Pandemic Center

n 27 September 2024, Rwanda’s Health Ministry confirmed the country’s first ever Marburg virus outbreak. It was a distressing national moment: a filovirus like Ebola, Marburg is lethal with fatality rates of up to 88%. Symptoms are dreadful, including intense feverishness, acute headaches, vomiting and bleeding from the eyes, gums and elsewhere – “bad news wrapped up in protein” as Nobel Laureate biologist Peter Medawar put it in 1974.

Six weeks later, on 15 November 2024, Rwanda’s Minister of Health Dr Sabin Nsanzimana, announced the discharge of the last of the Marburg patients. The virus sadly caused 15 early deaths, but of the 66 cases, 55 patients recovered.

He noted that it had been 48 days since the first case was reported, two weeks since the last new case and a month without further fatalities. If no new infections arise 42 days after the last case tests negative, the outbreak will be declared over by December 21.

It is an admirable achievement by any measure. In a context where the recent US presidential election and the controversial cabinet and agency nominations drive the news cycle, it is important to heighten the visibility of Rwanda’s achievement, of how a lower-middle-income country in mid Africa managed to contain an outbreak caused by one of the world’s most feared high-consequence pathogens.

What happened in Rwanda is captured by Louis Pasteur’s famous aphorism that “chance favours the prepared mind” or, as in this instance, the prepared response system.

In 2008, when Nelson Mandela hosted Nobel Laureate David Baltimore to give a science lecture on the origins of HIV, Baltimore travelled to South Africa via Rwanda at the invitation of President Paul Kagame where he was asked — far-sightedly — to give the country’s leaders advice on how to ground development in science.

In 2018 Rwanda was one of the first countries to conduct the World Health Organization’s Joint Evaluation Exercises in pandemic preparedness and response, which assessed the most critical gaps in their human and animal health systems and prioritised opportunities for enhanced preparedness, detection and response within the framework established by the 2005 International Health Regulations.
A National Action Plan for Health Security, a roadmap to strengthen the International Health Regulations’ core capacities, followed the Joint Evaluation Exercises. The Rwandan government, through its Ministry of Health and Rwanda Biomedical Centre, worked tirelessly to tick all the points by ensuring the readiness and the resilience of the system for any outbreak. The implementation was smooth and ready.

Rapid response
When Covid-19 hit, Rwanda responded quickly. The authorities imposed a six-week lockdown and introduced contact tracing and other interventions — 82% of the population received at least one dose of a Covid-19 vaccine.

The Australian think tank the Lowy Institute ranked 98 countries for their Covid-19 response and found that smaller populations and capable institutions were the most important factors in managing the global pandemic. Rwanda was the only African country in the top 10 achievers.

Rwanda therefore had been working hard over the long haul to upscale their preparedness. The hospital-based surveillance system gave an alert that triggered the national public health institute — the Rwanda Biomedical Centre — to detect the Marburg virus, which in turn switched on contact tracing, diagnostics and case management.

Co-infection with malaria (Marburg/Ebola share symptoms with malaria) slowed down detection of the first case. However, diagnostics were quickly scaled up and 7,408 tests were administered with a focus on healthcare workers who suffered 80% of the infections.

Epidemiologists ultimately traced the first case back to a 27-year-old mining cave worker. He was exposed to the reservoir of Marburg virus, the fruit bat Rousettus, and subsequently infected his pregnant wife who was admitted to the King Faisal Hospital’s ICU in Kigali.

In the following days, many healthcare workers were infected and fell ill. Rwanda has a sizeable and growing mining industry, and is a major exporter of the so-called 3Ts — tin, tantalum, tungsten — and increasingly gold. Some of the mines are close to Rwanda’s extensive network of 52 caves, some 2km long, many of which have large bat colonies.

At King Faisal and the rapidly deployed Marburg Treatment Centre at Baho International Hospital, patients received prompt intensive care support; use of high flow nasal canula; and intravenous fluids to manage high fever, nausea, vomiting and diarrhoea. Intubation and life support were provided to patients experiencing multiple organ failure. Two Marburg patients were extubated i.e. taken off life support, the first time in Africa.

Infection control measures were implemented in hospitals, including personal protective gear distributed to all health workers. Rwandan officials monitored the health of more than 1,000 community members and engaged in door-to-door surveillance in exposed neighbourhoods.

