A human volunteer challenge model using frozen bacteria of the new epidemic serotype, V. cholerae O139 in Thai volunteers

Abstract

A total of 35 volunteers were recruited for an IRB-approved inpatient dose-escalation challenge. The goal was to identify a dose that produced an observed cholera attack rate > or =80% and an illness of sufficient severity during the defined study period such that the model would be useful for determining vaccine protection. Volunteers were challenged in groups of 5 with V. cholerae O139 that had been reconstituted immediately before use. Only 2 out of 5 volunteers who received the lowest dose (4.3 x 10(4) cfu) had diarrhea. As the inoculum size increased, the attack rate of diarrhea increased to 3-4 of 5 volunteers. At the highest dose tested, approximately 5 x 10(7) cfu, the attack rate was 73%. We recommend the use of frozen V. Cholera O139 in a human experimental challenge model to assess cholera vaccine efficacy (VE) in a cholera endemic area but with 4 days observation period before initiation of tetracycline to allow assessment of severity.