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Malaria prevention advice for the traveller: part one

Caroline Turner
MBBS BSc MRCP DIPGUM
Clinical Research Associate

Jane Zuckerman
MD FRCP (Ed) FRCPath FFPM
Senior Lecturer and Honorary Consultant

The Academic Centre for Travel Medicine and Vaccines
WHO Collaborating Centre for Reference, Research and Training in Travel Medicine
London

The majority of cases of malaria in the UK arise in travellers visiting friends and family abroad. This article explores the issues around malaria protection to enable a reduction in the incidence of this preventable infection

In 2009 there were 1,495 cases of malaria in the UK of which there were six deaths.1 The majority of cases were in travellers visiting friends and family abroad. All these cases would have been avoidable if travellers had sought pre-travel advice and armed themselves with the ABCD rule of malaria protection. Throughout this article we shall be referring to the Heath Protection Agency (HPA) guidelines written in association with the Advisory Committee of Malaria Prevention (ACMP) and the National Travel Health Network and Centre (NaTHNaC).2,3

Malaria is one of the leading causes of death in the developing world. There are an estimated 860,000 deaths annually, with 16% of child deaths in Africa due to malaria.4 Malaria is currently endemic in over 100 countries that are visited by more than 125 million international travellers every year, 56 million of whom are from the UK alone. Between 2005 and 2009, an average of 1,600 cases of malaria were reported annually in travellers returning to or arriving in the UK from malaria endemic countries, the UK is one of Europe's largest importers of the disease.5 Of these cases, there were between five and 15 deaths reported each year.

In 2009, there were 1,495 malaria cases reported, with six deaths. A total of 79% of cases were caused by P falciparum, the severe form of malaria of which the majority (64%) were acquired in West Africa. Of those travellers that were resident in the UK and who gave a reason for travel, 69% (502/728) were visiting friends and family (VFR).

Every traveller who visits a malaria endemic country is at risk of contracting the disease. This includes migrants visiting their friends and family back in their country of birth. Any immunity they may have had disappears very quickly on migration and their children born in the UK will have no protection at all.
How can travellers protect themselves?
Follow the ABCD rule:

  • Awareness of the risk.
  • Bite avoidance strategies.
  • Malaria chemoprophylaxis.
  • Seeking medical diagnosis and treatment when unwell.

Awareness of the risk
Malaria is the serious clinical consequence of infection with a parasite called plasmodium. There are currently five species of plasmodium: P falciparum (the most serious), P vivax, P ovale, P malariae and P knowlesi. The parasite is transmitted via the bite of the female anopheles mosquito. Very rarely, transmission can occur via blood transfusion, intravenous needle sharing, organ transplantation or congenitally (from mother to the foetus).

The global burden of malaria is demonstrated by Figure 1, which clearly illustrates the worldwide distribution of malaria. The risk to which the traveller may be exposed varies from person to person (young age, pregnancy and HIV co-infection all increase the risk of severe malaria), and region to region even within the same country (for example, low risk in Western Malaysia and high risk in Eastern Malaysia).

[[Fig 1 Malaria]]

It is especially important that a detailed travel history is carried out making special reference to the traveller's itinerary, including specific cities, types of accommodation, season and style of travel. In addition pregnancy, past medical history and the presence of multi-drug resistant malaria at the destination may modify the risk assessment from low to high risk even within the same country.

The highest risk apart from geographical region applies to travellers visiting friends and relatives (VFR). These travellers specifically should be reminded that previous infection does not confer protection and that they are at risk of re-infection and preventive measures are still necessary.

