Summary of recommendations on malaria issues in special hosts

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 malaria issues related to special hosts. 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: All people visiting malaria endemic regions should use effective personal protective measures (PPM; topical repellants, bed nets, behavioural choices) and the prescribed chemoprophylaxis. Chemoprophylaxis for pregnant and breastfeeding women and for children requires careful consideration in the context of the pregnancy trimester, the age or size of the infant/child as well as their glucose-6phosphate dehydrogenase (G6PD) status. Recommendations for long-term travellers, expatriates and people visiting friends and relatives (VFRs) do not differ markedly from those for short-term travellers. Some underlying medical conditions may make individuals more vulnerable to malaria. In addition, some conditions or their treatment may preclude the use of one or more antimalarial medications. https://doi.org/10.14745/ccdr.v40i10a02 179 | CCDR – 15 May 2014 • Volume 40-10 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. Infections caused by P. falciparum have the highest fatality rates. The overall case-fatality rate of falciparum malaria varies from about 1% to 5% and increases to 20% for those with severe malaria (1). 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 one section 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 (2). These guidelines include a full description of the recommendations on risk assessment, prevention and treatment of malaria, a disease that is still uncommon in Canada. Two additional summaries of the guidelines are available focusing on prevention and treatment of malaria (3,4). Special groups of travellers have different risks of acquiring malaria infection compared with the average traveller. If unable to defer travel to areas with high risk of malaria, pregnant and breastfeeding women and small children should receive tailored antimalarial chemoprophylaxis, since some of the drugs are contraindicated in these groups. Long-term travellers, expatriates and travellers visiting friends and relatives (VFRs) may perceive malaria risk differently and may adhere differently to chemoprophylaxis. They require additional information about self-diagnosis and treatment. The issue of counterfeit drugs is addressed specifically for long-term travellers Methods The Malaria Subcommittee, a working group of CATMAT, developed the guidelines. The process undertaken to develop them has been described previously (3). It included a review of recent research and national and international epidemiological data, and the consideration of other factors, such as malaria epidemiology, and the anticipated values and preferences of travellers and health care providers. The evidence-based medicine recommendations for various malaria issues pertaining to special hosts were developed with associated rating scales for the strength and quality of the evidence. Recommendations The evidence-based CATMAT recommendations for malaria prevention and treatment in special hosts are summarized in Table 1. A discussion of some of the key recommendations follows. Children Malaria disproportionately affects children and can have nonspecific symptoms that mimic other common childhood illnesses, 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 (5). Young children should avoid travel to areas with significant malaria transmission, particularly of chloroquineresistant malaria (6). When travel to malaria-endemic areas is unavoidable consider the following:  All children should use effective personal protective measures (PPM: topical repellants, bed nets, behavioural choices) (7) and appropriate malaria chemoprophylaxis (1,8).  For chloroquine-resistant areas, mefloquine, doxycycline (for those  8 years) and atovaquone-proguanil ( 5 kg) are most appropriate (9-12)  Primaquine may be suitable for children who are unable to take the first-line prophylactic agents, once adequate G6PD (glucose-6-phosphate dehydrogenase) levels have been confirmed (13).  Prescribe antimalarial drugs for breastfeeding infants even if their mother is taking antimalarials (6,14).  Specific instructions related to dosing: 180 | CCDR – 15 May 2014 • Volume 40-10 o Prescribe sufficient tablets to allow a few doses to be vomited or spat out. Give clear instructions when to repeat doses that were not successfully ingested; o Have tablets pre-cut or crushed and inserted into capsules to increase the accuracy and ease of dosing; o Describe how to adjust the dose of medications to allow for an increase in children’s weight.  Explain that because there are few pediatric formulations, malaria tablets may be crushed and mixed with something sweet to disguise their unpleasant taste. Pregnant and breastfeeding women Pregnant women should defer travel to malaria-endemic areas and particularly to regions with drug-resistant falciparum malaria (15). Malaria increases the risk of maternal and neonatal death, miscarriage and stillbirth. Low birth-weight infants are more commonly born to women taking ineffective prophylaxis (15). If travel is unavoidable,  Pregnant and breastfeeding women should use PPM (topical repellents, insecticide-treated bed nets, and behavioural choices) (16).  Prescribe chemoprophylaxis based on destination: o Chloroquine in chloroquine-sensitive areas; o Mefloquine where exposure to chloroquine-resistant falciparum malaria is unavoidable (17-19); o Discuss the benefits and risks of atovaquone-proguanil after the first trimester in women who cannot avoid travel to mefloquine-resistant areas or who cannot take mefloquine (20,21); o Although safe in pregnancy, the combination of chloroquine and proguanil is inadequate as an antimalarial and cannot be recommended for chloroquine-resistant areas (22); o Doxycycline is contraindicated during pregnancy. Nursing women should continue to breastfeed if using chemoprophylaxis that is safe in infancy (chloroquine, mefloquine, atovaquone-proguanil in infants weighing  5 kg). Doxycycline absorption through breast milk is probably negligible, and breastfeeding is not an absolute contraindication to maternal use (23). Migrants Although in most cases disease will develop within three months of last exposure, malaria could be the reason for any fever that develops within 12 months of leaving a malaria-endemic region (24). The risk of malaria exists for migrants after their arrival in Canada:  For at least 12 months after migrants arrive in Canada, test for malaria in cases of unexplained fever.  Consider malaria screening in asymptomatic new migrants from highly endemic areas, and treat those with parasitemia (apart from the presence of gametocytes only) in blood smears.  Ask migrants from malaria-endemic countries about future travel plans to provide anticipatory guidance about malaria (25). Long-term travellers, expatriates and visiting friends and relatives Recommendations for preventing malaria in long-term travellers (travel for longer than one month), expatriates or visiting friends and relatives are very similar to the standard recommendations for the short-term traveller (26): use prescribed malaria chemoprohylaxis and PPM consistently, including insecticide-treated bed nets and topical repellents containing 20%–30% DEET or 20% icaridin. Some of the topics to cover when counselling expatriates and long-term travellers about malaria prevention include the following:  Possible concern about safety with prolonged use of chemoprophylaxis medication.  Use of PPM over the long term.  Cost of medication over the long term. 181 | CCDR – 15 May 2014 • Volume 40-10  Use of locally procured and possibly counterfeit drugs.  Conflicting counsel about chemoprophylaxis and self-treatment.  Need for ongoing adherence to chemoprophylaxis. Since overall nonadherence rates for chemoprophylaxis are as high as 61% (27), pre-travel advice should focus on these aspects:  Malaria symptoms and risk, emphasizing the need for early diagnosis and treatment.  Development of a plan for accessing competent medical care in case of illness.  Standby emergency therapy (self-treatment).  The affordability of chemoprophylaxis.  The likelihood that local malaria drugs are counterfeit (28).  The loss of partial immunity among visiting friends and relatives because of residence in a country without malaria (25). The risk of malaria among visiting friends and relatives is almost the same as for local residents, but the risk of severe disease is higher because of loss of partial immunity after having 