Schools and hospital visits were suspended and the number of people who could attend Marburg funerals was restricted. Even with relatively prompt detection, most of the deaths were of exposed healthcare workers.

The WHO supplied 12,000 personal protective items, sufficient to run the specially built 50-bed Marburg Treatment Centre with its clinical isolation units for 30 days. A joint WHO and Rwandan Ministry of Health infection prevention and control team trained 520 healthcare workers in infection control and prevention.

Gilead Sciences, a global biopharmaceutical company that revolutionised HIV treatment and prevention, donated 5,100 vials of remdesivir, a broad-spectrum antiviral medication previously used to treat Covid-19, as an emergency treatment measure.

With support from the United States’ Biomedical Advanced Research and Development Authority, Mapp Biopharmaceutical deployed a monoclonal antibody MBP091 that targets the Marburg virus. Almost all the initial doses were given to healthcare workers.

‘Ring vaccination’ strategy
The Sabin Vaccine Institute donated more than 1,700 doses of an investigational Marburg Phase II clinical trial vaccine (manufactured by the company ReiThera) to administer to high-risk groups, including healthcare workers, mine workers (exposed to virus-carrying bats in caves in mining districts), and individuals in contact with confirmed cases. Half received the vaccine immediately, and the other half 21 days later to align with the end of the disease’s incubation period. The “ring vaccination” strategy was deployed.

Marburg vaccine efforts must be seen against the background of a major effort under way to establish Rwanda as one of Africa’s leading vaccine manufacturers. BioNTech opened its first modular messenger mRNA vaccine manufacturing facilities in Kigali in April 2024.

The Coalition for Epidemic Preparedness Innovation landed its 100 Day Mission there, working with IQVIA (clinical trials), Ginkgo BioWorks (wastewater surveillance), the Rwanda Biomedical Centre and the Rwanda Development Board on end-to-end vaccine manufacturing prospects.

Regionally, Africa Centres for Disease Control and Prevention dispatched a team of experts on 29 September to aid response efforts. In collaboration with Rwanda’s neighbours — Burundi, Uganda, Tanzania and the Democratic Republic of the Congo — Africa Centres for Disease Control and Prevention provided guidance on regional surveillance and containment strategies.

It cautioned against using travel bans and movement restrictions targeted at African countries as inconsistent with international health guidelines that undermine public health responses, deepen economic challenges, ignite inequities and prompt mistrust.

Instead, what is required is the harmonisation of regional and global policies when an outbreak like this occurs.

Finally, there is the critical asset of leadership, with President Paul Kagame and his cabinet members, and Dr Sabin Nsanzimana, an epidemiologist and former director-general of the Rwanda Biomedical Centre, in command of the effort.

WHO Director-General Tedros Ghebreyesus praised Rwanda for its response, noting that “leadership from the highest levels of government is essential in any outbreak response, and that’s what we see here in Rwanda”. To symbolise Rwanda’s partnership with the continent-wide public health technical support agency the Africa Centres for Disease Control and Prevention, Dr Nsanzimana held his press briefings jointly with its director-general, Dr Jean Kaseya.

Even so, we can do even better, and we must learn much more. Rwanda’s response was exceptional, but it wasn’t perfect. Disease detection could have been much faster. The virus spread in the hospital before being picked up.

We need to get on top of the ecology and migration patterns of the bat carrying Marburg and other viruses, and better understand the impact of rising temperatures, altered rainfall patterns and habitat loss due to mining and human incursions that drive bats to new areas in search of food and shelter.

Climate affects food availability and causes nutritional stress, disrupts hibernation and breeding patterns, and droughts and floods can drive bats closer to human settlements, all opportunities for greater viral transmission. Upscaled surveillance of the pathogens, the disease and the ecology of bats can create a knowledge base for better interventions.

It is not a stretch to say that the world — including the developed world — can learn a great deal from Rwanda. This is the true meaning of global health, an exchange of knowledge, expertise and best practice between North and South, not one-way traffic from North to South. DM

Wilmot James is a Professor at the School of Public Health and Senior Advisor; Craig Spencer a Professor in the School of Public Health; Anne Wang a Research Assistant; and Bentley Holt Assistant Director of Communications and Outreach at the Pandemic Centre, Brown University, Providence, Rhode Island, USA.

