PROTOZOAL INFECTIONS
Malaria and advising the
traveller
Diana Ayoola Mabayoje
Nicky Longley
Abstract
Malaria is a preventable, mosquito-borne parasitic infection that re-
mains one of the leading causes of imported fever, hospitalization
and death in travellers returning from Sub-Saharan Africa. Early symp-
toms of malaria infection can mimic other common conditions pre-
senting to healthcare settings. A high index of suspicion and early
diagnosis and management, alongside patient education and preven-
tion methods, can greatly reduce morbidity and mortality from malaria
worldwide. In this article we aim to cover the different types of malaria,
individuals at particular risk of malaria acquisition, malaria prevention,
treatment and key advances. We will focus on falciparum malaria as
this causes the greatest morbidity and mortality.
Keywords Chemoprophylaxis; health promotion; health risk
assessment; malaria prevention; pre-travel advice; travel medicine
Introduction
Malaria remains one of the leading imported causes of fever,
hospitalization and death in UK travellers. In a 15-year study
conducted by the Hospital for Tropical Diseases, falciparum
malaria was the most common reason identified for admission in
all returned travellers from Africa.1
Around 1700 cases of imported malaria are reported annually in
the UK with a 2.1% annual increase reported from the most recent
figures.2 People visiting friends and relatives in their country of
origin (VFR travellers) accounted for 85% of imported malaria cases
where the reason for travel was known.2,3 The group most at risk of
acquiring malaria are UK residents of African heritage travelling to
West Africa who have not taken chemoprophylaxis, making them
an important target for pre-travel advice and community engage-
ment.3 It is important to address misconceptions about immunity for
people born in malaria-endemic areas returning to their countries of
origin: immunity acquired by people born in malaria-endemic
countries is rapidly lost after migration to the UK and previous
malaria does not protect from future attacks.
Plasmodium falciparum is the most common type of malaria
imported into the UK and is associated with the most morbidity
Diana Ayoola Mabayoje BSc MB BS DTM&H MSc MRCP FRCPath is a
Specialist Registrar in Infectious Diseases and Microbiology at
University College London Hospital, London, UK. Competing
interests: none declared.
Nicky Longley MB BS MRCP FRCPath MD (Res) is an Infectious Diseases
Consultant and Clinical Lead for Travel Medicine at the Hospital of
Tropical Diseases, and an Associate Professor at the London School
of Hygiene and Tropical Medicine, UK. Competing interests: none
declared.
MEDICINE 49:12
Key points
C Malaria is one of the most common and serious causes of
fever in travellers returning from malaria-endemic areas,
particularly Sub-Saharan Africa, with falciparum malaria
causing the most morbidity and mortality
C Travellers at high risk of malaria acquisition include people
returning to their countries of origin in West Africa, travellers
to rural areas and long-stay travellers. People with medical co-
morbidities, pregnant women and very young or elderly trav-
ellers are at increased risk of severe malaria. It is important to
address misconceptions about immunity for people born in
malaria-endemic areas returning to their countries of origin:
immunity acquired by people born in malaria-endemic coun-
tries is rapidly lost after migration to the UK and previous
malaria does not protect from future attacks
C The mainstay of malaria prevention is a combined strategy of
awareness of risk, bite avoidance, chemoprophylaxis and
prompt diagnosis
C Malaria causes a non-specific flu-like illness that can mimic
other infections. Unwell travellers returning from malaria-
endemic areas should seek urgent medical advice and have
rapid malaria testing
C Malaria should be considered in returned travellers up to a
year after travel to malaria risk areas
and mortality.2,3 The risk of dying from malaria is highest in
elderly individuals, tourists and those presenting for medical
help in areas where malaria is less regularly seen and treated,
emphasizing the importance of awareness along with prompt
diagnosis and treatment.4
Pathophysiology and epidemiology
Malaria is transmitted to humans through the bite of a female
Anopheles mosquito infected with the Plasmodium parasite
(Figure 1). Five species of Plasmodium cause disease in humans:
P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi.
Most life-threatening infections are caused by P. falciparum but
both P. vivax and P. knowlesi can cause severe disease.
Malaria is endemic throughout the tropics and subtropics;
90% of the burden of disease occurs in Sub-Saharan Africa,
which is the highest risk area for malaria acquisition and
importation to non-endemic countries (Figure 2). Falciparum
malaria predominates in Africa, followed by P. ovale and P.
malariae; vivax malaria predominates in South Asia, Central
America and China; and both falciparum and vivax species occur
in South-East Asia and South America. Plasmodium knowlesi, a
zoonotic malaria infecting crab macaque monkeys, occurs across
South-East Asia, particularly Malaysia.
The epidemiology of malaria is changing, with a declining
incidence and mortality in many endemic countries due to the
deployment of prevention strategies such as vector control along
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Figure 1 Source: Reproduced from Chiodini et al. (2021).2
with intermittent preventive treatment of high-risk groups such
as pregnant women and children. Despite these advances there
has been a recent plateauing of cases of malaria in some high-
burden countries and there are ongoing biological threats to
malaria control posed by parasite resistance to antimalarial drugs
and vector resistance to insecticides. Environmental degradation
has increased the spillover of zoonotic diseases such as P.
knowlesi malaria, with a predicted expansion of geographical
malaria risk areas because of climate change, deforestation and
human encroachment into wildlife habitats.
Presentation
The incubation period of P. falciparum malaria is typically 7
e14 days. For P. vivax or P. ovale malaria the incubation period
is around 12e18 days, although hypnozoites can be reactivated
after several months or occasionally years to cause illness. Ma-
laria causes a non-specific flu-like illness that can mimic other
infections. Viral haemorrhagic fevers (VHF) should also be
considered and risk-assessed in patients who have returned from
VHF-endemic areas.
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Major features of severe or complicated malaria are impaired
consciousness or seizures, renal impairment, hypoglycaemia,
acute respiratory distress syndrome and anaemia.
Diagnosis
Microscopic examination of thin and thick blood films for the
detection and species identification of malaria parasites by an
experienced microscopist is the gold standard for the diagnosis of
malaria.
Rapid diagnostic tests (RDTs) detecting parasite antigens such
as histidine-rich protein 2 (HRP2) are now widely available.
RDTs are particularly useful as an adjunct to microscopy in non-
endemic settings, especially in laboratories with limited experi-
ence of malaria microscopy. RDTs do not, however, give infor-
mation about parasite density and morphological features such
as the presence of schizonts in falciparum malaria, both of which
have prognostic value. Additionally, some P. falciparum para-
sites have mutations in the expression of HRP2, rendering them
undetectable using RDTs that detect this parasite antigen. Cur-
rent UK guidelines advise that three blood films over a 48-hour
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Figure 2 Origins, destinations, and flows of imported cases of malaria from endemic to non-endemic countries between 2005 and 2015. Source:
Reproduced from Tatem AJ, Jia P, Ordanovich D et al. The geography of imported malaria to non-endemic countries: a meta-analysis of nationally
reported statistics. Lancet Infect Dis 2017; 17: 98e107.

