Malaria is a life-threatening febrile illness caused by infection of red blood cells with a parasite called Plasmodium (UK Health Security Agency (UKHSA), 2023). This parasite is transmitted to humans via bites from infected female night biting Anopheles mosquitoes (World Health Organization (WHO), 2023). Six protozoan parasite species of the genus Plasmodium: P. falciparum, P. vivax, P. ovale wallikeri, P. ovale curtisi, P. malariae and P. knowlesi cause human malaria (European Centre for Disease Prevention and Control (ECDC), 2023). Two of these species; P. falciparum and P. vivax pose the greatest risk (WHO, 2023).
Malaria is a major global public health threat, with transmission occurring in large areas of Central and South America, Africa, Asia and Oceania (ECDC, 2023). The WHO estimates that, in 2021, there were 247 million cases of malaria, with 619 000 deaths. Africa carries a disproportionately high share of the world's malaria burden. In 2020, Africa was home to 95% of malaria cases and 96% of malaria deaths. Children under five years are the most vulnerable group affected by malaria; in 2021, they accounted for nearly 80% of all malaria deaths in Africa (WHO, 2023).
Malaria is a serious but preventable disease. P. falciparum can progress to severe and life-threatening illness, including cerebral malaria, if it is not diagnosed and treated promptly (UKHSA, 2019). Non-specific symptoms of malaria include fever, headache, sweats or chills, coughing diarrhoea malaise, muscle pain and tenderness.
Major features of severe or complicated falciparum malaria in adults are impaired consciousness or seizures, renal impairment, acidosis, hypoglycaemia, pulmonary oedema or acute respiratory distress syndrome, low haemoglobin, spontaneous bleeding or disseminated intravascular coagulation shock and haemoglobinuria (UKHSA, 2023).
Malaria in travellers
All travellers visiting areas where malaria is present are at risk of acquiring the disease, particularly UK residents who were born in malaria risk areas and return to visit friends and relatives in their country of birth. Certain travellers are at increased risk of severe disease such as:
- Anyone with an absent or poorly functioning spleen
- Babies and children
- Pregnant women
- Older travellers (NaTHNaC, 2021).
Malaria does not occur in the UK, but it is a risk for UK residents visiting malaria risk regions (UKHSA, 2019). The UKHSA advises travel- associated UK malaria cases are reported every year in returning travellers and individuals visiting the UK from malaria-endemic areas.
In 2019 (latest available UK data as of 30 March 2023), a total of 1719 imported malaria cases were reported in the UK: 1626 in England, 58 in Scotland, 25 in Wales and 10 in Northern Ireland. This is 2.1% higher than 2018 (1683 cases) and 6.6% above the mean number of 1612 cases reported annually from 2010 to 2019. In 2019, 15 malaria deaths were reported in the UK, which is an increase compared to the previous 10 years with an annual average of six deaths (UKHSA, 2021).
Other European countries also report a significant number of malaria cases in returning travellers. For 2020, the ECDC reported that 28 EU and European Economic Area (EEA) countries reported a total of 2377 malaria cases. France reported the highest number of cases, followed by Germany and Belgium. Most imported malaria cases in France were linked to West Africa. In 2020, due to COVID-19 restrictions, malaria case numbers were substantially lower than previous years. Pre-COVID-19, case numbers were higher; in 2019, a total of 8662 imported cases were reported in EU/EEA countries and between 2016 and 2019 reported cases numbers were all over 8000 annually (ECDC, 2023).
Approximately 2000 cases of malaria are diagnosed in the US each year. The vast majority of US cases are in travellers and immigrants returning from countries with malaria transmission in sub-Saharan Africa and South Asia (Centers for Disease Control and Prevention (CDC), 2023). In the UK in 2019, of the 15 malaria deaths 14 were from falciparum malaria acquired in Africa: Western Africa (six), Eastern Africa (five), Middle Africa (two) and Africa unknown country (one). The remaining death was in a traveller diagnosed with vivax malaria after visiting Southern Asia. Reason for travel was known for 11 cases; five travelled for holidays, three visited friends and relatives (VFR) and three were foreign visitors to the UK from malaria risk areas (UKHSA, 2021). Travellers to sub-Saharan Africa have the greatest risk of both getting malaria and dying from their infection. However, all travellers to countries where malaria is present may be at risk for infection (US CDC, 2022).
