Introduction

• Malaria remains a global health problem.

• WHO 2017, estimates there were 214 million new cases .The African
Region accounted for most global cases of malaria (88%), followed by
the South-East Asia Region (10%) and the Eastern Mediterranean
Region (2%), there were an estimated 438 000 malaria deaths.
• Malaria in humans is caused by five species of parasites belonging to
the genus Plasmodium.
• Plasmodium falciparum is the major cause of severe malaria.
• Severe malaria causes high mortality that need rapid and appropriate
treatment.

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Malaria-endemic Areas

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 P. knowlesi

Severe
Malaria
P. malariae P. ovale

P. falciparum P. vivax
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Clinical Presentation Malaria
• Early symptoms
• Headache
• Malaise
• Fatigue
• Nausea
• Muscular pains
• Slight diarrhea
• Slight fever, usually not intermittent
• Could mistake for influenza or gastrointestinal infection

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Clinical Presentation Malaria
• Signs
• Anemia
• Thrombocytopenia
• Jaundice
• Hepatosplenomegaly
• Respiratory distress syndrome
• Renal dysfunction
• Hypoglycemia
• Mental status changes
• Tropical splenomegaly syndrome
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Clinical Presentation Malaria
• Varies in severity and course
• Parasite factors
• Species and strain of parasite
• Geographic origin of parasite
• Size of inoculum of parasite
• Host factors
• Age
• Immune status
• General health condition and nutritional status
• Chemoprophylaxis or chemotherapy use

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Pathogenesis Malaria • Sporozoites injected during
mosquito feeding
Salivary gland • Invade liver cells
sporozoite • Exoerythrocytic schizogony
Liver stage
(merozoites)
• Merozoites invade RBCs
• Repeated erythrocytic
Midgut sporozoite
merozoite schizogony cycles
Mosquito • Gametocytes infective for
oocyst stage schizont
mosquito
• Fusion of gametes in gut
ookinete trophozoite
ring • Sporogony on gut wall in
zygote hemocoel
Blood stage
♀ • Sporozoites invade salivary
♂ + ♂♀
gametocytes glands
gametes
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Tabel2.Definition of severe malaria by the working group of
WHO 2010

Clinical features Laboratory findings

• Impaired consciousness or unrousable coma.
• Prostration, i.e. generalized weakness so that the
patient is unable walk or sit up without assistance
• Failure to feed.
• multiple convulsions – more than two episodes in
24 h.
• Deep breathing, respiratory distress (acidotic
breathing).
• Circulatory collapse or shock, systolic blood
pressure < 70 mm Hg in adults.
• Clinical jaundice plus evidence of other vital organ
dysfunction
• Haemoglobinuria.
• Abnormal spontaneous bleeding.
• Pulmonary oedema (radiological).
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• Hypoglycaemia (blood glucose < 2.2 mmol/l or < 40
mg/dl).
• Metabolic acidosis (plasma bicarbonate < 15
mmol/l).
• Severe normocytic anaemia (Hb < 5 g/dl, packed
cell volume < 15%).
• Haemoglobinuria.
• Hyperparasitaemia (> 2%/100 000/μl in low
intensity transmission areas or > 5% or 250 000/μl
in areas of high stable malaria transmission
intensity).
• Hyperlactataemia (lactate > 5 mmol/l).
• Renal impairment (serum creatinine > 265 μmol/l).
9
Tabel3.Definition of severe malaria by the working group of
WHO 2015
One / more of the following, occuring in the absence of an identified alternative cause and in the presence of
P. falciparum asexual.
• Impaired consciousness: GCS < 11 in adults.
• Prostration: Generalized weakness & unable to sit, stand, walk.
• Multiple convulsions: More than two episodes within 24hrs.
• Acidosis: A base deficit of > 8 mEq/L or bicarbonate level of < 15 mmol/L or plasma lactate >=5mmol/L.
respiratory distress
• Hypoglycaemia: RBS < 40mg/dL.
• Severe Malarial anaemia: HB < 5, haematocrit <1 5%.
• Renal impairment: creatinine>3mg/dl, blood urea > 20mmol/L.
• Jaundice: Sr bilirubin > 3mg/dL with a parasite count >1,00 000/µL.
• Pulmonary oedema: Radiologically confirmed oxygen saturation < 92% on room air, RR > 30/min,with chest
indrawing crepitations on auscultation.
• Significant bleeding: recurrent / prolonged bleeding from the nose, gums or venepuncture sites,
haematemesis or melaena.

