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, 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.

Malaria Effects on the Body

by

QUESTION

What are the effects of malaria on the body?

ANSWER

Malaria has a number of effects on the body. The parasite passes from the blood (where it enters via the bite of an infected mosquito) into the liver, where it reproduces and changes form. After a period of 1-4 weeks (usually – it can be longer) in the liver, the malaria parasite re-enters the blood and begins to infect red blood cells, undoing more reproduction inside the cells and then, in synchrony, bursting out once the cycle is complete. This process of reproduction and destroying red blood cells results in a build-up of toxins and debris in the blood; the resultant immune reaction produces side effects which are the common observable symptoms of malaria, such as fever, chills, nausea and aches.

One particular type of malaria, Plasmodium falciparum, is also able to modify the surface of red blood cells it infects. It causes these cells to become “sticky”, so they lodge in the small blood vessels leading up to major organs. This build-up is called sequestration, and results in reduced blood flow and oxygen deprivation in the organs. When sequestration occurs in the blood vessels in the brain, the patient may experience impaired consciousness, psychological disruption, coma and even death – this manifestation is called “cerebral malaria”.

If diagnosed and treated promptly, the malaria parasites in the blood can usually be killed rapidly and the patient will soon enjoy a complete recovery. With two forms of malaria, P. vivax and P. ovale, the parasite can remain dormant in the liver for months or even years, resulting in relapse of disease at a later date. To prevent this from occurring, patients with these types of malaria can sometimes take primaquine, a drug which kills the liver stages of the malaria parasite as well.

Malaria Symptoms

by

QUESTION

How does the virus cause the symptoms?

ANSWER

Malaria is actually not caused by a virus—it is caused by a microscopic single-celled parasite called Plasmodium. Several different species cause malaria in humans, the most common of which are P. vivax and P. falciparum.

To describe the process in a very oversimplified way, the malaria parasites cause disease by infecting red blood cells, multiplying inside them, then simultaneously bursting out again, destroying then red blood cell in the process. The sudden destruction of lots of red blood cells, plus the debris and waste products left behind by the malaria parasites, stimulate a rapid immune reaction, which itself causes the rapid spike of fever. The characteristic cycles of fever sometimes seen with malaria sufferers occurs because the malaria parasites synchronise their emergence from the red blood cells. The destruction of red blood cells, together with concurrent physiological changes associated with immune response and inflammation, can also lead to decreased haemoglobin levels and anaemia.

More severe clinical symptoms are often seen with P. falciparum malaria infection, particularly if not promptly diagnosed and treated. This is because the P. falciparum parasite infects a red blood cell, it changes the surface of the cell and makes it “sticky”; when the red blood cell then tries to pass through the small blood vessels that lead into the body’s organs, it becomes stuck. This process is known as “sequestration”. If enough red blood cells become sequestered in the organs, it can reduce blood flow to the organ, resulting in oxygen deprivation. When this happens in the blood vessels in the brain, the patient may experience impaired consciousness, confusion and even coma and death—this manifestation is known as “cerebral malaria.”

Dangerous

by

QUESTION

Why malaria so dangerous?

ANSWER

Malaria can be dangerous for a number of different reasons, some of which relate to each other. First of all, there are five different types of malaria that infect humans, and each varies in terms of its severity and potential for severe consequences. Even within these types, the severity of the disease caused (termed “virulence” by scientists and doctors), can even vary by strain or geography. Generally, the most dangerous form of malaria is caused by Plasmodium falciparum. One reason why this species of malaria is so dangerous is that is replicates very quickly in the blood. This means that infection levels can build up very quickly; if a person infected with P. falciparum does not get diagnosed and treated within a few days of feeling sick, the infection can progress to a point where the disease becomes very severe. This rapid accumulation of infection is also observed with P. knowlesi, a much rarer form of malaria found in south-east Asia. The parasites of P. knowlesi have a 24-hour reproductive cycle in the blood, the quickest for any type of malaria that infects humans. However, P. falciparum also has other characteristics which make it even more dangerous, and which do not occur with P. knowlesi. For example, when P. falciparum infects red blood cells, it causes their shape to change, and makes them “sticky”. This stickiness causes the red blood cells to become lodged in the blood vessels leading in to major organs, in a process known as sequestration. Sequestration creates blockages of these blood vessels, reducing blood flow and resulting in oxygen deprivation. When this process occurs in the blood vessels in the brain, the outcome is known as cerebral malaria, characterised by impaired consciousness, coma and even death. It is this pathology which is associated with most cases of severe malaria, and causes the most number of deaths.

