Table 2. Summary of the Published Cryptosporidium CHIM Studies.
| species isolate | study reference | dose | N | infectiona (%) | illnessa (%) | notes |
|---|---|---|---|---|---|---|
| C. parvum Iowa | DuPont, NEJM 1995 | 3 × 101–106 | 29 | 20–100 | 0–38 | · first Cryptosporidium human challenge study; ID50 established 132 oocysts |
| · oocyst purified from neonatal calves | ||||||
| · self-limited infection and illness observed; at dose ≥1000 oocysts: 100% infection, 71% enteric symptoms and 29% diarrheal illness observed | ||||||
| C. parvum Iowa | Okhuysen, Inf Imm 1998 | 5 × 102 | 19 | 84 | 58 | · rechallenge (extension of DuPont 1995) study in healthy adults |
| · fewer subjects shed oocysts after the second exposure (16%) than after the first exposure (63%) | ||||||
| · lower “intensity of diarrhea” with rechallenge | ||||||
| C. parvum Iowa | Chappell, AJTMH 1999 | 5 × 102–5 × 104 | 17 | 41 | 59 | · infectivity in pre-existing anti-C. parvum serum IgG |
| · ID50 is 1880 oocysts, 20× higher than in seronegative volunteers | ||||||
| · prior exposure provides protection from infection and illness at low oocyst doses | ||||||
| C. parvum Iowa | Okhuysen, JID 1999 | 3 × 101–105 | 29 | 40–100 | 52 | · virulence of 3 C. parvum isolates compared, Iowa and UCP, originally isolated from calves and passaged in calves; whereas TAMU isolated from a student who got infected from foal, also passaged in calves |
| C. parvum UCP | 5 × 102–104 | 17 | 10–100 | 59 | · ID50 for Iowa, UCP, and TAMU established as 87, 1042, and 9 oocysts, respectively, based on presumed infection | |
| C. parvum TAMU | 101–5 × 102 | 14 | 0–100 | 86 | · TAMU isolate induced higher diarrhea rate for a longer duration than Iowa or UCP isolates | |
| C. parvum Iowa/TAMU | Alcantara, AJTMH 2003 | 102–103 | 15 | 50–67 | 33–83 | · importance of intestinal inflammation in C. parvum challenge versus pediatric patients as measured by fecal IL8, lactoferrin, and TNFα |
| · significantly more inflammation in pediatric Cryptosporidium patients than adult volunteers | ||||||
| C. parvum UCP | Okhuysen, CID 1998 | 5 × 103–1 × 104 | 20 | 44–100 | 56–75 | · prophylactic effect of bovine hyperimmune anti-Cryptosporidium colostrum |
| hyperimmune colostrum not protective against infection | ||||||
| C. parvum Moredun | Okhuysen, JID 2002 | 102–3 × 103 | 16 | 33–75 | 60–75 | · oocysts originally isolated from red deer, passaged in sheep and later in calves |
| · ID50 300 oocysts; diarrheal illness was frequently associated with oocyst excretion | ||||||
| Healthy Volunteers Challenged with C. parvum: N = 176 | ||||||
| C. hominis TU502 | Chappell, AJTMH 2006 | 101–5 × 102 | 21 | 20–80 | 40–75 | · first C. hominis human challenge study, ID50 established 10–83 oocysts |
| · oocyst purified from gnotobiotic piglets | ||||||
| · infection and illness similar to C. parvum challenge studies | ||||||
| C. meleagridis | Chappell, AJTMH 2011 | 105 | 5 | 100 | 80 | · first C. meleagridis human high-dose challenge study |
| · oocyst purified from gnotobiotic piglets | ||||||
| · caused self-limited infection and mild diarrheal illness | ||||||
| C. muris | Chappell, AJTMH 2015 | 105 | 6 | 100 | 33 | · first C. muris human high-dose challenge study |
| · oocyst purified from Nu/Nu mouse | ||||||
| · caused persistent infection and self-limited diarrheal illness | ||||||
| · persistent shedders were treated with nitazoxanide, and the infection was resolved | ||||||
a
Note: In most studies, “illness” was defined as the passage of 3 unformed stools in 8 h or >3 unformed stools in 24 h accompanied by the presence of one or more enteric symptoms, including fever, nausea, vomiting, abdominal pain or cramps, and gas-related intestinal symptoms. “Infection” was defined as the excretion of oocysts in stool by a direct immunofluorescence assay (DFA) after a flow-through period of 36 h postchallenge.