Dr.

Nasser AL Amin
Medical Resident,QCH
Objectives
Definition of malaria
Types of malaria
Epidemiology
Pathophysiology of malaria
Clinical manifestations of malaria
Complications of malaria
Treatment and prevention of malaria
mal aria (bad air)

Malaria is an infectious disease

transmitted by female anopheles
mosquitoes. It is caused by minute
parasitic protozoa of the genus
Plasmodium, which infect human
and insect hosts alternately.
Malaria facts
40% of the world's population is exposed to the
risk of malaria
 500 million new cases a year
1 death every 30 seconds
 more than 80 countries in Africa, Asia and South
America affected by malaria
9.5 million mosquito nets impregnated with
insecticide have been distributed throughout
Africa since 2000
 Malaria History
Two Egyptian mummies who died more
than 3,500 years ago have provided clear
evidence for the earliest known cases of
malaria

Pathologist Andreas Nerlich at the Academic

Teaching Hospital , identified DNA for
the malaria parasite Plasmodium
falciparum in tissues from two mummies.
species Plasmodium
1. P. falciparum
2. P. vivax
3. P .malariae
4. P .ovale
5. P. knowlesi 

P. falciparum is the
most dangerous.
 P. knowlesi
  Human infection with P. knowlesi was first described among 120 patients in
Malaysia in 2004

 P. knowlesi appears morphologically similar to P. malariae by microscopy but

the species can be distinguished by PCR-based assays and gene sequencing

 P. knowlesi infection should be considered among individuals with severe

manifestations of malaria initially diagnosed as P. malariae by microscopy

 Severe manifestations include high parasite density (75,000 to 765,000

parasites/microL), hypotension, hypoglycemia, hepatorenal dysfunction, and
respiratory distress
Malaria Worldwide Distribution
Global distribution of P. falciparum and P. vivax in 2005
Seasonal Malaria Variation
For most people, symptoms begin 10 days to 4 weeks after being
bitten by a malaria-infected mosquito
 The Malaria Parasite Life Cycle
Infection Sporozoites

Liver

Merozoites Asexual
cycle

Transmission
to mosquito

Gametocytes
 The Malaria Parasite Life Cycle
1. Transmission
Female anopheles Infection Sporozoites
mosquito bites and
releases sporozoites
into the blood
stream. These
circulate for about
30 mins and then
invade the liver.

Liver

Merozoites Asexual
cycle

Transmission
to mosquito

Gametocytes
 The Malaria Parasite Life Cycle
2. Pre-erythrocytic phase
Infection Sporozoites Also called the “tissue” or
“hepatic” phase

Takes place in hepatocytes. The

sporozoites mature into
schizonts which rupture to
release merozoites. Duration of
this phase depends on the
species.

In P. vivax and P. ovale, the

schizont may also differentiate
Liver
into hypnozoites. These are
dormant forms of the parasite
Merozoites which may remain in the liver for
Asexual
several months or years and
cycle
cause relapse in the human host.
Transmission
to mosquito

Gametocytes
 The Malaria Parasite Life Cycle
Infection Sporozoites

Liver
3a. Asexual phase (Erythrocytic
schizogony)
Merozoites Merozoites invade red blood cells.
Asexual
Here they grow and mature into
cycle
trophozoites which appear as ring
Transmission forms. The trophozoites develop into
to mosquito schizonts. The infected red blood
cells then rupture to release
numerous merozoites from the
Gametocytes
schizont to infect other red cells.
Merozoite release results in fever,
chills, rigours and other symptoms of
malaria infection.
The Malaria Parasite Life Cycle
3b. Sexual phase Infection Sporozoites

Some merozoites differentiate into

male and female gametocytes, the
forms of Plasmodia infective to
mosquitoes. These are taken up by
a mosquito during another blood
meal. These fuse to form an
ookinette in the gut lumen of the
mosquito. The ookinette invades
the stomach wall to form the
oocyst. This in turn develops and
Liver
releases sporozoites which migrate
to the salivary gland of the
mosquito. This mosquito then goes Merozoites Asexual
on to infect another human host. cycle

