Opportunistic Infections: Treatment
Case 6: Discussion - Cystoisosporiasis
Background and Epidemiology
Cystoisospora belli, formerly known as Isospora belli, is a coccidian protozoal parasite endemic to many regions of the world outside of the United States, including the Caribbean, Central and South America, Africa, and Southeast Asia[1,21]. Most cases of cystoisosporiasis in the United States involve either persons who previously lived in an endemic region or recently traveled to an endemic region. Hispanic individuals living in the United States have approximately a 3.5-fold increased risk of developing this infection when compared with Caucasians. In a HIV-infected person, intestinal cystoisosporiasis lasting longer than 1 month constitutes a diagnosis of AIDS. In the United States, cystoisosporiasis is the initial AIDS-defining illness in less than 1% of persons diagnosed with AIDS. The number of cases of cystoisosporiasis declined following the widespread use of trimethoprim-sulfamethoxazole (Bactrim, Septra) for Pneumocystis pneumonia prophylaxis. Although cystoisosporiasis does not frequently occur among HIV-infected persons living in the United States, it frequently causes gastrointestinal illness among HIV-infected persons in the developing world, as shown by recent surveys in Latin America that reported isosporiasis as the cause of 7 to 14% of all cases of infectious diarrhea[5,6].
Life Cycle and Transmission
The transmission of C. belli occurs predominantly via ingestion of food or water contaminated with human feces laden with C. belli oocysts[1,7]. Most persons infected with C. belli excrete the oocysts in the stool in the non-infectious (unsporulated or partially sporulated) form; the organism requires a developmental phase (sporulation) outside the host before it transforms into an infectious form (mature oocyst with sporozoites) (Figure 1). Although one report from a case series suggested transmission of C. belli from oral-anal contact, others have concluded this mode of transmission probably occurs infrequently, given the substantial time required outside the host for the oocysts to transform to an infectious form. Moreover, one study found that sexual partners of infected individuals do not have an increased risk of developing cystisosporiasis. In rare circumstances, in place of (or in addition to) the normal development within the gastrointestinal tract, some sporozoites (or merozoites) leave the intestinal tract and invade extraintestinal sites, such as lymph nodes, spleen, and liver[1,9,10].
The three coccidian parasites that most commonly cause clinical disease in humans are C. belli, Cryptosporidium parvum, and Cyclospora spp. Cystisospora belli primarily causes gastrointestinal disease; typical symptoms include fever, watery diarrhea, nausea, vomiting, abdominal pain, dehydration, weight loss, and headache[4,11]. These symptoms often resemble those caused by infection with C. parvum and Cyclospora spp.. Prior to the HIV epidemic, enteritis caused by C. belli was usually considered a self-limited disease. Among patients with AIDS, however, it typically causes chronic disease leading to weight loss and malabsorption. In these patients, relapse frequently occurs in the absence of maintenance therapy[4,12]. Several reports have documented cases of extraintestinal disease, but such cases are rare. Extraintestinal sites have included lymph nodes and spleen[9,10,14]. In addition, one report described an AIDS patient with acalculous cystitis associated with C. belli infection.
Patients with cystoisosporiasis often demonstrate peripheral eosinophilia, bu this is a non-specific finding. The diagnosis of intestinal cystoisosporiasis requires identification of the characteristic oocysts in a stool sample. The most common techniques used on stool samples include wet mount examination, modified acid-fast stain, or Safranin stain. The Sheather sugar flotation method or the sedimentation concentration method may also be used[1,16]. To enhance the yield the stool sample should be concentrated prior to microscopic examination. For evaluation of HIV-infected persons with diarrhea, the preferred test is usually either a modified acid-fast stain or safranin stain, both of which stain the oocysts of C. belli, C. parvum and Cyclospora spp. oocysts a deep red color. The unsporulated Cystoisospora oocysts appear elliptical in shape, with one or both ends slightly tapered. Staining of the early phase oocyst often shows a internal granular mass (Figure 2), or as it matures, one or two internal sporoblasts may be seen (Figure 3). The C. belli oocysts are approximately 30 by 15 um in size and are distinctly larger and more oval than the C. parvum oocysts (4 to 6 um in diameter) and Cyclospora spp. oocysts (6 to 10 um in diameter) (Figure 4). The C. belli oocysts can also be visualized on wet mount samples using bright field microscopy, differential interference contrast, and UV fluorescence microscopy (Figure 5). Because fecal passage ofC. belli oocysts may be intermittent, multiple stool samples are recommended to enhance the diagnostic yield. Antigen detection testing is not commercially available. The diagnosis of extraintestinal cystoisosporiasis has historically been based on histologic findings that show tissue cysts that contain intracellular zoites. More recently, molecular diagnostic methods using PCR have shown promise as a diagnostic tool for C. belli in biopsy specimens.
