Tick-borne encephalitis: A comprehensive review of the epidemiology, virology, and clinical picture.

Tick-borne encephalitis virus (TBEV) is a flavivirus commonly found in at least 27 European and Asian countries. It is an emerging public health problem, with steadily increasing case numbers over recent decades. Tick-borne encephalitis virus affects between 10,000 and 15,000 patients annually. Infection occurs through the bite of an infected tick and, much less commonly, through infected milk consumption or aerosols. The TBEV genome comprises a positive-sense single-stranded RNA molecule of ∼11 kilobases. The open reading frame is > 10,000 bases long, flanked by untranslated regions (UTR), and encodes a polyprotein that is co- and post-transcriptionally processed into three structural and seven non-structural proteins. Tick-borne encephalitis virus infection results in encephalitis, often with a characteristic biphasic disease course. After a short incubation time, the viraemic phase is characterised by non-specific influenza-like symptoms. After an asymptomatic period of 2-7 days, more than half of patients show progression to a neurological phase, usually characterised by central and, rarely, peripheral nervous system symptoms. Mortality is low-around 1% of confirmed cases, depending on the viral subtype. After acute tick-borne encephalitis (TBE), a minority of patients experience long-term neurological deficits. Additionally, 40%-50% of patients develop a post-encephalitic syndrome, which significantly impairs daily activities and quality of life. Although TBEV has been described for several decades, no specific treatment exists. Much remains unknown regarding the objective assessment of long-lasting sequelae. Additional research is needed to better understand, prevent, and treat TBE. In this review, we aim to provide a comprehensive overview of the epidemiology, virology, and clinical picture of TBE.

Serum and cerebrospinal fluid phosphorylated neurofilament heavy subunit as a marker of neuroaxonal damage in tick-borne encephalitis.

Extensive axonal and neuronal loss is the main cause of severe manifestations and poor outcomes in tick-borne encephalitis (TBE). Phosphorylated neurofilament heavy subunit (pNF-H) is an essential component of axons, and its detection in cerebrospinal fluid (CSF) or serum can indicate the degree of neuroaxonal damage. We examined the use of pNF-H as a biomarker of neuroaxonal injury in TBE. In 89 patients with acute TBE, we measured CSF levels of pNF-H and 3 other markers of brain injury (glial fibrillary acidic protein, S100B and ubiquitin C-terminal hydrolase L1) and compared the results to those for patients with meningitis of other aetiology and controls. Serum pNF-H levels were measured in 80 patients and compared with findings for 90 healthy blood donors. TBE patients had significantly (P<0.001) higher CSF pNF-H levels than controls as early as hospital admission. Serum pNF-H concentrations were significantly higher in samples from TBE patients collected at hospital discharge (P<0.0001) than in controls. TBE patients with the highest peak values of serum pNF-H, exceeding 10 000 pg ml-1, had a very severe disease course, with coma or tetraplegia. Patients requiring intensive care had significantly higher serum pNF-H levels than other TBE patients (P<0.01). Elevated serum pNF-H values were also observed in patients with incomplete recovery (P<0.05). Peak serum pNF-H levels correlated positively with the duration of hospitalization (P=0.005). Measurement of pNF-H levels in TBE patients might be useful for assessing disease severity and determining prognosis.

[Pneumothorax, pneumomediastinum and subcutaneous emphysema as complica-tions of COVID-19].

Spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema are serious complications of COVID-19 infection caused by SARS-CoV-2, occurring in approximately 1% of hospitalized patients. The risk increases with the accumulation of risk factors, namely moderate or severe illness, high-flow oxygen therapy and noninvasive ventilation. The pathophysiology may be contributed to by patient self-inflicted lung injury. Hypoxia-induced respiratory effort in patients with pneumonia puts an enormous load on certain parts of their lungs, leading to subsequent progression of lung tissue damage. These complications start with destruction of the alveolar membrane, accompanied by emergence of a pulmonary bulla. Rupture of the bulla results in air leaking to the pleural space (pneumothorax). In the case of pneumomediastinum, the air spreads within the peribronchial interstitium along the airways to the mediastinum and subcutaneous tissues (Macklin effect). While pneumomediastinum and subcutaneous emphysema resolve spontaneously in most cases, pneumothorax treatment depends on its magnitude. While small pneumothorax may be managed conservatively, large pneumothorax usually requires active treatment with an acute chest drain; the latter is also associated with worse prognosis and a higher chance of death. We report air-leak complications in nine COVID-19 patients, of whom seven had spontaneous pneumothorax and four of them died. Three patients developed spontaneous pneumomediastinum together with subcutaneous emphysema, with two of them surviving. One patient with combination of pneumothorax, pneumomediastinum and subcutaneous emphysema died. These complications may accompany moderate or severe COVID-19-associated pneumonia, mostly the late phase of the disease. They should be considered when patients complain of sudden chest or back pain or worsening respiratory insufficiency.