Transmission
to mosquito

Gametocytes
Pathophysiology of malaria
malaria parasites first
damage the infected red
blood cells directly and
then initiate a chain
reaction of nonspecific
inflammatory processes
Clinical manifestations
Cardinal clinical symptoms
Fever
Rigors
Sweats
Flu-like" symptoms
Cough
Myalgia
Headache
Back pain
Occasional symptoms
Vomiting
Nausea
Diarrhea
signs
pallor & jaundice
splenomegally
malaria is one of causes tropical splenomegally
The fever and chills of malaria are associated with the rupture of schizonts in
erythrocytic stage
The clinical course of P. falciparum

Following a bite by an infected mosquito, many

people do not develop any signs of infection. If
infection does progress, the outcome is one of
three depending on the host and parasite factors
enumerated in the previous slides:

A. Asymptomatic parasitaemia (“clinical

immunity”)
B. Acute, uncomplicated malaria
C. Severe malaria
 A. Asymptomatic parasitaemia

•There are malaria parasites in the peripheral blood but

no symptoms.
•These individuals may be important reservoirs for
disease transmission.
.
 Severe and complicated malaria
Nearly all severe disease and the estimated >1 million deaths from malaria
are due to P. falciparum.

The following are 8 important severe manifestations of malaria:

1. Cerebral malaria 5. Acute renal failure

2. Severe malaria anaemia 6. Pulmonary oedema
7. Circulatory collapse, shock or
3. Hypoglycaemia
“algid malaria”
4. Metabolic acidosis 8. Blackwater fever
CEREBRAL MALARIA
Cerebral malaria
collectively involves the
clinical manifestations
of Plasmodium
falciparum malaria
that induce changes in
mental status and
coma.
 Cerebral malaria - pathophysiology

The consequences of this

include:
1. reduced cerebral blood
flow
2. cerebral hypoxia
3. release of cytokines
which in turn induce the
release of nitrous oxide, a
A 3 year old child with
known depressor of impaired consciousness,
consciousness grimacing and marked
extensor posturing of the
arms
Cerebral malaria - clinical .1

The most well-known severe

manifestation of malaria
Defined as:
unarousable coma persisting
for > one hour
with asexual forms of P.
falciparum in the peripheral
blood
other causes of
encephalopathy excluded*
Occurs most commonly in
young children although non-
immune adults are also at risk
A 4 year old boy who was deeply
comatose and had persistent
deviation of the eyes
CEREBRAL MALARIA
Dysconjugate
(asymmetric) gaze in a
comatose Gambian
child with cerebral
malaria. Convulsions,
which are often
prolonged and
multiple, complicate
over 60% of cases.
.Cerebral malaria – clinical con .1
Cerebral malaria can rapidly
progress to death, even with
appropriate treatment. Case
fatality is between 20-30%.
In survivors, resolution of coma
usually occurs within 1-2 days in
children and within 2-4 days in
adults but may be complicated
by neurological sequelae in ~5%
adults and >10% of children.
.Cerebral malaria – clinical con .1
The illness may start with
drowsiness and confusion and then
progress to coma.

The loss of consciousness is often

preceded by repeated convulsions.

 Retinal haemorrhages may be seen

on fundoscopy.
CEREBRAL MALARIA
Gambian child with
cerebral malaria,
exhibiting severe
opisthotonic
(extensor) posturing
Severe malaria anaemia
Defined as a haematocrit of <15% or
.haemoglobin concentration <5 g/dl

Occurs commonly in young children and

.pregnant women

Many patients require urgent

transfusion. The condition may be
rapidly fatal when blood transfusion is
.delayed
Marked pallor in an African
child with severe anaemia due
to P. falciparum infection

Bac
 3. Hypoglycaemia

Blood sugar <2.5 mmol/L

Increases the risk of mortality and sequel in

children with cerebral malaria; may present
with convulsions or a deterioration in level of
consciousness.
Hypoglycaemia .3
.con
 Results from a combination of factors:
1. reduced glycogen stores because of
reduced food intake
2. increase metabolism due to fever and
repeated convulsions
3. glucose consumption by malaria
parasites
4. cytokine or quinine-stimulated
hyperinsulinaemia
 4. Metabolic acidosis

