Determinants of Malaria Prophylaxis Among German Travelers to Kenya, Senegal, and Thailand

162 Determinants of Malaria Prophylaxis Among German Travelers to Kenya, Senegal, and Thailand Gwendolin Ropers, PhD, * Mirna Du Ry van Beest Holle, MD, MPH, EPIET, * Ole Wichmann, MD, MCTM, DTM&H, * Lutz Kappelmayer, MD, PhD, * Uwe Stüben, MD, PhD, Christian Schönfeld, MD, and Klaus Stark, MD, PhD * * Department of Infectious Disease Epidemiology, Robert Koch Institut, Berlin, Germany ; Medical Department, Lufthansa German Airlines, Frankfurt, Germany ; Institute of Tropical Medicine, Charité, University Medicine Berlin, Berlin, Germany DOI: 10.1111/j.1708-8305.2008.00188.x Background. Malaria chemoprophylaxis is a mainstay of malaria prevention in travelers. Adequate pretravel advice forms the basis for efficient malaria prophylaxis. This study assessed the determinants for seeking pretravel advice and evaluated the quality of advice from each source and its influence on the patterns and outcome of malaria prophylaxis intake. Methods. In March and April 2004, a self-administered questionnaire was distributed by cabin crews to passengers flying back to Germany from three popular tourist destinations: Kenya, Senegal, and Thailand. To evaluate the quality of advice and actual intake, figures were assessed against the official recommendations of the German Society of Travel Medicine and International Health (DTG). Results. A total of 1,001 passengers were included in the study (Kenya, 492; Senegal, 131; and Thailand, 378), of which 81% had sought any kind of pretravel health advice. Travelers age and time of pretravel consultation were associated with the source of information consulted. Seventy-five percent of travelers from Senegal and Kenya received DTG compliant advice compared to only 17% of travelers from areas with low malaria risk in Thailand. Travelers returning from Kenya and Senegal had used correct chemoprophylaxis in only 65 and 47% of trips, respectively. In multivariate analysis, the factors determining correct intake among Senegal and Kenya travelers were receiving pretravel advice (from nonmedical professionals: OR 4.4, 95% CI 1.9 10.0 and from medical professionals: OR 15.4, 95% CI 7.3 32.4), a correct risk perception (OR 2.9, 95% CI 1.9 4.5), 2 to 3 weeks of travel abroad (vs a duration >3 wk: OR 2.2, 95% CI 1.3 3.8), and travel to Kenya (OR 1.9, 95% CI 1.1 3.1). Conclusions. Malaria prevention among a large proportion of German travelers to tropical destinations is inadequate. Public health efforts should be made to raise awareness among travelers, travel agencies, and medical institutions in Germany. Malaria is one of the most important travelassociated diseases due to its widespread geographic distribution and its potential fatal outcome if untreated, especially in nonimmune individuals. 1,2 Of the more than 50 million trips abroad made by persons from Germany each year, about 3 to 4 million go to malaria-endemic destinations. 3 Germany accounts for around 10% of all reported malaria Corresponding Author: Klaus Stark, MD, PhD, Department of Infectious Disease Epidemiology, Robert Koch Institute, Seestrasse 10, 13353 Berlin, Germany. E-mail: starkk@rki.de cases imported to Europe. 4 6 Annual notifications ranged between 600 and 1,000 cases (2001 2005), with the highest number of fatal cases being 8 in 2001. 7 The majority (>85%) of infections were acquired in sub-saharan Africa. Previous studies from different countries showed that between 50 and 90% of travelers to malariaendemic countries seek any type of pretravel advice. 8 15 Such advice is provided by a variety of sources such as institutes and departments for tropical medicine, centers for travel medicine, and local public health offices. In Germany, a high proportion of general practitioners give consultations in travel medicine, and in European countries, many 2008 International Society of Travel Medicine, 1195-1982 Journal of Travel Medicine, Volume 15, Issue 3, 2008, 162 171

Malaria Prophylaxis Among German Travelers travelers also consult pharmacists and nonmedical sources like travel agents, family and friends, or the Internet. 15,16 In addition to bite avoidance and personal protective measures, travelers to endemic areas should take a course of tablets (chemoprophylaxis) to prevent malaria infection. An alternative in lowendemic countries is standby therapy, where travelers can carry a drug abroad, which can be used for emergency self-treatment if fever suggestive of malaria occurs while traveling, and no medical institution can be consulted within 24 hours. In Germany, the German Society of Tropical Medicine and International Health (DTG) provides regularly updated information on malaria risks and recommendations for prophylaxis. 17 Even though the society s recommendations can be regarded as a formal guideline for travel medicine practitioners, little is known about the quality of countryspecific advice on malaria prophylaxis in practice and about the factors that may influence the quality of such advice. The few studies on the quality of pretravel advice showed conflicting results. 18,19 Data on the type and accuracy of chemoprophylaxis actually performed by travelers in malaria-endemic countries are particularly scarce because most studies on travel health practices are performed among travelers waiting to depart for tropical countries. 