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Pathogenesis Severe Malaria
Inflammatory
Chill, fever, sweat
responses
Toxic mediators
metabolic hypoglycaemia
disturbances

Anemia

Hemolysis
Phagocytosis renal failure
Splenomegaly Black water fever
Adhere to
hepatomegaly
blood vessels
Cerebral malaria
Tissue hypoxia
Obstruct
Pulmonary edema
blood flow
Impaired
microcirculation DIC 11
 Roseting Endothelial cytoadherence
Receptor: Blood group antigens Receptor: CD31, CD36, CSA
CD36, CR1 and HS E-selectin, ICAM-1, TSP, and VCAM-1

Pathogenesis
Severe Malaria
Flow

IFN-
TNF-

Rolling on
Endothelial In situ rosetting Vascular occlusion
endothelium
activation
Receptor: ICAM-1 12
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Clinical Features Severe Malaria
• Impaired consciousness/coma.
• Prostration, i.e. generalized weakness so that the patient is unable
walk or sit up without assistance.
• Failure to feed.
• Multiple convulsions – more than two episodes in 24 h or activity of
subtle convulsion.
• Clinical jaundice.
• Deep breathing, respiratory distress / acidotic breathing.

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Clinical Features Cont…
• Circulatory collapse/shock (SBP < 80 mmHg).
• Clinical jaundice.
• Anuria.
• Abnormal spontaneous bleeding.
• Haemoglobinuria.
• Hyperpyrexia (Temperature >106°F or >42°C).
• Pulmonary oedema (radiological).

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Laboratory Findings Severe Malaria
• Hypoglycaemia (blood glucose < 2.2 mmol/l or < 40 mg/dl).
• Metabolic acidosis ( pH < 7.25 or plasma bicarbonate < 15 mmol/l).
• Severe normocytic anaemia (Hb < 5 g/dl, packed cell volume < 15%).
• Haemoglobinuria.
• Hyperparasitaemia (> 2%/100 000/μl in low intensity transmission.
areas or > 5% or 250 000/μl in areas of high stable malaria
transmission intensity).
• Hyperlactataemia (lactate > 5 mmol/l).
• Renal impairment (serum creatinine > 3 mg/dL).
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Laboratory Findings Cont…
• Decreased platelet count (< 50,000/L).
• Prolonged prothrombin time (> 3 s).
• Prolonged partial thromboplastin time.
• Decreased fibrinogen (< 200 mg/dL).

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Diagnosis Malaria
Microscopy
• Thick and thin blood
• gold standard for confirmation of diagnosis of malaria.
• Advantages :
1. Sensitivity is high.
It is possible to detect malaria parasites at low densities.
2. To quantify the parasite load.
3. To distinguish different species of malaria parasites and their different
stages.

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banana shaped gametocyte Schuffner’s dots

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Diagnosis Malaria
Rapid Diagnostic Test
• Based on the detection of circulating parasite antigens.
• Several types of RDTs are available.
• Some of them can only detect P.falciparum, while others can detect
other parasite species also.

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 Differetial Diagnoses
• Typhoid
• Respiratory and urinary tract
infections.
• Viral illnesses (such as
influenza, dengue fever etc)
Acute coma Renal failure
•viral encephalitis (herpes simplex, •Glomerulonephritis
•hypertension.
HIV, mumps, etc)
•bacterial meningoencephalitis •herbal medicines
(pyogenic and rarely tuberculous) •Snakebite
•fungal and protozoal
meningoencephalitis (African Jaundice and hepatomegaly
trypanosomiasis), •viral hepatitis
•cerebral typhoid, •alcohol
•brain abscess •drug-induced diseases
•heat stroke / CVA events •biliary disease
•hypertensive encephalopathy •yellow fever
•intoxications with drugs and •leptospirosis
poisons
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Treatment of Non-Severe Malaria
1. Malaria falciparum and Malaria vivax
Treatment of malaria falciparum and malaria vivax currently uses ACT
plus primaquine.
The ACT dose for malaria falciparum is the same as malaria vivax,
Primaquine for malaria falciparum is only given on the first day with a
dose of 0.25 mg / kgBB and malaria vivax for 14 days at a dose of 0.25
mg / kgBB.

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Treatment of Non-Severe Malaria
2. Relapse of Malaria vivax
Same regiment of ACT with increased dose of Primaquine
0,5mg/kgBB/day

3. Malaria Ovale
Regiment of ACT, DHP + Primaquine 0,25mg/kgBB/day for 14 days

4. Malaria Malariae
DHP for 3 days without primaquine

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Treatment of Non-Severe Malaria
5. Mixed infection P. falciparum + P. vivax / P. Ovale

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Treatment Severe Malaria
Patients with severe malaria should be treated in ICU
• Parenteral antimalarials, antipyretics, antibiotics, anticonvulsants.
• Intravenous infusion facilities.
• Special nursing for coma patients.
• Blood transfusion.
• Laboratory facilities.
• Facility for Oxygen, dialysis, ventilator, etc.

