CCDR: Volume 40-7, April 3, 2014

Canada Communicable Disease Report CCDR

ISSN 1481-8531 (On-line)


Summary of recommendations for the prevention of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT)

Boggild AFootnote I, Brophy JFootnote II, Charlebois PFootnote III, Crockett MFootnote IV, Geduld JFootnote V, Ghesquiere WFootnote VI, McDonald PFootnote VII, Plourde PFootnote VIII, Teitelbaum PFootnote IV, Tepper MFootnote X, Schofield SFootnote XI and McCarthy A (Chair) Footnote XII Footnote *

Abstract

Background: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill.

Objective: To provide guidelines on risk assessment and prevention of malaria.

Methods: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence.

Recommendations: Used together and correctly, personal protective measures (PPM) and chemoprophylaxis very effectively protect against malaria infection. PPM include protecting accommodation areas from mosquitoes, wearing appropriate clothing, using bed nets pre-treated with insecticide and applying topical insect repellant (containing 20%–30% DEET or 20% icaridin) to exposed skin. Selecting the most appropriate chemoprophylaxis involves assessment of the traveller's itinerary to establish his/her malaria risk profile as well as potential drug resistance issues. Antimalarials available on prescription in Canada include chloroquine (or hydroxychloroquine), atovaquone-proguanil, doxycycline, mefloquine and primaquine.

Introduction

Malaria is a serious infection caused by five different species of the genus Plasmodium: falciparum, vivax, ovale, malariae and knowlesi. Malaria is transmitted by the bite of infected female anopheline mosquitoes.

In 2009, 35% of Canadian travellers who went to a destination other than the United States visited a country that presented a risk of malaria, an increase of 131% from 2000 Footnote 1 Footnote 2. Between September 2009 and September 2011, 94 cases of malaria were diagnosed among returned Canadian travellers Footnote 3.

According to the Centers for Disease Control and Prevention (CDC), malaria risk for travellers from the United States Footnote 4 Footnote 5 Footnote 6 varied as follows:

  • Highest in west Africa and parts of Oceania;
  • Moderate for other parts of Africa, parts of South America and South Asia;
  • Lower for much of Central America, the Caribbean, Mexico and other parts of Asia and South America;
  • Minimal in urban centres of southeast Asia and Central and South America, and in large resort areas in the Caribbean and Mexico.

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada with ongoing and timely medical, scientific and public health advice relating to tropical disease and health risks associated with international travel. This is a summary of the CATMAT Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers,developed for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill Footnote 7. These guidelines include a full description of the recommendations on risk assessment and prevention of malaria, a disease that is still uncommon in Canada.

Methods

The Malaria Subcommittee, a working group of CATMAT, developed the guidelines. Each member is a volunteer, and none declared a relevant conflict of interest. Each chapter was updated by one to two members of the subcommittee and reviewed and approved by the full membership of CATMAT. The update was based on a thorough review of the literature. In addition, the Malaria Subcommittee reviewed all major sources of information on malaria prevention and treatment, including the World Health Organization Footnote 8, Centers for Disease Control and Prevention (CDC) Footnote 6 and the Health Protection Agency Advisory Committee on Malaria Prevention Footnote 9. The Malaria Subcommittee reviewed recent research, and national and international epidemiological data in order to tailor the recommendations to the Canadian context. Influencing factors include drug licensure, Canadian-specific travel patterns and related malaria epidemiology, and the anticipated values and preferences of travellers and health care providers. The evidence-based medicine recommendations for prevention of malaria were developed with associated rating scales for the strength and quality of the evidence.

CATMAT has taken into consideration both the need for protection and the potential for adverse effects of chemoprophylaxis. The guidelines also emphasize the varying degrees of endemicity in different regions. The health care provider should be properly informed to be able to provide appropriate guidance for the individual traveller.

Recommendations

The evidence-based CATMAT recommendations for malaria prevention are summarized in Table 1. A discussion of some of the key recommendations follows.