12,13,15 In a recent study among German travelers visiting malariaendemic countries, 20% did not carry any antimalarial drug neither for chemoprophylaxis nor for standby treatment with them. 20 We performed a survey among flight passengers returning from Kenya, Senegal, and Thailand to assess the frequency, sources, quality of pretravel advice (according to DTG recommendations), the actual intake of chemoprophylaxis, use of personal protection measures, frequency of carriage and actual intake of standby treatment drugs, and the extent of and reasons for noncompliance. An additional objective was to determine factors (including the source of information) that may influence the quality of travel advice and prophylaxis intake. Methods In March and April 2004, a self-administered questionnaire was distributed by cabin crews to all German-speaking passengers flying back to Germany from Mombasa (Kenya, five flights), Dakar (Senegal, six flights), and Bangkok (Thailand, four flights) on board Condor airlines (Condor Flugdienst). The questionnaire covered sociodemographic 163 characteristics, medical history, destination, type of travel, source and type of pretravel advice, recommendations of chemoprophylaxis, intake of and compliance to prophylaxis drugs, carriage and possible intake of standby treatment drugs, personal protection measures, and clinical signs and symptoms of travel-associated diseases. Questionnaires were collected by the airline personnel and sent to the Robert Koch Institute in Berlin. Completed questionnaires from passengers who had stayed at least 24 hours in one of these countries were included in the analysis. Definitions Correct advice on malaria prophylaxis was defined as the recommended malaria chemoprophylaxis or carriage of standby medication by destination as described in the national guidelines of the DTG as of 2003. 17 Redundant recommendations for chemoprophylaxis, which included the correct drugs plus the carriage of a standby medication, were considered to be correct advice. All travelers to Senegal (apart from those exclusively visiting the Cape Verde Island) and to Kenya were regarded at high risk of malaria. For those, recommended chemoprophylaxis was mefloquine, atovaquone/ proguanil, or doxycycline. Thailand was divided into three regions with different levels of risk: high risk (T2), low risk (T1), and no risk (T0) according to DTG standards. High risk applied for the areas near the northwest border to Myanmar (Tak province) and the southeast border to Cambodia (Trat province). The cities Bangkok, Chiang Mai, Chiang Rai, Pattaya, and the Islands Phuket and Ko Samui were regarded as no-risk areas. The rest of Thailand (eg, central region, coast) was defined as a low-risk area. Due to the high proportion of Plasmodium falciparum strains being resistant against chloroquine and mefloquine, standby treatment only with atovaquone/proguanil or artemether/lumefantrine is recommended by DTG for T1 areas and continuous prophylaxis with atovaquone/proguanil or doxycycline for T2 areas. Data Processing and Statistical Analysis The data were entered into an MS Access database by scanning the questionnaires with the help of Forms5 software (ReadSoft AB, Helsingborg, Sweden). A set of 44 consecutive questionnaires with 182 cross and numeric fields each from one of the batches in the middle of the study period were selected to check the scanner results with the original filled-out questionnaires. Data were

164 analyzed with SPSS (version 14.0 for Windows; SPSS Inc., Chicago, IL, USA). Multivariable analysis was performed using logistic regression models with stepwise forward selection of variables. Variables were included in the model when univariate analysis showed a significant association with the outcome ( p < 0.05) and remained in the model on the basis of the likelihood ratio statistic ( p < 0.05). Results Study Population During 15 flights to Germany, a total of 1,364 questionnaires were distributed to German-speaking adults, of which 1,030 (76%) were returned to the cabin crew. Overall, 1,001 (97%) travelers fulfilled the entry criteria and were included in the analysis. Of these, 492 (49%) returned from Kenya, 131 (13%) from Senegal, and 378 (38%) from Thailand. Fifty-two percent were males, and 95% were of German nationality. The median age was 47 years (range 18 79). The purpose and duration of travel as well as the type of accommodation are listed in Table 1. Ropers et al. Pretravel Advice Of all participants, 81% had sought any kind of pretravel health advice (Kenya 89%, Senegal 82%, and Thailand 70%). The main sources of advice ( n = 769) were general practitioners (48%), followed by tropical medicine institutes (22%), public health offices (9%), friends or family (6%), the Internet (5%), pharmacies (4%), travel agencies (4%), and others (2%). The majority of travelers (55%) obtained pretravel health advice 1 to 6 weeks before departure and 7% within the 7 days before departure. Timing of travel advice and age group had significant influence on the use of sources: last-minute advice seekers (<7 d before departure) and travelers below 40 years of age sought pretravel advice from nonmedical sourc es more often than other travelers (36% vs 17% and 39% vs 30%, respectively, for both p < 0.03). The main reasons for not seeking