Featured Infectious Disease: Malaria

Malaria is one of the oldest and most frequently occurring infectious diseases in humans. The malaria parasite, transmitted through the bite of an infected female mosquito, disables hundreds of millions of people worldwide each year.

In 1989 the World Health Organization (WHO) declared malaria control a global priority. However, several challenges must be overcome. For one thing, Plasmodium falciparum, the most lethal form of the infectious parasite, has developed resistance to many of the antimalarial drugs currently available. And social and political factors, particularly in Africa, further challenge efforts to institute effective control measures. Currently, the most powerful prevention tools available may be some of the oldest and most primitive—herbal remedies and insecticide-impregnated bednetting. Ongoing biomedical research is aimed at developing new drugs, vaccines, and other tools to reduce disease.

What is malaria?

Malaria is a disease caused by a single-celled parasite called Plasmodium. The parasite reproduces and matures in stages inside humans, using different tissues to support its development. When an infected mosquito bites a human host, the parasite moves from the insect's saliva into the host's blood. Parasitic sporozoites head immediately to the liver, where they hide inside liver cells. There they reproduce and mature into merozoites, the form of the parasite that infects red blood cells or erythrocytes. The clinical symptoms of malaria—typically, chills and fever—occur as the merozoites burst from infected erythrocytes to reinfect other red blood cells and repeat the cycle. Attacks can last as long as 36 hours and may kill the patient. They can also cause cerebral malaria, particularly in children, resulting in convulsions, coma, and death.

When did it start?

Malaria probably originated in Africa. Fossils of mosquitoes 30 millions years old show that the vector for malaria was present well before the earliest history of man. Early travelers likely brought strains of Plasmodium from Africa to the New World, a phenomenon that continues to this day as tourists bring malaria home from areas in which the disease is endemic.

Who gets the disease?

Malaria is one of the leading cause of death in young children and pregnant women in tropical areas. Some 300 to 500 million cases of malaria are reported each year, resulting in almost 3 million deaths worldwide. In Africa, malaria accounts for up to one-third of all hospital admissions and up to one-quarter of all deaths of children under five. The disease kills about 2,800 children a day in Africa, usually before they are old enough to build up any immunity. Pregnant women appear to be particularly susceptible to infection and infected mothers have low birthweight babies who have an increased risk of dying. People with sickle cell trait (generally those who are heterozygous for sickle cell anemia, a disorder of red blood cells frequently found in Africans and African-Americans) appear to be less susceptible to malaria.

Where is the disease found?

Malaria remains a potential health threat in more than 90 countries around the world. The greatest risk occurs in sub–Saharan Africa, but Plasmodium faciparum is also found in Asia, Oceania, and Central and South America. In 1990, 80 percent of the cases of malaria occurred in Africa, with the remaining cases spread throughout India, Brazil, Afghanistan, Sri-Lanka, Thailand, Indonesia, Vietnam, Cambodia, and China.

How does it spread?

People suspected that malaria was linked to mosquitoes as far back as 1600 BC. The association of malaria with stagnant water—now known to be a breeding ground for mosquitoes—led the ancient Romans to institute drainage programs, the first known malaria intervention. But it wasn't until almost the dawn of the 20th century that scientists discovered that malaria was caused by a parasite transmitted to humans through the bite of the female Anopheles mosquito.

The discovery of DDT in 1942 made controlling the global spread of malaria seem possible. But spraying with the insecticide never totally eradicated the mosquito vectors. In the 1970s, control measures were relaxed because people thought the disease had been eradicated. In addition, some mosquitoes had by then developed resistance to DDT. Accordingly, the decade saw a massive resurgence in the number of cases of malaria worldwide.

Is there a treatment?

The primary objective of malaria therapy is to eliminate the parasites from the blood. In the 17th century, native Peruvian Indians used the bitter bark of the cinchona tree—a source of the drug quinine—to treat malaria. In the 1930s, the drug chloroquine was developed and became a mainstay in the antimalaria arsenal. The drug functions by blocking the parasite's ability to convert heme (the iron-containing pigment that gives red blood cells their color and that is toxic to the parasite) to nontoxic hemozoin.

Treatment of malaria using chloroquine has been hampered by the spread of drug resistance in the Plasmodium population. Although the mechanisms are not completely understood, chloroquine resistance is linked to changes in the parasite's genes that result in a diminished accumulation of the drug inside the parasite.

Given the rise of drug-resistant parasites, one of the major questions malaria researchers are impelled to address is whether it will be possible to produce vaccines to prevent disease. For example, researchers at the National Institutes of Health are currently working on developing malaria vaccines, in part informed by sequencing the chromosomes of P. falciparum. Other researchers also hope to use Plasmodium DNA to create a vaccine that should be easier and less expensive to produce than conventional protein-based vaccines because it will not require refrigeration and can be easily altered to keep pace with the ever-evolving parasite.

Malaria References

Klayman, D.L. Qinghaosu (Artemisinin): an antimalarial drug from China. Science 228:1049-1055, 1985.

Conway, D.J., C. Roper, A.M.J. Oduola, et al. High recombination rate in natural populations of Plasmodium falciparum. Proceedings of the National Academy of Sciences, U.S.A. 96:4506-4511, 1999.

Redd, S.C. and C.C. Campbell. "Malaria," in Hoeprich, P.D., M.C. Jordan, and A.R. Ronald (Eds.) Infectious Diseases, 5th Edition, J.B. Lippincott Company, Philadelphia, 1994.

Müller, H.M., G. Dimopoulos, C. Blass, et al. A hemocyte-like cell line established for the malaria vector Anopheles gambiae expresses six prophenoloxidase genes. Journal of Biological Chemistry 274:11727-11735, 1999.

Ichino, M., G. Mor, J. Conover, et al. Factors associated with the development of neonatal tolerance after the administration of a plasmid DNA vaccine. Journal of Immunology 162:3814-3818, 1999.

Newton, P. and N. White. Malaria: new developments in treatment and prevention. Annual Review of Medicine 50:179-192, 1999.

Fried, M., F. Nosten, A. Brockman, et al. Maternal antibodies block malaria. Nature 395:851-852, 1998.

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