High consequence infectious diseases (HCIDs) are feared for their high lethality and easy interpersonal transmission, posing a particular threat to healthcare workers. This article provides a brief history and characteristics of HCIDs, the procedure for healthcare workers in the event of suspecting an HCID, the coordinating function of an epidemiologist, and the gradual involvement of all components of the integrated rescue system, leading to transporting the patient to the Department of Infectious Diseases of the Bulovka University Hospital in Prague. Activation of the Ministry of Health and the National Institute of Public Health aims to arrange HCID diagnosis in a laboratory abroad. An integral part of the measures is carrying out proper disinfection at the outbreak site and treating contacts with the HCID. Keywords: high consequence infectious diseases, outbreak, contact.

AIMS:Antiviral drugs are considered as potentially cardiotoxic, due to prolongation of QT interval which may affect incidence of severe ventricular arrhythmias. The main aim of this retrospective study was to assess the influence of treatment by three antiviral drugs on QT interval and to find patients who are at an increased risk of developing malignant ventricular arrhythmias.METHODS:The study included 23 patients (14 men, 9 women) who were treated with a combination of interferon alpha, ribavirin, and an NS3/4A protease inhibitor. The parameters from the 12 leads electrocardiograms were evaluated before treatment, and then 3 ± 1 and 6 ± 1 months after treatment.RESULTS:Heart rate (HR) 69 ± 12 / min and corrected QT interval (QTc) 412 ± 35 ms were obtained before the treatment and there was not observed a significant prolongation of intervals after 3 months (HR 72 ± 11 / min, QTc 412 ± 33 ms) and after 6 months (HR 64 ± 12 / min, QTc 405 ± 28 ms) respectively. In total QTc interval was prolonged from the baseline in 53% and in 43% of the patients 3 months respectively 6 months after treatment. A QTc prolongation over of 450 ms and new treatment-related repolarization change was noted in 1 (4%) patient.CONCLUSION:The study demonstrates that a combination therapy of 3 antiviral drugs does not significantly prolong the QTc interval and does not cause severe pathological changes on the ECG. Patients undergoing this treatment are not at risk of developing heart disease as an undesirable side effect.

Background: The diagnosis of SARS-CoV-2 is almost exclusively performed by PCR or antigen detection. The detection of specific antibodies has not yet been considered in official diagnostic guidelines as major laboratory evidence for a case definition. The aim the present study is to analyze antibody responses in outpatient and inpatient cohorts of COVID-19 patients in the Czech Republic over a 12-month period, and assess the potential of antibodies as a diagnostic tool. Methods: A total of 644 patients was enrolled in the prospective study. IgA, IgM and IgG antibody levels, as well as virus neutralization titers, were analyzed over a 12-month period. Results: Our study showed low antibody positivity levels at the admission. However, at 2 weeks after infection, 98.75% and 95.00% of hospitalized patients were IgA and IgG positive, respectively. Even in the outpatient cohort characterized by milder disease courses, the IgG antibody response was still sustained at 9 and 12 months. The data show a high correlation between the IgG levels and virus neutralization titers (VNTs). Samples from later time-points showed positive antibody responses after vaccination in both cohorts characterized by high IgG levels and VNT over 1:640. The samples from unvaccinated persons indicated a relatively high level of reinfection at 6.87%. Conclusions: Our results show that the detection of antibodies against the SARS-CoV-2 shows an increasing sensitivity from week 2 after infection and remains highly positive over the 12-month period. The levels of IgG antibodies correlate significantly with the VNTs. This suggests that the serological data may be a valuable tool in the diagnosis of SARS-CoV-2 infection.

