Novel chikungunya and dengue vaccines-travel medicine applications.

Recent epidemics of dengue and chikungunya have highlighted the urgent need for vaccines to reduce the risk of infection in travellers. Given challenges tracking chikungunya outbreaks in real-time and the widespread resurgence of dengue, broader indications for the use of the new chikungunya and dengue vaccines should be considered.

Preprocedural Computed Tomography Planning for Surgical Aortic Valve Replacement.

BACKGROUND: Selection of transcatheter valve size using preprocedural computed tomography (CT) is standardized and well established. However, valve sizing for surgical aortic valve replacement (SAVR) is currently performed intraoperatively by using sizers, which may result in variation among operators and risk for prosthesis-patient mismatch. This study evaluated the usefulness of CT annulus measurement for SAVR valve sizing. METHODS: This study included patients who underwent SAVR using Inspiris or Magna Ease and received preoperative electrocardiogram-gated CT imaging. Starting from June 2022, study investigators applied a CT sizing algorithm using CT-derived annulus size to guide minimum SAVR label size. The final decision of valve selection was left to the operating surgeon during SAVR. The study compared the appropriateness of valve selection (comparing implanted size with CT-predicted size) and prosthesis-patient mismatch rates without aortic root enlargement between 2 cohorts: 102 cases since June 2022 (CT sizing cohort) and 180 cases from 2020 to 2021 (conventional sizing cohort). RESULTS: Implanted size smaller than CT predicted size and severe prosthesis-patient mismatch were significantly lower by CT sizing than by conventional sizing (12% vs 31% [P = .001] and 0% vs 6% [P = .039], respectively). Interoperator variability was a factor associated with implanted size smaller than CT predicted with conventional sizing, whereas it became nonsignificant with CT sizing. CONCLUSIONS: Applying CT sizing to SAVR led to improved valve size selection, less prosthesis-patient mismatch, and less interoperator variability. CT sizing for SAVR could also be used to predict prosthesis-patient mismatch before SAVR and identify patients who need aortic root enlargement.

Knowledge, Attitudes, and Practices of European Healthcare Professionals towards Hepatitis A and Hepatitis B Vaccination in at-Risk Adults.

Despite the occurrence of several hepatitis A (hepA) and hepatitis B (hepB) outbreaks in Europe in the last few decades, not all European countries have implemented hepA and hepB vaccinations in their national immunization programs, especially for adults at risk for hepA and/or hepB infection, such as men who have sex with men or patients with chronic liver disease. Currently, little is known on the attitudes of European healthcare professionals (HCPs) towards hepA and hepB vaccinations for at-risk adults. We conducted an online survey among HCPs in Germany, Spain, and the United Kingdom to assess their awareness of and adherence to their national hepA and hepB vaccination guidelines for at-risk adults. Among the 698 HCPs who took the survey, most (91.1%) were familiar with their national vaccination recommendations and always followed them or followed them most of the time when advising or prescribing hepA or hepB vaccines. Major and moderate barriers for recommending or administering such vaccines were the non-disclosure of risk factors by the patient (53.0-57.6%) and the patient's lack of motivation or knowledge about the risk of the disease (50.3-52.9%). These results may help inform strategies to improve and accelerate hepA and hepB vaccination in European at-risk adults.

Influenza: seasonality and travel-related considerations.

