Malaria prophylaxis

Malaria prophylaxis is the prevention of malaria. Malaria is thought to be one of the oldest infectious diseases, evolving around 10,000 years ago. The development of virulence in the parasite has been demonstrated using genomic mapping of samples from this period, confirming the emergence of genes conferring a reduced risk of developing the malaria infection. References to the disease can be found in manuscripts from ancient Egypt, India and China, illustrating its wide geographical distribution. The first treatment identified is thought to be Quinine, one of four alkaloids from the bark of the Cinchona tree. Originally it was used by the tribes of Ecuador and Peru for treating fevers. Its role in treating malaria was recognised and recorded first by an Augustine monk from Lima, Peru in 1633. Seven years later the drug had reached Europe and was being used widely with the name ‘the Jesuit's bark’. From this point onwards the use of Quinine and the public interest in malaria increased, although the compound was not isolated and identified as the active ingredient until 1820. By the mid-1880’s the Dutch had grown vast plantations of cinchona trees and monopolised the world market.

Quinine remained to be the only available treatment for malaria until the early 1920’s. During the First World War German scientists developed the first synthetic antimalarial compound – Atabrin and this was followed by Resochin and Sontochin derived from 4-aminoquinoline compounds. American troops, on capturing Tunisia during the Second World War, acquired, then altered the drugs to produce Chloroquine.

The development of new antimalarial drugs spurred the World Health Organization in 1955 to attempt a global malaria eradication program. This was successful in much of Brazil, the US and Egypt but ultimately failed elsewhere. Efforts to control malaria are still continuing, with the development of drug-resistant parasites presenting increasingly difficult problems.

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Basic prevention

The ABCD of malaria prevention are:

• Awareness of risk;
• Bite prevention - Travelers to malarious areas are advised to wear long clothes that cover as much of the skin as possible. Exposed parts of the body should be treated with insect repellent. When sleeping, insecticide-impregnated bed nets should be used. See also: Indoor residual spraying
• Chemoprophylaxis; and
• rapid Diagnosis and treatment.

Suppressive prophylaxis

Chloroquine, proguanil, mefloquine, and doxycycline are suppressive prophylactics. This means that they are only effective at killing the malaria parasite once it has entered the erythrocytic stage (blood stage) of its life cycle, and therefore have no effect until the liver stage is complete. That is why these prophylactics must continue to be taken for four weeks after leaving the area of risk.

Causal prophylaxis

Causal prophylactics target not only the blood stages of malaria, but the initial liver stage as well. This means that the user can stop taking the drug seven days after leaving the area of risk. Malarone® and primaquine are the only causal prophylactics in current use.

Chemoprophylaxis

Prior to the emergence of widespread chloroquine resistance, malaria prophylaxis was very simple: one chloroquine tablet a week was sufficient cover. The aims of malaria treatment, in broad terms are to alleviate symptoms (caused by the erythrocytic phase), to prevent relapses (caused by the hypnozoites of vivax and ovale) and to prevent further transmission of the parasite (occurs through gametocytes using the anopheles mosquito as a vector). The principals of treatment depend on four factors, these being: the type of infection, [i|140|the severity of infection], the status of the host and any associated conditions or diseases present in the host. There are approximately 14 antimalarials that are advised for use in the prevention and treatment of uncomplicated malaria. These will be discussed individually with particular attention to the specific recommended usage for each drug.

Antimalarial drugs

Antimalarial drugs are designed to prevent or cure malaria. Some antimalarial agents, particularly chloroquine and hydroxychloroquine, are also used in the treatment of rheumatoid arthritis and lupus associated arthritis. There are many of these drugs currently on the market. This is a partial list.

Currently used for treatment

• mefloquine (Lariam)
• chloroquine
• fansidar (sulfadoxine-pyrimethamine)
• amodiaquine
• quinine/quinidine
• artemisinin/artemether/artesunate
• atovaquone
• lumefantrine

Currently used for prophylaxis

• mefloquine
• chloroquine
• proguanil
• pyrimethamine (daraprim)
• doxycycline
• hydroxychloroquine (Plaquenil)

Drug regimens

The following regimens are recommended by the WHO, UK HPA and CDC:

• chloroquine 300 to 310 mg once weekly, and proguanil 200 mg once daily (started one week before travel, and continued for four weeks after returning);
• doxycycline 100 mg once daily (started one day before travel, and continued for four weeks after returning);
• mefloquine 228 to 250 mg once weekly (started two-and-a-half weeks before travel, and continued for four weeks after returning);
• Malarone® 1 tablet daily (started one day before travel, and continued for 1 week after returning).

What regimen is appropriate depends on the country or region travelled to. This information is available from the UK HPA, WHO or CDC (links are given below). Doses depend also on what is available (e.g., in the US, mefloquine tablets contain 228 mg base, but 250 mg base in the UK). The data is constantly changing and no general advice is possible.

Doses given are appropriate for adults and children aged 12 and over.

Other chemoprophylactic regimens that are available:

• Dapsone 100 mg and pyrimethamine 12.5 mg once weekly (available as a combination tablet called Maloprim® or Deltaprim®): this combination is not routinely recommended because of the risk of agranulocytosis;
• Primaquine 30 mg once daily (started the day before travel, and continuing for seven days after returning): this regimen is not routinely recommended because of the need for G-6-PD testing prior to starting primaquine (see the article on primaquine for more information).
• Quinine sulphate 300 to 325 mg once daily: this regimen is effective but not routinely used because of the unpleasant side effects of quinine.

See also

• Malaria vaccine
• Antimalarial drug

References

• 2007 guidelines are available from the UK Health Protection Agency website as a PDF file and includes detailed country-specific information for UK travellers.
• The World Health Organisation provides country-specific advice on malaria prevention.
• The Centers for Disease Control and Prevention website hosts constantly updated country-specific information on malaria. The advice on this website is less detailed, is very cautious and may not be appropriate for all areas within a given country. This is the preferred site for travellers from the US.

HPA and WHO advice are broadly in line with each other (although there are some differences). CDC guidance frequently contradicts HPA and WHO guidance.