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Malaria


Malaria is a tropical disease, affecting 300 million people and causing 1-1.5 million deaths per year, although such estimates vary. As a global killer it is second only to TB (tuberculosis).

It is especially dangerous to young children and pregnant women in sub-Saharan Africa.

Causative organism: Plasmodium species
Malaria is caused by a microscopic single-celled organism - a protoctistan (also known as a protozoan) - living in the blood and also inside body organs. There are actually 4 different species: Plasmodium falciparum, P. vivax, P. malariae, P. ovale.
There are numerous differences in the details of their life cycles. P. vivax is the most widely distributed species ( between latitudes 60 N and 30 S), whereas P. falciparum, found in tropical areas, has more drastic effects and is sometimes known as malignant malaria.

Vector: the Anopheles mosquito
Malaria is spread from person to person by (bites from) a mosquito - specifically Anopheles, and in Africa one main species: Anopheles gambiae.

Like other mosquitoes, this species has an aquatic life-cycle involving eggs laid on the water surface hatching into larvae which live and feed beneath the water, but which occasionally visit the surface to take in atmospheric air via tubes at the tail end.

The larvae turn into pupae which also move in the water, and these in turn metamorphose into adults which leave the water and fly away (usually not far from water).
Anopheles gambiae adult
Anopheles (mosquito) larva in water
Anopheles pupa
Adult Anopheles mosquito taking a blood meal from human skin:
Note the characteristic tail-up posture
Larva of Anopheles in water:
Unlike other mosquito larvae, this species does not hang at an angle from the surface when taking in air
Anopheles pupa:
In the pupal stage, the mosquito is comparatively active, and pupae must also return to the water surface to take in air through tubes at the top of the head.
Adult males and females feed on plant juices including nectar but eventually after mating the females need a blood meal.

The malaria infection cycle

(Click here to see a fairly complex diagram as an overlay page)

N.b. Many parasites have life cycles involving 2 host species, within which they pass through a variety of different stages, often alternating between using asexual processes in order to build up numbers when conditions are appropriate and using sexual processes in other stages.
Passing the mouse pointer over the text below gives extra detail: the names of the stages involved.

The cycle starts when ...

A person infected with Plasmodium is bitten by a (female) Anopheles mosquito.

Biting insects often inject a small amount of saliva before sucking out blood. The saliva contains an anticoagulant which prevents blood clotting.

When the mosquito takes in blood, some Plasmodium passes in via the mosquito's digestive system and into the mosquito's salivary gland.

Male and female stages of the Plasmodium parasite fuse so that fertilisation occurs in the mosquito's gut and then Plasmodium passes through a variety of asexual stages inside the body of the mosquito, which is only a few mm in length. One stage enters the mosquito's salivary glands.

Plasmodium appears to have no major effects on Anopheles , i.e. it does not cause "illness" in any sense to the mosquito.

The next time the mosquito bites a human, it will inject Plasmodium along with its saliva.

Inside the human ...

The Plasmodium parasite passes into the blood stream, and quickly into the liver, although other body organs may be affected, including the brain.

When Plasmodium enters liver cells, effectively by-passing the immune system, it goes through a number of stages in its life cycle, dividing and reproducing asexually. It can also remain here for a long time, and may invade other liver cells.

Eventually large numbers of Plasmodium cells leave the liver and infect red blood cells and once again reproduce asexually inside them. They may form characteristic "ring stages" which can be detected by microscopic examination of the blood. These red blood cells then break open and release Plasmodium which infects yet other red blood cells. About 9-16 days after the initial infection, the body experiences a fever as a reaction to the cell debris produced by the infecting Plasmodium. Another linked symptom may be anaemia.

Some of the Plasmodium parasites turn into another (sexual) form - which will eventually form male and female gametes - which circulate in the blood. These forms are then taken up by biting mosquitoes and may spread the infection further ...


Interestingly, it is known that Plasmodium parasites migrate out of the liver and towards the skin at night time - which synchronises with the time at which mosquitoes are most likely to bite.

Some questions

What dietary components does blood provide that plant juices do not?
>protein - red blood cells contain haemoglobin.

