ndi
F.P.
Scappatura,
MD
D.
Lawee,
MD
E.
Gutman,
MD
Malaria
Prophylaxis:
Problems
and
Recent
Recommendations
SUMMARY
The
authors
of
this
paper
provide
an
overview
of
the
relative
risk
of
malaria
in
various
areas
of
the
world.
On
the
basis of
the
geographic
information
available,
they
discuss
both
chemoprophylaxis
and
treatment
for
this
disease,
and
make
recommendations
for
their
use.
(Can
Fam
Physician
1989;
35:901-906.)
SOMMAIRE
Les
auteurs
exposent
sommairement
le
risque
relatif
de
la
malaria
dans
differentes
regions
du
monde.
Sur
la
foi
des
renseignements
geographiquement
disponibles,
ils
discutent
la
chimioprophylaxie
et
la
therapeutique
de
cette
maladie
et
suggerent
quelques
recommandations
quant
a
leur
utilisation.
Key
words:
malaria,
chemoprophylaxis,
treatment
_
.B4
-1-N
Dr.
Lawee
is
a
member
of
the
Senior
Staff
of
the
Department
of
Family
Medicine
and
Director
of
Special
Family
Practice
Services
of
Toronto
General
Hospital.
He
is
also
a
Professor
in
the
Department
of
Family
and
Community
Medicine,
Faculty
of
Medicine
of
the
University
of
Toronto.
Dr.
Scappatura
is
Co-
ordinator
of
the
Travel
Inoculation
Clinic,
Toronto
General
Hospital,
and
lecturer
in
the
Department
of
Family
Medicine
at
the
University
of
Toronto.
Dr.
Gutman
is
Attending
Physician
of
the
Rotary
Laughlin
Centre
and
Baycrest
Hospital,
Toronto,
Staff
Physician
in
the
Travel
Inoculation
Clinic,
Toronto
General
Hospital,
and
Instructor
in
the
Department
of
Family
and
Community
Medicine
of
the
University
of
Toronto.
Requests
for
reprints
to:
Dr.
Lawee,
Toronto
General
Hospital,
200
Elizabeth
Street,
Toronto,
Ont.
M5G
2C4
IN
the
past
year,
three
publications
issued
recommendations
for
malar-
ia
prophylaxis.
These
publications
were
the
World
Health
Organization
(WHO)
"Vaccination
Certificate
Requirements
for
International
Travel,"'
the
Medical
Letter,
2
and
the
Centers
for
Disease
Control
(CDC)
"Health
Information
for
Inter-
national
Travel
1988."3
While
all
three
publications
sup-
ported
the
use
of
chloroquine
for
pro-
phylaxis
in
chloroquine-sensitive
areas,
there
is
wide
disagreement
concerning
prophylaxis
in
chloro-
quine-resistant
areas.
The
Medical
Letter
recommends
chloroquine
plus
self-treatment
with
three
tablets
of
pyrimethamine-sulfadoxine
(Fansi-
dar)
for
febrile
illness
when
medical
care
is
not
immediately
available
in
all
chloroquine-resistant
areas
with
three
major
exceptions.
The
first
of
these
excepted
areas
is
Africa
south
of
the
Sahara,
where
proguanil
(200
mg
daily)
during
exposure
and
for
four
weeks
afterwards
plus
the
self-
treatment
regimen
of
pyrimethamine-
sulfadoxine
is
added
to
the
chloro-
quine.
The
second
and
third
are
South-east
Asia
and
the
Amazon
ba-
sin,
where
chloroquine
plus
doxycy-
cline
(100
mg
daily)
during
exposure
is
suggested
as
the
best
available
regi-
men.
The
recommendations
of
the
CDC
are
similar
to
those
in
the
Medical
Letter,
with
two
exceptions.
The
CDC
does
not
recommend
proguanil
(it
is
not
available
in
the
U.S.),
although
the
CDC
does
acknowledge
that
limit-
ed
data
indicate
the
drug's
effective-
ness
in
Kenya.
The
recommendations
limit
doxycycline
use
to
rural
Thai-
land,
Burma,
and
Kampuchea.
The
WHo
recommendations
are
much
less
specific
and,
to
many,
more
confusing.