Accessing information about malaria, risk countries and current UK antimalarial recommendations
Malaria recommendations can change rapidly; therefore, this article does not provide specific antimalarial recommendations but directs prescribers to the non-commercial, publicly funded UK resources such as the National Travel Health Network and Centre (NaTHNaC), TRAVAX and UKHSA. All UK health professionals prescribing antimalarials should ensure they are familiar with the appropriate malaria guidelines. During the risk assessment process with the traveller, these resources must be used to access current malaria recommendation for specific countries. Malaria transmission is dynamic, advice and antimalarial recommendations can change quickly.
UKHSA recommends that UK health professionals use a single resource for malaria recommendations to optimise consistency of advice. Healthcare professionals working in England, Wales or Northern Ireland are advised to use the Advisory Committee on Malaria Prevention (ACMP) guidance in the UKHSA's Malaria prevention guidelines for travellers from the UK as their source of guidance: https://www.gov.uk/government/publications/malaria-prevention-guidelines-for-travellers-from-the-uk (UKHSA, 2023).
NaTHNaC's TravelHealthPro website country information pages provide destination-specific travel health worldwide. All malaria advice and antimalarial recommendations are consistent with current UKHSA/ACMP malaria guidance: https://travelhealthpro.org.uk/countries
Separate guidance is available in Scotland for health professionals, produced by the Scottish Malaria Advisory group – see the NHS Travax website: https://www.travax.nhs.uk/malaria/ (UKHSA, 2023).
Health professionals can also email malaria prophylaxis queries to the Malaria Reference Laboratory: https://www.gov.uk/government/publications/malaria-risk-assessment-form
Prescribers
Doctors are by far the largest group of prescribers. They have been joined by non-medical independent and supplementary prescribers from a range of other healthcare professions who are able to prescribe within their scope of practice once they have completed an approved education programme. Prescribers are also responsible for practising within their own scope of practice and competence, including delegating where appropriate, seeking support when required and using their acquired knowledge, skills and professional judgement (Royal Pharmaceutical Society (RPS), 2021).
Pharmacist prescribers
The RPS provides guidance for UK pharmacists, Supply of Anti-Malarials as Pharmacy Medicines: https://www.rpharms.com/resources/quick-reference-guides/supply-of-anti-malarials-as-pharmacy-medicines.
Nurse prescribers
Evidence shows that nurse prescribing improves patient care by ensuring timely access to medicines and treatment, and increasing flexibility for patients who would otherwise need to wait to see a doctor (Royal College of Nursing (RCN), 2014). In order to prescribe medicinal products, nurses and midwives must have recorded their prescriber qualification on the Nursing and Midwifery Council (NMC) register (NMC, 2023).
Malaria risk assessment
Malaria prevention involves a balance between ensuring that all people at risk of infection use appropriate prevention measures, while preventing adverse effects of those interventions among people using them unnecessarily (CDC, 2022). No travel health consultation should take place without conducting a travel risk assessment and documenting the information. The assessment forms the basis of all subsequent decisions, advice given, vaccines administered and the malaria prevention advice that is offered (RCN, 2018). Safe and effective malaria prevention requires a sound knowledge of the medical history of the traveller. Antimalarial recommendations should be appropriate for the destination and tailored to the individual, taking into account possible risks and benefits. As part of a stringent risk assessment it is essential that the prescriber obtains a full clinical history from the traveller. This must detail all current medication (including all drugs prescribed by hospitals which may not appear on GP repeat drug prescriptions lists), significant health problems and any known drug allergies (UKHSA, 2023).
Box 1.Resources
- Advisory Committee on Malaria Prevention: https://www.gov.uk/government/collections/advisory-committee-on-malaria-prevention-acmp
- ECDC Malaria Outbreak Reports: https://www.ecdc.europa.eu/en/malaria/threats-and-outbreaks
- Faculty of Travel Medicine of the Royal College of Physicians and Surgeons of Glasgow – Good Practice Guidance for Providing a Travel Health: https://rcpsg.ac.uk/documents/publications/1535-tm-guidancedoc-1020-final-hires-singlepages/file
- Malaria Reference Laboratory: https://www.gov.uk/government/collections/malaria-reference-laboratory-mrl
- NaTHNaC Risk Assessment/Risk Management: https://travelhealthpro.org.uk/factsheet/61/risk-assessment--risk-management-checklist
- NaTHNaC Insect and tick bite avoidance: https://travelhealthpro.org.uk/factsheet/38/insect-and-tick-bite-avoidance
- NHS Malaria: https://www.nhs.uk/conditions/malaria/
- Pan American Health Organization - Countries certified as malaria free by WHO: https://www.paho.org/en/topics/malaria/countries-certified-malaria-free-americas
- RPS Pharmacist Independent Prescribers: https://www.rpharms.com/recognition/all-our-campaigns/policy-a-z/pharmacist-independent-prescribers
- UKHSA Mosquito bite avoidance advice for travellers: https://www.gov.uk/government/publications/mosquito-bite-avoidance-for-travellers
- WHO Annual Malaria Report: https://www.who.int/publications/i/item/9789240064898
- UKHSA provides free information leaflets on mosquito bite avoidance in a variety of languages: English, Arabic, Bengali, French, Gujarati, Hausa, Igbo, Punjabi, Spanish, Swahili, Yoruba, Urdu, Xhosa and in British Sign Language, large print, braille and Easy Read: https://www.gov.uk/government/publications/mosquito-bite-avoidance-for-travellers
UKHSA recommend health professionals use a risk assessment template when prescribing antimalarials and they provided a template in Appendix 2 of their Guidelines for malaria prevention in travellers from the UK.
