Malaria is caused by five species of protozoan parasite of the genus Plasmodium, transmitted by mosquitoes of the genus Anopheles. After infecting the cells of the liver, the parasite proliferates through repeated cycles in the red blood cells.1 As the red cells rupture, the infected person displays febrile symptoms including the classic malarial rigors.2 Morbidity and mortality are greatest in children and in adults exposed to infection for the first time. Adults frequently exposed to infection since childhood may have stronger immunity3 and resistance to severe manifestations of the disease.4
Approximately half of the world’s population is at risk of malaria,5 Plasmodium species having occurred in environments as diverse as tropical forests and arctic tundra.6 However, the range of malaria has contracted in recent decades7 and it was declared absent from the WHO European region in 2016. Elsewhere, the infection is in steep decline in the northern and southern extremities of its range. All reports of malaria in Europe are considered to be imported, with rare exceptions of ‘cryptic’ or ‘airport’ malaria. The United Kingdom and France report approximately 50% of cases seen in European Union countries.
The global incidence of malaria decreased by about 41% between 2000 and 2015, and by 21% between 2010 and 2015. Plasmodium falciparum is responsible for 99% of the 430,000 deaths from malaria and over 90% of deaths are in sub-Saharan Africa. This makes great demands of countries facing other major health and social challenges.8 Of around an estimated 212 million malaria cases in 2015, 90% were in the WHO African Region followed by 7% in the WHO South-East Asia Region (which includes India) and 2% in the WHO Eastern Mediterranean Region (which includes part of East Africa). The proportion of mortality by region is similar to that of morbidity. It should not however be assumed that species other than P. falciparum do not kill. P. vivax is widespread outside Africa and causes about 3,100 deaths worldwide.
Of the 91 countries and territories with malaria transmission in 2015, 40 achieved a reduction in incidence of 40% or more between 2010 and 2015. Mortality rates are estimated to have declined by 62% globally between 2000 and 2015 and by 29% between 2010 and 2015. While 70% of those dying globally due to malaria are children aged under five, mortality in this group is estimated to have declined by 69% between 2000 and 2015 and by 35% between 2010 and 2015.
Surveillance and outcomes
Surveillance in Scotland supports prevention of malaria as it affects travellers to or from malarious countries by collating information on geography, demographics and behaviour associated with risk. Health Protection Scotland (HPS) continuously reviews local, national and international data9 on epidemiology,10,11 outbreaks12 and drug resistance13,14 to produce evidence-based malaria prevention guidance in conjunction with the Scottish Malaria Advisory Group. This guidance, with accompanying maps, is published on TRAVAX (www.travax.nhs.uk) and fitfortravel (www.fitfortravel.nhs.uk).
Scottish malaria data is monitored to ensure relevance and quality. Since 2013, all malaria specimens in Scotland are referred to the Scottish Parasite Diagnostic and Reference Laboratory (SPDRL) for confirmation and follow-up. Data on age, sex, diagnosis, parasite species, country of origin, travel, prophylaxis and ethnicity are routinely collated. Only speciated reports confirmed by PCR or microscopy are included in the data.
The Scottish data is submitted to the Malaria Reference Laboratory (MRL) in London which collates all data on malaria imported into the United Kingdom. Any reports from Scotland where the patient has given an address elsewhere are allocated to the appropriate part of the UK, and any Scottish residents diagnosed elsewhere are allocated to Scotland. The Scottish data for the period 2016 cited above was analysed using Microsoft Excel.
Some data fields were merged to simplify operations. People who identified as Indian, Bangladeshi or Pakistani were added to the Indian Subcontinent ethnicity group. Where Ethnicity, Country, Geographic region or Reason for Travel were Blank or Not Stated, these were recorded as Unspecified.
In addition to the latest data from 2016, four years of data since the beginning of enhanced surveillance in 2013 are considered here.
The United Kingdom malaria total for 2016 will be reported elsewhere and is not discussed here.
