Thursday, February 18, 2016

Cryptosporidium parvum: Pathogenesis of Cryptosporidiosis

            Cryptosporidiosis (is also called Crypto) is a diarrheal disease mainly caused by an obligate intracellular protozoan parasite, Cryptosporidium parvum, in which the parasite cannot complete its life cycle and reproduce in the absence of a suitable host. C. parvum acquired an ability to infect the intestinal epithelial cells in gastrointestinal (GI) tract of the hosts and then undergo both asexual and sexual cycles for their replications. According to the Center for Disease Control and Prevention (CDC) report, Crypto is one of the most common waterborne diseases in the United States. Between 2001 to 2010, Crypto was the leading cause of waterborne disease outbursts, which linked to recreational water in the United States (1). Most of the Crypto can be spread by drinking recreational water contaminated with Crypto, eating raw food, exposure to stool from an infected person or animal, but it is not spread through a contact with blood. Due to C. parvum high tolerance to chlorine, they can survive in chlorinated environment for a long period of time, and this is why people swallowing recreational water (such as water in swimming pool) have higher risks to get Crypto infection.
            Cryptosporidium parvum is one of several protozoan parasite that cause Crypto in both animals and humans. It has a monoxenous life cycle that is mainly stay in the GI tract of a single host. Also, C parvum lacks of host and organ specificity, ability for autoinfection, and resistance to antimicrobial (2), which result in many aspects of the nature and pathogenic mechanisms of C. parvum remains unclear due to its characteristics.
            For the Cryptosporidium life cycle, it has both asexual and sexual cycles to allow themselves to divide and replicate in host epithelial cells. The life cycle begins with ingestion of sporulated oocysts from the host, and excystation (emerge from a cyst) occurs once the oocysts enter to the GI tract, and they will release four sporozoites which will parasitize epithelial cells in GI tract (Figure 1). Within these infected epithelial cells, C. parvum can undergo two additional asexual replication and release merozoites, which then they will undergo sexual cycle and produce microgametes (male) and macrogametes (female), which give arise to the zygote (fusion of both male and female gametes) and form oocysts (Figure 1). Then the cycle repeats from the ingestion of oocysts from the hosts.
Figure 1. Life cycle for Cryptosporidiosis caused by C. parvum.   
            The pathogenesis of Cryptosporidium in which causing diarrhea is still poorly understand. The suggested mechanism may be involving a host-parasite interaction in which the attachment of C. parvum surface protein on the host surface cell is the initial step for Crypto to occur. One of the C. parvum surface protein has been identified that plays a role in mediating attachment and invasion on intestinal epithelial cells of the hosts (3). It is believed that C. parvum surface protein acts like a ligand that binds to a receptor on the surface of the host epithelial cell and initiates attachment and invasion process to allow oocysts enter the GI tract and begins cell divisions.
            Cryptosporidial infection can be transmitted from contaminated food and water, from animal to person contact, and via person to person contact. The infection mainly infects children due to their incomplete development of immune system. The major transmission pathway for cryptosporidial infection is going through the fecal-oral route from infected hosts directly or indirectly via contaminated water or ingestion of contaminated food. Crypto is one of the frequent cause of waterborne diarrhea because small infectious dose is enough to cause infection. Also, due to their oocysts’ high resistance to disinfectants and other chemicals used in recreational and drinking water, Cryptosporidium has emerged frequently in most of the waterborne diseases in the United States. In fact, the source for Crypto mainly comes from wild animals such as bovines, dogs, or cats that ingested C. parvum oocysts in the intestines. Once the humans accidently make a contact with the stools of infected animals or humans, including swallowing unsterilized water or eating uncooked food contaminated with Crypto. In addition, individuals with immunodeficiency (failure of the immune system) also have high risks for Crypto, such as the patients with AIDS (acquired immunodeficiency syndrome) or cancer.
            The major diagnosis of Crypto is going through an examination of stool samples from the patients or animals. Because of the detection of Crypto can be challenged, several techniques have developed to identify Cryptosporidium such as acid-fast staining, is one of the reliable and traditional method to detect the presence of cryptosporidial oocysts. Also, in a view of immunology, using enzyme-linked immunosorbent assay (ELISA) and antibody immunofluorescence assay (IFA) are the two alternative methods that using antibodies to detect Cryptosporidium. Both methods are used to detect protein-protein binding interaction between C. parvum surface protein and the host cell surface protein, which allows healthcare providers to identify the infection more efficient.
            From a genetic view of C. parvum infection, a complete genome of C. parvum has been recently identified (Abrahamsen, 2004). Several novel proteins of C. parvum cell surface and secreted proteins have been identified, and it is believed these proteins have crucial roles in host interaction and pathogenesis (4). In addition, targeting Cryptosporidium metabolic pathway or enzymes may also have potentials for drug development (5). Still, due to lack of sufficient information about C. parvum pathogenesis, more genetic analysis are required to identify what genes or proteins have contributions in attachment and invasion processes, and the virulence of Crypto.
            C. parvum is one of the parasite that cause waterborne diseases in humans, and the health problem have become a major concern in the United States. Because of C. parvum oocyst’s high resistance to common disinfectants, sterilizing of recreational and drinking water still becomes a challenge work today. Accurate detection with Cryptosporidial infections is also a major challenge to healthcare providers, and more research is needed to focus on pathogenesis of Crypto and development of drugs or therapies against C. parvum infection. Knowing mechanisms and transmission of C. parvum infection would allow researchers to be able to target the interaction between C. parvum surface protein and host cell surface protein, which will prevent the first crucial step of Cryptosporidial infection, attachment and invasion process. Therefore, a combination of both genetic and pathological analyses are the essential approaches to treat Crypto in future.

1.         General Information for the Public | Cryptosporidium | Parasites | CDC. (n.d.).      Retrieved November 23, 2015, from           info.html
2.         S. Tzipori, Cryptosporidiosis in animals and humans, Microbiol. Rev. 47 (1983), 84–96.
3.         M.W. Riggs, Immunology: host response and development of passive        immunotherapy and vaccines, in: R. Fayer (Ed.), Cryptosporidium and             Cryptosporidiosis, CRC Press Inc., New York, 1997, pp. 129–162.
4.         Abrahamsen, M. S., Templeton, T. J., Enomoto, S., Abrahante, J. E., Zhu, G., Lancto, C. a, … Kapur, V. (2004). Complete genome sequence of the       apicomplexan, Cryptosporidium parvum. Science (New York, N.Y.), 304(5669),     441–445.
5.         G. H. Coombs, Parasitol. Today 15, 333 (1999).     

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