A combined cross-sectional analysis and case-control study evaluating tick-borne encephalitis vaccination coverage, disease and vaccine effectiveness in children and adolescents, Switzerland, 2005 to 2022.

BackgroundTick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.AimTo estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0-17 years in Switzerland.MethodsVaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case-control analysis, matching TBE cases with SNVCS controls.ResultsOver the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1-5.5%) to 50.1% (95% CI: 48.3-52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1-2 doses) and completely (≥ 3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3-80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7-96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0-91.7) up to 10 years since last vaccination.ConclusionsEven children younger than 5 years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10 years against TBE.

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.

[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.

Transcatheter aortic valve replacement in patients with severe comorbidities: A retrospective cohort study.

OBJECTIVE: To investigate the long-term outcomes of patients with severe comorbidities (sCM) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: The benefit of TAVR may be limited among patients with sCM due to a lack of mortality- or quality-of-life-benefit. METHODS: All TAVR patients in the Allina Health System between January 1, 2011 and August 7, 2018 were included (n = 890, 82 ± 8 years, 55% men). sCM included: severe lung disease, severe liver disease, end-stage renal disease, severe, severe dementia, severe dilated cardiomyopathy, and frailty. Outcomes between patients with (n = 215, 24%) and without (n = 675, 76%) sCM were compared. RESULTS: At baseline, patients with sCM had worse symptoms, higher STS-PROM and a lower Kansas City Cardiomyopathy Questionnaire (KCCQ) score compared to those without. During a median follow-up of 15 months (IQR, 7-29 months), there were 208 (23%) deaths. Patients with sCM had a lower 3-year survival free from all-cause mortality (40% vs. 79%, p < .001), and lower 3-year survival free from the composite endpoint of all-cause mortality, re-hospitalization for heart failure, myocardial infarction or stroke (31% vs. 64%, p < .001) compared to those without sCM. The estimated monthly increase in KCCQ scores following TAVR was 1.5, 95%CI (1.3, 1.7), p < .001 irrespective of sCM grouping. From Cox regression analysis, severe comorbidities, with the exception of liver disease, were associated with an increased risk of all-cause mortality and any additional comorbidity was associated with a multiplicative increase in risk of mortality of 2.8 (95%CI 2.3, 3.6), p < .001. CONCLUSIONS: TAVR patients with sCM have poor 3-year outcomes but may experience improvements in their quality of life.

Natural history observations in moderate aortic stenosis.

BACKGROUND: The natural history of patients with moderate aortic stenosis (AS) is poorly understood. We aimed to determine the long-term outcomes of patients with moderate AS. METHODS: We examined patients with moderate AS defined by echocardiography in our healthcare system, and performed survival analyses for occurrence of death, heart failure (HF) hospitalization, and progression of AS, with accounting for symptoms, left ventricular dysfunction, and comorbidities. RESULTS: We examined 729 patients with moderate AS (median age, 76 years; 59.9 % men) with a median follow-up of 5.0 years (interquartile range: 2.0 to 8.1 years). The 5-year overall survival was 52.3 % (95 % confidence interval [CI]: 48.6 % to 56.0 %) and survival free of death or HF hospitalization was 43.2 % (95 % CI: 39.5 % to 46.9 %). Worse New York Heart Association (NYHA) functional class was associated with poor long-term survival, with mortality rates ranging from 7.9 % (95 % CI: 6.6-9.2 %) to 25.2 % (95 % CI: 20.2-30.3 %) per year. Among patients with minimal or no symptoms, no futility markers, and preserved left ventricular function, 5-year overall survival was 71.9 % (95 % CI: 66.4-77.4 %) and survival free of death or HF hospitalization was 61.4 % (95 % CI: 55.5-67.3 %). Risk factors associated with adverse events were age, NYHA class, low ejection fraction and high aortic valve velocity (all p < 0.05). CONCLUSIONS: Patients with moderate AS are at significant risk of death. Our findings highlight the need for more study into appropriate therapeutic interventions to improve the prognosis of these patients.

