INTERNATIONAL TRAVEL AND HEALTH - CHAPTER 7

Malaria

7.1 Background

Malaria is a common and life-threatening disease in many tropical and subtropical areas. There
is currently a risk of malaria transmission in 91 countries and territories, and these are visited
by more than 125 million international travellers every year.

Each year many international travellers fall ill with malaria while visiting countries/territories
where malaria is endemic, and well over 10 000 are reported to become ill with malaria after
returning home. However, under-reporting means that the real figure may be considerably
higher. International travellers to countries/territories with ongoing local malaria transmission
arriving from countries with no transmission are at high risk of malaria infection and its
consequences because they lack immunity. Migrants from countries/territories with malaria
transmission living in malaria-free countries and returning to their home countries to visit
friends and relatives are similarly at risk because of waning or absent immunity.
Travellers who fall ill during travel may find it difficult to access reliable medical care.
Those who develop malaria upon returning to a country that is malaria-free face particular
problems: medical personnel may be unfamiliar with malaria, the diagnosis may be delayed,
and effective antimalarial medicines may not be registered and/or available, resulting in
progression to severe malaria with complications and, consequently, high case fatality rates.
Fever occurring in a traveller within 3 months of leaving a country in which there is risk
of malaria is a potential medical emergency and should be investigated urgently to
exclude malaria. In the rare situations in which there is no rapid access to reliable
diagnostic facilities, standby emergency treatment (SBET) is indicated (see section 7.3.2).

7.1.1 Cause
Malaria is caused by the protozoan parasite Plasmodium. Human malaria is caused by five
different species of Plasmodium: P. falciparum, P. malariae, P. ovale, P. vivax and P.knowlesi.
Of these, P. falciparum and P. vivax are the most prevalent, and P. falciparum is the most
dangerous, with the highest rates of complications and mortality. This deadly form of malaria is
a serious public health concern in most countries in sub-Saharan Africa. P. knowlesi, a species
that normally infects animals, can occasionally infect humans. As yet there are no reports of
human-mosquito-human transmission of such “zoonotic” forms of malaria.

7.1.2 Transmission
The malaria parasite is transmitted by female Anopheles mosquitoes, which bite mainly between
dusk and dawn.
7.1.3 Nature of the disease
Malaria is an acute febrile illness with an incubation period of 7 days or longer. Thus, malaria
should always be considered when a febrile illness develops one week or more after the first
possible exposure.
The most severe form is caused by P. falciparum; variable clinical features include fever,
chills, headache, muscular aching and weakness, vomiting, cough, diarrhoea and abdominal
pain. Other symptoms related to organ failure may supervene, such as acute renal failure,
pulmonary oedema, generalized convulsions and circulatory collapse, followed by coma and
death. The initial symptoms are nonspecific and cannot be distinguished from those of other
common febrile illnesses in the locality, such as acute respiratory infections, dengue fever and
septicaemia.
It is important that the possibility of falciparum malaria is considered in all cases of
unexplained fever starting at any time between 7 days after the first possible exposure to
malaria and 3 months (or, rarely, later) after the last possible exposure. Any person who
experiences a fever during this period should immediately seek diagnosis and effective
treatment, and should inform medical personnel of the possible exposure to malaria infection.
Falciparum malaria may be fatal if treatment is delayed beyond 24 hours after the onset of
clinical symptoms.
Young children, pregnant women, people who are immunosuppressed and elderly travellers
are particularly at risk of severe disease. Malaria, particularly P. falciparum, in non-immune
pregnant travellers increases the risk of maternal death, miscarriage, stillbirth and neonatal
death.
Human malaria caused by other Plasmodium species results in significant morbidity and can
occasionally cause life-threatening disease. Cases of severe P. vivax malaria have been
reported among populations living in (sub)tropical countries with malaria risk. P. vivax and P.
ovale can remain dormant in the liver; relapses caused by the persistent liver forms
(“hypnozoites”) may appear months and, rarely, several years after exposure. Primaquine is
the only drug that kills the hypnozoites, and thus prevent relapses. Current chemoprophylatic
regimens do not prevent relapses. Latent blood infection with P. malariae may be present for
many years, but it is very rarely life-threatening.
P. knowlesi malaria is primarily a public health problem among populations living or working
in forested areas in south-east Asia. In recent years, sporadic cases of travellers’ malaria due to
P. knowlesi have been reported. Humans can be infected with this “monkey malaria” parasite
while staying in – or on the fringes of – rainforests, within the range of the natural monkey
hosts and mosquito vector of this infection. These areas include parts of Brunei Darussalam,
Cambodia, China, Indonesia, Lao People’s Democratic Republic, Malaysia, Myanmar,
Philippines, Singapore, Thailand and Viet Nam. Symptoms may be atypical of malaria. Severe
P. knowlesi malaria with organ failure may occur, and sporadic fatal outcomes have been
described. P. knowlesi has no persistent liver forms and relapses do not occur. Travellers to
forested areas of south-east Asia where human P. knowlesi infections have been reported
should protect themselves against mosquito bites between dusk and dawn to prevent infection
and take chemoprophylaxis where indicated (see Country list).
 7.1.4 Geographical distribution
The current distribution of malaria in the world is available from the WHO’s World
malaria report. 1 The risk for travellers of contracting malaria varies greatly from country to
country and even between areas within a country, and this must be considered in any
discussion of appropriate preventive measures.
In most countries/territories with malaria risk, the centres of large urban areas – though not
necessarily the peri-urban areas – are free of malaria transmission. However, malaria can be
transmitted throughout urban areas of Africa and, to a lesser extent, India. There is usually less
risk at altitudes above 1500 m, although in favourable climatic conditions the disease can be
contracted at altitudes up to almost 3000 m. The risk of infection may also vary according to
the season, being highest at the end of, or soon after, the rainy season.
There is no risk of malaria in many tourist destinations in south-east Asia, the Caribbean and
Latin America, and information on malaria risk in each country/territory is given in the
Country list.
Since 2000, there has been a significant increase in the number of countries that have moved
towards malaria elimination. Of the 106 countries with ongoing malaria transmission in 2000,
15 countries achieved malaria elimination and 57 achieved reductions in new malaria cases of
least 75% by 2015. Eighteen countries reduced their malaria cases by 50−75%.

