Cryptosporidium pathogenicity and virulence

Abstract

Cryptosporidium is a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation of Cryptosporidium virulence factors have been hindered by the renowned difficulties pertaining to the in vitro culture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors for Cryptosporidium. This progress has been accelerated since the publication of the Cryptosporidium parvum and C. hominis genomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge on Cryptosporidium infectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence.

Fig 1

Schematic representation of the Cryptosporidium parvum life cycle. After excysting from oocysts in the lumen of the intestine (a), sporozoites (b) penetrate host cells and develop into trophozoites (c) within parasitophorous vacuoles confined to the microvillous region of the mucosal epithelium. Trophozoites undergo asexual division (merogony) (d and e) to form merozoites. After being released from type I meronts, the invasive merozoites enter adjacent host cells to form additional type I meronts or to form type II meronts (f). Type II meronts do not recycle but enter host cells to form the sexual stages, microgamonts (g) and macrogamonts (h). Most of the zygotes (i) formed after the fertilization of the microgamont by the microgametes (released from the microgamont) develop into environmentally resistant, thick-walled oocysts (j) that undergo sporogony to form sporulated oocysts (k) containing four sporozoites. Sporulated oocysts released in feces are the environmentally resistant life cycle forms that transmit the infection from one host to another. A smaller percentage of zygotes (approximately 20%) do not form a thick, two-layered oocyst wall; they have only a unit membrane surrounding the four sporozoites. These thin-walled oocysts (l) represent autoinfective life cycle forms that can maintain the parasite in the host without repeated oral exposure to the thick-walled oocysts present in the environment. (Modified from reference with permission.)

Fig 2

Cryptosporidium virulence factors described to date and their contribution to the parasite life cycle.

Fig 3

Characteristics of the new family of telomeric Cryptosporidium proteins, Cops-1 and Chos-1. (A) Genomic positions of the Cops-1 and Chos-1 genes. (B) Predicted Cops-1 and Chos-1 proteins are 50 kDa, secreted, and serine rich; contain internal repeats; and are highly glycosylated. aa, amino acids; IEP, isoelectric point. (Modified from reference , which was published under a Creative Commons license.)

Fig 4

Total number of cryptosporidiosis cases detected in England and Wales by age group between 1989 and 2008, as reported by the Health Protection Agency (http://www.hpa.org.uk/).