NAIROBI — As a young boy growing up in rural Cameroon, Dr. Christian Happi couldn’t understand why his friends kept dying. The children would develop a high fever, start convulsing, and die soon after.
After being hospitalized for the fever himself, at the age of 9, he asked his mother why there was no cure for what they were experiencing. But she didn’t have an answer. He vowed to someday find the cure.
He later learned, while at university, that his friends had the symptoms of cerebral malaria.
His career led him down a path of researching drug resistance in malaria patients. In order to understand this, he learned to sequence genes, and then genomes — all the genes in an organism.
Now, Happi is a leading genomic sequencing expert on the African continent. He runs the African Center of Excellence for Genomics of Infectious Diseases at Redeemer's University, in the small city of Ede in southwestern Nigeria. In early March, his lab was the first on the continent to sequence the genome of SARS-CoV-2, the virus that causes the COVID-19 disease.
“I want genome sequencing to be more accessible and I want Africans to be in the driver's seat.”— Dr. Christian Happi, director, Center of Excellence for Genomics of Infectious Diseases
Genome sequencing is used to track mutations of the coronavirus. Different clades, or variations of the same strain, of the coronavirus are circulating globally, and any significant mutation could mean that a vaccine, drug, or diagnostic test could work in one part of the world but not another.
Researchers have contributed over 34,300 genome samples to a global database, GISAID, in order to keep track of the virus’ mutations. Of these, only 224 samples were sequenced in laboratories in nine countries on the African continent. This low number is partially because of capacity, but also because the number of confirmed cases on the continent is only 2% of the global caseload.
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But efforts to strengthen the capacities of African researchers to sequence genomes are underway, working to ensure the clades of SARS-CoV-2 circulating on the continent are integrated into the tools developed to fight the virus.
Decoding the virus
To sequence a genome, a swab — taken from a patient testing for COVID-19 — is sent to a lab.
The lab then converts the RNA of the virus into DNA so that it can be sequenced, and decodes the DNA into a letter combination. Researchers compare this code to sequences in a global database, to keep an eye on the virus, monitoring to see if a letter changes in that code, which signifies a mutation.
Every virus mutates but not every mutation is meaningful, said Greg Essert, commercial director for the Middle East and Africa at Illumina, the global leader in next-generation genome sequencing technologies. But sometimes these mutations can have an impact on whether a treatment, vaccine, or diagnostic test works. A mutation could also make a virus more contagious or deadly, as well as more benign.
“That's why it's so important to make sure that we do whole genome sequencing of the virus on a regular basis to monitor those mutations,” Essert said.
Currently, SARS-CoV-2 is not changing its structure significantly — the mutations are understood to be occurring less than the flu, he said.
But the virus is not under any pressure because there is no treatment or vaccine to combat it. Viruses can mutate to escape destruction by a treatment or vaccine. If sequencing shows new mutations in the virus, these mutations could lead to a treatment or vaccine becoming less effective.
Through genomic sequencing, researchers can also identify the origin of the virus, its evolution and spread, identify clusters of cases, as well as community transmission, according to experts.
With travel restrictions because of the pandemic, sending samples to be processed outside the continent is not ideal.
“If you'd have to send your samples abroad, it would take you ages before you get a result back. By that time, the virus has spread, it has mutated, and you cannot keep track of it,” Essert said.
Beyond speed, there is also concern that labs on other continents might de-prioritize sequencing genomes from beyond their borders.
“Each country is focusing on its own people ... They may not have enough time, or they may not wish to sequence samples from Africa when they still have to also deal with their own,” said George Michuki, founder and CEO of The Africa Genomics Centre and Consultancy, which is currently the only company offering sequencing genomes of SARS-CoV-2 in Kenya. The country has not yet contributed a sequenced genome to the international database because of delays caused by seeking patient consent.
“Getting the lab up and running in these circumstances, in this hostile environment, that is the greatest challenge.”— Greg Essert, commercial director for the Middle East and Africa, Illumina
When Ebola hit West Africa in 2014, Happi’s lab was the first to sequence a genome of the virus and make it publicly available — within the first few weeks of the outbreak in Sierra Leone.
This was the first time that this type of research was conducted during an outbreak and researchers used that information to guide the public health response, he said. In outbreaks prior to this, epidemiologists were sent to the field to collect samples and conduct the research after the outbreak.
But because it was a new approach, this tactic didn’t go over well with some, who called it unethical or illegal to conduct this type of research amidst an ongoing outbreak, he said.
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“When you do this for the first time, people call you names,’” Happi said. “The pressure was so much at some points, we almost felt like we wanted to give up because we had been blackmailed and we had been called names. But, fortunately, we stood our ground.”
As the Ebola outbreak progressed, other groups also started to sequence the Ebola virus.
In the years following, more genomic sequencing platforms were set up across Africa, and researchers have sequenced outbreaks of Lassa fever, monkeypox, yellow fever, malaria, among others.
Now it’s become more or less a standard practice to have ongoing research during an outbreak to inform the public health response, Happi said.
But expanding this access has challenges, mainly funding.
A whole-genome sequence can cost several hundreds of dollars, depending on the type of machine used, the number of samples that are run through that machine at a given time, and the quality of the sequencing, according to Dr. Mushal Allam, senior bioinformatics scientist at South Africa’s National Institute for Communicable Diseases. Allam’s lab sequenced the first SARS-CoV-2 samples in South Africa.
There are also challenges in building out this network during the pandemic. Border closures and travel restrictions make it harder to get supplies into countries, as well as experts who can train people on how to use the equipment, Essert said.
“Getting the lab up and running in these circumstances, in this hostile environment, that is the greatest challenge,” he said.
Responding to the pandemic
In December, the Africa Center for Disease Control and Prevention launched the Pathogen Genomics Intelligence Institute with the goal of creating a network of laboratories across the continent with capacity to genome sequence. Rather than setting up the capacity in every country, countries without the ability to sequence genomes can send their samples to one of the regional labs.
At the end of April, Illumina donated $1.4 million in equipment, software, and reagents — the main chemical ingredient needed to sequence the virus — through the Africa CDC, to 10 countries on the continent, to equip them with the tools to perform next-generation sequencing. It committed to supporting these countries for a year.
Genomes of SARS-CoV-2 have been sequenced in laboratories in the Democratic Republic of the Congo, Egypt, Gambia, Ghana, Nigeria, Senegal, South Africa, Tunisia, and Uganda. Algeria sent its samples to a laboratory in Paris.
The Institut National de Recherche Biomédicale in DRC is contributing nearly 60% of SARS-CoV-2 genome sequences from the African continent. Over the last couple of years, it built up this capacity during the ongoing Ebola outbreak in the eastern part of the country.
And it was Happi’s lab that sequenced the genome from the first COVID-19 case in sub-Saharan Africa, which was confirmed in Lagos, Nigeria, at the end of February. While Happi and his team spent much of their time in the following months testing for positive COVID-19 cases, they plan to release another 30 sequenced genomes this week.
“I'll probably never find a cure to malaria, but at least I'm very happy that we've been able to use genomic sequences as a way to address major public health problems in Africa,” he said.
“I want genome sequencing to be more accessible and I want Africans to be in the driver's seat.”
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