Table 1: Evidence-based medicine recommendations for prevention of malaria

Recommendation EBM ratingFootnote 1
1. Properly used malaria chemoprophylaxis is very effective Footnote 6. A I
2. Travellers should receive expert advice on malaria risks and strategies to avoid mosquitoes Footnote 10. B III
3. A detailed review of the travel itinerary to determine the expected level of malaria endemicity and duration of exposure is essential to provide an accurate risk assessment for travellers Footnote 6 Footnote 10 Footnote 11. B III
4. An assessment of the traveller’s health and risk tolerances is also important in making malaria prevention recommendations. B III
5. It is very important to adhere to recommended malaria prevention practices (e.g. use of chemoprophylaxis and PPM) Footnote 12 Footnote 13 Footnote 14 Footnote 15 Footnote 16 Footnote 17 Footnote 18 Footnote 19 Footnote 20 Footnote 21 Footnote 22. B III
6. Chloroquine (Aralen®) or hydroxychloroquine (Plaquenil®) is the drug of choice for travellers to areas with chloroquine-sensitive malaria Footnote 23. A I
7. Atovaquone-proguanil, doxycycline or mefloquine is the drug of choice for travellers to areas with chloroquine-resistant or mefloquine-sensitive malaria Footnote 12 Footnote 13 Footnote 14 Footnote 24 Footnote 25 Footnote 26 Footnote 27. A I
8. Atovaquone-proguanil and doxycycline are the drugs of choice for travellers to areas with mefloquine-resistant malaria. A I
9. Primaquine is recommended for malaria chemoprophylaxis for travellers to regions with chloroquine resistance who are not willing or able to use atovaquone-proguanil, doxycycline or mefloquine. A I
10. Standby malaria treatment with atovaquone-proguanil or quinine and doxycycline is recommended for travellers who are more than a day away from malaria diagnostic help. C III
11. Doxycycline is an antibiotic and should never be co-administered with any live, oral bacterial vaccines. Vaccination with live oral typhoid or cholera vaccines should be completed at least three days before the first dose of choloroquine, atovaquone-proguanil or mefloquine. B III
12. Concurrent use of chloroquine interferes with antibody response to intradermal administration of human diploid cell rabies vaccine. If intradermal rabies vaccine is administered to someone taking chloroquine, it is recommended that post-vaccine rabies antibodies be obtained to verify an adequate immunologic response. B III
13. Use insecticide-treated bed nets. A I
14. Use topical repellents on exposed areas of skin to prevent arthropod bites and to reduce the risk of exposure to malaria-carrying mosquitoes. A I
15. Products registered in Canada that contain 20%–30% DEET (N,N-Diethyl-meta-toluamide) or 20% icaridin should be the first choice for Canadian travellers. A II
16. Products that contain p-menthane-3,8-diol (a chemical originally derived from the lemon eucalyptus plant) and that are registered in Canada should be considered second-choice topical repellents. A II
17. Other active ingredients currently registered in Canada (e.g. citronella and soybean oil) are either not widely available and/or do not provide sufficiently long protection times against bites. These products are not recommended for protecting travellers against the bites of vectors. E II
18. Protect work and accommodation areas against mosquitoes by using screening on doors, windows and eaves (the open area between the roof and wall), eliminating holes in roofs and walls, and closing other gaps around a building. B I
19. Wear insecticide-treated clothing. B II
20. Wear appropriate clothing (e.g. full-length, loose-fitting and light-coloured clothing with sleeves rolled down and pants tucked into socks or boots). B III
21. Do not use/rely on other insecticide-based approaches, such as insecticide coils that are burned, insecticide vaporizers, aerosols and space sprays, and insecticide-treated bed sheets. E III
22. PPM that are either ineffective or that have not been convincingly shown to be efficacious against arthropod vectors and related diseases are not recommended. These include electronic (ultrasonic) devices; wristbands, neckbands and ankle bands impregnated with repellents; electrocuting devices (“bug zappers”); odour-baited mosquito traps; Citrosa plant (geranium houseplant); orally administered vitamin B1; and skin moisturizers that do not contain an approved repellent active ingredient. E II

Risk assessment

CATMAT suggests a two-component process for malaria risk assessment: an exposure assessment and a host assessment.

