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

Miscarriage Clinical Trial

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

Status Terminated

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Abortion, Spontaneous
• Cholera
• Miscarriage
• Stillbirth

• NCT number: NCT02499172
• Study type: Interventional
• Source: Johns Hopkins Bloomberg School of Public Health
• Status: Terminated
• Phase: N/A
• Start date: June 2015
• Completion date: October 30, 2016