Malaria

Guidelines for Malaria Prevention in Travellersfrom the United Kingdom

These practical guidelines from the Health Protection Agency AdvisoryCommittee on Malaria Prevention for UK Travellers update and combine the“Guidelines for malaria prevention in travellers from the United Kingdom for2003” and “Malaria prophylaxis for long-term travellers” in a new format. The guidelines are for use by healthcare workers who advise travellers but mayalso be of use to prospective travellers who wish to read about the optionsthemselves.

The ACMP prophylaxis guidelines are intended for UK-based visitors to malariaendemic areas and may not be appropriate for use by those residing inendemic areas.

Whilst these guidelines deal with malaria, malaria prevention is only one aspect of pre-travel advice. An overall risk assessment-based package of travel healthadvice should be provided.

These guidelines are also available on the Health Protection Agency websitewww.hpa.org.uk in topics A-Z under malaria. This site should be checkedregularly for subsequent updates.

Authorship

This guidance was written by Professor Peter Chiodini and a sub-group of theHealth Protection Agency Advisory Committee on Malaria Prevention in UKtravellers (ACMP) comprising Dr Barbara Bannister (Chair), Professor David Hill,Dr David Lalloo, Dr Gil Lea, Dr Eric Walker and Professor Christopher Whitty.

Acknowledgements

Marie Blaze and Valerie Smith (HPA Malaria Reference Laboratory) for advice on country tables and maps, Christian Statham (HPA) for drawing maps and Claire Swales (HPA) for support to the ACMP in editing and publishing the guidelines and Professor Chris Curtis and Dr Nigel Hill for advice on biteprevention.

Citation

Chiodini P, Hill D, Lalloo D, Lea G, Walker E, Whitty C and Bannister B.Guidelines for malaria prevention in travellers from the United Kingdom. London, Health Protection Agency, January 2007.

Cover Images

Travellers waiting in airport queue from Getty Images, generic tablet pack fromShutterstock and Anopheles gambiae mosquito taken by Jim Gathany/CDC.

G U I D E L I N E S F O R M A L A R I A P R E V E N T I O N I N

T R A V E L L E R S F R O M T H E U N I T E D K I N G D O M

ISBN: 0 901 144 83 5

ABBREVIATIONS

AIDS Acquired Immune Deficiency SyndromeACMP Advisory Committee on Malaria

Prevention for UK travellers BIS British Infection SocietyBNF British National FormularyCDC Centers for Disease Control

and PreventionDEET N,N diethyl-m-toluamide

(an insect repellent)EDTA Ethylene diamine tetraacetic acidFAQ Frequently Asked QuestionGP General PractitionerG6PD Glucose 6-phosphate dehydrogenase

(a metabolic enzyme)HIV Human Immunodeficiency VirusHPA Health Protection AgencyHTD Hospital for Tropical DiseasesINR International Normalized RatioIPS International Passenger SurveyIPT Intermittent Preventive TherapyLSHTM London School of Hygiene and

Tropical MedicineLSTM Liverpool School of Tropical MedicineNaTHNaC National Travel Health Network

and CentreNNRTI Non-Nucleoside Reverse Transcriptase

InhibitorMHRA Medicines and Healthcare products

Regulatory Agency MRL Malaria Reference Laboratory PI Protease InhibitorPCR Polymerase Chain ReactionPOM Prescription Only MedicineRDT Rapid Diagnostic TestRSTM&H Royal Society of Tropical Medicine

and HygieneSP Sulfadoxine/pyrimethamine SPC Summary of Product Characteristics

or ‘data sheet’UK United KingdomVFR Visiting Friends and Relatives WHO World Health Organisation

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2

Foreword 7

Chapter 1: General Issues 9

1.1 How to give the advice 11

1.2 Medical history of the traveller 11

1.3 Template for risk assessment and summary of advice given 12

Chapter 2: Awareness of Risk 17

2.1 What is malaria? 19

2.2 Life cycle 20

2.3 The malarial illness 21

2.4 Where is malaria found? 22

2.5 Level of risk of exposure to malaria and what affects it 22

2.6 Distribution of drug resistant malaria 23

Chapter 3: Bite Prevention 25

3.1 When do female Anopheles mosquitoes bite? 27

3.2 Measures to prevent mosquito bites 27

3.2.1 Repellents 27

3.2.2 Insecticides 28

3.2.3 Nets 28

3.2.4 Clothing 29

3.2.5 Room protection 29

3.2.6 Fallacies 29

Chapter 4: Chemoprophylaxis 31

4.1 Principles 33

4.2 The drugs 34

4.2.1 Chloroquine 34

4.2.2 Proguanil 35

4.2.3 Chloroquine plus proguanil 36

4.2.4 Mefloquine 36

4.2.5 Doxycycline 37

Contents



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4.2.6 Atovaquone plus proguanil 38

4.3 Dosage tables 39

4.4 Country tables 42

4.5 Popular destinations 53

4.6 Emergency Standby Treatment 54

Chapter 5: Diagnosis 59

5.1 Blood tests and how to request them 61

5.2 Rapid Diagnostic Tests (RDTs) 61

5.3 Blood film negative malaria 62

5.4 Resources for treatment advice 62

5.5 Notification 62

Chapter 6: Special Groups (Medical Conditions) 63

6.1 Smoking cessation 65

6.2 Pregnancy 65

6.3 Breastfeeding 66

6.4 Anticoagulants 66

6.5 Epilepsy 67

6.6 Glucose 6-phosphate dehydrogenase deficiency 67

6.7 Sickle Cell disease 68

6.8 Immunocompromised Travellers 68

6.8.1 Risks for transplant patients 68

6.8.2 Risks for HIV/AIDS patients 68

6.9 Liver disease 69

6.10 Renal impairment 69

6.11 Splenectomy 70

6.12 Acute porphyrias 70

Chapter 7: Special Categories 71

7.1 Children 73

7.2 Elderly travellers 74

7.3 Multi-trip travel 74

Contents



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7.4 Cruises 74

7.5 Oil rigs 75

7.6 Visits to national parks 75

7.7 Stopovers 75

7.8 Last minute travellers 75

7.9 Visiting friends and relatives 76

7.10 Students and children at boarding school 77

7.11 The long-term traveller 77

7.11.1 Risk Assessment 77

7.11.2 Chemoprophylaxis for long-term travellers 78

7.11.3 Specific considerations for women 80

7.11.4 Specific considerations for infants and older children 80

7.12 Long term visitors to the UK returning to live in

malarious parts of the world 80

7.12.1 Preventive measures appropriate to an endemic setting 82

7.12.2 Prophylaxis 82

Chapter 8: Frequently Asked Questions 83

8.1 What malaria prevention should be advised for

travellers going on cruises? 85

8.2 What alternative antimalarial drugs can be used for

India (and Sri Lanka) if chloroquine and proguanil

are unsuitable for a traveller? 85

8.3 Which antimalarial can I give to a traveller with a

history of psoriasis? 86

8.4 Which antimalarial can I give a traveller who is

taking warfarin? 86

8.5 How long is it safe to continue a course of

antimalarial tablets? 87

8.6 Which antimalarial drugs are suitable for women

during pregnancy? 88

Contents



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8.7 Which antimalarial drugs can be taken by breastfeeding

women? 89

8.8 Which malaria drugs can be given to babies and

young children? 89

8.9 What is the easiest way to calculate the correct dose of

chloroquine for babies and young children? 90

8.10 Many travellers I see intend to travel through several

areas where different anti-malarials are recommended

as they progress through their journey. How do we advise

these travellers? 90

8.11 Which antimalarial drugs can I advise for a traveller

who has epilepsy? 91

8.12 What do I advise for the traveller with Glucose 6-phosphate

dehydrogenase deficiency? 91

8.13 What do I advise people working on oil rigs? 92

8.14 What do I advise for the traveller on a stopover? 92

Chapter 9: Information Resources 93

9.1 Expert centres 95

9.1.1 Prophylaxis advice 95

9.1.2 Diagnostic advice 95

9.1.3 Treatment advice 95

9.2 Useful websites 95

9.3 Information leaflets 96

9.4 Reference list 97

Contents



6 Photograph courtesy of James Gathany, CDC



Foreword

Each year between 1500 and 2000 people are diagnosed with malaria on their return

to the UK. Anyone visiting a malarious area can become infected no matter what age

or sex or ethnic background. Malaria can kill very quickly if not diagnosed in time.

In 2005 there were 11 deaths from malaria in the UK.

However these deaths and illness are avoidable. We know that most people requiring

medical attention for malaria in the UK have not taken the correct precautions needed

for their visit. The Health Protection Agency is committed to ensuring a continuing

reduction in the risk of malaria to UK travellers by raising awareness of malaria before

people travel and helping to guide healthcare professionals in giving the best advice

available.

These guidelines from the Agency’s Advisory Committee on Malaria Prevention in UK

travellers update the 2003 advice. Both the web and book format have been designed

with the busy health care advisor in mind so that they are easy to use and give clear

simple guidance.

The general public may also find them useful to read before they visit their GP’s surgery

or a travel clinic for specific advice tailored to their needs; whether they are taking the

children to visit family in Africa or India for a month, backpacking for 6 months round

South America, taking a fortnight’s package holiday to Africa or working for a week in

the Middle East.

P R O F E S S O R PAT T R O O P C B E

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9

1 - General Issues

1.1How to give the advice. 11

1.2Medical history of the traveller. 11

1.3Template for risk assessment and summary of advice given. 12

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extend to risks from infectious agents

arising from work activities, ie risks to

non-employees. The MHSWR provide a

broad framework for controlling health

and safety at work. COSHH provides a

framework aimed at controlling the risks

from hazardous substances including

infectious agents.

Duties under Section 3 of the HSWA

6. If people working under the control

and direction of others are treated as

self-employed for tax and national

insurance purposes, they are nevertheless

treated as employees for health and

safety purposes. It may, therefore, be

necessary to take appropriate action to

protect them. If any doubt exists about

who is responsible for the health and

safety of a worker, this could be clarified

and included in the terms of a contract.

However, a legal duty under Section 3 of

HSWA cannot be passed on by means of

a contract and there will still be duties

towards others under Section 3 of HSWA.

If such workers are employed on the

basis that they are responsible for their

own health and safety, legal advice

should be sought before doing

Management of Health and Safety at

Work Regulations 1999

7. Under these Regulations the manager

of a spa pool is required to

• assess the risks in their workplace,

• use competent help to apply health

and safety legislation,

G U I D A N C E F R O M T H E H PA A D V I S O R Y C O M M I T T E E

O N M A L A R I A P R E V E N T I O N I N U K T R A V E L L E R S

• establish procedures to use if an

employee is presented with serious

and imminent danger, and

• co-operate and co-ordinate health

and safety if there is more than one

employer in a workplace.

Control of Substances Hazardous

to Health Regulations 2002

(as amended)

8. Under COSHH the manager is required

to

• assess the risks of exposure to

hazardous substances in their

workplace,

• prevent exposure or substitute with a

less hazardous substance or

process/method if possible,

• control exposure if prevention or

substitution are not reasonably

practicable,

• maintain, examine and test the control

measures, eg automatic dosing

systems,

• provide information, instruction and

training for their employees, and

• provide health surveillance of

employees if appropriate.

9. More information on COSHH in general

can be found in the COSHH Approved

Code of Practice (ACoP)4 and on

Legionella in Legionnaires’ disease: The

control of legionella bacteria in water

systems ACoP5 (L8).

1. General IssuesThe ACMP prophylaxis guidelines are intended for UK-based visitors tomalaria endemic areas and may not be appropriate for use by thoseresiding in endemic areas.

Whilst these guidelines deal with malaria, malaria prevention is only oneaspect of pre-travel advice. An overall risk assessment-based package oftravel health advice should be provided.

In these guidelines, which have been specifically developed for travellers from the UK, there are a small number of instances where the advice given differs from that in guidelines from other countries or the World Health Organisation. This is becausetravellers from the UK do not usually visit all possible localities of malaria-endemiccountries and may not visit the same localities as travellers from other countries.Many travellers from the UK who enter malaria-endemic countries are visiting friendsand relatives in localities from which people tend to migrate to the UK. They do nottherefore suffer exactly the same patterns of malaria exposure as permanent residentsor visitors from other cultures.

1.1 How to give the advice

Emphasise to the traveller the ABCD ofmalaria prevention:

Awareness of riskBite preventionChemoprophylaxisprompt Diagnosis and treatment

• Emphasise that whilst no regimen is100% effective, the combination ofpreventive measures advised will givesignificant protection against malaria.

• Make use of visual aids, especiallymalaria distribution maps and show examples of the preventivemeasures advised, such as aids to bite prevention.

• Discuss the choices ofchemoprophylaxis regimens and theirindividual advantages anddisadvantages, including cost.

• Provide the traveller with writteninformation on malaria and itsprevention. The Department of Healthhas an information leaflet available in11 different languages (see chapter 9).

1.2 Medical history of the traveller

It is essential that a full clinical history isobtained, to include current medication,significant health problems and anyknown drug allergies.

Safe and effective malaria preventionrequires a sound knowledge of themedical history of the traveller. When theirpatients seek pre-travel advice in primarycare, this information will be availablefrom their own practice records but in thecase of specialist travel clinics malariaprevention advice may be sought at thefirst attendance. The General MedicalCouncil (2001)1 states “If you providetreatment or advice for a patient, but arenot the patient's general practitioner, youshould tell the general practitioner theresults of the investigations, the treatmentprovided and any other informationnecessary for the continuing care of thepatient, unless the patient objects.”

ACMP suggests that a hand-held record ofthe malaria prevention measures advisedis given to the traveller so that they maypass it on to their GP.



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1.3 Template for risk assessment and summary of advice given

This template is suggested for use in gathering information required for riskassessment when advising on malaria prevention. It may be downloaded for use from the Health Protection Agency website at www.hpa.org.uk or adapted for theparticular circumstances of individual clinics.

Name

Age

Sex

Underlying condition:

* note first degree relatives are included in risk assessment as a precaution since riskof epilepsy and major depression is higher in first degree relatives of those in whomthese conditions have been diagnosed.

A condition in a first-degree relative may not contraindicate the use of an antimalarial,but may influence the choice of drug.

Condition Yes/No

Pregnancy Actual

Planned while on trip

Sickle cell Disease

Carrier

Thalassaemia Disease

Carrier

Epilepsy Patient

First degree relative*

Depression requiring medication

Psychosis Patient

First degree relative*

Liver disease

Renal failure

Diabetes mellitus

Cardiovascular Ischaemic heart disease

Arrythmias

Other

Immunocompromise

Psoriasis

Area to be visitedSee country tables and maps

** If the recommended regimens differ between the countries to be visited, see noteon multi-trips in chapter 7.

DestinationLengthof stay

Risk ofmalaria

Urban/rural/both

Prophylaxis advisedfrom country table**

Previous antimalarialchemoprophylactic agent taken

Describe any problems

Current medication Yes/No Comments

Antiarrhythmics

Anticonvulsants

Anticoagulants

Antiretrovirals

Corticosteroids

Oral contraceptives

Bupropion (Zyban ®)

Other

Allergies

Medication

Give details of allergies to drugs or other below



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14

Purpose of visit and type of accommodation: tick those that apply

Visiting friends and relatives Safari Backpacking

Business/work Study >6 months <6 months

House Hotel Hostel Tent

Oil Rig Cruise ship Urban Rural

Other please give details below

Advice given

Bite Prevention Please tick measures advised

Repellent Clothing spray Bed net

Coils / Electric vapourisers Insecticide sprays



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Chemoprophylaxis Warning: do NOT rely on homoeopathic or ‘natural’ antimalarial prophylaxis

Standby Emergency Medication For the vast majority of travellers standby emergency antimalarial medication isneither required nor recommended. Please undertake a risk assessment includinginformation on the distance and time away from medical facilities which apply in eachcase.

Standby emergency medication advised? Yes / No Please circle

If standby emergency medication is recommended, please tick the regimen advised

Atovaquone plus proguanil Co-artemether

Quinine plus doxycycline Quinine plus clindamycin

Standby emergency medication advice leaflet given Yes / No Please circle

AntimalarialTickregimenadvised

Dose DurationNo. pills orvolume ofsyrup

Chloroquine

Proguanil

Chloroquine/Proguanil

Mefloquine

Doxycycline

Atovaquone/Progaunil

Other (please specify)

No chemoprophylaxis

Awareness of risk including bite preventionmust still be recommended. Give advice toseek medical attention for any suspicioussymptoms (up to about a year later)

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2 - Awareness of Risk

2.1What is malaria? 19

2.2Life cycle. 20

2.3The malarial illness. 21

2.4Where is malaria found? 22

2.5Level of risk of exposure to malaria and what affects it. 22

2.6Distribution of drug resistant malaria. 23

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2. Awareness of Risk2.1 What is malaria?

