Marburg Outbreak In Rwanda – What You Should Know And U.S Actions

The Republic of Rwanda’s Ministry of Health has reported cases of Marburg Virus Disease (MVD), in seven districts around the country and declared an outbreak. As of October 6, 2024, Rwanda has reported 49 cases and 12 deaths from MVD.

In response to this development, the United States is taking a whole of government approach, working in partnership with the government of Rwanda, WHO, Africa CDC, and other international partners to support the response to the MVD outbreak.

Building on decades of partnership with the Government of Rwanda, and in accordance with commitments made under the International Health Regulations (IHR), the U.S. government has helped support the implementation of the IHR, by building and strengthening the country’s capacities to prevent, detect, and respond to a wide range of health threats, including HIV/AIDS, malaria, mpox, and rapidly sharing information necessary to prevent international public health emergencies.

The United State’s government support focuses on workforce development training, improving surveillance networks at the community and national level, development of national and provincial emergency operation centers and emergency management trainings, and strengthening supply chains for access to health commodities.

HHS Supporting Action Steps:

On-the Ground Support

• CDC’s Rwanda country office, which has been in place since 2002, immediately coordinated with Government of Rwanda counterparts and partners, including WHO and Africa CDC, to initiate the response and identify needs for public health assistance.
• Within days of learning of the MVD outbreak, CDC deployed three senior scientists to begin supporting Government of Rwanda in its response. The staff members include: a leading expert in viral hemorrhagic fever research and response, an expert in coordinating responses during viral hemorrhagic fever outbreaks, and an expert in infection prevention and control. Together, they have extensive experience in managing outbreak responses and building laboratory networks for testing, surveillance, and rapid response, and strengthening health systems and ensuring frontline health workers are equipped to manage diseases safely and effectively.
• The team in Rwanda is working with partners and the Ministry of Health to assess, discuss and update the response plan, the epidemiology of the outbreak, exit screening procedures, testing algorithms, and criteria for patients with MVD to be discharged from the treatment units.
• The team also hand-carried test kits and supplies from the CDC’s Atlanta offices to the Rwandan national reference laboratory and are working with CDC’s Rwanda country office to identify and prepare CDC staff who could deploy to the country, should more assistance be needed.
• CDC Marburg experts are developing a detailed map that will show which areas of Rwanda have a higher risk for spillover events (scenarios where the virus moves from wildlife into people). This will allow health officials to target areas for investigations into spillovers and for improved surveillance for potential illnesses in people.

U.S. Preparedness and Travel

• CDC issued a Health Alert Network (HAN) advisory to U.S. health departments and clinicians to make them aware of the outbreak and to provide advice should they receive a patient with Marburg symptoms and recent travel history to the outbreak area.
• On September 30, CDC issued a Level 2 Travel Health Notice for Rwanda, which includes recommendations for people traveling to Rwanda to practice enhanced precautions.
• On October 7, CDC issued a Level 3 Travel Health Notice for Rwanda, which includes recommendation for people traveling to Rwanda to reconsider nonessential travel.
• On October 3, CDC issued interim recommendations for public health management of U.S.-based healthcare personnel who were present in a healthcare facility in Rwanda during the previous 21 days and are returning home.
• Starting the week of October 7, CDC had health messages posted at the international arrival areas in three airports receiving travelers from Rwanda.
• Additionally, CDC is using an automated system to send general Marburg health text messages to international air travelers arriving from Rwanda. Text messaging allows CDC to provide relevant and timely public health information and instructions directly to travelers and further facilitates future communication between travelers and public health officials.
• Starting the week of October 14, CDC began public health entry screening of travelers entering the United States who have been in Rwanda in the past 21 days. This screening aims to reduce the risk of importation of Marburg cases into the United States and the spread within U.S. communities.

