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PEDIATRIC MANAGEMENT GUIDELINES FOR MALARIA TREATMENT Ammended for publication January 20, 2009 and are located on the local hospital network Principles of Care in Patients with Malaria 1. This is a medical emergency as death can result rapidly from untreated P. falciparum malaria. 2. All patients with malaria due to P. falciparum must be admitted to hospital or “observation unit” to ensure tolerance of treatment and to confirm decreasing parasitemia with treatment. 3. If the species is not unequivocally identified, treat as P. falciparum until further identified. 4. Treat all P. falciparum as chloroquine resistant (treatment may only be modified by Infectious Disease Service). 5. Severe or complicated disease requires management in an intensive care unit setting. (see Table 1) 6. Infectious diseases (ID) consult is required for all positive malaria smears. The Hematology Laboratory should also notify ID of all positive malaria smears. Initial Assessment of malaria Although anyone can have severe or complicated infection with malaria, children, pregnant women and ‘non-immune’ (those individuals who have never had prior infection with malaria) hosts are at greater risk of complications and/or death. Siblings or family members traveling with the index case of malaria should also be questioned about fever, headache and malaise since they also are at risk for malaria acquisition. Treatment of malaria in a non-immune host is a medical emergency. Patients who have malaria that is uncomplicated can be admitted and treated with oral medication. However, persons with severe or complicated malaria or those who cannot tolerate oral medication should be cared for in a monitored unit and treated with intravenous therapy. Criteria for severe malaria are listed in Table 1. Malaria parasites may be difficult to find on blood smear and even when identified, determining the species of plasmodium is often difficult. Furthermore, mixed infections with two types of malaria are also possible. Since prompt treatment is essential, we have prepared guidelines and admission orders for disease management in the setting where initial therapy is aimed at Plasmodium falciparum. Initial therapy should be given in the following clinical settings: Malaria parasites on blood smear but species not confirmed or P. falciparum confirmed. OR If the risk of malaria is high (based on clinical and epidemiologic grounds) and blood smear results are not immediately available, start empiric therapy as outlined in the Drug Therapy Section. Table 1: Criteria for Severe Falciparum Malaria 1. Asexual forms of Plasmodium falciparum on blood smear AND 2. Any one or more of the following clinical or laboratory features: Clinical: 1. Prostration, impaired consciousness or coma 2. Respiratory distress (acidotic breathing) 3. Pulmonary edema 4. Repeated generalized convulsions 5. Circulatory collapse, shock 6. Spontaneous bleeding/disseminated intravascular coagulation 7. Jaundice Laboratory 1. Severe normocytic anemia 2. Acidosis 3. Renal failure 4. Hypoglycemia 5. Hemoglobinuria 6. Hyperlactemia 7. Parasitemia of > 5% in non-immune individuals 1. General Admission Orders Malaria Admission Orders ADMIT TO: DIET: ACTIVITY: MONITORING: Ensure Infectious Diseases has been consulted and aware of admission Temp, HR, RR and BP and neurovitals q4H x 24 hrs, then reassess Notify physician if Glasgow Coma Scale is less than 14 and do stat blood glucose O2 saturation q4h x 24 hours, then reassess Notify physician if O2 saturation is less than 92% Call physician on call if blood glucose is < 4 mmol/L by finger prick Strict Intake/output x 24 hrs, then reassess If intravenous quinine is to be administered to a patient who has taken mefloquine or halofantrine in the previous 2 weeks, they should be monitored electrocardiographically (given possible risk of drug-induced cardiac arrhythmia) INVESTIGATIONS: STAT (to