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Malaria and travellers visiting friends and relatives
Travel Medicine and Infectious Disease (2010) 8, 161e168
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/tmid
Malaria and travellers visiting friends and relatives Androula Pavli a, Helena C. Maltezou b,* a
Office for Travel Medicine, Hellenic Center for Disease Control and Prevention, Athens, Greece Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, 3-5 Agrafon Street, Athens 15123, Greece b
Received 20 October 2009; received in revised form 12 January 2010; accepted 20 January 2010 Available online 19 February 2010
KEYWORDS Malaria; Imported; VFRs; Immigrants; Pre-travel advice
Summary Among all travel-acquired illnesses, malaria carries the greatest burden not only considering the number of imported cases but also the potential of a fatal outcome. The increased number of imported malaria cases in developed countries in the last decades has been attributed to the increasing number of travel to tropical destinations in combination with the enormous influx of immigrants. At present, immigrants visiting friends and relatives (VFRs) constitute the most significant group of travellers for malaria importation in developed countries, with sub-Saharan Africa destinations carrying the highest risk. VFRs typically demonstrate travel and behavioural patterns which render them at high risk for acquisition of this largely preventable infection. Pre-travel services are rarely sought by VFRs, whereas misconceptions that they possess life-long immunity against malaria make them less likely to receive or adhere to antimalarial chemoprophylaxis recommendations. There is an urgent need to increase awareness about malaria of this group of travellers. ª 2010 Elsevier Ltd. All rights reserved.
Introduction It is less than 40 years since malaria has been eradicated from Europe and North America as a result of ecologic interventions, urbanization, and, since the 1940s, the wide availability of antimalarial drugs and insecticides.1,2 However, malaria remains largely uncontrolled in many tropical and subtropical areas, with an estimated annual global burden of 350e500 million infections and
* Corresponding author. Tel.: þ30 210 5212 175, fax: þ30 210 5212 177. E-mail address: [email protected] (H.C. Maltezou).
approximately 1 million deaths, of which 90% occur in subSaharan Africa. Currently malaria is endemic in over 100 tropical and subtropical countries.3,4 International travel is growing rapidly. It has been estimated that international travel will reach approximately 1 billion by 2010 and 1.6 billion by 2020, with the largest increase in travel to tropical and subtropical areas.5 In developed countries, the increasing number of international travel in association with the considerable influx of immigrants from malaria-endemic countries had a significant impact on imported malaria cases.6,7 Currently malaria-endemic countries are visited by more than 125 million international travellers each year,8 whereas more than 30,000 malaria cases occur in European and North American travellers each year.9 Travellers visiting friends
1477-8939/$ - see front matter ª 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2010.01.003
162 and relatives (VFRs) account for up to 50% of international travellers from developed countries.10e13 In the last decade an epidemiological shift has been noted, with VFRs travelling to malaria-endemic countries accounting for an increasing proportion of cases of imported malaria in developed countries.6,11,12,14e26 At present, VFRs are emerging as the most significant group of travellers for importation of malaria in non-endemic countries.7,12,26e32 The aim of this report is to review the burden and trends of malaria associated with VFRs in developed countries. Epidemiologic and preventive aspects are discussed.
Methods A computerized search of the MEDLINE database through June 2009 was conducted using combinations of the words ‘‘imported’’, ‘‘malaria’’, ‘‘international travellers’’, and ‘‘VFRs’’. Publications presenting original data on malaria in VFRs were selected for review. Original articles were also identified from the reference lists of articles selected through the MEDLINE search. Review articles and book chapters were used. Data from public health organizations and travel statistics were also reviewed. Review of the literature revealed that apart from VFRs, terms used frequently include ethnic travellers, migrants, immigrants, foreign-born travellers, and non-nationals. In the current review VFRs are defined as immigrants living in a developed country, distinct ethnically and racially from the majority of population, who return to their homeland to visit friends and relatives.33 This group is also comprised by their children, either foreign-born or born in the country where they reside. Immunity exists in travellers who are recent immigrants born in malaria-endemic areas or in long-term travellers travelling from non-endemic to endemic areas with repeated malaria episodes. Non-immune travellers are short-term travellers or children of migrants born in a non-endemic area.21
Epidemiology and global burden of malaria Malaria is a parasitic disease transmitted to humans by the bite of Anopheles mosquitoes, predominantly between dusk and dawn. Four Plasmodium species (P. falciparum, P. vivax, P. ovale, and P. malariae) cause malaria in humans. Recently a fifth species, P. knowlesi, was implicated in human disease in Southeast Asia.34,35 There are also reports of imported simian malaria among travellers.36,37 Infection is caused predominantly by P. falciparum in sub-Saharan Africa and P. vivax in Southeast Asia, Central and South America, and the Indian subcontinent.38 Infection with P. malariae or P. ovale is rare. Severe disease concerns almost exclusively infection with P. falciparum, although P. vivax may cause life-threatening infections occasionally.4 In areas of stable transmission (most of subSaharan Africa, and parts of northern India, Indonesia, and South America), repeated mosquito bites provide some immunity throughout adulthood and thus severe disease concerns almost exclusively young children and newly arrived persons. In contrast, in unstable endemic areas (parts of India, Southeast Asia, Central and South America) transmission varies greatly from year to year and severe disease may occur throughout life.1,4
