Original Article
Biliary Cryptosporidiosis in HIV-Infected People after the Waterborne Outbreak of Cryptosporidiosis in Milwaukee
N Engl J Med 1996; 334:19-23January 4, 1996
- Abstract
Background
In March 1993, the municipal water supply in Milwaukee became contaminated with cryptosporidium and a widespread outbreak of cryptosporidiosis occurred.
Methods
We retrospectively studied the relations among the clinical presentation, CD4 count, and survival in a group of 82 patients infected with the human immunodeficiency virus (HIV) in whom cryptosporidiosis developed during the outbreak. Infection was documented by the finding of cryptosporidium in stool.
Results
There was a sharp increase in the number of HIV-infected patients with cryptosporidiosis after the period of water contamination. Four of 24 patients with biliary symptoms (17 percent) and 30 of 58 without biliary symptoms (52 percent) were alive one year after the outbreak (P = 0.003). Twenty-one of the patients with biliary symptoms had CD4 counts <50 per cubic millimeter, as compared with 36 of 57 patients without biliary symptoms (88 percent vs. 63 percent, P = 0.03). The CD4 count was not available for one patient in the latter group. Within one year, 41 of the patients with CD4 counts <50 per cubic millimeter had died, as compared with 6 of those with higher counts (72 percent vs. 25 percent, P<0.001). After adjustment for the CD4 count, independent predictors of death were older age and the presence of nausea and vomiting.
Conclusions
When HIV-infected patients are exposed to cryptosporidium, those with CD4 counts <50 per cubic millimeter are at increased risk for biliary symptoms and for death within one year after the infection.
Media in This Article
Figure 1
Cases of Cryptosporidiosis among HIV-Infected People in Relation to the Period of Water Contamination in Milwaukee (March 21 to April 5, 1993).Figure 2
Kaplan–Meier Estimates of Survival According to the CD4 Count (Panel A) and, among Patients with CD4 Counts ≤50 per Cubic Millimeter, According to the Presence or Absence of Biliary Symptoms (Panel B).Article Activity
- Article
In the spring of 1993, a waterborne outbreak of cryptosporidiosis occurred in Milwaukee. The municipal water supply became contaminated with cryptosporidium, affecting more than 400,000 people.1 Immunocompromised patients are susceptible to biliary infections with cryptosporidium,2 and a number of such patients have been described with biliary disease caused by cryptosporidiosis.3-9 However, many aspects of the disease in this population of patients, including its natural history, treatment, and outcome, remain uncertain.10 The Milwaukee outbreak allowed us to study the impact of a waterborne epidemic of cryptosporidiosis on a large number of people infected with the human immunodeficiency virus (HIV). We examined the relations among the clinical presentation, CD4 counts, and survival in a group of HIV-infected patients in whom cryptosporidiosis developed during the outbreak.
Methods
We retrospectively studied HIV-infected patients in whom cryptosporidiosis developed after the contamination of the Milwaukee water supply with cryptosporidium between March 21 and April 5, 1993. Each patient had been followed by one of us for months or years before the outbreak of cryptosporidiosis. Historical data preceding the outbreak were obtained from the patients' medical records. Stool specimens from patients who presented with diarrhea after the period of water contamination were examined for cryptosporidium by modified acid-fast staining or direct fluorescent-antibody staining.1 Stool specimens from 82 patients contained cryptosporidium. Fifty-eight of these patients had diarrhea and periumbilical cramping without pain in the right upper quadrant (the group without biliary symptoms). Twenty-four had constant or intermittent pain in the right upper quadrant (the group with biliary symptoms). Changes in liver-chemistry values were not required for inclusion in the group with biliary symptoms because infectious cholecystitis may not be associated with such changes.11 All patients were studied and treated by the investigators at academic medical centers, community hospitals, private practices, or clinics. No attempt was made to modify the approach to the investigation and treatment of patients at individual sites. Paromomycin (Humatin, Parke-Davis, Morris Plains, N.J.) and azithromycin (Zithromax, Pfizer, New York) were used to treat the cryptosporidium infection.
