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2.2 Haematology > Malaria > Flashcards

Malaria Flashcards

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
Q

Who discovered knowlesi and when

A

Franchiti discovered Knowlesi in 1927

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26
Q

Comment on the pathogenesis of Knowlesi

A

Prefer to invade young RBCs
We didn’t know it could affect humans until recent years

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27
Q

Comment on the history of malaria
(5)

A

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

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28
Q

When were the first advances in malaria made and what were they
(3)

A

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

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29
Q

Give an overview of the history of advancements in malaria research
(4)

A

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

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30
Q

Who discovered mosquitos transmitted disease and when

A

1881 -> Carlos Finlay discovered mosquitos transmitted disease

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31
Q

Who discovered mosquitos transmitted malaria and when

A

Ronald Ross discovered that mosquitoes transmitted malaria in 1898

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32
Q

Who discovered the first effective medicine for malaria and what is it

A

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

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33
Q

The malaria parasites of humans are caused by species of the genus plasmodium of what class?

A

Class Sporozoa

34
Q

What are the two cycles of reproduction of plasmodium sporozoa

A

Schizogony (asexual cycle)

Sporogony (sexual cycle)

35
Q

Where does the asexual cycle (schizogony) take place for plasmodium

A

In the rbcs of vertebrates

36
Q

Where does the asexual cycle (sporogony) take place for plasmodium

A

In mosquitos

37
Q

What are the clinical features of malaria
(5)

A

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
Q

What happens in the cold stage of a malaria attack

A

Sensation of cold and shivering

39
Q

What happens in the hot stage of a malaria attack

A

Fever of up to 104 degrees
Headaches
Vomiting
Seizures in young children

40
Q

What happens in the sweating stage of malaria
(3)

A

Sweats -> rbcs are bursting
Temperature begins to return to normal
Tiredness

41
Q

What does the malaria attack coincide with

A

Coincides with the rupture of schizont out of red cell and release of TNF

42
Q

What happens in severe malaria
(8)

A

Convulsions
Renal failure
Liver disfunction
Electrolyte/fluid disturbance
Anaemia
Pulmonary and cerebral oedema
Disseminated Intravascular Coagulation (DIC)
Shock

43
Q

What is the malaria transmission cycle
(7)

A

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
Q

The exogenous sexual phase (sporogony) can only happen in what type of mosquitos

A

Anopheles mosquitoes

45
Q

List the stages in the growth of plasmodium
(6)

A

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
Q

What happens to sporozoites in the liver
(3)

A

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
Q

How do merozoites get into rbcs?
(3)

A

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
Q

What happens to merozoites inside the rbc

A

They develop into a trophozoite

49
Q

What do trophozoites do inside an rbc
(3)

A

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
Q

What happens to the gametozytes
(4)

A

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
Q

What does an immature trophozoite look like in an rbc?

A

A ring

52
Q

What are the stages of malaria

A

The trophozite stage

The schizont stage

The gaemtocyte stage

53
Q

What are the three stages of malaria parasites

A

The trophozoite stage

The schizont stage

Gametocyte stage

54
Q

What is the trophozoite stage
(3)

A

Most commonly seen stage

Often referred to as the ring stage

Sometime takes the form of an incomplete ring

55
Q

What is the schizont stage

A

Schizogony

The parasite starts to divide in the liver

56
Q

What is the gametocyte stage
(3)

A

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
Q

What are the three types of malaria -> transmission dependent classification

A

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
Q

Who is most at risk of malaria

A

Pregnant women and children

People from non-malaria zones

59
Q

What are the haematological effects of malaria
(6)

A

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
Q

How does malaria affect the liver

A

Mildly elevated liver enzymes, LDH, bilirubin, CRP and procalcitonin

The prothrombin time and partial thromboplastin time can be prolonged with typically elevated fibrinogen

61
Q

How does malaria affect the wbcs

A

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
Q

How do we diagnose malaria in the lab
(5)

A

Microscopy
Rapid Diagnostic Tests
Nested PCR
Real-time PCR
Loop-mediated isothermal DNA amplification (LAMP)

63
Q

How do we use microscopy to diagnose malaria
(3)

A

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
Q

How do we assess a thick blood film
(3)

A

Create a thick blood film

Use fields stain

Parasites will show deep red chromatin and pale blue cytoplasm

65
Q

How do we asses a thin blood film
(4)

A

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
Q

What rapid diagnostic tests do we use
(3)

A

Binax NOW Pf HRP2 & pan aldolase

Carestart Pf HRP 2 & pan LDH

OptiMAL LDH Pf & pan

67
Q

How do rapid diagnostic tests work
(4)

A

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
Q

What is a nested PCR
(3)
Need to look up more about this

A

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
Q

What is LAMP for Malaria
(3)

A

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
Q

How does HbS protect against malaria

A

sickle cells -> cleared quicker than healthy cells

71
Q

How does HbC protect against malaria

A

CC haplotype does not support parasite growth

Due to resistance to bursting and releasing merozoites

72
Q

What rbc haplotype suits the growth of parasite

A

Haemoglobin AC rbcs

73
Q

What haemoglobin type results in poor parasite growth

A

Hb SC

74
Q

How does Haemoglobin E affect malaria

A

Parasitised EE and AE rbcs are phagocytosed more readily than AA RBCs

75
Q

How does thalassaemia and G6P deficiency affect malaria
(2)

A

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
Q

What is the best way of preventing malaria

A

Stopping yourself from getting bitten by mosquitos

77
Q

When was the malaria vaccine first approved

A

2015

78
Q

What is the malaria vaccine called

A

RTS, S/AS01

Mosquirix

79
Q

How was the malaria vaccine made

A

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
Q

What happened to the vaccine in 2021

A

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
Q

How should the vaccine be administered

A

Should be provided in a schedule of 4 doses in children from 5 months of age

82
Q

Who developed and funded the malaria vaccine
(2)

A

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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