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Oral cholera vaccine does not significantly increase risk of pregnancy loss
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An observational cohort study of pregnant women in Malawi showed no evidence that the oral cholera vaccine Shanchol significantly increased pregnancy loss, researchers said.
Shanchol (Shantha Biotechnics) is one of two oral inactivated cholera vaccines that have been pre-qualified by WHO, the other being Dukoral (Valneva). According to Mohammad Ali, PhD, senior scientist in the department of international health at the Johns Hopkins Bloomberg School of Public Health, and colleagues, cholera infection in pregnant women can lead to fetal loss if not treated promptly, but these patients are often excluded from vaccination campaigns because of poor evidence about the safety of oral cholera vaccine use during pregnancy.
Ali said the results of their study combined with results from retrospective studies in Tanzania and Guinea show pregnant women should not be excluded from cholera vaccination campaigns.
“Although not statistically significant, we noted a slightly higher risk of pregnancy loss among women exposed to the vaccine,” they wrote in The Lancet Infectious Diseases. “However, the potential additional risk of pregnancy loss associated with vaccine was very small (<1%). This hypothetical risk needs to be considered in the context of substantial risk of disease for the mother during an outbreak and a high risk of pregnancy loss (6–12%) if cholera does occur.”
Vaccine given during outbreak
Ali and colleagues compared pregnant women who received at least one dose of Shanchol during a deadly 2015 cholera outbreak in Malawi with pregnant women who were not vaccinated in the outbreak. The pregnant women were from the Nsanje district, where Shanchol was provided. The unvaccinated women were from neighboring Chikwawa district, where the vaccine was not offered because of insufficient supply.
According to Ali and colleagues, the Malawian Ministry of Health included pregnant women in the vaccination campaign after consultation with WHO and others.
The researchers analyzed 835 women in each cohort. Among the pregnant women who received Shanchol, there were six miscarriages and 17 stillbirths for a frequency of pregnancy loss of 27.54 per 1,000 pregnancies (95% CI, 18.41-41.23). In comparison, there were two miscarriages and 16 stillbirths in the nonvaccinated group for a frequency of pregnancy loss of 21.56 per 1,000 pregnancies (95% CI, 13.65-34.04).
Ali and colleagues calculated the adjusted relative risk of pregnancy loss in patients exposed to Shanchol as 1.24 (95% CI, 0.64-2.43, P = 0.52).
The rate of neonatal mortality — deaths occurring within 28 days of delivery — was 11.78 per 1,000 live births in the vaccinated group (95% CI, 5.92-23.46) compared with a rate of 8.91 per 1,000 live births in the unvaccinated patients (95% CI, 4.02-19.77) for a crude relative risk of 1.32 (95% CI, 0.46-3.84, P = 0.60).
Two infants in the vaccinated group and one in the unvaccinated group had malformations for a relative risk of 2.0 (95% CI, 0.18-22.04, P = 0.57), although Ali and colleagues said this estimate was unreliable because of the small number of outcomes.
‘We noted no evidence that oral cholera vaccine during pregnancy significantly increased pregnancy loss, consistent with findings from earlier retrospective studies,” Ali and colleagues wrote. “Our results also extend the observation that exposure to oral cholera vaccine while pregnant is not associated with an increased risk for neonatal death or newborn malformation. However, the number of malformations is too small to derive firm conclusions.”
Not available in the US
Although Shanchol is pre-approved by WHO, it is not available for use in the United States. The only cholera vaccine available in the U.S. is Vaxchora (PaxVax), a single-dose live oral vaccine that was approved by the FDA in June. It is approved for adults aged 18 to 64 years who are traveling to an area of active transmission.
According to the CDC, Vaxchora reduces the chance of severe diarrhea by 90% at 10 days after vaccination and 80% at 3 months after vaccination, but its safety and effectiveness in pregnant women is not known.
In a related editorial also published in The Lancet Infectious Diseases, Pedro L. Moro, MD, MPH, and Lakshmi Sukumaran, MD, MPH, both of the CDC’s Immunization Safety Office, said the study by Ali and colleagues provided evidence for the safety of Shanchol in pregnant women.
However, Moro and Sukumaran said gaps in knowledge remain, including the safety of Shanchol when administered in the first trimester.
“In areas endemic for cholera, pregnant women are at risk of severe diarrheal disease that can result in dehydration and pregnancy loss,” they wrote. “Although good sanitation measures (e.g., clean water and sewage systems) are ideal, these measures are beyond the reach of many areas, especially during cholera outbreaks. The available cholera vaccines recommended by WHO offer an additional preventive approach and, on the basis of available data, they can be safely used during pregnancy.” – by Gerard Gallagher
References:
Ali M, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(16)30523-0.
Moro PL and Sukumaran L. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30055-5.
Disclosures: The researchers report no relevant financial disclosures.