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Resolution of intestinal cryptosporidiosis after treatment of AIDS with AZT
GASTROENTEROLOGY 1989;97:1327-30
Resolution of Intestinal Cryptosporidiosis After Treatment of AIDS With AZT RONALD E. GREENBERG, FREDERICK P. SIEGAL
RABIA MIR, SIMMY BANK, and
Divisions of Gastroenterology and Hematology/Oncology, Department of Medicine, and the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York; and State University of New York at Stony Brook, Stony Brook, New York
Intestinal cryptosporidiosis commonly results in severe protracted diarrhea that contributes sign& cantly toward morbidity and mortality in patients with acquired immunodeficiency syndrome. No satisfactory therapy for cryptosporidiosis currently exists. We describe a patient with severe secretory diarrhea and malabsorption who had clinical, microbiologic, and histologic resolution of cryptosporidiosis after therapy with zidovudine.
C
in patients with acquired imryptosporidiosis munodeficiency syndrome (AIDS) frequently causes a severe diarrhea1 illness for which no effective therapy currently exists (1).We describe a patient with cryptosporidiosis and severe secretory diarrhea and malabsorption unresponsive to spiramycin, oral bovine transfer factor, and HLA-matched allogeneic lymphocyte transfusion, who experienced symptomatic, microbiologic, and histologic resolution after treatment with zidovudine (azidothymidine, AZT). We postulate that the beneficial effect was secondary to improved cell-mediated immune functions mediated by suppression of human immunodeficiency virus (HIV-l) by AZT. Case Report A 26-yr-old homosexual man was admitted for evaluation of diarrhea. In June 1985,he experienced fever and weight loss, and was seropositive for human immunodeficiency virus (HIV-l) by Western blotting. He subsequently developed ulcerative perianal herpes simplex infection and cutaneous Kaposi’s sarcoma. He received topical acyclovir, one tablet of trimethoprim-sulfamethoxazole daily, and rifabutin that was continued until December 1986,when he developed hives and marked pruritis. Shortly thereafter, he experienced 10-14 watery bowel movements per day with abdominal cramps and gaseous discomfort that resisted empiric treatment with metronidazole, lomotil, Pepto-Bismol (Procter & Gamble, Cin-
cinnati, Ohio) and deodorized tincture of opium, necessitating hospitalization in January 1987. Physical examination was notable for bilateral axillary adenopathy, numerous perianal ulcerations, and cutaneous Kaposi’s sarcoma. Abdominal examination was normal, and stool was Hemoccult-negative. A modified acidfast smear of the stool revealed numerous cryptosporidia. Stool examination was negative for Salmonella species, Shigeila species, Campylobacter, Giardia lamblia, Entamoeba histolytica, and lsospora belli, and Clostridium difficiie toxin was absent. Flexible sigmoidoscopy revealed mild mucosal edema and sigmoid biopsy (Figure 1A) demonstrated abundant oocysts of cryptosporidium and no evidence for herpes simplex virus infection. After 25 g of D-XylOSe, a 1-h level was 6 mg/dl and a 2-h level was 7 mg/dl (normal, >20 mg/dl). Serum gastrin, calcitonin, and vasoactive intestinal peptide levels were normal; pancreatic polypeptide levels were 763 and 290 pg/ml (normal, <150). Profuse, watery diarrhea, eventually as much as 16 L/day, persisted despite administration of spiramycin (1 g orally every 8 h for 3 wk). Similarly, sequential trials of allogeneic HLA-matched sibling lymphocyte infusion (3 x 10' viable lymphocytes), combined with a second course of spiramycin, oral bovine transfer factor, and paramomytin proved ineffective. In addition, empiric therapy with indomethacin (50 mg every 8 h), chlorpromazine (25 mg every 6 h), and verapamil (5 mg intravenously every 4 h) had no effect on stool volume. Treatment with parenteral zidovudine (100 mg i.v. every 4 h) was begun on February 26, 1987. The patient continued to receive parenteral acyclovir (500 mg every 8 h) for reactivation of perianal herpes simplex. These drugs were given for a period of 4 wk, during which stool volumes fell sequentially. The stools eventually became semiformed after 20 days of therapy. Repeat stool samples at weeks 3 and 4 showed few, then no cryptosporidia. The patient
Abbreviations used in this paper: AIDS, acquired immunodeficiency syndrome; AZT, azidothymidine. 0 1989 by tbe American Gastroenterological Association OOlE-5085/89/$3.50
1328
GREENBERGET AL.