RATIONALE FOR REVIEW: This review aims to summarize the transmission patterns of influenza, its seasonality in different parts of the globe, air travel- and cruise ship-related influenza infections and interventions to reduce transmission. KEY FINDINGS: The seasonality of influenza varies globally, with peak periods occurring mainly between October and April in the northern hemisphere (NH) and between April and October in the southern hemisphere (SH) in temperate climate zones. However, influenza seasonality is significantly more variable in the tropics. Influenza is one of the most common travel-related, vaccine-preventable diseases and can be contracted during travel, such as during a cruise or through air travel. Additionally, travellers can come into contact with people from regions with ongoing influenza transmission. Current influenza immunization schedules in the NH and SH leave individuals susceptible during their respective spring and summer months if they travel to the other hemisphere during that time. CONCLUSIONS/RECOMMENDATIONS: The differences in influenza seasonality between hemispheres have substantial implications for the effectiveness of influenza vaccination of travellers. Health care providers should be aware of influenza activity when patients report travel plans, and they should provide alerts and advise on prevention, diagnostic and treatment options. To mitigate the risk of travel-related influenza, interventions include antivirals for self-treatment (in combination with the use of rapid self-tests), extending the shelf life of influenza vaccines to enable immunization during the summer months for international travellers and allowing access to the influenza vaccine used in the opposite hemisphere as a travel-related vaccine. With the currently available vaccines, the most important preventive measure involves optimizing the seasonal influenza vaccination. It is also imperative that influenza is recognized as a travel-related illness among both travellers and health care professionals.

Travel vaccines-priorities determined by incidence and impact.

BACKGROUND: Infectious disease epidemiology is continuously shifting. While travel has been disrupted by the COVID-19 pandemic and travel-related epidemiological research experienced a pause, further shifts in vaccine-preventable diseases (VPDs) relevant for travellers have occurred. METHODS: We conducted a literature search on the epidemiology of travel-related VPD and synthesized data for each disease with a focus on symptomatic cases and on the impact of the respective infection among travellers, considering the hospitalization rate, disease sequela and case fatality rate. We present new data and revised best estimates on the burden of VPD relevant for decisions on priorities in travel vaccines. RESULTS: COVID-19 has emerged to be a top travel-related risk and influenza remains high in the ranking with an estimated incidence at 1% per month of travel. Dengue is another commonly encountered infection among international travellers with estimated monthly incidence of 0.5-0.8% among non-immune exposed travellers; the hospitalized proportion was 10 and 22%, respectively, according to two recent publications. With recent yellow fever outbreaks particularly in Brazil, its estimated monthly incidence has risen to >0.1%. Meanwhile, improvements in hygiene and sanitation have led to some decrease in foodborne illnesses; however, hepatitis A monthly incidence remains substantial in most developing regions (0.001-0.01%) and typhoid remains particularly high in South Asia (>0.01%). Mpox, a newly emerged disease that demonstrated worldwide spread through mass gathering and travel, cannot be quantified regarding its travel-related risk. CONCLUSION: The data summarized may provide a tool for travel health professionals to prioritize preventive strategies for their clients against VPD. Updated assessments on incidence and impact are ever more important since new vaccines with travel indications (e.g. dengue) have been licensed or are undergoing regulatory review.

Vaccine co-administration in adults: An effective way to improve vaccination coverage.

The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for adults, but coverage rates remain suboptimal. Although co-administration would improve vaccine uptake and timely immunization, this is not routine practice in adults. We review key data on co-administration of vaccines in children and adults to reassure healthcare providers about its safety and advantages. In European countries and the United States, combined tetanus, diphtheria, and acellular pertussis boosters as well as meningococcal and human papillomavirus vaccines are recommended for healthy adolescents and adults of certain ages. Vaccination against influenza (annually), pneumococcal disease, and herpes zoster is recommended for older adults and specific risk groups. While co-administration is well established in children, it is less common in adults. Travelers can also receive multiple co-administered vaccines. Pediatric and travel vaccine co-administration has a well-established positive benefit-risk profile and is an efficient and cost-saving strategy to improve coverage. Healthcare providers could more often recommend and practice vaccine co-administration; this would not risk patient safety and health, would improve protection against vaccine-preventable diseases, and would help comply with national vaccination calendars. Recommending bodies may consider revising vaccination schedules to reduce the number of visits.

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.

Development of a new travellers' diarrhoea clinical severity classification and its utility in confirming rifamycin-SV efficacy.

