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Malaria, the 'King of Diseases‘
Affects more than 500 million and kills
more than 3 million people every year.
Malarial belt.
A, B and C.
Plasmodia=malaria parasites
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Malaria is caused by protozoan parasites
called Plasmodia, belonging to the
parasitic phylum Apicomplexa. More than
200 species of the genus Plasmodium
(=plasma + eidos, form) have been
identified that are parasitic to reptiles, birds,
and mammals. Four Plasmodium species
have been well known to cause human
malaria, namely, P. falciparum, P. vivax, P.
ovale, and P. malariae. A fifth one, P.
knowlesi, has been recently documented
to cause human infections in many
countries of Southeast Asia.
P. falciparum
P. vivax
P. ovale
P. malariae
P. knowlesi
Distribution
80-90% of cases in
Africa, 40-50% of
cases in western
pacific and SE Asia,
4-30% in S Asia, S
America and rest of
tropics
70-90% of
cases in
most of Asia
and S
America, 5060% of cases
in SE Asia
and western
pacific, 110% in Africa
8% of cases
in parts of
Africa, stray
cases in Asia
2-3% in
Africa,
sporadic in
Asia and S
America
Reported
from SE Asia;
70% of cases
in some of
those areas
Tissue schizogony
5-6 days
8 days
9 days
13 days
8-9 days
Erythrocytic phase
48 hours
48 hours
49-50 hours
72 hours
24 hours
Red cells affected
All
Reticulocyte
Reticulocyte
Mature RBC's
?
Merozoites per tissue schizont
40000
Over 10000
15000
2000
?
Merozoites per red cell schizont
8-32
12-24
4-16
6-12
10-16
Relapse from persistent liver forms
No
Yes
(hypnozoit)
Yes
(hypnozoit)
No, but
blood forms
can persist
up to 30
years
No
Fever pattern
Tertian, sub tertian
Tertian
Tertian
Quartan
Quotidian
Severe malaria
Up to 24%
Up to 22%
Very rare
Very rare
6-10%
Drug resistance
Yes
Yes
No
No
No
Ring Forms of P. falciparum
Ring Forms of P. vivax
Ring Forms of P. ovale
Ring Forms of P. malariae
Ring Forms of P. knowlesi
Vector: pregnant female
Anopheles mosquito
Cytokines, cytoadherence
and rosetting
Atypical features is more
than typical.
Malaria can mimic any thing
and every thing.

Cold stage, Hot stage and Sweating stage. The
febrile episode starts with shaking chills, usually
at mid-day between 11 a.m. to 12 noon, and
this lasts from 15 minutes to 1 hour (the cold
stage), followed by high grade fever, even
reaching above 1060 F, which lasts 2 to 6 hours
(the hot stage). This is followed by profuse
sweating and the fever gradually subsides over
2-4 hours. These typical features are seen after
the infection gets established for about a
week. The febrile paroxysms are usually
accompanied by head aches, vomiting,
delirium, anxiety and restlessness.

In an endemic area, it is rather unusual to find cases
with typical fever pattern. Some patients may not
have fever at all and may present with other
symptoms listed below. Many present with fever of
various patterns - low grade to high grade, with or
without chills, intermittent to continuous, or even as
cases of prolonged fever. In the initial stages of the
illness, fever may be quotidian, with more than one
spike per day and this is due to the development of
multiple broods of the parasite. As the disease
progresses, these broods get synchronised and the
fever tends to be more uniform. However in cases of
P. falciparum malaria and mixed infections, this
pattern of multiple spikes may continue.
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Headache.
Body ache, back ache and joint pains.
Dizziness, vertigo.
Altered behaviour, acute psychosis.
Altered sensorium.
Convulsions, coma.
Cough.
Breathlessness.
Chest pain.
Acute abdomen.
Weakness.
Vomiting and diarrhoea.
Jaundice.
Pallor.
Puffiness of lids.
Secondary infections.
Hepatosplenomegaly.
Due to P.falciparum.
Death from acute P. vivax, P.
ovale or P. malariae
infections is rare.