period should be examined to exclude malaria if initial tests
prove negative.
Treatment
Treatment of malaria should be in accordance with the Public
Health England Advisory Committee on Malaria Prevention
malaria treatment guidelines in consultation with an infectious
disease or tropical medicine unit.5 The choice of treatment de-
pends on the causative species, clinical severity and patterns of
drug resistance. Uncomplicated P. falciparum malaria should be
treated with artemisinin combination therapy. Alternatively,
atovaquone/proguanil can be used as long as it was not used as
chemoprophylaxis. The treatment of choice for severe or
complicated malaria in adults and children is intravenous
artesunate. Quinine remains an effective antimalarial and should
be used for severe falciparum malaria when a supply of artesu-
nate is not immediately available.
Prevention
Prevention of malaria infection involves understanding the
disease process and the ‘ABCD’ of malaria prevention:
Awareness of risk, Bite avoidance from the Anopheles mosquito
vector, Chemoprophylaxis and prompt Diagnosis of infection
(Table 1).
High-risk groups for malaria
Pregnant women: pregnant women have an increased risk of
contracting malaria and of developing severe illness. If possible,

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they should avoid visiting areas that are endemic for malaria, Infants and children: infants are at increased risk of severe
particularly for P. falciparum. If this is not feasible, a discussion malaria because of an immature immune system. Administering
about suitable chemoprophylaxis and careful risk assessment chemoprophylaxis to babies and young children can be chal-
should be undertaken. lenging, so mosquito bite avoidance is extremely important in

