Norovirus acute gastroenteritis among US and European travellers to areas of moderate to high risk of travellers' diarrhoea: a prospective cohort study.

BACKGROUND: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact among travellers is limited. METHODS: Prospective, multi-site, observational cohort study conducted 2015-2017, among adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms while travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14days of return. Samples were tested for NoV by RT-qPCR, genotyped if positive, and tested for other common enteric pathogens by Luminex xTAG GPP. RESULTS: Of the 1109 participants included, 437 (39.4%) developed AGE symptoms resulting in an overall AGE incidence of 24.7 per 100 person-weeks (95% CI: 22.4; 27.1). Twenty NoV-positive AGE cases (5.2% of those tested) were identified at an incidence of 1.1 per 100 person-weeks (95% CI: 0.7; 1.7). NoV-positive samples belonged mostly to genogroup GII (18, 85.7%); None of the 13 samples sequenced belonged to genotype GII.4. Clinical severity of AGE was higher for NoV-positive than for NoV-negative cases (mean modified Vesikari Score 6.8 vs 4.9) with more cases classified as severe or moderate (25% vs 6.8%). Eighty percent of NoV-positive participants (vs. 38.9% in NoV-negative) reported at least moderate impact on travel plans. CONCLUSIONS: AGE is a prevalent disease among travellers with a small proportion associated with NoV. Post-travel stool sample collection timing might have influenced the low number of NoV cases detected; however, NoV infections resulted in high clinical severity and impact on travel plans. These results may contribute to targeted vaccine development and the design of future studies on NoV epidemiology.

Longitudinal study based on a safety registry for malaria patients treated with artenimol-piperaquine in six European countries.

BACKGROUND: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)-piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. METHODS: Participants were recruited through Health Care Provider's safety registry in 15 centres across 6 European countries in the period 2013-2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett's (QTcB) or Fridericia's (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. RESULTS: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). CONCLUSIONS: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942.

Location-cued visual selection-Placeholder dots improve target identification.

Visual cues help to select a target and attract attention to it. In the present study, a 50-ms exogenous cue was presented to select one of 80 tilted lines, and attention effects at various delays were measured as the time observers needed to identify this target. Like in earlier detection studies, there was a transient cuing effect; targets presented soon after the cue (delays of 50-300 ms) were identified particularly fast. This benefit was followed by a continuous decay of performance toward longer delays (measured up to 5 s), at which the necessary presentation time to identify the target was strongly increased. The decay was substantially reduced when placeholder dots were shown during the delay, at subsequent line positions. The simple presentation of a structured background in the form of random dots did not have this effect. When the presentation times for constant performance were taken to compute the presumed strength of underlying neural responses, the effect of placeholders was seen as a nearly constant addition to the cued target signals, with an additional transient peak about 100 ms after cue (and placeholders) onset.

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.

Retrospective clinical case series study in 2017 identifies Plasmodium knowlesi as most frequent Plasmodium species in returning travellers from Thailand to Germany.

Febrile illnesses are common in travellers returning from south-east Asia. However, malaria is a rare diagnosis in this population. A series of Plasmodium knowlesi infections was noted in German travellers returning from Thailand since 2012. Infectious disease and tropical medicine facilities registered by the German Society for Tropical Medicine and International Health were contacted in March 2017, and asked to report previous P. knowlesi cases. In addition, surveillance data from the Robert Koch-Institute were analysed. The facilities reported a total of six P. knowlesi-positive cases, all were returning travellers from Thailand. The P. knowlesi-positive cases made up 6/9 of all diagnosed malaria cases imported from Thailand in the time period 2012 to 2017. In 4/5 of cases where a malaria rapid diagnostic test had been applied it revealed a negative result. P. knowlesi is an important differential diagnosis in travellers returning from south-east Asia with itineraries that include Thailand. This study highlights the importance of this Plasmodium species in this patient subgroup. Whenever malaria is suspected in a returning traveller from Thailand, P. knowlesi should be taken into consideration and a differential PCR be executed as currently the unequivocal diagnosis of P. knowlesi is based on nuclear amplification techniques.

Corrigendum to "Detection of Gastrointestinal Pathogens from Stool Samples on Hemoccult Cards by Multiplex PCR".

[This corrects the article DOI: 10.1155/2017/3472537.].

Detection of Gastrointestinal Pathogens from Stool Samples on Hemoccult Cards by Multiplex PCR.