The response to medical or surgical therapy was determined by the patients' subjective assessment of symptom improvement. In patients without biliary symptoms, a decrease in stool frequency and the incidence of abdominal cramping was considered a partial response, complete resolution of diarrhea and cramping a complete response, and no change in the frequency of diarrhea or cramping a lack of response. In patients with biliary symptoms, complete relief of pain was considered a complete response, incomplete relief a partial response, and no relief a lack of response. The study period continued until April 5, 1994, one year after the end of the period of water contamination. The study was approved by the Human Subjects Review Board of Sinai Samaritan Medical Center.
Statistical Analysis
Results are presented as means ±SE. The primary outcome variable was the number of days from the diagnosis of cryptosporidiosis (base line) until death. The primary statistical analyses used the Cox proportional-hazards regression model12 to compare survival in the two groups after adjustment for clinically relevant base-line predictors such as the CD4 count (<50 cells per cubic millimeter or >50 cells per cubic millimeter), age, and the presence of nausea and vomiting. Relative risks are described in terms of the hazard ratio, along with associated 95 percent confidence intervals. Survival curves were estimated according to the method of Kaplan and Meier, and differences in survival were determined by the log-rank test.13 Two-way analysis of variance was used to compare the two groups after adjustment for the CD4 count (<50 cells per cubic millimeter or >50 cells per cubic millimeter), with regard to the following variables: age and levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin. The laboratory values were compared between the groups both before and during the illness and were log-transformed for statistical analysis. Fisher's exact test was used for dichotomous variables, and other comparisons were performed with the Mann–Whitney test. All statistical tests were two-tailed, and a P value of 0.05 or less was considered to indicate statistical significance.
Results
Clinical Course
In 1992 there were six cases of cryptosporidial diarrhea and one case of biliary cryptosporidiosis among HIV-infected patients at the participating centers. There was a sharp increase in the number of cases (Figure 1Figure 1
Cases of Cryptosporidiosis among HIV-Infected People in Relation to the Period of Water Contamination in Milwaukee (March 21 to April 5, 1993).) in April 1993, which corresponded with the period of water contamination in Milwaukee. The peak occurrence of biliary and nonbiliary symptoms was at approximately the same time (Figure 1). Fourteen of the 24 patients with biliary symptoms (58 percent) and 19 of the 58 patients without biliary symptoms (33 percent) had nausea and vomiting. In 7 of the 82 patients (8.5 percent), cryptosporidiosis was the illness that defined the presence of the acquired immunodeficiency syndrome (AIDS). Liver-chemistry values were similar in both groups before the illness but were significantly higher in the patients with biliary symptoms after the onset of the disease (Table 1Table 1
Clinical Characteristics of the 82 HIV-Infected Patients with Cryptosporidiosis, According to the Presence or Absence of Biliary Symptoms.). Twenty-two patients with biliary symptoms had an increase in alkaline phosphatase after the onset of pain. The two patients in this group who did not have a significant change in alkaline phosphatase levels were found to have acute cryptosporidial cholecystitis at surgery. Four patients with biliary symptoms were alive at one year (17 percent), as compared with 30 patients without biliary symptoms (52 percent, P = 0.003).Predictors of Outcome
CD4 counts ≤50 per cubic millimeter were a risk factor for the development of biliary symptoms. Twenty-one of the 24 patients with biliary symptoms (88 percent) had CD4 counts <50 per cubic millimeter, as compared with 36 of the 57 patients without biliary symptoms (63 percent, P = 0.03). The CD4 count was not available for one patient with no biliary symptoms, who survived. Cox regression analysis (Table 2Table 2
