Malaria

Severe Malaria

P. Falciparum and P. Knowlesi

For detailed information, please refer to Canadian Recommendations for the Prevention and Treatment of Malaria
http://www.canada.gc.ca/en/public-health/services/travel-health/information-travel-health-professionals.html

1. If there is a clinical suspicion of malaria, order Malaria Screen.
2. Need to consider alternative causes of fever in the returned traveller based on history of travel
3. If Malaria Screen positive, please consult ID immediately
4. STAT bloodwork – CBC, ABG, electrolytes, BUN, Cr, INR, PTT, AST, ALT, Alk Phos, bilirubin, GGT, group and screen, lactate, venous blood gases, glucose, blood cultures x 2, urine culture, nasopharyngeal swab for respiratory viruses (if indicated), stool cultures (if indicated)
5. Assess for signs of severe malaria

Clinical Manifestation	Laboratory Test
Prostration/impaired consciousness	Severe anemia Adults: haematocrit < 20%; Hgb < 70 g/L Children: haematocrit < 15%; Hgb < 50 g/L
Respiratory distress	Hypoglycemia (blood glucose < 2.2 mmol/L)
Multiple convulsions (>2 in 24 hours)	Acidosis (arterial pH < 7.25 or bicarbonate < 15 mmol/L)
Circulatory collapse / shock (SBP < 80 mmHG in adults or < 50mmHG in children)	Renal impairment (creatinine > 265 umol/L or greater than upper limit for age in children)
Pulmonary edema (radiological) / ARDS	Hyperlactatemia (lactate > 5 mmol/L)
Abnormal bleeding / DIC	Hyperparasitemia *
Jaundice (the total bilirubin > 50 umol/L)
Hemoglobinuria (macroscopic)

* ≥ 2% in children < 5 years
≥ 5% for non-immune adults and children ≥ 5 years
≥ 10% for semi-immune adults and children ≥ 5 yeaars
Non-immune = those born in non-endemic countries or low-transmission setting (e.g. travellers)
Semi-immune = individuals with recent long-term residence in an endemic country and prior episodes of malaria. Immunity is considered lost after a period of 6-12 months living outside of the malaria endemic country.

If there is one or more signs of severe malaria, start IV access, admit to hospital to a monitored setting, and call the inpatient pharmacy at site

• ARTESUNATE 2.4 mg/kg* (actual body weight) IV over 1-2 minutes as a bolus, give STAT then
  * for children under 20kg use 3mg/kg/DOSE *
  • 12 hours after first dose
  • 24 hours after first dose
  • 48 hours after first dose
• 4 hours after last dose of artesunate start (Note: may switch to oral therapy after 3rd dose if patient can tolerate oral therapy):
  • Atovaquone-proguanil (do not use as follow-on oral therapy if previously used as malaria chemoprophylaxis) OR
  • Doxycycline (do not use as follow-on oral therapy if used as malaria chemoprophylaxis; contraindications – pregnancy, breastfeeding, age < 8 years) OR
  • Clindamycin (only if unable to take doxycycline or atovaquone-proguanil): 10mg/kg (loading dose) IV followed by 5mg/kg IV q8h x 7 days (see chart below for oral doses)

DRUG	ADULT DOSE	PEDIATRIC DOSE
Malarone (atovaquone / proguanil) Adult tab: atovaquone 250mg / proguanil 100mg per tablet Pediatric tablet: atovaquone 62.5mg / proguanil 25mg per tablet	4 adult tabs (taken all at once with food) daily x 3 days	5-8 kg: 2 pediatric tabs daily x 3 days 9-10 kg: 3 pediatric tabs daily x 3 days 11-20 kg: 1 adult tab daily x 3 days 21-30 kg: 2 adult tabs daily x 3 days 31-40 kg: 3 adult tabs daily x 3 days > 40kg: 4 adult tabs daily x 3 days *give with food
Quinine sulphate (note: quinine sulphate 600mg = 500mg sulphate base)	600mg po q8h x 7 days	9mg/kg q8h x 7 days (max 600mg/dose)
Doxycycline	100mg po BID x 7 days	2mg/kg (max 100mg/dose) BID x 7 days
Clindamycin	300mg QID x 7 days	5mg/kg QID x 7 days

Patient MUST have CBC repeated weekly q4weeks for monitoring of late hemolysis following IV artesunate.
If there is a contraindication to ARTESUNATE (hypersensitivity, significant delay) OR unable to tolerate po but NO severe disease, consider IV quinine.

• Ensure patient is in a monitored setting with telemetry/cardiac monitor
• Accuchecks q2 hours and prn with any change in level of consciousness
• Quinine 5.8 mg/kg loading dose (quinine dihydrochloride [salt] 7 mg/kg) IV by infusion pump over 30 minutes
  • Omit loading dose if patient has received quinine or quinidine within preceding 24 hours or mefloquine in previous 2 weeks)
• Followed immediately by 8.3 mg base/kg (quinine dihydrochloride [salt] 10 mg/kg) diluted in 10 mL/kg isotonic fluid by intravenous infusion over 4 hours (maintenance dose). Repeat once every 8 hours until the patient can swallow
• THEN change therapy to
  • Atovaquone – proguanil 4 tablets (1000 mg atovaquone, 400 mg proguanil) PO daily x 3 days
  • OR notify ID if contraindications

Repeat Malaria screens q12 hours x 48 hours

Consider adding empiric antibiotics until cultures return

Notify ID prior to discharging patient

Non-Severe Malaria

All patients need repeat malaria screen 14 days after therapy

P. falciparum

• If unable to take oral therapy please see above orders for quinine
• Consider admission for 24 hours and repeat smears
• Atovaquone proguanil (do not use as follow-on oral therapy if previously used as malaria chemoprophylaxis)
  • Adults: 4 tablets (1000 mg atovaquone and 400 mg proguanil) daily for 3 days;
  • See table above for pediatric dosing
• If unable to tolerate or contraindications to Atovaquone-Proguanil notify ID

P. vivax / ovale

• G6PD screen STAT – if positive, notify ID prior to treatment
• If no history of travel to Papua New Guinea or Indonesia
  • Hydroxychloroquine 800 mg PO x 1, then 400 mg at 6, 24, 48 hours
  • Primaquine phosphate*: 30 mg base po q daily x 14 days
• If history of travel to Papua New Guinea or Indonesia
  • Atovaquone-Proguanil 4 tablets (1000 mg atovaquone and 400 mg proguanil) daily for 3 days;
  • Primaquine phosphate*: 30 mg base po q daily x 14 days

P. malariae

• Hydroxychloroquine 800 mg PO x 1, then 400 mg at 6, 24, 48 hours

P. knowlesi

• Hydroxychloroquine 800 mg PO x 1, then 400 mg at 6, 24, 48 hours

Pregnancy

For pregnant women, consult ID prior to treatment

• Primaquine phosphate is contraindicated in pregnancy or those who have severe G6PD deficiency