Biomedical Engineering Reference
In-Depth Information
occur mainly in children and pregnant women in Africa. 1,2 It is also the most
adept at acquiring and rapidly spreading resistance to anti-malarial drugs.
Once inside the human host, the parasite undergoes a complex life cycle that
includes (1) a maturation cycle in the liver that occurs before (2) entering the
bloodstream and infecting the host's red blood cells which initiates an asexual
intra-erythrocytic reproduction cycle. It is the intra-erythrocytic part of the
parasite life cycle that is responsible for the clinical symptoms of the disease. At
the end of a growth and multiplication phase of 48-72 h (depending on the
Plasmodium species) the parasites cause the infected red blood cell to rupture.
This results in anemia due to the destruction of erythrocytes and further pro-
blems due to the associated release of large amounts of free hemoglobin and
other inflammatory agents into host circulation. The process also results in the
liberation of free merozoites that then infect new red blood cells, and the
continuation of the intra-erythrocytic cycle. The first clinical symptoms usually
occur 10 days to 4 weeks after infection manifested as repeated cycles of chills
and fevers, though they can appear as early as 8 days or as long as a year after
infection. These symptoms correspond to the intra-erythrocytic cycle and occur
in cycles of 48-72 h, again depending on the species of infecting Plasmodium.
Malaria continues to be an enormous public health burden for developing
countries. 3 Up to 48% of the world's population, or 3 billion people, now live
in areas at risk of malaria. There are over 500 million cases of malaria annually
among the world's poorest populations, with the disease claiming nearly a
million children each year in Africa alone. 1 Implementation of control mea-
sures is often hampered by poor health-care infrastructure in many endemic
countries. 1 However, recent measures including the scale-up of malaria control
interventions such as the procurement and distribution of artemisinin-based
combination therapy (ACT), the anti-malarial drug class of choice, and
insecticide-treated bed nets (ITNs), as well as other mosquito vector control
measures have led to a fall in malaria transmission in some parts of Africa. 1,3-5
7.1.2 A Continuing Need for New Targets for Novel Anti-
Chloroquine, arguably the most outstanding anti-malarial ever developed, was
effective for many years as a chemoprophylaxis against Pf malaria around the
world. However, chloroquine resistance in parasites appeared in the 1970s in
two separate geographical locations and is now distributed globally while other
affordable anti-malarial drugs such as sulfadoxine/pyrimethamine are also
becoming less effective. 6,7 Artemisinin and its derivatives are arguably our last
line of defense and therefore recent documented cases of arteminisin-resistant
malaria along the Thai-Cambodia border are causing concern—it appears that
the spread of this resistance through neighboring countries or further afield is
inevitable. 4,5,8 Although there is increasing hope for an anti-malarial vaccine,
limited ecacy and challenges of widespread vaccination programs dictate that
control of malaria will continue to depend on drugs effective against the
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