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Malaria
is the most important parasitic disease that you will face in most
tropical and subtropical countries. A delay in diagnosis and treatment
can have fatal consequences. If you plan to travel to a malarious
region, there are five things you must do:
-
Estimate your risk of being exposed to malaria. You can find
out from the Destinations section of this website if there is
risk of malaria in the countries you will be visiting, what
regions are most infected, and what type of malaria is most
common.
-
Take measures to prevent insect bites. Use an insect repellent
(such as Ultrathon
or FITE
BITE 30) on your skin in conjunction with permethrin-treated
clothing. A permethrin-treated mosquito
net is often very useful. If you prevent mosquito bites,
your risk of malaria is virtually eliminated.
- Take
a prophylactic drug. These are listed below. Drug prophylaxis
is especially important in countries where there is the risk
of falciparum malaria. Don't skip prescribed doses.
-
Know the symptoms of malaria. A detailed description of the
disease can be found in the International
Travel HealthGuide, which you can download from this website.
-
Seek immediate medical treatment if symptoms of malaria occur.
Always consider malaria if you develop a fever after being in
a malarious area.
Virtually
all cases of malaria can be prevented. Unfortunately, a high proportion
of travelers who have acquired malaria most likely did not receive
appropriate information on, or did not comply with, malaria prevention
measures.
Chemoprophylaxis
Before departing for a malarious area, you and your doctor (or
travel clinic specialist)
should review your itinerary and decide if prophylaxis is indicated
and which drug you should take. In general, drug prophylaxis is
indicated if your risk of exposure will be moderate to high.
Factors
determining your need for, and choice of, prophylaxis include
(1) your itinerary; (2) the intensity and duration of your exposure
to mosquito bites, especially those transmitting P. falciparum
species of malaria parasites; (3) your own knowledge of malaria
and its symptoms; (4) your ability to obtain rapid, qualified
medical care should symptoms occur; (5) your medical history and
personal health status; (6) your history of known drug allergies
or known ability (or inability) to tolerate certain prophylactic
drugs; (7) your use of other medications that may be incompatible
with prophylactic drugs; (8) your age; and (9) your pregnancy
status, if applicable.
The
complexity of the situation is one reason why seeing a travel
medicine specialist is advisable when exposure to malaria
is likely.
Drugs
Used to Prevent Malaria
Atovaquone/Proguanil
(Malarone)
A combination of atovaquone (250 mg) and proguanil (100 mg) is
the newest drug for the prevention and treatment of malaria. In
multiple trials, atovaquone/proguanil (Malarone) has been shown
to be 95-100% effective against chloroquine-resistant and multidrug-resistant
strains of P. falciparum parasites, including those along
the borders of Thailand. Atovaquone/proguanil (Malarone) is active
against liver-stage parasites and requires only a short period
of pre-exposure and postexposure dosing.
Adult
dosageOne tablet, started 1-2 days before travel, taken
daily during exposure, and for 7 days after leaving the malarious
region.
Child
dosagePediatric-strength tablet (25 mg proguanil with 62.5
mg atovaquone) is available. The dosage is based on weight: 10
kg-20 kg, 1 pediatric-strength tablet; 21-30 kg, 2 pediatric-strength
tablets; 31-40 kg, 3 pediatric-strength tablets; and more than
40 kg, 1 adult-strength tablet.
Side
effectsSo far, atovaquone/proguanil (Malarone) has an enviable
safety record, with no reports of serious adverse side effects.
Patients with renal insufficiency, however, should not take atovaquone/proguanil
but should instead choose either mefloquine or doxycycline. Most
complaints include stomach upset, cough, and skin rash. Tablets
should be taken with food or a milky drink at the same time each
day. If vomiting occurs within 1 hour after dosing, a repeat dose
should be taken.
