Cryptosporidiosis (animal and human health)

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.

C. parvum has been categorized as a class B bioterrorist pathogen by the Center for Disease Control and Prevention (CDC).

Cryptosporidium parvum is zoonotic, meaning it can infect humans, particularly through contaminated water or direct contact with infected calves.

Cryptosporidium parvum is a protozoan parasite that primarily affects the gastrointestinal tract of young calves, causing cryptosporidiosis. It is a significant cause of diarrhea in neonatal calves, leading to substantial economic losses in the livestock industry and posing a zoonotic risk to humans.

It can lead to very substantial indirect costs for the farmer because of:

• reduced feed efficiency and growth rates, delaying the time to market;
• increased labor for managing sick calves and maintaining hygiene
• long-term impacts on productivity and fertility due to poor early development.

Human 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.

Animal Disease – Livestock

Cryptosporidiosis is a gastrointestinal disease in calves caused by protozoan parasites of the genus Cryptosporidium, most commonly Cryptosporidium parvum. It primarily affects neonatal calves (1–4 weeks old) and is a leading cause of diarrhea, dehydration, and poor growth in young livestock. C. parvum is the primary species affecting calves. The parasite infects the epithelial cells lining the intestines, disrupting the digestive system.

Treatment humans

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.

Treatment for neonatal calves

The standard treatment is not parasiticidal and thus may reduce oocyst shedding and severity but does not eliminate the infection. Nowadays, there is no universally effective anti-cryptosporidial drug currently available for calves.
Some antibiotics are used and registered for C. parvum but they are not effective. However they may be used to manage secondary bacterial infections.

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.

It could lead to a huge step forwards for immunocompromised patients.

Likewise it could represent a huge advantage in management of the neonatal calves without having to use antibiotics as legislation is not favourable for use of antibiotics in the food chain in many regions, esp. the European Union.