Encephalitis in HIV-negative immunodeficient patients: a prospective multicentre study, France, 2016 to 2019.

BackgroundData on infectious encephalitis in immunodeficient (ID) individuals are scarce. This population may present with atypical clinical symptoms, be infected by uncommon pathogens and develop poor outcomes.AimWe aimed to describe the epidemiology of infectious encephalitis among HIV-negative ID patients.MethodsPatients from the ENCEIF (Etude Nationale de Cohorte des Encéphalites Infectieuses en France) prospective cohort meeting criteria for infectious encephalitis between January 2016 and December 2019 were included. We compared clinical presentation, magnetic resonance imaging (MRI) results, biological results, infection causes and outcome of ID patients with immunocompetent (IC) patients using Pearson's chi-squared test and Student's t-test. We carried out logistic regression to assess the role of immunodeficiency as risk factor for poor outcome.ResultsID patients (n = 58) were older (mean 72 vs 59 years), had higher prevalence of diabetes (26% vs 12%), pre-existing neurological disorders (12% vs 5%) and higher case-fatality rate (23.6% vs 5.6%) compared to IC patients (n = 436). Varicella zoster virus was the primary cause of encephalitis in ID patients (this aetiology was more frequent in ID (25.9%) than in IC patients (11.5%)), with herpes simplex virus second (22.4% in ID patients vs 27.3% in IC patients). Immunodeficiency was an independent risk factor for death or major sequelae (odds ratio: 3.41, 95%CI: 1.70-6.85).ConclusionsVaricella zoster virus is the most frequent cause of infectious encephalitis in ID patients. Immunodeficiency is a major risk factor for poor outcome. ID encephalitis patients should benefit from stringent investigation of cause and early empiric treatment.

Infectious encephalitis in elderly patients: a prospective multicentre observational study in France 2016-2019.

PURPOSE: Data on encephalitis in elderly patients are scarce. We aimed to describe the characteristics, aetiologies, management, and outcome of encephalitis in patients older than 65 years. METHODS: We performed an ancillary study of ENCEIF, a prospective cohort that enrolled all cases of encephalitis managed in 46 clinical sites in France during years 2016-2019. Cases were categorized in three age groups: (1) 18-64; (2) 65-79; (3) ≥ 80 years. RESULTS: Of the 494 adults with encephalitis enrolled, 258 (52%) were ≥ 65 years, including 74 (15%) ≥ 80 years. Patients ≥ 65 years were more likely to present with coma, impaired consciousness, confusion, aphasia, and rash, but less likely to present with fever, and headache (P < 0.05 for each). Median cerebrospinal fluid (CSF) white cells count was 61/mm3[13-220] in 65-79 years, 62 [17-180] in ≥ 80 years, vs. 114 [34-302] in < 65 years (P = 0.01). The proportion of cases due to Listeria monocytogenes and VZV increased after 65 years (P < 0.001), while the proportion of tick-borne encephalitis and Mycobacterium tuberculosis decreased with age (P < 0.05 for each). In-hospital mortality was 6/234 (3%) in < 65 years, 18/183 (10%) in 65-79 years, and 13/73 (18%) in ≥ 80 years (P < 0.001). Age ≥ 80 years, coma on admission, CSF protein ≥ 0.8 g/L and viral encephalitis were independently predictive of 6 month mortality. CONCLUSION: Elderly patients represent > 50% of adults with encephalitis in France, with higher proportion of L. monocytogenes and VZV encephalitis, increased risk of death, and sequels. The empirical treatment currently recommended, aciclovir and amoxicillin, is appropriate for this age group.

A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis.

BACKGROUND: New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient's initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). METHODS: The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. RESULTS: As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. CONCLUSIONS: No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.

Herpes simplex virus encephalitis update.

