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Gabe's Locomotor > Eukaryotic parasites 3: malaria > Flashcards

Eukaryotic parasites 3: malaria Flashcards

1
Q

What type of an infection is malaria?

A

Blood infection

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2
Q

How is malaria transmitted?

A

By mosquitos

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3
Q

Is malaria transmitted by person-to-person contact?

A

No

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4
Q

Which organs can malaria affect?

A

Brain

Lungs

Placenta

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5
Q

What are the 2 main types of malaria?

A

P. falciparum

P. vivax

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6
Q

What is the most common strain of malaria?

A

P. falciparum

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7
Q

Why are 90% of all p. vivax infections in the Asia Pacific region?

A

Genetic mutations in the African population confer resistance to P. vivax.

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8
Q

Which region is most affected by malaria globally?

A

Sub-Saharan Africa

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9
Q

Which region is most affected by malaria locally?

A

Papua New Guinea

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10
Q

Which groups of people are at greatest risk from Malaria?

A

Young children and pregnant women

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11
Q

How many die from malaria each year?

A

1 million

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12
Q

How many cases of malaria are there per year?

A

300-500 million

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13
Q

What is the leading cause of childhood deaths globally?

A

Malaria

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14
Q

What is the effect of malaria in pregnancy?

A

Low birth weight

Miscarriages and stillbirths

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15
Q

What is the biggest risk factor for early infant death?

A

Low birth weight due to malaria infection

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16
Q

What are the socioeconomic impacts of malaria?

A

Impedes economic development

Impacts on learning and education

Compounds poverty

Mostly affects resource-poor communities

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17
Q

What are the obstacles to combating malaria?

A

No highly effective control measures available

No vaccine

Drug resistance widespread and increasing

Insecticide resistant

Economic, social and political factors

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18
Q

Is there cross-spread among malaria species?

A

No

Human malaria doesn’t infect other species and vice-versa

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19
Q

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

A

P. falciparum

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20
Q

How much of the population is at risk from P. falciparum infection?

A

2.2 billion

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21
Q

How much of the population is at risk from P. vivax infection?

A

2.6 billion

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22
Q

Which strain of malaria has a dormant liver stage?

A

P. vivax

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23
Q

What are the 4 strains of malaria?

A

P. falciparum

P. vivax

P. ovale

P. malariae

P. knowlesi

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24
Q

Which of the malaria species can actually be a zoonotic infection?

A

P. knowlesi

Present in macaques throughout SE Asia

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25
Q

How is P. falciparum transmitted?

A

By female Anopheles mosquitos

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26
Q

Does malaria have animal reservoirs?

A

No

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27
Q

At what stage in the malaria lifecycle is disease present?

A

During the blood stage

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28
Q

What is the immune response to malarai infection primarily against?

A

Blood stage parasites

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29
Q

What is involved in the immune response to blood stage malaria infections?

A

Both humoral and cellular responses

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30
Q

What is the lifecycle for the malaria parasite?

A

Injected as sporozoites by mosquito

Travels to liver

Matures into merozoites

Released from liver in blood cells

Matures into gametocytes in blood

Transmitted to mosquito when feeding

Matures into gamete, then zygote and then ookinete in mosquito gut

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31
Q

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

A

Flu-like illness

Fever, headaches and malaise

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32
Q

What are the clinical features of severe malaria?

A

Severe anaemia

Cerebral complications

Respiratory distress

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33
Q

Which cerebral complications exist in cerebral malaria?

A

Coma

Convulsions

Long-term neurological deficits

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34
Q

How does respiratory distress and metabolic acidosis manifest in severe malaria?

A

Reduced tissue perfusion

Lung damage

35
Q

What is the treatment for mild malaria?

A

Short course of effective anti-malarial tablets

36
Q

Which short course of effective anti-malarial tablets are used for mild malaria?

A

Artemisinin combination therapy (ACT)

E.g. Artemether-lumefantrine (AL)

37
Q

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

A

Primaquine

38
Q

Why does a patient need a 14 day course of primaquine?

A

Because p. vivax has a dormant stage in the liver

39
Q

Which drug is used to treat severe malaria?

A

Intravenous artemisinin or quinine (7-10 days)

40
Q

What else is required, other than IV artemisinin or quining, in severe malaria, if required?

A

IV fluids

Blood transfusion

Supportive treatment (Intensive care)

41
Q

Has there been much of an improvement in mortality rate for malaria treatments?

A

No

42
Q

When does immunity to malaria develop?

A

After many episodes of infection

43
Q

What are the 3 main types of immunity to malaria?

A

Immunity that prevents severe malaria

Immunity that prevents any malaria

Immunity to malaria in pregnancy

44
Q

Which two factors are responsible for slow development of immunity to malaria?

