[Cryptosporidiosis, a cause of acute diarrhea: A review and retrospective study of cases in Rouen university hospital's pediatrics department]. / La cryptosporidiose, une cause de diarrhée aiguë : revue de la littérature et étude rétrospective des cas dans le département de pédiatrie du CHU de Rouen.

Cryptosporidium is the most important diarrhea-causing protozoan parasite, with severe health consequences for very young, malnourished children living in endemic areas and for immunocompromised individuals. Cryptosporidium is widely distributed and disease transmission can occur through person-to-person or animal-to-person contact, or contaminated food or water (drinking or swimming), leading to large outbreaks. The zoonotic Cryptosporidium parvum and the anthroponotic Cryptosporidium hominis are responsible for the majority of human cases. Specific therapy, primarily nitazoxanide, has some effect in healthy individuals, but drugs effectively preventing or controlling this disease in all clinical situations are not yet available. In France, as elsewhere in Europe, little epidemiological and molecular information is available regarding the burden of cryptosporidiosis in children. Cryptosporidium is usually not tested in all fecal samples submitted for routine parasitological examination and only tested on special request, primarily in immunocompromised patients. Between January 2007 and October 2014, out of a total of 5337 immunocompetent children with diarrhea in Rouen university hospital's pediatrics department, the prevalence of Cryptosporidium infection was 0.97 % (52 infected children). The median age of infected children was 3 years (range, 5 months to 11 years) and 80 % of the cases occurred between July and November. Thirty-six (69.2 %) and 16 (30.8 %) infections were due to C. parvum and C. hominis, respectively. The fact that the species C. parvum, mainly the IIaA15G2R1 subtype, was detected in most locally infected children suggests that cryptosporidiosis must primarily be considered as a zoonotic disease in Upper Normandy.

Biliary tract cryptosporidiosis immunosuppressed rat model.

Rats immunosuppressed by hydrocortisone acetate and a low protein diet were challenged with Cryptosporidium Parvum oocysts and studied on days 10, 35 and 70 post-infection. The biliary tract was found to be a major site of parasite infection. C. parvum was visible in the biliary papillary area in association with a proliferation of highly convoluted tubular glands. The papillary lumen was narrowed, and an upstream dilation with bacterial proliferation was seen. The liver was initially free of lesions, and subsequently exhibited late lesions of cholestasis. Parasites were not found in the pancreatic duct, although pancreatitis was frequently observed. Oocysts were consistently present in the distal portion of the ileum. Both challenged and unchallenged immunosuppressed rats, exhibited widespread focal hepatic infarcts and pyelonephritis. Other organs appeared free of lesions. In addition to the intestine, data identified the biliary tract as a major site of C. parvum infection and as a potential protected reservoir which may sustain a chronic infection.

An immunosuppressed rat model for evaluation of anti-Cryptosporidium activity of sinefungin.

Cryptosporidium parvum causes life-threatening diarrhoea in immunocompromised, especially AIDS patients and the efficiency of proposed anti-cryptosporidial therapies is limited or doubtful. An immunosuppressed adult rat model of C. parvum infection was developed for screening molecules candidate for curative and preventive activity in human cryptosporidiosis. Among 31 drugs tested, lasalocid (2-10 mg/kg/24 h), and sinefungin (2-10 mg/kg/24 h), exhibited some activity against C. parvum infection. Oral sinefungin therapy resulted in a dose related suppression of oocysts shedding, which correlated with oocyst disappearance from ileum sections and was also efficient in preventing infection. Relapses were observed after discontinuation of curative sinefungin therapy, which suggests that the biliary tract, a major location and parasite reservoir which sustains persisting infection, was not cleared of parasites by the drug. Improved therapeutic procedures with sinefungin (or analogues) will result from current pharmacological studies.

Respiratory tract cryptosporidiosis in immunosuppressed rat is associated with an epithelial metaplasia.

Cryptosporidium parvum is an opportunistic protozoa that chronically infects the digestive tract of immunocompromised hosts. Respiratory cryptosporidiosis, which was reported in AIDS patients, is an uncommon feature of mammalian cryptosporidiosis models. In this study, we document the respiratory lesion; observed in an immunosuppressed rat model of cryptosporidiosis. Twenty rats were immunosuppressed with corticosteroids and low protein diet. They were challenged intratracheally with 10(6) C. parvum sporozoites. Lungs and ileums were examined on D3, D6, D10, D14. On D10 and D14, C. parvum were present in the respiratory tract of all animals in association with the progressive appearance of an immature malpighian metaplasia. On D14, an intestinal infection was also detected in 2/4 animals. The respiratory tract appears to be a fully permissive area for the protozoa in immunosuppressed rats. Introduction of parasites on the respiratory mucosa seems a requisite to induce respiratory cryptosporidiosis. This experimental protocol yields a low mortality rate, and so modelizes late and/or chronic stages of respiratory cryptosporidiosis.