Malaria in Scotland, 2016: results
In 2016, there were 58 reports of malaria in Scotland, an increase of 18.4% compared to the total in 2015 (N=49) (Figure 1). Age and sex were recorded for all 58 individuals with 77.6% male (N=45) and 22.4% female (N= 13) (Figure 2). Mean age for all reports was 38.0 years (SE+2.2). Mean age for females was 43.1 years (SE+5.6) and for males 36.6 years (SE+2.2). Reports peaked at 40-44 years for males (N=11) and at 25-29 years for females (N=4). Peak age groups for total reports was 40-44 years (N=12).
P. falciparum was the most common species at 77.6% (N=45) followed by P. vivax at 12.1% (N=7). Three (5.2%) infections were identified as P. malariae. The remaining reports comprised 1.7% (N=1) P. ovale, 1.7% (N=1) mixed P. falciparum/P. ovale and 1.7% (N=1) mixed P. falciparum/P. malariae (Figure 1).
No deaths from malaria were reported in Scotland in 2016.
Region and country of transmission
Region of transmission was recorded for 81.0% (N=47) of Scottish reports (Table 1). West Africa accounted for 53.2% (N=25) of the total where region was recorded. Within West Africa, most reports originated from Nigeria 60.0 % (N=15), Ghana 20.0% (N=5) and Gambia 8.0% (N=2). The proportion from East Africa where region was recorded was 23.4% (N=11). Within East Africa, 27.3% (N=3) came from Kenya, 27.3% (N=3) from Uganda, 18.2% (N=2) from Sudan and 18.2% (N=2) from Tanzania. One report (9.1%) came from Eritrea. Four (8.5%) reports where region was reported came from Southern Africa. All of these came from Angola. Central Africa provided 4.3% (N=2) of reports where region of transmission was recorded. Within Central Africa, both reports (100%) came from Cameroon. Four reports (8.5%) came from Asia (not South East or Far East), all from Pakistan and one (2.1%) came from South East Asia & Far East, country unspecified.
Region of transmission was recorded for 82.2% (N=37) reports of P. falciparum, of which 56.8% (N=21) came from West Africa. East Africa and Southern Africa contributed 21.6% (N=8) and 10.8% (N=4), respectively. There were two (5.4%) reports each from Central Africa and Asia (not South East or Far East). Region of transmission was recorded for six out of seven (85.7%) reports of P. vivax. Three (50.0%) of these came from East Africa, two (33.3%) from Asia (not South East or Far East) and one (16.7%) from Far East & South East Asia.
Reason for travel
Thirty-nine individuals (67.2%) gave a reason for travel (Table 2). Of these, people Visiting Friends & Relatives (VFR) accounted for 43.6% (N=17), while 25.6% (N=10) were Business/Professional Travellers. Holiday Travellers, Foreign Visitors and New Arrivals in the UK each contributed 10.3% (N=4) reports.
Taken together, people of Black African ethnicity (N=29) and African descent (N=4) comprised 61.1% (N=25) of the 54 whose ethnicity was specified (Table 3). Eleven individuals (20.4%) were recorded as White British. Five (9.3%) individuals were reported as being of Indian Subcontinent ethnicity, 3.7% (N=2) were of Mixed ethnicity. Black Caribbean, Other Black and Other White each contributed 1.7% (N=1) of the total where ethnicity was recorded.
Of the total data set, twenty-six (44.8%) individuals did not specify if chemoprophylaxis was used (Table 4). Twenty-eight (48.3%) reported that they took no chemoprophylaxis while three (5.2%) reported taking doxycycline and one (1.7%) reported taking atovaquone/proguanil. One individual reported taking chemoprophylaxis regularly.
Malaria in Scotland, 2013-2016: results
In the four years from 2013 to 2016, there were 242 reports of malaria in Scotland. There were 59 (24.4%) reports in 2013, 76 (31.4%) in 2014, 49 (20.2%) in 2015 and 58 (24.0%) in 2016 (Figure 1).