be done in Emergency department prior to transfer to ward): Peripheral Blood cultures x 2 sets CBC diff glucose Na, K, Cl, Creat, BUN, ALT, alkaline phosphatase Urine Analysis (Routine and Microscopy) Venous or arterial blood gas Routine Blood glucose by finger prick q4h x 24 hours Thick and thin malaria smear q12H x 36 hours, then daily CBC, glucose, Creat, ALT and AST daily MEDICATIONS: IV D5W/0.9% NaCl at _______________mL/hr. Antimalarial Therapy BEGIN STAT prior to transfer to ward, _____ Malaria IV Therapy (A) OR _____ Malaria Oral Therapy (B) SEE SEPARATE PRE-PRINTED ORDERS MALARIA DRUG THERAPY DISCHARGE INSTRUCTIONS: Please ensure patient has follow-up appointment for 1 week and 4 weeks after discharge with Infectious Diseases Please ensure that patient or parent has requisition for blood smears at day #4, #7 and #28 A. Oral Therapy Oral therapy may be given if patient does not meet the criteria for severe or complicated malaria (see Table 1) and is able to tolerate oral medication. The following combination therapies are recommended for the treatment of malaria (suspected to be P falciparum): 1. Atovaquone/ Proguanil (Malarone®) OR 2. quiNINE capsules or quiniDINE suspension Plus Doxycycline or clindamycin MEDICATIONS: Malarone® (atovaquone 250 mg + proguanil HCl 100 mg) x 3 days ____ < 8 kg: ½ tablet (50 mg proguanil HCl) po once daily x 3 days ____ 9 – 10 kg: ¾ tablet (75 mg proguanil HCl) po once daily x 3 days ____ 11 – 20 kg: 1 tablet (100 mg proguanil HCl) po once daily x 3 days ____ 21 – 30 kg: 2 tablets (200 mg proguanil HCl) po once x 3 days ____ 31 – 40 kg: 3 tablets (300 mg proguanil HCl) po once daily x 3 days ____ > 40 kg: 4 tablets (400 mg proguanil HCl) po once daily x 3 days Give with food or milk May crush tablets and mix with food or water May give via NG-tube Call physician if oral antimalarial medication is vomited or refused. If vomiting occurs within 30 minutes of last dose of medication, administer full dose of medication again. If vomiting occurs between 30 – 60 minutes, repeat half the dose. If vomiting recurs, call admitting physician to change to parenteral therapy. OR Alternative Oral Therapy: QUININE CAPSULES or QUINIDINE SUSPENSION PLUS DOXYCYCLINE or CLINDAMYCIN quiNINE CAPSULES or quiniDINE SUSPENSION X 7 days 1. quiNINE oral capsules (patients > 20 kg). (quiNINE sulfate 200 mg capsule = 166 mg quiNINE base) 20 – 24 kg: 3 capsules/day = 1 capsule po q8h x 7days 25 - 29 kg: 4 capsules/day = 1 capsule with breakfast 1 capsule with lunch and 2 capsules with supper po x 7 days 30 – 34 kg: 5 capsules/day = 1 capsule with breakfast 2 capsules with lunch and 2 capsules with supper po x 7 days 35 – 44 kg: 6 capsules/day = 2 capsules po q8h x 7days 45 – 49 kg: 7 capsules/day = 2 capsules with breakfast 2 capsules with lunch and 3 capsules with supper po x 7 days 50 – 59 kg: 8 capsules/day = 2 capsules with breakfast 3 capsules with lunch and 3 capsules with supper po x 7 days >60 kg: 9 capsules/day = 3 capsules po q8h x 7 days 2. quiniDINE oral suspension (patients < 20 kg or unable to swallow capsules). (CHEO 8.3 mg base/mL) ________ mg base po q 8h x 7days (28 mg base/kg/day to a maximum of 1,400 mg base/day) Give with food or milk Contains quiniDINE sulphate Additional Oral Therapy to be prescribed with quiNINE/quiniDINE: (Note: quiNINE/quiniDINE therapy requires additional therapy with doxycycline or clindamycin.) Delay administration to enhance quiNINE/quiniDINE tolerance: 1 –2 hours 24 hours Choose either Doxycycline ( > 8 years old) or Clindamycin (< 8 years old) Doxycycline 100 mg capsule _______ mg po BID x 7 days (4 mg/kg/day) Clindamycin 150 mg capsule or 15 mg/mL oral suspension _______ mg po q 8h x 7 days (20 mg/kg/day) Give with food or milk or full glass of water May open capsule and sprinkle contents on food Vomiting after Oral Capsule or Tablet If vomiting occurs within 30 minutes of the last dose of medication, administer one full dose of medication