Malaria

Disclaimer

These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common-sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.

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Aim

To guide PCH staff with the assessment and management of malaria.

Background

Malaria is a notifiable infectious disease in Western Australia.
The possibility of malaria should be considered in all children with a history of fever within 12 months of returning from a malaria endemic area.
- Refer to CDC Malaria table to determine malaria endemic areas
Incubation period ranges from 7 days to several weeks but exposure to antimalarial prophylaxis can delay the onset of symptoms by weeks or months. This is particularly important with P.vivax / P. ovale which produce dormant liver stage parasites.²
Young children (<5 years old) are more likely to develop severe disease.
Severe malaria is associated with a high rate of concurrent bacteraemia.¹
Malaria can be broadly classified according to plasmodium parasite species into:
- falciparum malaria (caused by Plasmodium falciparum - knowlesi infection can cause a similar clinical picture)
- non-falciparum malaria ( P. vivax, P. ovale, P. malariae).

Assessment

History and examination

History should include questions about:
- Location and timing of travel
- Be aware of increasing artemisinin resistence in malaria from the Greater Mekong (Thailand, Vietnam, Cambodia, Laos, Myanmar).³
- Whether malaria prophylaxis was used and which drugs
- What prior treatment (if any) has been given
- Recurrent P. malariae has occurred after artemether and lumefantrine therapy. In these patients, consider therapy with chloroquine or hydroxychloroquine (discuss with Infectious Diseases).
Examination findings suggestive of malaria include:
- Jaundice and / or pallor
- Hepatosplenomegaly
These features are not always present and their absence should not preclude further investigation.
Be conscious of features of severe malaria on history and examination.
Consider other causes of Fever in the returned traveller.

Severe malaria

Severe malaria is defined as one or more of the following features:

impaired consciousness / coma
seizures
prostration (unable walk or sit up without assistance)
vomiting / unable to tolerate oral intake
circulatory collapse / shock / hypotension
clinical jaundice plus evidence of other vital organ dysfunction
haemoglobinuria
spontaneous bleeding
respiratory distress / pulmonary oedema

Laboratory findings:

hyperparasitaemia (> 2%)
severe anaemia (Hb < 50 g/L)
hypoglycaemia (BGL < 2.2mmol)
metabolic acidosis (plasma bicarbonate < 15 mmol/L)
hyperlactataemia (lactate > 5 mmol/L)
renal impairment

Investigations

Diagnostic Testing (2 x EDTA tubes)
- Thick and thin films from finger prick or venepuncture
  and
- Rapid Diagnostic Test (RDT) for malaria antigen
  - One negative RDT / blood film does not exclude malaria
    (Sensitivity of a single blood film is 85%, sensitivity of RDT is 99% for P. falciparum, 86% for non-falciparum malaria)
  - Repeat 12-24 hourly (total 3 samples) if tests initially negative
  - Perform blood films and RDT in all children with a suggestive history – even if patient is not febrile at time of Emergency Department (ED) presentation
  - Urgent results from Binax^® RDT are available 24/7 through the haematology laboratory – mark samples as 'urgent' if required
  - Malaria polymerase chain reaction (PCR) / nucleic acid testing (NAT).

Additional investigations (in an unwell child) should include:

Blood gas (including glucose)
Full blood count (FBC), urea, electrolytes and creatinine (UEC), liver function tests (LFT), coagulation studies, blood culture
Blood group and hold
Urine pregnancy test (pregnant adolescents and women are at high risk of maternal and fetal complications)
Glucose-6-phosphate dehydrogenase (G6PD) assay (if known P. vivax / P. ovale infection prior to primaquine)
Sickle cell solubility test

Management

Please discuss all patients receiving treatment with Infectious Diseases on call.

For more information, refer to ChAMP monographs.
Ensure an interpreter is available for families with whom effective communication in English is not possible.

