Malaria

Malaria - What is Malaria?

Malaria is an infectious disease of tropical countries. It is spread by mosquitoes. It is manifested by fever along with chills and rigors. Unless it is diagnosed and treated promptly, it can be fatal. A single mosquito bite may be enough to cause the infection.

Symptoms of malaria

Features of malaria include high fever over 38C (100.4F) along with chills and sweating. There is intense muscle pain, headache, blurring of vision and dizziness. Some patients may develop diarrhea and vomiting as well. Symptoms develop within seven days after being bitten or may take between 10 to 15 days to appear.

High risk areas for malaria

Malaria is found mainly in the tropical countries all around the world. It is seen in large parts of Africa and Asia, Central and South America, Haiti and the Dominican Republic, some Pacific islands, such as Papua New Guinea and some parts of Middle East.

Malaria is not seen commonly in the United Kingdom. In the United States around 1,500 cases of malaria are reported every year. Worldwide around 3.3 billion people live in areas at risk of malaria transmission in 106 countries and territories.

In 2010, according to the World Health Organization, there were 216 million episodes of malaria and 655,000 deaths worldwide. Of these deaths around 91% were seen in the African Region, followed by the South-East Asian Region (6%), and the Eastern Mediterranean Region (3%). About 86% of deaths globally were in children.

Causes of malaria

Malaria is caused by a type of parasite known as Plasmodium. This is a microscopic parasite that is transmitted by certain species of mosquitoes. Although there are numerous types of Plasmodia parasites, only four cause malaria in humans. These include:

  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium ovale
  • Plasmodium malariae

There is a fifth species causing malaria in humans. It is called Plasmodium knowlesi. It is distributed across South East Asia and is often misdiagnosed as P. Malariae. The infection has a potentially more serious and even life-threatening course.

The Plasmodium parasite is mainly spread by female Anopheles mosquitoes, which are night-biting mosquitos.

Diagnosis and treatment of malaria

Malaria is diagnosed by looking at blood samples. The parasites are visible under the microscope. Once the diagnosis is made, treatment should be begun promptly. Almost all individuals make complete recovery.

Anti-malarial medication is used both to treat and prevent malaria. The type and duration of drugs depends on the type of malaria, its severity and if the patient is pregnant.

Malaria can sometimes become complicated. Some of the complications include:

  • severe anaemia
  • cerebral malaria
  • malaria during pregnancy
  • spleen rupture
  • acidosis
  • kidney damage
  • multi-organ failure etc.

These are more common with malaria caused by P. Falciparum

Prevention of malaria

Malaria can be prevented by taking several simple precautions. Awareness of the risk of malaria in high risk zones is the first step to preventing malaria. Mosquito bites can be prevented by using covered clothes and mosquito repellents.

While travelling to a malaria endemic zone, antimalarial tablets may be prescribed to prevent contracting malaria. Immediate diagnosis and treatment can help prevent complications and death.

Malaria Causes

Malaria is caused by a parasite belonging to the Plasmodium family. The parasite can be spread to humans through the bites of infected mosquitoes. There are numerous types of Plasmodium parasite, but only five types cause malaria in humans. These include:-

Plasmodium falciparum

This type is mainly found in Africa and is common cause of complicated and fatal malarias worldwide

Plasmodium vivax

This is common in Asia and Latin America. The symptoms caused by this type are less severe than Plasmodium falciparum, but it can stay in the liver for up to three years, which can result in relapses and repeat episodes.

Plasmodium ovale

This is relatively uncommon type of malaria usually found in West Africa. This can stay in the liver for years without obvious symptoms.

Plasmodium malariae

This is a rare type of malaria found in Africa

Plasmodium knowlesi

This was initially thought to be same as Plasmodium malariae but was later found to be distinctly different in its course which may be life threatening. It is found rarely and seen in some parts of Southeast Asia.

Malaria spread

The Plasmodium parasite is spread by the female Anopheles mosquitoes. These are night biting mosquitoes that bite between dusk and dawn. The male mosquitoes do not bite and do not feed on human blood like the female mosquitoes do. Once the mosquito bites a person infected with malaria, it can also become infected and spread the parasite on to others.

In the mosquitoes’ gut the parasite develops into sporozoite forms. These sporozoites remain in the mosquito saliva from where they infect the human.

The sporozoites enter the blood stream and go into the liver. The infection develops in the liver and the multiplied parasites re-enter the bloodstream. The sporozoites then form merozoites. This time they infect the red blood cells.

In certain species the sporozoites may lie dormant in the liver (when they are known as hypnozoites). The parasites grow and multiply in the red blood cells. At regular intervals of around 48 to 72 hours the infected blood cells burst, releasing more parasites into the blood. Each time they burst there is a bout of fever, chills and sweating.

The parasite remains is blood in the form of gametocytes to be taken up by a non-infected mosquito. In the mosquito’s gut the gametozytes fuse to form zygotes or sporozoites (sexual reproduction). The mosquito then transmits it to another individual. Thus the life cycle of the Plasmodium parasite is complete.

Malaria can also affect pregnant women living in high risk areas. There is a high risk of complications in this situation. The risk of premature birth, stillbirth and miscarriage also rises.

 

Malaria Mechanism

Malaria is caused by the transmission of the malaria parasite Plasmodium to humans by the bites of female Anopheles mosquitoes.

Life cycle of malaria parasites

Plasmodium parasites’ primary hosts and transmission vectors are female Anopheles mosquitoes. Humans and other vertebrates are secondary hosts. The mosquitoes first take in the parasite by feeding on the blood of an infected person.

