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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?

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
What is the treatment for mild malaria?
Short course of effective anti-malarial tablets Artemisinin combination therapy (ACT) Clearance of P vivax liver stage
26
Which artemisinin combination therapy is most widely used?
Artemether-lumefantrine
27
Which drug is used to clear the liver stage in a P vivax infection?
Primaquine
28
What is the treatment for severe malaria?
``` Anti-malarials - IV artemisinin/quinine for 7-10 days IV fluids Blood transfusion if needed Supportive treatment Anticonvulsant Anticoagulant ```
29
What is the pathogenesis of severe malaria?
``` Unrestricted replication of malaria in bloodstream > Accumulate in vital organs Inflammatory responses Destruction of RBCs > Severe illness ```
30
Does immunity to malaria exist?
Eventually develops after many episodes
31
What are the types of immunity that develop to malaria?
Prevents severe malaria Prevents any malaria In pregnancy
32
What are the parasite factors that contribute to slow development of immunity to malaria?
Multiple Ag targets Ag diversity = major targets show substantial diversity Ag variation = gene families allow switching to evade responses
33
What are the host factors that contribute to slow development of immunity to malaria?
Inadequate response, especially in young children Non-functional/irrelevant responses Poor development of memory responses
34
What does antigenic variation and diversity in Plasmodium enable?
Chronic and reactivated infections | Repeat infections
35
What genetic factors confer immunity and resistance to malaria?
Sickle cell trait Alpha thalassemia Blood groups
36
What innate immune factors confer immunity and resistance to malaria?
``` Plasma factors - Complement - Mannose-binding lectin Innate cells - NK cells - Specific T cell subsets ```
37
Which immune cells target sporozoites?
Abs > inhibit infection of hepatocytes | T cells
38
Which immune cells target infected hepatocytes?
CD8 T cells
39
Which immune cells target merozoites?
Abs
40
Which immune cells target infected RBCs?
Abs | T cells
41
What are the cell-mediated responses to the blood stage of malaria?
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
What are the humoral responses to the blood stage of malaria?
``` 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
What are the immune mechanisms behind building a vaccine to the sporozoite/liver stage of malaria?
Abs block entry to liver CD8 T cells inhibit parasite development in liver Prevent parasites entering bloodstream
44
What are the immune mechanisms behind building a vaccine to the merozoite/blood stage of malaria?
``` 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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