Follow-up of Pregnant Women After a Mass Vaccination of Oral Cholera Vaccine (ShancholTM) in Nsanje Malawi

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Brief Title

Follow-up of Pregnant Women After a Mass Vaccination of Oral Cholera Vaccine (ShancholTM) in Nsanje Malawi

Official Title

Follow-up of Pregnant Women After a Mass Vaccination of Oral Cholera Vaccine

Brief Summary

      This study, to be carried out immediately following an emergency, reactive cholera
      vaccination campaign in Nsanje District, Malawi, will be a cohort study to estimate the
      safety of killed oral cholera vaccine (OCV), in pregnant women as measured by ShancholTM, on
      pregnancy outcomes and birth defects. While limited evidence which suggests that the vaccine
      is safe in pregnant women, this setting will allow investigators to answer this question in a
      community where more than 100,000 people will receive vaccine with no restrictions on
      pregnancy status. In past cholera vaccine campaigns including clinical trials, pregnant women
      were excluded due to lack of safety data. However, in this campaign, the decision by the
      Ministry of Health is that the benefits of offering vaccine to all individuals regardless of
      pregnancy status far outweigh any theoretical risk. Here the investigators specifically
      propose to:

      Specific Objective 1: To conduct surveillance of pregnant women to detect adverse pregnancy
      outcomes within communities in Nsanje District, Malawi that received oral cholera vaccine in
      a reactive vaccination campaign that started on 30 March 2015. Through household surveying
      and enrollment of pregnant women with monthly follow-up visits, the investigators will
      determine the cumulative incidence of adverse pregnancy outcomes among vaccinated and
      unvaccinated women in Nsanje and Chikwawa Districts, Malawi.

      Specific Objective 2: To compare the cumulative incidence of pregnancy loss (miscarriage and
      stillbirth) of women who received oral cholera vaccine while they were pregnant to women who
      were vaccinated and became pregnant after the end of the final round of vaccination in Nsanje
      and Chikwawa Districts, Malawi.

      Specific Objective 3: To compare the incidence of newborn malformations in a cohort of
      infants that had fetal exposure to oral cholera vaccine compared to those without such
      exposure in Nsanje and Chikwawa Districts, Malawi.
    

Detailed Description

      Although there are good reasons for women of reproductive age to participate in interventions
      that prevent cholera, cholera vaccination programs and studies have generally excluded
      pregnant women since there is little specific information on the safety of the vaccine during
      pregnancy. However, there are several biological reasons why inactivated OCVs are unlikely to
      have a harmful effect on fetal development. First, the bacteria in the vaccine are killed and
      do not replicate. Second, the vaccine antigens act locally on the gastrointestinal mucosa,
      are not absorbed, and do not enter the maternal or fetal circulation. Finally, the vaccines
      do not trigger systemic reactions (e.g., fever) associated with miscarriage in early
      pregnancy.According to the latest WHO position paper in relation to OCV, vaccination in
      countries where cholera is endemic may include groups that are particularly vulnerable to the
      severe forms of cholera, and for whom the vaccines are not contraindicated, such as pregnant
      women and HIV-infected individuals.

      While the World Health Organization (WHO) recommends vaccination for pregnant women, the
      package inserts for Dukoral® and ShancholTM are more cautious and suggests that the vaccines
      are not recommended for use in pregnant women. Even so, the ShancholTM package insert states
      that, "Administration of ShancholTM to pregnant women may be considered after careful
      evaluation of the benefits and risks in case of a medical emergency or an epidemic". In the
      most recent results published in 2012, pregnant women inadvertently vaccinated with Dukoral®
      during the mass vaccination campaign in Zanzibar in 2009 did not experience any harmful
      effects. On the other hand, there is no information on the safety of ShancholTM vaccine in
      pregnant women. New evidence is needed to inform decisions on the true safety of this vaccine
      in pregnancy. If it is safe, this vaccine will be a valuable tool in reducing the burden of
      cholera in a population that disproportionately suffers from this disease.

      On January 13, 2015, the President of the Republic of Malawi declared a state of disaster
      following the persistent rains that resulted in floods affecting 15 of the 28 districts in
      the country. The first confirmed case of cholera was reported in Malawi on February 11, 2015.
      As of 4 March 2015, Malawi had registered 72 cases with 2 deaths. To stop the outbreak of
      cholera, a cholera vaccination campaign program was carried out between 30 March 2015 and May
      3 2015 targeting the camps and the nearby communities in Nsanje District. This campaign
      provided two doses of vaccine to all age eligible people irrespective of pregnancy status.
      This study is designed to do a follow-up of only the pregnant women aiming at the following
      objectives:

      Specific Objective: To conduct surveillance of pregnant women to detect adverse pregnancy
      outcomes within communities in Nsanje District, Malawi that received oral cholera vaccine in
      a reactive vaccination campaign that started on 30 March 2015. Through household surveying
      and enrollment of pregnant women with monthly follow-up visits, the investigators will
      determine the cumulative incidence of adverse pregnancy outcomes among vaccinated and
      unvaccinated women in Nsanje and Chikwawa Districts, Malawi.
    


Study Type

Interventional


Primary Outcome

Adverse Pregnancy Outcome


Condition

Miscarriage

Intervention

Shanchol

Study Arms / Comparison Groups

 Cohort 1
Description:  Cohort 1: Women who were pregnant and received at least one dose of ShancholTM during the mass OCV vaccination campaign.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

2758

Start Date

June 2015

Completion Date

October 30, 2016

Primary Completion Date

October 30, 2016

Eligibility Criteria

        Inclusion criteria:

          -  Women aged 15-49 years old at time of consent (all cohorts)

          -  Urine sample provided if pregnancy test required (Not required if experienced delivery
             outcome between March 30 and enrollment date, OR visibly pregnant AND has due date
             indicated in Health Passport) (all cohorts)

          -  Received at least one dose of OCV in 2015 (must be verified with OCV Vaccination Card)
             (Cohorts 1 & 2)

          -  Estimated last menstruation at least 3 weeks before the first dose of OCV received
             (Nsanje) or before March 30, 2015 (Chikwawa) (Cohorts 1 & 3)

          -  Estimated last menstruation at least 2 weeks after the final dose of OCV received
             (Nsanje) or after the last day of OCV Round 2 (Chikwawa) (Cohorts 2 & 4)

          -  Residing in Nsanje or Chikwawa Districts since the first day of the vaccination
             campaign (30 March 2015) (Cohorts 2 & 3)

          -  Provides informed consent (with additional consent by the parent or legal guardian for
             unmarried <18 years old) (All Cohorts)

        Exclusion criteria:

          -  Received at least one dose of OCV in 2015 (Cohorts 3 & 4)

          -  An otherwise eligible pregnant women who is unable to be contacted after the second
             attempt within 48 hours after the first attempt to enroll (All cohorts)
      

Gender

Female

Ages

15 Years - 49 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Mohammad Ali, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02499172

Organization ID

00006369


Responsible Party

Principal Investigator

Study Sponsor

Johns Hopkins Bloomberg School of Public Health

Collaborators

 Ministry of Health, Malawi

Study Sponsor

Mohammad Ali, PhD, Principal Investigator, Johns Hopkins Bloomberg School of Public Health


Verification Date

April 2019