advice ( n = 191) were that individuals considered themselves sufficiently informed (70%) or that they perceived no risk at their destination (overall 16%; Kenya 7%, Senegal 19%, and Thailand 20%). The proportion of travelers seeking pretravel advice did not differ by purpose of travel [travelers visiting friends or relatives (VFRs), 67%; tourist travelers, 70%; and expatriates, 77%]. Table 1 Frequencies (%) of characteristics and travel profile of study participants Kenya ( n = 492) Senegal ( n = 131) Thailand ( n = 378) Total ( n = 1,001) p Age group (y) ( n = 993) 18 39 29.9 32.0 28.7 31.1 ns 40 59 45.1 47.7 51.2 46.9 60+ 25.0 20.3 20.1 22.0 Sex ( n = 989) Male 48.7 44.2 58.7 51.9 0.002 Female 51.3 55.8 41.3 48.1 Residence ( n = 896) West Germany 67.3 90.1 83.8 76.5 <0.001 East Germany 32.7 9.9 16.2 23.5 Purpose of travel ( n = 990) Leisure 87.0 72.3 80.3 82.6 <0.001 Backpack 7.2 4.0 6.4 6.5 VFR 2.0 19.0 6.4 5.9 Expatriate 2.3 1.6 4.0 2.8 Other business 1.4 3.2 2.9 2.2 Accommodation ( n = 995) Hotel 89.0 65.9 88.0 85.6 <0.001 Apartment 5.1 10.9 5.9 6.1 Family 2.7 22.5 4.0 5.7 Tent, camping 2.9 0.8 0.8 1.8 Others 0.4 0 1.3 0.7 Duration (d) ( n = 983) 14 23.3 37.5 17.1 22.8 <0.001 15 21 53.2 39.8 53.2 51.5 >21 23.5 22.7 29.7 25.7 ns = not significant ( p value > 0.05); VFRs = visiting friends or relatives.

Malaria Prophylaxis Among German Travelers Travelers to Kenya and Senegal Risk Perception Of all travelers to Kenya or Senegal, less than half (43%) correctly perceived the risk of malaria as high (Kenya 45% vs Senegal 35%, p < 0.001), 45% considered it to be low, 2% perceived no risk, and 10% could not classify the risk. Travelers with pretravel advice were significantly more likely to correctly perceive a high risk than travelers without any pretravel advice (51% vs 32%, p = 0.006). 165 Recommendations for Malaria Chemoprophylaxis For both the Kenya travelers ( n = 402) and the Senegal travelers ( n = 85) with a prophylaxis recommendation, 91% had a recommendation for continuous prophylaxis and 9% for standby medication only. The drugs recommended for continuous intake were mefloquine (65%), atovaquone/proguanil (33%), and doxycycline (2%) (multiple response possible). However, chloroquine was recommended in 5% of travelers to either one of the two countries (2% alone and 3% in combination with proguanil, total of n = 18 travelers). Twenty-two travelers were not able to recall their drug recommendation. No significant differences between Kenya and Senegal travelers were found. If advice was given for standby medication only (Kenya 36 travelers and Senegal 8 travelers), the most frequently recommended drug was mefloquine (43%) followed by atovaquone/proguanil (27%). Chloroquine was recommended for standby treatment in six Kenya travelers (in 11% as monotherapy and in 2% in combination with proguanil). Other answers were don t know the medication (21%) and other (2%). Overall, in 76% of Kenya travelers (313/411) and in 70% of the Senegal travelers (64/92), pretravel chemoprophylaxis recommendations were DTG compliant ( Table 2 ). Chemoprophylaxis recommendations for Kenya and Senegal travelers were likely to be DTG compliant if they were provided by medical professionals: public health services (91%) and tropical medicine institutes (83%) ( Figure 1 ). Table 3 shows additional variables found to be associated with the correctness of chemoprophylaxis recommendations for travelers obtaining pretravel advice ( n = 503). DTG compliant recommendations were more frequently provided to travelers with a shorter (<21 d) duration of stay abroad ( p = 0.02), to those who consulted medical professionals ( p < 0.001), and to those who received advice between 6 weeks and 6 months before starting the journey ( p = 0.04). In multivariable analysis, the source of information remained significantly associated with correct advice. Travelers who had consulted institutions with medical professionals were almost four times more likely to receive correct advice (OR 3.9, 95% CI 2.2 6.8) compared to those who obtained their pretravel information from other sources. Chemoprophylaxis Intake A total of 66% travelers reported continuous intake of chemoprophylaxis: 69% in Kenya and 53% in Table 2 DTG compliant recommendations and correct prophylaxis intake in travelers visiting Kenya and Senegal Kenya ( n = 492) Senegal ( n = 124) Total ( n = 616) Travelers without pretravel advice 54 (11.0) 23 (18.5) 77 (12.5) Travelers with pretravel advice 438 (89.0) 101 (81.5) 539 (87.5) Type of advice (% of travelers with advice) Continuous chemoprophylaxis * 366 (83.6) 77 (76.2) 443 (82.2) Standby treatment advice only 36 (8.2) 8 (7.9) 44 (8.2) None 9 (2.0) 7 (6.9) 16 (3.0) Unknown 23 (5.3) 8 (7.9) 31 (5.8) Data missing 4 (0.9) 1 (1.0) 5 (0.9) DTG compliant advice 313 (76.2) 64 (69.6) 377 (75.0) Correct intake Among all travelers (% of all travelers ) 308 (65.1) 54 (47.4) 362 (61.7) Among travelers with advice (% of travelers with advice ) After DTG compliant advice 285 (91.9) 50 (78.1) 335 (89.6) After non-dtg compliant advice 14 (14.3) 2 (7.1) 16 (12.7) Among travelers without pretravel advice 8 (14.8) 2 (11.8) 10 (14.1) DTG = German Society for Tropical Medicine and In ternational Health. * This includes also non-dtg compliant antimalarial drugs (eg, chloroquine). For percentage, travelers with missing data excluded.

