Plasmodium falciparum - Virulence factors, Pathogenesis, Malaria in high risk-group

Virulence factors of Plasmodium falciparum

The virulence factors of Plasmodium falciparum include:

• High level of parasitemia

• Sequestration of the parasite

• Cytokines

High level of parasitemia

• In cases of infection by Plasmodium falciparum, the level of parasitemia is very high- more than 250,000 to 300,000/ml of blood

• around 30% to 40% of total host RBCs are infected by the malaria parasite as erythrocytes of all ages are susceptible to Plasmodium falciparum

• fatality occurs at a 25% level of parasitemia

Sequestration of the parasite

• This phenomenon is unique to Plasmodium falciparum due to its ability to cytoadhere

• Sequestration involves holding back the malaria parasite in host vital organs

• inside RBC, the merozoites produce a protein inside the erythrocyte surface membrane which results in a deformation called knobs

• these knobs produce high molecular weight and strain-specific adhesive protein which functions to mediate attachment of parasite on the endothelium of capillaries and venules

• as a result, RBCs of the small post-capillary venules of CNS, lungs, spleen, and kidneys are sequestrated

• the Plasmodium falciparum parasites interfere with the metabolism of the host as well as continue to process and destroy the spleen by evading the host's immune response

• only young ring forms are observed in the peripheral blood due to this factor

• in RBCs infected by gametocytes, knobs are not formed thus sequestration does not occur

Cytokines

• Plasmodium falciparum produces cytokines such as IL-1, TNF, and IFN-g

• these cytokines affect a number of receptors present on the surface of endothelial cells of the small capillaries and post-capillary venules

• they are also involved in the end-organ diseases of the kidney, lungs, and brain

Pathogenesis of Plasmodium falciparum

The Plasmodium falciparum malaria disease is not caused by developing stages of sporozoites, merozoites, and gametocytes but is rather primarily caused by the asexual intra-erythrocytic stage of Plasmodium falciparum. The clinical symptoms are caused due to:

• anemia resulted due to the destruction of a large number of erythrocytes

• tissue hypoxia due to reduced oxygen delivery and obstruction of blood flow by the parasitized erythrocytes

• the local and systemic immune response of the host to Plasmodium falciparum antigens

Plasmodium falciparum malaria in high risk-group

Malaria in pregnancy

• Plasmodium falciparum is an important cause of fetal death

• malaria in pregnant women may lead to low birth weight, premature birth, miscarriage, stillbirth

• pregnant primigravid women are 10 times more susceptible to contracting malaria than nongravid women

• although the mothers usually remain asymptomatic, they may develop hypoglycemia, anemia, and acute pulmonary edema

Malaria in children

• one of the major causes of death in children in endemic areas is malaria caused by Plasmodium falciparum

• in severe cases, hyperpyrexia, medical shock, cerebral malaria, acute renal failure, and acute pulmonary edema are some of the clinical syndromes

Congenital malaria

• caused by the transmission of erythrocytic asexual forms through the placenta if injured, during parturition, or due to high levels of parasitemia

• usually occurs within 7 days of birth

• occurs more frequently in non-immune infected mothers than in highly immune mothers

• rare and seen in highly endemic areas

Transfusion malaria

• occurs as a result of the use of contaminated needles by intravenous drug addicts or due to the transfusion of infected blood

• short incubation time

• pre-erythrocytic development

• clinically same as vector-borne malaria