Pathophysiology of Malaria

by

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, being Plasmodium 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.

 

Why do people die of malaria?

by

QUESTION:

Why is it that people die of malaria?

ANSWER:

The symptoms of malaria are caused by the malaria parasite reproducing inside the patient’s red blood cells and eventually destroying them. In this process, the malaria parasites also produce toxic waste chemicals and debris which build up in the patient’s blood stream. The body produces a strong immune response as a reaction to these toxic products and debris; most of the systemic symptoms associated with malaria, such as fever, aching muscles and joints and nausea, are related to this immune response. Infected red blood cells can also build up in internal organs, notably the spleen and the liver, causing them to swell.

Despite these nasty-sounding effects, most cases of malaria are relatively benign and don’t lead to death. However, in some cases, the manifestation of the disease can become more severe. Most commonly, this occurs when a patient is infected with Plasmodium falciparum, one of the four main kinds of malaria that infect humans, and by far the most severe. P. falciparum reproduces very rapidly in the human host, causing extremely high fever and a fast onset of symptoms. It also changes the structure of the red blood cells it infects, causing them to become “stuck” deep within tiny blood vessels and especially in major organs such as the brain, intestines, liver, heart and lungs. Stuck within these blood vessels, the infected red blood cells are effectively hidden from the immune system and are not cleared from the body via the spleen. This allows the malaria parasite’s reproduction to go unchecked, resulting in very high numbers of the parasite in the patient’s blood.

If left untreated, the build-up of infected red blood cells can result in severe anaemia, reduced local oxygen flow and the blocking of the immune reaction; the exact mechanisms are not fully understood. When these processes occur in the brain, the result is so-called “cerebral malaria”, characterised by impaired consciousness, and which can lead to convulsions, coma and death. Even if a patient recovers from the disease episode, they may be left with permanent neurological damage. Luckily, malarial comas are often rapidly reversed after treatment is administered, and in many cases, neurological damage is not permanent.

Can malaria cause kidney failure?

by

QUESTION:

Can malaria be a cause for kidney failure or brain fever?

ANSWER:

Malaria, and specifically Plasmodium falciparum malaria, the most severe and deadly form of the disease, can certainly cause both renal failure and brain fever. It usually does this by infecting red blood cells, which then become blocked in tiny blood vessels deep within organs. This process is called sequestration. When sequestration happens in the brain, the effect can be so-called “cerebral malaria” or brain fever. In the kidney, this can result in kidney failure. Given these severe consequences, it is crucially important to seek diagnosis and then treatment immediately if you are concerned you might be suffering from malaria.

Malaria Treatment

by

QUESTION:

What is the proper treatment for people with malaria symptoms?

ANSWER:

The proper treatment for malaria depends on the type of malaria parasite that the patient is infected with. Therefore, before treatment begins, the patient should be accurately diagnosed.

In most cases of non-Plasmodium falciparum malaria (the most deadly form of malaria, found throughout the world but most prevalent in sub-Saharan Africa), and even in some places where P. falciparum has not yet developed resistance, treatment with chloroquine is sufficient.

The dosage will depend on body weight (usually approximated by age). Where there is a risk of chloroquine-resistant malaria occurring, treatment of non-complicated cases will usually consist of orally-administered artemisinin-based combination therapy (or ACT) – again, the dosage will depend on age/weight.

For severe malaria, parenteral ingestion of drugs is required. For the treatment of cerebral malaria, caused by P. falciparum, quinine is the traditional drug of choice, though artemisinin has also been shown to be effective. Anti-convulsants and anti-pyretics (to reduce fever) should also be administered.

In cases of infection with P. vivax or P. ovale, the parasite can become dormant in the liver and result in a relapse of the disease if not treated properly. As such, patients with either of these forms of malaria should also be treated with primaquine.

If you have, or suspect you have a health problem, you should visit a physician for a medical diagnosis and treatment.