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Malaria is an infection spread to humans via the female anopheles mosquito.

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It accounts for between 1 and 3 million deaths annually and represents one of the most important parasitic infections in public health medicine. In medical terms, malaria is often considered to be ‘the great mimic’ with symptoms varying between people (even those exposed within the same geographic area) and clinical presentations encompassing many different symptoms. Common symptoms of acute malaria include fatigue, aching, and a progression through an initial shaking phase (known as rigors), then to a very high fever (often greater than 40 degrees) with associated agitation, nausea, vomiting, and convulsions, through to persistent sweating and reduction in temperature.

Reproductive Cycle and Transmission

The symptoms described above can be different depending on the particular type of malaria parasite that is transmitted. Currently, four types are known to infect humans are recognised: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. Of these, P. falciparum is responsible for the most serious forms of the condition. In each of the four types of malaria, the same process of infection is observed. During this process, the female mosquito bites a human host and injects her eggs into the human blood stream from her salivary glands. Once inside the human, the eggs travel around the bloodstream to the liver where they become incorporated into liver cells, once this stage of the cycle is complete the liver cell ruptures and thousands of smaller cells are released back into the blood. These smaller cells, merozoites, enter red blood cells and it is once they are in the blood cells that the clinical symptoms of malaria are seen. The time between entering the bloodstream initially and entering the red blood cells varies between the different forms of malaria and explains the different incubation periods for the infection.

The next stage of the cycle starts when the merozoites develop further and differentiate into male and female cells called gametes. Once the patient who is infected with malaria is bitten for a second time, these gametes are taken back up from the bloodstream into the mosquitos gut. Once in the gut, they combine to form a zygote. Once the zygote has formed, it develops further and then undergoes rupture to release the eggs that are then returned to the mosquito’s salivary glands where the infection can be spread once again and the cycle repeats.

The infection cycle can be seen as two organisms transmitting a parasitic organism between them, passing it back and forth and contributing to the spread of malaria. Neither the human nor the mosquito benefit from the infection, but the ‘natural’ process of the mosquito biting a human to obtain blood for nourishment is hijacked by the malarial parasite. For the malaria cycle to successfully recur, there are a number of steps that must occur.

  1. The mosquito must reproduce to provide enough of the mosquito hosts for the malaria parasite to be transmitted to humans
  2. Mosquitos need to bite humans and inject the parasite
  3. The liver cell must incorporate the parasite and allow it to develop
  4. Red blood cells must incorporate the parasite and allow it to develop
  5. The human host needs to be bitten a second time in order to repeat the transmit malaria back to the mosquito.
  6. The malarial parasite must develop and split within the mosquito.

If stages 2 through 4 occur, the person who is bitten will still be infected with malaria; if stages 1, 5, and 6 do not occur then the malarial parasite will be unable to repeat its reproductive cycle.

The incubation period for P. falciparum is usually 7 – 14 days but may extended up to 6 weeks in people who have partial immunity or who are only taking some of the preventative medication; in this example, stages 3 and 4 have been slowed and the reproductive cycle is delayed but not stopped. The other forms of malaria have incubation periods of between 12 and 40 days. P. ovale is unusual in that it can stay dormant within the liver and be reactivated months or years later.

Protecting against malaria infection

There are several ways of protecting against malaria infection. Some of these are specific to people who live in areas of high malaria risk, some are environmental or related to public health, and the remainder relate to adequate prevention of malaria and treatment of people who are infected.

In endemic areas, higher levels of genetic conditions affecting red blood cells are seen in people who live in these regions. For example, the medical conditions glucose-6-phosphate deficiency, thalassaemia trait, sickle-cell trait, and spherocytosis are more common. In these conditions the red blood cell can become distorted or non-receptive to the malaria parasite and therefore prevent it completing its reproductive cycle; similarly if the parasite is unable to enter the red blood cell, it does not produce the classic symptoms of malaria. On their own, some of these conditions, for example sickle-cell disease or thalassaemia will lead to medical problems in people who have them. In people who have sickle-cell or thalassaemia trait, where none or only of the characteristics of these conditions is seen, they appear to protect people against malaria. This is often given as an explanation of one medical problem, which on its own causes symptoms and may lead to early death, can be an advantage to people who have the trait and benefit from the reduced likelihood of malaria. Similarly, in people who live in high risk areas for malaria, they are constantly exposed to the malaria parasites and can develop some degree of immunity.

Malaria risk can also be reduced by reducing exposure to mosquitos or reducing the chance of being bitten. Common examples include the use of mosquito nets or repellents and insecticides, using smoke to reduce mosquito density and discourage mosquitos from entering certain areas, and by reducing large areas of water and wetland where mosquitos reproduce. These are common reasons why large tourist areas of certain countries where malaria exists are often considered safe due to the markedly reduced risk of being in contact with mosquitos. Risk increased, in more rural areas or where these measures are not taken.

Perhaps the most well-known way of reducing risk of malaria infection is through the use of anti-malaria medications or malaria prophylaxis. These are drugs that are taken by travellers to reduce the likelihood of the malaria parasite being able to reproduce and therefore unable to cause symptoms. It is also a common reason why malaria can be seen in people who stop taking malaria tablets immediately after their holiday finishes rather than continuing the tablets after arriving home.

A summary of the common preventative strategies is:

  1. Prior to entering a high risk (endemic) malaria region, travellers should take medications so that they have time to reduce risk before entry. Most can be started 1 week prior to travel, in the case of mefloquine, treatment should start 2-3 weeks before travel. The medications need to be continued for up to 4 weeks after returning home. Some newer medications, such as Malarone® can be started the day before travel and stopped 7 days after return.
  2. Whilst in the endemic region, it is sensible to use approved mosquito repellent and netting to the risk of being bitten. In addition to reducing malaria risk, this also reduces the risk of skin infections after being bitten by flying insects.
  3. Common medications include Malarone (which taken once daily), Mefloquine (which is taken weekly but is more likely to cause nausea, dizziness, or nervous/psychiatric reactions, and should not be taken by women who are pregnant), Doxycycline (which is taken daily but should not be used by children under 8 years or pregnant women), Primaquine (taken daily but can cause stomach upset), or Proguanil (often only used in low-risk areas, and taken as a daily dose).

Clinical Symptoms

In people who develop with a fever up to 1 year after travel to a high risk area, malaria should be considered. As described above, malaria can present in many ways depending on which part of the body is affected by the malarial parasite once released from the red blood cell; since blood is necessary for all parts of the body to function, all parts of the body can potentially be affected.

In more severe cases, malaria can lead to coma or neurological symptoms (cerebral malaria; the most important complication of P. falciparum infection), breathing difficulty which may be trigger by direct infection within the lungs or by anaemia caused by reduced functional red blood cells, kidney failure, low blood sugar, jaundice, or anaemia. One symptom that can be alarming to people who have malaria is ‘blackwater fever’. In this condition, the extensive rupture of red blood cells causes haemoglobin (the red protein in blood) to enter the urine. If haemoglobin comes into contact with certain medications used to treat malaria it turns a deep red/black colour and this affects the colour of the urine – hence the term ‘blackwater’.

In any person suffering these symptoms following potential exposure to malaria, urgent medical attention is required. In order to check your risk of exposure and review options for medication suitable for reducing malaria risk, visit the Fit for Travel website (www.fitfortravel.nhs.uk) where you can enter your travel destination and obtain appropriate advice.