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  Basic Principles for Preventing Malaria

(A) Be aware when there is a risk however small.
See the records on the country (s) concerned for details of the risk.
(B) Keep mosquito bites to a minimum
This includes using protective clothing, insect repellents and nets. See also preventing insect bites and insect repellents.
(C) Use chemoprophylaxis correctly
See the country (s) concerned for specific drug recommendations Your choice will depend not only on effectiveness but also on contraindications, side effects, cost and compliance.
Some drugs should be taken before departure. If a particular drug has not been used before, consider a trial course before departure to detect those likely to get side effects (e.g. 3 weeks for mefloquine, 1 week for chloroquine and a one or two days for proguanil, doxycycline and Malarone). Regardless of any trial course, drugs that are taken only once a week should be started at least one week before exposure to ensure adequate blood levels are achieved.
Take your medication continually while at risk. Tablets must be taken regularly according to the manufacturer's instructions.
Take your medication for the recommended period after leaving the risk area. Chloroquine, proguanil, mefloquine and doxycycline should be taken for 4 weeks after leaving an infected area to cover the 'incubation' period. Malarone should be taken for only 7 days after leaving an infected area.
Note: Delayed illnesses - the incubation period of benign (P. vivax and P.ovale) malaria may be greater than 4 weeks (up to a year or more). Four weeks prophylaxis after return may then not prevent these delayed, less serious, illnesses.
(D) Report any feverish illness promptly to a doctor and say you have been to a malarious area.

Avoiding insect bites

  • To avoid bites wear clothing that covers as much of the body as possible.
  • Use insect repellents on exposed surfaces.
  • Use a mosquito net when sleeping in unscreened accommodation. Mosquito nets should be impregnated with an insecticide. Many outdoor shops now stock nets and it can be helpful to practice erecting nets before departure.

Clinical features

Incubation period
P. falciparum has a short development phase within the human host and illness usually begins within 2-4 weeks of the infected bite. This period can be prolonged if partially effective or irregular chemoprophylaxis has been used, due to persistence of small numbers of parasites that multiply after prophylaxis is discontinued. This early development phase in P.vivax and ovale infection may be similar but is often longer due to the formation of hypnozoites as described above. This phase in P.malariae infections is up to 35 days..
Those affected
People of all ages can contract malaria and P.falciparum causes the most severe illness. Infants under 6 months may not develop such severe malaria if their mother has transferred to them a degree of temporary immunity and also because foetal haemoglobin retards parasite development. This does not apply to the non-immune visiting from a non-endemic country. Repeated infections may result eventually in less serious illness. Malaria in pregnancy frequently results in foetal loss or premature labour.
Prodrome and fever
Some times there is a prodrome of malaise, headache and muscle pains but the first major symptom is usually fever, irregular in falciparum malaria but usually occurring every 2nd day with P.vivax and P.ovale and every 3rd day with P.malariae. At this stage symptoms may be very similar to influenza. Rigors followed by profuse sweating occur, more so in vivax and ovale malaria. Malaria must be considered as a cause of any febrile illness in anyone who could have been exposed. Fevers can be less severe in those with some immunity or those on partially effective prophylaxis, which may confuse the unwary. A wide range of other symptoms can occur including diarrhoea abdominal pain and a dry cough.
Jaundice and cerebral malaria
Jaundice, which may make the unwary think the patient has hepatitis, and rapidly progressive anaemia due to massive haemolysis are usually the next major signs followed by impaired conscious level, coma (cerebral malaria) and circulatory collapse. In malignant infections due to P. falciparum, the illness can very rapidly progress. It is particularly fulminant in those who have had a previous splenectomy. The death rate at this stage even with the best intensive care can be up to 10%.
Other complications
These include haemoglobinurea (blackwater fever) which may be followed by renal failure, and pulmonary oedema (presenting as adult respiratory distress syndrome), often after the initial recovery phase. Convulsions and hypoglycaemia occur sometimes related to drug treatment. Secondary bacterial pneumonia or urinary tract infections can occur. In benign malaria, if the illness not promptly treated, thrombocytopaenia and splenomegaly are common with a possible danger of splenic rupture. Anaemia may develop, but life-threatening complications are unusual.

Drugs used for malaria prophylaxis


Chloroquine (licensed for prophylaxis in UK)
  • Preparations available: Avloclor® (Zeneca) and Nivaquine® (Rhône-Poulenc Rorer). Nivaquine is available in syrup form: adult dose is 2 tablets (each containing 150mg chloroquine as base) taken once a week.
  • Consider a trial course before departure, if using this regime for the first time, to detectif you are likely to get side effects (e.g. for two weeks). Otherwise, when possible, chloroquine should be started one week before exposure to ensure adequate blood levels, throughout exposure and for 4 weeks afterwards.
  • Nausea and sometimes diarrhoea can occur which may be reduced by taking tablets after food.
  • Headache, rashes, skin itch, disturbance of visual accommodation (often expressed as blurreddistance vision which may take up to 4 weeks to reverse) or hair loss may warrant changing to alternative drugs.
  • Retinopathy which can be permanent is unlikely to occur until more than 100g have been consumed (i.e. over 5 years treatment at prophylactic doses).
  • Caution in hepatic and renal impairment.
  • Can aggravate psoriasis and very occasionally causes a convulsion so it should not normally be used in those with epilepsy or when first degree relatives have idiopathic epilepsy.
  • Chloroquine is very toxic in overdose - parents must take special care to store the tablets safely.
  • It is generally accepted, as a result of long usage, to be safe in pregnancy.

