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Isosporiasis
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Epidemiology

Isosporiasis occurs worldwide but predominantly in tropical and subtropical regions. Immunocompromised persons, including those with AIDS, are at increased risk for chronic, debilitating illness (30Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353:1463-8., 1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34., 1362Guiguet M, Furco A, Tattevin P, Costagliola D, Molina JM. HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. HIV Med 2007;8:124-30., 1363Sorvillo FJ, Lieb LE, Seidel J, et al. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in Los Angeles County. Am J Trop Med Hyg 1995;53:656-9., 1364Certad G, Arenas-Pinto A, Pocaterra L, et al. Isosporiasis in Venezuelan adults infected with human immunodeficiency virus: clinical characterization. Am J Trop Med Hyg 2003;69:217-22., 1365DeHovitz 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., 1366Pape 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.). Although Isospora belli completes its life cycle in humans, the oocysts shed in the feces of infected persons must mature (sporulate) outside the host, in the environment, to become infective. On the basis of limited data, the maturation process is completed in approximately 1-2 days but might occur in <24 hours (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34.). Infection results from ingestion of sporulated oocysts (e.g., in contaminated food or water). After ingestion, the parasite invades enterocytes in the small intestine. Ultimately, immature oocysts are produced and shed in stool.

Clinical Manifestations

The most common manifestation is watery, nonbloody diarrhea, which may be associated with abdominal pain, cramping, anorexia, nausea, vomiting, and low-grade fever. The diarrhea can be profuse and prolonged, particularly in immunocompromised patients, resulting in severe dehydration, weight loss, and malabsorption (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34., 1362Guiguet M, Furco A, Tattevin P, Costagliola D, Molina JM. HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. HIV Med 2007;8:124-30., 1363Sorvillo FJ, Lieb LE, Seidel J, et al. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in Los Angeles County. Am J Trop Med Hyg 1995;53:656-9., 1364Certad G, Arenas-Pinto A, Pocaterra L, et al. Isosporiasis in Venezuelan adults infected with human immunodeficiency virus: clinical characterization. Am J Trop Med Hyg 2003;69:217-22., 1365DeHovitz 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., 1366Pape 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., 1367Forthal DN, Guest SS. Isospora belli enteritis in three homosexual men. Am J Trop Med Hyg 1984;33:1060-4., 1368Modigliani R, Bories C, Le Charpentier Y, et al. Diarrhoea and malabsorption in acquired immune deficiency syndrome: a study of four cases with special emphasis on opportunistic protozoan infestations. Gut 1985;26:179-87., 1369Whiteside ME, Barkin JS, May RG, et al. Enteric coccidiosis among patients with the acquired immunodeficiency syndrome. Am J Trop Med Hyg 1984;33:1065-72., 1370Bialek R, Overkamp D, Rettig I, Knobloch J. Case report: nitazoxanide treatment failure in chronic isosporiasis. Am J Trop Med Hyg 2001;65:94-5.). Acalculous cholecystitis (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34., 1371Benator 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.) and reactive arthritis (1372Gonzalez-Dominguez J, Roldn R, Villanueva JL, et al. Isospora belli reactive arthritis in a patient with AIDS. Ann Rheum Dis 1994;53:618-9.) have also been reported.

Diagnosis

Typically, infection is diagnosed by detecting Isospora oocysts (dimensions, 23-36 µm by 12-17 µm) in fecal specimens (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34.). Oocysts might be shed intermittently and at low levels, even by persons with profuse diarrhea. Diagnosis might be facilitated by repeated stool examinations with sensitive methods (e.g., oocysts stain bright red with modified acid-fast techniques and they autofluoresce when viewed by UV fluorescence microscopy) (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34., 1373Bialek R, Binder N, Dietz K, Knobloch J, Zelck UE. Comparison of autofluorescence and iodine staining for detection of Isospora belli in feces. Am J Trop Med Hyg 2002;67:304-5.). Infection also can be diagnosed by detecting oocysts in duodenal aspirates/mucus or developmental stages of the parasite in intestinal biopsy specimens (1361, 1369). Extraintestinal infection (e.g., in the biliary tract, lymph nodes, spleen, and liver) has been documented in postmortem examinations of patients with AIDS (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34., 1374Frenkel 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;50:682-4., 1375Restrepo C, Macher AM, Radany EH. Disseminated extraintestinal isosporiasis in a patient with acquired immune deficiency syndrome. Am J Clin Pathol 1987;87:536-42., 1376Bernard E, Delgiudice P, Carles M, et al. Disseminated isosporiasis in an AIDS patient. Eur J Clin Microbiol Infect Dis 1997;16:699-701.).

