Cryptosporidium parvum, a potential cause of colic adenocarcinoma

Abstract

BackgroundCryptosporidiosis represents a major public health problem. This infection has been reported worldwide as a frequent cause of diarrhoea. Particularly, it remains a clinically significant opportunistic infection among immunocompromised patients, causing potentially life-threatening diarrhoea in HIV-infected persons. However, the understanding about different aspects of this infection such as invasion, transmission and pathogenesis is problematic. Additionally, it has been difficult to find suitable animal models for propagation of this parasite. Efforts are needed to develop reproducible animal models allowing both the routine passage of different species and approaching unclear aspects of Cryptosporidium infection, especially in the pathophysiology field.ResultsWe developed a model using adult severe combined immunodeficiency (SCID) mice inoculated with Cryptosporidium parvum or Cryptosporidium muris while treated or not with Dexamethasone (Dex) in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. C. muris-infected mice showed high levels of oocysts excretion, whatever the chemical immunosuppression status. Pre-patent periods were 11 days and 9.7 days in average in Dex treated and untreated mice, respectively. Parasite infection was restricted to the stomach, and had a clear preferential colonization for fundic area in both groups. Among C. parvum-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. C. parvum-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma.ConclusionFor the first time C. parvum is associated with the formation of polyps and adenocarcinoma lesions in the gut of Dex-treated SCID mice. Additionally, we have developed a model to compare chronic muris and parvum cryptosporidiosis using SCID mice treated with corticoids. This reproducible model has facilitated the evaluation of clinical signs, oocyst shedding, location of the infection, pathogenicity, and histopathological changes in the gastrointestinal tract, indicating divergent effects of Dex according to Cryptosporidium species causing infection.

Prevalence of Cryptosporidium sp. In Patients with Colorectal Cancer

“…The above differences may stem from our selection of patients with colorectal cancer and from different diagnostic methods used. It should be noted that the studies conducted by Certad and colleagues (12)(13)(14)(15) have suggested a correlation between Cryptosporidium parvum infection and colorectal cancer carcinogenesis. Certad and colleagues (12) have demonstrated on an animal model a correlation between cryptosporidiosis and the development of gastrointestinal adenomatous polyps or adenocarcinomas.…”

“…Recent reports indicate the potential involvement of Cryptosporidium parvum in colorectal cancer carcinogenesis (12)(13)(14)(15). It appears justified to perform studies evaluating the prevalence of Cryptosporidium infection in patients with diagnosed colorectal cancer prior to the initiation of oncological treatment.…”

Development of Cryptosporidium parvum-Induced Gastrointestinal Neoplasia in Severe Combined Immunodeficiency (SCID) Mice: Severity of Lesions Is Correlated with Infection Intensity

“…In this work, we described the potential role of Cryptosporidium parvum in the development of colon neoplasia in experimentally infected severe combined immunodeficiency (SCID) mice treated with dexamethasone. 6 Herein, the ability of C. parvum to induce neoplastic changes could be established experimentally. In addition, we showed that deep immunosuppression alone did not entail neoplasia in uninfected hosts.…”

“…The rationale for selecting dates for euthanasia was based on our previous results. 6 The SCID mouse colony source of the mice used in this work is regularly evaluated for the absence of microbial or parasitologic infections, including Helicobacter . Experiments were performed according to the European guidelines (Council directives on the protection of animals for experimental and other scientific purposes.…”

“…Dex administration started 2 weeks before inoculation and was maintained during the whole experimentation as previously described. 6 Thirty-two SCID mice were randomly divided into eight groups of four in capped cages according to the dose of C. parvum oocysts inoculated and to the administration or not of Dex. Four groups of mice without Dex were inoculated by oral route with 10 5 , 10 6 , 10 7 , or 10 8 oocysts, respectively, in 200 μL of PBS.…”