Fulminant Cryptosporidiosis after Near-Drowning: a Human Cryptosporidium parvum Strain Implicated in Invasive Gastrointestinal Adenocarcinoma and Cholangiocarcinoma in an Experimental Model

Abstract

hIn the present work, we report the characterization of a Cryptosporidium parvum strain isolated from a patient who nearly drowned in the Deule River (Lille, France) after being discharged from the hospital where he had undergone allogeneic stem cell transplantation. After being rescued and readmitted to the hospital, he developed fulminant cryptosporidiosis. The strain isolated from the patient's stools was identified as C. parvum II2A15G2R1 (subtype linked to zoonotic exposure) and inoculated into SCID mice. In this host, this virulent C. parvum isolate induced not only severe infection but also invasive gastrointestinal and biliary adenocarcinoma. The observation of adenocarcinomas that progressed through all layers of the digestive tract to the subserosa and spread via blood vessels confirmed the invasive nature of the neoplastic process. These results indicate for the first time that a human-derived C. parvum isolate is able to induce digestive cancer. This study is of special interest considering the exposure of a large number of humans and animals to this waterborne protozoan, which is highly tumorigenic when inoculated in a rodent model.

Introducing Miltefosine as an Anti-cryptosporidial Agent in Immunocompromised Mice

“…Stephens et al [29] reported that chronic infections of the biliary tract with C. parvum in SCID mice developed triaditis, cholangitis and lobular hepatitis. Moreover dysplastic changes in the liver after C. parvum infection have been reported in SCID mice [30]. According to Abdou et al [31], only one experimental immunosuppressed mouse was demonstrating large cell dysplasia in the liver.…”

Prevalence of Cryptosporidium sp. In Patients with Colorectal Cancer

“…Certad and colleagues (12) have demonstrated on an animal model a correlation between cryptosporidiosis and the development of gastrointestinal adenomatous polyps or adenocarcinomas. In addition, the above authors have described a case of massive cryptosporidiosis in a patient post bone marrow transplantation (15). The infection of SCID mice with a C. parvum strain isolated from the above patient have caused the development of gastrointestinal adenocarcinomas and biliary tract 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.…”

“…The infection of SCID mice with a C. parvum strain isolated from the above patient have caused the development of gastrointestinal adenocarcinomas and biliary tract cancer. Cryptosporidium has been found in the neoplastic tissue of infected mice (15).…”

“…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.…”