Ref Number = ASPR0042
Treat Severe Malaria in Children
Suryadi Nicolaas Napoleon Tatura1,2*

1Pediatric Infectious and Tropical Disease Division, Department of Pediatrics, Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia; 2Indonesian National Expert Committee of Malaria, Ministry of Health, Republic of Indonesia
*E-mail: nicolae_n_sur@yahoo.co.id
Malaria is a common and life-threatening disease in many tropical and subtropical areas. There are currently over 100 countries and territories where there is a risk of malaria transmission, and these are visited by more than 125 million international travellers every year.1,2  Clinical symptoms of malaria ranging from mild, asymptomatic to severe, sometimes diagnosed as malignancy until bone marrow puncture has done.2,3 Factors that influence the severity of malaria symptoms are plasmodium species, host immunity, and therapy.4 Severe malaria in neonates can misdiagnosed as neonatal sepsis and involves various organs.5 The World Health Organization report 100% severe malaria mortality rate and can be reduced to 10-20% with good treatment.3
Severe malaria is most commonly caused by infection with Plasmodium falciparum, although P. vivax and P. knowlesi can also cause severe disease. The risk is increased if treatment of an uncomplicated attack of malaria caused by these parasites is delayed.5,6 Severe malaria is defined if one or more of the following criteria are obtained: impaired consciousness, prostatration, multiple convulsions, acidosis, hypoglycaemia, severe anemia, renal impairment, jaundice, pulmonary edema, significant bleeding, shock and hyperparasitaemia (P. falciparum parasitaemia >10%). Severe malaria vivax is same defined as falciparum but has no threshold, whereas  severe malaria knowlesi is defined as falciparum except hyperparasitaemia >100,000/microlitre or parasite density >20,000 microlitre with jaundice.6
In severe malaria, antimalarial drugs should be given parenterally for a minimum of 24h and replaced by oral medication as soon as it can be tolerated. For children, the recommended treatment is artesunate at 2.4mg/kg body weight given intravenously or intramuscularly at admission (time = 0), then at 12h, 24h, then once a day. 4,6,7 In primary health care, we can give quinine IM, artesunate IM, and arthemeter IM before referred the patient.8 Giving Arthemeter IM is better than quinine IM in terms of reducing mortality and neurology sequele at discharge.9 In circumstances where facilities are not available, rectal artesunate can be given before referred to reduce mortality, especially in children 6-72 months, but in older children and adults this is not useful.8 All children presenting with severe malaria in areas of intermediate and high malaria transmission should be given broad spectrum antibiotics in addition to antimalarial drugs.4,7
The commonest, most important complications of P. falciparum infection in children are cerebral malaria, severe anaemia, respiratory distress (acidosis) and hypoglycaemia. Severe anemia is common, but mortality is often caused by cerebral malaria.4 Management of convulsions: ABC approach, diazepam, and if the convulsions persist after two doses of diazepam, give a loading dose of phenytoin or phenobarbitone. Giving corticosteroids to cerebral malaria has not been beneficial in reducing death.10 Giving mannitol in cerebral malaria can reduce 19% mortality.11 Provision of lung protective ventilation helps reduce mortality in malaria with Acute Respiratory Distress Syndrome (ARDS).12 It is important to note that in malaria with ARDS is often co-existent with bacterial sepsis.13
Check and treat for hypoglycaemia and hypoxia (PaO2 < 90%). Hypoglycaemia (<3mmol/l) should be corrected with 5ml/kg of 10% dextrose through a peripheral line, followed by a slow intravenous infusion of 5ml/kg per hour of 10% or 10ml/kg per hour of 5% to prevent recurrence of hypoglycaemia.4,6
Correct fluid deficits over 3?4 h with 0.9% (?normal?) saline at 3?5 ml/kg/h, then switch to maintenance 5% dextrose (2?3 ml/kg/h). If solutions containing 0.45% saline/5% dextrose are available, then these are preferred for initial resuscitation.4,14,15 The need for blood transfusion must be assessed with great care for each child. In general, in high-transmission settings, a haematocrit of 
Keywords: malaria, child, severe, management
1. World Health Organization. Chapter 7:Malaria. 2014. [cited August 5, 2019]
Available from : https://www.who.int/ith/ITH_chapter_7.pdf
2. World Health Organization. Guidelines for the treatment of malaria: third edition. Italy: World Health Organization, 2015.
3. Tatura SNN, Gunawan S, Bernadus J, Sandjoto S. Plasmodium falciparum found in the bone marrow of a child in Manado City, East Indonesia: A case
report. Asian Pacific Journal of Tropical Medicine 2017;10(10):1015-1017.
4. World Health Organization. Tropical Medicine and International Health 2014;19 (Suppl. 1), 7?131. [cited August 5, 2019]. Available from : https://www.who.int/malaria/publications/atoz/who-severe-malaria-tmih-supplement-2014.pdf
5. Tatura, SNN. Wowor, EC, Mandei JM, Wilar R, Warouw SM, Rompis J, et al. Case report: Severe Plasmodium vivax Malaria Mimicking Sepsis in a Neonate. Am. J. Trop. Med. Hyg 2018;98(3):656-659.
6. World Health Organization. Management of Severe Malaria. Italy: World Health Organization, 2012.
7. Centers for Disease Control and Prevention. Treatment of Malaria: Guidelines For Clinicians (United States). 2019. [cited August 5, 2019]. Available from : https://www.cdc.gov/malaria/diagnosis_treatment/clinicians3.html
8. Okebe J, Eisenhut M. Pre-referral artesunate for severe malaria (Review). Cochrane Database of Systematic Reviews 2014;5. [cited August 10, 2019]. Available from : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463986/pdf/CD009964.pdf
9. Esu EB, Effa EE, Opie ON, Meremikwu MM. Arthemeter for severe malaria (Review). Cochrane Database of Systematic Reviews 2019;6. [cited August 10, 2019]. Available from : https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010678.pub3/pdf/abstract
10. Prasad K, Garner P. Steroid for treating cerebral malaria (Review). Cochrane Database of Systematic Reviews, 2019. [cited August 10, 2019]. Available from : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532619/pdf/CD000972.pdf
11. Okoromah CAN, Afolabi BB, Wall ECB. Manitol and other osmotic diuresis as adjuncts for treating cerebral malaria. Cochrane Database of Systematic Reviews, 2019. [cited August 10, 2019]. Available from : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018680/pdf/CD004615.pdf
12. Taylor WRJ, Hanson J, Turner GDH, White NJ, Dondorp AM. Respiratory Manifestations of Malaria. CHEST 2012;142(2):492-505.
13. Mohan A, Sharma SK, Bollineni S. Acute lung injury and acute respiratory distress syndrome in malaria. J Vector Borne Dis 2008;45:179-193.
14. Njuguna PW, Newton CRJC . Management of severe falciparum malaria Management of severe falciparum malaria. J Postgrad Med March 2004;50(1):45-50.
15. Ford N et al. Mortality after Fluid Bolus in Children with Shock Due to Sepsis or Severe Infection: A Systematic Review and Meta-Analysis. PLoS ONE 2012;7(8):1-8.
16. Maitland K, Olupot-Olupot P, Kiguli S, Chagaluka G, Alaroker F, Opoka RO, et al. Transfusion Volume for Children with Severe Anemia in Africa. N Engl J Med 2019;381:420-31. 
Disclaimer: The Views and opinions expressed in the articles are of the authors and not of the journal.
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