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Malaria prevention behaviour and risk awareness in French adult travellers
Travel Medicine and Infectious Disease (2010) 8, 13e21
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/tmid
Malaria prevention behaviour and risk awareness in French adult travellers Thierry Pistone a,d, Khaled Ezzedine a,b,*,d, Anne-Franc ¸oise Gaudin c, ¨lle Nachbaur c, Denis Malvy a Serge Hercberg b, Gae a
Service de Me´decine Interne et des Maladies Tropicales, Hoˆpital St-Andre´, CHU Bordeaux, Bordeaux, France UMR U557 INSERM, University of Paris XIII, Bobigny, France c Laboratoire GlaxoSmithKline, Marly-le-Roi, France b
Received 23 June 2009; received in revised form 22 October 2009; accepted 27 October 2009 Available online 24 November 2009
KEYWORDS Malaria; Travel; Chemoprophylaxis; Behaviour; Prophylaxis; Risk
Summary Travellers from Europe to tropical areas risk acquiring malaria against which they have no immunity. The objective of this study was to assess malaria protection measures in European travellers as a function of the risk of infection with malaria. This questionnaire-based, retrospective study evaluated 13,017 French adults. 3066 travellers to malaria-endemic countries were identified and data collected on duration and purpose of stay, knowledge of malaria, use of mechanical protection measures and chemoprophylaxis. Complete data on protection measures were available for 2225 travellers to malaria risk countries. Mechanical protection was used by 1735/2225 of travellers (94.9% of travellers to high-risk areas and 80.4% of travellers to low-risk areas). Appropriate chemoprophylaxis use rates were 47.6% for high-risk areas versus 9.5% for low-risk areas. Chemoprophylaxis compliance was low, even in the case of travellers to high risk areas (18.2%). Many travellers (38%) were unaware that malaria was potentially fatal. The only variables significantly associated with compliant use of appropriate chemoprophylaxis were awareness that malaria was serious (odds-ratio: 2.03; p Z 0.033) and receiving malaria information from a physician (odds-ratio: 3.01; p Z 0.042). Use of malaria chemoprophylaxis is very inadequate. Education campaigns are needed to improve the use of chemoprophylaxis and thus minimise the risk of acquiring malaria. ª 2009 Elsevier Ltd. All rights reserved.
* Corresponding author at: Service de Dermatologie, Ho ˆpital Saint Andre ´, CHU Bordeaux, 1, rue Jean Burguet, 33075 Bordeaux, France. Tel.: þ33 5 56 79 49 65; fax: þ33 5 56 79 58 80. E-mail address: [email protected] (K. Ezzedine). d The first two authors contributed equally to the study and to the preparation of the manuscript. 1477-8939/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2009.10.005
14
Introduction Individuals from non-endemic countries travelling to tropical areas are exposed to the risk of infection with tropical diseases against which they have not built up immunity. Malaria caused by Plasmodium falciparum is of particular concern in this respect, due to the widespread distribution of the infectious organism and its mosquito vector, to its high prevalence in tropical countries and to its potentially fatal outcome.1e4 France has a particularly high incidence of imported malaria, with over 5000 cases reported each year, principally in travellers returning from sub-Saharan Africa.5 Both these French data and recent surveillance data from the United Kingdom1 indicate that the incidence of imported malaria in Western Europe from sub-Saharan Africa may be increasing. We reported recently an incidence rate of imported malaria of 14.8 per month of exposure per 1000 travellers in a population-based cohort of 752 French adults travelling to endemic areas between 1994 and 1999.6 This can be compared with an incidence of imported malaria from East Africa of 15.2 per month of exposure per 1000 travellers from East Africa and of 24.2 per month of exposure per 1000 travellers from West Africa, reported previously by Steffen et al.7 in a survey of more than 40,000 European travellers. The risk of malaria can, however, be reduced dramatically by the use of appropriate chemoprophylaxis and mechanical protection measures.8 Nonetheless, a significant proportion of travellers neglect these effective ways of avoiding infection.6,7,9e13 In our previous study, only 42.3% of the sample reported the use of mechanical protection measures and 44% had taken appropriate prophylactic treatment.6 Several reasons may contribute to suboptimal use of chemoprophylaxis, including cost,14,15 limited awareness of risk,16e18 fear of side-effects19,20 and non-compliance.7,21,22 However, previous studies have not generally taken into account the risk of malaria when evaluating the extent of use of malarial prevention measures. It is particularly important to improve prevention of malaria by travellers to countries where the risk of infection is particularly high, notably to sub-Saharan Africa, where prevalence rates are high, infection risk exists throughout the territory and resistance to chemoprophylaxis is extensive. On the other hand, exposure to risk may be much lower for travellers to other countries where malaria is either not endemic or locally distributed. For example, in China, the risk of infection is restricted to the Yunnan province, rarely visited by foreign travellers. In Thailand, Vietnam and Brazil, there is no risk of malaria in urban centres and seaside resorts which are the most frequent destinations of travellers to these countries. In Mediterranean countries, such as Morocco, Tunisia and Turkey, exposure risk is even more marginal, and principally concerns Plasmodium vivax rather than P. falciparum malaria. The objective of this study was to assess the use of mechanical protection measures and chemoprophylaxis in a population-based cohort of French adults travelling to endemic countries and compare extent of use as a function of the risk of malarial infection. The secondary objectives were to assess malaria risk awareness and to evaluate
T. Pistone et al. determinants of compliance with recommended prophylaxis measures.
Study population and methods Study population and setting This retrospective cohort study was performed within the context of the SU.VI.MAX (Supplementation en Vitamines et Mine´raux AntioXydants) (SU.VI.MAX ) study, a large French randomised double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of antioxidant vitamin and mineral supplementation in reducing chronic morbidity and premature mortality.23 The study methodology of the SU.VI.MAX study has been described extensively elsewhere.24 Briefly, subjects were recruited through a national multimedia campaign in 1994. Approximately 80,000 applicants were screened. Entry criteria included age range 35e60 years for women and 40e 65 years for men, absence of severe disease, absence of obsessive behaviour regarding diet and health, willingness to comply with the protocol and no prior use of dietary supplementation with vitamins or minerals. Eligible subjects were stratified to ensure representation of the general population in terms of gender, age, smoking habits and geographic location. A total of 13,017 subjects were recruited and followed for eight years. Participants provided regular information on health events and behaviour, by completing computerised monthly questionnaires principally via the Minitel network. The system provided information on the SU.VI.MAX population and an opportunity to conduct cross-sectional surveys on other healthrelated topics using declarative data.
Data collection At the beginning of 2003, all subjects still participating in the SU.VI.MAX were sent a computerised questionnaire concerning trips abroad undertaken between 1999 and 2002. This questionnaire was made up of three separate files relating to (1) the countries visited, (2) the duration and purpose of stay, and (3) use of mechanical protection measures and chemoprophylaxis, and knowledge of malaria. Subjects could provide data on up to three individual trips during the reference period which were entered onto three separate questionnaires. With respect to mechanical protection measures, subjects were asked to specify whether they had used regularly or sporadically insecticide or repellent sprays, mosquito nets, long-sleeved clothing after dusk and air-conditioning at night. Respondents were required to provide yes/no answers to each item. With respect to chemoprophylaxis, they were asked which, if any, medication had been used and to provide information on the duration of use and compliance.
Data analysis Questionnaires were analysed for all subjects who reported at least one trip to a country in which malaria is present, according to the World Health Organisation classification,25
Malaria prevention behaviour and risk awareness and for whom all three questionnaire files had been submitted. Subjects were stratified into two groups, namely ‘high risk’ and ‘low risk’. High risk areas were defined as countries in which stable or quasi-stable rates of transmission of malaria can be observed throughout most of the year and included sub-Saharan Africa, the Horn of Africa, Madagascar, the Comoros archipelago and Melanesia. Low risk areas corresponded to all other countries. Four levels of chemoprophylaxis were defined, (1) no or inappropriate chemoprophylaxis, (2) recommended prophylaxis, defined as recommended in contemporary French national guidelines,26 (3) appropriate chemoprophylaxis, defined as the use of at least the minimum recommended treatment, if not a greater level of protection and (4) compliant with appropriate chemoprophylaxis, defined as using appropriate chemoprophylaxis during the entire stay in the endemic area and for at least four weeks after their return. French national guidelines in place at the time specified three chemoprophylaxis resistance zones: Zone 1 corresponds to WHO Zone A for which the recommended chemoprophylaxis is chloroquine; Zone 2 corresponds to WHO Zone B, together with West Africa, for which the recommended chemoprophylaxis is chloroquine/ proguanil; Zone 3 corresponds to WHO Zone C excluding West Africa, for which the recommended chemoprophylaxis is mefloquine or doxycyclin. Data were analysed by trip and by traveller. For the analysis by trip, when a traveller had visited more than one country during a single trip, only the protection measures taken for the highest risk country were taken into consideration for the analysis. For the analysis by traveller, each traveller could be taken into account once for travel to low risk countries and once for travel to high risk countries. Thus, travellers visiting both risk areas could be accounted for twice in the analyses by risk area. In case of multiple trips per traveller and per risk area, the trip with the highest risk for each traveller and each risk area was taken for analysis. Missing data were not replaced except for the compliance variable, where the following rules were applied: (1) for subjects undertaking a single trip, data on compliance were considered missing; (2) for subjects making multiple trips, when the traveller was compliant for all trips where data were available, any trip for which data were missing was considered non-evaluable and the data treated as missing; (3) for subjects making multiple trips, when the traveller was non-compliant for any trip where data were available, then the traveller was considered noncompliant for any trip for which data were missing as well.