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.Infections caused by P. falciparum have the highest fatality rates.The overall case-fatality rate of falciparum malaria varies from about 1% to 5% and increases to 20% for those with severe malaria (1).
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 one section 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 (2).These guidelines include a full description of the recommendations on risk assessment, prevention and treatment of malaria, a disease that is still uncommon in Canada.Two additional summaries of the guidelines are available focusing on prevention and treatment of malaria (3,4).
Special groups of travellers have different risks of acquiring malaria infection compared with the average traveller.If unable to defer travel to areas with high risk of malaria, pregnant and breastfeeding women and small children should receive tailored antimalarial chemoprophylaxis, since some of the drugs are contraindicated in these groups.Long-term travellers, expatriates and travellers visiting friends and relatives (VFRs) may perceive malaria risk differently and may adhere differently to chemoprophylaxis.They require additional information about self-diagnosis and treatment.The issue of counterfeit drugs is addressed specifically for long-term travellers

Methods
The Malaria Subcommittee, a working group of CATMAT, developed the guidelines.The process undertaken to develop them has been described previously (3).It included a review of recent research and national and international epidemiological data, and the consideration of other factors, such as malaria epidemiology, and the anticipated values and preferences of travellers and health care providers.The evidence-based medicine recommendations for various malaria issues pertaining to special hosts were developed with associated rating scales for the strength and quality of the evidence.