1
World malaria report 2016. Geneva: World Health Organization; 2016 (http://www.who.int/malaria/publications/world-malaria-
report-20156/en/, accessed 28 December 2016).
7.1.5 Risk for travellers
During the transmission season in countries/territories with malaria risk, all non-immune
travellers who are exposed to mosquito bites, especially between dusk and dawn, are at risk of
malaria. This includes previously semi-immune travellers who have lost or partially lost their
immunity during stays of 6 months or more in countries or areas of no risk. Children who
have migrated to countries and areas of no risk are at particular risk when they travel to
malarious areas to visit friends and relatives.
Most cases of falciparum malaria in travellers occur because of poor adherence to, or use of
inappropriate, prophylactic malaria drug regimens, combined with failure to take adequate
precautions against mosquito bites. Studies of travellers’ behaviour have shown that
adherence to chemoprophylaxis can be improved if travellers are informed of the risk of
infection and believe in the benefit of prevention strategies. Late-onset vivax and ovale
malaria may occur despite effective prophylaxis because these parasites cause relapses that
cannot be prevented with medicines that are currently recommended for chemoprophylaxis.
Malaria risk is not evenly distributed where the disease is prevalent. Travellers to any
country/territory in which malaria transmission varies by area should seek advice on the risk
of infection in the particular zones that they will be visiting. If specific information is not
available before travelling, it is recommended that precautions appropriate for the highest
reported risk in the country/territory should be taken. This applies particularly to individuals
backpacking to remote places and visiting areas where health facilities are not readily
available. Travellers staying in rural areas at night may be at highest risk.

7.2 Precautions

Travellers and their advisers should note the five principles – the ABCDE – of malaria
protection:
• Be Aware of the risk, the incubation period, the possibility of delayed onset, and the
main symptoms.
• Avoid being Bitten by mosquitoes, especially between dusk and dawn.
• Take antimalarial drugs (Chemoprophylaxis) when appropriate, at regular intervals to
prevent acute malaria attacks.
• Immediately seek Diagnosis and treatment if a fever develops 1 week or more after
entering an area where there is a malaria risk and up to 3 months (or, rarely, later) after
departure from a risk area.
• Avoid outdoor activities in Environments that are mosquito breeding places, such as
swamps or marshy areas, especially in late evenings and at night.

7.2.1 Protection against mosquito bites

All travellers should be advised that personal protection from mosquito bites between dusk
and dawn is their first line of defence against malaria.
Travellers may protect themselves from mosquitoes by the means outlined in the following
paragraphs.
Insect repellents are substances applied to exposed skin or to clothing to prevent human/vector
contact. The active ingredient in a repellent repels insects but does not kill them. Choose a repellent
containing DEET (N,N-diethyl-3-methylbenzamide), IR3535 (3-[N-acetyl-N-butyl]-
aminopropionic acid ethyl ester) or Icaridin (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-1-
methylpropylester). Insect repellents should be applied to provide protection at times when insects
are biting. Care must be taken to avoid contact with mucous membranes; insect repellents should
not be sprayed on the face, applied to the eyelids or lips, or applied to sensitive, sunburned or
damaged skin or deep skin folds. Always wash the hands after applying the repellent. Repeated
applications may be required every 3–4 h, especially in hot and humid climates when sweating may
be profuse. When the product is applied to clothes, the repellent effect lasts longer. However, label
instructions should be followed to avoid damage to certain fabrics. Repellents should be used in
strict accordance with the manufacturers’ instructions and the dosage must not be exceeded,
especially for young children and pregnant women.
Mosquito nets are excellent means of personal protection while sleeping. Nets can be used either
with or without insecticide treatment. However, treated nets are much more effective. Pretreated
nets may be commercially available. Nets should be strong and with a mesh size no larger than 1.5
mm. The net should be tucked in under the mattress, ensuring first that it is not torn and that there
are no mosquitoes inside. Nets for hammocks are available, as are nets for cots and small beds.
Mosquito coils are the best known example of insecticide vaporizer, usually with a synthetic
pyrethroid as the active ingredient. A more sophisticated product, which requires electricity, is an
insecticide mat that is placed on an electrically heated grid, causing the insecticide to vaporize.
Battery-operated vaporizers are also available. Such devices can also be used during daytime if
necessary.
Aerosol sprays intended to kill flying insects are effective for quick knockdown and killing. Indoor
sleeping areas should be sprayed before bedtime. Treating a room with an insecticide spray will
help to free it from insects, but the effect may be short-lived. Spraying before bedtime, combined
with the use of a vaporizer or a mosquito net, is recommended. Aerosol sprays intended for
crawling insects (e.g. cockroaches and ants) should be sprayed on surfaces where these insects
walk.
Protective clothing can help at times of the day when vectors are active. The thickness of the
material is critical. Insect repellent applied to clothing is effective for longer than it may be on the
skin. Extra protection is provided by treating clothing with permethrin or etofenprox, to prevent
mosquitoes from biting through clothing. In tick- and flea-infested areas, feet should be protected
by appropriate footwear and by tucking long trousers into the socks. Such measures are further
enhanced by application of repellents to the clothing.
Travellers camping in tents should use a combination of mosquito repellents and screens. The mesh
size of tent screens often exceeds 1.5 mm, so that special mosquito screens have to be deployed.
Screening of windows, doors and eaves reduces exposure to flying insects.
Accommodation with these features should be sought where available.
Air-conditioning is a highly effective means of keeping mosquitoes and other insects out of a room
as long as the room has no gaps around windows or doors. In air-conditioned hotels, other
precautions are not necessary indoors.