However, if treated promptly with the correct drugs, even P. falciparum malaria is usually easily controlled. Therefore, one of the additional reasons why malaria is so dangerous is that in many places, and particularly sub-Saharan Africa, people do not have access to medication, or not the right types of medication. Many strains of P. falciparum have become resistant to chloroquine, once the first line treatment for malaria, and so this drugs is now ineffective in many cases. Instead, the World Health Organisation recommends now that artemisinin-based combination therapies (ACTs, such as Coartem) should be given as first-line treatment against all uncomplicated malaria, to prevent additional resistance from developing.

Thalassaemia and Malaria

by

QUESTION

How can Thalassaemia effect Malaria infection?

ANSWER

Thalassaemia is the name given to a group of inherited genetic blood disorders, which result in reduced or no synthesis of one of the globin protein chains that combine to make haemaglobin. Haemaglobin is used to carry oxygen throughout the body and to its organs.

Thalassaemia can result in anaemia; in some cases, this is severe enough to require periodic blood transfusions. There has long been a hypothesis that thalassaemia might have persisted due to conveying protection against malaria infection; this was suggested due to the geographical distributions of populations with high prevalence of the alleles (gene types) that cause thalassaemia and areas with high levels of malaria transmission. However, scientifically confirming this association has proved challenging.

A recent study from Kenya demonstrated that children with either one copy of the thalassaemia allele or two copies appeared to have a reduced incidence of severe malaria, fewer deaths from malaria and were hospitalized less frequently for malaria. However, they were just as likely as non-thalassaemic children to have mild or sub-clinical malaria, and the same levels of parasitaemia (numbers of parasites in the blood).

A contrasting study from Vanuatu observed higher incidences of severe malaria in children with thalassaemia, though one potential confounding factor in comparing these studies is that the Vanuatu study looked at both P. falciparum and P. vivax, whereas the Kenya study only looked at P. falciparum malaria.

The difference is significant: one of the proposed mechanisms by which thalassaemia protects against malaria is by preventing modification of the surface of red blood cells, which causes the red blood cells to become “sticky” and sequester within the blood vessels that feed major organs, eventually restricting blood flow and causing major complications. This sequestration is only observed to occur during infection with P. falciparum, and so thalassaemia might not be as protective against other forms of malaria. More empirical research from the field is needed to understand the mechanisms relating malaria infection with thalassaemia more fully.

Frequent Urination and Malaria

by

QUESTION

Can malaria result in frequent urination, especially during night?

ANSWER

Malaria can affect the kidneys, especially malaria caused by P. falciparum. This could result in changes to urination patterns. However, at this stage in the infection, the patient would also be experiencing severe fever, chills and other symptoms associated with malaria. The fever would also likely be causing dehydration if the patient was not taking on sufficient fluids, which would result in less frequent urination.

Malaria in the Brain

by

QUESTION

I would like to know how dangerous is malaria in the brain?

ANSWER

Only a certain kind of malaria, Plasmodium falciparum, is usually associated with causing problems in the brain. The P. falciparum parasite infects red blood cells and changes their surface structure, causing them to become “sticky”. These sticky red blood cells become lodged in the small blood vessels that flow through organs, causing blockages and reducing oxygen flow.

When this process occurs in the brain, the result is called “cerebral malaria”, and can result in impaired consciousness, coma and even death. As such, once malaria-infected blood passes into the brain, it can be very dangerous. Luckily, however, if people are diagnosed promptly and given treatment, it is usually possible to stop the progression of P. falciparum malaria before it enters the brain, allowing for a swift and uncomplicated recovery.

