BACKGROUND: Oxidative stress and inflammation are considered predictors of diseases associated with aging. Markers of oxidative stress, inflammation, and endothelial activation were investigated in people with HIV on antiretroviral treatment to determine whether they had an immunosenescent phenotype that might predispose to the development of premature age-related diseases. PATIENTS AND METHODS: This study was conducted on 213 subjects with HIV. The control groups consisted of healthy HIV-negative adults. The level of oxidative stress was measured by assessing the production of malondialdehyde levels, which were detected by thiobarbituric acid reactive substance (TBARS) assay. The level of microparticles indicated the presence of inflammation and endothelial activation was measured by E-selectin levels. Significant differences were determined by appropriate statistical tests, depending on the distribution of variables. Relationships between continuous variables were quantified using Spearman's rank correlation coefficient. RESULTS: TBARS, and microparticle and E-selectin levels were significantly higher in untreated and treated subjects with HIV compared with HIV-negative controls (P<0.001). The levels of the investigated markers were not significantly different between untreated and treated patients and no significant correlation of these markers was found with CD4+ count, CD4+/CD8+ ratio, and the number of HIV-1 RNA copies. CONCLUSIONS: Elevated markers of oxidative stress, inflammatory and endothelial activation were independent of the virologic and immunologic status of people with HIV. These results support the hypothesis that residual viremia in cellular reservoirs of various tissues is a key factor related to the premature aging of the immune system and predisposition to the premature development of diseases associated with aging.

• MeSH
• Biomarkers blood   MeSH
• Adult MeSH
• E-Selectin * blood   metabolism   MeSH
• HIV Infections * drug therapy   immunology   metabolism   MeSH
• Thiobarbituric Acid Reactive Substances metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Cell-Derived Microparticles * metabolism   MeSH
• Oxidative Stress * MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Podle kvalifikovaných odhadů žije na světě 70–80 milionů osob s chronickou infekcí virem hepatitidy C (HCV). HCV se přenáší parenterální cestou. Před zavedením rutinního testování dárců krve (v ČR v roce 1992) se většina osob infikovala transfuzemi krve či krevních derivátů. Ve vyspělých státech ztratila tato cesta přenosu infekce na významu. Nejohroženější skupinou jsou nyní jednoznačně intravenózní narkomani, kteří si navzájem půjčují injekční stříkačky, jehly a další instrumentárium potřebné k aplikaci drogy. Podle doporučeného postupu EASL z roku 2020 musí být léčba přímo působícími virostatiky (DAA) bez otálení nabídnuta všem osobám s nedávno získanou i chronickou infekcí HCV. Primárním cílem léčby chronické HCV je vyléčení infekce, tedy dosažení setrvalé virologické odpovědi (SVR) definované jako nedetekovatelná HCV RNA v periferní krvi 12 nebo 24 týdnů po skončení antivirové léčby. Režimy používající DAA eliminují závažné nežádoucí účinky pegylovaného interferonu-α a ribavirinu (které se používaly v minulosti), nemají prakticky kontraindikace, nežádoucí účinky spojené s léčbou jsou minimální a účinnost terapie se blíží 100 %.

There are an estimated 70-80 million people living with chronic hepatitis C virus (HCV) infection worldwide. HCV is transmitted via the parenteral route. Before the introduction of routine testing of blood donors (in the Czech Republic in 1992), most people were infected through blood transfusions or blood derivatives. This route of transmission has lost importance in developed countries. The most at risk group is now clearly intravenous drug users, who share syringes, needles and other instrumentation needed to inject the drug. According to the 2020 EASL guidelines, treatment with directacting antivirals (DAAs) must be offered without delay to all persons with recently acquired and chronic HCV infection. The primary goal of treatment for chronic HCV is to cure the infection, i.e. to achieve a sustained virological response (SVR) defined as undetectable HCV RNA in peripheral blood 12 or 24 weeks after the end of antiviral treatment. Regimens using DAAs eliminate the serious adverse effects of pegylated interferon-α and ribavirin (which have been used in the past), have virtually no contraindications, treatment-related adverse effects are minimal, and treatment efficacy approaches 100%.