Mass gatherings medicine: public health issues arising from mass gathering religious and sporting events.

Mass gathering events are associated with major public health challenges. The 2014 Lancet Series on the new discipline of mass gatherings medicine was launched at the World Health Assembly of Ministers of Health in Geneva in May, 2014. The Series covered the planning and surveillance systems used to monitor public health risks, public health threats, and experiences of health-care providers from mass gathering events in 2012 and 2013. This follow-up Review focuses on the main public health issues arising from planned mass gathering events held between 2013 and 2018. We highlight public health and research data on transmission of infectious diseases and antibiotic-resistant bacteria, mass casualty incidents, and non-communicable diseases, including thermal disorders. In the events discussed in this Review, the combination of a large influx of people, many from countries with outbreak-prone infectious diseases, with a high degree of crowd interactions imposed substantial burdens on host countries' health systems. The detection and transmission of antibiotic-resistant bacteria in pilgrims attending the Kumbh Mela and the Hajj raise concern of possible globalisation from mass-gathering religious events. Priorities for further investments and opportunities for research into prevention, surveillance, and management of these public health issues are discussed.

Estimating the incidence of norovirus acute gastroenteritis among US and European international travelers to areas of moderate to high risk of traveler's diarrhea: a prospective cohort study protocol.

BACKGROUND: Acute gastroenteritis (AGE) is the leading cause of illness among returning travelers seeking medical care. Multiple types of enteric pathogens can cause travel-acquired AGE and, while bacterial pathogens have a predominant role, the importance of viruses, such as norovirus, is increasingly recognized. There is a lack of information on travel-acquired norovirus incidence among symptomatic and asymptomatic individuals irrespective of healthcare-seeking behavior. Our aim is to estimate the incidence of travel-acquired AGE due to norovirus and to characterize the burden of disease among international travelers from the United States and Europe. METHODS: We describe a prospective cohort study implemented in five US and European sites to estimate the role of AGE due to norovirus among adult international travelers. We enrolled individuals aged 18 years and older who are traveling to regions of moderate-high risk of AGE, or via cruise ship with an international port stop, with a trip duration of 3-15 days. The study will generate a wide range of health and travel-related data for pre-, during, and up to 6-months post-travel. We will identify laboratory-confirmed travel-acquired norovirus infections among both symptomatic and asymptomatic individuals from self-collected whole stool samples tested via quantitative RT-PCR. Coinfections will be identified in a subset of travelers with AGE using a multiplex molecular-based assay. DISCUSSION: This study is unique in design and breadth of data collected. The prospective collection of health and behavioral data, as well as biologic samples from travelers irrespective of symptoms, will provide useful data to better understand the importance of norovirus AGE among international travelers. This study will provide data to estimate the incidence of norovirus infections and AGE and the risk of post-infectious sequelae in the 6-month post-travel period serving as a baseline for future norovirus AGE vaccination studies. This study will contribute valuable information to better understand the role of norovirus in travel-acquired AGE risk and the impact of these infections on a broad set of outcomes.

The impact of obesity on cardiac surgery outcomes.

BACKGROUND: A survival benefit for obese patients has been observed in various medical and surgical populations. We examined the effect of obesity on outcomes after cardiac surgery from a large national database. METHODS: A total of 6 648 334 adult patients were identified from the Nationwide Inpatient Sample who underwent cardiac surgery between 1998 and 2011, of who 598 450 were obese. Multivariable regression analysis and propensity score matching were used for comparisons of outcomes and costs. RESULTS: In-hospital mortality was 2.0% for obese patients versus 2.3% for non-obese patients (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.84, 0.94). Obese patients were at increased risk for acute renal failure (OR, 1.20; CI, 1.16, 1.23) and wound infection (OR, 1.29; CI, 1.18, 1.40), but less likely to require blood transfusion (OR, 0.96; CI, 0.94, 0.98). Mean length of stay was the same (8.7 days), with greater mean total charges for obese patients ($103 645 vs $101 763, P < 0.001). CONCLUSION: Obesity is associated with lower in-hospital mortality rates, but a higher incidence of acute renal failure and wound infections.

