Safety of the Recombinant Chlorea Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy

Ramadhan Hashim, Ahmed Khatib, Godwin Enwere, Jin Park, Rita Reyburn, Mohammad Ali, Na Yoon Chang, Deok Ryun Kim, Benedikt Ley, Kamala Ley-Thriemer, Anna Lopez, John Clemens, Jacqueline Deen, Sunheang Shin, Christian Schaetti, Raymond Hutubessy, Maria Aguado, Marie Kieny, Lorenz Von Seidlein, David Sack & 5 others Stephen Obaro, Attiye J. Shaame, Said Mohammed Ali, Abdul A Saleh, Mohamed Saleh Jiddawi

    Research output: Contribution to journalArticleResearchpeer-review

    8 Downloads (Pure)

    Abstract

    Introduction: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.

    Methodology/Principal Findings:
    From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.

    Conclusions/Significance: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events.

    Trial Registration:
    ClinicalTrials.gov NCT00709410.
    Original languageEnglish
    Pages (from-to)1-8
    Number of pages8
    JournalPLoS Neglected Tropical Diseases
    Volume6
    Issue number7
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    Cholera Vaccines
    Vaccines
    Cholera
    Safety
    Pregnancy
    Bacterial Vaccines
    Pregnant Women
    Mothers
    Mass Vaccination
    Immunization Programs
    Tanzania
    Pregnancy Complications
    Rural Population
    Pregnancy Outcome
    Odds Ratio
    Parturition

    Cite this

    Hashim, Ramadhan ; Khatib, Ahmed ; Enwere, Godwin ; Park, Jin ; Reyburn, Rita ; Ali, Mohammad ; Chang, Na Yoon ; Kim, Deok Ryun ; Ley, Benedikt ; Ley-Thriemer, Kamala ; Lopez, Anna ; Clemens, John ; Deen, Jacqueline ; Shin, Sunheang ; Schaetti, Christian ; Hutubessy, Raymond ; Aguado, Maria ; Kieny, Marie ; Von Seidlein, Lorenz ; Sack, David ; Obaro, Stephen ; Shaame, Attiye J. ; Ali, Said Mohammed ; Saleh, Abdul A ; Jiddawi, Mohamed Saleh. / Safety of the Recombinant Chlorea Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy. In: PLoS Neglected Tropical Diseases. 2012 ; Vol. 6, No. 7. pp. 1-8.
    @article{6139eec484d44ff4bcf308e6a42725b1,
    title = "Safety of the Recombinant Chlorea Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy",
    abstract = "Introduction: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine. Methodology/Principal Findings: From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94{\%}) of the target women in the study site were interviewed. 1,151 (79{\%}) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83{\%}) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17{\%}) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies. Conclusions/Significance: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events. Trial Registration: ClinicalTrials.gov NCT00709410.",
    keywords = "cholera toxin B subunit, cholera vaccine, cholera toxin, inactivated vaccine, adolescent, adult, article, cholera, conception, drug safety, educational status, female, fetus outcome, human, immunosurveillance, interview, mass immunization, pregnancy, pregnancy outcome, pregnant woman, prenatal drug exposure, socioeconomics, spontaneous abortion, child, drug toxicity, genetics, immunology, male, middle aged, newborn, preschool child, Tanzania, Adolescent, Adult, Child, Child, Preschool, Cholera Toxin, Cholera Vaccines, Drug Toxicity, Female, Humans, Infant, Newborn, Male, Middle Aged, Pregnancy, Vaccines, Inactivated, Young Adult",
    author = "Ramadhan Hashim and Ahmed Khatib and Godwin Enwere and Jin Park and Rita Reyburn and Mohammad Ali and Chang, {Na Yoon} and Kim, {Deok Ryun} and Benedikt Ley and Kamala Ley-Thriemer and Anna Lopez and John Clemens and Jacqueline Deen and Sunheang Shin and Christian Schaetti and Raymond Hutubessy and Maria Aguado and Marie Kieny and {Von Seidlein}, Lorenz and David Sack and Stephen Obaro and Shaame, {Attiye J.} and Ali, {Said Mohammed} and Saleh, {Abdul A} and Jiddawi, {Mohamed Saleh}",
    year = "2012",
    doi = "10.1371/journal.pntd.0001743",
    language = "English",
    volume = "6",
    pages = "1--8",
    journal = "PLoS Neglected Tropical Diseases",
    issn = "1935-2727",
    publisher = "Public Library of Science (PLoS)",
    number = "7",