Atovaquone/proguanil
(Malarone) has not been adequately tested in pregnancy, and, therefore,
its use cannot be recommended; however, neither component drug
has shown teratogenic effects in animal models. The manufacturer
suggests that the drug may be used cautiously if the potential
benefit outweighs the potential risk to the fetus.
Chloroquine
For sensitive P. falciparum and P. vivax, chloroquine
remains the drug of choice to prevent malaria. The standard doses
are generally well tolerated and safe for pregnant women and children.
Because of widespread resistance, however, the use of chloroquine
against P. falciparum is limited to persons traveling in
Central America, the Caribbean, and parts of the Middle East.
While chloroquine remains effective against most strains of P.
vivax, P. ovale, and P. malariae, resistance
to P. vivax is increasing, particularly in the South Pacific,
Southeast Asia, and parts of South America (Guyana).
Adult
dosage500 mg salt (300 mg base) once weekly, beginning 1
week before and continuing 4 weeks after leaving the malarious
area.
Child
dosage8.3 mg/kg salt (5 mg/kg base) once weekly, up to a
maximum adult dose of 500 mg salt/week.
Side
effectsChloroquine is generally well tolerated and is safe
for children and pregnant women. Taking chloroquine with meals
can usually control gastrointestinal side effects, such as nausea.
Dizziness, headache, blurred vision, and itching may also occur,
but these symptoms will rarely require you to stop taking the
drug.
Doxycycline
Doxycycline is a tetracycline derivative that has the advantage
of being more than 90% effective against chloroquine-resistant
falciparum malaria, including the falciparum malaria found along
the borders of Thailand.
Adult
dosage100 mg daily. Doxycycline should be started 1 to 2
days prior to exposure. It must be continued daily in malarious
areas and for 4 weeks after departure from the malarious area.
Child
dosage (for children older than 8 years of age)2 mg per
kg of body weight per day up to the adult dose of 100 mg daily.
Side
effectsMost travelers tolerate doxycycline well, but nausea,
vomiting, and heartburn can occur. Doxycycline should be swallowed
in the upright position with sufficient liquid or food to ensure
complete passage of the tablet into the stomach. Doxycycline can
cause phototoxicity, which is an exaggerated sunburn reaction
to strong sunlight. The risk can be reduced by avoiding prolonged,
direct exposure to the sun, wearing a hat, and using a broad-spectrum
sunscreen. Women may develop a vaginal yeast infection and should
carry a self-treatment dose of an antifungal agent such as fluconazole
(Diflucan).
Doxycycline
is contraindicated for pregnant women and children under the age
of 8.
Mefloquine
Mefloquine (Lariam) is recommended for both short- and long-term
travel to countries where there is chloroquine-resistant P.
falciparum. The drug is also highly effective against P.
vivax, P. ovale, and P. malariae. In western
Cambodia and along the border areas of Thailand, however, the
incidence of mefloquine-resistant P. falciparum is as high
as 50%, and prophylaxis with Malarone (atovaquone/proguanil) or
doxycycline is recommended.
Adult
dosage250 mg (1 tablet) once weekly during travel in malarious
areas and for 4 weeks after leaving such areas. Mefloquine should
be started at least 1 week prior to departure.
Child
dosageChildren: 5-14 kg, 1/8 tablet weekly; 15-19 kg, 1/4
tablet weekly; 20-30 kg, 1/2 tablet weekly; 31-45 kg, 3/4 tablet
weekly; and >45 kg, 1 tablet weekly. Less than 5 kg, a proportionately
lower dose should be given.
Side effectsMefloquine (Lariam) in prophylactic doses is
generally well tolerated, but about 25% of users report mild-to-moderate
side effectsstrange dreams, insomnia, nausea, dizziness,
and weakness. Neuropsychological side effects (anxiety, depression,
agitation, nightmares) that are severe enough to require discontinuation
of the drug occur in about 3% of users; severe neuropsychiatric
side effects (psychosis, seizures) are extremely rare. Splitting
the weekly dose and taking one-half tablet twice weekly may reduce
side effects. Taking the drug with food lessens upset stomach.