166 Ropers et al. Figure 1 Accuracy of recommendations on malaria chemoprophylaxis for Kenya and Senegal by main source of travel advice ( n = 470). Senegal ( p = 0.001). Overall, DTG compliant drug intake was reported by 62% of all travelers to Kenya and Senegal (65% vs 47%, respectively, p < 0.001) ( Table 2 ). Of those with DTG compliant prophylaxis advice, 90% correctly took the chemoprophylaxis compared to only 13% of the travelers with inadequate chemoprophylaxis advice and 14% of persons without any pretravel advice ( Table 2 ). The main reasons for not taking chemoprophylaxis where recommended ( n = 56 answers available) were fear of adverse events (52%), previous experience of adverse events (25%), and no risk perceived (29%). Of the persons who considered themselves sufficiently informed and did not seek travel advice, only 18% (10/55) took the correct prophylaxis. Deviations from the recommended regimen, eg, by taking other drugs, dosages, or intake duration as recommended, were found in 8% of the Kenya travelers and in 21% of the Senegal travelers. Drugs taken for chemoprophylaxis were mefloquine (63%), atovaquone/proguanil (30%), doxycycline (2%) but also chloroquine (3%) and chloroquine/proguanil (3%). Overall, 9% ( n = 32) of the Kenya and Senegal travelers stopped taking their chemoprophylaxis before the recommended date. The main reasons for noncompliance were absence of mosquitoes (53%) and adverse events (22%). Among the total 209 travelers visiting Kenya or Senegal without continuous drug intake, 57 reported to have received a recommendation to carry a standby medication (88 without any recommendation and 64 with missing value), of which 64% actually carried the drug abroad. Table 3 shows variables (in addition to the variable DTG compliant pretravel advice ) that were associated with correct intake. In multivariable analysis, independent factors associated with correct chemoprophylaxis drug intake were travel to Kenya, pretravel advice from a medical professional, duration of stay abroad 15 to 21 days, and correct malaria risk perception ( Table 4 ). Travelers to Thailand Of all 378 Thailand travelers, 86% stayed in areas with a low malaria risk (T1, n = 325) and 13% in areas without any risk (T0, n = 49). Two persons traveled to high-risk areas (two travelers visited unknown areas). Risk Perception The majority of travelers to Thailand perceived the risk of malaria at their destination correctly (71%). For low-risk areas, this was true for 79%, whereas 13% had no risk awareness and 7% overestimated the risk. For no-risk areas, risk assessment was correct for 21%, but most travelers overestimated the malaria risk (72% low risk and 6% high risk). One of the travelers to high-risk areas perceived only low risk and the other no risk at all. Chemoprophylaxis Recommendations and Intake In total, 276 travelers (70%) had sought pretravel advice, 73% of those visiting areas with a low malaria risk and 55% of travelers to areas without malaria risk. One of the two high-risk area travelers reported having obtained travel advice. Of the 237 participants with pretravel advice traveling to lowrisk areas, 43% (99/232 respondents) received a recommendation for chemoprophylaxis or standby treatment: 12% chemoprophylaxis only, 6% chemoprophylaxis plus standby treatment, and 25% standby treatment only. Recommended drugs for chemoprophylaxis or standby were atovaquone/ proguanil (30%, 46%), mefloquine (34%, 28%),

Malaria Prophylaxis Among German Travelers 167 Table 3 Variables associated with factors determining DTG compliant prophylaxis recommendations by advice and correct intake in travelers visiting Kenya and Senegal Variables Correct DTG recommendation ( n = 503), % total p Value Correct intake ( n = 587), % total p Value Country n = 503 n = 587 Kenya 76.2 ns 65.1 <0.001 Senegal 69.6 47.4 Residency n = 449 n = 523 Former West Germany 72.4 0.029 60.9 ns Former East Germany 82.1 68.0 Purpose of travel n = 498 n = 580 Leisure, backpack 75.3 ns 63.4 0.008 VFR 65.5 50.0 Others (eg, expatriate, business) 73.3 34.8 Type of accommodation n = 501 n = 586 Hotel, tent, boat 76.2 ns 65.0 <0.001 Apartment, family/friends 66.7 40.0 Duration of journey (d) n = 493 n = 577 <14 76.6 0.019 57.4 <0.001 14 21 78.3 69.4 >21 64.4 50.4 Source of advice n = 495 n = 483 Medical 81.7 <0.001 75.5 <0.001 Nonmedical 49.4 46.2 Time of advice seeking n = 479 n = 488 >6 mo before 64.3 0.042 49.3 <0.001 6 wk to 6 mo before 82.8 74.4 1 and 6 wk before 76.2 74.5 <7 d before 75.0 55.2 Recommendation DTG compliant n = 504 Yes 89.6 <0.001 No 12.7 Subjective risk perception n = 458 n = 536 Correct 81.9 <0.001 75.3 Incorrect 66.1 48.0 <0.001 VFRs = visiting friends