The ‘ABCD’ of malaria prevention

Provide the traveller with written information on malaria and its prevention.
Awareness of risk
C A detailed travel itinerary is necessary to assess risk
C Review geographical risk areas
C Review the malaria transmission cycle
C Malaria transmission rates vary markedly between different regions, even within a country, and at different times of the year
C The highest risk region for malaria is Sub-Saharan Africa
C Travellers to malarious areas should be advised to have comprehensive travel insurance for the event that they will become unwell and require
specialist medical treatment
Bite avoidance
C Avoiding mosquito bites is essential and has the additional benefit of reducing the risk of other mosquito-borne diseases such dengue,
chikungunya and yellow fever
C The peak time for Anopheles mosquitoes to bite is from dusk to dawn
C Wear protective clothing
C 50% DEET is the gold standard insect repellent as it has the longest duration of action and needs fewer applications
C DEET can be used for children aged >2 months and in pregnant women
C Icaridin at a minimum concentration of 20% is also an effective insect repellent
C Travellers can prevent mosquito bites in sleeping areas by sleeping in rooms:
 With air conditioning
 With netting on the doors and windows
 That have been sprayed with an insecticide (pyrethroids)
 With working electricity, where a device can be plugged in to release insecticides during short trips in risk areas
C Travellers should sleep under bed netting impregnated with a residual insecticide such as permethrin
C Although resistance to pyrethroids has been reported for malaria vectors, they are still an effective part of bite avoidance
C ‘Natural’ insect repellents have a limited duration of activity and many commonly used malaria prevention measures (homeopathy, electronic
mosquito repellents, garlic, yeast extract, citronella) are not effective
Chemoprophylaxis (see Table 2)
C Consider medical history and other medications
C Consider previous experience with antimalarials
C Malaria chemoprophylactic agents are either causal (directed at the liver phase of the malaria parasite life cycle, which takes 7 days to develop)
or suppressive (directed at the red blood cell phase of the malaria parasite life cycle)
C Causal agents such as atovaquone/proguanil and primaquine should be continued for only 7 days after leaving a malarious area
C Suppressive prophylactic drugs such as mefloquine and doxycycline must be continued for 4 weeks after leaving a malarious area
C Recommendations for chemoprophylaxis should be based on the travel destination and tailored to the individual, taking into account the risks
and benefits
C Chemoprophylaxis recommendations vary worldwide, so UK clinicians should be familiar with local recommendations (Table 2). A full clinical
history should obtained, detailing current medication, significant health problems and known drug allergies
C Because of the risk of fake or substandard antimalarials purchased in the tropics, travellers should obtain malaria chemoprophylaxis from a
reputable source in the UK before leaving; this can be from a travel clinic or pharmacy. It is vital to stress the importance of compliance with
chemoprophylaxis in malaria prevention
Diagnosis
C A delay in diagnosing malaria is one of the main reasons that travellers become seriously ill and die from malaria
C Travellers should be made aware of the signs and symptoms of malaria (fever or flu-like illness) and be reminded that malaria can occur even up
to a year after returning from a risk areas
C Travellers who become unwell or have a fever on return from a country where malaria is present must seek medical advice and alert their
healthcare professional about their travel to a malarious area
C Consider a diagnosis of malaria in any traveller returning from an endemic area
C Arrange prompt diagnostic tests such as thick and thin blood films looking for the malaria parasites and/or RDTs

DEET, N,N-diethyl-meta-toluamide.

Table 1

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Antimalarial chemoprophylaxis options for UK travellers

