What is malaria?

Malaria is an infectious parasitic blood disease carried from person to person via the bites of infected female Anopheles mosquitoes.

Malaria destroys red blood cells in the body and interferes with the body's ability to make new red blood cells, which then starves the body of oxygen. 

Malaria is a common and serious illness worldwide, affecting hundreds of millions of people and killing hundreds of thousands every year, particularly children. [1] [2]  It is common in warm, equatorial regions, including parts of Africa, South-East Asia, and Latin America. Cases of malaria outside these regions are most often due to travellers returning from malaria-endemic countries.

Endemic

A disease, condition or infectious agent that is common to a geographic area or a population.

Red blood cells

Cells in the blood that transport oxygen from the lungs throughout the body and carbon dioxide from the body to the lungs.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Causes

Malaria is caused by the bite of a female Anopheles mosquito infected with the Plasmodium parasite. The parasite is a single-celled organism that cannot survive outside its human and mosquito hosts. There are many types of Plasmodium parasites, but only five types infect humans (see the 'Types' section below). They are all common to warm climates, because the parasite cannot reproduce in temperatures below 20°C.

Malaria is caused by a bite of a female Anopheles mosquito infected with the Plasmodium parasite. 

As malaria parasites are transmitted through the blood, infection can also occur when blood is exchanged between two people, such as during an organ transplant or blood transfusion, or by sharing an infected needle. A mother can also pass on the malaria parasite to her baby at birth; this is congenital malaria.

The Plasmodium parasites are injected into the human body in mosquito saliva and enter the bloodstream. Once in the blood, they change into a mobile form called sporozoites. These travel through the blood until they reach the liver, where they enter liver cells and develop into a different form, merozoites. The merozoites then burst the liver cells, return to the bloodstream and infect red blood cells again. There they stay for 2-3 days and multiply. When the red blood cells are each crammed with merozoites, the cells burst open and the parasites return to the bloodstream. The merozoites in the blood can now infect other red blood cells and the cycle repeats.

A small fraction of the parasites will transform into gametocytes and be uptaken by biting mosquitoes as part of a blood meal. They mate and produce offspring within the mosquito and begin the infection cycle again.

The Plasmodium parasite affects the liver and red blood cells. 

Immune response and immune evasion

The symptoms of malaria are caused during the infection of the blood by the Plasmodium parasite. When the merozoites burst from the cells, they release chemical waste products from the cells into the bloodstream. These chemicals trigger the body's immune response and produce the fever, chills and shivering symptoms.

After a few weeks of infection, the parasites' cycles synchronise, for reasons still unknown. This causes the distinctive cycles of fever mentioned in the previous section.

The Plasmodium parasite has the remarkable ability to evade our immune system's response. Among other mechanisms it employs, the parasite changes the molecules on its outer surface regularly and randomly. This change causes the immune system to 'lose the scent' of the parasite and allows it to evade recognition.

Fever

An increase in body temperature above the normal temperature range. Fever is often caused by the body's immune reaction to infection.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Parasite

An organism that lives off another organism.

Red blood cells

Cells in the blood that transport oxygen from the lungs throughout the body and carbon dioxide from the body to the lungs.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Risk factors

Anyone can become infected with malaria. People at particular risk are:

  • Those who live in, or visit, areas where malaria is widespread, especially people who do not or cannot take preventative measures (see the 'Prevention' section below);
  • Pregnant women, especially during their first or second pregnancies, and;
  • Very young children. Infants can receive protective antibodies from their immune mother before birth and via breastmilk. However, this protection is partial and wanes after the first few months. Young children are then highly susceptible to infection until their immune system matures at 2-5 years of age.

Antibodies

A protein molecule produced by the immune system. Antibodies bind specifically to foreign substances to neutralise them or target them for destruction.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Types

There are hundreds of kinds of Plasmodium parasites, but only five are known to infect humans.

Plasmodium falciparum

This type of Plasmodium multiplies rapidly in the blood. The large number of parasites in the blood can cause the infected person's condition to deteriorate quickly unless treated promptly. Found mainly in Africa, P. falciparum causes the most deaths and most complications of malaria worldwide. The incubation period for P. falciparum infection is normally around two weeks.

Plasmodium vivax

Plasmodium vivax is the most common type of malaria-causing parasite in the world, particularly outside Africa. Found mainly in Asia and Latin America, P. vivax is less dangerous than P. falciparum and causes milder symptoms.

P. vivax parasites can lie dormant within liver cells for several years. During this period it is difficult to identify the infection, since the infected person shows no sign of illness. In dormant mode the parasites are also not detected by blood tests, as they are hidden inside liver cells.

Plasmodium ovale

Less common than P. vivax and P. falciparum, this parasite is mostly found in West Africa and the Pacific region. Like P. vivax, which it closely resembles, P. ovale can also become dormant.