Malaria is a serious febrile illness due to infection of red blood cells with a parasitecalled Plasmodium. It is transmitted by mosquitoes.

Four species of Plasmodium commonly infect humans; see table 1 below.

Mixed infections with more than one species of malaria parasite are not commonlyreported (10 in 2005).

SPECIES COMMENT NUMBER OF CASES

REPORTED IN THE UK IN

2005 OUT OF 1754

Plasmodium The most dangerous, 1338 (76%)falciparum responsible for the vast

majority of malaria deaths worldwide

Plasmodium vivax A relapsing malaria 258 (15%)See life cycle

Plasmodium ovale A relapsing malaria 116 (7%)See life cycle

Plasmodium The species least 29 (2%)malariae commonly seen

in the UK.May present with late recrudescence after many years

P L A S M O D I U M S P E C I E S W H I C H I N F E C T H U M A N STA B L E 1

2.2 Life cycle

An infected mosquito inoculates 10 to 15 sporozoites when it bites. Eachsporozoite introduced into a human andsuccessfully entering a liver cell developsin the case of P. falciparum in five toseven days into a schizont containingapproximately 30,000 offspring(merozoites) which are released into thebloodstream when the schizont ruptures.Each merozoite has the potential toinfect a red blood cell. Once inside thered cell, the malaria parasite grows anddivides over 48 hours (P. falciparum, vivaxor ovale) to 72 hours

(P. malariae) to form between 8 and 32parasites whereupon the red cell bursts torelease them to infect new red cells.These cycles in the red cells continue,increasing the numbers of parasites in theinfected person and leading to clinicalillness. Some parasites in the red cells donot divide but form sexual stages(gametocytes) which mate if taken up bya biting female mosquito and thuscomplete the malaria life cycle. Figure 1shows the points in the life cycle at whichantimalarial preventive measures aretargeted.

Hypnozoites'awake'

and become schizonts(months after exposure)

Vivax and ovalemalaria also have a

dormant (hypnozoite)stage in the liver

Parasites releasedto invade and develop

in red blood cells

Parasites developto sporozoite stage

in mosquito

Parasites multiply inred blood cells

leading to clinical illness

Some do not multiply but become gametocytes to be

taken up by mosquitos

Taken upby the liver

'Causal' prophylaxisacts here

'Suppressive' prophylaxisacts here

Schizont inthe liver

Sporozoitesinjected

Biteprevention

All 4 species develop in the liver



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T H E M A L A R I A L I F E C Y C L E

The places in the life cycle targeted by the various preventative measures are shown.

F I G U R E 1

MOSQUITO



2.3 The malarial illness

Malaria can neither be confirmed norexcluded by clinical features alone. Thecommon symptoms and signs are shownin Table 2. There may be no physical signsapart from fever but it must be notedthat even the absence of fever itself does

not exclude the diagnosis in an ill patient.There is a risk of misdiagnosing malaria asinfluenza or other viral illness: viralhepatitis (if jaundice is present),gastroenteritis (if diarrhoea is evident) orlower respiratory tract infection (coughcan be a non-specific symptom).

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NON-SPECIFIC SYMPTOMS OF MALARIA

Fever/sweats/chillsMalaise (vague discomfort)Myalgia (muscle pain, tenderness)HeadacheDiarrhoeaCough

MAJOR FEATURES OF SEVERE OR COMPLICATED FALCIPARUM MALARIA

IN ADULTS

Impaired consciousness or seizures Renal impairment (oliguria < 0.4ml/kg bodyweight per hour or creatinine >265µmol/l))Acidosis (pH <7.3)Hypoglycaemia (<2.2mmol/l) Pulmonary oedema or acute respiratory distress syndrome (ARDS)Haemoglobin ≤ 8g/dLSpontaneous bleeding/disseminated intravascular coagulationShock (algid malaria)Haemoglobinuria (without G6PD deficiency)

MAJOR FEATURES OF SEVERE OR COMPLICATED MALARIA IN CHILDREN

Impaired consciousness or seizures Respiratory distress or acidosis (pH <7.3)HypoglycaemiaSevere anaemiaProstration (inability to sit or stand)Parasitaemia >2% red blood cells parasitized

C L I N I C A L S Y M P TO M S A N D S I G N S O F M A L A R I A

(from the ACMP Malaria Treatment Guidelines)

TA B L E 2

2.4 Where is malaria found?

Figure 2 shows the global distribution ofmalaria as assessed by the World HealthOrganization (WHO) in 20032.

In-country maps of prophylactic advicelinked to malaria distribution are availablein the web-based version of theseguidelines for use when advisingindividual travellers. The likelihood ofmalaria transmission may varyconsiderably within one country.

2.5 Level of risk of exposure tomalaria and what affects it

Exposure of individual travellers tomalaria is influenced by the number ofinfectious bites received. Conditionsaffecting number of infectious bitesreceived are given below.

Temperature, altitude and season• The optimum conditions for malaria

transmission are high humidity and anambient temperature in the range 20to 30°C3.

• Malaria transmission does not occur inregions with temperatures below the16°C isotherm (line on a weathermap joining all the places that havethe same temperature).

• Parasite maturation in the mosquitocannot take place at altitudes greaterthan 2000 metres.

• Seasonal rainfall increases mosquitobreeding.

Rural versus urban location • Malaria prevalence is generally higher

in rural than in urban areas, especiallyin Africa where the intensity oftransmission is on average about 8times higher in villages than towns4



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G L O B A L D I S T R I B U T I O N O F M A L A R I A A S A S S E S S E D B Y

T H E WO R L D H E A LT H O R G A N I Z AT I O N I N 2 0 0 3

F I G U R E 2

Malaria endemicity

Very high

High

Moderate

Low

No malaria

but the risk of contracting malaria inAfrican or other cities of malaria-endemic areas must not bediscounted5.

Type of accommodation • An impregnated bed net should be

used unless the accommodation isfitted with functioning air-conditioning and windows and doorswhich are sufficiently well sealed toprevent mosquito entry.

• Backpackers staying in cheapaccommodation have a higher risk ofbeing bitten compared to touristsstaying in air-conditioned hotels.

• The traveller should embark on theirjourney equipped with mosquitoprotection measures appropriate totheir particular circumstances.

Patterns of activity • Being outdoors between dusk and

dawn when Anopheles mosquitoesbite increases the risk.

Length of stay • The longer the stay, the higher the

risk of contracting malaria.

2.6 Distribution of drug resistantmalaria

• Chloroquine resistant falciparummalaria is now widespread. P. falciparum has also developedresistance to a variety of other agentsin certain areas. Further comment on the extent and severity of drugresistance is given in tables 7-12 inchapter 4.

• There is currently no recorded drugresistance to Plasmodium ovale andonly one report of drug-resistant P. malariae (to chloroquine)6.



• Chloroquine-resistant P. vivax is foundin Papua New Guinea and Irian Jaya;with sporadic reports from elsewherein Oceania, Asia, South America,Ethiopia and Somalia.

• P. vivax with reduced susceptibility toprimaquine (the Chesson strain) isfound in South-East Asia and Oceaniaand higher doses of primaquine arerequired to achieve radical cure of thisparasite.

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3 - Bite Prevention

3.1When do female Anophelesmosquitoes bite? 27

3.2Measures to prevent mosquito bites. 27

Repellents InsecticidesNetsClothingRoom protectionFallacies



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G U I D A N C E F R O M T H E H PA A D V I S O R Y C O M M I T T E E

O N M A L A R I A P R E V E N T I O N I N U K T R A V E L L E R S

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3. Bite PreventionEffective bite prevention should be the first line of defence against malarial infection.

3.1 When do female Anopheles mosquitoes bite?

Biting time varies between species, so travellers should assume they are at risk ofbeing bitten from dusk to dawn inclusive. The biting of the two main malaria vectorsin Africa peaks at about 2am so protection in bed is especially important. As otherspecies of mosquito e.g. those which transmit dengue fever bite during the daytime,it would be prudent to also maintain bite precautions during daylight hours.

3.2 Measures to prevent mosquito bites

3.2.1 Repellents

ACMP strongly recommends DEET-basedinsect repellents. If DEET is not tolerated(or is not available), an alternativepreparation should be used, but few areas effective as DEET (see below)

DEET

DEET (N,N-diethyl-m-toluamide) has beenin use as an insect repellent for morethan 50 years. It is available in a varietyof concentrations and in variouspreparations including sprays and a slowrelease polymer.

Duration of protection is 1 to 3 hours for20%, up to 6 hours for 30% and up to 12hours for 50% DEET. There is no furtherincrease in duration of protection beyonda concentration of 50%. Sweat-off timevaries with activity. The interval betweenapplications depends on this as well as theDEET formulation and concentration used.

When both sunscreen and DEET arerequired, DEET should be applied

afterwards. DEET reduces the efficacy ofsunblock, however sunscreens do notreduce the effectiveness of DEET7,8.

DEET is not recommended for infantsbelow the age of 2 months.

Use of 20% DEET in the second and thirdtrimesters of pregnancy was notassociated with adverse effects on infantsfrom those pregnancies followed for upto 12 months after birth9. Given theseriousness of malaria in pregnancy,ACMP recommends the use of DEET at aconcentration of up to 50% as part ofthe malaria prevention regimen forpregnant women, including those in thefirst trimester. DEET may be used at aconcentration of up to 50% in breastfeeding and for infants and children agedover 2 months.

ACMP advice on use of DEET forprotection from mosquito bites:

• DEET is suitable for all individuals overthe age of 2 months (unless allergic).

• 50% has the longest duration ofaction, and needs fewer applicationsper day

• There is no evidence that any group(including pregnant women and smallchildren) is at increased risk fromusing 50% DEET.

• Lower concentrations are available:they need more frequent applicationand may not be as effective as 50%-care must be taken to re-apply or usea higher concentration DEETpreparation if mosquito biting occursafter their use. Lower concentrationsare not suitable for individuals whomay expect prolonged exposure, suchas that encountered by backpackersand expedition travellers.

• ACMP considers concentrations below 20% inappropriate in anycircumstances.

• DEET applications can damage someplastic watch straps, watch 'glasses'and plastic jewellery; these itemsshould not be allowed to come intocontact with DEET.

p-menthane 3,8 diol (lemon eucalyptus)

p-menthane 3,8 diol (PMD) gives aboutthe same amount of protection affordedby 15% DEET10 but is reported to providea shorter period of protection thanextended duration (microencapsulated)DEET11.

Picaridin (Icaridin)

Picaridin (KBR3023) (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-,1-methyl-propylester) isreported to have repellent propertiescomparable to those of DEET12-14.Picaridin is sold in Europe as a 20%formulation whilst a 7% picaridinformulation is on sale in the US15. If atraveller elects to use picaridin formosquito bite prevention, ACMP advises

use of a 20% preparation.

3-ethlyaminopropionate

3-ethlyaminopropionate (IR3535) has ashorter duration of protection thanDEET13,16.

Oil of Citronella

Whilst oil of citronella-based products dohave repellent properties, they provideshort-lived protection16 and are notrecommended by ACMP. Citronella hasbeen withdrawn in Europe.

3.2.2 Insecticides

Permethrin and other syntheticpyrethroids have a rapid knock-downeffect on mosquitoes and are used to kill resting mosquitoes in a room.

3.2.3 Nets

If sleeping outdoors or in unscreenedaccommodation, insecticide-treatedmosquito nets should be used. Protectiveefficacy for travellers has been estimatedat 50%17.

Mosquito bed nets must be free of tearsand should be tucked in under themattress.

Insecticide (pyrethroid)-impregnated bednets improve protection because theyhelp to prevent (a) biting through the neton part of the body touching the net, (b)mosquitoes surviving long enough near anet to find any tears in the net which mayexist (c) diversion of mosquitoes fromsomeone under a net to someone in thesame room without a net18.



28

Nets need to be re-impregnated every 6 to 12 months (depending on howfrequently the net is washed) to remaineffective. If a traveller purchases animpregnated net, the 6 months startsfrom the date when it starts to be usedand washed, as washing and handling are the main factors removing thepyrethroid. Long-lasting nets, in whichthe pyrethroid is incorporated into thematerial of the net itself or bound to itwith a resin, are now available. Thesehave an expected useful life of 3 to 5years and are expected to supersedenets which require re-impregnation.

3.2.4 Clothing

Within the limits of practicality, cover upwith long-sleeved, loose-fitting clothing,long trousers and socks if out of doorsafter sunset, to minimise accessibility toskin for biting mosquitoes. There is noevidence that the colour of clothing isrelevant to mosquitoes. Clothing may be sprayed or impregnated withpermethrin19 or purchased pre-treated toreduce biting through the clothing. As analternative, cotton clothing (e.g. socks)can be sprayed with DEET.

3.2.5 Room protection

Air conditioning reduces the likelihood ofmosquito bite as a result of substantialreduction in night time temperature.Ceiling fans reduce mosquito nuisance.

Doors, windows and other possiblemosquito entry routes to sleepingaccommodation should be screened with fine mesh netting which must beclose-fitting and free from tears.



The room should be sprayed before duskwith a knockdown insecticide (usually apyrethroid) to kill any mosquitoes whichmay have entered the accommodationduring the day.

During the night, where electricity isavailable, use an electrically heateddevice to vapourise a “mat” (tablet)containing a synthetic pyrethroid in theroom. A new mat is needed each night.

Burning of a mosquito coil is analternative but is not as effective20 and is not recommended for indoor use.

3.2.6 Fallacies

Herbal remedies

The ACMP strongly advises against relyingon any herbal remedies for theprevention of malaria. Herbal remedieshave not been tested for their ability toprevent or treat malaria.

Homoeopathy

The ACMP strongly advises againstrelying on any homoeopathic remediesfor the prevention of malaria. There isno scientific proof that homoeopathicremedies are effective in eitherpreventing or treating malaria. In addition, the Faculty of Homeopathydoes not promote the use ofhomoeopathic remedies for diseaseprevention and notes that their use inmalaria prevention is unlikely to beacceptable to insurance providers.

29



30

Buzzers

Electronic buzzers (emitting highfrequency sound waves) are completelyineffective as mosquito repellents.Companies selling them have beenprosecuted and fined under the UKTrades Descriptions Act and ACMP adviceis that they should not be used.

Vitamin B1

There is no evidence that vitamin B1taken orally repels mosquitoes21,22.

Garlic

There is no evidence that garlic takenorally repels mosquitoes23.

Savoury yeast extract spread

It is sometimes stated that Marmite®taken orally repels mosquitoes either bygiving off a cutaneous odour repellent tomosquitoes or via its vitamin B1 content.There is no evidence that either assertionis true.

Tea tree oil

There is no evidence that tea tree oil isan effective mosquito repellent.

Bath oils

There is no evidence that proprietarybath oils provide effective protectionagainst mosquito bites.

“Once you get malaria it keepscoming back”

Hypnozoite-induced relapses occur invivax and ovale malaria, but can betreated successfully and further relapsesprevented. If the patient has received afull course of treatment with modernantimalarial drugs and has not been re-exposed to malaria, it is extremelyunlikely that a history of recurrent febrileillness over a number of years is theresult of chronic malaria.

4 - Chemoprophylaxis

4.1Principles. 33

4.2The drugs. 34

ChloroquineProguanilChloroquine plus proguanilMefloquineDoxycyclineAtovaquone plus proguanil

4.3Dosage tables. 39

4.4Country tables. 42

4.5Popular destinations. 53

4.6Emergency Standby Treatment. 54



31

32





33

4. ChemoprophylaxisGiven the possibility of antimalarials purchased in the tropics being fake24, travellersshould obtain the medication required for their chemoprophylaxis from a reputablesource in the UK before they travel. ACMP also advises against purchasing antimalarialdrugs over the internet.

4.1 Principles

Causal prophylaxis

Causal prophylaxis is directed against the liver stage of the malaria parasite, whichtakes approximately 7 days to develop (see life cycle in figure1). Successful drugactivity at this stage prevents the parasite from progressing to infect red blood cells.

Causal prophylactics need to be given for approximately 7 days after infection25, soACMP recommends that they are continued for 7 days after leaving a malarious area(see table 3 of drug regimens in chapter 4).

It is important not to confuse liver-stage schizonts with hypnozoites. All 4 species ofhuman malaria have liver-stage schizonts but only Plasmodium vivax and P. ovale havethe hypnozoite stage, against which causal prophylaxis is NOT effective.

Suppressive prophylaxis

Suppressive prophylaxis is directedagainst the red blood cell stages of themalaria parasite and thus needs to betaken for several weeks to preventinfection26.

Therefore, suppressive prophylactic drugsshould be continued for 4 weeks afterleaving a malarious area (see drugregimens in table 3, Chapter 4).

Prophylaxis against hypnozoites

Plasmodium vivax and P. ovale have adormant stage called the “hypnozoite”.The hypnozoite remains dormant formonths and then “wakes up” to developinto a liver schizont. The dormanthypnozoite explains why attacks of vivaxor ovale malaria can occur long after theend of chemoprophylaxis. This is not dueto drug failure as none of the

prophylactic drugs currently advised byACMP, acts against the hypnozoite stageof P. vivax or P. ovale.