Most
of
sub-Sahara
Africa,
South
America,
Asia,
the
In-
dian
subcontinent,
and
Oceania
are
consolidated
into
one
"zone."
The
WHO
lists,
as
follows,
possible
drug
regimens
for
this
"zone":
*
chloroquine
alone;
*
chloroquine
plus
proguanil
prophy-
laxis
alone;
or
*
either
of
the
above
regimens
in
CAN.
FAM.
PHYSICIAN
Vol.
35:
APRIL
1989
901
combination
with
self-treatment
regi-
mens.
Various
self-treatment
regimens
are
suggested:
pyrimethamine-
sulfadoxine,
metakelfin,
mefloquine,
or
quinine.
For
East
Africa,
Thai-
land,
Burma,
Laos,
Kampuchea,
Vietnam,
and
the
South-west
part
of
China,
WHo
recommends
mefloquine
alone
as
treatment
or
prophylaxis.
Mefloquine
is
available
only
in
Switz-
erland,
France,
and
Thailand.4
Several
problems
are
associated
with
any
regimen
of
prophylaxis
or
treatment
for
malaria.
When
deciding
which
drugs
to
use,
physicians
must
understand
the
malarial
life
cycle
and
the
actions
of
the
different
antimalar-
ial
agents.
Pharmaceutical
Agents
It
must
be
emphasized
to
the
tra-
veller
that
chemoprophylaxis
is
not
always
successful,
especially
in
areas
infested
with
Plasmodium
falciparum
that
is
resistant
to
multiple
drugs.
Routine
suppressive
prophylaxis
can-
not
prevent
relapse
of
P.
vivax
and
P.
ovale
infections.
Both
travellers
and
physicians
should
be
familiar
with
the
early
symptoms
of
malaria.
Travellers
must
also
understand
that
malaria
can
be
effectively
treated
early
in
the
course
of
the
disease
and
that
delayed
institution
of
appropriate
therapy
can
have
serious
consequences.
It
is
of
paramount
importance
that
travellers
be
warned
to
seek
immediate
medical
attention
and
inform
the
physician
of
their
travel
history
if
they
experience
malaria
symptoms
up
to
one
year
after
possible
exposure.
Malaria
symptoms
can
develop
as
early
as
eight
days
after
exposure
or
as
late
as
several
months
after
departure
from
a
malarious
area.
Patients
who
devel-
op
symptoms
of
malaria
should
have
a
prompt
assessment,
including
thick
and
thin
films,
as
soon
as
possible.
Chemoprophylactic
options
Prospective
travellers
should
con-
sult
a
physician
who
can
determine
the
appropriate
prophylactic
drug
and
dosage
according
to
the
area
to
be
visited
and
the
possible
drug
toler-
ance
or
side
effects
of
the
drug.
The
recommended
prophylactic
drug
for
malaria
protection
varies
according
to
the
risk
of
infection,
the
risk
of
fatal
outcomes,
efficacy
of
prophylaxis,
drug
toxicity,
efficacy
of
general
pro-
tective
measures
against
transmis-
sion,
the
age
of
the
traveller,
the
traveller's
previous
exposure
to
anti-
malarial
drugs,
the
length
of
stay,
and
drug
availability.
Common
chemoprophylaxis
for
malaria
falls
into
the
following
categories.
Causal
prophylaxis.
Certain
drugs
de-
stroy
the
primary
liver
stages
before
the
parasites
can
mature
and
enter
the
blood.
Suppression.
Suppressive
therapy
does
not
prevent
initial
infection
or
relapse,
but
prevents
symptoms
of
malaria
by
reducing
or
eliminating
blood
parasites.
Suppressive
Cure.
Malaria
can
be
eliminated
by
continuing
suppressive
medication
long
enough
to
exceed
the
duration
of
the
primary
liver
stage.
In
non-relapsing
malaria
(P.
falciparum
and
P.
malariae),
suppres-
sive
cure
is
usually
achieved
if
the
drug
is
continued
four
weeks
after
the
last
exposure
to
mosquitoes
infected
with
malaria.
Antimalarial
agents
Chloroquine.
The
usual
drug
of
choice
for
suppression
oft
infection
caused
by
all
susceptible
strains
of
malaria
is
chloroquine.
