MALARIA CEREBRAL

Dani Rosdiana, SpPD

 Tujuan Pembelajaran
• Definition
• Epidemiology
• Pathophysiology
• Clinical features
• Investigations
• Treatment
• conclusion
 PENDAHULUAN
• Malaria represents a medical emergency because
it may rapidly progress to complications and
death without prompt and appropriate
treatment.
• Malaria serebral merupakan komplikasi mayor
malaria yang paling sering menyebabkan
kematian.
• Kematian akibat malaria serebral berkisar 800
ribu orang per tahun diseluruh dunia, 89% dari
jumlah ini terjadi di Afrika dan 88% terjadi pada
anak dibawah 5 tahun.
 Malaria Threatens
40% world population
 Definition
• Manifestation /
Complication of severe
plasmodium falciparum
MALARIA
• Unarousable coma
more than 30 mts with
GCS <7/15 with
evidence of acute falc
inf (asexual form in
peripheral blood smear)
• Exclusion of other
causes
 EPIDEMIOLOGY
• World :
– 300 - 500 million cases (90% in Africa)
– 1,1 – 2,7 million deaths annually
• Severe malaria is a multisystem disease, cerebral
involvement is one of the features.
• Southeast Asia: 54% of the 1050 patients with strictly
defined severe malaria had cerebral malaria,
• Mortality in this last group was 19% compared to up
to 43% when multiple organs were involved
 Malaria Threatens
40% world population
 PATHOGENESIS OF CEREBRAL MALARIA
A conclusive pathophysiological model explaining the
reversible coma of cerebral falciparum malaria does not
exist

1. MECHANICAL HYPOTHESIS
- Sequestration of RBC in the brain by
Cytoadherence/rosetting
2. Toxin/cytokine HIPHOTESIS
Malarial toxin induced cytokines stimulating
excessive nitric oxide production
 MECHANICAL HYPOTHESIS
• Sequestration of
Cerebral Capillaries and
Venules

Rosetting: binding of 2 or
more uninfected RBC’s to an
infected RBC’s

Agglutination: the binding

of 2/more infected RBC’s
Mechanical Hypothesis

P. falciparum parasites in brain capillary

Section of brain showing blood vessels
blocked with developing
P. falciparum parasites
• Selective Cytoadherance results in rosetting

• Reduction of Microvascular Blood flow

• Hypoxia

• Dose not explain selective absence of

Neurological Deficits
 HUMORAL HYPOTHESIS
Malarial Toxin macrophages
activation TNF alpha & IL-6

UNCONTROLLED NITRIC
OXIDE PRODUCTION

Nitric Oxide diffuse blood brain barrier

IMPAIRS SYNAPTIC TRANSMISSION
(like general anaesthetics/ethanol)

COMA

TNF alpha >100pg/ml is associated with cerebral pathology and death

• Cerebral malaria mechanical hypothesis
can not explain relative absence of
neurological deficit even after days of
coma
• Toxin/cytokine hypothesis can explain the
rapid recovery of coma and absence of
neurological deficit
c
CLINICAL FEATURES
ONSET
Acute – following seizures
gradual
CONCIOUSNESS
drowsiness
confusion
disorientation
delirium
and agitation
SEIZURES
Repeated generalised
convulsions > 2/24 hrs
• Earliest Manifestations - ONSET
– Fever Acute – following seizures
– Loss of Appetite gradual
– Vomiting
CONCIOUSNESS
– Cough
drowsiness

• Specific for Cerebral confusion

Malaria disorientation
– Impaired consiousness delirium
– Gen. Convulsion with and agitation
Sequelae
– Coma SEIZURES
Repeated generalised
convulsions > 2/24 hrs
 OTHER CLINICAL FEATURES
• Mild neck stifness- no rigidity
• Papilloedema in < 1%
• Retinal haemorrhages – 15%
• Pupils and corneal reflex
• Transient dysconjugate gaze- no paresis
• Motor system:
– Decorticate rigidity
– decerebrate rigidity
– Opisthotonus
– Tone maybe increased, decreased or normal
 Associated Presentation
• Hypoglycaemia
• Metabolic Acidosis
• Shock
• Neurological deficits
• Other forms can Co-
exist
 SEQUELE and POST MALARIAL NEUROLOGICAL
SYNDROMES

