Malaria: Mode of Transmission

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QUESTION

What is the mode of transmission of Malaria?

ANSWER

Malaria is transmitted normally via the bite of an infected mosquito. These mosquitoes, always female and of the genus Anopheles, carry malaria parasites in their salivary glands. The parasites, at this part of their life cycle known as sporozoites, are introduced into the host’s blood when the mosquito takes a blood meal. From there, the sporozoites travel to the liver, reproduce (this process may take several weeks), then finally re-enter the blood stream. At this point, the patient will begin to experience symptoms. Eventually, the malaria parasites change again, into gametocytes, which are picked up by another mosquito, again when it bites the infected person. In this way, the life cycle of the malaria parasite continues.

Because malaria reproduces in the blood and in the liver, in some cases malaria can be transferred via organ transplant or blood transfusion. In addition, malaria parasites can cross the placenta, and so can be transmitted from a mother to her unborn child, either in the womb or during childbirth. This is known as congenital malaria.

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!

Malaria in Mosquitoes

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QUESTION

Why can’t mosquitoes become sick of malaria? What do they have in their system that prevent them from becoming sick yet they transmit the disease to humans?

ANSWER

First of all, mosquitoes do get “sick” when infected with malaria, though not in the same way as humans. This is due to the major differences between human and mosquito physiology and also differences in the life stage of the malaria parasite between the different hosts.

Humans get sick from malaria because the malaria parasite, when inside the human host, sequentially infects red blood cells, multiplying inside them and then destroying them. This process of destruction and the resultant debris in the blood results fever and other symptoms (some of which are exacerbated by the body’s immune response).

Mosquitoes are insects, and do not have blood in the same way as humans. Instead, in the mosquito, the malaria parasites differentiate into male and female life stages (called gametocytes) which fuse into the mosquitoes gut. After further reproduction, they eventually produce sporozoites that rupture out of the mosquito gut wall and migrate to the salivary glands, where they can be infected into a new human host.  

Mosquitoes also have a very different immune system to humans, and so the concept of “sick” is not the same for them as for humans. However, there is a lot of evidence that infection with malaria results in reduced reproductive success for the mosquito, as well as lower survival. This could be due to protective responses on the part of the mosquito, but also could be mediated by the malaria parasite, by diverted resources towards its own development that could have been used for mosquito reproduction or survival.

Transmission of Malaria

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QUESTION

Why can the malaria parasite be transmitted from mosquito to human, but not from human to human (via blood)?

ANSWER

This is a very good question, and actually, malaria can be transmitted via human blood directly to another person, but this occurs relatively rarely!

It has to do with the life cycle of the malaria parasite. When a mosquito bites a human host, it injects sporozoites from its salivary glands into the blood. This life stage first migrates to the liver, where it undergoes a cycle of multiplication, before entering the blood stream. Here, in the so-called “erythrocytic” portion of the life cycle, the parasite reproduces a series of times in red blood blood, before finally forming gametocytes, which are required to be ingested by a mosquito vector during another blood meal for the life cycle to be continued. As such, when blood is passed between people, they would have to pass infected red blood cells, and not gametocytes (which are not infective to humans, only to mosquitoes) in order for the other person to become infected.

As such, when a person who is infected with malaria donates blood, there is a chance that they might pass on some red blood cells which are infected with mature trophozoites or schizonts; these could then go on to infect more red blood cells in the person who received the blood. However, in most countries, blood is screened for malaria, and in fact, in many places, people who might have been exposed to malaria are not allowed to donate whole blood, only plasma (in which the red blood cells have been removed, and therefore there is no risk of transmission). Given the high levels of malaria prevalence in some endemic countries, however, preventing people from donating blood who are positive for malaria may result in too little blood being collected; in these cases, other strategies, such as treating donors or closely monitoring patients post-transfusion, may prove to be a better strategy.

malaria life cycle schematic CDC

Schematic of the malaria life cycle, courtesy of CDC (www.cdc.gov)

What are Gametocytes?

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QUESTION

What are Gametocytes?

ANSWER

Gametocytes are the sexually reproductive form of the malaria parasite. They circulate in the blood of the human/mammal host and are picked up by the mosquito when it takes a blood meal.

Inside the mosquito, the gametocytes undergo sexual reproduction in the mosquito midgut, producing oocysts which attach to the midgut wall and produce sporozoites, which are the stage that are infective to humans when the mosquito takes another blood meal (the sporozoites are passed into the blood via the saliva of the mosquito).

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.