Original Article
Microsporidia Infection in Patients with the Human Immunodeficiency Virus and Unexplained Cholangitis
N Engl J Med 1993; 328:95-99January 14, 1993
- Abstract
Background
Cholangitis in patients with the acquired immunodeficiency syndrome (AIDS) is usually associated with opportunistic infections by cryptosporidium species or cytomegalovirus, but in about a third of cases no opportunistic agent is identified. We suspected some of these cases of biliary disease might be explained by infection with the microsporidia species Enterocytozoon bieneusi, an obligate intracellular protozoan that causes chronic diarrhea in patients infected with the human immunodeficiency virus (HIV).
Methods
We studied eight HIV-infected homosexual men (in either group IV of the classification of the Centers for Disease Control and Prevention or group II, with a CD4 cell count of ≤ 10 per cubic millimeter) who were referred because of cholangitis for which no causative agent had been found by standard tests. All the patients underwent abdominal ultrasonography and endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography with collection of bile from the common bile duct. One patient had transhepatic biliary catheterization, and two others had cholecystectomy. Bile samples, duodenal- and liver-biopsy specimens, and gallbladder tissue were studied by light and electron microscopy.
Results
All eight patients with unexplained AIDS-related cholangitis had biliary microsporidiosis. Intraepithelial E. bieneusi spores (1 to 2 micrometers) and supranuclear plasmodia (3 to 8 micrometers) were identified in the six duodenal-biopsy specimens. May-Grunwald-Giemsa staining of bile samples revealed free forms of microsporidia in all eight patients, and the presence of E. bieneusi was confirmed by electron microscopy. E. bieneusi was also identified in ductal biliary cells on a liver biopsy, in one common-bile-duct smear, and in gallbladder epithelium (in two patients). Four patients were found to have associated but previously undetected biliary or duodenal cryptosporidiosis, whereas another had biliary infection associated with cytomegalovirus.
Conclusions
Infection of the biliary tract with E. bieneusi is associated with and may be a cause of AIDS-related cholangitis.
Media in This Article
Figure 1
Electron-Dense Spore of E. bieneusi in the Bile of an HIV-Infected Patient.Figure 2
Multinucleate Plasmodia of E. bieneusi.Article Activity
- Article
Cholangitis related to the acquired immunodeficiency syndrome (AIDS) has been described increasingly since the first report of acalculous cholecystitis in such a patient1-4. AIDS-related cholangitis is characterized by chronic abdominal pain, low-grade fever, and cholestasis with dilatation of the bile duct and irregularities of the bile-duct wall that are apparent on ultrasonography. The cause is unclear, but it would appear to be mainly related to opportunistic infections. Probable causative microorganisms are identified in about 60 percent of patients and include cryptosporidium species and cytomegalovirus.
No opportunistic agent is identified in about 40 percent of patients with AIDS-related biliary disease. It has been suggested that the immunodeficiency itself, human immunodeficiency virus (HIV) infection of the bile-duct mucosa, and other, unidentified pathogens may cause AIDS-related cholangitis. Several syndromes have been attributed to microsporidia infections in AIDS5-8. Two cases of biliary tract infection by Enterocytozoon bieneusi have now been described,9,10 suggesting that microsporidiosis could be involved in AIDS-related cholangitis. We therefore conducted a prospective study in an attempt to identify microbial causes of unexplained AIDS-related biliary vesicular disease, with special attention to microsporidia infections.
Methods
Patients
Over an 18-month period (April 1990 through September 1991), eight HIV-positive homosexual men were referred to our liver unit with unexplained chronic cholestasis or diarrhea. Their mean (±SD) age was 38 ±6 years, and HIV infection had been diagnosed a mean of 3.6 ±1.3 years previously.
