Malaria

A connection between swampy areas and fever was made centuries ago, and the word malaria reflects the popular belief that the illness was caused by bad air (Italian, mal aria). During the sixteenth century, people discovered that the disease could be treated using quinine, a compound derived from the bark of the tropical Cinchona tree. No vaccine for malaria has yet been developed, although preliminary trials for an initial vaccine were scheduled to begin in malaria-endemic areas in late 2003. Currently, the synthetic agent chloroquine is the most widely used antimalarial drug; it can clear nonresistant parasites from the blood in two to three days.

Chloroquine is often combined with the drug primaquine for malaria prophylaxis—that is, as protection for people who are at risk of becoming infected while visiting in malarial regions. Chloroquine attacks parasites that are circulating in the blood; primaquine is necessary to eradicate dormant parasites from the liver. Malaria prophylaxis begins one week before entering a malarial area and continues for several weeks after returning to unaffected areas, because of the complex nature of the parasite's life cycle and the potential for relapse.

Unfortunately, many persons experience extreme side effects from antimalarial medications. Further, chloroquine-resistant strains of falciparum malaria are on the increase worldwide. For this resistant parasite, the drug mefloquine is the preferred method of prophylaxis and treatment, although resistance to this drug may emerge rapidly, and resistant strains have been found in areas where the drug has never been used.

Efforts at preventing the disease have been directed at draining swampy areas and spraying for mosquitoes in areas where they breed. A DDT-spraying campaign undertaken in India was effective for several years, until the mosquitoes evolved resistance to the insecticide used against them and rebounded with a vengeance. (Further, the use of DDT is problematic as it has numerous environmental side effects; its use, though not its manufacture, is banned in the U.S.) Avoiding being bitten may be the best defense, and people in malarial areas are advised to avoid the outdoors during peak mosquito feeding times (dusk and dawn), to use window screens, and to sleep under nets treated with insecticide. However, there are millions of persons in malaria-infested regions who are too poor even to acquire window screens or netting.

In areas where malaria is endemic and ever-present, many individuals appear to be immune to the disease. In some populations, including those of India, Latin America, southern Europe, and especially Africa, the gene causing sickle-cell anemia is present. This gene is directly connected with malaria immunity: a person possessing one copy of the sickle-cell gene will be malaria-resistant, while a person possessing two copies of the gene will be both malaria-resistant and sickle-cell anemic. Further, even among persons who do not have the sickle-cell gene at all, not all infected individuals have symptoms; many individuals will host parasites within their bodies for months and years without showing symptoms. This suggests that a vaccine could be developed, if the mechanism of host immunity could be identified. Thus far, however, the complexity of the immune response and the diversity of the parasite's evasive mechanisms have prevented researchers from clinically assessing immunity. Evidently, each of the protozoan's developmental stages bears different antigens (the molecules that trigger the development of immunity in the host). What is more, these factors are different for each of the four strains of the parasite. This explains why no individual is known to be immune to all four malarial strains.

The fact that Europe and North America have not been afflicted by malaria since the early twentieth century has meant that for decades, relatively little research was done on malaria vaccines, new malarial drugs, or specialized insecticides. Of the 1,223 new drugs developed from 1975 to 1996, only three were antimalarials. However, first-world funding for malaria research has increased dramatically since the mid-1990s, and in 2002, researchers announced that they had completely characterized the genomes of the Plasmodium falciparum parasite and its vector (means of transmission), the Anopheles gambiae mosquito. It is hoped that this knowledge will increase understanding of parasite-host and parasite-vector relationships, symptom causation, and drug responses, and will accelerate vaccine development and suggest possibilities for new drugs. For instance, researchers may design drugs targeted to blocking the function specific genes essential to the survival of the parasite.