Mefloquine
is now considered safe for prophylaxis during pregnancy (and,
by extension, also safe for infants). The drug is contraindicated
for patients with a history of epilepsy or seizures, serious psychiatric
illness, or cardiac conduction disturbances associated with an
arrhythmia.
Factors
That Influence Antimalarial Prophylactic Drug Choice
| Factors |
Atovaquone/Proguanil
|
Chloroquine |
Doxycycline |
Mefloquine |
| Dosing/administration |
Once
daily |
Once
weekly |
Once
daily |
Once
weekly |
| Pre-exposure
dosing |
1-2
days |
7-14
days |
1-2
days |
7-14
days |
| Postexposure
dosing |
1
week |
4
weeks |
4
weeks |
4
weeks |
| Drug
discontinuation due to
adverse events |
<1% |
N/A |
N/A |
2-5% |
|
Cost for 2 weeks of travel* |
$86.24 |
$40.32 |
$4.40 |
$65.76 |
N/A
(not available)
*Cost based on average wholesale price as of August 2001
Cost of generic doxycycline
Note: Table lists drugs in alphabetical order.
Major
Contraindications for Antimalarial Prophylactic Drugs
| Contraindication
|
Atovaquone/Proguanil
|
Chloroquine |
Doxycycline |
Mefloquine |
| Seizure
disorder |
No |
No |
No |
Yes |
| Cardiac
conduction disturbance |
No |
No |
No |
Yes |
| History
of depression, mental illness |
No |
No |
No |
Yes |
| Drug
phototoxicity potential |
No |
No |
Yes |
No |
| Yeast
infections |
No |
No |
+/- |
No |
| Pregnancy |
Insufficient
data |
No |
Yes |
No |
| Pediatrics |
No |
No |
Yes |
No |
| Hepatic
insufficiency |
No |
Yes |
Yes |
No |
Renal insufficiency |
Yes |
No |
No |
No |
An
Alternative Drug for Malaria Prevention
Primaquine has long been used for the treatment of relapsing malaria,
but in the last decade it has been reexamined for malaria prevention.
When adults take a daily dose of 30 mg (or 0.5 mg/kg per day for
children), an effectiveness of 85-95% against P. falciparum
(as well as P. vivax and P. ovale) has been demonstrated.
Like atovaquone/proguanil, prophylactic primaquine should be started
1 day before exposure, taken daily during exposure, and for 7
days postexposure.
Because primaquine is capable of causing severe hemolytic anemia,
a G-6-PD enzyme-screening test is required before using this drug.
Primaquine is contraindicated in pregnant women.
NOTE:
At this time, primaquine is not routinely recommended, but some
physicians prescribe it for the traveler who cannot tolerate mefloquine
or doxycycline.
Recommendations
for Prophylaxis of Malaria
The best choice of prophylactic drug depends on many factors,
such as destination (Is there drug-resistant P. falciparum?),
duration of travel, dosing schedule (Will there be a problem with
compliance?), possible side effects, cost, and other factors.
-
Atovaquone/proguanil (Malarone): This is considered the drug
of choice for travelers taking relatively brief trips to chloroquine-resistant
areas because of its favorable safety profile and its short
period of pre-exposure and postexposure dosing. The dosing schedule
is ideal for frequent travelers, for travelers who depart on
short notice, and for those who live in the tropics and have
repeated short exposures outside urban areas.
- Chloroquine
(Aralen): The best choice for areas with chloroquine-sensitive
malaria. This includes Mexico and Central America, the Caribbean,
and parts of the Middle East.
- Doxycycline
(Doryx, Vibramycin): This drug is an option for travel to chloroquine-resistant
areas. Doxycycline is dosed daily and gives >90% protection
against P. falciparum, even in areas with multidrug-resistant
strains. It is an effective alternative for travelers who are
unable to tolerate atovaquone/proguanil or mefloquine or for
travelers who are concerned about the cost of prophylaxis.