GASTROENTEROLOGYVol. 97, No. 5
B Figure 1. A. Sigmoid colon biopsy demonstrating multiple cryptosporidium oocysts (arrows). (H&E, ~450.) B. Posttreatment autopsy demonstrating
absence of cryptosporidia.
colon at
(H&E, x450.)
gained weight, appropriately at first, but during the last few days of zidovudine therapy, he became dyspneic and tachycardiac. Pulmonary edema and cardiomegaly developed and the patient died of cardiac failure on March 29, 1987. At autopsy, there was cardiomegaly and a necrotizing granulomatous inflammation in lymph nodes, spleen, and lung (with a few acid fast bacilli in histiocytes in spleen only, not isolated on subsequent cultures). Conventional viral cultures were negative, and no morphologic evidence
for Pneumocystis carinii, cytomegalovirus, or other pathogens was identified. No neoplastic process was detected to account for the elevated pancreatic polypeptide level, which may have been due to stress and acute illness. The gastrointestinal tract was negative for cryptosporidia, in contrast to the intense colonic involvement recognized on the initial diagnostic biopsy specimens (Figure 1B). Periodically during therapy, lymphocyte subsets were quantitated and lymphocyte responsiveness to a panel of different mitogens was determined. At the onset of
November
CRYPTOSPORIDIOSIS AND AZT
1989
cryptosporidial diarrhea, analysis of lymphocyte phenotypes revealed 1% CD4, 38% CD8, and 60% CD2 with 7 CD4 per microliter. In addition, lymphocyte responsiveness to phytohemagglutinin, concanavalin A, and pokeweed mitogen was 5038, 967, and 1141 net counts per minute of H3 incorporation, respectively. However, 3 wk after initiation of AZT, at a time when marked symptomatic improvement had occurred, he had 7% CD4, 43% CD8, and 78% CD2, with 61 CD4 per microliter, and had a 322%, 228%, and 128% increase in mitogen responsiveness to phytohemagglutinin, concanavalin A, and pokeweed mitogen, respectively.
Discussion There is currently no effective anticryptosporidial therapy except for those patients whose immune deficiency can be reversed by discontinuation of immunosuppressive therapy (l), and spontaneous resolution in immunosuppressed patients is extremely rare. The most encouraging reports in treating AIDS patients has been with the macrolide antibiotic spiramycin. Portnoy et al. (2) reported that 5 of 9 patients with AIDS had resolution of their diarrhea and the remaining 4 patients had symptomatic improvement. Moskovitz et al. (3) have reported a favorable response in 28 of 37 patients with cryptosporidial diarrhea treated with spiramycin; 12 of the 28 had eradication of oocysts after 4-8 wk of therapy. Unfortunately, many patients have had a limited response to spiramycin, and those who have responded symptomatically continued to have cryptosporidia in their stool and experienced significant limiting side effects (4). Other antimicrobial agents have also been utilized with little success. Tzipori et al. (5) detected no benefit from 16 different antimicrobial agents in the treatment of experimental cryptosporidium infection in mice. Treatment with a-difluoromethylornithine significantly improved 3 of 5 AIDS patients with cryptosporidial diarrhea, although only 1 had a parasitologic response and toxicity proved to be limiting (1). Initial favorable reports with furazolidone, diloxanide furoate, and amprolium have not been corroborated (6,7). Passive immunotherapy with hyperimmune bovine colostrum or with oral bovine transfer factor has also produced mixed results (8,9). Oral bovine transfer factor failed to protect neonatal calves against experimentally induced cryptosporidiosis (10). However, a recent prospective double-blind study has yielded promising results (11). Treatment with the somatostatin analogue SMS 201-995 markedly decreased the volume of diarrhea in a patient with cryptosporidiosis, but failed to eradicate oocysts from the stool (12). Our patient experienced increasing diarrhea de-
1329
spite a full course of therapy with spiramycin and also had no clinical improvement with a brief course of oral bovine transfer factor or with HLA-matched lymphocyte transfusion given with spiramycin. Furthermore, nonspecific antidiarrheal agents and indomethacin, chlorpromazine, and verapamil (which have been used for secretory diarrhea) also proved ineffective (13). However, several weeks after initiation of treatment with AZT, the patient sustained progressive improvement of his diarrhea, associated with complete microbiologic and histologic resolution of cryptosporidiosis. Unfortunately, a rapidly progressive cardiomyopathy developed, eventuating in cardiogenic shock and death. At autopsy, no cryptosporidia were detected after thorough evaluation of the bowel. Two other reports have demonstrated resolution of cryptosporidial diarrhea with AZT. Chandrasekar (14) has reported 1 patient and Connolly et al. (4) reported 3 patients who had resolution of diarrhea and eradication of oocysts from stool, although neither report documented histologic resolution of infection. Clinical parasitic disease was related to the progressive decline in both helper T-cell (CD4) counts and in their functional capacity as reflected in falling proliferative responses to the plant lectins, phytohemagglutinin, concanavalin A, and pokeweed mitogen. Similarly, resolution of the clinical manifestations, as well as apparent eradication of cryptosporidiosis, was associated with a measurable increment in these immune parameters. These results, as well as those reported for oral bovine transfer factor, suggest that modest increases of immune function may be sufficient to inhibit this coccidial infection. In the previous reports, AZT was used alone (4,14). Our patient received a low dose of acyclovir in conjunction with full-dose zidovudine. Acyclovir is known to synergize with AZT in the in vitro suppression of human immunodeficiency virus; a recent preliminary clinical trial suggests its feasibility as a regular drug combination (15). In addition, AZT and acyclovir are not known to have direct antagonistic effects on cryptosporidium. Our experience suggests that attention to the underlying viral infection may be the best approach to certain otherwise intractable opportunistic infections that occur in AIDS.