PURPOSE OF REVIEW: HSV is the most frequently identified cause of infectious encephalitis, in Western countries. This article is an update on the topic based on a review of recent studies from 2017 to 2018. RECENT FINDINGS: Acyclovir is still the first line treatment, and no new drugs are currently available for clinical use. The major considerations for HSV encephalitis are as follows: point one, clinical evaluation remains the most important factor, as though CSF HSV PCR has a good sensitivity, in a small proportion of patients the initial testing might be negative. MRI brain is the first line imaging test, and mesial temporal lobe involvement and other typical findings are important for diagnosis; point 2, there should be emphasis on sequela, short-term, and long-term outcomes, and not just case fatality rated in future studies and clinical management. Auto-immune encephalitis can be triggered by HSV, and should be considered in patients who are not responding to treatment; point 3, future studies should be on better management of sequela, and better treatment regimens including those targeting the immune response. SUMMARY: Autoimmune encephalitis is a clearly identified complication of HSV encephalitis. Inflammatory mechanisms are linked to the clinical presentation as well as severity and poor outcome. Initial corticosteroid therapy has to be evaluated in order to prevent complications.

Anterior Thalamic Stimulation Induced Relapsing Encephalitis.

Deep brain stimulation of the anterior thalamic nucleus is one of the promising therapeutic options for epilepsy. Several studies are still under way to further strengthen and clarify the mechanism, efficacy, and complications. Contrary to hardware-related and operation-related events, the stimulation-related adverse effect is mild, target-dependent, and adjustable. We present a case of relapsing herpes simplex encephalitis (HSE) as a newly reported and potentially fatal stimulation-related adverse effect following stimulation of the anterior thalamic nucleus (ANT-DBS) accompanied by fever, confusion, and cognitive impairment in a 32-year-old epileptic patient with a history of herpes meningoencephalitis 31 years earlier. The T2-weighted/FLAIR high-signal intensity in the temporal lobe developed at a "distance" from the stimulation target. The positive polymerase chain reaction of herpes virus deoxyribonucleic acid in the cerebrospinal fluid confirmed the diagnosis. The condition improved partially on acyclovir and stimulation stopped. Seizures disappeared and then returned after few months. The unique case report presents a rationale for considering history of herpes encephalitis as a relative contraindication for ANT-DBS, and HSE relapse should be suspected in patients with post-stimulation fever and/or altered consciousness.

Inline Coupling of Electrokinetic Preconcentration Method to Taylor Dispersion Analysis for Size-Based Characterization of Low-UV-Absorbing Nanoparticles.

The inline coupling of the field-amplified sample injection (FASI) to Taylor dispersion analysis (TDA) was used to characterize low-UV absorbing carboxylated silica nanoparticles (cNPs). The hydrodynamic diameters (Dh) were measured by using a commercial capillary electrophoresis instrument. The proposed methodology did not require any complicated instruments or chromophoric dye to increase the detection sensitivity. A practical method based on a half-Gaussian fitting was proposed for the data processing. The results obtained by this method were compared with those derived from dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. From these results, it appeared that the size derived by TDA is in excellent agreement with those measured by DLS and TEM, as demonstrated by stable nanoparticles with narrow size distributions. Intermediate precision relative standard deviations less than 5% were obtained by FASI-TDA. The effect of the FASI-induced cNP peak dispersion on the reliability of the results was discussed in detail.

Serodiagnosis of Extraintestinal Amebiasis: Retrospective Evaluation of the Diagnostic Performance of the Bordier® ELISA Kit.

Soluble antigens from an axenic culture of Entamoeba histolytica were used to develop a commercial ELISA kit to quantify anti-E. histolytica antibodies in sera of patients with extraintestinal amebiasis in non-endemic settings. The diagnostic specificity and sensitivity of the test were assessed retrospectively using 131 human serum samples with amoebic serologic status available. They were selected according to their results in immunofluorescence (IFAT) and were separated in 2 sample categories: 64 sera with positive results by IFAT and 67 with negative results by IFAT. The sensitivity and specificity of the ELISA kit were assessed at 95.0% and 94.0% compared to the IFAT. The test can be useful to exclude a potential diagnosis of amebiasis and could be used as a screening method since ELISA is an automated technique.

Waning immunity against mumps in vaccinated young adults, France 2013.