Rat model for human cryptosporidiosis.

Effective treatment for Cryptosporidium infection in immunocompromised patients has yet to be found. We report a rodent model of persistent Cryptosporidium infection. Sprague-Dawley rats were injected subcutaneously twice a week for 8 weeks with 25 mg of hydrocortisone acetate. Fed a regular low-protein diet for 9 weeks, they were challenged once with 10(5) calf Cryptosporidium oocysts 5 weeks after the start of the hydrocortisone acetate regimen. Oocyst shedding was evaluated in feces daily by using a carbolfuchsin-staining method. Rats shed oocysts from days 2 to 9 after ingestion and developed a persistent infection for more than 38 days. Excretion was lower after subsequent parasite challenges, suggesting that a degree of protection developed progressively. The results suggest that this experimental model provides a procedure for screening candidate therapeutic agents.

Anti-cryptosporidial drug activity screened with an immunosuppressed rat model.

Cryptosporidium parvum, a coccidian parasite can cause mild or severe self-limiting diarrhea in immunocompetent humans, but chronic and life-threatening in immunocompromised individuals. An immunosuppressed rat model with persistent cryptosporidiosis was used to investigate the anti-cryptosporidial activity of drugs. Using curative procedures, no activity was found with 6 antibiotics assayed, including spiramycin (31-100%). Mepacrine at a dose of 100 mg/kg had mild activity (19%), while lasalocid (10 mg/kg) and sulfadimethoxine (60 mg/kg) exhibited a 0.1% and 13%, activity respectively. This experimental immuno-suppressed rat model appears suitable for screening candidate drugs either for preventive or curative treatment of cryptosporidiosis.

Curative and preventive anticryptosporidium activities of sinefungin in an immunosuppressed adult rat model.

An immunosuppressed rat model was used to investigate the anti-Cryptosporidium parvum activity of sinefungin. In infected animals, oral sinefungin therapy resulted in a dose-related suppression of oocyst shedding, which correlated with oocyst disappearance from ileal sections. When administered prior to or on the day of oocyst challenge, sinefungin successfully prevented infection. These data suggest that sinefungin could be considered as a candidate molecule in the treatment of human cryptosporidiosis, considered to be the most significant enteric opportunistic infection in AIDS.

Characterization of anti-Cryptosporidium IgA antibodies in sera from immunocompetent individuals and HIV-infected patients.

Human antibody response to Cryptosporidium parvum has been previously shown as involving immunoglobulin (Ig)M and IgG isotypes. The interest in anti-cryptosporidial IgA antibody response has been recently stimulated by studies on the therapeutic effects of secretory IgA antibodies to Cryptosporidium in animal models and in patients. In the present study, isotypes of serum anti-Cryptosporidium antibodies have been characterized in donors of the following categories: (a) healthy adults, (b) healthy children, (c) immunocompetent children with transient cryptosporidial diarrhea, (d) HIV-infected patients without clinical and parasitological evidence of Cryptosporidium infection and (e) AIDS patients with cryptosporidial diarrhea. Antibodies were detected using C. parvum oocysts purified by density gradient centrifugation from bovine faeces. The IgA antibodies were revealed using alpha-chain specific antibodies. Indirect immunofluorescence analysis with oocysts was used as control. Although high levels of serum antibodies of the IgA class were detected in some donors in the group of healthy adults, elevated values were consistently found in HIV-infected patients. Higher values were found in HIV patients with clinical cryptosporidiosis. The presence of a secretory component in serum IgA antibodies in these patients has been documented. Data indicate that IgA serum antibodies are produced as well as IgM and IgG antibodies upon contact with the parasite, and suggest that elevated IgA serum antibodies to Cryptosporidium are not associated with protection in HIV patients.

Assessment of candidate anticryptosporidial agents in an immunosuppressed rat model.

Cryptosporidium parvum causes life-threatening diarrhea in immunocompromised patients, especially those with AIDS. The efficiency of currently proposed anticryptosporidial therapies is limited or doubtful. In this report, molecular candidates for curative or preventive activity were investigated in an immunocompromised rat model that mimics severe human cryptosporidiosis. No significant anticryptosporidial activity was observed when using sulfadoxine-pyrimethamine, quinacrine, trimethoprim-sulfamethoxazole, bleomycin, elliptinium, daunorubicin, pentamidine, alpha-difluoro-methylornithine, diclazuril or N-methylglucamine. Vitamin A appeared to reduce oocyst shedding. Active agents included sinefungin (2-10 mg/kg/24 h), lasalocid A (2-10 mg/kg/24 h), metronidazole (25-50 mg/kg/24 h), and sulfadimethoxine (10-100 mg/kg/24 h). Sinefungin (10 mg/kg/24 h) and lasalocid A (10 mg/kg/24 h) displayed the highest anticryptosporidial activity.