Eff ectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis

Background Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the eff ectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study. Methods Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1–4 years, 5–15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors. Findings From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine eff ectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine eff ectiveness 63%, 95% CI 8–85). 27 (57%) of 47 cases had certifi ed vaccination versus 147 (78%) of 188 controls (vaccine eff ectiveness 58%, 13–80). Neither self-reported nor verifi ed vaccination was signifi cantly associated with non-cholera diarrhoea (vaccine eff ectiveness 18%, 95% CI –208 to 78 by self-report and –21%, –238 to 57 by verifi ed vaccination). Interpretation Bivalent whole-cell oral cholera vaccine eff ectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of eff orts to control cholera epidemics

Use of Oral Cholera Vaccine in Haiti: A Rural Demonstration Project

A cholera epidemic has claimed the lives of more than 8,000 Haitians and sickened 650,000 since the outbreak began in October 2010. Early intervention in the epidemic focused on case-finding, treatment, and water and sanitation interventions for prevention of transmission. Use of oral cholera vaccine (OCV) as part of a complementary set of control activities was considered but initially rejected by policymakers. In December 2011, the Minister of Health of Haiti called for a demonstration of the acceptability and feasibility of the use of OCV in urban and rural Haiti. This paper describes the collaborative activity that offered OCV to one region of the Artibonite Department of rural Haiti in addition to other ongoing treatment and control measures. Despite logistics and cold chain challenges, 45,417 persons were successfully vaccinated with OCV in the region, and 90.8% of these persons completed their second dose

Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti

Background: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae. Methodology/Principal Findings We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6–17 years), and 47 younger children (1–5 years) in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine. Conclusions/Significance: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae

Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis

Background: Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the effectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study. Methods: Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1–4 years, 5–15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors. Findings: From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine effectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8–85). 27 (57%) of 47 cases had certified vaccination versus 147 (78%) of 188 controls (vaccine effectiveness 58%, 13–80). Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI −208 to 78 by self-report and −21%, −238 to 57 by verified vaccination). Interpretation: Bivalent whole-cell oral cholera vaccine effectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of efforts to control cholera epidemics. Funding: National Institutes of Health, Delivering Oral Vaccines Effectively project, and Department of Global Health and Social Medicine at Harvard Medical School

OSP-specific IgA responses.

<p>OSP-specific IgA responses to <i>V. cholerae</i> O1 Ogawa (A) and Inaba (B) by age group at baseline (day 0) and 7 days after each immunization (day 7 and day 21). Statistically significant differences relative to baseline are indicated (**  =  <0.001).</p

Vibriocidal responses in Haitian versus Bangladeshi vaccinees.

<p>Geometric mean titer (+SEM) of vibriocidal responses to <i>V. cholerae</i> O1 Ogawa and Inaba at baseline (day 0) and 7 days after each immunization (day 7 and day 21) in adults (A and B) and children (C and D). Statistically significant differences across countries at a given day are indicated (*  =  <0.05).</p

Enrollment and follow-up of study participants.

<p>Enrollment and follow-up of study participants.</p

Seroconversion rates among Haitians receiving two doses of Shanchol.^*

<p><b>*vibriocidal ≥4-fold increase, OSP (O-Specific Polysaccharide) ≥2-fold increase in kinetic ELISA.</b></p

Vibriocidal responses.

<p>Geometric mean titer (+SEM) of vibriocidal responses to <i>V. cholerae</i> O1 Ogawa (A) and Inaba (B) by age group at baseline (day 0) and 7 days after each immunization (day 7 and day 21). Statistically significant differences relative to baseline are indicated (**  =  <0.001).</p