A. Pavli, H.C. Maltezou Despite the advances noted in several control programmes at country level, the global human and economic toll associated with malaria remains profound.2,3 In the last decades, the emergence and spread of resistance to common antimalarial drugs and insecticides in almost all endemic areas in association with the lack of a vaccine for clinical use has compromised further malaria control.1,2,4,12 Currently, malaria risk exists in 109 countries in Africa, Asia, the Middle East, Eastern Europe, Central and South America, the Caribbean, and Oceania.3 Sixty percent of malaria cases worldwide occur in sub-Saharan Africa and typically involve children under 5 years and pregnant women, groups that carry the highest morbidity and mortality of this disease.3,4,39 Overall, malaria causes 2% of all deaths worldwide, with an estimated more than 2000 young lives lost daily and global direct losses of 12 billion US$ each year.2,3,6
Malaria and VFRs Since the 1980s, the incidence of imported malaria has increased steadily in many developed countries. For example, the number of imported cases reported to the United States Centers for Disease Prevention and Control (CDC) increased from 930 in 1982 to 1564 in 2006 cases per year 6; similarly, 477 compared to 5898 imported cases were notified at the National Institute of Health in Italy in 1989 and 1997, respectively.7 These numbers may be underestimated because of underreporting or differences in surveillance systems, and also because a number of cases may develop while abroad. The increasing trends are attributed to the rapid growth of international travel to several tropical areas, reflecting on one hand the increasing popularity of these destinations among citizens of developed countries, and on the other hand the increasing number of immigrants from malaria-endemic countries to developed countries. Additional reasons include changes in travel patterns (e.g. more adventure travels and ecotourism) and more intense malaria transmission in certain endemic destinations.5e7,15e17,22,24e29,40,41 Furthermore, the increasing influx of immigrants from malaria-endemic countries constitutes the pool for the increasing numbers of VFRs. In the United Kingdom, a three-fold increase of VFRs has been recorded from 1982 through 2002.41 Given the global immigration trends towards developed countries and the expected improvement of the immigrants’ income, it is expected that this group of travellers will expand further. During the past two decades a shift in the profile of imported malaria in developed countries has been noted, with an increasing proportion of cases involving VFRs.6,12,15e19 Currently, VFRs are emerging as the most significant group of travellers for importation of malaria in non-endemic countries.12,24,25,40 We found in the MEDLINE 14 original studies reporting data on malaria among VFRs (Table 1); of them, 8 were from Europe, 5 from North America, and 1 from Australia.6,7,11,16,18,20e22,24,26,27,28e 30,42 A summary of their data revealed that VFRs accounted for 21.1e68.3% out of 54,221 reported imported malaria cases from 1984e2007, where such information was available. Significant variations in the proportion of VFRs among imported malaria cases were observed, even within
Original studies of imported malaria cases among VFRs. % of international travellersa
% of VFRs
Area of infection (%)
Appropriate chemoprohylaxis (%)b
Severe casesc (%)/fatality rate(%)
246
100
36.6d
NR
2.46/0
2005e2007
75
100
56
NR
NR
Italy16
1984e1993
175
100
21.1
1
9.1/0
Italy7
1989e1997
5898
97.8
66.9
40
NR/0.93
Italy21
2000e2004
380
100
40,5
26.2
23/0
Spain30
1989e2005
1579
99.9
40.7
Asia 40 Africa 13 America 2 Papua New Guinea 35 Solomon islands & Vanuatu 9 Multiple countries 2e Africa 57 Indian Subcontinent 43 Africa 91.4 Americas 4.0 Pacific islands 2.3 Southeast Asia 2.3 Africa 88.4 Asia 8.2 Americas 2.6 Oceania 0.4 Europe 0.4 Africa 94,5 Asia 4,5 Oceania & Americas 1 Africa 77,5 Asia 7,3 America 9 Oceania 0,2 Unknown 6
3.1
NR/0.045
Switzerland20
1994e2004
109
88.9
33
NR
37
Switzerland58 The Netherlands18
2004e2005 2000e2002
22 302
100 100
63.3% 68.3 (4.8: children of VFRs)
NR NR
NR NR
Country of study
Year (s)
Australia22
1990e1994
Greece42
No. of cases
Africa 82 Asia 5 Middle East 2 Americas 2 Unknown 10 Africa (mainly) Sub-Saharan Africa 86 Asia 7.8 Americas 6 Unknown 0.2
163
(continued on next page)
Malaria and VFRs
Table 1
164
Table 1 (continued ) Country of study
Year (s)
No. of cases
% of international travellersa
% of VFRs
Area of infection (%)
Appropriate chemoprohylaxis (%)b
Severe casesc (%)/fatality rate(%)
United Kingdom24
1987e2006
39,300
87.4 (reported travel history)
33.6
31
NR/0.46
United States26
2004
1324
99.6
52.6f
19.9g
NR/0.03
United States29
2005
1528
99.8
66.9f
20.9g
NR/0.45
United States6
2006
1564
100
50.9f
20.9g
NR/0.045
United States11
2007
1505
99.9
62.8f
Africa 71.6 South Asia 24.6 Far East & Southeast Asia 1.6 Americas & Caribbean 1.01 Oceania 1 Middle East 0.2 Africa 68 Asia 14.5 Americas 14.5 Oceania 3.0 Africa 66.9 Asia & Middle East 15.1 Americas 15.8 Oceania 2.0 Africa 69.6 Asia 18.0 Americas 10.5 Oceania 1.9 Africa 64.4 Asia 21.9 Americas 11.3 Oceania 2.3
20.3g
NR/0.06
A. Pavli, H.C. Maltezou
NR: not reported. a Those with reported travel history. b According to destination and duration of travel. c As reported by the studies ccording to destination and duration of travel. d Born in a country with endemic malaria. e Travel in 3 other areas. f Out of US civilians. g Out of travellers in whom this information was available.