7.2.2 Chemoprophylaxis
The most appropriate chemoprophylactic antimalarial drug for the destination should be
prescribed in the correct dosage (see Country list and Table 7.2).
Travellers and their doctors should be aware that no antimalarial prophylactic regimen
gives complete protection, but good chemoprophylaxis (adherence to the recommended
drug regimen) significantly reduces the risk of fatal disease. The following should also be
taken into account:
• Dosing schedules for children should be based on body weight.
• Weekly mefloquine should preferably be started 2–3 weeks before departure in order to
achieve protective drug blood levels and to allow possible side-effects to be detected
before travel so that possible alternatives can be considered. Before mefloquine is
prescribed, all users should be made aware of the adverse events associated with its use.
• Daily prophylaxis with doxycycline or atovaquone–proguanil should be started 1–2 days
before arrival in the malaria risk area (or earlier if drug tolerability needs to be checked
before departure).
• Weekly chloroquine should be started 1 week before arrival.
• All prophylactic drugs should be taken with unfailing regularity for the duration of the
stay in the malaria risk area, and should be continued for 4 weeks after the last possible
exposure to infection since parasites may still emerge from the liver during this
period. The single exception is atovaquone–proguanil, which can be stopped 1 week
after return because it is effective against early liver-stage parasites (liver schizonts).
However, if daily doses have been skipped while the traveller was exposed to malaria
risk, atovaquone–proguanil prophylaxis should also be taken for 4 weeks after return.
• Depending on the type of malaria at the destination, travellers should be advised about
possible late-onset malaria caused by the persistent hepatic forms of P. vivax and P.
ovale.

Depending on the type of malaria risk in the specific area of the country/territory visited
(see Country list), the recommended prevention method may be mosquito bite prevention
only, or mosquito bite prevention in combination with chemoprophylaxis and/or standby
emergency treatment, as shown in Table 7.1 (see also Table 7.2 for details of individual drugs).
All antimalarial drugs have specific contraindications and possible side-effects. Adverse
reactions attributed to malaria chemoprophylaxis are common, but most are minor and do
not affect the activities of the traveller. Serious adverse events – defined as events
constituting an apparent threat to life, requiring or prolonging hospitalization, or resulting in
persistent or significant disability or incapacity – are rare and normally identified in post-
marketing surveillance after a drug has been in use for some time. Severe neuropsychiatric
disturbances (seizures, psychosis, encephalopathy) occur in approximately 1 in 10 000
travellers receiving mefloquine prophylaxis, and have also been reported for chloroquine at a
similar rate. The risk of drug-associated adverse events should be weighed against the risk of
malaria, especially P. falciparum malaria, and local drug-resistance patterns.
Each of the antimalarial drugs is contraindicated in certain groups and individuals, and the
contraindications should be carefully observed (see Table 7.2) to reduce the risk of serious
adverse reactions. Pregnant women, people travelling with young children, and people with
chronic illnesses should seek individual medical advice. Travellers who develop severe
adverse effects while using an antimalarial should stop taking the drug and should seek
immediate medical attention so that they can switch to a different antimalarial drug. This
applies particularly to neurological or psychological disturbances experienced with mefloquine
prophylaxis. Mild nausea, occasional vomiting or loose stools should not prompt
discontinuation of prophylaxis, but medical advice should be sought if symptoms persist.

Long-term chemoprophylaxis

Adherence and tolerability are important aspects of chemoprophylaxis for people with
long-term exposure to risk of malaria infection. Few studies have been done on
chemoprophylaxis use for more than 6 months.
• The risk of serious side-effects associated with long-term prophylactic use of
chloroquine is low, but retinal toxicity is of concern when a cumulative dose of 100 g of
chloroquine is reached. Anyone who has taken 300 mg of chloroquine weekly for more
than 5 years and requires further prophylaxis should be screened twice yearly for
early retinal changes. If daily doses of 100 mg chloroquine have been taken, screening
should start after 3 years.
• Data indicate no increased risk of serious side-effects with long-term use of mefloquine
if the drug is tolerated in the short term. Pharmacokinetic data indicate that mefloquine
does not accumulate during long-term intake.
• Available data on long-term chemoprophylaxis with doxycycline (i.e. more than 12
months) are limited but reassuring. There are few data on long-term use of doxycycline
in women, but use of this drug is associated with an increased frequency of vaginitis due
to Candida.
• Atovaquone–proguanil is registered in European countries with a restriction on duration
of use (varying from 5 weeks to 1 year); such restrictions do not apply in the United
Kingdom or the United States.

7.3 Treatment

Patients who are non-immune are at high risk of malaria and its consequences. Early diagnosis
and appropriate treatment can be life-saving.
For travellers who are treated for malaria in countries or areas of no risk, the following
principles apply:
• All patients with suspected clinical malaria should be tested for malaria in a
reliable diagnostic centre with microscopy or rapid diagnostic test. If no parasites
are found in the first blood film, a series of blood samples should be taken at
intervals of 6–12 hours and examined very carefully. When laboratory
 diagnostic results are delayed, treatment should be started on the based on clinical
indicators and travel history.
• If the patient has taken malaria chemoprophylaxis, the same medicine should not
be used for treatment.
• The possibility of mixed P. falciparum–P. vivax infections must always be
considered.
• Travellers who acquire malaria while still in the malaria-endemic country should
be treated in accordance with the national policy of the country.

P. falciparum
Chemoprophylaxis and treatment of falciparum malaria are becoming more complex because
P. falciparum is increasingly resistant to various antimalarial drugs. Chloroquine can no longer
be used for prevention and treatment of falciparum malaria.
The following combination therapies are suitable for treatment of uncomplicated falciparum
malaria in travellers on return to countries or areas of no risk:
• artemether–lumefantrine
• dihydroartemisinin–piperaquine
• atovaquone-proguanil.
Note: The artemisinin combination therapies are preferred because treatment failures are
consistently lower than 5% in settings without resistance to the partner drug.