15 study population (Fig. 1). Five hundred and seventy-two trips (16.6%) involved a trip to a high malaria risk area and the remainder trips to a low risk area (2870 trips; 83.4%). It should be noted that information on protection measures in the third part of the questionnaire was not always complete. In fact, no data on mechanical protection were available for 543 trips and 92 travellers to low risk areas and 89 trips and nine travellers to high risk areas. Similarly, data on chemoprophylaxis were missing for sixteen travellers and 82 trips to low risk areas and seven travellers and 25 trips to high risk areas. The sociodemographic characteristics of the study population are shown in Table 1. The median age was 50 years and women were over-represented (58%) in the sample. The sample was relatively socially-privileged with 70% of subjects having obtained the baccalaureat or a higher diploma, and 61% being white-collar (office) workers or professionals.
Travel characteristics Most of the travellers (N Z 1292; 58.1%) had made only one trip to an at-risk area and 12.4% (N Z 276) had made three trips. The characteristics of the trips undertaken by the study sample are presented in Table 2. The vast majority of trips (>99%) lasted for three months or less. Most trips (83.3%) were to low-risk areas, with the only high-risk country figuring in the ten most frequently-visited destinations being Senegal. The three most visited destinations (Morocco, Egypt and Turkey) were Mediterranean countries where the risk of contracting malaria is minimal.
Malaria prevention Both mechanical protection against mosquito bites and chemoprophylaxis were assessed. Use of mechanical protection measures by trip and by traveller are shown in Table 3. Some form of mechanical protection was used by 1735/2225 of travellers (78%). This proportion was higher in travellers to high-risk areas (94.9%) than in travellers to low-risk areas (80.4%). The mechanical protection measures used most frequently were air-conditioning at
Results Study participants When the survey was initiated, 12,735 of the original participants of the SU.VI.MAX study (97.8%) were still continuing in the study. Of these, 6590 (51.7%) returned a travel medicine questionnaire. Nearly half of these (3066 subjects; 46.5%) had visited an at-risk country for malaria on at least one occasion. All three parts of the questionnaire were available for 2225 travellers (72.5%) who had made 3442 trips between them. These constituted the
Figure 1 Disposition of travellers and trips. LR: low-risk areas; HR: high-risk areas.
16
T. Pistone et al.
Table 1 Sociodemographic characteristics of the study sample (N Z 2225). Percentages are calculated after exclusion of subjects for whom data were missing. Age Median [range]
50 [35e74]
Gender Men (%) Women (%)
942 (42.3%) 1283 (57.7%)
Education level No diploma School certificate Baccalaureate or higher Missing data
41 (1.9%) 622 (28.5%) 1518 (69.6%) 44
Employment status Not in employment Self-employed Blue-collar (e.g. factory) workers White-collar (e.g. office) workers Professional Retired Missing data
266 108 269 717 633 205 27
(12.1%) (4.9%) (12.2%) (32.6%) (28.8%) (9.3%)
air conditioning, all mechanical protection measures were used significantly more frequently in travellers to high-risk areas than in travellers to low-risk areas (p < 0.001; c2 test), this being most striking for the use of sprayed mosquito nets, where a five-fold difference was observed. The reported use of chemoprophylaxis according to zone is shown according to the type of medication by trip in Table 4 and by conformity of chemoprophylaxis by traveller in Table 5. Some form of chemoprophylaxis was used by 511 travellers (23% of the study population). However, chemoprophylaxis was only appropriate for the zone visited for 290 travellers (13%), of whom 88 complied with the treatment (30.3% of travellers receiving appropriate prophylaxis). As with mechanical protection measures, the use of any chemoprophylaxis, appropriate chemoprophylaxis and compliance with chemoprophylaxis were significantly higher in travellers visiting high-risk areas (p < 0.01; c2 test). The form of chemoprophylaxis used most frequently was chloroquine/proguanil (419 trips), mefloquine (304 trips) and chloroquine (196 trips). Overall, the use of both appropriate chemoprophylaxis and mechanical protection measures was reported by 9.1% of travellers to low-risk areas and 44.8% of travellers to high-risk areas.
Knowledge of malaria night (1282/2225 travellers; 57.6%). If use of air conditioning, which may not be a conscious protection measure, was excluded then at least one mechanical protection measure was used on 59.1% of trips to low-risk areas and on 89.9% of trips to high-risk areas. With the exception of the
Participants were asked about their knowledge and beliefs about malaria (Table 6). Although most subjects were aware that malaria existed and could be prevented, only a minority thought that it could be cured and over a third were unaware that malaria was a serious and potentially
Table 2 Travel characteristics. Only the ten most frequently visited countries are indicated for each risk group. The figures in brackets refer to the chemoprophylaxis resistance zone as specified in French guidelines.26 Trips to low risk areas n Z 2870
Trips to high risk areas n Z 572
Trip length Three months Median length [range] > Three months Median length [range]
(n Z 2846) 2833 (99.5%) 12 [1e92] days 13 (0.5%) 153 [105e458] days
(n Z 566) 557 (98.4%) 14 [1e92] days 9 (1.6%) 183 [122e671] days
Destination
Morocco (1) Egypt (1) Turkey (1) China (3) Thailand (3) Vietnam (3) Mexico (1) Mauritius (1) Dominican Republic (1) India (1)
Reason for trip Professional Tourism Return to country of origin Humanitarian Other
(n Z 2833) 145 (5.1%) 2601 (91.8%) 13 (0.5%) 12 (0.4%) 62 (2.2%)
a
631 420 295 175 169 168 135 133 96 95
(22.0%) (14.6%) (10.3%) (6.1%) (5.9%) (5.9%) (4.7%) (4.6%) (3.3%) (3.3%)
Senegal (2) South Africa (3)a Kenya (3) Madagascar (2) Mauritania (2) Mali (2) Burkina Faso (2) Ivory Coast (2) Swaziland (3) Niger (2) (n Z 566) 38 (6.7%) 441 (77.9%) 5 (0.9%) 38 (6.7%) 44 (7.8%)
Only trips to South Africa including a visit to the high-risk Kruger Park region were considered.
175 72 52 51 40 31 30 23 22 20
(30.6%) (12.6%) (9.1%) (8.9%) (7.0%) (5.4%) (5.2%) (4.0%) (3.8%) (3.5%)
Malaria prevention behaviour and risk awareness
17
Table 3 Mechanical protection measures according to risk level by trip and by traveller. No data on mechanical protection were available for 543 trips and 92 travellers to low risk areas and 89 trips and 9 travellers to high risk areas. The classes of mechanical protection measures are not mutually exclusive. Similarly, 273 travellers visited both high- and low-risk areas and are thus not mutually exclusive either. Low risk areas
High risk areas
Trips N of mechanical protection measures None One Two Three Four
n Z 2870 n Z 2327 424 (18.2%) 715 (30.7%) 553 (23.8%) 472 (20.3%) 163 (7.0%)
N Z 572 n Z 483 27 (5.6%) 67 (13.9%) 107 (22.2%) 168 (34.8%) 114 (23.6%)
Type of mechanical protection Mosquito repellent Sprayed mosquito net Long-sleeved clothing after dusk Air-conditioning at night Other than air-conditioning
970 (41.7%) 250 (10.7%) 1101 (47.3%) 1599 (68.7%) 1375 (59.1%)
351 205 390 320 434
N Z 1982
N Z 480
705/1849 (38.1%) 137/1780 (7.7%) 770/1809 (42.6%) 1172/1833 (63.9%) 1520/1890 (80.4%)
353/459 179/436 338/451 286/452 446/471
Travellers Type of mechanical protection Mosquito repellent Sprayed mosquito net Long-sleeved clothing after dusk Air-conditioning at night Any mechanical protection
fatal disease. Three-quarters of the participants believed that taking medication was the best way to avoid contracting malaria. Most travellers claimed to obtain information about malaria from their physician and from travel agents or travel guides.
