week 5 - malaria Flashcards
where is malaria endemic?
asia
africa
latin america
oceania
how many of the world population live in areas where malaria is transmitted?
41%
how many reported cases of malaria were there in 2010?
219 million
how many deaths were there due to malaria in 2010?
0.6-1.2 million of which 75% are kids in Africa
malaria is the ___ leading cause of death
fourth
what transmits malaria?
pregnant female mosquitoes
malaria is transmitted when the insect vector____
takes a blood meal
how many different species of mosquito can transmit malaria?
30-40 anopheles species
what do males feed on?
nectar - vegetarian
Which is the most common mosquito to transmit malaria?
anopheles gambiae
Malaria is associated with which habitat?
still water - where mosquitoes utilise the water for breeding
Malaria is caused by what?
Apicomplexa protozoan parasite - genus Plasmodium
apicomplexan parasites are characterised by their cell biology. What is the common feature that they are named after?
apicomplast
non photosynthetic plastid related to chloroplasts. Involved in synthesis pathways.
essentially an apicomplast is what?
a chloroplast that has lost the ability to photosynthesise
Apicomplexans as well as an apicomplast have another key feature?
inner membrane complex.
series of membranous structures that underlie the cell membrane and the purpose of these structures is that it protects the cell, givers the cell shape, allows the cell to effectively move and glide over other surfaces
Which part of the apicomplexan gives the apical end of the parasite its shape?
the apical complex
a series of secretory organelles that are important for cell invasion gliding processes
in humans how many different Plasmodium species can cause malaria?
4
what are the 4 different species that cause malaria?
P.falciparum
P.vivax
P.malariae
P.ovale
which is the most common Plasmodium species to cause malaria?
80% of people will be infected with P.vivax
which Plasmodium species is the most important clinically and why?
P.falciparum
15% of malaria infections but 90% of deaths.
causes severe complications in terms of pathology
what are the 3 stages of malaria?
onset
developmental
severe (only if infected with p.vivax)
After infection by mosquito how many days does it take for the parasites to appear in the blood?
6-18
what is the pre-patent time?
the time to complete liver stage, there are no symptoms with liver infection
what is the pre patent time of the different species?
p. falciparum = 6-9days
p. vivax = 8-12 days
p. ovale = 10-14 days
p. malariae = 15-18 days
what is the incubation period?
the time between RBC infection and onset of symptoms
what is the incubation period of the different species?
p. falciparum = 7-14 days
p. vivax = 12-17days
p. ovale = 16-18days
p. malariae = 18-40 days
What are the classical symptoms in the developmental stage? (5)
chills fever sweating fever declines patient exhausted falls asleep and wakes up well
how long do the classical symptoms last?
4-8 hours
the classical symptoms are repeated how often?
2/3 days
Why does the classical symptom of malaria have a cyclical nature of fever?
When you look at the temperature of a particular individual suffering from the disease and different species fo the plasmodium parasite, correlates with the asexual life cycle of the parasite.
the temperature goes up when the rupturing of cells occurs.
the shift in temperatures give you a measure of how quickly the parasites can go through the asexual cycle.
the asexual cycle in p.vivax and p.ovale is how long?
2 days
the asexual cycle is how long in p.malariae?
3 days
the asexual cycle of p.falciparum?
almost continuous fever. this is one of the problems associated with p.falciparum
why cyclical nature of fever in one sentence?
synchronous development of parasites in human host - all parasites in RBC at same stage of development
what occurs in the body to cause the febrile episodes?
lysis of infected RBC
parasite antigens released into bloodstream
stimulate macrophages and immune effector cells to produce TNF alpha and other cytokines
why do people think there is a chance that a vaccine could be developed against malaria?
because as you age the symptoms observed get less severe
If malaria progresses to the development stage what are the symptoms?
symptoms intensify.
irregular high fever anxiety, delerium sweating severe exhaustion worsening GI symptoms enlarged spleen / liver (hepatosplenomegaly)
when does severe malaria occur?
in 10% of falciparum cases
what are the symptoms of severe malaria? (the 2 main types and then the symptoms associated with those types)
cerebral malaria:
non specific fever followed by loss of consciousness
severe headache, drowziness, neurological abnormalities
convulsions, vomiting
coma
severe anaemia:
drop in hematocrit
poor oxygen supply for organs and tissues
other pathologies that have been affected by severe malaria?
respiratory illness renal failure acidemia circulatory collapse jaundice hyperpyrexia
Severe malaria, what do we understand about the bioscience behind the severe pathologies?
