trans

TREATMENT OF PARASITIC DISEASES 441
of plasmodial dihydrofolate reductase by
proguanil.
TABLE 17.3
for malaria
Prophylactic and treatment strategies
Current status of malaria prophylaxis
and treatment
Malaria remains a major health problem for
residents of endemic regions and for travelers
to them. P. falciparum is the principal cause of
mortality. Intensive efforts have also been
directed toward the development of a malaria
vaccine. While the possibility of transient
immunity has been substantiated, the chance
of finding a vaccine that stimulates the development
of permanent or long lasting immunity
is still more a hope than a reality.
Plasmodium species are transmitted by the
bite of female anopheline mosquitoes. Sporozoites
are inoculated and spend approximately
half-an-hour in the bloodstream before entering
hepatocytes. The parasite then undergoes
development in the liver, the pre-erythrocytic
stage, which takes a week or longer, and is
asymptomatic. Eventually, merozoites are
released into the bloodstream and infect circulating
red blood cells, initiating the erythrocytic
stage of infection. The typical symptoms of
malaria, fever, myalgia, headache and malaise
are associated with the destruction of erythrocytes
and release of malarial antigens. In the
case of P. vivax and Plasmodium ovale, hypnozoites,
a latent form that causes no symptoms,
can persist in the liver for months to years
before maturing to release merozoites into the
bloodstream. This scenario can result in the
development of symptomatic malaria months
after a person departs from an endemic area.
Vector control should not be overlooked as a
means of protection against malaria. Bed nets
impregnated with permethrin or other insecticides,
and personal protective measures, such
as long-sleeved clothing and the topical application
of DEET, have been shown to decrease
Suppressive treatment refers to the continuous
administration of a drug to kill parasites in
erythrocytes after completion of the pre-erythrocytic
stage, thus preventing the development of
symptomatic malaria.
Suppressive cure is achieved when treatment with a
drug active against parasites in erythrocytes is
continued beyond the lifespan of the
pre-erythrocytic stage.
Clinical cure refers to the elimination of
intra-erythrocytic malaria with drugs such as
quinine, chloroquine or mefloquine resulting in
resolution of symptoms, but depending upon the
circumstances, leaving the subject susceptible to
recrudescence.
Radical cure refers to the elimination of both
pre-erythrocytic and erythrocytic forms and requires
the addition of a drug such as primaquine that is
active against the pre-erythrocytic stage in the liver.
the transmission of malaria, but they are only
partially protective.
Recommendations for the prophylaxis and
treatment of malaria are complicated and continuously
changing as drug resistance evolves
in different parts of the world. The optimal
regimen depends on the causative Plasmodium
species, its likelihood of being susceptible to
specific drugs (which varies among geographic
regions), the past medical history of
the patient, and the likelihood and severity of
side-effects.
Prophylactic and treatment strategies for
malaria vary (Table 17.3). Chloroquine, mefloquine
and many of the other anti-malarial drugs
act only on the erythrocytic stage. Suppressive
treatment refers to the continuous administration
of a drug to kill parasites in erythrocytes
after completion of the pre-erythrocytic stage,
thus preventing the development of symptomatic
malaria. Suppressive cure is achieved
when treatment with a drug active against
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