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

Children
Malaria disproportionately affects children and can have nonspecific symptoms that mimic other common childhood illnesses, 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 (5).
Young children should avoid travel to areas with significant malaria transmission, particularly of chloroquineresistant malaria (6).When travel to malaria-endemic areas is unavoidable consider the following:  All children should use effective personal protective measures (PPM: topical repellants, bed nets, behavioural choices) (7) and appropriate malaria chemoprophylaxis (1,8). For chloroquine-resistant areas, mefloquine, doxycycline (for those  8 years) and atovaquone-proguanil ( 5 kg) are most appropriate (9-12)  Primaquine may be suitable for children who are unable to take the first-line prophylactic agents, once adequate G6PD (glucose-6-phosphate dehydrogenase) levels have been confirmed (13). Prescribe antimalarial drugs for breastfeeding infants even if their mother is taking antimalarials (6,14). Specific instructions related to dosing: o Prescribe sufficient tablets to allow a few doses to be vomited or spat out.Give clear instructions when to repeat doses that were not successfully ingested; o Have tablets pre-cut or crushed and inserted into capsules to increase the accuracy and ease of dosing; o Describe how to adjust the dose of medications to allow for an increase in children's weight.
 Explain that because there are few pediatric formulations, malaria tablets may be crushed and mixed with something sweet to disguise their unpleasant taste.

Pregnant and breastfeeding women
Pregnant women should defer travel to malaria-endemic areas and particularly to regions with drug-resistant falciparum malaria (15).Malaria increases the risk of maternal and neonatal death, miscarriage and stillbirth.Low birth-weight infants are more commonly born to women taking ineffective prophylaxis (15).Discuss the benefits and risks of atovaquone-proguanil after the first trimester in women who cannot avoid travel to mefloquine-resistant areas or who cannot take mefloquine (20,21); o Although safe in pregnancy, the combination of chloroquine and proguanil is inadequate as an antimalarial and cannot be recommended for chloroquine-resistant areas (22); o Doxycycline is contraindicated during pregnancy.
Nursing women should continue to breastfeed if using chemoprophylaxis that is safe in infancy (chloroquine, mefloquine, atovaquone-proguanil in infants weighing  5 kg).Doxycycline absorption through breast milk is probably negligible, and breastfeeding is not an absolute contraindication to maternal use (23).

Migrants
Although in most cases disease will develop within three months of last exposure, malaria could be the reason for any fever that develops within 12 months of leaving a malaria-endemic region (24).The risk of malaria exists for migrants after their arrival in Canada:  For at least 12 months after migrants arrive in Canada, test for malaria in cases of unexplained fever. Consider malaria screening in asymptomatic new migrants from highly endemic areas, and treat those with parasitemia (apart from the presence of gametocytes only) in blood smears. Ask migrants from malaria-endemic countries about future travel plans to provide anticipatory guidance about malaria (25).

Long-term travellers, expatriates and visiting friends and relatives
Recommendations for preventing malaria in long-term travellers (travel for longer than one month), expatriates or visiting friends and relatives are very similar to the standard recommendations for the short-term traveller (26): use prescribed malaria chemoprohylaxis and PPM consistently, including insecticide-treated bed nets and topical repellents containing 20%-30% DEET or 20% icaridin.
Some of the topics to cover when counselling expatriates and long-term travellers about malaria prevention include the following:  Possible concern about safety with prolonged use of chemoprophylaxis medication. Use of PPM over the long term. Cost of medication over the long term.
 Use of locally procured and possibly counterfeit drugs.
 Conflicting counsel about chemoprophylaxis and self-treatment.
 Need for ongoing adherence to chemoprophylaxis.
Since overall nonadherence rates for chemoprophylaxis are as high as 61% (27), pre-travel advice should focus on these aspects:  Malaria symptoms and risk, emphasizing the need for early diagnosis and treatment. Development of a plan for accessing competent medical care in case of illness. Standby emergency therapy (self-treatment).
 The affordability of chemoprophylaxis. The likelihood that local malaria drugs are counterfeit (28).
 The loss of partial immunity among visiting friends and relatives because of residence in a country without malaria (25).
The risk of malaria among visiting friends and relatives is almost the same as for local residents, but the risk of severe disease is higher because of loss of partial immunity after having lived in a non-endemic area (25).
VFRs tend to show certain characteristics: Reliance on advice from family members or local providers at their destination (25,27,28,32,33).
 Stay in rural locations (with higher rates of malaria transmission than urban centres) and for longer visits (25). Stay with local family members rather than in air-conditioned and well-screened hotels (25). Travel with their Canadian-born children (25). Make last-minute emergency travel plans (25).