Purpose. Up to 30% of international travelers are affected by travelers' diarrhea (TD). Reliable data on the etiology of TD is lacking. Sufficient laboratory capacity at travel destinations is often unavailable and transporting conventional stool samples to the home country is inconvenient. We evaluated the use of Hemoccult cards for stool sampling combined with a multiplex PCR for the detection of model viral, bacterial, and protozoal TD pathogens. Methods. Following the creation of serial dilutions for each model pathogen, last positive dilution steps (LPDs) and thereof calculated last positive sample concentrations (LPCs) were compared between conventional stool samples and card samples. Furthermore, card samples were tested after a prolonged time interval simulating storage during a travel duration of up to 6 weeks. Results. The LPDs/LPCs were comparable to testing of conventional stool samples. After storage on Hemoccult cards, the recovery rate was 97.6% for C. jejuni, 100% for E. histolytica, 97.6% for norovirus GI, and 100% for GII. Detection of expected pathogens was possible at weekly intervals up to 42 days. Conclusion. Stool samples on Hemoccult cards stored at room temperature can be used in combination with a multiplex PCR as a reliable tool for testing of TD pathogens.

[Consensus paper treatment of acute traveler's diarrhea. Practice recommendation for travel advice]. / Konsensuspapier Therapie der akuten Reisediarrhö : Eine Praxisempfehlung für die Reiseberatung.

BACKGROUND: In times of mass tourism, traveler's diarrhea is one of the most common health problems of long-distance travel. Globally, some 40 million cases occur annually. Travellers to risk areas should therefore be comprehensively advised beforehand, as to what action to take in case of an acute traveler's diarrhea and what drugs to add to their first-aid kit. To date none, or hardly any specific studies or valid specific guidelines for the treatment of traveler's diarrhea are available for Germany. METHOD: Drafting a consensus paper based on results of a specialists' meeting to evaluate therapeutic options in the treatment of acute uncomplicated travelers' diarrhea. The foundation for the present consensus recommendations is current evidence on antidiarrheals available in Germany for symptomatic treatment of gastrointestinal infections, summarized in the S2k guideline for gastrointestinal infections and Whipple's disease. Further taken into account for the present consensus recommendations were Pubmed-listed publications on symptomatic treatment of traveler's diarrhea, practical aspects, and the experts' experience in travel medicine. RESULTS AND CONCLUSION: For the treatment of acute uncomplicated traveler's diarrhea - more than 90 % of all cases - the secretion inhibitor racecadotril is considered first choice, based on our evaluation criteria. The previously usual practice of recommending the antimotility drug loperamide as first choice should be reconsidered, in favor of the recent active ingredient racecadotril. Antibiotics should be used only in complicated cases. A large number of travelers who generally demand antibiotic therapy should be disabused of their expectations. Other therapeutic measures that are currently available for the treatment of acute diarrhea while traveling play a subordinate role.

Long-term kinetics of Zika virus RNA and antibodies in body fluids of a vasectomized traveller returning from Martinique: a case report.

BACKGROUND: The magnitude of the current Zika virus (ZIKV) epidemic has led to a declaration of a Public Health Emergency of International Concern by the WHO. Findings of viable viral particles in semen for several weeks are corroborating reports of sexual transmission of ZIKV. Serious consequences of a positive diagnostic result particularly in the pregnant patient are calling for precise diagnostic tools also at later time points after infection. Currently, recommendations suggest a diagnostic period of direct viral detection of 5 to 7 days after onset of symptoms in serum or plasma, and up to 3 weeks in urine samples. CASE PRESENTATION: A vasectomized 41-year-old German returning from Martinique presented at the outpatient clinic of the Department for Infectious Diseases and Tropical Medicine, Munich, with subfebrile temperature, rash, malaise, severe retro-orbital pain and occipital lymphadenopathy. The main complaints resolved after ten days without specific treatment. We are reporting on clinical course and results of direct and indirect detection methods of ZIKV in different sample types including whole blood, ejaculate, urine, serum, plasma and saliva samples up to 119 days post symptom onset. Ejaculate samples remained PCR positive for ZIKV until day 77, whole blood samples until day 101. CONCLUSIONS: The case presentation adds to the still limited knowledge of kinetics of detection of ZIKV by direct as well as indirect methods. Here, a complete data set including results from PCR, serology and cell culture is provided allowing an improved evaluation of optimum diagnostic periods for testing a variety of sample types. Moreover, a high viral load of ZIKV RNA was detected in ejaculate of the vasectomized patient. This finding sheds new light on the possible localizations of ZIKV replication in the human male reproductive tract.

