C H A P T E R 1 2
Antiprotozoal agents
165
disease. In addition, the protozoa that cause malaria
have developed strains resistant to the usual antimalarial
drugs. This combination of factors has led to a world-
wide public health challenge.
Life cycle of plasmodium
The parasites that cause human malaria spend part of
their life in the
Anopheles
mosquito and part in the
human host (see Figure 12.1). When a mosquito bites
a human who is infected with malaria, it sucks blood
infested with gametocytes, which are male and female
forms of the
Plasmodium
. These gametocytes mate in
the stomach of the mosquito and produce a zygote that
goes through several phases before forming sporozoites
(spore animals) that make their way to the mosquito’s
salivary glands. The next person who is bitten by that
mosquito is injected with thousands of sporozoites.
These organisms travel through the bloodstream, where
they quickly become lodged in the human liver and other
tissues, and invade the cells.
Inside human cells, the organisms undergo asexual
cell division and reproduction. Over the next 7 to
10 days, these primary tissue organisms called schizonts
grow and multiply within their invaded cells, using the
cell for needed nutrients (as
trophozoites
). Merozoites
are then formed from the primary schizonts and burst
from invaded cells when they rupture because of over-
expansion. These merozoites enter the circulation and
invade red blood cells. Here they continue to divide
until the blood cells also burst, sending more mero-
zoites into the circulation to invade yet more red blood
cells.
Eventually, there are a large number of merozoites
in the body, as well as many ruptured and invaded red
blood cells. At this point, the acute malarial attack
occurs. The rupture of the red blood cells causes chills
and fever related to the pyrogenic effects of the protozoa
and the toxic effects of the red blood cell components on
the system. This cycle of chills and fever usually occurs
about every 72 hours.
Infected anopheles
injecting sporozoites
into man
Sporozoites
Causal
prophylactic drugs
(Primary tissue schizont
in liver cell)
Pyrimethamine,
primaquine
Early
tropozoite
RBC
Mature
schizont
Ruptured RBC
releasing merozoites
Immature
gametocytes
Mature
gametocytes
Gametes
Fertilisation
Zygote
Ookinete
(penetrating
midgut wall)
Cycle in mosquito
Cycle in humans
Growth of
oocysts
Antirelapse drugs
(Second tissue
schizont in liver cell)
Primaquine
No effective
drug known
Infected
salivary
gland
Ruptured
oocyst with
sporozoites
Sporontocidal drugs
(Active against the
parasites developing
in the mosquito)
Pyrimethamine,
primaquine
Gametocytocidal drug
(Active against the
gametocytes of all
malaria parasites)
Primaquine
Gametocyte-sterilising drugs
Pyrimethamine
Anopheles taking
infected blood
from man
Schizontocidal drugs
(Active against the erythocytic phase)
Potent action: chloroquine, mefloquine
Limited action: pyrimethamine,
hydroxychloroquine
FIGURE 12.1
Sites of action of antimalarials
and other antiprotozoals. Antimalarials
block protein synthesis and cause cell death.
Other antiprotozoals block DNA synthesis,
prevent cell reproduction and lead to cell
death. RBC, red blood cell.
