Meet the scientists trying to stop the next global pandemic from starting in Africa

Even experienced doctors could be fooled by this disease.

A deadly hemorrhagic illness, it often looks like yellow fever, malaria, or typhoid. At first, an infected individual might feel weak, uneasy, and feverish; after a few days, headaches, sore throats, and nausea could begin. But in about 20% of infected individuals, patients start to feel like they’re suffocating as fluid leaks into their lungs; as the infection advances, they start bleeding out of their gums, eyes, and nose.

Lassa fever has been simmering in West Africa for at least half a millennium, killing roughly 5,000 people each year, according to the most recent estimates. But it was only 15 years ago when patients first started being diagnosed and treated in Nigeria, the result of two geneticists’ collaboration — Christian Happi at Redeemer’s University and Pardis Sabeti halfway across the world at the Broad Institute.

Together, they helped a local hospital set up PCR testing for Lassa and assisted it in procuring the antiviral ribavirin. Before not too long, patients began trooping in from hundreds of kilometers away just to be seen at this center. The experience taught Happi and Sabeti something profound: Society labels some viruses as novel or rare, not because they actually are but because nobody tests for them. In a recent paper reflecting on Lassa fever, Ebola, and Covid-19, they and co-authors wrote, “in many parts of the world, we are largely blind both to the prevalence of known infectious diseases and to the appearance of new threats.”

Since 2008, Happi and Sabeti have been building a disease surveillance system in West Africa known as Sentinel, officially launching it in 2020, one month before Covid-19 was declared a pandemic. By early February, they had deployed SARS-CoV-2 tests in hospitals across Sierra Leone, Senegal, and Nigeria — before any U.S. hospital had. In March, Happi’s lab confirmed the first case of Covid-19 in Nigeria, became the first African lab to sequence a SARS-CoV-2 genome, and shared these data with scientists worldwide.

Although the Covid-19 pandemic did not originate in Africa, the continent is a hot spot for emerging infectious diseases, with 140 disease outbreaks detected each year. However, surveillance in Africa has historically failed to meet the moment, from Lassa fever going undetected for decades despite annual outbreaks to Ebola being identified nearly three months after it struck the continent in 2014. Experts told STAT the problem is that disease surveillance is currently too centralized, run out of national headquarters thousands of kilometers from where diseases are actually spreading. “I have no idea why humanity has decided to just give pathogens a pass, and only care about them when they shut down society,” said Sabeti.

Sentinel hopes to shift surveillance toward a more bottom-up approach, bringing low-cost diagnostics to community settings and rural hospitals, as well as empowering frontline workers to track the spread of disease in real-time. The idea is to play offense against these deadly diseases, enlisting the vigilance of everyday Africans to catch pathogens early. But the hurdles facing Sentinel are steep, from integrating the program into national and global surveillance systems to sustaining the program long-term.

Still, if Happi and Sabeti successfully surmount these challenges, their work could change how disease surveillance is deployed worldwide and how we prevent the next pandemic before it starts. “Everybody in the world should be a sentinel, a sentinel not only for his own immediate community, for his own country — but a sentinel for the globe,” said Happi.

‘Three pillars of surveillance: detect, connect, empower’

Happi and Sabeti built Sentinel to address three key surveillance failures in Africa: pathogens are detected late, it takes too long to transmit data, and frontline health care workers don’t have the resources to succeed. “It’s not the kind of challenge that necessarily fits well into a typical private industry strategic development plan,” said Al Ozonoff, an associate professor of pediatrics at Harvard Medical School and the U.S. director for the Sentinel program.

Correspondingly, one of Sentinel’s tests is a paper strip that can detect common pathogens at the point of need — for just a few dollars a test. “Imagine doing a PCR on a sheet of paper. That’s basically the system that we’ve designed,” said Happi, adding that the SHINE test is so simple “that my grandmother could do it in our own village.”

But for now, this CRISPR-based diagnostic can test for only one virus or bacteria at a time, so if SHINE draws a blank, Sentinel escalates to the CARMEN test stationed in rural hospitals: It can simultaneously screen for up to 16 known pathogens and deliver results within a day.

If neither SHINE or CARMEN detects anything, the sample is escalated to the third and final tier where it is sequenced at a regional genomics hub, revealing every virus in the sample, known or unknown. It’s a feedback loop where, after sequencing, new, low-cost diagnostics can be rolled out to test for those previously unknown pathogens within a week, Ozonoff said.

Sabeti has filed patents for the technology and co-founded the company Sherlock Biosciences to commercialize these tests in the U.S. But she emphasized that access remains the goal: “Christian and I sit on the board of the 221b Foundation, which is Sherlock’s nonprofit, trying to get this at cost to low- and middle-income countries.”

But as the sluggish response to Ebola laid bare, disease detection is only as good as the ability to connect data in real time, with experts saying that much of West African public health currently happens on disconnected pieces of paper. As such, Sentinel has been deploying mobile apps that allow frontline workers to share symptoms and diagnostic data across geographically separated clinics and create visualizations to make these data more actionable. Importantly, this system is designed to work despite Nigeria’s notorious electricity and internet connectivity problems, according to Dolo Nosamiefan, Sentinel’s program manager.