    }

    Hashim, R, Khatib, A, Enwere, G, Park, J, Reyburn, R, Ali, M, Chang, NY, Kim, DR, Ley, B, Ley-Thriemer, K, Lopez, A, Clemens, J, Deen, J, Shin, S, Schaetti, C, Hutubessy, R, Aguado, M, Kieny, M, Von Seidlein, L, Sack, D, Obaro, S, Shaame, AJ, Ali, SM, Saleh, AA & Jiddawi, MS 2012, 'Safety of the Recombinant Chlorea Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy', PLoS Neglected Tropical Diseases, vol. 6, no. 7, pp. 1-8. https://doi.org/10.1371/journal.pntd.0001743

    Safety of the Recombinant Chlorea Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy. / Hashim, Ramadhan; Khatib, Ahmed; Enwere, Godwin; Park, Jin; Reyburn, Rita; Ali, Mohammad; Chang, Na Yoon; Kim, Deok Ryun; Ley, Benedikt; Ley-Thriemer, Kamala; Lopez, Anna; Clemens, John; Deen, Jacqueline; Shin, Sunheang; Schaetti, Christian; Hutubessy, Raymond; Aguado, Maria; Kieny, Marie; Von Seidlein, Lorenz; Sack, David; Obaro, Stephen; Shaame, Attiye J.; Ali, Said Mohammed; Saleh, Abdul A; Jiddawi, Mohamed Saleh.

    In: PLoS Neglected Tropical Diseases, Vol. 6, No. 7, 2012, p. 1-8.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Safety of the Recombinant Chlorea Toxin B Subunit, Killed Whole-Cell (rBS-WC) Oral Cholera Vaccine in Pregnancy

    AU - Hashim, Ramadhan

    AU - Khatib, Ahmed

    AU - Enwere, Godwin

    AU - Park, Jin

    AU - Reyburn, Rita

    AU - Ali, Mohammad

    AU - Chang, Na Yoon

    AU - Kim, Deok Ryun

    AU - Ley, Benedikt

    AU - Ley-Thriemer, Kamala

    AU - Lopez, Anna

    AU - Clemens, John

    AU - Deen, Jacqueline

    AU - Shin, Sunheang

    AU - Schaetti, Christian

    AU - Hutubessy, Raymond

    AU - Aguado, Maria

    AU - Kieny, Marie

    AU - Von Seidlein, Lorenz

    AU - Sack, David

    AU - Obaro, Stephen

    AU - Shaame, Attiye J.

    AU - Ali, Said Mohammed

    AU - Saleh, Abdul A

    AU - Jiddawi, Mohamed Saleh

    PY - 2012

    Y1 - 2012

    N2 - Introduction: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine. Methodology/Principal Findings: From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies. Conclusions/Significance: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events. Trial Registration: ClinicalTrials.gov NCT00709410.

    AB - Introduction: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine. Methodology/Principal Findings: From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies. Conclusions/Significance: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events. Trial Registration: ClinicalTrials.gov NCT00709410.

    KW - cholera toxin B subunit

    KW - cholera vaccine

    KW - cholera toxin

    KW - inactivated vaccine

    KW - adolescent

    KW - adult

    KW - article

    KW - cholera

    KW - conception

    KW - drug safety

    KW - educational status

    KW - female

    KW - fetus outcome

    KW - human

    KW - immunosurveillance

    KW - interview

    KW - mass immunization

    KW - pregnancy

    KW - pregnancy outcome

    KW - pregnant woman

    KW - prenatal drug exposure

    KW - socioeconomics

    KW - spontaneous abortion

    KW - child

    KW - drug toxicity

    KW - genetics

    KW - immunology

    KW - male

    KW - middle aged

    KW - newborn

    KW - preschool child

    KW - Tanzania

    KW - Adolescent

    KW - Adult

    KW - Child

    KW - Child, Preschool

    KW - Cholera Toxin

    KW - Cholera Vaccines

    KW - Drug Toxicity

    KW - Female

    KW - Humans

    KW - Infant, Newborn

    KW - Male

    KW - Middle Aged

    KW - Pregnancy

    KW - Vaccines, Inactivated

    KW - Young Adult

    U2 - 10.1371/journal.pntd.0001743

    DO - 10.1371/journal.pntd.0001743

    M3 - Article

    VL - 6

    SP - 1

    EP - 8

    JO - PLoS Neglected Tropical Diseases

    JF - PLoS Neglected Tropical Diseases

    SN - 1935-2727

    IS - 7

    ER -