1. Cerebral malaria – unrousable coma not attributable to any other
cause in a patient with falciparum malaria. The coma should persist for at
least 30 min (1 h in the 2000 definition) after a generalized convulsion to
make the distinction from transient postictal coma. Coma should be
assessed using the Blantyre coma scale in children or the Glasgow coma
scale in adults .
2. Severe anaemia – normocytic anaemia with haematocrit <15% or
haemoglobin <5 g/dL in the presence of parasitaemia more than 10
000/μL. Note that finger prick samples may underestimate the
haemoglobin concentration by up to 1 g if the finger is squeezed. If
anaemia is hypochromic and/or microcytic, iron deficiency and
thalassaemia/haemoglobinopathy must be excluded. (These criteria are
rather generous; and would include many children in high transmission
areas. A parasitaemia of >100 000/μL might be a more appropriate
threshold.)
3. Renal failure – defined as a urine output of <400 mL in 24 h in adults, or
12 mL/kg in 24 h in children, failing to improve after rehydration, and a
serum creatinine of more than 265 μmol/L (>3.0 mg/dL). (In practice for
initial assessment, the serum creatinine alone is used.)
4. Pulmonary oedema or adult respiratory distress syndrome.
5. Hypoglycaemia – defined as a whole blood glucose
concentration of less than 2.2 mmol/L (40 mg/dL).
6. Circulatory collapse(Algid malaria) or shock – hypotension (systolic
blood pressure <50 mmHg in children aged 1–5 years or <70 mmHg in
adults), with cold clammy skin or core-skin temperature difference
>10°C. (The more recent review declined to give precise definitions,
but noted the lack of sensitivity or specificity of core-peripheral
measurements.) Capillary refill time is not mentioned but recent
studies indicate this simple test provides a good assessment of
severity
7. Spontaneous bleeding from gums, nose, gastrointestinal tract, etc.
and/or substantial laboratory evidence of DIC. (This is relatively
unusual.)
8. Repeated generalized convulsions – more than two observed
within 24 h despite cooling. (In young children, these may be febrile
convulsions, and the other clinical and parasitological features need
to be taken into account.) Clinical evidence of seizure activity may
be subtle (e.g. tonic clonic eye movements, profuse salivation,
delayed coma recovery).
9. Acidaemia – defined as an arterial or capillary pH <7.35 (note
temperature corrections are needed as most patients are hotter
than 37°C; add 0.0147 pH unit per degree Celsius (°C) over 37°C), or
acidosis defined as a plasma bicarbonate concentration <15
mmol/L or a base excess >10. (Operationally, the clinical
presentation of ‘respiratory distress' or ‘acidotic breathing’ is
focused upon in the 2000 recommendations. Abnormal breathing
patterns are a sign of severity indicating severe acidosis, pulmonary
oedema or pneumonia.)
10. Macroscopic haemoglobinuria (Black water fever)– if definitely
associated with acute malaria infection and not merely the result of
oxidant antimalarial drugs in patients with erythrocyte enzyme
defects such as G6PD deficiency. (This is difficult to ascertain in
practice: if the G6PD status is checked following massive
haemolysis, the value in the remaining red cells may be normal
even in mild G6PD deficiency. This part of the definition is not very
useful.)
11. Postmortem confirmation of diagnosis. In fatal cases a diagnosis of
severe falciparum malaria can be confirmed by histological
examination of a postmortem needle necroscopy of the brain. The
characteristic features, found especially in cerebral grey matter, are
venules/capillaries packed with erythrocytes containing mature
trophozoites and schizonts of P. falciparum. (These features may not be
present in patients who die several days after the start of treatment,
although there is usually some residual pigment in the cerebral vessels.)
The 2000 recommendations also include the following:
12. Impairment of consciousness less marked than unrousable coma.
(Any impairment of consciousness must be treated seriously.
Assessment using the Glasgow Coma Scale is straightforward, but the
Blantyre Scale needs careful local standardization particularly in
younger children.)
13. Prostration: Inability to sit unassisted in a child who is normally able
to do so. In a child not old enough to sit, this is defined as an inability to
feed. This definition is based on examination not history.
14. Hyperparasitaemia – the relation of parasitaemia to severity of illness is
different in different populations and age groups, but in general very high
parasite densities are associated with increased risk of severe disease,
e.g. >4% parasitaemia is dangerous in non-immunes, but may be well
tolerated in semi-immune children. In non-immune children studied in
Thailand a parasitaemia ≥4% carried a 3% mortality (30 times higher than
in all uncomplicated malaria) but in areas of high transmission values
much higher may be tolerated well. Many use a threshold definition of
10% parasitaemia in higher transmission settings.
The followings were not considered criteria of severe malaria:
Jaundice – detected clinically or defined by a serum bilirubin
concentration >50 μmol/L (3.0 mg/dL). This is only a marker of severe
malaria when combined with evidence of other vital organ dysfunction
such as coma or renal failure.
Hyperpyrexia – a rectal temperature above 40°C in adults and children is
no longer considered a sign of severity.
Repeat blood film(MPS)
many times to catch
diagnosis