Malaria and VFRs the same country (e.g. 21.1e66.9% in Italy), which may be attributed to differences in migrant populations across the reporting countries. Most cases (57e94.5%) were contracted in Africa,6,7,11,16,18,20,21,24,26,28e30,42 with the exception of Australia, where Asia and Papua New Guinea constituted the most frequent areas of acquisition of infection (40% and 35% of cases, respectively).22 Overall, Asia was the second most common area of acquisition of infection, accounting for up to 26.2% of cases (Table 1). Similar data have been reported by the GeoSentinel Surveillance Network and the European Network on Surveillance of Imported Infectious Diseases.15,25,40 As a rule, the country of acquisition of malaria infection among VFRs corresponds with their country of origin. Due to the enhanced movement of populations between several developed countries and their ex-colonies (e.g. between Spain and Equator Guinea, and between France and the Comoros Islands), a considerable proportion of cases are acquired in the latter, mainly among VFRs.43,44 Malaria is contracted predominantly in rural areas; however, transmission may occur in urban areas of sub-Sahara Africa, and to a lesser extent in urban areas of India.45 Imported malaria cases in developed countries demonstrate seasonal patterns, that are determined by the timing of travel as well as the season of malaria transmission in travel destinations: imported P. falciparum cases peak in September and January, whereas imported P. vivax cases peak during summer.24,44 Symptoms of P. falciparum malaria develop most often within 30 days after arrival, whereas malaria caused by P. vivax may manifest several months or even a year later.11,38 Studies show that P. falciparum account for the majority of imported malaria cases acquired in Africa.24,25 Using the GeoSentinel surveillance network database and statistics from the World Travel Organization, the relative risks for acquiring malaria per region visited compared with a very low-risk area (e.g. Europe, North America) were as follows: Sub-Saharan Africa: 208, Oceania: 77, South Asia: 54, Central America: 38, Southeast Asia: 11.5, and South America: 8.25 A recent study of 17,009 imported malaria cases in children 18 years in 11 developed countries (8 European countries, Australia, United States, and Japan) during 1992e2002 showed that the highest risk for acquisition of infection were the Comoros Islands (1030/10,000 arrivals), followed by Democratic Republic of Congo (778), Central African Republic (444), and other African destinations.46 Of all paediatric cases with known country of infection, more than 75% were acquired in Africa, mainly West Africa, whereas the majority of children were migrants VFRs.46 Children VFRs account for a considerable number of imported malaria cases in developed countries.11,21,23,30 In an Italian study of 337 adults and 43 children with malaria, children VFRs develop significantly higher parasitaemia and significantly lower platelet counts compared to recent immigrants (p Z 0.016 and 0.042, respectively); in addition, time of parasitaemia clearance and duration of fever were longer in children VFRs compared to recent immigrants (p Z 0.014 and 0.0085, respectively).21 In this study, the ratio of severe to uncomplicated malaria cases was highest in the paediatric age group.21 Due to lack of any exposure to the parasite in the past, children of migrants raised in developed countries are at high risk for severe malaria.
165 Migrants from highly endemic areas generally develop disease-modifying immunity that diminishes malariarelated morbidity and mortality. Such immunity is lost progressively after a long period in the absence of repeated exposure to infective mosquito bites; however there is evidence that it still offers some level of protection.17,21 Long- lasting immunity has been found in VFRs who reside in non-endemic countries for at least four years, irrespective of the frequency of visits to their native country.47 It has been found that VFRs are less likely to develop complications (3.7% versus 6.3%) 15 or a fatal outcome (1.2% versus 2.3%) compared to non-immune travellers.7 Parasitaemia was also significantly lower in VFRs compared with other travellers in a study from Italy (mean levels of P. falciparum parasitaemia: 996 versus 9103; p < 0.001).17 Clinical and parasitological findings vary in relation to the status of immunity to malaria. Immune VFRs tend to develop significantly lower parasitaemia (p Z 0.0032), shorter parasite clearance time (p Z 0.025), and shorter duration of fever (p Z 0.0026) compared to non-immune VFRs.21 Overall, VFRs with malaria develop less often complications or have a fatal outcome compared with non-immune travellers.15,24
Why are VFRs at higher risk for malaria? VFRs travel frequently to rural areas with high malaria transmission rates, away from popular tourist destinations where living standards are far below those encountered in their country of residence and mosquito bite precautions may not be available. They demonstrate typical travel and behavioural patterns, which render them at high risk for acquisition of infection. Unless they use appropriate protective measures and adhere to chemoprophylaxis, in reality their risk for contracting malaria approximates the risk of the local population. Compared with other travellers, VFRs are younger, more likely to travel for longer periods and with their children or send their children to their family members in their country of origin. They are also more likely to stay at local people’s homes and less likely to travel on an organized trip.25,30,40,42,48 In addition to higher exposure, VFRs are less likely to take adequate preventive measures.49 No use of malaria chemoprophylaxis, or inadequate chemoprophylaxis, in terms of appropriate drug choice or adherence to it, is a common denominator in all studies of imported malaria, and it was reported by 59e99% of travellers with malaria reviewed by us (Table 1). VFRs are even less likely to use antimalarial chemoprophylaxis compared to other travellers (4% versus 36% among Italian citizens in a study).7 VFRs rarely seek pre-travel medical advice. A survey conducted in immigrants in Italy, revealed that the length of stay was the only factor associated with the use of pretravel advice and chemoprophylaxis among them.50 They may face difficulties in accessing health-care services because of economic, cultural, language, or legal issues. A significant reason for not seeking pre-travel advice is cost.25,40,42,50 Misconception about life-long immunity against malaria is popular among immigrants.10,30,48 A survey of immigrants travelling from Canada to India, revealed that although 69% of them considered malaria as
166 a moderate to severe illness, 41% believed that they were not at risk for acquisition of infection.49 In this study, intention to use antimalarial chemoprophylaxis or measures for protection from mosquito bites were reported by only 31% and <10% of them, respectively.49 Prescription of inappropriate chemoprophylaxis is also common.49
