Malaria Flashcards
Write a note on malaria
What is malaria?
(3)
A parasite that enters the blood
Derived from the Italian mal (bad) and aria (air) as it was thought to have been airborne
A protozoan called plasmodium
How many people get malaria a year
250 million
How many people die of malaria each year
1 million people die yearly
75% of deaths are African children below 5
Comment on the development of malaria symptoms
Depending on the type of malaria symptoms can develop within 8 days after being bitten but in some cases the parasite remains inactive for up to a year
Write a note on the incidence of malaria
(4)
Found in warmer climates
People travel to warm countries and bring the parasite back
Pregnant women at very high risk of dying from complications -> mosquito attracted to placenta of pregnant women
Only certain type of mosquito can give you malaria
What are the malaria zones of the world
(3)
Topical and sub-tropical areas
Africa, India, Middle east, southeast Asia, central and south America, Eastern Europe and the South Pacific
45% of the worlds population live in malaria zones
Malaria is transmitted by what mosquito
Female anopheles mosquito
What is the most common parasite that causes malaria
Plasmodium falciparum
Comment on plasmodium flaciparum
(4)
Most common -> 80% of cases
Most deadly -> 90% of deaths
Primarily found in south America and Africa
Drug-resistance is seen in this species -> resistant to chloroquine
List the five different types of plasmodium
(5)
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
Comment on plasmodium vivax
(5)
Causes 20% of infections
Half of infections come from India
Mostly found in Asia and Latin America
Less severe symptoms than falciparum
Can stay in the liver for up to three years which can result in relapses
How long can vivax stay in the liver
For up to 3 years
Comment on plasmodium ovale
(3)
Usually found in Africa
Relatively uncommon
Can stay in your blood for several years without producing any symptoms
How long can you have ovale without knowing
Several years
Comment on plasmodium malariae
Relatively rare
Usually it is only found in west africa
Comment on plasmodium knowlesi
(3)
Extremely rare
Was only recently found in the last 20 years in humans
Found in parts of southeast asia
When was malaria first described and by who?
P. malariae was first described in 1880 by Laveran
Comment on the pathogenesis of P. malariae
Has an affinity for mature or older RBCs
When was vivax discovered and by who
Named in 1890 by Grassi and Feletti
Comment on the pathogenesis of P. vivax
Prefers to invade young rbcs
Who discovered falciparum and when
Welch discovered falciparum in 1897
Comment on the pathogenesis of falciparum
(2)
Infects cells of all ages
Usually symptoms present within 1 month of returning from a malarious area but 10% present up to 3 months after travel
Who discovered ovale and when
P. ovale discovered in 1922 by Stephens
Comment on the pathogenesis of p.ovale
Prefer to invade young rbcs
Who discovered knowlesi and when
Franchiti discovered Knowlesi in 1927
Comment on the pathogenesis of Knowlesi
Prefer to invade young RBCs
We didn’t know it could affect humans until recent years
Comment on the history of malaria
(5)
One of the oldest known diseases
Described in ancient writing even in Europe when there was a warmer climate
King Tutankhamun died from malaria
References to malaria have been recorded for nearly 6000 years, starting in China
Malaria has been infecting humans for 50,000 + years
When were the first advances in malaria made and what were they
(3)
First advances were made by Charles Laveran, a French army doctor, in 1880
Laveran looked into infected rbcs and discovered the parasite was a protist
This was the first protist known to cause a disease
Give an overview of the history of advancements in malaria research
(4)
1881 -> Carlos Finlay discovered mosquitos transmitted disease
1898 - Ronald Ross discovered that mosquitoes transmitted malaria (Nobel Prize)
First effective medicine was discovered by Pierre Pelletier and Joseph Caventou. This medicine is called quinine, which comes from the bark of cinchona trees in Peru
Vaccines in development. Immunity as a result of multiple infections
Who discovered mosquitos transmitted disease and when
1881 -> Carlos Finlay discovered mosquitos transmitted disease
Who discovered mosquitos transmitted malaria and when
Ronald Ross discovered that mosquitoes transmitted malaria in 1898
Who discovered the first effective medicine for malaria and what is it
First effective medicine was discovered by Pierre Pelletier and Joseph Caventou. This medicine is called quinine, which comes from the bark of cinchona trees in Peru
The malaria parasites of humans are caused by species of the genus plasmodium of what class?
