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Malaria: prevention and treatment

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VOL: 98, ISSUE: 05, PAGE NO: 34

Carolyn Driver, MSc, RGN, RM, RHV, FPCert, is an independent travel health specialist nurse and chair of the British Travel Health Association

Malaria is a serious, potentially fatal disease and people travelling to infected areas should take appropriate preventive steps to reduce their risk of contracting it.

Malaria is a serious, potentially fatal disease and people travelling to infected areas should take appropriate preventive steps to reduce their risk of contracting it.

Prevention relies on a combination of chemoprophylaxis and bite avoidance. Chemoprophylaxis involves taking medication before and during a trip abroad and, in most cases, for four weeks afterwards. People are more likely to comply if they understand the nature of the risk and the drug they are being asked to take.

Chemoprophylaxis
One of the most worrying aspects of malaria is the ability of the causative organism, plasmodium, to develop resistance to combative drugs. Drug resistance develops over time and is not necessarily universal, so a drug may be appropriate in one country but not another, and different drugs may be required in different parts of the same country. It is essential, therefore, to advise tourists and business travellers to take medication that is appropriate for their destination.

The appropriateness of your choice of drug will depend on the type of malaria present at the patient's destination, the possibility of resistance and the person's age and medical history. The best way to check is to use a database that is updated daily (see further information box).

In sub-Saharan Africa, Amazonian regions of South America and parts of South-East Asia, the predominant type of malaria is Plasmodium falciparum, which is resistant to chloroquine. For these areas the following prophylactic drugs should be used (note that the doses given are for adults):

- Mefloquine: 250mg weekly, starting two-and-a-half weeks before travel;

- Doxycycline: 100mg daily, starting three days before travel;

- Atovaquone and proguanil: one tablet daily, starting one day before travel. It needs to be taken for only seven days after leaving an infected area.

All antimalarial drugs have side-effects, some of which have been highlighted, often out of context, by the media. Scaremongering can distract from the importance of preventing a potentially fatal disease. All available drugs can cause minor gastric upset, headache and neuropsychiatric symptoms.

It is important for health care professionals and tourists to realise that neuropsychiatric symptoms can range from headache, insomnia and dizziness through to serious psychotic episodes. Symptoms at the milder end of the spectrum are most common and can occur as readily with chloroquine and proguanil as with mefloquine. Choosing the most appropriate antimalarial drug is a balancing act between personal medical history, disease resistance and the degree of risk.

Mefloquine
This drug is effective against all malarial species. It acts on the parasite during the blood phase (Driver, 2002) and has a long half-life so it needs only to be taken weekly. Resistance to mefloquine has been observed in the Thai/Cambodian and Thai/Myanmar borders and is being monitored.

Mefloquine can be given to children aged three months and over and can be used in the second and third trimesters of pregnancy. Although there is no evidence of teratogenicity, it is best not to administer mefloquine during the first trimester. Because of its long half-life, women are also advised to avoid pregnancy for three months after taking the drug. However, inadvertent pregnancy while taking mefloquine is not considered to be grounds for termination.

Absolute contraindications to mefloquine are a history of epilepsy in either the client or a first-degree relative, or a history of depression or any other mental health disorder in the client. Caution is required if the client has a cardiac conduction disorder or is taking beta-blocking or calcium-channel-blocking drugs.

Doxycycline
Like mefloquine, doxycycline works during the blood phase of the disease. It is effective against P. falciparum and P. vivax, but has a relatively short half-life so it must be taken daily. It need only be taken for two to three days before entering an infected area, but must be taken continuously for four weeks after leaving it. There is no evidence of resistance to doxycycline, but it cannot be used during pregnancy or lactation, or be given to children under 12 years old. It is contraindicated in people with an allergy to tetracyclines.

Antacids containing aluminium, calcium or magnesium impair absorption, which can also be reduced by antiepileptic drugs. Women on the oral contraceptive pill need to take additional contraceptive precautions for the first two weeks of concurrent administration. Women may be more susceptible to candidal infection while taking doxycycline and should be advised to pack a self-treatment preparation.

Doxycycline can cause photosensitivity, but this may be reduced by using a sunscreen of factor 15 or above which blocks both UVA and UVB rays (Beallor and Kain, 2001).

Atovaquone and proguanil
In a breakthrough for chemoprophylaxis, the UK licensed the combination drug atovaquone and proguanil for malaria prevention last year. It destroys P. falciparum during the blood and hepatic phases, which means that it needs to be taken for just seven days after leaving an infected area and can be started only one day before arrival, offering a much shorter course of medication.