In the mosquitoes’ gut the gametocytes (male and female) from the infected person fuse to form ookinete that penetrates the gut lining and produces an oocyst in the gut wall. When the oocyst ruptures, it releases sporozoites that migrate through the mosquito's body to the salivary glands sporozoites. This is the phase of sexual reproduction. The mosquito then becomes ready to infect a new individual.

Only female mosquitoes feed on blood, thus males do not transmit the disease. The mosquitoes bite at night between dusk to dawn. Transmission is also possible by blood transfusions from an infected person.

Pathology of malaria within human hosts

Once within the humans the malaria parasite undergoes two phases - an exoerythrocytic and an erythrocytic phase.

Exoerythrocytic phase

The exoerythrocytic phase involves maturation and development of the parasite in the liver. When an infected mosquito transmits the infection or sporizoites as it takes in a blood meal the sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver.

The process of migration takes around 30 minutes after a bite. These sporozoites infect hepatocytes. This is followed by a multiplication of the sporozoites. This is known as asexual reproduction or multiplication. It takes around 6–15 days for this multiplication.

The parasite then forms thousands of merozoites within the hepatocytes. The numerous merozoites lead to rupture of their host cells and escape into the blood.

Sometimes the sporozoites may not immediately go into the exoerythrocytic-phase merozoites, but instead produce hypnozoites that lie dormant in the liver. This is seen with Plasmodium vivax and Plasmodium ovale. The periods of dormancy may range over several months (typically 6–12 months to around 3 years). Hypnozoites are responsible for long incubation and late relapses in these two species of malaria.

Erythrocytic phase

The involvement of the red blood cells is called the erythrocytic phase. In the RBCs the merozoites multiply further asexually and burst the RBCs as they multiply releasing the merozoites in blood. Each burst is associated with a bout of fever. The new merozoites then invade fresh red blood cells leading to further amplification.

Several such amplification cycles occur. Each such amplification is thus characterized by a wave of fever. Some of the merozoites develop into male and female gametocytes that may be further transmitted to mosquitoes. This completes the lifecycle.

Effect of malaria on the immune system

Plasmodium parasites exist in various forms within the liver and blood but manage to escape the immune system. This is because in most of its forms it resides within the liver and blood cells and is relatively invisible to immune surveillance.

Normally the RBCs undergo destruction in the spleen at regular intervals. Infected RBCs especially those with Plasmodium falciparum escape this destruction by developing adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels. This leads to sequestering the parasite from passage through the general circulation and the spleen.

These proteins are also thought to be the cause of complications caused by this type of malaria parasite. They are called PfEMP1, for Plasmodium falciparum erythrocyte membrane protein 1 and have a variety and diversity and thus cannot be targeted by the antibodies formed in the body.

Malaria Diagnosis

Diagnosis of malaria is made with the help of microscopic examination of the blood samples. The symptoms of malaria may resemble flu, gastroenteritis, typhoid or other viral fevers. Thus fever and other symptoms similar to malaria need careful evaluation to diagnose malaria.

Differential diagnosis

Conditions that mimic malaria and need to be ruled out before diagnosis of malaria include:-

  • Viral Hepatitis A, B or C
  • Typhoid fever
  • Dengue fever
  • Influenza
  • Viral fevers
  • HIV infection
  • Meningitis or encephalitis brain infections

Steps in diagnosis of malaria

  • History of travel to a high risk zone or a history of bite. Detailed history of travel to endemic areas even brief stopovers should be recorded.

  • Early diagnosis is important to ensure appropriate, presumptive and accurate treatment and to reduce the risk of life threatening complications and death. A blood sample is usually taken for diagnosis.

  • Thick and thin blood smears are taken on a glass slide. The samples best show a confirmatory diagnosis during a bout of fever when the parasite is present in the peripheral blood stream. The smears on the glass slides are then stained with Giemsa stain. The slides are viewed under the microscope and the parasite is identified. This is the gold standard method of diagnosis and remains one of the cheapest and most cost effective methods. Other advantages include high sensitivity and specificity when used by well-trained staff. Where the blood film is negative, at least 2 further films should be obtained over the next 48 hours before malaria is ruled out. A negative report does not necessarily mean the individual has no malaria. This is particularly the case in pregnancy when the parasites remain clustered in the placenta and may not be easily detected.
  • Rapid diagnostic tests (RDTs) are also employed for easy detection and take around 2 to 15 minutes. These tests detect parasite antigens. These can be used by relatively untrained staff.

  • Polymerase chain reaction (PCR) is a more sophisticated method of diagnosing malaria. It is expensive and less available at endemic zones. Parasite nucleic acids are detected using PCR. PCR is most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT.

  • Serology may also be used to detect antibodies against malaria parasites. This can be done using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past exposure.

  • Apart from detection of the parasite other tests are also ordered. These include complete blood counts that reveal anemia, low platelet counts and rarely high white blood cell counts.

  • G6PD activity is seen to prevent side effects of some anti-malarial drugs like primaquine.

  •  Liver and kidney functions are evaluated to rule out organ damage.

  • Urea and electrolytes are assessed to check for acidosis and low sodium and high creatinine levels.

  • Blood glucose is assessed as hypoglycaemia is common with falciparum malaria.

  • Other tests include assessment of blood gases, blood culture, blood clotting studies, chest X ray, urine and stool cultures and examination of the Cerebrospinal fluid (CSF) by lumbar puncture.