Why is Malaria Dangerous?

by

QUESTION

How does Malaria become so dangerous?

ANSWER

Malaria in humans can be caused by a number of different parasites – the most dangerous, and the one which is responsible for over 90% of the worldwide deaths from malaria, is Plasmodium falciparum.

The reason that P. falciparum is so dangerous is because it affects the behaviour of red blood cells. Red blood cells that are infected with P. falciparum become “sticky”, and as they pass through the the small blood vessels inside the body’s organs, they become stuck – this process is known as “sequestration”. As the number of red blood cells stuck inside the small blood vessels increases, blood flow to the organ is reduced, which can result in further complications. When sequestration occurs inside the blood vessels in the brain, the result is what is clinically recognised as cerebral malaria – complications can include impaired consciousness, coma and even death.

If diagnosed and treated promptly, most cases of P. falciparum can be resolved quickly and without complications, using oral medication. However, the parasite can reproduce very quickly, meaning that cases can become more serious within days and even hours. As such, if P. falciparum infection is suspected, and particularly in high-risk individuals such as young children, pregnant women and immunocompromised individuals, diagnosis should be sought immediately so that appropriate treatment can be delivered.

Is it Common to Die of Malaria?

by

QUESTION

is it common to die of malaria? Why? Why not?

ANSWER

Thankfully, these days it is not very common to die from malaria. Out of an estimated 250 million cases of malaria around the world every year, there are only about 700,000 fatalities. However, 700,000 deaths every year is still a lot!

If left undiagnosed and untreated, malaria can progress very rapidly and be a very serious disease. This is particular true of Plasmodium falciparum, a specific type of malaria which is found throughout tropical regions in South America, Africa and Asia.

It is dangerous because it reproduces very rapidly in the body and can cause red blood cells to clog up inside blood vessels in organs, restricted blood flow. When this occurs in blood vessels in the brain, the patient may suffer “cerebral malaria,” which can rapidly lead to loss of consciousness, coma and even death if not treated promptly.

The people most at risk from malaria are children under the age of 5 and pregnant women, and so it is particularly important for these people to seek medical care very quickly if they suspect they have malaria.

On a positive note, deaths from malaria are becoming less common around the world due to a number of factors. First of all, there have been many very successful prevention strategies, for example through distribution of long-lasting insecticide treated bednets to at-risk communities living in malaria endemic regions. Indoor residual spraying with insecticides have also drastically reduced the number of mosquitoes in households where this procedure has been carried out, thus reducing transmission. Moreover, improvements to point-of-care diagnostics and other health infrastructures have enabled poor people in developing countries to have access to ways in which their infections can be diagnosed, and then given the appropriate treatment. All of these measures have brought the number of annual deaths down from 1 million just a few years ago to 700,000 today.

The goal is yet more ambitious: organisations such as Malaria No More seek to eliminate deaths from malaria, all over the world, by the year 2015. So, we hope in 2015 we can add to this answer by saying it is now very rare indeed to die from malaria!

Malaria and the Brain

by

QUESTION

How long does it take malaria to reach your brain?

ANSWER

The process by which malaria affects the brain is complicated, and the amount of time also varies. First of all, only one species of malaria parasite is associated with the brain – this is Plasmodium falciparum, the most deadly form of malaria. It is dangerous because when it infects red blood cells, it makes them “sticky,” so that they become lodged in the small blood vessels in the body’s organs. This process is called sequestration, and results in reduced blood flow to the organs, which can result in further complications.

When infected red blood cells sequester in the brain, the result is so-called “cerebral malaria,” which can lead to impaired consciousness, coma and even death. P. falciparum reproduces rapidly, so if not treated promptly, cerebral manifestations of the infection could appear within a matter of a few days of the initial onset of malaria symptoms. The good news is that treatment is very safe and effective, especially when started early, so when malaria is suspected as the possible cause of an illness, a blood test should be performed immediately to test for malaria, and also to determine if the species is P. falciparum.

If you have taken medications for malaria, please help Malaria.com by taking our Malaria Medication Side-effects Survey: Treatment and Prophylaxis. Thank you!