Background Chronic hepatitis C (CHC) is associated with altered cell-mediated immune response. Objective The aim of the study was to characterize functional alterations in CD4+ T cell subsets and myeloid-derived suppressor cells (MDSCs) during chronic hepatitis C virus (HCV) infection. Methodology. The expression levels of the lineage-defining transcriptional factors (TFs) T-bet, Gata3, Rorγt, and Foxp3 in circulating CD4+ T cells and percentages of MDSCs in peripheral blood were evaluated in 33 patients with CHC, 31 persons, who had spontaneously cleared the HCV infection, and 30 healthy subjects. Analysis. The CD4+ T cells TFs T-bet (T-box expressed in T cells), Foxp3 (Forkhead box P3 transcription factor), Gata3 (Gata-binding protein 3), and Rorγt (retinoic-acid-related orphan receptor gamma) and activation of CD8+ T cells, as well as percentages of MDSCs, were measured by multicolor flow cytometry after intracellular and surface staining of peripheral blood mononuclear cells with fluorescent monoclonal antibodies. Result The patients with CHC had significantly lower percentages of CD4+ T cells expressing Rorγt and Gata3 and higher percentages of Foxp3-expressing CD4+ T cells than healthy controls and persons who spontaneously cleared HCV infection. The ratios of T-bet+/Gata3+ and Foxp3+/Rorγt+ CD4+ T cells were the highest in the patients with CHC. In the patients with CHC, the percentages of Gata3+ and Rorγt+ CD4+ T cells and the percentages of T-bet+ CD4+ T cells and CD38+/HLA-DR+ CD8+ T cells demonstrated significant positive correlations. In addition, the percentage of CD38+/HLA-DR+ CD8+ T cells correlated negatively with the percentage of MDSCs. Conclusion Chronic HCV infection is associated with downregulation of TFs Gata3 and Rorγt polarizing CD4+ T cells into Th2 and Th17 phenotypes together with upregulation of Foxp3 responsible for induction of regulatory T cells suppressing immune response.

Background Invasive infections caused by Capnocytophaga canimorsus are rare. Immunocompromised patients, who report being bitten by or having a close contact with an animal, represent a high-risk group for this infection. There are only few dozens of infections by this bacteria manifesting as purulent meningitis reported worldwide. The reported case is a first reported case of purulent meningitis caused by by Capnocytophaga canimorsus in Czech Republic with only a limited risk factor history. Case presentation The patient, a 74 years old man, was referred to the infectious diseases department of a teaching hospital with clear signs of developing purulent meningitis. His anamnestic data did not show any unusual findings. He was treated for compensated diabetes mellitus type II. The blood cultures were negative and the etiological agent did not grow from the cerebrospinal fluid (CSF) on common media. Eventually, it was identified by detecting pan-bacterial DNA and DNA sequencing. Subsequently, the pathogen was confirmed by anaerobic cultivation from CSF. Only after then the patient recalled being bitten by his German shepherd puppy during play. The patient was successfully treated intravenously by ceftriaxone. Conclusions Purulent meningitis caused by Capnocytophaga spp. is a rare disease, but it needs to be considered in patients at risk with pre-existing conditions, who report close contact with or being bitten by an animal. It is important to test for this microbe in cases with negative microbiological results for the more common agents.

Introduction: Fluoroquinolones are a frequently prescribed class of antibiotics, which has been blacklisted in recent years because of a growing evidence of the connection with serious undesirable effects, infections Clostridioides difficile, and a connection with the occurrence of multiresistant strains. Methods: In the University Hospital Hradec Kralove in the course of the years 2009-2019, several antibiotic stewardship restrictive and educational interventions were performed by the Antibiotic Centre aiming to decrease quinolone antibiotics administration.The data of the consumption of quinolone antibiotics were retrospectively evaluated and correlated with the development of sensitivity and occurrence of multiresistance of selected bacteria in the hospital.Results: In the period under investigation, consumption of fluoroquinolone antibiotics significantly decreased (p<0.001) in 10 years by 71.8% to 26.7 DDD/1000 patient day.Sensitivity of Escherichia coli and Pseudomonas aeruginosa to fluoroquinolones in the period under investigation increased by 4.8% (respectively by 15%); on the other hand, sensitivity of Staphylococcus aureus decreased by 4.2% to 85.5% share of sensitive strains.The incidence of the multiresistant isolates Pseudomonas aeruginosa decreased by 8.1%, but the occurrence of ESBL-producing Klebsiella pneumoniae was increased in the period under investigation.The occurrence of methicillin-resistant Staphylococcus aureus did not show a stable trend and finally it was moderately increased by 2.9%.Paterova et al.: Effect of fluoquinolone restriction on bacterial sensitivity 179 Conclusion: Implementation of programmes of antimicrobial stewardship for hospitalized patients resulted in a decrease and a rationalization of fluoroquinolone administration.The reduction of their consumption in our hospital resulted in a statistically insignificant increase in the sensitivity of Escherichia coli and Pseudomonas aeruginosa, but not Staphylococcus aureus.