Determinants of malaria prevention behaviour Certain features of trips to at-risk countries were associated with differences in malaria prevention behaviour. Use of appropriate chemoprophylaxis was greater when trips were longer (over two weeks) rather than shorter (less than one week), for single rather than multiple trips and for trips undertaken for humanitarian purposes (p < 0.001; Table 7). Similarly, compliance with appropriate chemoprophylaxis was more frequent for single trips and for humanitarian trips (p < 0.001; data not shown) and use of mechanical prevention measures more frequent for shorter trips and single trips (p < 0.001; data not shown). A multiple logistic regression analysis was also performed to evaluate potential associations between sociodemographic characteristics of the travellers (age, gender, educational level, employment status) and extent of knowledge about malaria (items in Table 6) on the one hand, and compliance with appropriate chemoprophylaxis on the other. The only significant associations observed were for awareness that malaria was a serious disease (odds ratio: 2.03 [95% CI: 1.06e3.87]; p Z 0.033) and for acquiring information about malaria from a physician (odds ratio: 3.01; [95% CI: 1.04e8.71]; p Z 0.042). However, when the analysis was reiterated for travellers to low and
(72.7%) (42.4%) (80.7%) (66.3%) (89.9%)
(76.9%) (41.1%) (74.9%) (63.1%) (94.9%)
p
<0.001
<0.001 <0.001 <0.001 0.95 <0.001
<0.001 <0.001 <0.001 0.77 <0.001
high risk areas separately, age was also identified as being significantly associated with compliant use of appropriate chemoprophylaxis for the high-risk area travellers only, with older travellers being less likely to be compliant (odds ratio: 0.95 per incremental year of age; [95% CI: 0.91e 0.99]; p Z 0.018).
Discussion The principal objective of this study was to compare the use of malaria prevention measures between travellers to countries with a high risk of malaria infection and those travelling to low-risk countries. With respect to the use of mechanical protection measures, the extent of use was higher (94.5%) in travellers to high risk countries compared to travellers to low risk countries (80.0%). The extent of the use of mechanical protection measures during travel to the former countries can therefore be considered as generally satisfactory. This is an important finding, since physical protection against mosquito bites should be considered the foremost initial method of protection against malaria infection.13 On the other hand, the situation for chemoprophylaxis is clearly unsatisfactory. The proportion of travellers taking an appropriate chemoprophylaxis seems higher for travellers to high-risk countries (47.6% versus 9.5%), although most of this difference can be accounted for by the low rate of chemoprophylaxis use in travellers to Zone 1 countries that are all considered to be low risk. When comparisons are stratified by zone, 39.3% of travellers to low risk
(9.5%) (1.8%) (41.3%) (18.8%) (2.0%) (0.2%) (0.5%) (2.2%) (2.4%) (21.2%) (0.6%) (1.9%) (2.5%) (19.3%)
52 10 226 103 11 1 3 12 13 116 (6.2%) (0.6%) (21.7%) (42.9%) (4.3%)
a
(2.2%) (0.6%) (55.5%) (3.2%) (2.2%) (43.3%)
(5.4%) (1.4%) (35.0%) (8.7%) (0.7%) e
1 10 3 1654
(0.1%) (0.6%) (0.2%) (92.0%)
15 4 97 24 2 e e 9 6 120 (4.0%) (0.1%) (1.9%) (1.2%) (0.1%) 72 1 34 21 1
Chloroquine alone Proguanil alone Chloroquine/proguanil Mefloquine Atovaquone/proguanila Doxycylin Other Unknown Multiple treatments None
In the last period of the survey (2002), the atovaquone/proguanil combination was introduced as a chemoprophylaxis option for Zone 3.
10 1 35 69 7 e 1 3 4 31 (10.9%) (2.3%) (49.5%) (8.8%) (1.0%) (0.3%) (0.5%) (2.3%) (2.3%) (22.0%) 57 5 62 156 12 7 e 16 4 396
(8.0%) (0.7%) (8.7%) (21.8%) (1.7%) (1.0%)
144 10 193 201 15 7 1 35 13 2169
(5.2%) (0.4%) (6.9%) (7.2%) (0.5%) (0.3%) (>0.1%) (1.3%) (0.5%) (77.8%)
All (N Z 2788) MQ or DCa
Zone 3 (N Z 714) Recommended CP
42 9 191 34 4 1 2 9 9 85
MQ or DCa
Zone 2 (N Z 386) Zone 2 (N Z 277)
CQ/PG
Zone 1 (N Z 1797)
CQ
CQ/PG
High risk areas Low risk areas
Zone 3 (N Z 161)
All (N Z 547)
T. Pistone et al. Table 4 Reported chemoprophylaxis use by trip according to risk area and chemoprophylaxis zone. Percentages are calculated with respect to the total number of trips for which information on chemoprophylaxis use was provided. Data were missing for 82 trips to low risk areas and 25 trips to high risk areas. CP: chemoprophylaxis; AV: atovaquone; CQ: chloroquine; PG: proguanil; MQ: mefloquine; DC: doxycyclin.
18
countries in Zone 2 reported appropriate chemoprophylaxis use compared to 52.7% of those travelling to high risk countries in this zone. Similarly, corresponding appropriate chemoprophylaxis percentages for Zone 3 were 20.1% in low risk and 40.3% in high risk. Regardless of the zone, less than half the travellers who received an appropriate prophylaxis actually complied. This unsatisfactory situation raises a number of challenges for improving the minimal risk behaviour of travellers. The first relates to the fact that one-quarter of travellers to high-risk countries and an even higher proportion of travellers to low risk countries were not receiving any chemoprophylaxis at all. This is consistent with previous studies which have shown that a significant minority of travellers to tropical countries fail to seek advice about the health risks to which they may be exposed.13,16,27 Posters displayed in general practitioners’ waiting rooms may be helpful in this respect but, most importantly, travel agents organising voyages to countries where malaria is endemic need to advise potential travellers systematically on the importance of consulting a trained physician or a Travel Health Centre with respect to prevention of tropical diseases such as malaria. The increasing use of the internet for purchasing travel on line means that a significant proportion of potential travellers do not have access to this type of information. Travel Health Centres, available in all large towns, are the reference source for this information in France and also provide vaccination and chemoprophylaxis prescription when necessary, but most travellers never make use of this facility and many are unaware of their existence. In addition, consultation at a Travel Health Centre is not reimbursed by the social security in France, which may discourage attendance. The second issue relates to the type of chemoprophylaxis prescribed when future travellers do consult a physician. Prescribing practice is clearly unsatisfactory with only 41% of travellers to high-risk areas receiving the recommended chemoprophylaxis. The small proportion of travellers receiving chemoprophylaxis appropriate for the zone visited is consistent with previously reported values.6,7,27e 30 For travellers to Zone 3 countries, a treatment that would be effective (mefloquine, atovaquone/proguanil or doxycycline) was prescribed for only 23.4% of trips, whereas chloroquine was prescribed for 7.7% of these trips. For Zone 2 countries, only 51.7% of prescriptions concerned the appropriate treatment (chloroquine/proguanil) or a higher level of treatment. Even for travel to Zone 1 countries, only half of the prescriptions were for chloroquine alone with a significant proportion being for treatments such as mefloquine, thus incurring unnecessary expense for the traveller. If general practitioners are not sure what is the recommended chemoprophylaxis for a particular country, since guidelines change over time, new treatments are introduced and countries may be reassigned to a different zone, then they should be encouraged either to refer the prospective traveller to a Travel Health Centre, or contact the Centre themselves by telephone in order to determine the appropriate chemoprophylaxis required. The fact that certain malaria chemoprophylaxis medications are expensive and not currently reimbursed may also be a barrier to the more
Malaria prevention behaviour and risk awareness
19
Table 5 Appropriateness of chemoprophylaxis use by traveller according to risk area and chemoprophylaxis zone. Percentages are calculated with respect to the travellers providing information on chemoprophylaxis use. Note that 273 travellers visited both high- and low-risk areas and the two groups are thus not mutually exclusive. For travellers having made multiple trips within the same risk group, only the trip associated with the highest level zone was considered in the overall total (‘All’ columns). Data were missing for sixteen travellers to low risk areas and seven travellers to high risk areas. Low risk areas
Any Recommended Appropriate Compliant
High risk areas
Zone 1 (N Z 1459)
Zone 2 (N Z 244)
Zone 3 (N Z 637)
All (N Z 1966)
Zone 2 (N Z 347)
Zone 3 (N Z 144)
All (N Z 473)
115 54 94 26
133 74 96 36
283 128 128 29
324 152 187 53
266 152 183 83
116 58 58 9
364 194 225 86
(7.9%) (3.7%) (6.4%) (1.8%)
(54.5%) (30.3%) (39.3%) (14.8%)
(44.4%) (20.1%) (20.1%) (4.6%)
widespread use of chemoprophylaxis, and some reimbursement of these medications may be a cost-effective public health policy for reducing the incidence of imported malaria in France.15 The third concern for improvement is compliance with prophylactic treatment, which was satisfactory in less than half of all travellers regardless of zone and risk area. Poor compliance with malaria chemoprophylaxis has been a consistent finding of many previous studies.6,7,13,21,22,31 It is thus incumbent on prescribing physicians as well as on dispensing pharmacists to impress upon travellers the need to take their treatment as prescribed and in particular to continue with it for the specified time upon return home from the trip. One of the secondary objectives of the study was to evaluate potential determinants of malaria prevention behaviour. It was postulated that, if certain demographic variables could be identified in association with inappropriate prevention behaviour, then education and information measures could be targeted at the most at-risk groups. However, no such variables could be identified. This study has a number of strengths and limitations. Among the strengths are the relatively large sample size, Table 6
Knowledge of malaria in travellers (N Z 2225).
