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, 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.

 

Malaria and Anemia

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QUESTION

How does malaria cause anemia?

ANSWER

Anemia is the result of a decrease in the number of red blood cells in the blood. Malaria specifically attacks red blood cells, invading them and then undergoing multiple cycles of reproduction inside them. Once replication has been completed, the malaria parasites burst out of the red blood cell, destroying it in the process. Over the course of an infection, this can destroy many red blood cells, resulting in anemia in the patient.

Malaria and Blood Cells

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QUESTION

What effect does malaria have on blood cells?

ANSWER

Malaria survives by invading red blood cells (erythrocytes), then replicating within them several times (the exact number and timing of replication depends on the species of malaria), then, once done with replication, bursts from inside the red blood cells, destroying it in the process. As such, malaria infection decreases the number of red blood cells in a patient’s blood, which can lead to anaemia. Moreover, the most severe species of malaria, Plasmodium falciparum, forces red blood cells to stick to the insides of tiny blood vessels deep within major organs such as the kidneys and even brain. This process is called sequestration.

Infection with malaria is also often associated with a decrease in the overall number of white blood cells, but elevated numbers of monocytes can sometimes be observed.

How does malaria enter the body?

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QUESTION:

What is the portal of entry for malaria?

ANSWER:

Malaria enters its human hosts via the bite of mosquitoes of the genus Anopheles. The malaria parasites are present in the mosquitoes saliva, and enter into the human bloodstream when the mosquito bites to take a blood meal.

Once in the human body, the malaria parasite then undergoes a number of different life stages, involving reproduction in the liver as well as inside red blood cells. Once the malaria parasite has undergone reproduction in the red blood cells, the new parasites burst out and back into the blood stream, where they can be ingested by another mosquito biting again. Inside the mosquito, the malaria parasites undergo more reproduction and life stage changes, until they are ready to be transferred into a human host again, via another bite. In this way, the cycle continues.

Why do people die of malaria?

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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.

How do mosquitoes cause malaria?

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QUESTION:

How can the mosquito cause malaria?

ANSWER:

Actually, mosquitoes don’t cause malaria themselves, they just transmit it from one person to another! The disease is actually caused by a tiny parasite, of the genus Plasmodium, several species of which infect humans. Part of the parasite’s life cycle takes place in the human host, and the other part in the mosquito; it needs to go through both to survive. Mosquitoes become infected when they feed on the blood of a human host that is infected; the parasites are then transmitted to a new, uninfected human hosts in the mosquitoes saliva, when they again take a blood meal.

How do you get malaria?

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QUESTION:

How do you get malaria?

ANSWER:

Malaria is caused by parasites called Plasmodium, of which different species cause different types of malaria. A person gets malaria when they are bitten by certain female mosquitoes (of the species Anopheles) that carry Plasmodium parasites in their saliva. The mosquitoes themselves pick up the parasite by feeding on the blood of people already infected with malaria.

Once a person has been bitten by an infected mosquito, the parasites are released into their bloodstream. Inside the body, they reproduce and multiply—different types of malaria have different lengths of reproductive cycle and different locations in the body where the life stages reside. It is the process of reproduction and movement through the body that causes the fever, chills and other symptoms that are associated with a malaria infection.

Causes of malaria

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QUESTION:

What are the causes of malaria?

ANSWER:

Malaria is caused by parasites of the genus Plasmodium. These are single-celled animals known as protozoans (from the Greek ‘protos’ and ‘zoia’ which together mean ‘first animal’) and they are transmitted via mosquitoes that feed on blood; the parasites need both mosquito and human hosts to complete their life cycle (see below a graphic of the complete life cycle, courtesy of CDC). In the process of reproducing, the malaria parasites destroy human red blood cells, which is what causes the clinical symptoms of disease that the patient experiences, such as fever, headaches and nausea.

Malaria life cycle CDC

Generalized malaria life cycle (courtesy of CDC: www.cdc.gov)

There are four main species of Plasmodium that infect humans: P. falciparum, P. vivax, P. malariae and P. ovale. P. falciparum causes the most severe manifestations of the disease and is responsible for the majority of human deaths from malaria. There is a fifth type of malaria, P. knowlesi, which usually infects macaque monkeys but has been known to pass into humans as well.

For more on this, please see Christina Faust’s excellent blog post about her research.

Causes of Malaria

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QUESTION:

What causes malaria?

ANSWER:

Malaria is a disease caused by a parasitic single-celled animal known as Plasmodium. There are different species of Plasmodium, which cause different kinds of malaria. The main types which infect humans are P. falciparum, P. vivax, P. ovale and P. malariae. The parasite is transmitted by certain species of mosquito; the parasite lives in the human blood stream and so goes in to the mosquito when the insect feeds. When the same individual mosquito then feeds on another person, it transmits parasites into a new host.

The symptoms of malaria are caused by the actions that the parasite undertakes while in the human host. For example, part of its reproductive cycle involves invading and then multiplying inside red blood cells. Once several cycles of reproduction have occurred, the new parasites burst out of the red blood cell, destroying it. The cycles are times so that all the new parasites burst out of the red blood cells at the same time; this coordinated destruction of the red blood cells, either every 24, 48 or 72 hours, depending on the malaria species, causes the one day, two day or three day cycles of fevers and chills that characterise malaria infection episodes.

What is malaria?

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QUESTION:

What is malaria?

ANSWER:

To answer your question, I have copied below the answer to an earlier post, published on the 1st of May, 2011, which also asked “What is malaria?”:

Malaria is a disease caused by parasites of the genus Plasmodium. Transmitted by mosquitoes, there are several different kinds of malaria distributed throughout the tropical and sub-tropical regions of the world, causing somewhere between 300-500 million cases of disease each year, and as many as 1 million deaths. In fact, malaria is one of the biggest killers of children under the age of five in sub-Saharan Africa, one of the regions of the world where the burden from malaria is the highest. Malaria is usually an acute disease, manifesting itself with severe fever, chills, headache and often nausea as well. Some types of malaria can have relapsing episodes over a time period of many years.

Having said this, malaria is easily preventable, through avoiding mosquito bites by wearing appropriate clothing and sleeping under insecticide-treated bednets, or through taking preventative medication (called prophylaxis). Malaria is also treatable once symptoms appear, through ingesting safe, effective and relatively cheap drugs. With such control measures at hand, you may ask why malaria is still such a huge problem in our world; the answer is that delivering control strategies and treatment to populations most at risk is difficult, and often countries with high malaria burdens don’t have efficient and effective health systems in place to coordinate control efforts.

International non-governmental organisations such as the World Health Organisation, as well as a multitude of non-profit organisations such as the Malaria Consortium and Malaria No More, work tirelessly to bring malaria control and treatment to the places that need it most, with the aim to eradicate malaria as a disease of public health importance.