Invasive infections caused by Capnocytophaga canimorsus are rare. Immunocompromised patients, who report being bitten by or having a close contact with an animal, represent a high-risk group for this infection. There are only few dozens of infections by this bacteria manifesting as purulent meningitis reported worldwide. The reported case is a first reported case of purulent meningitis caused by by Capnocytophaga canimorsus in Czech Republic with only a limited risk factor history. The patient, a 74 years old man, was referred to the infectious diseases department of a teaching hospital with clear signs of developing purulent meningitis. His anamnestic data did not show any unusual findings. He was treated for compensated diabetes mellitus type II. The blood cultures were negative and the etiological agent did not grow from the cerebrospinal fluid (CSF) on common media. Eventually, it was identified by detecting pan-bacterial DNA and DNA sequencing. Subsequently, the pathogen was confirmed by anaerobic cultivation from CSF. Only after then the patient recalled being bitten by his German shepherd puppy during play. The patient was successfully treated intravenously by ceftriaxone. Purulent meningitis caused by Capnocytophaga spp. is a rare disease, but it needs to be considered in patients at risk with pre-existing conditions, who report close contact with or being bitten by an animal. It is important to test for this microbe in cases with negative microbiological results for the more common agents.

Doporuceni pro diagnostiku a terapii infekce virem hepatitidy C byla vytvořena cleny pracovnich skupin pro virove hepatitidy Ceske hepatologicke spolecnosti CLS JEP a Spolecnosti infekcniho lekařstvi CLS JEP. Jsou založena předevsim na doporucenich vydaných Evropskou asociaci pro studium jater (EASL) v dubnu 2015. Doporuceni definuji preferovaný přistup k řeseni problematiky HCV infekce. V oblasti lecby chronicke HCV infekce je vždy zminěno několik variant postupu. Tato skutecnost je dana rychlým vývojem nových proti virových preparatů a jejich nerovnoměrným zavaděnim do rutinni praxe v jednotlivých zemich. Dostupnost preparatů proto může být v konkretnim připadě faktorem limitujicim užiti optimalniho postupu.

The article discusses possible prevention and prophylaxis of infectious diseases affecting the course of pregnancy with respect to the mother, fetus and newborn. Also mentioned are diseases for which there is no vaccination. The options for prevention targeted at the periods before and during pregnancy and after delivery are explained. Finally, practical procedures related to vaccination and diagnosis of infectious diseases in women of childbearing age are presented.

1 Katedra epidemiologie, Fakulta vojenského zdravotnictví, Univerzita obrany, Hradec Králové 2 Klinika nemocí kožních a pohlavních, Fakultní nemocnice Hradec Králové 3 Klinika infekčních nemocí, Lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Hradec Králové 4 Přírodovědecká fakulta, Univerzita Hradec Králové 5 Centrum pro základní a aplikovaný výzkum, Fakulta informatiky a managementu, Univerzita Hradec Králové 6 Katedra organizace vojenského zdravotnictví a managementu, Fakulta vojenského zdravotnictví, Univerzita obrany, Hradec Králové

Chronic hepatitis C is curable disease. Low detection rate could be one of the reasons of poor treatment uptake. It is important to identify HCV prevalence and anti-hepatitis C virus (HCV) positive patients in population by effective screening strategy such as risk-based or birth cohort screening programs. There are no national population-based estimates of the HCV prevalence in the Czech Republic (CZ). The most recent seroprevalence survey determined a prevalence of positive anti-HCV antibodies of 0.2% (in 2001). The aim of the study was to determine the seroprevalence of HCV, HCV viraemia and HCV genotype in the CZ adult population. We also estimated the number of persons living with chronic hepatitis C in CZ. The examined group included 3000 adults, 18-90 years of age enrolled in 2015. All serum samples were examined to determined anti-HCV antibodies positivity, HCV-RNA positivity and genotypes. Of the 3000 samples, 50 were found to be anti-HCV-positive, for a seroprevalence of 1.67% (2.39% in males, 0.98% in females). The overall prevalence of positive HCV RNA was 0.93%: 1.5% in males, 0.39% in females. HCV genotype (GT) 1a was determined in 25%, GT 1b in 25% and GT 3a in 46%. Since 2001, the HCV seroprevalence has increased 8-fold. The highest HCV seroprevalence occurred in males aged 30-44 years. We can estimate that there are more than 140,000 people with HCV antibodies and more than 80,000 people with chronic hepatitis C living in the CZ. The introduction of birth cohort HCV screening could be beneficial for the country.

