Scientific dynamic duo aims to stop the next pandemic before it starts

In the summer of 2014, a passenger landed with a fever at the airport in Lagos, Nigeria — a city of more than 20 million. At that time, neighboring countries were in the middle of what would become the largest Ebola outbreak ever, so health workers were deeply concerned.

"We were in the middle of a tragedy, on the precipice of a cataclysm," says Pardis Sabeti, a computational geneticist at the Broad Institute. "It could be unstoppable."

Scientists like Sabeti were especially worried because of a longstanding trend in this part of the world: A deadly disease would emerge in West Africa but go unnoticed or misdiagnosed — with fatal consequences.

The passenger was tested for Ebola by doctors at a public laboratory in Lagos, but the results were inconclusive — an all too common outcome, says Sabeti. "Globally, we are very bad at detecting outbreaks."

Christian Happi, a molecular biologist at Redeemer's University in Nigeria, agrees. "If you can't diagnose the disease," he says, "it's going to be very difficult to manage it."

These two — Happi and Sabeti — are a dynamic infectious disease fighting duo.

"She's what I call my better academic half," says Happi. Sabeti doesn't miss a beat. "I'd also call him my ride or die," she says. "And I just know he will always have my back."

The pair met while studying malaria 25 years ago and grew close while working together on a lassa fever project in Sierra Leone. Then came late 2013, when people began falling ill in Guinea in West Africa. It would start with a fever and could end with death, but it still took months before health authorities were sufficiently concerned to investigate and take blood samples. Even once they did, the tests were ploddingly slow.

"The sample[s] had to be shipped to France," says Happi, "and it took another three weeks for them to have the result."

That result was Ebola, a virus that triggers high fever, erodes the immune system and then wipes out the blood's ability to clot. It's in this final stage that "you're bleeding from all orifices," says Happi, "your nose and mouth, ears. And then you die of losing blood completely. And that blood that you are spreading contain[s] the virus."

WIth no early warning, health authorities played catch up

During the weeks and months it took to confirm that it was Ebola, the virus had been able to spread, mutate and kill. Then it barreled into Sierra Leone. Dozens of sick patients converged on a hospital where Sabeti had close collaborators. "It spread like wildfire through the clinical staff," she says. One of her dear friends at the hospital, Dr. Humar Khan, died from Ebola.

"People were devastated," says Sabeti, "and panicked. So I was reeling at that point" — in part, she says, because so much of this suffering was avoidable.

"Every major epidemic we've had recently is a virus or from a family of viruses we've known about for some time prior and that has likely been circulating in some form for millennia," explains Sabeti. "So if we got better at just diagnosing every case that came into the clinic, we would be prepared for every epidemic."

Sabeti and Happi considered an inspiring possibility: What if the active monitoring of viruses could happen on the ground in Africa by Africans?

"We really thought, 'OK, now it is time to empower the local health care workers, to detect these pathogens that are circulating,' " says Happi. In other words, to enable them to "do things by themselves."

So in early 2014, Happi and Sabeti co-founded the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID) in Nigeria, an organization whose mission is to spot and diagnose emerging illnesses, and then contain them.

'If I don't make it back, take care of the children.'

Happi became the director of ACEGID. And in a stroke of good fortune, it came into being just as the Ebola outbreak was unfolding.

So when the test of that feverish passenger in Lagos came back inconclusive, the authorities rang up Happi in hopes that maybe ACEGID could diagnose the man's disease. Happi prepared to join the effort.

"I knew I was going to be dealing with something very dangerous," says Happi. "And I remember telling my wife, 'If I make it back, fine. If I don't make it back, take care of the children.' And she told me, 'You've always said that you better die and save millions of people than to just let this thing spread. Go, God is gonna be with you.' "

Happi figured if it was a deadly pathogen, he would confront it either in the lab on his terms or later on when it found him and his loved ones. "It will meet you in your house," he says.

He drove an hour to the lab in the night along one of the most dangerous roads in the country, notorious for armed robberies. When he arrived, he and his colleague put on the PPE that Sabeti had sent over for a situation just like this. "We didn't have air condition[ing] in that lab," says Happi. "It was so hot."

They deactivated the virus and amplified its genetic material. Just before dawn, they had their answer.

"We were able to see that, oh my God, this is Ebola," he says.

Happi promptly rang the country's health minister. He then advised officials how to implement contact tracing, isolation and ongoing monitoring.

In Guinea, Liberia, and Sierra Leone, more than 11,000 people died of Ebola. But in Nigeria, there were only eight deaths, largely because Happi and ACEGID were able to diagnose Ebola there not in weeks or days, but in hours.

Sentinel: A pandemic early warning system

"To beat an outbreak, you need two things," says Happi. "First is speed of detection. These pathogens don't wait. And second is accuracy, you've got to be accurate about what you're detecting."

This is ACEGID's war plan for thwarting disease in the region, an early warning protocol they're calling Sentinel. Say someone shows up at a clinic or hospital with a fever.

"But you don't know whether it's malaria fever, or it's Ebola fever, or it's Lassa fever, or it's typhoid fever or it's yellow fever," says Happi. "Everything is fever!"

ACEGID has a battery of tests for each of these and more — the diseases we know. But if those don't return any hits, then they sequence the genetic material of the unknown pathogen, which can serve as a blueprint for creating a test for a previously unidentified disease.

"You can just immediately that day be off to the races with a working diagnostic," says Sabeti. She and her team are developing smarter and faster ways to make those diagnostics, which can then be pushed out to health facilities to track the outbreak, get a sense of its shape and velocity, assess its pandemic potential and take measures to contain it.

"With the spread of pathogens," says Sabeti, "what's happening in one village is going to directly, quickly impact another."

ACEGID is now empowering others to do this work themselves, across a growing footprint. They have trained over 1,500 people from 48 African countries.

One of them is Delia Doreen Djuicy, a virologist at the Centre Pasteur in Cameroon. This spring, Djuicy spent three weeks at an ACEGID workshop on how to sequence the DNA of the mpox virus, and left feeling inspired.

"My feeling is, wow, if ACEGID can do so, my own institution also can move to that level. And why not beyond?" she says.

The impact of all this effort was evident during the COVID-19 pandemic. In February 2020, the hospitals that ACEGID worked with in Nigeria, Sierra Leone and Senegal had COVID diagnostics before any U.S. hospital did. In addition, Happi says, Africans sequenced over 100,000 coronavirus genomes.

"People within the continent of Africa understood that their destiny should be in their hands," he says, "that they should take full responsibility when it comes to outbreak response. They see themselves as part of the solution."

Sabeti says she couldn't be prouder of what they have accomplished. "The most profound thing that ACEGID is doing is creating a continent of people who are classmates in the same enterprise together," she says. "That kind of coordination, that kind of camaraderie, that is the only way we're going to really stop pandemics."

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