Table 1: Evidence-based medicine recommendations for malaria prevention and treatment in special hosts
Recommendation EBM rating*

1.
Young children should avoid travel to areas with significant malaria transmission, particularly of chloroquine-resistant malaria (6).

2.
All children who travel to malaria-endemic areas should use PPM (7).A I
A I

4.
Primaquine chemoprophylaxis may be suitable for children who cannot take any of the first-line prophylactic agents, after confirmation of G6PD status (13).

5.
Pregnant women should avoid travel to areas with significant malaria transmission (15).C III

6.
Pregnant women who travel to malaria-endemic areas should use PPM, including appropriate topical repellents and insecticide-treated bed nets (16).
A I

7.
In chloroquine-sensitive areas, pregnant women should use chloroquine as chemoprophylaxis.A I

8.
Where exposure to chloroquine-resistant falciparum malaria is unavoidable, pregnant women should use mefloquine from conception through the first trimester (A II) and during the second and third trimesters (A I) (17)(18)(19).
A II, A I Recommendation EBM rating*

9.
There are no currently approved antimalarials for pregnant women travelling to mefloquine-resistant regions.Atovaquone-proguanil after the first trimester may be considered after careful discussion of the benefits and risks (20,21).

10.
Although safe in pregnancy, the combination of chloroquine and proguanil is inadequate as an antimalarial and cannot be recommended for chloroquine-resistant areas (22).

E I
Breastfeeding women

11.
Infants should receive their own appropriate chemoprophylaxis even if breastfed (23).A III

13.
Limited data suggest that doxycycline absorption through breast milk is negligible and that breastfeeding is not an absolute contraindication to maternal use (23).
C III

14.
For at least 12 months after migrants arrive in Canada, test for malaria in cases of unexplained fever.

15.
Consider malaria screening in asymptomatic new arrivals from highly endemic areas, and treat those who have parasitemia (apart from the presence of gametocytes only) in blood smears.

16.
Ask migrants from malaria-endemic countries about future travel plans.Doing so may provide the opportunity for anticipatory guidance about malaria (25).

C III
Long-term travellers or expatriates

17.
Guidelines for preventing malaria in long-term travellers or expatriates should not deviate considerably from the recommendations for short-term travellers (26).

18.
Training long-term travellers in the use of rapid diagnostic tests is reasonable (26,34).C III

19.
For long-term travellers who are more likely to buy drugs in countries without quality controls, provide education about counterfeit antimalarial medications (35)(36)(37).
C II

A I
Visiting friends and family (VFRs)

21.
Inform Canadian VFRs travelling to malaria-endemic countries about the risk of malaria, including the loss of partial immunity from living in Canada and the increased risk of severe disease in children and pregnant women (25).

23.
Discuss the affordability of chemoprophylaxis with Canadian VFRs travelling to malaria-endemic countries, taking cost into account in deciding about choices (25).

C III
Travellers with co-morbidities

24.
Individuals who are immunosuppressed or have co-morbidities should consult with a travel medicine or infectious disease expert (40).

25.
Potential drug interactions and overlapping toxicities warrant careful review before antimalarial drugs are prescribed for people with chronic medical conditions, including HIV infection (41).
A I

26.
HIV-infected individuals who are pregnant or have advanced immune suppression should be encouraged to choose non-malaria endemic locations or defer travel until after pregnancy or restoration of immune function.

27.
Provide standby antimalarial therapy for travellers with asplenia who may experience delays in accessing appropriate care for febrile illness.

28.
A pre-travel trial with INR (international normalized ratio) testing should be done if mefloquine, doxycycline or proguanil (including atovaquone-proguanil) are to be used by people taking warfarin A II Recommendation EBM rating* (42)(43)(44)(45).

29.
Avoid chloroquine and mefloquine in the presence of a chronic seizure disorder.E II

30.
Avoid chloroquine and mefloquine for travellers with myasthenia gravis.E III

31.
Carefully review mental health history before prescribing mefloquine to ensure that psychotic, depressive or anxiety disorders are absent (46).
A I

32.
Chloroquine may exacerbate psoriasis.Mefloquine, doxycycline and atovaquone-proguanil are preferable to chloroquine in patients with underlying psoriasis.

