Hewitt RG, Yiannoutsos CT, Higgs ES, et al. Paromomycin: No more effective than placebo for treatment of cryptosporidiosis in patients with advanced HIV infection. Clin Inf Dis 2000, 31:1084-92.

Holmberg SD, Moorman AC, Von Bargen JC, et al. Possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease. JAMA 1998, 279:384-6.

Miao YM, Awad-El-Kariem FM, Franzen C, et al. Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy. J Acquir Immune Defic Syndr 2000, 25: 124-9.

Pantenburg B, Cabada MM, White AC Jr. Treatment of cryptosporidiosis. Expert Rev Anti Infect Ther 2009, 7:385-91.

Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of Nitazoxanide. J Infect Dis 2001, 184:103-6.

Smith NH, Cron S, Valdez LM, Chappell CL, White AC Jr. Combination drug therapy for cryptosporidiosis in AIDS. J Infect Dis 1998, 178:900-3.

White AC, Cron SG, Chappell CL. Paromomycin in cryptosporidiosis. Clin Inf Dis 2001, 32:1516-7.

Advertisements

Leave a comment

Filed under 11. Opportunistic Infections, Cryptosporidiosis, Part 3 - AIDS

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s