P.vivax and P.ovale

The treatment for vivax or ovale malaria in travellers is as follows:
• An artemisinin-based combination therapy (ACT) (except artesunate + sulfadoxine-
pyrimethamine) or chloroquine, combined with primaquine, is the treatment of choice to
achieve radical cure (i.e. to cure both the blood-stage and liver-stage infections, and
thereby prevent both recrudescence and relapse).
• An ACT (except artesunate + sulfadoxine-pyrimethamine) should be given for
chloroquine-resistant vivax malaria. Where ACT is not available, quinine can be used
instead. All these treatments should be combined with primaquine.
• Travellers must be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency
before receiving primaquine anti-relapse treatment. Primaquine is contraindicated in
travellers with G6PD deficiency.
• In mixed (falciparum, vivax or ovale) infections, the treatment for P. falciparum will
usually also cure the attack of P. vivax. After G6PD testing, primaquine should be
given to achieve radical cure and prevent relapses.
Chloroquine resistance of P. vivax is still rare but increasing. Focal chloroquine resistance or
prophylactic and/or treatment failure of P. vivax has now been observed in 23 countries:
Afghanistan, Bolivia, Brazil, Cambodia, China, Colombia, Ethiopia, Guyana, India, Indonesia,
Madagascar, Malaysia (Borneo), Myanmar, Pakistan, Papua New Guinea, Peru, Republic of
Korea, Solomon Islands, Sri Lanka, Thailand, Turkey, Vanuatu and Viet Nam. Chloroquine-
 resistant P. malariae has been reported from Indonesia.

P. malariae
Malaria caused by P. malariae can be treated with the standard regimen of an ACT or
chloroquine, but it does not require radical cure with primaquine because no hypnozoites are
generated by this species. Chloroquine-resistant P. malariae has been reported from Indonesia.

P. knowlesi
On microscopy examination, the mature forms of P. knowlesi may be mistaken for P. malariae,
while its ring forms may resemble P. falciparum. Knowlesi malaria can be treated with a
standard regimen of chloroquine or with the antimalarials recommended for uncomplicated
falciparum malaria. The clinical condition of patients infected with P. knowlesi may deteriorate
quickly. Severe P. knowlesi malaria with organ failure may occur; treatment should be as for
severe falciparum malaria.
P. knowlesi infection should always be considered in patients with a microscopy diagnosis of
P. malariae and a history of travel to forested areas of south-east Asia, including areas where
malaria is not normally present.
The dosage regimens for the treatment of uncomplicated malaria are given in Table 7.3.
Details of the clinical management of severe malaria are addressed in other WHO
publications (see “Further reading” at the end of this chapter).

Severe malaria
Returning travellers with severe malaria should be managed in an intensive care unit.
Parenteral antimalarial treatment should be with artesunate (first choice), artemether or quinine.
If these medicines are not available, parenteral quinidine should be used, with careful clinical and
electrocardiographic monitoring.

7.3.1 Treatment during travel

A person who experiences a fever 1 week or more after entering an area with malaria risk
should consult a physician or qualified malaria laboratory immediately to obtain a correct
diagnosis and safe and effective treatment. In principle, travellers can be treated with an ACT
in accordance with the national policy in the country they are visiting.
National antimalarial drug policies for all countries/territories with risk are available from the
WHO website2, 3.
In light of the spread of counterfeit drugs in some malaria-endemic settings, travellers are
advised to buy sufficient antimalarial medicines from reliable sources before departure.

2
WHO Malaria website. See: http://www.who.int/malaria/areas/treatment/drug_policies/en/index.html (accessed).
3
World malaria report 2016. Geneva: World Health Organization; 2016 (http://www.who.int/malaria/publications/world-
malaria-report-20156/en/, accessed 28 December 2016).
7.3.2 Standby emergency treatment (SBET)
Many travellers will be able to obtain proper medical attention within 24 hours of the onset of
fever. For travellers staying in remote locations where prompt access to medical care may be
difficult, it is advisable to carry antimalarial drugs for self-administration (“standby emergency
treatment”, or SBET).
SBET may also be indicated for travellers in some occupational groups who make frequent
short stops in countries or areas with malaria risk over a prolonged period of time. Such
travellers may choose to reserve chemoprophylaxis for high-risk areas and seasons only.
However, they should continue to take measures to protect against mosquito bites and should
be prepared for an attack of malaria: they should always carry a course of antimalarial drugs
for SBET, seek immediate medical care in case of fever, and take SBET if prompt medical
help is not available.
Furthermore, SBET – combined with protection against mosquito bites – may be indicated
for short-term travellers spending 1 week or more in certain remote rural areas where there is
very low risk of infection (see Country list).
Studies on the use of rapid diagnostic tests have shown that untrained travellers experience
major problems in the performance and interpretation of these tests, with an unacceptably high
number of false-negative results. When performed by well-trained staff, good-quality rapid
diagnostic tests are reliable and several tests have good diagnostic performance .
Successful SBET depends crucially on travellers’ behaviour, and health advisers need to spend
time explaining the strategy. Travellers provided with SBET should be given clear and precise
written instructions on the recognition of symptoms, when and how to take the treatment,
possible side-effects, and the possibility of inadequate response to treatment. If several people
travel together, the individual dosages for SBET should be specified. Weight-based dosages for
children must be clearly indicated. Travellers should realize that self-treatment is a first-aid
measure and that they should still seek medical advice as soon as possible.
In general, travellers carrying SBET should observe the following guidelines:
• Consult a physician immediately if fever occurs 1 week or more after entering an area
with malaria risk.
• If it is impossible to consult a physician and/or establish a diagnosis within 24 hours of
the onset of fever, start the SBET and seek medical care as soon as possible for
complete evaluation and to exclude other serious causes of fever.
• Do not treat suspected malaria with the same drugs as were used for prophylaxis.
• Vomiting of antimalarial drugs is less likely if fever is first lowered with antipyretics.
A second full dose should be taken if vomiting occurs within 30 minutes of taking
the antimalarial medicine. If vomiting occurs 30–60 minutes after a dose, an
additional half-dose should be taken. Vomiting with diarrhoea may lead to treatment
failure because of poor drug absorption.
• Complete the SBET course and resume antimalarial prophylaxis 1 week after the first
treatment dose.
• The drug options for SBET are in principle the same as the options for treatment of
uncomplicated malaria (section 7.3). The choice will depend on the type of malaria in
 the area visited and the chemoprophylaxis regimen taken. Artemether–lumefantrine
has been registered (in Switzerland and the United Kingdom) for use as SBET for
travellers. Quinine is less feasible for SBET because it is less effective compared to
the ACTs, it has a long and complex treatment regimen and it has several dose-
dependent side-effects. If quinine is taken for SBET, at least 12 hours should elapse
between the last treatment dose of quinine and resumption of mefloquine prophylaxis to
reduce the risk of drug interactions. Table 7.3 provides details on individual drugs.