Choice of antimalarial for a particular individual should take into account:
- Risk of exposure to malaria (destination)
- Extent of drug resistance at destination
- Drug efficacy
- Potential side-effects
- Patient-related factors, such as age, pregnancy, renal or hepatic impairment, compliance with prophylactic regimen (National Institute for Health and Care Excellence (NICE); British National Formulary (BNF), 2023).
This also applies to an over-the-counter sale of a pharmacy-only medicine. For the recently reclassified atovaquone plus proguanil product, the manufacturers provide a pharmacist checklist which can usefully be used as part of such an assessment. The Advisory Committee on Malaria Prevention (ACMP) advises that a risk assessment for malaria chemoprophylaxis should be performed or checked by the pharmacist, is described specifically in the pharmacy standard operating procedures and a record be kept of the outcome of such an assessment. These principles should also apply to sales over the internet through registered e-pharmacies where an appropriate online risk assessment is conducted (UKHSA, 2023).
ABCD of malaria prevention
Malaria prevention advice involves a combination of preventive measures (the ABCD of malaria prevention) including (UKHSA, 2023):
- Awareness of risk
- Bite prevention
- Chemoprophylaxis (antimalarial tablets)
- Diagnose promptly and treat without delay.
Antimalarial options depend on the parasite species and presence of drug resistance (P. falciparum parasite resistance to chloroquine or other antimalarials) at the destination, as well as the traveller's medical history. Antimalarials are either causal (directed at the liver phase of the malaria parasite life cycle) like atovaquone plus proguanil or suppressive (directed at the red blood cell phase of the malaria parasite life cycle) such as chloroquine, doxycycline, mefloquine and proguanil. No antimalarial regimen is 100% effective, but combining preventive measures such as good bite avoidance, compliance with antimalarials and prompt medical treatment for symptoms provides significant protection against malaria (NaTHNaC, 2021a).
Using visual aids, especially malaria distribution maps (available on NaTHNaC, TRAVAX and UKHSA websites) helps travellers understand the malaria risk at their destination. Based on individual risk assessment; all antimalarial options, with their individual advantages and disadvantages, including cost, should be discussed with the traveller. Travellers should also be given a written record of all malaria prevention measures advised to give to their GP (UKHSA, 2023).
Malaria vaccines
Since October 2021, WHO recommends broad use of the RTS,S/AS01 malaria vaccine among children living in regions with moderate to high P. falciparum malaria transmission. This vaccine has been shown to significantly reduce malaria, including deadly severe malaria, in young children (WHO, 2022). There is currently no commercially available malaria vaccine for travellers (NaTHNaC, 2021a).
Travellers with specific needs
Asplenia
Travellers who do not have a spleen or whose spleen does not work properly are at particular risk of severe malaria. Visiting malarious areas should be avoided. If travel is essential, rigorous mosquito bite avoidance measures should be followed and appropriate antimalarials should be taken, even in low risk areas, where bite avoidance only is usually recommended for most travellers. If a traveller develops a fever or other symptoms that could be malaria during or after their visit, medical advice must be sought as a matter of urgency. In asplenia or hyposplenia malaria parasite blood levels can rise very quickly to high levels causing a life-threatening illness (NaTHNaC, 2021b).
Babies and young children
Babies and young children are at risk of severe and fatal malaria. Parents or guardians are advised not to take babies and young children to malaria risk areas. If travel is unavoidable they must be well protected against mosquito bites (DEET repellents of up to 50% are safe from two months) and receive appropriate malaria chemoprophylaxis. It is important that carers understand the importance of children completing the antimalarial course. Children should be supervised when taking antimalarials children's chemoprophylaxis and maximum recommended doses should not be exceeded, since antimalarials can be particularly toxic to children (UKHSA, 2023).
