It takes a life every 30 seconds and sickens almost 250 million people a year… but this is no AIDS epidemic; no newly emerged disease that medical science is scrambling to control. Malaria has been a scourge of mankind throughout recorded history, so what exactly is this disease and why has it proved so resistant to our efforts to eliminate it?
Malaria is caused by a microscopic parasite called Plasmodium. It is neither a virus nor a bacterium but a complicated single-cell creature more akin to an amoeba [1]. Unlike an amoeba, however, Plasmodium cannot live independently, but instead it lives inside the red blood cells of a human or other animal. Within two days of infection, a malaria parasite can entirely transform a red blood cell, digesting its contents and dividing into as many as 32 new parasites, which then burst out and invade new cells. These blood cells are a perfect hiding place for a parasite – they are full of protein, bathed in nutritious blood and protected from the immune system, which generally avoids attacking its own cells.
Since the parasite grows at such a fast rate, fever and anaemia are two common symptoms of malaria. Fever occurs when infected blood cells burst, releasing new parasites together with a flood of toxins. They tend to burst synchronously, which explains why a cyclic fever peaking every 2 days is a classic sign of malaria. Anaemia, meanwhile, can be lethal, particularly in infants, and this occurs when massive numbers of red blood cells are destroyed too fast for the body to replace them. The most dangerous form of malaria, however, is “cerebral” malaria: the patient falls into a coma and frequently dies, while those who survive are at risk of brain damage. Cerebral malaria is probably caused by infected red blood cells clogging the tiny vessels that supply the brain.
At least 90% of malaria deaths occur in babies or young children, whereas adults who are regularly infected can develop enough immunity to carry parasites without apparent symptoms. However, complete immunity is rare, so unlike measles or chicken pox, people tend to suffer from malaria repeatedly — even constantly — throughout their lives.
Transmission of malaria
The name “malaria” means “bad air”, since people once believed that it was caused by the damp air near swamplands. This is understandable, since malaria is actually spread by the Anopheles mosquitoes which breed in standing water. A mosquito sucks up parasites together with a blood meal; the parasites mate and divide inside the insect’s gut, then they are injected into a new host when the mosquito bites again. In fact, Plasmodium is a parasite of mosquitoes as well as humans, since it is harmful to both these species. Nevertheless, hijacking a flying insect is a great way for a parasite to get around!
Preventing and treating malaria
The easiest way to prevent malaria is to prevent mosquito bites. Malaria was eliminated from the USA and southern Europe in the 1940s and ‘50s simply by draining and spraying swamps with the insecticide DDT, thus killing off mosquitoes. These successes prompted a massive push to eliminate malaria from Africa and Asia in the same way. The campaign saw some success in the 1960s but it was thwarted by the rise of insecticide-resistant mosquitoes, plus the discovery that DDT was seriously toxic not only to insects but also to people and other animals.
Although these elimination efforts failed, the targeted use of pesticides remains a key strategy for controlling malaria today. Sleeping under an insecticide-treated net is highly effective, since it protects the sleeper and also kills any hungry mosquitoes that land on the net. Crucially, bed-nets can be used even in the poorest settings where no medical services are available, so the distribution of cheap or free nets has been a key element in recent malaria control efforts. Likewise, spraying the walls of houses with a long-lasting insecticide protects the inhabitants.
But what if a person still gets bitten? Despite a growing research effort, there are no good vaccines against malaria. The parasite has sophisticated strategies for avoiding the immune system, both by hiding in human cells and by regularly changing its appearance, so developing a vaccine that can protect us against all possible guises of the parasite is a huge challenge. More sophisticated strategies are also being pursued, such as making and releasing mosquitoes that cannot breed or cannot carry malaria, but they remain a long way from implementation. Drugs to treat the disease, meanwhile, have a long and troubled history.
Back in the 19th century, the first anti-malarial to become widely available was quinine, familiar to many of us as the bitter taste in tonic water [2]. This was followed by the related drug chloroquine. Chloroquine was a brilliant treatment: cheaper, safer, and more effective than quinine, it was used throughout the world for many decades. Unfortunately, it is now almost useless. Just as bacteria can evolve resistance to antibiotics, or mosquitoes to insecticides, Plasmodium eventually became resistant to chloroquine. Several new drugs have since been developed, but resistance is a huge recurring problem and some drugs have lasted just a few years before becoming useless. Today, the only really reliable drug we have left, artemisinin, has been combined with a second, longer-lasting drug in the hope that the double-whammy will prevent resistant parasites from developing. However, the regime has already proved difficult to enforce and the first reports of low-level artemisinin resistance emerged from Cambodia in 2009 — probably aided by cheap, black-market formulations of the single drug that are widely available in that region.
The outlook for malaria control
Almost a million people in tropical and sub-tropical regions died of malaria in 2009 — that’s about half the number killed by the much more widely-publicized AIDS epidemic. Add to this the estimated 243 million infected each year and the global burden of malaria is clearly enormous [3]. Nevertheless, a combination of strong funding and political commitment has seen several countries making great strides in the past decade, as the World Health Organization has aggressively pursued its “Roll Back Malaria” initiative, distributing bed nets and providing rapid, effective drug treatment. Meanwhile the charitable Gates Foundation has made a huge investment in malaria control, and in 2007 Bill Gates announced an ambitious goal of worldwide elimination of malaria. After the hubris and subsequent failure of malaria elimination in the 1960s, this appears both laudable and controversial. Whether or not it succeeds may depend largely on who wins the drug-resistance race: man and modern medicine, or malaria.
– Catherine Merrick studies malaria at the Harvard School of Public Health.
References:
1. Shah, Sonia. The Fever: How Malaria has Ruled Humankind for 500,000 years. New York: Farrar, Straus and Giroux, 2010.
2. Rocco, Fiammetta. The Miraculous Fever-Tree: Malaria, Medicine and the Cure that Changed the World. New York: HarperCollins, 2003.
3. World Health Organization ‘World Malaria Report 2009’: http://www.who.int/malaria/world_malaria_report_2009/en/index.html