Severe malaria
Medical emergency - admit all patients Most often caused by falciparum (occasionally P. knowlesi or P. vivax) ABC (caution with the use of IV fluid boluses) 1st line - IV artesunate immediately Dosing in Overweight and Obese Children: No information, dose based on actual body weight. Children ≥ 4 weeks old: 2.4 mg/kg/dose immediately¹³ Repeat at 12 and 24 hours then continue daily until oral therapy is tolerated For disease acquired in the Greater Mekong, addition of IV quinine dihydrochloride is recommended, dosing as below. Discuss with Infectious Diseases team. Switch to artemether plus lumefantrine (Riamet^®) oral treatment once patient improved. A full course of oral therapy should be given. AND IV ceftriaxone 50mg/kg/dose (max 2g) once daily for two days then reassess with blood culture results. AND PO Paracetamol 15mg/kg/dose (max 1g) 6 hourly for 72 hours. This has been shown to be renoprotective.^6,12 If meningitis suspected refer to Meningitis and Meningoencephalitis - ChAMP guideline Or if Artesunate not available: 2nd line - IV quinine dihydrochloride contact ward pharmacist or on-call pharmacist (after hours) for stock Ideal body weight should be used to calculate dosing in the obese patient. Refer to Guidelines for Drug Dosing in Overweight and Obese Children 2 to 18 Years of Age – Medication management Manual If previous prophylaxis / treatment (e.g., mefloquine) a loading dose may not be required. Discuss with the Infectious Diseases Consultant ≥ 4 weeks – 18 years: 20 mg/kg (maximum 1.4 g) over 4 hours as a loading dose¹³ Continue at a dose of 10mg/kg/dose (max 700mg) every 8 hours given over 4 hours starting 4 hours after the completion of the previous dose.¹³ Rapid administration may cause severe cardiotoxicity. Administer via slow IV infusion over 4 hours. Slow the rate of infusion if dysrhythmias occur.² If IV quinine is still needed after 48 hours a dose reduction may be required. Discuss with the Infectious Diseases Consultant.^2,3 Quinine may cause hypoglycaemia, arrhythmias and hypotension. Cardiac monitoring required, quinine should be administered in Paediatric Critical Care where possible. Monitor blood pressure and blood glucose levels (BGL) 4 hourly.

Severe malaria

Medical emergency - admit all patients
Most often caused by falciparum (occasionally P. knowlesi or P. vivax)
ABC (caution with the use of IV fluid boluses)
1st line - IV artesunate immediately
- Dosing in Overweight and Obese Children: No information, dose based on actual body weight.
- Children ≥ 4 weeks old: 2.4 mg/kg/dose immediately¹³
- Repeat at 12 and 24 hours then continue daily until oral therapy is tolerated
- For disease acquired in the Greater Mekong, addition of IV quinine dihydrochloride is recommended, dosing as below. Discuss with Infectious Diseases team.
- Switch to artemether plus lumefantrine (Riamet^®) oral treatment once patient improved. A full course of oral therapy should be given.

AND IV ceftriaxone 50mg/kg/dose (max 2g) once daily for two days then reassess with blood culture results.

AND PO Paracetamol 15mg/kg/dose (max 1g) 6 hourly for 72 hours. This has been shown to be renoprotective.^6,12

If meningitis suspected refer to Meningitis and Meningoencephalitis - ChAMP guideline

Or if Artesunate not available:

2nd line - IV quinine dihydrochloride
- contact ward pharmacist or on-call pharmacist (after hours) for stock
- Ideal body weight should be used to calculate dosing in the obese patient. Refer to Guidelines for Drug Dosing in Overweight and Obese Children 2 to 18 Years of Age – Medication management Manual
- If previous prophylaxis / treatment (e.g., mefloquine) a loading dose may not be required. Discuss with the Infectious Diseases Consultant
- ≥ 4 weeks – 18 years: 20 mg/kg (maximum 1.4 g) over 4 hours as a loading dose¹³
- Continue at a dose of 10mg/kg/dose (max 700mg) every 8 hours given over 4 hours starting 4 hours after the completion of the previous dose.¹³
- Rapid administration may cause severe cardiotoxicity. Administer via slow IV infusion over 4 hours. Slow the rate of infusion if dysrhythmias occur.²
- If IV quinine is still needed after 48 hours a dose reduction may be required. Discuss with the Infectious Diseases Consultant.^2,3
- Quinine may cause hypoglycaemia, arrhythmias and hypotension.
- Cardiac monitoring required, quinine should be administered in Paediatric Critical Care where possible.
- Monitor blood pressure and blood glucose levels (BGL) 4 hourly.

Uncomplicated malaria
Falciparum malaria Admit all children with P. falciparum (and P. knowlesi) malaria as deterioration may occur following initiation of treatment (selected patients with uncomplicated falciparum malaria may occasionally be suitable for outpatient management in discussion with Infectious Diseases⁷) 1st line - Artemether plus lumefantrine (Riamet^®) or 2nd line - Atovaquone plus proguanil (Malarone^®) Not to be used as treatment if previously used as prophylaxis
Non-falciparum malaria Admit under general paediatrics or consider outpatient management (in discussion with Infectious Diseases team) if: Parasite count <1% Tolerating oral medications The family has sufficient understanding to ensure compliance, follow-up and representation if required No significant co-morbidities and Age >5 years old 1st line - Artemether-lumefantrine (Riamet^®) or 2nd line - Atovaquone plus proguanil (Malarone^®) AND Hypnozoite eradication (all patients with P.vivax or P.ovale) Patients ≥ 6 months old: Primaquine - Check G6PD status prior to prescribing Patients < 6 months old: discuss with Infectious Diseases team.