BACKGROUND: travellers' diarrhoea (TD) is frequently reported with incidence up to 40% in high-risk destinations. Previous studies showed that the number of loose stools alone is inadequate to holistically predict the severity of TD. To improve the prediction of prognosis and to optimize treatments, a simple risk-based clinical severity classification has been developed. METHODS: pooled baseline data of signs and symptoms and number of loose stools from 1098 subjects enrolled in two double-blind Phase 3 trials of rifamycin-SV were analyzed with correlation, multiple correspondence analyses, prognostic factor criteria, and Contal and O'Quigley method to generate a TD severity classification (mild, moderate and severe). The relative importance of this classification on resolution of TD was assessed by Cox proportional model hazard model on the time to last unformed stool (TLUS). RESULTS: the analysis showed that TLUS were longer for the severe [hazard ratio (HR) 0.24; P < 0.001; n = 173] and moderate (HR 0.54; P = 0.0272; n = 912) vs mild. Additionally, when the treatment assigned in the studies was investigated in the severity classification, the results yielded that rifamycin-SV significantly shortened TLUS vs placebo for all subjects (HR 1.9; P = 0.0006), severe (HR 5.9; P = 0.0232) and moderate (HR 1.7; P = 0.0078) groups and was as equally efficacious as ciprofloxacin for all subjects, moderate and severe groups (HRs: 0.962, 0.9, 1.2; all P = NS, respectively). When reassessed by this classification, rifamycin-SV showed consistent efficacy with the Phase 3 studies. CONCLUSIONS: this newly developed TD clinical severity classification demonstrated strong prognostic value and clinical utility by combining patients' multiple signs and symptoms of enteric infection and number of loose stools to provide a holistic assessment of TD. By expanding on the current classification by incorporating patient reported outcomes in addition to TLUS, a classification like the one developed, may help optimize patient selection for future clinical studies.

Coronary Angiography Within 30 Days From Coronary Artery Bypass Graft Surgery: Indications, Findings, and Outcomes.

BACKGROUND: The incidence, indications, and outcomes of coronary angiography (CAG) performed within 30 days following coronary artery bypass graft surgery (CABG) have received limited study. METHODS: We reviewed patients who underwent CAG within 30 days following CABG between April 2018 and September 2021 at a large quaternary healthcare system. RESULTS: Of 2209 patients who underwent CABG during the study, 111 (5%) underwent CAG within 30 days following CABG. Mean age was 65 ± 10 years and they had high prevalence of comorbidities. Graft utilization was as follows: left internal mammary artery (LIMA) (84%); saphenous vein graft(s) (SVG) (81%); and right internal mammary artery (RIMA) (22%). The most common presentations/indications for angiography were cardiogenic shock (41%), ST-segment-elevation myocardial infarction (32%), and achieving complete revascularization by percutaneous coronary intervention (PCI) (16%). The LIMA, RIMA, and SVGs were completely/partially occluded in 41 (44%), 10 (42%), and 11 (50%) of patients, respectively. Of the 111 patients who underwent CAG, 55 (50%) underwent PCI, including 47 (85%) to the native vessel and 8 (15%) to the bypass graft, and 19 (17%) underwent repeat sternotomy. Overall, 29 patients (26%) required 30-day readmission following CAG and 19 (17%) died. CONCLUSION: The incidence of CAG within 30 days following CABG is approximately 5%. Patients who need CAG following CABG have high complication rates (26% readmission and 17% mortality, respectively, at 30 days).

Hepatitis A occurrence and outbreaks in Europe over the past two decades: A systematic review.

