- Email: [email protected]
Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
TMAID744_proof ■ 27 May 2014 ■ 1/7
+
MODEL
Travel Medicine and Infectious Disease (2014) xx, 1e7
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis Q7
Androula Pavli a, Paraskevi Smeti a, Athina Spilioti a, Chrysovalantis Silvestros a, Panagiotis Katerelos b, Helena C. Maltezou b,* a
Travel Medicine Office, Hellenic Center for Disease Control and Prevention, Athens, Greece Department for Interventions in Health Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece
b
Received 16 February 2013; received in revised form 14 March 2014; accepted 13 May 2014
KEYWORDS
Q1
Pre-travel; Vaccine; Prophylaxis; Long-term travellers; Typhoid; Rabies; Malaria
Summary The purpose of this prospective, questionnaire-based study is to assess pre-travel vaccinations and malaria prophylaxis for long-term travellers who receive pre-travel advice in Greece. A total of 4721 travellers were studied from January 1, 2009 through December 31, 2012. Travellers sought pre-travel advice at a mean of 19.7 days (range: 0e349 days) before departure. Long-term travellers (1 month) accounted for 2205 (46.7%) of all travellers. Long-term travellers had a mean age of 34.5 years. The majority of them were men (79.8%). In terms of destinations, 84% were visiting malaria-endemic countries and sub-Saharan Africa was the most common destination (17.7%). Most long-term travellers pursued trips for work purposes (70%), visited urban areas (79.6%) and stayed in hotels (29.2%). Yellow fever, typhoid fever, hepatitis A and tetanus/diphtheria vaccines were administered to 1647 (74.7%), 741 (33.6%), 652 (29.5%), and 589 (26.7%) travellers, respectively. Yellow fever vaccine was administered to 339 (87%) and 132 (71%) of long-term travellers to sub-Saharan Africa and South America respectively, whereas typhoid vaccine to 119 (90.8%) and 330 (84.6%) of those travelling to the Indian subcontinent and sub-Saharan Africa respectively. Rabies vaccine was administered to 14 (0.6%) of them. Malaria prophylaxis was recommended to 446 (20%) of long-term travellers. Mefloquine was the most commonly (49%) prescribed agent, and was prescribed to 26.7% of long-term travellers to sub-Sahara Africa. In conclusion, this study revealed that recommendations for vaccine and malaria prophylaxis for long-term travellers to developing countries should be more selective, based on the assessment of all travellers’ and travel characteristics, in order to provide adequate pre-travel preparation for this high risk group
* Corresponding author. Department for Interventions in Health-Care Facilities, Hellenic Centre for Disease Control and Prevention, 3-5 Agrafon Street, Athens, 15123, Greece. Tel.: þ30 210 5212 175; fax: þ30 210 5212 177. E-mail address: [email protected] (H.C. Maltezou). http://dx.doi.org/10.1016/j.tmaid.2014.05.003 1477-8939/ª 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 2/7
+
MODEL
2
A. Pavli et al. of travellers. More focused studies are suggested in order to understand the particular needs of long-term travellers. Increasing awareness of travellers and travel health consultants is very important. ª 2014 Elsevier Ltd. All rights reserved.
Long-term travel is defined typically as a travel of 1 month duration [1]. Reasons for long-term travels include tourism, diplomatic, missionary, Peace Corps Volunteer and humanitarian aid work, education and research, military operations, and corporate expatriation [2e6]. Long-term travels are associated with significant risk for specific health problems [1,5,7e14]. In particular, long-term travels to the tropics predispose to higher risk for acquisition of a wide range of infectious diseases compared to short-term travels, because of prolonged exposure to pathogens, limited environmental hygiene, close contact with the local population, poorly developed infrastructure for water supply and sewerage disposal, extreme climatic conditions, risk-taking behaviour, and lack of medical facilities [9,10]. The risk of malaria acquisition is higher in long-term compared to short-term travellers due to longer period of exposure to mosquito bites and poor compliance with chemoprophylaxis and preventive measures [5,11,14]. Malaria recommendations have been difficult to standardize due to the diversity of long-term travellers and their itineraries [14]. Furthermore, long-term travellers are at higher risk for vaccine-preventable diseases, including hepatitis A, typhoid fever, rabies, hepatitis B, Japanese encephalitis and meningitis [12]. The aim of this study is to assess vaccinations and malaria prophylaxis in long-term travellers from Greece travelling to tropical and subtropical countries.
health-care physicians working in the public or private sector. All international travellers who attended the 57 Regional Public Health Departments from January 1, 2009 through December 31, 2012 were asked to participate in a questionnaire-based study. The questionnaire was completed with the assistance of the health professional. The following data were collected prospectively using one standardized form per traveller: age, gender, nationality, date of departure, travel destination, duration and purpose of travel, type of accommodation, administration of routine and travel vaccines and chemoprophylaxis. Consent was requested from all participants. Approval for the study was given by the Hellenic Center for Disease Control and Prevention. Long-term travel was defined as a trip of 1 month duration, while short-term travel was defined as a trip of <1 month. Urban accommodation was defined as towns with a population of 5000 people, whereas rural accommodation was defined as villages of <5000 population or staying in the countryside. Statistical analysis was performed using the STATA 8.0 statistical package. c2 and t-test were used in order to investigate any possible relation of duration of travel with travellers’ and/or travel characteristics. P-values of 0.05 were considered statistically significant. The statistically significant parameters were used as independent variables in a logistic regression model with duration of travel as a dependant variable.
2. Methods
3. Results
In Greece pre-travel services are provided mainly in the 57 Regional Departments of Public Health, which are the solely authorized yellow fever vaccination centres in this country. Rabies, typhoid, tetravalent meningitis A,C,W135,Y, and cholera vaccines are also delivered exclusively through these centres; however other travel and routine vaccines are also administered. Pre-travel services are provided according to the guidelines of the Hellenic Centre for Disease Control and Prevention, the World Health Organization and the United States Centers for Disease Control and Prevention guidelines. Routine vaccines are administered in accordance with the National Vaccination Program of Greece, which include vaccines against: tetanusdiphtheria-pertussis, poliomyelitis, Haemophilus influenzae type B, measlesemumpserubella (MMR), hepatitis A, hepatitis B, pneumococcus, meningococcus serotype C, human papilloma virus, tuberculosis (Bacillus CalmetteGue ´rin vaccine), influenza (high risk groups), and rotavirus. These vaccines are administered mainly by paediatricians, but also by internal medicine physicians and primary
A total of 4721 international travellers participated in the study, with a participation rate ranging from 70% to 80% per Public Health Department. Most (40%) of participants were from the region of Attica. Travellers sought pre-travel advice at a mean of 19.7 days (range: 0e349 days) before departure. Long-term travellers accounted for 46.7% of all travellers. In terms of duration of travel, 600 (12.7%), 602 (12.8%) and 1003 (21.2%) long-term travellers travelled for 1e3, >3e6 months and >6 months, respectively. Travel characteristics and destinations in relation to duration of travel are shown in Table 1. The majority of long-term travellers were men (79.8%). Long-term travellers were younger than short-term travellers (mean age: 34.5 and 40.9, respectively). 84% of long-term travellers were visiting malaria-endemic countries. Sub-Saharan Africa was the most common destination (17.7%) followed by the Middle East (8.9%) and South America (8.4%). Most longterm travellers pursued trips for work purposes (70%) and recreation (26.7%), travel to urban areas (79.6%) and stayed in hotels (29.2%). Possible involvement in outdoor activities