and relatives; DTG = German Society for Tropical Medicine and International Health. doxycycline (7%, 5%), chloroquine/proguanil (9%, 3%), and chloroquine alone (7%, 4%) (don t know: 13%, 14%). More than half of the travelers to lowrisk areas received no recommendation for prophylaxis (56%). Overall, only 37 (17%) of 215 travelers to T1 areas with available information received a DTG compliant recommendation. Among the participants with pretravel advice for no-risk areas, 64% (16/25) were correctly counseled that malaria prophylaxis was not necessary. The traveler to the high-risk areas was advised to take continuous prophylaxis. Of the 315 travelers to low-risk areas in Thailand with pretravel advice, 6% took chemoprophylaxis (although not recommended by DTG) and 57% carried a standby medication. Of the travelers reporting a recommendation for standby ( n = 72), 68% carried an antimalarial drug abroad. Personal Protection Measures Against Mosquito Bites Among Kenya and Senegal travelers, the majority (78%) reported to have applied one or more preventive measure against mosquito bites. Measures (for Kenya n = 415 travelers and Senegal n = 101 travelers) included the use of mosquito nets (68 and 65%), insect repellents (75 and 59%), clothes completely covering arms and legs (50 and 48%), and use of impregnated clothes/mosquito nets (9 and 12%). Twenty-eight percent of these high-risk travelers used both personal protection measures and correct chemoprophylaxis. There was no association between correct personal protection measures and antimalarial chemoprophylaxis: 45% of travelers with correct chemoprophylaxis also used adequate personal protection measures against exposure compared to 41% of those without correct chemoprophylaxis ( p = 0.36).

168 Table 4 Multivariate analysis of factors determining correct antimalarial chemoprophylaxis intake for high-risk sub-saharan countries Kenya and Senegal Variables * OR 95% CI p Value Destination Senegal 1.00 Kenya 1.85 1.10 3.11 0.021 Source of advice No advice at all 1.00 By nonmedical 4.36 1.89 10.06 <0.001 professional By medical 15.39 7.30 32.44 <0.001 professional Duration of travel (d) >21 1.00 15 21 2.21 1.29 3.77 0.004 14 1.27 0.71 2.32 0.404 Risk perception correct: yes vs no 2.91 1.89 4.50 <0.001 * Destination: Kenya (1) versus Senegal (0); pretravel advice: medical professional (2), nonmedical (1), no advice at all (0); duration of journey: >21 days (0), 14 days (1), 15 to 21 days (2); and malaria risk perception appropriate: yes (1) versus no (0). Among Thailand travelers, one or more personal protection measures were applied in 57% while visiting low-risk areas (T1) and in 69% while visiting no-risk areas (T0). Among travelers with answers ( n = 299), personal protection measures consisted of the use of mosquito nets (T1 23% and T0 19%), insect repellents (74 and 79%), clothes completely covering arms and legs (45 and 43%), and impregnated net/clothes (5 and 10%). During pretravel advice, recommendations on personal protection measures were received by travelers with standby treatment advice in 44% (58/133). Health Problems and Standby Medication for Travelers to Kenya, Senegal, and Thailand Of all travelers, 27 (3% of n = 942 respondents) felt feverish during their journey: 11 in Kenya, 9 in Thailand, and 7 in Senegal. Ten reported a selfmeasured temperature of 38 C and more. Of the 20 feverish patients who responded to the question, 12 were taking continuous chemoprophylaxis. Of all 27 febrile travelers, 6 visited a physician to rule out malaria. Malaria was confirmed in one patient visiting Senegal who did not take continuous chemoprophylaxis. In total, five persons took a self- treatment (three with fever and two without fever). Seven febrile travelers reported having carried standby medication but did not use it for self-treatment according to the following reasons: temperature fell after using another treatment ( n = 3), temperature fell by itself Ropers et al. ( n = 3), and belief that the temperature was not dangerous ( n = 1). Discussion Malaria can effectively be prevented by using antimalarial drugs for continuous chemoprophylaxis. In our study, however, only 65% of travelers to Kenya and 47% of travelers to Senegal had used correct chemoprophylaxis. These figures are disturbingly low, even if one takes into account inaccurate recall in some participants and the fact that a few travelers stayed only for a couple of days. Malaria was the most frequent cause for systemic febrile illness among ill-returning travelers reported to the surveillance system GeoSentinel (352 cases per 1,000 febrile patients). 