Heterogeneity of post-COVID impairment: interim analysis of a prospective study from Czechia.

We stratified post-COVID patients into four newly established clinical groups based on the presence or absence of at least one subjective respiratory symptom and at least one objective sign of pulmonary involvement. Nearly half of outpatients and one third of hospitalized post-COVID patients had objective signs of pulmonary involvement without accompanying subjective respiratory symptoms three months after diagnosis.

Chronic Hepatitis C Virus Infection Modulates the Transcriptional Profiles of CD4+ T Cells.

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.

A rare case of purulent meningitis caused by Capnocytophaga canimorsus in the Czech Republic - case report and review of the literature.

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.

[Caring for women planning pregnancy or who are already pregnant: an infectious disease doctor's view].

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.

[Concurrent malaria and rickettsiosis in a patient returning from the Republic of South Africa].

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.

[Diagnosis and therapy of hepatitis B virus infection: Czech national guidelines].

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.

[Determination of the naturally occurring Q80K mutation in the HCV NS3 protease gene]. / Vysetrení prilrozene variant Q80K v genu pro proteázu NS3 HCV.

OBJECTIVES: The aim was to introduce a diagnostic method for detecting variants of hepatitis C virus (HCV) with protease NS3 resistance primarily to simeprevir (Q80K mutation in HCV genotype 1a) and its subsequent use in routine practice. MATERIAL AND METHODS: The detection of HCV resistance-associated variants in the NS3 protease gene by sequence analysis was introduced in the molecular biology laboratory of University Hospital Hradec Kralove in 2015. The primers were designed by sequence analysis software Custom Primers - OligoPerfect™ Designer. The method was optimized for HCV genotype 1a. The search for variants was performed using two programs. RESULTS: A total of 16 patients with genotype 1a chronic hepatitis C have been examined since 2015. In five of them, the Q80K variant was detected. CONCLUSION: The development of resistance to antiviral therapy for chronic hepatitis C gained importance after the introduction of direct-acting antivirals. Given the relatively high prevalence of the Q80K mutation in HCV genotype 1a, it is crucial to confirm its presence or absence before the therapy is initiated. The reported method enables clear and early detection of the Q80K mutation.

[Ocular toxoplasmosis - seeking a strategy for treatment]. / Ocní forma toxoplazmózy - hledání strategie lécby.

AIM: To compare the effectiveness of treatment for ocular toxoplasmosis with pyrimethamine + clindamycin (or sulfadiazine) + a corticoid (Group 1), or azithromycin or a combination of azithromycin with a corticoid or a corticoid alone (Group 2). To determine the relapse rate depending on the treatment approach. MATERIAL AND METHODS: A total of 25 patients treated for ocular toxoplasmosis over the last five years (2008-2013) were analyzed. Group 1 comprised 16 patients (3 were excluded) and Group 2 consisted of 6 patients. RESULTS: Visual improvement was more rapid in Group 1 (day 10.7) than in Group 2 (significant improvement on day 29.6). There were 5 cases of relapse in Group 1; in 13 cases, no relapse was noted; all patients in Group 2 relapsed (a total of 13 relapses). Twenty-three patients were positive for specific IgG antibodies. CONCLUSION: According to our experiences, pyrimethamine + clindamycin (or sulfadiazine) + a corticoid should be the treatment of choice in patients with ocular toxoplasmosis.

[Diagnosis and therapy of chronic hepatitis B: Czech national guidelines]. / Doporucený postup diagnostiky a lécby chronické hepatitidy B: Datum vydání doporucení: zárí 2014.

The new recommendations reflect the increase in knowledge that has been reported since the release of previous Czech guidelines in April 2009. According to qualified estimates, there are 350-400 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 seroprevalent study, 0.56 % of the Czech citizens were chronically infected with HBV in 2001. HBV infection can lead to serious life-threatening liver damage - fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The 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 can be achieved if HBV replication is suppressed in a sustained manner. Then, the accompanying reduction in histological activity lowers the risk of cirrhosis and HCC, particularly in non-cirrhotic patients. Currently, two different strategies for treating chronic hepatitis B are available. Treatment of finite duration is with pegylated interferon (PEG-IFN), entecavir (ETV), or tenofovir (TDV). A 48-week course of PEG-IFN is mainly recommended for HBeAg-positive patients with the best chance of anti-HBe seroconversion. Finite-duration of ETV or TDV treatment is available for HBeAg-positive patients who seroconvert to anti-HBe on treatment. However, treatment duration is unpredictable prior to the therapy as it depends on the timing of anti-HBe seroconversion and the treatment continuation following anti-HBe seroconversion (therapy should be prolonged for additional 12 months after anti-HBe seroconversion). Long-term ETV or TDV therapy is necessary for HBeAg-positive patients who do not develop anti-HBe seroconversion and for HBeAg-negative patients. This strategy is also recommended for patients with cirrhosis irrespective of the initial HBeAg status or anti-HBe seroconversion on treatment. The advantage of ETV and TDV is based on their high potency and optimal resistance profile.

