General Characteristics
Plasmodium falciparum invades all ages of RBCs, and the number of infected cells may exceed 50% (see Tables 1 to 3, Figures 1 to 3). Schizogony occurs in the spleen, liver, and bone marrow rather than in the circulating blood. Ischemia caused by the obstruction of vessels within these organs by parasitized RBCs will produce various symptoms, depending on the organ involved. A decrease in the ability of the RBCs to change shape when passing through capillaries or the splenic filter may lead to plugging of the vessels Also, only P. falciparum causes cytoadherence, a feature that is associated with severe malaria.
Table1. Plasmodium spp.: Clinical Characteristics of the Five Human Infections
Table2. Plasmodia in Giemsa-Stained Thin Blood Smears
Table2. Plasmodia in Giemsa-Stained Thin Blood Smears—cont’d
Table3. Malaria Characteristics with Fresh Blood or Blood Collected Using EDTA with No Extended Lag Time*
Fig1. The morphology of malaria parasites. Plasmodium vivax: 1, Early trophozoite (ring form). 2, Late trophozoite with Schüffner’s dots (note enlarged red blood cell). 3, Late trophozoite with ameboid cytoplasm (very typical of P. vivax). 4, Late trophozoite with ameboid cytoplasm. 5, Mature schizont with merozoites (18) and clumped pigment. 6, Microgametocyte with dispersed chromatin. 7, Macrogametocyte with compact chromatin. Plasmodium malariae: 1, Early trophozoite (ring form). 2, Early trophozoite with thick cytoplasm. 3, Early trophozoite (band form). 4, Late trophozoite (band form) with heavy pigment. 5, Mature schizont with merozoites (9) arranged in rosette. 6, Microgametocyte with dispersed chromatin. 7, Macrogametocyte with compact chromatin. Plasmodium ovale: 1, Early trophozoite (ring form) with Schüffner’s dots. 2, Early trophozoite (note enlarged red blood cell). 3, Late trophozoite in red blood cell with fimbriated edges. 4, Developing schizont with irregularly shaped red blood cell. 5, Mature schizont with merozoites (8) arranged irregularly. 6, Microgametocyte with dispersed chromatin. 7, Macrogametocyte with compact chromatin. Plasmodium falciparum: 1, Early trophozoite (accolé or appliqué form). 2, Early trophozoite (one ring is in headphone configuration/double chromatin dots). 3, Early trophozoite with Maurer’s dots. 4, Late trophozoite with larger ring and Maurer’s dots. 5, Mature schizont with merozoites (24). 6, Microgametocyte with dispersed chromatin. 7, Macro gametocyte with compact chromatin. Note: Without the appliqué form, Schüffner’s dots, multiple rings/cell, and other developing stages, differentiation among the species can be difficult. It is obvious that the early rings of all four species can mimic one another very easily. Remember: One set of negative blood films cannot rule out a malarial infection. (Reprinted by permission of the publisher from Garcia LS: Diagnostic medical parasitology, ed 5, Washington, DC, 2007, Copyright by American Society for Microbiology.)
Fig2. Morphology of malaria parasites. Column 1 (left to right): Plasmodium vivax (note enlarged infected RBCs). (1) Early trophozoite (ring form) (note one RBC contains 2 rings—not that uncommon); (2) older ring, note ameboid nature of rings; (3) late trophozoite with Schüffner’s dots (note enlarged RBC); (4) developing schizont; (5) mature schizont with 18 merozoites and clumped pigment; (6) microgametocyte with dispersed chromatin. Column 2: Plasmodium ovale (note enlarged infected RBCs). (1) Early trophozoite (ring form) with Schüffner’s dots (RBC has fimbriated edges); (2) early trophozoite (note enlarged RBC, Schüffner’s dots, and RBC oval in shape); (3) late trophozoite in RBC with fimbriated edges; (4) developing schizont with irregular-shaped RBC; (5) mature schizont with 8 merozoites arranged irregularly; (6) microgametocyte with dispersed chromatin. Column 3: Plasmodium malariae (note normal or smaller than normal infected RBCs). (1) Early trophozoite (ring form); (2) early trophozoite with thick cytoplasm; (3) late trophozoite (band form); (4) developing schizont; (5) mature schizont with 9 merozoites arranged in a rosette; (6) microgametocyte with compact chromatin. Column 4: Plasmodium falciparum. (1) Early trophozoites (the rings are in the headphone configuration with double chromatin dots); (2) early trophozoite (accolé or appliqué form); (3) early trophozoites (note the multiple rings/cell); (4) late trophozoite with larger ring (accolé or appliqué form); (5) crescent shaped gametocyte; (6) crescent-shaped gametocyte. Column 5: Plasmodium knowlesi—with the exception of image 5, these were photographed at a higher magnification (note normal or smaller than normal infected RBCs). (1) Early trophozoite (ring form); (2) early trophozoite with slim band form; (3) late trophozoite (band form); (4) developing schizont; (5) mature schizont with merozoites arranged in a rosette; (6) microgametocyte with dispersed chromatin. Note: Without the appliqué form, Schüffner’s dots, multiple rings per cell, and other devel oping stages, differentiation among the species can be very difficult. It is obvious that the early rings of all five species can mimic one another very easily. Remember: One set of negative blood films cannot rule out a malaria infection. (From Garcia LS: Malaria Clin Lab Med 30:93 129, 2010,with permission. Column 5 courtesy CDC.)