Staged repair of thoracoabdominal aneurysm with infra-renal elephant trunk graft.

A patient with residual thoracoabdominal aortic aneurysm and chronic dissection extending into the branch iliac arteries underwent staged open and endovascular repair. Open repair of the reno-visceral segment was performed with an "elephant trunk" trunk graft placed distally into a 12-cm infra-renal aorta. One month later, the patient underwent a successful completion endovascular aortic repair. This case demonstrates the utility of combining traditional and endovascular surgery to manage complex aortic pathologies.

Recurrent otorrhea in chronic suppurative otitis media: is biofilm the missing link?

Dispersal of bacteria from a biofilm in the middle ear, serving as a bacterial reservoir, could explain the recurrent and chronic nature of chronic suppurative otitis media (CSOM). The objective of this study is to investigate if the same strains of bacteria could be detected in repeated episodes of otorrhea in CSOM. In a prospective case series at a primary healthcare clinic in Nuuk, Greenland, patients with more than 14 days of otorrhea were included consecutively. Samples for culturing and biofilm analysis were taken at enrollment and at any subsequent episode with otorrhea. Participants were treated with daily saline irrigation and Ciprofloxacin eardrops for 7-14 days. Biofilm was identified in otorrhea in 81% (17/21) of participants at enrollment. Multispecies infections dominated with Non-typeable Haemophilus Influenzae (NTHI), Staphyloccocus aureus, and anaerobes being the most frequent pathogens. After the initial treatment, 19 (90%) had dry ears. Median observation period was 140 days (range 14-280) where 13 participants had one or more recurrences. Median time to first recurrence was 60 days (range 14-197). Among the 13 with recurrence, three individuals had the same genotype of bacteria at a subsequent episode. Another two had the same phenotype (NTHI). The remaining eight had new multispecies infections. We confirmed a high rate of biofilm in CSOM. However, the clinical implication might be of minor importance when treating with irrigation and antibiotic eardrops, as recurrent episodes of otorrhea were dominated by new pathogens in each episode.

Mucosal biofilm detection in chronic otitis media: a study of middle ear biopsies from Greenlandic patients.

The objectives of this study were to examine middle ear biopsies from Greenlandic patients with chronic otitis media (COM) for the presence of mucosal biofilms and the bacteria within the biofilms. Thirty-five middle ear biopsies were obtained from 32 Greenlandic COM patients admitted to ear surgery. All biopsies were examined by means of peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH), and if possible culture and polymerase chain reaction (PCR) of the 16s rDNA and sequencing. Light microscopy and confocal laser scanning microscopy were used. Skin biopsies from 23 of the patients served as controls. PNA-FISH showed morphological signs of biofilms in 15 out of 35 (43 %) middle ear biopsies. In the control skin biopsies, there were signs of biofilms in eight out of 23 biopsies (30 %), probably representing skin flora. PCR and 16s sequencing detected bacteria in seven out of 20 (35 %) usable middle ear biopsies, and in two out of ten (20 %) usable control samples. There was no association between biofilm findings and PCR and 16s sequencing. Staphylococci were the most common bacteria in bacterial culture. We found evidence of bacterial biofilms in 43 % of middle ear biopsies from patients COM. The findings may indicate that biofilms are a part of the pathogenesis in recurrent episodes of ear discharge in COM, but further investigations are necessary.

Traveler's diarrhea: a clinical review.

