Life Cycle of Malaria

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QUESTION

Why does the malaria parasite first enter the liver?

ANSWER

The malaria parasite enters the liver in order to transform from a sporozoite (which can infect liver cells) to a merozoite, which is capable of infecting red blood cells. Both stages also include a proliferation step, but in the blood, the merozoites are also able to differentiate into gametocytes, which are then taken back up by a mosquito during a blood meal, allowing the malaria parasite to continue its life cycle. If the red blood cell stage were first, followed by the liver, then it would be much harder for the gametocytes to be able to reach a new mosquito host, unless they were to enter the blood a third time.

The blood is also a difficult place for a parasite to survive, since it is the highway of the immune system, whereas the parasite is less easily destroyed when it is hiding out in the hepatocyte cells in the liver. It is also important to note that Plasmodium has a long evolutionary history, and may in some parts of its life cycle be constrained by physiological or life history characteristics of its evolutionary forebears, which may also contribute to our perception of the life cycle as being very complex!

Pathophysiology of Malaria

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QUESTION

What is the pathophysiology of malaria?

ANSWER

Malaria causes disease through a number of pathways, which depend to a certain extent on the species. Malaria is caused by a single-celled parasite of the genus Plasmodium; there are five species which infect humans, beingPlasmodium falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

All these species are introduced into the human blood stream through the bite of an infected mosquito; the life stage of malaria at this point is called a “sporozoite”, and they pass first to the liver, where they undergo an initial stage of replication (called “exo-erythrocytic replication”), before passing back into the blood and invading red blood cells (called “erythrocytes”, hence this is the “erythrocytic” part of the cycle). The malaria parasites that invade red blood cells are known as merozoites, and within the cell they replicate again, bursting out once they have completed a set number of divisions. It is this periodic rupturing of the red blood cells that causes most of the symptoms associated with malaria, as the host’s immune system responds to the waste products produced by the malaria parasites and the debris from the destroyed red blood cells. Different species of malaria rupture the red blood cells at different intervals, which leads to the diagnostic cycles of fever which characterise malaria; P. vivax, for example, tends to produce cycles of fever every two days, whereas P. malaria produces fever every three.

In addition, Plasmodium falciparum produces unique pathological effects, due to its manipulation of the host’s physiology. When it infects red blood cells, it makes them stick to the walls of tiny blood vessels deep within major organs, such as the kidneys, lungs, heart and brain. This is called “sequestration”, and results in reduced blood flow to these organs, causing the severe clinical symptoms associated with this infection, such as cerebral malaria.

More details on the exact biochemical mechanisms for sequestration and its effect on the pathology of the infection can be found on the Tulane University website.

Irregular Quotidian Fever

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QUESTION

Why quotidian fever is irregular?

ANSWER

Actually, the fever cycles associated with all types of malaria can be irregular. This is particular true in the initial stages of the fever, when the merozoites (the form of the parasite that leaves the liver to infect red blood cells) from different infection broods mature at different rates.

Over a few cycles of reproduction, the maturation synchronises and the parasites burst from the red blood cells in unison, creating more regular cycles of fever (no one really knows how the malaria parasites times emergence so closely!). P. falciparum may also always exhibit irregular cycles of fever, again due to asynchronous destruction of red blood cells.

Do Sporozoites in blood signal the end of prepatent period?

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QUESTION

Will the appearance of sporozoites in blood mark the end of prepatent period in malaria?

ANSWER

Actually, no. The presence of sporozoites indicates the start of the infection. Sporozoites are introduced into the bloodstream via the bite of an infected mosquit0. The sporozoites then have to make their way to the liver and infect hepatocyte cells, where they undergo pre-erythrocytic schizogony. This is where the malaria parasites produce multiple copies of their nucleus without dividing the cytoplasm of the cell; new copies of the cell are produced by budding. These new cells are called merozoites, and they are released back into the blood, where they search for erythrocytes (red blood cells) to infect.

This is the end of the pre-patent period in malaria, as the symptoms of disease will start once the merozoites infect and rupture the host’s red blood cells, and parasitaemia may also be detected at this stage through observation of peripheral blood samples.