Malaria

Malaria
Malaria is a tropical parasitic disease, it is caused by the transmission of a protozoan parasite which has the ability to infect RBCs. The most common route of transmission vessel for this disease is via the pregnant female anopheles mosquito.

It is the cause for a high morbidity and mortality rate in certain areas of the world, mostly distributed in tropical and subtropical areas. Malaria has been known to cause illness within the UK, this is generally due to importation. 

According to the WHO 2013 world malaria report. 97 countries had on-going malaria transmission, and an estimated 3.4 billion people were at risk, 1.2 billion being at high risk. In 2012, there were an approximate of 207 million cases with 670,000 deaths. 90% of deaths from malaria occur in sub-saharan Africa, with 77% being children under the age of 5 years old. All this information can be found on the WHO website. 

Malaria is a bigger problem in some areas more so than others, this can be for obvious reasons, such as the normal habitat for mosquitos, and varying climate types. Other reasons can also be due to lack of funding, and the cooperation of governments and charities. Education and preventative measures should be addressed also, such as teaching people in such areas to cover bare skin, and use insecticide sprays, buy nets etc, however access to these preventative measures is another factor as to the diseases abundance. Access to good doctors to provide a diagnosis, and varying types of treatments also affect where the disease can be most prominent, this is because the parasite can become resistant to the overuse of the same drug types. 

Malaria in the UK 
The ratio between cases of malaria from UK residents visiting friends and relatives, in comparison to cases of malaria acquired from holiday travellers is around 10:1. It should always be considered whether access to medical guidance is available before travelling, whether the guidance has been adhered to, full awareness of the risk and familiarity with the destination. Targeting these groups of peoples should be a priority. Other people within the UK who also tend to contract malaria, are those new to the country, foreign students studying in the UK, British citizens who have been working abroad in malaria strife countries, armed services and those who travel on business. 

An individuals risk can be determined by their awareness of areas which are at high risk areas, the time of year when they travel, the type of malarial parasite in the area, preventative measures taken and their immunity levels towards the disease.  

Transmission

• Mosquito bites
• Through the placenta (mother to child)
• Blood transfusions
• Transplantations
• Contaminated equipment
• Routes associated with air travel

Types

There are 5 main species of malarial parasites:

1. Plasmodium falciparum
2. Plasmodium vivax
3. Plasmodium ovale
4. Plasmodium malariae
5. Plasmodium knowlesi

Each one can be characterised through their differing features and symptoms. 

Plasmodium falciparum is the most common, and most severe form of malaria. The parasite has a cycle of development within the blood lasting around 36-48 hours and lasts within the liver for 8-10 days. The liver schizont contains around 40,000 merozoites, and a mature erythrocytic schizont contains 16-30 merozoites, although this is rarely seen unless the patient is extremely ill. Around 40% of all RBCs of varying maturity may be infected.

Plasmodium vivax has parasitaemia which is much lower than that of P. falciparum, its cycle of development within the blood lasts for around 48 hours, and all stages of the parasite are seen in the peripheral blood. Less merozoites are seen in the liver and erythrocyte stages. This parasite prefers to invade reticulocytes (immature RBCs making up around 1% of the overall RBCs in the body). This parasite has the ability to form dormant hypnozoites.

Plasmodium ovale is very similar to P. vivax, in that is also have a 48 hour erythrocytic stage, it also like prefers to invade reticulocytes and hypnozoites also can form. However it is more restricted in it's distribution, and there are around 8-12 merozoites seen in erythrocytic schizonts. 

Plasmodium malariae has an erythrocytic cycle of around 72 hours, it has low prevalence, and the liver and erythrocytic schizonts of this species produce fewer merozoites in comparison to other species, thus parasitaemia is low. Tends to infect older RBCs. 

Plasmodium knowlesi has a similar morphology to P. malariae, however it has a much higher parasitaemia, and can be fatal. It is found in Southeast Asia.  

Immunity 

Immunity to malaria is most commonly associated with the Plasmodium falciparum parasite, in an area where the transmission of this parasite is high, if a child survives to 5-6 years of age then their immunity is seen as high, however this immunity will begin to deplete if there is no regular exposure to the parasite. Immunity will be lowered in pregnant females, thus the pregnant, and children will be most at risk. 

Symptoms

Fever, chills, headache, flu-like symptoms, muscle ache, fatigue, anaemia, diarrhoea, vomiting and coughing

Diagnosis

Diagnosis within the laboratory can be carried out using a variety of techniques:

• Full blood count 
• Rapid diagnostic tests
• Quantitative buffy coat
• Polymerase chain reaction (PCR), this is mainly used in reference laboratories
• Thin and thick blood films

If malaria is detected via the use of a full blood count, the haematological changes observed will include normocytic and normochromic anaemia, this will be due to the removal of  damaged RBCs by the reticuloendothelial system, and suppression of normal RBC formation. Thrombocytopenia will also be witnessed, this is decrease in the number of platelets. WBC count usually stays normal, however in a severe state of the disease, the number can elevate. Further tests after this will have to be carried out to properly confirm the presence of malaria. 

A kit is available called the NOW malaria kit (Binax), this is a rapid immunodiagnostic assay, it is composed of 2 antibodies which have been immobilised on a test strip, one is specific for the histidine rich protein II associated with Plasmodium falciparum, and the other antibody is specific for an antigen found on all malaria types which can infect humans. A colour will form if the test is positive. The test only takes around 15 minutes. The problem with this is, it can state whether malaria is present however it doesn't show how much in abundance the parasite is. 

Another test used for diagnosis is the optimal-IT test, this test uses monoclonal antibodies for the enzyme parasitic lactate dehydrogenase (PLDH), the test has 2 antibodies, one for specifically Plasmodium falciparum and the other as a pan-specific. When a parasite is detected, PLDH will react with both of the antibodies. 

The positives of using these kits are that they are quick, cheap, easy to carry out, and can be used anywhere.

The negatives of using these kits is that they can provide false positives and also false negatives. 

The use of a quantitative buffy coat is also a means of diagnosis. Blood from the capillary of a patient is placed into a glass haematocrit tube, which also contains a stain which colours parasite DNA, acridine orange and an anticoagulant to stop blood clotting, potassium oxalate. A cylindrical float is then placed into the tube, and the tube will be centrifuged in order to separate the cells into their different densities. This forms bands, which are also made larger by the presence of the float. The tube is then placed into a holder, and examined under a light microscope with a UV adapter, thanks to the stain, any parasitic organisms will fluoresce. The negatives to this technique is that it is impossible to distinguish between different species, and to know how much in abundance the parasite is within the blood. Also, it is possible to gain false negatives from this technique. 

The polymerase chain reaction technique involves DNA amplification in vitro, it is highly sensitive and highly specific.

The advantages to this method is that is can detect and differentiate between different malarial parasite types, the technique is 10 fold more sensitive than microscopy, and it's also more reliable at identifying the species of malaria present. 

The disadvantages of this technique is that it is time consuming, expensive, and expertise is needed. 

Thin and thick blood films have been describe as being the 'gold standard' in malaria diagnosis.The advantages is that they're cheap, and can be used for species identification and also their quantification (checking the parasites abundance within the blood). Their disadvantages it that the parasites can be overlooked, especially if the parasitic levels are low, this technique can be time consuming and it also requires a level of expertise. 

Once a malaria case has been detected, the results are entered into a hospital computer system so medical staff can view them, a patient report form is then filled out and sent to the School of Tropical Medicine, and also to the Health Protection Agency/Public Health England.