1. Introduction
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 3/7
+
MODEL
Vaccine and malaria prophylaxis for long-term travellers Table 1
3
Characteristics and destinations of Greek international travellers by duration of travel, 2009e2012 (N Z 4721). Duration of travel <1 month
Nationality Greek Other nationality Gender Male Female Destinationa Sub-Saharan Africa South America Middle East Indian subcontinent South East Asia South Africa North Africa East Asia Central America Caribbean Europe North America Australia/Oceania World wide Unknown destination Type of travelb Organized trip Non-organized trip Cruise Purpose of travel Recreation Work Visiting Friends and Relatives (VFRs) Religious Other Place of stay Hotel Local residence Ship (sailors) Camping Other Area of stay Urban Urban& rural Rural Altitude > 3000 m a b
Wald statistic 1 month
Total
p-Value
N
(%)
N
(%)
N
(%)
2435 81
(96.8) (3.2)
2161 44
(98.0) (2.0)
4596 125
(97.4) (2.6)
0.009
1523 916
(62.4) (37.6)
1693 428
(79.8) (20.2)
3216 1344
(70.5) (29.5)
<0.001
1136 405 349 224 81 60 47 32 22 8 8 4 0 27 113
(45.2) (16.1) (13.9) (8.9) (3.2) (2.4) (1.9) (1.3) (0.9) (0.3) (0.3) (0.2) (0.0) (1.1) (4.5)
390 186 196 131 106 53 29 81 16 12 59 37 8 373 528
(17.7) (8.4) (8.9) (5.9) (4.8) (2.4) (1.3) (3.7) (0.7) (0.5) (2.7) (1.7) (0.4) (16.9) (23.9)
1526 591 545 355 187 113 (76) 113 38 20 67 41 8 400 641
(32.3) (12.5) (11.5) (7.5) (4.0) (2.4) (1.6) (2.4) (0.8) (0.4) (1.4) (0.9) (0.2) (8.5) (13.6)
<0.001
302.552
1609 625 4
(71.9) (27.9) (0.2)
1259 458 12
(72.8) (26.5) (0.7)
2868 1083 16
(72.3) (27.3) (0.4)
0.016
8.235
1664 620 82
(67.9) (25.3) (3.3)
580 1521 65
(26.7) (70.0) (3.0)
2244 2141 147
(48.5) (46.3) (3.2)
<0.001
147.718
(0.0) (0.3)
74 17
(1.6) (0.4)
73 10
(3.0) (0.4)
1 7
2006 212 183 43 8
(81.8) (8.6) (7.5) (1.8) (0.3)
628 289 1195 30 8
(29.2) (13.4) (55.6) (1.4) (0.4)
2634 501 1378 73 16
(57.2) (10.9) (29.9) (1.6) (0.3)
<0.001
1628 609 49 15
(70.8) (26.5) (2.1) (0.7)
1084 235 34 8
(79.6) (17.3) (2.5) (0.6)
2712 844 83 23
(74.1) (23.0) (2.3) (0.6)
<0.001
First destination. An organized trip was defined as a guided, package trip, mainly to popular tourist destinations.
was reported by 184 (8.3%) travellers and possible contact with animals by 103 (4.7%) of them. Table 2 shows vaccine recommendation rates for longterm travellers by vaccine. Yellow fever, typhoid fever, hepatitis A and tetanus vaccines were administered to 1647 (74.7%), 741 (33.6%), 652 (29.5%) and 589 (26.7%) of longterm travellers, respectively. Yellow fever vaccine was administered to 339 (87%) and 132 (71%) of long-term
travellers to sub-Saharan Africa and South America, respectively. The vaccination rate was higher than expected (approximately 30%), mainly for long-term travellers to South America. In particular, of 1647 long-term travellers who were vaccinated against yellow fever, 140 (8.5%) and 359 (21.8%) travelled to areas of sub-Saharan Africa and South America, respectively, for whom the vaccine is not or generally not recommended. Of those
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
Q4Q5
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 4/7
+
MODEL
4
A. Pavli et al. Table 2
Vaccination rates among international travellers from Greece by duration of travel, 2009e2012.
Vaccine
Duration of travel <1 month (N Z 2516) N (%)
Routine vaccinesa Hepatitis A Tetanus - Diphtheria Poliomyelitis Hepatitis B MeasleseMumpseRubella Influenza Pneumococcal Travel vaccines Yellow fever Typhoid fever Tetravalent meningococcal (A,C,W135,Y) Cholera Rabies Tick-born encephalitis Japanese encephalitis a
837 792 670 350 80 119 2
(33.2%) (31.5%) (26.6%) (13.9%) (3.1%) (4.7%) (0.08%)
1608 (63.9%) 531 (21%) 677 (26.9%) 26 26 2 2
(1%) (1%) (0.07%) (0.07%)
1 month (N Z 2205) N (%)
p-Value
Coefficient (B)
Wald statistic
Exp (B) (odds ratio)
(29.5%) (26.7% (23.2%) (19%) (7.3% (1%) (0%)
<0.001
0.389
10.740
0.678
<0.001 <0.001
1.768 3.355
53.951 74.560
5.859 0.035 8
1647 (74.7%) 741 (33.6% 448 (20.3%)
0.002 <0.001
0.395 1.808
9.970 234.922
1.485 6.101
<0.001
1.288
14.114
3.624
652 589 512 420 161 25 0
62 14 1 1
(2.8%) (0.6%) (0.04% (0.04%)
In accordance with the National Vaccination Program of Greece.
long-term travellers who received typhoid vaccine, 119 (90.8%) and 330 (84.6%) travelled to the Indian subcontinent and the sub-Saharan Africa respectively. The majority of long-term travellers to whom meningococcal vaccination was administered travelled to sub-Saharan Africa (389 travellers; 87%). Malaria prophylaxis was recommended to 446 (20%) longterm travellers. Mefloquine was the most commonly prescribed agent (49%), followed by atovaquone/proguanil (34%), chloroquine (2%) and doxycycline (1.3%). Mefloquine and atovaquone/proguanil were predominantly prescribed for sub-Saharan Africa, whereas chloroquine was prescribed only in few travellers to Central America and the Caribbean. Table 3 describes malaria prophylaxis according to destination. The majority of long-term travellers to whom chemoprophylaxis was prescribed travelled to sub-Saharan Africa, the Indian Subcontinent and South America. For sub-Saharan Africa, 26.7% and 14.1% of long-term travellers were prescribed mefloquine and atovaquone/proguanil respectively. Statistically significant parameters were used as independent variables in a logistic regression model with duration of travel as a dependant variable. There was a statistically significant association between long duration of travel, and age; short-term travellers were older than long-term travellers (mean age: 40.9 vs 34.5 years (p-value<0.001). The association of destination and purpose of travel with duration of travel was statistically significant; long-term travellers travelled more frequently for work, whereas for short-term travellers recreation was the most common purpose of travel (p-value < 0.001). In terms of routine vaccine recommendations, long-term travellers were more frequently vaccinated against MMR compared to short-term travellers (p-value < 0.001), whereas influenza and hepatitis A were more frequently administered to short-term travellers (p-value < 0.001 and 0.006 respectively). Regarding travel vaccines recommendations, Yellow
fever, typhoid and cholera vaccine were administered more frequently to long-term travellers than short-term travellers (p-value < 0.002, <0.001 and <0.001 respectively). Duration of travel was statistically significant with malaria prophylaxis. In addition, atovaquone/proguanil was more often prescribed to short-term travellers compared to longterm travellers (p-value Z 0.036).
4. Discussion Long-term travellers are at increased risk to exposure to many infections including vaccine-preventable diseases and malaria. In this study, we assess vaccinations and malaria prophylaxis for 2205 long-term international travellers from Greece who sought pre-travel services at Public Health Departments during 2009e2012. The majority of travellers have to seek advice at the Public Health Departments due to the exclusive availability of certain vaccines there. In Greece pre-travel advice, vaccinations, and antimalarial drugs are provided by the 57 Regional Departments of Public Health across the country which are the main travel health providers. Health professionals providing travel health services include physicians specialized in public health or primary care, nurses, and health visitors. However the number of travellers seeking pre-travel advice is very low; according to the National Statistics Authority (EL.STAT), nearly 76,000 travellers from Greece travelled to developing countries during 2009e2010, of whom 6975 (9.1%) were long-term travellers (1 month) [15]. Of them, approximately 31.6% sought pre-travel advice. This rate was comparable to 31e52% reported in other studies [16e18]. In our study, the proportion of long-term travellers was higher compared to data from the GeoSentinel Surveillance network and a United States study [7,19]. In accordance
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 5/7
+
MODEL
Vaccine and malaria prophylaxis for long-term travellers Table 3
5
Malaria prophylaxis recommendation according to destination for long-term travellers (N Z 2205).
