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Malaria prevention in the expatriate and long-term traveller |
Summary
The prevention of malaria in expatriates and long-term travellers is complex. The traveller's doctor needs to consider the destination, the nature of the travel, the effectiveness and potential adverse effects of antimalarial medication, and the general health of the traveller. A preventative regimen can be devised combining several strategies including mosquito avoidance measures, chemoprophylaxis, emergency standby treatment and rapid self-diagnosis of malaria.
Key words: chemoprophylaxis, chloroquine, doxycycline, mefloquine.
(Aust Prescr 2002;25:66-9)
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Introduction
In 1999, 3.2 million Australians travelled abroad, and travel to countries where malaria is endemic is becoming increasingly common. Each year an estimated 30 000 cases of malaria occur in non-immune travellers worldwide.1 Many people, including aid workers, missionaries, students and healthcare workers, are travelling to work and live in rural and remote malarial regions. The estimated mortality rate for falciparum malaria in non-immune adults is up to 5%, so the medical practitioner entrusted with providing safe and suitable travel health advice will need to carefully consider the need for antimalarial prophylaxis. When the traveller's stay in an endemic area exceeds six months the issues can become quite complex.
Issues to consider
There is no perfect choice of antimalarial regimen for long-term travellers and expatriates. Prevention involves careful consideration of a number of factors, which include:
- the prevalent endemic malarial species - prophylaxis needs to be seriously considered for travel to areas with significant levels of Plasmodium falciparum because of its associated mortality
- the susceptibility of malarial parasites to commonly used drugs - endemic chloroquine-resistant P. falciparum reduces the effectiveness of chloroquine-based regimens
- the intensity of malaria transmission - the higher the intensity, the greater the need for antimalarial prophylaxis
- the risk of exposure - includes issues such as urban or rural residence, the type of accommodation and the proximity of mosquito breeding grounds
- the duration of stay - the longer one stays the greater the cumulative risk of contracting malaria, but also the greater the problems of compliance and adverse effects
- the seasonal pattern - if transmission is seasonal, prophylaxis may only be required during the malarial season
- the availability of reliable diagnostic tests and medical care for malaria - if these are lacking malaria poses a greater health risk and so there is a greater need for prophylaxis
- the potential adverse effects of the prophylactic medications - may affect their suitability for the individual traveller
- compliance issues - these need to be considered as the traveller may be better served by a less effective regimen that can be adhered to, than a more effective regimen that cannot
- the traveller's characteristics - factors such as age, pregnancy, comorbidities and drug allergies all have a significant bearing on the choice of prophylaxis
- the traveller's preference - this needs to be strongly considered as it has a vital bearing on the ultimate success of any prophylactic regimen.
These issues need to be discussed openly with the traveller. A mutually acceptable plan for malaria prevention can then be developed.
Malarial protective measures
Protection against malaria in the long-term traveller can include some or all of the following:
- mosquito avoidance measures
- chemoprophylaxis
- emergency standby treatment
- self-diagnosis kits.
Mosquito avoidance measures
These measures are the mainstay of any long-term antimalarial prophylaxis regimen. They are important in reducing the risk of contracting malaria in any traveller, but because of the many difficulties and limitations of chemoprophylaxis they are vital in long-term travellers. Adequate time must be spent with the patient to educate them about measures to reduce:
- exposure to the female Anopheles mosquito (minimise outdoors activities during its feeding time from dusk to dawn, and protect living quarters from mosquitoes)
- attracting the mosquito (avoid dark clothing, aftershaves, perfumes)
- bites (covering exposed skin areas with clothes or diethyltoluamide (DEET)-containing repellents, use of mosquito nets, permethrin impregnated clothes and nets, and using insecticides or repellents inside dwellings).
Chemoprophylaxis
The currently available medications we feel should be considered
are summarised in Table 1.
| Table 1 | |||||||||
| Characteristics of recommended antimalarial prophylactic medications | |||||||||
|
|
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| Medication | Resistance* | Dose | Frequency | Pregnancy | Children | Time prior to entering a malarial endemic area | Time after leaving a malarial endemic area | ||
|
|
|||||||||
| Chloroquine | Yes | 300mg | weekly | Yes | Yes | 1 week | 4 weeks | ||
| Doxycycline | No | 100mg | daily | No | 8 years or older | 2 days | 4 weeks | ||
| Mefloquine | Yes† | 250mg | weekly | No‡ | > 5kg | 2 weeks | 4 weeks | ||
| Proguanil | Yes | 200mg | daily | Yes | Yes | 1 day | 4 weeks | ||
| Atovaquone / proguanil | No | 250mg / 100mg | daily | No | > 11 kg | 1 day | 1 week | ||
|
|
|||||||||
| *
for falciparum malaria † resistance reported in Northern Thailand, Cambodia and Myanmar ‡may be used in 2nd and 3rd trimesters |
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Doxycycline
Doxycycline is very effective prophylaxis for chloroquine-resistant P. falciparum.