Assessment and prevention of the risk of malaria There are several factors which influence the risk for acquisition of infection, including country destination, areas visited, season and duration of travel, type of accommodation (e.g. camping, air-conditioned hotel), and involvement in outdoor activities. Furthermore, accessibility to health-care services is also very important with regards to acquisition of infection. Malaria in travellers is largely a preventable infection. Malaria prevention for VFRs relies on: increasing awareness about malaria risk in travel destinations, preventive measures to reduce mosquito bite, antimalarial chemoprophylaxis, and prompt diagnosis and treatment.31 Mosquito bites can be prevented by using appropriate insect repellents, bed nets, and clothes. N,N-diethylmetatoluamide (DEET) is the most effective insect repellent, offering protection for up to 12 hours at 50% concentration. DEET is safe for use in infants 2 months, pregnants and breast-feeding women.31,51 Clothing that covers most of the body surface should be worn, especially between dusk and down. Clothes may be sprayed with permethrin. Pregnant women and parents with young children should be discouraged from travelling to malariaendemic areas if possible 46,52; if travel is inevitable, repellents, insecticide-treated bednets (ITNs), and chemoprophylaxis should be strongly recommended. When accommodations are not screened adequately or air conditioned, such as those visited by VFRs in rural areas, it is essential to use bednets. Pre-treated, long-lasting ITNs are most effective and can be purchased prior to travelling, or sprayed after. Bednets should be strong and with a mesh size of <1.5 mm and tucked under mattresses. It is particularly important to emphasize the use of ITNs for VFRs travelling for long periods.53 Malarial chemoprophylaxis is the most effective strategy for the prevention of severe complications and death caused by P. falciparum malaria, and should be administered before, during and after the exposure period (primary chemoprophylaxis). Terminal prophylaxis is used to prevent relapses or delayed onset malaria caused by hypnozoites of P. vivax or P. ovale.51 Chemoprophylaxis should be selected on the basis of individual risk, local drug resistance patterns, and underlying medical conditions of the traveller, taking into consideration the efficacy, safety, cost, and convenience of available drugs. The development of adverse events is a major cause of non-adherence to recommended regimens.31,51 Currently recommended drugs include mefloquine, chloroquine, atovaquone/proguanil, doxycycline, and primaquine.8,31,51 Mefloquine has a good safety profile for children without age and weight restriction, and a lower cost which makes it the preferred agent for children VFRs who are more likely to travel for long periods of time.54 It is important to stress to VFRs that
A. Pavli, H.C. Maltezou malaria chemoprophylaxis does not prevent infection but rather prevents clinical disease when the parasite emerges from the liver into the blood. If medication is discontinued sooner than recommended, a substantial risk of acquiring clinical malaria exists.10 They should also be advised to obtain sufficient supplies of antimalarial chemoprophylactic drugs before their departure. Health-care providers should consult the latest information on antimalarial resistance patterns before prescribing chemoprophylaxis, using the website of the World Health Organization or other public health organizations. Travellers should be informed that no preventive measure is completely effective, and that malaria is a medical emergency. Malaria may mimic several tropical as well as common cosmopolitan illnesses, and should be considered in any traveller who presents with fever or a history of fever between 7 days after entering a malariaendemic area and 6 months after his return, regardless of whether he has taken chemoprophylaxis; blood films should be tested immediately for parasites.55 Standby malaria treatment (or self-treatment) may be life-saving for travellers who are unable to access health-care services within 24 h after the onset of fever or those who are travelling to areas of low-risk for malaria transmission and may be the only affordable, tolerated option for long-term visitors.8,10,51 These persons still have to access medical care as soon as possible. Detailed instructions on the recognition of symptoms, drug dosing and adverse effects should be provided.8,51 Ideally, clinics attended frequently by immigrants could offer pre-travel services, since familiarity and easy access might encourage their use. Language barriers could be surpassed by multi-lingual health-care providers and information about precautions against malaria should be disseminated through posters and leaflets. Primary healthcare providers, who may also provide travel health advice, should take the opportunity and ask patients who were born in endemic countries, or have ethnic links to such countries whether they will be visiting friends and relatives in the future and provide with relevant travel health information.56 In urban centres which are home to large immigrant populations, a routine screen for high-risk travel and coordination of pre-travel care with paediatric preventive care may help secure the best possible pre-travel preparation in order to prevent travel-related morbidity before and after the trip.54 Perceptions of immunity and personal risk of VFRs which may influence usage of chemoprophylaxis should be explored, and both culturally and linguistically appropriate information should be provided.10,57 VFRs should be informed about the potential risks when purchasing lower quality drugs abroad. Travel health advisors may choose less expensive malaria prophylaxis. Policies must be reviewed to ensure that travel-related services are accessible, affordable, and appropriate for these diverse populations.
Conclusions Advance in travel medicine have been of little benefit to VFRs, as indicated by the increasing trends of imported malaria among them. This group of travellers is at an increased risk for acquisition of malaria because of their
Malaria and VFRs travel, behavioural, and cultural patterns while travelling to their country of origin. Pre-travel services are rarely used by VFRs. Popular beliefs that they have life-long immunity against malaria render VFRs less likely to receive or adhere to antimalarial chemoprophylaxis. New strategies should be explored to approach this group of travellers and increase awareness about malaria. Pre-travel services should be competent, affordable, convenient and accessible to VFRs. Medical and public health organizations should consider new approaches to disseminate information on travel health risks to VFRs such as community-based campaigns in areas with large foreign-born populations. Efforts to prevent VFRs morbidity will also contribute to global public health.
Conflict of interest We disclose no financial or personal relationship with other people or organizations that could inappropriately influence our work. Both authors have made substantial contributions to the conception and design of the article, review and interpretation of literature, drafting of the manuscript, and final approval of the submitted version.
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168 36. Simian malaria in a U.S. traveller e New York. MMWR Morb Mortal Wkly Rep 2008;2009(58):229e32. 37. Kantele A, Marti H, Felger I, Mu ¨ller D, Jokiranta TS. Monkey malaria in a European traveller returning from Malaysia. Emerg Infect Dis 2008;14:1434e6. 38. Muhlberger N, Jelinek T, Gascon J, Probst M, Zoller T, Schunk M. Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop. Malar J 2004;3:5. 39. Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic countries. Am J Trop Med Hyg 2001;64:28e35. 40. Leder K, Tong S, Weld L, Kain KC, Wilder-Smith A, von Sonnerburg Black, et al. Illness in travellers visiting friends and relatives: a review of the Geosentinel surveillance network. Clin Infect Dis 2006;43:1185e93. 41. National statistics travel trends. A report of the international passenger survey, http://www.statistics.gov.uk/downloads/ theme_transport/TTrends02.pdf; 2002 [accessed 24.11.09]. 42. Pavli A, Katerelos P, Pierroutsakos IN, Maltezou HC. Pre-travel counselling in Greece for travellers visiting friends and relatives. Trav Med Infect Dis 2009;7:312e5. 43. Millet JP, de Olalla PG, Gascon J, Prat JG, Trevino B, Pinazo MJ, et al. Imported malaria among African immigrants: is there still a relationship between developed countries and their excolonies? Malar J 2009;8:111. 44. Parola P, Soula G, Gazin P, Foucault C, Delmont J, Brouqui P. Fever in travellers returning from tropical areas: prospective observational study of 613 cases hospitalized in Marseille, France, 1999e2003. Trav Med Infect Dis 2006;4:61e70. 45. Hay SI, Guerra CA, Tatem AJ, Atkinson PM, Show RW. Urbanization, malaria transmission and disease burden in Africa. Nat Rev Microbiol 2005;3:81e90. 46. Stager K, Legros F, Krause G, Low N, Bradley D, Desai M. Imported malaria in children in industrialized countries, 1992e2002. Emerg Infect Dis 2009;15:185e91. 47. Bouchaud O, Cot M, Kony S, Durand R, Schiemann R, Ralaimazava P, et al. Do African immigrants living in France have long-term malarial immunity? Am J Trop Med Hyg 2005 Jan;72(1):21e5.