Six patients met the criteria for AIDS established by the Centers for Disease Control and Prevention (CDCP)11 (group IV-C1 or IV-D); the remaining two were asymptomatic (group II) but had low CD4 lymphocyte counts (8 and 10 per cubic millimeter). Six of the eight patients had p24 antigenemia (Table 1Table 1
Clinical and Biologic Data on Eight Homosexual Men at the Time of Diagnosis of Biliary Infection by E. bieneusi.). In six of the eight patients opportunistic infections and neoplasms preceded the onset of cholangitis or were present when it was diagnosed; they included cytomegalovirus chorioretinitis (three patients), Pneumocystis carinii pneumonia (two), cytomegalovirus viremia (one), oral candidiasis (one), meningeal cryptococcal infection (one), and Kaposi's sarcoma (two). All but one of the patients had chronic diarrhea or cholestasis (serum alkaline phosphatase and γ-glutamyltransferase activities at least 1.5 times the upper limit of normal). None had a history of biliary tract surgery. All the patients had abdominal pain (in the epigastric region in one, in the right upper quadrant in five, and in both locations in two). None had jaundice, five had persistent fever, and none had acute cholangitis before undergoing endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography. Six of the eight patients had marked weight loss (i.e., a loss of more than 10 percent of their normal weight) (Table 2Table 2
Clinical Data and Liver Tests in the Eight Homosexual Men at the Time of Diagnosis.). Serum alkaline phosphatase and γ-glutamyltransferase activities were elevated in most patients, with mean elevations 2.3 times the upper limit of normal (range, 0.6 to 7.6) and 2.7 times the upper limit of normal (range, 0.8 to 7.0), respectively. Serum aminotransferase activities were elevated in seven patients, with means of 2.9 and 2.1 times the upper limit of normal for aspartate aminotransferase and alanine aminotransferase, respectively (ranges, 0.7 to 13.2 and 0.5 to 8.4). The serum total bilirubin concentrations were below 1.0 mg per deciliter (17 μmol per liter) in all the patients (mean, 0.6 mg per deciliter [9.6 μmol per liter]) (Table 2).The cholestasis and chronic diarrhea were not explained by standard microbiologic investigations, including bacteriologic and parasitologic examinations of stool samples and repeat blood cultures, cytomegalovirus viremia, or anti-cytomegalovirus IgM antibody testing with standard methods. None of the patients had active or previous mycobacterial infection at the time of the diagnosis of AIDS-related cholangitis.
It is noteworthy that these eight patients had no epidemiologic relation to each other and were not clustered with respect to time or location. They had no exposure that was related to recent travel overseas.
Morphologic Procedures
All the patients underwent abdominal ultrasonography, and seven underwent endoscopic ultrasonography with the collection of a biliary sample by cannulation of the common bile duct. Four patients underwent ERCP, including endoscopic sphincterotomy in two patients. The morphologic diagnosis of cholangitis was based on Cello's criteria3. Two patients (Patients 7 and 8) underwent surgical cholecystectomy for acalculous cholecystitis associated with cholangitis. Endoscopy of the upper gastrointestinal tract (with duodenal biopsy) and colonoscopy (with staged colonic biopsies) were performed in seven and five patients, respectively.
Microbiologic Procedures
All bile and tissue samples were processed for microbiologic tests as described below. Bile samples were obtained after endoscopic papillary cannulation in seven patients. Further bile samples were obtained from Patient 3 by means of transhepatic catheterization and from Patient 8 during surgical cholecystectomy; a bile sample was obtained during cholecystectomy from the patient who did not undergo endoscopic ultrasonography (with this procedure, duodenal contamination is avoided). Papillary or choledochal biopsies were performed in four patients during ERCP, and transparietal liver-biopsy specimens were obtained from two patients. Biopsy specimens from the duodenum and liver, gallbladder tissue, and bile samples were studied by light and electron microscopy.
Microscopy
Light Microscopy
Touch preparations of the tissue samples and cytocentrifugation smears of bile were dried, stained with May-Grunwald-Giemsa for 30 minutes, fixed in Bouin's fixative for at least 4 hours, and then processed routinely. Slides of each specimen were stained with hematoxylin and eosin, May-Grunwald-Giemsa, Gram's, Ziehl-Neelsen, and methenamine-silver stains. Glutaraldehyde-fixed material for electron microscopy was also embedded in paraffin. Some sections were stained with toluidine blue and examined by light microscopy.
Electron Microscopy
Bile samples were centrifuged, and the pellets containing microsporidia spores were fixed in 2 percent glutaraldehyde in 1 percent 0.1 M sodium cacodylate buffer for two hours, rinsed in buffer, and postfixed in a medium containing 1 percent (vol/vol) osmium tetroxide and potassium ferricyanide in cacodylate buffer for one hour at room temperature. After ethanol dehydration, the material was embedded in Spurr's resin. Ultrathin sections were stained with uranyl acetate and lead citrate. They were observed with a Jeol transmission electron microscope (JEM 100CX) at 80 kV.
