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. falciparummust 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)

  1. 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. falciparumconfirmed.

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 TherapyBEGIN 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

  1. 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 withquiNINE/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 antimalarialtherapy.

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 antimalarialtherapy.

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 0.5Maintenance 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:Clindamycin ______mg IV q6h (25 to 40 mg/kg/day to a maximum of 3,600 mg/day)
Day 3: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. WHO guidelines for the treatment of malaria, 2006 [webpage];
  2. 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.
  3. Gilbert DN. The Sanford Guide to Antimicrobial Therapy 2006, 36th edition. Sperryville, VA, USA: Antimicrobial Therapy, Inc.
  4. Lau E, editor. 2007-2008 Formulary. The Hospital for Sick Children. Toronto, Ontario, Canada
  5. Taketomo C et al. Pediatric Dosing Handbook . 14th edition. Hudson, Ohio: Lexi-Comp; 2007.
  6. Medical Access to quiNINE for Malaria Treatment Streamlined in Canada through the Canadian Malaria Network. CCDR 2004-02-02.
  7. Bradly JS, Nelson JD. 2006-2007 Nelson’s Pocket Book of Pediatric Antimicrobial Therapy. 16th edition. Buenos Aires, Argentina: AWWE; 2006.
  8. 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