Malaria Flashcards
Who are the majority of deaths due to malaria in?
<5
What is hte main plasmodium species involved in malaria?
plasmodium falciparum
What are the other malaria plasmodium species?
plasmodium malariae; vivax and ovale
What form of the parasite is injected into the human when the mosquito injects anticoagulant?
sporozoite
Where do the sporozoites initially travel to?
liver
What type of repoduction do the parasites undergo in the liver?
asexual reproduction
What form are the parasites when tehy burst out of the liver and infect RBCs?
merozoites
Why do you get waves of symptoms in malaria?
parasites tend to burst out of cells at the same time
What life form of the parasite is capable of infecting a mosquito?
gametocyte
What type of replication do the parasites undergo in the blood?
asexual;, however a sub-population of intraerythocytic parasites switches to sexual development producng gametocytes
When do malarial symptoms appear in non-immune individuals?
after 7-15 days
What are the first symptoms of malaria?
fever; HA; chills and vomiting
What happens if not treated within 24 hours
sever anaemia; respiratory distress in relation to metabolic acidossi or cerebral malaria
What happens if you have been infected multiple times?
develop partial immunity
What happens to clinical immunity as endemicity decreases?
acquired slower
What genus of mosquito transmits plasmodium?
anopheles
How many species of anopheles mosquito can transfer plasmodium?
70
Where does sexual reproduction of the palsmodium take placei n the mosquito?
in the stomach
How does temperature affect the replication of plasmodium?
takes place much quicker at higher temperatures- e.g in colder temps, mosquito wont become infectious before it dies as takes too long for parasite to replicate
What is endophagy?
propensity to bite indoors
What is endophily
propensity to rest in the house after feeding
What is the huamn biting index?
propensity to bite humans
Where do mosquitoes lay their eggs?
in water
What are the 2 arms of current malarial interventions?
vector targets and human targets
What are hte vector targets of malarial interventions?
long-lasting insecticide-treated nets; indoor residual spraying; spatial repellents and larval control
What class of insecticde are used on bednets?
pyrethroids
What is the problem with all nets using pyrethroids?
lots of resistance
What are the current vaccine targets?
targeting of incoming parasites; blood-stage asexual development; transmsision stages
What is the first pre-erythrocyte vaccine?
mosquirix
What insecticides are thought to be between than pyrethroids?
PBO- however more expensive
What is another emerging rpoblem with bednets?
mosquitoes are increasingly starting to bite outside of night-time avoiding bed net coverage
Where does the majority of falciparum malaria occur?
sub-saharan africa
How long does the pre-erythrocytic liver stage of hte disease typically last before onset of hte blood stage?
1-2 weeks
What happens once male and female gamtes fuse in the mosquito midgut?
form a mobile ookinete which passes through the gut wall and becomes an oocyst
What happens to the oocyst?
releases sporozoites which migrate to the mosquito salivary glands completing the lifecycle
What can result in malarial relapses months or years after the intial infection?
a proportion of sporozoites become dormant hypnozoites
What is hte MOA of quinine?
kills sequestered parasites but not circulating rings which continue to develop after treatment
What is the MOA of artesunate?
acts against circulating rings and sequestered parasites; killing results in pyknotic parasite forms which the spleen removes by pitting–late haemolysis
When do symptoms of malaria devleop?
once the erythrocytic cycle produces a parasitamia above a certain threshold eg 100parasites per uL
What do the periodic fever spikes in malaria correspond to?
erythrocytic cycle length of the infecting species resulting from synchronisation of the devlopmental stages
What happens to erythrocytes containing P falciparum?
sequester inside small and medium sized vessels avoiding parasite clearance in the spleen but causing host endothelail cell injury and microvascualr obstruction
How does P falciparum mediate cytoadherence?
PfEMP1 which is set of protein exported to the infected RBC surface and encaded by the var gene family
What are the most common manifestations of severe malaria?
cerebral malaria; acute lung injury- can progress to ARDS; acute kidney injury and acidosis
What are the symtposm of uncomplicated malaria?
fever; chills; body-aches; HA; cough and diarrhoea
What is the main acid implicated in malarial acidosis?
lactic acid
What is the gold standard for malaria diagnosis?
light microscopy of stained blood films; thick films providing sensitivity and thin films allowing speciation and quntification
What now predominate as the first line investigation for malaria?
rapid diagnostic tests b
Waht is the p falciparum RDT based upon?
detection of PfHRP2 antigen
What should all patients diagnosed with severe malaria receive as treatment?
parenteral artseunate
Waht is the recommended treatment for falciparum malria or falciparum mixed with other species?
artemisinin-based combination treatments
What do ACTs consist of?
artemisinin derivative that rapidly reduces parasitaemia and a partner drug taht removes residual prasites over a longer period
What are the probelsm with quinine?
although efficacious, it needs a long course; is poorly tolerated and needs combination with a second agent
What are the causes of treatment failure?
drug resistance; high parasite densities; poor drug bioavailability; non-adherence; falsified/substandard antimalarials
What does repeated exposure over a long period to malaria result in?
premunition
What is premunition?
protection from disease but ongoing blood stage infection
What does premunition manifest as with P falciparum?
antibodies to PfEMP1 subtypes
Which species of plasmodium have the dormant stage in the liver?
P.vivax and P.ovale
What do sporozoites mature into in liver cells?
schizonts
What is the PfSPZ vaccine?
IV injection of irradiated-attenuated sporozoites –difficult to get durable protection agsint all relevant strains?
What do schizonts rupture to release?
merozoites
What is the name for the parasite in its ring stage in RBCs?
trophozoites
What do the ring stage trophozoites mature into?
schizonts
What is the parasites multiplication in the mosquito known as ?
sporogonic cycle
What is the function of targeting spoprozoite stages via one of the surface proteins with vaccination?
aims to reduce frequency of infection as the surface proteins mediate homing to thel iver and host cell invvasion
What is the target of the RTS S/AS01 vaccine?
targets circumsporozoite protein which is invovled in sporozoite hepatocyte binding
What have been the reuslts of the RTS S/AS01 vaccine?
efficacy was better in older children than younger; but didnt provide efficacy across all strains and longer term followup showed a higher incidence of malaria in vaccinated children, but long term mortality has not been released
What is the purpose of merozoite-stage proteins as vaccine targets?
reduce asexual replication rate and protect against disease rather than produce steril immunity
What is the theory behind transmission blocking vaccines?
generate antibodies against sexual-stage antigens which are ingested in the mosquito blood meal potentially providing immunity at ap opulation level