Source of information Physician Pharmacist Family Travel agency or guide Internet or other Knowledge and beliefs Aware of malaria Aware that preventive treatments exist Aware that malaria can be cured Aware that malaria is serious and potentially fatal Beliefs on the best way to avoid malaria Mechanical treatment Medication Air conditioning
1647 229 426 1537 406
(74.0%) (10.3%) (19.1%) (69.1%) (18.2%)
1971 (88.6%) 1931 (86.8%) 827 (37.2%) 1369 (61.5%)
409 (18.4%) 1620 (72.8%) 15 (0.7%)
(16.5%) (7.7%) (9.5%) (2.7%)
(76.7%) (43.8%) (52.7%) (23.9%)
(80.6%) (40.3%) (40.3%) (6.3%)
(77.0%) (41.0%) (47.6%) (18.2%)
the well-characterised study population and extensive and relatively complete data return, which can be attributed to the context of the study, with all subjects participating and actively followed up in the SU.VI.MAX cohort. Limitations include the incomplete representativity of the SU.VI.MAX population with respect to the French general population, in terms of age (younger adults excluded) and socio-economic status (better educated and middle-class subjects being over-represented).24 In particular, migrant workers returning from France to their countries of origin, who may be at high risk due to loss of acquired immunity, are likely to be under-represented or not represented at all. The second principal limitation relates to the retrospective nature of the data collection, which may limit the accuracy of the data obtained, for example with respect to the type of chemoprophylaxis taken and the degree of compliance. This is particularly relevant given that respondents could provide information on trips that had taken place up to four years before the time of the survey.
Table 7 Trip characteristics and malaria prevention behaviour. Appropriate prophylaxis for zone Yes Trip duration Less than 41 (8.3%) one week One to 231 (15.7%) two weeks More than 135 (24.4%) two weeks Trip frequency Single trip 222 (17.5%) Multiple trips 1045 (82.5%) Reason for travel Business 23 (16.5%) Tourism 263 (13.2%) Return to None country of origin Humanitarian 17 (51.5%) Other 23 (27.4%)
No
p
452 (91.7%) 1245 (84.3%)
<0.001
418 (75.6%)
68 (7.4%) 856 (92.6%) 116 (83.5%) 1727 (86.8%) 13 (100%)
16 (48.5%) 61 (72.6%)
<0.001
<0.001
20 The findings of this survey may be compared with those of our previous report of subjects from the same SU.VI.MAX population travelling to malaria endemic areas between 1994 and 1999.6 Between the two surveys, the reported use of physical protection measures increased dramatically. For example, the use of mosquito repellents was reported by 42% of trips to Zones 2 and 3 in the previous Palumax survey compared to 77% of trips to high risk areas (Zones 2 and 3) in the current survey. Indeed, the use of any physical protection measure had doubled from 42% in the previous survey to 80% (low-risk areas) and 95% (high risk areas) in this one. Our reported protection rates are also higher than those reported in a number of previous surveys implemented in the 1980s and 1990s from France 31,32 and elsewhere.7,10 It should be noted that some of the increase in use of mechanical protection measures between the two surveys may be accounted for by the presence of two possible response items (wearing long-sleeved clothing after dusk and use of air conditioning at night) that were not proposed in the Palumax study. These response items (particularly air-conditioning) are also not specific for malaria prevention, and were likely to be used principally for comfort rather than as a conscious malarial prevention measure. Nonetheless, air-conditioning does reduce the risk of mosquito bites, and travellers using it should be considered protected to a certain extent. Indeed, use of air conditioning is one of the recommendations systematically provided by Travel Health Centres in France. Although including use of air conditioning in the mechanical prevention measures may have led to some overestimate of the conscious use of protection measures for trips to lowrisk areas (air conditioning was the only mechanical measure used on 21.3% of trips to these areas), this was not the case for trips to high-risk areas, where a mechanical prevention measure other than air-conditioning was adopted on nine trips out of ten. On the other hand, no improvement was observed for the extent of the use of appropriate chemoprophylaxis between the two surveys. Indeed, the proportion of patients using appropriate chemoprophylaxis had actually declined, from 50.5% to 39.3% for travellers to Zone 2 countries and from 35.9% to 20.1% for Zone 3 countries whatever the level of risk. This disturbing finding reinforces the need for better awareness programmes both for physicians and the general public. In conclusion, our study reveals a largely inadequate use of malaria chemoprophylaxis in travellers from France to high risk areas. We therefore recommend the implementation of public education campaigns in the media as well as targeting general practitioners to improve prescription standards and compliance and thus minimise the risk of acquiring malaria when travelling to these areas.
Conflict of interest ‘‘AFG and GN are employees of GlaxoSmithKline laboratories, purveyors of atovaquone/proguanil, a medication used for the prevention of malaria in travellers.’’ The university-based authors have no conflicts of interest to declare.
T. Pistone et al.
Acknowledgments This study was supported financially by an educational grant from GlaxoSmithKline.
References 1. Smith AD, Bradley DJ, Smith V, Blaze M, Behrens RH, Chiodini PL, et al. Imported malaria and high risk groups: observational study using UK surveillance data 1987e2006. BMJ (Clinical Research Ed) 2008;337:a120. 2. Lalloo DG, Hill DR. Preventing malaria in travellers. BMJ (Clinical Research Ed) 2008;336(7657):1362e6. 3. Tada Y, Okabe N, Kimura M. Travelers’ risk of malaria by destination country: a study from Japan. Travel Med Infectious Disease 2008;6(6):368e72. 4. Zuckerman JN. Imported malaria in the UK. BMJ (Clinical Research Ed) 2008;337:a135. 5. Danis M, Legros F, Thellier M, Caumes E. Current data on malaria in metropolitan France]. Med Trop (Mars) 2002;62(3): 214e8. 6. Malvy D, Pistone T, Rezvani A, Lancon F, Vatan R, Receveur MC, et al. Risk of malaria among French adult travellers. Travel Med Infectious Disease 2006;4(5):259e69. 7. Steffen R, Heusser R, Machler R, Bruppacher R, Naef U, Chen D, et al. Malaria chemoprophylaxis among European tourists in tropical Africa: use, adverse reactions, and efficacy. Bull World Health Organ 1990;68(3):313e22. 8. Checkley AM, Hill DR. Prevention of malaria in long-term travelers. Trends Parasitol 2007;23(10):462e5. 9. Campbell H. Imported malaria in the UK: advice given by general practitioners to British residents travelling to malaria endemic areas. J R Coll Gen Pract 1987;37(295):70e2. 10. Kain KC, Harrington MA, Tennyson S, Keystone JS. Imported malaria: prospective analysis of problems in diagnosis and management. Clin Infect Dis 1998;27(1):142e9. 11. Semaille C, Santin A, Prazuck T, Bargain P, Lafaix C, Fisch A. Malaria chemoprophylaxis of 3446 French travelers departing from Paris to eight tropical countries. J Travel Med 1999;6(1): 3e6. 12. Svenson JE, MacLean JD, Gyorkos TW, Keystone J. Imported malaria. Clinical presentation and examination of symptomatic travelers. Arch Intern Med 1995;155(8):861e8. 13. Steffen R, Behrens RH. Travellers’ malaria. Parasitol Today 1992;8(2):61e6. 14. Badrinath P, Ejidokun OO, Barnes N, Ramaiah S. Change in NHS regulations may have caused increase in malaria. BMJ (Clinical Research Ed) 1998;316(7146):1746e7. 15. Pistone T, Schwarzinger M, Chauvin P, Ezzedine K, Receveur MC, Djossou F, et al. Reimbursement of malaria chemoprophylaxis for travellers from Europe to sub-Saharan Africa: cost-effectiveness analysis from the perspective of the French national health insurance system. Health Policy (Amsterdam, Netherlands) 2008;88(2e3):186e99. 16. Van Herck K, Zuckerman J, Castelli F, Van Damme P, Walker E, Steffen R. Travelers’ knowledge, attitudes, and practices on prevention of infectious diseases: results from a pilot study. J Travel Med 2003;10(2):75e8. 17. Ropers G, Du Ry van Beest Holle M, Wichmann O, Kappelmayer L, Stuben U, Schonfeld C, et al. Determinants of malaria prophylaxis among German travelers to Kenya, Senegal, and Thailand. J Travel Med 2008;15(3):162e71. 18. Namikawa K, Kikuchi H, Kato S, Takizawa Y, Konta A, Iida T, et al. Knowledge, attitudes, and practices of Japanese travelers towards malaria prevention during overseas travel. Travel Med Infectious Disease 2008;6(3):137e41.