In 2013, 15 clusters of mumps were notified in France; 72% (82/114) of the cases had been vaccinated twice with measles-mumps-rubella vaccine. To determine whether the risk of mumps increased with time since the last vaccination, we conducted a case-control study among clusters in universities and military barracks. A confirmed case had an inflammation of a salivary gland plus laboratory confirmation in 2013. A probable case presented with inflammation of a salivary gland in 2013 either lasting for > 2 days or with epidemiological link to a confirmed case. Controls had no mumps symptoms and attended the same university course, student party or military barracks. We collected clinical and vaccination data via web questionnaire and medical records. We calculated adjusted odds ratios (aOR) using logistic regression. 59% (50/85) of cases and 62% (199/321) of controls had been vaccinated twice. The odds of mumps increased for twice-vaccinated individuals by 10% for every year that had passed since the second dose (aOR 1.10; 95% confidence interval (CI): 1.02-1.19; p = 0.02). Mumps immunity waned with increasing time since vaccination. Our findings contributed to the French High Council of Public Health's decision to recommend a third MMR dose during outbreaks for individuals whose second dose dates > 10 years.

Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis.

Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

What is new about epidemiology of acute infectious encephalitis?

PURPOSE OF REVIEW: This review aims to describe new features on the epidemiology of encephalitis world-wide. As this neurological presentation is most frequently related to transmitted viruses, surveillance of encephalitis is of major importance to detect their emergence or re-emergence. RECENT FINDINGS: Rabies causes one of the most severe types of encephalitis as it is lethal in all cases, and it is endemic in some countries. It was thought that the virus had been eradicated in Western Europe, but it re-emerged in Greece and Italy. Physicians should be aware of this diagnosis in the case of severe encephalitis. Some viruses (Powassan, Nipah, and Hendra) are becoming endemic in some new parts of the world (USA and Australia). Because of their severity, they are healthcare concerns in those countries and for travelers (e.g. in Asia). Finally, a concept is emerging: herpes simplex virus is suspected to be a trigger for autoimmune encephalitis. This is of major importance for the future management of patients (corticosteroids early in the course of the disease?), and the epidemiology of sequelae. SUMMARY: Encephalitis is a good marker for the detection of emerging infections. New findings about the relationship between herpes simplex virus encephalitis and autoimmune encephalitis open a new concept for a better management of patients.

Characteristics, management and outcome of Herpes Simplex and Varicella-Zoster virus encephalitis: a multicentre prospective cohort study.

OBJECTIVE: To characterize differences between Herpes Simplex virus encephalitis and Varicella-Zoster virus encephalitis (HSVE and VZVE) and other aetiologies of infectious encephalitis (IE), and to investigate the impact of time-to-aciclovir (ACV) start, ACV dose and duration on outcome. METHODS: We compared 132 HSVE, 65 VZVE and 297 other IE enrolled in a prospective cohort (ENCEIF). We estimated associations between time-to-ACV start, dose or duration and outcome through adjusted odds ratio (aOR) using logistic regression analysis. RESULTS: Prevalence of immunodepression differed among aetiologies: 15/65 (23%) for VZVE, 13/132 (10%) for HSVE and 30/297 (10%) for other IE (p <0.05), as was presence of seizure at admission: 27/132 (20%) for HSVE, 4/65 (6%) for VZVE and 43/297 (14%) for other IE (p <0.05). Poor outcome at hospital discharge (Glasgow outcome scale ≤3) differed among the three groups: 40/127 (31%) for HSVE, 12/65 (18%) for VZVE and 38/290 (13%) for other IE (p <0.05). Time-to-ACV start was associated with outcome in HSVE (aOR 3.61 [1.25-10.40]), but not in VZVE (aOR 0.84 [0.18-3.85]). Increased ACV dose was not associated with outcome among HSVE (aOR 1.25 [0.44-3.64]) nor VZVE (aOR 1.16 [0.24-5.73]). DISCUSSION: HSVE and VZVE are distinct in clinical presentation, outcome and prognostic factors. The impact of early ACV initiation was more apparent for HSVE than for VZVE; however, this could be because of VZVE's smaller sample size and lower outcome rate leading to low statistical power or because of potential distinct IE pathophysiology.

Outcome and Sequelae of Autoimmune Encephalitis.