1. Lactic acidosis is a major contributor and probably

results from tissue anoxia and anaerobic glycolysis

2. Presents with deep, rapid respirations (as in diabetic

ketoacidosis)
5. Acute renal failure

occurs almost exclusively in adults and older

children in areas of unstable malaria

affected patients are usually oliguric (urinary

output <400 ml/day) or anuric

serum creatinine levels are elevated

 6. Acute pulmonary oedema

This is fatal manifestation of

severe falciparum malaria
occurs mainly in adults.
Hyperparasitaemia, renal failure
and pregnancy are recognised
predisposing factors
can develop even while the patient Acute pulmonary oedema,
developing shortly after
is being treated for malaria, is delivery in a woman with
unresponsive to any therapy severe P. falciparum malaria

Bac
Severe pulmonary edema in a patient with severe
P. falciparum malaria
7. Circulatory collapse, shock, “algid
malaria”

Features of circulatory collapse (cold/clammy skin,

hypotension, peripheral cyanosis, weak/thready pulses)
may be seen in patients with severe P. falciparum malaria.

“Algid malaria” is characterised by hypotension, vomiting,

diarrhoea, rapid respiration and oliguria. This condition is
associated with a poor prognosis.

Bac
8. Haemoglobinuria or “Blackwater Fever”

This results from massive intravascular

haemolysis. The condition presents with
severe pallor, jaundice and passage of
dark urine due to haemoglobinuria. It may
be associated with acute renal failure.

Typical, dark urine of

haemoglobinuria on day 0
which has cleared by day 3
Sickle cell trait & malaria
Case control studies have since
confirmed that sickle cell trait is
 90 percent protective against severe
and complicated malaria (cerebral
malaria and severe anemia)
 60 percent protective against
clinical malaria leading to hospital
admission
 there is some evidence for
protection against mild clinical
malaria
 — The mechanisms by which sickle
cell trait protects against P.
falciparum are not fully understood
 possibility is that the HbS polymer,
with its considerably right shifted
oxygen equilibrium curve, kills the
parasite by oxygen toxicity
 Diagnosis
Malaria is a multisystem disease. It presents with a wide variety of non-specific clinical
features: there are no pathognomonic symptoms or signs. Many patients have fever, general
aches and pains and malaise and are initially misdiagnosed as having “flu”.

P. falciparum malaria can be rapidly progressive and fatal. Prompt diagnosis saves lives

 A good history
 Residence or a recent visit (in the preceding 3 months) to a malaria endemic area
 History of fever (may be paroxysmal in nature)
 Recognise significance of non-specific clinical features such as vomiting, diarrhoea,
headache, malaise
 Physical examination
 Identify signs consistent with malaria: fever, pallor, jaundice, splenomegaly
 Exclude other possible causes of fever (e.g. signs of viral and bacterial infections)

The diagnosis of malaria should be considered in any

unwell person who has been in a malarious area
recently
 Investigations
Blood Film Examination
Thick and thin blood films (or “smears”) have
remained the gold standard for the diagnosis
of malaria.
Thick blood film - Used for detecting malaria: a
larger volume of blood is examined allowing
detection of even low levels of parasitaemia.
Also used for determining parasite density and
monitoring the response to treatment.
Thin blood film – Gives more information about
the parasite morphology and, therefore, is
used to identify the particular infecting species
of Plasmodium.
Appearance of P. falciparum in thin blood films

Ring forms or trophozoites;

many red cells infected –
some with more than one
parasite

Gametocytes (sexual stages); After a blood

meal, these forms will develop in the
mosquito gut
Erythrocytic schizont:
Mature female (F) and male (M) gametocytes and
trophozoites (T) of Plasmodium falciparum
Other methods of diagnosis of malaria

These are not routinely used in clinical practice. They

include :

a) Antigen capture kits.