Age and sex were recorded for 99.6% (N=241) of these, of which 72.2% (N=174) were male and 27.8% (N=67) were female. Mean age for males was 37.93 years (SE=1.1) and for females 35.7 years (SE=2.0). Age distribution peaked at years 25-29 years for females (N=13) and at 40-44 for males (N=29). Peak age for total reports was 40-44 (N=33) (Figure 3).
One hundred and eighty seven reports (77.3%) were P. falciparum while 14.5% (N=35) were P. vivax. P. ovale at 3.3% (N=8) and P. malariae at 3.3% (N=8) were less frequently seen. There were four (1.7%) mixed infections comprising one P. falciparum / P. malariae, one P. falciparum / P. vivax and one P. falciparum / P. ovale (Figure 1).
There was one death from P. falciparum in Scotland in 2013.
Region and country of transmission
Region of transmission was recorded for 225 (93.0%) reports (Table 5). Of these, West Africa contributed 52.9% (N=119), East Africa 15.1% (N=34) and Asia (not Far East or South East) 11.6% (N=26). Within West Africa, Nigeria and Ghana contributed the greatest number, with 47.1% (N=56) and 16.0% (N=19) respectively. Asia (Not Far East or South East) provided 26 reports (11.6%). Of these Pakistan 73.1% (N=19) was the source of the greatest number, with India contributing 26.9% (N=7).
Region of transmission was recorded for 92.5% (N=173) reports of P. falciparum, of which 61.5% (N=107) came from West Africa. Southern Africa and East Africa contributed 12.1% (N=21) each.
Central Africa provided 9.2% (N=16). Four percent (N=7) came from Asia, the Far East and South East Asia and Oceania collectively.
Region of transmission was recorded for 97.1% (N=34) reports of P. vivax. Of these, Asia (not South East or Far East) contributed 58.8% (N=20). East Africa provided 29.4% (N=10) of P. vivax reports. One report (2.9%) came from each of Oceania, Central & South America and West Africa.
Reason for travel
Of the 77.3% (N=187) reports where a reason for travel was given, VFR was commonest at 36.9% (N=69). This was followed by Business/Professional Travellers 24.1% (N=45), holiday travel 12.3% (N=23) and New entrants to the UK 8.0% (N=15). Foreign students contributed 6.4% (N=12) (Table 6).
Ethnicity was recorded in 224 reports. Of these, 51.3% (N=115) were of Black African or of African descent and 30.4% (76) were White British, while 9.8% (N=22) recorded their ethnicity as Indian Subcontinent or Indian/Pakistani/Bangladesh descent (Table 7).
Of the 242 episodes 155 (64.0%) indicated whether chemoprophylaxis was used (Table 8). Of these 111 might have originated in the UK (VFR, Business/ professional, holiday travel, UK Citizens abroad, British forces, Air crew). Of these 78 (70.3%) used no chemoprophylaxis.
Overview of surveillance
The number of reports of malaria in Scotland continues to fluctuate annually although the countries where infections were acquired tends to remain broadly consistent. Most malaria reported in Scotland is associated with travel to or from Africa, with West Africa being the main source of infection. Plasmodium falciparum is the species most frequently reported in Scotland; P. vivax is less commonly reported. Vivax malaria is absent from much of sub-Saharan Africa although as the episodes in East Africa demonstrate not exclusively so.
Groups at risk
Risk of malaria varies according to the traveller’s conditions of exposure. Two important characteristics are country of travel and reason for travel, with ethnicity having a strong influence on both of these.