Pre-travel advice, attitudes and hepatitis A and B vaccination rates among travellers from seven countries†.

BACKGROUND: Knowledge about the travel-associated risks of hepatitis A and B, and the extent of pre-travel health-advice being sought may vary between countries. METHODS: An online survey was undertaken to assess the awareness, advice-seeking behaviour, rates of vaccination against hepatitis A and B and adherence rates in Australia, Finland, Germany, Norway, Sweden, the UK and Canada between August and October 2014. Individuals aged 18-65 years were screened for eligibility based on: travel to hepatitis A and B endemic countries within the past 3 years, awareness of hepatitis A, and/or combined hepatitis A&B vaccines; awareness of their self-reported vaccination status and if vaccinated, vaccination within the last 3 years. Awareness and receipt of the vaccines, sources of advice, reasons for non-vaccination, adherence to recommended doses and the value of immunization reminders were analysed. RESULTS: Of 27 386 screened travellers, 19 817 (72%) were aware of monovalent hepatitis A or combined A&B vaccines. Of these 13 857 (70%) had sought advice from a healthcare provider (HCP) regarding combined hepatitis A&B or monovalent hepatitis A vaccination, and 9328 (67%) were vaccinated. Of 5225 individuals eligible for the main survey (recently vaccinated = 3576; unvaccinated = 1649), 27% (841/3111) and 37% (174/465) of vaccinated travellers had adhered to the 3-dose combined hepatitis A&B or 2-dose monovalent hepatitis A vaccination schedules, respectively. Of travellers partially vaccinated against combined hepatitis A&B or hepatitis A, 84% and 61%, respectively, believed that they had received the recommended number of doses. CONCLUSIONS: HCPs remain the main source of pre-travel health advice. The majority of travellers who received monovalent hepatitis A or combined hepatitis A&B vaccines did not complete the recommended course. These findings highlight the need for further training of HCPs and the provision of reminder services to improve traveller awareness and adherence to vaccination schedules.

Elevated Values of C-Reactive Protein Induced by Imported Infectious Diseases: A Controlled Cross-Sectional Study of 11,079 Diseased German Travelers Returning from the Tropics and Subtropics.

The present controlled cross-sectional study aimed to assess elevated values of C-reactive protein (CRP), a positive acute-phase protein, induced by imported infectious diseases (IDs) seen in patients consulting the University of Munich (1999-2015) after being in the tropics/subtropics. The analysis investigated data sets from 11,079 diseased German travelers (cases) returning from Latin America (1,986), Africa (3,387), and Asia (5,706), and from 714 healthy Germans who had not recently traveled (controls). The proportions of elevated values of CRP (> 0.5 mg/dL) were significantly larger among cases (44.3%) than among controls (20.7%). Among cases, this proportion was largest among males (49.2%) in comparison to females (39.9%), among travelers with short travel duration of 1-14 days (49.6%) in comparison to travelers with a travel duration of > 180 days (30.8%), and with travel destination in Africa (47.0%) in comparison to Asia (44.2%) and Latin America (39.9%), among all-inclusive travelers (47.4%) in comparison to business travelers (46.7%) and backpackers (44.1%), and among patients presenting with fever (70.9%) and arthralgia (54.3%). The study identified various imported IDs with significantly larger proportions of elevated values of CRP including viral (cytomegalovirus infection [94.7%], influenza [88.9%], infectious mononucleosis [71.8%]), bacterial (typhoid fever [100%], paratyphoid fever [92.9%], shigellosis [76.8%], rickettsiosis [74.2%], Salmonella enteritis [71.3%], Campylobacter infection [68.7%]), and protozoan (vivax malaria [100%], ovale malaria [100%], falciparum malaria [95.4%], noninvasive Entamoeba infection [65.9%]) IDs. This study demonstrates that elevated values of CRP can be a useful laboratory finding for travelers returning from the tropics/subtropics, as these findings are typically caused mainly by certain imported bacterial IDs, but also by viral and protozoan IDs.

Elevated Values of Clinically Relevant Transferases Induced by Imported Infectious Diseases: A Controlled Cross-Sectional Study of 14,559 Diseased German Travelers Returning from the Tropics and Subtropics.

