Chapter 2 – Prevention and risk assessment: 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 2 – Prevention and risk assessment

The components of malaria prevention are often described as the ABCDs of malaria. All travellers to areas where malaria is endemic need to:

1. Be aware of the risk of Acquiring malaria infection (described in this chapter),
2. Know how to avoid mosquito Bites (see Chapter 3),
3. Take Chemoprophylaxis, as appropriate (see Chapter 4), and
4. Understand the need to be urgently diagnosed and treated if they have a fever (see Chapters 6 and Chapter 7).

Appendix II provides a checklist for people preparing to travel to malarial areas.

Risk of acquiring malaria by destination

Although data that characterize risk of malaria by destination for Canadian travellers are not currently available, there are such data for other populations^{Reference 1}. For example, based on case reports and volume of travel to a given country, the Centers for Disease Control and Prevention (CDC) in the United States reported that risk of acquiring malaria was highest for those travelling to west Africa and parts of Oceania; moderate for other parts of Africa, parts of South America and south Asia; and lower for much of Central America, the Caribbean, Mexico and other parts of Asia and South America^{Reference 2}, ^{Reference 3}, ^{Reference 4}. This hierarchy accords with data from other surveillance networks, including GeoSentinel^{Reference 5}, ^{Reference 6}, ^{Reference 7}, ^{Reference 8}, ^{Reference 9}, ^{Reference 10}, ^{Reference 11} and with extrapolations from country-specific endemicity estimates^{Reference 12}, ^{Reference 13}, ^{Reference 14}. Given such consistency, the Committee to Advise on Tropical Medicine and Travel (CATMAT) considers that it is highly likely that the geographic risk stratification articulated by the CDC can be applied to Canadian travellers.

Appendix I shows a country-by-country characterization of malaria transmission areas. Regional and/or city-specific information is also sometimes provided. These data were extracted from travel-specific risk characterizations published by the World Health Organization, the CDC and the International Association for Medical Assistance to Travellers^{Reference 15}, ^{Reference 16}, ^{Reference 17}. These risk characterizations are generally consistent; the most obvious differences relate to difference in recommendations for chemoprophylaxis in areas with low endemicity. In these few countries (see Appendix 1); CATMAT uses a length-of-stay threshold and recommends the use of personal protective measures (PPM) and the optional use of chemoprophylaxis for short stays (see Box 2.1).

Assessing malaria risk

Many factors can affect the risk of acquiring malaria or the development of adverse outcomes. There are also health risks, although relatively uncommon, associated with malaria interventions, particularly chemoprophylaxis. Deciding on the way to prevent malaria involves balancing these risks with expected benefits and with individual preferences. Unfortunately, there is no easy-to- follow recipe that allows for this—malaria is a disease of subtleties and its prevention is similarly nuanced. Because of this complexity, CATMAT suggests a two-component process for malaria risk assessment: an exposure assessment and a host assessment.

Exposure assesment

CATMAT defines exposure assessment as an evaluation of the probability that an individual will be bitten by potentially infected mosquitoes. Depending on the species and location, malaria mosquitoes can bite inside and/or out and usually between late afternoon and morning. The number of vectors (and hence transmission intensity) tends to be higher in rural areas (at least partly because of the wider availability of sites for the larvae to develop), can vary seasonally and decreases with altitude so that risk is often absent or negligible in highland areas (> 2,000 m or 6,500 ft.) (see Appendix I for country-specific information on malaria risk and altitude). Although not always feasible, knowing the habits of the principal vector(s) in an area is useful for assessing exposure. The CATMAT Statement on Personal Protective Measures to Prevent Arthropod Bites provides additional information on this topic, and a number of publications provide information on malaria vectors by geographic area^{Reference 15}, ^{Reference 18}, ^{Reference 19}, ^{Reference 20}, ^{Reference 21}, ^{Reference 22}.