[COVID-19: diagnosis and treatment outside hospital].

COVID-19 is an acute infectious disease, predominantly affecting the respiratory tract, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

[Manual for physicians in COVID-19 units].

The manual contains basic information about the diagnosis, treatment and organization of care for COVID-19 patients staying in general wards.

[COVID-19: diagnosis and treatment].

The guidelines provide evidence-based recommendations for the management of COVID-19. The clinical manifestations of the disease are described and indication criteria for hospital admission of patients with COVID-19 are listed. Polymerase chain reaction and antigen testing are used in direct diagnostics. Indirect detection of infection by antibodies is currently of limited value. There are a number of hematological and biochemical laboratory test used to diagnose COVID-19. Pathological values of some laboratory parameters are associated with severity of COVID-19. Of the imaging studies, chest X-ray, chest computer tomography and lung ultrasound are used. COVID-19 therapy includes symptomatic and specific therapy (antivirals, immunotherapeutics and anticoagulants) and intensive care in the severe and critical forms of the disease. Remdesivir and favipiravir are available as antiviral agents. Immunotherapeutics include monoclonal antibodies (casirivimab/imdevimab, bamlanivimab/etesevimab), dexamethas one, baricitinib and tocilizumab. Low-molecular-weight heparin is a dominant form of anticoagulant therapy. The guidelines provide specific therapeutic recommendations for each stage of the disease. Antibiotics are recommended only if bacterial superinfection is suspected or demonstrated, which is not common in the early stages of the disease.

Early Diagnosis of Tularemia by Flow Cytometry, Czech Republic, 2003-20151.

We retrospectively assessed the utility of a flow cytometry-based test quantifying the percentage of CD3+ T cells with the CD4-/CD8- phenotype for predicting tularemia diagnoses in 64 probable and confirmed tularemia patients treated during 2003-2015 and 342 controls with tularemia-like illnesses treated during 2012-2015 in the Czech Republic. The median percentage of CD3+/CD4-/CD8- T cells in peripheral blood was higher in tularemia patients (19%, 95% CI 17%-22%) than in controls (3%, 95% CI 2%-3%). When we used 8% as the cutoff, this test's sensitivity was 0.953 and specificity 0.895 for distinguishing cases from controls. The CD3+/CD4-/CD8- T cells increased a median of 7 days before tularemia serologic test results became positive. This test supports early presumptive diagnosis of tularemia for clinically suspected cases 7-14 days before diagnosis can be confirmed by serologic testing in regions with low prevalences of tularemia-like illnesses.

Francisella tularensis Periprosthetic Joint Infections Diagnosed with Growth in Cultures.

Tularemia caused by Francisella tularensis is a zoonotic infection of the Northern Hemisphere that mainly affects the skin, lymph nodes, bloodstream, and lungs. Other manifestations of tularemia are very rare, especially those with musculoskeletal involvement. Presenting in 2016, we diagnosed two cases of periprosthetic knee joint infections (PJI) caused by Francisella tularensis in Europe (one in Switzerland and one in the Czech Republic). We found only two other PJI cases in the literature, another knee PJI diagnosed 1999 in Ontario, Canada, and one hip PJI in Illinois, USA, in 2017. Diagnosis was made in all cases by positive microbiological cultures after 3, 4, 7, and 12 days. All were successfully treated, two cases by exchange of the prosthesis, one with debridement and retention, and one with repeated aspiration of the synovial fluid only. Antibiotic treatment was given between 3 weeks and 12 months with either ciprofloxacin-rifampin or with doxycycline alone or doxycycline in combination with gentamicin. Zoonotic infections should be considered in periprosthetic infections in particular in culture-negative PJIs with a positive histology or highly elevated leukocyte levels in synovial aspiration. Here, we recommend prolonging cultivation time up to 14 days, performing specific PCR tests, and/or conducting epidemiologically appropriate serological tests for zoonotic infections, including that for F. tularensis.