An exposure assessment evaluates the probability of being bitten by infected mosquitoes. It takes three factors into account:

  • Expected level(s) of endemicity in the travel itinerary;
  • Presence/predominance of P. falciparum;
  • Duration of exposure.

A host assessment evaluates the traveller’s health in relation to the potential hazard(s) of clinical malaria and the indications for specific malaria chemoprophylactic agents while taking into account personal preferences regarding risk management. Factors to consider include the following:

  • General health of the traveller;
  • Drug–drug interactions;
  • Likelihood of access to appropriate medical care;
  • Risk tolerance and individual preferences.

The completed risk assessment can be used to decide whether to use malaria chemoprophylaxis and which chemoprophylactic agent to prescribe:

  • If malaria risk is minimal and the incidence of P. falciparum is nil or very low, CATMAT recommends using chemoprophylaxis (with PPM) for a stay longer than two weeks.
  • If malaria risk is minimal and the incidence of P. falciparum is higher, CATMAT recommends chemoprophylaxis (with PPM) for a stay longer than one week.

Travellers who decide not to use chemoprophylaxis have a higher risk of malaria but lower risk of chemoprophylaxis-associated adverse effects; the opposite is true for those who decide to use it.

A country-by-country characterization of malaria transmission areas is available in the complete guidelines Footnote 7. The Appendix provides chemoprophylaxis recommendations for the top 25 destinations with risk of malaria transmission that are visited by Canadians.

Personal protective measures

  • The risk of being bitten by a mosquito can be reduced by using physical and/or chemical barriers.
  • Physical barriers:
    • Screening on doors, windows, eaves and other gaps in the building Footnote 28 Footnote 29 Footnote 30;
    • Bed nets treated with insecticide Footnote 31 Footnote 32 Footnote 33;
    • Full-length, loose-fitting and light-coloured clothing (clothes can also be treated with insecticide).
  • Chemical barriers repel mosquitoes and/or kill them Footnote 34 Footnote 35. The main chemical modalities currently available are topical insect repellents for use on exposed skin and insecticides that impregnate bed nets and clothing Footnote 36 Footnote 37 Footnote 38 Footnote 39 Footnote 40.
    • Topical repellents should contain 20%–30% DEET or 20% icaridin.
    • Alternatively, second-choice topical repellents are those containing p-menthane-3,8-diol that are registered in Canada.

Travellers should also be encouraged to plan activities during periods when risk is reduced (e.g. during the daytime where the principal vectors are active in the evening) and to visit areas where transmission is less likely (e.g. urban centres, highland areas > 2000 m/6500 ft).

Chemoprophylaxis

Prescribing antimalarial drugs

Prescribe antimalarial chemoprophylaxis only after completing an individual risk assessment. For detailed descriptions of chemoprophylaxis and of chemotherapy see Chapter 8 of the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers Footnote 7. Selecting the most appropriate chemoprophylactic agent involves the following:

  1. Evaluate the traveller’s exact travel itinerary to determine his or her malaria risk profile.
  2. Review the advantages and disadvantages of different regimens:
    • Take into account the traveller's health status, other medications and the risks and character of adverse drug effects.
    • Consider only those medications that are least likely to exacerbate any past or present medical problem(s).
  3. Present all the available options to the traveller and, unless any medication is contraindicated, let travellers choose which first-line malaria chemoprophylactic regimens they prefer.
  4. Select the appropriate dosage of the medication:
    • Explain the dosing schedule, including the need to take the drug before, during and after visiting the area of risk, the desirability of taking the drug at the same time each day and advice on whether the prescribed medication should be taken with food, as well as any precautions regarding drug-specific side effects (e.g. sun exposure with doxycycline) Footnote 41 Footnote 42 Footnote 43 Footnote 44 Footnote 45 Footnote 46 Footnote 47.
  5. Suggest a drug trial to check for possible medication-associated adverse reactions.
  6. Discuss strategies to change medication if serious adverse effects arise during travel.
    • Advise the traveller to continue to take the prescribed malaria medication if it is well tolerated regardless of negative anecdotes about it. Long-term use of the chemoprophylactic agents currently recommended in Canada does not result in additional risks of severe adverse effects.

