Prevention of malaria

6.1  Introduction

About 2,000 cases of imported malaria are reported each year in the UK. While this total has changed little in recent years, the proportion due to the more severe Plasmodium falciparum has steadily increased. About seven people die from malaria each year in the UK and almost all these deaths are preventable.

Most cases of malaria are in those who failed to take, or comply regularly with, malaria prophylaxis. At particular risk are settled migrants returning to visit relatives abroad: they are often unaware that any natural immunity gained during residence in an endemic area rapidly wanes on leaving it. Malaria transmission may also have increased since they left. Most deaths from malaria have followed a delay in diagnosis because neither the returned traveller nor the doctor took prompt medical action for illness and/or fever.

Many warm climate countries are endemic for malaria and thus pose some risk to travellers. The level of risk may vary enormously between, and even within, countries and this will affect the type of prophylaxis recommended. Appropriate chemoprophylaxis combined with prudent behaviour can greatly reduce the risk, but the possibility of acquiring malaria remains whatever precautions have been taken. In all malarious areas the traveller must be aware of this risk and suspect any illness with fever to be possible malaria. This means getting prompt medical attention and, if back in the UK, pointing out to the doctor the history of travel to a malarious area.

6.2  Principles of malaria prevention

Since no chemoprophylactic regimen can be considered 100 per cent effective, chemoprophylaxis is only part of malaria prevention, which has four main components:

• A.  Awareness of the risk, by traveller and doctor.

  B.  Reducing Bites from anopheline mosquitoes.

  C.  Using appropriate Chemoprophylactic drugs.

  D.  Awareness of the residual risk, and prompt Diagnosis and treatment of clinical malaria.

6.3  Awareness of the risk

Both traveller and doctor need to be aware of the malaria risk during the planned visit, to select appropriate preventive measures, and to ensure prompt medical attention, diagnosis and treatment if malaria occurs in spite of precautions. The first is to prevent malaria, the second to prevent a fatal outcome and shorten the illness.

Malaria risk is set out in the previous pages by geographical region and by country, and these should be consulted. The situation in broad terms is as follows:

Most of Africa south of the Sahara is highly malarious and the vast majority of cases of falciparum malaria reported in England and Wales are acquired in East, West or Central Africa. The highest attack rates - around one to two per cent of travellers per visit in one study - occur in West Africa (Gambia, Ghana, Nigeria, Sierra Leone); attack rates in East Africa (Kenya and Uganda) are lower but more people visit this area and Kenya has been a particular source of fatalities. Some cities, but by no means all, are malaria-free. Chloroquine resistance is widespread throughout the continent and P.falciparum resistant to several common antimalarials occurs at varying levels throughout Africa south of the Sahara.

In southern Africa the risk of malaria is on the whole low, and large areas of Namibia and Botswana, parts of Zimbabwe, and South Africa except for certain game parks and rural regions in the north-east, are malaria-free. The areas affected and transmission of malaria may increase in times of heavy rainfall.

Thirty per cent of malaria imported into Britain is from the Indian subcontinent, mainly due to P.vivax. Some chloroquine resistance is reported.

Many popular tourist destinations in south east Asia are malaria free or have a very low risk. UK tourists infrequently visit regions of high transmission. Multi-drug resistant falciparum malaria occurs in Vietnam, Cambodia and the Thai-Cambodian border, making drug prophylaxis difficult.

In the Pacific, Papua New Guinea, Irian Jaya, the Solomon Islands and Vanuatu are malarious, and chloroquine resistant P.vivax as well as P.falciparum malaria is now reported. This is a cause for concern for future prophylaxis advice.

Latin America is a relatively infrequent destination for British travellers. In the central American republics, P.vivax predominates and although the risk is low, prophylaxis is recommended. In South America the whole Amazon basin is malarious with P.falciparum resistant to chloroquine (and often also sulphadoxine-pyrimethamine) present. Outside that large area risk is low in Brazil and negligible in its cities.

Different types of travel carry different risks. The package tourist who stays in one place will usually have a clearly defined risk (often high in Africa, but low in Asia), but beware the person with an urban destination who may add on visits to the countryside or game parks. Business travellers may be visiting downtown offices only, but they may be concerned with field projects or add a touristic weekend. Overland travellers are at particular risk, especially if young - they may be exposed to a variety of environments and are unlikely to stay in screened air-conditioned hotels. Prolonged travel increases the risk of contracting malaria and the temptation to relax compliance with preventive measures must be resisted. This also applies to expatriates intending to reside in malarious areas for years - they may benefit from specialist advice.