Hepatitis A (HA) is a vaccine-preventable liver disease with >170 million new cases occurring yearly. In recent outbreaks in the USA, hospitalization and case-fatality ratios were >60% and ~1%, respectively. In Europe, endemicity persists and outbreaks continue to occur. We performed a systematic literature review to understand the changes in HA occurrence in Europe over the past two decades. PubMed and Embase were systematically searched for peer-reviewed articles published between 1 January 2001 and 14 April 2021 using terms covering HA, 11 selected European countries, outbreaks, outcomes and HA virus circulation. Here, we focus on HA occurrence and outbreaks in the five countries with the largest population and the most comprehensive vaccination recommendations: France, Germany, Italy, Spain and the UK; 118 reports included data for these five European countries. Notification rates (≤9.7/100,000 population) and percentages of men among cases (≤83.0%) peaked in 2017. The number of person-to-person-transmitted cases and outbreaks decreased in children but increased in other risk groups, such as men who have sex with men (MSM). Sexually transmitted outbreaks in MSM clustered around 2017. Travel-related outbreaks were few; the proportion of travel-related cases decreased during the past two decades, while the number of domestic cases increased. Despite the existing risk-based vaccination recommendations, HA transmission shifted in proportions from travelers and children to other risk groups, such as MSM and older age groups. Because a substantial proportion of the European population is susceptible to HA, adherence to existing recommendations should be monitored more closely, and enhanced vaccination strategies should be considered.

Chikungunya: risks for travellers.

RATIONALE FOR REVIEW: Chikungunya outbreaks continue to occur, with changing epidemiology. Awareness about chikungunya is low both among the at-risk travellers and healthcare professionals, which can result in underdiagnosis and underreporting. This review aims to improve awareness among healthcare professionals regarding the risks of chikungunya for travellers. KEY FINDINGS: Chikungunya virus transmission to humans occurs mainly via daytime-active mosquitoes, Aedes aegypti and Aedes albopictus. The areas where these mosquitoes live is continuously expanding, partly due to climate changes. Chikungunya is characterized by an acute onset of fever with joint pain. These symptoms generally resolve within 1-3 weeks, but at least one-third of the patients suffer from debilitating rheumatologic symptoms for months to years. Large outbreaks in changing regions of the world since the turn of the 21st century (e.g. Caribbean, La Réunion; currently Brazil, India) have resulted in growing numbers of travellers importing chikungunya, mainly to Europe and North America. Viremic travellers with chikungunya infection have seeded chikungunya clusters (France, United States of America) and outbreaks (Italy in 2007 and 2017) in non-endemic countries where Ae. albopictus mosquitoes are present. Community preventive measures are important to prevent disease transmission by mosquitoes. Individual preventive options are limited to personal protection measures against mosquito bites, particularly the daytime-active mosquitos that transmit the chikungunya virus. Candidate vaccines are on the horizon and regulatory authorities will need to assess environmental and host risk factors for persistent sequelae, such as obesity, age (over 40 years) and history of arthritis or inflammatory rheumatologic disease to determine which populations should be targeted for these chikungunya vaccines. CONCLUSIONS/RECOMMENDATIONS: Travellers planning to visit destinations with active CHIKV circulation should be advised about the risk for chikungunya, prevention strategies, the disease manifestations, possible chronic rheumatologic sequelae and, if symptomatic, seek medical evaluation and report potential exposures.

[Tick-Borne Encephalitis (TBE) - Fundamentals]. / Frühsommer-Meningoenzephalitis (FSME).

Tick-Borne Encephalitis (TBE) - Fundamentals Abstract. There is widespread endemicity of tick-borne encephalitis (TBE) in all German-speaking countries. In most regions there is a gradual increase in incidence and further territorial spread. As a proportion of the cases is not diagnosed and since the clinical course is getting worse with growing age, substantial underreporting occurs particularly in the pediatric and adolescent patient population. Infected ticks are transmitting the TBE virus, a flavivirus, within a few minutes after the bite. After an incubation period of 4 to 28 days uncharacteristic flu-like symptoms usually occur during a first viremic phase. This is followed by a brief asymptomatic interval before a minority of patients suffer of a variety of symptoms associated with damage of different parts of the central nervous system. This often results in permanent neurological injury and in about 1% the clinical course is fatal. To establish a diagnosis, it is essential to suspect the infection and to obtain a history of exposure. Depending on the phase of illness IgM and/or IgG antibodies can be detected in the serum and/or in the cerebrospinal fluid. In the early phase of the infection the TBE virus may be detected by PCR.

Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy.

Over the past several decades, alcohol septal ablation has become an established therapy for selected patients, in whom there is clinical improvement in symptoms as well as objective functional capacity. Patient selection is essential to success, with continued emphasis on the procedure being performed by experienced operators as part of a multidisciplinary team. In many patients, the outcomes of alcohol septal ablation are comparable to the standard of surgical myectomy. The optimization of the outcomes of alcohol septal ablation is essential for the longitudinal care of patients with hypertrophic cardiomyopathy.

Bacterial travellers' diarrhoea: A narrative review of literature published over the past 10 years.

Travellers' diarrhoea (TD) is the most frequent illness experienced by international travellers to lower-income countries with bacterial agents considered to account for 80-90% of cases. In this review, we summarise evidence published on bacterial TD over the past 10 years, focusing on the epidemiology and aetiology of TD. Diarrhoeagenic Escherichia coli (DEC) continue to be the most commonly implicated bacteria in TD, although Enteropathogenic E. coli (EPEC) and Enteroaggregative E. coli (EAEC) now appear to be predominant where Enterotoxigenic E. coli (ETEC) was previously considered most prevalent globally. Where fluroquinolone resistance had primarily been documented for Campylobacter in Southeast Asia, widespread resistance has been observed in most regions of the world for multiple enteropathogens, including Shigella, Salmonella, ETEC and EAEC. Implementation of novel molecular methods for pathogen detection has led to identification of bacterial pathogens, including Clostridium difficile (with and without the use of prior antibiotics), Arcobacter species and Bacteroides fragilis, as aetiological agents in TD. The widespread resistance to first-line antibiotics in multiple bacterial enteropathogens warrants continued surveillance and re-evaluation of current treatment practices. Further investigations are required to determine the prevalence and geographical distribution of bacterial enteropathogens that have been more recently implicated in TD.

The changing epidemiology of human monkeypox-A potential threat? A systematic review.

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010-2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades-Central African 10.6% (95% CI: 8.4%- 13.3%) vs. West African 3.6% (95% CI: 1.7%- 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

Tick-borne encephalitis (TBE) in Switzerland: does the prolongation of vaccine booster intervals result in an increased risk of breakthroughs?

BACKGROUND: In 2006, the Swiss Federal Office of Public Health (FOPH) decided recommending a prolongation of vaccine booster intervals after the third dose for the prevention of tick-borne encephalitis (TBE) from 3 to 10 years. METHODS: To ascertain whether this amendment resulted in an increased rate of vaccine breakthroughs, we conducted a retrospective analysis of surveillance data collected 2000-19 by mandatory reporting to the Swiss FOPH. Fractions of breakthroughs [with 95% confidence intervals (CIs)]-0-3 years vs >3-10 years after the third vaccination dose-were compared across time periods and age groups. RESULTS: Among 3205 notified TBE cases, known vaccination status was reported in 2562 (79.9%), including 103 patients with ≥3 vaccine doses (4.0%). Among those, there were 39 patients who had received the last dose within 3 years and 48 patients in the >3-10 years group. During the 2010-19 period in which the new booster strategy was implemented there were 23 and 38 breakthroughs, respectively, and the annual breakthrough rate was 7.7 (95% CI 5.0-11.7) cases during the first 3 years after the last dose, and 5.4 (95% CI 3.9-7.5) cases in following 7 years. We observed no significant trend of TBE breakthroughs with increasing age. Increasing numbers of TBE and of vaccine breakthroughs over time have been associated with spreading endemicity and higher vaccination coverage in Switzerland. CONCLUSIONS: There is no indication that extended booster intervals resulted in an increased rate of breakthroughs, but there was a marked public health benefit with respect to increased acceptability of TBE immunization in the general population.