Edson Rwagasore is the Division Manager of Public Health Surveillance and Emergency Preparedness and Response, Rwanda Biomedical Centre, Kigali.

Jeanine Condo is an Adjunct Associate Professor at the University of Rwanda and Tulane University and CEO of the Centre for Impact, Innovation and Capacity Building for Health Information and Nutrition, Kigali.

Marburg virus is notorious for its killing ability. In past outbreaks, as many as 9 out of 10 patients have died from the disease. And there are no approved vaccines or medications.

That was the grim situation in Rwanda just over a month ago, when officials made the announcement that nobody wants to make: The country was in the midst of its first Marburg outbreak.

Now those same Rwandan officials have better news to share. Remarkably better.

“We are at a case fatality rate of 22.7% — probably among the lowest ever recorded [for a Marburg outbreak],” said Dr. Yvan Butera, the Rwandan Minister of State for Health at a press conference hosted by Africa Centers for Disease Control and Prevention on Thursday.

There’s more heartening news: Two of the Marburg patients, who experienced multiple organ failure and were put on life support, have now been extubated — had their breathing tubes successfully removed — and have recovered from the virus.

“We believe this is the first time patients with Marburg virus have been extubated in Africa,” says Tedros Adhanom Ghebreyesus, director general of the World Health Organization. “These patients would have died in previous outbreaks.”

The number of new cases in Rwanda has also dwindled dramatically, from several a day to just 4 reported in the last two weeks, bringing the total for this outbreak to 66 Marburg patients and 15 deaths.

“It's not yet time to declare victory, but we think we are headed in a good direction,” says Butera. Public health experts are already using words like “remarkable,” “unprecedented” and “very, very encouraging” to characterize the response.

How did Rwanda — an African country of some 14 million — achieve this success? And what can other countries learn from Rwanda’s response?

Doing the basics really well
Rwanda is known for the horrific 1994 genocide — one of the worst in modern times. Since then, the country has charted a different path. In 20 years, life expectancy increased by 20 years from 47.5 years old in 2000 to 67.5 years old in 2021 — about double the gains seen across the continent. And Rwanda has spent decades building up a robust health-care system.

“The health infrastructure, the health-care providers in Rwanda — they're really, really great,” says Dr. Craig Spencer, an emergency physician and professor at Brown University School of Public Health. Spencer specializes in global health issues and has been following the Rwandan outbreak closely.

There are well-run hospitals and well-trained nurses and doctors, he says. There are laboratories that can quickly do diagnostic testing. There is personal protective equipment for medical workers.

For this outbreak, there was the know-how and infrastructure to set up a separate Marburg treatment facility. That's been a boon for other patients and medical staff, preventing exposure to the virus — which crosses over from bats to humans and can be transmitted through bodily fluids like blood, sweat and diarrhea.

And even though there aren't approved medications to treat Marburg, patients in Rwanda have received good supportive care for all their symptoms — like the IV fluids critical for symptoms like high fevers, nausea, vomiting and diarrhea.

This stands in stark contrast to the response in past Marburg scenarios. For example, the Democratic Republic of Congo — next door to Rwanda — had an outbreak between 1998 and 2000. Dr. Daniel Bausch, now a professor at the London School of Hygiene and Tropical Medicine and an expert in tropical diseases like Marburg, provided care in that outbreak. He says what the country’s health centers were able to offer patients was rudimentary at best.

“We called it a care center or treatment center, but really it was a separate mud hut that people were placed in. We didn't have really anything available to us,” he remembers. “People were lucky that they got paracetamol, or Tylenol, and some fluids to drink, if they could get them down without the nausea and vomiting preventing them.”

In the world's 18 recorded Marburg outbreaks, the mortality rate varies considerably. Several small outbreaks have had fatality rates below 30% but the largest outbreak — in Angola in 2004 and 2005 — had a case fatality rate of 90% with 252 cases and 227 deaths.

Rwanda’s “more modern medical centers” make a big difference, Bausch says.

Getting to patients lickety-split
It wasn’t just the caliber of care that made a difference. It’s also the speed with which patients get care.