Uncomplicated malaria

Falciparum malaria

Admit all children with P. falciparum (and P. knowlesi) malaria as deterioration may occur following initiation of treatment (selected patients with uncomplicated falciparum malaria may occasionally be suitable for outpatient management in discussion with Infectious Diseases⁷)

1st line - Artemether plus lumefantrine (Riamet^®)

2nd line - Atovaquone plus proguanil (Malarone^®)

Not to be used as treatment if previously used as prophylaxis

Non-falciparum malaria

Admit under general paediatrics or consider outpatient management (in discussion with Infectious Diseases team) if:
- Parasite count <1%
- Tolerating oral medications
- The family has sufficient understanding to ensure compliance, follow-up and representation if required
- No significant co-morbidities and
- Age >5 years old
1st line - Artemether-lumefantrine (Riamet^®)

2nd line - Atovaquone plus proguanil (Malarone^®)

AND

Hypnozoite eradication (all patients with P.vivax or P.ovale)
- Patients ≥ 6 months old: Primaquine - Check G6PD status prior to prescribing
- Patients < 6 months old: discuss with Infectious Diseases team.

Follow up

Malaria statutory notification requirements - all cases should be notified to public health via the WA Health Department website
Monitor blood glucose, blood film / parasitaemia (daily), blood gases, FBC and UEC in all patients admitted to the ward.
Consult the infectious diseases team for all admitted patients.
All children require follow up in Infectious Diseases clinic a week after discharge with repeat blood film.
- Blood film should be repeated again at ~28 days post treatment to ensure cure. Consider screening other family members for malaria (if similar travel history).
- Prior to discharge, consult with Infectious Diseases on-call regarding any child treated for malaria to arrange appropriate follow up.
Ensure all children have a discharge letter stating that they have been admitted with malaria.

References

Church J, Maitland K. Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review. BMC Med. 2014;12:31-.
Organisation WH. Guidelines for the Treatment of Malaria: Third Edition. 2015.
Guidelines T. Therapeutic Guidelines, Version 16.Therapeutic Guidelines, Version 162019.
Stauffer WM, Cartwright CP, Olson DA, Juni BA, Taylor CM, Bowers SH, et al. Diagnostic performance of rapid diagnostic tests versus blood smears for malaria in US clinical practice. Clin Infect Dis. 2009;49(6):908-13.
Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2012(6):Cd005967.
Kofoed P-E, Ursing J, Rodrigues A, Rombo L. Paracetamol versus placebo in treatment of non-severe malaria in children in Guinea-Bissau: a randomized controlled trial. Malaria Journal. 2011;10(1):148.
Cherian S, Burgner D. Selective ambulatory management of Plasmodium falciparum malaria in paediatric refugees. Arch Dis Child. 2007;92(11):983-6.
Grynberg S, Lachish T, Kopel E, Meltzer E, Schwartz E. Artemether-lumefantrine compared to atovaquone-proguanil as a treatment for uncomplicated Plasmodium falciparum malaria in travelers. Am J Trop Med Hyg. 2015;92(1):13-7.
Gogtay N, Kannan S, Thatte UM, Olliaro PL, Sinclair D. Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria. Cochrane Database Syst Rev. 2013(10):Cd008492.
Visser BJ, Wieten RW, Kroon D, Nagel IM, Belard S, van Vugt M, et al. Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review. Malar J. 2014;13:463.
Stéphane Jauréguiberry MT, Papa Alioune Ndour, Flavie Ader, Camille Roussel, Romain Sonneville, Julien Mayaux, Sophie Matheron, Adela Angoulvant, Benjamin Wyplosz, Christophe Rapp, Thierry Pistone, Bénédicte Lebrun-Vignes, Eric Kendjo, Martin Danis, Sandrine Houzé, François Bricaire, Dominique Mazier, Pierre Buffet, Eric Caumes, and French Artesunate Working Group. Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013. Emerging Infectious Diseases. 2015;21(5):804-12.
Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria: A Randomized, Controlled, Open-Label Trial - PMC (nih.gov)
Australian Medicines Handbook Pty Ltd 2022 [Internet] Quinine; [Last modified: July 2023. Cited: 5 October 2023] Available from: Quinine - Australian Medicines Handbook (health.wa.gov.au)

Endorsed by:	CAHS Drug & Therapeutic Committee	Date:	Oct 2023
		Review date:	Sep 2026

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