[Treponema pallidum subspecies pallidum -- the causative agent of neurosyphilis]. / Treponema pallidum, subspecies pallidum - puvodce neurosyfilis.

Neurosyphilis is defined as infection of central nervous system by Treponema pallidum subspecies pallidum. Neurosyphilis can develop at any stage after initial infec-tion and is reflected in laboratory results. The pathogenesis of neurosyphilis is similar to that of classical form of syphilis. Individuals with persistent abnormalities in the cerebrospinal fluid are at risk of the development of clinical manifestations. Proper understanding of particular forms of neurosyphilis for differential diagnosis is important to determine potential risk of the development of progressive disease in neurology.

Triple Combination with Direct Acting Antivirals in the Treatment of Hepatitis C Does not Prolong the QT Interval.

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.

[Highly contagious diseases with human-to-human transmission]. / Vysoce nebezpecne nakazy s mezilidskym prenosem.

Highly contagious diseases are caused by various biological agents that pose a risk to individuals and may have a potential for public health impact. They result in high mortality and morbidity rates, might cause public panic and therefore require special measures. The pathogens that can be easily disseminated or transmitted from person to person are the riskiest for clinicians (Ebola virus, Marburg virus, Lassa virus, Crimean-Congo hemorrhagic fever virus, Variola major, SARS virus and Yersinia pestis). Human-to-human transmission has not been confirmed for the other biological agents and therefore they pose a very low risk for population.

[Question marks concerning serological tests in congenital toxoplasmosis - a case report]. / Serologicke otazniky kongenitalni toxoplazmozy - kazuistika.

Two weeks after delivery of a healthy term neonate, the mother developed lymph node syndrome, which corresponded serologically to acute toxoplasmosis. The blood of the newborn showed positive IgM, IgG and IgA antibody titers against Toxoplasma gondii with a low avidity of IgG. The newborn did not show any clinical signs or organ damage connected to toxoplasmosis either at the beginning or during the follow-up. The IgA and IgM titers exhibited a decrease over time, while the KFR, IgG antibody titers and avidity had an increasing trend. A sharp increase of KFR, IgE and IgA antibody titers was detected during the sixth month of life, probably due to maturation of the immune system in the setting of an asymptomatic infection with T. gondii. This short increase was followed by a subsequent decrease in titers of these antibodies until they reached negative levels during the 21st month of life. The evaluation of serological results in newborns infected with T. gondii is always difficult and should be performed by an expert physician. Children at risk should be placed under a long-term follow-up to avoid potential development of toxoplasma chorioretinitis.

Long-Term Antibody Response and Vaccination Efficacy in Patients with COVID-19: A Single Center One-Year Prospective Study from the Czech Republic.

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.

Prevalence of hepatitis C virus in adult population in the Czech Republic - time for birth cohort screening.

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.

Effect of antiviral treatment of chronic hepatitis C on the frequency of regulatory T cells, T-cell activation, and serum levels of TGF-beta.

The aim was to analyze T-regulatory cells (Tregs), activated CD8(+) T cells, and transforming growth factor-beta (TGF)-ß 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-ß 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-ß serum levels decrease.

A repeated syphilis infection imported from Thailand in an HIV positive couple of men-who-have-sex-with-men in Czech Republic.

Coinfection by HIV and syphilis has become a growing problem due to the re-appearance of unsafe sexual practices in the era of potent anti-retroviral drugs. We describe a repeated import of syphilis by a couple of men-who-have-sex-with-men from Thailand to Czech Republic likely due to non-adherence of the patients to physician recommendations. Such cases can become foci for dissemination of once locally rare infections and present a danger for the community.