A. Pavli, H.C. Maltezou 48. Angell SY, Cetron MS. Health disparities among travellers visiting friends and relatives abroad. Ann Intern Med 2005;142: 67e72. 49. Dos Santos CC, Anvar A, Keystone JS, Kain KC. Survey of use of malaria prevention measures by Canadians visiting India. CMAJ 1999;160:195e9. 50. Scolari C, Tedoldi S, Casalini C. Knowledge, attitudes, and practices on malaria preventive measures of migrants attending a public health clinic in Northern Italy. J Travel Med 2002;9:160e2. 51. Centers for Disease Control and Prevention. Traveller’s health e yellOW book. Prevention of specific infectious diseases: malaria, http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx [accessed 24.11.09]. 52. Lindsay S, Ansell J, Selman C, Cox V, Hamilton K, Walraven G. Effect of pregnancy on exposure to malaria mosquitoes. Lancet 2000;355:1972. 53. Rossi I, Genton B. Malaria prevention for long-term travellers. Rev Med Suisse 2009;5:1007e11. 54. Hagmann S, Benavides V, Neugebauer R, Purswani M. Travel health care for immigrant children visiting friends and relatives abroad: retrospective analysis of a hospital-based travel health service in a US Urban underserved area. J Travel Med 2009;16: 407e12. 55. Lalloo DG, Shingadia D, Pasvol G, Chiodini PL, Whitty CJ, Beeching NJ, et al. United Kingdom malaria treatment guidelines. J Infect 2007;54:111e21. 56. Health Protection Agency. Foreign travel associated illnessa focus on those visiting friend and relatives. Report, http:// 194.74.226.162/web/HPAwebFile/HPAweb_C/1231419800356; 2008 [accessed 24.11.09]. 57. Pistone T, Guilbert P, Gay F, Malvy D, Ezzedine K, Receveur MC, et al. Malaria risk perception, knowledge and prophylaxis practices among travelers of African ethnicity living in Paris and visiting their country of origin in sub-Saharan Africa. Trans R Soc Trop Med Hyg 2007;101:990e5. 58. Fenner L, Weber R, Steffen R, Schlagenhauf P. Imported infectious disease and purpose of travel, Switzerland. Emerg Infec Dis 2007;13:217e22.
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/tmid
Malaria and travellers visiting friends and relatives Androula Pavli a, Helena C. Maltezou b,* a
Office for Travel Medicine, Hellenic Center for Disease Control and Prevention, Athens, Greece Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, 3-5 Agrafon Street, Athens 15123, Greece b
Received 20 October 2009; received in revised form 12 January 2010; accepted 20 January 2010 Available online 19 February 2010
KEYWORDS Malaria; Imported; VFRs; Immigrants; Pre-travel advice
Summary Among all travel-acquired illnesses, malaria carries the greatest burden not only considering the number of imported cases but also the potential of a fatal outcome. The increased number of imported malaria cases in developed countries in the last decades has been attributed to the increasing number of travel to tropical destinations in combination with the enormous influx of immigrants. At present, immigrants visiting friends and relatives (VFRs) constitute the most significant group of travellers for malaria importation in developed countries, with sub-Saharan Africa destinations carrying the highest risk. VFRs typically demonstrate travel and behavioural patterns which render them at high risk for acquisition of this largely preventable infection. Pre-travel services are rarely sought by VFRs, whereas misconceptions that they possess life-long immunity against malaria make them less likely to receive or adhere to antimalarial chemoprophylaxis recommendations. There is an urgent need to increase awareness about malaria of this group of travellers. ª 2010 Elsevier Ltd. All rights reserved.
Introduction It is less than 40 years since malaria has been eradicated from Europe and North America as a result of ecologic interventions, urbanization, and, since the 1940s, the wide availability of antimalarial drugs and insecticides.1,2 However, malaria remains largely uncontrolled in many tropical and subtropical areas, with an estimated annual global burden of 350e500 million infections and
* Corresponding author. Tel.: þ30 210 5212 175, fax: þ30 210 5212 177. E-mail address: [email protected] (H.C. Maltezou).
approximately 1 million deaths, of which 90% occur in subSaharan Africa. Currently malaria is endemic in over 100 tropical and subtropical countries.3,4 International travel is growing rapidly. It has been estimated that international travel will reach approximately 1 billion by 2010 and 1.6 billion by 2020, with the largest increase in travel to tropical and subtropical areas.5 In developed countries, the increasing number of international travel in association with the considerable influx of immigrants from malaria-endemic countries had a significant impact on imported malaria cases.6,7 Currently malaria-endemic countries are visited by more than 125 million international travellers each year,8 whereas more than 30,000 malaria cases occur in European and North American travellers each year.9 Travellers visiting friends
1477-8939/$ - see front matter ª 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2010.01.003
162 and relatives (VFRs) account for up to 50% of international travellers from developed countries.10e13 In the last decade an epidemiological shift has been noted, with VFRs travelling to malaria-endemic countries accounting for an increasing proportion of cases of imported malaria in developed countries.6,11,12,14e26 At present, VFRs are emerging as the most significant group of travellers for importation of malaria in non-endemic countries.7,12,26e32 The aim of this report is to review the burden and trends of malaria associated with VFRs in developed countries. Epidemiologic and preventive aspects are discussed.