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Group at Risk of Severe Malaria
• These are people whose immunity to malaria is low
• People of all ages in areas of low malaria endemicity
• Pregnant women especially during the 1st and 2nd pregnancies
• Travelers from non-endemic ares
• People returning to endemic areas after a long(more than 6 months)
stay in non malaria areas
• People with HIV/AIDs
• Persons with Sickle cell anemia

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Supportive Treatment Severe Malaria
• Supportive measures: oxygen, ventilatory support, cardiac
monitoring, pulse oximetry
• Unconscious pts require lumbar puncture to rule out concomitant
bacterial meningitis
• Repeat clinical assessment should be preformed every 2-4 hrs & lab
investigations every 6 hrs to detect & treat complications
• If coma score decreases, investigatons should focus on possibility of
seizures, hypoglycemia or worsening anemia
• Predictors for fatality include acidosis, impaired consciousness,
elevated blood urea nitrogen etc

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Fluid Therapy in Severe Malaria
Fluid requirements should be assessed individually. Adults with severe
malaria are very vulnerable to fluid overload.
Giving fluids appropriately by:
• Maintenance 30 ml/kg, if there is dehydration can be added fluids as
dehydration, added 10% mild, 20% moderate and 30% severe.
• The temperature rise every 1oC plus 10% of the required maintenance
fluids.
• Insert of CVP (central venous pressure) to accurately monitor fluid.
• Used dextrose 5% to prevent hypoglycemia.
• When there hyponatremia (Na <120 mEq / L) can use NaCl.

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WHO 2015 Recommendation
• Treat adults with severe malaria (including pregnant women in all
trimesters and lactating women) with IV or IM artesunate for at least
24 h and until they can tolerate oral medication.
• Once a patient has received at least 24 h of parenteral therapy and
can tolerate oral therapy, complete treatment with 3 days of an ACT
(add single dose primaquine in areas low transmission).
• If parenteral artesunate is not available, use IM artemether in
preference to quinine for treating children and adults with severe
malaria.

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Anti malarial Therapy
• Artesunate: 2.4 mg/kg i.v. or i.m. on admission 0 hour then at 12 &
24 hours, then once a day (dilute artesunate in 5% Sodium
bicarbonate until they can tolerate oral medication, complete
treatment with 3 days of an ACT .
• Artemether: 3.2 mg/kg i.m. given on admission then 1.6 mg/kg per
day, until they can tolerate oral medication, complete treatment with
3 days of an ACT.
• Quinine: 20 mg/kg on admission (i.v. infusion in 5% dextrose over 4
hours), maintenance dose :- 10 mg/kg 8 hourly, beyond 48 hours:- 7
mg/kg 8 hourly. Never give bolus injection !!

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Site of Action ACT

Artemisinin

Quinine

Artemisinin
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Management of Complications
Manifestation or complication
Coma(Cerebral malaria)
Hyperpyexia
Convulsions
Hypoglycaemia
Immediate management
Maintain airway, place patient on his or her side, exclude other
treatable causes of coma(e.g. hypoglycaemia, bacterial
meningitis); avoid harmful ancillary treatments, intubate if
necessary.
Administer tepid sponging, fanning a cooling blanket and
paracetamol
Maintain airways; treat promptly with intravenous or rectal
diazepam, lorazepam, midazolam or intramuscular paraldehyde.
Check blood glucose.
Check blood glucose, correct hypoglycemia and maintain with
glucose-containing infusion. Although hypoglycaemia is defined
as glucose <2.2mmol/L or <40 mg/dL, the threshold for
intervention is <3mmol/L for children <5 years and <2.2
mmol/L for older children and adults
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Management of Complications (Cont…)
Severe anaemia Transfuse with screened fresh whole blood.
Acute Pulmonary edema Prop patient up at an angle of 45◦, give oxygen, give a diuretic,
stop intravenous fluids, intubate and add positive end-
expiratory pressure or continuous positive airway pressure in
life-threatening hypoxaemia.

Acute kidney injury Exclude pre-renal causes, check fluid balance and urinary
sodium, if in established renal failure, add haemofiltration or
haemodialysis, or if not available, peritoneal dialysis.

Spontaneous bleeding and Transfuse with screened fresh whole blood (cryoprecipitate,
coagulopathy fresh frozen plasma and platelets, if available); give vitamin K
injection

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Management of Complications (Cont…)
Metabolic acidosis Exclude or treat hypoglycaemia, hypovalaemia and septicaemia. If
severe, add haemofiltration or haemodialsis.
Shock Suspect septicaemia, take blood for cultures; give parenteral
broad-spectrum antimicrobials, correct haemodynamic
disturbances.

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Not Recommended Treatments
The following treatments for cerebral malaria are considered either useless
or dangerous and should not be given
• Heparin
• High dose-corticosteroid
• Prostacyclin
• Desferroxamine
• Pentoxifylline
• Anti-TNF antibody
• N-acetylcysteine
• Mannitol
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Summary
• Severe malaria is potentially life-treatening.
• Blood film microscopy is the gold standart for diagnosis malaria.
• ACT and Primaquine is treatment for non-severe malaria.
• Parentral treatment is required in severe malaria.
• The recommended treatment is intravenous artesunate.
• General care, suppotrive and complication treatmens are essential to
survival.

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