Malaria Flashcards
What type of organisms are malaria
Eukaryotic protozoan
How is malaria plasmodium spread?
Via female Anopheles mosquito
What genus is malarial protozoan under?
Plasmodium
What is Sporozoite
First stage of infection transmitted from the mosquiro to the human host
What are 5 specied of plasmodium that can infect humans
P. vivax P. ovale P. malariae P. falciparum P. knowlesi
Why should we care about malaria?
2.4 billion people are exposed. 200-300 million new cases a year. Most predominant in Sub-Saharan Africa
Where is P. vivax most present?
In Southeast Asia and Pacific Islands.
Africans don’t have receptor on RBC for P. vivax
130-400 million cases anually.
Where is P. falciparum most pesent?
In Sub-Saharan Africa
90% of people are exposed
80% of clinical cases of P. falciparum are from here.
120 million cases anually
UK cases of malaria
1500 new cases recently, has been on the uprise
Mostly P. falciparum but P. vivax is on the rise
Clinical presentation of malaria
Similar to viral infections.
Symptoms occur in cyclic manner and matches stage in replication cycle.
Fever peaks 36-72 hours depending on strain of plasmodium.
Schizont ruptures to release toxins that cause fever
Diagnosis
Gold standard is looking at blood sample under a microscope.
Sample is stretched air dried, fixed with ethanol and stained.
Also can do dipstick test of urine (inaccurate) or PCR (expensive and time consuming)
ELISA observing the reaction between parasite specific antigen and antibody.
Treatment
Quinine and Riamet for P. falciparum and unkown
Chloroquine for P. malariae and P. knowlesi
P. vivax has developed resistant strains in Malaysia so need Primaquine
Combination therapy also used in response to increased resistance
How does death occur in malaria
When trophozite or schizont occlude blood vessel in important part of the body
What are hypnozoites
Dormant forms of plasmodium found in all malarial infections except P. falciparum
What is the life cycle of P. falciparum plasmodium
Oocyte taken up into the saliva which matures sporozoite.
Sporozoite inoculated into host and travels to the liver, where it matures into trophozoite.
In the liver trophozoite undergoes asexual reproduction to form hepatic schizont.
Schizont ruptures by schizogeny to produce merozoite
In blood, merozoite attaches to RBC undergoes replicative cycle
Merozoite -> trophozoite -> schizont -> schizogony -> merozoites
Merozoite continues infecting RBC until triggers the immune system
Parasites differentiate into gametocytes
What happens when a mosquito bites an infected person?
Takes up the female and male gametocytes to form the oocyte
Is the liver phase symptomatic?
No
When does infection occur in malaria
Once the has bound to the RBC
How does schizont rupture lead to pathogenesis of malaria?
Triggers sentinel cells that cause inflammation by the release of inflammatory mediators.
IFN g
TNF a
IL-1
IL-12
In low concentrations they are helpful, but when dysregulated cause heamolysis of RBC, failure to produce normal RBCs and anaemia.
What is PfEMP1
P. falciparum Erythrocyte Membrane protein
Polymorphic proteins encoded by gene family VAR
How does PfEMP cause disease?
Antibodies direct towards specific PfEMP, and sub-population alter their expression leading to reactivation and reinfection.
Also PfEMP bind to epithelial cells in blood vessels, occluding them.
Consequences of occluded blood vessels
Fetal loss
Respiratory distress
Stroke
Heart attack
Why is it difficult to eradicate plasmodium causing malaria
Sporozoite evades immune system
Latent forms are not targeted by drugs
Many years of repeated infection needed to gain sligh immunology
Mechanisms of immune responses to malaria
Antibodies to sporozoite
IFN g and CD8 T cells inhibit parasite development in hepatic cells
Antibodies to merozoite
Antibodies to toxins
Kill parasites intracellularly during asexual RBC stage
Gametocytes coated in antigen
Antibodies that block PfEMP
How is inhibition of sporozoites via CD8 T cells not effective
The CD8 T cells take some time to develop. Antibodies cannot enter the hepatocytes. During this time the sporozoite matures into merozoite and escapes to the bloodstream.
How does IFN g destroy intracellular hepatic storozoite
NO dependent intracellular mechanism
Why target the merozoite asexual reproduction stage?
Highest chance of eliminating the parasite. Agglutination by coating with ADC1 makes the cells more active and prone to phagocytosis.
Why develop antibodies to toxins?
Reduce the inflammatory response
Why develop antibodies to he gametocytes?
Prevent them from forming a zygote
