Wednesday, July 25, 2007

Plasmodium falciparum Causes Malaria

Malaria is caused by a small protozoan parasite called Plasmodium falciparum (left). The Plasmodium is a single-celled organism with a complex life cycle. It is classified in the nebulous Protist kingdom within the phylum Apicomplexa [NCBI Taxonomy].

The life cycle is described in many places but one of the best comes from the Applied Biosystems website.
Human malaria is caused by infection with intracellular protozoan parasites of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Four species of Plasmodium infect humans: P. falciparum, P. vivax, P. ovale, and P. malariae, with P. falciparum accounting for the majority of infections and being the most lethal. The causative agent of malaria was discovered in 1880 by Charles Alphonse Louis Laveran (Ref.1).

Plasmodium falciparum is exclusively transmitted by female Anopheles mosquitoes, mainly from members of the Anopheles gambiae complex. The parasites have a complicated life cycle that requires a vertebrate host for the asexual cycle and a female Anopheles mosquito for completion of the sexual cycle. Infection of humans by P. falciparum is initiated by injection of sporozoites into the bloodstream by an Anopheles mosquito (Ref.2). During a mosquito blood meal,infectious Sporozoites in the mosquito's saliva enter the host bloodstream and invade its hepatocytes. While some evidence indicates that Sporozoites are first trapped by Kupffer cells and then transported to hepatocytes,other findings suggest that Sporozoites home to hepatocytes directly. Sporozoite reaches liver via bloodstream in 30 minutes....

In the hepatocytes asexual multiplication (exoerythrocytic schizogony) occurs, leading to the production of several thousand merozoites. In 1 to 2 weeks, a single sporozoite can give rise to 30,000 merozoites. During this pre-erythrocytic stage,no illness is induced by malaria. In P. vivax infections, which are characterized by relapses,a dormant stage, called the hypnozoite, remains in the liver. From this stage relapsing infections may occur at a later stage. P. falciparum infection relapses do not occur. It is, therefore, assumed that the sporozoites of this species develop uniformly producing pre-erythocytic schizonts at the same time and these schizonts, once formed,discharge all the merozoites simultaneously; do not remain dormant as in P. vivax (Ref.3).

These Merozoites are released into the bloodstream and invade erythrocytes. The asexual erythrocytic cycle begins when a single merozoite invades a host red blood cell and is enclosed within a parasitophorous vacuole,separate from the host cell cytoplasm. Three morphologically distinct phases are then observed. The ring stage,lasting approximately 24 h in P. falciparum, accounts for about half of the intraerythrocytic cycle, but it is metabolically nondescript. It is followed by the trophozoite stage; a very active period during which most of the red blood cells cytoplasm is consumed. Finally,parasites undergo 4-5 rounds of binary divisions during the schizont stage, producing 8-36 new merozoites that burst from the host cell to invade new erythrocytes,beginning another round of infection. This phase of the infection (erythrocytic schizogony) is responsible for malaria pathogenesis. Much of the morbidity and mortality associated with malaria is caused by the rupture of iRBCs (Infected Red Blood Cells) during the asexual reproductive stages of the parasite. Intense fever, occurring in 24-72 hour intervals, is accompanied by nausea, headaches,and muscular pain among other symptoms. The characteristic fever spike has been correlated with incremental rises in serum levels of TNF-Alpha associated with the release of parasite proteins during erythrocytic rupture. Furthermore,a variety of potentially fatal symptoms,including liver failure, renal failure,and cerebral disease are associated with untreated P. falciparum. These symptoms are consequences of the unique ability of the parasite to bind to endothelial surfaces; this adherence inhibits circulation and causes localized oxygen-deprivation and sometimes hemorrhaging. It has been proposed that ICAM1 (Intercellular Adhesion Molecule-1), E-selectin,VCAM1 (Vascular Cell Adhesion Molecule-1), and CSA (Chondroitin Sulfate-A), and CD36 are some of the surface molecules responsible for parasite-endothelial adherence (Ref.4).

Instead of producing new schizonts, some merozoites, after invasion of the erythrocyte, arrest their cell cycle and develop into male (micro) or female (macro) gametocytes, the forms that are required for transmission to the mosquito (asexual parasites do not survive ingestion by the insect). Inside the mid-gut of the mosquito, fertilization occurs, producing zygotes, which develop into ookinetes. The ookinetes form oocysts, which then grow and divide and rupture to give rise to sporozoites, which migrate to the salivary glands. Then the infectious cycle of malaria can repeat itself (Ref.5). While all four species of Plasmodium have a haemolytic component ie. when a new brood of parasites break out of the red blood cell this is usually of little consequence. The exception is falciparum malaria where the parasites multiply very rapidly and may occupy 30% or more of the red blood cells causing a very significant level of haemolysis. One reason for this is that P. falciparum invades red cells of all ages whereas P. vivax and P. ovale prefer younger red cells, while P. malariae seeks mature red cells. Malaria places an increasing burden on global public health resources. In the face of growing resistance of the malaria parasite to available antimalarial drugs, there is a need for new drugs and the identification of new chemotherapeutic targets (Ref.6).

Image Credits:

Plasmodium falciparum, the parasite that causes malaria in humans, needs a living host in …. [Photograph]. Retrieved July 25, 2007, from Encyclopædia Britannica Online:

Life Cycle diagram is from Don Forsdyke.

The red blood cell image is from The Scripps Research Institute.


  1. The first (well, only) malaria victim I've seen up close was during my military service.

    [Well, not so military perhaps. Our group had opted to work on nature preserves. Forestry, building service stations of all kinds including elongating and completely restoring a house, tallying animals and plants. Rather relaxing and edifying, actually.]

    In the middle of the service period the poor thing got a P. vivax relapse - hit him from the blue pretty bad for a few days. So I respect that disease, considering it was the less serious one.

    Turned out he had picked it up in Africa while bird watching. (He was genuinely spontaneous and wouldn't bother with preventatives.) As the creationists say, an interest in biology can be a dangerous thing.

  2. I think a bad error occured in the article:
    The picture does not show Plasmodium falciparum!!
    It is definitely a nematode (maybe Caenorhabditis elegans)

  3. I'm sorry, but all these quotes from Darwin ruined this site for me. I'm a Christian, and while I respect science, you cannot have it without some faith in something other than yourself and random chance.
    Chritianity isn't a religion, it's a belief. (and a true one at that)
    Genesis 1:1

  4. Hey, my name is Harry, and I was wondering if I could use the picture of the plasmodium for a biology assignment.

  5. This is not a Plasmodium, this is a nematode, a mulitcellular organism.
    So even if you think you are smarter than the rest of the scientific community (Evolution), get your basic facts straight when publishing stuff in the internet.

  6. anonymous says,

    This is not a Plasmodium, this is a nematode, a mulitcellular organism.
    So even if you think you are smarter than the rest of the scientific community (Evolution), get your basic facts straight when publishing stuff in the internet.

    I've replaced the original picture with one that shows Plasomdium in the context of a cell so you can get a better impression of scale.

  7. thank you for this information...I hope i can use this information for my research for carica papaya as antimalarial (P.falciparum) once again thank you for everything...

  8. is malaria a very serious disease to get nowadays?my big bro got it and he is at his college hospital unable to come home.will he be ok ?i hope they look after him well