Specific pathogens (parasites) Flashcards
What is malaria?
Type of unicellular plasmodium parasite.
What are 5 plasmodium that are known to infect humans?
P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi
Malaria symptoms
Most frequently fever, chills. Often cyclic, every 2-3 days. Can be accompanied by headache, myalgias, arthralgias, weakness, vomiting, and diarrhoea.
Splenomegaly, anaemia, thrombocytopenia, hypoglycaemia, pulmonary or renal dysfunction, and neurologic changes
Pathogenesis of P.falciparum
Can progress to severe potentially fatal cerebral malaria (central nervous system involvement), acute renal failure, severe anaemia and adult respiratory distress syndrome.
Pathogenesis of P.vivax
Complications tend to include splenomegaly and (rarely) splenic rupture.
Pathogenesis of P.malariae
Complications tend to include nephrotic syndrome.
What age leads to more severe malaria symptoms?
Younger ages
How is malaria infection initiated?
Injection of sporozoites into the dermis by a feeding female anopheline mosquito.
What is the vector of malaria?
Female anopheline mosquito.
What happens once sporozoites enter ECF?
Move to penetrate blood vessel by gliding motility
Where are sporozoites transported to in the blood?
Transported to the liver, where they exit the sinusoids through Kupffer or endothelial cells and enter a hepatocyte.
How do sporozoites survive inside hepatocytes?
Forming a transient vacuole (surrounded by a PVM)
What happens to sporozoites inside the PVM?
Multiply and mature into merozoites
What happens to merozoites produced in the hepatocyte?
Daughter merozoites are released in packets of merosomes into the vasculature.
There they encounter erythrocytes and begin a chronic cycle of asexual schizogony in the bloodstream
Where do merozoites replicate?
Inside red blood cells
How long is the merozoite schizogony?
1-3 days (reflects cyclic fevers)
How do mosquitos become infected?
Merozoites pre-commit to form gametocytes.
Formation of male and female gametocytes in erythrocytes leads to burst which can be ingested by female anopheles mosquito.
How is malaria diagnosed?
Blood smears
How do merozoites enter erythrocytes?
Specific ligand-receptor interaction, mediated by proteins of the EBA and PfRh family members.
What is an antimalarial drug?
Chloroquine
How does chloroquine work?
The parasite must degrade haemoglobin to acquire essential amino acids - chloroquine enters the digestive vacuole, then becomes protonated so cannot leave the vacuole. It caps hemozoin molecules to prevent further biocrystallization of heme, leading to heme buildup.
This ultimately results in cell lysis and parasite cell auto digestion
Why is chloroquine not a permanent solution?
Multiple chloroquine resistant strains have emerged.
Mutants neutralize the drug by draining chloroquine away from the schizont.
What has been shown to increase malarial sensitivity to choroquine?
Verapamil
Pathology of erythrocytes in malaria?
Increased coagulation and platelet adhesion
Increased inflammation and oxidative stress
Increased endothelial leakage
Reduced microvascular flow
Blocked blood vessels in cerebral malaria