Plasmodium malariae

An uncommon strain of malaria parasite, P. malariae has a three-day cycle, compared to the two-day cycle of other species of human Plasmodium. It causes a relatively mild but often long-lasting form of malaria.

Plasmodium knowelsi

An uncommon form of malaria, found mostly in Malaysia, the Philippines, Thailand and Singapore, P. knowelsi was only recently identified as a separate species. It infects primates - it was first identified in macaque monkeys - as well as humans. Its incubation period can be relatively short, and its lifecycle lasts one day rather than two. This rapid progress makes P. knowelsi a dangerous form of malaria if not diagnosed and treated promptly.

Blood tests

During a blood test, blood can be drawn using a needle or by a finger prick. Your blood can then be analysed to help diagnose and monitor a wide range of health conditions.

Dormant

Present but currently inactive.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Parasites

An organism that lives off another organism.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Signs and symptoms

A person infected with malaria may feel feverish and weak, though symptoms usually take some time to appear. Symptoms can appear within 1-4 weeks, but can appear more slowly and be less severe in people previously exposed to malaria, or who are taking certain medications.

Some types of the malaria parasite can also enter a dormant mode. It can stay in the body for several months, or even years, without causing any symptoms to appear.

The malaria paroxysm

If you have been infected, you are likely to experience the group of symptoms most associated with a malaria infection, known as the malaria paroxysm. It is the result of the life cycle of the malaria parasite. The paroxysm commonly lasts 6-10 hours and goes through three stages. The first is the cold stage, in which you suddenly feel very cold and experience shaking chills and shivers. This is followed by the hot stage, when you feel feverish and restless. The third stage - the sweating stage - is characterised by profuse sweating.

The paroxysm can appear every day in the first stages of the disease. After several weeks, it usually stabilises and can appear only once every 2-3 days.

Other signs and symptoms

Other signs and symptoms of malaria include:

  • Weakness and an unwell feeling;
  • Headache;
  • Coughing;
  • Nausea;
  • Vomiting;
  • Diarrhoea;
  • Jaundice;
  • Trouble breathing;
  • Dark urine;
  • Confusion;
  • Muscle pain;
  • Anaemia, and;
  • Blood in stools.

Anaemia

A deficiency in red blood cells or haemoglobin in the body.

Dormant

Present but currently inactive.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Jaundice

A yellowing of the skin, the whites of the eyes and the mucous membranes, due to an accumulation of bilirubin in the blood. Often a symptom of liver problems.

Parasite

An organism that lives off another organism.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Diagnosis

Because malaria is a potentially life-threatening disease, quick and effective diagnosis is important. It is diagnosed by a blood smear test. Your doctor can take a drop of your blood and smear it on a microscope slide, then stain the blood sample with a staining agent and look through the microscope for signs of the parasite. In Australia, this test will usually be performed in a laboratory.

The test may need to be repeated several times, as sometimes there are not enough parasites in the blood to enable detection. Taking antimalarial drugs or antibiotic medication can also delay the appearance and detection of parasites.

There are also rapid molecular blood tests that can detect malaria. These tests are quick, but often cannot provide conclusive diagnosis of an infection (or of its absence). They are also unable to diagnose the exact type of Plasmodium parasite. Therefore, these tests need to be followed by a blood smear test.

Antibiotic

Chemical substances that kill or suppress the growth of bacteria.

Blood tests

During a blood test, blood can be drawn using a needle or by a finger prick. Your blood can then be analysed to help diagnose and monitor a wide range of health conditions.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Parasite

An organism that lives off another organism.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Types of treatment

If you are concerned you may have the symptoms of malaria while, or after, travelling to a malaria-prone area, it is imperative to seek a medical diagnosis and treatment as soon as possible. Even if you are taking preventative medication you can still contract malaria.

If you have been diagnosed with malaria, you will receive antimalarial medication. Medications can be prescribed either singly or in combination. Different antimalarial drugs target different parasites and the different life stages of each parasite type. Specific courses of treatment take many factors into account, such as geographical region, the age and immune status of the patient and drug resistance.

Some antimalarial medications help prevent infection or delay symptoms, while others treat people already infected. Some medications can be used for both purposes. Antimalarial drugs vary in the type of parasite they work against, their intended use, the length of their course of treatment, their interactions with other medication and their possible side effects.

Malaria parasites are growing more resistant to the traditionally effective medications. This requires the development and use of newer drugs, as well as treating patients with combinations of drugs.

Chloroquine has long been the drug of choice for treating malaria, but resistance to it is spreading. Artemisinin, and its derivatives, are a newer class of drug that are effective in treating some drug-resistant strains. Other anti-malarial medications include mefloquine (Lariam), quinine, quinidine, primaquine (effective against dormant liver forms). Medications such as doxycycline and clindamycin can be used in combination with quinine. 

Dormant

Present but currently inactive.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Parasites

An organism that lives off another organism.

