The life cycle of plasmodia is complex (
Fig. 12.8 ). As mosquitoes feed on human blood, sporozoites are introduced from the saliva and within a few minutes infect liver cells. Here the parasites multiply rapidly to form a schizont containing thousands of merozoites. After a period of days to several weeks that varies with the Plasmodium species, the infected hepatocytes release the merozoites, which quickly infect red cells. Intraerythrocytic parasites either continue asexual reproduction to produce more merozoites or give rise to gametocytes capable of infecting the next hungry mosquito. During their asexual reproduction in red cells, each of the four forms of malaria develops into trophozoites. The asexual phase is completed when the trophozoites give rise to new merozoites, which escape by lysing the red cells.
Fatal falciparum malaria often involves the small vessels of the brain, a complication known as cerebral malaria. Normally, red cells bear negatively charged surfaces that interact poorly with endothelial cells. Infection of red cells with P. falciparum induces the appearance of positively charged surface knobs containing parasite-encoded proteins, which bind to adhesion molecules expressed on activated endothelium. Several endothelial cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), appear to mediate this interaction, which leads to the trapping of red cells in postcapillary venules. In an unfortunate minority of patients, mainly children, this process involves cerebral vessels, which become engorged and occluded.
Fig. 12.8 LifecycleofPlasmodium falciparum. ICAM-1, Intercellularadhesionmolecule-1;RBC, redbloodcell.(Drawn by Dr. Jeffrey Joseph, Department of Pathology, Beth Israel Deaconess Hospital, Boston, Massachusetts.) http://ebooksmedicine.net
MORPHOLOGYRedcelltrophozoitesfromeachPlasmodium specieshaveasomewhatdistinctiveappearance,allowingexpertobserverstodeterminewhichspeciesisresponsibleforaninfectionfromexaminationofappropriatelystainedthicksmearsofperipheralblood. Thedestructionofredcellsleadstohemolytic anemia,withitsattendantfeaturesandlaboratoryfindings.Acharacteristicbrownmalarialpigmentderivedfromhemoglobincalledhematin isreleasedfromtherupturedredcellsandproducesdiscolorationofthespleen,liver,lymphnodes,andbonemarrow.Activationofdefensemechanismsinthehostleadstoamarkedhyperplasiaofmononuclearphagocytes,producingmassive splenomegaly andoccasionalhepatomegaly.
Showers of new merozoites are released from the red cells at intervals of approximately 24 hours for P. knowlesi, 48 hours for P. vivax, P. ovale, and P. falciparum, and 72 hours for P. malariae. Episodic shaking, chills, and fever coincide with this release. Hemolytic anemia of varying severity is a constant feature. Cerebral malaria associated with P. falciparum is rapidly progressive; convulsions, coma, and death usually occur within days to weeks. Fortunately, falciparum malaria more often pursues a chronic course that may be punctuated at any time by blackwater fever. The trigger is obscure for this uncommon complication, which is associated with massive intravascular hemolysis, hemoglobinemia, hemoglobinuria, and jaundice.
With appropriate chemotherapy, the prognosis for patients with most forms of malaria is good; however, falciparum malaria is becoming more difficult to treat due to the emergence of drug-resistant strains. Because of the potentially serious consequences of the disease, early diagnosis and treatment are important. The ultimate solution is an effective vaccine, which is long sought but still elusive.