In 2016, where ethnicity was recorded, 61.1% of reports in Scotland were people recorded as Black African or of African Descent. The largest single group in the past four years where ethnicity and reason for travel are recorded are Black African VFR travellers. The next largest group is White British Business/Professional travellers indicating malaria is not only a risk for those whose recent heritage lies in malarious countries. Only 12.0% of the Scottish episodes in 2016 whose reason for travel indicated travel abroad from the UK any chemoprophylaxis use (Table 4). If we include those who have an address in the UK then that percentage is 11.1% (four out of 36; data not presented). In the years 2013-2016, of the Scottish episodes whose reason for travel indicated travel abroad from the UK only 29.3% indicated any chemoprophylaxis use; this drops to 23.1% (36/156) if we include those with UK residence. These observations demonstrate the importance of obtaining, understanding and following appropriate prevention advice. Public Health England (PHE) noted that in 2015,85% of malaria patients who had travelled abroad from the UK had taken no antimalarial chemoprophylaxis, among those from whom this information was obtained.15
Some VFR travellers may have a misplaced confidence in their innate immunity16 or the safety of their destination and thus disregard adequate prevention. Travellers returning home to malarious countries after living in the UK may disregard risk if they have not recently experienced serious malaria due to immunity acquired since childhood.17 However, immunity wanes quickly without exposure, placing the traveller at risk if exposed to infection after months or years away.
Business travellers may depart at short notice without adequate preparation or appropriate advice. Some longer term travellers and UK citizens abroad may form a similar group to new entrants from endemic countries in that they may have high exposure to infection and may eschew chemoprophylaxis and use medication only in the event of clinical malaria. Healthcare providers are encouraged to advise these groups of malaria risks faced, particularly if they are pregnant or travelling with children. The possibility of malaria should always be considered in a febrile patient arriving from a malarious country,18 whether the patient belongs to a perceived high-risk group or otherwise. New arrivals in the UK are also at risk of malaria, although prevention is outside the purview of health professionals here. It remains important that clinicians should be aware of the possibility of malaria, particularly in members of migrant communities arriving from Africa.
Malaria from Africa
P. falciparum is widespread in sub-Saharan Africa and is medically very significant in the traveller. Of the four species of malaria occurring in Africa, P. falciparum is the only one likely to kill the infected person. P. vivax has been reported in travellers from East Africa in recent years and three such infections were reported in Scotland in 2016. P. vivax is rarer in UK travellers returning from East Africa, as the endemic areas are only infrequently visited by tourists and business people. However, P. vivax should not be a surprising diagnosis in migrants or refugees from the Horn of Africa,19,20 Asia, including South East and Far East.
In 2016, around 50,000 people travelled from Scotland to India and Pakistan.21 Despite this number, many of them VFR travellers, only four reports of malaria acquired in Pakistan were received in Scotland. There were no reports from India. A large proportion of malaria in these two countries is P. vivax, which is often refractory to chemoprophylaxis.22 The epidemiological trend although declining can be unstable, so the need for chemoprophylaxis varies.23 In the past decade, reports of malaria from South East Asia and the Far East have been infrequent in the UK. There are only two such reports in the four-year Scottish data set considered here. Nonetheless, malaria is widespread in South East Asia and must be considered in a traveller’s risk assessment.