Certain individuals are at higher risk of severe malaria and need to be fore-warned. These include pregnant women (see 15.2), and asplenic individuals. Malaria in pregnancy is often a life-threatening infection and the wisdom of travelling to a malarious area should always be questioned.

6.4  Protection against mosquito bites

It is important to reduce the chance of an infective mosquito bite as far as possible. Anopheles mosquitoes bite only between dusk and dawn, and most intensively during the night. To avoid being bitten travellers should be advised to take the precautions mentioned below.
 

6.5  Chemoprophylaxis

UK chemoprophylaxis regimens should always be advised in conjunction with advice on personal protection and recognition of malaria symptoms. Weekly drug regimens should be started at least one week before departure (preferably two to three weeks for mefloquine) and continued compliantly until four weeks after return. The first part of this advice is so that side effects or reactions may occur before departure, and can be dealt with before travelling. The continued use of drugs on return will deal with infection contracted towards the end of the stay. Possible side effects should be discussed. Minor side effects are frequent with all regimens. Users should be warned to get further advice if they are concerned about side effects or they are too severe to continue the medication. The chemoprophylactic should be taken after meals.

Travellers should also be warned that if they buy antimalarials abroad, the strength of the tablets may be different; they may need to take expert advice about how many to take to avoid unwittingly under-dosing.

Specialist advice is needed on antimalarial drugs for those with severe hepatic or renal impairment.

Chloroquine

In the absence of chloroquine resistant parasites, the adult dose of chloroquine 300mg (as base) (two tablets) weekly gives good protection against malaria attacks safely and with few side effects. This will not prevent establishment of the dormant liver stages of vivax and ovale malaria which can occasionally give rise to late attacks of malaria up to a year after travel.

Chloroquine plus proguanil

In areas with moderate to high chloroquine resistance, such as in sub-Saharan Africa, this combination now provides substantially less protection than mefloquine. For areas with limited chloroquine resistance chloroquine plus proguanil is still widely recommended and still has important advantages over newer regimens. It has a wide safety margin with no severe or permanent toxicity and has been used for many years in pregnancy and in infants, with no record of fetal toxicity. Folate supplements are recommended during pregnancy. For adults, the recommended doses are chloroquine 300mg (as base) (two tablets) weekly and proguanil 200mg (two tablets) daily. Compliance with daily dosing may be poor. Adverse reactions include nausea, diarrhoea, dyspepsia and itching. Chloroquine, but not proguanil, is available as a syrup; crushing proguanil tablets, for example in jam or butter, remains an unsatisfactory method of administering it to infants and young children.

Mefloquine

For areas such as sub-Saharan Africa where highly chloroquine resistant falciparum malaria occurs, weekly mefloquine (adult dose 250 mg weekly) is an effective regimen, and can be recommended for journeys up to one year in length. In Africa and the Pacific its efficacy is estimated to be 90 per cent, however resistance is high in parts of Cambodia and in Thailand on the Myanmar and Cambodia borders. Its single weekly dose appeals to travellers. Despite much media attention to them, major adverse events (convulsions, coma and psychotic disturbances) are rare - reported in about one in every 10,000 users taking prophylactic doses. Lesser side effects occur with a frequency similar to side effects from chloroquine and proguanil. For mefloquine these lesser side effects include dizziness, strange dreams, mood swings, insomnia, headaches and diarrhoea. These could affect the ability to drive, pilot a plane or operate machinery. The drug is only slowly excreted.

Mefloquine should not be given to people with a history of psychiatric disturbance or epilepsy. Mefloquine is currently not routinely advised during pregnancy. Where a pregnant traveller cannot be dissuaded from visiting areas with a high risk of highly chloroquine resistant P.falciparum malaria, it can be used cautiously during the second and third trimesters; data so far suggest it is also safe in the first trimester. Mefloquine is secreted in breast milk and in view of limited data, the manufacturer does not recommend its use during breastfeeding.

Malarone

Malarone is a combination of proguanil and atovaquone. It has proved highly effective in clinical trials in Africa as a prophylactic against P.falciparum malaria, with an overall efficacy of 98 per cent. It has been licensed for treatment of malaria in many countries including the UK for some time. It is now licensed in the UK for malaria prophylaxis in adults for up to 28 days. The PHLS Malaria Advisory Committee considers it an alternative to mefloquine or doxycycline to be considered for adults traveling to chloroquine resistant areas, particularly in Africa and SE Asia. It is taken as a single daily tablet and as it appears to act against the pre-erythrocytic stages of P.falciparum it only needs to be continued for seven days post travel.