Methods A computerized search of the MEDLINE database through June 2009 was conducted using combinations of the words ‘‘imported’’, ‘‘malaria’’, ‘‘international travellers’’, and ‘‘VFRs’’. Publications presenting original data on malaria in VFRs were selected for review. Original articles were also identified from the reference lists of articles selected through the MEDLINE search. Review articles and book chapters were used. Data from public health organizations and travel statistics were also reviewed. Review of the literature revealed that apart from VFRs, terms used frequently include ethnic travellers, migrants, immigrants, foreign-born travellers, and non-nationals. In the current review VFRs are defined as immigrants living in a developed country, distinct ethnically and racially from the majority of population, who return to their homeland to visit friends and relatives.33 This group is also comprised by their children, either foreign-born or born in the country where they reside. Immunity exists in travellers who are recent immigrants born in malaria-endemic areas or in long-term travellers travelling from non-endemic to endemic areas with repeated malaria episodes. Non-immune travellers are short-term travellers or children of migrants born in a non-endemic area.21
Epidemiology and global burden of malaria Malaria is a parasitic disease transmitted to humans by the bite of Anopheles mosquitoes, predominantly between dusk and dawn. Four Plasmodium species (P. falciparum, P. vivax, P. ovale, and P. malariae) cause malaria in humans. Recently a fifth species, P. knowlesi, was implicated in human disease in Southeast Asia.34,35 There are also reports of imported simian malaria among travellers.36,37 Infection is caused predominantly by P. falciparum in sub-Saharan Africa and P. vivax in Southeast Asia, Central and South America, and the Indian subcontinent.38 Infection with P. malariae or P. ovale is rare. Severe disease concerns almost exclusively infection with P. falciparum, although P. vivax may cause life-threatening infections occasionally.4 In areas of stable transmission (most of subSaharan Africa, and parts of northern India, Indonesia, and South America), repeated mosquito bites provide some immunity throughout adulthood and thus severe disease concerns almost exclusively young children and newly arrived persons. In contrast, in unstable endemic areas (parts of India, Southeast Asia, Central and South America) transmission varies greatly from year to year and severe disease may occur throughout life.1,4
A. Pavli, H.C. Maltezou Despite the advances noted in several control programmes at country level, the global human and economic toll associated with malaria remains profound.2,3 In the last decades, the emergence and spread of resistance to common antimalarial drugs and insecticides in almost all endemic areas in association with the lack of a vaccine for clinical use has compromised further malaria control.1,2,4,12 Currently, malaria risk exists in 109 countries in Africa, Asia, the Middle East, Eastern Europe, Central and South America, the Caribbean, and Oceania.3 Sixty percent of malaria cases worldwide occur in sub-Saharan Africa and typically involve children under 5 years and pregnant women, groups that carry the highest morbidity and mortality of this disease.3,4,39 Overall, malaria causes 2% of all deaths worldwide, with an estimated more than 2000 young lives lost daily and global direct losses of 12 billion US$ each year.2,3,6
Malaria and VFRs Since the 1980s, the incidence of imported malaria has increased steadily in many developed countries. For example, the number of imported cases reported to the United States Centers for Disease Prevention and Control (CDC) increased from 930 in 1982 to 1564 in 2006 cases per year 6; similarly, 477 compared to 5898 imported cases were notified at the National Institute of Health in Italy in 1989 and 1997, respectively.7 These numbers may be underestimated because of underreporting or differences in surveillance systems, and also because a number of cases may develop while abroad. The increasing trends are attributed to the rapid growth of international travel to several tropical areas, reflecting on one hand the increasing popularity of these destinations among citizens of developed countries, and on the other hand the increasing number of immigrants from malaria-endemic countries to developed countries. Additional reasons include changes in travel patterns (e.g. more adventure travels and ecotourism) and more intense malaria transmission in certain endemic destinations.5e7,15e17,22,24e29,40,41 Furthermore, the increasing influx of immigrants from malaria-endemic countries constitutes the pool for the increasing numbers of VFRs. In the United Kingdom, a three-fold increase of VFRs has been recorded from 1982 through 2002.41 Given the global immigration trends towards developed countries and the expected improvement of the immigrants’ income, it is expected that this group of travellers will expand further. During the past two decades a shift in the profile of imported malaria in developed countries has been noted, with an increasing proportion of cases involving VFRs.6,12,15e19 Currently, VFRs are emerging as the most significant group of travellers for importation of malaria in non-endemic countries.12,24,25,40 We found in the MEDLINE 14 original studies reporting data on malaria among VFRs (Table 1); of them, 8 were from Europe, 5 from North America, and 1 from Australia.6,7,11,16,18,20e22,24,26,27,28e 30,42 A summary of their data revealed that VFRs accounted for 21.1e68.3% out of 54,221 reported imported malaria cases from 1984e2007, where such information was available. Significant variations in the proportion of VFRs among imported malaria cases were observed, even within
Original studies of imported malaria cases among VFRs. % of international travellersa
% of VFRs
Area of infection (%)
Appropriate chemoprohylaxis (%)b
Severe casesc (%)/fatality rate(%)
246
100
36.6d
NR
2.46/0
2005e2007
75
100
56
NR
NR
Italy16
1984e1993
175
100
21.1
1
9.1/0
Italy7
1989e1997
5898
97.8
66.9
40
NR/0.93
Italy21
2000e2004
380
100
40,5
26.2
23/0
Spain30
1989e2005
1579
99.9
40.7
Asia 40 Africa 13 America 2 Papua New Guinea 35 Solomon islands & Vanuatu 9 Multiple countries 2e Africa 57 Indian Subcontinent 43 Africa 91.4 Americas 4.0 Pacific islands 2.3 Southeast Asia 2.3 Africa 88.4 Asia 8.2 Americas 2.6 Oceania 0.4 Europe 0.4 Africa 94,5 Asia 4,5 Oceania & Americas 1 Africa 77,5 Asia 7,3 America 9 Oceania 0,2 Unknown 6
3.1
NR/0.045
Switzerland20
1994e2004
109
88.9
33
NR
37
Switzerland58 The Netherlands18
2004e2005 2000e2002
22 302
100 100
63.3% 68.3 (4.8: children of VFRs)
NR NR
NR NR
Country of study
Year (s)
Australia22
1990e1994
Greece42
No. of cases
Africa 82 Asia 5 Middle East 2 Americas 2 Unknown 10 Africa (mainly) Sub-Saharan Africa 86 Asia 7.8 Americas 6 Unknown 0.2
163
(continued on next page)
Malaria and VFRs
Table 1
164
Table 1 (continued ) Country of study
Year (s)
No. of cases
% of international travellersa
% of VFRs
Area of infection (%)
Appropriate chemoprohylaxis (%)b
Severe casesc (%)/fatality rate(%)
United Kingdom24
1987e2006
39,300
87.4 (reported travel history)
33.6
31
NR/0.46
United States26
2004
1324
99.6
52.6f
19.9g
NR/0.03
United States29
2005
1528
99.8
66.9f
20.9g
NR/0.45
United States6
2006
1564
100
50.9f
20.9g
NR/0.045
United States11
2007
1505
99.9
62.8f
Africa 71.6 South Asia 24.6 Far East & Southeast Asia 1.6 Americas & Caribbean 1.01 Oceania 1 Middle East 0.2 Africa 68 Asia 14.5 Americas 14.5 Oceania 3.0 Africa 66.9 Asia & Middle East 15.1 Americas 15.8 Oceania 2.0 Africa 69.6 Asia 18.0 Americas 10.5 Oceania 1.9 Africa 64.4 Asia 21.9 Americas 11.3 Oceania 2.3
20.3g
NR/0.06
A. Pavli, H.C. Maltezou
NR: not reported. a Those with reported travel history. b According to destination and duration of travel. c As reported by the studies ccording to destination and duration of travel. d Born in a country with endemic malaria. e Travel in 3 other areas. f Out of US civilians. g Out of travellers in whom this information was available.