While Happi and Sabeti emphasize the promise of their technology, they said that what distinguishes Sentinel from other disease surveillance systems is its focus on empowerment. They realized from the beginning that, “if we really want to do this well, there needs to be a real exchange of education — people on my team spending long periods of time in Africa, people on the African team spending long periods of time with us,” said Sabeti.

She described how, since 2009, African scientists have come to Boston from Nigeria, Senegal, Liberia, Ghana, Togo, and Cameroon, exchanging knowledge about molecular diagnostics and genetics, as well as going canoeing, playing volleyball, and forming a rock band. “It’s that shared language — and also that friendship,” said Sabeti, with Broad Institute researchers traveling to Redeemer’s University as well. “If we were to say, ‘What’s our legacy?’ It’s probably that education.”

 Challenges ahead of Sentinel

 To a certain extent, Sentinel’s ambitions are running ahead of its reality.

“Sentinel is conceptually a great idea,” according to Chikwe Ihekweazu, head of the World Health Organization Hub for Pandemic and Epidemic Intelligence, but he said that, for now, it’s only a research lab, not a public health tool. When Ihekweazu was director of Nigeria Centre for Disease Control and Prevention, Happi helped them sequence the first batch of Covid-19 samples, but this was a one-off collaboration. “Until you systematize that type of effort where samples are routinely sent, analyzed, and decisions are made, it doesn’t fall into the bracket of surveillance,” said Ihekweazu. “It falls into the bracket of research because someone is interested.”

Ozonoff clarified that Sentinel’s goal “is not to build a parallel system or something that is not contributing to the larger surveillance picture in Nigeria.” While integration efforts were delayed due to the shock of the pandemic, he said that Sentinel started working with local and state public health officers earlier this year, developing personal relationships and learning how the program could support their work. “Christian is engaged very closely with Nigeria CDC,” Ozonoff added. “So he’s working from the top down; we’re doing some of the bottom-up work. I think we’re going to meet in the middle.”

Happi and Sabeti acknowledged that Sentinel is still in the research phase, field testing and piloting tools like SHINE and CARMEN. But they also said they’ve been laying the groundwork to kick Sentinel into full gear, training 1,500 scientists from 42 African countries on genomic surveillance. “Between March and December 2020, Africa had only about 5,000 genomes,” said Happi, primarily generated by his lab and a few others. “But then with the training we provided, by September 2021, Africa went from 5,000 genomes to more than 100,000.”

Gerald Mboowa, a bioinformatics implementation expert at Africa CDC, celebrates this work, but he said that training people isn’t the same as retaining them. “Today you may have trained people from 40 countries,” but within six months, “half of them are moving either to Europe or the USA,” Mboowa said.

The problem is multifactorial, including grievances with facilities and supply chain issues, but he believes this brain drain ultimately comes down to pay. “Some of them say, ‘Can you pay me a minimum of $1,000 USD a month?’ Many of these governments cannot pay that money,” said Mboowa. “So obviously, if you don’t pay them their worth, they will look for the next opportunity, and most of these will be outside the continent.”

Even if retainment is improved, these funding issues run deep to the very existence of Africa’s genomic centers. “We also fear that many of the previous investments in smaller laboratories may be discontinued. And that could be very sad for the world, if we cannot act quickly to a new pandemic,” said Tulio de Oliveira, director of the Centre for Epidemic Response and Innovation in South Africa. “We may have the equipment, we may have the people, but we don’t have the funding and the reagents to react.”

So, Sentinel could continue training scientists, but without addressing some of these structural realities in Africa, the continuity of the program remains in jeopardy. “If we cared about outbreak responses as much as we care about baseball, good God, what would we be able to do,” said Sabeti.

A template for future collaborations

Africa has long had a problem of helicopter science, in which Western scientists land in the continent, establish temporary partnerships, and then leave after they’ve extracted what they needed, or the funding has runs out, according to Sentinel’s Nosamiefan. “There are things that you can learn only from being here and having grown up here,” he added. “Even with $10 million, if they come to try and do a study in Africa, it wouldn’t work because they don’t understand how people think.”

But with Happi and Sabeti, it’s a relationship built on genuine respect and friendship; and they have fostered a similar culture in each of their teams, Nosamiefan said. “Each of them find it really important to empower the people under them,” he continued. “They both have a hope for where they see public health in Africa going and public health globally going.”

In May, the WHO launched the International Pathogen Surveillance Network to coordinate pandemic prevention between public health agencies, academic centers, and philanthropies — under Ihekweazu’s leadership. While he views Sentinel as only in its research phase, he believes in its broader potential and looks forward to collaborating with the program to realize its public health value.

For Mboowa, he’s not betting on Sentinel itself but Happi and Sabeti, given their track record in tracking infectious diseases and their long-standing commitment to West Africa. “Each of them has a responsibility to continue sustaining the endeavor they’ve built together over 15 years,” Mboowa said. While there’s plenty of obstacles in creating a better model for disease surveillance, he emphasized that it’s also one of the most important challenges of our time.

With such rich biodiversity in Africa, “we can’t just afford to keep exporting these pathogens,” Happi said. “We should rather export solutions to pathogens.”