Plasmodium and begin to replicate rapidly giving rise

Plasmodium is the deadliest member of the
protozoan family. There are over 2billion people at risk of disease contraction
with 500million cases of malaria a year resulting in around 1million deaths (Greenwood et
al., 2008; Vaughan et al., 2008) .
Malaria in humans is caused by four Plasmodium species: P.falciparum, P.vivax, P.ovale, and P.malariae. P.falciparum
is responsible for the majority of the malaria morbidity (Tuteja,
The parasite is transmitted via female Anopheles mosquito hence the
geographical distribution of the vector make malaria endemic to the tropical
and sub-tropical region. (Tuteja, 2007)

suffering from malaria display a variety of symptoms allowing for categorization
of the disease as either uncomplicated or serious. As shown in the numbers
above, the majority of people have uncomplicated malaria which is characterized
by fever and non-specific symptoms such as vomiting or diarrhea. Severe malaria
in children presents as respiratory distress, severe anaemia and/or cerebral
malaria. In adults, it results in multiple-organ damage. The reasons behind
particular disease patterns in an individual are unknown. Malaria is
particularly dangerous in pregnancy as the parasites attach to the placenta
which can cause damage to both the mother and the child. (Greenwood et
al., 2008; Miller et al., 2002; Tuteja, 2007)

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Upon a bite of
Anopheles mosquito, the P.falciparum
sporozoites are released into the skin. Some of the parasites will be killed by
host’s immune system, some will glide until they reach a draining lymph node or
a blood vessel. Parasites that managed to reach the blood vessel will enter the
circulation and eventually reach the liver. Sporozoites enter liver through
Kupffer cells, liver-specific macrophages, and they migrate through several hepatocytes
before reaching the final one where they establish themselves inside
parasitophorous vacuole and begin to replicate rapidly giving rise to thousands
of merozoites. Liver stages do not cause any symptoms in humans. (Silvie et
al., 2008; Vaughan et al., 2008)

Eventually, merozoite-filled
vesicles will detach from the liver, re-enter the circulation and free
merozoites will be release into circulation in pulmonary capillaries. (Vaughan et
al., 2008)  Merozoites invade red blood cells, actively
remodel it and begin division. (Haldar and Mohandas,
2007)  Each full division cycle results in the development
of mature schizont containing around 20 merozoites that are released upon RBC
destruction. Freed merozoites infect new RBCs and the cycle start anew. A
single development cycle takes about 48hrs in P.falciparum and the merozoites are released relatively
synchronously explaining the clinical symptoms of periodic fevers that
accompany RBC stage of the disease. (Tuteja,

While asexual
reproduction of the merozoite is responsible for the clinical disease in
humans, this parasite stage cannot transmit the disease through the insect
vector. A small percentage of merozoites develops into gametocytes which upon a
mosquito feeding produce gametes and undergo fertilization to produce ookinete.
Ookinete gives rise to oocyst in the mosquito midgut. Sporozoites develop
within the oocyst and upon oocyst rupture, they home to insect salivary gland where
they can be transmitted to a new host when the vector feeds. (Tuteja,



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