IMPORTANCE: Acute diarrhea is the most common illness that affects travelers to low-income regions of the world. Although improved hygiene has reduced the risk of traveler's diarrhea in many destinations, the risk remains high in others. OBJECTIVE: To review the current state of knowledge on the etiology, risk factors, prevention, and management of traveler's diarrhea. EVIDENCE REVIEW: A search of the PubMed, Google Scholar, and Cochrane Library databases for the period 2012-April 2014 was performed for articles on traveler's diarrhea. The database search yielded 2976 articles, of which 37 were included in this review. These were added to 85 articles previously identified by the authors. FINDINGS: Improved hygiene has reduced the risk of traveler's diarrhea from 20% or more (for a 2-week stay) to between 8% and 20% in some parts of the world. Acquiring traveler's diarrhea causes 12% to 46% of travelers to change their travel plans. Returning travelers seeking medical care have a diagnosis of gastrointestinal disturbance in approximately one-third of all cases. Postinfectious irritable bowel syndrome may occur in 3% to 17% of patients who have had traveler's diarrhea. Prevention of traveler's diarrhea by dietary avoidance measures is often not successful. Chemoprophylaxis should be restricted to travelers who are at risk of severe complications of diarrhea. Ciprofloxacin is the standard treatment in self-therapy of traveler's diarrhea except when patients are in South or Southeast Asia, where azithromycin is preferred. CONCLUSIONS AND RELEVANCE: Diarrhea remains a common problem for international travelers. Persons intending to travel to at-risk countries should be counseled regarding prevention measures and may be given a travel pack that includes medications for self-treatment should they become ill.

Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients.

Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.

New Insights and Perspective on Bioprosthetic Valve Fracture From Bench Testing and Computed Tomography Analysis.

Background: Bioprosthetic valve fracture (BVF) during valve-in-valve TAVR (transcatheter aortic valve replacement) is a procedural adjunct designed to optimize the expansion of the transcatheter heart valve and reduce patient-prosthesis mismatch by using a high-pressure balloon to intentionally fracture the surgical heart valve (SHV). Methods: We performed bench testing on 15 bioprosthetic SHV to examine the optimal balloon size and pressure for BVF. We assessed morphological changes and expansion of SHV by computed tomography angiography. Successful BVF was defined as balloon waist disappearance on fluoroscopy and/or sudden pressure drop during balloon inflation. Results: Nine valves met the definition of BVF, 3 of which were confirmed by disruption of the stent frame. We classified surgical valves into 3 subsets: 1) fracturable with metal stent frame (MSF), 2) fracturable with polymer stent frame (PSF) and 3) nonfracturable. In general, valves with MSF were fractured using a balloon size = true internal diameter plus 3-5 mm inflated at high pressure (16-20 ATM) whereas valves with PSF could be fractured with a balloon size = true internal diameter plus 3-5 mm and lower balloon pressure (6-14 ATM). Gains in computed tomography angiography derived inflow area after BVF were 12.3% for MSF and 3.6% for PSF SHV. Conclusions: Gains in CT-determined valve area after BVF depend on the physical properties of the SHV, which in turn influences pressure thresholds and balloon sizing strategy for optimal BVF. Elastic recoil of PSF valves limits the gains in inflow area after BVF.

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.

[Mass gatherings - health risks and preventive strategies]. / Massenveranstaltungen - Gesundheitsrisiken und Präventive Strategien.

Experience from mass gatherings - usually attended by at least 25'000 persons - shows that approximately one in a thousand participants will consult with an on-site medical emergency service. Communicable diseases usually play a minor role. Historically outbreaks of meningococcal disease were recorded after the hajj, but this has been well controlled in the past few years subsequent to vaccinations and other measures required by the Kingdom of Saudi Arabia health authorities. Major stress of the regional public health system is associated with accidents and non-communicable diseases, the majority being trivial. Host and environmental risk factors can result in a dramatic increase in the rate of consultations: Age and pre-existing illness play a decisive role particularly in pilgrims, be that in Mecca or Lourdes. Emotional factors may influence behavior; aggressions can develop. Alcohol and drugs, also the duration of an event may play a decisive role. Extreme climatic conditions, both heat and cold, also exhaustion result in a dramatic increase of emergency consultations. Infrastructure must be adapted for the crowd size, particularly stampede associated disasters can be avoided. The World Health Organization and other interested expert groups have in the past few years formulated interdisciplinary programs for prevention.

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.

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.

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.

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.