As soon as the outbreak started, Rwandan officials jump-started a major operation to trace the contacts of those who were infected, monitoring the health of over 1,000 family members, friends, health-care workers and others at risk. They also started door-to-door surveillance in neighborhoods where there might have been an exposure.

And they did a lot of testing – over 6,000 tests, especially among health-care workers, who’ve comprised 80% of the Marburg patients in this outbreak.

Spencer says many of these capabilities were built up during the COVID pandemic and could be rolled out rapidly. “In Rwanda, you have providers able — within hours really of this outbreak being declared — to get tested,” says Spencer, who has worked with Doctors Without Borders treating Ebola patients. “[Rwanda’s testing is] absolutely remarkable in terms of the response.”

This surveillance and testing allowed “us to detect cases quickly and provide them with treatments in the very, very early phases of their diseases,” explains Butera. He says that caring for patients before they become critically ill likely helped lower the mortality rate.

Embracing experimental vaccines and medications
Rwanda’s speed carried over into other anti-Marburg efforts.

“Everything I have witnessed was really expedited,” says WHO’s Ghebreyesus, who visited Rwanda last week and said what he saw was “very, very encouraging.”

While there are no vaccines or treatments approved for Marburg, Rwanda acted quickly to get experimental vaccines and treatments to people at the center of the outbreak.

“I can't imagine another scenario in which a country went from identifying this outbreak to just over a week later having investigational [experimental] vaccines in country already being provided to frontline health-care workers,” says Spencer, who adds the doses started being administered the same day they arrived in the country. The nonprofit Sabin Vaccine Institute provided the doses, which were developed with major support from the U.S. government.

“I rarely, rarely use the word unprecedented in global health response” Spencer says, but this speed was “unprecedented.”

The vaccine itself is still in development. Testing has shown that it’s safe — but not whether it actually works. Nonetheless, Rwanda decided to inoculate those at risk, hoping that it would help.

Those officials also decided to vaccinate without a randomized controlled trial, where a segment of the recipients get a placebo. Some in the international scientific community say this was a missed opportunity to start learning whether the vaccine is effective — although they concede that it’s far more complicated and slow to roll out a trial. And the size of the outbreak was unlikely to yield enough data to be conclusive.

Did the vaccines help stop the spread or reduce the mortality rate? It’s impossible to know, says Bausch. He points out that in the first recorded Marburg outbreak — in 1967 in Marburg, Germany and what was then Yugoslavia — the mortality rate was 23% with only good supportive care.

Meanwhile, in Rwanda, the next round of vaccines will go to at-risk groups, including mine workers who are in close proximity to the fruit bats that can spread Marburg; that vaccine effort will be randomized.

In addition to the vaccines, Rwanda very swiftly started giving patients two medications — an antiviral called Remdesivir and a monoclonal antibody. As with the vaccine, they hoped these treatments would help even though they haven’t been approved for Marburg.

An early stumble, a course correction
In addition to the speed and high-quality patient care, there’s another less glamorous — but equally important — dimension to quashing Marburg and other viruses, says Bausch. It’s infection control: basically, ensuring Marburg patients don’t infect others. In the hospital, this means that staff take precautions like wearing gowns, masks and double gloves. In public, it can mean sanitizing shared items like motorcycle helmets and installing handwashing stations in public places, as Rwanda has done.

Rwanda stumbled early on with infection control. That’s because it took a couple weeks to diagnose the disease in the individual who is considered the first patient in this outbreak — and the first known Marburg case in the country.

That individual, who likely contracted the virus from exposure to fruit bats in a mining cave, also had a severe case of malaria. Clinicians did not determine that Marburg was also present until other people around that patient started falling ill. As a result, many health care workers were exposed before infection control measures were improved.

While Rwanda rapidly improved their infection control once officials understood what they were dealing with — and not just in health facilities. The mining community linked to the initial patient has seen several cases. So surveillance needs to be sure to cover those populations, says Rob Holden, WHO’s incident manager for Marburg.

“As we go forward, we fine tune, we refine, we reinforce all our surveillance systems, our contact follow ups, our investigations, and we leave no stone unturned,” he says. “If we let our guard down, then I think we'll end up with some nasty surprises and a very long tail on this outbreak.”

