The Outbreak Observatory post on May 18 addressed the ongoing Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) that began in late April. After initial concern that the outbreak was growing rapidly, reports late last week suggested that the outbreak was considerably smaller than previously feared. In fact, as of May 31, the WHO reported no new confirmed, probable, or suspect cases of EVD—the last confirmed case was May 11—leaving the current case counts at 2 confirmed, 3 probable, and 12 suspect—including 4 deaths. The remaining 72 contacts are expected to complete their monitoring period on June 2.
On May 29, regulatory and ethics officials in DRC approved a ring vaccination protocol that paves the way for the use of the rVSV-ZEBOV (Merck) vaccine in response to the ongoing outbreak. The vaccination protocol is aimed at healthcare workers and contacts of confirmed cases (ie, those at the highest risk of exposure). The vaccine received considerable attention after a small clinical trial, conducted in Guinea and Sierra Leone as the West Africa epidemic waned, indicated that the vaccine was highly effective against the Zaire strain of Ebolavirus. With limited existing data available on which to evaluate the vaccine, conducting a clinical trial in the DRC and in future Ebola outbreaks could be critical to determining the vaccine’s efficacy and safety profile. Having taken the time and effort to develop a trial protocol and vet it through both regulatory and ethics boards, DRC positioned itself to swiftly implement the protocol should it become warranted.
On the surface, it seems like electing to use a vaccine in response to an Ebola outbreak should be an easy decision, especially in light of the devastation resulting from the West Africa epidemic. While even limited data from such a trial could be beneficial to evaluating the rVSV-ZEBOV—particularly because Ebola outbreaks are fairly rare and typically result in only a handful of cases—conducting the trial poses considerable challenges, both financial and logistical. First, the vaccine must be stored at -80°C (-112°F), which requires specialized equipment to maintain the temperature in the absence of a reliable source of electricity. Second, the outbreak is taking place in a remote part of DRC, which is not easily accessible. In fact, there are no paved roads in the affected area, and responders are currently being transported by small boats, motorcycles, helicopters. While a stockpile of the vaccine does exist, thanks to a US$5 million agreement between Gavi and Merck, implementing a clinical trial would likely require considerable financial resources in addition to the cost of the vaccine itself. At a minimum, a vaccine trial would require transportation for the vaccines and personnel to DRC and to the site of the outbreak, portable freezers to maintain cold chain integrity, personnel to implement the trial and train local responders to administer the vaccine, and equipment to collect, store, and analyze the required specimens. Additionally, 76% of official models forecast no additional cases in the next month. If existing interventions—including contact tracing, infection control and hygiene, safe burial practices, and community education—would prevent further transmission on their own, this could significantly skew data from the clinical trial and/or subject trial participants to potential adverse effects from the vaccine without providing any real health benefit, which poses severe ethical issues.
While the clinical trial protocol has been approved—and despite the recommendations of the its Strategic Advisory Group of Experts (SAGE) on Immunization—the WHO is not currently advising deployment of the vaccine. They are, however, coordinating with DRC and MSF to develop plans for immediate deployment should a confirmed EVD case be identified outside the known transmission chains. Despite some initial calls, including by world-renowned experts, to immediately deploy the vaccine stockpile, DRC and WHO are making the difficult decision to rely on proven public health interventions while also developing an effective and ethical trial protocol. In an ideal world, we could immediately deploy a proven vaccine; however, under the existing limitations, WHO and DRC are aiming to make the best use of limited available resources while preparing themselves to respond rapidly in the event that the outbreak worsens.