Effect of Prognostic Factors on Survival.) showed that the strongest base-line predictor of mortality was a CD4 count <50 per cubic millimeter (hazard ratio, 4.10; 95 percent confidence interval, 1.72 to 9.76; P<0.001). Other independent predictors included increasing age and the presence of nausea and vomiting. After adjustment for these factors, biliary disease was not associated with poorer survival. These findings were substantiated by the Kaplan–Meier survival curves, which demonstrated a significantly higher mortality rate among patients with CD4 counts <50 per cubic millimeter than among those with higher counts (P<0.001) (Figure 2AFigure 2Kaplan–Meier Estimates of Survival According to the CD4 Count (Panel A) and, among Patients with CD4 Counts ≤50 per Cubic Millimeter, According to the Presence or Absence of Biliary Symptoms (Panel B).). When patients with CD4 counts below 50 per cubic millimeter were analyzed according to the presence or absence of biliary symptoms, there was no significant difference in survival (P = 0.22) (Figure 2B).Diagnostic Studies and Therapeutic Interventions
Forty-one diagnostic studies were performed in the 24 patients with biliary symptoms: 17 abdominal ultrasound examinations, 7 biliary scintiscans, 7 computed tomographic scans of the abdomen, and 10 endoscopic retrograde cholangiopancreatograms. On ultrasonography, dilatation of the common bile duct was seen in 14, thickening of the gallbladder wall in 7, and dilatation of the intrahepatic ducts in 6. Of the three patients with normal ducts at ultrasonography, two had dilated ducts on subsequent computed tomographic scans and one had thickening of the gallbladder wall and pericholecystic accumulation of fluid that was later shown at cholecystectomy to be due to cryptosporidial cholecystitis. Eight diagnostic studies were performed in the 58 patients without biliary symptoms: five abdominal ultrasound examinations and three abdominal computed tomographic scans, which were done to evaluate other conditions related to AIDS.
Ten of the 24 patients with biliary symptoms (42 percent) underwent endoscopic retrograde cholangiopancreatography, and all were found to have a dilated common bile duct (range, 10 to 16 mm in diameter) and a narrowing in the distal duct consistent with the presence of papillitis or papillary stenosis. Three patients had intrahepatic ductal strictures, and one had a dilated pancreatic duct. Endoscopic ampullary biopsies or examination of cytologic samples from the biliary tract revealed cryptosporidium in 5 of these 10 patients. Two of the five patients with negative results on testing of endoscopic samples subsequently underwent cholecystectomy, and cryptosporidial cholecystitis was found in both. Cytomegalovirus was not found on biopsies or in analysis of brushings in any of the patients.
Nine of the 10 patients with biliary symptoms who underwent endoscopic retrograde cholangiopancreatography also underwent endoscopic sphincterotomy; sphincterotomy could not be completed in the 10th patient because he became agitated. Sphincterotomy did not completely relieve the pain in any of the patients: three had partial relief, and six had no significant change in the level of pain. Sphincterotomy did not significantly change the values for aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or bilirubin (P>0.1 for all values). There was no correlation between changes in laboratory values and the relief of pain.
In four patients with biliary symptoms, symptoms of acute cholecystitis developed, and cholecystectomy was performed. None of these four had gallstones, and histologic analysis revealed cryptosporidial cholecystitis in all of them. Three had complete relief of pain after cholecystectomy. None of the other patients with biliary symptoms underwent endoscopic retrograde cholangiopancreatography, because they either were too ill or refused. One patient had severe pain that was unresponsive to analgesics, and a celiac-ganglion block was performed, with partial relief of pain.
A definitive diagnosis was established in nine patients with biliary symptoms (38 percent) by the demonstration of cryptosporidium in the biliary tree on analysis of biliary brushings obtained by endoscopy, on biopsy, or on histologic examination of the gallbladder. In these nine patients, the CD4 count and levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin were not significantly different from those in the rest of the patients with biliary symptoms (P>0.25 for all).
