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Revision Notes for Malaria
OU Coursework
Different types of Malaria:
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Plasmodium
Plasmodium
Plasmodium
Plasmodium
Plasmodium

falciparum (Pf)
vivax (Pv)
malariae (Pm)
yoelii (Py)
knowlesi (Pk)
The different types of malaria

Plasmodium falciparum
• Plasmodium falciparum is the most common strain of malaria and
also the deadliest
...

• Malignant tertian or subtertian malaria
...

• Iron~ (Fe) deficiency in Pf erythrocyte parasites bind onto
receptors
...
Seen
most in Pf
...
This is done by erythrocytic schizonts being
accumulated, tissue hypoxia already there due to anaemia
...

• Multiples more quickly in blood
...


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Plasmodium vivax
• Found in Asia and Central America, with small outbreaks in West
and Eastern Africa, categorized as a benign form of the disease, P
...
P
...

• The incubation period is 12 – 17 days; with fever cycles of 48
hours
...
vivax
...
Relapses occur as a result
...

Plasmodium yoelii
Rodent form of the malaria infection, can be passed onto humans in the
lab
...
malariae categorized as a benign form of the disease, have a
preference for mature red blood cells
...

• The fever cycle occurs every 72 hours and may last for 8 -10 hours
at a time
...

• Acute glomerulonephritis is common, lowering of albumin level in
plasma & elevation of globulin (particularly γ – globulin) level with
little change in [total plasma]
...

Plasmodium knowlesi
• Originally from macaque monkeys
...


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Malaria therapies
Chloroquine
H
N

N
CH3

N

CH3
CH3

Cl

Usually oral – but in very ill or patients who can’t retain drug due
to vomiting
...

No resistance occurring in Pv or Pm
...

1
...

2
...
7
...
CQ caps haemozoin molecules to prevent further
biocrystallisation of haeme
...

4
...
To form
Fe – CQ complexes
...

5
...

In essence, the parasite drowns in own metabolic products
...

▪ Causes severe skin reactions
...

Leads to a failure of nuclear division and time of schizont formation in
erythrocytes and liver
...

Action of sulphonamides exploits difference between mammal cells and
other kinds of cells in their folic acid metabolism
...
Hence the reason the folic acid MUST be synthesised
by the Protozoa from the para – aminobenzoic acid
...

❖ Pyrimethamine and dapsone
❖ Causes bone marrow failure, particularly in combination with CQ
...
However evidence suggests
that it could generate reactive Oxygen (O2) species or by interfering with
electron (e-) transport in the parasite
...


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Amodiaquine
N

H3C
H3C

N

Cl

NH

HO

6 – Amino anti-inflammatory agent, is as least as effective as CQ &
effective against same strains which are resistant to CQ
...
Results in accumulation
of free haeme, which is toxic to parasites
...

Lumefantrine

Exact mechanism not known
...


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Mefloquine

Produces swelling of Pf food vacuoles
...

Artemisinin
Artemisia annua or Sweet Wormwood / Sweet Annie or Qing Hao
= Crop used for the base products of the artemisinin analogues
...

• Locus affecting yield – hybridising plants to increase yield
...
Used to be controlled by
chloroquine salt
...

• Artensunate monotherapy in [high], Absolute Neutrophil Count
lower at 6 and 14 days
...

• Overexpression of PF
...
(2011 study)
• Thailand government clinics treat with Altequin and primaquine
...

• Intramuscular artensunate may be better than intramuscular
artemether in severe Pf patients
...
Annua tea was used in pregnancy – 2
miscarriages but all other babies born normally
...

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• Dihydroartemisinin more stable and 10x more effective than
artemisinin
...

• Resistance in Py = Multifunctional, two main kinds:
1
...
TCTP (Translationally Controlled Tumor Protein) different
Comparison in studies with CQ
CQ helped the lungs in emphysema – Artemisinin only mildly helped
...

Taken from a 2012 study on P berghei (a rodent form of
Plasmodia spp
...

Artemisinin from plant

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Artemether
H
H3C

CH3

O
O

O
H

H
O
OMe

Artensunate
H
H3C

O
O O
HO

CH3

H
CH3
OCO(CH2)2CO2Na

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Artemisinin mode of action

The biological aspect of the haeme (Iron containing part of the Red
Blood Cells), which the artemisinin works on
...

The parasite has a mechanism which it is protected against the toxicity
by haematin undergoes biomineralisation to form haemozoin (malaria
pigment)
...


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There are two mechanisms of the mechanism of how the artemisinin
works, mechanism (a) is the Reductive scission model and mechanism
(b) is the Open peroxide model
...

Low valent transition ions – ferrous haeme or non haeme endogenous
Fe2+, where found to bind to artemisinin and trigger e- transfer reductive
scission of the peroxide bridge to produce oxygen centred radicals that
rearrange to give us carbon centred radicals
...
Fe acts like a Lewis acid to facilitate ionic, as
opposed to radical bioactivation of the artemisinin – which have a short
life too short to have any molecular interaction
...
The
oxygen atom is providing stabilisation of the positive charge, thus which
according to transition state theory – lowers the energy required for the
ring opening to occur
...
Fenton
degradation which occurs with the hydroperoxide produces a hydroxyl
radical – a species which can oxidise target amino acid residues
...


Alkylation of a haeme model – the diethyl ester of haeme, by a 1°
carbon centre radical derived from bioactivation of artemisinin
...


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Medications that have artemisinin in their structure
ACT Therapies:
Coartem – Artemether + Lumefantrine
...

Sulphamon plus 500 – Artensunate + Sulphadoxine/Pyrimethamine
...


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