The aim of this controlled cross-sectional study was to assess the clinical validity of elevated values of three clinically relevant transferase enzymes (aspartate transaminase [AST], alanine transaminase [ALT], and gamma-glutamyl transferase [GGT]) induced by imported infectious diseases (IDs) seen among patients consulting the Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (from 1999 to 2014) after being in the sub-/tropics. Data sets of 14,559 diseased German travelers returning from Latin America (2,715), Africa (4,574), or Asia (7,270) and of 1,536 healthy controls of German origin without recent travels were analyzed. Among the cases, the proportions of those with elevated values of AST (7.8%) and of ALT (13.4%) were significantly larger than among controls (4.0% and 10.6%, respectively), whereas for GGT, no significant difference was found (cases: 10.0%; controls: 11.4%). The study identified IDs with significantly larger proportions of both AST and ALT (hepatitis A [100%/100%], cytomegalovirus [CMV] infection [77%/81%], chronic hepatitis C [67%/67%], infectious mononucleosis [65%/77%], typhoid fever [50%/50%], cyclosporiasis [45%/66%], dengue fever [43%/35%], malaria [20%/27%], and rickettsiosis [20%/24%]), of AST alone (paratyphoid fever [42%]), of ALT alone (giardiasis [20%]), and of GGT (hepatitis A [100%], infectious mononucleosis [71%], CMV infection [58%], rickettsiosis (20%], and dengue fever [19%]). The study demonstrates that the determination of AST and ALT among travelers returning from the sub-/tropics has a high clinical validity, as their elevated values are typically caused by several imported viral, bacterial, and protozoan IDs, whereas no additional clinical validity was found by the determination of GGT.

Lymphocytosis and Lymphopenia Induced by Imported Infectious Diseases: A Controlled Cross-Sectional Study of 17,229 Diseased German Travelers Returning from the Tropics and Subtropics.

The present controlled cross-sectional study aimed to assess relative and absolute lymphocytosis and lymphopenia induced by imported infectious diseases (IDs) seen among patients consulting the Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (1999-2014) after being in the tropics and subtropics. The analysis investigated data sets from 17,229 diseased German travelers returning from Latin America (3,238), Africa (5,467), and Asia (8,524), and from 1,774 healthy controls who had not recently traveled. Among the cases, the proportion of those with relative lymphopenia (10.5%) and absolute lymphopenia (8.0%) was significantly higher than among controls (3.2% and 3.6%, respectively), whereas relative lymphocytosis was significantly lower among cases (6.1%) than among controls (8.0%). The study identified IDs with significantly larger proportions of relative lymphocytosis (cytomegalovirus [CMV] infection [56%], infectious mononucleosis [51%], and dengue fever [11%]); absolute lymphocytosis (infectious mononucleosis [70%] and CMV infection [63%]); relative lymphopenia (streptococcal pharyngitis [56%], malaria [34%], Campylobacter infection [19%], salmonellosis [18%], and shigellosis [17%]); and of absolute lymphopenia (human immunodeficiency virus infection [53%], malaria [45%], dengue fever [40%], salmonellosis [16%], and Campylobacter infection [11%]). This study demonstrates that relative and absolute lymphocytosis and lymphopenia are useful laboratory findings for travelers returning from the tropics and subtropics, as they are typically caused by imported viral, bacterial, and protozoan IDs.

Spectrum of Imported Infectious Diseases: A Comparative Prevalence Study of 16,817 German Travelers and 977 Immigrants from the Tropics and Subtropics.

The aim of this study was to assess the spectrum of imported infectious diseases (IDs) among patients consulting the University of Munich, Germany, between 1999 and 2014 after being in the sub-/tropics. The analysis investigated complete data sets of 16,817 diseased German travelers (2,318 business travelers, 4,029 all-inclusive travelers, and 10,470 backpackers) returning from Latin America (3,225), Africa (4,865), or Asia (8,727), and 977 diseased immigrants, originating from the same regions (112, 654 and 211 respectively). The most frequent symptoms assessed were diarrhea (38%), fever (29%), and skin disorder (22%). The most frequent IDs detected were intestinal infections with species of Blastocystis(900),Giardia(730),Campylobacter(556),Shigella(209), and Salmonella(183). Also frequently observed were cutaneous larva migrans (379), dengue (257), and malaria (160). The number of IDs with significantly elevated proportions was higher among backpackers (18) and immigrants (17), especially among those from Africa (18) and Asia (17), whereas it was lower for business travelers (5), all-inclusive travelers (1), and those from Latin America (5). This study demonstrates a large spectrum of imported IDs among returning German travelers and immigrants, which varies greatly based not only on travel destination and origin of immigrants, but also on type of travel.