Results
Six of the eight patients with unexplained chronic diarrhea or cholestasis had AIDS-related cholangitis at the time of their first admission, as shown by abdominal ultrasonography, endoscopic ultrasonography, or ERCP. The morphologic abnormalities included dilatation of both the intrahepatic and the common bile ducts, irregularities of the bile-duct wall, and an abnormal gallbladder (with wall thickening, distention, or sludge). Papillary stenosis was also present in one patient, and hyperalgesic cholecystitis associated with intrahepatic and extrahepatic abnormalities necessitated cholecystectomy in two patients. One patient (Patient 2), with a seven-month history of unexplained diarrhea, had a normal ERCP; four months later, a second ERCP confirmed the diagnosis of cholangitis. Another patient (Patient 6) had a normal biliary tract on repeated ultrasonography and endoscopic ultrasonography and remained free of biliary disease after 12 months of follow-up, despite the onset of AIDS. Finally, a typical AIDS-related cholangitis appeared 15 months after the diagnosis of biliary infection with microsporidia. Despite normal morphologic findings, this infection was diagnosed in both these patients at the time of the first ERCP (see below).
Standard endoscopic exploration of the upper digestive tract and colon was either normal or showed nonspecific abnormalities in the seven and five patients who underwent the respective procedures.
The results of microbiologic tests using light and electron microscopy are summarized in Table 3Table 3
Results of Microbiologic Analysis by Light and Electron Microscopy in the Eight Patients.. Intraepithelial E. bieneusi spores (1 to 2 micrometers) and supranuclear plasmodia (3 to 8 micrometers) were found in duodenal-biopsy specimens (with hematoxylin-eosin and May-Grunwald-Giemsa staining) from six patients. Bile cultures were negative in all but one patient, in whose case they yielded Klebsiella pneumoniae (in a bile specimen obtained by ERCP). May-Grunwald-Giemsa staining revealed free forms of microsporidia in the bile of all eight patients. Toluidine-blue-stained slides and electron microscopy (when performed) of the duodenal-biopsy specimen and bile confirmed the presence of E. bieneusi (Figure 1AFigure 1Electron-Dense Spore of E. bieneusi in the Bile of an HIV-Infected Patient. and Figure 1B). Intracellular plasmodia were identified in common-bile-duct smears from one patient and in samples of gallbladder epithelium from two patients. Intraepithelial plasmodia and spores of E. bieneusi were found in ductal biliary cells in the liver-biopsy specimen from one patient (Figure 2Figure 2Multinucleate Plasmodia of E. bieneusi.).Duodenal cryptosporidiosis, which had not previously been detected by repeated stool examinations, was associated with duodenal and biliary microsporidiosis in one patient, whereas biliary cryptosporidiosis was associated with biliary microsporidiosis in three patients, one of whom had no evidence of duodenal cryptosporidiosis. One patient (Patient 8) with biliary microsporidiosis had cytomegalovirus and microsporidia infection of the gallbladder; his liver-biopsy specimen contained microsporidia, cytomegalovirus, and Mycobacterium avium-complex infection.
Three patients received metronidazole treatment (1 g twice daily for 15 days), and one was given quinacrine (125 g twice daily for 15 days), with no effect on diarrhea, cholestasis, or biliary microsporidia.
Discussion
Infection of the bile ducts with microsporidia appears to be far from rare. It was found in all eight patients with AIDS-related cholestasis whom we observed over an 18-month period and who were free of the usual pathogens encountered in this setting, namely cryptosporidium and cytomegalovirus.
Infections due to microsporidia are reported increasingly in immunosuppressed patients, and as a result pathologists are more aware of this organism5-10,12-16. The diagnosis is based on the examination of smears with May-Grunwald-Giemsa staining and tissue sections stained with hematoxylin and eosin, together with electron microscopy to distinguish species. Our results confirm that light microscopy is efficient in screening for microsporidia-related biliary infections in HIV infection12-15. The optimal stain for light microscopy was toluidine blue on resin-embedded material; this stain gives good contrast between the spores and the background and permits histologic diagnosis at lower magnification.