Primaquine is active against hypnozoites(present only in P.vivax and P.ovale) andalso has causal prophylactic activityagainst the liver stage schizonts of all 4 malaria parasites of humans27.Primaquine is occasionally used forterminal prophylaxis (also known aspresumptive anti-relapse therapy) toeradicate hypnozoites of P.vivax andP.ovale. However, the routine use ofprimaquine for prophylaxis is notrecommended by ACMP. Practitionersconsidering the use of primaquine as aprophylactic agent should consult anexpert centre (see Chapter 9).

Primaquine is an oxidant drug and canlead to haemolysis in G6PD-deficientindividuals.

4.2 The drugs

The British National Formulary (BNF)contains full listings of drug actions,dosages, side effects, interactions andcontraindications summarised here andshould be consulted as required whenrecommending malaria chemoprophylaxis.

Chapter 6 of this book also providesdetails of contraindications for differentmedical conditions such as pregnancyand renal impairment.

NOTE: All adverse events of medication,including attacks of malaria, should bereported. Members of the public andhealthcare professionals can report anysuspected side effects from malariamedicines via the Yellow Card Scheme onthe Medicines and Healthcare productsRegulatory Agency (MHRA) website.www.mhra.gov.uk

These drugs are not listed in order ofpreference.

4.2.1 Chloroquine

Mode of action

Chloroquine is concentrated in themalaria parasite lysosome and isthought to act by interfering withmalaria pigment formation, causinggeneration of a ferriprotoporphyrin IX-chloroquine complex which is highlytoxic to the parasite.

Efficacy

Chloroquine-resistant falciparum malariais now reported from all WHO regionsexcept Central America north of thePanama Canal and the Island of

Hispaniola (Haiti & the DominicanRepublic). Prophylaxis with chloroquine asa single agent is therefore rarelyappropriate (see tables 7-12). It remainseffective against most P. vivax, all P. ovaleand virtually all P. malariae.

Side-effects

The main side effects are gastrointestinaldisturbances and headache. Convulsionsare recorded. Chloroquine may causeitching in persons of African descent.

Interactions

Drugs: Amiodarone (increased risk ofventricular arrhythmias); ciclosporin(increased risk of toxicity); digoxin(possibly increases plasma concentrationof digoxin); mefloquine (increased risk ofconvulsions); moxifloxacin (increased riskof ventricular arrhythmias; avoidconcomitant use).

Vaccines: Chloroquine may suppress theantibody response to pre-exposureintradermal human diploid cell rabiesvaccine28. This interaction is not seenwhen rabies vaccine is givenintramuscularly (the currentlyrecommended mode of vaccination inthe UK).

Contraindications

Chloroquine prophylaxis may exacerbatepsoriasis and myasthenia gravis. It iscontraindicated in those with a history of epilepsy.



34

Cautions

Chloroquine is highly toxic in overdosage,so should be stored out of the reach of children. In long term use, eyeexaminations every 6-12 months shouldbe considered at 6 years prophylacticusage, though the risk of retinopathydeveloping on prophylactic dosage isconsidered to be very low29. See alsolong-term traveller section in chapter 7.

Methods of administration

Tablets contain 155 or 150 mgchloroquine base; syrup containschloroquine base 50 mg/5 ml (seepaediatric dosages in tables 4 and 5).Adult dose 300 mg (2 tablets) weekly,starting one week before entering amalarious area, continuing throughoutthe time in the area and for 4 weeksafter leaving the area.

4.2.2 Proguanil

Mode of action

Proguanil is converted to an activemetabolite cycloguanil which inhibits theenzyme dihydrofolate reductase andinterferes with the synthesis of folic acid.It acts as a suppressive and also as acausal prophylactic30. Proguanil itself has a second mode of action, mediatedby the parent drug rather than itsmetabolite, which produces synergy with atovaquone (see atovaquone plusproguanil).

Efficacy

There are very few regions in the worldwhere the local Plasmodium falciparumstrains are fully sensitive to proguanil, so



prophylaxis with proguanil as a singleagent is rarely appropriate (see countrytables 7-12, chapter 4).

Side-effects

The principal side effects of proguanil aremild gastric intolerance and diarrhoea.Mouth ulcers and stomatitis occuroccasionally, particularly when combinedwith chloroquine.

Interactions

Drugs: May enhance the anticoagulanteffect of warfarin. Absorption reducedby oral magnesium salts. Antifolate effectis increased when given withpyrimethamine.

Vaccines: None reported

Contraindications

Allergy to proguanil

Cautions

Renal impairment. Pregnancy (folatesupplements required).


100mg tablets only. Adult dose 200 mgdaily, starting one week before entering amalarious area, continuing throughoutthe time in the area and for 4 weeksafter leaving the area.

35



36

4.2.3 Chloroquine plus proguanil

For side effects, interactions,contraindications and methods ofadministration, please see individualagents.

ACMP does not recommend the useof chloroquine plus proguanil fortravellers to sub-Saharan Africa. If no alternative is felt to beappropriate, the matter should bediscussed with an expert centre(see chapter 9).

4.2.4 Mefloquine

Mode of action

Mefloquine’s mode of action has notbeen determined, but is thought to beunrelated to that of chloroquine and notto involve an anti-folate action. It acts asa suppressive prophylactic.

Efficacy

The protective efficacy of mefloquine isapproximately 90% in Africa31. At thepresent time, significant resistance of P. falciparum to mefloquine is a problemonly in some areas of south-East Asia32,but is reported sporadically from theAmazon basin.

Side-effects

Attention has focused onneuropsychiatric problems withmefloquine prophylaxis. Increasedmoderate problems have been foundespecially in women using mefloquinewhen compared with those receivingdoxycycline, or atovaquone plus

proguanil, but not those takingchloroquine plus proguanil33 but there is no evidence that mefloquine useincreases the risk of first-time diagnosisof depression34 and no associationbetween mefloquine prescriptions andhospitalisation35. Overall, mefloquineremains an important prophylactic agentwhich is tolerated by the majority oftravellers who take it36.

Interactions

Drugs: Mefloquine antagonises theanticonvulsant effect of antiepilepticsand interacts with a number of cardiacdrugs.

Contraindications

Mefloquine prophylaxis is contraindicatedin those with a current or previoushistory of depression, neuropsychiatricdisorders or epilepsy; or withhypersensitivity to quinine.

Cautions

Pregnancy; (see Chapter 6,specialgroups) breast-feeding; (see Chapter 6,special groups) cardiac conductiondisorders. Not recommended in infantsunder 3 months (5kg).

Can mefloquine be taken by thosewho plan to undertake underwaterdiving?

If the individual tolerates mefloquineprophylaxis, there is no evidence thatthey cannot physically performunderwater diving. However, it should benoted that some sub-aqua centres do notpermit those taking mefloquine to dive.



37

Although mefloquine may be suitable for scuba divers who have taken andtolerated the drug before, or those ableto start taking it early to ensure that noadverse events occur, it should usually beavoided: it lowers the seizure threshold(and may therefore add to thecomplications of decompression ornarcosis events) and someneuropsychiatric adverse events, thoughexcessively rare, can be sudden in onset.

Airline pilots

The UK Civil Aviation Authority advisesthat mefloquine should not beadministered to airline pilots, althoughthere is no evidence that mefloquineimpairs function.


Oral. 250mg tablets. Weekly dosage,starting 2-3 weeks before entering amalarious area to assess tolerability,continuing throughout the time in thearea and for 4 weeks after leaving themalarious area.

4.2.5 Doxycycline

Mode of action

Doxycycline is lipophilic and actsintracellularly, binding to ribosomalmRNA and inhibiting protein synthesis. It acts as a suppressive prophylactic.

Efficacy

Doxycycline is of comparableprophylactic efficacy to mefloquine37.

Side-effects

Doxycycline hydrochloride preparationshave a low pH and may produceoesophagitis, especially if taken on anempty stomach and/or just before lyingdown. Rarely, doxycycline may causephotosensitivity which is mostly mild andtransient38. Doxycycline is a broadspectrum antibiotic and may predisposeto vaginal candidiasis.

Interactions

Drugs: The metabolism of doxycycline isaccelerated by carbamazepine andphenytoin. At present, there are no datato support a change in the dose ofdoxycycline used for malaria prophylaxisin individuals taking one or more ofthese agents. Tetracyclines possiblyenhance the anticoagulant effect ofcoumarins (e.g. warfarin), and mayincrease plasma concentration ofciclosporin. It may temporarily reducethe contraceptive effect of oestrogens(see FAQs in Chapter 8).

Vaccines: Possibly reduces the efficacy oforal typhoid vaccine if givensimultaneously. Should be separated by24 hours.

Contraindications

Children under 12 years of age.Pregnancy and breast feeding. Allergy totetracyclines.

Cautions

Hepatic impairment. Patients takingpotentially hepatotoxic drugs. Myastheniagravis. Systemic lupus erythematosus.


Capsules (50 or 100mg) or dispersible100mg tablets only (consult summary ofproduct characteristics pertaining toindividual products). Dose 100mg daily,starting 1 to 2 days before entering amalarious area, continuing whilst thereand for 4 weeks after leaving.

Precautions in use

The prescriber should warn againstexcessive sun exposure (and advise onthe correct use of sunscreen), the risk ofvaginal candidiasis and the risk ofoesophagitis if taken on an emptystomach and/or lying down too soonafter taking it. Doxycycline should beswallowed whole with plenty of fluidduring meals while sitting or standing.

4.2.6 Atovaquone plus proguanil(Malarone®)

Mode of action

Atovaquone works by inhibiting electrontransport in the mitochondrialcytochrome b-c1 complex, causingcollapse in the mitochondrial membranepotential. This action is potentiated byproguanil and is not dependent uponconversion to its metabolite cycloguanil.Indeed, the combination remainseffective in cycloguanil-resistantparasites39. Atovaquone/proguanilprevents development of pre-erythrocytic (liver) schizonts (but not

hypnozoites). It acts as a causalprophylactic agent, so needs to becontinued for only 7 days after leaving amalarial area40. It also has activity againstthe erythrocytic stages of malariaparasites and is useful for treatment.

Efficacy

Prophylactic efficacy against P. falciparumis in excess of 90%41-48. There is lesspublished data on protection against P. vivax, but data available indicate thatatovaquone-proguanil is effective in theprevention of primary attacks of vivaxmalaria44,49. However, like chloroquine-proguanil, mefloquine and doxycycline, itwill not protect against hypnozoite-induced episodes of P.vivax (or P.ovale)malaria.

Side-effects

The most frequent side-effects areheadache and gastrointestinal upsets.

Interactions

For proguanil see proguanil section(above).

Drugs: Plasma concentration ofatovaquone is reduced by rifabutin andrifampicin (possible therapeutic failure ofatovaquone), tetracycline (clinicalsignificance of this is not known) andmetoclopramide.

Antiretrovirals: Atovaquone possiblyreduces plasma concentration ofindinavir. Atovaquone possibly inhibitsmetabolism of zidovudine (increasedplasma concentration).

Vaccines: None reported.



38

Contraindications

Pregnancy: The BNF states “Manufactureradvises avoid unless essential.” ACMPadvises against the use ofatovaquone/proguanil for antimalarialchemoprophylaxis in pregnancy.Inadvertent conception when usingatovaquone/proguanil is not anindication to consider termination of thepregnancy, as no evidence of harm hasemerged in data so far available.

Atovaquone/proguanil should generallybe avoided in breast feeding, but ACMPadvises that atovaquone/proguanil canbe used when breast-feeding if there isno suitable alternative antimalarial.

Cautions

Renal impairment (See also the renalimpairment section in chapter 6),diarrhoea or vomiting (reducedabsorption of atovaquone).


Tablets containing proguanil 100 mg andatovaquone 250 mg. Paediatric tabletscontaining proguanil 25 mg andatovaquone 62.5 mg. Adult dose onetablet daily starting 1 to 2 days beforeentering a malaria endemic area,continuing throughout the time thereand for 1 week after leaving. Paediatricdosage given in table 6.

4.3 Dosage tables



39

REGIMEN DOSE FOR USUAL AMOUNT

CHEMOPROPHYLAXIS PER TABLET (mg)

Areas of chloroquine resistant P. falciparum

Mefloquine 1 tablet weekly 250

Doxycycline 1 tablet/capsule daily 100

Atovaquone-proguanil 1 tablet daily 250 (atovaquone) plus 100(proguanil)

Areas of little chloroquine resistance; poorly effective where extensiveresistance

Proguanil plus 2 tablets daily plus 100

chloroquine 2 tablets weekly 150 (base)

Areas without drug resistance

Chloroquine 2 tablets weekly 150 (base)

Proguanil 2 tablets daily 100

P RO P H Y L AC T I C R E G I M E N S AG A I N S T M A L A R I A I N A D U LT STA B L E 3



40

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41

WEIGHT IN kg NUMBER OF 5ML PROPORTION AGE

MEASURES (THERE IS OF ADULT

OFTEN A HALF SIZE DOSE

MEASURE AT THE OTHER

END OF THE SPOON)

Under 4.5 kg 0.5 0.083 Under (2.5 ml) 6 weeks

4.5 - 7.9 1.0 0.167 6 weeks - (5.0 ml) 5 months

8.0 - 10.9 1.5 0.250 6 months - (2.5 ml plus 5 ml) 12 months

11.0 - 14.9 2.0 0.333 13 months -(2 x 5 ml) 2yrs 11 mths

15.0 - 16.5 2.5 0.417 3 years - (2.5 ml plus2 x 5 ml) 3 yrs 11 mths

TA B L E O F D O S E S B Y S P O O N O R S Y R I N G E * M E A S U R E S F O R

C H L O RO Q U I N E S Y RU P

TA B L E 5

WEIGHT PROPORTION NUMBER OF

IN kg OF ADULT DOSE PAEDIATRIC

TABLETS

Under 11 Do not use Not recommended

11 – 20 0.25 1 paediatric



Over 40 1.00 4 paediatricor 1 adult

TA B L E O F PA E D I AT R I C D O S E O F ATOVAQ U O N E / P RO G UA N I LTA B L E 6

N.B. These dose-steps are not the same as for chloroquine tablets, which differ from the syrup in chloroquinecontent. Chloroquine syrup (Nivaquine ®) contains 50mg chloroquine base in 5ml.

* Chemists may dispense dosing syringes for child doses.



42

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ical

att

entio

n fo

r an

y su

spic

ious

sym

ptom

s (u

p to

abo

ut a

yea

rla

ter)

but

tab

lets

not

con

side

red

nece

ssar

y.

See

tabl

es 3

-6 fo

r de

tails

of

regi

men

s

AC

MP

REC

OM

MEN

DED

REG

IMEN

ALT

ERN

ATIV

ER

EGIM

EN IF

REC

OM

MEN

DED

REG

IMEN

UN

SUIT

ABL

E

CO

UN

TRY

R

ISK

4.4 Country tables



43

Ang

ola

Beni

nBu

rkin

a Fa

soBu

rund

iC

amer

oon

Cen

tral

Afr

ican

Rep

ublic

Cha

dC

omor

os

Ris

k hi

gh

Chl

oroq

uine

resi

stan

cew

ides

prea

d

Ris

k lo

w

Mef

loqu

ine

OR

Dox

ycyc

line

OR

Ato

vaqu

one/

Prog

uani

l

Aw

aren

ess*

Seek

exp

ert

advi

ce

(see

cha

pter

9)

MA

LA

RIA

CH

EM

OP

RO

PH

YL

AX

IS I

N S

UB

-SA

HA

RA

N A

FR

ICA

TA

BL

E 8

See

tabl

es 3

-6 fo

r de

tails

of

regi

men

s *A

war

enes

s of

sm

all r

isk

of m

alar

ia; a

void

mos

quito

bite

s an

d se

ekm

edic

al a

tten

tion

for

any

susp

icio

us s

ympt

oms

(up

to a

bout

a y

ear

late

r) b

ut t

able

ts n

ot c

onsi

dere

d ne

cess

ary.

AC

MP

REC

OM

MEN

DED

REG

IMEN

ALT

ERN

ATIV

ER

EGIM

EN IF

REC

OM

MEN

DED

REG

IMEN

UN

SUIT

ABL

E

CO

UN

TRY

R

ISK

Bots

wan

a (o

nly

in t

he n

orth

ern

half

of t

he c

ount

ry,N

ovem

ber-

June

)Et

hiop

ia (

belo

w 2

000m

,no

risk

in A

ddis

Aba

ba)

Mau

rita

nia

(yea

r ro

und

in t

he s

outh

;in

nort

h Ju

ly-O

ctob

er)

Nam

ibia

(no

rthe

rn t

hird

onl

y,N

ovem

ber-

June

;all

year

alo

ng K

avan

go &

Kun

ene

Riv

ers)

Sout

h A

fric

a (n

orth

eas

t,lo

w a

ltitu

de a

reas

of M

pum

alan

ga &

Nor

ther

n Pr

ovin

ces,

incl

udin

g th

e K

ruge

r N

atio

nal P

ark,

Nor

th E

ast

Kw

aZul

u-N

atal

as

far

sout

h as

Tug

ela

Riv

er).