Chemoprophylaxis
Mefloquine
Atovaquone/proguanil
Chloroquine
Doxycycline
p-Value <0.001
N (%) High malaria endemicity (undisputed indication of malaria prophylaxis) Sub-Saharan Africa 104 (26.7) 55 (14.1) 2 (0.5) Variable malaria transmission (variable indication of malaria prophylaxis) North Africa 6 (20.7) 2 (6.9) 0 (0) South Africa 4 (7.5) 10 (18.9) 0 (0) Indian Subcontinent 39 (29.8) 33 (25.2) 0 (0) Southeast Asia 6 (5.7) 12 (11.3) 0 (0) Eastern Asia 2 (2.5) 1 (1.2) 0 (0) Middle East 4 (2) 7 (3.6) 0 (0) South America 32 (17.2) 12 (6.5) 0 (0) Central America 1 (6.3) 2 (12.5) 4 (25) Caribbean 1 (8.3) 0 (0) 5 (41) Malaria not endemic (no indication of malaria prophylaxis) Europe 0 (0) 0 (0) 0 (0) North America 1 (2.7) 0 (0) 0 (0) Australia 0 (0) 0 (0) 0 (0) p-Value 0.036
a
4 (1) 0 0 1 0 0 0 0 0 0
(0) (0) (0.8) (0) (0) (0) (0) (0) (0)
0 (0) 0 (0) 0 (0)
a
These destinations are 2nd or 3rd travel destinations.
with the latter studies [7,19], most long-term travellers were young and mainly men and Africa constituted their prevalent destination. The majority of long-term travellers pursued trips for work purposes, whereas the GeoSentinel analysis showed that most of them travelled for volunteer activities and business [7]; the proportion of VFRs among long-term travellers was lower in the studied population compared to that of a recent French study [20]. Common vaccine-preventable diseases in international travellers include enteric fever, acute hepatitis and influenza [7,21]. In the current study, yellow fever vaccine was the most commonly delivered vaccine to long-term travellers; the difference between “requirement” and “recommendation” for yellow fever vaccination may not be always perceived clearly by travel health consultants [22]. Although, considering the travel destination solely the recommendation of yellow fever vaccination was generally justified, other travel characteristics such as area and place of stay, duration of travel and possible involvement in high risk activities should have been considered [22]. Typhoid vaccine was the second most commonly administered vaccine. In particular, typhoid vaccine was delivered to >90% of long-term travellers travelling to highly endemic areas. In the GeoSentinel study, typhoid fever was a common diagnosis among cases of vaccinepreventable diseases, accounting for 47.6% of them [21]. The analysis from the GeoSentinel Surveillance network demonstrated that the rate of enteric fever was higher in long-term compared to short-term travellers (9/1000 vs 5/ 1000) [7]. Typhoid vaccination rates in the current study were within expectations. Hepatitis A vaccine was recommended to less than one third of long-term travellers, although nearly 100% of them travelled to destinations of high or medium endemicity. In
contrast, in other studies hepatitis A was the most frequently administered vaccine to international travellers before departure [19]. Data from the GeoSentinel Surveillance network indicate that the rate of hepatitis A is higher in long-term than in short-term travellers (3/1000 vs 2/ 1000) [7]. Hepatitis A vaccination should be recommended to susceptible people travelling for any purpose, frequency, or duration to countries with high or intermediate hepatitis A endemicity [25e27]. The lower vaccination rates in the current study could be related to possible pre-existing immunity [18], given the fact that almost all long-term travellers were of Greek nationality. Meningococcal vaccination was recommended to nearly all long-term travellers to sub-Saharan Africa. Tetravalent meningococcal vaccine (A, C, W135, Y) is indicated for longterm travellers, and particularly for those living in close contact with the indigenous population [27], therefore meningococcal vaccination rates in the current study were within expectations. Hepatitis B vaccine recommendation was lower than expected. In the GeoSentinel study, hepatitis B was also a common cause of vaccine-preventable disease [21]. Unvaccinated people travelling to countries with intermediate to high levels of endemic hepatitis B transmission for long period of time are at higher risk of contracting hepatitis B due to possible exposure to casual and unprotected sexual contact or through medical treatment [25,28]. Previous immunization and poor perception of the risk of hepatitis B infection may be potential reasons for low hepatitis B vaccination rates in our study [15,29,30]. Rabies vaccination was recommended to only a small proportion of our long-term travellers to rabies-endemic areas, which is much lower compared to the results of a recent French (31%) [31] and a United States study (23%)
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 6/7
+
MODEL
6 [19]. Rabies vaccine should be recommended for long-term travellers to areas with a significant risk of exposure [32,33]. In the current study 4.7% of long-term travellers reported potential contact with animals. The low vaccination rates against rabies may be related to travellers’ poor awareness and/or travel health consultants’ lack of knowledge about the risks of rabies exposure, as shown in a recent study from Greece [34]. Long-term travellers living in countries where vaccinepreventable diseases are more prevalent should receive appropriate booster doses of their routine vaccinations [1,11,12]. In the current study, poliomyelitis, MMR, and influenza low vaccination rates may be associated with previous immunization, since these vaccines are provided also by other health providers [15]. An estimated 30,000 cases of travel-associated malaria are imported annually in industrialized countries [35]. Malaria is diagnosed more frequently among long-term travellers compared to short-term travellers (68/1000 vs 39/ 1000 respectively) [7,11,14], which is attributed to the poor adherence of the former to chemoprophylaxis and personal protection measures. The use of counterfeit drugs is a serious problem for long-term travellers [1,6,11,14]. Mefloquine is the most commonly recommended antimalarial by most travel health consultants for long-term travellers travelling to chloroquine-resistant destinations. However, mefloquine may not be well prescribed among long-term travellers, primarily because of the fear of neuropsychiatric side-effects [1,6,11,14]. Recommendations in regards to the continuous use of atovaquone/proguanil depend on the national guidelines of each country [1,11]. According to the Hellenic National Organization for Medicines guidelines, atovaquone/proguanil is only recommended for short-term travellers. Cost could be a limiting factor for long-term prophylaxis also [1,14]. Longterm travellers rarely use doxycycline, mainly because of the fear of side-effects during the extended periods of travel [1,11,14]. In our study, malaria prophylaxis prescription for longterm travellers was lower than expected. In the USA study, this rate was higher; mefloquine and doxycycline were prescribed to 59% and 61% respectively to travellers pursuing trips >28 days [19]. Stand By Emergency Treatment (SBET) and Primaquine as a primary prophylaxis were never recommended in the current study. Retrospective analysis of the data about duration of travel, destination, area and place of stay and possible activities, that malaria prophylaxis was under-prescribed particularly for travellers to subSaharan Africa (20% lower than expected). This may be related to inadequate assessment by travel health consultants about risk regarding acquisition of malaria and more selective malaria recommendations [38]. Furthermore travellers may be reluctant to take antimalarials for several months. The limitations of the current study include lack of data about travellers’ pre-existing immunization status and about those who declined vaccinations or chemoprophylaxis. Furthermore there was no information about destination in 23.9% of long-term travellers. However, the large number of participants gave us the opportunity to study a wide range of travellers’ characteristics and assess travel vaccine and malaria prophylaxis.
A. Pavli et al. In conclusion, our results show that there is a wide variability in vaccination and prescription of malaria chemoprophylaxis for long-term travellers from Greece travelling to tropical and subtropical countries and recommendations should be more selective, based on careful risk assessment. More focused studies are suggested in order to understand the particular needs of long-term travellers. Public health strategies should be developed in order to increase travellers’ awareness in particular of high risk groups such as long-term travellers about travel risks and the importance of pre-travel consultation. Travel health providers should increase their efforts through training-education and regular access to reference resources for updated information and consistent guidance in order to improve their awareness.