Malaria prevention behaviour and risk awareness 19. Jute S, Toovey S. Knowledge, attitudes and practices of expatriates towards malaria chemoprophylaxis and personal protection measures on a mine in Mali. Travel Med Infectious Disease 2007;5(1):40e3. 20. Dupouy-Camet J, Yera H, Tourte-Schaeffer C. Problems in prescribing malaria chemoprophylaxis for travelers. Fundam Clin Pharmacol 2003;17(2):161e9. 21. Behrens RH, Taylor RB, Pryce DI, Low AS. Chemoprophylaxis compliance in travelers with malaria. J Travel Med 1998;5(2):92e4. 22. Chatterjee S. Compliance of malaria chemoprophylaxis among travelers to India. J Travel Med 1999;6(1):7e11. 23. Hercberg S, Galan P, Preziosi P, Roussel AM, Arnaud J, Richard MJ, et al. Background and rationale behind the SU.VI.MAX study, a prevention trial using nutritional doses of a combination of antioxidant vitamins and minerals to reduce cardiovascular diseases and cancers. SUpplementation en VItamines et Mineraux AntioXydants study. Int J Vitam Nutr Res 1998;68(1):3e20. 24. Hercberg S, Preziosi P, Briancon S, Galan P, Triol I, Malvy D, et al. A primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers in a general population: the SU.VI.MAX studydesign, methods, and participant characteristics. SUpplementation en VItamines et Mineraux AntioXydants. Control Clin Trials 1998;19(4):336e51.
21 25. World Health Organisation. International travel and health. Geneva: WHO; 1995. 26. World Health Organisation. Health recommendations for travellers. Bull Epide´miol Hebd 1998;21. 27. Hamer DH, Connor BA. Travel health knowledge, attitudes and practices among United States travelers. J Travel Med 2004; 11(1):23e6. 28. Durrheim DN, Braack LE, Waner S, Gammon S. Risk of malaria in visitors to the Kruger National Park, South Africa. J Travel Med 1998;5(4):173e7. 29. 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(6):298e303. 30. Lobel HO, Baker MA, Gras FA, Stennies GM, Meerburg P, Hiemstra E, et al. Use of malaria prevention measures by North American and European travelers to East Africa. J Travel Med 2001;8(4):167e72. 31. Danis M, Legros F, Gay F, Brousse G, Bricaire F, Gentilini M. Paludisme d’importation en France. Med Mal Inf 1999; 29(Suppl. 3):257e73. 32. Nicolas X, Le Guen P, Chapalain JC, Decam C, Chevalier B, Bietrix P. Malaria: a myth or reality for the traveller? Presse Med 2001;30(38):1880e1.
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Malaria prevention behaviour and risk awareness in French adult travellers Thierry Pistone a,d, Khaled Ezzedine a,b,*,d, Anne-Franc ¸oise Gaudin c, ¨lle Nachbaur c, Denis Malvy a Serge Hercberg b, Gae a
Service de Me´decine Interne et des Maladies Tropicales, Hoˆpital St-Andre´, CHU Bordeaux, Bordeaux, France UMR U557 INSERM, University of Paris XIII, Bobigny, France c Laboratoire GlaxoSmithKline, Marly-le-Roi, France b
Received 23 June 2009; received in revised form 22 October 2009; accepted 27 October 2009 Available online 24 November 2009
KEYWORDS Malaria; Travel; Chemoprophylaxis; Behaviour; Prophylaxis; Risk
Summary Travellers from Europe to tropical areas risk acquiring malaria against which they have no immunity. The objective of this study was to assess malaria protection measures in European travellers as a function of the risk of infection with malaria. This questionnaire-based, retrospective study evaluated 13,017 French adults. 3066 travellers to malaria-endemic countries were identified and data collected on duration and purpose of stay, knowledge of malaria, use of mechanical protection measures and chemoprophylaxis. Complete data on protection measures were available for 2225 travellers to malaria risk countries. Mechanical protection was used by 1735/2225 of travellers (94.9% of travellers to high-risk areas and 80.4% of travellers to low-risk areas). Appropriate chemoprophylaxis use rates were 47.6% for high-risk areas versus 9.5% for low-risk areas. Chemoprophylaxis compliance was low, even in the case of travellers to high risk areas (18.2%). Many travellers (38%) were unaware that malaria was potentially fatal. The only variables significantly associated with compliant use of appropriate chemoprophylaxis were awareness that malaria was serious (odds-ratio: 2.03; p Z 0.033) and receiving malaria information from a physician (odds-ratio: 3.01; p Z 0.042). Use of malaria chemoprophylaxis is very inadequate. Education campaigns are needed to improve the use of chemoprophylaxis and thus minimise the risk of acquiring malaria. ª 2009 Elsevier Ltd. All rights reserved.
* Corresponding author at: Service de Dermatologie, Ho ˆpital Saint Andre ´, CHU Bordeaux, 1, rue Jean Burguet, 33075 Bordeaux, France. Tel.: þ33 5 56 79 49 65; fax: þ33 5 56 79 58 80. E-mail address: [email protected] (K. Ezzedine). d The first two authors contributed equally to the study and to the preparation of the manuscript. 1477-8939/$ - see front matter ª 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2009.10.005
14
Introduction Individuals from non-endemic countries travelling to tropical areas are exposed to the risk of infection with tropical diseases against which they have not built up immunity. Malaria caused by Plasmodium falciparum is of particular concern in this respect, due to the widespread distribution of the infectious organism and its mosquito vector, to its high prevalence in tropical countries and to its potentially fatal outcome.1e4 France has a particularly high incidence of imported malaria, with over 5000 cases reported each year, principally in travellers returning from sub-Saharan Africa.5 Both these French data and recent surveillance data from the United Kingdom1 indicate that the incidence of imported malaria in Western Europe from sub-Saharan Africa may be increasing. We reported recently an incidence rate of imported malaria of 14.8 per month of exposure per 1000 travellers in a population-based cohort of 752 French adults travelling to endemic areas between 1994 and 1999.6 This can be compared with an incidence of imported malaria from East Africa of 15.2 per month of exposure per 1000 travellers from East Africa and of 24.2 per month of exposure per 1000 travellers from West Africa, reported previously by Steffen et al.7 in a survey of more than 40,000 European travellers. The risk of malaria can, however, be reduced dramatically by the use of appropriate chemoprophylaxis and mechanical protection measures.8 Nonetheless, a significant proportion of travellers neglect these effective ways of avoiding infection.6,7,9e13 In our previous study, only 42.3% of the sample reported the use of mechanical protection measures and 44% had taken appropriate prophylactic treatment.6 Several reasons may contribute to suboptimal use of chemoprophylaxis, including cost,14,15 limited awareness of risk,16e18 fear of side-effects19,20 and non-compliance.7,21,22 However, previous studies have not generally taken into account the risk of malaria when evaluating the extent of use of malarial prevention measures. It is particularly important to improve prevention of malaria by travellers to countries where the risk of infection is particularly high, notably to sub-Saharan Africa, where prevalence rates are high, infection risk exists throughout the territory and resistance to chemoprophylaxis is extensive. On the other hand, exposure to risk may be much lower for travellers to other countries where malaria is either not endemic or locally distributed. For example, in China, the risk of infection is restricted to the Yunnan province, rarely visited by foreign travellers. In Thailand, Vietnam and Brazil, there is no risk of malaria in urban centres and seaside resorts which are the most frequent destinations of travellers to these countries. In Mediterranean countries, such as Morocco, Tunisia and Turkey, exposure risk is even more marginal, and principally concerns Plasmodium vivax rather than P. falciparum malaria. The objective of this study was to assess the use of mechanical protection measures and chemoprophylaxis in a population-based cohort of French adults travelling to endemic countries and compare extent of use as a function of the risk of malarial infection. The secondary objectives were to assess malaria risk awareness and to evaluate
T. Pistone et al. determinants of compliance with recommended prophylaxis measures.
Study population and methods Study population and setting This retrospective cohort study was performed within the context of the SU.VI.MAX (Supplementation en Vitamines et Mine´raux AntioXydants) (SU.VI.MAX ) study, a large French randomised double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of antioxidant vitamin and mineral supplementation in reducing chronic morbidity and premature mortality.23 The study methodology of the SU.VI.MAX study has been described extensively elsewhere.24 Briefly, subjects were recruited through a national multimedia campaign in 1994. Approximately 80,000 applicants were screened. Entry criteria included age range 35e60 years for women and 40e 65 years for men, absence of severe disease, absence of obsessive behaviour regarding diet and health, willingness to comply with the protocol and no prior use of dietary supplementation with vitamins or minerals. Eligible subjects were stratified to ensure representation of the general population in terms of gender, age, smoking habits and geographic location. A total of 13,017 subjects were recruited and followed for eight years. Participants provided regular information on health events and behaviour, by completing computerised monthly questionnaires principally via the Minitel network. The system provided information on the SU.VI.MAX population and an opportunity to conduct cross-sectional surveys on other healthrelated topics using declarative data.