Zim

babw

e (a

reas

bel

ow 1

200m

,Nov

embe

r-Ju

ne;a

ll ye

ar in

Zam

bezi

val

ley.

Ris

kne

glig

ible

in H

arar

e or

Bul

away

o)

Cap

e Ve

rde

(som

e ri

sk o

n Sã

o T

iago

)M

auri

tius

Con

goD

jibou

ti Eq

uato

rial

Gui

nea

Eritr

ea

Gab

onG

ambi

aG

hana

Gui

nea

Gui

nea-

Biss

auIv

ory

Coa

stK

enya

Libe

ria

Mad

agas

car

Mal

awi

Mal

iM

ozam

biqu

e

Nig

erN

iger

ia

Prin

cipe

Rw

anda

São

Tom

éSe

nega

lSi

erra

Leo

neSo

mal

ia

Suda

nSw

azila

ndTa

nzan

ia

Togo

Uga

nda

Zai

reZ

ambi

a

Ris

k hi

ghC

hlor

oqui

nere

sist

ance

high

Ris

k va

riab

leC

hlor

oqui

nere

sist

ance

usua

llym

oder

ate

Ris

k lo

w

Mef

loqu

ine

O

RD

oxyc

yclin

eO

RA

tova

quon

e/Pr

ogua

nil

Chl

oroq

uine

plus

pro

guan

il

Aw

aren

ess*

Chl

oro

quin

epl

us p

rogu

anil

Mef

loqu

ine

OR

Do

xycy

clin

eO

RA

tova

quo

ne/

Pro

guan

il

MA

LA

RIA

CH

EM

OP

RO

PH

YL

AX

IS I

N S

OU

TH

AS

IAT

AB

LE

9

See

tabl

es 3

-6 fo

r de

tails

of

regi

men

s *A

war

enes

s of

sm

all r

isk

of m

alar

ia; a

void

mos

quito

bite

s an

d se

ekm

edic

al a

tten

tion

for

any

susp

icio

us s

ympt

oms

(up

to a

bout

a y

ear

late

r) b

ut t

able

ts n

ot c

onsi

dere

d ne

cess

ary.

AC

MP

REC

OM

MEN

DED

REG

IMEN

ALT

ERN

ATIV

ER

EGIM

EN IF

REC

OM

MEN

DED

REG

IMEN

UN

SUIT

ABL

E

CO

UN

TRY

R

ISK

Bang

lade

sh (

only

in C

hitt

agon

g H

ill T

ract

Dis

tric

ts)

Indi

a (A

ssam

)

Bhut

an (

sout

hern

dis

tric

ts o

nly)

Indi

a (e

xcep

t fo

r A

ssam

whe

re h

igh

risk

,and

for

area

s lis

ted

belo

w

whe

re lo

w r

isk)

Nep

al (

belo

w 1

500m

,esp

ecia

lly T

erai

dis

tric

ts;n

o ri

sk in

Kat

hman

du)

Paki

stan

(be

low

200

0m)

Sri L

anka

(ri

sk n

orth

of V

avun

iya)

Bang

lade

sh (

exce

pt C

hitt

agon

g H

ill T

ract

s,se

e ab

ove)

.In

dia

(low

ris

k in

Sou

ther

n st

ates

of K

eral

a;Ta

mil

Nad

u;K

arna

taka

;Goa

and

Sout

hern

And

hra

Prad

esh

incl

udin

g H

yder

abad

,and

the

city

of M

umba

i(B

omba

y).

Low

to

no r

isk

in R

ajas

than

;Utt

ar P

rade

sh;H

arya

na;P

unja

b;D

elhi

;Utt

aran

chal

;Him

acha

l Pre

desh

;Jam

mu

& K

ashm

ir.Fo

r ot

her

area

s se

eab

ove.

Sri L

anka

(lo

w r

isk

in a

ll ar

eas

exce

pt n

orth

of V

avun

iya,

see

abov

e)



44



45

I N D I A S H OW I N G T H E S TAT E S W I T H A P P RO P R I AT E

C H E M O P RO P H Y L A X I S R E C O M M E N D E D

F I G U R E 3

Bangalore

Jaipur

Chennai (Madras)

Lucknow

Srinagar

Mumbai(Bombay)

Agra

Cochin

PAKISTAN CHINA

BA

NG

LAD

ESH

NEPALBHUTAN

MYANMAR

ANDAMAN & NICOBARISLANDS

RRRRRRRRAJASTHANJAAS HAA AASTHHAANAAJASTTHANNAAJAASSTTHHAANNA ASTHAN

Hyderabad

KERR

KERER

KEER

KER

KE

ALL

ALLL

ALL

AL

AAAAAAAA

TTTTTTAMILNAAMILLNAAMMIILLNAAMMILLNNTTTTT ADUAADDUAADDUAADDUU

UTTUTTUTTTUTTTUUTTTUT AR PR

R PRAR PRAR PR PRRAARR PATTTTTTTTT

ADESHHADESHAADEDESHHADES

DESHHAADEDESAD

PUNJABNNJPUUNJAPUUNNJJAB

JAMMU & KASHMIRA MU K H RAAMMU & KKASHHMIRRJAAMMMMUU && KKAASSHHMMIIRRJAMMMMUU && KKAASSHHMMIIRRJAAMMMU & KASHMIR

HIMAH MAAHHIMMAAHHIMMAHHIMACHAL C ALLCCHALLCCHALCCHALPRPRPPRP ADESHDESHADDEESHHADESH

SIKKIM ARUNA

PRADESH

MANIPUR

NAGALAND

MIZORAM

HALAYA AAYY

TRIPURP A

LAKSHADWEEP

DELHIDELEELHDE HIDDEELLHIDELHI

HHHHH

AAAAAARRRRYYYYRRR AAAAAAAAY NNNNNAAAAA

UUUUUUTTTTTTTTAAAATTTTT

RRRRRRAAAAAANNNCCCCHHHHHAAAAAAALLLLL

KKKKKKKAAAAAAA

RRRRRRRRAAAATTTTAAAAA AAAAAATT

KKKKKKKKAAAAAAK

BAY OF BENGAL

Bhopal

Pune

ANDHRA HAANDHHRAANNDDHHRRANDHRA PRA PRAA PRRA PRADESHA HADESHHAADDEESSHHADESH

GOA

Kolkata(Calcutta)

Panaji

NEW DELHI

KeyRisk high + resistance, take tablets: mefloquine OR doxycycline OR atovaquone proguanil recommended

Risk low, awareness and bite prevention

Other Countries

Risk variable, take tablets: Chloroquine plus proguanil recommended.



46

B A N G L A D E S H S H OW I N G T H E A R E A W H E R E


F I G U R E 4

Key

Risk high + resistance, take tablets: mefloquine OR doxycycline OR atovaquone proguanil recommended


Other Countries

NEPAL

INDIA

INDIA

INDIA

MYANMAR(Burma)

Barisal

Mungla

Jessore

Khulna

Pabna

Comilla

Chittagong

Cox'sBazar

SylhetJamalpur

Rangpur

Dinajpur

Rajshahi

Brahmanbaria

Mymensingh

. GANGES

R. BAHMAPUTRA

BAY OF BENGAL

INDIAN OCEAN

DHAKA



47

S R I L A N K A S H OW I N G T H E A R E A W H E R E


F I G U R E 5

Key


Other Countries

Risk variable, take tablets: chloroquine plus proguanil recommended

BAY OF BENGAL

INDIAN OCEAN

GULF OF MANNAR

INDIA

COLOMBO

Chilaw

Galle

Matale

Batticaloa

Trincomalee

Jaffna

Mannar

Hambantota

Anuradhapura

Matara

Kandy

Badulla

Ratnapura

Kotte

Vavuniya



48

See tables 3-6 for details of regimens *Awareness of small risk of malaria; avoid mosquito bites and seek medical attention forany suspicious symptoms (up to about a year later) but tablets not considered necessary.

Cambodia (western provinces)Thailand (near mainland borders with Cambodia, Laos and Myanmar; low risk and bite avoidance only ChiangRai and Kwai bridge)Myanmar (eastern part of Shan State)

Cambodia (except no risk in Phnom Penh)China (only in Yunnan and Hainan; chloroquine in otherremote areas of China)East Timor (= Timor-Leste)Papua (Irian Jaya) (part of Indonesia)Laos (except no risk in Vientiane)Lombok (part of Indonesia)Myanmar (formerly Burma [see above for Shan State])Malaysia East (Sabah only except Kota Kinabalu whereawareness and bite prevention advised)Vietnam (except areas listed below that are low risk)

Indonesia (except Bali and cities where low risk; forPapua (Irian Jaya) and Lombok mefloquine or doxycyclineor atovaquone-proguanil recommended)Philippines (rural below 600m; no risk in cities, nor Cebu,Bohol and Catanduanes)Malaysia West (peninsular) Inland forested areas (notCameron Highlands) and Malaysia East (inland forestedareas of Sarawak)

Bali (part of Indonesia)BruneiChina (main tourist areas including Yangtze cruises)Hong KongMalaysia East (except Sabah (see above) and Sarawak(chloroquine plus proguanil) Malaysia West (low risk including Cameron Highlandsexcept inland forested areas where chloroquine plus proguanil)North Korea (a few southern areas have limited risk)South Korea (limited risk in extreme Northwest)SingaporeThailand (prophylaxis only advised for areas listed above) Vietnam (see above for high risk areas; low risk in cities,coast between Ho Chi Minh and Hanoi, and the MekongRiver until close to the Cambodian border)

Risk high

WidespreadchloroquineANDmefloquineresistance

Risk high

Chloroquineresistancecommon

Risk variable

Somechloroquineresistance

Risk very low

Doxycycline OR Atovaquone/Proguanil

MefloquineORDoxycyclineORAtovaquone/Proguanil

Chloroquine plusproguanil

Awareness*

M A L A R I A C H E M O P RO P H Y L A X I S I N S O U T H E A S T A S I ATA B L E 1 0

ACMPRECOMMENDED

REGIMEN

COUNTRY RISK



49

Ris

k hi

gh

Chl

oro

quin

ere

sist

ance

high

Dox

ycyc

line

OR

Mef

loqu

ine

OR

Ato

vaqu

one/

Prog

uani

l

Chl

oro

quin

epl

uspr

ogu

anil

(Lim

ited

pro

tect

ion)

MA

LA

RIA

CH

EM

OP

RO

PH

YL

AX

IS I

N O

CE

AN

IAT

AB

LE

11

See

tabl

es 3

-6 fo

r de

tails

of

regi

men

s

AC

MP

REC

OM

MEN

DED

REG

IMEN

ALT

ERN

ATIV

ER

EGIM

EN IF

REC

OM

MEN

DED

REG

IMEN

UN

SUIT

ABL

E

CO

UN

TRY

R

ISK

Papu

a N

ew G

uine

a be

low

180

0mSo

lom

on Is

land

sVa

nuat

u



50

Bolivia (Amazon basin area)Brazil (Amazon basin (i.e. ‘Legal Amazon’area, see map); elsewhere very low risk and no chemoprophylaxis)Colombia (most areas below 800m)Ecuador (Esmeraldas Province; see belowfor elsewhere) French Guiana (especially border areas)Guyana (all interior regions, lesser risk at coast)Peru (Amazon basin area)Suriname (except Paramaribo and coast)Venezuela (all areas south of and includingthe Orinoco river; north of the riverchloroquine plus proguanil recommendedsee below)Amazon basin areas of Bolivia andVenezuela and Peru

Bolivia (rural areas below 2500m)Ecuador (areas below 1500m; no malaria in Galapagos Islands nor Guayaquil)Panama (east of canal, canal zone itself no risk)Peru (Other rural areas East of the Andesand West of the Amazon Basin below1500m)Venezuela (north of the Orinoco river;Caracas free of malaria; south and includingOrinoco river, risk high see above)

Argentina (rural areas along northernborders only)Belize (rural except Belize district)Costa Rica (rural below 500m)Dominican RepublicEl Salvador (only Santa Ana province in west)Guatemala (below 1500m)HaitiHondurasMexico (in states of Oaxaca & Chiapas)NicaraguaPanama (west of canal, canal zone itself no risk)Paraguay (some rural areas)

Risk high

Markedchloroquineresistancepresent

Risk variable or high

Chloroquineresistancepresent

Risk variableto low

Nochloroquineresistancepresent

MefloquineORDoxycyclineORAtovaquone/Proguanil

Chloroquineplus proguanil

Chloroquine

Chloroquineplusproguanil

MefloquineOR Doxcycline OR Atovaquone/Proguanil

Proguanil

M A L A R I A C H E M O P RO P H Y L A X I S I N S O U T H A M E R I C A

A N D C A R I B B E A N

TA B L E 1 2

See tables 3-6 for details of regimens

ACMPRECOMMENDED

REGIMEN

ALTERNATIVEREGIMEN IF

RECOMMENDEDREGIMEN

UNSUITABLE

COUNTRY RISK



51

M A P O F A M A Z O N B A S I N A R E A S H OW I N G S P R E A D AC RO S S

S E V E R A L S O U T H A M E R I C A N C O U N T R I E S

F I G U R E 6

Consult table 12 and figure 7 for details of prophylaxis advised for individual countries.

Key

Amazon Basin area where high risk and resistance present, tablets recommended: mefloquine OR doxycycline OR atovaquone/proguanil

Other Countries

SOTHERN OCEAN

ECUADOR

PACIFICOCEAN

ATLANTICOCEAN

CARIBBEAN SEA

PACIFIC OCEAN

ATLANTIC OCEAN

CENTRAL AMERICA

URUGUAY

CHILE

FALKLAND ISLANDS

(U.K)

SOUTH GEORGIA ISLANDS

(U.K)

FRENCHGUIANA

SURINAME

GUYANA

ARGENTINA

BRAZIL

PERU

BOLIVIA

Tropic of Capricorn

Equator

PARAGUAY

COLOMBIA

VENEZUELA

M A P O F B R A Z I L S H OW I N G T H E S TAT E S W H E R E

C H E M O P RO P H Y L A X I S I S R E Q U I R E D

F I G U R E 7



52

KeyRisk high + resistance, take tablets: mefloquine OR doxycycline OR atovaquone proguanil recommended

Other Countries


GoiasGoo asGoGooiasGo a

BRASILIA

PARAGUAY

Atlantic Ocean

Vitoria

Atlantic Ocean

Pacific Ocean

Salvador

Rio Grande

Aracaju

Maceio

Natal

URUGUAY

ARGENTINA

BOLIVIA

PERU

FRENCH GUIANA

VENEZUELA

COLOMBIA

Santos

Florianopolis

Rio de Janeiro

Porto Alegre

Itabuna

Montes Carlos

SaoPaulo

Belo Horizonte

Cuiaba

Palmas

Sao Luis

Teresina

Fortaleza

Campo Grande

Goiana

Recife

Manaus

Porto Velho

Maraba

Belem

Macapa

RioBranco

Icana

Boa Vista

Curitiba

GUYANA SURINAME

MatMMaMaMMaatMMaato Gro GGrGroo GGro Grossosoooossooo soDo SulDo SSuulSuDoo SSuulD S l

BahiaB iBBahiaBahiaBah a

PiauiPiauuPiauuiPiauuiP

CearCe rCeCeearaaa

Minas GerM n GeM nass GerMinass GGerMi as Geraissaisaisi

Espirito Santo

Rio de Janeiro

Sao Po PSaao PSaao PSa aulooauulooauulooau o

PPPPararrraranaaaaanaa

Rio GrRRio GGrRRioo GrRio Gra aaaDo SulD SulDo ulD ulDDoo SullDo ul

PPPPereeerernambucomb oammb cmbnammbbucconamb

SergipeAlagA aos

Rio GrandeDo Norte

PPPPPPararaararaibaaibabaaibaa b



53

M A L A R I A C H E M O P RO P H Y L A X I S F O R P O P U L A R

TO U R I S T D E S T I N AT I O N S

TA B L E 1 3

* awareness of small risk of malaria; avoid mosquito bites and seek medical attention forany suspicious symptoms (up to about a year later) but tablets not considered necessary.

Angel Falls

Angkor Wat

Bali

Chiang Rai

Galapagos Islands

Goa

Iguacu Falls

Kwai Bridge

Mekong Delta

Turkey (south coast)

POPULAR DESTINATION

Doxycycline OR Mefloquine OR Atovaquone/Proganil

Doxycycline OR Mefloquine OR Atovaquone/Proganil

Awareness*

Awareness*

Minimal risk

Awareness*

Awareness*

Awareness*

Awareness*, unless close to theCambodia border when Mefloquine OR Doxycycline OR Atovaquone/ Proguanil

Awareness* in tourist resorts, forAdana and the far eastern area:chloroqine.

