Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 48, Num. 3, 2002, pp. 215-216

Journal of Postgraduate Medicine, Vol. 48, Issue 3, 2002 pp. 215-216

Cryptosporidiosis in HIV-Infected Patients

Dionisio D

Infectious Diseases Unit, Pistoia Hospital, Piazza Giovanni XXIII, 51100, Pistoia, Italy.

Code Number: jp02074

Although involved in biliary disease, hepatitis, pancreatitis, arthritis, and possibly respiratory tract infections also, the protozoan organism Cryptosporidium parvum is primarily responsible for watery diarrhoea.^1,2 A mean infective dose of 132 oocysts has been proved to be adequate in producing infection in healthy volunteers.² Diarrhoea is self-limited in immunocompetent individuals or in those whose CD4 cell counts are more than 200/mm³, but may be severe, sometimes cholera-like, and unremitting or relapsing in severely immunodeficient patients (CD4 cell counts below 100/mm³). In these cases chronic infection can lead to dehydration, malnurtrition, malabsorption, wasting and frequently, death.³ Biliary cryptosporidiosis is more frequent in patients with CD4 cell counts below 50/mm³ and commonly presents with right upper quadrant pain, nausea, fever, and vomiting. Diarrhea may be absent, and laboratory findings may include elevated serum alkaline phosphatase and bilirubin levels, with only scant elevation of liver transaminase levels. Coinfection with cytomegalovirus or microsporidia has frequently been found in biliary cryptosporidiosis.^2,4 Some cases of pneumatosis cystoides intestinalis in AIDS-associated cryptosporidiosis have been reported, suggesting a pathogenetic role for the parasite.^5,6

Despite long-term excretion of cryptosporidium oocysts in infected people after clinical resolution,² recent results suggest that isolation of adult patients with cryptosporidial diarrhea is not necessary to prevent roommate-to-roommate transmission.⁷

Cryptosporidiosis occurs in 3% to 11% of patients with AIDS in all risk groups but is most frequent in men who have sex with males, so relating to the gay-bowel syndrome.^1,3 Other AIDS-defining illnesses precede the onset of cryptosporidiosis in 85% of cases.¹ All segments of the gastrointestinal tract may be involved, but the small bowel is the main target organ followed by the colon.¹ Esophageal cryptosporidiosis, with parasites attached to the squamous mucosa and the luminal borders of submucosal glands and ducts, has been described both in adults and in children with AIDS.¹ Gastric cryptosporidiosis, possibly inducing partial gastric outlet obstruction, is quite common and may present with haemorrhagic erosions.^8,9 Intestinal coinfection by C. parvum and cyclospora species or cytomegalovirus is not rarely documented.^10,11

Diagnosis of cryptosporidiosis is made by identification of the organisms in either duodenal aspirates, stool, or tissue samples. The organisms can be clearly observed on Giemsa or H&E-stained sections as rows or clusters of spherical structures 2 to 4 mm in diameter attached to the microvillous border of the epithelial cells. In the small intestine, tips and lateral aspects of villi show the greatest numbers of organisms, whereas in the colon an equal involvement of crypts and surface epithelium appears.

Infection begins with ingestion of the oocysts. Excystation of the oocysts within the small intestine leads to the release of sporozoites that enter epithelial gut cells and develop into trophozoites. Trophozoite location is,though extracytoplasmic, intracellular beneath the host cell membrane. The intracellular location is not obvious by light microscopy; only electron microscopy demonstrates the thin rim of epithelial cytoplasm surrounding the organisms.¹

C. parvum can be regarded as a minimally invasive mucosal pathogen, since it invades the surface cells lining the intestinal tract but does not invade deeper layers. In spite of this, infection can present with pronounced watery diarrhea and marked mucosal inflammation.¹² Postulated pathogenetic factors including a secretory state mediated by enterotoxin production in the proximal small bowel have not been confirmed.¹³ Based on the evidence that infections extensively involving both the small and large bowel produce the most severe disease, it was hypothesised that cryptosporidium diarrhea might be caused by malabsorption from a reduced absorptive surface.^14,15 Nothwithstanding, no correlation between histological intensity of cryptosporidiosis and clinical severity have been found so far.¹⁶ In addition, in vitro results indicate that gut cryptosporidiosis may induce epithelial barrier disruption with marked changes in permeability to macromolecules.¹⁴ Finally, recent evidence suggests that epithelial apoptosis mediated by cytotoxic host T cells might play a role in the development of colonic lesions in AIDS-related cryptosporidiosis.¹⁷

No established therapy for this parasitosis is available yet. Paromomycin is only transiently effective on symptoms, and conclusive agreement is lacking about the literature results supporting a direct effectiveness of azithromycin or nitazoxanide.^18-20 Increasing evidence suggests, however, that combination antiretroviral therapy may be curative.^21-23

Because of the lack of specific drug treatments, studies aiming at proper drug choices for HIV-related cryptosporidiosis are needed. They ought to state the patients's immunodeficiency levels, their symptoms and concurrent infections or treatments. Information as to how stool samples were collected must be included as it is crucial to assess the reliability of microbiological results reported. Long-term follow-up should be done on stool samples after the end of therapy to exclude recurrence. Moreover quantitative estimation of the parasite load in the stool should be done before and after the treatment to evaluate the effectiveness of the treatment properly. Indeed, there is general agreement about the correspondence between parasite reduction both in stool and enterocyte surface following effective therapy.

Lack of these criteria, as listed above, would make it impossible to assess whether the reported clinical improvement was due to the chosen regimen itself or to other unknown factors or just a casual occurrence. Indeed, there is established knowledge about the extreme variability of the clinical course of cryptosporidiosis in severely immunodeficient patients with AIDS.

The paper by Kadappu and co-workers²⁴ published in this issue of the journal meets the criteria mentioned above and adds useful information about the therapeutic potential of short-term azithromycin in this setting.

Dionisio D

Infectious Diseases Unit, Pistoia Hospital, Piazza Giovanni XXIII, 51100, Pistoia, Italy.

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