A 43-year-old male inmate with stage C3 HIV/AIDS presents with loose, watery stools, abdominal cramping, sweats, fevers, poor appetite (2 months) and 15 lbs weight loss. He is taking Combivir one tablet bid and Nelfinavir 1,000 mg tid, and trimethoprim/sulfamethoxazole for secondary pneumocystis carinii pneumonia (PCP) prophylaxis. He reports good adherence, with an undetectable viral load and a CD4 count of 100 cells/mm3
. He was diagnosed with HIV and PCP when he entered the U.S. from Mexico one year ago, at which time he had a CD4 count of 2 cells/mm3
and "high" HIV-1 viral load. He is an injecting drug user and has sex only with men. He reports unprotected sex with two anonymous partners two to three months ago when he traveled to Mexico. He weighs 130 lbs and is afebrile with normal blood pressure, genital and neurologic exam. His pharynx was without thrush; there was no scleral jaundice, some temporal wasting, no rash, abdominal tenderness, organomegaly, lymphadenopathy, or peripheral edema.
Q: What is the differential diagnosis?
A: Opportunistic pathogens such as disseminated Mycobacterium avium complex (MAC), PCP, and cytomegalovirus (CMV), should be considered, though PCP does not typically cause GI disease. He is also at risk for Entamoeba histolytica, Dientamoeba fragilis, Blastocystis hominis, Giardia lamblia, Campylobacter jejuni, Shigella spp, Salmonella spp, C. difficile, syphilis and herpes simplex virus. Because of recent travel to Mexico, Escherichia coli, Vibrio parahaemolyticus, Yersinia spp, rotaviruses, and Norwalk-like viruses are also in the differential. Additionally, this inmate could have diarrhea and wasting from HIV itself. It is not likely that Nelfinavir is causing his diahhrea as he tolerated this drug for nine to ten months and only recently developed diarrhea. Though the Nelfinavir may not be the cause of the diarrhea, it may be aggravating it.
Q: What tests should you perform/order?
Stool samples should be sent for WBCs, to help differentiate inflammatory from non-inflammatory causes of diarrhea (history of watery as opposed to bloody diarrhea suggests non-inflammatory). Stool samples should also be sent for culture for enteric pathogens, smear for ova and parasites, Giardia antigen, Clostridium difficile
toxins A and B, and acid-fast bacilli (AFB) smear and culture. Tests for ova and parasites, C. difficile
toxins, and smears for AFB should be repeated twice, as it often takes multiple evaluations before some of these pathogens are detected. Blood should be sent for AFB culture and routine bacterial culture. If there is no temporal association of the onset of diarrhea with antiretroviral therapy and the stool and blood studies are negative, the next step in the evaluation is a colonoscopy. The highest yield for colonoscopy is typically in patients with fever, weight loss, and a CD4 count of fewer than 200 cells/mm3
Concentrated exam of the stool showed many cysts of Giardia lamblia and Entamoeba histolytica. This diagnosis should be reported to the local public health department. Many Entamoeba coli cysts, many Endolimax nana cysts, and moderate Iodamoeba butschlii cysts were also seen. On auramine stain, moderate cryptosporidia were detected.
Q: What treatment(s) should you offer this inmate? Are there drug-drug interactions to consider?
A: Endolimax nana, Entamoeba coli, and Iodamoeba butschlii are nonpathogenic commensals and as such require no treatment. They are however markers of exposure to human feces and are often found in patients who are also infected with pathogenic organisms. Giardia and Entamoeba histolytica can cause invasive disease and should generally be treated. The drug of choice for giardiasis is metronidazole 250 mg tid for seven days, which also has activity against E. histolytica. Unfortunately, there are no reliable therapies for Cryptosporidiosis, though paromomycin or nitazoxanide may have activity and offer benefit. Supportive care with hydration and nutrition, as well as institution of an effective antiretroviral regimen, are crucial aspects of care since improvement in the immune system often helps eradicate the infection. In immunocompetent hosts, cryptosporidiosis is usually self-limited. It may be in this inmate's best interest to change his medications to a more potent antiretroviral regimen in an effort to improve his T-cell response and minimize his gastrointestinal side effects. If the regimen is not changed, the dose of Nelfinavir should be changed to 1,250 mg po bid as this dose is easier to take and is associated with fewer loose stools compared to the tid dose. There are no known drug-drug interactions between metronidazole, paromomycin, or nitazoxanide and the antiretrovirals he is currently taking. There is a drug-drug interaction between the oral solution form of the protease inhibitor amprenavir and metronidazole. This is not true for the capsule formulation of amprenavir.
Q: What infection-control measures should you recommend?
A: To minimize secondary transmission to others via fecal-oral spread, it is important to educate the inmate and staff on good hand-washing skills, particularly before and after meals and use of the restroom. He should be excluded from any kitchen work until his diarrhea has resolved and his stool is cleared of all organisms.
Bethany Weaver, D.O., M.P.H., is Acting Instructor of Medicine at the University of Washington Center for AIDS & STD Research (CFAR) and Northwest Correctional Medicine Education Program. Disclosures: Stockholder, Pfizer.
- Amadi B, Mwiya M, Musuku J, Watuka A, Sianongo S, Ayoub A, Kelly P. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet. 2002 Nov 2;360(9343):1375-80.
- Connolly GM, Foirbes A, Gazzard BG. Investigation of seemingly pathogen-negative diarrhea in patients infected with HIV-1. Gut 1990;31:886-89.
- DeHovitz JA, Pape JW, Boncy M, Johnson WD Jr. Clinical manifestations and therapy of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1986;315:87-90.
- Guerrant RL, Bobak DA. Bacterial and protozoal gastroenteritis. N Engl J Med 1991;325:327-40.
- Guerrant RL, Thielman NM. Emerging enteric protozoa: Cryptosporidium, Cyclospora and microsporidia. In: Scheld WM, Armstrong D, Hughes JM, eds. Emerging Infections. Washington, DC: ASM Press; 1997:233-45.
- Kotler DP, Francisco A, Clayton F, et al. Small intestinal injury and parasitic diseases in AIDS. Ann Intern Med. 1990;113:444-49.
- Laughon BE, Druckman DA, Vernon A, et al. Prevalence of enteric pathogens in homosexual men with and without acquired immunodeficiency syndrome. Gastroenterology. 1988;94:984.
- Oldfield EC III. Evaluation of chronic diarrhea in patients with human immunodeficiency virus infection. Rev Gastroenterol Disord. 2002 Fall;2(4):176-88. Review.
- Pape JW, Verdier RI, Boncy M, et al. Cyclospora infection in adults infected with HIV. Clinical manifestations, treatment, and prophylaxis. Ann Intern Med. 1994;121:654-57.
- 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 Jul 1;184(1):103-6.
- Rossignol JF, Hidalgo H, Feregrino M, Higuera F, Gomez WH, Romero JL, Padierna J, Geyne A, Ayers MS. A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg. 1998 Nov-Dec;92(6):663-6.
- Parasites and Parasitologic Resources of the Ohio State University www.biosci.ohio-state.edu/~parasite/.