Antimalarial Dose Schedule Additional information

Atovaquone/proguanil
(Malarone or Maloff )
Mefloquine (Lariam)
Doxycycline
Atovaquone 250 mg/ Start 1 day before travel, take every
proguanil 100 mg day while away and continue for
One tablet daily (if >40 kg) 7 days after leaving the malaria-
endemic area
Take with food or a milky drink to
increase absorption
The tablet should be swallowed
whole, not crushed
Mefloquine Start 2e3 weeks before travel, take
Variable dosing depending every week while away and
on weight, please consult continue for 4 weeks after return
the BNFa Take with or after food
Doxycycline 100 mg Start 1 day before travel, take every
One tablet daily (age >12 day while away and continue for
years) 4 weeks return
It is important to take the capsules
with plenty of fluid and well before
going to bed
The capsule should be swallowed
whole. Doxycycline can be taken
with or after food
Common adverse effects include:
C Headache/dizziness
C Gastrointestinal upset
C Sleep disturbance
C Change in mood
Less common adverse effects include hair loss
and mouth ulcers
Atovaquone/proguanil should generally be
avoided in pregnancy. The ACMP advises that
if there are no other options, use can be
considered in the second and third trimesters
after careful risk assessment
Avoid in breastfeeding
Avoid in renal impairment
Suitable for use in pregnancy
Common adverse effects include:
C Headache/dizziness
C Gastrointestinal upset
C Sleep disturbance
C Depression/anxiety
Avoid in patients with previous psychiatric
illness. Patients receiving mefloquine for ma-
laria prophylaxis should be informed to dis-
continue its use if neuropsychiatric symptoms
occur and seek immediate medical advice so
that mefloquine can be replaced with an
alternative antimalarial.
Mefloquine antagonizes the anticonvulsant
effect of anti-epileptics and can increase the
risk of convulsions
Contraindicated during pregnancy and in
children under 12 years of age
Avoid in breastfeeding
Adverse effects include:
C Heartburn
C Gastrointestinal disturbance
C Skin reactions (particularly if exposed to
strong sunlight)
C Vaginal thrush

ACMP, Advisory Committee on Malaria Prevention.

a
Please consult the British National Formulary (BNF) for adult dosing.

Table 2

this group. Dosing recommendations for paediatric patients are
available in the British National Formulary.
Asplenic/hyposplenic individuals (including people with
sickle cell anaemia): this group is very vulnerable to severe
malaria and should be dissuaded from travel to malaria risk
areas. If travel is essential, they should be encouraged to take
strict malaria prevention measures.
Immunocompromised individuals: malaria can be more severe
in immunocompromised people and is often complicated by
bacterial sepsis.
Older travellers (>65 years of age): older travellers are more
likely to have co-morbidities that increase their risk of severe and
fatal malaria. There is also the risk of polypharmacy when pre-
scribing malaria chemoprophylaxis.
Renal disease: the management of malaria infection is more
difficult in renal disease, and medications used for malaria pro-
phylaxis and treatment can affect renal function.
Other groups: long-stay travellers require personalized advice
about long-term prophylaxis. Travellers to rural areas are at

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increased risk of getting malaria, and may require a specialized
approach such as emergency standby malaria treatment if they
are unlikely to be within 24 hours of medical attention.
Other approaches
There is currently no commercially available malaria vaccine for
travellers. A sporozoite-based vaccine has shown partial efficacy
in children in malaria-endemic settings in Africa. However, this
vaccine was not designed for or tried in a non-immune population.
Novel vector control strategies such as the deployment of sterile
mosquitos are being investigated to counteract the growing
insecticide resistance. Antimalarial drugs with novel mechanisms
of action are needed both as treatment and for prophylaxis. A
KEY REFERENCES
1 Marks M, Armstrong M, Whitty CJ, Doherty JF. Geographical and
temporal trends in imported infections from the tropics requiring
inpatient care at the Hospital for Tropical Diseases, London e a 15
year study. Trans R Soc Trop Med Hyg 2016; 110: 456e63.
2 Chiodini PL, Patel D, Goodyer L, Ranson H. Guidelines for malaria
prevention in travellers from the United Kingdom, 2021. London:
Public Health England, March 2021.
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3 Public Health England. Malaria imported into the United
Kingdom: 2019. Implications for those advising travellers. 2021,
https://assets.publishing.service.gov.uk/government/uploads/
system/uploads/attachment_data/file/989677/Malaria_
imported_into_the_United_Kingdom_in_2019.pdf (accessed 12
August 2021).
4 Checkley AM, Smith A, Smith V, et al. Risk factors for mortality from
imported falciparum malaria in the United Kingdom over 20 years:
an observational study. BMJ 2012; 344: e2116.
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FURTHER READING
Healthcare professionals working in England, Wales or Northern
Ireland should use the Public Health England Advisory Committee
on Malaria Prevention guidelines (available at https://
travelhealthpro.org.uk) as their preferred source of guidance for
malaria prevention.
Separate guidance is produced in Scotland for Scottish health pro-
fessionals by the Scottish Malaria Advisory Group.
Walker NF, Nadjm B, Whitty CJM. Malaria. Medicine 2018; 46: 52e8.
https://doi.org/10.1016/j.mpmed.2017.10.012
779 Ó 2021 Published by Elsevier Ltd.