Preventing Exposure

Not applicable to residents of the United States.

Preventing Disease

In some settings, chemoprophylaxis with TMP-SMX has been associated with a lower incidence or prevalence of isosporiasis (30Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353:1463-8., 1362Guiguet M, Furco A, Tattevin P, Costagliola D, Molina JM. HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. HIV Med 2007;8:124-30., 1363Sorvillo FJ, Lieb LE, Seidel J, et al. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in Los Angeles County. Am J Trop Med Hyg 1995;53:656-9.). In a randomized, placebo-controlled trial, daily TMP-SMX (160/800 mg) was protective against isosporiasis in persons with early-stage HIV infection (WHO clinical stage 2 or 3 at enrollment) (30Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353:1463-8.). In an observational study, the incidence of isosporiasis decreased after widespread introduction of ART, except among persons with CD4+ counts <50 cells/µL (1362Guiguet M, Furco A, Tattevin P, Costagliola D, Molina JM. HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. HIV Med 2007;8:124-30.). After adjustment for the CD4+ count, the risk of isosporiasis was substantially lower among persons receiving prophylaxis with TMP-SMX, sulfadiazine, or pyrimethamine (unspecified regimens). In analyses of data from a county AIDS surveillance registry during the pre-ART era, the prevalence of isosporiasis was lower in persons with (vs. without) a history of PCP-indirect evidence of a protective effect from use of TMP-SMX for PCP (1363Sorvillo FJ, Lieb LE, Seidel J, et al. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in Los Angeles County. Am J Trop Med Hyg 1995;53:656-9.). However, insufficient evidence is available to support a general recommendation for primary prophylaxis for isosporiasis per se (DIII).

Treatment of Disease

Clinical management includes fluid and electrolyte support for dehydrated patients and nutritional supplementation for malnourished patients (AIII). TMP-SMX is the antimicrobial agent of choice for treatment of isosporiasis (AI). It is the only agent whose use is supported by substantial published data and clinical experience. Therefore, potential alternative therapies should be reserved for patients with documented sulfa intolerance or treatment failure (AIII).

Three studies among HIV-infected patients in Haiti have demonstrated the effectiveness of various treatment regimens of TMP-SMX and the need for and effectiveness of secondary prophylaxis (1365DeHovitz 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., 1366Pape 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., 1377Verdier 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.). The patients were not receiving ART, and laboratory indicators of immunodeficiency (e.g., CD4+ counts) were not specified. On the basis of the initial studies (1365DeHovitz 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., 1366Pape 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.), the traditional treatment regimen has been a 10-day course of TMP-SMX (160/800 mg) administered four times a day (AII) (505Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.). In a more recent study, TMP-SMX (160/800 mg) administered twice a day was effective (BI) (1377Verdier 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.). Although experience using two versus four daily doses of TMP-SMX (160/800 mg) is limited, one approach would be to start with this regimen but to increase the daily dose and/or the duration of therapy (up to 3-4 weeks) (1365DeHovitz 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., 1369Whiteside ME, Barkin JS, May RG, et al. Enteric coccidiosis among patients with the acquired immunodeficiency syndrome. Am J Trop Med Hyg 1984;33:1065-72.) if symptoms worsen or persist (BIII). Intravenous administration of TMP-SMX should be considered for patients with potential or documented malabsorption.

Limited data suggest that therapy with pyrimethamine-sulfadiazine and pyrimethamine-sulfadoxine might be effective (1361Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34., 1368Modigliani R, Bories C, Le Charpentier Y, et al. Diarrhoea and malabsorption in acquired immune deficiency syndrome: a study of four cases with special emphasis on opportunistic protozoan infestations. Gut 1985;26:179-87., 1369Whiteside ME, Barkin JS, May RG, et al. Enteric coccidiosis among patients with the acquired immunodeficiency syndrome. Am J Trop Med Hyg 1984;33:1065-72., 1378Mojon M, Coudert J, de Landazuri EO. Serious isosporosis by Isospora belli: a case report treated by Fansidar [Abstract]. Southeast Asian J Trop Med Public Health 1981;12:449-50., 1379Ebrahimzadeh A, Bottone EJ. Persistent diarrhea caused by Isospora belli: therapeutic response to pyrimethamine and sulfadiazine. Diagn Microbiol Infect Dis 1996;26:87-9., 1380Trier JS, Moxey PC, Schimmel EM, et al. Chronic intestinal coccidiosis in man: intestinal morphology and response to treatment. Gastroenterology 1974;66:923-35.). However, the combination of pyrimethamine plus sulfadoxine is not typically recommended for use in the United States (CIII); it has been associated with an increased risk of severe cutaneous reactions, including Stevens-Johnson syndrome (125Navin TR, Miller KD, Satriale RF, Lobel HO. Adverse reactions associated with pyrimethamine-sulfadoxine prophylaxis for Pneumocystis carinii infections in AIDS. Lancet 1985;1:1332.), and pyrimethamine and sulfadoxine are slowly cleared from the body after therapy is discontinued.