21 Data from 3,752 German travelers reported with falciparum malaria between 1993 and 2004 showed that 60% did not take any chemoprophylaxis. If malaria occurred despite chemoprophylaxis, the intake was still able to significantly reduce fatality rates. 22 These figures underline the importance of continuous chemoprophylaxis in travelers visiting high-risk areas, especially in sub-saharan Africa. Our study highlights two important steps in advance of actual drug intake that contributed to this situation of inadequate malaria prophylaxis: determinants seeking pretravel advice and receipt of correct recommendations during this advice. We found that good advice was the strongest predictor for good intake practice. Of all 149 travelers in highrisk areas without accurate intake, three quarters had not obtained accurate advice prior to their trip. Among travelers without pretravel advice, usage of correct chemoprophylaxis was particularly poor. Besides the fact that these individuals considered themselves already sufficiently informed, perceiving no risk at their destination was the predominating reason for not seeking advice. Previous studies identified VFRs as a risk group seeking pretravel advice less often than tourist travelers. 23 25 Among 5,067 passengers surveyed at European airports prior to departure, only 31% of VFRs had sought pretravel advice compared to 61% of tourists. 15 Probably as a consequence, immigrant VFRs were found in another study to be four times more likely to receive a diagnosis of malaria than did tourist travelers. 25 In our study, VFRs did not seek pretravel advice significantly less often (67%) when compared to tourist travelers (77%). Regarding chemoprophylaxis intake, however, VFRs were significantly less likely to use correct chemoprophylaxis than other groups. Possible explanations for

Malaria Prophylaxis Among German Travelers this discrepancy could be barriers due to the cost of the drugs or beliefs to be somehow not at personal risk. 26 Overall, the validity of perceived risk for malaria among travelers to Senegal and Kenya was surprisingly low at 43% but higher in travelers visiting Thailand (71%). The findings of the European Airport Study were different: 77% of travelers visi t- ing high-risk malaria-endemic areas perceived the risk as high, while only 40% of travelers visiting lowrisk areas perceived the risk as low. 15 In our study, correct risk perception was associated with a higher frequency of correct chemoprophylaxis intake but not with a higher frequency of performed preventive measures against mosquito bites. The quality of received advice was assessed by comparing it to the official recommendations of the DTG. Of those travelers to the African countries with pretravel advice, the vast majority (Kenya 93% and Senegal 85%) received a recommendation for chemoprophylaxis or at least standby treatment. However, the recommended chemoprophylaxis did not concur with the official guidelines in a significant proportion of travelers. Thus, the quality of pretravel advice should be improved in addition to improving the percentage of travelers who receive advice. Overall, travelers were significantly more likely to receive correct chemoprophylaxis recommendations if they consulted medical sources. Recommendations provided by public health offices were most often in accordance with DTG guidelines, followed by institutes of tropical medicine. A reason for the slightly lower frequency of DTG compliant advice at tropical institutes might be that these institutions with broad expertise in travel medicine tailored the advice according to the needs and characteristics of the individual traveler. As a consequence, their advice could differ from DTG standard recommendations but still may be correct after taking into account duration, purpose, and route of the journey. 27 Recommendations by pharmacists were with 70% accuracy for Kenya, the best of all nonmedical sources, comparable with a previous observation among Swiss pharmacists with 74% accuracy for Kenya. 28 Interestingly, half of the travelers using the Internet as the main source reported accurate recommendations, which is unexpectedly high compared with other recent studies on the quality of travel health on the Web. 29,30 Of the travelers with accurate recommendations, 10% failed to take the prophylaxis mainly because of fear of adverse events. In recent studies, this reason for noncompliance was also observed. 31,32 Furthermore, participants traveling longer than 169 3 weeks were more than twice as likely to take incorrect or no drugs compared to those traveling 2 to 3 weeks. For long-term travelers, individually tailored malaria prophylaxis schemes (rather than strictly standardized recommendations) should be provided by travel medicine experts. 