Epidemiology, Pathogenesis, Clinical Features, and

Diagnosis of
Malaria

INTRODUCTION
Human malaria : Sp Plasmodium 1. Plasmodium falciparum 2. Plasmodium vivax 3. Plasmodium ovale 4. Plasmodium malariae

Animal Monkey Plasmodium knowlesi,

The majority of malaria infection is caused by :

P. falciparum or P. Vivax

Most malaria-associated deaths are due to P. falciparum

Mixed infection due to more than one malarial species occurs in 5 to 7 percent of infections.

Malaria infection has been increasing over recent years due to a combination of factors including: Increasing resistance of malarial parasites to chemotherapy

Increasing resistance of the Anopheles mosquito vector to insecticides

Ecologic and climate changes

Increased international travel to malaria-endemic areas

EPIDEMIOLOGY
Approximately 300 to 500 million cases of malaria and 700,000 to 2.7 million deaths occur annually worldwide in children in tropical developing countries P. falciparum predominates in tropical Africa, Southeast Asia, Oceania, Haiti, the Amazon basin of South America, and the Dominican Republic, P. vivax is most prevalent in Central America, the Middle East, and India.

Approximately 30,000 travelers from industrialized countries contract malaria each year

The intensity of transmission in different regions affects the risk of acquiring malaria for travelers.
The approximate relative risk of malaria for travelers who stay in an endemic region for one month and do not take chemoprophylaxis is as follows: Oceania Sub-Saharan Africa Indian subcontinent Southeast Asia South America Central America 1:30 or higher 1:50 1:250 1:1,000 1:2,500 1:10,000

TRANSMISSION
Malaria transmission is predominantly via the bite of a female Anopheles sp. Mosquito
Other potential mechanisms for transmission include: congenitally acquired disease, blood transfusion, sharing of contaminated needles, and organ transplantation

LIFE CYCLE Human infection by all four Plasmodia spp occurs by transmission of sporozoites via a bite from an infected anopheline mosquito. The sporozoites travel from the salivary glands of the mosquito through the bloodstream of the host to the liver. In the liver, they invade hepatocytes and divide many 1000-fold until mature tissue schizonts, each containing thousands of daughter merozoites, are formed. This exoerythrocytic stage is asymptomatic. The liver schizonts rupture after 6 to 16 days and release thousands of merozoites into the bloodstream, where they interact with specific erythrocyte membrane proteins and invade red blood cells This the erythrocytic stage is symptomatic

LIFE CYCLE OF PLASMODIUM

LIFE CYCLE OF PLASMODIUM

PATHOGENESIS
Four malaria parasite species digest red cell proteins and hemoglobin. The parasites derive energy from anaerobic glycolysis of glucose to lactic acid, which can cause hypoglycemia and lactic acidosis. The parasites also alter the red cell membrane, making it less deformable and resulting in hemolysis and accelerated splenic clearance, which ultimately causes anemia. Release of proinflammatory cytokines, Tumor necrosis factor (TNF)-alpha, is stimulated by red cell lysis, TNF-alpha suppresses hematopoiesis - anemia.

The liver and spleen enlarge over time; the latter may become massively enlarged [ 12] .
Thrombocytopenia is caused by increased splenic sequestration and decreased platelet survival time (ie, hypersplenism).

Microvascular disease and sequestration

P. falciparum potential to cause severe or fatal disease. P falciparum parasites mature within red blood cells, P falcifarum induce the formation of sticky knobs - erythrocytes These knobs bind to receptors on endothelial cells in capillaries and venules - sequestration of red cells within these small vessels obstruction to blood flow. The cytoadherence and sequestration of red cells within these small vessels leads to microvascular pathology and obstruction to blood flow. Infected red cells also stick to uninfected red cells and form rosettes that clog the microcirculation.

 Rosetting is mediated by an interaction between P. falciparum erythrocyte membrane protein 1, which is exposed to the exterior at the knobs on the surface of infected red cells, and receptors on the surface of uninfected red cells, such as complement-receptor 1 (CR1) Ultimately, secondary organ dysfunction and severe complications in the host can occur. Of interest, it has been reported that a promoter polymorphism of red cell CR1 leads to CR1 deficiency and decreased red cell rosetting, and is significantly associated with protection from P. falciparum malaria

IMMUNITY

Comparison of the four malaria species

P. falciparum Global prevalence RBC preference Incubation period Prepatent period Cycle in red cell Parasitemia level Relapses from liver Disease severity Common RBCs of all ages 12 days (8 to 25) 11 days 48 hours Can be very high, - 60 % No End organ damage and death can occur P. vivax Common Young RBCs (reticulocytes) P. ovale Uncommon Young RBCs (reticulocyte s) 15 days (10 to 20) 12 days 48 hours Usually <1 % Yes P. malariae Uncommon Older RBCs

14 days (10 to 30) (occ-ally months)

12 days 48 hours Usually <1 % Yes Severe disease uncommon (occasional splenic rupture)

18 days (15 to 35) (occ-ally months)

32 days 72 hours Usually low, <<1% No Severe disease rare (occasional neprhitic syndrome)

Severe disease uncommon

Clinical and laboratory indicators of poor prognosis

Age <3 years
Deep coma Convulsions Papilloedema and/or retinal oedema

Absent corneal reflexes, decerebrate/decorticate rigidity or opisthotonus

Organ dysfunction, respiratory distress or circulatory collapse Hyperparasitmeia (>250,000/ul or >5 percent) Peripheral schizonts and/or mature pigmented parasites Haematocrit <15 percent and/or haemoglobin <5 g/dl

Clinical and laboratory indicators of poor prognosis

Peripheral white cell count >12,000/ul
Blood glucose <2.2 mmol/l (<40 g/dl) Serum urea >60 mg/dl or creatinine >265 umol/l (>3.0 mg/dl) Venous lactic acid >5 mmol/l Aminotransferases >3-times normal High CSF lactic acid (>6 mmol/l) and low CSF glucose Increased plasma 5'-nucleotidase Low antithrombin III levels

High plasma TNF concentration