As there is no
vaccine against malaria, chemoprophylaxis can offer protection
Every year, more than 125 million people visit over 100 countries
endemic for malaria. Each year up to 30 000 travelers are estimated to contract malaria
and late or wrong malaria diagnosis in their home country may make things worse for them.
Fever occurring in a traveler within three months of leaving a malaria-endemic area is
considered a medical emergency and should be investigated urgently.
As there is no vaccine available for
protection against malaria despite decades of research, there is a need for an alternative
method that offers a fairly reliable protection against malaria. And as malaria can be
severe in the non-immune, all visitors from non-malarious area to a malarious area should
be protected. Anti malarial drugs offer protection against clinical attacks of malaria.
The risk of
contracting malaria depends on the region visited, the length of
stay, time of visit, type of activity, protection against mosquito
bites, compliance with chemoprophylaxis etc. Pregnant women, infants
and young children and people who have undergone splenectomy should
avoid travel to a malarious area as these people are at higher risk
of severe malaria. If travel is unavoidable, these people should
take strict precautions to avoid mosquito bites and also take
adequate chemoprophylaxis without fail.
Chemoprophylaxis:
Use of anti-malarial
drugs to prevent the development of malaria is known as
chemoprophylaxis.
The choice of chemoprophylaxis varies
depending on the species and drug resistance prevalent in a country.
It must be remembered
that no chemoprophylaxis regime provides 100% protection. Therefore it
is essential to prevent mosquito bites as well as to comply with
chemoprophylaxis. A possibility of malaria should be considered if
a febrile illness develops after a week of entering a malarious
area as well as up to over a year after visiting such an area, although it is
more likely within the first 3 months of return.
Other
residents of a malarious area are not advised chemoprophylaxis. It should not be
prescribed as a remedy to prevent re-infections in an endemic area.
Primary Prophylaxis: Use of antimalaria drugs at recommended dosage,
started 2-20 days before departure to a malarious area and continued
for the duration of stay and for 1-4 weeks
after return.
-
Causal prophylaxis:
This prevents the establishment of infection in the liver by
inhibiting the pre-erythrocytic schizogony. Primaquine and proguanil
are effective as causal prophylactic drugs. Potential adverse
effects on long term use and non-availability of primaquine make it
a difficult drug for this purpose. In one study in the Papua- New
Guinea, it was found to be effective as a prophylactic agent. It is
however not yet recommended for general use. Daily doses of proguanil provide
causal prophylaxis in areas where resistance to this drug is not
present.
-
Suppressive prophylaxis: Use of blood schizonticides suppresses
the blood forms of the malaria parasite and thus protects against
clinical illness. However, P. vivax and P. ovale may
cause relapses from the hypnozoites and to prevent this, terminal
prophylaxis may be needed. [See below]
Terminal Prophylaxis: Terminal prophylaxis is the
administration of primaquine for two weeks after returning from
travel to tackle the hypnozoites of P. vivax and P. ovale
that can cause relapses of malaria. It is
indicated only for persons who have had prolonged exposure in
malaria-endemic regions, such as expatriates and long-term travelers
like missionaries and Peace Corps volunteers. Primaquine is administered after the traveler leaves an
endemic area and usually in conjunction with chloroquine during the last
2 weeks of the 4-week period of prophylaxis after exposure in an
endemic area has ended.
|
Drugs
and dosage for chemoprophylaxis
|
Drugs |
Dosage |
Pros and Cons |
Adverse Effects |
Adults |
Children |
|
Atovaquone plus Proguanil
(Malarone®) |
Adult tablet of 250 mg atovaquone and 100 mg proguanil - 1 tab. daily |
Pediatric tablet of 62.5 mg atovaquone and 25 mg proguanil:
5-8 kg: 1/2 tablet daily
>8-10 kg: 3/4 tablet daily
>10-20 kg: 1 tablet daily
>20-30 kg: 2 tablets daily
>30-40 kg: 3 tablets daily
>40 kg: 1 adult tablet daily |
Daily dosing; only
have to continue for 7 days after exposure; not in
pregnancy and lactation |
Nausea, vomiting,
abdominal pain, diarrhea,
increased liver enzyme levels;
rarely seizures, rash, mouth
ulcers |
|
Chloroquine
(Tablet with 150mg
base) |
300 mg base once weekly |
5mg/kg base weekly;
maximum 300 mg |
Long-term safety
known; chloroquine resistance reported from most parts of the world;
not for persons with epilepsy, psoriasis |
Pruritis, nausea,
headache, skin eruptions, nail and mucous membrane
discoloration,
partial hair loss, photophobia,
nerve deafness,
myopathy, blood dyscrasias, psychosis and
seizures |
|
|
| Proguanil |
200 mg daily |
< 2 yrs: 50 mg/day;
2-6 yrs:100 mg/d
7-9 yrs: 150 mg/day;
>9 yrs: 200 mg/d |
Used in combination |
|
|
|
Doxycycline (100mg) |
100mg once daily |
1.5mg base/kg once daily
(max. 100 mg)
<25kg or <8 yr: Not given
25-35kg or 8-10 yr: 50mg
36-50kg or 11-13 yr: 75mg
>50kg or >14 yr: 100mg |
Daily dosing required; not in pregnancy and
lactation |
Abdominal
discomfort, vaginal candidiasis,
photosensitivity, worsening of renal function tests in renal
diseases, allergic reactions, blood dyscrasias, esophageal
ulceration |
|
|
Mefloquine
(Tablet with 250mg base, 274mg salt) |
250 mg base once weekly |
<15 kgs: 5mg of salt/kg;
15-19 kg: ¼ tab/wk;
20-30 kg: ½ tab/wk;
31-45 kg: ¾ tab/wk;
>45 kg: 1 tab/wk |
Weekly dosing; occasional reports of
severe intolerance; not in first trimester of pregnancy, breast feeding, high
altitudes or deep sea diving, patients with epilepsy, psychosis, heart
blocks, receiving β blockers |
Dizziness, headache, sleep disorders,
nightmares, nausea, vomiting, diarrhea, seizures,
abnormal coordination, confusion, hallucinations, forgetfulness,
emotional
problems including anxiety, aggression, agitation, depression,
mood changes, panic attacks, psychotic or paranoid
reactions, restlessness, ?suicidal ideation and suicide |
Chemoprophylaxis Regimen: Preferably, it should be started 1-2
weeks prior to travel to a malarious area. In addition to assuring adequate blood levels
of the drug, this regimen allows for evaluation of any potential side effects.