33.
Primaquine should not be used as chemoprophylaxis in the presence of G6PD deficiency.E II

34.
Atovaquone-proguanil may be the preferred choice for malaria prophylaxis in the presence of porphyria.

Long-term safety of chemoprophylaxis and PPM
Long-term use of chemoprophylaxis recommended for short-stay travellers does not result in additional risk of severe adverse events although data on the effectiveness and tolerance of recommended regimens are limited.Table 2 summarizes the safety of chemoprophylaxis with long-term use.

Chloroquine
Requires an ophthalmologic examination at least every 2 years (30).However, chloroquine is seldom indicated because of extensive drug resistance.
Mefloquine tolerance improves over time, possibly because any adverse events become apparent relatively early (47).Consequently, there does not appear to be increased risk with long-term use (28).

Atovaquone-proguanil
Although data on prolonged use of atovaquone-proguanil are limited, the individual components have been used for extended periods (30).

Doxycycline
Although data are limited, the drug and the related minocycline have been used for extended periods for other indications (31).
Currently, no long-lasting, insecticide-treated nets are registered for use in Canada.Insecticide-treated bed nets can be obtained from some Canadian travel health clinics and other domestic and international suppliers (8):  The insecticide in most bed nets starts to lose its effect after six months (8). Liquid permethrin used to treat bed nets is not available in Canada. Travellers should renew the insecticide treatment of their bed nets at the start of rainy seasons.

Counterfeit drugs
Many expatriates and long-term travellers may have the opportunity to buy their antimalarial chemoprophylaxis and antimalarial drugs over the counter at local pharmacies where they are staying and cannot evaluate the authenticity of these drugs.Encourage all travellers and expatriates to buy a supply of medication in countries with strict quality control measures (35)(36)(37).
If travellers are buying outside of Canada bear in mind the following:  Coartem® (artemether-lumefantrine) is not yet licensed for distribution in Canada but is recommended by the World Health Organization as first-line treatment for P. falciparum malaria.Travellers should buy it in Europe, the USA or other countries where counterfeiting is unlikely (39). Atovaquone-proguanil prophylaxis may be too expensive for most long-term use.Long-term travellers and expatriates may choose to purchase enough for one or two self-treatment courses (51).

Rapid diagnostic tests
Rapid diagnostic tests are essential diagnostic tools when malaria microscopy results are not available within two hours (26).Rapid diagnostic tests are simple to use, require no equipment or specialized laboratory skills and can be valuable adjuncts in diagnosing malaria (52).However, many travellers are unable to complete the procedures or interpret the results correctly (26,53,54).Without adequate training of laboratory staff, the usefulness of Rapid diagnostic tests may be no better among expatriates (34,55).Nevertheless, key members of a reasonably stable expatriate community could be trained in their use and in administration of appropriate selftreatment (26,34).

Standby emergency self-treatment
Self-treatment is a temporary, life-saving measure for 24 hours while medical attention is sought.Travellers to high-risk regions should never rely exclusively on self-treatment (40,(56)(57)(58).Self-treatment regimens by region are summarized in Table 3.
Reasons for self-treatment include travelling/staying in these areas:  Sub-Saharan Africa, where 90% of global malaria morbidity and mortality occurs.
 Remote regions where access to health care is a problem. Regions where malaria risk is small and self-treatment is preferable to long-term prophylaxis (26,28,56,59).
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.

Terminal prophylaxis
P. vivax and P. ovale parasites can persist in the liver and cause relapses for as long as five years after the person has left a malaria-endemic area.Primaquine anti-relapse therapy (PART) decreases the risk of relapses by acting against the liver stages of P. vivax and P. ovale.PART is usually administered during or after the last two weeks of chemoprophylaxis to those who have been in malaria-endemic regions (most malarial areas of the world except Haiti and the Dominican Republic) (26,38,39,64).Primaquine is contraindicated for use as PART in people with G6PD deficiencies, in pregnancy and in nursing mothers if the infant is G6PD deficient.

Travellers with co-morbidities
Interactions between malaria and other underlying medical conditions may result in increased susceptibility to and severity of malaria or complications of the underlying conditions.Some underlying health conditions may be exacerbated by or preclude using one or more antimalarial medications.
Routinely undertake a drug interaction check to avoid any potential adverse drug interactions unless the traveller's medications are known to be safely used with the proposed antimalarial agent.

Immunocompromised hosts
Immunocompromised travellers should carefully adhere to both PPM and chemoprophylaxis.