The new recommendations reflect the increase in knowledge that has been reported since the release of previous Czech guidelines in September 2014. The basis for these guidelines were the European Association for the Study of the Liver guidelines from April 2017. According to qualified estimates, there are 240 million people with chronic hepatitis B (HBV) infection worldwide. The Czech Republic is among the countries with a low prevalence of HBV infection. According to the latest seroprevalence study, 0.56 % of the Czech citizens were chronically infected with HBV in 2001. A similar study conducted in only two regions of the Czech Republic in 2013 showed a prevalence of only 0.064 %. HBV infection can lead to serious life-threatening liver damage - fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The main goals of treatment are to prolong the length of life and improve its quality by preventing the progression of chronic hepatitis to cirrhosis, cirrhosis decompensation and development of HCC. The goals may be achieved if HBV replication is suppressed in a sustained manner. Additional goals are prevention of vertical transmission from mother to newborn, inhibition of HBV reactivation and therapy of HBV-related extrahepatic manifestations. Generally, there are two different strategies of chronic hepatitis B therapy available - treatment with nucleoside or nucleotide inhibitors (NIs) or with pegylated interferon alfa. Currently, the vast majority of Czech and European patients are treated with NIs. The NIs that have been approved for HBV treatment in the European Union include lamivudine, adefovir dipivoxil, entecavir (ETV), telbivudin (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). TAF and TBV have not yet been marketed in the Czech Republic. The main advantages of treatment with potent NIs with a high barrier to resistance (ETV, TDF, TAF) are their predictable high long-term antiviral efficacy leading to undetectable HBV DNA levels in the vast majority of compliant patients as well as their favorable safety profiles. These drugs can be used in any HBV infected patient and represent the only treatment option for patients with decompensated liver cirrhosis, liver transplants, extrahepatic HBV-related manifestations, severe acute hepatitis B or chronic HBV reactivation.

Definitive diagnosis and therapy proved challenging in the case of a 60-year-old male with malaria and rickettsiosis. Returning travellers who are unwell can present practical difficulties in diagnosis and treatment and the focus here is on conditions relevant to the Republic of South Africa. Malaria, rickettsiosis and Q fever are discussed.