• 3% in adults, 10% in children

– 50% recover completely
– 25% partial recovery
– 25% no recovery
• Hemiparesis, hemisensory deficits, cortical blindness
• Cranial nerve palsies, foot drop
• Extrapiramidal symptoms (chorea, athetosis, tremors)
• Sudden blindness due to vitreous haemorrhage
• Cerebellar ataxia
• Psychiatric disturbances
– Depression, amnesia, psycosis, personality changes, delusion and
hallucinations
 LABORATORIUM FINDING
• Thrombocytopenia is the most common laboratory
abnormality (60% of cases)
• hyperbilirubinemia (40%),
• Anemia (30%),
• elevated hepatic aminotransferase levels (25%)
• The leukocyte count is usually normal or low
• procalcitonin are almost invariably elevated.

Thrombocytopenia and hyperbilirubinemia had a positive

predictive value of 95% for Malaria
LABORATORY DIAGNOSIS
Diagnosis of Falciparum Malaria

• Conventional Microscopy
»Giemsa Stain
»Field Stain
Microscopic examination of blood film is gold
standard for diagnosis of malaria
• Thick blood film
– Species specific and inexpensive
• Thin blood film
– Rapid, species specific and inexpensive
• PfHRP2 dipstick card test
– Rapid and sensitive, detects only p falc
• Role of PCR
– Most sensitive and specific
– Results only after 24 hrs
Stages of P. falciparum
 CEREBRAL
INVOLVEMENT
• Clinical

• CSF - Increased Lactic Acid

• CT, MRI
 SUPPORTIVE &
ADJUNCTIVE THERAPY
• Nursing Care
• Catherization
• Nasogastric tube
• Fluid & Electrolyte
• Monitor level of coma & vital signs
• Antipyretics
• Anticonvulsants
• Reduction in ICT
• Correction of Hypoglycaemia
• Exchange Transfusion
• IncreaseMicrocirculatory Flow - Pentoxyfylline
• Desferrioxamine
• Correction of Anaemia, Acidosis, Dehydration
 TREATMENT
• Medical emergency requires ICU care
• Ventilatory support, cardiac monitoring
• Correction of fluids, electrolytes and acid base balance
• Blood transfusion (where fascilities are available)
• Specific treatment:
– Artesunate is a drug choice:
– Quinine in case of first trimester of pregnancy: 20 mg/kg in
Dekstrose 5% saline in 4 hrs then 8th hourly orally to complete 7
days
– Doksisikline 3,5 mg/kg/day for 7 days
– Tetracycline /clindamisin (children and pregnancy)
• ACT : Artesunate combination therapy
 TREATMENT : QUININE
• An initial loading dose Should be administered as soon as
possible, followed by the maintenance dose.

• Maintenance: should be given by a rate-controlled

intravenous infusion (infusion pump)  be carefull of
cardiotoxic

• This delay may allow sequestration of trophozoites causing

major organ dysfunction
 QUININE……
• DOSE : 20 mg quinine salt/kg on admission (i.v.
infusion in 5% dextrose/dextrose saline over a
period of 4 hours)
• followed by maintenance dose of 10 mg/kg 8
hourly; infusion rate should not exceed 5 mg/kg per
hour.
• Loading dose of 20 mg/kg should not be given, if the
patient has already received quinine.
• NEVER GIVE BOLUS INJECTION OF QUININE. If
parenteral quinine therapy needs to be continued
beyond 48 hours, dose should be reduced to 7 mg/kg
8 hourly.
 ARTEMETER
• Artemether: 3.2 mg/kg i.m. given on admission
then 1.6 mg/kg per day.
• Patients receiving artemisinin derivatives should get
full course of oral ACT.
• ACT containing mefloquine should be avoided in
cerebral malaria due to neuropsychiatric
Complications.
 ARTESUNATE
• Artesunate 2.4 mg/kg iv bolus and then 1.2
mg/kg iv daily
 CONCLUSION
• Changing profile of clinical features of
plasmodium falciparum – cerebral malaria
jaundice/ renal failure/MODS
• Cytoadherence, rossetting nitric oxide and
biomass of brain are important pathogenic
mechanisms in cerebral malaria
• Quinine or artemeter iv  important for
cerebral malaria