Vaccines and Therapeutics

• As part of ASPR’s preparedness mission, the agency has invested approximately $365 million dollars to develop a vaccine and antibody treatment against Marburg virus, has made known.
• ASPR has invested over $235 million into the development of Sabin’s ChAd3-based filovirus vaccine candidates that target Marburg and Sudan viruses.
• Another $129 million has been invested into the development of Mapp Biopharmaceutical’s MBP-091 monoclonal antibody which is the leading therapeutic candidate for treatment of infected individuals.
• These investments, coupled with ASPR’s expertise, have advanced the two countermeasures through preclinical safety and efficacy and Phase I clinical trials.
• Doses of the ChAd3-SUDV were shipped to Uganda in preparation for a ring vaccination study just prior to the end of the latest Sudan ebolavirus outbreak and both ChAd3-SUDV and ChAd3-MARV are currently in Phase 2 trials in Uganda and Kenya.
• In partnership with the Rwanda Ministry of Health and international colleagues, ASPR has made an initial quantity of MBP-091 and ChAd3-MARV available in Rwanda to enable patient treatment and vaccination of contacts and healthcare workers.
• As of October 6, vaccination and treatment has begun on the ground in Rwanda.
  • These investigational therapeutics and vaccines are being used under clinical trial protocols approved by Rwandan Regulatory and Ethics Authorities.

Research

In 2023, researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), published these Marburg virus (MVD), studies potentially relevant to the current situation in Rwanda:

• An experimental MVD vaccine was safe and induced an immune response in a small, first-in-human clinical trial involving 40 volunteers (Hamer et al. The Lancet 2023). The vaccine uses a modified chimpanzee adenovirus (cAd3), which can no longer replicate or infect cells, and displays a glycoprotein found on the surface of MVD to induce immune responses against the virus. Earlier studies of this cAd3 MVD vaccine in non-human primates demonstrated it elicited a protective immune response within a week that lasted as long as one year (Hunegnaw et al. Sci Transl Med 2022).
• Scientists investigated the fast-acting potential of an experimental Marburg vaccine using a vesicular stomatitis virus platform (VSV-MVD), by challenging cynomolgus macaques with MVD 14 or 7 days after a single low-dose VSV-MVD vaccination. The researchers found that 100% of the animals survived when vaccinated at either timepoint (ODonnell et al. EBioMed 2023). The VSV platform is the same used in the licensed Ebola vaccine.
• Following on the prior study, blood sample analysis showed activation of immune system and antiviral protection in cynomolgus macaques following VSV-MVD vaccination (Prator et al. Emerg Microbes Inf 2023). This data highlights the applicability of the VSV-MVD vaccine in outbreak situations.
• Because Ebola virus (EBOV), and MVD have overlapping geographies, scientists used cynomolgus macaques previously vaccinated with VSV-MVD and protected against MVD challenge. After a 9-month resting period, animals were vaccinated with VSV-EBOV and challenged with EBOV, resulting in 75% survival. Surviving animals developed EBOV antibodies and no virus in the blood or clinical disease signs. This study demonstrates that VSV-based filovirus vaccines can be successfully used in individuals with pre-existing VSV vector immunity, highlighting the platform’s applicability for consecutive outbreak response. (Marzi et al., J Infect Dis 2023)
• The NIAID Centers of Excellent in Translational Research (CETR), program supported development of MBP-091, a single monoclonal antibody that demonstrates efficacy in protection against MVD challenge in the rhesus macaque model. This product is now being further developed by BARDA. Additional studies by this CETR demonstrated that a half-life extended MVD mAb in combination with remdesivir extended the window of therapeutic intervention in a Rhesus Macaque model.
• The same CETR grant supported evaluation of Auro vaccine’s panfilovirus vaccine candidate, which showed protection against MVD challenge in a cynomologous macaque model.
• NIAID is supporting the preclinical development of additional mAb and vaccine candidates for MVD, including ABV-103 and Auro vaccine’s candidates.
• NIAID intramural and extramural investigators participate in the MVDAC, a WHO-coordinated consortium to promote international collaboration for the development of MVD vaccines. The consortium builds on the previous success of WHO working groups on COVID-19 preclinical models and assays that accelerated the development of COVID-19 vaccines by rapidly sharing scientific findings and protocols.

This consortium includes shareholders from industry, nonprofit organizations, government, and academia in order to maximize its effectiveness.

This joint venture is supported by the following principles:

1. Sharing of assays and reagents;
2. Promoting access to laboratory networks in MVD-endemic countries; and
3. Promoting structural support for preclinical development of upcoming MVD vaccine and therapeutic candidates. MVDAC has been rapidly convened in response to the current outbreak.