For millenniums, whenever humanity has faced that which it could not explain, we have invoked magic or witchcraft. If we could not explain it, it could only be supernatural phenomena, perhaps the wrath of unhappy gods or ancestors.

Such is the case with rare diseases in African society. Most people do not know what they are or how to explain the “strange” symptoms that occur in those affected by them. In fact, we simply do not talk about rare diseases in African society. At least, very few do. We need to change this.

Let’s start with the facts. Rare diseases have nothing to do with supernatural phenomena. A rare disease, by definition, is a condition that affects one person out of 20,000 people. They are called rare because they affect a small number of people.

However, because there are so many different rare diseases, more than 6,000 of them, collectively they affect between 3.5% and 5.9% of the world’s population. In Africa, they affect an estimated 50 million people. Hence, while rare in terms of individual prevalence, in Africa, one in 26 people is affected by a rare disease.

The vast majority of known rare diseases, an estimated 72% of them, have a genetic cause. That means they occur because something has gone awry in our genes, the chemical code that instructs the body and all its parts how to develop, grow, function and maintain themselves.

Important link between genes and susceptibility to illnesses

Aberrations in the genes can lead to a deviation from normal function, causing illness. That is why understanding the association between the genes that people carry and the illnesses they are susceptible to due to their genes is so important. The remaining 28% of rare diseases do not have a genetic origin but are caused by infectious, immunological or environmental factors.

Rare diseases affect the individual in brutal ways. They are often life-threatening, causing lifelong, tremendous pain and suffering. They tend to be chronic in nature, causing progressive, degenerative, debilitating illnesses. They can delay development in children or cause the degeneration of muscles and neurons, eventually causing disability.

Though there are more than 6,000 rare diseases and their impact on quality of life is severe, only 5% of them have a known therapeutic intervention. Why is this? Because each condition has a low prevalence, each disease affects relatively few people. Therefore, for each rare condition, there tends to be relatively little knowledge and medical expertise available.

Investment into rare disease research also remains low; after all, individually, they affect relatively few people and thus fail to garner the interest of funding bodies. Hence, scientists are still to gain a molecular and epidemiological understanding of most rare diseases.  

Consequently, when it comes to patients, most of them are left undiagnosed and without treatment or care options. Diagnosis, treatment and care, when available, however, make a huge difference – significantly extending life expectancy and the quality of life of not just the affected patients but entire families.

Rare diseases impact families, communities and African society in significant ways, so there is a great need for investment in them. One would think that the severe societal impact rare diseases have would make for a compelling investment case. Alas, in a world that measures the return on investment in purely financial terms, this may not be the case.

Burgeoning burden of disease

So, how does one make an investment case for rare diseases on a continent creaking under the weight of a burgeoning burden of disease and a million-and-one competing health priorities, most of which are not being addressed?

Simple – by making a case for investing in strengthening health systems to equip them to provide society with a variety of services needed to meet all the needs of entire national populations, and not just the politically visible problems like HIV, TB and malaria as we do now. Health systems should have scope to provide desperately needed services for rare diseases also.

Africa’s health priorities are driven by the Western-centric global health security paradigm that seeks to minimise the infectious disease threat that Africa poses to the West. Consequently, most investment in the African healthcare context goes into pathogen genomics, that is, the analysis of genetic material of disease-causing micro-organisms.

For instance, the Africa Centres for Disease Control and Prevention’s (CDC’s) Institute for Pathogen Genomics made significant investments in pathogen genomic surveillance during the Covid-19 pandemic. This enabled Africa to incorporate pathogen genomics to improve disease surveillance and manage the SARS-CoV-2 pandemic on the continent.

Pathogen genomics is also the recommended tool for the surveillance of TB, malaria, HIV and antimicrobial resistance. This genomic capacity is expected to become the backbone of future outbreaks and epidemic responses. However, between pandemics, we can lose this investment if not actively sustained.

So, a critical question is how do we maintain it?

One possible solution is to use the African genomic screening muscle in the interpandemic periods to perform population-based human genomic studies for a range of health problems afflicting African society, including rare diseases.

Africa has already been using this genomic muscle for widespread genomic testing for pathogens like HIV, TB and malaria. When the Covid-19 pandemic hit us, that expertise was quickly adapted for SARS-CoV-2 testing.

With a few tweaks, it could be as easily adapted to provide essential services for problems confronting people on the African continent today, like non-communicable diseases, and just as easily, for rare diseases, 72% of which are of genomic origin, as mentioned above.

On average, rare diseases in Africa are only diagnosed after five to seven years

Today, though, if you are a rare-disease patient in Africa, it takes an average of five to seven years to get diagnosed. This perpetuates health inequity and delays access to treatment and health services that are so critical to improving the quality of life of individuals affected by rare diseases and their families.

While only 5% of rare diseases have a medical intervention today, having one’s rare disease accurately diagnosed almost always opens up improved care possibilities that have a positive impact on the patient’s quality of life.

One part of the problem with rare disease diagnosis in African countries is that African health systems are severely underfunded and undercapacitated and have virtually nothing in place to provide care for rare disease patients.

Another part of the problem is that African genes are significantly underrepresented in global reference databases that capture the association between genomes and disease. Hence, when trying to make a diagnosis of a rare disease, the lack of pertinent reference data makes it difficult to interpret genomic sequence data from individuals of African ancestry. This, in turn, can lead to the misinterpretation of data or to the wrong attribution of the cause of illness.

For instance, it is common that a person with a rare genetic disease gets misdiagnosed as having an infectious disease, which may present with similar symptoms. Indeed, retrospective analysis of past data has confirmed significantly higher misclassification of rare diseases in people of African ancestry.

Many genetic variants responsible for rare diseases identified in African populations are novel. And for them to be picked out during diagnostic genetic screening, they must be present in genomic reference databases.

But for this to happen, we must fix the lack of African participation in global genomic studies and the limited availability of genomic data of African origin in reference databases.

The reason they are underrepresented is simple. To date, African populations have been largely excluded from global genomic studies. Few genomic studies are done on the African continent, but this is beginning to slowly change.

Nevertheless, this limits our understanding of the genetic variants and their prevalence in African populations, and consequently, our ability to fully interpret genomic data of African origin.

In essence, this puts beyond reach innovations such as diagnostics by next-generation sequencing which enables simultaneous analysis of multiple genetic abnormalities and helps patients get diagnoses faster.

Improving African participation in genomic studies is something within our power to change, if more investment is made to support genomic studies on the African continent. Such an investment would help improve diagnosis and standards of care for rare diseases in the African context.

Genomic research in Africa is growing

Among the myriad things that are needed, improving diagnosis is a good first step towards improving standards of care and health outcomes for rare diseases in the African context. Recent developments suggest that winds of change are blowing and genomic research on the continent is growing. A growing network of institutions and organisations are performing genomic studies on the continent and advocating for Africa’s rare disease patients to access research through participation in clinical trials.

With time, this will inevitably unveil new therapeutic targets based on currently unidentified novel rare variants in the African genome. Given that only 5% of rare diseases have a medical intervention and African genomes carry more variations than European genomes because they have a longer evolutionary history, they offer more insights into potential new therapeutic targets for detecting and treating rare diseases.

That is why investing in a Pan-African genome initiative would provide great returns. We must advocate increased investment in this important work that would benefit all of humanity, not just Africans. DM