Biliary microsporidiosis is associated with microsporidiosis of the small intestine in persons infected with HIV type 1, and it usually results in AIDS-related cholangiopathy, including cholangitis or acalculous cholecystitis. However, cholangitis developed in one of our eight patients with E. bieneusi infection of the bile after 15 months of follow-up. Biliary microsporidiosis might be thought to result from duodenal contamination during retrograde endoscopic procedures, but the identification of E. bieneusi in biliary cells obtained by liver biopsy, transhepatic catheterization, or cholecystectomy rules out this possibility. Furthermore, the intraepithelial presence of parasites confirms tissue invasion by microsporidia. Although a causal relation between microsporidia infection of the biliary tract and AIDS-related cholangitis is difficult to prove, the presence of E. bieneusi in the bile of these patients with AIDS-related cholangitis strongly suggests a causative role, by analogy with intraepithelial biliary cryptosporidiosis and cytomegalovirus infection. Interestingly, biliary cryptosporidium infection was associated with biliary microsporidia infection in two patients who did not excrete cryptosporidium in the feces. Although cryptosporidium and cytomegalovirus-associated infection of the biliary tract is rare, a dual protozoal infection was observed in one third of the patients with AIDS-related cholangitis.
Cholangitis is considered to be a late complication of AIDS3. Two of the eight patients with biliary microsporidia infections belonged to group II of the CDCP classification and had AIDS only months later, suggesting that microsporidia cholangitis should be added to group IV. Indeed, all the patients concerned had very low CD4 cell counts, and most had p24 antigenemia.
It is noteworthy that all eight patients with biliary microsporidiosis were homosexual men, which tends to confirm our view that homosexual behavior is associated with an increased risk of AIDS-related cholangitis4 due to specific sexual practices, as has been proposed for Kaposi's sarcoma17. Indeed, it has recently been established in experiments in animals that bacterial overgrowth of the small intestine can induce histologic inflammation of the portal tract, with bile-duct destruction and proliferation in which cholangiographic abnormalities resemble primary sclerosing cholangitis18; in addition, the process was prevented by antibiotic therapy19,20. Bacterial or parasitic invasion of the biliary system through the portal venous system20 and retrograde infection are two possibilities. Together with the immunodeficiencies related to homosexuality21 and HIV infection, this could explain the frequency of AIDS-related cholangitis in homosexual men.
Unfortunately, we were unable to evaluate the prevalence of cholangitis during the same period that was due to causes other than microsporidia infection. Indeed, the study patients were referred to our unit from other institutions where routine examinations had ruled out cryptosporidiosis and cytomegalovirus infection. However, in a retrospective study of our first 15 cases of AIDS-related cholangitis, biliary infections with cryptosporidia or cytomegalovirus were identified in 9 patients (60 percent)4. Comparable figures have been found in other geographic areas3,22.
Empirical antiprotozoal chemotherapy with metronidazole (1 g twice daily for 15 days) had no clinical benefit with respect to cholestasis or diarrhea, in contrast to its efficacy in microsporidiosis of the small intestine14.
E. bieneusi infection of the biliary tract could account for at least some of the cases of AIDS-related cholangitis that are not explained by cryptosporidium or cytomegalovirus infection. Microsporidia biliary infection usually occurs in patients with severe immunodeficiency, and associated infections with cryptosporidium and microsporidia may be present.
We are indebted to Drs. M. Stern, W. Lowenstein, K. Gillet-Juvin, and J.-L. Dumont for their helpful comments and assistance; to Mr. J.-P. Monnet for his technical help; and to Miss D. Jourdat and Mr. D. Young for their assistance in the preparation of the manuscript.
Source Information
From the Units of Hepatology (S.P., P.B.), Parasitology (C.A.R., J.-F.P.), and Anatomy and Pathology (F.C.), Hopital Necker-Laennec; the Centre d'Endoscopie Digestive Gastrolouvre (P.A.); the Service of Neurohistology, Hopital Pitie-Salpetriere (S.R.); and INSERM U-313 (I.D.-L.) and U-99 (S.P., P.B.) -- all in Paris.
Address reprint requests to Dr. Pol at the Unite d'Hepatologie, Hopital Laennec, 42 Rue de Sevres, 75340 Paris CEDEX 07, France.
- References
References
1
Pitlik SD ,Fainstein V ,Rios A ,Guarda L ,Mansell PWA ,Hersh EM . Cryptosporidial cholecystitis. N Engl J Med 1983;308:967-967
Web of Science | Medline2
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 | Medline3
Cello JP . Acquired immunodeficiency syndrome cholangiopathy: spectrum of disease. Am J Med 1989;86:539-546
CrossRef | Web of Science | Medline4
Bouche H, Housset C, Dumont J-L, et al. AIDS-related cholangitis: features and course in 15 patients. J Hepatol (in press).
