Malaria is a protozoan (genus Plasmodium) infection transmitted by the bite of an infected female Anopheles mosquito and rarely via a contaminated blood transfusion. It is extremely common, affecting more than 500 million persons and resulting in more than 1 million deaths each year.
There are four species of the genus Plasmodium that cause malaria in man. These are P. falciparum, P. vivax, P. ovale, and P. malariae. From a clinical standpoint one must be able to distinguish between P. falciparum and non falciparum (all the others) malaria. The reasons for this approach are that P. falciparum malaria is often chloroquine resistant, and almost all malaria deaths are due to this species. The severity of P. falciparum malaria is due to the parasites’ ability to invade red cells of all ages and not just young red cells (as for the other species of malaria), and to the release of more P. falciparum merozoites than with other species. Each infected hepatocyte releases 30,000 merozoites of P. falciparum compared with 10,000 for P. vivax and 15,000 for P. ovale and P. malariae.
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Epidemiology
Malaria (so-called because in the Pontine marshes outside Rome, bad air (mal aria) was thought to be the cause of the disease) occurs in most tropical areas of the world. Plasmodium falciparum predominates in Africa, New Guinea, and Haiti, whereas Plasmodium vivax predominates in the Indian subcontinent and Central America. These two species are almost equal in prevalence in South America, East Asia, and Oceania. Changing global climate conditions have had an effect on the epidemiology of malaria. Malaria cases increased by one-third in the year following an El Niño event, and malaria mortality and morbidity increased an average of 36% in Venezuela in years following an El Niño event.
As a result of rapid worldwide travel, imported malaria can be present in countries that do not have indigenous malaria. Malaria was endemic throughout much of the United States in the nineteenth and early twentieth centuries. There have been three outbreaks of locally acquired malaria in the United States in the 1990s. Thus every physician regardless of practice location should be familiar with the diagnosis and treatment of malaria. Diagnosis of malaria is often delayed, resulting in an increase in mortality. Indeed there was a 24-fold higher case-fatality rate from malaria for patients treated in civilian hospitals compared with those treated in military or Veterans Administration hospitals. Currently about 1000 cases of imported malaria occur in the United States each year, and there are 700 cases per year in Canada. The Canadian rate is 4 to 5 times higher than the U.S. rate on a per capita basis, reflecting the higher rate of immigration to Canada from malarious areas.
It is instructive to review the 1994 U.S. malaria surveillance data. There were 1014 cases diagnosed, a 20% decrease from the 1275 cases reported for 1993. P. vivax, P. falciparum, P. malariae, and P. ovalae accounted for 44%, 44%, 4% and 3% of the cases, respectively. In 5%, the infecting species was not determined. Of the U.S. civilians who acquired malaria while travelling to a foreign country, 18% had followed a recommended chemoprophylactic drug regimen. Four deaths were attributed to malaria.
Malaria life cycle
Malarial parasite development in the anopheles mosquito
The mosquito ingests blood from an infected human. The parasite then undergoes a life cycle in the mosquito; this is known as sporogony. The sexual cycle takes place only in mosquitoes. The gametocytes are ingested and mature in the stomach into male and female gametes. The male cells exflagellate, producing 8 long, thin, mobile flagella or microgametes that break away from the parent body. One microgamete penetrates a female cell and fertilizes it. The male and female nuclei fuse and the ookinete so formed grows larger and becomes very active, eventually piercing an epithelial cell wall below the lining membrane and secreting a cyst wall around itself. The nucleus undergoes mitotic division around which cytoplasma condenses to produce large numbers of the infective parasite forms or sporozoites. After about 1 to 2 weeks the cyst ruptures, and the sporozoites are discharged into the hemocele and invade all parts of the insect, some eventually reaching the acinar cells of the salivary glands. This entire process takes 5 to 15 days in the mosquito. When the insect bites, the sporozoites penetrate the cell membrane and are injected with the acinar fluid (saliva) into the human host. The sporozoites enter small blood vessels and remain in circulation for <1 hour.
Life cycle in humans
Sporozoites enter the circulation from the bite of an infected mosquito. There are two phases to malarial parasite development in humans, the exoerythrocytic and the erythrocytic. Exoerythrocytic schizogony takes place in the liver. On entering the hepatocyte the sporozoite rounds up, and the nucleus undergoes repeated division. Over 6 to 16 days the exoerythrocytic schizont matures and divides to produce small single nucleated merozoites. The liver cell ruptures, and the merozoites escape either into the blood stream or into contiguous liver cells where they may initiate a secondary exoerythrocytic phase. In P. falciparum infection, no secondary infection of liver cells occurs. In other species it does and provides the mechanism for relapse of infection after eradication of the erythrocytic phase. Therefore, medications that eradicate the exoerythrocytic forms are needed to cure the nonfalciparum malarias.