Malaria Flashcards
History of malaria:
- Literally means bad air
- Hippocrates described clinical symptoms
- Jesuit brother Salumbrino observed bark of cinchona tree against it
What causes malaria?
Plasmodium parasites
Where does stand malaria stand on the eukaryotic tree?
TSAR, Sar, Alveolata, Apicomplexa, Plasmodium
What are the 4 different types of Plasmodium causing malaria?
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium ovale
What is the distribution of Plasmodium falciparum?
- 90% in africa
- 50% in South-East Asia
What is the distribution of Plasmodium vivax?
90% in Asia, South America
50% in South-East Asia
What is the distribution of Plasmodium malariae?
2% in Africa
Sporadic in Asia and South America
What is the distribution of Plasmodium ovale?
8% in Africa
What are the distinguishing features of Plasmodium falciparum?
Majority of deaths globally
Causes cerebral malaria
Is Plasmodium falciparum dormant in liver stage?
No
What are the distinguishing features of Plasmodium vivax?
Immunity of people with Duffy antigen
Severe malaria in 1/5 cases
Is Plasmodium vivax dormant in liver stage?
Yes
What are the distinguishing features of Plasmodium malariae?
Milder symptoms
Is Plasmodium malariae dormant in liver stage?
No
What are the distinguishing features of Plasmodium ovale?
Milder symptoms
Is Plasmodium ovale dormant in liver stage?
Yes
Summaries the global impact of malaria?
300-500 million cases 1.5-2.7 million deaths per year Eradicated from temperate zones 80% of cases concentrated in 15 countries 82% deaths are children in sub-Saharan
What is malaria?
Vector borne disease
Why is malaria a vector borne disease?
- Insect vector
- Human host
- Transmitted by anopheline mosquitoes
- Female only
- No animal reservoir
Define sporozoites:
Motile spore-like stage in like cycle of parasitic sporozoans
Typically infective introduced into host
Define merozoites:
Non-motile stage
Define trophozoite:
Activated, feeding stage in the life cycle of certain protozoan parasites
Define hypnozoite:
sleeping stage
Describe the Plasmodium life cycle:
- Sporozoite in salivary hangs - infected with salvia
- Invade liver cells - within 30 to 60 minutes
- In hepatocyte divide asexually leading to schizonts in 6 to 7 days
- Each schizonts in hepatocyte = gives birth to to 1000s of merozoites released into blood from ruptured hepatocytes
- Merozoites actively invade red blood cells
- Trophozoite: parasite ingest the cytoplasm
- Schizont stage: Schizogony - asexual replication involving nuclear division without cytoplasmic division followed by budding to form merozoite
- Invade new erythrocytes
- Red blood cells: parasites enter sexual cycle and differentiate into micro or macro gametocytes which circulate into the blood
What does the apex of sporozoite and merozoite contain?
Complex organelles specialised for penetrating host cells and tissues
Apicoplasts (type of plastids)
What is crucial for malaria infection?
Liver cell invasion by sporozoites
Why are liver cell invasion by sporozoites is crucial for infections?
- Plasmodium sporozoites migrate through several hepatocytes before infecting a final one
- Migration through hepatocytes occur by breaching their plasma membranes
- Sporozoites do not have flagella - migration uses the actin cytoskeleton
What does merozoites actively invade?
Red blood cells
How do merozoites actively invade red blood cells?
- Plasmodium app target erythrocytes of different ages
- Specific engagement of erythrocyte receptors define target cell tropism
- Downstream events result in physical penetration of erythrocyte (powered by parasite actomyosin cytoskeleton)
How does Plasmodium infection lead to disease?
- Malaria is associated with regular episodes of fever
- Occurs during simultaneous bursting of infected red blood cells
What is the advantage of life in a red blood cells?
- Red blood cell is rigid = supports shear stress exerted by blood flow
- Parasite is hidden from the immune system
What is the disadvantage of life in a red blood cells?
- Nutrient-poor environment
- Cells have relative short life
- Cells are continuously recycled in the liver/spleen = exposed to the immune system
What are three modifications of red blood cells by Plasmodium falciparum?
- Promote formation of new channels for the import and export of nutrients
- Break down haemoglobin into amino acids
- Place adhesive proteins on surface of infected red blood cells that induce rosetting and adherence to the endothelium avoiding clearance by host
What are key survival factor for Plasmodium in its human host?
Protein PfEMP1
What does PfEMP1 stand for?
Plasmodium falciparum erythrocytes membrane protein 1
What does PfEMP1 do?
- Ligand to bind receptors on endothelial cells
- Infected cells adhere to the endothelium
- Sequestration can obstruct blood vessels
- Leads to haemorrhage and hypoxia
- Cerebral malaria (most severe form of the disease) - haemorrhage and rupture of blood brain barrier
What does Plasmodium exhibits?
Antigenic variation
What are PfEMP1 proteins?
Encoded by a large multigenerational family called var
How many different genes each produce a different PfEMP1?
60
What does recombination of genes allow of PfEMP1s?
Creation of new varients
What does switching between different PfEMP1 variants present?
Host from mounting an effective immune response
Why is the vaccine development against malaria difficult?
Switching between different variants
What is the only vaccine approved?
RTS,S
What does RTS,S require?
Four infections and relatively low efficacy
When does WHO not recommend to use RTS,S vaccine?
In babies between 6 to 12 weeks of age
How do you control vector control?
- No animal reservoir
- Insecticide impregnated mosquito nets and clothing
- Sleep under ITN
- Indoor residual spraying
How is malaria diagnosed?
- Examining stained blood smears
- Rapid diagnostic tests also available
What is an issue with malaria diagnostics?
False negatives
What are malaria treatments?
-Drugs viable (quinine, chloroquine, artemisinin)
What are problems of malaria treatments?
Resistance of parasites