Chemoprophylaxis should continue during the stay in malarious area and for
1-4 weeks after
departure from the area.
The following factors should be
considered while choosing an appropriate chemoprophylactic regimen:
-
The travel itinerary should be reviewed in
detail and compared with the information on areas of risk within a given country to
determine whether the traveler will actually be at risk of acquiring malaria.
-
The risk of acquiring chloroquine
resistant P. falciparum malaria (CRPF) is another consideration.
-
Any previous allergic or other reaction to
the antimalarial drug of choice and the accessibility of medical care during travel must
also be determined.
Areas with chloroquine sensitive P. falciparum |
| Chloroquine |
Start one week before exposure, continue
during exposure and for 4 weeks thereafter |
|
Areas with chloroquine resistant P. falciparum
(low degree, not wide spread) |
| Chloroquine Plus |
Start one week before,
continue during exposure and for 4 weeks thereafter |
| Proguanil
|
Start 1-2 days before,
continue during exposure and for 4 weeks thereafter |
|
Areas with chloroquine resistant P. falciparum
(High degree, widespread) |
| Chloroquine Plus Proguanil
|
As
above |
|
| OR Mefloquine |
Start 2-3 weeks before, continue during
exposure and for 4 weeks thereafter |
|
| OR Doxycycline |
Start 2 days before, continue during
exposure and for 4 weeks thereafter |
|
|
OR Atovaquone Plus
Proguanil |
Start 2 days before, continue during
exposure and for 7 days thereafter |
See
Country-wise Chemoprophylaxis Recommendations
Asia/Middle East |
Europe/CIS |
Africa |
Australia/Oceania |
North/Central America |
South America
Recommendations
for travelers to malaria endemic areas:
All travelers to malaria-endemic areas
are at risk of contracting malaria and being non-immune, P. falciparum infection in these
individuals can become severe. Therefore, all travelers to malaria endemic areas are
advised to use an appropriate chemoprophylaxis and personal protection measures to prevent
malaria. However, it should be remembered that, regardless of methods employed, malaria
can still be contracted. Symptoms can develop as early as 8 days after initial exposure in
a malarious area and as late as several months after departure from a malarious area.
Malaria is easily treatable early in the course of the disease but delay in treatment can
lead to serious or even fatal consequences. Therefore, individuals who develop symptoms of
malaria should seek prompt medical help, including blood smear (or QBC test) for malaria. Chemoprophylaxis is
NOT recommended for residents of endemic area
Personal
Protection Measures:
Anopheles mosquitoes bite at nights, with
peak biting between 10pm and 4am and malaria transmission occurs at these hours.
Travelers must take personal protective measures against mosquito bites at nights.
Remaining in well-screened areas, using mosquito nets, and wearing clothes that cover most
of the body are some simple but effective measures. In addition, mosquito repellents like N,N diethylmetatoluamide (DEET) can be used. It is better to have a pyrethrum-containing
space spray to use in living and sleeping areas during evening and night hours.
See
malaria control
Prophylaxis
During Pregnancy:
Malaria infection in pregnant women may
be more severe than in non-pregnant women. In addition, the risk of adverse pregnancy
outcomes, including prematurity, abortion, and stillbirth, may be increased. For these
reasons, and because chloroquine has not been found to have any harmful effects on the
fetus when used in the recommended doses for malaria prophylaxis, pregnancy is not a
contraindication to malaria prophylaxis with chloroquine or hydroxychloroquine. However,
because no chemoprophylactic regimen is completely effective in areas with CRPF, women
who are pregnant or likely to become so should avoid travel to such areas.