Discuss the importance of seeking medical advice urgently if a fever develops while the traveller is in a malaria-endemic area or within one year of leaving.

Selecting antimalarial drugs for specific regions of drug resistance

Monitor appropriate sources (e.g. Public Health Agency of Canada, CDC, ProMED) to stay abreast of new information about malaria risks before giving pre-travel care. This is especially relevant for minimal-risk regions because changes may directly affect the recommendations for chemoprophylaxis.

Table 2: Selecting antimalarial drugs for specific regions of drug resistance

Area/region Footnote 6 Footnote 48 Footnote 49 Footnote 50 Drugs of choice
Chloroquine-sensitive regions:
Haiti, the Dominican Republic, Central America north of the Panama Canal, parts of Mexico, parts of South America, north Africa, parts of the Middle East, and west/central China
Chloroquine (Aralen®)
Hydroxychloroquine (Plaquenil®) is an acceptable equivalent alternative Footnote 51, as are the three drugs used in chloroquine-resistant areas (see below).
Chloroquine-resistant regions:
Most of sub-Saharan Africa, South America, Oceania and Asia. See below for regions that are both chloroquine- and mefloquine-resistant.
Atovaquone-proguanil Footnote 41 Footnote 42 Footnote 44 Footnote 45 Footnote 46 Footnote 47 Footnote 52
Doxycycline Footnote 41 Footnote 42 Footnote 44 Footnote 45 Footnote 46 Footnote 47 Footnote 52
Mefloquine Footnote 41 Footnote 42 Footnote 44 Footnote 45 Footnote 46 Footnote 47 Footnote 52
Chloroquine- and mefloquine-resistant regions:
Various countries in Asia, Africa and the Amazon basin. However, it is a significant problem only in rural, wooded regions where Thailand borders with Myanmar (Burma), Cambodia and Laos, and in southern Vietnam.
Atovaquone-proguanil Footnote 44 Footnote 53 Footnote 54
Doxycycline Footnote 44 Footnote 53 Footnote 54

Note: See the Appendix, ‘Top 25 countries for malaria risk and recommended chemoprophylaxis’, or a more complete list in the Canadian Recommendations for the Prevention and Treatment of Malaria among International Travellers Footnote 7.

Discontinuing antimalarial drugs

Fatal malaria has occurred in travellers who have discontinued all chemoprophylaxis or effective chemoprophylaxis in favour of something less protective Footnote 24 Footnote 51 Footnote 55 Footnote 56. Discontinuation of all chemoprophylaxis is NOT a reasonable option.

Other travellers and/or health care providers may suggest changing or stopping antimalarial medication. For the most part, such advice should be ignored or questioned. Medications used in other areas of the world may be less effective, may be associated with serious adverse effects or may not be manufactured to Canadian standards. Examples include proguanil alone (Paludrine®), pyrimethamine (Daraprim®), dapsone-pyrimethamine (Maloprim®) and mefloquine-sulfadoxine-pyrimethamine (Fansimef®).

However, if the traveller experiences significant adverse events because of the chemoprophylactic agent, the medication can be changed, especially if the advice is provided by a health care provider (preferably the one who provided the initial advice).

Adherence to chemoprophylaxis

The reasons for non-adherence include lack of knowledge that malaria was a threat; fear of or past experience with adverse effects of chemoprophylactic agents; the false belief that prior malaria infections have conferred long-term immunity; the cost of medications; and confusion arising from contradictory recommendations. However, there is little information on how to enhance adherence.

