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2.2 Haematology > Malaria > Flashcards

Malaria Flashcards

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1
Q

Write a note on malaria
What is malaria?
(3)

A

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

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2
Q

How many people get malaria a year

A

250 million

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3
Q

How many people die of malaria each year

A

1 million people die yearly

75% of deaths are African children below 5

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4
Q

Comment on the development of malaria symptoms

A

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

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5
Q

Write a note on the incidence of malaria
(4)

A

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

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6
Q

What are the malaria zones of the world
(3)

A

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

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7
Q

Malaria is transmitted by what mosquito

A

Female anopheles mosquito

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8
Q

What is the most common parasite that causes malaria

A

Plasmodium falciparum

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9
Q

Comment on plasmodium flaciparum
(4)

A

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

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10
Q

List the five different types of plasmodium
(5)

A

Plasmodium falciparum

Plasmodium vivax

Plasmodium ovale

Plasmodium malariae

Plasmodium knowlesi

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11
Q

Comment on plasmodium vivax
(5)

A

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

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12
Q

How long can vivax stay in the liver

A

For up to 3 years

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13
Q

Comment on plasmodium ovale
(3)

A

Usually found in Africa

Relatively uncommon

Can stay in your blood for several years without producing any symptoms

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14
Q

How long can you have ovale without knowing

A

Several years

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15
Q

Comment on plasmodium malariae

A

Relatively rare

Usually it is only found in west africa

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16
Q

Comment on plasmodium knowlesi
(3)

A

Extremely rare

Was only recently found in the last 20 years in humans

Found in parts of southeast asia

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17
Q

When was malaria first described and by who?

A

P. malariae was first described in 1880 by Laveran

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18
Q

Comment on the pathogenesis of P. malariae

A

Has an affinity for mature or older RBCs

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19
Q

When was vivax discovered and by who

A

Named in 1890 by Grassi and Feletti

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20
Q

Comment on the pathogenesis of P. vivax

A

Prefers to invade young rbcs

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21
Q

Who discovered falciparum and when

A

Welch discovered falciparum in 1897

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22
Q

Comment on the pathogenesis of falciparum
(2)

A

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

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23
Q

Who discovered ovale and when

A

P. ovale discovered in 1922 by Stephens

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24
Q

Comment on the pathogenesis of p.ovale

A

Prefer to invade young rbcs

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25
Who discovered knowlesi and when
Franchiti discovered Knowlesi in 1927
26
Comment on the pathogenesis of Knowlesi
Prefer to invade young RBCs We didn't know it could affect humans until recent years
27
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
28
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
29
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
30
Who discovered mosquitos transmitted disease and when
1881 -> Carlos Finlay discovered mosquitos transmitted disease
31
Who discovered mosquitos transmitted malaria and when
Ronald Ross discovered that mosquitoes transmitted malaria in 1898
32
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
33
The malaria parasites of humans are caused by species of the genus plasmodium of what class?
Class Sporozoa
34
What are the two cycles of reproduction of plasmodium sporozoa
Schizogony (asexual cycle) Sporogony (sexual cycle)
35
Where does the asexual cycle (schizogony) take place for plasmodium
In the rbcs of vertebrates
36
Where does the asexual cycle (sporogony) take place for plasmodium
In mosquitos
37
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
38
What happens in the cold stage of a malaria attack
Sensation of cold and shivering
39
What happens in the hot stage of a malaria attack
Fever of up to 104 degrees Headaches Vomiting Seizures in young children
40
What happens in the sweating stage of malaria (3)
Sweats -> rbcs are bursting Temperature begins to return to normal Tiredness
41
What does the malaria attack coincide with
Coincides with the rupture of schizont out of red cell and release of TNF
42
What happens in severe malaria (8)
Convulsions Renal failure Liver disfunction Electrolyte/fluid disturbance Anaemia Pulmonary and cerebral oedema Disseminated Intravascular Coagulation (DIC) Shock
43
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
44
The exogenous sexual phase (sporogony) can only happen in what type of mosquitos
Anopheles mosquitoes
45
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
46
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
47
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
48
What happens to merozoites inside the rbc
They develop into a trophozoite
49
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
50
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
51
What does an immature trophozoite look like in an rbc?
A ring
52
What are the stages of malaria
The trophozite stage The schizont stage The gaemtocyte stage
53
What are the three stages of malaria parasites
The trophozoite stage The schizont stage Gametocyte stage
54
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
55
What is the schizont stage
Schizogony The parasite starts to divide in the liver
56
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
57
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
58
Who is most at risk of malaria
Pregnant women and children People from non-malaria zones
59
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
60
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
61
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
62
How do we diagnose malaria in the lab (5)
Microscopy Rapid Diagnostic Tests Nested PCR Real-time PCR Loop-mediated isothermal DNA amplification (LAMP)
63
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)
64
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
65
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
66
What rapid diagnostic tests do we use (3)
Binax NOW Pf HRP2 & pan aldolase Carestart Pf HRP 2 & pan LDH OptiMAL LDH Pf & pan
67
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
68
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
69
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
70
How does HbS protect against malaria
sickle cells -> cleared quicker than healthy cells
71
How does HbC protect against malaria
CC haplotype does not support parasite growth Due to resistance to bursting and releasing merozoites
72
What rbc haplotype suits the growth of parasite
Haemoglobin AC rbcs
73
What haemoglobin type results in poor parasite growth
Hb SC
74
How does Haemoglobin E affect malaria
Parasitised EE and AE rbcs are phagocytosed more readily than AA RBCs
75
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
76
What is the best way of preventing malaria
Stopping yourself from getting bitten by mosquitos
77
When was the malaria vaccine first approved
2015
78
What is the malaria vaccine called
RTS, S/AS01 Mosquirix
79
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
80
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
81
How should the vaccine be administered
Should be provided in a schedule of 4 doses in children from 5 months of age
82
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

2.2 Haematology (38 decks)

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