Biomedical Engineering Reference
In-Depth Information
Mosquito
Gametocyte
Sporozoite
Bite
Bite
Gametocytes
Hepatic schizont
Erythrocytic
schizonts
Merozoite
Erythrocyte
Liver
Blood
Human
FIGURE 21.5
A mosquito belonging to the genus
Anopheles
pumps salvia into dermis of humans through
the proboscis during feeding. If the mosquito is infected with malarial parasites, the salvia also will contain
sporozoites, which will infect liver cells. In the liver, the parasites will develop into merozoites, which will be
released into the blood by rupture of the liver cells. In the red blood cells, the merozoites will proliferate. At
certain intervals, the red blood cells will rupture to release merozoites and male and female gametocytes. If
a mosquito takes a blood meal on an infected human, the intraerythrocytic schizonts will be digested but the
extraerythrocytic gametocytes will undergo a sexual proliferation in the mosquito enabling the mosquito to
infect a new human.
Today the major burden of malaria is restricted to the tropical world: India, South East Asia,
SubSaharan Africa, and Central and South America, but the endemic area of malaria besides the
tropics also encompasses the subtropics and the major part of the temperate zones. During the
1950s and 1960s, a combined use of dichlorodiphenyltrichloroethane (DDT) for control of the vector
mosquitoes and chloroquine (
21.7
) (refer to Figure 21.8) for the control of the parasites almost eradi-
cated malaria from the Indian subcontinent. Resistance of the parasites toward chloroquine and of
the mosquitoes toward DDT and the environmental consequences of extended use of DDT led to
discontinuation of the project and return of the malaria burden.
21.5 DRUGS AGAINST MALARIA
In the absence of vaccines, malaria therapy relies on small molecule drugs. A number of antibiotics
are used successfully either individually or more common in combination with other drugs. It may
be surprising that antibiotics display considerable activity against the eukaryotic malarial parasite.
This contradiction can be explained by the presence of two essential organelles in the parasites,
namely, the mitochondria and the apicoplasts (Figure 21.6).
The apicoplast, probably, is a remnant of endosymbiotic cyanobacteria, which in plants have
developed into the photosynthetic chloroplasts. Even though the apicoplasts do not perform photo-
synthesis, their metabolic pathways are still essential for the parasites. Both organelles have their
own machinery for replication. Most antibiotics used in malaria therapy affect the apicoplasts.
21.5.1 D
RUGS
T
ARGETING
H
EMOZOIN
F
ORMATION
The ultimate diagnosis of malaria is microscopic observation of parasites in the erythrocytes of a
thick blood i lm. The presence of the malaria pigment, hemozoin in the erythrocytes, unequivocally
reveals the presence of parasites. Hemozoin is formed from the heme (ferroprotoporphyrin IX,
21.5
)
remaining after digestion of the peptide part of hemoglobin (Figure 21.7). The digestion proceeds in