Fig3. Plasmodium falciparum. A, Ring forms; B, oocyte; and C, sporozoites. (Courtesy Dr. Henry Travers, Sioux Falls, S.D.)
The asexual and sexual forms circulate in the blood stream during infections by four of the Plasmodium species. However, in P. falciparum infections, as the parasite grows, the RBC membrane becomes sticky and the cells adhere to the endothelial lining of the capillaries of the internal organs. Thus, only the ring forms and the gametocytes (occasionally mature schizonts) normally appear in the peripheral blood. Periodicity of the cycle will not be established during the early stages, and the presumptive diagnosis may be totally unrelated to a possible malaria infection. If the fever does develop a synchronous cycle, it is usually a cycle of 36 to 48 hours. Because P. falciparum infects young and old RBCs, very heavy parasitemia can occur. The RBCs are all sizes; there is no true stippling, but Maurer’s dots (coarse granulation in the cytoplasm of RBCs) are sometimes present; often there are multiple rings per RBC and the rings are delicate and often have two dots of chromatin, appliqué or accolé forms (ring forms identified within the marginal regions of the erythrocytes); and the gametocytes are crescent-shaped.
Pathogenesis and Spectrum of Disease
The onset of a P. falciparum malaria attack occurs 8 to 12 days after infection and is characterized by 3 to 4 days of vague symptoms such as aches, pains, headache, fatigue, anorexia, or nausea. This stage is followed by fever, a more severe headache, and nausea and vomiting, with occasional severe epigastric pain. At the onset of fever, there may be a feeling of chilliness. As with the other Plasmodium spp., periodicity of the cycle will not be established during the early stages.
Severe or fatal complications can occur at any time and are related to the obstruction of vessels in the internal organs (liver, intestinal tract, adrenal glands, intravascular hemolysis/black water fever, and kidneys). Blackwater fever is a complication of malaria that is a result of red blood cell lysis, releasing hemoglobin into the bloodstream and urine, causing discoloration. The severity of the complications may not correlate with the peripheral blood parasitemia, particularly in P. falciparum infections in a patient who has never been exposed to malaria before (immunologically naïve).
Disseminated intravascular coagulation is a rare com plication and is seen with a high parasitemia, pulmonary edema, anemia, and cerebral and renal complications. Vascular endothelial damage from endotoxins and bound parasitized blood cells may lead to clot formation in small vessels. Cerebral malaria is more common in P. falciparum malaria, but can occur in the other species. If the onset is gradual, the patient becomes disoriented or violent or may develop severe headaches and pass into coma. However, some patients, including those with no prior symptoms, may suddenly become comatose. Physical signs of central nervous system involvement vary, and there is no correlation between the severity of the symptoms and the parasitemia.
Extreme fevers, 41.7° C (107° F) or higher, may occur in an uncomplicated malaria attack or in cases of cerebral malaria. Without vigorous therapy, the patient usually dies. Cerebral malaria is considered to be the most serious complication and the major cause of death with P. falciparum; it occurs in up to 10% of all P. falciparum patients admitted to the hospital and is responsible for 80% of fatal cases.
