Perceptions of tick-borne encephalitis risk: a survey of travellers and travel clinics from Canada, Germany, Sweden and the UK.

Background: While the worldwide endemicity of tick-borne encephalitis (TBE) has been increasing, a lack of awareness of the risks of this life-threatening disease may be leading to an underutilization of preventive measures among travellers to TBE-endemic regions. This study's objectives were to assess travellers' awareness of TBE and advice-seeking attitudes, and to evaluate practices of travel clinics regarding pre-travel advice. Methods: We used an online questionnaire to identify individuals aged 18-65 years residing in the UK, Germany, Canada and Sweden, who had travelled to TBE-endemic countries between 2013 and 2016. This sample was defined as the visit-risk sample. Of these, the first 375 respondents who reported that they had engaged in pre-defined at-risk activities (e.g. hiking in forests) were asked to complete an additional online survey and were included in the activity-risk sub-sample. We also used an online/phone questionnaire to interview travel clinic personnel. Results: The TBE visit-risk sample included 4375 individuals; 69% had heard of the disease and 32% had heard of a TBE vaccine. Before travelling, travellers most commonly sought information online (26%); fewer travellers consulted family doctors (8%) or travel clinics (5%). In the activity-risk sample, 79% of the travellers were aware of at least one correct TBE prevention measure; however, only 15% reported being vaccinated within the past 3 years, with 11% of vaccinated travellers doing so following a clinic's recommendation. One hundred and eighty travel clinic representatives responded and reported that TBE vaccination was recommended to an average of 61% of travellers to endemic regions. Vaccination-reminder services such as follow-up appointments, e-mail and text reminders were offered by 50% of the clinics. Conclusions: There is a need to increase awareness of the risk and prevention of TBE among travellers to endemic countries, and travel clinics could play an important role in this process. 5975671594001tay062media15975671594001.

Perceptions of rabies risk: a survey of travellers and travel clinics from Canada, Germany, Sweden and the UK.

Background: Extensive global experience shows that rabies pre-exposure prophylaxis (PrEP) through vaccination is effective and well tolerated, yet many travellers opt not to be vaccinated when travelling to rabies-endemic countries. Previous research has identified several factors influencing the choices travellers make to reduce the risk of rabies, including cost, time constraint and perspective on the importance of vaccination. The objectives of this study were to assess travellers' awareness of rabies and advice-seeking attitudes and to evaluate travel clinics practices regarding rabies pre-travel advice. Methods: We surveyed individuals aged 18-65 years residing in the UK, Germany, Canada and Sweden who had travelled to rabies-endemic countries between 2013 and 2016 and defined this as the rabies visit-risk sample. The first 850 respondents from the visit-risk sample who had undertaken pre-defined at-risk activities (e.g. contact with animals during the trip) completed an additional 15-min online questionnaire and were included in the activity-risk subsample. We also interviewed travel clinic personnel using a 25-min online or phone questionnaire. Results: The visit-risk sample included 4678 individuals. Many sought pre-travel health information online (33%) or talked to a family doctor (24%). Within the activity-risk subsample, 83% of travellers were aware of at least a few basic facts about rabies, and 84% could identify at least one correct rabies prevention measure; 49% were aware of a rabies vaccine, however, only 8% reported receiving PrEP vaccination within the past 3 years. Among 180 travel clinic respondents, 21% reported recommending PrEP against rabies to all travellers to rabies-endemic countries. Travel clinics estimated that 81% of travellers complete their travel vaccination schedules and reported sending reminders by e-mails (38%), text (38%), phone calls (37%) or by using vaccination cards (37%). Conclusions: These findings suggest that although travellers had frequently heard of rabies, awareness of the risks of this serious infectious disease was relatively low. 5975671594001tay062media15975671594001.

Short-Term Immunogenicity and Safety of an Accelerated Pre-Exposure Prophylaxis Regimen With Japanese Encephalitis Vaccine in Combination With a Rabies Vaccine: A Phase III, Multicenter, Observer-Blind Study.

BACKGROUND: The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study. METHODS: Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57. RESULTS: Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine. CONCLUSIONS: This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated regimen, if licensed, could potentially be a valid alternative for individuals requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis on short notice.

Evaluation of mood profiles during malaria chemoprophylaxis: a randomized, double-blind, four-arm study.

BACKGROUND: To objectively compare the mood profiles of users of malaria chemoprophylaxis regimens (atovaquone-proguanil, chloroquine-proguanil, doxycycline, or mefloquine) in a group of nonimmune tourists to sub-Saharan Africa. METHODS: In a randomized, double-blind, four-arm study with placebo run-in phase conducted at travel clinics in Switzerland, Germany, and Israel, we compared moods and feelings in chemoprophylaxis users (n= 547) by administering the standardized "Profile of Mood States" (POMS) questionnaire. This is designed to provide data on six categories of feelings: tension, depression, anger, vigor, fatigue, and confusion. The questionnaire was administered at four time points: recruitment (T1), 13 to 11 days before departure (T2), 6 to 4 days before departure (T3), and 7 to 14 days after return from Africa (T4). RESULTS: There were no significant differences with respect to overall mood impact between the medication arms. All scores were in the normal range, and no means were more than 1 SD from the norm. The POMS data were reanalyzed with respect to sex, age, medication group, and control time points (T1-T4). There were significant interaction effects between sex and medication group--women in the mefloquine group showed more "fatigue" (p= .011) and "confusion" (p= .011) than men. Significant effects of age group (below median age 34 y vs median age and above) were noted on the "tension" and "fatigue" scales in that less "tension" (p= .045) and less "fatigue" (p= .000) were noted in those aged 34 years and older. Younger participants, aged <34 years, reported more "confusion" (p= .013) at T2 than at T1 and T4. CONCLUSIONS: Although the overall mood profiles were similar for the users of any of the standard malaria chemoprophylaxis regimens, we found that women using mefloquine showed more fatigue and confusion than men and that younger persons aged less than 34 years, regardless of chemoprophylaxis used, reported more tension and fatigue than their older counterparts.

Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study.

OBJECTIVE: To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. DESIGN: Randomised, double blind, study with placebo run-in phase. SETTING: Travel clinics in Switzerland, Germany, and Israel. MAIN OUTCOME MEASURE: Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. PARTICIPANTS: 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. RESULTS: A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n = 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013). CONCLUSIONS: Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.