Malaria and VFRs the same country (e.g. 21.1e66.9% in Italy), which may be attributed to differences in migrant populations across the reporting countries. Most cases (57e94.5%) were contracted in Africa,6,7,11,16,18,20,21,24,26,28e30,42 with the exception of Australia, where Asia and Papua New Guinea constituted the most frequent areas of acquisition of infection (40% and 35% of cases, respectively).22 Overall, Asia was the second most common area of acquisition of infection, accounting for up to 26.2% of cases (Table 1). Similar data have been reported by the GeoSentinel Surveillance Network and the European Network on Surveillance of Imported Infectious Diseases.15,25,40 As a rule, the country of acquisition of malaria infection among VFRs corresponds with their country of origin. Due to the enhanced movement of populations between several developed countries and their ex-colonies (e.g. between Spain and Equator Guinea, and between France and the Comoros Islands), a considerable proportion of cases are acquired in the latter, mainly among VFRs.43,44 Malaria is contracted predominantly in rural areas; however, transmission may occur in urban areas of sub-Sahara Africa, and to a lesser extent in urban areas of India.45 Imported malaria cases in developed countries demonstrate seasonal patterns, that are determined by the timing of travel as well as the season of malaria transmission in travel destinations: imported P. falciparum cases peak in September and January, whereas imported P. vivax cases peak during summer.24,44 Symptoms of P. falciparum malaria develop most often within 30 days after arrival, whereas malaria caused by P. vivax may manifest several months or even a year later.11,38 Studies show that P. falciparum account for the majority of imported malaria cases acquired in Africa.24,25 Using the GeoSentinel surveillance network database and statistics from the World Travel Organization, the relative risks for acquiring malaria per region visited compared with a very low-risk area (e.g. Europe, North America) were as follows: Sub-Saharan Africa: 208, Oceania: 77, South Asia: 54, Central America: 38, Southeast Asia: 11.5, and South America: 8.25 A recent study of 17,009 imported malaria cases in children 18 years in 11 developed countries (8 European countries, Australia, United States, and Japan) during 1992e2002 showed that the highest risk for acquisition of infection were the Comoros Islands (1030/10,000 arrivals), followed by Democratic Republic of Congo (778), Central African Republic (444), and other African destinations.46 Of all paediatric cases with known country of infection, more than 75% were acquired in Africa, mainly West Africa, whereas the majority of children were migrants VFRs.46 Children VFRs account for a considerable number of imported malaria cases in developed countries.11,21,23,30 In an Italian study of 337 adults and 43 children with malaria, children VFRs develop significantly higher parasitaemia and significantly lower platelet counts compared to recent immigrants (p Z 0.016 and 0.042, respectively); in addition, time of parasitaemia clearance and duration of fever were longer in children VFRs compared to recent immigrants (p Z 0.014 and 0.0085, respectively).21 In this study, the ratio of severe to uncomplicated malaria cases was highest in the paediatric age group.21 Due to lack of any exposure to the parasite in the past, children of migrants raised in developed countries are at high risk for severe malaria.
165 Migrants from highly endemic areas generally develop disease-modifying immunity that diminishes malariarelated morbidity and mortality. Such immunity is lost progressively after a long period in the absence of repeated exposure to infective mosquito bites; however there is evidence that it still offers some level of protection.17,21 Long- lasting immunity has been found in VFRs who reside in non-endemic countries for at least four years, irrespective of the frequency of visits to their native country.47 It has been found that VFRs are less likely to develop complications (3.7% versus 6.3%) 15 or a fatal outcome (1.2% versus 2.3%) compared to non-immune travellers.7 Parasitaemia was also significantly lower in VFRs compared with other travellers in a study from Italy (mean levels of P. falciparum parasitaemia: 996 versus 9103; p < 0.001).17 Clinical and parasitological findings vary in relation to the status of immunity to malaria. Immune VFRs tend to develop significantly lower parasitaemia (p Z 0.0032), shorter parasite clearance time (p Z 0.025), and shorter duration of fever (p Z 0.0026) compared to non-immune VFRs.21 Overall, VFRs with malaria develop less often complications or have a fatal outcome compared with non-immune travellers.15,24
Why are VFRs at higher risk for malaria? VFRs travel frequently to rural areas with high malaria transmission rates, away from popular tourist destinations where living standards are far below those encountered in their country of residence and mosquito bite precautions may not be available. They demonstrate typical travel and behavioural patterns, which render them at high risk for acquisition of infection. Unless they use appropriate protective measures and adhere to chemoprophylaxis, in reality their risk for contracting malaria approximates the risk of the local population. Compared with other travellers, VFRs are younger, more likely to travel for longer periods and with their children or send their children to their family members in their country of origin. They are also more likely to stay at local people’s homes and less likely to travel on an organized trip.25,30,40,42,48 In addition to higher exposure, VFRs are less likely to take adequate preventive measures.49 No use of malaria chemoprophylaxis, or inadequate chemoprophylaxis, in terms of appropriate drug choice or adherence to it, is a common denominator in all studies of imported malaria, and it was reported by 59e99% of travellers with malaria reviewed by us (Table 1). VFRs are even less likely to use antimalarial chemoprophylaxis compared to other travellers (4% versus 36% among Italian citizens in a study).7 VFRs rarely seek pre-travel medical advice. A survey conducted in immigrants in Italy, revealed that the length of stay was the only factor associated with the use of pretravel advice and chemoprophylaxis among them.50 They may face difficulties in accessing health-care services because of economic, cultural, language, or legal issues. A significant reason for not seeking pre-travel advice is cost.25,40,42,50 Misconception about life-long immunity against malaria is popular among immigrants.10,30,48 A survey of immigrants travelling from Canada to India, revealed that although 69% of them considered malaria as
166 a moderate to severe illness, 41% believed that they were not at risk for acquisition of infection.49 In this study, intention to use antimalarial chemoprophylaxis or measures for protection from mosquito bites were reported by only 31% and <10% of them, respectively.49 Prescription of inappropriate chemoprophylaxis is also common.49
