Malaria affects 270 million people each year and has a mortality rate of 1%. Endemic and epidemic malaria are found in all countries between latitudes 300S and 400N. Malaria is primarily a disease of hot, humid countries at altitudes less than 2200 m above mean sea level, where conditions are ideal for prolific breeding of the mosquito vector, Anopheles. It is endemic in India, in parts of Africa and parts of South and Central America. Malaria may also be transmitted by the importation of infected mosquitoes by air, so-called airport malaria.
In humans, malaria is caused by four species of Plasmodium:
P. vivax, P. ovale, P. falciparum and P. malariae. The four species are distinguishable from each other on examination of peripheral blood smears. P. ovale has been reported predominantly from East and West Africa. P. vivax is the major species in temperate zones, whereas in the tropics all forms of malaria are seen. With present-day ease and speed of travel, sporadic cases of malaria are being increasingly recognized. Unfortunately, the initial impact of the WHO eradication programme lost its impetus in several countries in the early 1970s and malaria has once more become a major cause of morbidity and mortality in tropical and subtropical countries. In addition, the emergence of drug chloroquine) and insecticide (DDT) resistance has also become a major problem. Humans, the intermediate hosts, are infected following the bite of an infected female Anopheles mosquito, the definitive host. The parasite can also be transmitted by blood transfusion, transplacentally, and, increasingly, between drug addicts who use improperly cleaned syringes. The introduction of sporozoites, the infective form of the parasite, through the skin by the Anopheles mosquito heralds the commencement of the human cycle. The following stages occur. Pre-erythrocytic schizogony During this phase clinical symptoms are absent and humans are not infective. Those sporozoites that are not removed by the body’s defence mechanisms undergo development within the liver. A variable number of days later, micromerozoites are liberated (primary attack). Other sporozoites (P. vivax and probably P. ovale) remain in a latent form in the liver as hypnozoites. Erythrocytic schizogony This is the phase when red blood cells (RBCs) become infected by the micromerozoites. In the RBCs they pass through several stages of development, namely trophozoites, schizonts and finally merozoites. These asexual parasitic forms are found in peripheral blood about 12 days after inoculation of the sporozoites in P. vivax infection and 9 days in P. falciparum infection. The different Plasmodium species differ in their ability to invade RBCs. P. falciparum is capable of invading all RBCs, especially young RBCs. It therefore has the potential to produce the most severe form of malaria. P. vivax and P. ovale preferentially invade reticulocytes and young RBCs, whereas P. malariae invades senescent RBCs. Each cycle in the RBCs terminates with rupture of the cell and release of merozoites into the circulation. This occurs every 48 hour in P. [alciparum infection, every 48-72 hours in P. vivax and P. ovale infection, and approximately every 72 hours in P. malariae.
The erythrocytic phase may continue for a considerable period of time before the stage of gametogony occurs. In this stage a few merozoites develop into the sexual form of the parasites known as gametocytes. Of these only the mature forms are found in peripheral blood. At this stage the patient is infective.
This fourth stage, which occurs in the liver, is found only with P. vivax, probably P. ovale and possibly P. malariae infections. It does not occur with P. falciparum infection and is believed to be responsible for the relapses in P. vivax and P. ovale infections. The parasites in this phase are referred to as hypnozoites. When an Anopheles mosquito ingests human blood containing gametocytes it marks the commencement of the sexual cycle in the mosquito. The external incubation period varies from 7 to 20 days.
The severity of malaria can be explained partly on the magnitude of the parasitaernia, with P. falciparum causing severe disease as it can invade RBCs of any age.
Immunity may be natural or acquired. Natural immunity is present in individuals of West African extraction who are blood group Duffy-negative (FyFy) and therefore lack the specific receptor on the RBC surface to which the merozoites attach. They cannot develop P. vivax malaria. The presence of haemoglobin S, glucose-6-phosphate dehydrogenase deficiency, thalassaemia and pyruvate kinase deficiency also offer resistance against P. falciparum. The presence of abnormal haemoglobins or altered RBC metabolism retards P. falciparum maturation and reduces the severity of the disease. Certain HLA antigens have been show to be protective against P. [alaparum in Gambian children. The spleen plays an important role in natural immunity, since splenectomized individuals are highly susceptible to the malarial parasite. Infants are protected by the transfer of maternal IgG antibodies across the placenta. Partial immunity may be acquired following an attack of malaria, and is attributed to macrophage stimulation by T cells.
CYTOKINES. Tumour necrosis factor-a (TNF-a) blood evels correlate with the severity of the disease but a cause-and-effect relationship has not been shown.