ACMP RECOMMENDED REGIMEN

4.5 Popular destinations



54

4.6 Emergency Standby Treatment

Emergency standby treatment should be recommended for those takingchemoprophylaxis and visiting remoteareas where they are unlikely to be within 24 hours of medical attention.

It is intended for those travellers whobelieve that they may have malaria and isnot a replacement for chemoprophylaxis.

It is particularly important that theindividual traveller is sufficiently wellbriefed to be able to use standbyemergency treatment appropriately, so written instructions for its use arerequired, not least because studies fromoutside the UK have reported standbytreatment often being usedinappropriately50.

Standby emergency treatment should be started if it is impossible to consult adoctor and/or reach a diagnosis within24 hours of the onset of fever.

Medical attention should be sought assoon as possible for full assessment andto exclude other serious causes of fever.This is particularly important as manyillnesses other than malaria may presentwith fever.

The traveller should complete thestandby treatment course andrecommence their antimalarialchemoprophylaxis 1 week after takingthe first treatment dose, except in thecase of mefloquine prophylaxis, whichshould be resumed 1 week after the lasttreatment dose if quinine was used forstandby treatment. Antipyretics shouldbe used to treat fever. A second full

treatment dose of the antimalarialshould be taken if vomiting occurs within30 minutes of taking it (half-dose ifvomiting occurs after 30–60 minutes)51.

The agent used for emergency standbytreatment should be different from thedrugs used for chemoprophylaxis, bothto minimise drug toxicity and due toconcerns over drug resistance51.

Individuals for whom emergency standbytreatment is advised must be providedwith written instructions for its use. Inparticular, they must be informed aboutsymptoms suggesting possible malaria,including fever of 38°C and above,indications for starting the standbytreatment, how to take it, expected side-effects and the possibility of drugfailure51.

ACMP recommended regimens foremergency standby treatment are givenin table 14.

Specifically, sulfadoxine/pyrimethamine(SP) is NOT recommended due to reportsof widespread resistance to this agentamong P. falciparum strains. Halofantrineis no longer recommended due toconcerns over its association withsometimes fatal cardiac arrhythmias52.

ACMP advises against purchasingantimalarial drugs over the internet.

Antimalarials purchased in the tropicsmay be fake24 and travellers shouldobtain the medication required for their emergency standby treatment from a reputable source in the UK beforethey travel.



55

E M E R G E N C Y S TA N D B Y T R E AT M E N T F O R A D U LT STA B L E 1 4

Chloroquine doses are given as the base. Quinine plus clindamycin (or chloroquine alone in the very few non-resistant areas) is the only regimen to be used in pregnancy.

Chloroquine orMulti-drugresistantfalciparummalaria



Recommendedwhere nochloroquineresistancepresent

NB Now appliesto very fewgeographicalareas

Pregnancy

SITUATIONFOR USE

STANDBYTREATMENTREGIMEN

USUALAMOUNT PERTABLET

ADULT DOSE

Co-artemether

(Riamet)

Atovaquone plus Proguanil

Quinine plusDoxycycline

Chloroquine

(Nivaquine /Avloclor)

Quinine plusClindamycin

20 mgartemether plus120 mglumefantrine

250 mg plus100 mg

300 mg quinineand100 mgdoxycycline

150 mgchloroquinebase(Nivaquine) or155 mgchloroquinebase (Avloclor)

300 mg quinine

75 or 150 mg(150 mgpreferred)clindamycin

4 tablets initially,followed by 5 furtherdoses of 4 tabletseach given at 8, 24,36, 48 and 60 hours.Total 24 tablets overa period of 60 hours

Tablets should betaken with food toenhance drugabsorption.

4 tablets as a singledose on each of threeconsecutive days

Quinine 2 tablets 3times a day for 3days, accompanied by1 tablet ofdoxycycline twicedaily for 7 days

4 tablets on days 1 &2, 2 tablets on day 3

Quinine 2 tablets 3times a day for 5-7days

Clindamycin 3 tablets(450 mg) 3 times aday for 5 days



56

Emergency Standby MedicationTraveller Information LeafletAvailable to download from the HPA website www.hpa.org.uk

You have been advised to carry emergency standby antimalarial medicationwith you on your forthcoming trip. This leaflet provides you with advice onwhen and how to use it. Please keep it safely with your medication. If you aretravelling with a companion, please ask them to read this leaflet as they maybe able to assist you in following its advice in the event of your becoming ill.

Incubation period of malariaThe minimum period between being bitten by an infected mosquito anddeveloping symptoms of malaria is 8 days, so a febrile illness starting withinthe first week of your arrival in a malarious area is not likely to be due tomalaria.

Symptoms and signs of malariaMalaria usually begins with a fever. You may then feel cold, shivery, shaky andvery sweaty. Headache, feeling sick and vomiting are common with malariaand you are also likely to experience aching muscles. Some people developjaundice (yellowness of the whites of the eyes and the skin). It is notnecessary for all these symptoms to be present before suspecting malaria asfever alone may be present at first.

When to take your Emergency Standby MedicationIf you develop a fever of 38°C [100°F] or more, more than one week afterbeing in a malarious area, please seek medical attention straight away.

If you will not be able to get medical attention within 24 hours of yourfever starting, start your standby medication and set off to find andconsult a doctor.

How to take your Emergency Standby MedicationFirst, take medication (usually paracetamol) to lower your fever. If your feveris controlled, it makes it less likely that you will vomit your antimalarial drugs.

Then, without delay, take the first dose of your emergency standbyantimalarial medication.

If you do vomit and it is within 30 minutes of taking the antimalarial drugs,repeat the first dose of them (but do not repeat the paracetamol). If youvomit 30–60 minutes after taking the first dose of the antimalarial drugs,repeat the treatment, but take only HALF the first dose.

Continue the treatment as instructed for the particular drugs prescribed for you.

Please remember that this emergency standby medication has beenprescribed based on your particular medical history and should be taken only by you as it may not be suitable for others.

Once you have completed your emergency standby medication you shouldrestart your malaria prophylactic drug(s) one week after you took the firsttreatment dose of. emergency standby medication. If your preventivemedication consists of mefloquine and your standby treatment includedquinine, you should wait a week after completing the course of quininebefore you restart mefloquine.

57





5 - Diagnosis

5.1Blood tests and how to request them. 61

5.2Rapid Diagnostic Tests (RDTs). 61

5.3Blood film negative malaria. 62

5.4Resources for treatment advice. 62

5.5Notification. 62

59

60



5. DiagnosisSuspected malaria is a medical emergency.

Consider malaria in every ill patient who has returned from the tropics in the previousyear, especially in the previous three months.

Fever on return from the tropics should be considered to be malaria until provenotherwise.

Malaria cannot be diagnosed with certainty by clinical criteria alone. Suspected casesshould be investigated by obtaining a blood film diagnosis as a matter of urgency.There is no need to wait for fever spikes before taking blood; this only delays diagnosisand the fever pattern seldom conforms to text book periodicity, especially in the case of Plasmodium falciparum.

5.1 Blood tests and how to requestthem in the UK

An EDTA-anticoagulated venous bloodsample should be taken.

The sample should be received in thelaboratory within one hour of being taken as falciparum malaria may increasein severity over a few hours and themorphology of malaria parasites in EDTAdeteriorates over time, rendering accuratelaboratory diagnosis more difficult.

Finger-prick samples smeared directlyonto microscope slides at the bedside aresub-optimal for modern diagnosis as thelaboratory then has no additional materialto make and stain further smears,undertake rapid diagnostic tests (RDTs) or refer for PCR testing.

All laboratories making a diagnosis ofmalaria should send blood films and aportion of the blood sample on which the diagnosis was made to the HPAMalaria Reference Laboratory (MRL) for

confirmation (The MRL webpages areavailable at http:// www.malaria-reference.co.uk

5.2 Rapid Diagnostic Tests (RDTs)

ACMP does not recommend travellers useRapid Diagnostic Tests (RDTs) for selfdiagnosis.

RDTs, sometimes known as “dipsticks”,permit the detection of malaria parasitesin human blood without microscopy. Used correctly, they can confirm theclinical diagnosis of malaria in placesremote from medical attention53 howeverthere is evidence of travellers beingunable to use them correctly and thusfailing to detect parasites54.

RDTs do have a place in the medical kitcarried by a doctor or nurseaccompanying an expedition to remotemalarious regions, provided care is takento transport and store them correctly andthus prevent deterioration in theirperformance in the field.



61

5.3 Blood film negative malaria

One negative blood film does notexclude a diagnosis of malaria. Wheremalaria is suspected blood films shouldbe examined every 12 to 24 hours for 3 days whilst other diagnoses are alsoconsidered. If all three films are negativeand malaria is still considered a possiblediagnosis, expert advice should besought from a specialist in tropical orinfectious diseases. It is particularlyimportant to seek such advice early inthe care of pregnant patients withsuspected malaria, as the main parasitebiomass may be sequestered in theplacenta such that peripheral blood filmsare negative despite the patient havingmalaria (see chapter 9 for expert advicelisting).

5.4 Resources for treatment advice

The treatment of malaria is outside thescope of this document and will beaddressed in ACMP malaria treatmentguidelines. Expert advice on malariatreatment may be obtained from:

The Hospital for Tropical Diseaseshttp://www.thehtd.org/

The Liverpool School of Tropical Medicinehttp://www.liv.ac.uk/lstm/

Your local infectious diseases unit

See also the British Infection Society (BIS) website http://www.britishinfectionsociety.org/for a malaria treatment algorithm

5.4 Notification

Malaria is a statutorily notifiable disease.The clinician caring for the patient mustcomplete a notification form.

The Malaria Reference Laboratory (MRL)reporting form (MRL websitewww.malaria-reference.co.uk) should alsobe completed and should be sent to theMRL separately or along with referredspecimens.



62

6 - Special Groups(Medical Conditions)

6.1Smoking cessation. 65

6.2Pregnancy. 65

6.3Breastfeeding. 66

6.4Anticoagulants . 66

6.5Epilepsy. 67

6.6Glucose 6-phosphate dehydrogenase deficiency. 67

6.7Sickle Cell disease. 68

6.8Immunocompromised Travellers. 68

Risks for transplant patientsRisks for HIV/AIDS patients

6.9Liver disease. 69

6.10Renal impairment. 69

6.11Splenectomy. 70

6.12Acute porphyrias. 70



63

64





65

6 Special Groups (Medical Conditions)6.1 Smoking cessation

Chloroquine or mefloquine should not be used in those taking Zyban® (bupropionhydrochloride SR) as the chances of seizure may be increased.

6.2 Pregnancy

Pregnant women are advised to avoid travel to malarious areas.

In the event that travel is unavoidable, the pregnant traveller must be informed of the risks which malaria presents and the risks and benefits of antimalarialchemoprophylaxis.

Pregnant women have an increased risk of developing severe malaria and a higher risk of fatality compared to non-pregnant women.

Diagnosis of falciparum malaria in pregnancy can be particularly difficult as parasitesmay not be detectable in blood films due to sequestration in the placenta.

Expert advice is required at an early stage if malaria is suspected in a pregnantwoman. Complications, including severe haemolytic anaemia, hypoglycaemia,jaundice, renal failure, hyperpyrexia and pulmonary oedema, may ensue. The resultmay be miscarriage, premature delivery, maternal and/or neonatal death.

Congenital malaria is rare, but occurs more commonly with Plasmodium vivax thanwith the other malaria parasites of humans.

Avoidance of mosquito bites is extremely important in pregnancy as pregnant womenare particularly attractive to mosquitoes. Ideally, pregnant women should remainindoors between dusk and dawn. If they have to be outdoors at night they shouldadhere rigorously to bite precautions (see chapter 3).

DEET should be used in a concentration of not more than 50%. DEET has a goodsafety record in children16 but ingestion should be avoided. Nursing mothers shouldwash repellents off their hands and breast skin prior to handling infants. See Chapter3 for further details on DEET.

• Chloroquine and proguanil: safe in all trimesters of pregnancy. Their majordisadvantage is the relatively poor protection they give in many geographical areasdue to the presence of drug-resistant P. falciparum. Pregnant women takingproguanil should receive supplementation with 5 mg folic acid daily.

• Mefloquine: caution advised (see below). • Doxycycline: contraindicated in pregnancy. • Atovaquone/proguanil: lack of evidence on safety in pregnancy.

The long-term traveller guidelines55

describe the evidence for prescribingmefloquine during pregnancy. Briefly, itseems unlikely that mefloquine isassociated with adverse foetal outcomes.There is no strong association betweenmefloquine in treatment doses56,57, andstillbirths or miscarriages in the secondand third trimesters although a lack ofdata on its use in the first trimester hasencouraged caution. The decisionwhether or not to advise mefloquineprophylaxis in pregnancy thereforerequires a careful risk-benefit analysis.Where the levels of transmission anddrug resistance (see country tables inchapter 4) make mefloquine an agent offirst choice it is generally agreed thatmefloquine may be advised in thesecond and third trimesters ofpregnancy. Given the potential severity offalciparum malaria in a pregnant woman,its use may also be justified in the firsttrimester in areas of high risk of acquiringfalciparum malaria such as sub-SaharanAfrica, after taking expert advice (seechapter 9).

Women who have taken mefloquineinadvertently just prior to or during thefirst trimester should be advised that thisdoes not constitute an indication toterminate the pregnancy.

Chemoprophylaxis prior toconceptionIf a female traveller is planning toconceive during a visit to a destinationwith a high risk of contractingchloroquine-resistant falciparum malaria,expert advice should be sought (seechapter 9 for advice centres).

Time to allow after finishing a course ofan antimalarial before attempting toconceive:• Mefloquine: 3 months. • Doxycycline: 1 week. • Atovaquone/proguanil: 2 weeks.

6.3 Breastfeeding

• Mefloquine: experience suggests safeto use during lactation.

• Doxycycline: contraindicated (do notuse).

• Atovaquone/proguanil: notrecommended because of theabsence of data however, can be usedwhen breast-feeding if there is nosuitable alternative antimalarial.

Nursing mothers should be advised totake the usual adult dose of antimalarialappropriate for the country to be visited.

The amount of medication in breast milkwill not protect the infant from malaria.Therefore, the breastfeeding child needshis or her own prophylaxis, which forchildren of breastfeeding age will beeither chloroquine plus proguanil ormefloquine. Atovaquone/proguanil maybe used if the child weighs 11kg or more.

6.4 Anticoagulants

Travellers who take anticoagulants shouldensure their INR (International NormalisedRatio) or clotting time is stable prior todeparture.

Patients on warfarin may have underlyingcardiovascular disease and may be oncardiovascular medication. Interactionswith other medication together with the



66

individuals' medical history should betaken into account when deciding onappropriate malaria chemoprophylaxis.

• Chloroquine: no interaction betweenwarfarin and chloroquine documentedin the BNF, although there is a cautionin the SPC for Nivaquine.

• Proguanil: an isolated report of anenhanced effect of warfarin whentaken together with proguanil58.

• Mefloquine: not considered to be aproblem for those taking warfarin. The manufacturer states that 'althoughno drug interaction is known withanticoagulants, effects of mefloquineon travellers should be checked beforedeparture.' Please see below for howthis can be monitored.

• Doxycycline: the anticoagulant effectof coumarins (including warfarin) ispossibly enhanced by tetracyclines59.

• Atovaquone / proguanil: unknownwhether there are interactionsbetween atovaquone/proguanil andwarfarin, although there have beenisolated reports of an enhanced effectof warfarin when taken together withproguanil (see above under proguanil).

Advice for travelers needing malariachemoprophylaxis who are takingwarfarin:

• Travellers should start taking theirmalaria tablets more than 1 week (and ideally 2-3 weeks in the case ofmefloquine) prior to their departure.

• A baseline INR should be checked priorto starting chemoprophylaxis, and re-checked after 1 week of takingchemoprophylaxis.



• If a traveller is away for a long periodof time the INR should be checked atintervals at the destination. (However,the sensitivity of thromboplastinreagent used by some laboratories in different countries may vary60).

• Once chemoprophylaxis has beencompleted, the INR should be checkedagain to re-stabilise anticoagulanttherapy.

6.5 Epilepsy

Proguanil alone (200 mg daily) isrecommended for malarious areaswithout chloroquine resistance. For areaswith a high risk of chloroquine-resistantmalaria, such as sub-Saharan Africa,doxycycline or atovaquone/proguanil can be used.

• Chloroquine: unsuitable. • Mefloquine: unsuitable.• Doxycycline: half-life may be reduced

by phenytoin, carbamazepine, andbarbiturates, so in theory its doseshould be increased for patients takingthese drugs. However, there iscurrently no direct evidence that this is necessary.