Class Sporozoa
What are the two cycles of reproduction of plasmodium sporozoa
Schizogony (asexual cycle)
Sporogony (sexual cycle)
Where does the asexual cycle (schizogony) take place for plasmodium
In the rbcs of vertebrates
Where does the asexual cycle (sporogony) take place for plasmodium
In mosquitos
What are the clinical features of malaria
(5)
Patient from a malarious area with fever or recent history of fever of any pattern
Classic attack lasting 6-10 hours
A cold stage
A hot stage
A final sweating stage
What happens in the cold stage of a malaria attack
Sensation of cold and shivering
What happens in the hot stage of a malaria attack
Fever of up to 104 degrees
Headaches
Vomiting
Seizures in young children
What happens in the sweating stage of malaria
(3)
Sweats -> rbcs are bursting
Temperature begins to return to normal
Tiredness
What does the malaria attack coincide with
Coincides with the rupture of schizont out of red cell and release of TNF
What happens in severe malaria
(8)
Convulsions
Renal failure
Liver disfunction
Electrolyte/fluid disturbance
Anaemia
Pulmonary and cerebral oedema
Disseminated Intravascular Coagulation (DIC)
Shock
What is the malaria transmission cycle
(7)
Sporozoite produced in mosquito
Mosquito bites human -> sporozoite released into human via saliva
Sporozoite travels to liver and starts to replicate -> no symptoms yet -> asexual reproduction
Sporozoites now move to circulation and attack rbcs
Symptoms begin
Second mosquito bites and ingests rbcs -> parasites are in the rbcs
Sexual reproduction occurs in mosquito
The exogenous sexual phase (sporogony) can only happen in what type of mosquitos
Anopheles mosquitoes
List the stages in the growth of plasmodium
(6)
Mosquito -> Sporozoite -> human
Liver -> liver schizonts which release merozoites into circulation
RBC -> trophozoite -> schizonts -> daughter merozoites released from each rbc
Some trophozoites develop into gametocytes -> mosquito
Gametes -> sexual reproduction -> ookinete
Ookinete forms an oocyst containing sporozoites -> migrate to salivary glands
What happens to sporozoites in the liver
(3)
They remain in the liver for 7-28 days and invade hepatocytes
While in the liver they undergo cell division to produce liver schizonts
Liver schizonts release merazoites into the blood stream
How do merozoites get into rbcs?
(3)
Merozoites invade rbcs by attaching to red cell membrane receptors
Merozoite and red cell form tight
junctions
Red cell membrane wraps around the merozoite and allows its entry through transmembrane
proteins
What happens to merozoites inside the rbc
They develop into a trophozoite
What do trophozoites do inside an rbc
(3)
They feed on Hb and use the amino acid for protein synthesis and release digested haemoglobin as haemozoin pigment
They then divide and multiply to produce schizonts -> over a 2-3 day period which will rupture and release merozoites to continue the cycle
Some trophozoites develop into gaemetozytes which will infect a biting mosquito
What happens to the gametozytes
(4)
They infect another mosquito
Then they undergo sexual reproduction in the mosquitos stomach
Sporozoites are then stored in salivary glands
Infected mosquito bites another human to inject sporozoites and repeat the cycle
What does an immature trophozoite look like in an rbc?
