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Malaria is a serious illness causedby infection with one of five

species of Plasmodium. There areapproximately 2000 cases of malariareported to Public Health England (PHE)and an average of nine deaths eachyear in the UK.1 Approximately 75 percent of these infections are caused byP. falciparum, which is associated withmore severe disease than other speciesand is responsible for almost all fatalcases.

Although malaria is easy to treat,delayed diagnosis as a result of low diag-nostic suspicion and difficulty accessingtesting facilities has probably con-tributed to the mortality that is seen inimported cases in the UK and, for thisreason, strategies that focus on preven-tion of malaria are particularly importantin travellers to endemic countries. Thetwo main interventions aim to protecttravellers by preventing mosquito bitesand to kill malarial parasites with chemo-prophylaxis before they can establishclinical infection.

The risks of acquiring malariaFigure 1 is a world map of malariaendemicity, showing the proportion ofchildren positive for P. falciparum at anyone time.2 It provides an overview of theburden of disease in endemic communi-ties, which is one of the most importantfactors when considering the risk posedto a traveller.

The risk of acquiring malaria, how-ever, also varies with geography, seasonand type of travel. Conditions that favourmosquito breeding and thereforemalaria transmission are high humidity,standing water and an ambient temper-ature in the range 20–30°C.3 Malariatransmission does not occur in regionswith ambient temperatures below 16°Cor at altitudes greater than approxi-mately 2000 metres. Malaria is verymuch more common in rural rather thanurban areas.4 Individuals staying in poor-quality accommodation are more likelyto be bitten than those in air-conditionedhotels and the risk is increased in thoseoutdoors between dusk and dawn.

Malaria prophylaxis: guidance for general practiceAlastair McGregor MSc, MRCP, FRCPath

Strategies that focus on theprevention of malaria areimportant in travellers toendemic countries. Here, theauthor describes the vitalrole of the GP in educatingtravellers on malaria risk andprevention and providingprophylactic medicationswhere appropriate.

SPL

Managing the risk of malariaDetermining the risk posed to a traveller,and balancing these risks with the costand side-effects of prophylaxis, is animprecise art and needs to be tailoredto individual circumstances. Guidelinessuch as PHE’s Guidelines for MalariaPrevention in Travellers from the UK (seeResources) provide didactic, country-specific advice but it is important thatthese recommendations are not seen asrules and that the assessment of risk toa traveller includes consideration of allthe factors discussed above.

Bite avoidanceBite avoidance is the first line of defenceagainst malaria. Mosquito bites can bereduced by using chemical agents thatare toxic or noxious to mosquitoes (topi-cal repellents, insecticide-containingcoils or vapourisers and knock-downinsecticidal sprays) or methods thatphysically prevent contact between mos-quito and skin (nets, long clothing,closed windows).

The most effective topical repellentis DEET (N,N-diethyl-m-toluamide), whichhas been in use as an insect repellentfor more than 50 years and is usedsafely by 200 million people each year.5

A wide variety of formulations and con-

centrations of DEET are available. In gen-eral, the duration of protection frombites is a function of the concentrationof DEET and, as a guide, concentrationsof 20 per cent will give one to threehours of protection while 50 per cent willprovide up to 12 hours.5

DEET has not been associated withadverse effects in pregnancies and maybe used at a concentration of up to 50per cent in breast-feeding and for infantsand children aged over two months.6

There is no evidence that homeo-pathic or herbal medicines preventmalaria (they may actually increase therisk by providing false reassurance).Similarly, electronic buzzers (emittinghigh-frequency sound waves) do notrepel mosquitoes, and commonly sug-gested ‘repellents’ such as vitamin B1

and B12, garlic, yeast extract (Marmite)and tea tree oil have never been shownto be effective.7

ChemoprophylaxisSporozoites introduced into a humanwhen a mosquito bites enter liver cellsand develop into merozoites within fiveto seven days. These are released intothe bloodstream and infect erythro-cytes. Once inside the red cell, themalaria parasite grows and divides over

24 hours (P. knowlesi), 48 hours (P. fal-ciparum, vivax or ovale) or 72 hours (P.malariae). Infected cells burst, releas-ing new merozoites to infect other ery-throcytes.

Chemoprophylaxis of malaria may becausal (drugs that are active against theprimary liver stage of malaria) or sup-pressive (active only against the bloodstages). Causal prophylaxis needs to becontinued for seven days after exposureto malaria but suppressive prophylaxisneeds to be continued for a month afterexposure because it is only activeagainst parasites that have emergedfrom the liver.

The emergence of drug resistancehas complicated the practice of malariachemoprophylaxis in the past fewdecades. Chloroquine resistance is nowwidespread in P. falciparum and thisdrug can only be recommended in areaswhere P. vivax (but not P. falciparum) isprevalent (the Middle East and CentralAmerica). For areas where resistant P.falciparum is a risk, prophylaxis with ato-vaquone-proguanil, mefloquine (Lariam)or doxycycline is recommended.7 Thecharacteristics of these drugs are sum-marised in Table 1.