Some current issues in malaria
Drug resistance in P. falciparum occurs sporadically over a wide geographic range and is especially well-recognised in South East Asia. The possibility of artemisinin resistance in highly populated countries such as India24 is a matter of particular concern, as is the risk of its development to Africa where endemicity has proven most intractable.25 Recently, artemisinin resistance by various mechanisms26,27 in P. falciparum has been recorded in isolates from patients infected in Angola, Equatorial Guinea, Liberia and Uganda. In this regard, development of an effective malaria vaccine remains an important goal. In April 2017 the World Health Organization announced its collaboration with Ghana, Kenya, and Malawi in the Malaria Vaccine Implementation Programme (MVIP) that will trial the RTS,S/AS01 malaria vaccine (trade name Mosquirix™) in selected areas of those three countries.28 The programme is expected to end in 2022 and is intended to examine the safety, efficacy and feasibility of routine wide-scale delivery in endemic countries. Malaria control depends on socioeconomic improvement as well as on biological factors. Declining economy and infrastructure can lead to a deteriorating malaria picture, as exemplified by the worsening situation in Venezuela. Malaria case numbers have increased since the beginning of the present decade. In 2016, case numbers rose to about 240,000, an increase of about 75% compared to 2015. Almost 45% of cases are in the state of Bolívar, where there has been a rapid expansion of gold mining. Prevention and treatment measures are unavailable or inconsistently applied, while economic activity draws migrants from other regions and countries into malarious areas where conditions are conducive to sustained, intense transmission.29
Countries in South East Asia have had noteworthy successes in malaria reduction but economic change continues to help sustain some transmission. P. knowlesi is the most important malaria in some South East Asian countries: its presence in people depends on an overlap between human and macaque populations. This occurs frequently where people work in forestry operations, or in the farming activities that often follow.30 P. knowlesi should be considered in risk assessment for travellers to rural or peri-urban areas in endemic countries where this species may be present but poorly recorded.
In recent years there has been concern about safety of antimalarial chemoprophylaxis with particular attention given to mefloquine.31 Debate about the potential for adverse effects32 is likely to continue, but mefloquine remains a valuable drug in appropriate settings. Consideration of appropriate antimalarials should always form part of the pre-travel risk assessment based on context and contraindications.33
Advice to travellers
Travellers from Scotland visit malarious areas in considerable numbers each year. The Scottish malaria reports confirm the importance of chemoprophylaxis: where this is taken as directed, the risk of malaria is small. Risks associated with VFR and business travel, particularly to Africa, are further confirmed. Travellers to malarious countries should always seek pre-travel evidence-based advice from specialist health professionals and be aware of the malaria risk associated with specific intended destinations. TRAVAX (www.travax.nhs.uk) provides travel health professionals with evidence-based guidance to advise travellers.34,35 Fitfortravel (www.fitfortravel.nhs.uk), also produced by HPS is aimed at members of the travelling public.
All travellers should follow the ‘ABCD’ of malaria prevention.
A--be Aware of the risk
B--prevent mosquito Bites
C--take appropriate Chemoprophylaxis if required (or advised)
D--early Diagnosis can be life-saving.
HPS would like to thank the Public Health England Malaria Reference Laboratory for collating and supplying data, and also the various laboratories in Scotland who have supplied enhanced data to Health Protection Scotland via the Scottish Parasite Diagnostic and Reference Laboratory.
- National Institute of Allergy and Infectious Diseases. Malaria Parasite, Mosquito, and Human Host. Available from: https://www.niaid.nih.gov/diseases-conditions/malaria-parasite. (accessed 22 June 2017).
- Manson’s Tropical Diseases, 21st Edition, eds Cook GC & Alimuddin Zumla. Elsevier 2003.
- Pinkevych M, Petravic J, Chelimo K et al. The dynamics of naturally acquired immunity to Plasmodium falciparum infection. PLOS Computational Biology. 2012. Available from: http://dx.doi.org/10.1371/journal.pcbi.1002729. (accessed 22 June 2017).
- Boutlis CS, Yeo TW, Anstey NM. Malaria tolerance – for whom the cell tolls? Trends in Parasitology. 2006;22(8):371-7. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766419/. (accessed 22 June 2017).
- World Health Organisation. World Malaria Report 2016. Available at: http://www.who.int/malaria/publications/world-malaria-report-2016/en/. (accessed 22 June 2017).
- Hackett LW. Malaria in Europe: an ecological study. Oxford University Press, 1937.
- Hay SI, Guerra CA, Tatem AJ et al. The global distribution and population at risk of malaria: past, present, and future. Lancet Infectious Diseases. 2004;4(6):327-336. Available from: http://www.sciencedirect.com/science/article/pii/S1473309904010436. (accessed 22 June 2017).