Spencer agrees. But he is optimistic. He says that Rwanda’s robust health infrastructure and speedy response has helped protect the rest of the world from a much bigger Marburg outbreak.

Rwanda is battling its first outbreak of Marburg virus, a severe and often fatal disease. Discovered less than two weeks ago, the outbreak is already the third largest on record, accounting for 58 confirmed cases and 13 deaths as of October 10.


Despite the ostensible delay in detection, once the outbreak was recognized and declared on September 27, 2024, the Rwandan Ministry of Health launched an ambitious response to contain the spread—scaling up clinical care resources, dramatically expanding testing, and reaching out to global partners for international expertise and access to experimental medical countermeasures.


Rwanda's response to Marburg has been helped by its health system, which has rebuilt from the ashes of the genocide three decades ago to become one of the strongest in the region. Even with this infrastructure, the emergency has posed a significant challenge and important lessons are emerging about preparing for and responding to future outbreaks and global health security.


Having worked in the field response to multiple outbreaks, including as physician and a country-level epidemiologist in Guinea during Ebola in 2014, I know the next few weeks could be even harder as they work to get it under control and prevent further spread, especially among their own health-care workforce and to other countries.

Yet we've already seen promising signs.


Marburg, Briefly Explained

Marburg belongs to the same virus family as Ebola (filoviruses), and the approach to containing each disease is similar. Like Ebola, Marburg spreads from human to human via infected body fluid and has a similar incubation period (2–21 days). Both diseases can cause fever, headache, diarrhea, and severe bleeding. Fatality rates up to 88% have been reported for Marburg, but good clinical care can lower that figure.

The Marburg virus was first discovered in 1967 when laboratory workers in Marburg and Frankfurt-am-Main, West Germany, and Belgrade, Serbia (then Yugoslavia), simultaneously fell ill after handing African green monkeys imported from Uganda.

In total, 18 Marburg outbreaks have been reported; their frequency appears to be increasing, with five outbreaks in the last three years alone.


Rwanda's Health System, Clinical Care Needs, and Early Promise

Building on expertise learned during the COVID pandemic, Rwanda's contact tracing for Marburg was quickly put in place in an effort to understand the different chains of transmission. This labor-intensive work requires epidemiologists to compile exhaustive lists of any people who could have been in contact with a confirmed case. Each identified contact is then followed for 21 days to record symptoms, monitor temperature, and refer anyone for testing. Rwanda has reported that it is following more than 400 contacts.

The current Marburg outbreak in Rwanda is in many ways typical for filovirus outbreaks. As is often the case, recognition and confirmation of the diagnosis was delayed. Epidemiologic analysis has tied the index case back to September 8, nearly three weeks before the outbreak was declared late in the month. No case of Marburg had ever been reported in Rwanda, which likely delayed the initial diagnosis. Similarly, the index case tested positive for malaria, ostensibly providing an explanation for his symptoms and preventing any further exploration of his death.


More than 80% of the initial Marburg cases were in health-care workers, a common finding in the early days of filovirus outbreaks, when disease spread takes place within health structures. Providers often come in close contact with patients who present for care at the most infectious phase of their illness.


In developing clinical capacity for Marburg outbreaks, two goals are critical: reduce the risk of infection for providers while providing high-quality clinical care to patients. Both are resource and labor intensive, requiring a sufficient supply of personal protective equipment and the implementation of strict protocols to reduce exposure risk.


No vaccines or therapeutics for Marburg are currently approved, but experimental treatments—including monoclonal antibodies and an antiviral drug—have already reached Rwanda and are being used in patient care.

Otherwise, the mainstay of treatment is early and intensive supportive care, which can help lower mortality. This requires medical providers to perform frequent assessment of vital signs and address any abnormalities, appropriately replace fluid losses, monitor laboratory results (including kidney and liver function), and perform potentially more clinically demanding and higher risk interventions such as renal dialysis or intubation. This also requires vast quantities of personal protective equipment and strict adherence to protocols created for safely using it, particularly for properly removing it when the risk of exposure is highest.