Twenty-two patients with biliary symptoms (92 percent) and 43 patients without such symptoms (74 percent) received paromomycin as treatment for cryptosporidiosis. Twelve (18 percent) had a complete response, all of whom had no biliary symptoms; 22 (34 percent) had a partial response (12 with biliary symptoms and 10 without such symptoms); and 31 (48 percent) had no response (10 with biliary symptoms and 21 with no biliary symptoms). In 19 of the patients who had a partial response or no response to paromomycin, azithromycin was administered. One of these patients, who had intestinal cryptosporidiosis, had a complete response with the addition of azithromycin; 8 had no response, and 10 had a partial response. The mean CD4 count in the patients who had a complete response to therapy was 157±66 per cubic millimeter; in those with a partial response it was 33±8 per cubic millimeter; and in those with no response it was 29±6 per cubic millimeter (P = 0.25). Somatostatin was used in 8 patients with biliary symptoms (33 percent) and 16 patients without such symptoms (28 percent).
Fourteen patients with biliary symptoms (58 percent) and 10 without such symptoms (17 percent) were given total parenteral nutrition. Three patients with biliary symptoms (12 percent) and 26 without such symptoms (45 percent) did not need to be hospitalized (P =0.005). Patients with CD4 counts <50 per cubic millimeter spent longer periods in the hospital than those with higher counts (22±5 vs. 7±3 days, P = 0.003).
Discussion
Waterborne outbreaks of cryptosporidiosis have been described in the United States and other countries,14,15 but there are few data on the effects of such outbreaks on people infected with HIV. Defining biliary cryptosporidiosis in clinical practice is difficult. The results of noninvasive studies and retrograde cholangiography in HIV-infected patients are nonspecific and similar to those in other disorders, such as cytomegalovirus infection5 and microsporidiosis.16 Furthermore, symptoms may not be related to the findings on imaging studies: asymptomatic patients may be found to have cholangiopathy on retrograde cholangiography.17 The demonstration of cryptosporidium in the biliary tree of a symptomatic patient with an abnormal cholangiogram or histologic demonstration of cryptosporidial cholecystitis provides a definitive diagnosis, but such studies cannot be done in patients who are too ill to undergo invasive procedures.
We found that when HIV-infected persons were exposed to cryptosporidium, a CD4 count <50 per cubic millimeter was a significant risk factor for the development of biliary symptoms. Patients with biliary symptoms tended to have cholestasis with the onset of pain and abnormal findings on imaging studies of the biliary tree. Patients with CD4 counts ≤50 per cubic millimeter had a long hospital stay and decreased survival (as compared with patients with CD4 counts >50 per cubic millimeter). The peaks in the onset of diarrhea and biliary symptoms occurred at similar times, which suggests that biliary disease develops soon after susceptible patients acquire cryptosporidia.
In a recent placebo-controlled study of patients with AIDS and intestinal cryptosporidiosis, treatment with paromomycin decreased stool frequency and oocyst excretion, but biliary disease progressed despite long-term suppressive therapy.18 Our data support these observations. In some uncontrolled studies, sphincterotomy has been reported to result in rapid and sustained relief of right-upper-quadrant pain in the majority of patients with AIDS and biliary cryptosporidiosis,19 whereas in other studies it afforded only partial relief.20 In anecdotal reports involving extended periods of follow-up, pain has been described as a persistent problem after sphincterotomy in patients with AIDS.9 Some studies reported initial improvement in liver-chemistry values after sphincterotomy, but longer follow-up showed that the values subsequently worsened.20 Comparisons of such studies are difficult because the duration of follow-up was not specified in some, and others did not distinguish between partial and complete relief of pain.
In our study, the results of sphincterotomy for relief of pain were disappointing. Most patients continued to have severe pain that required treatment with narcotics. The most dramatic relief of biliary pain was in patients presenting with acute cholecystitis. Three of four such patients were free of pain after cholecystectomy, but only one of these patients was alive one year later.