6.6 Glucose 6-phosphatedehydrogenase deficiency

Glucose 6-phosphate dehydrogenase(G6PD) is an enzyme that helps protectthe red cell against oxidative damage.Absence of G6PD renders the red cellliable to haemolysis in the presence ofsome drugs.

All G6PD-deficient travellers to malariousareas should take appropriatechemoprophylaxis despite someprotection against infection beingconferred by the most common G6PDdeficiency allele in Africa (G6PD A-)61.

67

Chloroquine: theoretical risk ofhaemolysis in some G6PD-deficientindividuals. Haemolysis does not appearto be a problem when chloroquine isgiven in the dose recommended formalaria chemoprophylaxis so there is no need to withhold chloroquineprophylaxis from those known to beG6PD-deficient. This risk is acceptablein acute malaria59 and G6PD levels arenot usually checked before usingchloroquine in treatment doses.

Primaquine: not currently recommendedas a first line agent for malariaprevention in UK travellers, but may beconsidered in special circumstances onexpert advice27. There is a definite risk ofhaemolysis in G6PD-deficient individuals.The traveller’s G6PD level must bechecked before primaquine is prescribed:G6PD deficiency contraindicates its usefor prophylaxis.

6.7 Sickle Cell disease

Presence of the sickle cell trait conferssome protection against malaria, thoughindividuals with the sickle cell trait stillrequire antimalarial prophylaxis.

For those with homozygous sickle-celldisease, malaria is regarded as asignificant cause of morbidity andmortality, producing further haemolysisagainst the background of that due tosickle-cell disease itself62. Therefore, it isessential that individuals with sickle-celldisease travelling to malaria-endemicareas receive rigorous antimalarialprotection.

6.8 Immunocompromised travellers

6.8.1 Risks for transplant patients

A review on the prevention of infection in adult travellers after organtransplantation63 recommended thatciclosporin levels should be monitored if chloroquine is co-administered.

6.8.2 Risks for those with HIV/AIDS

All of the HIV protease inhibitors (PIs) in current use, as well as the non-nucleoside reverse transcriptaseinhibitors (NNRTIs) delavirdine andefavirenz, interact with the same liverenzymes which metabolise most drugsused for malaria prophylaxis andtreatment. This can result in alteredmetabolism of antimalarials orantiretrovirals, though the extent of thisand the clinical significance is oftenunclear. The prescriber should check onan individual agent basis.

The extra risk of increased severity ifmalaria is contracted by an HIV-infectedtraveller is unclear. Most reported studieshave been done in those living inendemic areas where HIV infectionincreases the risks for contracting anddeveloping severe malaria and increasingimmunosuppression reduces treatmentsuccess64 although this varies by area65.Co-infected pregnant women are at riskfrom higher parasite density, anaemiaand malarial infection of the placenta.Children born to women with HIV andmalaria infection have low birth weightand are more likely to die during infancy.It is unclear whether malaria duringpregnancy increases the risk of mother-to-child transmission of HIV66.



68

6.9 Liver disease

Most antimalarial drugs are excreted ormetabolised by the liver. Thus, there is arisk of drug accumulation in severe liverimpairment.

• Severe liver disease: all antimalarialdrugs are contraindicated, with thepossible exception of atovaquone plusproguanil.

• Moderate impairment: proguanil, oratovaquone plus proguanil ormefloquine may be used.

• Mild impairment: chloroquine, orproguanil, or chloroquine plusproguanil, or atovaquone plusproguanil or mefloquine may be used.Doxycycline should be used only withcaution.

The choice of chemoprophylaxis shouldbe made after discussion with thepatient’s specialist, who will be able toassess their degree of hepaticimpairment. The Child-Pugh classification



is often used for grading liver functionand can be found athttp://www.emea.europa.eu/pdfs/human/ewp/233902en.pdf

6.10 Renal impairment

Chloroquine is partially excreted via thekidneys while proguanil is wholly excretedvia the kidneys.

• Chloroquine: dose reduction forprophylaxis is required only in severerenal impairment.

• Proguanil: should be avoided or thedose reduced as shown in table 15.Not to be used in patients receivingrenal dialysis.

• Atovaquone/proguanil: notrecommended for patients with acreatinine clearance of less than30mL/minute59. Not to be used inpatients receiving renal dialysis.

Doxycycline or mefloquine may be usedin severe renal failure. There is no needto reduce the dose of mefloquine inrenal dialysis59.

69

D O S E S O F P RO G UA N I L I N A D U LT S W I T H R E N A L FA I L U R ETA B L E 1 5

(none)

mild

moderate

severe

RENALIMPAIRMENTGRADE

SERUMCREATININEµMOL/LITRE

CREATININECLEARANCEML/MIN/1.73M2

PROPHYLACTICDOSAGE OFPROGUANIL

<150

150-300

300-700

>700

≥ 60

20-59

10-19

<10

200mg daily (standarddose)

100mg daily

50mg every secondday

50mg once weekly

6.11 Splenectomy

Those who have no spleen or whosesplenic function is severely impaired areat particular risk of severe malaria and,where possible, should avoid travel tomalarious areas.

If travel is essential, every effort shouldbe made to avoid infection by rigoroususe of antimosquito precautions andstrict adherence to appropriatechemoprophyaxis. If the travellerbecomes unwell during or after theirvisit, medical attention is required as a matter of urgency, as malarialparasitaemia in asplenic individuals may rise rapidly to very high levels (e.g. greater than 50% with P.falciparum).

6.12 Acute porphyrias

Doxycycline is unsafe in porphyria59

so should not be used for antimalarialchemoprophylaxis in patients with acute porphyria.



70

7.9Visiting friends and relatives. 76

7.10Students and children at boarding school. 77

7.11The long-term traveller. 77

Risk AssessmentChemoprophylaxis for long-term travellersSpecific considerations for womenSpecific considerations for infants and older children

7.12Long term visitors to the UK returning to live in malarious parts of the world. 80

Preventive measures appropriate to anendemic setting Prophylaxis

7.1Children. 73

7.2Elderly travellers. 74

7.3Multi-trip travel. 74

7.4Cruises. 74

7.5Oil rigs. 75

7.6Visits to national parks. 75

7.7Stopovers. 75

7.8Last minute travellers. 75

7 - Special Categories



71

7472





73

7. Special Categories7.1 Children

Children are at particular risk of severe and fatal malaria; therefore, parents areadvised against taking infants and young children to malarious areas.

If travel is unavoidable, infants and children should be well protected againstmosquito bites and receive appropriate malaria chemoprophylaxis.

It is important that the child’s carers understand the importance of trying to ensurethat the child properly completes the full course of prophylactic medication.

Parents should supervise children’s chemoprophylaxis, as some regimens can bedifficult even for adults to follow.

Parents must be cautious not to exceed maximum recommended doses, sinceantimalarials can be particularly toxic to children.

Paediatric doses of antimalarials for prophylaxis are shown in tables 4-6 in chapter 4:

• Chloroquine: Take care to ensure that tablets are actually swallowed, as they have a bitter taste. Sweetenedchloroquine syrup is available. Storesafely away from children since anoverdose can be fatal.

• Proguanil: as for adults more effectivewhen taken with chloroquinealthough chloroquine resistance ispresent in many areas. Difficult to usefor children since proguanil is onlyavailable in adult formulations and,dependent on the weight of thechild, the adult-dose tablets must bebroken and powdered into food.

• Chloroqine plus proguanil: seeindividual agents above.

• Mefloquine: Problem in administeringcorrect dosage because there iscurrently no suspension available andadult-dose tablets must be broken.

• Doxycycline: Only licensed in the UKfor children over the age of 12 yearsdue to the bone damaging effects ofthe drug. This age limit variesbetween countries; tablets should be swallowed whole and must not be crushed.

• Atovaquone/proguanil: Paediatrictablets are available in the UK formalaria prophylaxis in children from11 kg upwards. The tablets are aquarter of the strength of adulttablets and can be crushed ifnecessary for ease of administration.

Whilst it is preferable to avoid breakingand crushing tablets, the appropriatedose of proguanil or mefloquine oratovaquone/proguanil may be crushed ifnecessary and mixed with jam, honey,chocolate spread or similar food to aidadministration to young children. Tablet-cutters can be purchased from somepharmacies or travel shops.

Children with malaria may deterioratevery rapidly to become critically ill.Those looking after children on theirreturn from malarious areas -familymembers, friends, professional carers, orschool nursing and medical staff - shouldbe made aware that such children needmedical attention and a blood test formalaria without delay if they becomeunwell within a year of leaving amalarious area.

Healthcare professionals should strive toimprove access to advice on malariaprevention for families with children,especially travellers “Visiting Friends andRelatives”.

7.2 Elderly travellers

The elderly are at particular risk frommalaria51. No reduction in antimalarialdosage is required on the basis ofadvanced age. However, elderly travellersare more likely to have underlyingdisorders, for example renal impairment,which may necessitate antimalarial dosereduction. Furthermore, the increasedlikelihood of elderly travellers takingadditional medication, for example forcardiac conditions, will influence thechoice of chemoprophylactic agent intheir particular case.

7.3 Multi-trip travel

Some travellers, for example businesspersons or expatriate contractemployees, may make several shortvisits to malarious areas in the sameyear. For instance someone working inthe tropics four weeks on, four weeksoff, might be taking chemoprophylaxisfor most or all of the year whenincluding the periods before and aftertravel that prophylaxis is required. Thestrategy for chemoprophylaxis will thenbe mainly influenced by the level ofmalaria risk in the area(s) to be visited.For example, in the highly malariousregions of West Africa, the risk-benefitassessment is strongly in favour oftaking chemoprophylaxis, even if itmeans year-round administration. Forless frequent trips, the regions visitedshould determine the chemoprophylacticagents from which to choose. When thechoice lies between mefloquine ordoxycycline or atovaquone/proguaniland the traveller wishes tablet-freeperiods between visits, the shorterperiod of 7 days post exposure foratovaquone/proguanil prophylaxisversus the alternatives may be helpful.

7.4 Cruises

All travellers on cruises should use insectbite avoidance measures.

Cruises are a growing part of theholiday market. Most travellers oncruises are only ashore during daylighthours when Anopheles bites rarelyoccur, and therefore do not requiremalaria chemoprophylaxis. However,the cruise itinerary must be reviewedcarefully to determine the risk ofexposure to malaria.



74

As examples, cruises in the Caribbeanmay include several days travelling alongthe Amazon in Brazil, or Orinoco River inVenezuela. Cruises along the East Africancoast may include a stop for a night ormore in the port of Mombasa, Kenya andpassengers may be ashore or on deckafter dusk. These itineraries will requiremalaria chemoprophylaxis.

In addition cruises that have an overnightstay in any other malaria endemic regionof the world require malariachemoprophylaxis.

7.5 Oil rigs

There is a large number of staffemployed in the oil industrypredominantly based around West Africa.Employees commonly travel to theseareas every 4-6 weeks, followed by asimilar period of leave back in the UK. Oil rigs may be based in river estuaries ormany miles offshore. Thus, the level ofrisk may be difficult to assess until oneperiod of work has been completed andtherefore antimalarial chemoprophylaxisshould be taken for the whole of this firsttrip, by when the situation will be known.

Antimalarial chemoprophylaxis is advisedfor those workers on oil rigs based inriver estuaries.

Offshore rigs pose little risk andantimalarial chemoprophylaxis may onlybe needed if staying overnight onshoreduring transit.



7.6 Visits to national parks

Travellers visiting countries wheremalaria is restricted in distribution mayplan to make day trips to national parksin malarious regions of the country.They should be advised on awarenessof risk, bite precautions and the needfor prompt attention in the event offever during the succeeding year. Ifthey plan to stay overnight in themalarious area, e.g. in a safari lodge,they should also take chemoprophylaxis.

7.7 Stopovers

Many stopovers are in urban or touristareas (particularly in Asia) and haveminimal malaria risk. They are oftensituated in countries which may havemalaria transmission in parts. Therefore,in order to assess risk it is essential toestablish where overnightaccommodation will be.

Stopovers in most of Sub-Saharan Africa,including main cities, present a risk ofmalaria and antimalarial prophylaxisshould be recommended.

7.8 Last minute travellers

Last minute visits to malarious regions,whether for vacation, business or familyreasons, are now commonplace. This may leave the traveller little timeto seek and act on travel advice.

Retail pharmacy outlets can supply over-the-counter antimalarials (chloroquineand/or proguanil) and antimosquitoproducts, but mefloquine, doxycyclineand atovaquone/proguanil are currentlyprescription only medicines (POMs).

75

If the traveller cannot obtain a GPappointment at short notice, somecommercial travel clinics cater for walk-inattendees.

Doxycycline or atovaquone/proguanilshould be started 2 days before travel toa malarious area. Chloroquine orproguanil or chloroquine plus proguanilone week before, and mefloquine 2-3weeks before (to ensure tolerance).Nevertheless, it is better to startchemoprophylaxis late than not to take it at all, as suppressive prophylactics willbegin to work by the end of theincubation period.

Where the recommended choice for theregion to be visited is mefloquine ordoxycycline or atovaquone/proguanil, itwould be sensible to avoid mefloquinefor last-minute prophylaxis if the travellerhas not taken and tolerated mefloquinein the past.

ACMP does not recommend loadingdoses of any prophylactic antimalarial.The dosages recommended in theseguidelines should be followed.

7.9 Visiting friends and relatives

(Adapted from the HPA Travel andMigrant Health Report 200667)

In the UK, malaria predominantly affectsthe non UK born population and theirfamilies, particularly those from Africaand south Asia, largely due to their highrates of travel to malarious areas.

Data suggest that people visiting friendsand relatives are significantly less likely totake antimalarial prophylaxis than othertravellers to Africa. Reasons for this may

be that those visiting friends and relativesin Africa substantially underestimate therisk of acquiring malaria, andoverestimate the amount of protectionthat having been brought up in Africamay give them.

Awareness needs to be raised thatmalaria is not a trivial disease. Thoseborn in malarious countries need to beaware that any immunity they may haveacquired is rapidly lost after migration tothe UK. The view that this group isrelatively protected is a dangerous myth.Migrants from malarious areas also needto be made aware that second-generation members of their familieshave no clinically relevant immunity ofany kind to malaria, and that theirchildren are particularly vulnerable.

Effective chemoprophylaxis takencorrectly should reduce the risk ofmalaria by around 90%, especially ifcombined with sleeping underinsecticide-treated nets.

Appropriately tailored health informationshould be targeted to migrantcommunities, especially of Africandescent, to stress the importance ofchemoprophylaxis. Health advisers forthis group, including primary carepractitioners working in areas with largenumbers of migrants, can have a majorrole to play.

Those who feel unwell following any tripto tropical areas should be encouragedto present to their doctors early, and toinform the doctors that they are at risk ofmalaria. Patients of African origin, andoccasionally even doctors, canunderestimate the severity of malaria inthis group.



76

7.10 Students and children atboarding school

Many people from malaria-endemic areascome to the UK for secondary or highereducation.

Those who stay in Britain for a year ormore will lose a significant degree of anymalarial immunity they had acquired andbecome more susceptible to clinicalmalaria. When they return home theyshould be advised as for the section onlong term visitors to the UK returning tolive in malarious parts of the world

Those who are making short visits home(e.g. in school or college vacations) shouldbe considered as VFR travellers and shouldbe advised to use chemoprophylaxis inaddition to personal protective measuresagainst mosquito bites.

Students may become infected duringtheir school or college vacations but thefirst symptoms of clinical malaria mayactually occur in term time whilst theyare in the UK. Therefore, it is essentialthat school/college nursing and medicalstaff consider malaria from the outset inany pupil from, or with a history of travelto, a malarious region and arrange ablood test for malaria without delay.



7.11 The long-term traveller

7.11.1 Risk assessment

The long term traveller is defined here as those travelling through, or visitingmalaria-endemic countries for over sixmonths.

One major problem for the long-termtraveller is the variable access to andquality of medical care availableoverseas68. The provision of details ofhealthcare facilities or points ofinformation could be crucial.

The main issues influencing the choice ofmalaria chemoprophylaxis on a long-termbasis are the same as for short-term use,i.e. malaria risk, adverse events profile,compliance and efficacy. However, thelicensing criteria for antimalarial drugsoften restrict the recommended periodsof administration (usually due to a lack offormal trials of long-term administration,rather than from evidence of adverseeffects). This leads to uncertainly aboutthe safety of long-term prescribing.