5
Canning EU ,Hollister WS . Enterocytozoon bieneusi (Microspora): prevalence and pathogenicity in AIDS patients. Trans R Soc Trop Med Hyg 1990;84:181-186
CrossRef | Web of Science | Medline6
Shadduck JA . Human microsporidiosis and AIDS. Rev Infect Dis 1989;11:203-207
CrossRef | Medline7
Desportes I ,Le Charpentier Y ,Galian A , et al. Occurrence of a new microsporidan: Enterocytozoon bieneusi n. g., n. sp., in the enterocytes of a human patient with AIDS. J Protozool 1985;32:250-254
Medline8
Rijpstra AC ,Canning EU ,Van Ketel RJ ,Eeftinck Schattenkerk JKM ,Laarman JJ . Use of light microscopy to diagnose small-intestinal microsporidiosis in patients with AIDS. J Infect Dis 1988;157:827-831
CrossRef | Web of Science | Medline9
McWhinney PHM ,Nathwani D ,Green ST ,Boyd JF ,Forrest JAH . Microsporidiosis detected in association with AIDS-related sclerosing cholangitis. AIDS 1991;5:1394-1395
CrossRef | Web of Science | Medline10
Pol S ,Romana C ,Richard S , et al. Enterocytozoon bieneusi infection in acquired immunodeficiency syndrome-related sclerosing cholangitis. Gastroenterology 1992;102:1778-1781
Web of Science | Medline11
Classification system for human T-lymphotropic virus type III/lymphadenopathy-associated virus infectionsMMWR Morb Mortal Wkly Rep 1986;35:334-339
Medline12
Simon D ,Weiss LM ,Tanowitz HB ,Cali A ,Jones J ,Wittner M . Light microscopic diagnosis of human microsporidiosis and variable response to octreotide. Gastroenterology 1991;100:271-273
Web of Science | Medline13
Peacock CS ,Blanshard C ,Tovey DG ,Ellis DS ,Gazzard BG . Histological diagnosis of intestinal microsporidiosis in patients with AIDS. J Clin Pathol 1991;44:558-563
CrossRef | Web of Science | Medline14
Weber R ,Bryan RT ,Owen RL , et al. Improved light-microscopical detection of microsporidia spores in stool and duodenal aspirates. N Engl J Med 1992;326:161-166
Full Text | Web of Science | Medline15
Eeftinck Schattenkerk JKM ,van Gool T ,van Ketel RJ , et al. Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals. Lancet 1991;337:895-898
CrossRef | Web of Science | Medline16
Orenstein JM ,Chiang J ,Steinberg W ,Smith PD ,Rotterdam H ,Kotler DP . Intestinal microsporidiosis as a cause of diarrhea in human immunodeficiency virus-infected patients: a report of 20 cases. Hum Pathol 1990;21:475-481
CrossRef | Web of Science | Medline17
Beral V ,Bull D ,Darby S , et al. Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet 1992;339:632-635
CrossRef | Web of Science | Medline18
Lichtman SN ,Keku J ,Clark RL ,Schwab JH ,Sartor RB . Biliary tract disease in rats with experimental small bowel bacterial overgrowth. Hepatology 1991;13:766-772
CrossRef | Web of Science | Medline19
Lichtman SN ,Keku J ,Schwab JH ,Sartor RB . Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline. Gastroenterology 1991;100:513-519
Web of Science | Medline20
Sung JY ,Shaffer EA ,Olson ME ,Leung JWC ,Lam K ,Costerton JW . Bacterial invasion of the biliary system by way of the portal-venous system. Hepatology 1991;14:313-317
CrossRef | Web of Science | Medline21
Kornfeld H ,Vande Stouwe RA ,Lange M ,Reddy MM ,Grieco MH . T-lymphocyte subpopulations in homosexual men. N Engl J Med 1982;307:729-731
Full Text | Web of Science | Medline22
Dowsett JF ,Miller R ,Davidson R , et al. Sclerosing cholangitis in acquired immunodeficiency syndrome: case reports and review of the literature. Scand J Gastroenterol 1988;23:1267-1274
CrossRef | Web of Science | Medline
- Citing Articles (56)
Citing Articles
1
Sebastian B. Lucas, Sherif R. Zaki, Bernard C. Portmann. 2012. Other viral and infectious diseases and HIV-related liver disease. , 403-466.
