Why is AIDS so much more common in Africa?

Why is AIDS so much more prevalent in Africa than in other parts of the world? The question is both important and controversial. It is important because two-thirds of those infected with HIV, the virus that causes the disease, live on that continent. It is controversial because some of the explanations are behavioural, and are seen by many as racist slurs.

Broadly, there are three proposed explanations. One is that because AIDS started in Africa, it has had more time to spread there. The second—the behavioural one—is that both formal and informal polygamy are more common in Africa than elsewhere. The third is that African physiology is unusually susceptible to the disease.

All three probably play a part. But a paper just published in Cell Host & Microbe suggests that a significant part of the answer may indeed be physiological. Weijing He of the University of Texas Health Science Centre, in San Antonio, and his colleagues have discovered that a genetic variation which is common in Africa both makes people more susceptible to infection and keeps them in a symptom-free state for longer, allowing them to pass the disease on.

Surface tension

This variation involves the flipping of a single genetic “letter” in a gene called DARC (the Duffy antigen receptor for chemokines). This gene, as its name suggests, encodes a protein that regulates the level in the bloodstream of inflammation-causing chemicals called chemokines. That protein sits, among other places, on the surfaces of red blood cells. Or, rather, in the variant, it doesn’t. The mutation means that Duffy receptor proteins are not made in red cells.

Since other chemokine receptors are known to be involved in AIDS, and since two-thirds of sub-Saharan Africans lack the Duffy receptor on their red blood cells although such a lack is rare in other groups of people, it seemed an obvious candidate for investigation. Unfortunately, the team did not have a suitable group of Africans available for study. They did, however, have access to a group of American airmen, some of whom are of African descent. America is good at looking after its servicemen’s health and, in exchange, many of those airmen have agreed to be part of a long-term medical study that looks at all sorts of health-related questions. Indeed, some have participated in this study for 22 years.

Dr He and his colleagues looked at the genes of airmen who classified themselves as black and found that the ones infected with HIV were more likely to lack red cells bearing the Duffy receptor than chance would suggest. Moreover, and more unexpectedly, such people took two years longer to progress from the point where they were infected with the virus to the one where they began to show the first symptoms of AIDS. That is two years when a man ignorant of his infection would be less likely to take precautions to stop it spreading. The upshot, when the team crunched the numbers, was that the variant form of DARC may be responsible for 11% of the African epidemic.

The mystery is why the variant of DARC that leaves red blood cells without receptors should be so harmful. The team also did some laboratory experiments, which showed that HIV binds to the receptor. Although that mops up HIV from the bloodstream, the virus then passes from the red blood cells to the white immune-system cells most susceptible to infection. An absence of receptors should therefore be a good thing, because it closes off a shortcut to infection. Clearly it is not, nor do the team know why their absence prolongs the period that the disease is latent.

That is an important lesson about the difficulty of extrapolating laboratory results into the real world. Had the two arms of the study not been carried out in parallel, future researchers might have travelled up an expensive and time-consuming blind alley.

Another question is why such a disastrous mutation should have spread so widely in Africa. The answer is probably that it once protected against another disease, malaria. Indeed, it still does, to a certain extent. The variant form of DARC stops the growth of Plasmodium vivax, one of the four parasites that can cause malaria. This parasite is not, however, as deadly as Plasmodium falciparum, the main cause of malarial mortality. Nor is it as widespread in Africa. But it is not just people who evolve to evade pathogens. Pathogens evolve to evade the evasions. And that is what Robin Weiss of University College, London, another member of the team, suspects has happened. He reckons falciparum was once controlled by variant DARC. But no longer. It has managed to escape that control, and left humanity with a genetic weakness that another pathogen, HIV, has exploited.

The Economist, July 19-25th, 2008