Data collection At the beginning of 2003, all subjects still participating in the SU.VI.MAX were sent a computerised questionnaire concerning trips abroad undertaken between 1999 and 2002. This questionnaire was made up of three separate files relating to (1) the countries visited, (2) the duration and purpose of stay, and (3) use of mechanical protection measures and chemoprophylaxis, and knowledge of malaria. Subjects could provide data on up to three individual trips during the reference period which were entered onto three separate questionnaires. With respect to mechanical protection measures, subjects were asked to specify whether they had used regularly or sporadically insecticide or repellent sprays, mosquito nets, long-sleeved clothing after dusk and air-conditioning at night. Respondents were required to provide yes/no answers to each item. With respect to chemoprophylaxis, they were asked which, if any, medication had been used and to provide information on the duration of use and compliance.
Data analysis Questionnaires were analysed for all subjects who reported at least one trip to a country in which malaria is present, according to the World Health Organisation classification,25
Malaria prevention behaviour and risk awareness and for whom all three questionnaire files had been submitted. Subjects were stratified into two groups, namely ‘high risk’ and ‘low risk’. High risk areas were defined as countries in which stable or quasi-stable rates of transmission of malaria can be observed throughout most of the year and included sub-Saharan Africa, the Horn of Africa, Madagascar, the Comoros archipelago and Melanesia. Low risk areas corresponded to all other countries. Four levels of chemoprophylaxis were defined, (1) no or inappropriate chemoprophylaxis, (2) recommended prophylaxis, defined as recommended in contemporary French national guidelines,26 (3) appropriate chemoprophylaxis, defined as the use of at least the minimum recommended treatment, if not a greater level of protection and (4) compliant with appropriate chemoprophylaxis, defined as using appropriate chemoprophylaxis during the entire stay in the endemic area and for at least four weeks after their return. French national guidelines in place at the time specified three chemoprophylaxis resistance zones: Zone 1 corresponds to WHO Zone A for which the recommended chemoprophylaxis is chloroquine; Zone 2 corresponds to WHO Zone B, together with West Africa, for which the recommended chemoprophylaxis is chloroquine/ proguanil; Zone 3 corresponds to WHO Zone C excluding West Africa, for which the recommended chemoprophylaxis is mefloquine or doxycyclin. Data were analysed by trip and by traveller. For the analysis by trip, when a traveller had visited more than one country during a single trip, only the protection measures taken for the highest risk country were taken into consideration for the analysis. For the analysis by traveller, each traveller could be taken into account once for travel to low risk countries and once for travel to high risk countries. Thus, travellers visiting both risk areas could be accounted for twice in the analyses by risk area. In case of multiple trips per traveller and per risk area, the trip with the highest risk for each traveller and each risk area was taken for analysis. Missing data were not replaced except for the compliance variable, where the following rules were applied: (1) for subjects undertaking a single trip, data on compliance were considered missing; (2) for subjects making multiple trips, when the traveller was compliant for all trips where data were available, any trip for which data were missing was considered non-evaluable and the data treated as missing; (3) for subjects making multiple trips, when the traveller was non-compliant for any trip where data were available, then the traveller was considered noncompliant for any trip for which data were missing as well.
15 study population (Fig. 1). Five hundred and seventy-two trips (16.6%) involved a trip to a high malaria risk area and the remainder trips to a low risk area (2870 trips; 83.4%). It should be noted that information on protection measures in the third part of the questionnaire was not always complete. In fact, no data on mechanical protection were available for 543 trips and 92 travellers to low risk areas and 89 trips and nine travellers to high risk areas. Similarly, data on chemoprophylaxis were missing for sixteen travellers and 82 trips to low risk areas and seven travellers and 25 trips to high risk areas. The sociodemographic characteristics of the study population are shown in Table 1. The median age was 50 years and women were over-represented (58%) in the sample. The sample was relatively socially-privileged with 70% of subjects having obtained the baccalaureat or a higher diploma, and 61% being white-collar (office) workers or professionals.
Travel characteristics Most of the travellers (N Z 1292; 58.1%) had made only one trip to an at-risk area and 12.4% (N Z 276) had made three trips. The characteristics of the trips undertaken by the study sample are presented in Table 2. The vast majority of trips (>99%) lasted for three months or less. Most trips (83.3%) were to low-risk areas, with the only high-risk country figuring in the ten most frequently-visited destinations being Senegal. The three most visited destinations (Morocco, Egypt and Turkey) were Mediterranean countries where the risk of contracting malaria is minimal.
Malaria prevention Both mechanical protection against mosquito bites and chemoprophylaxis were assessed. Use of mechanical protection measures by trip and by traveller are shown in Table 3. Some form of mechanical protection was used by 1735/2225 of travellers (78%). This proportion was higher in travellers to high-risk areas (94.9%) than in travellers to low-risk areas (80.4%). The mechanical protection measures used most frequently were air-conditioning at
Results Study participants When the survey was initiated, 12,735 of the original participants of the SU.VI.MAX study (97.8%) were still continuing in the study. Of these, 6590 (51.7%) returned a travel medicine questionnaire. Nearly half of these (3066 subjects; 46.5%) had visited an at-risk country for malaria on at least one occasion. All three parts of the questionnaire were available for 2225 travellers (72.5%) who had made 3442 trips between them. These constituted the
Figure 1 Disposition of travellers and trips. LR: low-risk areas; HR: high-risk areas.
16
T. Pistone et al.
Table 1 Sociodemographic characteristics of the study sample (N Z 2225). Percentages are calculated after exclusion of subjects for whom data were missing. Age Median [range]
50 [35e74]
Gender Men (%) Women (%)
942 (42.3%) 1283 (57.7%)
Education level No diploma School certificate Baccalaureate or higher Missing data
41 (1.9%) 622 (28.5%) 1518 (69.6%) 44
Employment status Not in employment Self-employed Blue-collar (e.g. factory) workers White-collar (e.g. office) workers Professional Retired Missing data
266 108 269 717 633 205 27
(12.1%) (4.9%) (12.2%) (32.6%) (28.8%) (9.3%)
air conditioning, all mechanical protection measures were used significantly more frequently in travellers to high-risk areas than in travellers to low-risk areas (p < 0.001; c2 test), this being most striking for the use of sprayed mosquito nets, where a five-fold difference was observed. The reported use of chemoprophylaxis according to zone is shown according to the type of medication by trip in Table 4 and by conformity of chemoprophylaxis by traveller in Table 5. Some form of chemoprophylaxis was used by 511 travellers (23% of the study population). However, chemoprophylaxis was only appropriate for the zone visited for 290 travellers (13%), of whom 88 complied with the treatment (30.3% of travellers receiving appropriate prophylaxis). As with mechanical protection measures, the use of any chemoprophylaxis, appropriate chemoprophylaxis and compliance with chemoprophylaxis were significantly higher in travellers visiting high-risk areas (p < 0.01; c2 test). The form of chemoprophylaxis used most frequently was chloroquine/proguanil (419 trips), mefloquine (304 trips) and chloroquine (196 trips). Overall, the use of both appropriate chemoprophylaxis and mechanical protection measures was reported by 9.1% of travellers to low-risk areas and 44.8% of travellers to high-risk areas.