- Sachs J, Malaney P. The economic and social burden of malaria. Nature. 2002;415:680-85. Available from: http://www.nature.com/nature/journal/v415/n6872/full/415680a.html. Accessed 22 June 2017.
- Boyne L, Genasi F, Redman C, et al. Reviewing the evidence for malaria advice and maps for TRAVAX® and Fitfortravel® - update. HPS Weekly Report. 2011;45(2011/03):33-5. Available from: http://www.hps.scot.nhs.uk/ewr/redirect.aspx?id=46829. (accessed 22 June 2017).
- Snow RW, Hay SI. Comparing methods of estimating the global morbidity burden from Plasmodium falciparum malaria [comment]. American Journal of Tropical Medicine & Hygiene. 2006;74(2):189-190. Available from: http://www.ajtmh.org/content/74/2/189.full. (accessed 22 June 2017).
- Peterson AT. Shifting suitability for malaria vectors across Africa with warming climates. BMC Infectious Diseases. 2009;9(59). Available from: http://www.biomedcentral.com/1471-2334/9/59. (accessed 22 June 2017).
- Kesteman T, Rafalimanantsoa SA, Razafimandimby H, Rasamimanana HH. Multiple causes of an unexpected malaria outbreak in a high-transmission area in Madagascar. Malaria Journal. 2016;15:57. Available from: https://malariajournal.biomedcentral.com/articles/10.1186/s12936-016-1113-0. Accessed 22 June 2017.
- Sutherland CJ, Haustein T, Gadalla N, et al. Chloroquine-resistant Plasmodium falciparum infections among UK travellers returning with malaria after chloroquine prophylaxis. Journal of Antimicrobial Chemotherapy. 2007;59(6):1197-9. Available from: http://jac.oxfordjournals.org/content/59/6/1197.full. (accessed 22 June 2017).
- Frosch AEP, Venkatesan M, Laufer MK. Patterns of chloroquine use and resistance in sub- Saharan Africa: a systematic review of household survey and molecular data. Malaria Journal. 2011;10:116. Available from: http://www.malariajournal.com/content/10/1/116. (accessed 22 June 2017).
- Public Health England. Malaria imported into the United Kingdom in 2016: Implications for those advising travellers. 2016. Available from: https://www.gov.uk/government/publications/malaria-in-the-uk-annual-report. (accessed 22 June 2017).
- Doolan DL, Doban C, Baird JK. Acquired immunity to malaria. Clinical Microbiology Reviews. 2009;22(1):13-36. Available from: http://cmr.asm.org/content/22/1/13.abstract. (accessed 22 June 2017).
- Lalloo DG, Shingadia D, Bell DJ et al. UK malaria treatment guidelines 2016. Journal of Infection. 2016;72,635-649. Available from: http://www.sciencedirect.com/science/article/pii/S0163445316000475. (accessed 22 June 2017).
- Kopel E, Schwartz E, Amitai Z et al. Relapsing vivax malaria cluster in Eritrean refugees, Israel, June 2010. Eurosurveillance. 2010;15(26). Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19601. (accessed 22 June 2017).
- Saidel-Odesa L, Riesenberga K, Schlaeffera F et al. Eritrean and Sudanese migrants presenting with malaria in Israel. Travel Medicine and Infectious Disease. 2011;9(6):303-05. Available from: http://www.sciencedirect.com/science/article/pii/S1477893911000901. (accessed 22 June 2017).
- Sondén K, Castro E, Trönnberg L et al. High incidence of Plasmodium vivax malaria in newly arrived Eritrean refugees in Sweden since May 2014. Eurosurveillance. 2014;19(35). Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20890. (accessed 22 June 2017).
- United Kingdom Office for National Statistics. Travel Trends 2016: Data and commentary from the International Passenger Survey. ONS. 2017. Available at: https://www.ons.gov.uk/releases/traveltrends2016. (accessed 22 June 2017).
