Point/Counter

Should pregnant women receive an Ebola vaccine despite WHO recommendations?

POINTCOUNTER

POINT 

Inclusion of pregnant women in live vaccine trials is an ethical imperative.

The nearly universal fetal, neonatal and maternal mortality associated with Ebola infections in pregnancy necessitates development of a strategy to improve perinatal outcomes. Immunization of pregnant women with live-attenuated vaccines usually is contraindicated because of theoretical concerns of fetal damage via transplacental acquisition of the virus. Although there has been a pervasive presumption of exclusion of pregnant women in live vaccine trials and clinical initiatives, inclusion of these women is an ethical imperative in the setting of this devastating disease.

W. Christopher Golden

Data on pregnant women receiving the live-attenuated rubella vaccine (including those with inadvertent immunization) have demonstrated no adverse outcomes (ie, congenital rubella syndrome). Furthermore, the deaths of Ebola-infected pregnant women and their newborns during the 2014 Sierra Leone epidemic and the reported safety and immunogenicity of attenuated Ebola vaccines currently in clinical trials suggest that the risk of vaccination to the mother and fetus will be significantly less than natural infection.

Jeanne S. Sheffield

In Ebola-endemic regions, immunization should be offered (with informed consent) to pregnant women to reduce perinatal mortality, coordinated with prospective monitoring of maternal and neonatal outcomes. This strategy is in concert with the long-standing tenet, “Do not penalize a woman for being pregnant.” Additionally, future clinical trials of immunotherapy against Ebola designed to delineate further potential benefits should include pregnant women and women of childbearing age. Respectful engagement and collaboration between international organizations (such as WHO), clinical researchers and governmental leaders will facilitate improved outcomes in these vulnerable populations.

References:

Badilla X, et al. Pediatr Infect Dis J. 2007;doi:10.1097/INF.0b13e318124a9f4.

Bar-Oz B, et al. Am J Med Genet A. 2004;doi:10.1002/ajmg.a.30225.

Lévy Y, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)31710-0.

Lyman M, et al. Int J Gynaecol Obstet. 2018;doi:10.1002/ijgo.12490.

W. Christopher Golden, MD, is a neonatologist, medical director of the newborn nursery at Johns Hopkins Hospital, and assistant professor of pediatrics at Johns Hopkins University School of Medicine. Jeanne S. Sheffield, MD, is director of the division of maternal-fetal medicine at Johns Hopkins Hospital and professor of gynecology and obstetrics at Johns Hopkins University School of Medicine. Disclosures: Golden and Sheffield report no relevant financial disclosures.

COUNTER 

An unlicensed Ebola vaccine could be given to pregnant women now only if both DRC and WHO agree.

There is a clear and collaborative answer to this question. Realistically, the way forward should first involve stakeholders in the DRC who are fighting this Ebola epidemic. It is their country. For the benefit of patients now and in the future — pregnant and nonpregnant — no unlicensed Ebola vaccine should be given “despite WHO recommendations.” To do so would jeopardize the collaborative efforts between the DRC and WHO in gaining the trust of the patients, their contacts and their communities. This trust is essential to stop Ebola epidemics.

Instead, the DRC and WHO should agree to convene an international meeting as soon as possible this October to address all aspects of this issue, including ethical, medical, risk communication, regulatory, and more. All safety data should be shared regarding pregnant women who received this vaccine in West Africa and among the 13,000 vaccines in the DRC so far in 2018.

Daniel R. Lucey

Truly informed consent must be obtained, and comprehensive monitoring for safety and efficacy must be carried out, if the decision is made to offer this unlicensed vaccine to pregnant women. Such a timely meeting would follow the recent example of the meeting on Aug. 27, 2018, convened by the DRC and WHO to update advice on five investigational Ebola treatments (posted on the WHO website Sept. 7).

My perspective is influenced by having provided care for many patients with Ebola virus disease in 2014 in West Africa. At a Médecins Sans Frontières Ebola Treatment Unit, two of our patients were pregnant. Our best efforts failed to help them survive. During the 2016 yellow fever epidemic in the DRC, I met with Congolese colleagues who are now fighting Ebola for the third time since 2017.

Daniel R. Lucey, MD, MPH, is a senior scholar with the O’Neill Institute for National and Global Health Law, an adjunct professor of medicine and infectious diseases at Georgetown University Medical Center, and a research associate in anthropology at the Smithsonian National Museum of Natural History. Disclosure: Lucey reports no relevant financial disclosures.