The combination seems to be well tolerated. Reported adverse events have been mainly gastrointestinal - abdominal pain, dyspepsia, gastritis, and diarrhoea - although headaches are also commonly reported.

Doxycycline

In recent years increasing use of doxycycline for malaria prophylaxis in UK travellers has revealed few problems, although the overall number of users has been relatively low, partly due to its previously unlicensed status as a prophylactic in the UK. Doxycycline is now licensed for malaria prophylaxis and experience in its use for this indication is likely to increase.

Doxycycline is recommended for travellers to areas where P.falciparum strains are resistant to other drugs eg sub-Saharan Africa, western provinces of Camdodia and on the Thai-Myanmar and Thai-Cambodian borders. It is also recommended as an equal alternative to mefloquine for those areas of the Pacific Islands where malaria is endemic. In addition it is available as a second line regimen where mefloquine or chloroquine are unsuitable.

For travel to most areas of sub-Saharan Africa chloroquine plus proguanil has been the traditional alternative regimen, however doxycycline is considered, on the basis of trials outside Africa, to give greater protection than this combination. Those who are travelling to Africa for whom high levels of protection against malaria are desirable, but for whom mefloquine is unsuitable, may be recommended to use doxycycline.

Its main side effects are diarrhoea (but it can also provide protection against bacterial diarrhoeas), vaginal thrush and photosensitive dermatitis. The latter may be particularly relevant to those on beach holidays. It is not recommended for children under 12 years or during pregnancy and lactation. It is not considered appropriate for long term travel, its use generally being limited to up to six months.

Maloprim

Maloprim (a fixed combination of dapsone and pyrimethamine), not to be confused with malarone (see above), is a second-line drug which is sometimes useful where other drugs are unsuitable. The usual adult regimen is chloroquine 300mg with maloprim one tablet, both weekly. The therapeutic ratio is narrow: severe bone marrow toxicity has been reported when two tablets weekly have been taken instead of one. Minor adverse reactions are seen with a similar frequency to other regimens. Caution should be exercised in pregnancy (especially in the first trimester). Maloprim should only be considered during pregnancy where travel to high risk areas is unavoidable and other drugs are unsuitable. Folate supplements are then required.

6.6  Prescribing stand-by therapy

Travellers who will be out of reach of prompt medical attention, particularly in malarious areas where chemoprophylaxis is either not recommended or of limited efficacy, could be provided with a drug regimen to self-treat an episode of malaria. This must be accompanied by careful counselling on the presenting symptoms of malaria, the indications for use of the drug and how to use it safely. If possible, the traveller should try to seek a medical opinion before starting the treatment, but if assistance is not available within eight hours of the onset of symptoms, a full course of therapy should be taken while continuing with other preventive measures. Self-diagnostic tests for falciparum malaria are in development and may be useful in the future for confirming the diagnosis of malaria.
 

Quinine frequently causes adverse reactions such as tinnitus and people should be forewarned (see page 88 for adverse reations to other drugs).

6.7  Malaria symptoms

Malaria can present any time from about a week to up to a year or more after exposure. Early and rapid diagnosis is necessary to reduce complications and death. All travellers to malarious areas should be advised about the varied symptoms of malaria (see below), which can be non-specific. Travellers should be encouraged to seek medical advice for any new symptoms. Extra doses of chemoprophylactic drugs should be specifically discouraged as this may interfere with diagnosis (and cause adverse reactions). The urgency to make the diagnosis cannot be over-emphasised. Deaths have occurred within 24 hours of the first symptoms. Travellers should be warned that no prophylaxis is 100 per cent effective.
 

TABLE 1 Doses of prophylactic antimalarial drugs for adults*

  

* See BNF for contraindications
 

TABLE 2 Doses of prophylactic antimalarial drugs for children^† (in fraction of adult doses)
 

Caution - in other countries tablet size may vary

* Not recommended

         ^†See BNF for contraindications

        ^†† Weight is a better guide, ages are given as guidelines
 

TABLE 3 Doses of prophylactic antimalarial drugs for children^† (in tablets)
 

Caution - in other countries tablet size may vary

* Not recommended

         ^† See BNF for contraindications

        ^†† Weight is a better guide, ages are given as guidelines
 

TABLE 4 Chloroquine - doses by 5ml spoon measure for children
 

^†† Weight is a better guide, ages are given as guidelines