Infection 2: Pathogenesis of malaria Flashcards

1
Q

Incidence of malaria

A

21% global decrease in malaria incidence between 2010 and 2015

219 million cases globally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Mortality of malaria

A

29% decrease in global malaria mortality rates between 2010 and 2015

435000 deaths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Malaria interventions

A

Insecticide treated mosquito nets

Indoor residual spraying

Diagnostics

Treatment

Prevention in pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Issues in UK

A

Malaria is the single most common imported infection in travellers

1792 UK cases notified in 2017

Approximately 6 deaths a year

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Blood stage parasite of malaria

A

Gametocytes picked up during blood meal by anopheles mosquitos

Start another cycle of growth and multiplication in the mosquito

Mosquito takes another blood meal from another human

Infective sporozoites injected with saliva and start another human infection- infect liver cells first

From here enter blood stream as merozoites, then enter RBC for cycles of replication within the peripheral and microvasculature

Merozoites mature into trophozoites which mature into schizonts, which then rupture releasing more merozoites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Most common in UK

A

Plasmodium falciparum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Blood film diagnosis

A

Take blood sample and drop blood on slide

Dry, fix with alcohol

Dry, treat with Giema stain to stain parasites

Dry, look through microscope

Can identify species and number of parasites

  • no fixative
  • RBCs lyse
  • increased sensitivity
  • cell fixed intact in monolayer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Rapid diagnostic testing

A

Detects parasite specific antigens or enzymes

Less sensitive than microscopy

Useful if skilled microscpoist is not available

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Uncomplicated

A

Parasitaemia <2% and no schizonts and no clinical complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Severe

A

Parasitaemia >2%

Or

Parasitaemia <2% plus either scizonts reported on blood film or complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Multi system disease

A

Rapid progression to death

Mortality of 10-40% in first 24 hours

Medical emergency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Plasmodium falciparum erythrocyte membrane PfEMP-1

A

On the surface of Infected RBC

Encoded by a family of 60 var genes. A single cell only expresses one of these at any time

The parasite regularly exchanges the expressed var gene, leading to antigenic variation. As an antibody response forms to 1 PfEMP, there is a switch of expression to alternative PfEMPs, escaping the immune response and maintaining infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical spectrum of severe malaria in childhood

A

Cerebral malaria

Anaemia

Jaundice

Respiratory distress

Renal impairment

Blackwater fever

Hypoglycaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cerebral malaria

A

Unrousable coma in oresence of peripheral parasitaemia where other causes of encephalopathy excluded

In children, Blantyre coma score used

Diffuse cerebral dysfunctions, generalised convulsions

Focal neurological signs and brainstem signs

Abnormalities of posture and muscle tone

Differential diagnosis: meningitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Effects of IV quinine

A

Hypoglycaemia

Arrhythmias

Potentially lethal hypotension in rapid infusion

Significant mortality still: cerebral malaria has a treated mortality rate of 15-20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

IV artesunate

A

Safer and easier to administer

Reduces parasite burden more rapidly

Kills circulating ring-stage parasites as well as schizonts

17
Q

Sickle cell trate

A

HbS relatively protected

18
Q

Duffy negative

A

Persons who are negative for the duffy blood group have RBC that are resistant to infection by P.vivax

P.vivax is rare in Africa south of the Sahara

19
Q

Key drivers of antimalarial drug resistance

A

Unusual genetic structure of malaria parasites in regions known for antimalarial drug resistance

Artmisinin drug use without complementary combination treatment such as lumefantrine

Unregulated or poorly administered antimalarial drug use

Counterfeit or substandard treatments: cause 25% of all malaria deaths

20
Q

Parasite factors

A

Drug resistance

Mulitplication rate

Invasion pathways

Cytoadherence

Rosetting

Antogenic polymorphism

Antigenic variation (PfEMP1)

Malaria toxin

21
Q

Host factors

A

Immunity

Proinflammatory cytokines

Genetics (sickle cell trait, thalassaemia, ovalocytosis)

Age

Pregnancy

22
Q

Geographical and social factors

A

Access to treatment

Cultural and economic factors

Political stability

Transmission to intensity