References Soave R, Armstrong D. Cryptosporidium and cryptosporidiosis. Rev Infect Dis 1986;8:1012-23. Portnoy D, Whiteside ME, Buckley E, Macleod CL. Treatment of intestinal cryptosporidiosis with spiramycin. Ann Intern Med 1984;101:202-&. Moskovitz BL, Stanton TL, Kusmierek JJE. Spiramycin ther-
1330 GREENBERG ET AL.
apy for cryptosporidial diarrhea in immunocompromised patients. J Antimicrobial Chemotherapy 1988;22S:189-91. 4. Connolly GM, Dryden MS, Shanson DC, Gazzard BG. Cryptosporidial diarrhea in AIDS and its treatment. Gut 1988;29:593-7. 5. Tzipori SR, Campbell I, Angus KW. The therapeutic effect of 16 antimicrobial agents on cryptosporidium infection in mice. Aus J Exp Biol Med Sci 1982;80:187-90. 6. Cryptosporidiosis. Assessment of chemotherapy of males with acquired immune deficiency syndrome (AIDS). MMWR 1982;31:589-92. 7. Veldhuyzen Van Zante SJO, Lange JMA, Saverwein HP, et al. Amprolium for coccidiosis in AIDS. Lancet 1984;ii:345-6. 8. Saxon A, Weinstein W. Oral administration of bovine colostrum anti-cryptosporidia antibody fails to alter the course of human cryptosporidiosis. J Parasitol 1987;73:413-5. 9. Louie E, Borkowsky W, Klesius PH, et al. Treatment of cryptosporidiosis with oral bovine transfer factor. Clin Immuno1 Immunopathol1987;44:329-34. 10. Fayer R, Klesius PH, Andrews C. Efficacy of bovine transfer factor to protect neonatal calves against experimentally induced clinical cryptosporidiosis. J Parasitol 1987;73:1061-2. 11. McMeeking A, Borkowsky W, Klesius PH, et al. Controlled trial of specific immune bovine transfer factor therapy for
GASTROENTEROLOGY Vol. 97, No. 5
cryptosporidiosis in AIDS patients (abstr). Clin Res 1988; 36:621A. 12. Cook DJ, Kelton JG, Stanisz AM, Collins SM. Somatostatin treatment for cryptosporidial diarrhea in a patient with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988;108:708-9. 13. Krejs GJ. Secretory diarrhea. In: Bayless TM, ed. Current therapy in gastroenterology and liver disease, 1984-85. 1st ed. St. Louis: Mosby, 1984:255-g. 14. Chandrasekar PH. “Cure” of chronic cryptosporidiosis during treatment with azidothymidine in a patient with the acquired immune deficiency syndrome. Am J Med 1987;83:187. 15. Surbone A, Yarchoan R, McAtee N, et al. Treatment of the acquired immunodeficiency syndrome (AIDS) and AIDSrelated complex with a regimen of 3’-azido-2’,3’-dideoxythymidine (Azidothymidine or zidovudine) and acyclovir. Ann Intern Med 1988;108:534-l0.
