Biliary Cryptosporidiosis in HIV-Infected People after the Waterborne Outbreak of Cryptosporidiosis in Milwaukee

Vakil, Nimish B.; Buggy, Brian P.; Brummitt, Charles F; Kherellah, Mazen; Letzer, David; Gilson, Ian; Jones, Paula G.

doi:10.1056/nejm199601043340104

Cited by 148 publications

(80 citation statements)

References 21 publications

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“…[3][4][5] Although the intestinal disease is selflimited and biliary abnormalities are not seen in immunecompetent individuals, C. parvum infection in AIDS patients is a chronic, debilitating condition, and involvement of the biliary tract is associated with a much poorer prognosis than with intestinal infection alone. 4 Although the actual frequency of biliary cryptosporidiosis in patients with AIDS is unclear and is related not only to the clinical stage of the disease, but also to the occurrence of episodes of water contamination with C. parvum, 6 some series report clinically detectable biliary infection in up to 15% of patients with advanced AIDS. 7 To date, there is no effective medical treatment for either intestinal or biliary cryptosporidiosis, and in AIDS patients, the infection is rarely spontaneously cleared.…”

mentioning

confidence: 99%

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Chen¹,

Levine²,

Tietz³

et al. 1998

Hepatology

101

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While the clinical features of sclerosing cholangitis secondary to opportunistic infections of the biliary tree in patients with acquired immunodeficiency syndrome (AIDS) are well known, the mechanisms by which microbial pathogens such as Cryptosporidium parvum associated with this syndrome actually cause disease are obscure. We established an in vitro model of biliary cryptosporidiosis employing a human biliary epithelial cell line. Using morphological and biochemical techniques, we examined the interaction of C. parvum with cultured human cholangiocytes. When the apical plasma membrane of polarized, confluent monolayers of human biliary epithelial cells was exposed to C. parvum oocysts that had been excysted in vitro, sporozoites attached to and invaded the cells in a time-, dose-, temperature-, and pH-dependent manner. The infectious process was both plasma membrane domain-and cell-specific, because no attachment or invasion occurred when the basolateral membrane of cholangiocytes was exposed to the parasite, or when a human hepatocyte cell line (HepG2) was used. Time-lapse video microscopy and scanning electron microscopy (SEM) showed that sporozoite attachment was rapid, involved extensive cholangiocyte membrane ruffling, and culminated in parasite penetration into a tight-fitting vacuole formed by invagination of the plasma membrane similar to those found in naturally occurring infection in vivo. Transmission electron microscopy (TEM) showed that C. parvum organisms formed parasitophorus vacuoles and were able to undergo a complete reproductive cycle, forming both asexual and sexual reproductive stages. Unexpectedly, direct cytopathic effects were noted in infected monolayers, with widespread programmed cell death (i.e., apoptosis) of biliary epithelial cells as assessed both morphologically and biochemically beginning within hours after exposure to the organism. The novel finding of specific cytopathic invasion of biliary epithelia by C. parvum may be relevant to the pathogenesis and possible therapy of the secondary sclerosing cholangitis seen in AIDS patients with biliary cryptosporidiosis. (HEPATOLOGY 1998;28:906-913.)

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mentioning

confidence: 99%

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Chen¹,

Levine²,

Tietz³

et al. 1998

Hepatology

101

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“…Protozoa such as Cryptosporidium sp have become important with the advent of AIDS, being the main cause of infectious gastrointestinal tract diseases (17,18,28,31). Cryptosporidium sp.…”

Section: Introductionmentioning

confidence: 99%

“…was recognized by Tyzzer (30) in 1907. Cryptosporidium parvum is a protozoan species in human infections, invading and residing in epithelial cells of the large intestine; it can also be found in epithelial cells of the bile duct, pancreatic duct, esophagus, stomach, and respiratory tract (4,17,18,29,31). In prolonged infections, it causes liquid diarrhea, dehydration, obstruction of the bile and pancreatic ducts, and pancreatitis, especially in AIDS (17,18,29).…”

Section: Introductionmentioning

confidence: 99%

“…In prolonged infections, it causes liquid diarrhea, dehydration, obstruction of the bile and pancreatic ducts, and pancreatitis, especially in AIDS (17,18,29). Vakil et al (31) and Flanigan et al (12) have reported more serious cryptosporidiosis in advanced HIV sufferers and with low CD4 + T lymphocyte counts, generally less than 50 cells/mm 3 .…”

Section: Introductionmentioning

confidence: 99%

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Cryptosporidium SP in HIV-infected individuals attending a Brazilian University Hospital

Langoni-Júnior¹,

Souza²

2007

J. Venom. Anim. Toxins incl. Trop. Dis

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ABSTRACT:The aim of the current work was to evaluate the occurrence of Cryptosporidium sp in AIDS patients in a region of São Paulo State, Brazil. Patients were divided into groups according to CD4 + T lymphocyte count and use of potent antiretroviral treatment. Two hundred and ten fecal samples from 105 patients were fixed in 10% formalin and subjected to centrifuge formol-ether sedimentation. Slides were stained with auramine and confirmed by modified Ziehl-Neelsen.Cryptosporidiosis occurrence was 10.5% with no relationship among gender, age or the presence of diarrhea. The number of oocysts in all samples was small, independent of CD4 + T lymphocyte count, HIV plasma viral load, and presence of diarrhea. These results may be due to the reduced prevalence of opportunistic infections in AIDS individuals after the advent of highly active antiretroviral therapy.

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“…Immunocompetent persons rapidly cleared the infection on their own, but among those with HIV infection, the course of infection was protracted and associated with symptomatic biliary obstruction and death. 1 Therapy of Cryptosporidium has been symptomatic or focused on correcting immunosuppression by replacing deficient immunoglobulins, stopping immunosuppressive drugs, or treating HIV. No drug has been effective in eliminating infection with Cryptosporidium, although poorly absorbable antimicrobials, such as paromomycin, can reach levels that are cidal in tissue culture of epithelial cell lines.…”

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confidence: 99%

New perspectives on the pathogenesis ofCryptosporidium biliary disease

Owen

1998

Hepatology

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Biliary Cryptosporidiosis in HIV-Infected People after the Waterborne Outbreak of Cryptosporidiosis in Milwaukee

Abstract: When HIV-infected patients are exposed to cryptosporidium, those with CD4 counts < or = 50 per cubic millimeter are at increased risk for biliary symptoms and for death within one year after the infection.

Cited by 148 publications

References 21 publications

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Cryptosporidium parvum is cytopathic for cultured human biliary epithelia via an apoptotic mechanism

Cryptosporidium SP in HIV-infected individuals attending a Brazilian University Hospital

New perspectives on the pathogenesis ofCryptosporidium biliary disease

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