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Ebola and Marburg virus disease – how long can these deadly viruses remain neglected?

Recent cases highlight the need to do more to strengthen early warning and detection systems and advance the development of a Marburg vaccine.

This past week the WHO released a report on a case of Ebola in the North Kivu region of the Democratic Republic of Congo. The patient was a 46-year-old woman who presented at a hospital in July and died 23 days later. Postmortem samples were positive for Ebola virus. Several exposures had occurred in the hospital and the community. Many hospital workers had been vaccinated but the vaccination status of other exposed individuals is being determined. Prior to this case, the Equateur province in DRC has been dealing with Ebola cases and had declared on 22 July 2022 that the latest outbreak was over. This was the third Ebola outbreak in four years.

Ebola virus outbreaks have gripped the human imagination. A deadly hemorrhagic disease that is well suited to be the protagonist in a blockbuster Hollywood movie. Despite its morbid movie star quality, the disease remains hidden from our consciousness until massive epidemics occur. What would it take to do more to prevent these outbreaks?

Ebola virus is a filovirus. Filoviruses consist of three major families: Ebola virus, Marburg virus and Cuevavirus (a rare virus only detected in bats in Spain). The Ebola virus consists of six different sub viruses. The four that are known to cause human disease are indigenous to Africa. Ebola virus was first identified in 1976 when two outbreaks occurred in the Zaire (now DRC) and Sudan. It initially known as Ebola hemorrhagic fever as many of the early cases had major hemorrhage as a clinical feature. Observations from the 2014 West Africa outbreak suggest that hemorrhage is not a universal feature but often occurs in the late stages of illness and pregnancy. An infected individual will often present with a viral syndrome that may include fever, headache, fatigue, malaise, nausea, vomiting and diarrhea. In the early stages, it can resemble clinical conditions such as malaria or typhoid that are very common in regions that experience Ebola outbreaks. This clinical mimicry of common diseases often leads to late diagnoses resulting in exposure of many healthcare workers and community members prior to recognition of an outbreak. Case fatality rates may be very high ranging from 40% to 90%. Among those that survive the acute infection, virus has been detected in some individuals for several months to years after the initial diagnosis. EVD in survivors can also lead to prolonged symptoms that include weakness, fatigue, muscle pain, joint pain, uveitis, hearing loss, ringing in the ears, symptoms of depression and anxiety.

In 2019 Merck advanced the development and approval of an Ebola vaccine ERBEVO. The vaccine’s initial R&D was driven by the Canadian National Microbiology Laboratory. Other manufacturers such as J&J and GSK also developed vaccines on other platforms. Small molecule antivirals as well as monoclonal antibodies were developed. Vaccines and ring vaccination strategies have played a critical role in controlling some of the recent outbreaks.

The DRC has been dealing with Ebola virus since its initial discovery in the 1970s. Case counts would typically rise and fall with scores of affected patients, and minimal spread beyond a local region. The disease was largely overlooked until 2014. In 2014 the Zaire sub species of Ebola virus appeared in West Africa and led to a massive outbreak with over 28,000 cases and over 11,000 deaths. I remember the 2014 outbreak very well. At that time, I split my time between a hospital in Africa and one in the US. I remember attending meetings with our local World Health Organization (WHO) Afro representative on setting up Ebola screening, treatment centers in our setting. I also vividly remember returning to the US and undergoing hospital required training for Ebola preparedness. I was struck by the institutional anxiety and my personal levels of protection in the donning and doffing PPE in a well resource setting versus putting on garden gumboots and a jumpsuits in an African setting. It was also evident to me that wealthy resilient healthcare systems could better withstand the shocks that an epidemic of this nature would provide. I knew that the fragile system that I worked in in Africa would fumble if presented with a handful of cases. It was evident then, as it is now, that true pandemic preparedness needs a robust health systems infrastructure as its foundation. Without this pandemic preparedness does not exist.

Earlier this summer we were alerted to two cases of Marburg virus among farmers in two different locations within the Ashante region of Ghana. Both of them died. This is a region that had not previously experienced cases of Marburg. Marburg and Ebola belong to the same family and Marburg virus has been isolated from bats in many countries in Africa. A simple push into the wrong environment can lead to a cross species transmission.

The reservoir for Marburg virus is the African fruit bat. The bat does not show signs of carrying the virus and can travel over 90 kilometers for a nightly feed. The bat is widespread in Africa. Cases of Marburg have been reported in Uganda, South Africa, Zimbabwe, DRC, Congo, Kenya, Angola, Ghana. A large outbreak of Marburg occurred in Angola in 2004/2005 with a virulent strain with increased lethality. The case fatality was around 90%, with 227 deaths among 252 cases. Unfortunately, such a devastating infection was not sufficient to attract sufficient investments for vaccine development and there are currently no licensed vaccines for Marburg.

These outbreaks may herald what is to follow. It may be a matter of time before another outbreak of high mortality or a new ecological niche for the reservoirs of both Ebola and Marburg is found (unfortunately the animal reservoir for Ebola remains unknown). Although vaccines are truly lifesaving, strengthening health systems is a critical component of pandemic preparedness. Communicable diseases whether in pandemic or endemic form reflect the health of both the individual and their community. Health systems strengthening is a critical component of pandemic preparedness. Weak health systems in resource limited settings are unable to detect and adequately respond to and contain local outbreaks.

It’s often hard to care about disease such as Ebola, Marburg, Nipah because the people that have them typically are out of sight and do not travel on planes. But this is not always the case. In the last Ebola outbreak we saw the virus spreading from rural communities into urban areas and beyond leading to thousands of cases and international spread. So although we are often isolated from the problems of the poor those problems are actually just a few hours away and can easily show up in a Dallas suburb as they do in a neighboring country. Strengthening health systems for the poor is a critical component of pandemic preparedness. Governments in low and middle income countries with fragile healthcare systems need to invest more in systems strengthening. Global partners should support models that are sustainable, with holistic approaches that respect local knowledge and health beliefs while focusing on education and prevention to minimize the need for expensive curative services.

Despite the challenges associated with developing a vaccine for a disease whose pattern is not predictable and where the market may not be consistent, the cost of inaction may be too high. Incentivizing the pharmaceutical development of promising Marburg vaccines candidates should be a key priority.

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Wise advice. Thanks for this history lesson. May the world take note.

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