Received November 14, 1988. Accepted May 19, 1989. Address requests for reprints to: Ronald E. Greenberg, M.D., Division of Gastroenterology, Room 170, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Resolution of Intestinal Cryptosporidiosis After Treatment of AIDS With AZT RONALD E. GREENBERG, FREDERICK P. SIEGAL
RABIA MIR, SIMMY BANK, and
Divisions of Gastroenterology and Hematology/Oncology, Department of Medicine, and the Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York; and State University of New York at Stony Brook, Stony Brook, New York
Intestinal cryptosporidiosis commonly results in severe protracted diarrhea that contributes sign& cantly toward morbidity and mortality in patients with acquired immunodeficiency syndrome. No satisfactory therapy for cryptosporidiosis currently exists. We describe a patient with severe secretory diarrhea and malabsorption who had clinical, microbiologic, and histologic resolution of cryptosporidiosis after therapy with zidovudine.
C
in patients with acquired imryptosporidiosis munodeficiency syndrome (AIDS) frequently causes a severe diarrhea1 illness for which no effective therapy currently exists (1).We describe a patient with cryptosporidiosis and severe secretory diarrhea and malabsorption unresponsive to spiramycin, oral bovine transfer factor, and HLA-matched allogeneic lymphocyte transfusion, who experienced symptomatic, microbiologic, and histologic resolution after treatment with zidovudine (azidothymidine, AZT). We postulate that the beneficial effect was secondary to improved cell-mediated immune functions mediated by suppression of human immunodeficiency virus (HIV-l) by AZT. Case Report A 26-yr-old homosexual man was admitted for evaluation of diarrhea. In June 1985,he experienced fever and weight loss, and was seropositive for human immunodeficiency virus (HIV-l) by Western blotting. He subsequently developed ulcerative perianal herpes simplex infection and cutaneous Kaposi’s sarcoma. He received topical acyclovir, one tablet of trimethoprim-sulfamethoxazole daily, and rifabutin that was continued until December 1986,when he developed hives and marked pruritis. Shortly thereafter, he experienced 10-14 watery bowel movements per day with abdominal cramps and gaseous discomfort that resisted empiric treatment with metronidazole, lomotil, Pepto-Bismol (Procter & Gamble, Cin-
cinnati, Ohio) and deodorized tincture of opium, necessitating hospitalization in January 1987. Physical examination was notable for bilateral axillary adenopathy, numerous perianal ulcerations, and cutaneous Kaposi’s sarcoma. Abdominal examination was normal, and stool was Hemoccult-negative. A modified acidfast smear of the stool revealed numerous cryptosporidia. Stool examination was negative for Salmonella species, Shigeila species, Campylobacter, Giardia lamblia, Entamoeba histolytica, and lsospora belli, and Clostridium difficiie toxin was absent. Flexible sigmoidoscopy revealed mild mucosal edema and sigmoid biopsy (Figure 1A) demonstrated abundant oocysts of cryptosporidium and no evidence for herpes simplex virus infection. After 25 g of D-XylOSe, a 1-h level was 6 mg/dl and a 2-h level was 7 mg/dl (normal, >20 mg/dl). Serum gastrin, calcitonin, and vasoactive intestinal peptide levels were normal; pancreatic polypeptide levels were 763 and 290 pg/ml (normal, <150). Profuse, watery diarrhea, eventually as much as 16 L/day, persisted despite administration of spiramycin (1 g orally every 8 h for 3 wk). Similarly, sequential trials of allogeneic HLA-matched sibling lymphocyte infusion (3 x 10' viable lymphocytes), combined with a second course of spiramycin, oral bovine transfer factor, and paramomytin proved ineffective. In addition, empiric therapy with indomethacin (50 mg every 8 h), chlorpromazine (25 mg every 6 h), and verapamil (5 mg intravenously every 4 h) had no effect on stool volume. Treatment with parenteral zidovudine (100 mg i.v. every 4 h) was begun on February 26, 1987. The patient continued to receive parenteral acyclovir (500 mg every 8 h) for reactivation of perianal herpes simplex. These drugs were given for a period of 4 wk, during which stool volumes fell sequentially. The stools eventually became semiformed after 20 days of therapy. Repeat stool samples at weeks 3 and 4 showed few, then no cryptosporidia. The patient
Abbreviations used in this paper: AIDS, acquired immunodeficiency syndrome; AZT, azidothymidine. 0 1989 by tbe American Gastroenterological Association OOlE-5085/89/$3.50
1328
GREENBERGET AL.