Single-agent therapy with pyrimethamine has been used with anecdotal success for treatment and prevention of isosporiasis (1362Guiguet M, Furco A, Tattevin P, Costagliola D, Molina JM. HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. HIV Med 2007;8:124-30., 1381Weiss LM, Perlman DC, Sherman J, et al. Isospora belli infection: treatment with pyrimethamine. Ann Intern Med 1988;109:474-5., 1382Jongwutiwes S, Sampatanukul P, Putaporntip C. Recurrent isosporiasis over a decade in an immunocompetent host successfully treated with pyrimethamine. Scand J Infect Dis 2002;34:859-62.). Pyrimethamine (50-75 mg/day) plus leucovorin (10-25 mg/day) to prevent myelosuppression might be an effective treatment alternative (e.g., it is the traditional option for sulfa-intolerant patients) (BIII).

Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome (IRIS)

Patients should be monitored for clinical response and adverse events. Among patients with AIDS, TMP-SMX therapy is commonly associated with side effects (e.g., rash, fever, leukopenia, thrombocytopenia, elevated transaminase levels). IRIS has not been reported in association with treatment of isosporiasis.

Management of Treatment Failure

If symptoms worsen or persist despite approximately 5-7 days of TMP-SMX therapy, the possibilities of noncompliance, malabsorption, and concurrent infections/enteropathies should be considered; the TMP-SMX regimen (i.e., daily dose, duration, and mode of administration) also should be reevaluated. For patients with documented sulfa intolerance or treatment failure, use of a potential alternative agent (e.g., pyrimethamine) should be considered. Ciprofloxacin might be considered as a second-line agent (CI). On the basis of limited data from a randomized, controlled trial in Haiti, ciprofloxacin (500 mg twice daily for 7 days) is less effective than TMP-SMX but might have modest activity against I. belli (1377Verdier 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.).

Unsubstantiated or mixed data are available for albendazole (1382Jongwutiwes S, Sampatanukul P, Putaporntip C. Recurrent isosporiasis over a decade in an immunocompetent host successfully treated with pyrimethamine. Scand J Infect Dis 2002;34:859-62., 1383Dionisio D, Sterrantino G, Meli M, et al. Treatment of isosporiasis with combined albendazole and ornidazole in patients with AIDS. AIDS 1996;10:1301-2., 1384Zulu I, Veitch A, Sianongo S, et al. Albendazole chemotherapy for AIDS-related diarrhoea in Zambia-clinical, parasitological and mucosal responses. Aliment Pharmacol Ther 2002;16:595-601.), nitazoxanide (1385Romero Cabello R, Guerrero LR, Muoz Garcia MR, et al. Nitazoxanide for the treatment of intestinal protozoan and helminthic infections in Mexico. Trans R Soc Trop Med Hyg 1997;91:701-3., 1386Doumbo O, Rossignol JF, Pichard E, et al. Nitazoxanide in the treatment of cryptosporidial diarrhea and other intestinal parasitic infections associated with acquired immunodeficiency syndrome in tropical Africa. Am J Trop Med Hyg 1997;56:637-9.), doxycycline (1387Meyohas MC, Capella F, Poirot JL, et al. Treatment with doxycycline and nifuroxazide of Isospora belli infection in AIDS. Pathol Biol 1990;38:589-91.), the macrolides roxithromycin and spiramycin (1379Ebrahimzadeh A, Bottone EJ. Persistent diarrhea caused by Isospora belli: therapeutic response to pyrimethamine and sulfadiazine. Diagn Microbiol Infect Dis 1996;26:87-9., 1388Gaska JA, Tietze KJ, Cosgrove EM. Unsuccessful treatment of enteritis due to Isospora belli with spiramycin: a case report. J Infect Dis 1985;152:1336-8., 1389Musey KL, Chidiac C, Beaucaire G, et al. Effectiveness of roxithromycin for treating Isospora belli infection. J Infect Dis 1988;158:646.), and the veterinary anticoccidial agent diclazuril (1390Limson-Pobre RN, Merrick S, Gruen D, et al. Use of diclazuril for the treatment of isosporiasis in patients with AIDS. Clin Infect Dis 1995;20:201-2., 1391Kayembe K, Desmet P, Henry MC, et al. Diclazuril for Isospora belli infection in AIDS. Lancet 1989;1:1397-8.) (CIII). Limited data suggest that drugs such as metronidazole, quinacrine, iodoquinol, paromomycin, and furazolidone are ineffective (DIII) (1367Forthal DN, Guest SS. Isospora belli enteritis in three homosexual men. Am J Trop Med Hyg 1984;33:1060-4., 1379Ebrahimzadeh A, Bottone EJ. Persistent diarrhea caused by Isospora belli: therapeutic response to pyrimethamine and sulfadiazine. Diagn Microbiol Infect Dis 1996;26:87-9., 1380Trier JS, Moxey PC, Schimmel EM, et al. Chronic intestinal coccidiosis in man: intestinal morphology and response to treatment. Gastroenterology 1974;66:923-35., 1381Weiss LM, Perlman DC, Sherman J, et al. Isospora belli infection: treatment with pyrimethamine. Ann Intern Med 1988;109:474-5., 1388Gaska JA, Tietze KJ, Cosgrove EM. Unsuccessful treatment of enteritis due to Isospora belli with spiramycin: a case report. J Infect Dis 1985;152:1336-8., 1390Limson-Pobre RN, Merrick S, Gruen D, et al. Use of diclazuril for the treatment of isosporiasis in patients with AIDS. Clin Infect Dis 1995;20:201-2.). Apparent or partial responses, if noted, might be attributable to treatment of concomitant infections or to nonspecific effects.

