Malaria

Symptoms

• Fever
• Chills
• Rigors
• Sweating
• Headache
• Generalized body and joint pain
• Nausea and/or vomiting
• Loss of appetite
• Abdominal pain (especially in children)
• Irritability and refusal to feed (in infants)

Signs

• Fever
• Mild pallor
• Mild jaundice
• Splenomegaly

Investigations

• Microscopy - thick and thin blood films for malaria parasites
• Rapid Diagnostic Test (RDT)
• FBC
• Other tests as indicated

Treatment

Treatment objectives

• To avoid progression to severe malaria
• To limit the duration of the illness
• To minimize the development of drug resistant parasites

Non-pharmacological treatment

• In children, tepid sponging to reduce body temperature

Pharmacological treatment
1st Line Treatment
Evidence Rating: [A]

• Artesunate + Amodiaquine, oral, (See Tables below)
  Or
• Artemether + Lumefantrine, oral, (See Table below)
  Or
• Dihydroartemisinin + Piperaquine, oral, (See Table below)

Artesunate + Amodiaquine co-blistered formulation (Regimen for ONCE DAILY DOSING)

The dose in mg/body weight is: Amodiaquine 10 mg/kg + Artesunate 4 mg/kg, taken as a single dose daily for three (3) days, after meals.

Artesunate + Amodiaquine co-blistered formulation (Regimen for TWICE DAILY DOSING)

The dose in mg/body weight is: Amodiaquine 10 mg/kg + Artesunate 4 mg/kg, taken as two divided doses daily for three (3) days, after meals.

Artesunate and Amodiaquine Fixed Dose Combination (Standard Regimen, using the 3 available dosing strengths)

Each Fixed Dose Combination tablet contains both Artesunate (AS) and Amodiaquine (AQ), at the dosages indicated. The product packaging clearly indicates which dosing strength applies to which age group. The maximum daily dose of Artesunate/Amodiaquine is 200 mg/600 mg

Artemether and Lumefantrine (Dosing Regimen)

Dihydroartemisinin and Piperaquine (Dosing Regimen)

Severe or ‘complicated malaria’ can arise from delay in diagnosis or inappropriate treatment of uncomplicated malaria. It mostly occurs in children under 5 years of age, pregnant women and non-immune individuals. The events causing most deaths in severe malaria are related to cerebral involvement (cerebral malaria), severe anaemia, hypoglycaemia, severe dehydration, renal failure and respiratory acidosis.

The diagnosis of severe malaria is based on clinical features and confirmed with laboratory testing. Not all cases of severe malaria have high parasitaemia and initial blood film examination may be negative. Where the diagnosis is suspected, treatment must be started without delay while awaiting confirmation.

Symptoms

• Poor oral intake (e.g. breast milk in children)
• Repeated profuse vomiting
• Dark or ‘cola-coloured’ urine
• Passing of very little urine
• Difficulty in breathing
• Generalised weakness, inability to walk or sit without assistance
• Altered consciousness (change of behaviour, confusion, delirium, coma)
• Repeated generalized convulsions

Signs

• Hyperpyrexia (axillary temperature > 38.5°C)
• Extreme pallor (severe anaemia; Hb < 5 g/dl)
• Marked jaundice
• Circulatory collapse or shock (cold limbs, weak rapid pulse)
• Tachypnoea (Rapid breathing)
• Crepitations on chest examination
• Sweating (due to hypoglycaemia)
• Haemoglobinuria (dark or ‘cola-coloured’ urine)
• Oliguria
• Spontaneous unexplained heavy bleeding (disseminated intravascular coagulation)
• Altered consciousness (change of behaviour, confusion, delirium, coma)

Investigations

• Rapid diagnostic test
• Blood film for malaria parasites - thick and thin blood films (should be done where available)
• FBC
• Sickling test
• Random blood glucose
• BUE and creatinine
• Blood grouping and cross-matching
• Lumbar puncture in the convulsing or comatose patient to exclude meningitis or encephalitis

Treatment

Treatment objectives

• To ensure rapid clearance of parasitaemia
• To provide urgent treatment for life threatening complications or conditions e.g. convulsions, hypoglycaemia, dehydration, renal impairment
• To provide appropriate supportive care

Non-pharmacological treatment

• Place patients who are unconscious or having seizures in an appropriate position to prevent aspiration

Pharmacological treatment
Evidence Rating: [A]:

Pre-referral treatment

• Artesunate, IM,
  Adults and Children > 20 kg: 2.4 mg/kg
  Children < 20 kg: 3 mg/kg
  Or
• Artemether, IM,
  Adults and Children: 3.2 mg/kg
  Or
• Quinine, IM, 10mg/kg
  Or
• Artesunate, rectal, 10 mg/kg (preferred in children under 6 years;

The dosage for IM Quinine is 10 mg (0.2 ml) per kg of bodyweight every 8 hours.

