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MD1 Locomotor > Eukaryotic Parasites 3: Malaria > Flashcards

Eukaryotic Parasites 3: Malaria Flashcards

1
Q

Can malaria be transmitted person to person?

A

No

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2
Q

What happens if malaria is not treated?

A 
Often fatal
Affects
- Brain
- Lungs
- Placenta
- Other organs
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3
Q

What are the two main types of malaria?

A

Plasmodium falciparum

Plasmodium vivax

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4
Q

Which type of malaria is most relevant to the Asia-Pacific region?

A

P vivax

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5
Q

Which region has the greatest burden of P falciparum?

A

Sub-Saharan Africa

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6
Q

Which regions have the greatest burden of P vivax?

A

Asia-Pacific

South America

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7
Q

Which demographics are at the greatest risk?

A

Young children

Pregnant women

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8
Q

What are the effects of malaria in pregnancy?

A

Infection can get into placenta
Low birth weight
Miscarriages and stillbirths

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9
Q

What is the socio-economic burden of malaria?

A

Impedes economic development
Impacts on learning and education
Compounds poverty

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10
Q

What are the obstacles to combating malaria?

A 
No highly effective control measures
- Partially effective measures
- Poorly applied
No vaccine
Drug resistance widespread and increasing
Insecticide resistance
Economic, political, and social factors
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11
Q

What are the species of Plasmodium that infect humans?

A 
P falciparum
P vivax
P ovale
P malariae
P knowlesi
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12
Q

Which species of Plasmodium causes the majority of severe malaria disease and death?

A

P falciparum

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13
Q

Which species of Plasmodium has a dormant liver stage that can reactivate at any time after treatment?

A

P vivax

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14
Q

Which species of Plasmodium has a limited distribution and causes mild disease?

A

P ovale

P malariae

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15
Q

Which species of Plasmodium is a zoonotic infection, that is present in macaques throughout south-east Asia?

A

P knowlesi

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16
Q

What is the vector for malaria?

A

Female Anopheles mosquito

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17
Q

What is the animal reservoir for malaria?

A

None, except for P knowlesi

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18
Q

How long is the P falciparum cycle?

A

48 hours

19
Q

What is the dormant liver stage of malaria?

A

In P vivax

Some infected hepatocytes remain infected and dormant

20
Q

When does disease occur during the malaria cycle?

A

During blood stage

21
Q

What are the immune responses primarily against in malaria?

A

Blood stage parasites

Involve humoral and cellular responses

22
Q

What is the life cycle of Plasmodium?

A
  1. Malaria infected mosquito inoculates sporozoites into human
  2. Sporozoites infect liver cells
  3. Mature into schizonts
  4. Rupture and release merozoites
  5. Merozoites infect RBCs
  6. Inside RBC: immature trophozoite (ring-stage) > mature trophozoite > schizont > ruptured schizont > release merozoites
  7. Some immature trophozoites differentiate into gametocytes
  8. Gametocytes ingested by mosquito via blood meal
  9. Zygotes generated in mosquito’s stomach
  10. Become motile ookinetes
  11. Invade midgut wall > develop oocysts
  12. Oocysts grow > rupture > release sporozoites > travel to mosquito’s salivary glands
23
Q

What are the clinical features of uncomplicated (mild) malaria?

A

Flu-like illness
Fever
Headache
Malaise

24
Q

What are the clinical features of severe malaria?

A 
Severe anaemia
Cerebral malaria
- Coma
- Convulsions
- Long-term neurological deficits
Respiratory distress and metabolic acidosis
- Reduced tissue perfusion
- Lung damage
Other
- Hypoglycaemia
- Kidney failure
- Blood clotting problems
25
Q

What is the treatment for mild malaria?

A

Short course of effective anti-malarial tablets
Artemisinin combination therapy (ACT)
Clearance of P vivax liver stage

26
Q

Which artemisinin combination therapy is most widely used?

A

Artemether-lumefantrine

27
Q

Which drug is used to clear the liver stage in a P vivax infection?

A

Primaquine

28
Q

What is the treatment for severe malaria?

A 
Anti-malarials
- IV artemisinin/quinine for 7-10 days
IV fluids
Blood transfusion if needed
Supportive treatment
Anticonvulsant
Anticoagulant
29
Q

What is the pathogenesis of severe malaria?

A 
Unrestricted replication of malaria in bloodstream >
Accumulate in vital organs
Inflammatory responses
Destruction of RBCs >
Severe illness
30
Q

Does immunity to malaria exist?

A

Eventually develops after many episodes

31
Q

What are the types of immunity that develop to malaria?

A

Prevents severe malaria
Prevents any malaria
In pregnancy

32
Q

What are the parasite factors that contribute to slow development of immunity to malaria?

A

Multiple Ag targets
Ag diversity = major targets show substantial diversity
Ag variation = gene families allow switching to evade responses

33
Q

What are the host factors that contribute to slow development of immunity to malaria?

A

Inadequate response, especially in young children
Non-functional/irrelevant responses
Poor development of memory responses

34
Q

What does antigenic variation and diversity in Plasmodium enable?

A

Chronic and reactivated infections

Repeat infections

35
Q

What genetic factors confer immunity and resistance to malaria?

A

Sickle cell trait
Alpha thalassemia
Blood groups

36
Q

What innate immune factors confer immunity and resistance to malaria?

A 
Plasma factors
- Complement
- Mannose-binding lectin
Innate cells
- NK cells
- Specific T cell subsets
37
Q

Which immune cells target sporozoites?

A

Abs > inhibit infection of hepatocytes

T cells

38
Q

Which immune cells target infected hepatocytes?

A

CD8 T cells

39
Q

Which immune cells target merozoites?

A

Abs

40
Q

Which immune cells target infected RBCs?

A

Abs

T cells

41
Q

What are the cell-mediated responses to the blood stage of malaria?

A

RBCs lack MHC molecules
CD4 T cells involved in protection
Splenic clearance of parasitised RBCs by macrophages
IFN-gamma production associated with protection
Excessive pro-inflammatory cytokines associated with severe disease

42
Q

What are the humoral responses to the blood stage of malaria?

A 
Passive transfer of Abs protective
Abs to merozoites
- Inhibit RBC invasion and growth
Abs to infected RBCs
- Parasite Ags expressed on surface of RBCs
- Opsonisation for phagocytosis
43
Q

What are the immune mechanisms behind building a vaccine to the sporozoite/liver stage of malaria?

A

Abs block entry to liver
CD8 T cells inhibit parasite development in liver
Prevent parasites entering bloodstream

44
Q

What are the immune mechanisms behind building a vaccine to the merozoite/blood stage of malaria?

A 
Block infection of RBCs
- Directly
- Via interaction with complement
Opsonise merozoites for phagocytic clearance
Prevent replication in bloodstream

MD1 Locomotor (17 decks)

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