Malaria Prophylaxis in Different Age Groups

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1 Malaria Prophylaxis in Different Age Groups Marie-Louise Mittelholzer, Michael Wall, Robert Steflen, and Dieter Stiirchler Background: There is a perceived increased health risk in senior visitors to malaria endemic countries. Methods: The authors sought to compare effectiveness and tolerability of malaria chemoprophylaxis in senior travelers (260 years) those in younger travelers (20-59 years). The Malpro 2 database consists of more than 100,000 questionnaires completed by travelers on charter planes returning from East Africa to Europe during July 1988-December Among them, 9106 (9.1%) of the travelers were 60 years or older, and 84,562 (84.6%) of the travelers reported to be years. Variables of demography, travel data, and the effectiveness and tolerability of chemoprophylaxis were compared in the two subgroups. Results: Malaria in Africa was reported by 8 (1/1000) elderly travelers and by 189 (2.2/1000) travelers aged years. Adjusting for age, sex, prophylaxis, and duration of stay in Africa in a logistic regression model, malaria was significantly more frequent in younger than in senior travelers (p<.05). Any travel-associated illness was reported by 7.0% in the senior age group and by 13.6% in the younger age group (p<.05). The rates of travelers who indicated they had side effects attributable to malaria prophylaxis varied between 9.7% in the elderly and 15.5% in the younger travelers (p<.05). Conclusion: Senior travelers tolerate malaria chemoprophylaxis and visits to the tropics at least as well as younger travelers. As the volume of international travel increases, there is an increase of people >60 years of age traveling to tropical countries. Few papers, however, have addressed in particular the m edd problems and needs of senior citizens visiting malarious areas2the literature has reflected a particular concern that senior travelers could have more problems than younger travelers antmalarial chemoprophylaxis because they often use more concomitant drugs, which could result in a higher susceptibility to adverse reactions. Age-related changes of pharmacokinetics could result in lower antimalarial blood concentrations, which could also influence effectiveness. We decided to compare the effectiveness and tolerability of malaria chemoprophylaxis in senior travelers (260 years) those in younger travelers (20-59 years). Marie-Louise Mittelholzer: Pharmaceuticals Division, Business Development & Strategic Marketing, F. Hoffmann- La Roche Ltd., Basel, Switzerland; Michael Wall, PhD: Basel, Switzerland; Robert Steffen, MD; nstitute for Social and Preventive Medicine, University of Zurich, Switzerland; and Dieter Sturchler, MD: Swiss Federal Office of Public Health, Liebefeld, Switzerland. This paper was presented at the Fourth nternational Conference on Travel Medicine, April 23-27, 1995, Acapulco, Mexico. Reprint requests: Marie-Louise Mittelholzer, Pharmaceuticals Division, Business Development & Strategic Marketing, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland J Travel Med 1996; 4: Methods An existing data set (Malpro 2)4-which consists of more than 100,000 self-administered questionnaires completed during the flight home to Europe from Africa during 1988-December 1991-was reevaluated. The population was divided into two groups: senior travelers (aged 60 years or more) and the younger age group (including travelers aged years).these two groups were subdivided based on malaria prophylaxis into travelers who had taken mefloquine, travelers who had taken other drugs, and travelers who didn t take any chemoprophylaxis. Results were tabulated and simple proportions were calculated for young and senior travelers.the influence of age was tested by means of multiple logistic regression (p<.05 were considered significant). Effectiveness of malaria chemoprophylaxis in this study was determined based on whether the traveler answered The doctor ident$ed malaria by blood-test and/or (in contrast to the evaluation previously p~blished)~ The doctor concluded it was malariafrom the symptoms afmy illness. n the logistic regression model, age, sex, duration of stay in Africa, and prophylaxis were influence factors. Tolerability to the malaria chemoprophylaxis during the traveler s stay in Africa was evaluated by the traveler s answer to the question Have you noticed anything that you believe might be a side efect.fa drug you have been taking as prophylaxis against malaria (therefore, instead 0f adverse events the term side effect is used in this article). n a list of side effects, the traveler could indicate mild moderate or severe. Tolerability was also analyzed based on the traveler s answer to the question Did you 219