Assessment and prevention of the risk of malaria There are several factors which influence the risk for acquisition of infection, including country destination, areas visited, season and duration of travel, type of accommodation (e.g. camping, air-conditioned hotel), and involvement in outdoor activities. Furthermore, accessibility to health-care services is also very important with regards to acquisition of infection. Malaria in travellers is largely a preventable infection. Malaria prevention for VFRs relies on: increasing awareness about malaria risk in travel destinations, preventive measures to reduce mosquito bite, antimalarial chemoprophylaxis, and prompt diagnosis and treatment.31 Mosquito bites can be prevented by using appropriate insect repellents, bed nets, and clothes. N,N-diethylmetatoluamide (DEET) is the most effective insect repellent, offering protection for up to 12 hours at 50% concentration. DEET is safe for use in infants 2 months, pregnants and breast-feeding women.31,51 Clothing that covers most of the body surface should be worn, especially between dusk and down. Clothes may be sprayed with permethrin. Pregnant women and parents with young children should be discouraged from travelling to malariaendemic areas if possible 46,52; if travel is inevitable, repellents, insecticide-treated bednets (ITNs), and chemoprophylaxis should be strongly recommended. When accommodations are not screened adequately or air conditioned, such as those visited by VFRs in rural areas, it is essential to use bednets. Pre-treated, long-lasting ITNs are most effective and can be purchased prior to travelling, or sprayed after. Bednets should be strong and with a mesh size of <1.5 mm and tucked under mattresses. It is particularly important to emphasize the use of ITNs for VFRs travelling for long periods.53 Malarial chemoprophylaxis is the most effective strategy for the prevention of severe complications and death caused by P. falciparum malaria, and should be administered before, during and after the exposure period (primary chemoprophylaxis). Terminal prophylaxis is used to prevent relapses or delayed onset malaria caused by hypnozoites of P. vivax or P. ovale.51 Chemoprophylaxis should be selected on the basis of individual risk, local drug resistance patterns, and underlying medical conditions of the traveller, taking into consideration the efficacy, safety, cost, and convenience of available drugs. The development of adverse events is a major cause of non-adherence to recommended regimens.31,51 Currently recommended drugs include mefloquine, chloroquine, atovaquone/proguanil, doxycycline, and primaquine.8,31,51 Mefloquine has a good safety profile for children without age and weight restriction, and a lower cost which makes it the preferred agent for children VFRs who are more likely to travel for long periods of time.54 It is important to stress to VFRs that
A. Pavli, H.C. Maltezou malaria chemoprophylaxis does not prevent infection but rather prevents clinical disease when the parasite emerges from the liver into the blood. If medication is discontinued sooner than recommended, a substantial risk of acquiring clinical malaria exists.10 They should also be advised to obtain sufficient supplies of antimalarial chemoprophylactic drugs before their departure. Health-care providers should consult the latest information on antimalarial resistance patterns before prescribing chemoprophylaxis, using the website of the World Health Organization or other public health organizations. Travellers should be informed that no preventive measure is completely effective, and that malaria is a medical emergency. Malaria may mimic several tropical as well as common cosmopolitan illnesses, and should be considered in any traveller who presents with fever or a history of fever between 7 days after entering a malariaendemic area and 6 months after his return, regardless of whether he has taken chemoprophylaxis; blood films should be tested immediately for parasites.55 Standby malaria treatment (or self-treatment) may be life-saving for travellers who are unable to access health-care services within 24 h after the onset of fever or those who are travelling to areas of low-risk for malaria transmission and may be the only affordable, tolerated option for long-term visitors.8,10,51 These persons still have to access medical care as soon as possible. Detailed instructions on the recognition of symptoms, drug dosing and adverse effects should be provided.8,51 Ideally, clinics attended frequently by immigrants could offer pre-travel services, since familiarity and easy access might encourage their use. Language barriers could be surpassed by multi-lingual health-care providers and information about precautions against malaria should be disseminated through posters and leaflets. Primary healthcare providers, who may also provide travel health advice, should take the opportunity and ask patients who were born in endemic countries, or have ethnic links to such countries whether they will be visiting friends and relatives in the future and provide with relevant travel health information.56 In urban centres which are home to large immigrant populations, a routine screen for high-risk travel and coordination of pre-travel care with paediatric preventive care may help secure the best possible pre-travel preparation in order to prevent travel-related morbidity before and after the trip.54 Perceptions of immunity and personal risk of VFRs which may influence usage of chemoprophylaxis should be explored, and both culturally and linguistically appropriate information should be provided.10,57 VFRs should be informed about the potential risks when purchasing lower quality drugs abroad. Travel health advisors may choose less expensive malaria prophylaxis. Policies must be reviewed to ensure that travel-related services are accessible, affordable, and appropriate for these diverse populations.
Conclusions Advance in travel medicine have been of little benefit to VFRs, as indicated by the increasing trends of imported malaria among them. This group of travellers is at an increased risk for acquisition of malaria because of their
Malaria and VFRs travel, behavioural, and cultural patterns while travelling to their country of origin. Pre-travel services are rarely used by VFRs. Popular beliefs that they have life-long immunity against malaria render VFRs less likely to receive or adhere to antimalarial chemoprophylaxis. New strategies should be explored to approach this group of travellers and increase awareness about malaria. Pre-travel services should be competent, affordable, convenient and accessible to VFRs. Medical and public health organizations should consider new approaches to disseminate information on travel health risks to VFRs such as community-based campaigns in areas with large foreign-born populations. Efforts to prevent VFRs morbidity will also contribute to global public health.
Conflict of interest We disclose no financial or personal relationship with other people or organizations that could inappropriately influence our work. Both authors have made substantial contributions to the conception and design of the article, review and interpretation of literature, drafting of the manuscript, and final approval of the submitted version.
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