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diarrhea

Cryptosporidium Diarrhea

David Swoboda, MS4, Arpan Patel, MD, PGY1, and Alex Rico, MD
Florida State University College of Medicine and Orlando Regional Medical Center, FL

A 41-year-old Venezuelan male with history of HIV, not currently on HAART, presents to the emergency department with nausea, vomiting, diarrhea, and abdominal cramps for 2 weeks. Patient had a recent candida infection and was treated with fluconazole for 14 days. 

Physical exam noted hyperactive bowel sounds and mild tenderness to palpation in lower, left quadrant (LLQ). No white plaques or ulcers were found in the oral cavity and no LAD or rashes were noted. The rest of the physical exam was unremarkable. 

abdomen ct

Figure 1. An abdomen CT scan shows multiple air fluid levels in the abdomen and small bowel intussusception. Because of lack of severe abdominal tenderness on serial physical examinations, the finding was determined to be an artifact due to edematous bowel. 

On day of admission, basic metabolic panel showed serum sodium of 125, chloride of 101, potassium of 1.9, bicarbonate of 13, BUN of 35, creatinine of 1.7, calcium of 8.3, AST 70, and ALT 66. CBC, hepatitis panel, and lipase were all within normal limits. MAC, TB, CMV, and parasitic causes of the diarrhea were considered in the initial differential diagnosis. CD4+ count, stool leukocyte, giardia, cryptosporidium antigen, and clostridium difficile toxin assay were ordered. A CT abdomen was also ordered (Figure 1). CD4 count was 37. 

The patient was started on HAART and TMP-SMX for PCP prophylaxis. Azithromycin was also started for MAC prophylaxis. Cryptosporidium antigen was positive in stool (Figure 2).

Treatment. The patient was started on supportive therapy which included potassium replacement, nitazoxanide, and loperamide. After 10 days of therapy, a colonoscopy was performed to rule out any other possible underlying conditions affecting the bowel. Once electrolytes were stabilized and diarrhea was at a minimum, the patient was discharged with HAART therapy, loperamide, nitazoxanide and ondansetron. The patient was instructed to follow up with his infectious disease physician in 1 week. 

ileum biopsy

Figure 2. The patient’s terminal ileum biopsy shows the characteristic appearance of cryptosporidium parasites (see black arrow tips) lining the brush border in the crypts of the terminal ileum. Cryptosporidium also causes blunting of the villi (not shown above), which leads to malabsorption and profuse diarrhea. 

Discussion. Cryptosporidiosis is a disease caused by the microscopic parasite cryptosporidium. It affects the immunocompetent (mostly children under five) and immunocompromised individuals, especially patients with HIV. Cryptosporidium causes diarrhea that can be self-limited in the immunocompetent or life threatening in the immunocompromised.1

In the immunocompromised patient, HAART therapy has been used as the mainstay of therapy. Improving the CD4 count has been shown to reduce the severity of the cryptosporidium infection, but is not curative and the symptoms can remit once immune status worsens. Many different antimicrobial treatments have also been attempted in the treatment of cryptosporidium including nitazoxanide, paromomycin, rifabutin, and macrolides (azithromycin, clarithromycin, and spiramycin). Studies in efficacy of these agents thus far have shown either limited efficacy or no significant effects.1

Nitazoxanide is an anti-parasitic that interferes with the pyruvate ferredoxin oxidoreduction dependent electron transfer reaction, an enzyme involved in anaerobic metabolism.2 It has been shown to be efficacious in the immunocompetent patient but in immunocompromised patients, results have been mixed with some studies showing positive results while other showing effects are insignificant. Because the drug is well-tolerated with limited side effects it is still used in the treatment of cryptosporidium diarrhea in HIV patients. However, there are no specific indications for this.2,3

References:

1.  Abubakar I, Aliyu SH, Arumugam C, et al. Prevention and treatment of cryptosporidiosis in immunocompromised patients. Cochrane Database Syst Rev. 2007;(1):CD004932. 

2.  Fox L, Saravolatz L. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis. 2005;40:1173-1180. 

3.  Rossigmol JF. Nitazoxanide in the treatment of acquired immune deficiency syndrome-related cryptosporidiosis: results of the United States compassionate use program in 365 patients. Aliment Pharmacol Ther. 2006;24:887-894.