Conflict of interest statement
Q2
None declared.
Uncited references
Q6
[23], [24], [36] and [37].
References [1] Toovey S, Moerman F, van Gompel A. Special infectious disease risks of expatriates and long-term travellers in tropical countries. Part I: malaria. J Travel Med 2007;14:42e9. [2] Gamble KL, Lovell-Hawker DM. Expatriates. In: Keystone JS, Kozarsky PE, Freedman DO, Nothdurft HD, Connor BA, editors. Travel medicine. Spain: Mosby, Elsevier Ltd; 2004. pp. 287e303. [3] Leutscher PDC, Bagley SW. Health-related challenges in United States Peace Corps volunteers serving for two years in Madagascar. J Travel Med 2003;10:263e7. [4] Patel D, Easmon C, Seed P, Dow C, Snashall D. Morbidity in expatriates e a prospective cohort study. Occup Med 2006;56: 345e52. [5] Hamer DH, Ruffing R, Callahan MV, Lyons SH, Abdullah AS. Knowledge and use of measures to reduce health risks by corporate expatriate employees in western Ghana. J Travel Med 2008;15:237e42. [6] Dahlgren AL, Deroo L, Avril J, Bise G, Loutan L. Health risks and risk-taking behaviors among International Committee of the Red Cross (ICRC) expatriates returning from humanitarian missions. J Travel Med 2009;16:382e90. [7] Chen LH, Wilson ME, Davis X, Loutan L, Schwartz E, Keystone JS, et al. Illness in long-term travellers visiting GeoSentinel clinics. Emerg Infect Dis 2009;15(11): 1773e82. [8] Toovey S, Moerman F, van Gompel A. Special infectious disease risks of expatriates and long-term travellers in tropical countries. Part II: infections other than malaria. J Travel Med 2007;14:50e60. [9] Schlagenhauf P, Petersen E. Standby emergency treatment of malaria in travellers: experience to date and new developments. Expert Rev Anti Infect Ther 2012;10:537e46. [10] Waner S, Durrheim DN, Leggat PA, Ross MH. Preventing infectious diseases in long-term travellers to rural Africa. J Travel Med 2001;8:304e8. [11] Schlagenhauf P, Petersen E. Malaria chemoprophylaxis: strategies for risk groups. Clin Microbiol Rev 2008;21:466e72.
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
Q3
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46
TMAID744_proof ■ 27 May 2014 ■ 7/7
+
MODEL
Vaccine and malaria prophylaxis for long-term travellers [12] Dijkstra JA, Chappuis F, Loutan L. Vaccine-preventable diseases in long-term expatriates. J Travel Med 2005;12(Suppl. 1):S47e57. [13] Peytremann I, Baduraux M, O’Donovan S, Loutan L. Medical evacuations and fatalities of United Nations High Commissioner for Refugees Field Employee. J Travel Med 2001;8: 117e21. [14] Chen LH, Wilson ME, Schlagenhauf P. Prevention of malaria in long-term travellers. JAMA 2006;296:2234e44. [15] Hellenic Statistical Authority (ELSTAT). Available at: http:// www.statistics.gr/portal/page/portal/ESYE. [last accessed: 15.01.13]. [16] Hamer DH, Connor BA. Travel health knowledge, attitudes and practices among United States travellers. J Travel Med 2004; 11:23e6. [17] Van Herck K, Van Damme P, Castelli F, Zuckerman J, Nothdurft H, Dahlgren AL, et al. Knowledge, attitudes and practices in travel-related infectious diseases: the European airport survey. J Travel Med 2004;11:3e8. [18] Wilder-Smith A, Khairullah NS, Song JH, Chen CY, Torresi J. Travel health knowledge, attitudes and practices among Australasian travellers. J Travel Med 2004;11:9e15. [19] Larocque RC, Rao SR, Lee J, Ansdell V, Yates JA, Schwartz BS, et al. Global TravEpiNet: a national consortium of clinics providing care to international travellers e analysis of demographic characteristics, travel destinations, and pretravel healthcare of high-risk US international travellers, 2009e2011. Clin Infect Dis 2012;54:455e62. [20] Aubry C, Gaudart J, Gaillard C, Delmont J, Parola P, Brouqui P, et al. Demographics, health and travel characteristics of international travellers at a pre-travel clinic in Marseille, France. Travel Med Infect Dis 2012;10:247e56. [21] Boggild AK, Castelli F, Gautret P, Torresi J, von Sonnenburg F, Barnett ED, et al. Vaccine preventable diseases in returned international travellers: results from the GeoSentinel Surveillance Network. Vaccine 2010;28:7389e95. [22] World Health Organization. International travel and Health. Available at: http://www.who.int/ith/chapters/ith2012en_ countrylist.pdf [last accessed: 20.06.12]. [23] Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM, et al. Typhoid fever in travellers: who should be targeted for prevention? Clin Infect Dis 2004;39:186e91. [24] Keller A, Frey M, Schmid H, Steffen R, Walker T, Schlagenhauf P. Imported typhoid fever in Switzerland, 1993 to 2004. J Travel Med 2008;15:248e51.
7 [25] Askling HH, Rombo L, Andersson Y, Martin S, Ekdahl K. Hepatitis A risk in travellers. J Travel Med 2009;16:233e8. [26] Centers for Disease Control and Prevention. Available at: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3infectious-diseases-related-to-travel/hepatitis-a.htm [last accessed: 15.01.13]. [27] World Health Organization. International Travel and Health. Available at: http://www.who.int/ith/chapters/ith2012en_ chap6.pdf [last accessed: 15.01.13]. [28] Sonder GJ. Hepatitis B vaccination in travellers. Expert Rev Vaccines 2008;7:673e7. [29] Leggat PA, Zwar NA, Hudson BJ, Travel Health Advisory Group, Australia. Hepatitis B risks and immunisation coverage amongst Australians travelling to Southeast Asia and East Asia. Travel Med Infect Dis 2009;7:344e9. [30] Zuckerman JN, Hoet B. Hepatitis B immunisation in travellers: poor risk perception and inadequate protection. Travel Med Infect Dis 2008;6:315e20. [31] Gautret P, Parola P. Rabies vaccination for international travellers. Vaccine 2012;30:126e33. [32] Centers for Disease Control and Prevention. CDC health information for International Travel 2012. New York: Oxford University Press; 2012. [33] Pandey P, Shlim DR, Cave W, Springer MF. Risk of possible exposure to rabies among tourists and foreign residents in Nepal. J Travel Med 2002;9:127e31. [34] Pavli A, Saroglou G, Hadjianastasiou S, Patrinos S, Ouzounidou Z, Maltezou HC. Knowledge and practices about rabies among travel medicine consultants in Greece. Travel Med Infect Dis 2011;9:32e6. [35] Malaria. International travel and health. Available at: http:// www.who.int/ith/ITH2010chapter7.pdf [accessed on 28.12.10]. [36] Field V, Gautret P, Schlagenhauf P, Burchard GD, Caumes E, Jensenius M, et al. Travel and migration associated infectious diseases morbidity in Europe, 2008. BMC Infect Dis 2010;10: 330. http://dx.doi.org/10.1186/1471-2334-10-330. [37] Mu ¨hlberger N, Jelinek T, Gascon J, Probst M, Zoller T, Schunk M, et al. Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop. Malar J 2004;3:5. [38] Pavli A, Smeti P, Spilioti A, Vakali A, Katerelos P, Maltezou HC. Descriptive analysis of malaria prophylaxis for travellers from Greece visiting malaria-endemic countries. Travel Med Infect Dis 2011;9:284e8.