CrossRef2
Kaya Ghosh, Louis M. Weiss. (2011) T cell response and persistence of the Microsporidia. FEMS Microbiology Reviewsn/a-n/a
CrossRef3
Elisabeth Krones, Ivo Graziadei, Michael Trauner, Peter Fickert. (2011) Evolving concepts in primary sclerosing cholangitis. Liver Internationaln/a-n/a
CrossRef4
Gwenn E. McLaughlin, Andrew C. Argent. 2011. Acquired Immune Dysfunction. , 1302-1314.
CrossRef5
Takao Watanabe, Kouji Joko, Tomoyuki Yokota, Yuichi Kobayashi, Yoshinori Oono, Shunji Takechi, Yumi Ooshiro, Masanori Abe, Hidehiro Murakami, Bunzo Matsuura, Yoichi Hiasa, Morikazu Onji. (2010) Pancreatitis and Cholangitis Due to Cytomegalovirus in a Patient With Hyperimmunoglobulin E Syndrome. Pancreas 39:6, 940-942
CrossRef6
Alan Curry. 2010. Microsporidiosis. .
CrossRef7
Gabriel A. Schmunis, Francisco J. López-Antuñano. 2010. World-Wide Importance of Parasites. .
CrossRef8
Joseph Misdraji. 2010. Liver and Bile Duct Infections. , 255-295.
CrossRef9
JOSE JESSURUN, STEFAN PAMBUCCIAN. 2009. Infectious and Inflammatory Disorders of the Gallbladder and Extrahepatic Biliary Tract. , 823-843.
CrossRef10
David W. Kindelberger, Helen H. Wang. 2009. Gastrointestinal Tract. , 197-220.
CrossRef11
HELEN H. WANG. 2009. Diagnostic Cytology of the GI Tract. , 39-50.
CrossRef12
Francis Derouin, Marie Lagrange-Xelot. (2008) Treatment of parasitic diarrhea in HIV-infected patients. Expert Review of Anti-infective Therapy 6:3, 337-349
CrossRef13
John Hwa Lee. (2007) Prevalence and molecular characteristics of Enterocytozoon bieneusi in cattle in Korea. Parasitology Research 101:2, 391-396
CrossRef14
Axel Holstege, Peter Zolinski, Ludwig Woidy, Willibald Permanetter. (2007) The patient with unexplained elevated serum liver enzymes. Best Practice & Research Clinical Gastroenterology 21:3, 535-550
CrossRef15
Rupert Abdalian, E. Jenny Heathcote. (2006) Sclerosing cholangitis: A focus on secondary causes. Hepatology 44:5, 1063-1074
CrossRef16
Dirk Domagk, Wolfgang Fegeler, Beate Conrad, Josef Menzel, Wolfram Domschke, Torsten Kucharzik. (2006) Biliary Tract Candidiasis: Diagnostic and Therapeutic Approaches in a Case Series. The American Journal of Gastroenterology 101:11, 2530-2536
CrossRef17
John Fung, Bijan Eghtesad, Kusum Patel-Tom, Michael DeVera, Holly Chapman, Margaret Ragni. (2004) Liver transplantation in patients with HIV infection. Liver Transplantation 10:S10, S39-S53
CrossRef18
Naozumi Shibata, Hidetaka Matsui, Eiji Takeshita, Tomoyuki Yokota, Yuichi Kobayashi, Yoshiou Ikeda, Yoshihiro Yakushijin, Takaaki Hato, Bunzo Matsuura, Norio Horiike, Morikazu Onji. (2004) Case of AIDS-related cholangitis treated by endoscopic sphincterotomy. Digestive Endoscopy 16:3, 234-236
CrossRef19
Tony E. Yusuf, Todd H. Baron. (2004) AIDS cholangiopathy. Current Treatment Options in Gastroenterology 7:2, 111-117
CrossRef20
Sarah Lean, Richard CG Pollok. (2003) Management of protozoa-related diarrhea in HIV infection. Expert Review of Anti-infective Therapy 1:3, 455-469
CrossRef21
Tracie L Miller. (2003) Nutritional aspects of HIV-infected children receiving highly active antiretroviral therapy. AIDS 17, S130-S140
CrossRef22
K. Sestak, P.P. Aye, M. Buckholt, K.G. Mansfield, A.A. Lackner, S. Tzipori. (2003) Quantitative evaluation of Enterocytozoon bieneusi infection in simian immunodeficiency virus-infected rhesus monkeys. Journal of Medical Primatology 32:2, 74-81