UKHSA Malaria prevention guidelines for travellers from the UK provide clear guidance, including contraindications and weight/dose tables.
Epilepsy
Chloroquine and mefloquine are both contraindicated in individuals with a current or past history of epilepsy or seizures. Atovaquone plus proguanil or doxycycline can be prescribed. However, the half- life of doxycycline may be reduced by phenytoin, carbamazepine and barbiturates. If another antimalarial is not possible or acceptable, increase the dose of doxycycline to 100 mg twice daily and discuss measures to minimise adverse events. A history of febrile convulsions only does not contraindicate use of any currently available UK antimalarials (UKHSA, 2023).
Mental health
Mefloquine may induce psychiatric symptoms such as anxiety disorders, paranoia, depression, hallucinations and psychosis. Psychiatric symptoms such as insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion are regarded as prodromal for a more serious event. Cases of suicide, suicidal thoughts and self- endangering behaviour such as attempted suicide have been reported (EMC, 2022).
As with any antimalarial, stringent risk assessment is required before advising mefloquine use. Any current or previous history of depression, generalised anxiety disorder, psychosis, schizophrenia, suicide attempts, suicidal thoughts, self-endangering behaviour or any other psychiatric disorder is a contraindication (UKHSA, 2023). Eating disorders such as anorexia nervosa and bulimia nervosa are mental health conditions (Royal College of Psychiatrists, 2020) and are, therefore, contraindications to mefloquine.
Risk of serious mental health disorders is higher in first-degree relatives of those in whom these conditions have been diagnosed, so they should be considered as part of risk assessment. A condition in a first-degree relative may not contraindicate the use of an antimalarial but may influence the choice of drug (UKHSA, 2023). Specific guidance on the contraindications and precautions associated with Mefloquine can be found in the manufacturers summary of product characteristics: https://www.medicines.org.uk/emc/product/9670/smpc.
Pregnancy
Pregnant women should be informed of the risks associated with visiting malarious countries and should consider postponing their trip, unless they feel travel is unavoidable. Pregnancy makes women more susceptible to mosquito bites and so more vulnerable to malaria. All pregnant women travelling to countries with malaria and other mosquito-borne diseases like Zika should avoid mosquito bites day and night. Malaria in pregnancy increases the risk of maternal death, miscarriage, stillbirth and low birth weight, with associated risk of neonatal death. Diagnosing falciparum malaria in pregnancy can be difficult, as parasites may not be detectable in blood films due to sequestration in the placenta (NaTHNaC, 2023a).
- Atovaquone/proguanil: There is a lack of evidence on safety in pregnancy. If there are no other appropriate options, its use may be considered in the second and third trimesters after careful risk assessment. Folic acid 5 mg daily should be taken for the length of time that atovaquone/proguanil is taken in pregnancy and also by women trying to become pregnant (UKHSA, 2023)
- Chloroquine and proguanil: Safe in all trimesters of pregnancy. Their major disadvantage is the relatively poor protection they give in many geographical areas due to the presence of drug- resistant P. falciparum parasites. Pregnant women taking proguanil should also take 5mg folic acid daily for the length of time that proguanil is taken (UKHSA, 2023)
- Doxycycline: Contraindicated in pregnancy. However, under special circumstances, if required before 15 weeks' gestation it should not be withheld if other options are unsuitable. The course of doxycycline, including the four weeks after travel, must be completed before 15 weeks' gestation (UKHSA, 2023)
- Mefloquine: Caution in first trimester but can be used in all trimesters for travellers to high-risk areas. It is unlikely that mefloquine is associated with adverse foetal outcomes. The decision whether to advise mefloquine prophylaxis in pregnancy always requires a careful harm-benefit analysis. In areas where malaria transmission levels and drug resistance make mefloquine an agent of first choice, it is generally agreed that mefloquine may be advised in the second and third trimesters. Given the potential severity of falciparum malaria in pregnancy, its use is also justified in the first trimester for travel to areas of high risk of acquiring falciparum malaria such as sub-Saharan Africa (UKHSA, 2023). DEET repellents at a concentration of up to 50% are recommended as part of the malaria prevention regimen for pregnant women, including those in the first trimester (UKHSA, 2023).