The
recom-
mended
adult
dose
is
500
mg
of
chlo-
roquine
phosphate
(equivalent
to
300
mg
base)
taken
once
weekly,
one
week
before
entering,
during
travel
in,
and
for
four
weeks
after
leaving
the
infected
area.
Chloroquine
is
effective
only
against
the
blood
stages
of
malaria
in-
fection
and
has
no
effect
on
the
ex-
oerythrocytic
stage
in
the
liver;
hence
it
does
not
prevent,
but
rather
sup-
presses
symptoms
of
infection.
In
sensitive
P.
falciparum
and
P.
malariae
infections,
chloroquine
usu-
ally
produces
a
suppressive
cure
when
continued
for
four
weeks
after
the
last
exposure.
For
travel
to
areas
of
risk
where
chloroquine-resistant
P.
falciparum
has
not
been
reported
or
is
at
a
low
level,
chloroquine
alone
is
recom-
mended.
Unfortunately,
this
is
the
case
only
in
Central
America,
Haiti,
North
Africa,
and
the
Middle
East.
It
has
been
suggested,
however,
that
chloroquine
may
reduce
the
severity
of
chloroquine-resistant
P.
falcipa-
rum
(CRPF).
Serious
adverse
reactions
to
sup-
pressive
doses
of
chloroquine
are
rare.
Minor
side
effects,
such
as
gas-
trointestinal
disturbances,
headache,
dizziness,
blurred
vision,
pruritus,
and
possibly
exacerbation
of
psoriasis
902
may
occur,
but
rarely
require
discon-
tinuation
of
the
drug.
Some
of
these
effects
may
be
reduced
by
taking
the
drug
after
meals
or
by
dividing
the
dose
in
half
and
taking
a
half
dose
twice
weekly.
High
dose
chloroquine
taken
for
prolonged
periods
can
cause
severe
retinopathy
with
loss
of
central
vision
and
pigmentation
of
the
macula.
Some
recommend
ophthalmologic
examination
after
the
total
cumulative
chloroquine
dose
ex-
ceeds
100
gm
base,
which
requires
about
six
years
of
weekly
treatments5.
Proguanil
(Paludrine).
The
use
of
proguanil,
a
dihydrofolate
reductase
inhibitor,
declined
as
the
resistance
of
P.
vivax
and
P.
falciparum
became
widespread.
Interest
in
proguanil
in-
creased
after
it
was
found
to
retain
its
prophylactic
effect
against
P.
falciparum
despite
erythrocytic
schi-
zont
resistance.
Proguanil
is
a
very
safe
drug;
mouth
ulcers
have
been
re-
ported
as
a
rare
side
effect.
Although
limited
data
are
avail-
able,
studies
to
date
suggest
moder-
ate
protective
efficacy
in
East
Africa,3
but
little
or
no
benefit
in
South-east
Asia
and
Oceania.5
Adult
travellers
taking
proguanil
should
take
a
daily
200-mg
dose
in
combina-
tion
with
a
weekly
regimen
of
chloro-
quine.
Pyrimethamine-Sulfadoxine.
Pyrime-
thamine-sulfadoxine
is
a
combination
of
enzyme
inhibitors
that
act
syner-
gistically
in
the
folic
acid
cycle.
The
drug
has
been
implicated
in
causing
a
number
of
serious
and
occasionally
fatal
side
effects
including
blood
dys-
crasias,
liver
damage,
Stevens-
Johnson
syndrome,
toxic
epidermal
necrolysis,
and
fever
with
eosinophi-
lia.
Studies
have
suggested
that
the
incidence
of
severe
cutaneous
ad-
verse
reactions
is
one
in
5
000
to
8
000
users
and
the
mortality
rate
is
one
in
11
000
to
25
000
when
used
weekly.3
As
a
result,
pyrimethamine-sulfa-
doxine
is
no
longer
used
as
a
first-line
drug
for
malaria
chemoprophylaxis,
but
has
a
role
as
an
agent
for
pre-
sumptive
treatment.
The
adult
dose
is
three
tablets
together
if
the
traveller
develops
symptoms
of
malaria
(fever,
chills,
flu-like
illness)
while
travelling
and
medical
help
is
not
available.
It
is
contraindicated
in
pregnancy,
in
G6PD
deficiency,
in
sulfonamide
allergy,
and
in
patients
receiving
oral
anti-
coagulants.