A decision on whether chemoprophylaxisis continued on a long-term basis may beinfluenced by the overall length of stay,seasonal risk in the area, and access tomedical facilities. Travellers living orbackpacking in rural areas may be farfrom appropriate medical attention andthe need for standby emergencymedication should also be considered.The continued use of chemoprophylaxiswill also depend on current personalhealth, current medication, previousmedical history, pregnancy, and relevantfamily medical history. However, long-term travellers are at high risk frommalaria, and should not neglectnecessary prophylaxis. 77

Health risks for the long-term travellerwill vary considerably, depending in parton the reasons for travel including:

Visiting friends and relatives (VFR) Individuals who originate from countrieswhere malaria is transmitted, but whohave settled in the UK. They may latervisit their country of origin and remainthere for long periods of time whileworking or visiting friends and relatives.They may perceive little risk from malariainfection or believe they are immune.This is not true (see section on VFR in thischapter).

Expatriates Usually based at a single location wherethe risk of malaria is known, they oftenhave access to medical care, a goodstandard of accommodation and areusually more aware of the malaria risks.However, up to 30% of some expatriatesdevelop malaria within two years andmany cases can be attributed to poorcompliance with prophylaxis69.

Backpackers Often younger than expatriates, theymay be less careful of their personalsafety and less adherent to medicaladvice, in addition to having lessexperience of overseas travel in general.They have less control over theirenvironment as they are constantlymoving on.

7.11.2 Chemoprophylaxis for long-termtravellers

Adverse eventsThe cumulative risk of contractingmalaria is roughly proportional to the

length of stay in a malarious area overthe first few months. A three-month visitcarries a risk around six times greaterthan a visit of two weeks.

Whilst the risk of new adverse events fallsoff over time, the risk of contractingmalaria continues to increase roughlylinearly as exposure to malaria continues(see figure 8). Thus, chemoprophylaxis inhighly malarious areas is even moreimportant for long-term visitors than it isfor short-term travellers. Indeed, long-term travellers may wish to considerusing malaria prophylaxis, or havestandby medication, when short-termtravellers might not, because of theirsustained exposure to a small risk ofinfection.

Adherence to chemoprophylaxisCompliance has been shown to decreasewith the duration of travel70, exceptwhere military-style discipline tends tosupport compliance. There is alsoevidence of weekly regimens havingincreased compliance over dailyregimens70.

Possible reasons for reduced compliancein long-term travellers may include:• Fear of long-term side effects.• Actual adverse events on one or more

regimens.• Conflicting advice.• Complex regimen/daily tablets.• Reduced confidence if intercurrent

fever misdiagnosed as malaria.• Perception from anecdotal evidence

that chemoprophylaxis isunnecessary71.

In addition, long-term travellers mayoverlook personal protective measuresagainst mosquitoes72.



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Efficacy of regimensIt is important to stress that nochemoprophylactic regimen is 100%effective and that anti-mosquitomeasures should also be used.Travellers should be encouraged tocontinue chemoprophylaxis despitesuffering what they believe to be amalarial illness. Many febrile episodes inlong-term travellers or expatriates areincorrectly diagnosed as malaria.

Licensing restrictionsThe specific problem relating toprophylaxis advice for long-termtravellers is that long-term use of manyof the currently advised malaria drugsfalls outside the terms of their currentMarketing Authorisation (Licence).

C U M U L AT I V E R I S K O F A DV E R S E E V E N T S A N D O F M A L A R I AF I G U R E 8

There have been a number ofapproaches in response to this timelimit:• Switching from one

chemoprophylactic regimen toanother as the time limit is reached.

• Using chloroquine and proguanil, theonly regimen licensed for long-termuse but considered to givesuboptimal protection in areas ofmarkedly chloroquine-resistantfalciparum malaria.

• Discontinuing prophylaxis in favourof access to local advice andstandby or physician-guidedtreatment

• Continuing with one prophylacticregimen beyond its licensed length of use.

Numberofadverseeventsand risk ofmalaria

Time

Fewer new eventsMalaria risk

Most new events

General advice for all regimens• Once an individual is compliant on

one prophylactic regimen and istolerating it well, transfer to anotherregimen increases the likelihood ofthe development of side effects due to the introduction of a different drug.

• There is no evidence of new sideeffects emerging during long-termuse of any currently availableprophylactics, though it is oftenthought that there may be risksassociated with long-term use ofchloroquine, see below.

• Evidence for safety in long-term usecomes more from an accumulatinglack of evidence of harm than fromscientific evidence of safety.

• Individual risk assessments areimportant when deciding what adviceshould be given. In particular adviceon prophylaxis may be influenced byother measures that might be used bythose staying in areas where the risk isseasonally variable.

• Simplicity in regimen can, as always,be expected to improve compliance.The safest option is compliance withone of the most effective regimens.

• Minimising exposure to infection isimportant, especially takingprecautions against being bittenwhilst asleep.

• It is essential to seek medical advicepromptly if symptoms develop.

ACMP advice on long-term use of specificantimalarials is summarised in table 16.

7.11.3 Specific considerations for women

See section on pregnancy andbreastfeeding in chapter 6 which

includes advice on chemprophylaxis priorto conception.

7.11.4 Specific considerations for infantsand older children

Refer to section on children above.

Evidence in support of long-term use ofantimalarials in infants and older childrenis limited. Advice for long-term use inthese age groups is the same as foradults.

• Chloroquine: safe for both infants andyoung children.

• Proguanil: safe for use by infants andyoung children73.

• Mefloquine: well tolerated74. Long-term use of mefloquine is reported tobe safe, well tolerated and notassociated with an increase in adverseeffects75-77.

• Doxycycline: Not for use in thoseunder 12 years of age. No dataavailable on the long-term use ofdoxycycline; however, long-term useof other tetracyclines for otherindications is generally welltolerated78.

• Atovaquone plus proguanil: bothhighly effective and safe42.

7.12 Long term visitors to the UKreturning to live in malarious partsof the world

Persons returning to their original homesin malarious regions after prolongedresidence in the UK are likely to havesuffered a decline in the partial immunityto malaria that develops duringchildhood and is maintained by repeatedexposure in endemic regions. They may



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L O N G T E R M C H E M O P RO P H Y L A X I S F O R A D U LT S U P DAT E D

F RO M T H E 2 0 0 3 AC M P G U I D E L I N E S O N M A L A R I A

P RO P H Y L A X I S F O R L O N G - T E R M T R AV E L L E R S 5 5

TA B L E 1 6

* Considered safe for long-term use but considerable concern regarding level ofprotective efficacy of the combination of chloroquine plus proguanil in certaingeographical areas where the regimen used to be useful

Chloroquine

Proguanil

Mefloquine

Doxycycline

Atovaquone/Proguanil

MALARIACHEMOPROPHYLAXIS

ACMP ADVICE ON LONG-TERM USE

Considered safe for long-term use.*

Consider ophthalmic examination 6 to12 monthly, commencing at 6 years’prophylactic usage

Considered safe for long-term use*

No evidence of harm in long-termuse if tolerated in the short term.

Suggest can be used safely for up tothree years in the absence of sideeffects.

No evidence of harm in long-termuse. Evidence suggests that it may beused safely for periods of at least upto two years.

No evidence of harm in long-termuse. Suggest can be used confidentlyfor travel up to one year and possiblylonger, but only with caution untilmore post-licensing experience isavailable.

H A L F - L I V E S O F S E L E C T E D A N T I M A L A R I A L D RU G STA B L E 1 7

Chloroquine

Mefloquine

Doxycycline

Atovaquone

Proguanil

DRUG HALF-LIFE

Can extend from 6 to 60 days

2 to 3 weeks

12 to 24 hours

2 to 3 days

14 to 21 hours

therefore be at increased risk ofsuffering an acute attack of malariaafter returning home.

Pregnant women and small children areat higher risk than others of sufferingsevere disease.

Risk assessment and personal counsellingis essential to warn individuals of the riskof suffering from malaria, emphasisingavoidance measures, and the need forimmediate diagnosis and treatment ofacute feverish illnesses

7.12.1 Preventive measures appropriateto an endemic setting79

BednetsBed nets and other personal barrierprotective measures (e.g. suitableclothing) are very low-cost, are effectivelong-term, have virtually no side-effectsand will also help to protect from othermosquito-borne infections.

Intermittent Preventive Therapy (IPT)If IPT is local policy in their destinationcountry to prevent malaria in pregnancyand childhood, the returning visitorshould be advised to seek medical adviceon this immediately on arrival.

Case management of illnessPeople should be advised to seekmedical attention immediately if eitherthey or their children become feverishafter repatriation in the endemiccountry. They should be warned that amalaria attack may be more seriousbecause of diminished immunity.

GuidanceSee the World HealthOrganisation/national country guidanceon the appropriate measures in endemicsettings which include IPT, insecticide-treated bednets and case-managementof illness with therapy.

7.12.2 Prophylaxis

Intended useThe ACMP prophylaxis guidance is fortemporary protection for the UK traveller.This is not appropriate for individualswho are returning to permanentresidence in their country of origin.

Exception for pregnant women andyoung childrenA limited period of prophylaxis of four tosix weeks for pregnant women andyoung children may be appropriate insome circumstances, to allow them tosettle and arrange for future healthcareafter arrival in the endemic country.

Standby treatmentOffering standby treatment isinappropriate where there are likely to behealth services to diagnose and managemalaria.



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8.8Which malaria drugs can be given to babies and young children? 89

8.9What is the easiest way to calculate the correct dose of chloroquine for babies and young children? 90

8.10Many travellers I see intend to travel through several areas where different anti-malarials arerecommended as they progress through their journey. How do we advise these travellers? 90

8.11Which antimalarial drugs canI advise for a traveller who has epilepsy? 91

8.12What do I advise for the traveller with Glucose 6-phosphatedehydrogenase deficiency? 91

8.13What do I advise people working on oil rigs? 92

8.14What do I advise for the traveller on a stopover? 92

8.1What malaria prevention should be advised for travellers going on cruises? 85

8.2What alternative antimalarial drugs can be used for India (and Sri Lanka) if chloroquine and proguanil are unsuitable for a traveller? 85

8.3Which antimalarial can I give to a traveller with a history of psoriasis? 86

8.4Which antimalarial can I give a traveller who is taking warfarin? 86

8.5How long is it safe to continue a course of antimalarial tablets? 87

8.6Which antimalarial drugs are suitable for women during pregnancy? 88

8.7Which antimalarial drugs can be taken by breastfeeding women? 89

8 - Frequently Asked Questions



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8. Frequently Asked QuestionsQ1. What malaria prevention should be advised for travellers going on cruises?

A. Cruises are a growing part of the holiday market. Most travellers on cruises are onlyashore during daylight hours when the Anopheles vector of malaria is not feeding,and therefore do not require malaria chemoprophylaxis. Occasionally this is not thecase and therefore the cruise itinerary must be reviewed to determine if there will beexposure to malaria.

As examples, cruises in the Caribbean may include several days travelling along theAmazon in Brazil, or Orinoco River in Venezuela. Cruises along the East African coastmay include a stop for a night or more in the port of Mombasa, Kenya andpassengers may be ashore or on deck after dusk. These itineraries will require malariachemoprophylaxis.

In addition cruises that have an overnight stay in any other malaria endemic region ofthe world require malaria chemoprophylaxis. Risks in specific destinations can bedetermined by referring to the country tables 7-12 in chapter 4.Based on the destination, duration of exposure, and health of the traveller, the choiceof malaria chemoprophylaxis can be made using the advice in these guidelines.All travellers on cruises should use insect bite avoidance measures (see chapter 3).

Q2. What alternative antimalarial drugs can be used for India (and Sri Lanka)if chloroquine and proguanil are unsuitable for a traveller?

A. Chloroquine plus proguanil are the recommended chemoprophylaxis for India(apart from Assam state in Northern India where either mefloquine, doxycycline oratovaquone / proguanil are the drugs of choice) and Sri Lanka. If a traveller is unableto take the combination of chloroquine plus proguanil, the alternative is a choicebetween one of three prescription drugs available: mefloquine, doxycycline oratovaquone / proguanil.

It depends on the reason why chloroquine and proguanil are not suitable as to whichalternative is considered (e.g. those unable to take chloroquine due to epilepsy shouldnot take mefloquine; if a traveller does not tolerate proguanil, then they should avoidatovaqone/ proguanil (Malarone®) as this also contains proguanil). For advice onmalaria prevention in pregnant women there is a specific FAQ below.

Chloroquine plus proguanil remain the first choice agents in India and Sri Lankabecause for most areas in these countries, Plasmodium vivax is the most prevalentspecies of malaria present and chloroquine is highly effective against this species.Because there is some P. falciparum present, the addition of proguanil to chloroquineprovides additional protection against strains of P. falciparum that may be resistant tochloroquine alone. Where there is frequent or high level resistance, such as the Assamregion discussed above, alternative agents are used.

Q3. Which antimalarial can I give to a traveller with a history of psoriasis?

A. Proguanil, atovaquone / proguanil, doxycycline and mefloquine do not causeproblems in those with psoriasis. Chloroquine and chloroquine-related drugs canexacerbate psoriasis and should be avoided in those with generalised psoriasis or ahistory of such. Travellers with mild psoriasis can consider chloroquine if they areaware of the possible risks. The benefit of chemoprophylaxis with chloroquine mayoutweigh the risk of exacerbation of psoriasis, but each case should be considered onan individual basis.

Q4. Which antimalarial can I give a traveller who is taking warfarin?

A. Travellers on anticoagulants should ensure their clotting time is stable prior todeparture. It should be noted that patients on warfarin may have underlying cardiacdisease and may be on cardiac medication. Interactions with other medicationtogether with the individuals' medical history should be taken into account whendeciding on appropriate malaria chemoprophylaxis.Documented interactions between warfarin and antimalarial tabletsChloroquineThere is no interaction between warfarin and chloroquine documented in the BNF,although there is a caution in the Summary of Product Characteristics for Nivaquine.ProguanilThere has been an isolated report of an enhanced effect of warfarin when takentogether with proguanil58. MefloquineMefloquine is not considered to be a problem for those taking warfarin. Themanufacturer states that 'although no drug interaction is known with anticoagulants,effects of mefloquine on travellers should be checked before departure.'Please see below for how this can be monitored.Atovaquone / proguanil (Malarone®)It is unknown whether there are interactions between Malarone and warfarin,although there have been isolated reports of an enhanced effect of warfarin whentaken together with proguanil (see above under proguanil). DoxycyclineThe anticoagulant effect of coumarins (including warfarin) is possibly enhanced bytetracyclines59.

Advice for travellers needing malaria chemoprophylaxis who are taking warfarin

Travellers should start taking their malaria tablets at least 1 week (and ideally 2-3weeks in the case of mefloquine) prior to their departure. A baseline INR should bechecked prior to starting chemoprophylaxis, and re-checked after 1 week of takingchemoprophylaxis. If a traveller is away for a long period of time the INR should bechecked at intervals at the destination. However, the sensitivity of thromboplastinreagent used by some laboratories in different countries may vary60.



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Q5. How long can a traveller take different antimalarial drugs?

A. Guidelines for the long term use of malaria tablets are summarised in chapter 7and were originally published in 2003 by the ACMP55.

The main issues influencing the choice of malaria chemoprophylaxis on a long-termbasis are the same as for short-term, i.e. adverse event profile, ease of complianceand efficacy. However, the specific issue relating to advice on chemoprophylaxis forthe long-term traveller relates to current licensing restrictions. Long term use ofmalaria chemoprophylaxis outside licensing restrictions is based on the cumulativeevidence of lack of harm rather than positive evidence of safety. This situation isunlikely to change. ChloroquineChloroquine has been taken safely for periods of many years at doses used for malariachemoprophylaxis. However, there has been concern expressed about the possibledevelopment of retinal toxicity with long term use of chloroquine (orhydroxychloroquine, often used to treat rheumatologic disorders). Retinal toxicity hasbeen described in those on daily chloroquine dosage for rheumatic disorders. As aresult, two thresholds for the risk of retinopathy have been suggested:• A total cumulative dose of 100g of chloroquine base • A daily dose of 250mg base (4mg / kg)80.

The first threshold would require an adult to take chloroquine continuously, weekly,for a period of six years. The second threshold is far in excess of the prophylacticdosage. It has been concluded that the risk of retinopathy from prophylactic dosagealone is negligible29. Further reassurance can be gained from the fact thatretinopathy has only rarely been reported in patients taking weekly prophylacticdosages80,81.

ACMP advice suggests that chloroquine can be taken on a long-term basis. However,physicians should consider an ophthalmologic examination every 6 -12 months ,beginning at 6 years' cumulative use for those on long-term chloroquine.ProguanilThere is no time limit specified for the use of proguanil. Therefore, it can be takencontinuously for several years.MefloquineThere are few data on the use of mefloquine for periods exceeding two years,although there is no evidence of cumulative toxicity, and mefloquine taken for over 1 year is well tolerated. The product licence suggests mefloquine can be takencontinuously for a period of up to 12 months. However, advice from the ACMPindicates that there is no evidence of harm in long term use if the drug is tolerated inthe short term, and suggests that mefloquine can be used safely for up to three yearsin the absence of side effects.