Peripheral smear examination for
malarial parasite is the gold-standard in
confirming the diagnosis of malaria. Thick
and thin smears prepared from the
peripheral blood are used for the
purpose.
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The immunochromatographic tests for
the detection of malaria antigens,
developed in the past decade, have
opened a new and exciting avenue in
malaria diagnosis. However, their role in
the management and control of malaria
appears to be limited at present.
Chloroquine resistant is now
worldwide.
Age in years
Dose of Chloroquine (as base)
(Each 250 mg tablet contains 150
mg base and
each 5 ml of suspension contains
50 mg base)
Dose of Primaquine
For 14 days
(P. vivax and P. ovale only)
1st
dose
(Tab)
2nd
dose
(Tab)
8h
3rd
dose
(Tab)
24 h
4th
dose
(Tab)
48 h
0-1
75 mg
(½)
37.5
mg
(¼)
37.5
mg
(¼)
37.5
mg
(¼)
Nil
1-5
150
mg (1)
75 mg
(½)
75 mg
(½)
75 mg
(½)
2.5 mg
5-9
300
mg (2)
150
mg (1)
150
mg (1)
150
mg (1)
5 mg
9-14
450
mg (3)
225
mg
(1½)
225
mg
(1½)
225
mg
(1½)
10 mg
>14
600
mg (4)
300
mg (2)
300
mg (2)
300
mg (2)
15 mg
0h
Dosing of Artesunate + Mefloqine (WHO, 2010)
Age
Dose of Artesunate
(50mg) Tablet
Dose of Mefloquine
(250mg) Tablet
5-11 months
HALF tablet once daily
for 3 days
HALF tablet on second
day
≥1-6 years
ONE tablet once daily for ONE tablet on second
3 days
day
≥7-13 years
TWO tablets once daily
for 3 days
TWO tablets on second
day, ONE tablet on third
day
>13 years
FOUR tablets once daily
for 3 days
FOUR tablets on second
day, TWO tablets on third
day
Dosing of Artemether + Lumefantrine Tablets (WHO, 2010)
Weight (kgs)
Age (years)
Dose (No. of 20/120mg
tablet) Twice daily for 3 days
5-14
<3
20/120 (1 tablet)
15-24
3-8
40/240 (2 tablets)
25-34
9-14
60/360 (3 tablets)
>35
>14
80/480 (4 tablets)
Dosing of Artemether + Lumefantrine Suspension
Weight (kg)
Dose of suspension (5 ml containing 15 mg artemether and
90 mg lumefantrine) once daily for 3 days
5
7 ml
5-7.5
10 ml
7.5-10
14 ml
10-15
20 ml
First trimester :Quinine + Clindamycin for
7 days. ACT should be used if it is the only
effective treatment available.
 Second and third trimesters :ACT known
to be effective in the country/region or
artesunate + clindamycin to be given for
7 days or quinine + clindamycin to be
given for 7 days.
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Treatment of Severe P. falciparum Malaria
First Drug
Follow-on Treatment (Full course of any ACT)
Artesunatea 2.4 mg/kg bw iv or im on
admission; then at 12 h and 24 h, then once
a day for at least 24 hours, followed by full
course of ACT
•Artesunate plus Sulfadoxine-pyrimethamine
•Artesunate plus Amodiaquine
•Artesunate plus clindamycin or doxycycline
[See below for dose]
OR Artemetherb 3.2 mg/kg bw i.m. given on
admission then 1.6 mg/kg bw per day for at
least 24 hours, followed by full course of ACT
Artemether plus Lumefantrine
Quinineb,c 20 mg salt/kg bw on admission (iv
infusion or divided im injection), then 10
mg/kg bw every 8 h; infusion rate should not
exceed 5 mg salt/kg bw per hour; course for
3 days for malaria acquired in Africa and
South America, 7 days for malaria acquired
in SE Asia
Doxycyclined 100mgs BID (2.2mg/kg BID for
<45kgs[5]) for 7 days OR Clindamycin 20mg
base/kg/day divided in three doses for 7
days[5] in pregnancy
Quinidine gluconatec 10 mg salt/kg
(equivalent to 6.2 mg base/kg) iv infused
over 1–2 hours, followed immediately by
0.02 mg/kg/min salt (equivalent to 0.0125
mg/kg/min base) continuous iv infusion;
course for 3 days for malaria acquired in
Doxycycline OR Clindamycin as above
a.Recommended by WHO in low transmission areas or outside malaria
endemic areas.
b.Recommended by WHO for children in high transmission areas; regimen
1 can also be used.
c.For areas where artesunate or artemether are not available, mainly the
US. National Vector Borne Disease Control Programe in India
recommends quinine as the treatment for severe malaria in pregnancy.
Loading dose should not be administered to patients who received
quinine, quinidine, halofantrine, or mefloquine within the preceding 12
hours.
d.Not for children below 8 years of age and pregnant women
e.Mefloquine has important neuropsychiatric and cardiac adverse
effects; not an ideal drug for pregnancy; cannot be used concomitantly
with quinine or quinidine.
f.For pregnant women. Clindamycin 5 mg/kg (usually 300 mg) po or iv
every 8 hours can be administered if the patient is unable to take
doxycycline.
Insecticide treated bed nets.
Repellents.
Chemoprophylaxis.
No 100% protection.
Antimalarial chemoprophylaxis
Weight adjusted dose for
children
Adult dose
CHLOROQUINE-SENSITIVE MALARIA
Chloroquine
5 mg base/kg weekly
300 mg base
3.5 mg/kg daily
200 mg base
and/or
Proguanil
CHLOROQUINE-RESISTANT MALARIA
Mefloquine
5 base/kg weekly
250 mg base
1.5 mg/kg daily
100 mg
0.5 mg base/kg daily with food
30 mg base
4/1.6 mg/kg daily
250/100 mg
Or
Doxycycline
Or
Primaquine
Or
Atovaquoneproguanil(Malaron)
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Chloroquine should not be taken by people with a history of
seizures, generalized psoriasis or pruritus previously on
chloroquine.
b Mefloquine is not recommended for babies <3 months of age.
Mefloquine should not be taken by people with psychiatric
disorders, epilepsy, or those driving heavy vehicles, trains,
aeroplanes etc. or deep sea diving.
c Doxycycline may cause photosensitivity. Use of sunscreens is
recommended.Not for childern under 8 years.
d Chloroquine, pyrimethamine and proguanil are all considered
safe in pregnancy, but are now largely ineffective against P.
falciparum. Mefloquine is considered safe, although there are
uncertainties as treatment use has been associated with stillbirth
in one large series. Tetracyclines and primaquine are
contraindicated in pregnancy (although some argue that they
are safe in first trimester before the formation of fetal bones and
dentition, and before the risk of acute fatty liver), and
atovaquone-proguanil has not been evaluated.
e The use of antimalarial prophylaxis by children living in an
endemic area has been shown to reduce mortality; in The
Gambia administration of pyrimethamine and dapsone
(Maloprim) in the 1–4 year age group reduced mortality by 25%.
a
Malarial nephropathy(Quartan
nephropathy).
Tropical splenomegaly(hyper
reactive malarial
splenomegaly) syndrome.
Chronic anemia .
Failure to thrive.