Pyrimethamine-sulfadoxine
is
pres-
CAN.
FAM.
PHYSICIAN
Vol.
35:
APRIL
1989
ently
unavailable
in
Canada,
but
can
be
purchased
in
most
countries
where
chloroquine-resistant
malaria
is
present.
Doxycycline.
Tetracyclines
have
re-
cently
been
reconsidered
as
antima-
larial
drugs
because
of
progressive
spread
of
CRPF.
They
have
long
been
known
to
be
a
causal
prophylactic
for
infections
with
strains
of
CRPF
found
in
South-east
Asia.
Doxycycline
has
proven
to
be
an
effective
therapeutic
agent
against
CRPF
and
is
probably
the
only
practi-
cal
prophylactic
form
of
tetracycline
because
of
its
long
half-life
(17
to
22
h).9
Tetracycline
is
not
a
satisfactory
causal
prophylactic
against
P.
vivax,
but
does
have
a
suppressive
effect
against
the
erythrocytic
stage;
there-
fore,
if
chloroquine
is
not
used
in
conjunction,
doxycycine
should
be
taken
for
six
weeks
after
exposure.
Doxycycline
is
particularly
appro-
priate
for
those
with
a
history
of
sul-
fonamide
intolerance
or
those
who
are
at
risk
in
an
area
infested
with
strains
resistant
to
chloroquine
and
pyrimethamine-sulfadoxine.
Significant
adverse
effects
include
severe
photosensitivity,
allergic
reac-
tions,
gastrointestinal
disturbance,
and
overgrowth
of
nonsusceptible
mi-
cro-organisms,
especially
fungi.
Te-
tracyclines
are
contraindicated
in
pregnancy
and
in
children
younger
than
eight
years
of
age.
Mefloquine.
Mefloquine
is
a
4-
quinolinemethanol
with
a
very
long
half-life
and
is
well
tolerated.
It
is
a
rapidly
acting
schizonticide,
highly
ef-
ficacious
against
P.
vivax
and
P.
falciparum.
Mefloquine
alone
or
a
combination
of
mefloquine
(500
mg)
and
pyrime-
thamine-sulfadoxine
is
used
in
a
few
areas
of
the
world
(e.g.,
Thailand)
as
a
therapeutic
agent
for
acute
infec-
tions
with
strains
of
P.
falciparum
presumed
resistant
to
other
drugs.
The
prophylactic
dose
is
250
mg
weekly
one
week
before
and
during
exposure
(this
dose
varies
depending
on
length
of
stay).
The
most
common
side
effects
as-
sociated
with
mefloquine
are
nausea,
vomiting,
diarrhea,
and
dizziness
in
Figure
1
Recommendations
for
Malaria
Drug
Prophylaxis
by
Area,
1989
A
MAURITUS
Chemo-
Stand-by
Area
prophylaxis
Treatments
Comments
A
Chloroquine
None
Risk
generally
low
and
seasonal,
nil
in
many
areas
(e.g.,
urban
areas).
P.
falciparum
absent
or
sensitive
to
chloroquine.
B
Chloroquine
plus
Pyrimethamine-
Risk
high
in
most
areas
in
Africa
except
in
some
urban
and
high
proguanil
sulfadoxine
altitude
areas.
Chloroquine
may
fail
to
prevent
infection
with
P.
falciparum,
but
is
likely
to
alleviate
it.
The
addition
of
proguanil
is
likely
to
increase
both
prevention
and
alleviation.
C
Chloroquine
Pyrimethamine-
Highest
risk
in
northeast
part
of
India.
Risk
in
urban
and
rural
sulfadoxine
areas.
D
Chloroquinea
Pyrimethamine-
Increasing
reports
or
both
chloroquine
and
pyrimethamine-
sulfadoxine
sulfadoxine
resistance.
Risk
is
in
rural
areas,
except
in
interior
or
mefloquine
Amazon
basin,
where
some
urban
risk
exists.
a.
Except
in
Thailand,
Laos,
Kampuchea,
Burma,
Vietnam,
and
Papua
New
Guinea,
where
chloroquine
and
doxycycline
prophylaxis
are
recommended.
Use
of
doxycycline
is
recommended
for
special
cases
in
the
Amazon
basin.
VANUATU
CAN.