POINTCOUNTER

POINT 

Inclusion of pregnant women in live vaccine trials is an ethical imperative.

The nearly universal fetal, neonatal and maternal mortality associated with Ebola infections in pregnancy necessitates development of a strategy to improve perinatal outcomes. Immunization of pregnant women with live-attenuated vaccines usually is contraindicated because of theoretical concerns of fetal damage via transplacental acquisition of the virus. Although there has been a pervasive presumption of exclusion of pregnant women in live vaccine trials and clinical initiatives, inclusion of these women is an ethical imperative in the setting of this devastating disease.

W. Christopher Golden

Data on pregnant women receiving the live-attenuated rubella vaccine (including those with inadvertent immunization) have demonstrated no adverse outcomes (ie, congenital rubella syndrome). Furthermore, the deaths of Ebola-infected pregnant women and their newborns during the 2014 Sierra Leone epidemic and the reported safety and immunogenicity of attenuated Ebola vaccines currently in clinical trials suggest that the risk of vaccination to the mother and fetus will be significantly less than natural infection.

Jeanne S. Sheffield

In Ebola-endemic regions, immunization should be offered (with informed consent) to pregnant women to reduce perinatal mortality, coordinated with prospective monitoring of maternal and neonatal outcomes. This strategy is in concert with the long-standing tenet, “Do not penalize a woman for being pregnant.” Additionally, future clinical trials of immunotherapy against Ebola designed to delineate further potential benefits should include pregnant women and women of childbearing age. Respectful engagement and collaboration between international organizations (such as WHO), clinical researchers and governmental leaders will facilitate improved outcomes in these vulnerable populations.

References:

Badilla X, et al. Pediatr Infect Dis J. 2007;doi:10.1097/INF.0b13e318124a9f4.

Bar-Oz B, et al. Am J Med Genet A. 2004;doi:10.1002/ajmg.a.30225.

Lévy Y, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)31710-0.

Lyman M, et al. Int J Gynaecol Obstet. 2018;doi:10.1002/ijgo.12490.

W. Christopher Golden, MD, is a neonatologist, medical director of the newborn nursery at Johns Hopkins Hospital, and assistant professor of pediatrics at Johns Hopkins University School of Medicine. Jeanne S. Sheffield, MD, is director of the division of maternal-fetal medicine at Johns Hopkins Hospital and professor of gynecology and obstetrics at Johns Hopkins University School of Medicine. Disclosures: Golden and Sheffield report no relevant financial disclosures.

COUNTER 

An unlicensed Ebola vaccine could be given to pregnant women now only if both DRC and WHO agree.

There is a clear and collaborative answer to this question. Realistically, the way forward should first involve stakeholders in the DRC who are fighting this Ebola epidemic. It is their country. For the benefit of patients now and in the future — pregnant and nonpregnant — no unlicensed Ebola vaccine should be given “despite WHO recommendations.” To do so would jeopardize the collaborative efforts between the DRC and WHO in gaining the trust of the patients, their contacts and their communities. This trust is essential to stop Ebola epidemics.

Instead, the DRC and WHO should agree to convene an international meeting as soon as possible this October to address all aspects of this issue, including ethical, medical, risk communication, regulatory, and more. All safety data should be shared regarding pregnant women who received this vaccine in West Africa and among the 13,000 vaccines in the DRC so far in 2018.

Daniel R. Lucey

Truly informed consent must be obtained, and comprehensive monitoring for safety and efficacy must be carried out, if the decision is made to offer this unlicensed vaccine to pregnant women. Such a timely meeting would follow the recent example of the meeting on Aug. 27, 2018, convened by the DRC and WHO to update advice on five investigational Ebola treatments (posted on the WHO website Sept. 7).

My perspective is influenced by having provided care for many patients with Ebola virus disease in 2014 in West Africa. At a Médecins Sans Frontières Ebola Treatment Unit, two of our patients were pregnant. Our best efforts failed to help them survive. During the 2016 yellow fever epidemic in the DRC, I met with Congolese colleagues who are now fighting Ebola for the third time since 2017.

Daniel R. Lucey, MD, MPH, is a senior scholar with the O’Neill Institute for National and Global Health Law, an adjunct professor of medicine and infectious diseases at Georgetown University Medical Center, and a research associate in anthropology at the Smithsonian National Museum of Natural History. Disclosure: Lucey reports no relevant financial disclosures.