Preventing malaria in travellers

Factors determining individual risk

A detailed itinerary is necessary to assess risk. The degree of transmission varies markedly between different regions, even within a country, and at different times of the year. For example, the risk of acquiring malaria in West Africa may reach 6% per month of travel but on the Kenyan coast is 1% per month; in the Kenyan capital, Nairobi, transmission is extremely low.

In addition to geographical factors, an individual’s risk depends on the time spent in the endemic area and activities undertaken: camping in a jungle for three weeks poses a much higher risk than a three day visit to an urban area with air conditioned accommodation.

Four main species of malaria parasites infect humans after the bite of an infected Anopheles spp mosquito: P falciparum, P vivax, P ovale and P malariae. P falciparum and P vivax are the most common. Falciparum malaria predominates in sub-Saharan Africa, and vivax malaria in the Indian subcontinent, Mexico, Central America, and China; both species occur in South East Asia and South America.

Groups at particular risk

Less than half of travellers who acquire malaria have taken advice before travelling. Analysis of imported malaria indicates that certain groups are at particular risk, such as those taking last minute holidays and those visiting friends and relatives abroad.7 Travellers visiting friends and relatives abroad (also known as VFR travellers) account for 70% of all of the malaria imported into the UK1; limited evidence suggests that these travellers do not think of malaria as a serious or potentially fatal disease, are less likely to consult general practitioners or travel medicine specialists, and often travel to areas of high risk such as West Africa.7 8 Using intervention strategies for travellers visiting friends and relatives—such as increasing awareness in the community, dispelling myths about immunity or subsidising antimalarials—could considerably reduce imported malaria.9

Areas where P falciparum is resistant to chloroquine

Three main drug options exist for prevention in the areas where P falciparum is resistant to chloroquine: atovaquone plus proguanil, doxycycline, and mefloquine. Some countries (such as the UK) also advocate chloroquine plus proguanil for the limited areas of low level resistance, such as parts of India and Indonesia. Randomised controlled trials show that the three main options all have similar efficacy (close to 90%) against P falciparum.15 16 Mefloquine should not be used for the limited areas of multidrug resistance, such as the rural, forested areas where Thailand has borders with Cambodia and Burma.14

Travellers must continue prophylactic regimens (except atovaquone plus proguanil) for four weeks after leaving the risk area as the drugs work by killing parasites during their development in the red blood cells (suppressive prophylaxis). The combination of atovaquone plus proguanil prevents the development of liver forms (causal prophylaxis) and therefore needs to be taken only for a week after leaving the risk area, making it ideal for short trips. However, atovaquone/proguanil is considerably more expensive than the other prophylactic regimens. P vivax and P ovale may persist as hypnozoites in the liver, and therefore infection may re-emerge many months after return (relapse) despite compliance with chemoprophylaxis.16

Areas where malaria is sensitive to chloroquine

Only Mexico and parts of Central America (areas north and west of the Panama Canal), of the Caribbean (Haiti and the Dominican Republic), of the Middle East, of North Africa, and of China have malaria sensitive to chloroquine (figure⇓ ). Chloroquine or exceptionally proguanil may be used in these regions.

Malaria transmission and drug sensitivity across the world. Adapted from Canada Communicable Disease Report. Vol 30S1. Health Canada, 2004

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Other drugs

Primaquine has been used for treating hypnozoites of P vivax and P ovale for more than 50 years. Randomised controlled trials have also shown its efficacy as a “causal prophylactic” and in preventing establishment of hypnozoites.20 In the US, primaquine has recently been recommended as second line prophylaxis. However, it is contraindicated in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and this enzyme must be checked before the drug is prescribed. Although not currently recommended in the UK, primaquine may be useful for short trips in travellers who have contraindications to other antimalarials.

Tafenoquine has similar properties to primaquine and has been shown to be effective in randomised controlled trials.21 It may be given in monthly or weekly doses and is well tolerated in individuals with a normal glucose-6-phosphate dehydrogenase level but is not yet licensed or released.

Malaria vaccine

A wholly protective vaccine for travellers will not be available in the near future. Considerable funding and research have led to a sporozoite based vaccine that has shown partial protection in African children. Nevertheless, awareness, bite prevention, and chemoprophylaxis will remain the mainstay of prevention for some time.

Pregnancy and breast feeding

Pregnant women have an increased risk of contracting malaria and of developing severe illness. If possible, they should be dissuaded from visiting risk areas. Extensive clinical experience shows that chloroquine and proguanil (with additional folate) are safe, but this combination has limited efficacy in areas where P falciparum is resistant to chloroquine. Doxycycline is contraindicated owing to its effects on skeletal development, and there are insufficient data (although no theoretical risk) for atovaquone plus proguanil. Some evidence supports the safety of mefloquine in the second and third trimesters, and it therefore remains the drug of choice for chloroquine resistance areas.6 24 Caution is needed with mefloquine in the first trimester because of limited data. DEET seems to be safe in pregnancy.13 Impregnated nets may be particularly useful for pregnant mothers.

Data are limited on the excretion of antimalarials in breast milk. Drugs that are contraindicated in pregnancy should not be taken if the mother is breast feeding. The amount of drug excreted in breast milk is insufficient to protect the infant, so separate medication is needed for the infant. Caution is needed with children at the lowest end of the weight band when both mother and child are taking mefloquine.

Children

Apart from doxycycline, all drugs can be used in children over 10 kg. Chloroquine plus proguanil can be used from birth, and mefloquine can be prescribed in those over 5 kg.6 Impregnated nets may be particularly useful for children.

Long term travellers

Long term travellers (those spending six months or more overseas) need a preventive strategy with a well tolerated regimen that will be followed consistently.25 Although few antimalarials are licensed for more than a year, this reflects a lack of controlled studies on long term use rather than evidence of harm. Knowing the epidemiological pattern of malaria and the degree of risk is also helpful in matching prevention to an individual. Continuous use of chloroquine for more than five years should be accompanied by ophthalmological screening.