These are only two small foci so far, but they are being closely scrutinized. In both Equatorial Guinea and Tanzania, 9 and 8 cases of Marburg virus fever (MARV) have been officially declared since February and are under constant surveillance by national health authorities and the Organization World Health Organization (WHO). In addition to the destructive power of a hemorrhagic fever virus, a cousin of Ebola, the emergence of potential epidemic outbreaks constitutes a first test in real conditions for the development of a response almost in real time.
It is based on the lessons learned from the Ebola fever epidemic (2013-2016) and the Covid-19 pandemic, which the WHO launched, as soon as the Marburg epidemic passed in August 2022 in Ghana the MARVAC consortium . Created in September and managed by the R program
Because research on the disease, although started as soon as it was discovered in 1967, has not yet led to the approval of a serum or even a specific curative treatment. Currently, 28 vaccine candidates are in the pipeline, MARVAC members state in a recent publication in the journal PLOS Pathogens, exploiting all "possible approaches: multi-dose, single-dose, rapid-acting, live attenuated, non-replicating and replicating viral vector”. But none of these products are in the industrial development stage and only a few candidates have successfully passed stage 1 trials testing their safety. The WHO clarified during its press briefing on March 29 that MARVAC made doses available to governments on the continent for clinical field evaluations.
“Equatorial Guinea and Tanzania, WHO explained to World Africa, are currently considering introducing these research phases into their response and we are preparing to support national authorities to facilitate the process if necessary. »
The UN agency, which knows that the subject of vaccination and clinical trials is sensitive on the continent, particularly after the Covid pandemic where real distrust was expressed, made a point of specifying that these activities "are part of a collaborative approach that puts ministries of health and national researchers at the heart of all research efforts”. Its boss, Tedros Adhanom Ghebreyesus, even made a point of recalling at the end of March that "no country will cede its sovereignty to the WHO", denouncing the numerous "fake news circulating on social networks, but also in traditional media" at the subject of the agreement being drawn up to improve the response capacity of States to future epidemics.
"We must understand that epidemic outbreaks are unique opportunities to advance research on vaccines and treatments that target these hemorrhagic fevers, explains Sylvain Baize, head of the Biology of Emerging Viral Infections Unit, specialist in Lassa hemorrhagic fever. It was, for example, thanks to the Ebola virus disease epidemic that struck West Africa that the VSV-Ebola vaccine was approved in 2015. The first publications on this vaccine dated from 2005 and, in 2014 , there had only been a few phase 1 clinical trials.”
However, to carry out phase 3 clinical trials, which evaluate the efficacy of vaccines essential for their approval before marketing, it is necessary to recruit volunteer patients infected with the targeted virus. “We are currently working on a vaccine against Lassa fever, illustrates Sylvain Baize, whose phase 1 results which have just been published are promising. For a phase 3 trial outside of an epidemic outbreak that results in statistically significant data, you need to recruit 30,000 to 40,000 people. »
Defiance on the continent
In the absence of a major epidemic, a clinical trial of this size would therefore be very long, very expensive and even "infeasible", insists Mr. Blaize. However, hemorrhagic fevers are not priorities for manufacturers. "It's a real problem when it comes to scaling up to industrial production," he says, welcoming the interest of consortia such as MARVAC. “Lassa fever is also the focus of accelerated vaccine development efforts with support from the Coalition for Epidemic Preparedness and Innovations (CEPI). It is also something we owe to the Ebola experience. Offering standardized evaluation protocols makes it possible to effectively compare the products in development and it is really the opinions of independent experts that guide the choice of the product or products whose development is supported as a priority. »
The WHO said on Wednesday it "looks forward to working with the governments of the two countries affected" by the Marburg virus "to start these trials" if the conditions are met. It is indeed not certain that clinical studies can be carried out in the coming days while the two emerging outbreaks seem to be circumscribed.
But the efforts made within MARVAC since mid-February are not in vain. They will allow the actors involved to be very reactive if outbreaks should occur in the weeks to come. Especially since MARV can reach an 88% mortality rate and lead to death in less than ten days. In a recent document, the consortium therefore displayed an ambitious objective: to be able to launch an evaluation protocol within fifteen days after the official declaration of the start of an epidemic.