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92
TMAID744_proof ■ 27 May 2014 ■ 1/7
+
MODEL
Travel Medicine and Infectious Disease (2014) xx, 1e7
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis Q7
Androula Pavli a, Paraskevi Smeti a, Athina Spilioti a, Chrysovalantis Silvestros a, Panagiotis Katerelos b, Helena C. Maltezou b,* a
Travel Medicine Office, Hellenic Center for Disease Control and Prevention, Athens, Greece Department for Interventions in Health Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece
b
Received 16 February 2013; received in revised form 14 March 2014; accepted 13 May 2014
KEYWORDS
Q1
Pre-travel; Vaccine; Prophylaxis; Long-term travellers; Typhoid; Rabies; Malaria
Summary The purpose of this prospective, questionnaire-based study is to assess pre-travel vaccinations and malaria prophylaxis for long-term travellers who receive pre-travel advice in Greece. A total of 4721 travellers were studied from January 1, 2009 through December 31, 2012. Travellers sought pre-travel advice at a mean of 19.7 days (range: 0e349 days) before departure. Long-term travellers (1 month) accounted for 2205 (46.7%) of all travellers. Long-term travellers had a mean age of 34.5 years. The majority of them were men (79.8%). In terms of destinations, 84% were visiting malaria-endemic countries and sub-Saharan Africa was the most common destination (17.7%). Most long-term travellers pursued trips for work purposes (70%), visited urban areas (79.6%) and stayed in hotels (29.2%). Yellow fever, typhoid fever, hepatitis A and tetanus/diphtheria vaccines were administered to 1647 (74.7%), 741 (33.6%), 652 (29.5%), and 589 (26.7%) travellers, respectively. Yellow fever vaccine was administered to 339 (87%) and 132 (71%) of long-term travellers to sub-Saharan Africa and South America respectively, whereas typhoid vaccine to 119 (90.8%) and 330 (84.6%) of those travelling to the Indian subcontinent and sub-Saharan Africa respectively. Rabies vaccine was administered to 14 (0.6%) of them. Malaria prophylaxis was recommended to 446 (20%) of long-term travellers. Mefloquine was the most commonly (49%) prescribed agent, and was prescribed to 26.7% of long-term travellers to sub-Sahara Africa. In conclusion, this study revealed that recommendations for vaccine and malaria prophylaxis for long-term travellers to developing countries should be more selective, based on the assessment of all travellers’ and travel characteristics, in order to provide adequate pre-travel preparation for this high risk group
* Corresponding author. Department for Interventions in Health-Care Facilities, Hellenic Centre for Disease Control and Prevention, 3-5 Agrafon Street, Athens, 15123, Greece. Tel.: þ30 210 5212 175; fax: þ30 210 5212 177. E-mail address: [email protected] (H.C. Maltezou). http://dx.doi.org/10.1016/j.tmaid.2014.05.003 1477-8939/ª 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 2/7
+
MODEL
2
A. Pavli et al. of travellers. More focused studies are suggested in order to understand the particular needs of long-term travellers. Increasing awareness of travellers and travel health consultants is very important. ª 2014 Elsevier Ltd. All rights reserved.
Long-term travel is defined typically as a travel of 1 month duration [1]. Reasons for long-term travels include tourism, diplomatic, missionary, Peace Corps Volunteer and humanitarian aid work, education and research, military operations, and corporate expatriation [2e6]. Long-term travels are associated with significant risk for specific health problems [1,5,7e14]. In particular, long-term travels to the tropics predispose to higher risk for acquisition of a wide range of infectious diseases compared to short-term travels, because of prolonged exposure to pathogens, limited environmental hygiene, close contact with the local population, poorly developed infrastructure for water supply and sewerage disposal, extreme climatic conditions, risk-taking behaviour, and lack of medical facilities [9,10]. The risk of malaria acquisition is higher in long-term compared to short-term travellers due to longer period of exposure to mosquito bites and poor compliance with chemoprophylaxis and preventive measures [5,11,14]. Malaria recommendations have been difficult to standardize due to the diversity of long-term travellers and their itineraries [14]. Furthermore, long-term travellers are at higher risk for vaccine-preventable diseases, including hepatitis A, typhoid fever, rabies, hepatitis B, Japanese encephalitis and meningitis [12]. The aim of this study is to assess vaccinations and malaria prophylaxis in long-term travellers from Greece travelling to tropical and subtropical countries.
health-care physicians working in the public or private sector. All international travellers who attended the 57 Regional Public Health Departments from January 1, 2009 through December 31, 2012 were asked to participate in a questionnaire-based study. The questionnaire was completed with the assistance of the health professional. The following data were collected prospectively using one standardized form per traveller: age, gender, nationality, date of departure, travel destination, duration and purpose of travel, type of accommodation, administration of routine and travel vaccines and chemoprophylaxis. Consent was requested from all participants. Approval for the study was given by the Hellenic Center for Disease Control and Prevention. Long-term travel was defined as a trip of 1 month duration, while short-term travel was defined as a trip of <1 month. Urban accommodation was defined as towns with a population of 5000 people, whereas rural accommodation was defined as villages of <5000 population or staying in the countryside. Statistical analysis was performed using the STATA 8.0 statistical package. c2 and t-test were used in order to investigate any possible relation of duration of travel with travellers’ and/or travel characteristics. P-values of 0.05 were considered statistically significant. The statistically significant parameters were used as independent variables in a logistic regression model with duration of travel as a dependant variable.
2. Methods
3. Results
In Greece pre-travel services are provided mainly in the 57 Regional Departments of Public Health, which are the solely authorized yellow fever vaccination centres in this country. Rabies, typhoid, tetravalent meningitis A,C,W135,Y, and cholera vaccines are also delivered exclusively through these centres; however other travel and routine vaccines are also administered. Pre-travel services are provided according to the guidelines of the Hellenic Centre for Disease Control and Prevention, the World Health Organization and the United States Centers for Disease Control and Prevention guidelines. Routine vaccines are administered in accordance with the National Vaccination Program of Greece, which include vaccines against: tetanusdiphtheria-pertussis, poliomyelitis, Haemophilus influenzae type B, measlesemumpserubella (MMR), hepatitis A, hepatitis B, pneumococcus, meningococcus serotype C, human papilloma virus, tuberculosis (Bacillus CalmetteGue ´rin vaccine), influenza (high risk groups), and rotavirus. These vaccines are administered mainly by paediatricians, but also by internal medicine physicians and primary
A total of 4721 international travellers participated in the study, with a participation rate ranging from 70% to 80% per Public Health Department. Most (40%) of participants were from the region of Attica. Travellers sought pre-travel advice at a mean of 19.7 days (range: 0e349 days) before departure. Long-term travellers accounted for 46.7% of all travellers. In terms of duration of travel, 600 (12.7%), 602 (12.8%) and 1003 (21.2%) long-term travellers travelled for 1e3, >3e6 months and >6 months, respectively. Travel characteristics and destinations in relation to duration of travel are shown in Table 1. The majority of long-term travellers were men (79.8%). Long-term travellers were younger than short-term travellers (mean age: 34.5 and 40.9, respectively). 84% of long-term travellers were visiting malaria-endemic countries. Sub-Saharan Africa was the most common destination (17.7%) followed by the Middle East (8.9%) and South America (8.4%). Most longterm travellers pursued trips for work purposes (70%) and recreation (26.7%), travel to urban areas (79.6%) and stayed in hotels (29.2%). Possible involvement in outdoor activities