A ring
What are the stages of malaria
The trophozite stage
The schizont stage
The gaemtocyte stage
What are the three stages of malaria parasites
The trophozoite stage
The schizont stage
Gametocyte stage
What is the trophozoite stage
(3)
Most commonly seen stage
Often referred to as the ring stage
Sometime takes the form of an incomplete ring
What is the schizont stage
Schizogony
The parasite starts to divide in the liver
What is the gametocyte stage
(3)
Parasites become male/female in preparation for next stage which takes place in stomach of anopheline mosquito
Gametocytes are crescent shaped/banana shaped depending on species
Males are more pink in colour than females
What are the three types of malaria -> transmission dependent classification
Transfusion malaria -> people transfused with rbcs containing parasite
Placental malaria -> babies born with malaria
Airport malaria -> people who got bit in the airport when getting connecting flights
Who is most at risk of malaria
Pregnant women and children
People from non-malaria zones
What are the haematological effects of malaria
(6)
Normochromic, normocytic anaemia with gradually dropping Hb
White cell count may be normal but can be raised in severe disease
Monocytosis, eosinopenia and reactive eosinophilia in recovery can be seen as well as activated neutrophils
Thrombocytopenia is common
Mildly elevated liver enzymes, LDH, bilirubin, CRP and procalcitonin
The prothrombin time and partial thromboplastin time can be prolonged with typically elevated fibrinogen
How does malaria affect the liver
Mildly elevated liver enzymes, LDH, bilirubin, CRP and procalcitonin
The prothrombin time and partial thromboplastin time can be prolonged with typically elevated fibrinogen
How does malaria affect the wbcs
White cell count may be normal but can be raised in severe disease
Monocytosis, eosinopenia and reactive eosinophilia in recovery can be seen as well as activated neutrophils
How do we diagnose malaria in the lab
(5)
Microscopy
Rapid Diagnostic Tests
Nested PCR
Real-time PCR
Loop-mediated isothermal DNA amplification (LAMP)
How do we use microscopy to diagnose malaria
(3)
Thick blood films
Thin blood films
Identification of parasite and its stages (Look at lecture notes and lab to be able to do this)
How do we assess a thick blood film
(3)
Create a thick blood film
Use fields stain
Parasites will show deep red chromatin and pale blue cytoplasm
How do we asses a thin blood film
(4)
Use freshly prepared Giemsa stain
Examine monolayer
Alkaline pH vital for clear differentiation of nuclear and cytoplasmic material and to visualise inclusion such as Schuffner’s/James’s dots in red cells
Count number of parasitized cells
What rapid diagnostic tests do we use
(3)
Binax NOW Pf HRP2 & pan aldolase
Carestart Pf HRP 2 & pan LDH
OptiMAL LDH Pf & pan
How do rapid diagnostic tests work
(4)
They look for antigen expression in the rbcs
We lyse open the rbcs and look for the parasites
All tests will pick up falciparum but not all the other types
Some species are acquiring gene deletions so we have to design our tests to allow for these changes -> this is why we don’t rely on these
What is a nested PCR
(3)
Need to look up more about this
This is more so seen in research labs than clinical labs
Buy in a kit with genus specific primers followed by species specific primers
Fluorescent if malaria present
What is LAMP for Malaria
(3)
Uses primers targeting different sequences in Plsamodium mitochondrial DNA
Test has been optimised to detect down to 1-5 parasites per micro litre of blood in less than an hour
Samples can be fresh or frozen or blood dried on filter paper
How does HbS protect against malaria
sickle cells -> cleared quicker than healthy cells
How does HbC protect against malaria
CC haplotype does not support parasite growth
Due to resistance to bursting and releasing merozoites
What rbc haplotype suits the growth of parasite
Haemoglobin AC rbcs
What haemoglobin type results in poor parasite growth
Hb SC
How does Haemoglobin E affect malaria
Parasitised EE and AE rbcs are phagocytosed more readily than AA RBCs
How does thalassaemia and G6P deficiency affect malaria
(2)
RBCs do not support the division of P. falciparum due to sensitivity to oxidant stress
However there is a problem using malaria drugs in these patients
What is the best way of preventing malaria
Stopping yourself from getting bitten by mosquitos
When was the malaria vaccine first approved
2015
What is the malaria vaccine called
RTS, S/AS01
Mosquirix
How was the malaria vaccine made
Engineered using genes from the outer protein of P. falciparum malaria parasite and a portion of a hepatitis B virus plus a chemical adjuvant to boost the immune response
What happened to the vaccine in 2021
WHO recommended the widespread use of the vaccine among children in sub-Saharan Africa and in other regions with moderate to high falciparum malaria transmission
How should the vaccine be administered
Should be provided in a schedule of 4 doses in children from 5 months of age
Who developed and funded the malaria vaccine
(2)
Research and development by GSK and partnership with PATH
The Bill and Melinda Gates Foundation funded late-stage development