Autoimmune etiologies are a common cause for encephalitis. The clinical syndromes consistent with autoimmune encephalitis are both distinct and increasingly recognized, but less is known about persisting sequelae or outcomes. We searched PubMed for reports on outcomes after autoimmune encephalitis. Studies assessing validated, quantitative outcomes were included. We performed a narrative review of the published literature of outcomes after autoimmune encephalitis. We found 146 studies that produced outcomes data. The mortality rates were 6%-19% and the relapse risks were 10%-62%. Most patients achieved a good outcome based on a score on the modified Rankin Scale (mRS) of ≤2. Forty-nine studies evaluated outcomes beyond mRS; these studies investigated cognitive outcome, psychiatric sequelae, neurological deficits, global function, and quality-of-life/patient-reported outcomes using various tools at varying time points after the index hospital discharge. These more-detailed assessments revealed that most patients had persistent impairments, with frequent deficits in cognitive function, especially memory and attention. Depression and anxiety were also common. Many of these sequelae continued to improve over months or even years after the acute illness. While we found that lasting impairments were common among survivors of autoimmune encephalitis, additional research is needed to better understand the nature and impact of these sequelae. Standardized evaluation protocols are needed to improve the ability to compare outcomes across studies, guide rehabilitation strategies, and inform outcomes of interest in treatment trials as the field advances.

Outcome and Sequelae of Infectious Encephalitis.

Acute infectious encephalitis is a widely studied clinical syndrome. Although identified almost 100 years ago, its immediate and delayed consequences are still neglected despite their high frequency and possible severity. We reviewed the available data on sequelae and persisting symptoms following infectious encephalitis with the aim of characterizing the clinical picture of these patients at months to years after hospitalization. We searched PubMed for case series involving sequelae after infectious encephalitis. We carried out a narrative review of the literature on encephalitis caused by members of the Herpesviridae family (herpes simplex virus, varicella zoster virus, and human herpesvirus-6), members of the Flaviviridae family (West Nile virus, tick-borne encephalitis virus, and Japanese encephalitis virus), alphaviruses, and Nipah virus. We retrieved 41 studies that yielded original data involving 3,072 adult patients evaluated after infectious encephalitis. At least one of the five domains of cognitive outcome, psychiatric disorders, neurological deficits, global functioning, and quality of life was investigated in the reviewed studies. Various tests were used in the 41 studies and the investigation took place at different times after hospital discharge. The results showed that most patients are discharged with impairments, with frequent deficits in cognitive function such as memory loss or attention disorders. Sequelae tend to improve within several years following flavivirus or Nipah virus infection, but long-term data are scarce for other pathogens. Further research is needed to better understand the extent of sequelae after infectious encephalitis, and to propose a standardized assessment method and assess the rehabilitation efficacy in these patients.

Treatment of tularemia in pregnant woman, France.

A pregnant woman who had oropharyngeal tularemia underwent treatment with azithromycin and lymph node resection and recovered without obstetrical complication or infection in the child. Azithromycin represents a first-line treatment option for tularemia during pregnancy in regions where the infecting strains of Francisella tularensis have no natural resistance to macrolides.

Characteristics, management, and outcomes of patients with infectious encephalitis requiring intensive care: A prospective multicentre observational study.

PURPOSE: Infectious encephalitis (IE) is a severe disease which requires intensive care unit (ICU) admission in up to 50% of cases. We aimed to describe characteristics, management and outcomes of IE patients who required ICU admission. MATERIALS AND METHODS: Ancillary study focusing on patients with ICU admission within the ENCEIF cohort, a French prospective observational multicentre study. The primary criteria for outcome was the functional status at hospital discharge, categorized using the Glasgow outcome scale (GOS). Logistic regression model was used to identify risk factors for poor outcome, defined as a GOS ≤ 3. RESULTS: We enrolled 198 ICU patients with IE. HSV was the primary cause (n = 72, 36% of all IE, 53% of IE with microbiological documentation). Fifty-two patients (26%) had poor outcome at hospital discharge, including 22 deaths (11%). Immunodeficiency, supratentorial focal signs on admission, lower cerebrospinal fluid (CSF) white cells count (<75/mm3), abnormal brain imaging, and time from symptoms onset to acyclovir start >2 days were independent predictors of poor outcome. CONCLUSION: HSV is the primary cause of IE requiring ICU admission. IE patients admitted in ICU have a poor prognosis with 11% of in-hospital mortality and 15% of severe disabilities in survivors at discharge.

