| Background Element |
| Malaria Genetics and Epidemiology |
Malaria
The Parasite
Malaria is caused by parasitic protozoa of the genus Plasmodium, with four species (Plasmodium falciparum, Plasmodium
ovale, Plasmodium vivax and Plasmodium malariae) infectious to man. The life cycle of these parasites is complex.
Mammalian malaria parasites are parasites of erythrocytes that require a vector host for transmission and sexual reproduction.
The life cycle in the vertebrate begins with the bite of a mosquito. During a blood meal, a malaria-infected female Anopheles
mosquito inoculates sporozoites into the human host. Despite the fact that the salivary glands of an infected mosquito are
likely to contain many thousands of sporozoites (11,000 in Plasmodium berghei infections of Anopheles stephensi, for
example (Sinden, 1997)), less than 100 of these are believed to be transmitted in any one bite (Rosenberg et al., 1990). These
sporozoites (typically around 11um in length, and 1 um in diameter for P. falciparum) then enter the bloodstream and within
30-45 minutes migrate to the liver where they invade hepatocytes. This is achieved by the binding of the thrombospondin
domains of the circumsporozoite and thrombospondin-related adhesive proteins (CSP and TRAP, respectively), to heparin
sulphate proteoglycans on hepatocytes (Frevert et al., 1993). Here they undergo asexual reproduction (schizogony), lasting
for 5-15 days, the end product of which is around 10,000 – 30,000 merozoites. In P. vivax and P. ovale a dormant stage
[hypnozoites] can persist in the liver and cause relapses by invading erythrocytes weeks, or even years later (Mangoni et al.,
2003). These are released into the bloodstream, following rupture of the hepatocyte, where they invade red blood cells.
Merozoites are approximately 1.5 um in length, and 1um in width, and contain 3 membrane bound organelles at the apical end
(dense granules, rhopteries and micronemes), characteristic of all Apicomplexan parasites
Invasion of erythrocytes by merozoites involves an initial low affinity interaction between proteins on the surface coat of the
merozoite (possibly merozoite surface protein-1 (MSP1)) and the surface of the erythrocyte. The merozoite then orientates
itself so that the apical prominence is in contact with the surface of the red blood cell, and there follows the release of the
contents of the rhoptries, dense granules and micronemes. These assist with the penetration of the merozoite into the host
cell (Chitnis and Blackman, 2000). Inside the erythrocytes the merozoites commence feeding and are now known as
trophozoites. These in turn become schizonts after undergoing another asexual reproductive stage (erythrocytic schizogony),
and release more merozoites into the bloodstream, causing lysis of the host .
As well as releasing merozoites (that are able to invade more red blood cells), some parasites undergo gametocytogenesis
within the erythrocyte, producing micro- and macrogametocytes, male and female respectively, that remain in the blood
circulation where they are available for ingestion by a feeding mosquito. Inside the insect mid-gut the gametocytes undergo
gametogenesis, in which the female macrogametocyte escapes from the erythrocyte membrane, and the male
microgametocyte undergoes the process of exflagellation which produces 8 motile microgametes. The micro- and macro-
gametes fuse to form a zygote that in turn becomes an ookinete (the only diploid stage of the parasite) that crosses the gut
wall and encysts. This oocyst then undergoes several rounds of division, producing thousands of sporozoites that are
subsequently released into the haemocoel of the mosquito where they migrate to the salivary glands (Sinden, 1998; Beier and
Vanderberg, 1998; Frevert and Crisanti A., 1998; Barnwell and Galinski, 1998).
References
Sinden,R.E. (1997). Infection of mosquitoes with rodent malaria. In Crampton,J.M., Beard,C.B., and Louis,C. (Eds.), Molecular Biology of Insect
Disease Vectors: A Methods Manual, . Chapman and Hall, London, pp. 67-91.
Rosenberg,R., Wirtz,R.A., Schneider,I., and Burge,R. (1990). An Estimation of the Number of Malaria Sporozoites Ejected by A Feeding Mosquito.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 84, 209-212.
Frevert,U., Sinnis,P., Cerami,C., Shreffler,W., Takacs,B., and Nussenzweig,V. (1993). Malaria Circumsporozoite Protein Binds to Heparan-Sulfate
Proteoglycans Associated with the Surface-Membrane of Hepatocytes. Journal of Experimental Medicine, 177, 1287-1298.
Mangoni,E.D., Severini,C., Menegon,M., Romi,R., Ruggiero,G., and Majori,G. (2003). Case report: An unusual late relapse of Plasmodium vivax
malaria. American Journal of Tropical Medicine and Hygiene, 68, 159-160.
Chitnis,C.E. and Blackman,M.J. (2000). Host cell invasion by malaria parasites. Parasitology Today, 16, 411-+.
Sinden,R.E. (1998). Gametocytes and sexual Development. In Sherman,I.W. (Ed.), Malaria:Parasite biology, Pathenogenesis and Protection, . ASM
Press, Washinton DC, pp. 25-48.
Beier,J.C. and Vanderberg,J.P. (1998). Sporogenic development in the mosquito. In Sherman,I.W. (Ed.), Malaria:Parasite biology, Pathenogenesis
and Protection, . ASM Press, Washinton DC, pp. 49-62.
Frevert,U. and Crisanti A. (1998). Invasion of Vertebrate Cells: Hepatocytes. In Sherman,I.W. (Ed.), Malaria:Parasite biology, Pathenogenesis and
Protection, . ASM Press, Washinton DC.
Barnwell,J.W. and Galinski,M.R. (1998). Invasion of Vertebrate Cells: Erythrocytes. In Sherman,I.W. (Ed.), Malaria:Parasite biology,
Pathenogenesis and Protection, . ASM Press, Washinton DC.
