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neuropsychiatric responses, including severe
depression and frank psychosis, are well documented
in previously healthy recipients. Many
travelers now refuse the drug, and some physicians
have become increasingly wary of
prescribing it. As in the case of chloroquine,
primaquine must be administered in those
infected with P. vivax and P. ovale to eradicate
hypnozoites in the liver and thus to prevent
late relapses.
Doxycycline
This drug acts at the ribosomal level to inhibit
protein synthesis, and is an important alternative
to mefloquine for prophylaxis among
travelers to areas of chloroquine resistance.
Doxycycline and other tetracyclines act too
slowly to be used alone in the treatment of
acute malaria. The short half-life of doxycycline
necessitates daily administration. Like
chloroquine and mefloquine, doxycycline is
continued for 4 weeks after exposure to malaria
in order to ensure suppressive cure of P. falciparum.
It is not active against hypnozoites
of P. vivax or P. ovale. The major side-effects
include gastrointestinal symptoms, which are
lessened if the drug is taken with meals.
Photosensitivity dermatitis occurs in approximately
3% of recipients, candidal vaginitis is a
potential problem in women, and pseudomembranous
colitis can occur in anyone taking
broad-spectrum antibiotics, but the risk is
greatest in the elderly.
Atovaquone/proguanil
The most recent FDA-approved anti-malarial
is the fixed combination of atovaquone/
proguanil (Malarone). Although proguanil is a
dihydrofolate reductase inhibitor, it appears to
act synergistically to enhance the effects of atovaquone
on electron transport in the parasite’s
mitochondrion. Atovaquone/proguanil has
activity against erythrocytic and pre-erythrocytic
stages of P. falciparum, and only a week
of post-exposure prophylaxis is recommended.
Data on the efficacy of the combination for
the prophylaxis and treatment of P. vivax and
P. ovale are limited, but relapses are well documented
after treatment of acute P. vivax infections.
Therefore, terminal prophylaxis with
primaquine is needed.
Both atovaquone and proguanil have short
half-lives, so the combination must be administered
daily. Although gastrointestinal sideeffects
can occur, they are usually mild. These
drugs have not been associated with the neuropsychiatric
side-effects of mefloquine or the
photosensitivity dermatitis or candidal vaginitis
of doxycycline. The major concerns with
atovaquone/proguanil are cost and the potential
for the emergence of resistance, which can
occur to either atovaquone or proguanil with
single point mutations. The widespread use of
the combination may be followed by the rapid
emergence of resistance.
Primaquine
Primaquine, an 8-aminoquinoline, is the only
drug licensed in the United States with activity
against the hypnozoites of P. vivax and P. ovale.
The mechanism of action is uncertain, but
primaquine is active only after metabolism by
the host. It is administered after treatment of
P. vivax or P. ovale malaria to prevent late relapse
and in travelers who have had significant exposure
to these Plasmodium species. Relapses
occur in a variable percentage of persons
after primaquine and are more common in
some geographic areas, such as Southeast Asia,
than others. The recommended dosage varies
with geographic location. Daily primaquine
has also been used successfully in a limited
number of persons as prophylaxis against
MEDICAL APPLICATIONS