1. Introduction
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 3/7
+
MODEL
Vaccine and malaria prophylaxis for long-term travellers Table 1
3
Characteristics and destinations of Greek international travellers by duration of travel, 2009e2012 (N Z 4721). Duration of travel <1 month
Nationality Greek Other nationality Gender Male Female Destinationa Sub-Saharan Africa South America Middle East Indian subcontinent South East Asia South Africa North Africa East Asia Central America Caribbean Europe North America Australia/Oceania World wide Unknown destination Type of travelb Organized trip Non-organized trip Cruise Purpose of travel Recreation Work Visiting Friends and Relatives (VFRs) Religious Other Place of stay Hotel Local residence Ship (sailors) Camping Other Area of stay Urban Urban& rural Rural Altitude > 3000 m a b
Wald statistic 1 month
Total
p-Value
N
(%)
N
(%)
N
(%)
2435 81
(96.8) (3.2)
2161 44
(98.0) (2.0)
4596 125
(97.4) (2.6)
0.009
1523 916
(62.4) (37.6)
1693 428
(79.8) (20.2)
3216 1344
(70.5) (29.5)
<0.001
1136 405 349 224 81 60 47 32 22 8 8 4 0 27 113
(45.2) (16.1) (13.9) (8.9) (3.2) (2.4) (1.9) (1.3) (0.9) (0.3) (0.3) (0.2) (0.0) (1.1) (4.5)
390 186 196 131 106 53 29 81 16 12 59 37 8 373 528
(17.7) (8.4) (8.9) (5.9) (4.8) (2.4) (1.3) (3.7) (0.7) (0.5) (2.7) (1.7) (0.4) (16.9) (23.9)
1526 591 545 355 187 113 (76) 113 38 20 67 41 8 400 641
(32.3) (12.5) (11.5) (7.5) (4.0) (2.4) (1.6) (2.4) (0.8) (0.4) (1.4) (0.9) (0.2) (8.5) (13.6)
<0.001
302.552
1609 625 4
(71.9) (27.9) (0.2)
1259 458 12
(72.8) (26.5) (0.7)
2868 1083 16
(72.3) (27.3) (0.4)
0.016
8.235
1664 620 82
(67.9) (25.3) (3.3)
580 1521 65
(26.7) (70.0) (3.0)
2244 2141 147
(48.5) (46.3) (3.2)
<0.001
147.718
(0.0) (0.3)
74 17
(1.6) (0.4)
73 10
(3.0) (0.4)
1 7
2006 212 183 43 8
(81.8) (8.6) (7.5) (1.8) (0.3)
628 289 1195 30 8
(29.2) (13.4) (55.6) (1.4) (0.4)
2634 501 1378 73 16
(57.2) (10.9) (29.9) (1.6) (0.3)
<0.001
1628 609 49 15
(70.8) (26.5) (2.1) (0.7)
1084 235 34 8
(79.6) (17.3) (2.5) (0.6)
2712 844 83 23
(74.1) (23.0) (2.3) (0.6)
<0.001
First destination. An organized trip was defined as a guided, package trip, mainly to popular tourist destinations.
was reported by 184 (8.3%) travellers and possible contact with animals by 103 (4.7%) of them. Table 2 shows vaccine recommendation rates for longterm travellers by vaccine. Yellow fever, typhoid fever, hepatitis A and tetanus vaccines were administered to 1647 (74.7%), 741 (33.6%), 652 (29.5%) and 589 (26.7%) of longterm travellers, respectively. Yellow fever vaccine was administered to 339 (87%) and 132 (71%) of long-term
travellers to sub-Saharan Africa and South America, respectively. The vaccination rate was higher than expected (approximately 30%), mainly for long-term travellers to South America. In particular, of 1647 long-term travellers who were vaccinated against yellow fever, 140 (8.5%) and 359 (21.8%) travelled to areas of sub-Saharan Africa and South America, respectively, for whom the vaccine is not or generally not recommended. Of those
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
Q4Q5
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 4/7
+
MODEL
4
A. Pavli et al. Table 2
Vaccination rates among international travellers from Greece by duration of travel, 2009e2012.
Vaccine
Duration of travel <1 month (N Z 2516) N (%)
Routine vaccinesa Hepatitis A Tetanus - Diphtheria Poliomyelitis Hepatitis B MeasleseMumpseRubella Influenza Pneumococcal Travel vaccines Yellow fever Typhoid fever Tetravalent meningococcal (A,C,W135,Y) Cholera Rabies Tick-born encephalitis Japanese encephalitis a
837 792 670 350 80 119 2
(33.2%) (31.5%) (26.6%) (13.9%) (3.1%) (4.7%) (0.08%)
1608 (63.9%) 531 (21%) 677 (26.9%) 26 26 2 2
(1%) (1%) (0.07%) (0.07%)
1 month (N Z 2205) N (%)
p-Value
Coefficient (B)
Wald statistic
Exp (B) (odds ratio)
(29.5%) (26.7% (23.2%) (19%) (7.3% (1%) (0%)
<0.001
0.389
10.740
0.678
<0.001 <0.001
1.768 3.355
53.951 74.560
5.859 0.035 8
1647 (74.7%) 741 (33.6% 448 (20.3%)
0.002 <0.001
0.395 1.808
9.970 234.922
1.485 6.101
<0.001
1.288
14.114
3.624
652 589 512 420 161 25 0
62 14 1 1
(2.8%) (0.6%) (0.04% (0.04%)
In accordance with the National Vaccination Program of Greece.
long-term travellers who received typhoid vaccine, 119 (90.8%) and 330 (84.6%) travelled to the Indian subcontinent and the sub-Saharan Africa respectively. The majority of long-term travellers to whom meningococcal vaccination was administered travelled to sub-Saharan Africa (389 travellers; 87%). Malaria prophylaxis was recommended to 446 (20%) longterm travellers. Mefloquine was the most commonly prescribed agent (49%), followed by atovaquone/proguanil (34%), chloroquine (2%) and doxycycline (1.3%). Mefloquine and atovaquone/proguanil were predominantly prescribed for sub-Saharan Africa, whereas chloroquine was prescribed only in few travellers to Central America and the Caribbean. Table 3 describes malaria prophylaxis according to destination. The majority of long-term travellers to whom chemoprophylaxis was prescribed travelled to sub-Saharan Africa, the Indian Subcontinent and South America. For sub-Saharan Africa, 26.7% and 14.1% of long-term travellers were prescribed mefloquine and atovaquone/proguanil respectively. Statistically significant parameters were used as independent variables in a logistic regression model with duration of travel as a dependant variable. There was a statistically significant association between long duration of travel, and age; short-term travellers were older than long-term travellers (mean age: 40.9 vs 34.5 years (p-value<0.001). The association of destination and purpose of travel with duration of travel was statistically significant; long-term travellers travelled more frequently for work, whereas for short-term travellers recreation was the most common purpose of travel (p-value < 0.001). In terms of routine vaccine recommendations, long-term travellers were more frequently vaccinated against MMR compared to short-term travellers (p-value < 0.001), whereas influenza and hepatitis A were more frequently administered to short-term travellers (p-value < 0.001 and 0.006 respectively). Regarding travel vaccines recommendations, Yellow
fever, typhoid and cholera vaccine were administered more frequently to long-term travellers than short-term travellers (p-value < 0.002, <0.001 and <0.001 respectively). Duration of travel was statistically significant with malaria prophylaxis. In addition, atovaquone/proguanil was more often prescribed to short-term travellers compared to longterm travellers (p-value Z 0.036).
4. Discussion Long-term travellers are at increased risk to exposure to many infections including vaccine-preventable diseases and malaria. In this study, we assess vaccinations and malaria prophylaxis for 2205 long-term international travellers from Greece who sought pre-travel services at Public Health Departments during 2009e2012. The majority of travellers have to seek advice at the Public Health Departments due to the exclusive availability of certain vaccines there. In Greece pre-travel advice, vaccinations, and antimalarial drugs are provided by the 57 Regional Departments of Public Health across the country which are the main travel health providers. Health professionals providing travel health services include physicians specialized in public health or primary care, nurses, and health visitors. However the number of travellers seeking pre-travel advice is very low; according to the National Statistics Authority (EL.STAT), nearly 76,000 travellers from Greece travelled to developing countries during 2009e2010, of whom 6975 (9.1%) were long-term travellers (1 month) [15]. Of them, approximately 31.6% sought pre-travel advice. This rate was comparable to 31e52% reported in other studies [16e18]. In our study, the proportion of long-term travellers was higher compared to data from the GeoSentinel Surveillance network and a United States study [7,19]. In accordance
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 5/7
+
MODEL
Vaccine and malaria prophylaxis for long-term travellers Table 3
5
Malaria prophylaxis recommendation according to destination for long-term travellers (N Z 2205).