Non-adherence to or suboptimal use of chemoprophylaxis and other preventive interventions is common, particularly among backpacking travellers; immigrants returning to visit their country of origin; people travelling for longer than one month; travellers aged 40 years or less; and those using chemoprophylactic agents that must be taken daily Footnote 12 Footnote 13 Footnote 14 Footnote 15 Footnote 16 Footnote 17 Footnote 18 Footnote 19 Footnote 20 Footnote 21 Footnote 23 Footnote 25 Footnote 26 Footnote 27 Footnote 57.

Health care providers themselves need to be properly informed to be able to provide appropriate guidance Footnote 58. Travellers who use one qualified information source, such as a family physician trained in travel medicine, are significantly more likely to be compliant with malaria prophylaxis than those who collect information from multiple sources that could contradict each other Footnote 58 Footnote 59.

Summary

A summary of the key changes made to the 2014 Guidelines are noted in Table 3.

Table 3: Summary of key additions and changes to the 2014 Guidelines pertaining to prevention of malaria Footnote 7

Additions
1. The addition of a length-of-stay threshold for use of malaria chemoprophylaxis so that health care providers can better tailor individualized risk assessments (see Chapter 2).
2. A new insect repellent, 20% icaridin, is recognized as an equivalent to DEET as a first-line choice for mosquito repellent (see Chapter 3).
3. The guidelines have been expanded for populations requiring special attention – children, migrants, expatriates and travellers visiting friends and relatives, women who are pregnant or breastfeeding, and travellers with co-morbidities (Chapter 5).
4. A new “Malaria Card” that can be given to travellers with information about their malaria chemoprophylaxis and an important reminder to seek medical attention in the event of a fever illness after travel.
Changes
1. Chapter 4, “Prevention – Chemoprophylaxis Regimens,” has been refined to make it easier to navigate the drug choices available. These changes include a simplified, step-wise approach to selecting malaria prophylaxis; comprehensive listings of medications and malaria risk by country/area in tabular form; and expanded explanation of the differences in approaches to malaria prophylaxis in other jurisdictions.
2. Chapter 8, “Drugs for the Prevention and Treatment of Malaria,” includes an update on primaquine use for malaria prophylaxis and prevention; additional up-to-date information on pediatric dosing of atovaquone/proguanil; and general updates to Table 8.11: Drugs (generic and trade name) for the treatment and prevention of malaria. Revisions have also been made to the following sub-sections related to malaria prevention: chloroquine and mefloquine (with increased emphasis on selection or avoidance of this drug according to individual tolerability).

Acknowledgements

CATMAT acknowledges and appreciates the contribution of Joanna Odrowaz, Elspeth Payne to the development of the summaries and Manisha Kulkarni for her contribution to the statement.

CATMAT Members: Boggild A, Brophy J, Bui YG, Crockett M, Ghesquiere W, Greenaway C, Henteleff A, Libman M, Teitelbaum P and McCarthy A (Chair).

Liaison members: Hui C (Canadian Paediatric Society) and Gershman M (US Centers for Disease Control and Prevention).

Ex-officio members: Marion D (Canadian Forces Health Services Centre, Department of National Defence), McDonald P (Division of Anti-Infective Drugs, Health Canada), Schofield S (Directorate of Force Health Protection, Department of National Defence), and Tepper M (Directorate of Force Health Protection, Department of National Defence).

Member Emeritus: Jeanes CWL.

Conflict of interest

There are no conflicts of interest to declare.

Funding

This work was supported by the Public Health Agency of Canada.