FAM.
PHYSICIAN
Vol.
35:
APRIL
1989
903
frequency
comparable
to
those
associ-
ated
with
chloroquine.
Mefloquine
should
not
be
used
by
those
receiving
beta-blockers,
calcium
channel
block-
ers,
or
other
drugs
that
prolong
cardi-
ac
conduction
because
of
an
associa-
tion
with
bradycardia
and
prolonged
Q-T
interval.
Lack
of
availability
is
the
greatest
problem
associated
with
mefloquine.
Primaquine.
Primaquine
is
used
to
prevent
relapse
of
P.
vivax
and
P.
ovale
by
acting
against
the
liver
stages
of
these
species.
It
is
usually
adminis-
tered
with
chloroquine
after
the
tra-
veller
leaves
the
endemic
area
during
the
final
two
weeks
of
chloroquine
prophylaxis.
Most
malarious
areas
of
the
world
(except
Haiti)
have
at
least
one
relapsing
species
of
malaria;
however,
the
risk
to
the
traveller
is
ha}
d
to
quantify
and
is
normally
small.
Primaquine
prophylaxis
is
gen-
erally
indicated
only
in
those
with
prolonged
exposure
in
endemic
areas.
In
individuals
with
G6PD
deficiency,
exposure
to
primaquine
may
give
rise
to
life-threatening
hemolysis;
there-
fore
G6PD
levels
must
be
assayed
be-
fore
beginning
therapy.
Malaria
prophylaxis
during
pregnancy
Malaria
in
pregnant
women
may
be
more
severe
than
in
non-pregnant
women
and
increases
the
risk
of
poor
pregnancy
outcome.
Chloroquine
and
proguanil
are
thought
to
be
safe
in
pregnancy.
Pyrimethamine-sulfa-
doxine
should
be
avoided
in
pregnan-
cy
because
pyrimethamine
is
terato-
genic
in
laboratory
animals
and
sulfa-
doxine,
like
other
sulfonamides
administered
late
in
pregnancy,
could
exacerbate
neonatal
jaundice.
Doxy-
cycline
is
contraindicated
for
malaria
prophylaxis
in
pregnancy
because
of
the
frequent
occurrence
of
dental
dysplasia
and
disruption
of
bone
growth.
Primaquine
could
cause
life-
threatening
hemolysis
in
utero
in
a
fe-
tus
with
G6PD
deficiency
and,
hence,
Table
1
Prophylaxis
and
Treatment
of
Malaria
by
Continent
and
Region
Continent
Region
North
of
the
Sahara
Africa
South
of
the
Sahara
Middle
East
Central
China
South-east
Asia
Southern
provinces
of
China
and
Hainan
Island
Asia
Indian
subcontinent
Thailand,
Laos,
Kampuchea,
Burma,
Vietnam,
Papua
New
Guinea
Central
Areas
west
of
and
the
Andes
South
America
Amazon
basin
and
areas
east
of
the
Andes
Prophylaxis
Chloroquine
Proguanil
Chloroquine
Chloroquine
Chloroquine
Chloroquine
plus
doxycycline
Alternative
Prophylaxis
or
Standby
Self-Administered
Treatment
Chloroquine
Self-administered
pyrimethamine-
sulfadoxine
Proguanil
(if
unable
to
take
chloroquine)
Self-administered
pyrimethamine-
sulfadoxine
Doxycycline
Self-administered
pyrimethamine-
sulfadoxine
Quinine
treatment
Mefloquine
prophylaxis
or
treatment
Chloroquine
Proguanil
(if
unable
to
take
chloroquine)
Chloroquine
Self-administered
pyrimethamine-
sulfadoxine
Doxycycline
prophylaxis
for
high-risk
travel
should
not
be
used
in
pregnancy.
Treatment
of
CRPF
in
pregnancy
can
be
complex,
and
a
pregnant
traveller
who
develops
fever
should
seek
im-
mediate
medical
attention.10","
Prophylaxis
while
breast-feeding
Very
small
amounts
of
antimalarial
agents
are
secreted
in
breast
milk
and
are
not
thought
to
have
harmful
ef-
fects
on
the
nursing
infant.
Infants
who
require
chemoprophylaxis
are
not
adequately
protected
by
the
quantity
of
drug
transferred
in
breast
milk.
