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Protozoan infectivity studies

Graham Vesey gvesey at RNA.BIO.MQ.EDU.AU
Tue Mar 12 18:25:52 EST 1996

Have a look at the following:

Miller,RA; Bronsdon,MA; Morton,WR (1990): 
Experimental cryptosporidiosis in a primate model. J. 
Infect. Dis. 161(2, Feb), 312-315.
<Cryptosporidium causes a disease in infant 
macaques that is clinically, histologically, and 
microbiologically indistinguishable from that seen in 
young children. A reproducible experimental model of 
cryptosporidiosis has been developed in pigtailed 
macaques (Macaca nemestrina) and used to studied the 
infectious dose of oocysts and the effect of inoculum 
size on severity of disease. Inoculation with either 
2 x 10(5) or 10 oocysts via nasogastric tube resulted 
in clinical enteritis and the fecal passage of large 
numbers of cryptosporidial oocysts in all four 
primates studied. The size of the inoculum had no 
apparent effect on the severity or duration of 
disease. Rechallenge 2 weeks after resolution of the 
primary infection demonstrated partial acquired 
immunity. The small inoculum size coupled with the 
passage of large numbers of oocysts contributes to 
the highly contagious nature of cryptosporidiosis 
among captive primates and may be relevant to the 
epidemiology and control of cryptosporidiosis in 

Finch,GR; Daniels,CW; Black,EK; Schaefer,FW; 
Belosevic,M (1993): Dose response of cryptosporidium 
parvum in outbred neonatal cd 1 mice. Appl. Environ. 
Microbiol. 59(11, Nov), 3661-3665.
       (Univ Alberta, Dept Civil Engn, Edmonton T6G 
2E9, Alberta, Canada)
<Cryptosporidium parvum infectivity in a 
neonatal CD-1 mouse model was used to determine the 
dose needed to infect 50% of the population. The 50% 
infective dose was estimated to be 79 oocysts. It was 
observed that a mean oral inoculum of 23 oocysts 
produced infection in 2 of 25 neonatal mice 7 days 
postinoculation. All animals became infected when the 
mean oral dose exceeded 310 oocysts per animal. The 
dose response of C. parvum was modeled with a logit 
dose-response model suitable for use in water 
disinfection studies.>

Blewett,DA; Wright,SE; Casemore,DP; Booth,NE; 
Jones,CE (1993): Infective dose size studies on 
cryptosporidium parvum using gnotobiotic lambs. 
Water. Science. and. Technology. 27(3-4), 61-64.
       (Moredun Res Inst, 408 Gilmerton Rd, Edinburgh 
Eh17 7Jh, Midlothian, Scotland . Glan Glwyd Gen Hosp, 
Cryptosporidium Reference Unit, Phls, Rhyl, Wales. 
Lothian Reg Council, Dept Water & Drainage, Marine 
Esplanade, Edinburgh, Scotland)
<Natural waterbourne transmission of 
cryptosporidiosis was studied by a simulation using 
low-level accumulative dosing. Gnotobiotic lambs were 
fed on a diet artificially contaminated to a 
predetermined level with cryptosporidium parvum 
oocysts and the faecal output of cysts was measured. 
Results indicate a minimum infectious dose as low as 
one oocysts.>

Dupont,HL; Chappell,CL; Sterling,CR; Okhuysen,PC; 
Rose,JB; Jakubowski,W (1995): The infectivity of 
cryptosporidium parvum in healthy volunteers. N. 
Engl. J. Med. 332(13, 30 Mar), 855-859.
       (Dupont HL ST LUKES EPISCOPAL HOSP 6720 
<Background. Small numbers of Cryptosporidium 
parvum oocysts can contaminate even treated drinking 
water, and ingestion of oocysts can cause diarrheal 
disease in normal as well as immunocompromised hosts. 
Since the number of organisms necessary to cause 
infection in humans is unknown, we performed a study 
to determine the infective dose of the parasite in 
healthy adults. Methods. After providing informed 
consent, 29 healthy volunteers without evidence of 
previous C. parvum infection, as determined by the 
absence of anti-cryptosporidium-specific antibodies, 
were given a single dose of 30 to 1 million C. parvum 
oocysts obtained from a calf. They were then 
monitored for oocyst excretion and clinical illness 
for eight weeks. Household contacts were monitored 
for secondary spread. Reuslts. Of the 16 subjects who 
received an intended dose of 300 or more oocysts, 14 
(88 percent) became infected. After a dose of 30 
oocysts, one of five subjects (20 percent) became 
infected, whereas at a dose of 1000 or more oocysts, 
seven of seven became infected. The median infective 
dose, calculated by linear regression, was 132 
oocysts. Of the 18 subjects who excreted oocysts 
after the challenge dose, 11 had enteric symptoms and 
7 (39 percent) had clinical cryptosporidiosis, 
consisting of diarrhea plus at least one other 
enteric symptom. All recovered, and there were no 
secondary cases of diarrhea among household contacts. 
Conclusions. In healthy adults with no serologic 
evidence of past infection with C. parvum, a low dose 
of C. parvum oocysts is sufficient to cause 
infection. [References: 31]>

Rendtorff RC.  The experimental transmission of human
intestinal protozoan parasites. II. Giardia lamblia
cysts given in capsules.  Am. J. Hyg. 59:209-220, 1954.

Graham Vesey
Australian Environmental Flow Cytometry Group                                        
School of Biological Sciences,     .-.--:_:\
Macquarie University,            _/         \
Sydney,                         :   AEFCG    |
Australia NSW 2109.             \_          /
Tel- 612 850 8150                 '-''''\__/
Fax- 612 850 8174                        V  

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