Encephalitis in travellers: a prospective multicentre study.

BACKGROUND: As the epidemiology of encephalitis varies from one country to another, international travel may be an important clue for the diagnostic workout of this puzzling disease. METHODS: We performed an ancillary study using the ENCEIF prospective cohort conducted in 62 clinical sites in France from 2016 to 2019. All cases of encephalitis in adults that fulfilled a case definition derived from the International Encephalitis Consortium were included. Travellers were defined as patients who spent at least one night in a foreign country within the last six months. RESULTS: Of the 494 encephalitis patients enrolled, 69 (14%) were travellers. As compared to non-travellers, they were younger (median age, 48 years [interquartile range, 36-69] vs 66 [49-76], P < 0.001), less likely to be immunocompromised: 2/69 (3%) vs 56/425 (13%), P = 0.02, and reported more arthralgia: 7/69 (10%) vs 11/425 (3%), P = 0.007. The risk of poor outcome at hospital discharge (Glasgow outcome scale ≤3), was similar for travellers and for non-travellers after adjustment (aOR 0.80 [0.36-1.80], P = 0.594). Arboviruses were the main causes of encephalitis in travellers: 15/69 (22%) vs 20/425 (5%) in non-travellers, P < 0.001, and Herpes simplex virus (HSV) was the second (9/69, 13%). Of note, in 19% (13/69) of cases, the risk of encephalitis in travellers may have been decreased with a vaccine. CONCLUSION: The two primary causes of encephalitis in travellers are arboviruses and HSV. Empirical treatment of encephalitis in travellers must include acyclovir. Pre-travel advice and vaccination may decrease the risk of encephalitis in travellers.

Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France.

BACKGROUND: A prospective study of infectious encephalitis was conducted in France in 2007. In total, 253 patients were enrolled with a proven etiological diagnosis for 52%. The cohort of surviving patients with encephalitis was assessed for sequelae and impairment 3 years after enrollment. METHODS: Patients, their family, and general practitioners (GPs) were interviewed by phone to document persisting symptoms, return to work, and past and current leisure activities, with standardized questionnaires. The IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) was completed with relatives. The global outcome was determined in all patients with the Glasgow outcome scale. RESULTS: In 2010, 20 patients (10%) were unavailable for follow-up, 2 (1%) were excluded, and 18 (9%) had died since hospital discharge. Data were available for 167 survivors and 9 patients whose death was related to the encephalitis. The outcome was favorable in 108 of 176 patients (61%) (71 with complete resolution), 31 (18%) were mildly impaired, 25 (14%) were severely impaired, and 3 (1%) were in a vegetative state. The most frequent symptoms were difficulty concentrating (42%), behavioral disorders (27%), speech disorders (20%), and memory loss (19%). Fifteen of 63 patients (24%) previously employed were still unable to resume work. Long-term outcome was significantly associated with comorbid conditions, age, level of education, and the causative agent of encephalitis. CONCLUSIONS: Most patients with encephalitis experienced a favorable outcome 3 years after hospital discharge. However, minor to severe disability persists in a high number of cases with consequences for everyday life. Physical and mental impairment should be evaluated in all patients with encephalitis, and neuropsychological rehabilitation implemented whenever needed.

Systemic antifungal therapy in critically ill patients without invasive fungal infection*.