Proguanil (licensed for prophylaxis in UK)
  • Preparations available: Paludrine® (Zeneca. Adult dose is 200mg daily.
  • Can normally be used continuously for a period of at least 5 years.
  • One or two doses should be taken before departure. It should be continued throughout exposure and for 4 weeks afterwards.
  • Anorexia, nausea, diarrhoea and aphthous (simple) mouth ulcers can occur.
  • Can delay the metabolism of the anticoagulant, warfarin, and result in bleeding. If it has to be used, restabilising the prothrombin time in advance of departure is advised.
  • Caution in renal impairment.
  • Safe in pregnancy, but folate supplement is advised.

Mefloquine® (licensed for prophylaxis in UK)
  • Preparations available: Lariam® (Roche) Adult dose is 250mg weekly.
  • One dose should be taken a week before departure and it should be continued throughout exposure and for 4 weeks afterwards however three (3) doses at weekly intervals prior to departure are advised if the drug has not been used before - this can detect, in advance, those likely to get side effects so that an alternative can be prescribed.
  • Although not a licensed regime, some authorities recommend 1/2 tablet twice a week (instead of one tablet once a week) to try an minimise any 'hang-over' feeling the day after taking a dose. If this is done it may take longer for the traveller to reach stable protective blood levels so the regime should be started well in advance of exposure.
  • Licensed for 1 year's continuous use in Britain but there is no evidence that use for periods of up to 3 years carries any greater risk of side-effects.
  • Nausea, diarrhoea, dizziness, abdominal pain, rashes and pruritis can occur.
  • Headache, dizziness, convulsions, sleep disturbances (insomnia, vivid dreams) and psychotic reactions such as depression have been reported. These reactions most commonly begin within 2-3 weeks of starting the drug and may be worse if alcohol is taken around the same time as the mefloquine.
  • Avoid in those with epilepsy (or when first degree relatives have idiopathic epilepsy) or when there is a history of psychiatric illness.
  • Caution, and avoid if alternatives are available, in severe renal or liver failure and those with cardiac conduction defects. Also caution in those taking digoxin, beta or calcium channel blockers when arrhythmias and bradycardia can occur.
  • Although there is no evidence to suggest that mefloquine has caused harm to the foetus it should normally be avoided during the first trimester of pregnancy or if pregnancy is considered possible within 3 months of stopping prophylaxis.
  • Approximate cost is £2.50 per week

Doxycycline (licensed for prophylaxis in UK)
  • Preparations available: Doxycycline (non-proprietary), Vibramycin® (Invicta). Adult dose is 100mg daily.
  • No guidance is given by the manufacturers on prolonged usage for malaria prevention but has been used for periods of up to 2 years for acne without an increased risk of side effects.
  • Consider a trial course before departure, if you are using this regime for the first time, to detect if you are likely to get side effects (e.g. for one week). Otherwise doxycycline need only be started just before exposure (e.g. 2 days), continued through exposure and for 4 weeks afterwards.
  • When tetracyclines are being already used for acne this will provide protection against malaria so long as an adequate dose is taken (equivalent to 250mg oxytetracycline four times a day or 100 doxycycline per day)
  • Erythema (sun burn) due to sunlight photosensitivity can occur. Sunscreens are important and if severe alternative prophylaxis should be used.
  • Heartburn is common if capsules release their contents into the oesophagus so they should be taken with a full glass of water and preferably while standing upright.
  • Contraindicated in pregnancy (including one week after completing the course), breast feeding, in those with systemic lupus erythematosis, porphyria and children under 12 years because permanent tooth discoloration can occur.
  • It must be remembered that anti-epileptic drugs (phenytoin, barbiturates and carbamazapine) may reduce the efficacy of the doxycycline (some authorities increase the dose but whether this is necessary is unclear).
  • It may theoretically reduce the effectiveness of the oral contraceptive pill for about 4 weeks after starting the doxycycline.
  • Occasionally anorexia, nausea, diarrhoea, candida infection and sore tongue (glossitis) have been reported and rarely hepatitis, colitis and blood dyscrasias.

