As health officials work to contain the continuing outbreak of Ebola in the Democratic Republic of Congo, lessons from that crisis can be applied to more equitably battle Lassa fever, another deadly infectious disease.
As 2019 begins, the Ebola outbreak in the DRC is a public health dilemma of tragic proportions. This outbreak, the second largest in history, disproportionally affects women of childbearing potential. Unfortunately, the only available Ebola vaccine has characteristics that make it problematic for use in women who are pregnant. Although they are at high risk of becoming infected and dying, clear recommendations to support giving the vaccine to pregnant women have not been forthcoming.
As a consequence, pregnant women are not being given the chance to decide for themselves whether they want to be vaccinated, despite calls — some from pregnant women living in outbreak zones — to make the vaccine available to them. Pregnant women and their babies remain unprotected, leaving them at continued risk.
The global health community must learn from this experience as we confront Lassa fever, another re-emerging infection that, like Ebola, causes severe disease and death during pregnancy. This year marks the 50th anniversary of the discovery of the Lassa fever virus. On January 16, the first international conference on Lassa fever will be held in Nigeria, where the virus was discovered. The disease is endemic in West Africa, with hundreds of thousands of cases and several thousand deaths each year. In an ongoing outbreak in Nigeria, more than 600 people have been infected; one-quarter of them have died.
During the conference, experts will discuss how best to protect populations against Lassa fever. Vaccine development will be on the table. This meeting represents a perfect moment for the equity interests of pregnant women and their babies to figure prominently, a perfect moment to set in motion the steps necessary to ensure that what is happening now with Ebola does not happen in the future with Lassa fever.
Lassa fever is on the World Health Organization’s R&D Blueprint of priority diseases and the Coalition for Epidemic Preparedness and Innovation (CEPI) has invested in the development of several candidate vaccines against Lassa fever, some of which will enter clinical trials this year.
Lassa fever is particularly severe late in pregnancy, with maternal deaths and/or fetal losses reported in up to 80 percent of women who become infected during their third trimester. For this reason, the WHO’s Target Product Profile for a Lassa virus vaccine specifically lists suitability for use in pregnancy as a preferred characteristic. As vaccine candidates are considered and clinical development plans created, now is the time to think specifically and strategically about how to best address the needs of women who are pregnant or lactating and their infants.
The Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group, of which we are members, has created a road map for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in epidemic preparedness and in the development and deployment of vaccines against emerging pathogens. Several PREVENT recommendations are particularly relevant to Lassa fever, as targeted studies are being conducted to improve understanding of the epidemiology of Lassa virus infection and preclinical and early-stage clinical vaccine research are begun:
- Pregnancy status should be routinely included in Lassa case investigation forms and reports so the burden of this disease in pregnancy can be more precisely estimated.
- Vaccines suitable for use in pregnancy should be among those included in the development portfolio. It may be that novel vaccine platforms — replication-deficient vectors, nucleic acid vaccines, and the like — will need to be considered along with the subunit vaccines that have been traditionally recommended for use in pregnancy.
- Necessary non-clinical studies, such as non-human reproductive toxicology studies, should be completed early in clinical development so pregnant women are able to participate in vaccine trials when promising vaccine candidates have been identified and the likely benefits of participating outweigh the risks.
- Whenever vaccine trials include women of childbearing potential, some participants will unknowingly be pregnant at the time of vaccination or become pregnant soon thereafter. With that in mind, research protocols should be designed to systematically collect data on pregnancy-specific safety indicators from these vaccine exposures.
As plans are being made now to advance the important work necessary to combat Lassa fever, it is essential that the interests of women who are pregnant or lactating and their infants are addressed from the very outset. CEPI has paved the way, not only by prioritizing Lassa fever vaccine development but by underscoring the importance of conducting research specific to pregnancy and considering how best to move PREVENT recommendations forward.
Developing a Lassa fever vaccine that can be offered to pregnant women will be an important double win for global health. It will not only help ensure that pregnant women and their infants are protected against a deadly disease, but will also provide a model for future development of vaccines for use in epidemics.
Ruth A. Karron is director of the Center for Immunization Research and director of the Johns Hopkins Vaccine Initiative. Carleigh Krubiner is a policy fellow at the Center for Global Development. Ruth R. Faden is the founder of the Johns Hopkins Berman Institute of Bioethics.