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302 Scientific basis of medicine > Infection 2) Pathogenesis of human malaria > Flashcards

Infection 2) Pathogenesis of human malaria Flashcards

1
Q

How many cases of malaria are there per year?

A

216 million

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2
Q

How many deaths from malaria per year?

A

435,000

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3
Q

Where do 90% of malaria cases occur?

A

Sub-saharan Africa

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4
Q

How can malaria be prevented?

A

Vector control
Diagnostics
Treatment
Prevention in pregnancy

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5
Q

What are the 5 plasmodium species in humans?

A 
Falciparum
Vivax
Ovale
Malaria
Knowlesi
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6
Q

How do the species of malaria differ?

A

Geographical distribution
Lifecycle
Clinical features

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7
Q

Describe the difference in malaria severity in children and adults in endemic areas

A

More severe in children

More likely asymptomatic and uncomplicated in adults

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8
Q

How is uncomplicated malaria defined?

A

Parasitaemia below 2%
No schizonts
No clinical complications

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9
Q

How is severe malaria defined?

A

Parasitaemia above 2% or

Parasitaemia below 2% and schizonts or complications

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10
Q

Describe the plasmodium life cycle

A

1) Gametocytes picked up during blood meal by anopheles mosquitoes
2) Start cycle of growth and multiplication in mosquito
3) Mosquito takes another blood meal from another human
4) Infective sporozoites are injected with saliva and start another human infection by infecting liver cells
5) Enter bloodstream as merozoites
6) Enter RBC for cycles of replication within peripheral and microvasculature
7) Merozoites mature into trophozoites (ring stage)
8) Mature into schizonts which rupture and release more merozoites

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11
Q

How does the lifecycle of plasmodium vivax and ovale differ from the other species?

A

They have a dormant stage in the liver (hypnozoites) which can cause relapses by invading into the bloodstream weeks or years later

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12
Q

Why aren’t rapid diagnostic tests as good as microscopy?

A

Less sensitive by 10-100X

Can’t determine % paraistaemia or parasite stage

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13
Q

What do RDTs detect?

A

Parasite-specific antigens or enzymes produced by malaria parasite which are present in blood of infected individuals

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14
Q

When are RDTs falsely positive?

A

In patients who have been recently treated or come from malaria endemic area and have low-level asymptomatic parasitaemia

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15
Q

How do RDTs work?

A

Blood obtained by finger prick
Dye-labelled antibody binds to parasite antigen
Resultant complex is captured on strip by a band of bound antibody to form a visible line

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16
Q

What is the method for Giemsa-stained film?

A

1) take blood sample
2) drop of blood on slide and dry
3) fix with alcohol and dry
4) treat with giemsa stain and dry
5) identify under microscope

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17
Q

What does microscopy allow identification of?

A

Species
Number of parasites
Parasite stage

18
Q

What is the difference between a thick and thin film?

A

Thick film has no fixative, RBCs lyse, increased sensitivity

Thin film has cells fixed intact in monolayer, quantification of parasites, used for plasmodium species speciation

19
Q

What is the consequence of cytoadherence of infected RBCs?

A

Sequestration and blocking of cerebral capillaries

20
Q

Describe how sequestration has a pathological base of severe manifestation of malaria

A

Blood flow impairment causes local hypoxia
Enhances parasite replication and sticking of infected RBCs to non-infected RBCs
Effects of parasite toxins and stimulation of host immune response is more localised causing focused production of inflammatory mediators and tissue damage

21
Q

What is PfEMP-1?

A

Expressed by parasite on surface of infected RBC

Parasite exchanges expressed var gene causing antigenic variation allowing immune response to be escaped

22
Q

What are the consequences of severe malaria in children?

A 
Hypoglycaemia
Blackwater fever
Renal impairment
Respiratory distress
Jaundice
Anaemia
Cerebral malaria
23
Q

Why does anaemia occur in severe malaria?

A

Haemolysis of infected RBC
Haemolysis of uninfected RBCs
Bone marrow suppression (dyserythropoiesis)

24
Q

What is cerebral malaria?

A

Unarousable coma in presence of peripheral parasitaemia where other causes of encephalopathy have been excluded
Diffuse cerebral dysfunctions
Generalised convulsions

25
Q

What are the differential diagnoses of cerebral malaria?

A

Meningitis
Encephalitis
Brain abscess

26
Q

What drug used to be used to treat malaria?

A

IV quinine

27
Q

Why is quinine no longer used?

A

Severe complications
Hypoglycaemia, arrhythmia, potential lethal hypotension in rapid infusion
Still had significant mortality

28
Q

What drug is used to treat malaria?

A

IV artesunate

29
Q

How does artesunate work?

A

Kills circulating ring-stage parasites and schizonts

Active against pathological cytoadhering stages that sequester in venues and capillaries of vital organs

30
Q

How do vivax and ovale differ in their treatment compared to other species?

A

They need additional primaquine

31
Q

What is EIR?

A

Number of infectious bites per person per year

32
Q

What is a stable endemic transmission?

A

EIR > 10 per year

Severe disease in very young before acquisition of immunity

33
Q

What is unstable epidemic transmission?

A

EIR below 1-5 per year

Severe disease is possible in all ages

34
Q

What are the 2 genetic protective factors for malaria?

A

Sickle cell trait

Duffy negative

35
Q

Why is the sickle cell trait protective against malaria?

A

HbS is protected

36
Q

Why is Duffy negative protective against malaria?

A

RBCs are resistant to infection by P.vivax

37
Q

Why is antimalarial drug resistance common?

A

Unusual genetic structural of malarial parasites
Artemisinin drug use without complementary combination treatment such as lumefantrine
Unregulated or poorly administered antimalarial drug use
Counterfeit or substandard treatments

38
Q

What are some parasite factors that impact clinical outcome?

A 
Drug resistance
Multiplication rate
Invasion pathways
Cytoadherence
Rosetting
Antigenic polymorphism
Antigenic variation
Malaria toxin
39
Q

What are some host factors that impact clinical outcome?

A 
Immunity
Proinflammatory cytokines
Genetics (sickle cell trait, thalassaemia, ovalocytosis etc.)
Age
Pregnancy
40
Q

What are some geographic and social factors that impact clinical outcome?

A

Access to treatment
Cultural and economic factors
Political stability
Transmission intensity

302 Scientific basis of medicine (28 decks)

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