7.3.3 Multidrug-resistant malaria

Multidrug-resistant malaria is defined as malaria that is resistant to drugs of more than two
different chemical families. The term is most often used when, in addition to chloroquine and
sulfadoxine-pyrimethamine resistance, resistance of P. falciparum to mefloquine and/or
artemisinins has been reported.

Mefloquine resistance
Mefloquine resistance affects travellers’ choices of prophylaxis and SBET, and is currently
reported in Cambodia, south-eastern Myanmar, and Thailand. In these areas, the choice of
chemoprophylaxis is limited to doxycycline and atovaquone–proguanil.

Artemisinin resistance
WHO’s Global Malaria Programme issues regular updates about the status of artemisinin
resistance in affected countries4. Artemisinin resistance has no implication for the choice of
prophylaxis but it has an impact on treatment; it is reported in Cambodia, Myanmar, Thailand
and Viet Nam, and most recently in the Lao People’s Democratic Republic. In these countries,
SBET options are limited to atovaquone–proguanil only. Local treatment should be with the
ACTs recommended at national level. To reduce the danger of spreading artemisinin-resistant
parasites to other endemic parts of the world, all malaria patients who have travelled to these
areas should be promptly diagnosed and treated effectively. The addition of a single oral
dose of primaquine (0.25 mg base/kg body weight) to treatment will accelerate the removal of
P. falciparum gametocytes and thereby reduce the risk of onward transmission in other
endemic areas. Medical staff should follow national reporting requirements, especially for
imported falciparum malaria cases that originated from travel to the above areas of multidrug-
resistance.

7.4 Special groups

Some groups of travellers, especially young children, pregnant women and immunosuppressed
persons, are at particular risk of serious consequences if they become infected with malaria.
Recommendations for these groups are difficult to formulate because drug safety data are
limited.

4
See the WHO website for updates on artemisinin resistance at: http://www.who.int/malaria/areas/drug_resistance/updates/en/
(accessed 26 December 2016).
Immigrants increasingly travel to their place of origin to visit friends and relatives (VFR). VFRs
from endemic countries/territories who live in malaria-free countries and return to their home
countries are at increased risk of travel related malaria. Because of familiarity with their place of
origin, they may perceive less risk, which may result in lower rates of malaria prophylaxis, higher
risk of exposure and insufficient protective measures. Improving the access of VFRs to pre-travel
health counselling is of increasing public health importance.

7.4.1 Pregnant women

Malaria in a pregnant woman increases the risk of maternal death, miscarriage, stillbirth and
low birth weight with associated risk of neonatal death. Pregnant women should be advised to
avoid travelling to areas where malaria transmission occurs. When travel cannot be avoided, it
is very important to follow the recommendations given below.

Mosquito bite prevention during pregnancy

Pregnant women are particularly susceptible to mosquito bites and should therefore be
vigilant in using protective measures, including insect repellents and insecticide-treated
mosquito nets. They should take care not to exceed the recommended usage of insect
repellents.

Chemoprophylaxis during pregnancy

In areas with exclusively P. vivax transmission, chloroquine prophylaxis may be used. In P.
falciparum transmission areas, mefloquine prophylaxis may be given. In light of the danger
of malaria to mother and fetus, experts increasingly agree that travel to a P. falciparum
transmission area during the first trimester of pregnancy should be avoided or delayed;
if this is truly impossible, good preventive measures should be taken, including
prophylaxis with mefloquine where this is indicated. Doxycycline is contraindicated during
pregnancy. Data on the safety of exposure to atovaquone–proguanil during pregnancy are
limited and this combination is therefore not recommended for use in pregnancy or is
recommended only with relevant risk information/warning.

Treatment during pregnancy

Clindamycin and quinine are considered safe, including during the first trimester of
pregnancy. ACTs can be used to treat uncomplicated malaria in the second and third
trimesters, and in the first trimester only if no other adequate medicines are available.
Chloroquine can be safely used for treatment of vivax malaria during pregnancy, but
primaquine anti-relapse treatment should be postponed until after delivery. Pregnant women
treated for vivax malaria should continue weekly chloroquine prophylaxis post-treatment until
delivery to avoid relapse during the pregnancy.
The recommended treatment for uncomplicated falciparum malaria in the first trimester is
quinine +/– clindamycin. For the second and third trimesters, the options are: ACT in
accordance with national policy; artesunate + clindamycin; or quinine + clindamycin.
Pregnant women with falciparum malaria, particularly in the second and third trimesters of
pregnancy, are more likely than other adults to develop severe malaria, often complicated by
hypoglycaemia and pulmonary oedema. Maternal mortality in severe malaria is
approximately 50%, which is higher than in non-pregnant adults. Fetal death and premature
labour are common. Pregnant women with severe malaria must be treated without delay
with full doses of parenteral antimalarial treatment: artesunate is the treatment of choice, and
artemether or quinine should be used if artesunate is not available. Treatment must not be
delayed and should be started immediately. Information on the safety of antimalarial drugs
during breastfeeding is provided in Tables 7.2 and 7.3.