• Uses a dipstick and a finger prick blood sample.
Rapid test - results are available in 10-15 minutes.
Expensive and sensitivity drops with decreasing
parasitaemia.
b) PCR based techniques.
• Detects DNA or mRNA sequences specific to
Plasmodium. Sensitivity and specificity high but test
is expensive, takes several hours and requires
technical expertise.
Other methods of diagnosis of malaria

c) Fluorescent techniques.
• Relatively low specificity and sensitivity. Cannot
identify the parasite species. Expensive and requires
skilled personnel.
d) Serologic tests.
• Based on immunofluorescence detection of
antibodies against Plasmodium species. Useful for
epidemiologic and not diagnostic purposes.
 Malaria in pregnancy
More than 45 million women (30 million in
Africa) become pregnant in malaria endemic
areas each year.

The WHO now recommends intermittent

preventive treatment (IPT):
the administration of anti-malarial drugs (e.g.
sulphadoxine-pyrimethamine) during
antenatal care whether or not women show
symptoms. IPT has been shown to
substantially reduce the risk of maternal
anaemia in the mother and low birth weight in
the newborn.
Malaria Prevention

vector control

personal protection measures such as insecticide-

treated bed nets

preventive treatment with antimalarial drugs

Antimalarial drugs
Chloroquine phosphate
 
Quinine

Pyrimethamine
sulfadoxine

Doxycycline

artemiser & artesunate

mefloquine

Primaquine
tablets/suspension Chloroquine
 Children dose:
10 mg of base per kg followed by
5 mg/kg 6-8 h later and 5 mg/kg
on each of the following 2 days.

 Adults dose
20 mg of base per kg followed by
10 mg/kg 6-8 h later and
10mg/kg on each of the
following 2 days.
QUININE
The IV dose of quinine
is 20mg/kg of quinine
stat
 Then 10 mg/kg
quinine IV q 8hor for
2 days then 600 mg
quinine orally every
eight hours.
 Treatment should be
given for seven days
Primaquine (Malirid)
 largely used to prevent relapse
of P. ovale and P. vivax malaria
by eradicating hypnozoite forms
that may remain dormant in the
liver
 presumptive anti relapse
therapy (PART) with
primaquine to prevent relapse
 an adult dosage of 1 tablet
(equivalent to 15 mg base) daily
for 14 days
 is contraindicated in
individuals with (G6PD)
deficiency and in pregnant
women
severe falciparum malaria treatment

nonpregnant adults : intravenous artesunate

children : intravenous quinine /7 days
pregnant women: second and third ,intravenous
artesunate .first trimester,intravenous quinine/7day

Artesunate dose:
2.4mg/Kg intravenously on the first day followed by
1.2mg/Kg daily until the patient can take orally
artesunate
artemisinin group
CHLOROQUINE RESISTANT MALARIA
defined by epidemiologistss as

persistent parasitemia (eg, not decreasing) after four

days of chloroquine therapy
or
recurrent parasitemia within 28 days following
chloroquine therapy
CHLOROQUINE RESISTANT MALARIA
 First-line treatment of uncomplicated malaria due to
chloroquine resistant P. falciparum consists of one of
the following agents
 Artemisinin derivative combinations
Atovaquone-proguanil (Malarone)
Quinine-based regimen (in combination with
doxycyline or clindamycin)
Mefloquine (Lariam) (in combination with
doxycycline)
Saudi Arabia Malaria Map
Recrudescense
a repeated attack of malaria (short term relapse or
delayed)
due to the survival of malaria parasites in red blood
cells
To prevent relapse of P. vivax, primaquine should be
dosed 30 mg/day for 14 days
To prevent relapse of P. ovale, primaquine should be
dosed 15 mg base/day for 14 days

www.malariasite.com
Vector control for the prevention of malaria
:includes

Insecticide-treated bed nets

 Source reduction (larval control).

Indoor residual spraying

Treated Bed Nets - Insecticide
Mothers and children under mosquito nets,
south Sudan
Indoor residual spraying
‫انتشر يف عام ‪1949‬م وباء املالريا‪ .‬ويرى يف الصورة‬
‫أحد األطباء من ارامكو يأخذ عينات من املزارع‬
‫أعدت أرامكو فصوال لتعليم أفراد احلملة‬
‫متابعة عملية الرش‪ ،‬وجرد البيوتات اليت مرت هبا محلة‬
‫مكافحة املالريا‬
‫مدينة القطيف ‪ 1975‬م‬