Preventing Recurrence

Patients with CD4+ counts <200 cells/µL should receive secondary prophylaxis (chronic maintenance therapy) with TMP-SMX (AI). In studies in Haiti, approximately 50% of patients who did not receive secondary prophylaxis had symptomatic recurrences approximately 2 months after completing a course of TMP-SMX therapy, relapses rapidly responded to retreatment, and secondary prophylaxis decreased the risk for relapse (1365DeHovitz 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., 1366Pape 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., 1377Verdier 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.). In a randomized, placebo-controlled trial, no symptomatic recurrences were noted among patients who received maintenance therapy with thrice-weekly TMP-SMX (160/800 mg) (AI) (1366Pape 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.). Daily TMP-SMX (160/800 mg) and thrice-weekly TMP-SMX (320/1,600 mg) have been effective (BIII) (1364Certad G, Arenas-Pinto A, Pocaterra L, et al. Isosporiasis in Venezuelan adults infected with human immunodeficiency virus: clinical characterization. Am J Trop Med Hyg 2003;69:217-22., 1369Whiteside ME, Barkin JS, May RG, et al. Enteric coccidiosis among patients with the acquired immunodeficiency syndrome. Am J Trop Med Hyg 1984;33:1065-72.).

In sulfa-intolerant patients, pyrimethamine (25 mg/day) with leucovorin (5-10 mg/day) has been used (BIII) (1381Weiss LM, Perlman DC, Sherman J, et al. Isospora belli infection: treatment with pyrimethamine. Ann Intern Med 1988;109:474-5.). Ciprofloxacin (500 mg thrice weekly) might be considered as a second-line alternative (CI) (1377Verdier 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.).

Discontinuing Secondary Prophylaxis

The concern of discontinuing prophylaxis has not been evaluated in a clinical trial. Chemoprophylaxis probably can be safely discontinued in patients without evidence of active I. belli infection who have a sustained increase in the CD4+ count to levels >200 cells/µL for >6 months after initiation of ART (BIII).

Special Considerations During Pregnancy

TMP-SMX is usually the agent of choice for primary treatment and secondary prophylaxis in pregnant women, as it is for nonpregnant women. Although first-trimester exposure to trimethoprim might be associated with a small increased risk of birth defects (173Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Reprod Toxicol 2001;15:637-46., 174Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608-14., 175Hernandez-Diaz S, Werler MM, Walker AM. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001;153:961-8., 176Jungmann EM, Mercey D, DeRuiter A, et al. Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities? Sex Transm Infect 2001;77:441-3.), in the setting of maternal symptomatic I. belli infection, therapy with TMP-SMX should be provided. Because of concerns about possible teratogenicity associated with drug exposure during the first trimester, clinicians might withhold secondary prophylaxis during the first trimester and treat only symptomatic infection. Although pyrimethamine has been associated with birth defects in animals, limited human data have not suggested an increased risk of defects (228Deen JL, von Seidlein L, Pinder M, Walraven GE, Greenwood BM. The safety of the combination artesunate and pyrimethamine-sulfadoxine given during pregnancy. Trans R Soc Trop Med Hyg 2001;95:424-8.). Human data about the use of ciprofloxacin during several hundred pregnancies have not suggested an increased risk of birth defects or cartilage abnormalities (395Nahum GG, Uhl K, Kennedy DL. Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risks. Obstet Gynecol 2006;107:1120-38.).