7.4.2 Women who may become pregnant during or after travel

Malaria prophylaxis may be taken, but pregnancy should preferably be avoided during the
period of drug intake and for 1 week after doxycycline, 3 weeks after atovaquone–proguanil,
and 3 months after the last dose of mefloquine prophylaxis. If pregnancy occurs during
antimalarial prophylaxis, this is not considered to be an indication for pregnancy termination.

7.4.3 Young children

Falciparum malaria in a young child is a medical emergency. It may be rapidly fatal. Early
symptoms are atypical and difficult to recognize, and life-threatening complications can occur
within hours of the initial symptoms. Medical help should be sought immediately if a child
develops a febrile illness within 3 months (or, rarely, later) of travelling to a malaria-endemic
country or territory. Laboratory confirmation of diagnosis should be requested immediately,
and treatment with an effective antimalarial drug should be initiated as soon as possible. In
infants, malaria should be suspected even in non-febrile illness. Parents should be advised not
to take infants or young children to areas where there is risk of falciparum malaria. If
travel cannot be avoided, children must be very carefully protected against mosquito bites
and given appropriate chemoprophylactic drugs. Long-term travellers and expatriates should
adjust the chemoprophylaxis dosage according to the increasing weight of the growing child.

Mosquito bite prevention for young children

Infants should be kept under insecticide-treated mosquito nets as much as possible between
dusk and dawn. The manufacturer’s instructions on the use of insect repellents should be
followed diligently, and the recommended doses must not be exceeded.

Chemoprophylaxis in young children

Chloroquine and mefloquine are considered compatible with breastfeeding. Breastfed, as well
as bottle-fed, infants should be given chemoprophylaxis since they are not protected by the
mother’s prophylaxis. Dosage schedules for children should be based on body weight, and
tablets should be crushed and ground as necessary. The bitter taste of the tablets can be
disguised with jam or other foods. Chloroquine is safe for infants and young children but its
use is now very limited because of chloroquine resistance. Mefloquine may be given to
infants of more than 5 kg body weight. Atovaquone–proguanil is generally not recommended
for prophylaxis in children who weigh less than 11 kg, because of limited data; in Belgium,
Canada, France and the United States, atovaquone–proguanil is given for prophylaxis in
infants of more than 5 kg body weight. Doxycycline is contraindicated in children below 8
years of age. All antimalarial drugs should be kept out of the reach of children and should be
stored in childproof containers; chloroquine is particularly toxic in case of overdose.
 Treatment of young children
Acutely ill children with falciparum malaria require careful clinical monitoring as their condition
may deteriorate rapidly. Every effort should be made to give oral treatment and to ensure that it
is retained. ACT may be used, in accordance with national policy, as first-line treatment while
abroad. Oral treatment options for SBET and returning travellers are: artemether–lumefantrine,
atovaquone–proguanil, dihydroartemisinin–piperaquine, and quinine plus clindamycin. Quinine
plus doxycycline is an option for children aged 8 years and older. Parenteral treatment and
admission to hospital are indicated for young children who cannot swallow antimalarials reliably.
Chloroquine or dihydroartemisinin−piperaquine or artemether−lumefrantrine can be safely given
to treat P. malariae, P. ovale or P. vivax infections in young children. The lower age limit for
anti-relapse treatment with primaquine is 6 months. Information on the safety of drugs for
prophylaxis and treatment of young children is provided in Tables 7.2 and 7.3.

7.4.4 Immunosuppressed travellers

Immunosuppressed travellers are at increased risk of malaria disease, and prevention of

malaria through avoidance of mosquito bites and the use of chemoprophylaxis is particularly
important. Individual pre-travel advice should be diligently sought. There may be an increased
risk of antimalarial treatment failure in people living with HIV/AIDS. At present, however,
there is insufficient information to permit modifications to currently recommended treatment
regimens for this specific population group.

Table 7.1 Malaria risk and type of prevention

Malaria risk Type of prevention

Type A Very limited risk of malaria Mosquito bite prevention only transmission

Type B Risk of P. vivax malaria only Mosquito bite prevention plus chloroquine, or
doxycycline or atovaquone−proguanil or mefloquine
chemoprophylaxis (select according to parasite
sensitivity, reported side-effects and
contraindications)a
Type C Risk of P. falciparum with reported Mosquito bite prevention plus malaria, atovaquone–
chloroquine and sulfadoxine– proguanil or doxycycline or mefloquine
pyrimethamine resistance chemoprophylaxis (select according to reported side-
effects and contraindications) a
Type D Risk of P. falciparum malaria in Mosquito bite prevention plus atovaquone–proguanil
combination with reported multidrug or doxycycline or mefloquine chemoprophylaxis
resistance (select according to reported drug-resistance pattern,
side-effects and contraindications)a,b

a
Alternatively, for travel to rural areas with low risk of malaria infection, mosquito bite prevention can be
combined with SBET.
b
In certain areas with multidrug-resistant malaria, mefloquine chemoprophylaxis is no longer recommended. At
present these areas include Cambodia, south-eastern Myanmar, and Thailand.
 Table 7.2 Use of antimalarial drugs for prophylaxis in travellers

Use in special groups

Generic name Dosage regimen Duration of Pregnancy Breastfeeding Children Main Commentsa
prophylaxis contraindicationsa

One dose daily. Start 1 day No data, not No data, not Not recommended Hypersensitivity to Take with food or milky
Atovaquone– before recommended recommended < 11 kg (< 5kg in atovaquone and/or drink to increase absorption.
proguanil 11–20 kg: 62.5 mg atovaquone departure Belgium, Canada, proguanil; severe Registered in European
combination plus 25 mg proguanil (1 and continue France and the renal insufficiency countries for
tablet paediatric tablet) daily for 7 days after United States) (creatinine clearance chemoprophylactic use with a
return because of limited < 30 ml/min) restriction on duration of use
21–30 kg: 2 paediatric tablets data (varying from 5 weeks to 1
daily year).
Plasma concentrations of
31–40 kg: 3 paediatric tablets atovaquone are reduced when
daily it is co-administered with
rifampicin, rifabutin,
> 40 kg: 1 adult tablet (250 mg metoclopramide or
atovaquone plus 100 mg tetracycline.
proguanil) daily May interfere with live
typhoid vaccine.
The non-recommended status
in pregnancy has been
replaced with a warning label
in France.