Chloroquine and Proguanil are the
preferred chemoprophylactic drugs against malaria in the first 3 months of pregnancy.
Mefloquine can be given during the second and third trimesters if the situation demands.
Mefloquine and doxycycline can be used in
non-pregnant women with child bearing potential, but pregnancy should be avoided for 3
months after mefloquine use and for one week after doxycycline use. However, in case of
unplanned pregnancy, malaria chemoprophylaxis is not considered an indication for
termination of pregnancy.
Doxycycline, a tetracycline, is generally
contraindicated for malaria prophylaxis during pregnancy. Adverse effects of tetracyclines
on the fetus include discoloration and severe dysplasia of the teeth and inhibition of
bone growth. In pregnancy, therefore, tetracyclines would be indicated only if required to
treat life-threatening infections due to multi-drug resistant P. falciparum.
Primaquine should not be used during
pregnancy because the drug may be passed transplacentally to a G6PD-deficient fetus and
cause life-threatening hemolytic anemia in utero. Whenever radical cure or terminal
prophylaxis with primaquine is indicated, chloroquine should be given once a week until
delivery, at which time the decision to give primaquine may be made.
Prophylaxis while breast feeding:
Very small amounts of antimalarial drugs
are secreted in the breast milk of lactating women. The amount of drug transferred is not
thought to be harmful to the nursing infant; however, more information is needed. Because
the quantity of antimalarials transferred in breast milk is insufficient to provide
adequate protection against malaria, infants who require chemoprophylaxis should receive
the recommended dosages of antimalarials.
Chemoprophylaxis
for Children:
Children of any age can contract malaria.
WHO advises against taking babies and young children to malarious areas, in particular
where there is transmission of chloroquine-resistant P. falciparum. Malaria can rapidly
cause complications in children and therefore any child suffering from fever after
returning from a malarious area should be considered to have malaria until proved
otherwise. Since it may be difficult to administer drugs to children and since paediatric
formulations and accurate dosage may not be available, it is best to protect babies and
children against mosquito bites.
The indications for prophylaxis are
identical to those described for adults. Doxycycline is contraindicated
for children less than 8 years of age.
Chloroquine phosphate, which is
manufactured in the United States in tablet form only, tastes quite bitter. Pediatric
doses should be calculated carefully according to body weight. Pharmacists can pulverize
tablets and prepare gelatin capsules with calculated pediatric doses. Mixing the powder in
food or drink may facilitate the weekly administration of chloroquine to children.
Alternatively, chloroquine in suspension is widely available overseas.
OVERDOSE OF ANTIMALARIAL DRUGS CAN BE
FATAL. THE MEDICATION SHOULD BE STORED IN CHILDPROOF CONTAINERS OUT OF THE REACH OF
CHILDREN.
Chemoprophylaxis
for Long Term Travelers:
Long-term travelers intending to stay for
more than 1-3 months should seek the advice of local health care professionals familiar
with the management of malaria in non-immune foreigners. The risk of serious side effects
associated with long term use of chloroquine and proguanil are low. However, twice yearly
screening for the detection of early retinal changes should be performed in anyone who has
taken 300 mg of chloroquine (as base) weekly for over five years and requires further
prophylaxis. If changes are observed, an alternative regimen should be considered. Data
indicate no increased risk of serious side effects with long term use of mefloquine. The
risk of long term use of doxycycline are not known. These two latter drugs should be
reserved for those with greatest risk of infection.
Chemoprophylaxis for Frequent
Travelers:
Frequent travelers such as members of the
aircraft crew may reserve chemoprophylaxis for high risk areas only. They should maintain
rigorous self-protection against mosquito bites and be prepared for an attack of malaria
and should carry a course of antimalarials as stand-by.
Multi-drug
resistant malaria: In areas of Thailand near the borders with Cambodia and Myanmar
and in Western Cambodia, P. falciparum infections do not respond to chloroquine or
pyrimethamine-sulfadoxine, and sensitivity to quinine is reduced. Treatment failures of
over 50% are also being reported.
In these areas, chemoprophylaxis with
doxycycline is recommended along with rigorous personal protection measures. Doxycycline
is contraindicated in pregnant women and children below the age of 8 years, and therefore
they should avoid traveling to these areas.
Atovaquone plus Proguanil - Malarone: See http://www.cdc.gov/travel/diseases/malaria/malarone.htm
Chemoprophylaxis
for travelers to India:
 |
Most parts of India
have a high transmission of P. vivax malaria and Chloroquine resistant P.
falciparum is reported from the North-Eastern states of India. The high altitude
states of Jammu and Kashmir, Himachal Pradesh and Sikkim are free from malaria. Malaria
transmission is low or very low in areas at an altitude >2000 metres. For visitors to
North Eastern India, Mefloquine is recommended as the first choice and Chloroquine +
Proguanil as the second choice. For visitors to other areas, Chloroquine + Proguanil is
advised. Atovaquone+Proguanil can also be used. No prophylaxis is needed for visitors to areas with low transmission.
For details click on your destination over the
map at left
Also see: Malaria
in India and Malaria in Mangalore |
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Also See
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