A

Parasite factors

Host factors

45
Q

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

A

Multiple antigenic targets (~5000 genes)

Antigenic diversity: major targets show substantial polymorphism

Antigenic variation: gene families allow switching to evade responses

46
Q

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

A

Inadequate response (especially young children)

Non-functional/irrelevant responses

Poor development of memory responses

47
Q

What is the result of antigenic variation and diversity of plasmodium?

A

Chronic and recrudescent infections

Repeat infections

48
Q

How does antigenic variation of plasmodium occur in the individual?

A

In antigenically distinct waves of parasitaemia

49
Q

What are the antibody components of the immune response to malaria infection?

A

Neutralisation

Opsonisation

Complement

50
Q

What are the cellular response components of the immune response to malaria infection?

A

CD4+ T cells

CD8+ T cells

Activated macrophages

51
Q

What is the end result of immune response to malaria inflection?

A

Memory B and T cells

52
Q

Which genetic factors contribute to immunity and resistance to malaria?

A

Sickle cell trait (haemoglobin defect)

Alpha-thalassemia (haemoglobin defect)

Blood groups

53
Q

Which 3 components of innate immunity contribute to immunity and resistance to malaria?

A

Plasma factors

Innate cellular responses

Activated macrophages

54
Q

Which plasma factors contribute to immunity and resistance to malaria?

A

Complement

Mannose-binding lectin

55
Q

Which innate cellular responses contribute to immunity and resistance to malaria?

A

NK cells

Specific T cell subsets

56
Q

What do antibodies against malaria do?

A

Inhibit infection of hepatocytes

57
Q

Which immune cells are involved in the liver stage of malaria?

A

CD8+ T-cells against infected hepatocytes

58
Q

Are antibodies effective in the liver stage of malaria?

A

No

59
Q

Why is naturally-acquired immunity to liver stage malaria very limited?

A

Low parasite load

Short duration of infection

60
Q

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

A

Protection and disease pathogenesis

61
Q

What role do RBCs play in the blood stage of malaria?

A

RBCs lack MHC molecules

62
Q

Which T cells are involved in protection in blood stage malaria?

A

CD4+ T cells

63
Q

Where are parasitised RBCs cleared?

A

In the spleen

64
Q

Why cytokine is associated with protection in blood stage malaria?

A

IFNγ

65
Q

Which cytokine response is associated with severe malaria?

A

Pro-inflammatory cytokine response (e.g. TNFα)

66
Q

What is the role of monocytes and macrophages in blood stage malaria?

A

Clearance of infected RBCs (mainly in the spleen)

67
Q

What is the role of antibodies in blood stage malaria?

A

Passive transfer of antibodies is protective

68
Q

What are antibodies in blood stage malaria against?

A

Merozoites

69
Q

What do antibodies in blood stage malaria do?

A

Inhibit RBC invasion and growth

Direct inhibition by antibodies

Antibody-dependent cell mediated inhibition of parasite growth

Antibodies to infected RBCs

Parasite antigens expressed on the surface of RBCs

Opsonization for phagocytosis

70
Q

What can block invasion by plasmodium falciparum?

A

Antibodies and drugs

71
Q

How does antibody-mediated killing of malaria blood-stage paraistes occur?

A

Antibodies opsonize merozoites and parasitized RBCs for killing by immune cells (monocytes, macrophages, neutrophils)

72
Q

What blocks infection of RBCs?

A

Antibodies

73
Q

Do antibodies to a specific antigen protect against malaria?

A

Yes

74
Q

What may lack of effective immunity may arise from?

A

Wrong immune response

Wrong target antigen

Right antigens, wrong epitope

Right target, right epitopes → antigenic diversity

Inability to mount a response to a specific antigen/epitope

75
Q

What blocks entry of sporozoites into the liver?

A

Antibodies

Prevents parasites entering blood stream

76
Q

What role do CD8+ T cells play in the sporozoite/liver stage of malaria?

A

Inhibit parasite development in the liver

Prevents parasites entering blood stream

77
Q

What blocks infection of RBCs by merozoites?

A

Antibodies

Opsonise merozoites for phagocytic clearance

Prevent replication in blood stream

78
Q

What is the major antigen of sporozoites?

A

CS protein

79
Q

What is the RTS,S vaccine?

A

Segment of CS protein

Presented in a virus-like particle (VLP) with hepatitis B surface antigen

80
Q

What are nearly all malaria vaccines in trial against?

A

P. falciparum

81
Q

Where do malaria parasites replicate?

A

In RBCs

82
Q

What does acquired immunity to malaria predominantly target?

A

Blood-stages of Plasmodium, and liver stage to a lesser extent

83
Q

What do the blood stage immune responses mainly involve?

A

Antibodies

84
Q

What do the liver stage immune responses mainly involve?

A

T cells

Gabe's Locomotor (9 decks)

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