Choroquine 5 mg base/kg weekly in one dose, Start 1 week Safe Safe Safe Hypersensitivity to Concurrent use of
or 10 mg base/kg weekly divided before chloroquine; chloroquine may reduce the
in 6 daily doses. departure and history of epilepsy; antibody response to
continue for psoriasis intradermally administered
Adult dose: 300 mg chloroquine 4 weeks after human diploid-cell rabies
base weekly in one dose, or 600 return. vaccine.
mg chloroquine base weekly If daily doses,
divided over 6 daily doses of 100 start 1 day
mg base (with one drug-free day before
per week) departure

a
See package insert for full information on contraindications and precautions.
 Table 7.2 Use of antimalarial drugs for prophylaxis in travellers (continued)

Use in special groups

Generic name Dosage regimen Duration of prophylaxis Pregnancy Breastfeeding Children Main Commentsa
contraindicationsa
Doxycycline 1.5 mg salt/kg Start 1 day before Hypersensitivity to Doxycycline makes the skin
daily departure and continue Contraindicated Contraindicated Contraindicated tetracyclines; liver more susceptible to sunburn.
for 4 weeks after return under 8 years of dysfunction People with sensitive skin
Adult dose: 1 tablet age should use a highly
of 100 mg daily protective (UVA) sunscreen
and avoid prolonged direct
sunlight, or switch to another
drug.
Doxycycline should be taken
with plenty of water to
prevent oesophageal
irritation. Doxycycline may
increase the risk of vaginal
Candida infections. Studies
indicate that the monohydrate
form of the drug is better
tolerated than the hyclate.

Mefloquine 5 mg/kg weekly Start at least 1 week Safe Safe Not Hypersensitivity to Do not give mefloquine
(preferably 2–3 weeks) recommended mefloquine; within 12 hours of quinine
Adult dose: 1 before departure and under 5 kg psychiatric treatment. Mefloquine and
tablet of 250 mg continue for 4 weeks because (including other cardioactive drugs may
weekly after return of lack of data depression) or be given
convulsive disorders; concomitantly only under
history of severe close medical supervision.
neuropsychiatric Ampicillin, tetracycline and
disease; concomitant metoclopramide may
halofantrine increase mefloquine blood
treatment; treatment levels.
with mefloquine in Do not give concomitantly
previous 4 weeks with oral typhoid vaccine.
In the United States,
mefloquine is recommended
as a chemoprophylaxis option
for all trimesters of
pregnancy.

a
See package insert for full information on contraindications and precautions.
 Table 7.3 Use of antimalarial drugs for treatment of uncomplicated malaria in travellers
Use in special groups

Generic name Dosage regimen Pregnancy Breastfeeding Children Main Commentsa

contraindicationsa

Artemether– 3-day course of 6 doses in total, Limited data Safe Apparently Hypersensitivity to Must be taken with fatty foods to improve
lumefantrine taken at 0, 8, 24, 36, 48 and 60 hours in first safe in artemether and/or absorption.
combination trimester children < 5 lumefantrine A flavoured dispersible paediatric formulation is
tablet 5–14 kg: 1 tablet (20 mg artemether kg, but now available, enhancing its use in young
plus 120 mg lumefantrine) per dose limited data children.

15–24 kg: 2 tablets per dose

25–34 kg: 3 tablets per dose

> 35 kg: 4 tablets per dose

Atovaquone– One dose daily for 3 consecutive No data, not No data, not Apparently Hypersensitivity to Take with food or milk drink to increase
proguanil days recommended recommended safe in atovaquone absorption.
combination children and/or proguanil; Plasma concentrations of atovaquone are
tablet 5–8 kg: 2 paediatric tablets daily > 5 kg, but severe renal reduced when the drug is co-administered with
(at 62.5 mg atovaquone plus 25 mg limited insufficiency rifampicin, rifabutin, metoclopramide or
proguanil per tablet) data (creatinine tetracycline.
clearance < 30 May interfere with live typhoid vaccine.
9–10 kg: 3 paediatric tablets daily ml/min)

11–20 kg: 1 adult tablet (250 mg

atovaquone plus 100 mg proguanil)
daily

21–30 kg: 2 adult tablets daily

31–40 kg: 3 adult tablets daily

> 40 kg: 4 adult tablets (1 g

atovaquone plus 400 mg proguanil)
daily
Chloroquine 25 mg base/kg divided in daily dose Safe Safe Safe Hypersensitivity to Use only for malaria caused by P. vivax, P.
(10, 10, 5 mg base/kg) for 3 days chloroquine; history ovale, P. malariae or P. knowlesi.
of epilepsy; psoriasis Concurrent use of chloroquine may reduce the
antibody response to intradermally administered
human diploid-cell rabies vaccine.
a
See package insert for full information on contraindications and precautions.
 Table 7.3 Use of antimalarial drugs for treatment of uncomplicated malaria in travellers (continued)

Use in special groups

Generic name Dosage regimen Pregnancy Breastfeeding Children Main Commentsa

contraindicationsa

Clindamycin Under 60 kg: 5 mg base/kg 4 times Safe Safe Safe Hypersensitivity to Use in combination with quinine in areas of
daily for 5 days clindamycin emerging quinine resistance.
or lincomycin;
> 60 kg: 300 mg base 4 times history of gastro-
daily for 5 days intestinal disease,
particularly colitis;
severe liver or kidney
impairment

Dihydro- One dose daily for 3 consecutive Limited data Safe Safe in Hypersensitivity to
artemisinin– days in first children dihydroartemisinin
piperaquine trimester ≥ 5 kg and/or piperaquine
Target dose = 4 mg/kg per day
dihydroartemisinin and 18 mg/kg
per day piperaquine