33 Noncompliance with chemoprophylaxis once started appears to be another substantial problem among travelers: travelers visiting Kenya and Senegal admitted to have ceased the prophylaxis intake too early in 10 and 20%, respectively. An even lower adherence to chemoprophylaxis was observed in a study among adult travelers to sub-saharan Africa using electronic monitoring. 34 Interestingly, absence of mosquitoes was the most frequently selfreported reason for noncompliance (50%) followed by adverse events in only 22% (independent on the source of pretravel advice). It seems that more education is needed regarding the fact that not observing mosquitoes does not mean no risk of malaria. Furthermore, behavior in case of febrile illness has to be improved: only 22% of travelers with fever consulted a health practitioner to rule out malaria. Thailand is a country with areas of no or low risk for malaria but with high risk in border areas to Burma and Cambodia. This fact seems to make correct (DTG compliant) advice more difficult: almost 20% of travelers visiting low-risk areas received the recommendation for continuous chemoprophylaxis during pretravel advice consultation and only 25% received the correct advice to carry a standby medication only. Nonetheless, malaria is transmitted in Thailand, and the reemergence of the disease in some southern parts of the country led recently to infections in two travelers from Israel and in one German traveler. 35,36 A few limitations of our study have to be considered. In some travelers, there was a considerable time period between the advice prior to travel and the completion of the questionnaire at the end of the trip, which might have introduced recall problems. The response rate of 73% among the flight passengers fulfilling the inclusion criteria was high. Nevertheless, the proportion of correct chemoprophylaxis intake among those nonparticipating travelers is likely to be lower than in travelers interested in filling out the questionnaire. Thus, the true frequency of correct intake might have been even worse than calculated from the questionnaires we received. In conclusion, this present study shows that medical background of the pretravel health information source and correct travelers risk perception are the most important determinants for both

170 DTG compliant recommendation and correct intake. The study has significant implications for improved pretravel advice to reduce malaria risks for travelers to popular tourist destinations. First, it is necessary that more travelers receive adequate pretravel advice. Travel agencies may play a pivotal role to motivate their clients to seek travel advice from competent institutions and experts in travel medicine on time. Public health campaigns concerning travelers health would also contribute to better malaria prophylaxis and immunization coverage among travelers. Second, the quality of pretravel advice concerning malaria chemoprophylaxis should be improved. Whereas the information obtained from medical sources is generally of high quality, there should be efforts to raise the standards of malaria prophylaxis recommendations provided by nonmedical sources. Additional training in travel medicine for general practitioners is also warranted. Acknowledgments We thank Ms Froese (Lufthansa) and Ms Roshan- Moniri (Condor Flugdienst GmbH of Lufthansa Airlines, Medical Service, Frankfurt, Germany) for their logistic support of this study. No financial support was received for the study. Declaration of Interests The authors state that they have no conflicts of interest. References 1. Castelli F. Human mobility and disease: a global challenge. J Travel Med 2004 ; 11 : 1 2. 2. Steffen R. Malaria prophylaxis: setting the scene. J Travel Med 2003 ; 10 : 3 9. 3. Statistisches Bundesamt. Fachserie 8, R6 Luftverkehr 2004. Available at : http://www.destatis.de. ( Accessed 2006 Dec 11 ) 4. Schoeneberg I, Stark K, Altmann D, Krause G. Malaria in Germany 1993 to 2003. Data from the Robert Koch Institute on affected groups of people, countries traveled to and treatment. Dtsch Med Wochenschr 2005 ; 130 : 937 941. 5. Muentener P, Schlagenhauf P, Steffen R. Imported malaria (1985-95): trends and perspectives. Bull World Health Organ 1999 ; 77 : 560 566. 6. Sabatinelli G, Ejov M, Joergensen P. Malaria in the WHO European region (1971-1999). Euro Surveill 2001 ; 6 : 61 65. 7. Robert Koch-Institut. Infektionsepidemiologisches Jahrbuch Meldepflichtiger Krankheiten für 2005. Berlin: RKI, 2006. Available at : http://www.rki.de. Ropers et al. 8. Lobel HO, Phillips-Howard PA, Brandling-Bennett AD, et al. Malaria incidence and prevention among European and North American travellers to Kenya. Bull World Health Organ 1990 ; 68 : 209 215. 