Dose-finding Study of WS6788A, DS37-4 and H10407 Enterotoxigenic Escherichia Coli (ETEC) Challenge Strains
Dose-finding Study of WS6788A, DS37-4 and H10407 Enterotoxigenic Escherichia Coli (ETEC) Challenge Strains
Five subjects will be admitted to the General Clinical Research Center (GCRC). The next day
 they will eat a light breakfast, fast for 90 minutes, ingest ETEC strain H10407, and fast for
 90 more minutes. After this challenge they will be monitored closely , and all stools will be
 collected, graded and weighed. On Day 5, or sooner if indicated, they will begin antibiotics
 to eradicate the challenge strain. They will be scheduled for discharge on Day 7 but may
 leave a few days earlier if early antibiotic treatment is given.

 Hypothesis:

 A challenge dose of 10(9) colony forming unit (CFU) of ETEC strain H10407, will cause
 diarrhea in at least 60% of subjects.
The rationale for validation H10407 in the challenge study proposed at Johns Hopkins
 University is that this initial challenge study will support additional challenge studies
 planned for the future. In these future studies, a bovine milk immunoglobulin containing high
 levels of antibodies specific for colonization factor antigen (CFA/I) or CFA/I-derived
 colonization factor will be investigated as a potential oral prophylaxis to neutralize
 subsequent challenge against CFA/I-expressing H10407 in the clinical setting. The goal here
 is therefore to validate a challenge dose of 1x109 h10407 organisms in the hands of the Johns
 Hopkins investigative team and to then use this dose in the future prophylaxis/challenge
 studies. Challenge doses equal to or comparable to the 1x109 dose proposed for the Johns
 Hopkins University (JHU) study have been used in 6 of the 9 challenge studies that have been
 done with the H10407 strain. The subsequent challenge studies using H10407 will be registered
 as part of other protocols.
Inclusion Criteria:

 -  Healthy adults age 18 to 45 years old who are willing to participate, complete
 training on ETEC and diarrhea and procedures of the protocol, pass the test
 documenting knowledge of the study, and give informed consent.

 Exclusion Criteria:

 1. age<18 or >45 years

 2. Chronic illness, chemical dependency, or significant medical illness as determined by
 the investigator.

 3. immunosuppressive condition or IgA (Immunoglobulin A) deficiency

 4. HIV antibody positive

 5. hepatitis B surface antigen positive

 6. hepatitis C antibody positive

 7. travel to ETEC endemic area within 2 years

 8. vaccination or other exposure to ETEC, cholera, or heat labile toxin (LT) toxin within
 3 years

 9. pregnancy as defined by + serum or urine - human chorionic gonadotropin (HCG) on the
 day before immunization

 10. inability to pass the written examination

 11. use of antibiotic, H2 blocking agent or proton pump inhibitor within 7 days of
 challenge

 12. regular use of laxatives antacids or other agents to lower stomach acidity

 13. significant abnormality in screening lav hematology and chemistry tests as determined
 by the investigator.

 14. significant abnormality on EKG for those 40 to 50 years old as determined by the
 investigator.

 15. allergy to quinolones, penicillin's and Bactrim.

 16. abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day).