OBJECTIVE: To determine the number of adult or pediatric intensive care unit patients without documented invasive fungal infection who receive systemic antifungal therapy. DESIGN: A 1-day cross-sectional cohort study. SETTING: One hundred sixty-nine intensive care units in France and Belgium. PATIENTS: All patients staying in the participating intensive care units. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: A hierarchical mixed model was used to identify center-based and patient-based determinants of systemic antifungal therapy use. Day 28 mortality was compared in patients with and without systemic antifungal therapy. Two thousand forty-seven patients were recruited. Systemic antifungal therapy was used in 154 (7.5%) patients, including 100 without and 54 with a proven invasive fungal infection. Overall, systemic antifungal therapy consisted of monotherapy of fluconazole (60%), caspofungin (24%), voriconazole (8%), or liposomal amphotericin B (5%). Independent predictors of systemic antifungal therapy included patient-related factors (severity, emergency surgery, malignancy, Candida colonization, and severe sepsis) and center-related factors (hospital with <800 beds, solid organ transplantation activity, higher annual incidence of candidemia, uncontrolled use of fluoroquinolones, and routine systemic antifungal therapy in patients with unresolved documented or undocumented sepsis). The group given systemic antifungal therapy had greater disease severity and higher rates of sepsis and organ failures. Nevertheless, crude 28-day mortality in the systemic antifungal therapy group was not significantly higher than in the group not given systemic antifungal therapy (20% vs. 19.2%; hazard ratio, 0.97 [0.61-1.52]; p = .88). CONCLUSIONS: Systemic antifungal therapy was used in 7.5% of intensive care unit patients. Two-thirds of patients given systemic antifungal therapy had no documented invasive fungal infection. Our results warrant a trial of systemic antifungal therapy in severely ill intensive care unit septic patients without documented invasive fungal infection based on their severity of illness and the presence of Candida colonization.

[Adult vaccination coverage: surveys in four populations - Isère (France), 2002-2003]. / La couverture vaccinale des adultes : enquêtes dans quatre populations d'Isère (France), 2002-2003.

In order to assess their vaccination policy, the public health authorities in Isère (France) conducted several surveys to determine the vaccination coverage rate among adults. In France, the current state of knowledge in this area is limited. Four separate surveys were conducted in 2002-2003: (1) a telephone survey of 976 adults, 18% of whom had vaccination certificates; (2) a survey of 44 general practitioners (805 patients); (3) a survey of occupational health centers (82 practitioners and 1,119 employees); and (4) a survey of 1,214 patients vaccinated at the international vaccination center in Grenoble (France). The same data were recorded in all four surveys (last vaccination date, either declared by the patient or proven by a vaccination certificate). Based on certified evidence, vaccination coverage for tetanus, diphtheria, and poliomyelitis ranged from 31.6% to 83.9%, from 24.1% to 44.0%, and from 25.9% to 71.9%, respectively. Compared to general practitioners, vaccination coverage was higher among staff working at the occupational health center and lower in the general population. The four surveys covered only part of the adult population and provided only an estimate of vaccination coverage. The study found that tetanus vaccination coverage was the highest, but was still below expected levels. For the other vaccines, vaccination coverage among adults appears to be inadequate. The findings suggest that all health professionals involved in adult vaccination (occupational health doctors, general practitioners, hospital doctors, etc.) should be invited to participate in working groups on vaccination.

ESCMID rapid guidelines for assessment and management of long COVID.

SCOPE: The aim of these guidelines is to provide evidence-based recommendations for the assessment and management of individuals with persistent symptoms after acute COVID-19 infection and to provide a definition for this entity, termed 'long COVID'. METHODS: We performed a search of the literature on studies addressing epidemiology, symptoms, assessment, and treatment of long COVID. The recommendations were grouped by these headings and by organ systems for assessment and treatment. An expert opinion definition of long COVID is provided. Symptoms were reviewed by a search of the available literature. For assessment recommendations, we aimed to perform a diagnostic meta-analysis, but no studies provided relevant results. For treatment recommendations we performed a systematic review of the literature in accordance with the PRISMA statement. We aimed to evaluate patient-related outcomes, including quality of life, return to baseline physical activity, and return to work. Quality assessment of studies included in the systematic review is provided according to study design. RECOMMENDATIONS: Evidence was insufficient to provide any recommendation other than conditional guidance. The panel recommends considering routine blood tests, chest imaging, and pulmonary functions tests for patients with persistent respiratory symptoms at 3 months. Other tests should be performed mainly to exclude other conditions according to symptoms. For management, no evidence-based recommendations could be provided. Physical and respiratory rehabilitation should be considered. On the basis of limited evidence, the panel suggests designing high-quality prospective clinical studies/trials, including a control group, to further evaluate the assessment and management of individuals with persistent symptoms of COVID-19.