The Scottish model of vancomycin dosing and therapeutic drug monitoring improves both efficacy and safety of vancomycin therapy.

OBJECTIVE: Vancomycin therapeutic drug monitoring (TDM) is recommended for better treatment efficacy and safety. The Scottish Antimicrobial Prescribing Group model recommends weight-based loading dose, next 3-4 doses based on creatinine clearance and maintenance doses according to trough concentrations. METHODS: Retrospective cohort study of all adult patients treated with vancomycin before and after introducing the guideline in a large Czech hospital in 2015 compares the success rate in achieving recommended trough concentrations (10-20 mg/l) during first measurement and efficiency of maintaining these concentrations subsequently. Assessment of vancomycin related nephrotoxicity is included. RESULTS: In 2014, 74/163 (45.4 %) patients achieved recommended concentrations in the first measurement, compared to 101/160 (63.1 %) patients in 2016 (χ2; p = 0.001). Recommended trough concentrations in more than half of subsequent measurements were detected in 51/105 patients (48.6 %) in 2014 and in 80/117 patients (68.4 %) in 2016. Not a single level in subsequent measurements within the range was detected in 28 (26.7 %) cases in 2014 and in 10 (8.5 %) cases in 2016 (Mann-Whitney; p = 0.026). There was no difference in nephropathy occurrence (χ2; p = 0.286). CONCLUSION: The adopted Scottish model of vancomycin TDM resulted in very significantly higher achievement of recommended trough concentrations during first measurements and significantly more effective maintenance of subsequent concentrations, without increased nephrotoxicity. Key words: guideline - therapeutic drug monitoring - vancomycin.

[The challenges of diagnostic reasoning or "how doctors think"]. / Nástrahy diagnostického procesu aneb "zamyslení nad myslením lékaru".

Basic overview of diagnostic errors with particular focus on cognitive biases and strategies to minimize or avoid them.

Effect of intermittent rifampicin on the pharmacokinetics and safety of raltegravir.

OBJECTIVES: Previous studies of raltegravir and rifampicin have not studied the interaction when rifampicin is dosed intermittently. This study aimed to assess the pharmacokinetics of twice daily raltegravir and intermittently dosed rifampicin. METHODS: This was a prospective, open, single-arm, three-part, controlled study in healthy volunteers. Over a period of 38 days subjects received 5 days of standard-dose raltegravir (400 mg twice daily) followed by 28 days of standard-dose raltegravir plus rifampicin three times a week followed by 5 days of high-dose (800 mg twice daily) raltegravir plus rifampicin three times a week. Pharmacokinetic sampling was performed on days 5, 33 and 38. Raltegravir pharmacokinetic parameters were determined by non-compartmental analysis and reported as geometric means and 90% CIs. ClinicalTrials.gov: NCT01424826. RESULTS: Sixteen subjects (12 females) completed the study. Raltegravir trough plasma concentration (C12) was significantly lower in the presence of rifampicin when dosed at 400 mg twice daily (40%), which was not observed with 800 mg twice daily dosing. Raltegravir Cmax and AUC0-12 were both significantly higher in the presence of rifampicin when dosed at 800 mg twice daily (76% and 84%, respectively), but this dose was well tolerated. CONCLUSIONS: This study suggests that rifampicin induction of raltegravir is comparable between daily and intermittent rifampicin. In the absence of definitive clinical efficacy data to suggest otherwise, doses of 800 mg of raltegravir twice daily with rifampicin thrice weekly are well tolerated and yield higher AUCs and comparable C12 when compared with raltegravir alone.

Burden of serious fungal infections in the Czech Republic.

We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care.

