Pathogenesis of malaria

Question 1

EPIDEMIOLOGY

i) how many cases are there worldwide per year? how many countries have ongoing transmission?
ii) which area of the world do 95% of cases occur in?
iii) what is the main way to reduce transmission?

Answer 1

i) 241 million cases per year
- 85 countries have ongoing transmission

ii) 95% of cases in sub saharan africa
iii) vector control > insecticide treated nets and indoor sprays

Question 2

MALARIA LIFE CYCLE

i) which parasite is responsible for malaria? which mosquito?
ii) which human cells are infected first? which cells does the parasite replicate in?
iii) what are the two cycles of replication? what happens at the end of both?
iv) what does the mosquito inject when it takes a blood meal (bite) from a human?
v) name two plasmodium variatns that have a dormant stage and can persist in liver > relapses weeks/years later?

Answer 2

i) plasmodium - anopheles mosquito
ii) infect liver cells first > replicates in red blood cells

iii) exo-erythrocytic (liver cell rep) and erythrocytic (RBC)
- replicate and then the cell ruptures in both stafes > releasing merozites that go on and infect more cells

iv) injection of sporozoites
v) P. vivax and P. ovale

Question 3

MALARIA SUBTYPES

i) what is the most common type in the UK?
ii) which group of people have the lowest chance of developing severe disease?
iii) what severity of disease is most common in children?

Answer 3

i) P. falciparum
ii) adult living in an endemic area
iii) uncomplicated if P.falicparum

Question 4

TESTING FOR MALARIA

i) what is seen on a blood film? what stain is used?
ii) what are rapid diagnostic tests used for? are they more or less sensitive than microscopy?
iii) what is the difference between a thick and thin blood smear? which one is fixed in methanol?
iv) which time of blood smear is useful for detecting the presence of parasites? which is used to look at specific species?
v) what three things should be reported from microscopy

Answer 4

i) see giemsa-stained blood film
- treat with giemsa stain to stain parasites

ii) rapid tests are used to detect parasite specific antigens or enzymes (not live parasite) - doesnt mean they have malaria
- less sensitive than microscopy

iii) thick is a drop of blood on a glass slide (not fixed in methanol)
thin is a drop of blood that is thinly smeared across a large area of the slide (fixed in methanol)

iv) thick smear > detect parasites
thin smear > look at species

v) species, parasitemia (density) and parasite syage

Question 5

CLASSIFICATION OF MALARIA

i) what is uncomplicated? (3)
ii) what two things can mean severe?
iii) what is the mortality of severe malaria in first 24hrs?

Answer 5

i) uncomplicated = parasitaemia <2%, no schizonts (big cell with dots in) and no clinical complications
ii) severe = parasitaemia >2% or <2% byt with schiztonts on blood film or complications
iii) 10-40% > medical emergency

Question 6

PATHOGENESIS

i) what adhesive molecule is expressed on the surface of infected red blood cells?
ii) how do the cells consequently escape immune response?
iii) what does this cell surface molecule allow cells to do in the capillaries? what type of manifestations of malaria is this responsible for?
iv) what three main things are seen in severe malaria pathogenesis in relation to RBC?

Answer 6

i) PfEMP1
ii) PfEMP1 is encoded by var gene > parasite regularly exchanges the expressed var gene to evade antibody response when antibodies to PfEMP1 are produced

iii) PfEMP1 is an adhesive molecule > allows binding to endothelial cells of cerebral capillaries > sequestration and blocking of caps
- contributes to severe manifestations of malaria inc cerebral malaria, impaired blood flow > hypoxia

iv) haemolysis of both infected and uninfected RBC and bone marrow supression

Question 7

CLINICAL SPECTRUM OF SEVERE MALARIA

i) what levels of RBC are seen? what is seen in the kidneys? is there a metabolic acid or alkalosis?
ii) name five things that are seen in severe malaria?

Answer 7

i) low levels of RBC due to rupture and adhesion
- renal impair with metabolic acidosis

ii) cerebral malaria, anaemia, jaundice, resp distress, renal impair, hypoglycaemia, shock, pulm oedema, blackwater fever

Question 8

CEREBRAL MALARIA

i) when should be be suspected?
ii) what score in used in children?
iii) name three other things that may be seen?
iv) name two other differentials?

Answer 8

i) any alteration in conciousness with malaria
ii) blantyre score - 3 or less = CM
iii) diffuse cerebral dysfunc, general convulsions, focal neiol signs, abnormal posture and tone
iv) meningitis, TB, encephalitis

Question 9

MANAGEMENT OF SEVERE MALRIA

i) what is the primary objective? what is the objective in cerebral malaria? in pregnancy?
ii) what treatment was previously given for severe malaria? name three downsides of this
iii) what is given now? why? (3)/
iv) what stage does the new treatment target
v) which treatment should be added if P vivax or P ovale are found?

Answer 9

i) to prevent death
- CM > prevent neurological deficit
- pregnancy > save life of the mother

ii) IV quinine > hypogly, arrhythmia, lethal hypotension if rapid infusion
- still had signif mortaltiy

iii) now use IV artesunate
- safe and easy to admin and reduces parasite burden more rapidly

iv) artesunate prevents maturation of the younger parasite stages and therefore prevents sequestration and microcirc obstruc
v) add primaquine

Question 10

MALARIA IMMUNITY

i) what does the nature of malaria clinical disease depend on?
ii) what does it mean for transmission of malaria to be stable?
iii) what is seen in areas of unstable epidemic transmission?
iv) which two conditions provide protection against malaria? what area of the world are these most commonly seen?
v) which combination therapy may be used to reduce risk of resistance? what is the main problem with this?

Answer 10

i) dep on background level of acquired protective immunity - outcome of the pattern and intesntiy of malaria transmission in area of residence
ii) when it is accepted that partial immunity and severe manifestations might be acquired in early childhood

iii) rates fluctaute greatly over seasons and years
- all age groups are at high risk of prgoression to severe malaria if left untreated

iv) sickle cell trait and duffy negative blood group (resis to P vivax)
- seen more in africa/west africa

v) ateminisin combination therapy
- problem is counterfeit or substandard treatments

Question 11

SUMMARY

i) what marks the start of symptomatic infection?
ii) name three features of severe malaria

Answer 11

i) fever
ii) metabolic acidosis, severe anaemia, cerebral malaria