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