References

Appendix

Top 25 countries for malaria risk and recommended chemoprophylaxis (6,60-66)

Country Malaria transmission area Chemoprophylaxis recommended by CATMAT* Season Plasmodium falciparum (%)
1 Uganda All areas ATQ-PG, DOXY or MFQ Year-round > 85
2 Ghana All areas ATQ-PG, DOXY or MFQ Year-round > 90
3 Democratic Republic of Congo All areas ATQ-PG, DOXY or MFQ Year-round 90
4 Burkina Faso All areas ATQ-PG, DOXY or MFQ Year-round 80
5 Kenya Little to no malaria transmission at elevations > 2500 m or in Nairobi None; use PPM Year-round 85
All areas at elevations < 2500 m, except Nairobi ATQ-PG, DOXY or MFQ
6 Zambia All areas ATQ-PG, DOXY or MFQ Year-round > 90
7 Pakistan All areas at elevations < 2000 m. Risk is due to both P. vivax and P. falciparum. Risk lower in the north, including Islamabad, especially during winter months because of cool temperatures ATQ-PG, DOXY or MFQ Year-round 30
8 Ethiopia No malaria transmission at elevations > 2200 m, including Addis Ababa None. n/a n/a
All areas at elevations < 2200 m, including Axum (2139 m), Dire Dawa (1262 m), Harar (1848 m) and Nazret (1725 m) ATQ-PG, DOXY or MFQ Year-round 60-70
9 Malawi All areas ATQ-PG, DOXY or MFQ Year-round 90
10 Niger All areas ATQ-PG, DOXY or MFQ Year-round 85
11 United Republic of Tanzania At elevations < 1800 m ATQ-PG, DOXY or MFQ Year-round > 85
12 Mali All areas ATQ-PG, DOXY or MFQ Year-round 85
13 Côte d’Ivoire (Ivory Coast) All areas ATQ-PG, DOXY or MFQ Year-round 85
14 Burundi All areas ATQ-PG, DOXY or MFQ Year-round 86
15 Nigeria All areas ATQ-PG DOXY or MFQ Year-round 85
16 Indonesia No malaria transmission in Jakarta Municipality, major metropolitan areas including Ubud or major tourist resorts in Bali and Java None n/a n/a
In general, risk is higher in more easterly regions of Indonesia, in particular, the provinces of East Nusa Tenggara, Maluku, North Maluku, Papua (Irian Jaya) and West Papua. There is also risk on Lombok Island and the rural areas of Kalimantan Island (Borneo). There is a low risk of transmission in rural Java and Bali, and sporadic cases have been reported among travellers to rural areas of Bali. In the other parts of the country, there is malaria risk in some districts. ATQ-PG, DOXY or MFQ Year-round 66
17 Mozambique All areas ATQ-PG, DOXY or MFQ Year-round 90
18 Sierra Leone All areas ATQ-PG, DOXY or MFQ Year-round 85
19 Angola All areas ATQ-PG, DOXY or MFQ Year-round 90
20 Liberia All areas ATQ-PG, DOXY or MFQ Year-round 85
21 Guinea All areas ATQ-PG, DOXY or MFQ Year-round 85
22 Benin All areas ATQ-PG, DOXY or MFQ Year-round 85
23 South Sudan All areas ATQ-PG, DOXY or MFQ Year-round 90
24 India No malaria transmission at elevations > 2000 m in parts of the states of Himachal Pradesh, Jammu and Kashmir, and Sikkim None n/a n/a
All other areas, including most urban areas such as Bombay (Mumbai) and Delhi.
Risk is lower in most of the southernmost regions of India.
Risk is low in central urban areas of Agra and Bangalore.
ATQ-PG, DOXY or MFQ PPM alone can be considered for stays of
< 1 week in central urban areas of Delhi, Agra and Bangalore
Year-round > 40
25 Sudan All areas. Risk of malaria transmission is highest in the southern parts of the country. Risk is lower and follows a seasonal pattern in the north. Risk along the Red Sea coast is very limited. ATQ-PG, DOXY or MFQ Year-round (predominantly during wetter season in the north) 90

* Chemoprophylaxis is recommended only in the risk areas identified during the transmission season identified. Chemoprophylaxis should always be used in conjunction with PPM. ATQ-PG, atovaquone-proguanil; DOXY, doxycycline; MFQ, mefloquine

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