1. Greenwood B. (2014) Treatment of malaria — a continuing challenge. New England Journal of Medicine 371:474–475.

2. Shetty N. Tang J.W. and Andrews J. (2009) Infectious disease: Pathogenesis Prevention and Case Studies (1st edition). Chichester UK: Wiley-Blackwell.

Potential complications

Severe malaria

Severe malaria is the most common complication of malaria and treated as a medical emergency. It is caused mainly by a Plasmodium falciparum infection that overruns the body and leads to serious organ failures. The infected person can show any of the following signs:

People who are partially immune to malaria can sometimes show very different signs of severe malaria, particularly diarrhoea.

Cerebral malaria

Cerebral malaria is a potentially fatal complication of severe malaria. It affects hundreds of thousands of people a year, particularly children. [3]

A person with cerebral malaria will often become confused and drowsy, and experience weakness, nausea and severe headaches. In children, seizures are common. The person will then slip into a coma. If a person survives, they can be left with permanent brain damage.

Hyperreactive malarial syndrome (HMS)

Hyperreactive malarial syndrome, or hyperreactive malarial splenomegaly (HMS), is the result of an overreaction of the body's immune system to the malaria parasites. It can occur when a person is repeatedly exposed to malaria infections. It is an uncommon but dangerous complication of malaria and often causes pain and swelling of the abdomen.

Coma

A state of deep and prolonged unconsciousness.

Gastrointestinal tract

The membrane-lined series of organs extending from the mouth to the anus through which food passes during digestion.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Inflammation

A body’s protective immune response to injury or infection. The accumulation of fluid, cells and proteins at the site of an infection or physical injury, resulting in swelling, heat, redness, pain and loss of function.

Joint

A connecting surface or tissue between two bones.

Parasites

An organism that lives off another organism.

Seizures

A sudden, involuntary contraction of muscle groups caused by abnormal electrical activity in the brain.

Convulsions

Involuntary, abnormal contractions of muscles, leading to uncontrolled shakes and jerks of the body.

3. Lukianova-Hleb E.Y. Campbell K.M. Constantinou P.E. et al. (2014) Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proceedings of the National Academy of Sciences 111:900–905.

Prognosis

Malaria is treatable and in many cases, a preventable condition. Uncomplicated malaria, if treated correctly, eventually subsides. The complications of malaria, as noted above, can lead to serious illness, permanent damage and death.

Malaria relapse

As mentioned above, P.ovale and P.vivax are able to enter a dormant stage in the liver for months or years. The parasite emerging from its dormancy can cause a relapse of malaria long after the original infection has passed.

Dormant

Present but currently inactive.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Liver

A large, internal organ of the body, located on the upper right-hand side of the abdomen. The liver has hundreds of distinct functions, including producing bile, regulating the body's metabolism and detoxifying the blood.

Parasite

An organism that lives off another organism.

Relapse

The return of a medical condition or certain symptoms from which a person had previously appeared to recover.

3. Lukianova-Hleb E.Y. Campbell K.M. Constantinou P.E. et al. (2014) Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proceedings of the National Academy of Sciences 111:900–905.

Prevention

Multiple prevention approaches are available and can often be used together for maximum effect, although complete success is not guaranteed.

Bite prevention methods

The best way of avoiding malaria is to not get bitten by mosquitoes in the first place. In malarial areas, you can protect yourself by taking the following measures:

  • Using insect repellent, insecticides and mosquito-control devices (coils, zappers);
  • Staying indoors around dusk, night-time and dawn, when mosquitoes are most active;
  • Fitting flyscreens in windows, doors and gutters of buildings;
  • Avoiding staying near freshwater puddles, pools and lakes;
  • Sleeping under mosquito nets treated with insect repellent;
  • Wearing long, light-coloured clothes that cover as much skin as possible;
  • Avoiding perfumes and other artificial body scents, and;
  • Being aware of the risks and early signs of malaria infection.

Medication

If you are travelling to, or living in, an area where malaria is common, you can begin a course of preventative antimalarial medication in advance, to lessen your chances of infection.

Mosquito control

In countries where malaria is widespread, public health programs aim to reduce mosquito numbers. Strategies used in this area include insecticide spraying in malaria-afflicted areas and draining or covering open bodies of water where mosquitoes breed.

Vaccine development

There is currently no vaccine for malaria. However, several research efforts have been directed at developing one for some time now, with hopeful results. The most promising of these is the RTS,S/AS01 vaccine, currently in advanced trial stages. If successful, it may be available as early as 2016. [4]

Even when available, a vaccine will not provide complete protection against malaria. So for the foreseeable future, such a vaccine will be added to existing control measures rather than replace them.

Infection

Entry into the body of microorganisms that can reproduce and cause disease.

Vaccine

A preparation containing a microorganism (that causes a specific disease) in a dead or weakened state, or parts of it, for the purpose of inducing immunity in a person to that microorganism.

4. Packard R.M. (2014) The origins of antimalarial-drug resistance. New England Journal of Medicine 371:397–399.