Drug therapy for treatment and chronic maintenance therapy of AIDS-associated opportunistic infections in adults and adolescents: Isospora belli infection
Preferred therapy, duration of therapy, chronic maintenanceAlternative therapyOther options/issues
Preferred therapy for acute infection:
transparent gifgrey bulletTMP-SMX (AI) (160 mg/800 mg) PO (or IV) qid for 10 days (AII); or
transparent gif
transparent gifgrey bulletTMP-SMX (160 mg/800 mg) PO (or IV) bid for 7-10 days (BI)
transparent gif
transparent gifgrey bulletMay increase daily dose and/or duration (up to 3-4 weeks) if symptoms worsen or persist (BIII)
transparent gif
Alternative therapy for acute infection
transparent gifgrey bulletPyrimethamine 50-75 mg PO daily plus leucovorin 10-25 mg PO daily (BIII); or
transparent gif
transparent gifgrey bulletCiprofloxacin 500 mg PO bid x 7 days (CI) -- as a second-line alternative
transparent gif

Fluid and electrolyte management in patients with dehydration (AIII)

Nutritional supplementation for malnourished patients (AIII)

Immune reconstitution with ART may result in fewer relapses (AIII)

Preferred chronic maintenance therapy (secondary prophylaxis)

In patients with CD4+ count <200/µL,
transparent gifgrey bulletTMP-SMX (160 mg/800 mg) PO tiw (AI)
transparent gif
Alternative chronic maintenance therapy (secondary prophylaxis)
transparent gifgrey bulletTMP-SMX (160 mg/800 mg) PO daily or (320 mg/1,600 mg) tiw (BIII)
transparent gif
transparent gifgrey bulletPyrimethamine 25 mg PO daily + leucovorin 5-10 mg PO daily (BIII)
transparent gif
transparent gifgrey bulletCiprofloxacin 500 mg tiw (CI) -- as a second-line alternative
transparent gif

References

30. Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999;353:1463-8.
125. Navin TR, Miller KD, Satriale RF, Lobel HO. Adverse reactions associated with pyrimethamine-sulfadoxine prophylaxis for Pneumocystis carinii infections in AIDS. Lancet 1985;1:1332.
173. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Reprod Toxicol 2001;15:637-46.
174. Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608-14.
175. Hernandez-Diaz S, Werler MM, Walker AM. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001;153:961-8.
176. Jungmann EM, Mercey D, DeRuiter A, et al. Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities? Sex Transm Infect 2001;77:441-3.
228. Deen JL, von Seidlein L, Pinder M, Walraven GE, Greenwood BM. The safety of the combination artesunate and pyrimethamine-sulfadoxine given during pregnancy. Trans R Soc Trop Med Hyg 2001;95:424-8.
395. Nahum GG, Uhl K, Kennedy DL. Antibiotic use in pregnancy and lactation: what is and is not known about teratogenic and toxic risks. Obstet Gynecol 2006;107:1120-38.
505. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001;32:331-51.
1361. Lindsay DS, Dubey JP, Blagburn BL. Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbiol Rev 1997;10:19-34.
1362. Guiguet M, Furco A, Tattevin P, Costagliola D, Molina JM. HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV. HIV Med 2007;8:124-30.
1363. Sorvillo FJ, Lieb LE, Seidel J, et al. Epidemiology of isosporiasis among persons with acquired immunodeficiency syndrome in Los Angeles County. Am J Trop Med Hyg 1995;53:656-9.
1364. Certad G, Arenas-Pinto A, Pocaterra L, et al. Isosporiasis in Venezuelan adults infected with human immunodeficiency virus: clinical characterization. Am J Trop Med Hyg 2003;69:217-22.
1365. 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.
1366. 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.
1367. Forthal DN, Guest SS. Isospora belli enteritis in three homosexual men. Am J Trop Med Hyg 1984;33:1060-4.
1368. Modigliani R, Bories C, Le Charpentier Y, et al. Diarrhoea and malabsorption in acquired immune deficiency syndrome: a study of four cases with special emphasis on opportunistic protozoan infestations. Gut 1985;26:179-87.
1369. Whiteside ME, Barkin JS, May RG, et al. Enteric coccidiosis among patients with the acquired immunodeficiency syndrome. Am J Trop Med Hyg 1984;33:1065-72.
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