Patients with CD4 counts <50 per cubic millimeter had a significantly higher risk of death than those with higher counts. However, the survival rate among patients with CD4 counts <50 per cubic millimeter was similar in patients with and those without biliary symptoms, suggesting that the CD4 count, and not the presence of biliary disease, was the primary determinant of outcome. Flanigan et al.21 have reported that HIV-infected patients with CD4 counts ≤140 per cubic millimeter tend to have persistent cryptosporidium infection — an association that would explain our finding of a poor outcome in patients with low CD4 counts. In our study, proportional-hazards analysis suggested that increasing age, the presence of nausea and vomiting, and CD4 counts <50 per cubic millimeter were independent predictors of mortality, but the presence or absence of biliary disease was not.
Infection with cryptosporidium is a reportable disease in only a few states, and there is no national surveillance for infections with this organism.22 Public water supplies that meet current federal and state standards for drinking water may still become contaminated with cryptosporidial oocysts and cause large outbreaks,14 as occurred in Milwaukee.1
Presented at the annual meeting of the American Gastroenterological Association, San Diego, Calif., May 14–17, 1995.
Supported by the Mount Sinai Hospital Foundation.
We are indebted to Linda Eichhorst, Thomas Taft, M.D., and Gerald Dorff, M.D., for their assistance, and to Keith Bourgeois and Michael McDermott of the Department of Biostatistics, University of Rochester, for assistance with the statistical analysis.
Source Information
From the Departments of Medicine, University of Wisconsin Medical School (N.B.V., S.M.S., B.P.B., C.F.B., I.H.G., P.G.J.) and the Medical College of Wisconsin (M.K., D.M.L.) — both in Milwaukee.
Address reprint requests to Dr. Vakil at the University of Wisconsin Medical School–Milwaukee Campus, Sinai Samaritan Medical Center, 945 N. 12th St., Rm. A 324, Milwaukee, WI 53233.
- References
References
1
Mac Kenzie WR ,Hoxie NJ ,Proctor ME , et al. A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply. N Engl J Med 1994;331:161-167
Full Text | Web of Science | Medline2
Soave R ,Danner RL ,Honig CL , et al. Cryptosporidiosis in homosexual men. Ann Intern Med 1984;100:504-511
Web of Science | Medline3
Pitlik SD ,Fainstein V ,Garza D , et al. Human cryptosporidiosis: spectrum of disease: report of six cases and review of the literature. Arch Intern Med 1983;143:2269-2275
CrossRef | Web of Science | Medline4
Kavin H ,Jonas RB ,Chowdhury L ,Kabins S . Acalculous cholecystitis and cytomegalovirus infection in the acquired immunodeficiency syndrome. Ann Intern Med 1986;104:53-54
Web of Science | Medline5
Margulis SJ ,Honig CL ,Soave R ,Govoni AF ,Mouradian JA ,Jacobson IM . Biliary tract obstruction in the acquired immunodeficiency syndrome. Ann Intern Med 1986;105:207-210
Web of Science | Medline6
Schneiderman DJ ,Cello JP ,Laing FC . Papillary stenosis and sclerosing cholangitis in the acquired immunodeficiency syndrome. Ann Intern Med 1987;106:546-549
Web of Science | Medline7
Godwin TA . Cryptosporidiosis in the acquired immunodeficiency syndrome: a study of 15 autopsy cases. Hum Pathol 1991;22:1215-1224
CrossRef | Web of Science | Medline8
Bouche H ,Housset C ,Dumont J-L , et al. AIDS-related cholangitis: diagnostic features and course in 15 patients. J Hepatol 1993;17:34-39
CrossRef | Web of Science | Medline9
Forbes A ,Blanshard C ,Gazzard B . Natural history of AIDS related sclerosing cholangitis: a study of 20 cases. Gut 1993;34:116-121
CrossRef | Web of Science | Medline10
Petersen C . Cryptosporidiosis in patients infected with the human immunodeficiency virus. Clin Infect Dis 1992;15:903-909
CrossRef | Web of Science | Medline11
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;121:663-664
Web of Science | Medline12
Cox DR . Regression models and life-tables. J R Stat Soc [B] 1972;34:187-22013
Armitage P, Berry G. Statistical methods in medical research. 2nd ed. Oxford, England: Blackwell Scientific, 1987.