Adults > 50 kg: 3 tablets daily for 3

days

Doxycycline Adults > 50 kg: 800 mg salt over 7 Contraindicated Contraindicated Contra- Hypersensitivity to Used in combination with quinine in areas of
days, taken as 2 tablets (100 mg salt indicated tetracyclines; emerging quinine resistance.
each) 12 hours apart on day 1, under 8 years liver dysfunction
followed by 1 tablet daily for 6 days of age

Children 8 years and older:

25–35 kg: 0.5 tablet per dose
36–50 kg: 0.75 tablet per dose
> 50 kg: 1 tablet per dose

a
See package insert for full information on contraindications and precautions.
 Table 7.3 Use of antimalarial drugs for treatment of uncomplicated malaria in travellers (continued)

Use in special groups

Generic name Dosage regimen Pregnancy Breastfeeding Children Main Commentsa

contraindicationsa

Mefloquine 25 mg base/kg as split dose (15 Not Safe Mefloquine is used with artesunate as artemisinin-
mg/kg plus 10 mg/kg 6–24 hours recommended Apparently Hypersensitivity to based combination therapy (ACT).
apart) by producer in safe in children mefloquine; Do not give mefloquine within 12 hours of last
first trimester < 5kg, but psychiatric dose of quinine treatment.
because of limited data (including Mefloquine and other related compounds (such as
lack of data depression) quinine and quinidine chloroquine) may be given
(see or convulsive concomitantly only under close medical
Comments) disorders; history of supervision because of possible additive cardiac
severe toxicity and increased risk of convulsions; co-
neuropsychiatric administration of mefloquine with anti-arrhythmic
disease; concomitant agents, beta-adrenergic blocking agents, calcium
halofantrine channel blockers, antihistamines including H1-
treatment; treatment blocking agents, and phenothiazines may
with mefloquine in contribute to prolongation of QTc interval.
previous 4 weeks Ampicillin, tetracycline and metoclopramide may
increase mefloquine blood levels.
In the United States, mefloquine is recommended
as a treatment option for all trimesters of
pregnancy.

Primaquine 0.25mg base/kg with food once Contra- Contra- Contra- G6PD deficiency; Used as anti-relapse treatment for P. vivax and P.
daily for 14 days indicated indicated for indicated active rheumatoid ovale infections.
mothers < 6 months of arthritis; lupus
In Oceania and south-east Asia the breasfeeding age erythematosus;
dose should be 0.5 mg base/kg infants < 6 conditions that
months of age predispose to
granulocytopenia;
concomitant use of
drugs that may
induce
haematological
disorders

a
See package insert for full information on contraindications and precautions.
 Table 7.3 Use of antimalarial drugs for treatment of uncomplicated malaria in travellers (continued)

Use in special groups

Generic name Dosage regimen Pregnancy Breastfeeding Children Main Commentsa

contraindicationsa

Quinine 8 mg base/kg 3 times daily for 7 Safe Safe Safe In areas of emerging resistance to quinine, give in
days Hypersensitivity to combination with doxycycline, tetracycline or
quinine or quinidine; clindamycin.
tinnitus; optic Quinine may induce hypoglycaemia, particularly
neuritis; haemolysis; in (malnourished) children, pregnant women and
myasthenia gravis. patients with severe disease.
Use with caution in
persons with atrial
fibrillation, with
cardiac conduction
defects or heart
block. Quinine may
enhance effect of
cardiosuppressant
drugs. Use with
caution in persons
using beta-blockers,
digoxin, calcium
channel blockers,
etc.

a
See package insert for full information on contraindications and precautions.
7.5 Countries and territories with malarious areas
The following list shows all countries/territories for which some malaria information is
included in the Country list. In some of these countries/territories, malaria is present only in
certain areas or up to a particular altitude. In many countries, malaria has a seasonal pattern.
Some countries have not reported any cases in recent years. These details as well as
information on the predominant malaria species, status of resistance to antimalarial drugs and
recommended type of prevention are provided in the Country list.
(* = P. vivax risk only)

Afghanistan Gabon Panama

Algeria* Gambia Papua New Guinea
Angola Georgia* Paraguay*
Argentina* Ghana Peru
Azerbaijan* Greece* Philippines
Bangladesh Guatemala Russian Federation*
Belize Guinea Rwanda
Benin Guinea-Bissau Sao Tome and Principe
Bhutan Guyana Saudi Arabia
Bolivia, Plurinational State of Haiti Senegal
Botswana Honduras Sierra Leone
Brazil India Solomon Islands
Burkina Faso Indonesia Somalia
Burundi Iran, Islamic Republic of South Africa
Cambodia Iraq*
Cameroon Kenya Sudan
Cape Verde Korea, Democratic People’s South Sudan
Republic of*
Central African Republic Korea, Republic of* Suriname
Chad Kyrgyzstan* Swaziland
China Lao People’s Democratic Syrian Arab Republic*
Republic
Colombia Liberia Tajikistan
Comoros Madagascar Thailand
Congo Malawi Timor-Leste
Congo, Democratic Malaysia Togo
Republic of the Mali Turkey*
Costa Rica Mauritania Uganda
Côte d’Ivoire Mayotte United Republic of
Tanzania
Djibouti Mexico Uzbekistan*
Dominican Republic Mozambique Vanuatu
Ecuador Myanmar Venezuela, Bolivarian
Republic of
Egypt Namibia Viet Nam
El Salvador Nepal Yemen
Equatorial Guinea Nicaragua Zambia
Eritrea Niger Zimbabwe
Ethiopia Nigeria
French Guiana Oman
Pakistan
Further reading
The documents listed below are available on the WHO Global Malaria Programme website
at: http://www.who.int/malaria.
• Guidelines for the treatment of malaria, third edition. Geneva: World Health
Organization; 2015.
• Malaria vector control and personal protection: report of a WHO Study Group.
Geneva: World Health Organization; 2006 (WHO Technical Report Series, No. 936).
• Management of severe malaria: a practical handbook, third edition Geneva: World
Health Organization; 2012.
• World malaria report 2016. Geneva: World Health Organization; 2016.