Initial management of patients with intestinal cystoisosporiasis requires adequate rehydration and replacement of any deficient electrolytes. A 10-day course of trimethoprim-sulfamethoxazole is recommended as the initial antimicrobial treatment of choice. The alternative regimens of pyrimethamine (Daraprim) or ciprofloxacin (Cipro) are reserved for those unable to take trimethoprim-sulfamethoxazole (Figure 6)[11,18,19]. In adequate data exist to support the use of other agents, such as albendazole (Albenza), nitazoxanide (Alinia), doxycycline, or spiramycin. Patients who have a CD4 count less than 200 cells/mm3 should take trimethoprim-sulfamethoxazole both for chronic maintenance therapy and for Pneumocystis pneumonia prophylaxis. Patients with a CD4 count greater than 200 cells/mm3 who experience a relapse after completing treatment should re-initiate full-dose therapy and should be considered for maintenance therapy following retreatment. Anecdotal information suggests that effective antiretroviral therapy with immune reconstitution would reduce the risk of relapse or the need for secondary prophylaxis, but data are lacking. The opportunistic infections treatment guidelines recommend considering discontinuation of secondary prophylaxis in patients who sustain a CD4 count greater than 200 cells/mm3 for longer than 3 months.
1 Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev. 1997;10:19-34. PubMed Abstract
2 Sorvillo FJ, Lieb LE, Seidel J, Kerndt P, Turner J, Ash LR. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in Los Angeles County. Am J Trop Med Hyg. 1995;53:656-9. PubMed Abstract
3 Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1-19.CDC and Prevention
4 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. PubMed Abstract
5 Certad G, Arenas-Pinto A, Pocaterra L, Ferrara G, Castro J, Bello A, Nunez L. Isosporiasis in Venezuelan adults infected with human immunodeficiency virus: clinical characterization. Am J Trop Med Hyg. 2003;69:217-22.PubMed Abstract
6 Silva CV, Ferreira MS, Borges AS, Costa-Cruz JM. Intestinal parasitic infections in HIV/AIDS patients: experience at a teaching hospital in central Brazil. Scand J Infect Dis. 2005;37:211-5. PubMed Abstract
7 Pape JW, Johnson WD Jr. Isospora belli infections. Prog Clin Parasitol. 1991;2:119-27. PubMed Abstract
8 Forthal DN, Guest SS. Isospora belli enteritis in three homosexual men. Am J Trop Med Hyg. 1984;33:1060-4.PubMed Abstract
9 Michiels JF, Hofman P, Bernard E, et al. Intestinal and extraintestinal Isospora belli infection in an AIDS patient. A second case report. Pathol Res Pract. 1994;190:1089-94. PubMed Abstract
10 Restrepo C, Macher AM, Radany EH. Disseminated extraintestinal isosporiasis in a patient with acquired immune deficiency syndrome. Am J Clin Pathol. 1987;87:536-42. PubMed Abstract
11 Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(RR-4):1-207.CDC and Prevention
12 Pape JW, Verdier RI, Johnson WD Jr. Treatment and prophylaxis of Isospora belli infection in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1989;320:1044-7. PubMed Abstract
13 Bernard E, Delgiudice P, Carles M, et al. Disseminated isosporiasis in an AIDS patient. Eur J Clin Microbiol Infect Dis. 1997;16:699-701. PubMed Abstract
14 Frenkel JK, Silva MB, Saldanha J, et al. Isospora belli infection: observation of unicellular cysts in mesenteric lymphoid tissues of a Brazilian patient with AIDS and animal inoculation. J Eukaryot Microbiol. 2003;50 Suppl:682-4. PubMed Abstract
15 Benator DA, French AL, Beaudet LM, Levy CS, Orenstein JM. Isospora belli infection associated with acalculous cholecystitis in a patient with AIDS. Ann Intern Med. 1994;121:663-4. PubMed Abstract
16 Ng E, Markell EK, Fleming RL, Fried M. Demonstration of Isospora belli by acid-fast stain in a patient with acquired immune deficiency syndrome. J Clin Microbiol. 1984;20:384-6. PubMed Abstract
17 Centers for Disease Control and Prevention, Division of Parasitic Diseases. DPDx: Laboratory identification of parasites of public health concern. Isosoporiasis.CDC and Prevention
18 Weiss LM, Perlman DC, Sherman J, Tanowitz H, Wittner M. Isospora belli infection: treatment with pyrimethamine. Ann Intern Med. 1988;109:474-5. PubMed Abstract
19 Verdier RI, Fitzgerald DW, Johnson WD Jr, Pape JW. Trimethoprim-sulfamethoxazole compared with ciprofloxacin for treatment and prophylaxis of Isospora belli and Cyclospora cayetanensis infection in HIV-infected patients. A randomized, controlled trial. Ann Intern Med. 2000;132:885-8.PubMed Abstract
20 Barta JR, Schrenzel MD, Carreno R, Rideout BA. The genus Atoxoplasma (Garnham 1950) as a junior objective synonym of the genus Isospora (Schneider 1881) species infecting birds and resurrection of Cystoisospora (Frenkel 1977) as the correct genus for Isospora species infecting mammals. J Parasitol. 2005;91:726-7.PubMed Abstract
21 Murphy SC, Hoogestraat DR, Sengupta DJ, Prentice J, Chakrapani A, Cookson BT. Molecular diagnosis of cystoisosporiasis using extended-range PCR screening. J Mol Diagn. 2011;13:359-62.PubMed Abstract
Copyright © 2004-2013 University of Washington