Coccidia characterized by thick-walled oocysts excreted in feces In Humans Cryptosporidium Isospora Cyclospora Toxoplasma Sarcocystis

GENERAL APICOMPLEXAN LIFE CYCLE

Cryptosporidium fecal-oral transmission (monoxenous) wide range of animal hosts (C. parvum)? several host-adapted species? C. hominis for human species first human case reported in 1976 self-limiting diarrhea in immunocompetent persons profuse, watery diarrhea associated with AIDS (life threatening)

Extracytoplasmic Location microvilli extend and fuse to enclose zoite close association between parasite and host intestinal epithelial cell called adhesive zone, feeder organelle, etc

Cryptosporidium Life Cycle Merogony = schizogony produce merozoites Gametogony = gamogony or = gametocytogenesis produce micro- and macrogametes Sporogony produce sporozoites completed on host cell thin (autoinfection) or thick walled oocysts

Water Borne Outbreaks of Cryptosporidiosis in the USA Modified from Graczyk et al, Parasitol. Today 13:348 (1997)

The Milwaukee Outbreak NEJM 331:161 (1994) massive cryptosporidiosis outbreak following spring thaw >400,000 people may have been affected based on clinical symptoms (acute watery diarrhea) ~100-fold higher prevalence of Cryptosporidium oocysts in stools than normal other enterics (including Giardia, bacteria, viruses) were at ~normal levels treated water had high levels of turbidity 3/23-4/5/1993 oocysts identified in ice made during this period

Waterborne Cryptosporidiosis Factors Favoring Waterborne Cryptosporidiosis small size of oocysts (4-5 mm) reduced host specificity and monoxenous development close associations between human and animal hosts large number of oocysts excreted (up to 100 billion per calf per day) low infective dose (<30) robust oocysts; resistant to chlorine

Human Cryptosporidiosis associated with epidemic diarrhea in institutions and hospitals highly transmissible (19% household members)

Molecular Epidemiology 2 major genotypes identified: genotype 1 only human sources non-infective for mice or calves anthroponotic transmission genotype 2 human and bovine sources infective for mice and calves zoonotic transmission recently proposed genotype 1 = C. hominis other genotypes (eg, C. felis, dog type, etc) rare isolated only from AIDS patients

Symptoms of 205 patients with Confirmed Cases of Cryptosporidiosis During the Milwaukee Outbreak

Pathogenesis DIARRHEA enterocytes damaged or killed villus atrophy (blunting)  Na+ absorption  intercellular permeability crypt cell hyperplasia  Cl- secretion inflammation in lamina propria cytokines and neurohormones? enhanced secretion of antibodies (IgA)? DIARRHEA enterocyte malfunction (osmotic) impaired absorption enhanced secretion inflammatory diarrhea mucosal invasion leukocytes in stools secretory diarrhea toxin associated watery

Isospora belli wide geographical distribution (higher prevalence in warmer climates) monoxenous, probably not zoonosis invades intestinal epithelial cells often asymptomatic (seldom reported) symptoms range from mild gastro-intestinal distress to severe dysentery often self-limiting, but can become chronic (wasting, anorexia) symptoms more severe in AIDS patients

Cyclospora cayetanensis first human case in 1979 named in 1993 initially called ‘cyano-bacteria like body’ (CLB) or large Cryptosporidium related to Eimeria life cycle similar to Isospora oocysts mature in environment (days-weeks) no known animal reservoir more common in tropical and sub-tropical areas

Cyclosporiasis Outbreaks in U.S. and Canada Date Location Vehicle Source May-June 1995 New York food? ? May 1995 Florida raspberries? Guatemala? May-June 1996 US, Canada raspberries Guatemala March-April 1997 mesclun Peru? April-May 1997 June-July 1997 Wash., DC basil September 1997 Virginia fruit plate December 1997 Peru May 1998 Ontario Georgia fruit salad? May 1999 berry dessert fruit (berry) July 1999 Missouri Mexico or US June 2000 Pennsylvania

Transmission and Clinical Features associated with food-borne outbreaks luncheons, social events, weddings, etc. possible source always involved foreign country and fresh fruit or vegetables raspberries from Guatemala salad from Peru presumed source: contaminated water or human waste as fertilizer symptoms similar to Cryptosporidium and Isospora watery diarrhea/frequent stools 1-2 week duration typical relapses over 1-2 months

Intestinal Coccidia Diagnosis Treatment demonstration of oocysts in feces acid-fast stain (all three) autofluorescence (Isospora and Cyclospora) direct observation (Isospora) Treatment paromomycin for Cryptosporidium modest benefit lowers parasitemia in AIDS trimethoprim-sulfamethoxazole for Cyclospora and Isospora

Cryptosporidium Cyclospora Isospora belli 4-5 mm oocysts 4 sporozoites no sporocysts Cyclospora 8-10 mm oocyts 2 sporocysts 2 sporozoites each Isospora belli 30 x 12 mm oocyts 4 sporozoites each

Cryptosporidium Cyclospora Isospora belli 4-5 mm oocysts 4 sporozoites no sporocysts Cyclospora 8-10 mm oocyts 2 sporocysts 2 sporozoites each Isospora belli 30 x 12 mm oocyts 4 sporozoites each

Cryptosporidium Cyclospora Isospora belli 4-5 mm oocysts 4 sporozoites no sporocysts Cyclospora 8-10 mm oocyts 2 sporocysts 2 sporozoites each Isospora belli 30 x 12 mm oocyts 4 sporozoites each