Opinions of citizens of the Czech Republic on the role of nurses in primary care during the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVE: In spite of the general current decrease in COVID-19 incidence, the epidemiological situation on the territory of the Czech Republic is still unfavourable. Nurses play an essential role in the fight against this disease. MATERIAL AND METHODS: A non-standardized questionnaire was used to discover the expectations regarding nursing care provided during the COVID-19 pandemic. The sample of respondents was constructed using quota selection. The sample consisted of 1,815 respondents. RESULTS: The study identified a significant correlation between the age of respondents and the method used to contact general practitioners (p < 0.001). The oldest respondents (65+) more likely contacted GPs by phone. Respondents with basic education used outpatient services more often before than during the pandemic (p < 0.05). The behaviour of nurses was considered as professional and accommodating. The oldest respondents (65+) reported nurses did not to make them feel rushed. Other age groups rated nurses more critically (p < 0.01). Respondents, especially women, described the psychological burden on nurses during the COVID-19 pandemic as demanding (p < 0.01). Women, more than men, reported that nurses lacked protective equipment during the pandemic (p < 0.05). The use of an online system was significantly influenced by respondent education (p 0.001). Respondents with lower education were less likely to welcome this option. CONCLUSIONS: Due to the persisting COVID-19 incidence on the territory of the Czech Republic, citizens` opinions of the position of nurse in primary care in the period of COVID- 19 pandemics need to be known.The behaviour of nurses was considered to be accommodating and satisfactory.

Serum matrix metalloproteinase-9 (MMP-9) as a biomarker in paediatric and adult tick-borne encephalitis patients.

Matrix metalloproteinases (MMPs) play an important role in central nervous system infections. We analysed the levels of 8 different MMPs in the cerebrospinal fluid (CSF) of 89 adult patients infected with tick-borne encephalitis (TBE) virus and compared them with the levels in a control group. MMP-9 was the only MMP that showed significantly increased CSF levels in TBE patients. Serum MMP-9 levels were subsequently measured in 101 adult TBE patients at various time points during the neurological phase of TBE and at follow-up. In addition, serum MMP-9 was analysed in 37 paediatric TBE patients. Compared with control levels, both paediatric and adult TBE patients had significantly elevated serum MMP-9 levels. In most adult patients, serum MMP-9 levels peaked at hospital admission, with higher serum MMP-9 levels observed in patients with encephalitis than in patients with meningitis. Elevated serum MMP-9 levels were observed throughout hospitalisation but decreased to normal levels at follow-up. Serum MMP-9 levels correlated with clinical course, especially in patients heterozygous for the single-nucleotide polymorphism rs17576 (A/G; Gln279Arg) in the MMP9 gene. The results highlight the importance of MMP-9 in the pathogenesis of TBE and suggest that serum MMP-9 may serve as a promising bioindicator of TBE in both paediatric and adult TBE patients.

HIV-positive Ukrainian refugees in the Czech Republic.

OBJECTIVE: Over 480 000 Ukrainian refugees have arrived in the Czech Republic since the Russian invasion of Ukraine in 2022, including over 500 people with HIV. This study describes the demographics, characteristics, and management of Ukrainian refugees with HIV in the Czech Republic. DESIGN: Retrospective, observational, noninterventional study. METHODS: Ukrainian nationals registering at HIV centers in the Czech Republic with war refugee status were included. Data were collected from medical records between 1 March and 31 July 2022. The study was registered with the Czech State Institute for Drug Control, ID number 2301200000. RESULTS: Four hundred and eighty-two patients were included in the study. Most patients were female (69.5%; n  = 335/482) with well-controlled HIV. The median [interquartile range] CD4 + cell count was 597 [397] cells/µl of blood, and 79.3% ( n  = 361/455) of patients had HIV RNA <40 copies/ml. Coinfections of hepatitis C virus, hepatitis B virus, and/or tuberculosis were reported for 17.4% ( n  = 78/449), 9% ( n  = 40/446) and 1.3% ( n  = 6/446) of patients, respectively. In Ukraine, 85.7% ( n  = 384/448) of patients had been receiving an integrase strand transfer inhibitor-based regimen and most (69.7%; n  = 310/445) did not switch therapy upon arrival in the Czech Republic. CONCLUSION: Migration from Ukraine is changing the characteristics of HIV epidemiology in the Czech Republic. Ukrainian refugees with HIV have been provided with a high standard of medical care in the Czech Republic. Improved coordination between medical services within the Czech Republic and between countries in the European Union is necessary to optimize patient care.