To the Editor: Our patient was a 9-year old girl who has been managed for cystic fibrosis. Genetic analysis determined PhE deletion on position 508 (D F508/1898 + 1G-A). This represents one of the common pathogenic mutations in CFTR gene, which is typical for the European region. In April 2012, the girl was treated at the Department of Infectious Diseases to eradicate Pseudomonas aeruginosa infection detected in sputum. At admission, the patient was afebrile and without pain, with loose cough expectorating white-colored sputum. Before hospitalization, she suffered from headache and general fatigue. Ciproxlofacine iv was administered to eradicate early infection and to prevent further colonization. Shortly after admission varicella skin lesions were detected. Rash consisting of sporadic papules and vesicles without impetiginization signs was present. At the age of 2 years, the child was vaccinated against varicella with 1 dose of live-attenuated vaccine (Varilrix, GSK, Czech Republic). Varicella-zoster virus (VZV) infection was probably acquired by a close contact at the place of residence. The rash intensity was mild with an afebrile course and, thus, no antiviral therapy was indicated. Ten days after admission, the girl reported increased fatigue. Her body temperature increased during the night, there was facial pallor. Her VZV skin lesions had crust formation without signs of impetiginization. On the day 11, the girl developed febrile peaks up to 40°C during the night hours. Antipyretic treatment was started with only short-time effect. One day later, her general status improved, the patient was afebrile with only residual varicella lesions present. On the day 19 the girl was discharged. Sterile swabs were used to scrub the base of the unroofed vesicular lesions and DNA from these swabs was analyzed as described previously.1 In Czech Republic, the most common clades of VZV are the European clades 1 and 3.2 Surprisingly the genetic analysis demonstrated that our clinical specimen was clade 5 (Table 1) with additional variant detected at position 95333 nt (ORF 54)—C instead of T. This clade is also known as the African/Indian clade as it is found mostly throughout Africa and India. All genomic loci refer to the published sequences for the Dumas strain (GenBank #9625875) and CA123 strain (GenBank DQ 457052).TABLE 1: Genotypic Comparison of the Isolated Virus with Reference StrainsIn 2006, the Advisory Committee on Immunization Practices approved a routine 2-dose varicella vaccination schedule for children. Several recent reports have shown that breakthrough cases remain a problematic issue especially in patients with alteration of the immune status.3,4 Vaccination of children with CF induces postvaccination antibody levels comparable with those in healthy children, when using identical doses of individual vaccines. In children with CF, no special contraindications for vaccination exist, therefore contraindication criteria are similar to those applied in the healthy children population. As much as 30% of acute exacerbations in CF patients are due to viral infections, so the indication for vaccination against viral infections is clearly reasonable. Differences between individual VZV strains are now defined on the basis of gene content and sequence similarities and/or differences. Several studies have demonstrated a distinctive geographic distribution of the major VZV clades in temperate versus tropical regions on the basis of molecular genetics analyses. The regional dominance of specific VZV clades may be dependent on environmental factors, evolutionary conditions, host–virus interactions and import of viral strains through immigration or travel. Because live-attenuated varicella vaccines were used during the past decades in childhood immunization programs in some countries, the changes of distribution of VZV viral strains both in individual countries and worldwide could occur.1,5 In this article, we report the third case of VZV clade 5 infection that represents the first case manifesting as varicella. In addition, it also represents a rare breakthrough infection after vaccination. Sauerbrei et al6 monitored prevalence of VZV clades in Germany. In varicella cases, they detected clade 3 in 45.5%, clade 1 in 30% and clade 5 in 21.1%. They also found significantly higher frequency of clade 5 in patients with varicella compared with zoster. In primary VZV infection in Germany, nearly 20% of clade 1 has been replaced by clade 5. They hypothesized that clade 5 infects population earlier during childhood and that it might spread more effectively in the population. Our case is the first clade 5 infection manifesting as varicella in the Czech Republic. It may thus indicate that the spread of clade 5 has been continuing throughout the Europe. Clearly though, more such cases are necessary to make any general conclusions. Vanda Bostik, MS, PhD Faculty of Military Health Sciences University of Defence Hradec Kralove, Czech Republic Petr Prasil, MD, PhD Stanislav Plisek, MD, PhD Renata Kracmarova, MD, PhD Pavel Kosina, MD, PhD Department of Infectious Diseases Charles University Medical School and Faculty Hospital Hradec Kralove, Czech Republic Miloslav Salavec, MD, PhD Department of Dermatology Charles University Medical School and Faculty Hospital Hradec Kralove, Czech Republic Radek Sleha, MS, PhD Roman Chlibek, MD, PhD Pavel Bostik, MD, PhD Faculty of Military Health Sciences University of Defence Hradec Kralove, Czech Republic

The aim was to analyze T‐regulatory cells (Tregs), activated CD8+ T cells, and transforming growth factor‐beta (TGF)‐β in hepatitis C patients. We enrolled 31 patients with chronic genotype 1 hepatitis C virus (HCV) infection, 30 seropositive persons with spontaneous HCV elimination, and 23 healthy volunteers. The patients were examined at the beginning of the interferon‐alpha (IFN‐α)‐based therapy (baseline) and at weeks 4 (W4) and 12 (W12) of the therapy. The percentage of Tregs and the expression of activation markers CD38 and HLA‐DR on CD8+ T cells were analyzed in the peripheral blood by flow cytometry. Serum levels of TGF‐β were measured in a multiplex assay using flow cytometry. The percentage of Tregs in patients was higher than in controls and seropositive persons. Similarly, the percentage of CD8+ T cells expressing CD38 and HLA‐DR was higher in patients compared with controls and seropositive persons. Chronic HCV infection is associated with elevated circulating Tregs and activated CD8+ T cells. During IFN‐α‐based therapy these cells gradually increase, whereas TGF‐β serum levels decrease.