Prophylaxis
for
children
Doxycycline
is
contraindicated
for
children
younger
than
eight,
and
py-
rimethamine-sulfadoxine
is
contrain-
dicated
for
children
younger
than
two
months
of
age.
Chloroquine
is
very
bitter
and
must
be
crushed
and
mixed
with
food
to
encourage
children
to
swallow
it.
Chloroquine
suspension
is
generally
available
overseas.
Overdoses
of
antimalarial
agents
can
may
be
fatal
in
children,
so
the
medication
must
be
kept
in
child-
proof
containers
in
a
location
not
ac-
cessible
to
children.
Drug
resistance
A
problem
that
may
arise
with
widespread
use
of
any
drug
prophy-
laxis
is
drug
resistance.
There
is
widespread
resistance
to
chloroquine
(and
now
pyrimethamine-sulfa-
doxine).
Plasmodium
falciparum
re-
sistant
to
mefloquine
has
already
been
reported
from
East
Africa
and
South-east
Asia12'4.
Some
drug
com-
binations
seem
to
be
effective
in
one
area
but
not
in
others
(Figure
1).
The
combination
of
weekly
chloroquine
and
daily
proguanil
is
fairly
effective
in
East
Africa,
but
its
effectiveness
is
not
so
well
established
in
West
Afri-
ca,
the
Indian
subcontinent,
and
the
Amazon
basin.
Furthermore,
there
is
evidence
that
this
combination
is
in-
effective
in
South-east
Asia.
Recommendations
for
Malaria
Prophylaxis
by
Area
Tables
1
and
2
summarize
malaria
prophylaxis
protocols
used
by
the
Travel
and
Inoculation
Service
of
the
Toronto
General
Hospital
and
shows
the
drugs
used
in
view
of
drug
avail-
ability
in
Canada.
Figure
1
represents
the
geographical
distribution
of
ma-
laria
risk
and
identifies
prophylactic
drugs
in
relation
to
geographic
areas
CAN.
FAM.
PHYSICIAN
Vol.
35:
APRIL
1989
A
4
1%
I
904
of
their
effectiveness.
Table
2
lists
rec-
ommendations
for
drug
prophylaxis
and
treatment
by
geographic
area.
Area
A
In
Area
A
(Figure
1),
malaria
in-
fections
are
sensitive
to
chloroquine
and
the
risk
of
malaria
is
generally
low
and
seasonal;
often
urban
centres
are
risk
free.
Plasmodium
falciparum
is
absent
or
sensitive
to
chloroquine.
Chloroquine
alone
is
recommended
for
this
area.
Area
B
Area
B
is
in
Africa,
where
the
risk
of
malaria
is
generally
very
high
and
is
present
in
most
urban
and
rural
areas.
The
addition
of
proguanil
to
chloroquine
prophylaxis
is
found
to
enhance
the
prevention
of
P.
falciparum
in
this
area
(particularly
East
Africa).
The
addition
of
a
(three-tablet)
dose
of
pyrimetha-
mine-sulfadoxine
for
self-treatment
seems
to
be
a
reasonable
and
safe
op-
tion
for
the
high-risk
traveller,
be-
cause
data
on
the
efficacy
of
the
com-
bination
of
chloroquine
and
proguanil
are
limited.
Area
C
In
Area
C,
the
Indian
subconti-
nent,
chloroquine
resistance
is
limit-
ed
and
no
resistance
to
pyrimetha-
mine-sulfadoxine
has
been
reported.
Therefore,
chloroquine
alone
is
rec-
ommended,
except
for
the
long-term
or
high-risk
traveller,
who
should
car-
ry
a
treatment
dose
of
pyrimetha-
mine-sulfadoxine.
Area
D
Prevalent
strains
in
Area
D
are
chloroquine
resistant,
and
variable
degrees
of
pyrimethamine-sulfa-
doxine
resistance
have
been
report-
ed.
The
risk
is
almost
exclusively
in
rural
areas,
except
for
some
urban
risk
in
the
interior
Amazon
basin.
We
recommend
chloroquine
prophylaxis
for
all
these
areas.