[Catheter related blood stream infections--prevalence and interventions]. / Katétrové infekce krevního reciste--prevalence a intervence.

BACKGROUND: Catheter related blood stream infections are a significant complication of intensive care with worldwide prevalence rate around 5 cases per 1000 catheter-days. Only scanty Czech data have been published. Our study monitored the occurrence of catheter-related blood stream infections in a high dependency unit of regional hospital. METHODS: In 2008 we commenced to monitor the occurrence rate of catheter-related blood stream infections in short-term central venous catheters without antimicrobial coating. We organized a training session for medical staff and started to strictly adhere to published guidelines. After two years of keeping a register we analysed individual cases as proven, possible, or not proven blood stream infections. RESULTS: From March 2008 to March 2010 we inserted 142 central venous catheters for total time of 1423 catheter days (median 9 days). Ten catheters were removed after median of 17 days due to unexplained pyrexia. Blood stream infection was proven in 4 cases and possible in 2 cases. We have noted total 2.81 proven cases, and 4.22 proven and/or possible cases of blood stream infection per 1000 catheter-days. CONCLUSION: The register of catheter related blood stream infections is an inexpensive and time-efficient tool that improves the quality of intensive

Rapid Progression of COVID-19-Associated Fatal Capillary Leak Syndrome.

Several cases of capillary leak syndrome (CLS) related to COVID-19 or vaccination against SARS-CoV-2 have been described in the literature. We present a case of a 42-year-old, previously healthy male, presenting with a mild form of COVID-19, who suddenly developed severe shock with hypotension and severe hemoconcentration within hours of admission to the hospital. Volume resuscitation was not effective, increasing hemoglobin (198 g/L on admission, 222 g/L 9 h later) suggested fluid leak into peripheral tissues. After cardiac arrest, the patient was resuscitated and connected to extracorporeal membrane oxygenation, but died shortly afterwards due to refractory heart failure. Retrospective investigation of blood samples confirmed diagnosis of CLS by progressive hypoalbuminemia (40 g/L on admission, 14 g/L 19 h later) and monoclonal gammopathy kappa (4.7 g/L). Patient's CLS was triggered by COVID-19, either a first attack of idiopathic CLS called Clarkson's disease or a COVID-19-induced secondary CLS.

Encephalitozoon cuniculi genotype I as a causative agent of brain abscess in an immunocompetent patient.

A brain abscess caused by Encephalitozoon cuniculi genotype I together with Streptococcus intermedius occurred in a patient without major immunocompromise and with diabetes. The distinguishing clinical signs were hemiparesis and epilepsy. The microsporidium was observed in the abscess aspirate, and its specific DNA was also detected in stool and urine. The patient was successfully treated with albendazole and mebendazole.

[Listeria infection of a prosthetic hip joint]. / Listeriový infekt umelé kloubní náhrady.

A 74-year-old male with type 2 diabetes, coronary artery disease with history of CABG, hypertension and chronic obstructive pulmonary disease had total left hip replacement in another medical facility five years prior to admission. Since the early postoperative period, he had manifestations of dormant infection and was with empirical antibiotics. On the index admission, his X-ray showed signs of loosening of the prosthetic components with resorption of the bone. Periprosthetic infection was managed by a two-stage surgery. First, the infected prosthesis was removed and replaced with a spacer with antibiotics. One month later, a revision prosthesis, was implanted using cement with antibiotics. Cultures of the excised tissues and materials yielded massive growth of Listeria monocytogenes and scarce growth of Staphylococcus epidermidis. This is the 18th published case of arthroplasty infection caused by Listeria. The presented patient most likely had dormant staphylococcal infection on which Listeria superinfection developed and accelerated the loosening. A literature review suggested several mechanisms that can make conservative management of Listeria infection difficult. They include marked stimulation of the immune system (with resulting resorption of the bone), survival in the macrophages (unavailability to antibiotics susceptible in vitro) and capability to form biofilm as well as settle in biofilms produced by other organisms. Better yield and reliability of microbiological investigations may be achieved by guided intrarticular fluid aspiration from a microincision, prolonged culture and sonification of the extracted material, two-step surgical management and follow-up intraarticular fluid aspiration prior to reimplantation of revision prosthesis.

Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease.

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.