Malaria Health Article

MALARIA

Malaria is the most clinically important parasitic disease worldwide. It kills as many as 2.7 million people annually. The human suffering and economic costs are enormous. Although malaria has been eradicated from temperate zones, it continues to pose a major public health threat to more than forty percent of the world's population.

EPIDEMIOLOGY AND TRANSMISSION

Currently, malaria occurs in one hundred countries and territories inhabited by a total of 2.4 billion people (see Figure 1). The World Health Organization estimates that there are 300 million to 500 million clinical cases annually, resulting in approximately 1.5 million to 2.7 million deaths. Ninety percent of the deaths are in children under five years of age living in sub-Saharan Africa. Other risk groups include pregnant women, internally displaced persons and refugees, and international travelers.

Malaria transmission occurs by the bite of an infective female Anopheles sp. mosquito. Although most cases are transmitted by mosquito, the infection can be passed from mother to the unborn child, or through contaminated blood products, needle sharing, or organ transplantation.

AGENT AND LIFE CYCLE

Human malaria infection is caused by one or more of four species of the intracellular parasite of the genus plasmodium. Plasmodium falciparum, P. vivax, P. ovale, and P. malariae differ in geographic distribution, microscopic appearance, clinical characteristics, and potential for conferring immunity in the host. Although P. vivax is the most common form of malaria worldwide, P. falciparum is the most severe, contributing to most of the morbidity and mortality.

The life cycle of the four species of human malaria consists of two phases: the sexual (sporogony) and asexual phases (schizogony; see Figure 2). Schizogony begins when an infective female anopheline mosquito injects sporozoites into the human host while taking a blood meal. The sporozoite stage of the parasite disappears from circulation within thirty minutes. Those avoiding the host immune system invade the liver and undergo development and multiplication to form schizonts. Over the next five to fifteen days, the schizonts mature, rupture the liver cell, and invade the circulation as merozoites. These merozoites bind to the red blood cell wall. They then penetrate the red blood cell, where they develop as ring forms and grow into trophozoites. Further division creates red blood cell merozoites which form a mature schizont. The blood cell swells and ruptures, releasing merozoites that go on to invade other red blood cells. Clinical symptoms result when the blood cell ruptures and releases cellular debris from infected cells into the bloodstream. The host response to these toxins produces the

Figure 1

classic paroxysms of fever and chills, which are closely timed with the cycles of red blood cell schizogony. The timing of the blood cell phase differs depending on the species of the parasite. P. vivax and P. ovale classically have cycles of forty-eight hours, P. malariae seventy-two hours, and P. falciparum forty-eight hours, although this may vary.

After a period of time, some of the merozoites develop into male and female sexual forms called gametocytes. The gametocytes are ingested by the female anopheline mosquito during a blood meal. Inside the mosquito's stomach, the male and female gametocyte fuse to form a zygote, which quickly becomes a mobile oökinete, which penetrates the stomach wall to form an oöcyst. The oöcyst then bursts, releasing sporozoites that migrate to the salivary glands, ready to be injected into a human host, thus completing the cycle. The parasite generally develops within the mosquito (sporogony) in nine to twelve days, but this time varies according to parasite species and external temperature.

P. vivax and P. ovale differ from the other two species in that some hepatic trophozoites, called hypnozoites, may remain dormant and persist in the liver for months to up to four years. Periodic release of merozoites formed from these hypnozoites can produce recurrent parasitemia and clinical symptoms. Recurrent parasitemia can also occur with P. falciparum and P. malariae, although these species do not form hypnozoites. Infection with these parasites may remain in the blood at subclinical levels because of either the host immune system or use of antimalarial drugs

Figure 2

that do not completely clear the blood-stage parasites. The level of parasitemia can increase weeks to months later, giving rise to another clinical attack. While P. falciparum rarely returns more than several months after the initial infection, P. malariae may become active again up to forty years after the infection.