How to give Intramuscular Quinine: 

 Intramuscular Quinine in Young Children:

• Weigh the child
• Prepare a Quinine dilution of 50 mg/ml: Use a 10 ml sterile syringe and needle to draw up 5 mls of sterile water for injection or saline (not dextrose). Then into the same syringe draw up 300 mg (1ml) from an ampoule of Quinine. The syringe now contains 50 mg Quinine per ml.
• The dosage is 10 mg (0.2 ml) per kg or body weight every 8 hours. Calculate the volume to give based on body weight. 
• Administer by intramuscular injection to the thigh. If the diluted volume exceeds 3 ml, inject half the dose into each thigh.

Intramuscular Quinine in Adults:

• Use a Quinine dilution of 100 mg/ml. To prepare this, draw 2 mls of Quinine 600 mg and add 4 mls of sterile water or saline (not dextrose)
• The dosage is 10 mg/kg body weight of Quinine given 8 hourly by deep IM injection, to a maximum dose of 600 mg
• Small adults (weighing less than 60 kg) should be weighed to calculate the correct dose. Larger adults will simply receive the maximum dose (600 mg)
• If the required volume is more than 5 ml, divide it into two and inject at separate sites

Rectal Artesunate:

Treatment in Referral Centre

Parenteral antimalarials and follow-on treatment.The current recommendation is to give parenteral antimalarials in the treatment of severe malaria for a minimum of 24 hours (irrespective of the patient’s ability to tolerate oral medication) until the patient is able to tolerate oral medication as follow-on treatment. Recommended follow-on treatments include ACTs and Quinine + clindamycin.

• Artesunate, IV or IM (See section below for reconstitution advice)

Adults and Children > 20 kg:
2.4 mg/kg 12 hourly
Given at time 0 hour (i.e. on admission), at 12 hours and 24 hours
Then
2.4 mg/kg daily until patient can swallow (max. 7 days)
Then
A full 3-day course of recommended oral artemisinin combination therapy (ACT)

Children < 20 kg:
3 mg/kg 12 hourly
Given at time 0 hour (i.e. on admission), at 12 hours and 24 hours
Then
3.0 mg/kg daily until patient can swallow (max. 7 days)
Then
A full 3-day course of recommended oral ACT

Or

• Artemether, IM

  Adults and Children
  3.2 mg/kg stat.
  Then (8 hours later)
  1.6 mg/kg
  Then (24 hours after initiation of treatment)
  1.6 mg/kg once daily until patient can swallow (up to 5 days)
  Then
  A full 3-day course of recommended oral artemisinin combination therapy (ACT)

Or

• Quinine, IV (in Dextrose saline or in 5% Dextrose [5-10 ml/kg])

  Adults and Children:
  10 mg/kg (max. dose 600 mg) infused over 4-8 hours.
  Repeat infusion 8 hourly until patient can swallow.
  Then
• Quinine, oral, 10 mg/kg 8 hourly to complete 7 days of treatment

and

• Clindamycin, oral, 10 mg/kg, 12 hourly for 7 days

Clindamycin should be administered with food and copious amounts of water.
Quinine, IV, should always be given by a slow infusion, never by bolus intravenous injection as this may cause severe hypotension.

Or

• Quinine, IM

  Adults and Children
  10 mg/kg (max. dose 600 mg), 8 hourly until patient can swallow
  Then
• Quinine, oral, 10 mg/kg 8 hourly to complete 7 days of treatment

and

• Clindamycin, oral, 10 mg/kg, 12 hourly for 7 days

Referral Criteria
Patients diagnosed as having severe malaria or who fail to respond to the recommended antimalarial medications must be referred. Appropriate treatment as indicated above must be initiated prior to transferring the patient. If referral is not possible immediately, continue the treatment regimen as shown above for severe malaria until referral is possible.

Artesunate reconstitution for parenteral injectionUse a syringe to draw and inject the solvent (sodium bicarbonate 50mg/ml solution) into the vial of artesunate powder. Shake the vial until the powder is completely dissolved and the solution is clear.

For intravenous injection: Add either glucose 50 mg/ml (i.e. 5% Dextrose solution) or sodium chloride 9 mg/ml (i.e. 0.9% Normal saline solution) to the reconstituted artesunate solution to create a 10 mg/ml solution of artesunate. (see table below) Draw required volume and give slowly by IV at about 3-4 ml/min. 

For intramuscular injection: Add either glucose 50 mg/ml (i.e. 5% Dextrose solution) or sodium chloride 9 mg/ml (i.e. 0.9% Normal saline solution) to the reconstituted artesunate solution to create a 20 mg/ml solution of artesunate (see table below). Draw required volume and give slowly by IM anterior thigh. If the required volume is more than 5 ml, divide it into two and inject at separate sites. 

Calculation of dose of Artesunate needed (ml):Adults:For IV route: 2.4 mg x body weight (kg)                  (IV Artesunate solution concentration 10 mg/ml)

For IM route: 2.4 mg x body weight (kg)                 (IM Artesunate solution concentration 20 mg/ml)

Children < 20kg:For IV route: 3 mg x body weight (kg)                           (IV Artesunate solution concentration 10 mg/ml)For IM route: 3 mg x body weight (kg)                          (IM Artesunate solution concentration 20 mg/ml)

Precautions:

• Inject immediately after reconstitution and discard if not used within 1 hour
• Discard if solution is not clear
• Do not use in IV drip, Give slowly by direct IV injection at about 3-4 ml/min