Exposure to malaria is dependent on the number of bites sustained by the traveller from an infected anopheles mosquito. This can be affected by the following issues:

  • Climate. Humid and warm conditions (20-30°C) favour malaria transmission. Rainfall increases mosquito breeding; however, altitudes greater than 2,000 m prevent parasite maturation.
  • Rural location. The prevalence of malaria is higher in rural locations than in urban locations. It has been shown that the transmission of malaria in African villages was eight times higher than that in African towns; however, the risk of contracting malaria in Africa or other endemic countries must not be ignored.6
  • Accommodation. A bed net impregnated with permethrin should be used unless the traveller is staying in air-conditioned accommodation with the windows and doors tightly sealed to prevent mosquito entry. Backpackers staying in basic accommodation have a higher risk of being bitten compared with travellers staying in air-conditioned accommodation. Travellers should, therefore, arm themselves with protective bite avoidance measures before their departure.
  • Length of stay. The longer the stay the higher the risk of being bitten and consequently the greater the risk of contracting malaria.
  • Activity. The female anopheles mosquito bites between dawn to dusk; therefore, activity during this time increases the risk of acquiring malaria. Bite avoidance measures should be observed fully during this time.

What makes the individual more at risk of acquiring malaria?
Pregnancy
Infection in pregnant women can be more severe and, consequently, life threatening both for mother and foetus. Malaria in pregnancy is associated with an increased incidence of severe malaria with maternal death and adverse pregnancy outcomes, such as miscarriage, stillbirth and low birth weight, with associated risk of neonatal death.

In a pregnant woman the malaria parasite can sequester in the placenta, giving rise to false negative malaria films or a falsely low parasitaemia. It is for these reasons that travel to a malaria endemic country should be avoided. If it is unavoidable there are limitations with current chemoprophylaxis due to possible teratogenic effects, eg doxycycline. Specialist travel health advice should be sought and strict observance of bite avoidance measures should be emphasised.

The immunocompromised
Children. Infants are more at risk of severe malaria due to their immature immune systems, their inability to communicate their symptoms and atypical clinical presentations. Life-threatening complications can occur within hours of the initial symptoms. Bite avoidance strategies are particularly important in this group. Parents should be advised not to take infants or young children to areas with a risk of P falciparum malaria or, at the very least, give very careful consideration to taking young infants and seek specialist travel health advice.

Older people. Older people are at particular risk of malaria due to their likely co-morbidities (such as diabetes and renal dysfunction). Chemoprophylaxis may be challenging with the need for dose modification (renal/hepatic dysfunction) and the exclusion of some antimalarials due to drug interactions eg. warfarin and proguanil.

HIV infection. Coinfection with malaria is associated with an adverse outcome in patients in Africa.7 It is associated with progression of HIV infection and increased incidence of severe malaria, treatment failure and death. Recent data have suggested an interaction with common antiretrovirals and atovaquone/proguanil and mefloquine.8 It is not known whether this has a clinical effect or not and further research in this area is needed to clarify this. When prescribing chemoprophylaxis, or indeed any medicine, it is important to check for any drug interactions with antiretrovirals that could impact upon the travellers HIV treatment and hence prognosis.
Asplenia/steroids/immunomodulators. By definition, an impaired immune system increases the risk of severe disease. Particular attention should be paid to immunomodulatory drugs, such as prednisolone, azathioprine, tacrolimus and ciclosporin. It is vital that such travellers have comprehensive antimalarial protection and adhere to bite avoidance strategies.

Bite avoidance strategies
The mosquito that transmits malaria tends to bite more often at night, making bed net protection especially important.

Repellents
DEET (N, N-diethyl-m-toluamide) has been used for over 50 years and there are no data to suggest that it is unsafe, even if used in infants over two months of age for a prolonged time.
The duration of protection is dependent on the concentration of the product; for example, 20% DEET should be reapplied after one to three hours and 50% DEET every 12 hours. There is no benefit in duration of action for higher concentrations.

Sunscreens with DEET incorporated should not be used as reapplication in accordance with sun exposure protection can lead to DEET overexposure. However, they can be used together in different preparations. Sunscreen should be applied first with DEET afterwards, as if DEET is used first it can reduce the efficacy of sunblock; however, sunscreens do not reduce the effectiveness of the DEET.9

A study analysing the safety of DEET in pregnancy showed that the use of 20% DEET in the second and third trimesters of pregnancy was not associated with adverse events in infants from those pregnancies followed up for 12 months after birth.10 Malaria prevention in pregnant women is paramount since it is this group with the highest morbidity and mortality. With this in mind, the Advisory Committee of Malaria Prevention (ACMP) recommends the use of DEET up to 50% concentration, including for pregnant women in the first trimester. In addition, DEET can be used in breastfeeding mothers, and in children and infants over two months of age. DEET less than 20% is not recommended.

