Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam.

OBJECTIVE: To evaluate a killed oral cholera vaccine produced in Viet Nam, and to compare the Vietnamese vaccine with one that is licensed internationally. METHOD: Two-dose regimens of a locally produced, bivalent, anti-O1, anti-O139 killed oral whole-cell cholera vaccine (biv-WC) and of a commercially available, monovalent (anti-O1) oral recombinant B subunit-killed whole-cell cholera vaccine (rBS-WC) were compared in two trials in Viet Nam. In the first trial, 144 adults were randomized to biv-WC with or without buffer, rBS-WC with buffer, or placebo without buffer. In the second, 103 children aged 1-12 years were randomized to biv-WC without buffer, rBS-WC with buffer, or placebo without buffer. FINDINGS: No regimen was associated with significant side-effects. In adults, ca 60% of recipients of either vaccine exhibited at least fourfold serum anti-O1 vibriocidal antibody responses and ca 40% of recipients of biv-WC demonstrated anti-O139 vibriocidal responses. Both anti-O1 (ca 90% in each vaccine groupand anti-O139 (68% in the biv-WC group) vibriocidal responses occurred more frequently in children. The responses to biv-WC were unaffected by the receipt of buffer. CONCLUSION: It was concluded that biv-WC was safe and immunogenic, that it could be administered without buffer, and that it could elicit robust immune responses even in children, for whom the risk of endemic cholera is highest.

Cost of immunization with a locally produced, oral cholera vaccine in Viet Nam.

Policy decisions regarding whether to incorporate new vaccines into routine public health practice in developing countries will depend in part on the costs of vaccine purchase and of vaccine delivery. In March, 1997, a large-scale effectiveness trial of a locally produced, orally administered bivalent vaccine against Vibrio cholerae 01 and 0139 began in Viet Nam. Empirical data obtained from the trial was used to determine the costs of the immunization campaign from the government perspective. The study population, including the children less than one year of age and pregnant women who were ineligible for immunization, was 353926. A total of 289041 persons received two doses of vaccine, and 13340 persons received one dose of vaccine. Two-dose vaccine coverage was 83.4%. The total cost of vaccine delivery during the immunization campaign was $66527. The cost of each dose of vaccine was $0.31. Therefore, the total cost of the immunization campaign was $0.44 per dose administered, and $0.91 per fully immunized person. Attempts to reduce the cost per dose of vaccine (e.g. the use of a monovalent vaccine against serogroup 01) are likely to have a large impact on the cost of future similar immunization campaigns.

Field trial of a locally produced, killed, oral cholera vaccine in Vietnam.

BACKGROUND: Several studies have shown that orally administered killed cholera vaccines are safe and protective in populations at risk of cholera in developing countries. However, these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children. We have tested an inexpensive, killed whole-cell cholera vaccine developed and produced in Vietnam. METHODS: The efficacy of the vaccine was assessed in a large-scale, open field trial in people at least 1 year old residing in 22,653 households in the central coastal city of Hue. Alternate households were assigned vaccine (67,395 people; two doses per person) or no vaccine (67,058 people). Surveillance for cholera was conducted in all Ministry of Health facilities serving this population. Analysis was by intention to treat. FINDINGS: During an outbreak of El Tor cholera 8-10 months after vaccination, 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group, and 92 cases among age-eligible people allocated to the no-vaccine group (protective impact 60% [95% CI 40-73]). Among the 51,975 people who received the complete two-dose vaccine regimen, the protective efficacy was 66% (46-79): in this subset, the protective efficacy was similar for children aged 1-5 years (68%) and for older people (66%). INTERPRETATION: These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children, who are at highest risk of cholera in endemic settings. An inexpensive, locally produced, and effective oral cholera vaccine may be within reach of the limited health-care budgets of poor countries with endemic cholera, if our findings can be replicated in a randomised double-blind trial.

PIP: Vibrio cholera 01, El Tor biotype, entered Vietnam in 1964 and during 1990-94 an average of 3240 cases were reported annually with a case-fatality rate of about 1%. The efficacy of an inexpensive, killed whole-cell cholera vaccine developed in Vietnam was assessed in a large-scale, open field trial in the city of Hue. The vaccine contained V. cholera 01 constituents: heat-killed V. cholera Inaba, heat-killed V. cholera Ogawa, and formalin-killed V. cholera Inaba. All 134,453 residents, aged 1 year or older, of 22,653 households in 19 communes were eligible to take part in the trial. Alternate households were assigned vaccine (67,395 people; 77% received 2 doses per person) or no vaccine (67,058 people serving as controls) during December 1992 and January 1993 by 80 vaccination teams. Following the vaccination no cases of cholera were detected until late August 1993. Between August 20 and October 4, 1993, there were 129 cases of cholera requiring inpatient care among age-eligible participants. The isolates were 01 serogroup and Ogawa serotype. There were 37 cases of cholera in the vaccine group and 92 cases in the control group. The risk of cholera was 0.5/1000 and 1.4/1000, respectively. The protective impact was 60% (95% confidence interval [CI] 40-73; p 0.001). Among 51,975 recipients of 2 vaccine doses the protective efficacy was 66% (CI 46-79; p 0.001). The protective efficacy was similar for children 1-5 years old (68%) and for older people (66%). The protective efficacy was somewhat higher among the vaccinated living in homes with unclean water sources (74% vs. 62%). The protective efficacy was also higher against severe than against non-severe cholera (76% vs. 58%). Oral killed whole-cell vaccines can protect against El Tor type cholera in children who are highest risk. The government has lately added a killed V. cholera 0139 strain to the existing formulation. Phase 2 tests of safety are under way, and a large-scale, randomized, double-blind field trial will start in 1997.