9. Steffen R, Heusser R, Mächler R, et al. Malaria chemoprophylaxis among European tourists in tropical Africa: use, adverse reactions, and efficacy. Bull World Health Organ 1990 ; 68 : 313 322. 10. Kollaritsch H, Wiedermann G. Compliance of Austrian tourists with prophylactic measures. Eur J Epidemiol 1992 ; 8 : 243 251. 11. Tiemann F, Grote H, Grote ST. Impfschutz und Infektionsprophylaxe bei Fernreisenden; eine schriftliche Befragung von Fernreisenden auf dem Rückflug aus ausgewählten Reisegebieten. Infektionsepidemiol Forschung 1998 ; 2 : 18 23. 12. Nothdurft HD, Wachinger W. Infektionsprophylaxe von Reisenden vor Fernreisen. Immunol & Impfen 1999 ; 2 : 29 31. 13. Schunk M, Wachinger W, Nothdurft HD. Vaccination status and prophylactic measures of travelers from Germany to subtropical and tropical areas: results of an airport survey. J Travel Med 2001 ; 8 : 260 262. 14. Laver SM, Wetzels J, Behrens RH. Knowledge of malaria, risk perception, and compliance with prophylaxis and personal and environmental preventive measures in travelers exiting Zimbabwe from Harare and Victoria Falls International Airport. J Travel Med 2001 ; 8 : 298 303. 15. Van Herck K, Castelli F, Zuckerman J, et al. Knowledge, attitudes and practices in travel-related infectious diseases: the European Airport Survey. J Travel Med 2004 ; 11 : 3 8. 16. Ropers G, Krause G, Tiemann F, et al. Nationwide survey on the role of travel medicine in primary care in Germany. J Travel Med 2004 ; 11 : 287 294. 17. Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit. Empfehlungen zur Malariaprophylaxe 2003. Hamburg. Available at : http:// www.dtg.mwn.de. 18. Weinke T, Weber G, Schultes U, et al. Malaria prophylaxis in travellers to tropical Africa. Klin Wochenschr 1990 ; 68 : 277 280. 19. Hatz C, Krause E, Grundmann H. Travel advice: a study among Swiss and German general practitioners. Trop Med Int Health 1997 ; 2 : 6 12. 20. Rack J, Wichmann O, Kamara B, et al. Risk and spectrum of diseases in travelers to popular tourist destinations. J Travel Med 2005 ; 12 : 248 253. 21. Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure among ill returned travellers. N Engl J Med 2006 ; 354 : 119 130. 22. Krause G, Schöneberg I, Altmann D, Stark K. Chemoprophylaxis and malaria death rates. Emerg Infect Dis 2006 ; 12 : 447 451. 23. Angell SY, Behrens RH. Risk assessment and disease prevention in travelers visiting friends and relatives. Infect Dis Clin North Am 2005 ; 19 : 49 65.

Malaria Prophylaxis Among German Travelers 24. Schlagenhauf P, Steffen R. Migrants as a major risk group for imported malaria in European countries. J Travel Med 2002 ; 10 : 106 107. 25. Leder K, Tong S, Weld L, et al. Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. Clin Infect Dis 2006 ; 43 : 1185 1193. 26. Morgan M, Figueroa-Munoz JI. Barriers to uptake and adherence with malaria prophylaxis by the African community in London, England: focus group study. Ethn Health 2005 ; 10 : 355 372. 27. Farquharson L, Noble LM, Barker C, Behrens RH. Health beliefs and communication in the travel clinic consultation as predictors of adherence to malaria chemoprophylaxis. Br J Health Psychol 2004 ; 9 : 201 217. 28. Kodkani N, Jenkins JM, Hatz CF. Travel advice given by pharmacists. J Travel Med 1999 ; 6 : 87 93. 29. Horvath LL, Murray CK, DuPont HL. Travel health information at commercial travel websites. J Travel Med 2003 ; 10 : 272 279. 30. Sing A, Salzman JR, Sing H, Sing D. Evaluation of health information provided on the internet by airlines with destinations in tropical and sub-tropical 171 countries. Commun Dis Public Health 2000 ; 3 : 195 197. 31. Shanks GD, Edstein MD. Modern malaria chemoprophylaxis. Drugs 2005 ; 65 : 2091 2110. 32. Schlagenhauf P, Tschopp A, Johnson R, et al. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-saharan Africa. BMJ 2003 ; 327 : 1078. 33. Knobloch J. Long-term malaria prophylaxis. J Travel Med 2004 ; 11 : 373 378. 34. Landry P, Iorillo D, Darioli R, et al. Do travelers really take their mefloquine malaria chemoprophylaxis? Estimation of adherence by an electronic pillbox. J Travel Med 2006 ; 138 : 8 14. 35. Weitzel T. Malaria - Germany ex Thailand. In : ProMED-mail [ online ]. Boston, MA : International Society for Infectious Diseases, 2006 May 11. Archive No.: 20060511.1345. Available at : http://www. promedmail.org/. (Accessed 2006 Jan 12) 36. GeoSentinel. Malaria - Israel ex Thailand. In : ProMED-mail [ online ]. Boston, MA : International Society for Infectious Diseases, 2006 May 20. Archive No.: 20060520.1431. Available at : http://www. promedmail.org/. (Accessed 2006 Jan 12)