Atovaquone and proguanil is highly effective against P. falciparum and appears to be well tolerated. Like all antimalarial drugs, headache and gastric disturbance may occur. This drug is contraindicated in anyone with severe renal impairment or a known hypersensitivity to either component. There is not enough data to support its use during pregnancy and its UK licence is for use in people weighing over 40kg only, so it should not be used for young children or infants. It is licensed for use for one day before arrival in an infected area, up to 28 days while at risk, plus seven days after leaving the area (a maximum of 36 days).

Chloroquine
Taken in a weekly dose of 300mg, chloroquine is a cheap and effective drug that has been in use for 50 years. It is contraindicated in anyone with a family history of epilepsy and people with generalised psoriasis, but is safe to use during pregnancy. Its side-effects are generally mild to moderate and include gastric disturbance, headache, dizziness, sleep disturbance and pruritus. Most of Central America shows no chloroquine resistance, and although parts of South America and South-East Asia have limited chloroquine resistance, a combination of chloroquine and proguanil will provide a good level of protection.

Proguanil
Taken in a daily dose of 200mg, proguanil is rarely used alone, although it is useful in chloroquine-sensitive areas when chloroquine is contraindicated. It can be used in combination with weekly chloroquine if there is evidence of chloroquine resistance. This combination is no longer a first-line choice, but is used where alternative regimens are contraindicated.

There are no absolute contraindications to proguanil, but caution is advised in severe renal impairment. While it is safe in pregnancy, folate supplements are recommended. The side-effects are similar to those associated with chloroquine, with headache and gastric disturbance most common. Mouth ulcers can also occur, usually after prolonged use.

It is generally recommended that chloroquine and proguanil are taken a week before entering infected areas and continued for four weeks after leaving.

Travel advice
Travel advice involves describing all available drugs, some of which may be eliminated by age or medical history, and allowing the client to make an informed choice. All medications, except chloroquine and proguanil, require a private prescription from a GP, with the client purchasing them from a pharmacy at the retail price.

Antimalarial drugs are not cheap and can add a significant cost to the travel plans of large families. Those who have been well advised will understand why it is vital that they buy the correct medication and will not allow the cost to deter them. Equally, travel health advisers must ensure that they are using good information sources so that they are not recommending drugs where there is no risk or where alternatives would be appropriate.

Personal protection measures
None of the available drugs offer complete protection against malaria, so it is important to try to avoid being bitten by mosquitoes. By avoiding bites, clients may also avoid contracting other insect-borne diseases, many of which cannot be prevented by vaccination or chemoprophylaxis. There are various ways to deter mosquitoes, including the use of:

- Clothing - the more skin that is covered the less opportunity insects have to bite;

- Insect repellents - these should contain diethyltoluamide (DEET). Up to 50% strength can be applied to adult skin; 10-20% concentration is recommended for infants and children. Repellents should be applied to all exposed skin;

- Insecticides - these may be used in the environment as a knock-down spray or can be sprayed on to clothing (natural fibres only) or cotton wrist and ankle bands;

- Mosquito nets - these should be treated with an insecticide such as permethrin. It is essential to sleep under a net if not in air-conditioned accommodation.

- Vaporisers - these plug into the electricity supply and heat a permethrin-soaked mat or coils that release a pyrethroid vapour.

Anopheline mosquitoes are at their most active between dusk and dawn, so precautions are necessary in the evening and during the night. However, other species of mosquito, which can carry diseases such as yellow fever and dengue fever, are more active during the day, so it is best to avoid being bitten at all times.

Treatment
Treatment usually requires admission to hospital as falciparum malaria can be fatal within a few days. In addition, the increasing resistance of plasmodium to several antimalarial drugs makes close observation necessary. The same antimalarial agents are often used to prevent and treat malaria, so if a patient has contracted malaria despite the use of appropriate preventive medication, an alternative product should be used to combat the possibility of resistance.

Conclusion
To prevent malaria, people need to have a good understanding of how the disease is transmitted and the methods used to avoid infection. They must also be aware of the persistent risk and should report their travel history if they have a severe febrile illness for anything up to two years after their return from an infected area. Travellers should be taught the ABCD of malaria:

A = awareness;

B = bite avoidance;

C = chemoprophylaxis;

D = diagnosis.

Travel health advisers should ensure that they know about the prevention of malaria, keep up to date and use the most reliable sources of information when advising clients.

- Part one, published last week, described the life cycle of the causative organism and the signs, symptoms and diagnosis of malaria

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