Anopheles mosquito

The WHO (World Health Organization) estimates that between 300 and 500 million people fall ill from malaria every year. More than one million die from the consequences of the infection. Malaria is found in many tropical and subtropical countries.

Malaria is caused by one-celled parasites (plasmodia). They enter the blood system through the bite of a female anopheles mosquito. We distinguish between four types of malaria pathogens. The most dangerous is Plasmodium falciparum, which causes malaria tropica. It is responsible for most of the fatalities from malaria. The countries in black Africa are most severely affected. The consequences of an infection include violent attacks of fever, anaemia and serious damage to organs.

Plasmodia destroy blood cells

Inadequate Protection by the Immune System
Building up a certain amount of protection from the pathogen is possible only for people who live long enough in a malaria area and are regularly subjected to infections by the parasites native to that particular region. We call this semi-immunity. Once it has been built up, the body's own defences can keep the plasmodia more or less under control. While it is true that the infected people never get completely rid of the parasites and suffer from recurring relapses, the attacks of malaria are milder.

Sickle Cell Anaemia Protects from Malaria. This hereditary disease occurs more frequently in countries in which the rate of infection with malaria parasites is especially high. Sickle cell anaemia is a disease resulting from a genetic defect which prevents the blood dye haemoglobin from bonding properly with oxygen and causes the red blood corpuscles to be broken down more quickly. If physical activity, for example, causes a lot of oxygen to be withdrawn from the defective haemoglobin, it clumps together and deforms the blood cells into a sickle shape. The plasmodia cannot develop well in the oxygen-poor surroundings and ultimately die along with the sickle cells. People who have the sickle cell genes are therefore largely protected from more serious forms of malaria. But in exchange they suffer all their lives from a mild form of anaemia.

However, people who come into contact with malaria parasites very rarely and cannot build up adequate defences are at high risk. That is why so many of the malaria fatalities in black Africa are children under the age of five. Travellers are also unable to acquire any immunity to the plasmodia during their short stays in malaria areas. Since no effective vaccine has yet been developed for malaria, the only help comes from medications which kill the parasites. But even this is not guaranteed in every case as there are some resistant plasmodia strains which cannot be stopped by anti-malaria medicines.

The Life Cycle of Malaria Parasites (Plasmodia) Malaria pathogens have an extremely unusual life cycle. The parasite reproduces sexually when in the malaria mosquito, asexually when in humans. The plasmodia go through a series of development stages, changing their form in every phase. This is why malaria parasites are viewed as especially tricky quick-change artists.

When a malaria mosquito bites a human, the plasmodia enter the blood along with the mosquito's saliva. At this stage, the parasites are known as sporozoites. It takes only 30-60 minutes for the sporozoites to infect liver cells. Here a radical transformation takes place. Thousands of merozoites form from a single sporozoite. After one to two weeks, the liver cell bursts and washes the merozoites into the blood. However, sporozoites can survive in a kind of hibernation in the liver and cause malaria attacks even years later. The merozoites penetrate red blood cells and divide there until the red corpuscles burst. About twenty merozoites are released and then attack new blood cells. This growth and reproduction process repeats itself a number of times, generally every two to three days. Part of the merozoites transform themselves into female or male gametocytes (precursors of germ cells). If, while enjoying a drink of blood, a mosquito ingests these gametocytes, it becomes infected. The parasites now go through a number of sexual development and reproduction steps. Within a week, sporozoites once again form, and the anopheles mosquito can infect more people.

Starting the malaria cycle

Immune Defence against Malaria
Malaria parasites with their transformation tricks put the human immune defence to a severe test. The most effective defence strategy is to stop the parasites in the stages when they are swimming freely in the bloodstream (sporozoites, merozoites, gametocytes) with the help of antibodies. However, the defence must conduct a fight on several fronts, for the three parasite stages have different shells and also change their surface structures (antigens) constantly. Many of the antibodies which have formed remain ineffective because they do not find the right targets (antigens).

Reproduction of sporozoites

An effective immune response is also made more difficult by the fact that the parasites spend most of the time inside body cells. Sporozoites reproduce in the liver. When hidden here, they can be fought only by killer T cells (cytotoxic T cells). But according to our current state of knowledge, this form of defence against malaria is limited in its effectiveness.

The merozoites are even cleverer. They reproduce in red blood cells. In contrast to other cells, the red blood cells lack MHC-I molecules with which they could display fragments of the parasites on their surface. So the killer cells do not have the "enemy image" they require and are unable to intervene.

The merozoites have yet another trick up their sleeve to help them to survive: they induce the infected red blood cells to form certain surface molecules. These molecules act like "glue" and cause the blood cells to stick to the vessel walls. This prevents them from being transported into the spleen, which normally destroys infected blood cells. The merozoites in the "parking" erythrocytes are in safety and can reproduce in peace and quiet.

The malaria parasites even understand how to turn defence actions by the body to their advantage. As a reaction to the pathogen, the phagocytes release the messenger substance TNF (tumour necrosis factor alpha).

In low concentration, the parasites are killed. But if a certain concentration is exceeded, the glue effect is reinforced. More and more red blood cells, even ones which are not infected, stick to the vessel walls and clump together. This congestion in the blood vessels is further strengthened by antibodies which attach themselves to the "glue molecules" of the infected blood cells. Useful to the malaria parasite - they reproduce best in a low-oxygen environment - this situation can become mortal danger to the human being: poor oxygen transport and inadequate blood supply destroy organs such as liver, kidneys or brain.

Protection from Malaria
In spite of substantial efforts, no proven vaccine which protects from malaria has been developed. This is above all a consequence of the complicated life cycle of the parasites which use camouflage and deception to fool the immune defence again and again.

Moreover, scientists have not yet found a way to cultivate the malaria parasites on a large scale, which would facilitate production of a vaccine. As an alternative, synthetically produced antigens could be used. But it has not yet become clear which surface antigens of the pathogen lead to an effective defence by the antibodies. One example: the vaccine SPF 66 developed by Manuel Patarroyo, a cocktail of various synthetically produced vaccines, proved to be ineffective. Experiments with other vaccines have also failed to produced the hoped-for breakthrough.

Vaccine experiment in Africa

We remain dependent on anti-malaria medicine which disrupts the parasites' metabolism and kills them. However, these important weapons in the fight against malaria are becoming increasingly dull. Some plasmodia strains no longer respond to long-proven medications. The pathogens have become resistant to certain substances.

The simplest protection from malaria infection consists of protecting yourself from the bite of the anopheles mosquito. Since the female bites only in the early evening hours and at night, so-called repellents (defensive substances which are applied to the skin) and mosquito nets impregnated with insecticides can help. Anyone going to a malaria area as a tourist should consult a physician before leaving and, as appropriate, take the recommended anti-malaria medicine according to the doctor's instructions.