CrossRef23
Claire Westrope, Ashoka Acharya. (2001) DIARRHEA AND GALLBLADDER HYDROPS IN AN IMMUNOCOMPETENT CHILD WITH CRYPTOSPORIDIUM INFECTION. The Pediatric Infectious Disease Journal 20:12, 1179-1181
CrossRef24
Louis M. Weiss. (2001) Microsporidia: emerging pathogenic protists. Acta Tropica 78:2, 89-102
CrossRef25
Sylvia F. Costa, Louis M. Weiss. (2000) Drug treatment of microsporidiosis. Drug Resistance Updates 3:6, 384-399
CrossRef26
U. Szewzyk, R. Szewzyk, W. Manz, K.-H. Schleifer. (2000) M
ICROBIOLOGICAL SAFETY OF DRINKING WATER . Annual Review of Microbiology 54:1, 81-127
CrossRef27
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
CrossRef28
Kimon C Zachary. (2000) Systemic manifestations of HIV infection. Clinics in Dermatology 18:4, 441-446
CrossRef29
Hadžić, Nedim, Pagliuca, Antonio, Rela, Mohamed, Portmann, Bernard, Jones, Alison, Veys, Paul, Heaton, Nigel D., Mufti, Ghulam J., Mieli-Vergani, Giorgina, . (2000) Correction of the Hyper-IgM Syndrome after Liver and Bone Marrow Transplantation. New England Journal of Medicine 342:5, 320-324
Full Text30
David T. Walden. (1999) Biliary problems in people with HIV disease. Current Treatment Options in Gastroenterology 2:2, 147-153
CrossRef31
Marco Ricci, Anibal O. Puente, Robert E. Rothenberg, Kenneth Shapiro, Cynthia de Luise, Raymond D. LaRaja. (1999) Open and laparoscopic cholecystectomy in acquired immunodeficiency syndrome: Indications and results in fifty-three patients. Surgery 125:2, 172-177
CrossRef32
ANDREW P. KEAVENY, MICHAEL S. KARASIK. (1998) Hepatobiliary and Pancreatic Infections in AIDS: Part II. AIDS Patient Care and STDs 12:6, 451-456
CrossRef33
Lawrence J. Burgart. (1998) Cholangitis in Viral Disease. Mayo Clinic Proceedings 73:5, 479-482
CrossRef34
Burton C. West, Ronald Silberman, Warren N. Otterson. (1998) Acalculous Cholecystitis and Septicemia Caused by Non-O1 Vibrio cholerae: First Reported Case and Review of Biliary Infections with Vibrio cholerae. Diagnostic Microbiology and Infectious Disease 30:3, 187-191
CrossRef35
Nathalie Boige, Marc Bellaïche, Dominique Cornet, Robert Busuttil, Gérard Béal, Pierre Foucaud. (1998) Hydrops-Like Cholecystitis Due to Cryptosporidiosis in an HIV-Infected Child. Journal of Pediatric Gastroenterology & Nutrition 26:2, 219-221
CrossRef36
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
CrossRef37
Jean-Michel Molina, Jérome Goguel, Claudine Sarfati, Claude Chastang, Isabelle Desportes-Livage, Jean-François Michiels, Caroline Maslo, Christine Katlama, Laurent Cotte, Catherine Leport, François Raffi. (1997) Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection. AIDS 11:13, 1603-1610
CrossRef38
Joseph A. Nash, Seth A. Cohen. (1997) GALLBLADDER AND BILIARY TRACT DISEASE IN AIDS. Gastroenterology Clinics of North America 26:2, 323-335
CrossRef39
Rayhan Hashmey, Robert M. Genta, A. Clinton White. (1997) Parasites and Diarrhea. I: Protozoans and Diarrhea. Journal of Travel Medicine 4:1, 17-31
CrossRef40
Stuart R. Framm, Rosemary Soave. (1997) AGENTS OF DIARRHEA. Medical Clinics of North America 81:2, 427-447
CrossRef41
Marc Barthet, Eric Chauveau, Eric Bonnet, Nathalie Petit, Jean-Paul Bernard, Jean-Albert Gastaut, José Sahel. (1997) Pancreatic ductal changes in HIV-infected patients
. Gastrointestinal Endoscopy 45:1, 59-63
CrossRef42
