Pathogenesis of malaria Flashcards
Epidemiology
- Cases per annum
- Deaths
- Number of countries affected
216 million cases per annum
445,000 deaths
- 70% deaths are in children<5
91 countries ongoing transmission
- Affects sub-Saharan African the most (90% of cases)
Top 6 countries with the highest burden of malaria
Nigeria
Demographic republic of Congo
Tanzania
Uganda
Mozambique
Ivory Coast
Main methods of malaria prevention
Vector control:
- Insecticide treated mosquito nets
- Indoor residual spraying of insecticide
Prevention in pregnancy
Malaria vector
Female anopheles mosquito
Different malaria species (5)
All plasmodium:
- Falciparum
- Vivax
- Ovale
- Malarie
- Knowlesi
Fever paroxysms of plasmodium species
Presentation of fever depending on the species.
- According to when the rbc` ruptures and merozoite invades
Falciparum- Malignant tertian Vivax- Benign tertian Ovale- Tertian (fever every 2 days) Malarie- Quartan (fever every 3 days) Kowlesi- Quotidian (fever everyday)
Human liver stages of malaria pathogenesis
- Mosquito injects sporozoites as it takes blood.
- Sporozoites infect liver cells and divides to form schizont.
- The schizont ruptures and ruptures hepatocytes, merozoites then enter the blood stream.
Human blood stages of malaria pathogenesis
- Merozoites from ruptured schizont in blood infect red blood cells.
- Merozoites mature into trophozoites.
- Trophozoites mature into schizonts.
- Schizonts rupture the abc and release more merozoites
Gametocytosis of malaria
Immature trophozoite in abc can mature into gametocytes.
Gametocytes then develop and are taken up by mosquito.
Mosquito stages of malaria
- Mosquito takes up gametocytes when it takes up blood.
- Extraflagellated micro gametocyte enters macrogamete to form ookinete.
- Ookinete develops into Oocyst
- Oocyst ruptures to release sporozoites, which mosquito injects into blood.
Diagnosing malaria
Giemsa-stained blood film
Rapid diagnostic tests (RDT)
Giemsa-stained blood film in diagnosing malaria
Blood sample is taken.
- No fixative
Red blood cells would have lyse in malaria
With fixative
- Parasites can be seen inside abc and quantified
- Can identify plasmodium species, parasitemia (density), and the parasite stage
Rapid diagnostic tests in diagnosing malaria
Detects parasite specific antigens enzymes.
- Less sensitive than microscopy
- Blood is put in square hole
- Buffer in round hole
- If antigens/enzymes are present, labelled Ab capture the Ag to form complex.
- Ab-Ag complex binds to ab on test band to give positive results
Problems with RDTs
Less sensitive than microscopy
Detects antigen rather than live parasite
- Can be positive in patient recently treated
No way of determining parasitaemia or stage of parasite
Malaria classes of severity
Uncomplicated - <2% parasitaemia AND - No schizonts - No clinical complications
Severe
- Parasitaemia >2%
- Parasitaemia <2% AND schizonts/ complications
Parasite sequestration
Parasite infected red blood cells adhere to endothelium
= cytoadherence
- Expresses Plasmodium falciparum erythrocyte membrane (PfEMP-1)
Uninfected cells also contribute by rolling mechanism
- Also sticks to infected cells (rosetting)
Plasmodium falciparum erythrocyte membrane (PfEMP-1)
Adhesive molecule on infected red blood cells (IRBC)
- Only one type is expressed on a cell
Parasites can exchange the genes for this (var) and escape immune infection.
- Ab created against 1 PfEMP will not be complementary to new PfEMP
Cerebral malaria
Unrousable coma with peripheral parasitaemia where encephalopathy has been ruled out.
Presents (before LOC):
- General convulsions
- Focal neurologic signs
- Brainstem signs
- Abnormal posture + muscle tone
Blantyre coma score and malaria
Scale of Consciousness for children <13.
<3 = cerebral malaria
Old malaria drug
- Side effects
IV quinine
side effects:
- Hypoglycaemia
- Arrhythmia
- Lethal hypotension in rapid infusion
Malaria treatment
IV artesunate
- Inhibits the formation of trophozoite (ring stage)
- Inhibits maturation of schizont
- prevents sequestration by inhibiting cytoadhering stage
Primaquine
- for P.vivax/ ovale
- Eradicates liver hypnozoite stage
Parasite factors that affect the clinical outcomes of malaria (6)
Drug resistance
Multiplication rate
Invasion pathways
Cytoadherence/ Rosetting
Antigenic polymorphism/ Variation
Malaria toxin
Host factors that affect the clinical outcomes of malaria
Immunity
Proinflammatory cytokines
Genetics (SCT, thalassaemia)
Age (no cerebral malaria in infants)
Pregnancy
Environmental factors that affect the clinical outcomes of malaria
Access to treatment
Cultural and economic factors
Political stability
Transmission intensity
Artemisinin combination therapy
Malaria treatment that prevents malaria resistance
Artemisinin is combined with another drug i.e lumefantrine.
Genetic protective factors against malaria
Sickle cell trait
Duffy negative
- RBC resistant to infection by P.vivax
- Common in most of africans
Entomological inoculation rate (EIR)
Number of infectious bites per person, per year.
Stable endemic transmission
= <10
- Partial immunity acquired in early childhood
- Severe disease in young before acquired immunity
Unstable epidemic transmission
= <1-5
- Acquired immunity developed much later
- Severe disease possible in all
Signs of severe malaria (7)
Anaemia
Jaundice
Respiratory distress
Renal impairment
Blackwater fever (dark red/ black urine due to haemolysis + kidney failure)
Hypoglycaemia
Cerebral malaria