In
addition,
be-
Table
2
Malaria
Prophylaxis
Protocols
Used
by
TGH
Travel
and
Inoculation
Service
Pediatric
Dose
Chemoprophylaxis
Brand
Names
Adult
Dose
5
mg/base/kg
(max
2
tablets)
Drug
of
Choice
Chloroquine
phosphate
250-mg
tablet
(150
mg
base)
or
Sulphate
Aralen
Avlochlora
Resochina
Nivaquine
syrupa
500
mg
(2
tablets)
once
weekly
and
continued
for
6
weeks
after
last
exposure
in
a
malarious
area
1
year:
1/4
tablet
2-3
years:
1/3
tablet
4-6
years:
2/3
tablet
7-1
1
years:
11/2
tablets
11-16
years:
13/4
tablets
(approximate
dosages)
Alternative
Drugs
Proguanil
(Chloroguanide
Paludrine
hydrochloride)
Prophylaxis
in
Areas
with
Chloroquine-Resistant
P.
Falciparum
(CRPF)
Take
chloroquine
as
recommended
above
and
add
one
of
the
following
drugs
if
indicated:
Proguanil
(Paludrine)
200
mg
orally,
once
daily
<15
kg:
50
mg;
<30
kg:
100
mg
<45
kg:
150
mg;
<60
kg:
200
mg
Doxycyclineb
(Vibramycin)
1
00
mg
orally,
once
daily
>8
yrs
of
age:
2.0
mg/kg/d
of
body
weight,
orally,
up
to
adult
dose
of
100
mg/day
Treatment
of
Presumptive
Malaria
Infection
Pyrimethamine-
(Fansidar)C
sulfadoxine
Mefloquined
Mefloquined
Tablets
(75
mg
pyrimethamine
and
1500
mg
sulfadoxine),
orally,
taken
as
a
single
dose
6-11
mos:
¼Atablet
1-3
yrs:
1/2
tablet
4-8
yrs:
1
tablet
9-14
yrs:
2
tablets
a.
Unavailable
in
Canada
or
the
United
States.
Widely
available
overseas,
but
may
require
a
prescription.
b.
Use
is
contraindicated
in
pregnancy
and
children
younger
than
eight.
The
US
FDA
considers
the
use
of
tetracyclines
as
antimalarial
agents
to
be
investigational.
Physicians
who
prescribe
doxycycline
as
malaria
chemoprophylaxis
should
advise
their
patients
to
limit
direct
exposure
to
the
sun
to
minimize
the
possibility
of
a
photosensitivity
reaction.
Vaginal
yeast
infections
occur
commonly
in
women
receiving
tetracyclines.
c.
Use
is
contraindicated
in
persons
with
history
of
sulfonamide
or
pyrimethamine
intolerance,
in
pregnancy
at
term,
and
in
infants
younger
than
two
months.
Physicians
who
prescribe
the
drug
to
be
used
as
presumptive
treatment
in
the
event
of
a
febrile
illness
when
professional
medical
care
is
not
readily
available
should
ensure
that
such
prescriptions
are
clearly
labelled
with
instructions
to
be
followed
in
the
event
of
a
febrile
illness.
If
used
as
weekly
prophylaxis,
travellers
should
be
advised
to
discontinue
the
use
of
the
drug
immediately
if
they
notice
a
possible
adverse
effect,
especially
if
any
mucocutaneous
signs
or
symptoms
develop.
d.
For
resistant
infections,
mefloquine
is
an
alternative
drug.
(Fansi-mef
is
a
combination
drug
of
pyrimethamine-sulfadoxine
and
mefloquine.)
Take
three
tablets
at
once
as
treatment.
These
drugs
may
be
available
in
Bangkok
by
prescription
from
a
local
physician.
Check
exact
dosage
with
local
physician.
CAN.
FAM.
PHYSICIAN
Vol.
35:
APRIL
1989
905
cause
of
more
widespread
resistance
to
pyrimethamine-sulfadoxine,
we
recommend
doxycycline
daily
for
all
night-time
rural
travellers
in
Thai-
land,
Laos,
Kampuchea,
Burma,
and
Vietnam,
and
for
travellers in
high-
risk
(remote)
areas
in
the
Amazon
ba-
sin
and
Papua
New
Guinea.
Travellers
in
Area
D
who
are
taking
chloroquine
alone
should
carry
a
treatment
dose
of
pyrimethamine-sulfadoxine
(or
pre-
ferably,
mefloquine
if
available).