Malaria is caused by parasitic protozoa of the genus Plasmodium, with four species (Plasmodium falciparum, Plasmodium
ovale, Plasmodium vivax and Plasmodium malariae) infectious to man. The life cycle of these parasites is complex.
Mammalian malaria parasites are parasites of erythrocytes that require a vector host for transmission and sexual reproduction.
The life cycle in the vertebrate begins with the bite of a mosquito. During a blood meal, a malaria-infected female Anopheles
mosquito inoculates sporozoites into the human host. Despite the fact that the salivary glands of an infected mosquito are
likely to contain many thousands of sporozoites (11,000 in Plasmodium berghei infections of Anopheles stephensi, for
example (Sinden, 1997)), less than 100 of these are believed to be transmitted in any one bite (Rosenberg et al., 1990). These
sporozoites (typically around 11um in length, and 1 um in diameter for P. falciparum) then enter the bloodstream and within
30-45 minutes migrate to the liver where they invade hepatocytes. This is achieved by the binding of the thrombospondin
domains of the circumsporozoite and thrombospondin-related adhesive proteins (CSP and TRAP, respectively), to heparin
sulphate proteoglycans on hepatocytes (Frevert et al., 1993). Here they undergo asexual reproduction (schizogony), lasting
for 5-15 days, the end product of which is around 10,000 – 30,000 merozoites. In P. vivax and P. ovale a dormant stage
[hypnozoites] can persist in the liver and cause relapses by invading erythrocytes weeks, or even years later (Mangoni et al.,
2003). These are released into the bloodstream, following rupture of the hepatocyte, where they invade red blood cells.
Merozoites are approximately 1.5 um in length, and 1um in width, and contain 3 membrane bound organelles at the apical end
(dense granules, rhopteries and micronemes), characteristic of all Apicomplexan parasites
Invasion of erythrocytes by merozoites involves an initial low affinity interaction between proteins on the surface coat of the
merozoite (possibly merozoite surface protein-1 (MSP1)) and the surface of the erythrocyte. The merozoite then orientates
itself so that the apical prominence is in contact with the surface of the red blood cell, and there follows the release of the
contents of the rhoptries, dense granules and micronemes. These assist with the penetration of the merozoite into the host
cell (Chitnis and Blackman, 2000). Inside the erythrocytes the merozoites commence feeding and are now known as
trophozoites. These in turn become schizonts after undergoing another asexual reproductive stage (erythrocytic schizogony),
and release more merozoites into the bloodstream, causing lysis of the host .
As well as releasing merozoites (that are able to invade more red blood cells), some parasites undergo gametocytogenesis
within the erythrocyte, producing micro- and macrogametocytes, male and female respectively, that remain in the blood
circulation where they are available for ingestion by a feeding mosquito. Inside the insect mid-gut the gametocytes undergo
gametogenesis, in which the female macrogametocyte escapes from the erythrocyte membrane, and the male
microgametocyte undergoes the process of exflagellation which produces 8 motile microgametes. The micro- and macro-
gametes fuse to form a zygote that in turn becomes an ookinete (the only diploid stage of the parasite) that crosses the gut
wall and encysts. This oocyst then undergoes several rounds of division, producing thousands of sporozoites that are
subsequently released into the haemocoel of the mosquito where they migrate to the salivary glands (Sinden, 1998; Beier and
Vanderberg, 1998; Frevert and Crisanti A., 1998; Barnwell and Galinski, 1998).
References
Sinden,R.E. (1997). Infection of mosquitoes with rodent malaria. In Crampton,J.M., Beard,C.B., and Louis,C. (Eds.), Molecular Biology of Insect
Disease Vectors: A Methods Manual, . Chapman and Hall, London, pp. 67-91.
Rosenberg,R., Wirtz,R.A., Schneider,I., and Burge,R. (1990). An Estimation of the Number of Malaria Sporozoites Ejected by A Feeding Mosquito.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 84, 209-212.
Frevert,U., Sinnis,P., Cerami,C., Shreffler,W., Takacs,B., and Nussenzweig,V. (1993). Malaria Circumsporozoite Protein Binds to Heparan-Sulfate
Proteoglycans Associated with the Surface-Membrane of Hepatocytes. Journal of Experimental Medicine, 177, 1287-1298.
Mangoni,E.D., Severini,C., Menegon,M., Romi,R., Ruggiero,G., and Majori,G. (2003). Case report: An unusual late relapse of Plasmodium vivax
malaria. American Journal of Tropical Medicine and Hygiene, 68, 159-160.
Chitnis,C.E. and Blackman,M.J. (2000). Host cell invasion by malaria parasites. Parasitology Today, 16, 411-+.
Sinden,R.E. (1998). Gametocytes and sexual Development. In Sherman,I.W. (Ed.), Malaria:Parasite biology, Pathenogenesis and Protection, . ASM
Press, Washinton DC, pp. 25-48.
Beier,J.C. and Vanderberg,J.P. (1998). Sporogenic development in the mosquito. In Sherman,I.W. (Ed.), Malaria:Parasite biology, Pathenogenesis
and Protection, . ASM Press, Washinton DC, pp. 49-62.
Frevert,U. and Crisanti A. (1998). Invasion of Vertebrate Cells: Hepatocytes. In Sherman,I.W. (Ed.), Malaria:Parasite biology, Pathenogenesis and
Protection, . ASM Press, Washinton DC.
Barnwell,J.W. and Galinski,M.R. (1998). Invasion of Vertebrate Cells: Erythrocytes. In Sherman,I.W. (Ed.), Malaria:Parasite biology,
Pathenogenesis and Protection, . ASM Press, Washinton DC.