A remarkable achievement is the arrival of an experimental Marburg vaccine just days after the outbreak was reported. More than 700 doses were provided by the Sabin Vaccine Institute, a nonprofit organization promoting global vaccine development, and another 1,000 doses will reportedly arrive soon in the country. These vaccines were developed with significant financial and research backing from the Administration for Strategic Preparedness and Response (ASPR) and the National Institutes of Health (NIH), highlighting the importance of U.S. contributions to supporting global health response.

The swift deployment of vaccines in Rwanda contrasts sharply with that for previous filovirus outbreaks, when complicated paperwork and formal bureaucracy often delayed arrival of vaccines and other medical countermeasures until after the period they could be used in a trial, most recently in the 2022 Ebola Sudan outbreak in Uganda.


Yet these vaccine doses arrived in Rwanda within a week of the request and were already being administered to frontline providers the day they arrived.


International Risk: Avoiding Past Missteps

Outside the confines of its hospitals, Rwanda will face different challenges in containing this outbreak. Cases were initially reported from seven of Rwanda's 30 districts, with most concentrated in and around the capital city, Kigali. During the 2014–2016 West Africa Ebola outbreak, transmission to capital cities led to a dramatic rise in case counts given the greater level of potential exposure.


Similarly, Rwanda's capital is a global travel hub and booming tourist destination, with more then 1.4 million arrivals last year and direct connections to London, Paris, and many other country destinations. As a result, Rwanda has put in place guidelines and issued travel advisories, as has the Centers for Disease Control and Prevention (CDC) in an effort to "inform clinicians and health departments" about the outbreak. On October 7, the U.S. Department of Health and Human Services issued a press release outlining a plan to begin, next week, public health entry screening of travelers entering the United States who have been in Rwanda in the past 21 days to "reduce the risk of importation of Marburg cases."

The following day, the Africa CDC released a statement criticizing any travel bans or restrictions, arguing these measures are "inconsistent with international health guidelines and risk undermining public health responses, deepening economic challenges, and reigniting the inequities and mistrust that surfaced during the COVID-19 pandemic."

Potentially more concerning is the risk of international spread to Rwanda's neighbors, notably in Burundi and Democratic Republic of Congo where instability, weak health infrastructure, and the ongoing mpox outbreak would hamper the ability to launch the scale of response needed to contain Marburg.


The Give and Take of Information Sharing

A week into the outbreak, global experts outside the country expressed frustration with a perceived deficiency of important data. Virologists wanted more genomic information, epidemiologists wanted greater clarity on the contact tracing, and health-care providers wanted more clinical data.


Given my field experience with the 2014 Ebola response, I understand how difficult and time consuming it is to conduct this disease detective work, especially while trying to manage requests from an influx of international experts, setting up auxiliary structures for isolation and clinical care, ramping up testing capacity, and overseeing a growing number of meetings and interview requests. This data gathering and reporting is sometimes a challenge even in countries with excellent technical capacity, as evidenced by the current response to H5N1 bird flu outbreak in the United States.

During the COVID-19 pandemic, society became accustomed to nearly instantaneous updates on the number of new cases or hospital capacity. These are important metrics to help guide response but take significant time and effort to step up, especially in the early days of any new outbreak. International requests come as leaders haggle over the pandemic agreement—and to what degree low- or middle-income countries should receive medical products in return for sharing information on emerging outbreaks.


African nations are increasingly seeking to assert their independence on public health. They have not forgotten the inequitable distribution of COVID-19 vaccines that put many African countries last in the global queue. The Africa Union recently set a goal to produce 60% of the vaccines needed on the continent by 2040, up from less than 1% today. To that end, Rwanda recently opened a mRNA vaccine manufacturing facility in Kigali.


They have also not forgotten the punitive travel bans put in place after scientists in South Africa first discovered the COVID-19 variant omicron in November 2021. The bans targeted seven southern African countries, lasted more than a month, hobbled the region's much-needed tourism industry, and ultimately did little to prevent the new variant's spread. If the global community expected greater transparency in future disease outbreaks, reassurances that their pronouncements won't be met with unscientific and stigmatizing repercussions will be needed.


Rwanda's swift response to Marburg is a testament to the country's growing health infrastructure and resilience. However, the real challenge ahead lies in managing regional vulnerabilities and balancing international expectations while working to effectively contain the outbreak at its source.

Commentary piece by Pandemic Center Affiliate Dr. Craig Spencer.