Colour DNA sequence Credit: Gio_tto/ / iStock/ Getty Images
Genomic data that largely excludes Africa’s extremely diverse populations poses a significant threat to the development of effective next-generation diagnostics and vaccines. Genomics experts warn that the current dearth of equity in research development pipelines is jeopardizing the efficiency of drugs, vaccines and diagnostics, posing preventable health risks, especially for understudied populations.
The experts argue that understanding the structure and variation of African genes would deliver critical insights, including which populations are at higher risk for certain diseases, and how they will respond to available medications.
According to Collen Masimirembwa , president of the African Institute of Biomedical Science and Technology, analysis of genetic variants has shown a 25% greater genetic diversity in African populations compared to other groups, with significant differences even within the continent.
In addition, medication response rates vary dramatically, with some as low as 30%, often due to individual immune system responses. This highlights the importance of understanding the impacts of genetic variations for optimal therapeutic outcomes, he said during a seminar delivered to the Stellenbosch Institute for Advanced Study. “Specifically, we need to ask: Will a drug work the same in people of African ancestry as it works in people of other ancestry groups?”
Evidence from the field
A newly published genome-wide genetic analysis of African babies in West Africa, which identified important genetic factors potentially impacting immunological response to the only available vaccine against tuberculosis (TB), is a case in point.
Entitled Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa, the study confirmed that several complement genes impact affect the cytokine response following BCG vaccination. Notably, the researchers also found limited overlap between the West African infants and cohorts of Western Europeans.
Although the Bacille Calmette-Guerin (BCG) vaccine is nearly 100 years old, its efficacy and how long immunity lasts following vaccination in infancy continues to stimulate considerable debate. Given that more than one-third of global TB deaths occur in Africa, with more than 500 000 African lives lost annually to the disease, the significance is clear.
“These data reveal strong population-specific genetic effects on cytokine production, and may indicate new opportunities for therapeutic intervention and vaccine development in African populations,” the authors wrote.
Other studies of European populations have also revealed genetic variation as one of the major factors driving inconsistent immune responses.
During his seminar in 2021, Masimirembwa highlighted another example, this time of the varying side-effects experienced by African and European HIV-positive patients receiving the antiretroviral drug, Efavirenz, in the early 2000s. More neuropsychiatric adverse responses were recorded in African patients, due to a higher frequency of a gene variation preventing efficient metabolism of the drug.
“We developed a genetic test and an algorithm for identifying at-risk individuals, and implemented dose adjustments for safe outcomes,” he explained.
Representation, balance and equity
Christian Happi, director of the African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer’s University in Nigeria, said the West African TB vaccine study further demonstrated the importance of sequencing an African genome.
But he said that while knowledge of African genetics was essential for more precise and focused administration of vaccines, the achievement of full understanding would require the sequencing of massive numbers of African genomes.
Importantly, Happi added, this is an issue not only of representation, but also of equity: “If the data we are using is skewed to one particular population, we won’t see equity in the design of the next generation of vaccines and diagnostics.”
Boahen concurred that lack of representation and lack of equity were closely related.
“It is becoming crystal clear that skewed genetic and epigenetic studies are limiting our understanding of most diseases.”
Thomas Scriba, deputy director of Immunology at the South African TB Vaccine Initiative, said efficacy of therapeutics could be significantly impacted by the fact that genetic regulation of immune responses in one setting was not universally translatable.
African populations may respond to a greater or lesser degree to a vaccine developed and tested in Europe or North America, resulting in higher or lower immune responses, or a different type of immune response altogether, he explained.
“African populations have been understudied, partly due to under-resourcing of African science, and less priority being placed on Africa,” Scriba added, stressing that much larger studies, with many more participants, were essential.
Another study in 2022, by largely African researchers, sought to identify the major barriers impeding the implementation of genomic medicine in African countries. Entitled A View on Genomic Medicine Activities in Africa: Implications for Policy, it drew responses from 12 African countries.
Lack of infrastructure and technologies to support research and clinical translation was cited as an impediment by 81% of respondents, while 64% said efforts were hampered by limited information about determinants of disease susceptibility in local populations.
Happi described Africa as “horribly behind”, a situation he said needed to be urgently remedied in light of the continent’s spiralling rates of infectious and noncommunicable diseases, complicated by socio-economic factors and fragile health systems.
“Africa constitutes 15% of the world’s population, but carries 25% of the global disease burden,” Masimirembwa said, stressing that a shift away from the one-treatment-fits-all approach was a critical requirement for long-term optimal, equitable health care.