There are no known serious adverse events from its long-term use, however daily
dosing is a disadvantage and may lead to poor compliance. Vaginal thrush and
photosensitivity may be troublesome adverse effects. It should be swallowed
with food or an adequate quantity of water to avoid oesophagitis. An advantage
of doxycycline is that it may provide some protection against infectious diarrhoea,
tick-borne infections, scrub typhus, leptospirosis and some sexually transmitted
diseases such as chlamydia. It is contraindicated in pregnant or breastfeeding
women and children under eight years of age.
Mefloquine
Mefloquine has been extensively used and is very effective prophylaxis for people
living in areas where chloroquine-resistant P. falciparum is endemic.
Weekly administration helps compliance, and there has been no increase in adverse
events with long-term use.2
In prophylactic doses it is generally well tolerated with studies showing no
significant differences in adverse events compared to other antimalarial regimens
apart from atovaquone/proguanil.2
Although severe neuropsychiatric adverse events are rare (estimated 1:10 000
users), it is not recommended for those who have underlying neuropsychological
problems (e.g. epilepsy, depression). Some people experience mild neuropsychological
effects such as headache, dizziness, mood changes, insomnia and vivid nightmares.
As most adverse effects will occur within the first month of use, a trial of
mefloquine for 3-4 weeks before departure to test its tolerability in long-term
travellers is often worthwhile. We do not recommend mefloquine in the first
trimester of pregnancy unless there is a significant risk of chloroquine-resistant
P. falciparum malaria, although there is mounting evidence to support
its safety. It is also not recommended for children less than 5 kg in weight.
Atovaquone/proguanil hydrochloride
This combination is highly effective prophylaxis for chloroquine-resistant falciparum
malaria. Although gastrointestinal symptoms can occur it is well tolerated,
and comparative studies show it to be better tolerated than mefloquine, doxycycline
and chloroquine/proguanil for prophylaxis.1
The use of the combination by long-term travellers is limited by its expense,
a lack of long-term safety data and concerns about the development of resistance.
We therefore currently do not routinely recommend its use for prophylaxis.
Chloroquine
Chloroquine has the advantage of improved compliance because it is taken weekly.
It can be used by pregnant women and young children and is generally well tolerated.
The main adverse effects are gastrointestinal upsets and a bitter taste. Long-term
use is safe, however regular retinal screening is recommended after five years
of continuous use as there is a potential risk of cumulative retinal toxicity.
Chloroquine reduces the effectiveness of intradermal rabies vaccine necessitating
vaccination by the intramuscular route.
The use of chloroquine is limited by the resistance of P. falciparum parasites.
It may still have a role, taken alone or combined with proguanil, in areas with
low resistance rates or low transmission risk (e.g. India) or where medical
care is readily accessible. Chloroquine may also be used if the patient is intolerant
of or reluctant to take other regimens or will have problems with compliance.
Proguanil
The use of proguanil is limited by the widespread resistance of P. falciparum
parasites, and lack of compliance with its daily dosing. It is mainly used in
combination with chloroquine. Long-term use is safe, but there is a low incidence
of adverse effects (mouth ulcers). It can be used in pregnancy and childhood.
Emergency standby treatment (Table
2)
| Table 2 | |||||
| Malarial standby treatment regimens | |||||
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| Medication | Resistance | Adult dose | Reduce dose for children | ||
|
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| Atovaquone / proguanil | No | four tablets (250 mg/100 mg) daily for three days |
< 40 kg | ||
| Mefloquine | Yes* | 500 mg immediately, repeated eight hours later† |
< 50 kg | ||
| Sulphadoxine-pyrimethamine | Yes | three tablets (500 mg/25 mg) | < 13 years | ||
| Quinine | No | 600 mg three times daily for seven days‡ |
< 50 kg | ||
|
|
|||||
| *
Resistance has been reported in Thailand, Cambodia and Myanmar † If < 60 kg use 250 mg for second dose ‡ Combined with sulphadoxine-pyrimethamine (in sensitive areas, three tablets) or doxycycline (100 mg twice daily for seven days) |
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Long-term travellers may choose not to take chemoprophylaxis, but instead rely
on mosquito avoidance measures and the use of a reliable treatment if they become
infected. If symptoms suggestive of malaria develop, they either seek urgent
medical attention, if available within 24 hours, or take an emergency self-treatment
course effective for the local malarial resistance patterns, preferably after
using a self-diagnosis malarial kit. For standby treatment to be an option,
the traveller needs to be well educated about the various symptoms that suggest
malarial infection, and be precisely instructed on how to take the treatment.