DoxycyclineDoxycycline is licensed for up to two years or more in the treatment of acne in thesame dose as is used for malaria prophylaxis. The ACMP have concluded that there isno evidence of harm in long-term use of doxycycline and it may be taken safely forperiods of at least up to two years.Atovaquone / proguanil (Malarone®)Both components of Malarone® have been used individually on a long term basis,although there is little experience of long-term use of the combination. Manycountries do not restrict the length of time atovaquone/proguanil can be takenalthough the UK product license states it can only be taken for travel up to 28 days.

There is a report of atovaquone/proguanil use for periods from 9 to 34 weeks, inwhich there was no excess of adverse effects and no appearance of unexpectedadverse effects82. The ACMP concludes that there is no evidence of harm in long-term use and suggests that it can be taken confidently for travel up to one year orlonger. Nevertheless, long-term use of atovaquone/proguanil should be prescribedwith careful consideration until additional post licensing experience is available.

Q6. Which antimalarial drugs are suitable for women during pregnancy?

A. Malaria during pregnancy is a serious illness for both the mother and the fetus.Pregnant women should be advised against travel to an area with malaria, particularlyit there is chloroquine resistant Plasmodium falciparum.

Doxycycline and atovaquone / proguanil (Malarone®) are both unsuitable for useduring pregnancy.

Results of animal studies indicate that tetracyclines cross the placenta, are found infetal tissues and can have toxic effects on the developing foetus (often related toretardation of skeletal development). Evidence of embryotoxicity has also been notedin animals treated early in pregnancy (SPC).

The safety of atovaquone and proguanil hydrochloride when administeredconcurrently for use in human pregnancy has not been established and the potentialrisk is unknown. Animal studies showed no evidence for teratogenicity of thecombination. The individual components have shown no adverse effects onparturition or pre- and post-natal development (SPC). Women should be reassuredthat taking Malarone inadvertently prior to or during the first trimester is not anindication to terminate a pregnancy.

The data available from studies on the prophylactic use of mefloquine in pregnancy isgenerally reassuring. Most experts recommend that mefloquine is avoided during thefirst trimester, but can be offered to women during the second and third trimesters. The risk of adverse effects of mefloquine use in pregnancy should be balancedagainst the risk of contracting malaria and the complications that can result. Thedecision on whether to recommend mefloquine should be carefully discussed withthe traveller.



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Women of childbearing age should take contraceptive precautions while takingmefloquine and for three months after the last dose. However, they should bereassured that taking mefloquine inadvertently prior to or during the first trimester isnot an indication to terminate a pregnancy.

Both chloroquine and proguanil have been taken safely during pregnancy for manyyears although this combination offers insufficient protection in areas withchloroquine resistant P. falciparum. Folic acid supplements should be taken ifproguanil is used in those who are pregnant or seeking to become pregnant.

Q7. Which antimalarial drugs can be taken by breastfeeding women?

A. Breastfeeding women should not take doxycycline or atovaquone / proguanil(Malarone®). Chloroquine plus proguanil can be used during breastfeeding althoughthis combination provides suboptimal protection for the mother in areas ofchloroquine resistant Plasmodium falciparum malaria.

There is little data on the use of mefloquine during breastfeeding (see Breastfeedingsection in chapter 6). Although mefloquine is excreted in breast milk in small amountsthere is not enough data to draw conclusions regarding potential harmful effects onthe infant.

Mefloquine may be considered for breastfeeding mothers travelling to areas ofchloroquine resistant P. falciparum. Each traveller should be assessed individually,weighing the potential risks and benefits of taking mefloquine whilst breastfeeding,and taking into consideration the risk of malaria at the destination.

The small amounts of antimalarials that pass into breast milk are not enough toprotect the baby. Breastfeeding infants therefore need to take their own prophylaxis.If both mother and infant are taking mefloquine there is a concern that the amountof mefloquine the infant may receive will exceed the recommended maximum,particularly in infants in the lower weight range. However, this possible effect is likelyto be short lasting as the weight of the child increases and the contribution ofmefloquine in breast milk to the total prophylactic dose becomes relatively small.

Q8. Which antimalarial drugs can be given to babies and young children?

A. Both chloroquine and proguanil can be given from birth. Chloroquine is available assyrup but proguanil will need to be crushed and given with jam or food.

Mefloquine can be given to infants weighing 5 kg or more (see Summary of ProductCharacteristics). Atovaquone / proguanil (Malarone®) can be given to infants weighing11 kg or more; paediatric tablets are available.

Doxycycline is unsuitable for children under 12 years.

One of the main challenges in giving malaria tablets to babies and young children willbe the practical aspects of administration.

All dosages for malaria chemoprophylaxis in children are found in tables 4-6 inchapter 4, and in the British National Formulary (BNF). The dose for children will bedependent on the weight / age of the infant or child.

Mosquito bite avoidance is extremely important for this age group.

Q9. What is the easiest way to calculate the correct dose of chloroquine forbabies and young children?

A. The dose steps for chloroquine syrup are not the same as for chloroquine tabletsand a child may be prescribed a different dose of chloroquine depending on whetherthey take tablets or syrup (see tables 4 and 5, chapter 4). The main reason for anydifferences is due to the different amount of chloroquine base within the syrup andthe tablets. The chloroquine syrup formulation contains 50 mg chloroquine base / 5mls syrup. The amount of chloroquine base contained within the tablets is 150mg(Nivaquine) and 155mg (Avloclor).

An additional factor which might be confusing is that the packet insert forchloroquine phosphate (Avloclor) gives different dosages (usually lower) for childrenthan in these guidelines and the BNF. The ACMP guidelines and BNF dosages shouldbe used.

While there is an optimum dose of chloroquine base for children of every weight, thefinal dosage given to the child will depend, in part, on the practicality ofadministering the formulation of chloroquine available (i.e. either tablet or syrup).E.g., when dividing tablets for children, it is not possible to break a tablet into thirds,so the dosages will involve either a half or a quarter of a tablet.

The tables in chapter 4 have been calculated based on weight and surface area andthe most accurate dose according to the weight is recommended. Althoughdifferences occur, all recommended dosages in the tables fall within accepted limitsof toxicity. It is important not to overdose children with chloroquine as severe toxicitycan occur.

A practical approach when calculating children's dosages for chloroquine is todecide on the most appropriate preparation (either tablet or syrup) for the childand calculate the dose appropriate to that preparation, according to the tables inchapter 4.

Q10. Many travellers I see are travelling through areas where different anti-malarials are recommended as they progress through their journey. How dowe advise these travellers?

A. Travellers planning extensive journeys across continents will often travel into areaswhich have different malaria chemoprophylaxis recommendations. In these situationsit is important that the traveller is protected in all areas of risk and the choice ofmedication needs to reflect the overall risk.

It may be possible to move from one regimen to another, although for shorter tripsthis may not be practical. For example, a traveller visiting parts of India for 2 weeks(where chloroquine plus proguanil may be recommended) and then going on to areasin Myanmar and Cambodia for 6 weeks (where mefloquine, doxycycline oratovaquone/proguanil may be recommended) would be advised to take eithermefloquine, doxycycline or atovaquone/proguanil for the whole of the visit ratherthan change from chloroquine and proguanil to one of the other agents.



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Q11. Which antimalarial drugs can I advise for a traveller who has epilepsy?

A. Both chloroquine and mefloquine are unsuitable for those with epilepsy. For areaswith a high risk of chloroquine resistant Plasmodium falciparum, doxycycline oratovaquone / proguanil can be used. However for children under the age of 12 theonly suitable antimalarials under these circumstances will be atovaquone / proguanil(Malarone®) (bearing in mind the length of travel). Proguanil alone can be given formalarious areas without chloroquine resistance.

Phenytoin, carbamazepine and barbiturates reduce the half life of doxycycline; intheory the dose should be increased for those taking these drugs. However, there isno evidence that this is necessary, and a dose adjustment is not recommended.

Q12. What do I advise for the traveller with Glucose 6-phosphatedehydrogenase deficiency?

A. Glucose 6-phosphate dehydrogenase (G6PD) is an enzyme in the hexosemonophosphate shunt of the glycolytic pathway. This shunt supports the red cell’sprotection against oxidative damage. Absence of G6PD renders the red cell liable tohaemolysis in the presence of some drugs.

The most common G6PD deficiency allele in Africa (G6PD A-) has been shown toconfer some resistance to malaria in both hemizygous males and heterozygousfemales61. Nevertheless, all G6PD-deficient travellers to malarious areas still requireappropriate chemoprophylaxis.

ChloroquineThere is a theoretical risk of haemolysis in some G6PD-deficient individuals whoreceive chloroquine. This risk is acceptable in acute malaria59 and G6PD levels are not usually checked before using chloroquine in treatment doses. Haemolysis doesnot appear to be a problem when chloroquine is given in the dose recommended formalaria chemoprophylaxis so there is no need to withhold chloroquine prophylaxisfrom those known to be G6PD-deficient.

PrimaquineThis drug is not currently recommended as a first line agent for malaria prevention inUK travellers, but may be considered in special circumstances on expert advice27.There is a definite risk of haemolysis in G6PD-deficient individuals. The traveller’sG6PD level must be checked before primaquine is prescribed and G6PD deficiencycontraindicates its use for prophylaxis.

Q13. What do I advise people working on oil rigs?

A. There is a large number of staff employed in the oil industry predominantly basedaround West Africa. Employees commonly travel to these areas every 4-6 weeks,followed by a similar period of leave back in the UK. Oil rigs may be based in riverestuaries or many miles offshore. Therefore the level of risk may be difficult to assessuntil one period of work has been completed and antimalarial chemoprophylaxisshould be taken for the whole of this first trip.

Antimalarial chemoprophylaxis is advised for those workers on oil rigs based in riverestuaries.

Offshore rigs pose little risk and antimalarial chemoprophylaxis may only be needed ifstaying overnight onshore during transit.

Q14. What do I advise for the traveller on a stopover?

A. Many stopovers are in urban or tourist areas (particularly in Asia) and have minimalmalaria risk. They are often situated in countries which may have malaria transmissionin parts. Therefore, in order to assess risk it is essential to establish where overnightaccommodation will be.

Stopovers in most of sub-Saharan Africa, including main cities, present a risk ofmalaria and antimalarial prophylaxis should be recommended.



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9 - InformationResources

9.1Expert centres. 95

Prophylaxis adviceDiagnostic adviceTreatment advice

9.2Useful websites. 95

9.3Information leaflets. 96

9.4Reference list. 97

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9. Information Resources

9.1 Expert centres

9.1.1 Prophylaxis advice

Malaria Reference Laboratory (MRL)http://www.malaria-reference.co.uk Advice line for healthcare professionals: 020 7636 3924

National Travel Health Network and Centre(NaTHNaC) http://www.nathnac.org/ Advice line for healthcare professionals: 0845 602 6712

Liverpool School of Tropical Medicine (LSTM)http://www.liv.ac.uk/lstm/

TRAVAX (Health Protection Scotland)http://www.travax.nhs.uk/

9.1.2 Diagnostic advice

Malaria Reference Laboratory (MRL)http://www.malaria-reference.co.ukDiagnostic advice for health care professionals020 7927 2427

The Hospital for Tropical Diseases (HTD)http://www.thehtd.org/

The Liverpool School of Tropical Medicine(LSTM) http://www.liv.ac.uk/lstm/ Advice line for Healthcare professionals 0151 708 9393

9.1.3 Treatment advice

The treatment of malaria is outside the scopeof this document and will be addressed inACMP malaria treatment guidelines. Expert advice on malaria treatment may beobtained from:

The Hospital for Tropical Diseases (HTD)http://www.thehtd.org/ Requests for emergency admission or veryurgent clinic attendance should be made tothe Duty Doctor, who is bleeped viaswitchboard. Telephone: 0845 1555 000Bleep 5845

The Liverpool School of Tropical Medicine(LSTM) http://www.liv.ac.uk/lstm/ Advice line for Healthcare professionals 0151 708 9393

Your local infectious diseases unit

British Infection Society (BIS)http://www.britishinfectionsociety.org/ (malaria treatment algorithm)

9.2 Useful websites

British National Formulary (BNF)http://www.bnf.org

British Infection Society (BIS)http://www.britishinfectionsociety.org/

Department of Healthhttp://www.dh.gov.uk

Electronic Medicines Compendium(for Summaries of Product Characteristics)http://www.emc.medicines.org

Liverpool School of Tropical Medicine (LSTM)http://www.liv.ac.uk/lstm/

London School of Hygiene and TropicalMedicine (LSHTM)http://www.lshtm.ac.uk/

Malaria Reference Laboratory (MRL)http://www.malaria-reference.co.uk

Medicines and Healthcare products RegulatoryAgency (MHRA)http://www.mhra.gov.uk

National Travel Health Network and Centre(NaTHNaC) http://www.nathnac.org/

Health Protection Agency (HPA)http://www.hpa.org.uk/

Royal Society of Tropical Medicine andHygiene (RSTM&H)http://www.rstmh.org/

TRAVAX (Health Protection Scotland)http://www.travax.nhs.uk/

World Health Organization (WHO)International Travel and Healthhttp://www.who.int/ith/en/

9.3 Information LeafletsThe Department of Health produces“Think Malaria” leaflets, order codeMAL/1, which are available in 11 differentlanguages and can be obtained from theDH Publications Orderline by writing toDH Publications Orderline, PO Box 777London SE1 6XH or telephoning 0870155 5455 or by email [email protected].

For further information please see theDepartment of Health websitehttp://www.dh.gov.uk



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41 Camus D, Djossou F, Schilthuis HJ et al.Atovaquone-proguanil versuschloroquine-proguanil for malariaprophylaxis in nonimmune pediatrictravelers: results of an international,randomized, open-label study.Clinical Infectious Diseases.2004;38:1716-23.

42 Faucher JF, Binder R, Missinou MA et al.Efficacy of atovaquone/proguanil formalaria prophylaxis in children and itseffect on the immunogenicity of liveoral typhoid and cholera vaccines.Clinical Infectious Diseases.2002;35:1147-54.



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44 Ling J, Baird JK, Fryauff DJ et al.Randomized, placebo-controlled trialof atovaquone/proguanil for theprevention of Plasmodium falciparumor Plasmodium vivax malaria amongmigrants to Papua, Indonesia. ClinicalInfectious Diseases. 2002;35:825-33.

45 Marra F, Salzman JR, Ensom MH.Atovaquone-proguanil for prophylaxisand treatment of malaria. Annals ofPharmacotherapy. 2003;37:1266-75.

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47 Shanks GD, Gordon DM, Klotz FW et al. Efficacy and safety ofatovaquone/proguanil as suppressiveprophylaxis for Plasmodiumfalciparum malaria. Clinical InfectiousDiseases. 1998;27:494-9.

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49 Soto J, Toledo J, Luzz M, Gutierrez P,Berman J, Duparc S. Randomized,double-blind, placebo-controlledstudy of Malarone for malariaprophylaxis in non-immuneColombian soldiers. American Journalof Tropical Medicine & Hygiene.2006;75:430-3.

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Membership of the HPA AdvisoryCommittee on Malaria Prevention in UK travellers

Chair: Dr B Bannister (Infection Services, Royal Free Hospital, London)

Members: Dr R Behrens (Travel Clinic, Hospital for Tropical Diseases London)

Professor P Chiodini (Director of the HPA Malaria Reference Laboratory, London)

Ms F Genasi (Health Protection Scotland) from July 2006

Wing Commander A Green (Defence Consultant Advisor in Communicable Diseases, Ministry of Defence)

Professor D Hill (Director of NaTHNaC, Honorary Professor LSHTM, National Travel Health Network and Centre, London)

Dr G Kassianos (General Practitioner, Berkshire)

Dr D Lalloo (Clinical Director, Reader in Clinical Tropical Medicine, Liverpool School of Tropical Medicine)

Dr G Lea (Chief Travel Medicine Advisor Trailfinders Travel Clinic, London)

Mr D Mehta (Executive Editor, British National Formulary, London)

Professor G Pasvol (Department of Infection & Tropical Medicine Imperial College London)

Dr M Powell (Medical & Healthcare Products Regulatory Agency (MHRA), London)

Dr Delane Shingadia (Consultant/Hon Senior Lecturer in Paediatric Infectious Diseases, Great Ormond Street Hospital)

Dr E Walker (Consultant Physician & Epidemiologist (Travel Medicine) Health Protection Scotland) to July 2006

Professor D Warrell (Centre for Tropical Medicine, University of Oxford)

Professor P Winstanley (University of Liverpool)

Professor C Whitty (Gates Malaria Partnership, London School of Hygiene and Tropical Medicine).

Health Protection Agency Expert Advice Support Office61 Colindale Avenue London NW9 5EQ

Tel: +44(0)20 8327 6688Tel: +44(0)20 8327 6007Email: [email protected]

www.hpa.org.uk

9 780901 144836

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Printed January 2007ISBN 0 901144 83 5© Health Protection AgencyThis report is printed on chlorine-free paper

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