Mosquitoes (Malaria) Flashcards
Types of plasmodium which cause malaria in humans:
P. falciparum P. vivax P. malariae P. ovale P. knowlesi
Infective stage of plasmodium parasite (for humans)
Sporozoite
Why is P.vivax not present in West Africa?
High % (95) population are negative for erthyrocytic receptors called Duffy Antigen. Duffy antigen is proinflammatory chemokine receptor used by P. vivax (Langhi and Bordin, 2006).
Diseases that confer malaria resistance
Sickle cell anaemia
Thalassemia
G6PD deficiency
- RBC more liley to die from oxidative stress when infected
What happens in the first 1-2 weeks of infection by P. falciparum, P. malariae and P. knowlesi?
Multiply asexually and mature from sporozoites to merozoites in the liver.
Where do the malaria parasite first go when they infect a human?
Hepatic sclerenchymal cells
Does the liver stage have any outward symptoms?
No, asymptomatic.
What happens in the months and years of initial infection by P. vivax and P. ovale?
Dormant hepatic stage = hypnozoites (don’t divide)
Wait then turn into merozoites.
Preferred RBC targets for P. falciparum and P. ovale
red blood cells of all ages
Preferred RBC targets for P. vivax
reticulocytes ( young and immature red blood cells)
Preferred RBC targets for P. malariae and P. knowlesi
older red blood cells
Stages of th erythrocytic phase
Early trophozoite (ring)
Late trophozoite
Shizont (merozoites inside)
Rupture schizont (releases merozoites)
What does the rupturing of the shizont cause?
Release of inflammatory cytokines -> temperature spikes (fevers) Extreme fatigue Headaches Jaundice Abnormally enlarged spleen (splenomegaly)
Sexual reproduction stages
Human
Early trophozoite -> gametogony
Taken up by mosquito in blood meal
Travel to gut - mature and fuse into zygote
Ookinete
Oocyst - ruptures and releases sporozoites
What are fever paroxyms?
The pattern of fever occurrence, e.g. every 24hrs.
What are the different fever paroxysms of the species of malaria that infect humans?
P. malariae = 72hrs
P. vivax ad P. ovale = 48hrs
P. knowlesi = 24hrs
P. falciparum = variable (24/48 hrs)
How do malaria parasites get into the mosquito gut?
Uses chitinases to burst into gut
How can mosquitos defend agains plasmodium?
Encapsulate oocysts
Why do wild-type mosquitoes not encapsulate?
The energetic expense of encapsulating oocysts is greater than the fitness cost of being infected.
What is the time bomb theory?
Parasite is too fast for mosquito immune system.
What does Plasmodium use to travel through cells quickly?
subtilisin2 (protease)
What is the formula for the Ross-MacDonald model for malaria transmission?
Ro = (m.a^2.p^n.b)/(-rln(p))
What do the letters stands for in this formula: Ro = (m.a^2.p^n.b)/(-rln(p))?
m = bites per person per night a = probability of mosquito to take human meal p = daily mosquito survival rate n = Number of days to complete mosquito lifecycle b = susceptibility to infection human/mosquito r = rate of recovery of infected humans
What are the assumptions of the Ross-MacDonald model for malaria transmission?
no host immunity (humans)
mosquitoes bite at random
humans and mosquito populations homogenous
Ways to sample mosquitoes (7)
Tent trap Biting catch Plant catch Light trap Resting catch Exit catch Spray catch
What is exflagellation?
Gametocyte bursts to release microgametocytes.
What triggers exflagellation?
Drop in temperature
Drop in [CO2]
Increase in pH
Presence of xanthurenic acid (broaden pH range exflagellation will occur in)
Why does P. falciparum cause the worst infections?
short answer
Puts sticky protein coat on infected blood cells
- > clumping of RBCs
- > blocking of blood vessels
What are the complications of P. falciparum?
haemolytic anaemia + ischemic damage
Cerebral malaria Bilious malaria (liver) Lungs + Kidneys + Spleen = sepsis-like symptoms
What can cerebral malaria cause?
Seizures
Coma
Altered mental state
What can bilious malaria cause?
diarrhoea
vomitting
jaundic
liver failure
Diagnosis of malaria
Blood smear Low platelet count Elevated lactate dehydrogenase Normochromic and normocytic anaemia PCR Fever pattern (paroxysms)
What are the two types of blood smear and what do they show?
Thick blood smear - % of infection (parasite in RBCs)
Thin blood cells - species identification
What is normochromic and normocytic anaemia?
Normal colour, normal size, low red blood cells
What causes elevated lactate dehydrogenase in malaria sufferers?
Haemolysis (RBCs)
Types of recurrent malaria
Recrudescence
Relapse
Reinfection
What is recrudescence?
The recurrence of malaria in an individual due to ineffective treatment.
What is relapse (in terms of malaria infection)?
The recurrence of malaria in an individual due to treatment killing merozoites, but live hypnozoites remaining in the liver.
What is reinfection?
The recurrence of malaria in an individual after effective treatment due to a new infection (no immunity).
Methods for prevention of infection (mosquito focus)
Full body clothing
Insecticide-covered mosquito nets
Indoor insecticide spray
Empty stagnant water
Why does P. falciparum cause RBCs to clump? (survival)
With other species, the spleen destroys most infected RBCs. By clumping and blocking blood vessels, it prevents infected cells from going to the spleen.
Two scientific options for malaria control
Monoclonal anitbodies
Knocking out genes (in mosquito)
Current available malaria treatment (humans)
Suppressive treatment/chemo prophylaxis
Radical treatment
Therapeutic treatment
What is the name of the protein which makes read blood cells sticky in P. falciparum infection?
PfEMP1 (Plasmdium falciparum erythrocyte membrane protein 1) - blood group O only
RIFINs to form rosettes with group A RBCs??
(Goel et al., 2015)
How does P. falciparum avoid antibodies?
Changes sticky membrane protein on outside of infected cells (e.g. PfEMP1 - blood group O only (Goel et al., 2015))
What is red blood cell rosetting?
the formation of clusters in which uninfected red blood cells (RBCs) aggregate around a central Plasmodium falciparum-infected RBC (iRBC) - because of stickiness?
Possible targets for future treatment research
Merozoite surface protein 1
Enzymes for entry of gametcytes into mosquito gut - allosamidin (inibits chitinases)
Adhesion to midgut of mosquito (basal lamina)
Enzyme for cutting through cells rapidly (subtilisin2 (protease))
