Making Tough Vaccine Choices Amidst The Ebola Public Health Emergency

WHO’s declaration last week calling the Ebola outbreak in the Democratic Republic of the Congo (DRC) a Public Health Emergency of International Concern has been shadowed by growing questions over vaccine strategy in a crisis that has dragged on for a year, and now threatens to spread across borders. Until now, a ring vaccination strategy focusing on health workers and direct contacts of Ebola victims has been used, but questions are growing over whether that can really snuff out the epidemic, and whether a second vaccine should also be deployed alongside the first-line Merck vaccine that has proven so highly effective. Two senior Médecins Sans Frontières (MSF/Doctors Without Borders) officials – Dr Isabelle Defourny, MSF Director of Operations, and Dr Anne-Marie Pegg, Clinical Lead for Epidemic Response and Vaccination, who is currently in DRC – unwrap these issues here.

Nurse preparing the Merck Ebola vaccine in Bikoro, DRC, in 2018. Photo: MSF/Louise Annaud

Health Policy Watch: What’s happening with the response to the Ebola epidemic in DRC?

Dr Isabelle Defourny

Dr Isabelle Defourny: The Ebola epidemic in east Democratic Republic of Congo is still not contained. More than 1,600 deaths from the Ebola virus have been reported since the outbreak was first declared on August 1, 2018, and, during the first seven months of the epidemic (August 2018 to March 2019), over 1,000 confirmed and probable cases were declared. Between March and June 2019, this number doubled, with 1,000 new cases in what’s a short period of time. The end of April was the peak, with more than 120 cases a week. There’s still a huge amount of new cases, between 75 and 100 every week. In a context like this, it’s extremely difficult to accurately track the epidemic’s chains of transmission.

During the outbreak in 2014, all that could be done was to isolate patients and administer them largely ineffective drugs. With the vaccines and experimental drugs available to us in 2019, we’re now able to offer people the chance to protect themselves individually as well as access to promising treatments.

According to the information provided after the epidemic broke out, most confirmed cases’ personal contacts were vaccinated and then monitored by the Ministry of Health’s teams. Very probably, this helped contain the epidemic for a while. It’s the first time vaccination has been implemented on such a large scale, which is an extremely positive development.

HPW: Is this approach still possible today?

ID: Let’s say it needs to be adapted and enhanced. Right now, “ring” vaccination is being used. This entails vaccinating anyone who’s been in contact with someone infected with Ebola as well as all of their contacts. The reasoning behind the method isn’t bad per se. But, implementing it is time-consuming and challenging (problems with identifying each and every person’s individual contacts) and it’s not adapted to the insecurity affecting North Kivu. In addition, the number of people vaccinated is too small to contain the spread of the epidemic. The teams also have issues transporting from Kinshasa vaccines that must be stored at a constant temperature of -60°C.

HPW: A change of strategy is therefore necessary to contain the epidemic?

ID: Absolutely. In fact, in May, the SAGE group’s experts recommended modifying the vaccination strategy in DRC so that more people can be vaccinated. Until now, the main obstacle to implementing extended vaccination has been the small stock of Merck vaccine — the only one shown to be effective in an epidemic. According to the WHO’s latest information, 600,000 Merck vaccine doses are now available.* If this is the case, there’s no longer any good reason for not immediately stepping up vaccination.

People in DRC understand the usefulness of vaccination and, in fact, are asking to be immunised. However, with just around 50 contacts of one confirmed case vaccinated, it’s likely that only one-quarter to one-third of those at risk are protected. DRC’s stock of vaccines is extremely low, usually less than 1,000 doses. With its supply only sporadic, and issues with contact tracing, we’re not yet able to say this is an emergency response strategy.

Whereas some anticipate a rapid end to the epidemic, we see no signs to back up such predictions. Quite the contrary as there’ve been alerts only recently in Uganda and near the border with south Sudan.