2 220 Journal of Travel Medicine, Volume 3, Number 4 Table 1 Prophylactic Antimalarial Medication Used During Trip to Africa , , fah i/l while on this trip to Africa? nfluence factors in the multiple logistic regression models for side effects as well as for illness were age, sex, prophylaxis, and comedication taken. Results Study Population From the total Malpro 2 population, 84,562 questionnaires in the young age group and 9106 in the senior travelers group were included, while 5400 travelers aged 0-19 years and 1193 missing age data were excluded. The prophylactic medication used against malaria by the study group is shown in Table 1. Of the senior travelers to Africa, 56.4% were Swiss, 19.3% were UK, and 4.4% were German residents. The travelers chemoprophylactic regimens differed as a result of varied recommendations given in different countries of residence (Table 2).At the time of Malpro 2, mefloquine was not yet recommended in the UK; therefore, only 4.3% among young and 2.9% among senior travelers used this drug. n Switzerland and Germany, however, the respective proportions were much higher.there was no difference concerning compliance between the two age groups (Table 3). Senior travelers on average tended to stay longer in Africa than younger travelers: the total (proportion) of senior tourists who stayed abroad 2 weeks was 5139 (56.5%), as compared to 57,788 (68.4%) in the younger group (Fig. 1). For 2355 (25.996) of the senior travelers, this stay in Africa was the first visit to the tropics; in the young group, it was the first trip for 39,697 (46.9%). Measures against mosquito bites were clearly more fiequently used by younger than by senior travelers (Fig. 2). Travel Associated llness The proportion of younger travelers who ticked the answer fell ill, but malaria was not suspected was significantly higher than in the senior travelers: 13.6% compared to 7.0% (pc.05). For comparison of the subgroups and choice of possible answers, see Figure 3. Malaria in Africa Eight travelers (1/1000) in the senior group reported that malaria was confirmed in Africa: in two cases based on symptoms (both were on mefloquine prophylaxis) and in six cases based on blood tests (one on mefloquine, two on chloroquine, one on proguanil, one on Fansimef, and one on chloroquine plus proguanil). n the younger population, 189 (2.2/1000) travelers reported they had malaria in Africa: 35 did not take chemoprophylaxis, 46 took mefloquine, and 108 took other drugs. Multiple logistic regression the influence factors age, sex, duration of stay in Africa, and prophylaxis gave a significant difference for the incidence of malaria experienced in Africa between senior and younger travelers. Table 2 Country of Residence of Travelers on Mefloquine, Travelers on Other Antimalarials, and Travelers Who Did Not Take Chemoprophylaxis Travelers Mefluquine Other Antimalarials No Antimahrials County Age Group (4 (4 FA) (4 FA) (n) PA) Switzerland ,507 24, Germany ,299 11, , UK * , , * Other *73.2%/67.7% on chloroquine plus proguanil.

3 Mittelhoizer et al, Malaria Prophylaxis in Different Age Groups 221 Table 3 How Malaria Prophylaxis Tablets Were Taken During Stay in Africa A@ Mefloquine Others Group ntake (n)?a) (4 (%) years Regularly as prescribed 38, or 2 doses too late At irregular intervals stopped tabng the tablets before leaving Africa No answer years Regularly as prescribed or 2 doses too late At irregular intervals stopped taking the tablets before leaving Africa No answer , Adverse Events Of the senior travelers on mefloquine, 9.9% ticked yes when asked Have you noticed anything that you believe might be a side eflect. fa drug you have been taking as prophylaxis against malaria compared to 14.4% among younger travelers (Table 4). Of the seniors on all other antimalarials, 10.3% ticked yes compared to 17.7% of the younger travelers.the significance of these dfferences was confirmed by the multiple logistic regression model. Even in the no antimalarials taken group, 108 of the 3363 younger travelers ticked 254 side effects in total, ~~ n 2 60 years rn years Air cond room --- Mosquito net r?, nsect spray 1 Repellents Electric devices -11:- - ~ Vitamin B tab1 --.~- Others 7--- r - -r % Figure 2 Responses to question Whatmeasures did you take to avoid being bitten by mosquitoes during the night? (260 years, n=9106; years, n=84,562). and in the senior group 13 of 450 ticked an aggregate of 17 side effects. Figure 4 shows the rates of all the noticed side effects in the two age groups on mefloquine; Figure 5 shows the same for the travelers on all other antimalarials. The difference between senior and younger travelers on mefloquine as well as on other drugs was especially high for the side effects of nausea and dizziness.trave1- ers on other drugs showed similar differences; in this group, the difference between younger and senior travelers was especially high for the side effects of headache and mouth ulcers. Comedications The influence of concomitant medication is reported in more detail elsewhere.s Briefly, 50.7% ofthe younger travelers and 44.8% of the senior travelers reported use years rn years % o > 60 years rn 2&59 years 30 11L M o others no mmtiaolher~ no melb dhen no mello~lhen no mello Omen no 5 1 week zweeks Jweeks weeks > 1 year meliqane olhen no rnellcqu~~~ olhers M melloquine ofhen no No, was always healthy fell ill, but malaria fell ill malaria or while in Africa was not suspected malaria was suspected Figure 1 Responses to question How long were you in Africa on this rrip? (260 years, n=9106; years, n=84,562). Figure 3 Responses to questions Did you fall il on this trip to Africa? and Was malaria suspected or confirmed? (260 years, n=9106; years, 1144,562).