Chemoprophylaxis
Mefloquine
Atovaquone/proguanil
Chloroquine
Doxycycline
p-Value <0.001
N (%) High malaria endemicity (undisputed indication of malaria prophylaxis) Sub-Saharan Africa 104 (26.7) 55 (14.1) 2 (0.5) Variable malaria transmission (variable indication of malaria prophylaxis) North Africa 6 (20.7) 2 (6.9) 0 (0) South Africa 4 (7.5) 10 (18.9) 0 (0) Indian Subcontinent 39 (29.8) 33 (25.2) 0 (0) Southeast Asia 6 (5.7) 12 (11.3) 0 (0) Eastern Asia 2 (2.5) 1 (1.2) 0 (0) Middle East 4 (2) 7 (3.6) 0 (0) South America 32 (17.2) 12 (6.5) 0 (0) Central America 1 (6.3) 2 (12.5) 4 (25) Caribbean 1 (8.3) 0 (0) 5 (41) Malaria not endemic (no indication of malaria prophylaxis) Europe 0 (0) 0 (0) 0 (0) North America 1 (2.7) 0 (0) 0 (0) Australia 0 (0) 0 (0) 0 (0) p-Value 0.036
a
4 (1) 0 0 1 0 0 0 0 0 0
(0) (0) (0.8) (0) (0) (0) (0) (0) (0)
0 (0) 0 (0) 0 (0)
a
These destinations are 2nd or 3rd travel destinations.
with the latter studies [7,19], most long-term travellers were young and mainly men and Africa constituted their prevalent destination. The majority of long-term travellers pursued trips for work purposes, whereas the GeoSentinel analysis showed that most of them travelled for volunteer activities and business [7]; the proportion of VFRs among long-term travellers was lower in the studied population compared to that of a recent French study [20]. Common vaccine-preventable diseases in international travellers include enteric fever, acute hepatitis and influenza [7,21]. In the current study, yellow fever vaccine was the most commonly delivered vaccine to long-term travellers; the difference between “requirement” and “recommendation” for yellow fever vaccination may not be always perceived clearly by travel health consultants [22]. Although, considering the travel destination solely the recommendation of yellow fever vaccination was generally justified, other travel characteristics such as area and place of stay, duration of travel and possible involvement in high risk activities should have been considered [22]. Typhoid vaccine was the second most commonly administered vaccine. In particular, typhoid vaccine was delivered to >90% of long-term travellers travelling to highly endemic areas. In the GeoSentinel study, typhoid fever was a common diagnosis among cases of vaccinepreventable diseases, accounting for 47.6% of them [21]. The analysis from the GeoSentinel Surveillance network demonstrated that the rate of enteric fever was higher in long-term compared to short-term travellers (9/1000 vs 5/ 1000) [7]. Typhoid vaccination rates in the current study were within expectations. Hepatitis A vaccine was recommended to less than one third of long-term travellers, although nearly 100% of them travelled to destinations of high or medium endemicity. In
contrast, in other studies hepatitis A was the most frequently administered vaccine to international travellers before departure [19]. Data from the GeoSentinel Surveillance network indicate that the rate of hepatitis A is higher in long-term than in short-term travellers (3/1000 vs 2/ 1000) [7]. Hepatitis A vaccination should be recommended to susceptible people travelling for any purpose, frequency, or duration to countries with high or intermediate hepatitis A endemicity [25e27]. The lower vaccination rates in the current study could be related to possible pre-existing immunity [18], given the fact that almost all long-term travellers were of Greek nationality. Meningococcal vaccination was recommended to nearly all long-term travellers to sub-Saharan Africa. Tetravalent meningococcal vaccine (A, C, W135, Y) is indicated for longterm travellers, and particularly for those living in close contact with the indigenous population [27], therefore meningococcal vaccination rates in the current study were within expectations. Hepatitis B vaccine recommendation was lower than expected. In the GeoSentinel study, hepatitis B was also a common cause of vaccine-preventable disease [21]. Unvaccinated people travelling to countries with intermediate to high levels of endemic hepatitis B transmission for long period of time are at higher risk of contracting hepatitis B due to possible exposure to casual and unprotected sexual contact or through medical treatment [25,28]. Previous immunization and poor perception of the risk of hepatitis B infection may be potential reasons for low hepatitis B vaccination rates in our study [15,29,30]. Rabies vaccination was recommended to only a small proportion of our long-term travellers to rabies-endemic areas, which is much lower compared to the results of a recent French (31%) [31] and a United States study (23%)
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID744_proof ■ 27 May 2014 ■ 6/7
+
MODEL
6 [19]. Rabies vaccine should be recommended for long-term travellers to areas with a significant risk of exposure [32,33]. In the current study 4.7% of long-term travellers reported potential contact with animals. The low vaccination rates against rabies may be related to travellers’ poor awareness and/or travel health consultants’ lack of knowledge about the risks of rabies exposure, as shown in a recent study from Greece [34]. Long-term travellers living in countries where vaccinepreventable diseases are more prevalent should receive appropriate booster doses of their routine vaccinations [1,11,12]. In the current study, poliomyelitis, MMR, and influenza low vaccination rates may be associated with previous immunization, since these vaccines are provided also by other health providers [15]. An estimated 30,000 cases of travel-associated malaria are imported annually in industrialized countries [35]. Malaria is diagnosed more frequently among long-term travellers compared to short-term travellers (68/1000 vs 39/ 1000 respectively) [7,11,14], which is attributed to the poor adherence of the former to chemoprophylaxis and personal protection measures. The use of counterfeit drugs is a serious problem for long-term travellers [1,6,11,14]. Mefloquine is the most commonly recommended antimalarial by most travel health consultants for long-term travellers travelling to chloroquine-resistant destinations. However, mefloquine may not be well prescribed among long-term travellers, primarily because of the fear of neuropsychiatric side-effects [1,6,11,14]. Recommendations in regards to the continuous use of atovaquone/proguanil depend on the national guidelines of each country [1,11]. According to the Hellenic National Organization for Medicines guidelines, atovaquone/proguanil is only recommended for short-term travellers. Cost could be a limiting factor for long-term prophylaxis also [1,14]. Longterm travellers rarely use doxycycline, mainly because of the fear of side-effects during the extended periods of travel [1,11,14]. In our study, malaria prophylaxis prescription for longterm travellers was lower than expected. In the USA study, this rate was higher; mefloquine and doxycycline were prescribed to 59% and 61% respectively to travellers pursuing trips >28 days [19]. Stand By Emergency Treatment (SBET) and Primaquine as a primary prophylaxis were never recommended in the current study. Retrospective analysis of the data about duration of travel, destination, area and place of stay and possible activities, that malaria prophylaxis was under-prescribed particularly for travellers to subSaharan Africa (20% lower than expected). This may be related to inadequate assessment by travel health consultants about risk regarding acquisition of malaria and more selective malaria recommendations [38]. Furthermore travellers may be reluctant to take antimalarials for several months. The limitations of the current study include lack of data about travellers’ pre-existing immunization status and about those who declined vaccinations or chemoprophylaxis. Furthermore there was no information about destination in 23.9% of long-term travellers. However, the large number of participants gave us the opportunity to study a wide range of travellers’ characteristics and assess travel vaccine and malaria prophylaxis.
A. Pavli et al. In conclusion, our results show that there is a wide variability in vaccination and prescription of malaria chemoprophylaxis for long-term travellers from Greece travelling to tropical and subtropical countries and recommendations should be more selective, based on careful risk assessment. More focused studies are suggested in order to understand the particular needs of long-term travellers. Public health strategies should be developed in order to increase travellers’ awareness in particular of high risk groups such as long-term travellers about travel risks and the importance of pre-travel consultation. Travel health providers should increase their efforts through training-education and regular access to reference resources for updated information and consistent guidance in order to improve their awareness.