14
Hayes EB ,Matte TD ,O'Brien TR , et al. Large community outbreak of cryptosporidiosis due to contamination of a filtered public water supply. N Engl J Med 1989;320:1372-1376
Full Text | Web of Science | Medline15
Richardson AJ ,Frankenberg RA ,Buck AC , et al. An outbreak of waterborne cryptosporidiosis in Swindon and Oxfordshire. Epidemiol Infect 1991;107:485-495
CrossRef | Web of Science | Medline16
Pol S ,Romana CA ,Richard S , et al. Microsporidia infection in patients with the human immunodeficiency virus and unexplained cholangitis. N Engl J Med 1993;328:95-99
Full Text | Web of Science | Medline17
Chan MF ,Cello JP . Prevalence of AIDS-associated cholangiopathy in asymptomatic patients. Hepatology 1992;16:127A-127A abstract.
CrossRef | Web of Science18
White AC Jr ,Chappell CL ,Hayat CS ,Kimball KT ,Flanigan TP ,Goodgame RW . Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial. J Infect Dis 1994;170:419-424
CrossRef | Web of Science | Medline19
Benhamou Y ,Caumes E ,Gerosa Y , et al. AIDS-related cholangiopathy: critical analysis of a prospective series of 26 patients. Dig Dis Sci 1993;38:1113-1118
CrossRef | Web of Science | Medline20
Cello JP . Acquired immunodeficiency syndrome cholangiopathy: spectrum of disease. Am J Med 1989;86:539-546
CrossRef | Web of Science | Medline21
Flanigan T ,Whalen C ,Turner J , et al. Cryptosporidium infection and CD4 counts. Ann Intern Med 1992;116:840-842
Web of Science | Medline22
Berkelman RL ,Bryan RT ,Osterholm MT ,LeDuc JW ,Hughes JM . Infectious disease surveillance: a crumbling foundation. Science 1994;264:368-370
CrossRef | Web of Science | Medline
- Citing Articles (37)
Citing Articles
1
Yannick Beauséjour, Claude Fortin, Marc Ghannoum, Valéry Lavergne. (2011) Immune reconstitution inflammatory syndrome following cryptosporidial cholangitis. AIDS 25:14, 1801-1803
CrossRef2
E. D. Nel, H. Rabie, J. Goodway, M. F. Cotton. (2011) A Retrospective Study of Cryptosporidial Diarrhea in a Region with High HIV Prevalence. Journal of Tropical Pediatrics 57:4, 289-292
CrossRef3
Yiming Gao, Kathryn Chin, Yehia Y. Mishriki. (2011) AIDS Cholangiopathy in an Asymptomatic, Previously Undiagnosed Late-Stage HIV-Positive Patient from Kenya. International Journal of Hepatology 2011, 1-6
CrossRef4
Aaron R. Jex, Huw V. Smith, Matthew J. Nolan, Bronwyn E. Campbell, Neil D. Young, Cinzia Cantacessi, Robin B. Gasser. 2011. Cryptic Parasite Revealed. , 141-173.