P.falciparum infections only ring stage parasite found in peripheral blood.
mature trophozoite and schizont infected erythrocytes are sticky and attach to the endothelium of venules (cytoadherence)
mature trophozoite and schizont infected erythrocytes not found in peripheral blood but organs
the very pathogenic strains of falciparum malaria do which process at a higher rate than the other strains?
determined in vivo
Rosetting and clumping
what is rosetting?
adhesion of infected RBCs to non infected RBCs
what is clumping?
adhesion between infected RBCs
The analysis of the clumping of RBC showed what?
mature trophozoite and schizont infected erythrocytes have altered surface morphology.
Presence of electron dense protrusions
What do the electron dense protrusions on infected RBC contain?
parasite proteins, all produced and secreted by parasite then transferred toward the erythrocyte surface
each parasite sp. secretes different proteins
The electron dense knobs contain parasite proteins that are not exposed on the outer surface of the erythrocyte, why?
they are localised toward the erythrocyte cytoplasm, the function is unknown, but perhaps reorganising the erythrocyte cytoskeleton
What is the significance of the EMP proteins secreted by the parasite?
They are expressed by var gene family.
Parasite genome contains 40-60 var genes, at least 40-60 immungoenic EMP1 isoforms.
The var genes are adjacent to telomeres and serve more or less the same function at an immunological level as the VSG or VSP found in t.brucei.
Mediate antigenic variation
Summary of the severe malaria pathology?!
Cytoadherence occurs - the non infected and infected RBCs stick to each other and the blood vessel endothelium
blood vessels become clogged and haemorrhage
induces production of cytokines. Causes expression of endothelial adhesins and makes endothelial cells more sticky
reduces blood flow (anaemia)
Why is it that you can get acquired immunity to malaria?
because the parasite has a repertoire of genes it can call on and with time the effectiveness of this repertoire diminishes
What explains why kids and people from non malarious regions are more susceptible to malaria?
people living in endemic areas acquire immunity through natural exposure to the parasite with time - age related - this is why the disease predominantly affects children.
acquired immunity occurs only after continued exposure from multiple infections over time.
acquired immunity limits high density parasitemia, however it does not lead to sterile protection
clinical immunity provides protection against severe effects of malaria but fails to provide strong protection against infection with malaria parasites
what are 3 methods used to diagnose malaria?
microscopy
antigen (cannot distinguish between types)
PCR (expensive)
what are some of the main drugs used to treat malaria?
quinine chloroquine mefloquine (Lariam) doxycycline artemisin sulfadoxine-pyrimethamine (fansidar) atovaquone-proquanil (Malarone)
What are some control measures for malaria? (4)
insecticide sprays
bed nets
drainage
wear socks!
EMP1a exhibit a high degree of sequence variability and have similar overall conserved, multi domain structure. The different isoforms have various numbers of _______ in various arrangements
cystine rich domains
What does the varying cystine rich domains between different EMPs isoforms allow the parasite to do?
allows the parasite to bind to different receptors expressed by different epithelial cells found with different organs. this is why the pathology of the disease can change.
Antigenic variation is simply an in situ switching mechanism.
What governs which organ that particular parasite can interact with to elicit the severe pathologies mentioned?
dependent upon which isoform of EMP1 the cell population is expressing
EMP1 exhibits allelic exclusion what does this mean?
out of 40-60 var genes only 1 expressed by a population
how does antigenic variation happen in malaria parasites?
knobs only contain 1 PfEMP1 isoform – they are identical within a population
each PfEMP1 isoform is antigenically distinct in response to immune system parasites switch to new PfEMP1 variants (antigenic variation) switching is promoter driven switching frequency ~2% of population switch per cycle switching to a new, antigenically distinct PfEMPs results in new infected erythrocyte having different adhesion phenotype
