Malaria Flashcards

1
Q

How long does it take for malaria parasite to transfer from person-mosquito-person?

A

approximately 2 weeks

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2
Q

What are the two main types of malaria parasite?

A

P. falciparium: Causes a lot of morbidity and mortality

P. vivax: Cause of severe illness. Has a dormant stage in the liver

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3
Q

Where in the world is P. falciparium a major problem?

A

Sub-sahara Africa and PNG

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4
Q

Where in the world is P. vivax a major problem?

A

90% in Asia and south central America

Not common in Africa due to mutations that make people resistant

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5
Q

Who is at high risk of complications from malaria infection?

A

Pregnant women: causes low birth weight in neonate (most severe indicator of health)

Children: impacts on education and development and compounds poverty

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6
Q

What are some obstacles that need to be overcome to combat malaria?

A

More effective control measures (so far only have bed- nets doused with insecticides)

No vaccine currently available

Insecticide and drug resistance increasing

Social, economic and political factors

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7
Q

Can malaria be passed between species?

A

NO. The only exception is P. knowlesi

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8
Q

Describe the life cycle of P. falciparum?

A

Infected female mosquito bites host > Enters hepatocytes > replicates in hepatocytes > burst hepatocytes > enter blood > Merozoite undergoes sexual reproduction > new female mosquito takes up parasite > matures in mosquito

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9
Q

How long does it take for the parasite to enter the liver?

A

1-2 hours

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10
Q

How long does it take for the parasite to burst the hepatocyte and enter the RBC stage?

A

7-10 days

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11
Q

Is the entire lifecycle of malaria symptomatic for the host?

A

NO. The liver stage is asymptomatic

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12
Q

What are the clinical features of uncomplicated malaria?

A

‘Flu-like’ - fever, headache, malaise

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13
Q

What are the clinical features of severe malaria?

A
Severe anaemia
Cerebral complications (coma, convulsions, neuro deficits - 15-30% of children with this will die)
Respiratory destress and metabolic acidosis (reduced tissue perfusion and lung damage.
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14
Q

What is the treatment for mild malaria?

A

3 day course of anti-malarial tablets (90% effective)
Aremisinin combination therapy

for P. vivax clearance of liver stage: primaquine

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15
Q

What is the treatment for severe malaria?

A

ASAP: anti-malarials IV artemisinin or quinine (7-10 days)

Supportive therapy: IV fluids, blood transfusion, anti-convulsives, anti-coagulants and anti-inflam drugs

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16
Q

Describe the illness associated with malaria?

A

Parasite accumulation in vital organs
Inflammatory response
Destruction of RBC from spleen (even uninfected cells)

17
Q

Can immunity to malaria develop?

A

Eventually yes but the individual will have 20-30 episodes of infection

18
Q

What are the types of immunity to malaria?

A

Immunity to prevent: severe malaria (specific antigens are recognised) OR any malaria (Ab targeting conserved epitopes or antibodies for all serotypes)

Immunity to malaria in pregnancy

19
Q

Why is there slow development of immunity to malaria?

A

There is a lot of antigenic variation - polymorphic evades the immune system

Can switch on/off genes to evade responses

Host immune response may be inadequate, non-functional or develop poor memory

20
Q

What are the important adaptive immune system responses to malaria?

A

B cells: Antibodies for neutralisation, opsinization (phagocytosis) ans complement binding (lysis)

T cells: CD4 and CD8 (and activated Macrophages

21
Q

Can people become immune to malaria? If so, how?

A

YES.
Genetic factors: sickle cell trait, alpha thalassaemia or some particular blood groups can be resistant.
Innate immunity: Plasma type (complement, MBL), innate cell response (NK cell) and activated macrophage
Acquired immunity

22
Q

How does acquired immunity to malaria work?

A

This can occur at different stages of infection in malaria life cycle.

  1. Sporozoite stage: Ab and Tcell response inhibit infection of hepatocytes
  2. Liver stage: T cell response CD8+ againstinfected hepatocytes
  3. Merozoite stage: Ab response
  4. Infected RBC: Ab and T cells. RBC lack MHC so CD8+ cells are of no use. CD4+ cells play a supportive role in splenic clearance (and macrophage phagocytosis) of infected RBC. Ab to merozoites inhibit invasion of RBC or Ab to proteins on RBC surface can cause opsinisation of RBC for phagocytosis (PROBLEM: lots of variation)
23
Q

Why is it important to have a good understanding of how immunity develops

A

Vaccine development

24
Q

Does the cell mediated immune response in the blood stage of malaria infection contribute to disease?

A

It depends on what cytokines are produced. IFN-gamma is associated with protection but the pro-inflammatory cytokines (TNF-a) are associated with severe disease

25
Q

What are some challenges in delivering treatment to remote communities?

A

Communication with the locals: may need to set up meetings
Road block due to weather
Participation
The treating team has to bring all equipment with them.

26
Q

What are some current issues with gaining immunity from malaria?

A

The Ab may be for the wrong stage of the parasites lifecycle
Ab are specific, and malaria has a lot of antigenic variation and some are not important for virulence
May have the right antigen but wrong epitope (e.g. for sites not involved in invasion)

27
Q

What are some types of vaccines in development?

A
  1. for the sporozoite/liver stage: Ab to block entry to liver and CD8+ cells to kill infected hepatocytes
  2. Merozoite: Ab to block infection of RBC
  3. Transmission stage: block the gamete transmission
28
Q

How successful have vaccine trials been?

A

S vaccine may be useful for P. falciparium by inducing Ab response to a major antigen of the sporozoite (CS)
30-65% effective in malaria episodes and 50% effective in reducing hospital admissions for severe malaria. Duration of protection is 2 years

29
Q

What are some challenges in producing vaccines?

A

Complex lifecycle and antigenic diversity
Need higher efficacy and increased duration of protection
Need to be cheap and easy to deliver to resource poor communities
Vaccines for P.vivax
Public health: immunizing children first, need boosters throughout tlife