- Baird JK. Suppressive chemoprophylaxis invites avoidable risk of serious illness caused by Plasmodium vivax malaria. Travel Medicine and Infectious Disease. 2013;11(1):60-65. Available from: http://www.travelmedicinejournal.com/article/S1477-8939(13)00004-5/abstract. (accessed 22 June 2017).
- Behrens RH, Bisoffi Z, Björkman A et al. Malaria prophylaxis policy for travellers from Europe to the Indian Sub Continent. Malaria Journal. 2006;5:7. Available from: http://www.malariajournal.com/content/5/1/7. (accessed 22 June 2017).
- Mishraa N, Prajapatia SK, Kaitholiaa K et al. Surveillance of artemisinin resistance in Plasmodium falciparum in India using the kelch13 molecular marker. Antimicrobial Agents and Chemotherapy. 2015;59(5):2548-2553. Available from: http://aac.asm.org/content/59/5/2548.full. (accessed 22 June 2017).
- Slater HC, Griffin JT, Ghani AC, Okell LC. Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malaria Journal. 2016;15:10. Available from: http://malariajournal.biomedcentral.com/articles/10.1186/s12936-015-1075-7. (accessed 22 June 2017).
- Sutherland CJ, Lansdell P, Sanders M et al. Pfk13-independent treatment failure in four imported cases of Plasmodium falciparum malaria given artemether-lumefantrine in the UK . Antimicrobial Agents and Chemotherapy 2017; 61(3): e02382-16. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328508/. (accessed 22 June 2017).
- Zhou, Zhu HG, Tang T et al . Emergence of indigenous artemisinin-resistant Plasmodium falciparum in Africa. The New England Journal of Medicine 2017; 376: 991-993. Available from: http://www.nejm.org/doi/full/10.1056/NEJMc1612765#t=article. (accessed 22 June 2017).
- Malaria Vaccine Initiative. Ghana, Kenya, and Malawi to take part in WHO malaria vaccine pilot programme. 24 April, 2017. Available from: http://www.malariavaccine.org/malaria-and-vaccines/first-generation-vaccine/rtss. (accessed 22 June 2017).
- Pan American Health Organisation /World Health Organisation. Epidemiological Alert. Increase in cases of malaria 15 February 2017. Available from: http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=38146&lang=en. (accessed 22 June 2017).
- Grigg MJ, Cox J, William T, Jelip J et al. Individual-level factors associated with the risk of acquiring human Plasmodium knowlesi malaria in Malaysia: a case-control study. The Lancet Planetary Health 2017;1: e97–104. Available from: http://www.sciencedirect.com/science/article/pii/S2542519617300311. (accessed 22 June 2017).
- House of Commons Defence Committee. An acceptable risk? The use of Lariam for military personnel. Fourth Report of Session 2015-16. Available from: http://www.parliament.uk/business/committees/committees-a-z/commons-select/defence-committee/inquiries/parliament-2015/inquiry. (accessed 22 June 2017).
- Nevin RL, Croft AM. Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives. Malaria Journal. 2016;15:332. Available from: http://malariajournal.biomedcentral.com/articles/10.1186/s12936-016-1391-6. (accessed 22 June 2017).
- Schlagenhauf P, Hatz C, Behrens R et al. Mefloquine at the crossroads? Implications for malaria chemoprophylaxis in Europe. Travel Medicine and Infectious Disease. 2015;13(2):192-6. Available from: http://www.sciencedirect.com/science/article/pii/S1477893915000459. (accessed 22 June 2017).
- Chen LH, Wilson ME, Schlagenhauf P. Prevention of malaria in long-term travelers. Journal of the American Medical Association. 2006;296(18):2234-44. Available from: http://jama.jamanetwork.com/article.aspx?articleid=203969. (accessed 22 June 2017).
- Spira AM. Preparing the traveller. Lancet. 2003;361(9366):1368-81. Available from: http://www.sciencedirect.com/science/article/pii/S0140673603130759. (accessed 22 June 2017).