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Eukaryotic parasites 3: malaria Flashcards

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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
How is P. falciparum transmitted?
By female Anopheles mosquitos
26
Does malaria have animal reservoirs?
No
27
At what stage in the malaria lifecycle is disease present?
During the blood stage
28
What is the immune response to malarai infection primarily against?
Blood stage parasites
29
What is involved in the immune response to blood stage malaria infections?
Both humoral and cellular responses
30
What is the lifecycle for the malaria parasite?
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
31
What are the clinical features of uncomplicated (mild) malaria?
Flu-like illness Fever, headaches and malaise
32
What are the clinical features of severe malaria?
Severe anaemia Cerebral complications Respiratory distress
33
Which cerebral complications exist in cerebral malaria?
Coma Convulsions Long-term neurological deficits
34
How does respiratory distress and metabolic acidosis manifest in severe malaria?
Reduced tissue perfusion Lung damage
35
What is the treatment for mild malaria?
Short course of effective anti-malarial tablets
36
Which short course of effective anti-malarial tablets are used for mild malaria?
Artemisinin combination therapy (ACT) E.g. Artemether-lumefantrine (AL)
37
Which drug is used to clear P. vivax in the liver stage?
Primaquine
38
Why does a patient need a 14 day course of primaquine?
Because p. vivax has a dormant stage in the liver
39
Which drug is used to treat severe malaria?
Intravenous artemisinin or quinine (7-10 days)
40
What else is required, other than IV artemisinin or quining, in severe malaria, if required?
IV fluids Blood transfusion Supportive treatment (Intensive care)
41
Has there been much of an improvement in mortality rate for malaria treatments?
No
42
When does immunity to malaria develop?
After many episodes of infection
43
What are the 3 main types of immunity to malaria?
Immunity that prevents severe malaria Immunity that prevents any malaria Immunity to malaria in pregnancy
44
Which two factors are responsible for slow development of immunity to malaria?
Parasite factors Host factors
45
What parasite factors contribute to the slow development of malaria immunity?
Multiple antigenic targets (~5000 genes) Antigenic diversity: major targets show substantial polymorphism Antigenic variation: gene families allow switching to evade responses
46
What host factors contribute to the slow development of malaria immunity?
Inadequate response (especially young children) Non-functional/irrelevant responses Poor development of memory responses
47
What is the result of antigenic variation and diversity of plasmodium?
Chronic and recrudescent infections Repeat infections
48
How does antigenic variation of plasmodium occur in the individual?
In antigenically distinct waves of parasitaemia
49
What are the antibody components of the immune response to malaria infection?
Neutralisation Opsonisation Complement
50
What are the cellular response components of the immune response to malaria infection?
CD4+ T cells CD8+ T cells Activated macrophages
51
What is the end result of immune response to malaria inflection?
Memory B and T cells
52
Which genetic factors contribute to immunity and resistance to malaria?
Sickle cell trait (haemoglobin defect) Alpha-thalassemia (haemoglobin defect) Blood groups
53
Which 3 components of innate immunity contribute to immunity and resistance to malaria?
Plasma factors Innate cellular responses Activated macrophages
54
Which plasma factors contribute to immunity and resistance to malaria?
Complement Mannose-binding lectin
55
Which innate cellular responses contribute to immunity and resistance to malaria?
NK cells Specific T cell subsets
56
What do antibodies against malaria do?
Inhibit infection of hepatocytes
57
Which immune cells are involved in the liver stage of malaria?
CD8+ T-cells against infected hepatocytes
58
Are antibodies effective in the liver stage of malaria?
No
59
Why is naturally-acquired immunity to liver stage malaria very limited?
Low parasite load Short duration of infection
60
What are cell-mediated responses involved in in the blood stage of malaria?
Protection and disease pathogenesis
61
What role do RBCs play in the blood stage of malaria?
RBCs lack MHC molecules
62
Which T cells are involved in protection in blood stage malaria?
CD4+ T cells
63
Where are parasitised RBCs cleared?
In the spleen
64
Why cytokine is associated with protection in blood stage malaria?
IFNγ
65
Which cytokine response is associated with severe malaria?
Pro-inflammatory cytokine response (e.g. TNFα)
66
What is the role of monocytes and macrophages in blood stage malaria?
Clearance of infected RBCs (mainly in the spleen)
67
What is the role of antibodies in blood stage malaria?
Passive transfer of antibodies is protective
68
What are antibodies in blood stage malaria against?
Merozoites
69
What do antibodies in blood stage malaria do?
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
What can block invasion by plasmodium falciparum?
Antibodies and drugs
71
How does antibody-mediated killing of malaria blood-stage paraistes occur?
Antibodies opsonize merozoites and parasitized RBCs for killing by immune cells (monocytes, macrophages, neutrophils)
72
What blocks infection of RBCs?
Antibodies
73
Do antibodies to a specific antigen protect against malaria?
Yes
74
What may lack of effective immunity may arise from?
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
What blocks entry of sporozoites into the liver?
Antibodies Prevents parasites entering blood stream
76
What role do CD8+ T cells play in the sporozoite/liver stage of malaria?
Inhibit parasite development in the liver Prevents parasites entering blood stream
77
What blocks infection of RBCs by merozoites?
Antibodies Opsonise merozoites for phagocytic clearance Prevent replication in blood stream
78
What is the major antigen of sporozoites?
CS protein
79
What is the RTS,S vaccine?
Segment of CS protein Presented in a virus-like particle (VLP) with hepatitis B surface antigen
80
What are nearly all malaria vaccines in trial against?
P. falciparum
81
Where do malaria parasites replicate?
In RBCs
82
What does acquired immunity to malaria predominantly target?
Blood-stages of Plasmodium, and liver stage to a lesser extent
83
What do the blood stage immune responses mainly involve?
Antibodies
84
What do the liver stage immune responses mainly involve?
T cells

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