malaria

Introduction

malaria, infectious parasitic disease that can be either acute or chronic and is frequently recurrent. Malaria is common in Africa, Central and South America, the Mediterranean countries, Asia, and many of the Pacific islands. In the United States it was found in the South and less frequently in the northern and western parts of the country.

Plasmodium falciparum is the most deadly of all the five Plasmodium parasites that typically cause malaria in humans. All the species require both the Anopheles mosquito and humans to complete the life cycle. Sexual reproduction of the protozoans occurs in the mosquito; an immature form is then transmitted to the human via the bite of the mosquito. In a person the parasite goes to the liver, replicates, and moves into the bloodstream, where it attacks red blood cells for their hemoglobin. Some of the plasmodia become sexually mature and are transmitted back to another biting mosquito. P. knowlesi, however, is primarily transmitted from monkeys to humans via mosquitoes.

Treatment and Control

The bark of the cinchona and its product, quinine, have been used in the treatment of malaria for centuries. After World War II, they were largely replaced by the synthetic analog chloroquine. The use of chloroquine, in addition to the use of DDT for mosquito control, was expected to eradicate the disease, but a World Health Organization campaign (1955–69) to eradicate the disease globally (by controlling mosquitoes long enough to allow the human population to become disease free) proved unsuccessful. Despite that, spraying successfully eradicated the disease in some areas (Sardinia, Japan, and Taiwan). In the United States, the disease, which had been endemic in many SE states, was eradicated in 1951.

In the 1960s several strains of the malarial parasite developed resistance to chloroquine. This, plus the growing immunity of mosquitoes to insecticides, caused malaria to become one the of world's leading re-emerging infectious diseases, infecting some 225 million people a year and killing more than 650,000 in 2010. Those numbers may be significant underestimates. By 2010, however, the number of infections was again falling due to improved malaria control in Africa.

Mefloquine may be used in areas where the disease has become highly resistant to chloroquine, but some strains are now resistant to it and other drugs. Artemisinin (derived from sweet wormwood) or a derivative such as artesunate or dihydroartemisinin in combination with other drugs is now in many cases the first-line treatment in many cases, but resistance to artemisinins also has developed, in parts of SE Asia and sub-Saharan Africa. Dihydroartemisinin in combination with piperaquine is now a common treatment, but resistance to that combination has developed in parts of SE Asia. Amodiaquine in combination with sulfadoxine and pyrimethamine has also been shown to be effective, and malarone (atovaquone and proguanil) also is used for resistant strains. The use of combinations of drugs with different modes of actions increases the effectiveness of treatment and helps reduce the development of drug resistance.

Vaccines against malaria remain experimental. Spraying is still used to control malaria-transmitting mosquitoes, and more recently the use of mosquito nets treated with a long-lasting insecticide has become widespread. Fish that feed on mosquito larvae also have been employed to control mosquitoes.

Immune Response

P. falciparum creates protein knobs on the surfaces of the red blood cells it attacks. These knobs attach the cell to the lining of the blood vessel, preventing its removal to the spleen for destruction. The parasite slows detection by the immune system by changing the makeup of the knobs periodically, substituting or rearranging its 150 “var” (variability) genes, a strategy unique to malaria. A pattern of remission and relapse results as the immune system learns each new “code” only to have it again changed. Patients with malaria gradually do develop immunity that modifies the course of the disease, but this immunity has a degree of strain specificity. Some of the Plasmodium species have the ability to persist in the liver and cause a new infection years after the original one.

Symptoms

At the onset of malaria, bouts of chills (ague) and fever lasting several hours and occurring every three or four days are the usual symptoms. If the disease is not treated, the spleen and the liver become enlarged, anemia develops, and jaundice appears. Death may occur from general debility, anemia, or clogging of the vessels of cerebral tissues by affected red blood cells. Cerebral malaria is most commonly seen in infants, pregnant women, and nonimmune travelers to endemic areas.

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