Plasmodium falciparum - Clinical manifestations, Complications

Clinical manifestations of Plasmodium falciparum

Clinical syndromes associated with Plasmodium falciparum malaria include:

• Malaria paroxysm preceding the prodromal period

• Anemia

• Hepatosplenomegaly

Malaria paroxysm preceding the prodromal period

The Plasmodium falciparum malaria paroxysm preceding the prodromal period consists of:

• Prodromal period

• Malarial paroxysm

Prodromal period

• the prodromal period, which varies from a few days to several days, is followed by a malarial paroxysm

• during this period, non-specific symptoms include malaise, myalgia, headache, fatigue

• other localized symptoms include chest pain, abdominal pain, and arthralgia

Malarial paroxysm

• this classical manifestation is associated with fever, chill, and rigor

• the irregular fever, which occurs every 48 hours, happens due to the rupture of RBC infected with malaria

• the rupture of RBC also releases erythrocytic schizont debris which activates the tissue macrophages when in turn produces mononuclear cell-derived cytokines such as IL1, TNF

• overproduction of these cytokines induces fever, chill, and sweat in the host

Anemia

• anemia, which is severe in Plasmodium falciparum malaria, is normochromic and normocytic

• the pathogenesis of anemia is due to

  • lysis of both parasitized and non-parasitized RBC

  • suppression of erythropoiesis in the bone marrow

  • in some cases, autoimmune destruction of RBC

  • spleen clears non-parasitized RBC

Hepatosplenomegaly

In uncomplicated cases of malaria infection, physical examination reveals moderate splenomegaly, tender hepatomegaly, or in some cases, no abnormalities. Lymphadenopathy does not occur in malaria.

Complications of Plasmodium falciparum

The complications of Plasmodium falciparum infection can be separated into acute malaria and chronic/severe malaria. When more than 3% to 5% of erythrocytes are parasitized (hyperparasitemia), the condition is known as severe/chronic malaria.

The complications of acute malaria include:

• Black water fever

• cerebral malaria

• renal impairment

• pulmonary edema

• hypoglycemia with lactic acidosis

• Other complications

Black water fever

• occurs due to repeated infection by Plasmodium falciparum when treated inadequately with quinine

• characterized by rapid and massive intravascular hemolysis of both parasitized and non-parasitized erythrocytes

• associated with high levels of breakdown products of hemoglobin in the blood and urine

• clinical syndromes include high fever, vomiting, jaundice, hemoglobinuria, hemoglobinemia, renal failure, circulatory collapse

• kidney failure is an immediate cause of death with mortality rates between 20% to 50%

• called black water fever due to the dark red to brown-black appearance of urine which is due to the presence of free hemoglobin as methemoglobin or oxyhemoglobin

• protein, cases and epithelial cells are also present in the urine

• in the majority of cases, the parasites are not found in peripheral blood due to it being destroyed during hemolysis

• erythrocytic autoantibodies produced in previous malaria infection combines with the auto-antigens present in newer infection by the same strain of Plasmodium falciparum resulting in hemolysis

• the parasitized and quininized erythrocytes function as autoantigens and autoantibodies are produced against it

Black water fever mostly occurs in cases of:

• non-immune individuals who have been repeatedly infected by Plasmodium falciparum

• atypical immune response during reinfection

• hypersensitivity to quinine

• ingestion of oxidant antimalarials in G6PD deficient patients

Cerebral malaria

• defined as any anomaly in the mental status of a person with malaria

• is a symmetric encephalopathy which is believed to represent metabolic encephalopathy

• most frequent, a serious complication of malaria with a mortality rate of 15% in children and 20% in adults

• cerebral malaria is sudden onset with a severe headache accompanied by high fever (108° F), convulsions, changes in mental status (abnormal behavior, delirium), coma

• convulsions in 50% of cases- both in adults and children

• circulatory stasis and hypoxia are caused by the plugging of capillaries of rosettes of sequestered parasitized RBC and adherence of parasitized erythrocytes to the endothelium of cerebral venules and capillaries

• death may occur within a few hours

Renal impairment

• occurs in adults than in children

• high mortality rate

• caused by adherence of Plasmodium falciparum-infected erythrocytes to the microvasculature in the cortex of the kidney- resulting in kidney failure

• it is typically reversible

Pulmonary edema

• the most serious complication – with a mortality rate of 80%

• occurs during pregnancy or after childbirth – in cases of severe malaria even after treatment with antimalarial drugs

• pathological changes in the lungs include microvascular congestion with or without thrombus formation, interstitial edema, and formation of hyaline membrane

Hypoglycemia with lactic acidosis

• commonly, children and pregnant women with severe or uncomplicated malaria are affected by hypoglycemia with lactic acidosis

• associated with quinine treatment

• due to impaired hepatic glycogenolysis, gluconeogenesis, increased consumption by anaerobic glycolysis in hypoxic tissue as well as by host hyperinsulinemia, and consumption by a parasite, reduced glucose supply occurs which leads to hypoglycemia

• this condition worsens if quinine is administered to treat Plasmodium falciparum infection

• Quinine stimulates the islet of cells of the pancreas which increases the secretion of insulin and thus reduces the level of blood glucose

• another cause of hypoglycemia is the overproduction of TNF

• hypoglycemia also leads to sweating and tachycardia which is associated with poor prognosis

Other complications

• Gran-negative septicemia

• gastrointestinal bleeding

• diarrhea

• aspiration pneumonia

• secondary bacterial infections

The complications of chronic malaria include:

• Tropical splenomegaly syndrome (TSS)

• Falciparum recrudescence

• Latent malaria

Tropical splenomegaly syndrome (TSS)

• also known as hyperreactive malarial splenomegaly

• found in endemic areas of Africa, New Guinea, and Indonesia

• characterized by massive splenomegaly, elevated serum IgM malarial antibodies, and moderately enlarged liver with hepatic sinusoidal lymphocytosis

• also associated with peripheral B-cell lymphocytosis (in Africa) or production of cytotoxic lymphocytes (CD8+) and IgM antibodies

• patients with TSS have also presented with abdominal mass, and sharp abdominal pain suggesting perisplenitis or dragging sensation in the abdomen

• also, TSS patients are susceptible to skin infections, respiratory infections, normocytic anemia, leucopenia, thrombocytopenia

• parasites not found in peripheral blood

• prolong treatment of antimalarial drugs is needed

Falciparum recrudescence

• recrudescence refers to the occurrence of clinical malaria following a previous Plasmodium falciparum infection

• caused by an increase in the number of merozoites present in the erythrocytes

• different from true relapse caused by P. vivax or P. ovale, which is caused due to hypnozoites

• falciparum recrudescence is caused by inadequate treatment with antimalarial drugs and is seen mostly in cases of drug resistance, pregnant women, or drug resistance

• occurs within 15 days of treatment of falciparum resistant to antimalarials or a few weeks to months from a previous attack

Latent malaria

Latent malaria is the state of asymptomatic malaria harboring Plasmodium falciparum gametocytes in the peripheral blood. Individuals in this stage are infectious to mosquitos as they are reservoirs for the disease.