Classification: Taxonomic ranks under review (cf. Illustrated Guide to Protozoa, 2000. Allen Press)
Protista (unicellular eukaryotes)
Cryptosporidium spp. [these species cause cryptosporidiosis in vertebrates, especially neonates]
Parasite morphology: The parasites form three developmental stages: meronts, gamonts and oocysts. Endogenous developmental stages appear as small basophilic bodies (3-6µm) attached to the luminal surface of host epithelial cells; while exogenous oocysts appear as ovoid phase-bright ovoid bodies (5-7 x 4-6µm) containing four sporozoites and an eccentric residual body.
Host range: Infections have been detected throughout the world in numerous species of mammals, birds, reptiles and fish. Parasite species were originally described primarily on the basis of host occurrence, site of infection, type of disease and, occasionally, differences in oocyst morphometrics. Epidemiological and experimental cross-transmission studies, however, suggested that different parasite species were specific for individual vertebrate classes rather than individual host species. More recently, molecular characterization studies conducted on clinical isolates have identified a range of genotypes (and subgenotypes) that vary in their specificity for mammals; some being highly specific for individual host species (e.g. C. hominis) while others were found in multiple host species (e.g. C. parvum). Genetic markers used for parasite characterization have included the small subunit (18S) of nuclear ribosomal DNA (SSU rDNA), second internal transcribed spacer of rDNA (ITS-2), 70 kDa heat shock protein (hsp-70), Cryptosporidium oocyst wall protein (cowp), thrombospondin-related adhesive protein (TRAP), actin, ?-tubulin, 60 kDa glycoprotein (gp60), and microsatellite loci (ML1 and ML2). The significance of such parasite variation has been used to indicate the anthroponotic and/or zoonotic potential of isolates.
Pathogenesis: Infections vary markedly in their presentation ranging from asymptomatic to mild acute to severe chronic disease. Endogenous intestinal stages may cause microvillus destruction, villus atrophy, impaired glucose and electrolyte transport, impaired carbohydrate and protein digestion manifesting in malabsorptive and maldigestive disease. Most clinical infections in immunocompetent individuals involve transient acute disease characterized by profuse watery foul-smelling diarrhoea or acute respiratory signs. Neonates and malnourished individuals are most susceptible, whereas older animals become resistant (immune) to infection. Infections may persist in immunocompromised individuals (those with congenital or acquired immunodeficiencies or those undergoing immunosuppressive therapy) resulting in protracted chronic disease which may prove fatal (especially in AIDS patients). In contrast, infections in reptiles (and possibly fish) cause chronic gastritis typified by postprandial regurgitation.
Mode of transmission: Oocysts excreted by infected hosts contaminate the environment and initiate infections when ingested by susceptible hosts (faecal-oral transmission). Some (thin-walled) oocysts are thought to be auto-infective and may excyst in the same host. Most infections are transmitted by fomites between individuals held in close confinement, such as in child day-care centres, hospitals, zoos, and intensive animal rearing facilities. In addition, oocysts are being detected with increased frequency in treated and untreated water supplies. Many water-borne outbreaks of public health significance have been reported involving contamination of potable and recreational waters (lakes, pools, water parks) by sewage and/or agricultural waste. While conventional methods of water treatment (filtration and chlorination) may reduce contamination levels (quantified by log removal and concentration-time parameters), the small tough oocysts are quite resistant and enough persist to pose a significant problem for water providers. Food-borne transmission has also been recorded (involving milk, cider, salads, sausages), probably attributable to contaminated water being used in food production.
Differential diagnosis: Infections are conventionally diagnosed by the detection of oocysts in smears or concentrates of faecal material or respiratory exudates. Unstained oocysts may be confused with yeasts but they are acid-fast and stain well with basic fuchsin stains. Alternatively, phase-contrast or differential interference contrast microscopy can be used to reveal internal oocyst features, as can vital dyes (DAPI) and fluorescent nucleic acid stains (MPR71059). Although some parasite species can be cultured in vitro (in tissue cultures) or in vivo (in laboratory or neonatal domestic animals), considerable variation has been observed in parasite infectivity and growth. More success has been reported in detecting oocysts in clinical and environmental samples using specific monoclonal antibodies for immunomagnetic separation or as fluorescent markers for microscopy or flow cytometry. Researchers have also developed several highly sensitive techniques using polymerase chain reaction (PCR) amplification of partial gene sequences followed by electrophoretic fingerprinting.
Treatment and control: There is currently no effective chemotherapeutic treatment for cryptosporidiosis, although variable success has been reported using paromomycin and nitazoxanide. Supportive treatment by oral or parenteral rehydration may help alleviate symptoms. Some promising results have been obtained using hyperimmune bovine colostrum for passive immunotherapy. Control measures include identification of the source of infection, isolation of infected individuals, maintaining high standards of hygiene, proper effluent disposal and disinfection of contaminated surfaces. Public health authorities also recommend boiling water during outbreak situations and also more regularly for high-risk patients groups (such as HIV-positive individuals).