A detailed review of the travel itinerary is critical to determine whether the traveller will be visiting malaria-endemic areas (Appendix I). If so, then evaluation of the risk of exposure should be done. Factors to consider include:

• Expected level of endemicity in the area(s) in the travel itinerary: as noted above, transmission intensity is highest in west Africa and Oceania, moderate in other areas of Africa and in some areas of South America and south Asia, and low through much of the Caribbean, Central America, Mexico and other areas of South America and of Asia^{Reference 2}, ^{Reference 3}, ^{Reference 4};
• Presence/predominance of Plasmodium falciparum: infections caused by P. falciparum have the highest fatality rates;
• Duration of exposure: longer periods of travel are generally associated with increased risk (see Box 2.1);
• Destination: rural travel is generally more likely to result in exposure than peri-urban travel, and peri-urban travel is more likely to result in exposure than urban travel. CATMAT considers the risk of malaria in urban centres of southeast Asia and Central and South America and in large resort areas in the Caribbean and Mexico to be minimal;
• Season: risk can be higher during or soon after the rainy season due to larger mosquito populations;
• Night-time exposure;
• Presence of drug-resistant malaria (see Appendix I): chloroquine-resistant P. falciparum is widespread in all malaria-endemic areas of the world, except for Mexico, the Caribbean, Central America west of the Panama Canal, and parts of the Middle East^{Reference 23}. Chloroquine- and mefloquine-resistant P. falciparum has been confirmed in the Thai-Cambodia, Thai-Burma (Myanmar), China-Burma (Myanmar) and Lao-Burma (Myanmar) border areas, as well as in the western provinces of Cambodia, the eastern states of Burma (Myanmar) and southern Vietnam;
• Availability and likelihood of use of other interventions (e.g. PPM); and
• Availability of information to suggest that endemicity for a given area has changed. Health care providers providing pre-travel care should monitor appropriate sites (e.g. Public Health Agency of Canada and CDC websites, ProMed) to stay abreast of new information about malaria risks. This is especially relevant for regions considered as being minimal risk because changes might mean the difference between not recommending and recommending the use of malaria chemoprophylaxis.

Host assessment

CATMAT defines host assessment as an evaluation of the individual traveller's health as it relates to the potential hazard(s) of clinical malaria and the indications for specific malaria chemoprophylaxis. Host assessment should also involve evaluating individual preferences regarding risk management. Factors to consider include:

• General health of the individual: primary considerations include factors that might cause adverse outcomes (e.g. age, pregnancy, chronic illnesses such as HIV, etc.) or that might affect the choice of chemoprophylactic agent(s) (e.g. age, pregnancy, cardiac or neurological conditions) (see Chapters 3, 5 and 8);
• Possibility of drug-drug interactions (see Chapters 3 and 8);
• Likelihood that the traveller will be able to readily access appropriate medical care: travellers should be informed that reliable malaria diagnostics and treatments might not be available in some travel destinations^{Reference 24}. Self-diagnosis and concomitant treatment of malaria based on symptoms only, without laboratory diagnostic testing is not ideal. However, some travellers going to more remote locations might have few alternatives (see Chapters 3 and 5); and
• Risk tolerance and individual-specific preferences: this is especially pertinent where malaria chemoprophylaxis might or might not be used (see Box 2.1 and Appendix 1). Indeed, for a given area and for otherwise identical exposure and host assessments, some individuals might prefer not to use chemoprophylaxis while others would. Travellers who decide not to use chemoprophylaxis have higher risk of malaria but lower risk of chemoprophylaxis-associated adverse effects; the opposite is true for those who decide to use it.

Converting malaria risk assessment to recommendations for preventive measures

Once complete, the risk assessment can be used to help inform whether to use malaria chemoprophylaxis and which to use (Appendix I shows country/region-specific advice on malaria risk and recommended chemoprophylaxis). Nevertheless, clinical judgment remains important, for example, to select the most appropriate chemoprophylactic agent and/or to provide individual- specific preventive guidance (see Box 2.1: The CATMAT approach to recommendations for malaria chemoprophylaxis).

Box 2.1: The CATMAT approach to recommendations for malaria chemoprophylaxis

Table 2.1: Evidence-based medicine recommendations

Recommendation	EBM rating
Travellers should receive expert advice on malaria risks and strategies to avoid mosquitoesReference 1.	B III
Properly used malaria chemoprophylaxis is very effectiveReference 4.	A I
A detailed review of the travel itinerary to determine the expected level of malaria endemicity and duration of exposure is essential to providing an accurate risk assessment for travellersReference 1, Reference 4, Reference 6.	B III
An assessment of the traveller's health and risk tolerances is also important in making malaria prevention recommendations.	B III
Abbreviation: EBM, evidence-based medicine. Note: For a description of the categories and quality of evidence of the recommendations, see Appendix IV.

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