Self-treatment should always be followed by a medical consultation as soon as
possible.
Atovaquone/proguanil hydrochloride
This regimen is highly effective for all forms of malaria, there is no reported
resistance and adverse effects are minimal. The combination can be used after
any of the chemoprophylactic drugs. Its major disadvantage is that it is significantly
more expensive than other regimens.
Mefloquine
This is an effective treatment in areas without reported resistance. A disadvantage
is the high risk of adverse reactions (28-59%) associated with a treatment course.3
There are rare reports of severe neurological disturbances such as depression,
psychosis and seizures.4
Emergency treatment with mefloquine is not recommended for people taking mefloquine
for prophylaxis as there is an increased risk of adverse events.
Sulphadoxine-pyrimethamine
This offers a simple, inexpensive and well-tolerated
regimen. However, it is no longer recommended in Africa, South America and South-East
Asia because of increasing resistance. Uncommon, but serious, complications
such as Stevens-Johnson syndrome and agranulocytosis, further limit its use.
Quinine
This is highly effective against chloroquine-resistant malaria. However, its
use is limited by a high incidence of adverse effects, and a complex, prolonged
regimen requiring combination with another drug.
Halofantrine
This is an effective treatment which is active against chloroquine-resistant
P. falciparum. It is available via the Special Access Scheme, however,
we do not recommend it because of its potential for fatal cardiac arryhthmias
(especially in those on mefloquine chemoprophylaxis) and the availability of
safer, effective alternative drugs.
Self-diagnosis kits
Relatively inexpensive kits (e.g. ICT, Parasight F, RAPIMAL) have been developed
which allow the rapid self-diagnosis of malaria. They are immunochromatographic
card tests that use a drop of blood to detect malarial antigens. These tests
have been shown in numerous laboratory studies to be very sensitive and specific
for falciparum malaria. As such they are well suited to long-term travellers
who may not be taking prophylaxis, or who are taking a less effective prophylactic
regimen, especially in those who are living without close access to medical
care. They are easy to carry, simple to use, and give a quick result. However,
studies have shown that many travellers have difficulty using them accurately
in the field. These kits should therefore only be prescribed after appropriate
instruction and training in their use.5
Summary
There is no ready solution to antimalarial prophylaxis for
the long-term traveller or expatriate. Their doctor needs to be familiar with
malarial epidemiology and drug resistance patterns in the area to be visited,
the pros and cons of the various prophylaxis and treatment options, and the
medical history and personality of the traveller involved. With this in mind,
and with the provision of sufficient time for discussion with, and education
of, the traveller, a suitable and safe regimen can usually be devised.
E-mail: obriendp@hotmail.com
References
- Kain KC, Shanks GD, Keystone JS. Malaria chemoprophylaxis in the age of drug resistance. I. Currently recommended drug regimens. Clin Infect Dis 2001;33:226-34.
- Lobel HO, Kozarsky PE. Update on prevention of malaria for travelers. JAMA 1997;278:1767-71.
- Yung AP, Ruff TA. Manual of travel medicine. Melbourne:Victorian Infectious Diseases Service, Royal Melbourne Hospital; 1999.
- Brown GV. Chemoprophylaxis of malaria. Med J Aust 1993;159:187-96.
- Jelinek T, Grobusch MP, Nothdurft HD.
Use of dipstick tests for the rapid diagnosis of malaria in nonimmune travelers.
J Trav Med 2000;7:175-9.
F U R T H E R R E A D I N G
See resources on the following web sites:
US Centers for Disease Control and Prevention www.cdc.gov/travel
World Health Organization www.who.int/ith/
Health Canada www.travelhealth.gc.ca
Department of Public Health and Travel Medicine, James Cook University www.jcu.edu.au/school/phtm/PHTM/putravel.htm
Conflict of interest: none declared
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