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302: Scientific basis of medicine > Pathogenesis of malaria > Flashcards

Pathogenesis of malaria Flashcards

1
Q

Epidemiology

  • Cases per annum
  • Deaths
  • Number of countries affected
A

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)

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2
Q

Top 6 countries with the highest burden of malaria

A

Nigeria

Demographic republic of Congo

Tanzania

Uganda

Mozambique

Ivory Coast

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3
Q

Main methods of malaria prevention

A

Vector control:

  • Insecticide treated mosquito nets
  • Indoor residual spraying of insecticide

Prevention in pregnancy

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4
Q

Malaria vector

A

Female anopheles mosquito

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5
Q

Different malaria species (5)

A

All plasmodium:

  • Falciparum
  • Vivax
  • Ovale
  • Malarie
  • Knowlesi
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6
Q

Fever paroxysms of plasmodium species

A

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)
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7
Q

Human liver stages of malaria pathogenesis

A
  1. Mosquito injects sporozoites as it takes blood.
  2. Sporozoites infect liver cells and divides to form schizont.
  3. The schizont ruptures and ruptures hepatocytes, merozoites then enter the blood stream.
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8
Q

Human blood stages of malaria pathogenesis

A
  1. Merozoites from ruptured schizont in blood infect red blood cells.
  2. Merozoites mature into trophozoites.
  3. Trophozoites mature into schizonts.
  4. Schizonts rupture the abc and release more merozoites
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9
Q

Gametocytosis of malaria

A

Immature trophozoite in abc can mature into gametocytes.

Gametocytes then develop and are taken up by mosquito.

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10
Q

Mosquito stages of malaria

A
  1. Mosquito takes up gametocytes when it takes up blood.
  2. Extraflagellated micro gametocyte enters macrogamete to form ookinete.
  3. Ookinete develops into Oocyst
  4. Oocyst ruptures to release sporozoites, which mosquito injects into blood.
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11
Q

Diagnosing malaria

A

Giemsa-stained blood film

Rapid diagnostic tests (RDT)

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12
Q

Giemsa-stained blood film in diagnosing malaria

A

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
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13
Q

Rapid diagnostic tests in diagnosing malaria

A

Detects parasite specific antigens enzymes.
- Less sensitive than microscopy

  1. Blood is put in square hole
  2. Buffer in round hole
  3. If antigens/enzymes are present, labelled Ab capture the Ag to form complex.
  4. Ab-Ag complex binds to ab on test band to give positive results
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14
Q

Problems with RDTs

A

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

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15
Q

Malaria classes of severity

A 
Uncomplicated
- <2% parasitaemia
AND
- No schizonts
- No clinical complications

Severe

  • Parasitaemia >2%
  • Parasitaemia <2% AND schizonts/ complications
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16
Q

Parasite sequestration

A

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)

17
Q

Plasmodium falciparum erythrocyte membrane (PfEMP-1)

A

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

18
Q

Cerebral malaria

A

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
19
Q

Blantyre coma score and malaria

A

Scale of Consciousness for children <13.

<3 = cerebral malaria

20
Q

Old malaria drug

- Side effects

A

IV quinine

side effects:

  • Hypoglycaemia
  • Arrhythmia
  • Lethal hypotension in rapid infusion
21
Q

Malaria treatment

A

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
22
Q

Parasite factors that affect the clinical outcomes of malaria (6)

A

Drug resistance

Multiplication rate

Invasion pathways

Cytoadherence/ Rosetting

Antigenic polymorphism/ Variation

Malaria toxin

23
Q

Host factors that affect the clinical outcomes of malaria

A

Immunity

Proinflammatory cytokines

Genetics (SCT, thalassaemia)

Age (no cerebral malaria in infants)

Pregnancy

24
Q

Environmental factors that affect the clinical outcomes of malaria

A

Access to treatment

Cultural and economic factors

Political stability

Transmission intensity

25
Q

Artemisinin combination therapy

A

Malaria treatment that prevents malaria resistance

Artemisinin is combined with another drug i.e lumefantrine.

26
Q

Genetic protective factors against malaria

A

Sickle cell trait

Duffy negative

  • RBC resistant to infection by P.vivax
  • Common in most of africans
27
Q

Entomological inoculation rate (EIR)

A

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

28
Q

Signs of severe malaria (7)

A

Anaemia

Jaundice

Respiratory distress

Renal impairment

Blackwater fever (dark red/ black urine due to haemolysis + kidney failure)

Hypoglycaemia

Cerebral malaria

302: Scientific basis of medicine (28 decks)

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