Conflict of interest statement
Q2
None declared.
Uncited references
Q6
[23], [24], [36] and [37].
References [1] Toovey S, Moerman F, van Gompel A. Special infectious disease risks of expatriates and long-term travellers in tropical countries. Part I: malaria. J Travel Med 2007;14:42e9. [2] Gamble KL, Lovell-Hawker DM. Expatriates. In: Keystone JS, Kozarsky PE, Freedman DO, Nothdurft HD, Connor BA, editors. Travel medicine. Spain: Mosby, Elsevier Ltd; 2004. pp. 287e303. [3] Leutscher PDC, Bagley SW. Health-related challenges in United States Peace Corps volunteers serving for two years in Madagascar. J Travel Med 2003;10:263e7. [4] Patel D, Easmon C, Seed P, Dow C, Snashall D. Morbidity in expatriates e a prospective cohort study. Occup Med 2006;56: 345e52. [5] Hamer DH, Ruffing R, Callahan MV, Lyons SH, Abdullah AS. Knowledge and use of measures to reduce health risks by corporate expatriate employees in western Ghana. J Travel Med 2008;15:237e42. [6] Dahlgren AL, Deroo L, Avril J, Bise G, Loutan L. Health risks and risk-taking behaviors among International Committee of the Red Cross (ICRC) expatriates returning from humanitarian missions. J Travel Med 2009;16:382e90. [7] Chen LH, Wilson ME, Davis X, Loutan L, Schwartz E, Keystone JS, et al. Illness in long-term travellers visiting GeoSentinel clinics. Emerg Infect Dis 2009;15(11): 1773e82. [8] Toovey S, Moerman F, van Gompel A. Special infectious disease risks of expatriates and long-term travellers in tropical countries. Part II: infections other than malaria. J Travel Med 2007;14:50e60. [9] Schlagenhauf P, Petersen E. Standby emergency treatment of malaria in travellers: experience to date and new developments. Expert Rev Anti Infect Ther 2012;10:537e46. [10] Waner S, Durrheim DN, Leggat PA, Ross MH. Preventing infectious diseases in long-term travellers to rural Africa. J Travel Med 2001;8:304e8. [11] Schlagenhauf P, Petersen E. Malaria chemoprophylaxis: strategies for risk groups. Clin Microbiol Rev 2008;21:466e72.
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
Q3
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46
TMAID744_proof ■ 27 May 2014 ■ 7/7
+
MODEL
Vaccine and malaria prophylaxis for long-term travellers [12] Dijkstra JA, Chappuis F, Loutan L. Vaccine-preventable diseases in long-term expatriates. J Travel Med 2005;12(Suppl. 1):S47e57. [13] Peytremann I, Baduraux M, O’Donovan S, Loutan L. Medical evacuations and fatalities of United Nations High Commissioner for Refugees Field Employee. J Travel Med 2001;8: 117e21. [14] Chen LH, Wilson ME, Schlagenhauf P. Prevention of malaria in long-term travellers. JAMA 2006;296:2234e44. [15] Hellenic Statistical Authority (ELSTAT). Available at: http:// www.statistics.gr/portal/page/portal/ESYE. [last accessed: 15.01.13]. [16] Hamer DH, Connor BA. Travel health knowledge, attitudes and practices among United States travellers. J Travel Med 2004; 11:23e6. [17] Van Herck K, Van Damme P, Castelli F, Zuckerman J, Nothdurft H, Dahlgren AL, et al. Knowledge, attitudes and practices in travel-related infectious diseases: the European airport survey. J Travel Med 2004;11:3e8. [18] Wilder-Smith A, Khairullah NS, Song JH, Chen CY, Torresi J. Travel health knowledge, attitudes and practices among Australasian travellers. J Travel Med 2004;11:9e15. [19] Larocque RC, Rao SR, Lee J, Ansdell V, Yates JA, Schwartz BS, et al. Global TravEpiNet: a national consortium of clinics providing care to international travellers e analysis of demographic characteristics, travel destinations, and pretravel healthcare of high-risk US international travellers, 2009e2011. Clin Infect Dis 2012;54:455e62. [20] Aubry C, Gaudart J, Gaillard C, Delmont J, Parola P, Brouqui P, et al. Demographics, health and travel characteristics of international travellers at a pre-travel clinic in Marseille, France. Travel Med Infect Dis 2012;10:247e56. [21] Boggild AK, Castelli F, Gautret P, Torresi J, von Sonnenburg F, Barnett ED, et al. Vaccine preventable diseases in returned international travellers: results from the GeoSentinel Surveillance Network. Vaccine 2010;28:7389e95. [22] World Health Organization. International travel and Health. Available at: http://www.who.int/ith/chapters/ith2012en_ countrylist.pdf [last accessed: 20.06.12]. [23] Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM, et al. Typhoid fever in travellers: who should be targeted for prevention? Clin Infect Dis 2004;39:186e91. [24] Keller A, Frey M, Schmid H, Steffen R, Walker T, Schlagenhauf P. Imported typhoid fever in Switzerland, 1993 to 2004. J Travel Med 2008;15:248e51.
7 [25] Askling HH, Rombo L, Andersson Y, Martin S, Ekdahl K. Hepatitis A risk in travellers. J Travel Med 2009;16:233e8. [26] Centers for Disease Control and Prevention. Available at: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3infectious-diseases-related-to-travel/hepatitis-a.htm [last accessed: 15.01.13]. [27] World Health Organization. International Travel and Health. Available at: http://www.who.int/ith/chapters/ith2012en_ chap6.pdf [last accessed: 15.01.13]. [28] Sonder GJ. Hepatitis B vaccination in travellers. Expert Rev Vaccines 2008;7:673e7. [29] Leggat PA, Zwar NA, Hudson BJ, Travel Health Advisory Group, Australia. Hepatitis B risks and immunisation coverage amongst Australians travelling to Southeast Asia and East Asia. Travel Med Infect Dis 2009;7:344e9. [30] Zuckerman JN, Hoet B. Hepatitis B immunisation in travellers: poor risk perception and inadequate protection. Travel Med Infect Dis 2008;6:315e20. [31] Gautret P, Parola P. Rabies vaccination for international travellers. Vaccine 2012;30:126e33. [32] Centers for Disease Control and Prevention. CDC health information for International Travel 2012. New York: Oxford University Press; 2012. [33] Pandey P, Shlim DR, Cave W, Springer MF. Risk of possible exposure to rabies among tourists and foreign residents in Nepal. J Travel Med 2002;9:127e31. [34] Pavli A, Saroglou G, Hadjianastasiou S, Patrinos S, Ouzounidou Z, Maltezou HC. Knowledge and practices about rabies among travel medicine consultants in Greece. Travel Med Infect Dis 2011;9:32e6. [35] Malaria. International travel and health. Available at: http:// www.who.int/ith/ITH2010chapter7.pdf [accessed on 28.12.10]. [36] Field V, Gautret P, Schlagenhauf P, Burchard GD, Caumes E, Jensenius M, et al. Travel and migration associated infectious diseases morbidity in Europe, 2008. BMC Infect Dis 2010;10: 330. http://dx.doi.org/10.1186/1471-2334-10-330. [37] Mu ¨hlberger N, Jelinek T, Gascon J, Probst M, Zoller T, Schunk M, et al. Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop. Malar J 2004;3:5. [38] Pavli A, Smeti P, Spilioti A, Vakali A, Katerelos P, Maltezou HC. Descriptive analysis of malaria prophylaxis for travellers from Greece visiting malaria-endemic countries. Travel Med Infect Dis 2011;9:284e8.
Please cite this article in press as: Pavli A, et al., Vaccinations and malaria prophylaxis for long-term travellers travelling from Greece: A prospective, questionnaire-based analysis, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/ j.tmaid.2014.05.003
47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92