On July 23, an outbreak report in The Lancet Infectious Diseases documented the case of a female Ebola survivor who transmitted the virus to family members more than a year later. This is the first known instance of a female survivor with persistent capacity to transmit the virus long after infection (it was already known that the virus can persist in semen for up to two years and be sexually transmitted).
But perhaps the most notable aspect of this case is that the woman was pregnant—at the time of suspected primary infection and again just before the recurrence of disease when she passed the virus onto family members.
This raises new questions about how pregnancy may impact the presentation of Ebola virus disease (EVD), not just for women in the near term but across multiple pregnancies, and potentially as the source of new outbreaks.
This case also underscores the need to be more attentive to and inclusive of the interests of pregnant women in our approaches to surveillance and preparedness, research of new biomedical interventions, and the public health response to outbreaks. This includes:
Capturing indicators relevant to pregnancy status and maternal, obstetric, neonatal, and child outcomes in infectious disease surveillance
Developing interventions that are safe and effective for use in pregnancy—with appropriate studies to evaluate interventions in pregnant women
Ensuring pregnant women are not inappropriately denied access to beneficial interventions like vaccines and drugs during epidemic responses
Pregnancy and Ebola: What We Know and What We Need to Know
As dire as Ebola infection is among the general population, it can be especially grim for pregnant women. Although there is limited data on EVD in pregnancy, case fatality rates among pregnant women in previous epidemics have been as high as 89-91 percent. Moreover, Ebola infection in pregnancy is associated with 100 percent miscarriage, stillbirth, or neonatal death. To make matters worse, given the fear associated with Ebola transmission via bodily fluids, pregnant women struggle during epidemics to find care providers who will attend their births or assist them with complications of miscarriage—further compounding maternal mortality. Articles in The Lancet and Scientific American have highlighted the many ways that Ebola can disproportionately impact pregnant women.
This new case in Liberia sets off alarm bells for how pregnancy and the immune system changes it induces can further jeopardize the health of pregnant women and their families well beyond the period of initial infection. The researchers hypothesize that re-emergence of clinical EVD was due to unique pregnancy-associated changes in the immune system that can exacerbate disease in the post-partum period—effectively causing latent infections to re-manifest as more severe and transmissible disease.
While this is just one case, it underscores the need to collect better data to understand the pathophysiology of EVD in pregnancy, with potentially serious implications for how to protect female Ebola survivors and their contacts across future pregnancies and prevent future outbreaks. As countries and partners continue to invest in strengthening infectious disease surveillance systems, it is critical that relevant indicators of maternal, obstetric, and newborn outcomes are captured. Further, these surveillance systems need to be integrated and effectively communicate with routine health information systems that track various pregnancy-related outcomes to detect new signals and ultimately better inform scientific and public health responses to emerging pathogenic threats like Ebola.
Ebola Drugs and Vaccines in Pregnancy: Missed Opportunities and Compounded Inequities
It may be surprising to some that despite the serious risk of exposure among pregnant women and the dire consequences of Ebola infection, pregnant women were categorically excluded from all drug and vaccine trials that took place during the 2013-2016 epidemic in Liberia, Guinea, and Sierra Leone. Even after initial findings of benefit from the rVSV-ZEBOV vaccine ring trial led to expanded eligibility for children, pregnant women were still denied opportunities to participate. An account of how events unfolded surrounding these trials, including the unheeded recommendations from expert panels and ethics committees to include pregnant women, is provided in the appropriately titled article, “Protected to death: systematic exclusion of pregnant women from Ebola virus disease trials.”
This exclusion represents a deep injustice on two accounts:
First, individual pregnant women facing the imminent risk of EVD were unfairly denied opportunities to receive experimental interventions that could have saved their lives.
Second, the global health and research community missed a critical opportunity to generate evidence on the safety and efficacy of Ebola vaccines and treatments in pregnancy to inform their use in future epidemics.
Studies with pregnant women are needed because pregnancy alters the immune system, metabolism, cardiac output, and a variety of physiological mechanisms, so we cannot assume that drugs and vaccines given in pregnancy will work the same or require the same dosing as in non-pregnant adults. Moreover, the lack of rigorous studies in pregnant women can lead to limited and delayed adoption of safe and effective interventions by policymakers, providers, and women themselves. This has been a recurring story for various interventions in pregnancy, including delayed uptake of vaccines and non-ideal coverage of maternal immunizations due to low vaccine confidence in pregnancy.
Now there may be even greater support for developing interventions like vaccines that pregnant women can safely use. If it turns out to be true that pregnancy can trigger new outbreaks by re-manifesting disease among post-partum female survivors, vaccines could not only protect pregnant women and their unborn children from initial Ebola exposures, but might avert future outbreaks altogether.
Toward a Better Response for Ebola and Other Epidemic Threats in Pregnancy
These new findings further highlight the ways in which infectious disease outbreaks can severely—and at times uniquely—affect the health interests of pregnant women and their offspring. It is clear that more work is needed to proactively consider the interests of pregnant women and their offspring in efforts to combat epidemic threats.
Because research with pregnant women and the use of interventions with limited evidence in pregnancy can be ethically, scientifically, and legally complex, guidance is sorely needed on the conditions under which it is ethically acceptable, if not morally required, to offer investigational drugs and vaccines to pregnant women that might protect them and their offspring from the ravages of emerging infectious diseases.
For the last two years, I’ve been working on the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Project—a project funded by the Wellcome Trust—to develop consensus-driven, policy-relevant guidance to tackle these challenges in the case of epidemic vaccines. The guidance, coauthored by 17 experts in bioethics, maternal immunization, maternal-fetal medicine, philosophy, public health, and vaccine research and policy, will be released in September 2018. It puts forth 22 concrete recommendations to provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens.
As the pace of research and development accelerates and investments are being made to develop vaccines and therapies for a range of dangerous pathogens—many of which have severe presentations in pregnancy—there is an opportunity, now, to forge a path for more inclusive preparedness, R&D, and response that will ensure pregnant women and their offspring fairly benefit from investments and scientific advancements in the fight against emerging infectious diseases.
Carleigh Krubiner is a Global Health Policy Fellow at CGD and serves as the PREVENT Project Director and a Co-Principle Investigator. The PREVENT Project is supported by a multi-year grant from the Wellcome Trust (203160/Z/16/Z). It is led by researchers at the Johns Hopkins Berman Institute of Bioethics and Bloomberg School of Public Health, the Kennedy Institute of Ethics at Georgetown University, and the UNC Center for Bioethics. For more information, contact Carleigh Krubiner, visit vax.pregnancyethics.org, and follow the project on Twitter @pregnancyethics.