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Working With Marburg in the Lab: An MRIGlobal Investigator Explains

General Global Health Surveillance Human Health

This article was originally posted on April 17, 2023 at InfectionControlToday.com.

Since the Marburg virus is deadly, what would it be like to work with it in a laboratory setting? And what can be done to protect those who work with patients with Marburg?

What is it like to come face-to-face with a killer, even a microscopic one like the Marburg virus? Gene Olinger, PhD, MBA, chief science advisor, MRIGlobal, knows, and he told Infection Control Today® (ICT®). He began writing on Ebola and Marburg, beginning in 2005, and he is one of very few scientists who’ve worked with the Marburg virus in a laboratory environment. Olinger also discussed what protocols and guidelines are necessary for anyone in the infection prevention and control field to prevent the spread of the deadly virus and protect patients and staff.

ICT: Marburg is very deadly, and it is often compared with Ebola. Why is that?
Gene Olinger, PhD, MBA: Marburg and Ebola are from the same family of filoviruses, of which six are known to infect humans, including the Sudan Ebola virus that was the cause of cases in Uganda in late 2022. Most outbreaks in humans and non-human primates have occurred in Africa. Each virus in this family has unique features that make them different. Marburg was the first virus identified from this family in 1967, while Ebola was first identified in 1976. They look very similar to long tubes (filamentous) and virions and are nearly indistinguishable even with electron micrograph imaging. All are zoonotic diseases, meaning a spillover event occurs from a natural source, likely fruit bats. Like Ebola, Marburg has similar clinical signs and symptoms of the disease that can lead to hemorrhagic fever and capillary leakage.

ICT: What protocols and guidelines do you give anyone in the infection prevention and control space to prevent the spread of the Marburg virus?
GO: Since there are limited treatment options, prevention is the primary objective. Patients must be isolated and cared for while an epidemiologist closely contacts these cases to determine if their exposure will lead to disease. This stops further transmission. Most initial cases of these diseases likely occur through contact with an infected animal, such as a fruit bat or nonhuman primate. This is the spillover event. Once symptomatic, the patients are highly infectious to those who care for them, as the virus then spreads from human to human, leading to small and large outbreaks. The virus is then found in the blood and other body fluids at high concentrations, while the virus required for infection is very low. Contaminated objects, bedding, clothes, needles, and medical instruments can infect caretakers. Semen and breast milk from survivors can also infect others even when there are no disease symptoms.

Treatment units should be equipped with essential medicines and supplies to deliver safe, optimized, supportive care, including personal protective equipment (PPE), monitoring devices, point-of-care laboratory testing, intravenous fluids, and supportive oxygen devices. Clinical experts and organized, bio-secured patient flow circuits are used to limiting disease transmission. Over time, isolation areas and treatment centers can manage suspected and confirmed patients according to WHO guidelines and standards. For established patients, access to investigational products should be provided within the locally approved expanded access protocols under the MEURI ethical framework. In contrast, the Randomized Clinical Trial (RTC) protocol can be considered for emergency use/compassionate use therapies. While potential treatments and vaccines are under development, they must be assessed under controlled clinical studies in these outbreaks.

ICT: Would you please describe what working with Marburg Virus was like in the laboratory and how you came to be able to do so?
GO: Despite my years of experience, my first contact in a maximum containment laboratory was Marburg, which was disconcerting. I was working on sucrose-purified stock with my mentor/trainer, making assays for detecting infection. A single virus can cause a lethal infection, and we were working with one of a dozen tubes with more than 10 billion viruses in each tube. That is a moment you realize the mystery and complexity of nature at the microscopic level.

In a high-technology laboratory designed for this work, many protections are placed between the scientist and the virus, such as an encapsulating suit and gloves. However, when working in the field during an outbreak, these rules change, creating another level of respect and practices needed for protection. Fortunately, I had many years of working and growing HIV from patient samples, which gave me the experience to respect and reduce the risk of working with a lethal virus. While some feel that HIV is not as scary as the dangerous and exotic viruses studied in BSL4/P4 laboratory, the reality is that the virus is nearly 100 percent lethal; it just takes a long time. When I worked with the HIV virus, there were few treatments, and death was common from infection. That work and learning from a scientist with more than 30 years of experience working in a BSL4 set the basis for working with Marburg, Ebola, and other exotic viruses.

ICT: Would you please explain what Athena is?
GO: During the initial response to the 2014 Ebola outbreaks in Guinea and Sierra Leone, the medical staff there depended on local laboratories not near the remote outbreak epicenters, so the turn-around to run tests was more than 24 hours. As you can imagine, a patient who is symptomatic and ill enough to visit for testing needs a prompt diagnosis and immediate care.

To help speed up the response, we were asked to design, fabricate, equip, deploy, and operate containerized mobile diagnostic laboratories to each of those countries deployed in 2015. These laboratories were designed to meet customer requirements and provide diagnostic capabilities in areas without robust public health systems. For this response, our on-site engineering proved necessary for on-site setup and operation. Our staffing of these mobile diagnostic laboratories then helped support prompt and accurate testing of up to 110 samples per day, reducing sample turn-around times to less than four hours.

Upon our return from the field, this platform served as the basis for the development of the Athena Mobile Laboratory, a ground-up redesign of the mobile lab system concept. This new container provides a greatly enhanced mobile laboratory workspace capable of rapid worldwide deployment. The custom-built platform eliminates the limitations of modifying a shipping container into a lab. This allows for an enhanced structural design and better insulation to provide a more ergonomic workspace better protected from harsh environmental conditions.

Should they be needed in response to this or other outbreaks, we have Athena Mobile Laboratories ready for deployment. They can be quickly equipped and deployed to meet the needs on the ground and even staffed by our team, supporting the field-forward response.

ICT: What vaccines or medications do you know about to curb Marburg’s spread and treat it when it does spread?
GO: There are a variety of vaccines and therapies under development that could be used for compassionate use in these outbreaks. They are similar to those developed for Ebola but are specific for Marburg. These include vaccines that can be used to prevent disease, even in close contact, antibody treatments, and small molecules (drugs) that could lower the infections’ overall lethality.

Care for survivors is also critical. Many people have long-term clinical sequela after infection, not unlike long COVID patients. Hearing loss, cognitive function impacts, and fatigue are not uncommon. Care for men may be key to protecting others from a transient virus that appears in semen over time after infection. Patients and their families suffer social, economic, and psychological issues following the infection. In large outbreaks, numerous orphans have suffered the loss of their parents.

CBC News offered insight into this in a broadcast from a few years ago (https://www.youtube.com/watch?v=QcRQM7PF4V0).

ICT: Do you have anything else you would like to add?
GO: Nature is full of good and bad, and zoonotic diseases like Marburg are part of our world. We must better understand the factors that lead to these spillover events and find ways to prevent these infections from impacting us and our planet. Unfortunately, these diseases are often neglected, and research is not funded as well as other human and animal diseases. We have so much to learn, and in doing so, we can prevent the mortality of these diseases, the morbidity (short- and long-term impacts), and socio-economic impacts. We need creative ideas that prevent these diseases from emerging, and some solutions are not medical.

This article has been edited for clarity.