Sept. 9, 2011, 11:28 a.m.
Many people think of malaria as a single disease. It isn’t.
26 May, 2011
“WHEN is a disease not a disease?” sounds like a childhood riddle. One answer, though, might be, “when it is vivax malaria.” No one could accuse the global medical establishment of ignoring malaria. There is, indeed, an entire international organisation, the Global Fund to Fight AIDS, Tuberculosis and Malaria, that is explicitly aimed at getting rid of it. Yet malaria comes in several versions, two of which are widespread. They are caused by related parasites, Plasmodium falciparum and Plasmodium vivax. They are both transmitted by Anopheles mosquitoes. And many actions, such as draining swamps where mosquitoes breed, and many drugs, such as artemisinin, work against both. But that does not mean the diseases are identical. In practice, most of the world’s antimalarial effort is directed against falciparum. Those who study vivax sometimes feel that the object of their attention is invisible.
In the past, the focus on falciparum made sense. Money was tight. Falciparum kills 1m people a year, most of them children. Vivax often debilitates, but rarely kills. Now, though, health has moved up the international agenda, and the supply of money to deal with it has increased over the past decade as politicians and aid agencies have come to understand that infectious diseases are not merely causes of suffering and death—though that is bad enough—but are significant barriers to economic development, too. In this context a more sophisticated approach is needed, in the view of those who study vivax.
Numbers are hard to come by, but Ric Price, of Oxford University, reckons that between 80m and 390m people suffer the effects of vivax every year. The cost, to the sufferers alone, is between $1.4 billion and $4 billion a year—and that does not take account of consequential damage to the economies of the countries they live in. These include places like Central Asia and the Caucasus, where falciparum is unknown—for, unlike falciparum, which is genuinely a tropical disease, vivax can thrive in temperate climes. Indeed, in the first half of the 20th century it was found as far north as Archangel, in Russia.
A big part of the problem is knowing just how many people really are infected. Figures like Dr Price’s are based on confirmed diagnoses. Some researchers think the true numbers are much larger. The disease can be identified definitively only by putting blood smears under a microscope. Even then, the invaders are hard to detect. Unlike falciparum, vivax infects only the youngest red blood cells, those freshly emerged from bone marrow. As Lee Hall, chief of parasitology and international programmes at America’s National Institute of Allergy and Infectious Diseases, observes, you rarely get a blood smear with hundreds of parasites obvious in it. You have to hunt for them. That is, assuming a skilled technician with a microscope is on hand to do the hunting—not a safe assumption, given where most of those infected with malaria live. Millions of cases may therefore go undiagnosed.
That matters, because the diseases really are not the same. Comparing vivax and falciparum is a bit like comparing a monkey and an ape, according to Daniel Hartl, a population geneticist at Harvard University. To the man in the street, the two look pretty similar. To a zoologist, they are strikingly different. The parasites evolved, for example, in separate hosts. Falciparum was confined to apes for many millions of years and jumped, in Africa, from gorillas into humans some time in the past 300,000 years. Vivax is related to monkey parasites and probably originated in South-East Asia. That means the species have different biochemistries. Not all drugs that work on falciparum also work on vivax. For example, only primaquine can kill vivax once it has entered the liver.
The two parasites also piggyback from host to host on different species of Anopheles. Distributing bednets and spraying insecticide on the walls of houses—strategies that have worked against falciparum—are much less use against vivax because the 40-odd mosquito species which transmit it do much of their biting outdoors.
The parasites also have different effects. Though falciparum is far deadlier than vivax, it is cleared from the body in a few weeks. Vivax, by contrast, hides in the liver. An individual infected with it may remain symptomless for several years and then relapse. And the fevers, chills and paroxysms such relapses create are so intense that malariologists have a saying: the disease may not kill you, but you’ll wish you were dead. Severe or repeated bouts can lead to respiratory distress, mental disability, wasting disease and, at the extreme, rupture of the spleen. Moreover, those carrying dormant vivax parasites in this way cannot be identified, which means there is a huge reservoir of infected people who are in effect invisible.
That is not a bad strategy for a pathogen. Killing the host is terminal for the parasite as well as the person. Becoming dormant means you live to fight another day. It has also, in the jargon of evolutionary biology, pre-adapted vivax to a threat it has not evolved to deal with. The main selective force acting against falciparum at the moment is the efforts of global health agencies. As Jane Carlton, who studies vivax’s genomics at New York University, observes, “to be blunt, vivax doesn’t kill children in Africa, so it’s low on the funders’ priority list.”
And not just funders. Dr Carlton and her colleagues recently submitted a paper on vivax to PLoS Neglected Tropical Diseases, an online journal published by the Public Library of Science. She thought the pathogen fitted all the journal’s criteria for publication. It is chronic, infectious, a plague on both rural and urban poor, and, in her view at least, neglected. But the journal felt malaria, regardless of type, was “already sucking up too much attention,” she says. “They didn’t want any malaria papers at all. We really had to work hard to persuade the editorial board that vivax is a very different thing.”
They succeeded. PLoS did ultimately accept the paper and will publish it next month. Last year, too, it published a map (reproduced at the beginning of this article) of the distribution of vivax, independently of falciparum. Maybe soon, then, the riddle will have a different answer, as the world pays more attention to this invisible, horrible disease.