genomics revolution

Tests developed to treat white people may be unsuitable for Africans.

Scientists have been pushing to improve health care by tailoring to the environment, lifestyle and genes of individuals. Few have taken this precision-medicine approach in Africa, but that’s changing.

Ethiopia banned the painkiller codeine because many Ethiopians carry a gene variant that makes them convert the drug to morphine, which can cause breathing problems.

Ethiopia banned the painkiller codeine because many Ethiopians carry a gene variant that makes them convert the drug to morphine.

Botswana opted for a more expensive HIV drug because 13 percent of the population had a gene variant that caused problems with a cheaper drug.

Precision public health is a new approach to precision medicine that bases decisions on populations and communities rather than on individuals.

From Nature.com. Story by Linda Nordling.

It took a public-health disaster for the Zimbabwean government to recognize the power of precision medicine. In 2015, the country switched from a standard three-drug cocktail for HIV to a single-pill combination therapy that was cheaper and easier for people to take every day. The new drug followed a World Health Organization recommendation to incorporate the antiretroviral drug efavirenz as a first-line therapy for public-health programs. But as tens of thousands of Zimbabweans were put onto the drug, reports soon followed about people quitting it in droves.

Collen Masimirembwa, a geneticist and founding director of the African Institute of Biomedical Science and Technology in Harare, was not surprised. In 2007, he had shown that a gene variant carried by many Zimbabweans slows their ability to break down efavirenz. For those with two copies of the variant — about 20 percent of the population — the drug accumulates in the bloodstream, leading to hallucinations, depression and suicidal tendencies. He had tried to communicate this to his government, but at the time efavirenz was not a staple of the country’s HIV program, and so the health ministry ignored his warnings.

Masimirembwa continued to publish his research, but the authorities took no heed until there was trouble. A lot of confusion could have been avoided if the government had listened, he says, “It’s not a bad drug. We just know it can be improved in Africa.”

Masimirembwa is a rare breed. Although scientists worldwide have been pushing for ways to improve health care by tailoring diagnostics and treatment to the environment, lifestyle and genes of individual patients, few researchers have taken this precision-medicine approach in Africa.

That may be changing. In the past five years, international research-funding organizations have invested more than US$100 million in projects to boost genetic research on people in Africa. These studies could lead to improved treatments for Africans as well as for people of recent African descent in Europe and the Americas, who tend to experience more ill health than other ethnicities — a situation that is often attributed to socioeconomic challenges, but which some scientists say could also have genetic roots.

Although few would question the importance of African genomics, opinions differ on whether this will translate into better care. Globally, precision medicine has failed to live up to its promise, even in countries that spend lots of money on health. And some argue that the money spent on investigating genes should instead be used to improve basic health care on the continent.

Many African scientists bristle at that simple calculus. They are frustrated that they have been left out of research on everything from health to human origins — a field that has particularly benefited from African genome data — and they want Africans to gain from the work. For Masimirembwa and others, the money presents an opportunity to take control of how genetic data are collected and used. “Unless capacity is built on the continent, Africans won’t have a chance to participate,” he says.

Population-scale precision

There’s a big problem, however. Precision medicine is expensive. For a continent that, for the most part, struggles to provide even basic health care, tailor-made treatments for individual patients may seem like an unaffordable luxury.

Enter “precision public health” — a new approach to precision medicine that bases health decisions on populations and communities rather than on individuals. It would use genomic insights into a country’s population to inform general treatment programs. For instance, a country might tweak its essential medicines list that specifies the drugs it buys in bulk at reduced rates from pharmaceutical companies, to avoid medicines that are known to cause problems in its population.

This is already happening in some places. Botswana — a middle-income country — stopped using the three-in-one drug containing efavirenz in 2016, opting instead for a newer and better-performing, but more expensive, drug called dolutegravir. The gene variant that causes problems with efavirenz is common in Botswana — around 13.5 percent of the population has two copies of it. And in 2015, Ethiopia banned the use of the painkiller codeine, because a high proportion of people in the country carry a gene variant that causes them to rapidly convert the drug into morphine, which can cause breathing problems or even death.

Africa is where humanity originated and where humans have lived the longest, so populations there have diverged more than on other continents. Its people have genetic variants that are found nowhere else.

These two factors mean that scientists are missing a big piece of the puzzle when it comes to human genetics, says Charles Rotimi, founding director of the National Institutes of Health’s Center for Research on Genomics and Global Health in Bethesda, Maryland. Tests developed to inform treatment options for white people might be unsuitable for Africans and people of recent African descent. “We are in a position to make wrong diagnoses,” he says.

Rotimi is one of the founders of the Human Heredity and Health in Africa (H3Africa) Initiative, created in 2010 by the London-based biomedical charity the Wellcome Trust and the U.S. National Institutes of Health. Aiming to build genomics research capacity in Africa, the first round of the program distributed $70 million to African scientists who teamed up with partners from the U.S. and Europe. A second round, worth around $64 million, is at the application stage.

The research targets conundrums that have dogged clinicians for some time — such as why Africans have a higher risk of developing chronic kidney disease, and do so at a younger age, than do white people.

Nephrologist Dwomoa Adu at the University of Ghana Medical School in Accra, one of the principal investigators in the H3Africa Kidney Research Network, says there are no known environmental factors that explain this. But many Africans carry variants in the gene for apolipoprotein L1 (APOL1) that seem to confer an increased risk of developing kidney disease3. These variants have probably flourished in Africa because they confer resistance to trypanosomiasis, or sleeping sickness, a parasitic disease transmitted by the tsetse fly. But as life expectancy has increased in African countries, the incidence of kidney disease has risen markedly. And because there is little dialysis or kidney-transplant capacity on the continent, most people who develop the condition die, says Adu. “It’s a nightmare illness.”

Adu’s study is testing the link between the APOL1 gene and kidney disease in Africa at a greater sensitivity than previous studies. But being able to predict the disease with a gene test will be of little use in places where treatment is inaccessible. So Adu is also looking to understand the mechanism by which the gene causes disease, in the hope that this will lead to new, more-affordable, treatments. “It might be possible to block the mechanism,” he says.

Other H3Africa projects are looking for genetic clues to people’s varying susceptibility to HIV progression, type 2 diabetes and stroke.

Cost and capacity

The attention that genomics research is getting in Africa has not been without critics. Cost is a major concern. Like most developing regions, Africa is seeing a rapid rise in non-communicable diseases such as cancer.

In developed countries, cancer treatments are profoundly informed by genomics. But many African nations have only a handful of cancer specialists, and limited capacity for diagnosis and treatment. Although breast-cancer rates, for example, are lower in parts of Africa than in developed countries, more Africans die from the disease and not just because of a lack of access to care — standard treatments sometimes seem less efficient in some African women.

Still, basic cancer-therapy equipment may be higher on the wish list than new genomic tests tailored to African people’s tumors. In April last year, for example, Uganda’s only radiotherapy machine broke down, forcing people to travel to neighboring Kenya for treatment, at their own cost.

Reinhard Hiller, director of the Centre for Proteomic and Genomic Research, a non-profit bioinformatics organization in Cape Town, is pleased that there is growing interest in African genomics.

His lab is one of the few in Africa that can do genomic sequencing. At the moment, most of its therapeutic work is for the private health sector in South Africa. But he’s hopeful that genomic medicine can make it into the public sector. The main constraint, besides the cost, is the lack of technicians and counselors.

The slow pace of government policy in Africa presents another stumbling block for the rollout of precision medicine.

Read more at Nature.com.

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