GASTROENTEROLOGYVol. 97, No. 5
B Figure 1. A. Sigmoid colon biopsy demonstrating multiple cryptosporidium oocysts (arrows). (H&E, ~450.) B. Posttreatment autopsy demonstrating
absence of cryptosporidia.
colon at
(H&E, x450.)
gained weight, appropriately at first, but during the last few days of zidovudine therapy, he became dyspneic and tachycardiac. Pulmonary edema and cardiomegaly developed and the patient died of cardiac failure on March 29, 1987. At autopsy, there was cardiomegaly and a necrotizing granulomatous inflammation in lymph nodes, spleen, and lung (with a few acid fast bacilli in histiocytes in spleen only, not isolated on subsequent cultures). Conventional viral cultures were negative, and no morphologic evidence
for Pneumocystis carinii, cytomegalovirus, or other pathogens was identified. No neoplastic process was detected to account for the elevated pancreatic polypeptide level, which may have been due to stress and acute illness. The gastrointestinal tract was negative for cryptosporidia, in contrast to the intense colonic involvement recognized on the initial diagnostic biopsy specimens (Figure 1B). Periodically during therapy, lymphocyte subsets were quantitated and lymphocyte responsiveness to a panel of different mitogens was determined. At the onset of
November
CRYPTOSPORIDIOSIS AND AZT
1989
cryptosporidial diarrhea, analysis of lymphocyte phenotypes revealed 1% CD4, 38% CD8, and 60% CD2 with 7 CD4 per microliter. In addition, lymphocyte responsiveness to phytohemagglutinin, concanavalin A, and pokeweed mitogen was 5038, 967, and 1141 net counts per minute of H3 incorporation, respectively. However, 3 wk after initiation of AZT, at a time when marked symptomatic improvement had occurred, he had 7% CD4, 43% CD8, and 78% CD2, with 61 CD4 per microliter, and had a 322%, 228%, and 128% increase in mitogen responsiveness to phytohemagglutinin, concanavalin A, and pokeweed mitogen, respectively.
Discussion There is currently no effective anticryptosporidial therapy except for those patients whose immune deficiency can be reversed by discontinuation of immunosuppressive therapy (l), and spontaneous resolution in immunosuppressed patients is extremely rare. The most encouraging reports in treating AIDS patients has been with the macrolide antibiotic spiramycin. Portnoy et al. (2) reported that 5 of 9 patients with AIDS had resolution of their diarrhea and the remaining 4 patients had symptomatic improvement. Moskovitz et al. (3) have reported a favorable response in 28 of 37 patients with cryptosporidial diarrhea treated with spiramycin; 12 of the 28 had eradication of oocysts after 4-8 wk of therapy. Unfortunately, many patients have had a limited response to spiramycin, and those who have responded symptomatically continued to have cryptosporidia in their stool and experienced significant limiting side effects (4). Other antimicrobial agents have also been utilized with little success. Tzipori et al. (5) detected no benefit from 16 different antimicrobial agents in the treatment of experimental cryptosporidium infection in mice. Treatment with a-difluoromethylornithine significantly improved 3 of 5 AIDS patients with cryptosporidial diarrhea, although only 1 had a parasitologic response and toxicity proved to be limiting (1). Initial favorable reports with furazolidone, diloxanide furoate, and amprolium have not been corroborated (6,7). Passive immunotherapy with hyperimmune bovine colostrum or with oral bovine transfer factor has also produced mixed results (8,9). Oral bovine transfer factor failed to protect neonatal calves against experimentally induced cryptosporidiosis (10). However, a recent prospective double-blind study has yielded promising results (11). Treatment with the somatostatin analogue SMS 201-995 markedly decreased the volume of diarrhea in a patient with cryptosporidiosis, but failed to eradicate oocysts from the stool (12). Our patient experienced increasing diarrhea de-
1329
spite a full course of therapy with spiramycin and also had no clinical improvement with a brief course of oral bovine transfer factor or with HLA-matched lymphocyte transfusion given with spiramycin. Furthermore, nonspecific antidiarrheal agents and indomethacin, chlorpromazine, and verapamil (which have been used for secretory diarrhea) also proved ineffective (13). However, several weeks after initiation of treatment with AZT, the patient sustained progressive improvement of his diarrhea, associated with complete microbiologic and histologic resolution of cryptosporidiosis. Unfortunately, a rapidly progressive cardiomyopathy developed, eventuating in cardiogenic shock and death. At autopsy, no cryptosporidia were detected after thorough evaluation of the bowel. Two other reports have demonstrated resolution of cryptosporidial diarrhea with AZT. Chandrasekar (14) has reported 1 patient and Connolly et al. (4) reported 3 patients who had resolution of diarrhea and eradication of oocysts from stool, although neither report documented histologic resolution of infection. Clinical parasitic disease was related to the progressive decline in both helper T-cell (CD4) counts and in their functional capacity as reflected in falling proliferative responses to the plant lectins, phytohemagglutinin, concanavalin A, and pokeweed mitogen. Similarly, resolution of the clinical manifestations, as well as apparent eradication of cryptosporidiosis, was associated with a measurable increment in these immune parameters. These results, as well as those reported for oral bovine transfer factor, suggest that modest increases of immune function may be sufficient to inhibit this coccidial infection. In the previous reports, AZT was used alone (4,14). Our patient received a low dose of acyclovir in conjunction with full-dose zidovudine. Acyclovir is known to synergize with AZT in the in vitro suppression of human immunodeficiency virus; a recent preliminary clinical trial suggests its feasibility as a regular drug combination (15). In addition, AZT and acyclovir are not known to have direct antagonistic effects on cryptosporidium. Our experience suggests that attention to the underlying viral infection may be the best approach to certain otherwise intractable opportunistic infections that occur in AIDS.