HIV/AIDS
There is a significant and complex interaction between human immunodeficiency virus (HIV) and P. falciparum.Assess for drug interactions, and consider the risk of overlapping adverse effect profiles (65).CATMAT recommends consulting with a travel/tropical medicine/infectious disease expert and the traveller's HIV specialist (40).

Asplenia
Asplenia increases the risk, magnitude and duration of parasitemia, even among partially immune individuals in malaria-endemic countries (41), and enhances the risk of severe and fatal malaria in travellers with this condition (66).Recommend standby self-treatment in addition to prophylactic measures if the traveller is heading to remote regions and/or access to care is limited.Since fever may be due to malaria or bacterial infection, provide antibacterial standby treatment (67).

Other conditions
A list of other conditions and their effects on the choice of malaria chemoprophylaxis are summarized in Table 4.

Abnormal coagulation
Mefloquine, doxycycline and proguanil may potentiate warfarin (42)(43)(44)(45)68).Conduct a medication trial several weeks in advance of travel and International Normalized Ratio (INR) serial testing to allow adjustment of the anticoagulant dose both before and after travel.

Seizure disorders
Chloroquine and mefloquine may exacerbate seizures, so prescribe alternative agents.There is no evidence that febrile seizures in children are a contraindication for these drugs.Concurrent use of anticonvulsant drugs that induce hepatic microsomal enzymes (e.g.barbiturates, phenytoin, carbamazepine) may decrease serum levels and the half-life of doxycycline, and may require dosage adjustment (45).

Myasthenia gravis
Malaria infections may exacerbate myasthenia gravis.Optimal prevention through adherence to chemoprophylaxis and PPMs should be reinforced.Avoid chloroquine, mefloquine and doxycycline as they have been associated with worsening of myasthenic symptoms.Doxycycline may be considered in stable patients, particularly for those with only ophthalmologic symptoms, though CATMAT recommends a pre-travel therapy trial.A pre-travel trial of atovaquone-proguanil therapy is recommended, since proguanil monotherapy has been reported to worsen myasthenic symptoms (69).
Primaquine has not been associated with myasthenic symptoms and may be an option for P. falciparum prophylaxis (after ruling out G6PD deficiency) in myasthenic travellers who are unable to tolerate doxycycline and atovaquone-proguanil.

Psychiatric disorders
Assess for history of depression, generalized anxiety disorder or psychosis before prescribing mefloquine (46,70).Dose-related neuropsychiatric adverse effects are well recognized with mefloquine and to a lesser extent with chloroquine (71,72).

Hepatic or renal dysfunction
Moderate to severe hepatic or renal dysfunction may alter antimalarial medication levels.*If necessary, consult with a travel/tropical medicine expert.

Psoriasis
Avoid chloroquine as it may trigger acute flares of psoriasis (73,74).

Glucose-6phosphate dehydrogenase (G6PD) deficiency
Primaquine is associated with a potentially life-threatening risk of hemolysis.Although G-6PD deficiency is raised as a concern by the manufacturers of chloroquine, experts do not consider this a contraindication, since significant hemolysis is unlikely at prophylactic doses.

Porphyria
Apart from atovaquone-proguanil ( 75), all the first-line malaria chemoprophylactic agents may be porphyrinogenic.Use with caution.* See Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers, Table 5.4.3:Antimalarial drug considerations for people with renal or hepatic disease.

Conclusion
Special groups of travellers require additional information for prevention and management of malaria.In addition, they should recognize the importance of adherence to recommendations for chemoprophylaxis and PPM.Treatment varies according to the species of Plasmodium, the severity of disease and the region where the malaria was acquired, as well as potential interactions between chronic medications and recommended antimalarial therapy.
Be less likely to seek out or comply with preventive travel health advice (29-31), possibly because of o Financial or time restrictions (25); o Misconceptions about risk of disease and immunity; oro Evidence-based medicine.The EBM ratings are as follows: Strength of recommendation: A = Good evidence to support a recommendation for use B = Moderate evidence to support a recommendation for use C = Poor evidence to support a recommendation for or against use D = Moderate evidence to support a recommendation against use E = Good evidence to support a recommendation against use Quality of evidence: I = Evidence from at least one properly randomized, controlled trial II = Evidence from at least one well-designed clinical trial without randomization; from cohort or case-controlled analytic studies, preferably from more than one centre; from multiple time series; or from dramatic results in uncontrolled experiments III = Evidence from opinions of respected authorities on the basis of clinical experience, descriptive studies or reports of expert committees.