Of the three, atovaquone-proguanilis the only causal prophylactic. It is more

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70%

0%

P. falciparum free

PfAPI <0.1%

PfPR2–10

Figure 1. World map of malaria endemicity for children (P. falciparum) in 2010; PfAPI = areas of no risk and unstable risk, PfPR2–10 = P. falci-parum parasite rate in 2–10 year olds; after reference 2

than 90 per cent effective against falci-parum malaria8 and side-effects are veryuncommon but it is, unfortunately,expensive and not recommended inpregnancy.9 The protective efficacy ofatovaquone-proguanil is at least 90 percent10 and currently resistance is onlyconsidered a problem in some areas ofsouth-east Asia.11 Atovaquone-proguanilis only taken weekly and is well toleratedby the great majority of individuals whotake it.10 There is some evidence thatatovaquone-proguanil use may increasethe risk of psychosis and anxiety reac-tions and its use is contraindicated inthose with a psychiatric history.12

The efficacy of doxycycline is similarto atovaquone-proguanil.13 It is generallywell tolerated but can be associated withphotosensitivity, gastro-oesophagitis and

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Table 1. Characteristics of the three main antifalciparum chemoprophylactic agents in current use, as well as chloroquine-proguanil

Drug Doxycycline Atovaquone- Mefloquine Chloroquine-proguanil proguanil

Frequency daily daily weekly daily – proguanilweekly – chloroquine

Efficacy against >90% >90% >90% unreliableP. falciparum

Resistance rare rare pockets of SE Asia widespread resistance inP. falciparum; mostnonfalciparum strainsremain sensitive

Children contraindicated if paediatric suspension dose adjustment but no dose adjustmentage <12 years paediatric formulation

Pregnancy contraindicated recommended to avoid safe not contraindicated butunless after first benefit unlikely totrimester and high risk resistance is widespread;of malaria proguanil should be

taken with folatesupplement

Breast feeding BNF recommends to avoid – may be used if safe safeavoid, American no alternativeAcademy of Pediatricsstates that risk isacceptable17

Notable adverse gastro-oesophagitis headache slightly increased risk of chloroquine mayreactions photosensitivity generally very well psychiatric events exacerbate myaesthenia

vaginal candidosis tolerated gravis and psoriasis

Resources for Guidance for Malaria Prophylaxis

This article is not supposed to provide definitive advice but merely an overview of therationale and strategies for the prevention of malaria. The following resources providemore detailed and country-specific advice for GPs and travellers.

Public Health England: Guidelines for malaria prevention in travellers from the UnitedKingdom 2013 Available from www.hpa.org.uk

National Travel Health Network and Centre (NathNaC)Telephone advice for health professionals. Tel: 0845 602 6712.www.nathnac.org/pro/factsheets/malaria.htm

HPA Malaria Reference Laboratory (MRL) (at London School of Hygiene and TropicalMedicine): www.malaria-reference.co.ukFaxed advice for complicated cases that are not covered by the guidelines: 020 7637 0248

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vaginal candidosis.14,15 Doxycycline iscontraindicated in children under 12and pregnant and breastfeeding women.

The role of the GPThe GP has a vital role in educating trav-ellers about the risk of acquisition ofinfections (both malarial and nonmalar-ial) while abroad, as well as offering sug-gestions (and prophylactic medications,if appropriate) as to how these risks canbe mitigated. This needs careful evalua-tion of data from a variety of resourcesand a good understanding of the travelplans so risk is managed appropriatelywithout unnecessary medication orexpense.

GPs also need to have a low thresh-old for considering acute malaria in areturning traveller with undifferentiatedfever, given the consequences thatdelayed diagnosis may have.

References1. Public Health England. Imported malariacases and deaths, United Kingdom:1994–2013. http://bit.ly/1q84DSz. 2. Malaria Atlas Project. The spatial distribu-tion of Plasmodium falciparum malariaendemicity map in 2010 globally. http:/bit.ly/1l2mChe. 3. White NJ. Malaria. In Cook GC, et al (eds.).Manson’s tropical diseases. Elsevier Science,2009;1202.4. Hay SI, et al. Nat Rev Microbiol 2005;3:81–90.5. Frances SP. Efficacy and safety of repel-lents containing DEET. In Debboun M, et al(eds.) Insect repellents. Principles, methods,and uses. CRC Press. Boca Raton, 2007;311–25.6. McGready R, et al. Am J Trop Med Hyg2001;65:285–9.7. Lalloo DG, et al. J Infection 2007;54(2):111–21.8. Nakato H, et al. J Antimicrob Chemother2007;60(5):929–36.

9. Pasternak B, et al. Arch Intern Med2011;171(3):259–60.10. Schlagenhauf P, et al. Malaria Journal2010;9:357.11. Wongsrichanalai C, et al. LancetInfectious Diseases 2002;2:209–18.12. Meier CR, et al. Drug Safety2004;27:203–13.13. Ohrt C, et al. Annals of Internal Medicine1997;126:963–72.14. Bryant SG, et al. Pharmacotherapy1987;7:125–9.15. Tan KR, et al. Am J Trop Med Hyg2011;84(4):517–31.

Declaration of interestsNone to declare.

Dr McGregor is a specialist registrar atthe Hospital for Tropical Diseases,University College London HospitalNHS Foundation Trust