Other vaccines exist. They should be tested in an epidemic zone to be prepared should this one spread and to be able to dispose of a wider range of vaccines in the event of future outbreaks.

HPW: Regarding the Johnson & Johnson vaccine – I understand it hasn’t been field tested as rigorously as the Merck version, and it takes longer to confer immunity, but once it does so, it actually protects against multiple strains of Ebola and is available in 1.5 million doses. Can you just clarify then the opportunities as well as communications barriers to deploying this now that a PHEIC has been declared; and if used in a periphery zone, periphery in DRC, or border zones of neighboring countries?

Dr Anne-Marie Pegg

Dr Anne-Marie Pegg: Obviously, with over 170,000 doses now administered, there is more data available with regards to vaccine tolerance, as well as “real-world” conditions for vaccination activity. It is true that studies of a similar scale and intent have not been conducted with the Johnson & Johnson vaccine, but immunobridging data (which refers to an evaluation of human immunogenicity against a model that describes immunogenicity and survival in non-human primates) supports clinical benefit. Additionally safety studies in well over 2,000 participants support the safety of the vaccine.

As mentioned, once the full 2-dose regimen is received, it protects not only against Ebola Zaire (the strain of virus responsible for this epidemic) but also other strains of Ebola virus, as well as Marburg (another hemorrhagic-fever-causing virus).

The optimal strategy for the deployment of this vaccine remains under discussion and review. If the vaccine were to be deployed in the “periphery” of the epidemic, this could mean zones that are neighbouring those currently experiencing high transmission (particularly those where population movements are known to be frequent). It could also be used in a preventative manner for front line health workers and others who may be at high risk in neighbouring countries (where the Merck vaccine has been deployed) in order to maintain the Merck stock for reactive efforts.

HPW: Regarding the Merck vaccine – what is hindering Merck production of more doses? Is it a financial barrier or something else? Particularly since this vaccine was developed with Canadian public funds and then merely purchased by Merck, it would seem there is a public obligation to speed things up. Finally in terms of counting remaining doses, of the original 300,000 vaccine doses made available some 170,000 were already administered. Then even if the dose was halved, it would seem that only about 430,000 doses (available now) remain at that?*

AP: That would need to be clarified with Merck directly. Recently there has been a renewed scale-up of production, with additional doses said to available in the early part of 2020. However the supply chain as to how many will be available and with what delivery schedule (all at once? several thousand per month?) remains unclear.

HPW: Anything else you care to note about the complexity of the community outreach mission on the ground. Please include any other messages that you believe are important.

AP: MSF supports expanding access to vaccination, regardless of the vaccine deployed in these efforts. Effective vaccine is one real innovation that has come out of research done in previous outbreaks, and it has the potential to significantly alter the course of the epidemic. Vaccination demand is high – but the current strategy is not well adapted to the actual epidemic situation. This is not a criticism of the efforts deployed by surveillance teams – it is the reality of trying to track a huge volume of people in a complex, often insecure context with high population density and significant population movement. A strategy more adapted to this context – such as geographic targeting of hotspots – needs to be deployed quickly and efficiently to rapidly scale up the numbers of at-risk people who are able to be vaccinated.

*According to a subsequent statement by Merck to Health Policy Watch, there are currently 245 1.0mL doses available now for shipment to the DRC, yielding 490,000 vaccines at the .5 mL strength currently being used by emergency teams, while more production is planned over the coming 6-18 months.

Dr Isabelle Defourny is a specialist doctor in gynaecology-obstetric and has worked in emergency and medical projects of MSF for nearly a decade. Isabelle is Director of Operations for MSF in France, a role she held since 2015.

Dr Anne-Marie Pegg has worked with MSF for 11 years in different contexts, including armed conflicts and epidemics, as emergency coordinator and medical coordinator. She is now part of the medical department of MSF in Paris.

Image Credits: MSF/Louise Annaud.

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