References Soave R, Armstrong D. Cryptosporidium and cryptosporidiosis. Rev Infect Dis 1986;8:1012-23. Portnoy D, Whiteside ME, Buckley E, Macleod CL. Treatment of intestinal cryptosporidiosis with spiramycin. Ann Intern Med 1984;101:202-&. Moskovitz BL, Stanton TL, Kusmierek JJE. Spiramycin ther-
1330 GREENBERG ET AL.
apy for cryptosporidial diarrhea in immunocompromised patients. J Antimicrobial Chemotherapy 1988;22S:189-91. 4. Connolly GM, Dryden MS, Shanson DC, Gazzard BG. Cryptosporidial diarrhea in AIDS and its treatment. Gut 1988;29:593-7. 5. Tzipori SR, Campbell I, Angus KW. The therapeutic effect of 16 antimicrobial agents on cryptosporidium infection in mice. Aus J Exp Biol Med Sci 1982;80:187-90. 6. Cryptosporidiosis. Assessment of chemotherapy of males with acquired immune deficiency syndrome (AIDS). MMWR 1982;31:589-92. 7. Veldhuyzen Van Zante SJO, Lange JMA, Saverwein HP, et al. Amprolium for coccidiosis in AIDS. Lancet 1984;ii:345-6. 8. Saxon A, Weinstein W. Oral administration of bovine colostrum anti-cryptosporidia antibody fails to alter the course of human cryptosporidiosis. J Parasitol 1987;73:413-5. 9. Louie E, Borkowsky W, Klesius PH, et al. Treatment of cryptosporidiosis with oral bovine transfer factor. Clin Immuno1 Immunopathol1987;44:329-34. 10. Fayer R, Klesius PH, Andrews C. Efficacy of bovine transfer factor to protect neonatal calves against experimentally induced clinical cryptosporidiosis. J Parasitol 1987;73:1061-2. 11. McMeeking A, Borkowsky W, Klesius PH, et al. Controlled trial of specific immune bovine transfer factor therapy for
GASTROENTEROLOGY Vol. 97, No. 5
cryptosporidiosis in AIDS patients (abstr). Clin Res 1988; 36:621A. 12. Cook DJ, Kelton JG, Stanisz AM, Collins SM. Somatostatin treatment for cryptosporidial diarrhea in a patient with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1988;108:708-9. 13. Krejs GJ. Secretory diarrhea. In: Bayless TM, ed. Current therapy in gastroenterology and liver disease, 1984-85. 1st ed. St. Louis: Mosby, 1984:255-g. 14. Chandrasekar PH. “Cure” of chronic cryptosporidiosis during treatment with azidothymidine in a patient with the acquired immune deficiency syndrome. Am J Med 1987;83:187. 15. Surbone A, Yarchoan R, McAtee N, et al. Treatment of the acquired immunodeficiency syndrome (AIDS) and AIDSrelated complex with a regimen of 3’-azido-2’,3’-dideoxythymidine (Azidothymidine or zidovudine) and acyclovir. Ann Intern Med 1988;108:534-l0.
Received November 14, 1988. Accepted May 19, 1989. Address requests for reprints to: Ronald E. Greenberg, M.D., Division of Gastroenterology, Room 170, Long Island Jewish Medical Center, New Hyde Park, New York 11042.