People visiting friends and family
In the UK, malaria predominantly affects non- UK born residents, particularly those from Africa and South Asia, largely due to their high rates of travel to risk areas. Data suggest VFR travellers are significantly less likely to take antimalarials than other travellers. VFR travellers born in Africa may substantially underestimate their malaria risk and overestimate the protection being brought up in Africa may give them. Those born in malarious countries need to be aware that any immunity they may have is rapidly lost after migration to the UK. The view that this group is relatively protected is a dangerous myth (UKHSA, 2023) and their UK-born children will have no protection from the disease (NaTHNaC, 2021). Also they are unlikely to be aware of the possibility that any non-malarious areas where they lived previously may now be malarious (NICE/BNF, 2023).
Malaria consultation with VFRs should explore their values and beliefs and the health professional should try to deliver advice accordingly. The importance of health risks should be stressed, such as how essential it is to take appropriate antimalarials when travelling to malaria endemic areas (RCN, 2018). VFRs should be advised antimalarials purchased in the tropics could potentially be fake or sub-standard, so they should obtain antimalarials from a reputable UK source before travel. Travellers purchasing antimalarial drugs over the internet should ensure that they are dealing with a genuine supplier or website (UKHSA, 2023).
UKHSA provides specific advice for travellers visiting friends and family abroad: https://www.gov.uk/government/publications/travelling-overseas-to-visit-friends-and-relatives-health-advice/visiting-friends-and-relatives-abroad-advice-for-travellers
Returning travellers
Malaria is always a serious disease and can be deadly. Travellers who become ill with a fever or flu-like illness either while travelling in a malaria-risk area or after returning home (for up to one year) should seek immediate medical attention and should tell the health professional treating them their travel history (CDC, 2022).
Travellers must be made aware that suspected malaria is a medical emergency and that they must get urgent medical help. Fever on return from the tropics should be considered malaria until proven otherwise. Suspected cases must be investigated as a matter of urgency. As the clinical features of malaria are non-specific, there is a significant risk that imported cases of malaria may be wrongly diagnosed as COVID-19, influenza, or another infectious illness, resulting in delayed access to treatment with severe or fatal consequences. Death in the UK due to misdiagnosis of imported falciparum malaria as COVID-19 has already occurred (UKHSA, 2023).
Conclusion
Malaria, an almost completely preventable but potentially fatal disease, remains an important issue for UK travellers. Failure to take antimalarials is associated with the majority of cases of malaria in UK residents travelling to malaria-risk areas (UKHSA, 2021). In 2017, the Malaria Reference Laboratory reported four cases of treatment failure among UK patients receiving artemether-lumefantrine for P. falciparum malaria. Since then, a further 21 suspected cases have been reported and are under investigation (UKHSA, 2023). In September 2022, the first UK case of artemisinin drug resistant malaria was reported in a UK resident who visited Uganda. These cases of drug treatment resistant malaria highlights the importance of malaria prevention for travellers visiting malaria risk countries. This includes good compliance with antimalarial drug regimens, as the current preventive measures are more than 90% effective when used correctly (NaTHNaC, 2023b).
While the focus of this article is on prescribing antimalarials, it should be emphasised that malaria prevention is only one aspect of pre-travel advice. Travel consultations also allow consideration of other destination specific hazards. An overall risk assessment-based package of travel health advice should be provided to the traveller (UKHSA, 2023).
Optimal and effective pre-travel advice seeks to map travellers' expectations with evidence based practice (Chiodini et al, 2020).
Key Points
- Travellers need to provide a full medical history, including all medication and clear details of planned destinations
- Potential drug interactions must be considered
- Health professionals must keep updated with changes in malaria advice and recommendation by using the appropriate resources
CPD reflective questions
- Lola is taking her five-month-old baby girl Ruby to Lagos in Nigeria to meet her grandparents for the first time. What anti-malarials would you discuss? What other advice would you give?
- Richard, 30 is travelling to French Guiana for work – he will be filming in remote jungle regions. He has a history of febrile convulsions as a child, but is otherwise well. What advice would you give?
- Marina is 28 and going on honeymoon to Zanzibar in three weeks time. She has just found out she's pregnant, but does not want to cancel her honeymoon. What are her options?
- Reuben, 66 and his wife June, 63 are going on a package holiday to Senegal in two weeks. Reuben has well controlled epilepsy. He took atovaquone plus proguanil when he visited the Gambia two years ago, but he experienced headaches and nausea. What other information do you need him to provide? What anti-malarials are contraindicated for Reuben?
- What resources and information could you share with travellers who have concerns about taking anti-malarials?