Chapter 5.1 – Malaria issues in special hosts-Children: Canadian recommendations for the prevention and treatment of malaria

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An Advisory Committee Statement (ACS) from the
Committee to Advise on Tropical Medicine and Travel (CATMAT)

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada (PHAC) with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.

Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Chapter 5: Malaria issues in special hosts

5.1 Prevention in special hosts—children

Malaria prevention in children

Health care providers should clearly advise travellers of the risks of taking young children to areas with Plasmodium falciparum malaria. The majority of the over 650,000 deaths per year due to malaria are among children^{Reference 1}. A study found that malaria was the most common cause of febrile illness (35%) among returned pediatric travellers, and the most common single diagnosis overall (8%)^{Reference 2}; however these findings cannot be generalized to all children travelling internationally. Travel to sub-Saharan Africa accounts for the vast majority of childhood cases of falciparum malaria, with most travellers visiting friends and relatives^{Reference 2}, ^{Reference 3}, ^{Reference 4}. Malaria also disproportionately affects children. Of the Canadians diagnosed with malaria who were reported to the Public Health Agency of Canada from 1998 to 2008, 23% were 19 years old or younger whereas only 8.7% of international travellers in 2011 were in that age group^{Reference 5}. From August 2001 to August 2012, 195 cases of severe or complicated malaria were reported to the Canadian Malaria Network (CMN). Of these, 21.1% were children (< 18 years old), and 11.6% were 0 to 4 years old (Personal communication, A. McCarthy and J. Geduld, 2012).

Of the 7,542 malaria cases reported between 2006 and 2010 to the Centers for Disease Control and Prevention (CDC) in the United States, 1,418 (18.0%) were children (< 18 years old) and 360 (4.8%) were aged 0 to 4 years old (Personal communication, K. Cullen and P. Arguin, 2012; Domestic Response Unit, Malaria Branch, Division of Parasitic Diseases, CDC and Prevention, United States).

Malaria can present with nonspecific symptoms that mimic other common childhood diagnoses, leading to delays in diagnosis. Severe or complicated malaria, such as cerebral malaria, severe anemia, shock or even death, may develop more quickly in children^{Reference 6}. CMN data from June 2001 to September 2011 indicate that 22% of the complicated malaria cases requiring treatment with intravenous quinine or artesunate were in children, the majority of whom were foreign-born (61%)^{Reference 7}.

To reduce the risk of infection when travel to malaria-endemic areas is unavoidable, all children should be well protected against mosquito bites (see Chapter 3) and receive appropriate malaria chemoprophylaxis^{Reference 7}, ^{Reference 8}. Infants do not receive sufficient medication through breast milk to protect them and should be prescribed antimalarial drugs even if their mother is taking antimalarials^{Reference 9}, ^{Reference 10}.

Making sure that young children take antimalarial drugs may be difficult because of the lack of pediatric formulations and the unpleasant taste. Malaria tablets may be crushed and mixed with chocolate syrup, jam, cereal, bananas or formula to mask the taste. Prescribe sufficient tablets to allow a few doses to be vomited or spat out, with clear instructions as to when doses that were not successfully ingested should be repeated. Health care providers should consider enlisting the help of compounding pharmacies that can pre-cut tablets and/or crush and insert portions into capsules to increase the accuracy and ease of dosing.

Deaths due to inadvertent overdose have been reported; these medications should, therefore, be kept out of reach of infants and children and stored in childproof containers^{Reference 11}.

Families who are travelling over the long term should be told how to adjust the dose of medications to allow for an increase in children’s weight over time.

Chemoprophylaxis for children

Chloroquine is the preferred chemoprophylactic agent in areas with chloroquine-sensitive malaria (see Appendix I for specific recommendations for areas). Chloroquine sulfate (e.g. Nivaquine®) is widely available as syrup in malaria-endemic areas, and this is often more easily administered to children than are tablets. However, it is not available in Canada, and those purchasing products outside of Canada need to take care to minimize the risk of counterfeit medication (see “Preventing Malaria in the Long-Term Traveller or Expatriate”). If parents plan to use this syrup, inform them that the dose must be carefully determined according to the child’s weight and that there is a risk of overdosing.

Mefloquine is one of the drugs of choice in chloroquine-resistant regions (see Appendix I for specific recommendations for different areas); however, there are no studies that analyze its bioavailability and rate of metabolism in children. Although the manufacturer recommends that mefloquine not be given to children smaller than 5 kg (11 lb), mefloquine should be considered for all children at high risk of acquiring chloroquine-resistant P. falciparum, at a dose of 5 mg base/kg once weekly^{Reference 12}.

Young children are less likely to suffer major neuropsychiatric side effects from mefloquine^{Reference 13} but may be more likely to have emesis^{Reference 14}.

While chloroquine and mefloquine may exacerbate seizure disorders, in which case other agents should be used, there is no evidence that febrile seizures in children are a contraindication to these drugs.

Atovaquone-proguanil is licensed for the prophylaxis and treatment of malaria in children weighing 11 kg (25 lb) or more or who are older than 3 years^{Reference 15}. Clinical trials using atovaquone-proguanil to treat malaria in children weighing as low as 5 kg (11 lb) suggest it may be safe for infants of this size when required^{Reference 16}. Daily doses for small infants have been extrapolated from those used in treatment trials (one-quarter of the treatment dose, or 5 mg/kg/doses and 2 mg/kg/doses of the atovaquone and proguanil components, respectively). Based on a pediatric tablet of 62.5 mg atovaquone/25 mg proguanil, the daily doses is half of a pediatric tablet for those children weighing 5 kg to 8 kg (11–17 lb) and three-quarters of a pediatric tablet for those children weighing 8 kg to 10 kg (17–22 lb)^{Reference 16}.

Doxycycline has been studied as pediatric prophylactic medication^{Reference 17}. It can be used at a daily dose of 2 mg/kg (maximum: 100 mg/d) in children aged 8 years and older^{Reference 9}, ^{Reference 18}. Primaquine can be given to children 9 years and older who are unable to take any of the first-line prophylactic agents^{Reference 19}, although it is not licensed in Canada for this indication. As there is no age limit for primaquine when used for radical cure of P. vivax or P. ovale, it may be an option for children of any age as long as they have been screened for adequate glucose-6-phosphate dehydrogenase (G6PD) levels. Consultation with a travel medicine or infectious disease expert is advisable unless the prescriber has experience with this medication in the pediatric population.

Table 5.1.1: Evidence-based medicine recommendations

Recommendation	EBM rating
Young children should avoid travel to areas with significant malaria transmission, particularly of chloroquine-resistant malariaReference 9.	C III
Effective PPM should be used by all children who travel to malaria-endemic areasReference 20.	A I
For children travelling to or residing in chloroquine-resistant areas, mefloquine, doxycycline (≥ 8 years) and atovaquone–proguanil (≥ 5 kg) are the drugs of choice for chemoprophylaxis Reference 12, Reference 15, Reference 17, Reference 21.	A I
Primaquine chemoprophylaxis may be suitable for children who are unable to take any of the first-line prophylactic agentsReference 19.	B II
Abbreviation: EBM, evidence-based medicine; PPM, personal protective measures. Note: For a description of the categories and quality of evidence of the recommendations, see Appendix IV.

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