again. If the vomiting had occurred between 30 – 60 minutes of the last dose, repeat one-half of the dose. If vomiting recurs a second time or with a second dose, the patient’s physician should be contacted as the patient may require intravenous antimalarial therapy. Vomiting after Oral Liquid If vomiting occurs in less than 10 minutes of the last dose of medication, administer one full dose of medication again. If the vomiting had occurred between 10 – 15 minutes of the last dose of medication, repeat one-half of the dose. If vomiting recurs a second time or with a second dose, the patient’s physician should be contacted as the patient may require intravenous antimalarial therapy. B. Parenteral Therapy Parenteral therapy is indicated if: • the patient meets criteria for severe malaria (See Table 1 ) or • the patient is unable to tolerate oral drugs (refused or vomiting) Physician Orders–IV Drug Therapy for patients receiving Intravenous Therapy MEDICATIONS: Day 1, Hour 0: Loading Dose of IV quiNINE: _____ Omit loading dose if patient received quiNINE, quiniDINE, or mefloquine in previous 24 hours _____ quiNINE base 5.8 mg/kg = __________ mg base _________ mg base x 1.22 = __________ mg quiNINE dihydrochloride (300 mg/mL – supplied as 600 mg/2 mL vial) (300 mg quiNINE dihydrochloride = 245 mg quiNINE base) quiNINE dihydrochloride MAX dose = 600 mg If patient is less than 10 kg, dilute to 5 mg/mL D5W/0.9% NaCl If patient is greater than or equal to 10 kg, dilute in 50 mL 0.9% NaCl If patient is greater than or equal to 20 kg, dilute in 100 mL 0.9% NaCl Give STAT over 30 minutes Day 1 to 2, Hour 0.5 Maintenance Dose of IV quiNINE: _____ quiNINE base 8.3 mg/kg/dose = __________ mg base IV q8h _________ mg base x 1.22 = __________ mg quiNINE dihydrochloride (300 mg/mL – supplied as 600 mg/2 mL vial) (300 mg quiNINE dihydrochloride = 245 mg quiNINE base) quiNINE dihydrochloride MAX dose = 600 mg If patient is less than 10 kg, dilute to 2 mg/mL D5W/0.9% NaCl If patient is greater than or equal to 10 kg, dilute in 250 mL D5W/0.9% NaCl If patient is greater than or equal to 20 kg, dilute in 500 mL D5W/0.9% NaCl Start immediately after loading dose and give over 4 hours Hour 6 : Day 3: Clindamycin _______mg IV q6h (25 to 40 mg/kg/day to a maximum of 3,600 mg/day) Continuation Dose: Continue Clindamycin IV Decrease maintenance Dose of IV quiNINE: _____ quiNINE base 3 mg/kg/dose = __________ mg base IV Q8h _________ mg base x 1.22 = __________ mg quiNINE dihydrochloride (300 mg/mL – supplied as 600 mg/2 mL vial) (300 mg quiNINE dihydrochloride = 245 mg quiNINE base) quiNINE dihydrochloride MAX dose = 300 mg If patient is less than 10 kg, dilute to 2 mg/mL D5W/0.9% NaCl If patient is greater than or equal to 10 kg, dilute in 250 mL D5W/0.9% NaCl If patient is greater than or equal to 20 kg, dilute in 500 mL D5W/0.9% NaCl Give over 4 hours References 1. 2. 3. 4. 5. 6. 7. 8. WHO guidelines for the treatment of malaria, 2006 [webpage]; http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf. Severe and complicated malaria. 2nd ed. Trans Roy Soc Trop Med Hyg 1990; 84 (Suppl). Adapted in: Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers. CATMAT 2004-06-28. Gilbert DN. The Sanford Guide to Antimicrobial Therapy 2006, 36th edition. Sperryville, VA, USA: Antimicrobial Therapy, Inc. Lau E, editor. 2007-2008 Formulary. The Hospital for Sick Children. Toronto, Ontario, Canada Taketomo C et al. Pediatric Dosing Handbook . 14 th edition. Hudson, Ohio: Lexi-Comp; 2007. Medical Access to quiNINE for Malaria Treatment Streamlined in Canada through the Canadian Malaria Network. CCDR 2004-02-02. Bradly JS, Nelson JD. 2006-2007 Nelson’s Pocket Book of Pediatric Antimicrobial Therapy. 16 th edition. Buenos Aires, Argentina: AWWE; 2006. Pickering LK, Baker CJ, Long SS, McMillan JA, editors. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th edition. Elk Grove Village, IL: Academy of Pediatrics; 2006. 18 February 2009