- Mefloquine
(Lariam): Mefloquine, if tolerated, may be preferable for long-term
travel (>2-3 weeks) because of its lower cost (compared to
atovaquone/proguanil) and weekly, rather than daily, dosing
schedule.
- Primaquine:
Although it is not FDA-approved for prophylaxis, its off-label
use may be appropriate for some short-term travelers or those
who are intolerant of the other drugs.
Malaria
Prophylaxis According to Geographic Area1
| Chloroquine-Sensitive
Areas |
First-Line
Drug |
Alternative
Drugs |
Central
America
Caribbean
Middle East
North Africa |
Chloroquine |
Mefloquine,
doxycycline,
or
atovaquone/proguanil
|
| Chloroquine-Resistant
Areas |
First-Line
Drug |
Alternative
Drugs |
| South
America |
Atovaquone/proguanil,
mefloquine, or
doxycycline |
Primaquine3 |
| Africa2
(sub-Saharan) |
Atovaquone/proguanil,
mefloquine, or
doxycycline |
Primaquine3 |
| Indian
Subcontinent |
Atovaquone/proguanil,
mefloquine, or
doxycycline |
Primaquine3 |
Southeast
Asia
Oceania (Papua New Guinea,
Vanuatu, Solomon Islands) |
Atovaquone/proguanil,
mefloquine, or
doxycycline |
Primaquine3 |
| Thailand4
(border areas only) |
Atovaquone/proguanil
or
doxycycline |
Primaquine3
|
1In
Central America, South America, and Southeast Asia, travelers
are generally at risk only in rural areas during evening and
nighttime hours. In sub-Saharan Africa and Oceania, malaria
is often transmitted in both urban and rural areas.
2Atovaquone/proguanil can be carried for use as emergency treatment
in remote areas if malaria is suspected in travelers not using
this drug for prophylaxis and not having access to medical care
in 24-48 hours.
3Off-label use. Requires G-6-PD enzyme-screening test.
4A combination of proguanil and a sulfonamide is an alternative
for travelers in Thailand unable to take doxycycline or atovaquone/proguanil.
Dosage: proguanil, 200 mg daily, plus either sulfisoxazole,
75 mg/kg daily, or sulfamethoxazole, 1500 mg daily. Mefloquine
resistance is common along the Thai/Myanmar and Thai/Cambodian
borders.
Standby
Treatment
Is chemoprophylaxis always necessary? The answer is almost always
yes in areas with falciparum malaria, but less compelling where
the main risk is vivax malaria. A few European countries are considering
a change in their efforts to prevent malaria. Realizing that malaria
is extremely rare in travelers to some areas, they are now moving
toward "standby therapy" instead of continuous chemoprophylaxis
for travelers to most parts of Central and South America as well
as parts of Asia. Travelers qualifying for "standby therapy"
should:
-
be well-informed and educated;
- consult
with a travel medicine expert and be provided with doses of
the standby drug to carry with them (i.e., not given a prescription
for the medication); and
- be
advised to seek prompt medical diagnosis and treatment in case
of illness.
Travelers
who are supplied with standby treatment must have precise instructions
regarding how to recognize malarial symptoms, how to take the
medication, and warnings about adverse effects from the medication.
However, while such advice appears to be straightforward and logical,
there are potential problems, including the following:
-
Noncompliance with the advice to consult a medical professional
within 24 hours of taking the standby medication, especially
if the traveler feels better.
- Overdiagnosis
of malaria by physicians in endemic countries.
- The
inadvertent use of the malaria standby medication for other
illnesses, such as travelers' diarrhea.
- Adverse
side effects from some of the drugs presently available for
standby treatment (e.g., quinine, mefloquine). One agent, halofantrine,
is no longer used; it has been associated with several fatalities.
Click
here for more information
on Malaria.
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