Doxycycline
may
be
discontinued
on
departure
from
a
malarious
area,
but
chloroquine
should
be
continued
for
an
additional
four
weeks.
General
Measures
Malaria
is
transmitted
through
the
bite
of
Anopheles
mosquitoes,
which
bite
at
night.
No
antimalarial
drug
in
current
use
guarantees
100%
protec-
tion
against
malaria;
consequently,
the
CDC,
WHO,
and
Medical
Letter
em-
phasize
the
need
for
travellers
to
pro-
tect
themselves
from
mosquito
bites
by
adhering
to
the
following
mea-
sures.
*
From
dusk
to
dawn,
wear
light-col-
oured,
long-sleeved
clothing
and
long
pants
that
cover
the
arms
and
legs.
Travelling
to
a
malaria-free
urban
area
does
not
normally
entail
risk
of
contracting
malaria,
provided
all
nights
(from
dusk
to
dawn)
are
spent
in
such
areas.
If
the
traveller
spends
any
time
after
sunset
in
a
surrounding
malarious
rural
area,
however,
the
risk
of
malaria
justifies
chemopro-
phylaxis.
*
Apply
a
non-aerosol
mosquito
re-
pellent
(preferably
liquid)
containing
diethyltoluamide
(DEET)
to
exposed
skin
(such
as
Muskol
or
Deep
Woods).
Extensive
applications
of
highly
concentrated
solutions
on
in-
fants
should
be
avoided.
*
Sleep
in
properly
screened
lodging.
*
Use
mosquito
nets
on
all
beds
at
night.
A
nylon
mosquito
bed-net
(16
x
18
mesh)
offers
good
protection.
*
Use
other
mosquito-repellent
mea-
sures,
such
as
knock-down
sprays
and
plug-in
electric
insecticide
dispensers,
and
burn
mosquito
coils.
An
optimal
program
of
protection
against
malaria
would
include:
*
Following
the
general
measures
listed
above;
i
Checking
with
a
physician,
a
health
authority,
or
other
informed
source
about
the
malaria
risk,
the
available
prophylactic
drugs,
and
measures
ap-
propriate
for
the
area
being
visited;
*
Awareness
that
malaria
infection
may
occur
in
spite
of
adherence
to
the
above
precautions
and
to
the
rec-
ommended
prophylaxis.
Since
signs
and
symptoms
of
malaria
are
not
spe-
cific,
travellers
should
seek
medical
attention
and
inform
their
physician
of
the
possibility
of malaria
whenever
they
develop
fever
up
to
one
year
(and
particularly
within
the
first
two
months)
after
exposure.
It
is
equally
important
for
the
physician
to
obtain
a
travel
history
whenever
the
cause
of
a
fever
is
not
readily
discernible.
Overview
The
best
protection
against
malaria
is
to
avoid
mosquito
bites.
The
choice
of
chemoprophylaxis
should
depend
on
the
area
visited,
the
traveller's
previous
experience
with
antimalarial
prophylaxis,
and
the
availability
of
drugs.
Prescribing
drugs
for
malaria
prophylaxis
will
remain
a
difficult
clinical
decision
because
the
exact
prevalence
of
malaria
and
associated
drug
resistance
in
many
areas
is
un-
known,
and
experts
differ
significant-
ly
about
the
best
chemoprophylactic
regimen.
Physicians
should
entertain
a
high
degree
of
suspicion
whenever
a
traveller
returming
from
a
malarious
area
presents
with
a
fever,
keeping
in
mind
chemoprophylaxis
is
not
always
effective.
l
References
1.
World
Health
Organization.
Vaccination
Certificate
Requirements
&
Health
Advice
for
International
Travel
sit-
uation
as
on
1
January
1989.
Geneva:
Global
Epidemiological
Surveillance
&
Health
Situation
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World
Health
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1988.
2.
Drugs
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Parasitic
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Med
Lett
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Centers
For
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Atlanta,
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Cook
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A,
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Failure
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Treatment
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Rackow
JC,
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late
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HK,
Pavanand
K,
Thosingha
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II
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Bygbjerg
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A,
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Gomme
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resis-
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Hoffman
SL,
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CAN.
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Vol.
35:
APRIL
1989
