Séverine Caluwaerts and Françoise Baylis lament the fact that in an epidemic as deadly as Ebola, pregnant women were denied access to potentially life-saving vaccination solely on the grounds of pregnancy.
In August 2015 an effective Ebola vaccine (Merck, rVSV-ZEBOV vaccine) became available for people who had been exposed to a case of Ebola virus disease. In ideal circumstances vaccination would happen immediately or very shortly after exposure. In practice, however, not all at-risk individuals were eligible for vaccination. To explain, the rVSV vaccine was not tested in pregnant women because of a theoretical risk to the developing fetus. So, when this vaccine became available, doctors were not authorized to give it to pregnant women who had been exposed to Ebola.
This does not mean that no pregnant women were vaccinated against Ebola. There was no standard pregnancy testing prior to vaccination and so women who did not know that they were pregnant or who did not disclose their pregnancy status would have been vaccinated. Women who were obviously pregnant, however, or who did disclose that they were pregnant, would not have been vaccinated.The health care workers administering the vaccine knew from a previous epidemic with the Ebola Zaire strain that mortality in pregnant women was more than 50%. As well, in the earlier epidemic 15 infants were born to Ebola-positive women and all of them died within 21 days of birth (presumably of Ebola). Considering these facts – an extremely high mortality rate for pregnant woman and not a single baby having survived transplacental Ebola – many of the doctors wanted to vaccinate pregnant women who had been exposed to the virus. This did not happen, however, despite a specific request to Merck by Médecins Sans Frontières and the World Health Organization.
In October 2015, in the province of Forécariah, in rural Guinea, a 25-year-old woman went to the local Ebola treatment centre bleeding from her gums. She was extremely sick and had a very high Ebola viral load in her blood. She had been caring for a woman in her village who had died of Ebola. After this exposure she should have been vaccinated along with all others who had been in contact with the woman. She was not vaccinated, however, because she had the bad luck of being pregnant.
The treatment centre in Forécariah preferred not to care for pregnant women with Ebola (because of all of the blood and amniotic fluid at delivery) and so this woman was transferred by ambulance to Médecins Sans Frontières in Nongo, Conakry (the capital of Guinea). On arrival her risk of death was estimated at 90% and the fetus’s risk of death was estimated at a 100%. She was treated with Favipiravir, an experimental antiviral drug that had shown limited success in previous small human studies. Access to this experimental drug was possible because of earlier negotiations with the manufacturer Toyama Chemical to allow for emergency use of Favipiravir in pregnant Ebola-positive patients. Four days after admission, the patient went into spontaneous labour and delivered a baby girl, later named Nubia. After delivery the woman’s health deteriorated and seven hours later she died of postpartum bleeding complicated by a clotting disorder that is caused by Ebola.
The newborn, who presumably would have received Favipiravir transplacentally, was treated immediately with ZMapp (manufactured by Mapp Biopharmaceutical). In total, she received four doses of ZMapp and was also treated with GS5734 (an experimental broad-spectrum antiviral drug) and white blood cells of an Ebola survivor. Nubia survived and left the Ebola treatment centre after more than a month in care. She is now a healthy one-year-old.
This case raises a number of troubling ethical issues. The pregnant woman was denied access to the VSV vaccine that might have saved her life on the grounds of hypothetical risk to the developing fetus. How can this be justified when available evidence suggested that fetuses exposed to Ebola all died?
The pregnant woman also was denied access to ZMapp because the U.S. National Institutes of Health determined that this experimental treatment would only be available to research participants in the randomized control trial they were sponsoring. The Médecins Sans Frontières doctors would not agree to a 50% chance that the pregnant woman would be randomized to receive no treatment. For this reason she was treated with Favipiravir. Yet, the fetus, once born alive, was given immediate access to ZMapp without any expectation of trial participation.
What do these policy choices tell us about the value placed on the lives of pregnant women?
When the next Ebola epidemic comes will we do the same and once more prevent pregnant women from accessing potentially life-saving vaccinations and treatments?
Note: This story does not include the mother’s name since she died and is unable to give consent. The father has given consent for the disclosure and use of Nubia’s name.
Séverine Caluwaerts, Médecins Sans Frontières and the Institute of Tropical Medicine, Antwerp, Belgium.