The nephrotic syndrome, with albuminuria,
hypoalbuminaemia, oedema and variable
renal impairment, is common in the
tropics.Repeated or continuous P. malariae
infection is associated with childhood
nephrotic syndrome in West Africa and
Papua New Guinea. In the past, quartan
nephropathy was also described in eastern
Asia. It has disappeared from countries
where P. malariae has been eradicated,
such as Guyana, where Giglioli first
described the relationship between malaria
and nephrosis.

This is also known as the tropical splenomegaly
syndrome. It occurs where transmission of
malaria is intense and has been reported
throughout the tropics. The highest incidence
of hyper-reactive malarial splenomegaly (HMS)
yet reported was in the Upper Watut Valley of
Papua New Guinea, where 80% of adults and
older children had large spleens. Genetic
factors undoubtedly also play a role because
within a malarious area the geographical
distribution of HMS does not follow closely that
of malaria transmission. In Ghana first degree
relatives have a four times higher incidence of
HMS than age and location matched controls.

There is gross splenomegaly with normal architecture, and
lymphocytic infiltration of the hepatic sinusoids with Kupffer cell
hyperplasia. The massively enlarged spleen leads to
hypersplenism with anaemia, leucopenia and
thrombocytopenia. There is a polyclonal
hypergammaglobulinaemia with high with high serum
concentrations of IgM. High titres of malaria antibodies and a
variety of autoantibodies (antinuclear factor, rheumatoid factor)
are usually present. The hypergammaglobulinaemia is believed
to result from polyclonal B-cell activation in the absence of
adequate numbers of CD8+ suppressor T-cells, which have been
removed by an antibody-dependent cytotoxic mechanism.
Cell-mediated immune responses are otherwise normal.
Immunoglobulin gene rearrangements have been
demonstrated in a sub-group of patients with HMS. This indicates
clonal lymphoproliferation and the potential for progression to
malignant lymphoma or leukaemia.