Malaria: Plasmodium, Species, and Epidemiology

• The topic is Malaria
• The lecture is taught by Nilda J. Zapata, MD, for the Infectious Diseases II Course -MIC 644, Microbiology Division

Plasmodium

• It is an obligate intracellular protozoa
• Asexual reproduction happens in humans
• Sexual reproduction takes place in mosquitos

Plasmodium Species

• P. falciparum
• P. vivax
• P. malariae
• P. ovale
• P. knowlesi

Epidemiology

• 1-3 million deaths occur per year in Africa due to malaria
• In the USA, about 800 travelers are diagnosed with malaria
• Worldwide, 300-500 million malaria infections develop each year

Distribution of Malaria

• P. vivax is the most common type in temperate regions
• P. falciparum is found in the tropics
• P. ovale is present in Africa

Transmission

• Malaria transmits through the bite of an infected anopheline mosquito
• It can also transmit via inoculation of infected blood

Infective Stage-Sporozoites

• Infection starts from mosquito salivary glands
• Sporozoites circulate to the liver
• They invade hepatic parenchymal cells
• Sporozoites multiply in stages called exoerythrocytic forms
• Next, they become hepatic schizonts

Schizonts Rupture

• Development takes 1-2 weeks
• Each schizont releases thousands of merozoites
• Merozoites enter the circulation
• They invade erythrocytes but never invade the liver

Invasion of Erythrocytes

• Ring forms develop
• Trophozoites increase in cytoplasm
• Schizonts undergo nuclear division

P. vivax- P. ovale

• They have primary exoerythrocytic forms
• Rupture results in parasitemia
• Some remain in the liver for months or years
• Hypnozoites are in latent forms
• Relapses may occur when rupture occurs

Schizogony

• The asexual cycle lasts 48-72 hours
• It involves the process of intracellular maturation leading to the development of a schizont and its ultimate rupture
• Schizogony occurs in humans
• P. malariae lasts 72 hrs during schizogony
• Others last 48 hours

Sporogony

• The sexual cycle is 10 days
• It begins with gametocytes from merozoites
• Female anopheline mosquitoes ingest gametocytes
• Exflagellation occurs within the gut, forming male gametes
• Next microgametes fertilize macrogametes, forming a zygote
• Ookinetes from the zygote invade the gut epithelium
• Oocysts form in the gut wall, where sporozoites develop
• Migration to salivary glands takes place

Pathogenesis

• Only the asexual intraerythrocytic parasite can cause disease

Pathogenic Mechanisms

• Fever
• Anemia
• Tissue hypoxia
• Immunopathologic events

Fever Development

• Direct association between schizont rupture and fever exists
• Parasites may liberate pyrogen
• Endogenous pyrogen secrets by tissue macrophages
• Tumor necrosis factor-cachectin is associated with periodic fevers

Anemia Development

• Hemolysis is caused by infected erythrocytes and their rupture
• Splenic sequestration of erythrocytes occurs
• Maybe caused by an autoimmune basis

Tissue Hypoxia Development

• Anemia and alterations of microcirculation cause tissue hypoxia
• Tissue hypoxia causes pulmonary edema, acute renal failure, cerebral dysfunction, and malabsorption
• Gram negative sepsis

Immunopathologic Events

• Increase in circulating immunoglobulins
• Thrombocytopenia, antibody-mediated splenic sequestration
• Glomerulonephritis as deposition of immune complexes primarily affects P. malariae

Clinical Manifestations

• Periodic fevers and chills
• Splenomegaly
• Anemia

Non-Specific Symptoms

• Occur days before parasitemia: -Gen malaise -Headache -Myalgia -Fatigue -Chest, abdominal pain -Arthralgias

Cold Period

• Cold, pale skin
• Cyanosis of lips
• Cyanosis of nail beds
• Peripheral vasoconstriction

Hot Period

• Temperature rises up to 40°C
• Warm, dry skin
• Tachycardia, tachypnea, dry cough
• Severe headache, backache
• Abdominal pain
• Nausea, vomiting, delirium

Physical Examination Findings

• Splenomegaly, which may rupture
• Tender hepatomegaly
• Jaundice
• Urticaria, petechial rash
• Conjunctiva suffusion
• Hemorrhage
• Pulmonary edema

Complication – P. falciparum

• Hypoglycemia-impaired glycogenolysis
• Pulmonary edema
• Bleeding, severe hemolysis
• Lactic acidosis-increased anaerobic glycolysis
• Hypoxic tissues
• Renal failure

Cerebral Malaria

• The most serious complication of malaria
• Death occurs up to 50% of those infected
• Sequestration of parasitized erythrocytes in cerebral capillaries
• Disturbance of consciousness ranges from somnolence to coma
• Acute organic brain syndromes
• Seizures
• Focal neurologic deficit

Selective Advantages Against Malaria

• G-6-PD deficiency is essential for parasite metabolis
• HbS causes premature death of erythrocyte forms of P. falciparum

Diagnosis

• Blood smears use Geimsa stains with thin and thicks smears
• Indirect hemaglutination
• Indirect fluorescent antibody
• PCR
• Other rapid tests like dipstick tests

Therapy

• Promotes control of acute clinical attack by rapid elimination of asexual erythrocyte parasites
• Prevents relapses of vivax and ovale by destruction of hypnozoites
• Prevents transmission by using mosquito insect repellent DEET (diethyltoluamide)