Malaria Life Cycle

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Life Cycle of Malaria

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Malaria is an ancient disease transmitted by the Anopheles mosquito that predates recorded history. Historically it was common in the swampy areas around Rome, and was believed that the tainted air in those locations made people very sick, the disease was therefore named malaria for the Latin root words bad air. Malaria is caused by small parasitic protozoa of the genus Plasmodium which infects both humans and mosquitoes in a cyclical process. It is carried by only by female mosquitoes residing in tropical and subtropical areas and is injected into unsuspecting human hosts by the bite of an infected mosquito. This particular Plasmodium is highly specific to infecting humans as we are the only vertebrates infected and the Anopheles mosquitoes are the vectors. (1). This papers main focus shall be the process by which a malarial plasmodium colonizes and infects a human host, the methods the body employs to control the infection and the continuous life cycle completed between the two hosts.

To understand any disease in humans one must first understand how it arrives into the body and what processes ensue. The following shall first describe the transmition of the disease and then the colonization that takes place.

During a blood meal on a human a female mosquito must inject her saliva containing an anticoagulant agent to ensure and even flow of blood into the mouth (1). With the saliva comes malarial sporozoites which, within minutes of direct contact with the blood take an immediate route with the circulation of blood to the liver of the human (2). Research has indicated that once the sporozoites arrive in the livers sinusoidal cavities they stop their movement by using two major surface proteins, the circumsporozoite and the thormbospondin-related adhesive protein (3). Research

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conducted by Pradel et al. suggests that the sporozoites use these surface proteins to attach to proteoglycans in the sinusoidal extracellular matrix to slow their travel through the liver and then bind to chondroiten and heparin sulfate proteoglycans on the Kupfer cells. The Kupfer cells then become the doorways through which the sporozoite leaves the circulatory system and enters the underlying hepatocytes.

Once the sporozoites invade the hepatocytes they are protected from the immune system by a parasitophosphorous (4) vacuole that does not colocalize with the normal signals for acidifying organelles (2). Because the body doesn’t recognize the vacuole as a threat at this point it remains safely with in the hepatic cell where it will stay for 9-16 days and differentiate into haploid cells called schizont which contain nearly 30,000 compact cells called merozoites (1). At the end of this period the mass production of merozoites within the schizont cause it to rupture, which releases the merozoites into the cytoplasm of the hepatic cell, killing it. With the death of the hepatic cell thousands of merozoites spill into the blood stream, progressing the disease into what is known as liver stage malaria (4).

Once in the blood stream the merozoites immediately invade the closest erythrocytes. Once entering the cell they multiply rapidly through mitosis while feasting on hemoglobin. Each merozoite forms another schizont and after two days bursts open releasing 16-32 new merozoites which go on to colonize more red blood cells; this point is known as blood stage malaria. Soon after, two out of every three red blood cells are colonized, producing fever and chills in the host (4). Once the erythrocyte is infected it becomes sticky and attaches to the walls of the blood vessels. If enough of

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these cells build up in the same area blood vessels can become blocked and may rupture. If one ruptures in the brain (cerebral malaria) the damage caused to the surrounding tissue can be fatal due to localized ischemia. In addition, if left untreated the victim may suffer other severe complications including anemia, kidney failure and pulmonary edema (5,6).

While it isn’t entirely understood how P. falsiparum manages to both invade the body and keep the immune system at bay, there has been research investigating this very mystery. A study conducted by Nobes et al. discovered that at the erythrocitic stage phagocytic Kupfer cells in the liver grow larger and begin to break down infected erythrocytes circulating though the sinusoidal cavities . While the exact trigger mechanism isn’t completely understood Nibes et al. hypothesized that the Kupfer cells are activated by phagocytosable particles, namely