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.

Mefloquine at the crossroads? Implications for malaria chemoprophylaxis in Europe.

Since its introduction to the market in 1985, mefloquine has been used for malaria chemoprophylaxis by more than 35 million travellers. In Europe, in 2014, the European Medicines Agency (EMA) issued recommendations on strengthened warnings, prescribing checklists and updates to the product information of mefloquine. Some malaria prevention advisors question the scientific basis for the restrictions and suggest that this cost-effective, anti-malarial drug will be displaced as a first-line anti-malaria medication with the result that vulnerable groups such as VFR and long-term travellers, pregnant travellers and young children are left without a suitable alternative chemoprophylaxis. This commentary looks at the current position of mefloquine prescribing and the rationale of the new EMA recommendations and restrictions. It also describes the new recommendations for malaria prophylaxis that have been adapted by Switzerland, Germany, Austria and Italy where chemoprophylaxis use is restricted to high-risk malaria-endemic areas.

Evidence for significant influence of host immunity on changes in differential blood count during malaria.

BACKGROUND: Malaria has been shown to change blood counts. Recently, a few studies have investigated the alteration of the peripheral blood monocyte-to-lymphocyte count ratio (MLCR) and the neutrophil-to-lymphocyte count ratio (NLCR) during infection with Plasmodium falciparum. Based on these findings this study investigates the predictive values of blood count alterations during malaria across different sub-populations. METHODS: Cases and controls admitted to the Department of Infectious Diseases and Tropical Medicine from January 2000 through December 2010 were included in this comparative analysis. Blood count values and other variables at admission controlled for age, gender and immune status were statistically investigated. RESULTS: The study population comprised 210 malaria patients, infected with P. falciparum (68%), Plasmodium vivax (21%), Plasmodium ovale (7%) and Plasmodium malariae (4%), and 210 controls. A positive correlation of parasite density with NLCR and neutrophil counts, and a negative correlation of parasite density with thrombocyte, leucocyte and lymphocyte counts were found. An interaction with semi-immunity was observed; ratios were significantly different in semi-immune compared to non-immune patients (P <0.001).The MLCR discriminated best between malaria cases and controls (AUC = 0.691; AUC = 0.741 in non-immune travellers), whereas the NLCR better predicted severe malaria, especially in semi-immune patients (AUC = 0.788). CONCLUSION: Malaria causes typical but non-specific alterations of the differential blood count. The predictive value of the ratios was fair but limited. However, these changes were less pronounced in patients with semi-immunity. The ratios might constitute easily applicable surrogate biomarkers for immunity.

A phase II study of an investigational tetravalent influenza vaccine formulation combining MF59®: adjuvanted, pre-pandemic, A/H5N1 vaccine and trivalent seasonal influenza vaccine in healthy adults.

An investigational tetravalent vaccine combining pre-pandemic, MF59®-adjuvanted A/H5N1 vaccine with non-adjuvanted, trivalent, seasonal influenza vaccine has been developed, which has the potential to be used for pre-pandemic priming and to improve levels of compliance and coverage. It is important to determine whether the safety and immunogenicity of the combination vaccine is equivalent to that of the two separate vaccines when administered concomitantly. Healthy adults (n=601) were randomly assigned to three vaccination groups to receive either: (1) tetravalent vaccine and placebo concomitantly (in separate arms) on Day 1, followed by A/H5N1 vaccine on Day 22; (2) A/H5N1 vaccine and placebo concomitantly on Day 1, followed by tetravalent vaccine on Day 22; or (3) A/H5N1 and seasonal vaccines concomitantly on Day 1, followed by A/H5N1 vaccine on Day 22. Antibody responses were measured using single radial hemolysis (SRH), haemagglutination inhibition (HI), and microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse reactions were recorded for seven days after vaccination. Spontaneous adverse events were recorded throughout the study. The tetravalent vaccine elicited antibody titers equivalent to those for separate A/H5N1 and seasonal vaccines, and sufficient to meet the European licensure criteria against A/H5N1 and all three seasonal strains. Local and systemic reactions were mainly mild to moderate. No vaccine-related serious adverse events occurred. These findings demonstrate that MF59-adjuvanted A/H5N1 and seasonal influenza vaccines had an acceptable safety profile and could be effectively administered as a tetravalent formulation, supporting the possibility of integrating pre-pandemic priming into seasonal influenza vaccination programs.