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.

Malaria Effects on the Body

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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.

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.

Did I have malaria before?

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I am from East Africa. On July 3rd,2011 I had chills and I consulted a doctor, he did a blood test and told me I had malaria and gave me medication.

Then after 10 days I had neck pain and I went again to the doctor, who did another blood test, diagnosed malaria and gave medication. Then after 10 days it repeated.

It’s now the 22nd august,2011. I have pain in my neck and I went to another doctor he told to take blood test and he told for the last one month you didn’t get attacked by malaria. Can I know whether I suffered from malaria for the past 1 month? Also he has told me to take saline with some medicine to flush out that malaria medication. Is it correct? Please advise me.

ANSWER:

One of our collaborating medical doctors has kindly assisted in providing this answer. If recurrent symptoms of malaria were from one exposure to malaria earlier this year, then a drug-resistant strain of Plasmodium vivax is likely. OR, he/she simply needs to take primaquine for 4-6 weeks to eradicate the liver phase. The recurrent blood phase (symptomatic phase) may be due to smoldering infection in the liver. In order to confirm this hypothesis, you would need to know what drugs you were given on your earlier trips to the doctor, as well as the type of malaria the doctor diagnosed, if possible.

 

Malaria After Blood Transfusion

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QUESTION:

How many days does it take to become symptomatic after a blood transfusion of malaria infected blood to patient?

ANSWER:

This depends on the strain and burden of malaria parasites in the blood being transfused. Onset of malaria symptoms can be very rapid if infected red blood cells begin to rupture immediately, say within 24-48 hours, or conversely symptoms can be very delayed (days/weeks/months) if only a few parasites are transfused. Depending on strain, the malaria parasites may need to cycle through the liver to mature before they infect the red cells (such as in the case of Plasmodium vivax or P. ovale).  Then, depending on the strain (P. vivax most commonly), the infected red cell “burden” often needs to approach 0.5 to 1% before synchronized rupture of red cells and release of the parasites is sufficient to produce acute fever and symptoms.