CrossRef5
Jesús Fortún Abete, Pilar Martín-Dávila. (2010) La infección intraabdominal en el paciente inmunodeprimido. Enfermedades Infecciosas y Microbiología Clínica 28, 11-17
CrossRef6
S. Collinet-Adler, H. D. Ward. (2010) Cryptosporidiosis: environmental, therapeutic, and preventive challenges. European Journal of Clinical Microbiology & Infectious Diseases 29:8, 927-935
CrossRef7
J. N. Velásquez, C. di Risio, E. Marta, O. G. Astudillo, C. Etchart, M. A. Cucher, A. V. Chertcoff, E. Perissé, S. Carnevale. (2010) Occurrence of bile-duct/duodenal abnormalities in nine AIDS patients co-infected with <I>Cryptosporidium</I> <I>hominis</I> and/or <I>C.</I> <I>parvum</I>. Annals of Tropical Medicine and Parasitology 104:3, 257-263
CrossRef8
Jean-François Rossignol. (2010) Cryptosporidium and Giardia: Treatment options and prospects for new drugs. Experimental Parasitology 124:1, 45-53
CrossRef9
C. N. Kotton, R. Lattes, . (2009) Parasitic Infections in Solid Organ Transplant Recipients. American Journal of Transplantation 9, S234-S251
CrossRef10
C. C. McOliver, H. B. Lemerman, E. K. Silbergeld, R. D. Moore, T. K. Graczyk. (2009) Risks of Recreational Exposure to Waterborne Pathogens Among Persons With HIV/AIDS in Baltimore, Maryland. American Journal of Public Health 99:6, 1116-1122
CrossRef11
Archana Bhaskaran, A Clinton White. 2009. Cryptosporidiosis. .
CrossRef12
Aaron R. Jex, Robin B. Gasser. (2008) Analysis of the genetic diversity within Cryptosporidium hominis and Cryptosporidium parvum from imported and autochtonous cases of human cryptosporidiosis by mutation scanning. ELECTROPHORESIS 29:20, 4119-4129
CrossRef13
Oluma Y. Bushen, Richard L. Guerrant. 2008. Etiology and Management of Diarrhea in HIV-infected Patients and Impact on Antiretroviral Therapy. , 737-745.
CrossRef14
David K. Hong, Cynthia J. Wong, Kathleen Gutierrez. (2007) Severe cryptosporidiosis in a seven-year-old renal transplant recipient - Case report and review of the literature. Pediatric Transplantation 11:1, 94-100
CrossRef15
David B. Huang, A. Clinton White. (2006) An Updated Review on Cryptosporidium and Giardia. Gastroenterology Clinics of North America 35:2, 291-314
CrossRef16
Penny Lewthwaite, Geoffrey V Gill, C Anthony Hart, Nicholas J Beeching. (2005) Gastrointestinal parasites in the immunocompromised. Current Opinion in Infectious Diseases 18:5, 427-435
CrossRef17
Tony E. Yusuf, Todd H. Baron. (2004) AIDS cholangiopathy. Current Treatment Options in Gastroenterology 7:2, 111-117
CrossRef18
JAMES MCLAUCHLIN, CORINNE F. L. AMAR, SUSANA PEDRAZA-DÍAZ, GIORGINA MIELI-VERGANI, NEDIM HADZIC, E. GRAHAM DAVIES. (2003) Polymerase chain reaction-based diagnosis of infection with Cryptosporidium in children with primary immunodeficiencies. The Pediatric Infectious Disease Journal 22:4, 329-334
CrossRef19
Rebecca A. Dillingham, Aldo A. Lima, Richard L. Guerrant. (2002) Cryptosporidiosis: epidemiology and impact. Microbes and Infection 4:10, 1059-1066
CrossRef20
Peter F. M. Teunis, Cynthia L. Chappell, Pablo C. Okhuysen. (2002) Cryptosporidium Dose-Response Studies: Variation Between Hosts. Risk Analysis 22:3, 475-485
CrossRef21
Chen, Xian-Ming, Keithly, Janet S., Paya, Carlos V., LaRusso, Nicholas F., . (2002) Cryptosporidiosis. New England Journal of Medicine 346:22, 1723-1731