How does Plasmodium by-pass the immune system?
>By quickly entering liver cells and red blood cells it does not expose its antigens on the outside of the cell.
Plasmodium is a single celled protoctistan. How does a protoctistan differ from a bacterium?
>Protoctistan cells have a true nucleus, and other internal organelles, such as mitochondria (and they are slightly larger cells).
When we use words like Anopheles, or Plasmodium, what level of classification are we using?
>Genus clue: starts with a capital letter.

Can you explain why the symptoms of malaria tend to recur, without sufferers being re-exposed, i.e they do not need to be bitten again?
>Some parasites enter a dormant state in the liver and become re-activated months later.

Control Measures

- against the vector (mosquito)

- against the parasite

Quinine - a product of the bark of the Cinchona tree - is the main ingredient in tonic water, a favourite drink (with gin!) for some people in hot places - a trend started by tea planters?
Chloroquine is used both to help prevent and treat malaria - it should be started 1 to 2 weeks before travelling into an area in which malaria is present. It should be taken the entire time in the area, and for 4 weeks after leaving.

It is known that strains of mosquito resistant to these insecticides have developed in some parts of the world.

Lariam (almost an anagram for malaria!), aka mefloquine, is a more modern drug taken before going (on holiday?) to affected areas - but with a fairly chequered background - neuropsychiatric side effects
Artemisinin is a drug derived from a plant of the Wormwood family Artemisia spp., which often produce bitter chemical compounds. Other members of the wormwood family have been known to produce herbal remedies as well as flavourings for alcoholic drinks such as Vermouth and Absinthe. Although the extract of the species Artemisia anuum (known as qinghaosu) has been used in China for several hundred years, it has only recently been investigated in the West using scientific principles. Several other compounds with a similar molecular structure have been developed, and are currently being tested.

Click here to see the molecular structure of these antimalarial compounds

Vaccine
only limited progress so far!
In some areas human populations have a limited amount of natural acquired immunity to malaria based on antibodies produced as a result of regular exposure to Plasmodium. This immunity may even be passed on from mothers to babies - antibodies crossing the placenta - resulting in passive immunity.

Points of interest

The name mal aria means bad air - a possible reference to the supposed influence of unknown substances emanating from swampy areas where the condition is rife.

Malaria used to be endemic in Britain (especially Romney marshes) up to the completion of the Royal Military Canal in 1806, which greatly improved the drainage of the area.
With global warming (and foreign travel) it may return!

Spirogyra It has been said that the main food for Anopheles mosquitoes is the filamentous alga Spirogyra, so removing this physically may reduce populations of mosquitoes.

Tyre dump Tyre dumps are a major problem in affected areas. No matter which way they are arranged, tyres stored outdoors will always trap a small volume of rainwater which is enough to harbour mosquito larvae in a sheltered environment from which adult mosquitoes may emerge and bite humans.

Red blood cells showing sickling Sickle cell anaemia (an inherited genetic condition) probably gives a degree of protection against infection by Plasmodium. Red blood cells contain a modified version of the haemoglobin molecule, which although much less efficient at carrying oxygen, makes red blood cells infected with Plasmodium more likely to be broken down. The distribution of sickle cell anaemia and malaria are closely correlated. Although people with a double dose of the sickle cell allele (homozygotes) suffer, it is thought that people with a single dose of the sickle cell allele (heterozygotes) are more able to resist Plasmodium in these hotter areas of the world. This is known as heterozygote advantage.
A similar situation is thought to occur with the blood condition thalassemia.

Approximate geographic distribution of malaria


The details of the life-cycle of Plasmodium and Anopheles and their interaction were discovered by Dr Ronald Ross (18571932) who obtained a Nobel prize for his work. However it is interesting that he concentrated on the effects of the parasite on birds, but disproved a previous theory that merely drinking water contaminated with mosquito larvae could pass on the disease. In fact Giovanni Grassi (1854-1925) made the final connections with malaria in humans as a result of direct experimentation on human volunteers using mosquitoes from infested areas within Italy. He also carried out large scale experimentation on railway workers, dividing them into groups with and without screened houses for protection after dusk!

limberger cheese Anopheles mosquitoes are known to be attracted to chemicals produced by the human body, such as sweat, especially from the foot region. Similar compounds are given off by some types of cheese!

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