4 222 Journal of Travel Medicine, Volume 3, Number 4 % Mefloquine wars rn vears % n 2 60 years rn years rnemomers DO -oolhwa no mellaomers no memolhera M melloolhsro no Blood-pressure Bern-blacker Hem drug Antidiarrheal Other drugs lowering drug Figure 4 Responses by travelers who took mefloquine question "Which side effects did you experience?" (260 years, n=9106; years, n=84,562). Figure 6 Responses to question "Did you take any medication other than antimalarial drugs while in Africa?"(260 years, n=9106; years, n=84,562). of other drugs. As expected, elderly travelers took more cardiovascular drugs (2193/9106) compared to younger travelers (3645/84,562) but less antidiarrheals (18% vs. 28%) (Fig. 6). Discussion and Conclusions The perceived increased health risks of senior travelers who are known to have an increased rate of comorbidity and comedication is not supported by Malpro 2 data. n contrast, senior travelers tolerate malaria prophylaxis and in particular mefloquine prophylaxis at least as well as younger travelers. Surprisingly, in both age groups, travelers chemoprophylaxis did not take more additional measures against mosquito bites compared to travelers who took antimalarials. Despite the fact that mefloquine tablets have a bitter taste, compliance was comparable to that of other drugs or even better. The apparent well-being of the study group's senior travelers can be explained in several ways: a bias by selfselection; elderly travelers' expected preference for recreational holidays a lower risk for illness'; and senior increased travel experience in tropical countries. Regarding concomitant medication, younger travelers appeared to use more additional drugs than senior travelers. However, if oral contraceptives are excluded from the analysis, the number of comedications per traveler was 1.0 in the young age group and 1.3 in the senior age group. Our analysis does not confirm that drug intake in seniors is associated an unacceptably high susceptibility to adverse drug reactions. A recently reported pharmacokinetic study' showed that the pharmacokinetic parameters of mefloquine following a single oral dose of 250 mg in elderly subjects (age range years) were not significantly different (p>.05) from those determined in a control group of % Other Drugs 0 ~60years yean Figure 5 Responses by travelers who took chemoprophylaxis other than mefloquine to question "Which side effects did you experience?"(260 years, n=9106; years, n=84,562/. ache "Bss Table 4 "Have You Noticed Anything That You Believe Might Be a Side Effect of a Drug You Have Been Taking as Prophylaxis Against Malaria?" Age Group ntake years Yes No " don't know" No answer 260 years Yes No " don't know" No answer *95% C, ;+95% C, Mefloquine in) f%) (4 Others * , , t

5 Mittelholzer et al, Malaria Prophylaxis in Different Age Groups 223 young subjects (age range years). Only the C,,,ax 2. value was significantly decreased by 15%.The report concluded that this decrease is assumed to be clinical consequences, and a dose adjustment is not 3. recommended in the elderly. However, it cannot be 4. excluded that lower Cmaxvalues might have an influence on tolerability. n conclusion our data support the safety of anti- 5. malarial prophylaxis in senior travelers who visit Africa. References 1. World Tourism Organization News 1995;1:2, Drunat 0, Lutzler Uizien A, et al. La personne Pgee en voyage. La revue du l racticien-mkdecine G6nerale 1995;306: Swift CG. Pharmacokinetics and prescribing in the elderly. J Antimicrob Chemother 1994;34A: Steffen R, Fuchs E, Schildknecht J, et al. Mefloquine compared other malaria chemoprophylactic regimens in tourists visiting East Africa. Lancet 1993;341: Handschin J,Wd M, Steffen R, et A. Mefloquine and comedication in travellers (manuscript in preparation). Ahlm C, Lundberg S, FessC K, et al. Health problems and selfmedication among Swedish travellers. Scand J nfect Dis 1994;26: Crevoisier C. Pharmacokinetic report. l3asel:hoffniann-la Roche AG,code MK109,1995. Palace Gardens in central ndia. Submitted by J.S. Keystone, M.D.