Knowledge of malaria night (1282/2225 travellers; 57.6%). If use of air conditioning, which may not be a conscious protection measure, was excluded then at least one mechanical protection measure was used on 59.1% of trips to low-risk areas and on 89.9% of trips to high-risk areas. With the exception of the
Participants were asked about their knowledge and beliefs about malaria (Table 6). Although most subjects were aware that malaria existed and could be prevented, only a minority thought that it could be cured and over a third were unaware that malaria was a serious and potentially
Table 2 Travel characteristics. Only the ten most frequently visited countries are indicated for each risk group. The figures in brackets refer to the chemoprophylaxis resistance zone as specified in French guidelines.26 Trips to low risk areas n Z 2870
Trips to high risk areas n Z 572
Trip length Three months Median length [range] > Three months Median length [range]
(n Z 2846) 2833 (99.5%) 12 [1e92] days 13 (0.5%) 153 [105e458] days
(n Z 566) 557 (98.4%) 14 [1e92] days 9 (1.6%) 183 [122e671] days
Destination
Morocco (1) Egypt (1) Turkey (1) China (3) Thailand (3) Vietnam (3) Mexico (1) Mauritius (1) Dominican Republic (1) India (1)
Reason for trip Professional Tourism Return to country of origin Humanitarian Other
(n Z 2833) 145 (5.1%) 2601 (91.8%) 13 (0.5%) 12 (0.4%) 62 (2.2%)
a
631 420 295 175 169 168 135 133 96 95
(22.0%) (14.6%) (10.3%) (6.1%) (5.9%) (5.9%) (4.7%) (4.6%) (3.3%) (3.3%)
Senegal (2) South Africa (3)a Kenya (3) Madagascar (2) Mauritania (2) Mali (2) Burkina Faso (2) Ivory Coast (2) Swaziland (3) Niger (2) (n Z 566) 38 (6.7%) 441 (77.9%) 5 (0.9%) 38 (6.7%) 44 (7.8%)
Only trips to South Africa including a visit to the high-risk Kruger Park region were considered.
175 72 52 51 40 31 30 23 22 20
(30.6%) (12.6%) (9.1%) (8.9%) (7.0%) (5.4%) (5.2%) (4.0%) (3.8%) (3.5%)
Malaria prevention behaviour and risk awareness
17
Table 3 Mechanical protection measures according to risk level by trip and by traveller. No data on mechanical protection were available for 543 trips and 92 travellers to low risk areas and 89 trips and 9 travellers to high risk areas. The classes of mechanical protection measures are not mutually exclusive. Similarly, 273 travellers visited both high- and low-risk areas and are thus not mutually exclusive either. Low risk areas
High risk areas
Trips N of mechanical protection measures None One Two Three Four
n Z 2870 n Z 2327 424 (18.2%) 715 (30.7%) 553 (23.8%) 472 (20.3%) 163 (7.0%)
N Z 572 n Z 483 27 (5.6%) 67 (13.9%) 107 (22.2%) 168 (34.8%) 114 (23.6%)
Type of mechanical protection Mosquito repellent Sprayed mosquito net Long-sleeved clothing after dusk Air-conditioning at night Other than air-conditioning
970 (41.7%) 250 (10.7%) 1101 (47.3%) 1599 (68.7%) 1375 (59.1%)
351 205 390 320 434
N Z 1982
N Z 480
705/1849 (38.1%) 137/1780 (7.7%) 770/1809 (42.6%) 1172/1833 (63.9%) 1520/1890 (80.4%)
353/459 179/436 338/451 286/452 446/471
Travellers Type of mechanical protection Mosquito repellent Sprayed mosquito net Long-sleeved clothing after dusk Air-conditioning at night Any mechanical protection
fatal disease. Three-quarters of the participants believed that taking medication was the best way to avoid contracting malaria. Most travellers claimed to obtain information about malaria from their physician and from travel agents or travel guides.
Determinants of malaria prevention behaviour Certain features of trips to at-risk countries were associated with differences in malaria prevention behaviour. Use of appropriate chemoprophylaxis was greater when trips were longer (over two weeks) rather than shorter (less than one week), for single rather than multiple trips and for trips undertaken for humanitarian purposes (p < 0.001; Table 7). Similarly, compliance with appropriate chemoprophylaxis was more frequent for single trips and for humanitarian trips (p < 0.001; data not shown) and use of mechanical prevention measures more frequent for shorter trips and single trips (p < 0.001; data not shown). A multiple logistic regression analysis was also performed to evaluate potential associations between sociodemographic characteristics of the travellers (age, gender, educational level, employment status) and extent of knowledge about malaria (items in Table 6) on the one hand, and compliance with appropriate chemoprophylaxis on the other. The only significant associations observed were for awareness that malaria was a serious disease (odds ratio: 2.03 [95% CI: 1.06e3.87]; p Z 0.033) and for acquiring information about malaria from a physician (odds ratio: 3.01; [95% CI: 1.04e8.71]; p Z 0.042). However, when the analysis was reiterated for travellers to low and
(72.7%) (42.4%) (80.7%) (66.3%) (89.9%)
(76.9%) (41.1%) (74.9%) (63.1%) (94.9%)
p
<0.001
<0.001 <0.001 <0.001 0.95 <0.001
<0.001 <0.001 <0.001 0.77 <0.001
high risk areas separately, age was also identified as being significantly associated with compliant use of appropriate chemoprophylaxis for the high-risk area travellers only, with older travellers being less likely to be compliant (odds ratio: 0.95 per incremental year of age; [95% CI: 0.91e 0.99]; p Z 0.018).
Discussion The principal objective of this study was to compare the use of malaria prevention measures between travellers to countries with a high risk of malaria infection and those travelling to low-risk countries. With respect to the use of mechanical protection measures, the extent of use was higher (94.5%) in travellers to high risk countries compared to travellers to low risk countries (80.0%). The extent of the use of mechanical protection measures during travel to the former countries can therefore be considered as generally satisfactory. This is an important finding, since physical protection against mosquito bites should be considered the foremost initial method of protection against malaria infection.13 On the other hand, the situation for chemoprophylaxis is clearly unsatisfactory. The proportion of travellers taking an appropriate chemoprophylaxis seems higher for travellers to high-risk countries (47.6% versus 9.5%), although most of this difference can be accounted for by the low rate of chemoprophylaxis use in travellers to Zone 1 countries that are all considered to be low risk. When comparisons are stratified by zone, 39.3% of travellers to low risk
(9.5%) (1.8%) (41.3%) (18.8%) (2.0%) (0.2%) (0.5%) (2.2%) (2.4%) (21.2%) (0.6%) (1.9%) (2.5%) (19.3%)
52 10 226 103 11 1 3 12 13 116 (6.2%) (0.6%) (21.7%) (42.9%) (4.3%)
a
(2.2%) (0.6%) (55.5%) (3.2%) (2.2%) (43.3%)
(5.4%) (1.4%) (35.0%) (8.7%) (0.7%) e
1 10 3 1654
(0.1%) (0.6%) (0.2%) (92.0%)
15 4 97 24 2 e e 9 6 120 (4.0%) (0.1%) (1.9%) (1.2%) (0.1%) 72 1 34 21 1
Chloroquine alone Proguanil alone Chloroquine/proguanil Mefloquine Atovaquone/proguanila Doxycylin Other Unknown Multiple treatments None
In the last period of the survey (2002), the atovaquone/proguanil combination was introduced as a chemoprophylaxis option for Zone 3.
10 1 35 69 7 e 1 3 4 31 (10.9%) (2.3%) (49.5%) (8.8%) (1.0%) (0.3%) (0.5%) (2.3%) (2.3%) (22.0%) 57 5 62 156 12 7 e 16 4 396
(8.0%) (0.7%) (8.7%) (21.8%) (1.7%) (1.0%)
144 10 193 201 15 7 1 35 13 2169
(5.2%) (0.4%) (6.9%) (7.2%) (0.5%) (0.3%) (>0.1%) (1.3%) (0.5%) (77.8%)
All (N Z 2788) MQ or DCa
Zone 3 (N Z 714) Recommended CP
42 9 191 34 4 1 2 9 9 85
MQ or DCa
Zone 2 (N Z 386) Zone 2 (N Z 277)
CQ/PG
Zone 1 (N Z 1797)
CQ
CQ/PG
High risk areas Low risk areas
Zone 3 (N Z 161)
All (N Z 547)
T. Pistone et al. Table 4 Reported chemoprophylaxis use by trip according to risk area and chemoprophylaxis zone. Percentages are calculated with respect to the total number of trips for which information on chemoprophylaxis use was provided. Data were missing for 82 trips to low risk areas and 25 trips to high risk areas. CP: chemoprophylaxis; AV: atovaquone; CQ: chloroquine; PG: proguanil; MQ: mefloquine; DC: doxycyclin.