Full Text22
Margaret Kosek, Cirle Alcantara, Aldo AM Lima, Richard L Guerrant. (2001) Cryptosporidiosis: an update. The Lancet Infectious Diseases 1:4, 262-269
CrossRef23
Naomi E. Aronson, Christopher Cheney, Vicky Rholl, David Burris, Neal Hadro. (2001) Biliary Giardiasis in a Patient With Human Immunodeficiency Virus. Journal of Clinical Gastroenterology 33:2, 167-170
CrossRef24
Xian-ming Chen, Susan A. Levine, Patrick L. Splinter, Pamela S. Tietz, Amanda L. Ganong, Christian Jobin, Gregory J. Gores, Carlos V. Paya, Nicholas F. LaRusso. (2001) Cryptosporidium parvum activates nuclear factor кB in biliary epithelia preventing epithelial cell apoptosis. Gastroenterology 120:7, 1774-1783
CrossRef25
Rafiq A. Sheikh, Thomas P. Prindiville, Sury Yenamandra, Robert J. Munn, Boris H. Ruebner. (2000) Microsporidial AIDS cholangiopathy due to Encephalitozoon intestinalis: case report and review. The American Journal of Gastroenterology 95:9, 2364-2371
CrossRef26
Xian-Ming Chen, Nicholas F. LaRusso. (2000) Mechanisms of attachment and internalization of Cryptosporidium parvum to biliary and intestinal epithelial cells. Gastroenterology 118:2, 368-379
CrossRef27
Jeanne A. Lumadue, Yukari C. Manabe, Richard D. Moore, Peter C. Belitsos, Cynthia L. Sears, Douglas P. Clark. (1998) A clinicopathologic analysis of AIDS-related cryptosporidiosis. AIDS 12:18, 2459-2466
CrossRef28
Xian-Ming Chen, Susan A. Levine, Pamela Tietz, Eugene Krueger, Mark A. McNiven, Douglas M. Jefferson, Megan Mahle, Nicholas F. LaRusso. (1998) Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism. Hepatology 28:4, 906-913
CrossRef29
Robert L. Owen. (1998) New perspectives on the pathogenesis ofCryptosporidium biliary disease. Hepatology 28:4, 1159-1160
CrossRef30
Andrew Carr, Deborah Marriott, Andrew Field, Eva Vasak, David A Cooper. (1998) Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. The Lancet 351:9098, 256-261
CrossRef31
Holly R. Frisby, David G. Addiss, William J. Reiser, Beth Hancock, James M. Vergeront, Neil J. Hoxie, Jeffrey P. Davis. (1997) Clinical and Epidemiologic Features of a Massive Waterborne Outbreak of Cryptosporidiosis in Persons With HIV Infection. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 16:5, 367-373
CrossRef32
Joseph A. Nash, Seth A. Cohen. (1997) GALLBLADDER AND BILIARY TRACT DISEASE IN AIDS. Gastroenterology Clinics of North America 26:2, 323-335
CrossRef33
Joan B. Rose. (1997) ENVIRONMENTAL ECOLOGY OF CRYPTOSPORIDIUM AND PUBLIC HEALTH IMPLICATIONS. Annual Review of Public Health 18:1, 135-161
CrossRef34
Cyrus R. Kapadia. (1997) Oxides, Onions, and Other Matters Gastrointestinal-1996-A Perspective. Journal of Clinical Gastroenterology 24:3, 133-139
CrossRef35
Stuart R. Framm, Rosemary Soave. (1997) AGENTS OF DIARRHEA. Medical Clinics of North America 81:2, 427-447
CrossRef36
Rayhan Hashmey, Nathaniel H. Smith, Stanley Cron, Edward A. Graviss, Cynthia L. Chappell, A. Clinton White. (1997) Cryptosporidiosis in Houston, Texas. Medicine 76:2, 118-139
CrossRef37
Ted S. Steiner, MD, Nathan M. Thielman, MD, Richard L. Guerrant, MD. (1997) PROTOZOAL AGENTS: What Are the Dangers for the Public Water Supply?. Annual Review of Medicine 48:1, 329-340
CrossRef