Malarone® (licensed for prophylaxis in UK)
  • Adult dose is one tablet daily - each tablet contains 250mg atovaquone plus 100mg proguanil.
  • DO NOT confuse with Maloprim® which is not now advised for prophylaxis since more effective alternatives are available.
  • Should be taken to 1 or 2 days before entering the malarious area, throughout exposure, and for 7 days after leaving the infected area.
  • Licensed for stays in malarious areas for periods of up to 28 days but can be used safely for up to 3 months (and possibly 6 months or longer). Specialist advice should be sought for long-term prophylaxis.
  • Protection against benign malaria: Malarone acts on blood forms of P. vivax and ovale malaria. However, it does not eliminate latent 'hypnozoites' from the liver and therefore will not prevent delayed primary attacks occurring after the drug is discontinued, sometimes months or rarely years after exposure. Malignant malaria due to P. falciparum does not have a hypnozoite stage, so delayed primary attacks are much rarer and Malarone is normally effective unless resistance is present.
  • Rashes, abdominal pain, headache, anorexia, nausea, diarrhoea, coughing and aphthous (simple) mouth ulcers can occur
  • Absorption may be reduced in diarrhoea and vomiting and blood levels are significantly reduced with concomitant use of tetracyclines, metoclopramide and especially rifampicin or rifabutin
  • Proguanil can delay the metabolism of the anticoagulant, warfarin, and result in bleeding.
  • If it has to be used, re-stabilising the prothrombin time in advance of departure is advised.
  • Caution in renal impairment.
  • Lack of experience in pregnancy and during breast feeding means that it should be avoided in these circumstances unless there is no suitable alternative. Ideally pregnancy should also be avoided for 2 weeks after stopping the the medication.
  • Approximate cost is £22 per week.

Occasionally used drugs (Expert advice should normally be taken before using these drugs)
Primaquine (unlicensed)
  • Ideal adult dose is 30mg daily.
  • Can precipitate serious haemolysis in G6PD deficiency, especially in those of Mediterranean origin, so blood levels must be checked before use.
  • Does not need to be taken for more than one week after leaving the infected area since it destroys hepatic forms of the parasite.
  • Cost (approximately): £14 per week

Maloprim® (unlicensed)
  • Adult dose is one tablet once a week - each tablet contains dapsone 100mg plus pyrimethamine 12.5mg
  • Also called Deltaprim in many European countries.
  • DO NOT CONFUSE with Malarone (see above).
  • Not often used, resistance is widespread and it is rarely used.
  • Side effects at recommended doses are rare.
  • At higher doses or if given for prolonged periods, cyanosis due to methhaemoglobinaemia, haemolytic or megaloblastic anaemia, thrombocytopaenia, agranulocytosis, psychosis, and insomnia have been reported.
  • Maloprim is contraindicated in those with a sulphonamide sensitivity.
  • Cost (approximately): £3 per week.

Malaria prophylaxis in Pregnancy

  • It is important to take prophylaxis during pregnancy when there is a risk of contracting the disease because malaria in pregnancy can be very dangerous for the mother and for the baby. An attack frequently precipitates miscarriage, premature labour or/and foetal death, most especially in the non-immune traveller.
  • Proguanil and/or chloroquine are generally accepted as being safe in pregnancy due to long expereince in its use. When proguanil is used in pregnancy, or when conception is anticipated, folic acid 5mg daily should be taken to prevent macrocytic anaemia in the mother and neural tube defects in the foetus which have been associated with folate deficiency. However resistance is common making it of limited value in many countries (see the country record concerned).
  • Mefloquine is only advised by the manufacturers in pregnancy when there are 'compelling medical reasons' which presumably means when the patient is at significant risk and there are no alternatives. However there is no evidence to suggest that mefloquine has caused foetal abnormalities and it has been used extensively for travellers from the USA where proguanil is not available. It is usual to avoid its use during the first trimester or if pregnancy is considered possible within 3 months of stopping prophylaxis.
  • Doxycycline should not normally be used in pregnancy since it may interfere with bone and tooth development in the foetus.
  • Malarone, in the absence of evidence as to its safety one way or the other, the manufacturers say it should only be used when there are no alternatives.
  • Sometimes it is necessary to advise the pregnant traveller NOT to go to highly endemic areas unless absolutely essential, especially if medical facilities are likely to be poor and/or there is a substantial drug resistance problem.

Malaria prophylaxis for Infants and Children

  • When prophylaxis is advised it should be taken by infants from birth.
  • Infants who are being breast fed warrant prophylaxis in their own right because the dose in breast milk is unlikely to be adequate.
  • Chloroquine and proguanil can be used from birth at the appropriate child's dosage.
  • Chloroquine is available as a child's syrup but proguanil tablets have to be divided and crushed.
  • Doxycycline should not be used by a mother who is breast feeding to avoid tooth and bone problems in the child. Doxycycline is contraindicated in children under around 12 years because it can cause teeth and bone growth defects.
  • Mefloquine and Malarone® are not normally used until infants are 5kg and 11kg in weight respectively and should be avoided by breast feeding mothers. While it has been suggested that young children are less likely to get side-effects this can be because problems such difficulty sleeping, vivid dreams and anxiety can be difficult to recognise in the very young.
  • Sometimes it is necessary to advise parents that very young children should NOT to go to highly endemic areas unless absolutely essential, especially if medical facilities are likely to be poor or there is a substantial drug resistance problem.
You may need to take a supply of personal emergency treatment abroad with you if you are going to be away from medical facilities since treatment should always be started promptly.
     
     
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