C.Mel Wilcox, Linda Rabeneck, Scott Friedman. (1996) AGA technical review: Malnutrition and cachexia, chronic diarrhea, and hepatobiliary disease in patients with human immunodeficiency virus infection. Gastroenterology 111:6, 1724-1752
CrossRef43
Julio Collazos, José Mayo, Eduardo Martínez, Ana Callejo, Iñaki Blanco. (1996) Celiac Plexus Block As Treatment for Refractory Pain Related to Sclerosing Cholangitis in AIDS Patients. Journal of Clinical Gastroenterology 23:1, 47-49
CrossRef44
Vakil, Nimish B., Schwartz, Steven M., Buggy, Brian P., Brummitt, Charles F., Kherellah, Mazen, Letzer, David M., Gilson, Ian H., Jones, Paula G., . (1996) Biliary Cryptosporidiosis in HIV-Infected People after the Waterborne Outbreak of Cryptosporidiosis in Milwaukee. New England Journal of Medicine 334:1, 19-23
Full Text45
ISABELLE DESPORTES-LIVAGE, STEFAN CHILMONCZYK, RONALD HEDRICK, CÉCILE OMBROUCK, DANIELLE MONGE, IBRAHIM MAIGA, MARC GENTILINI. (1996) Comparative Development of Two Microsporidian Species: Enterocytozoon bieneusi and Enterocytozoon salmonis, Reported in AIDS Patients and Salmonid Fish, Respectively. The Journal of Eukaryotic Microbiology 43:1, 49-60
CrossRef46
Tom van Gool, Jacob Dankert. (1995) Human microsporidiosis: Clinical, diagnostic and therapeutic aspects of an increasing infection. Clinical Microbiology and Infection 1:2, 75-85
CrossRef47
P. Caramello, M. Romeo, A. Ullio, A. Lucchini, B. Forno, T. Brancale, P. Gioannini, G. Mazzucco, G. DeRosa, A. Macor, C. Preziosi. (1995) Clinical and microscopical features of small-intestinal microsporidiosis in patients with AIDS. Infection 23:6, 362-368
CrossRef48
GOVINDA S. VISVESVARA, GORDON J. LEITCH, NORMAN J. PIENIAZEK, ALEXANDRE J. DA SILVA, SARA WALLACE, SUSAN B. SLEMENDA, RAINER WEBER, DAVID A. SCHWARTZ, LEO GORELKIN, C. MEL WILCOX, RALPH T. BRYAN. (1995) Short-Term In Vitro Culture and Molecular Analysis of the Microsporidian, Enterocytozoon bieneusi. The Journal of Eukaryotic Microbiology 42:5, 506-510
CrossRef49
William S. MacMorran, Andrew D. Badley, Walter R. Wilson. (1995) 26-Year-Old Man With HIV Infection and Abdominal Pain. Mayo Clinic Proceedings 70:9, 885-888
CrossRef50
H.L. DuPont, G.D. Marshall. (1995) HIV-associated diarrhoea and wasting. The Lancet 346:8971, 352-356
CrossRef51
Richard Willson, Robert Harrington, Brian Stewart, Thomas Fritsche. (1995) Human immunodeficiency virus 1—associated necrotizing cholangitis caused by infection with Septata intestinalis. Gastroenterology 108:1, 247-251
CrossRef52
DAVID W. CHUI, ROBERT L. OWEN. (1994) AIDS and the gut. Journal of Gastroenterology and Hepatology 9:3, 291-303
CrossRef53
Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., McNeely, Betty U., Wanke, Christine A.Mattia, Anthony R.. (1993) Case 51-1993. New England Journal of Medicine 329:26, 1946-1954
Full Text54
H. Silveira, E. U. Canning, J. A. Shadduck. (1993) Experimental infection of athymic mice with the human microsporidian Nosema corneum. Parasitology 107:05, 489
CrossRef55
Alan Curry, Elizabeth U. Canning. (1993) Human microsporidiosis. Journal of Infection 27:3, 229-236
CrossRef56
Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., McNeely, Betty U., Golde, David W.Rubin, Daniel. (1993) Case 40-1993. New England Journal of Medicine 329:15, 1108-1115
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