Lemon eucalyptus is a natural alternative to DEET and gives about the same protection as 15% DEET. The duration of protection of eucalyptus, however, is less than DEET and so should be reapplied more frequently.

Insecticides
Permethrin is used as a knock down spray/vapouriser to kill resting mosquitoes in a room. It can be used as outlined below.
Bed nets. Bed nets impregnated with permethrin (or other synthetic pyrethroids) should be used if sleeping in areas with no screen protection. Their effectiveness increases if the net is tucked in under the mattress, free of tears and re-impregnated every six to 12 months. There are newer bed nets available with permethrin incorporated into the material with the aid of a resin, which give it a use life of three to five years, eliminating the need to re-impregnate.
Clothing. Travellers should wear long-sleeved, loose clothing, long trousers and socks if outside after sunset to minimise accessibility to biting mosquitoes. Clothing may be impregnated with permethrin or, alternatively, if clothing is cotton, it can be sprayed with DEET and worn afterwards. Care must be observed with DEET and synthetic materials including nail varnish and sunglasses.
Room protection. Before dusk a knock-down insecticide should be sprayed into the room to kill any mosquitoes that may have entered the room during the day. Fine mesh screens on all doors and windows should be closely fitted and free of tears, and during the night a synthetic pyrethroid vaporiser should be plugged in if electricity is available and reliable. However, it should be noted that efficacy is reduced if a window is open and vaporisers do not work with air conditioning. Air conditioning itself reduces the likeliness of mosquito bites by reducing the night-time temperature, and ceiling fans can also help.

What is not recommended?
Picaridin (KBR3032) is reported to have the same repellent properties as DEET if used at a minimum concentration of 20% and Citronella does have some repellent properties; but these are short lived. The ACMP and the Faculty of Homeopathy strongly advise against the use of homeopathic remedies and their use is unlikely to be accepted by insurance companies.2 There is no clinical evidence for the effectiveness of herbal remedies, buzzers emitting high frequency sound waves, vitamin B12, garlic, spreads such as Marmite, tea tree oil and other bath oils and, consequently, the ACMP strongly advises against their use. 

References

  1. Health Protection Agency (HPA). Imported malaria cases and deaths, United Kingdom: 1990-2009. Available from: www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Malaria/Epidemiolo...
  2. Chiodini P, Hill D, Lalloo D, Lea G, Walker E, Whitty C, Bannister B. Guidelines for malaria prevention in travellers from the United Kingdom 2007. London: Heath Protection Agency; 2007. Available from: www.hpa.org.uk/web/HPAwebFile/HPAweb_C/120349694352
  3. National Travel Health Network and Centre (NaTHNaC). Health Information for Overseas Travel (the “Yellow Book”) 2010. London: NaTHNaC; 2010.
  4. World Health Organization (WHO). International Travel and Health 2010. Geneva: WHO; 2010.
  5. Health Protection Agency (HPA). Malaria. Available from: www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Malaria
  6. Hay SI, Guerra CA, Tatern AJ, Atkinson PM, Snow RW. Urbanization, malaria transmission and disease burden in Africa. Nat Rev Microbiol 2005;3:81-90.
  7. Whitworth J, Morgan D, Quigley M et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet 2000;356:1051-6.
  8. Van Luin M, Van der Ende ME, Richter C et al. Lower atovaquone/proguanil concentrations in patients taking efavirenz, lopinavir/ritonavir or atazanavir/ritonavir. AIDS 2010;(24)8:1223-6.
  9. Montemarano AD, Gupta RK, Burge JR, Klein K. Insect repellents and the efficacy of sunscreens. Lancet 1997;349:1670-1.
  10.  McGready R, Hamilton KA, Simpson JA et al. Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy. Am J Trop Med Hyg 2001;65:285-9.