Cryptosporidium infection

Healt burden

Cryptosporidium parvum is an obligate parasite of the phylum Apicomplexa that infects the small intestine of many mammalian hosts including humans. Considered as a major waterborne pathogen (drinking and recreational water) that can also be transmitted through contaminated foods, C. parvum outbreaks have been widely reported in numerous countries from all continents. This parasite can remain infectious for months in a humid environment. As a result, C. parvum has been categorized as a class B bioterrorist pathogen by the Center for Disease Control and Prevention (CDC).

Disease

C. parvum causes self-limiting watery diarrhea or persistent and severe diarrhea depending on the age and the immune status of the patient. Indeed, C. parvum infection has been reported to be life-threatening in AIDS patients, among which the prevalence of cryptosporidiosis was determined to be 14% in developed countries and 24% in developing countries. Cryptosporidium spp., along with Giardia spp., has also been identified as the leading cause of chronic or persistent diarrhea in children in a context of malnutrition or immunodeficiency. The Global Enteric Multicenter Study identified Cryptosporidium as one of the top five pathogens causing mild to severe diarrhea in children under the age of 2 in developing countries. Studies have shown that Cryptosporidium infections in young children have often resulted in stunting and lead to poor cognitive functions later in childhood. However, currently available treatments have demonstrated limited effect in these vulnerable populations.

Treatment

Nitazoxanide, the only American Food and Drug Association (FDA) approved drug to treat cryptosporidiosis in immunocompetent patients, has shown little activity to fight against C. parvum infections in AIDS patients. Similarly, paromomycin, the currently used drug to treat C. parvum infections in AIDS patients, has shown modest activity and limited results in different case studies. With no efficient way to treat immunocompromised patients, many drugs have been tested over the years, but very few have shown consistent activity (Mead and Arrowood, 2014). There is an urgent need to identify treatment options for immunocompromised individuals.

D121

Convincing in vitro and in vivo preclinical results in C. Parvum have been documented, and show the potential of this compound to treat these indications.