18
countries in Zone 2 reported appropriate chemoprophylaxis use compared to 52.7% of those travelling to high risk countries in this zone. Similarly, corresponding appropriate chemoprophylaxis percentages for Zone 3 were 20.1% in low risk and 40.3% in high risk. Regardless of the zone, less than half the travellers who received an appropriate prophylaxis actually complied. This unsatisfactory situation raises a number of challenges for improving the minimal risk behaviour of travellers. The first relates to the fact that one-quarter of travellers to high-risk countries and an even higher proportion of travellers to low risk countries were not receiving any chemoprophylaxis at all. This is consistent with previous studies which have shown that a significant minority of travellers to tropical countries fail to seek advice about the health risks to which they may be exposed.13,16,27 Posters displayed in general practitioners’ waiting rooms may be helpful in this respect but, most importantly, travel agents organising voyages to countries where malaria is endemic need to advise potential travellers systematically on the importance of consulting a trained physician or a Travel Health Centre with respect to prevention of tropical diseases such as malaria. The increasing use of the internet for purchasing travel on line means that a significant proportion of potential travellers do not have access to this type of information. Travel Health Centres, available in all large towns, are the reference source for this information in France and also provide vaccination and chemoprophylaxis prescription when necessary, but most travellers never make use of this facility and many are unaware of their existence. In addition, consultation at a Travel Health Centre is not reimbursed by the social security in France, which may discourage attendance. The second issue relates to the type of chemoprophylaxis prescribed when future travellers do consult a physician. Prescribing practice is clearly unsatisfactory with only 41% of travellers to high-risk areas receiving the recommended chemoprophylaxis. The small proportion of travellers receiving chemoprophylaxis appropriate for the zone visited is consistent with previously reported values.6,7,27e 30 For travellers to Zone 3 countries, a treatment that would be effective (mefloquine, atovaquone/proguanil or doxycycline) was prescribed for only 23.4% of trips, whereas chloroquine was prescribed for 7.7% of these trips. For Zone 2 countries, only 51.7% of prescriptions concerned the appropriate treatment (chloroquine/proguanil) or a higher level of treatment. Even for travel to Zone 1 countries, only half of the prescriptions were for chloroquine alone with a significant proportion being for treatments such as mefloquine, thus incurring unnecessary expense for the traveller. If general practitioners are not sure what is the recommended chemoprophylaxis for a particular country, since guidelines change over time, new treatments are introduced and countries may be reassigned to a different zone, then they should be encouraged either to refer the prospective traveller to a Travel Health Centre, or contact the Centre themselves by telephone in order to determine the appropriate chemoprophylaxis required. The fact that certain malaria chemoprophylaxis medications are expensive and not currently reimbursed may also be a barrier to the more
Malaria prevention behaviour and risk awareness
19
Table 5 Appropriateness of chemoprophylaxis use by traveller according to risk area and chemoprophylaxis zone. Percentages are calculated with respect to the travellers providing information on chemoprophylaxis use. Note that 273 travellers visited both high- and low-risk areas and the two groups are thus not mutually exclusive. For travellers having made multiple trips within the same risk group, only the trip associated with the highest level zone was considered in the overall total (‘All’ columns). Data were missing for sixteen travellers to low risk areas and seven travellers to high risk areas. Low risk areas
Any Recommended Appropriate Compliant
High risk areas
Zone 1 (N Z 1459)
Zone 2 (N Z 244)
Zone 3 (N Z 637)
All (N Z 1966)
Zone 2 (N Z 347)
Zone 3 (N Z 144)
All (N Z 473)
115 54 94 26
133 74 96 36
283 128 128 29
324 152 187 53
266 152 183 83
116 58 58 9
364 194 225 86
(7.9%) (3.7%) (6.4%) (1.8%)
(54.5%) (30.3%) (39.3%) (14.8%)
(44.4%) (20.1%) (20.1%) (4.6%)
widespread use of chemoprophylaxis, and some reimbursement of these medications may be a cost-effective public health policy for reducing the incidence of imported malaria in France.15 The third concern for improvement is compliance with prophylactic treatment, which was satisfactory in less than half of all travellers regardless of zone and risk area. Poor compliance with malaria chemoprophylaxis has been a consistent finding of many previous studies.6,7,13,21,22,31 It is thus incumbent on prescribing physicians as well as on dispensing pharmacists to impress upon travellers the need to take their treatment as prescribed and in particular to continue with it for the specified time upon return home from the trip. One of the secondary objectives of the study was to evaluate potential determinants of malaria prevention behaviour. It was postulated that, if certain demographic variables could be identified in association with inappropriate prevention behaviour, then education and information measures could be targeted at the most at-risk groups. However, no such variables could be identified. This study has a number of strengths and limitations. Among the strengths are the relatively large sample size, Table 6
Knowledge of malaria in travellers (N Z 2225).
Source of information Physician Pharmacist Family Travel agency or guide Internet or other Knowledge and beliefs Aware of malaria Aware that preventive treatments exist Aware that malaria can be cured Aware that malaria is serious and potentially fatal Beliefs on the best way to avoid malaria Mechanical treatment Medication Air conditioning
1647 229 426 1537 406
(74.0%) (10.3%) (19.1%) (69.1%) (18.2%)
1971 (88.6%) 1931 (86.8%) 827 (37.2%) 1369 (61.5%)
409 (18.4%) 1620 (72.8%) 15 (0.7%)
(16.5%) (7.7%) (9.5%) (2.7%)
(76.7%) (43.8%) (52.7%) (23.9%)
(80.6%) (40.3%) (40.3%) (6.3%)
(77.0%) (41.0%) (47.6%) (18.2%)
the well-characterised study population and extensive and relatively complete data return, which can be attributed to the context of the study, with all subjects participating and actively followed up in the SU.VI.MAX cohort. Limitations include the incomplete representativity of the SU.VI.MAX population with respect to the French general population, in terms of age (younger adults excluded) and socio-economic status (better educated and middle-class subjects being over-represented).24 In particular, migrant workers returning from France to their countries of origin, who may be at high risk due to loss of acquired immunity, are likely to be under-represented or not represented at all. The second principal limitation relates to the retrospective nature of the data collection, which may limit the accuracy of the data obtained, for example with respect to the type of chemoprophylaxis taken and the degree of compliance. This is particularly relevant given that respondents could provide information on trips that had taken place up to four years before the time of the survey.
Table 7 Trip characteristics and malaria prevention behaviour. Appropriate prophylaxis for zone Yes Trip duration Less than 41 (8.3%) one week One to 231 (15.7%) two weeks More than 135 (24.4%) two weeks Trip frequency Single trip 222 (17.5%) Multiple trips 1045 (82.5%) Reason for travel Business 23 (16.5%) Tourism 263 (13.2%) Return to None country of origin Humanitarian 17 (51.5%) Other 23 (27.4%)
No
p
452 (91.7%) 1245 (84.3%)
<0.001
418 (75.6%)
68 (7.4%) 856 (92.6%) 116 (83.5%) 1727 (86.8%) 13 (100%)
16 (48.5%) 61 (72.6%)
<0.001
<0.001
20 The findings of this survey may be compared with those of our previous report of subjects from the same SU.VI.MAX population travelling to malaria endemic areas between 1994 and 1999.6 Between the two surveys, the reported use of physical protection measures increased dramatically. For example, the use of mosquito repellents was reported by 42% of trips to Zones 2 and 3 in the previous Palumax survey compared to 77% of trips to high risk areas (Zones 2 and 3) in the current survey. Indeed, the use of any physical protection measure had doubled from 42% in the previous survey to 80% (low-risk areas) and 95% (high risk areas) in this one. Our reported protection rates are also higher than those reported in a number of previous surveys implemented in the 1980s and 1990s from France 31,32 and elsewhere.7,10 It should be noted that some of the increase in use of mechanical protection measures between the two surveys may be accounted for by the presence of two possible response items (wearing long-sleeved clothing after dusk and use of air conditioning at night) that were not proposed in the Palumax study. These response items (particularly air-conditioning) are also not specific for malaria prevention, and were likely to be used principally for comfort rather than as a conscious malarial prevention measure. Nonetheless, air-conditioning does reduce the risk of mosquito bites, and travellers using it should be considered protected to a certain extent. Indeed, use of air conditioning is one of the recommendations systematically provided by Travel Health Centres in France. Although including use of air conditioning in the mechanical prevention measures may have led to some overestimate of the conscious use of protection measures for trips to lowrisk areas (air conditioning was the only mechanical measure used on 21.3% of trips to these areas), this was not the case for trips to high-risk areas, where a mechanical prevention measure other than air-conditioning was adopted on nine trips out of ten. On the other hand, no improvement was observed for the extent of the use of appropriate chemoprophylaxis between the two surveys. Indeed, the proportion of patients using appropriate chemoprophylaxis had actually declined, from 50.5% to 39.3% for travellers to Zone 2 countries and from 35.9% to 20.1% for Zone 3 countries whatever the level of risk. This disturbing finding reinforces the need for better awareness programmes both for physicians and the general public. In conclusion, our study reveals a largely inadequate use of malaria chemoprophylaxis in travellers from France to high risk areas. We therefore recommend the implementation of public education campaigns in the media as well as targeting general practitioners to improve prescription standards and compliance and thus minimise the risk of acquiring malaria when travelling to these areas.
Conflict of interest ‘‘AFG and GN are employees of GlaxoSmithKline laboratories, purveyors of atovaquone/proguanil, a medication used for the prevention of malaria in travellers.’’ The university-based authors have no conflicts of interest to declare.
T. Pistone et al.
Acknowledgments This study was supported financially by an educational grant from GlaxoSmithKline.
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