• MeSH
• Antiviral Agents pharmacology   therapeutic use   MeSH
• Hepatitis C, Chronic * epidemiology   drug therapy   complications   MeSH
• Hepatitis C * epidemiology   drug therapy   complications   MeSH
• Pregnancy Complications, Infectious MeSH
• Humans MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Review MeSH

• MeSH
• Respiratory Tract Infections diagnosis   MeSH
• Polymerase Chain Reaction methods   MeSH
• COVID-19 Testing methods   MeSH
• Virology MeSH
• Virus Diseases diagnosis   MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• pneumologie a ftizeologie
• diagnostika

BACKGROUND: The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We aimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. METHODS: In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18 years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30 days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. FINDINGS: We screened 2802 patients and enrolled 233 participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28 years (IQR 22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. INTERPRETATION: Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. FUNDING: US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.

• MeSH
• Bacterial Vaccines immunology   administration & dosage   MeSH
• Adult MeSH
• Phylogeny MeSH
• Genetic Variation genetics   MeSH
• Genome, Bacterial MeSH
• Genomics MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Molecular Epidemiology * MeSH
• Cross-Sectional Studies MeSH
• Whole Genome Sequencing * MeSH
• Syphilis * epidemiology   microbiology   MeSH
• Treponema pallidum * genetics   immunology   MeSH
• Treponema MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• United States MeSH

Poprvé se jedná o samostatný český doporučený postup, který se věnuje pouze infekci HDV. Dosud byla infekce HDV zmiňována jen v doporučených postupech týkajících se infekce virem hepatitidy B (HBV), v kapitolách HBV/HDV koinfekce. Základem pro napsání tohoto doporučeného postupu byla doporučení Evropské asociace pro studium jater (EASL) z července 2023. HDV může infikovat vnímavého hostitele současně s HBV (koinfekce), nebo superinfikovat osobu chronicky infikovanou HBV. HBV/HDV koinfekce obvykle vede k akutní hepatitidě s širokým klinickým spektrem od asymptomatického průběhu, přes mírnou hepatitidu až po akutní jaterní selhání. Do chronicity však přechází jen malá část případů (kolem 2 %). Naopak superinfekce HDV na chronickou infekci HBV vede velmi často k těžké akutní hepatitidě, která přechází až v 90 % případů do chronické hepatitidy D (CHD), která je spojena se závažnějšími chronickými výsledky než monoinfekce HBV. Prokázána je častější a rychlejší progrese CHD do jaterní cirhózy, než je tomu u monoinfekce HBV. Odhaduje se, že celosvětově je 4,5–13 % osob s pozitivitou HBsAg infikováno HDV, což představuje v absolutních číslech 12–72 milionů osob infikovaných HDV. Infekce HDV je zatím v České republice ojedinělá – jedná se maximálně o několik desítek pacientů, a to téměř výlučně cizinců přicházejících z endemických oblastí, především z Mongolska a jiných asijských zemí. S rostoucí migrací osob z endemických oblastí může incidence a prevalence hepatitidy D v naší zemi rychle narůstat. Podle odhadu odborníků je prevalence HDV mezi HBsAg pozitivními pacienty v České republice okolo 1 %. Až do roku 2020 byla léčba založená na interferonu (IFN) α jedinou možností léčby CHD. Postupně se ukázalo, že léčba pegylovaným interferonem (PEG ‐IFN) α je účinnější než léčba klasickým (konvenčním, standardním) IFNα – 25 vs. 17 % virologické odpovědi na konci 48týdenní léčby. Následně však u více než poloviny dosud úspěšně léčených pacientů došlo po léčbě k virologickému relapsu. Prodloužením doby léčby PEG ‐IFNα na 2 roky se podle výsledků většiny klinických studií úspěšnost léčby nezvýšila. Bulevirtid (BLV) je syntetický lipopeptid, skládající se ze 47 aminokyselin z domény preS1 velkého proteinu HBsAg, který se váže na NTCP, a tím brání vstupu HDV do hepatocytu. V klinických studiích byla testována úspěšnost a bezpečnost léčby BLV v dávkách 2, 5 a 10 mg jednou denně podkožně, a to samostatně, nebo v kombinaci s PEG ‐IFNα. Protože dosud nebyla stanovena optimální doba léčby BLV, nebyla zatím možnost posoudit setrvalou virologickou odpověď, protože léčba BLV se ve studiích neukončovala. Podle výsledků klinických studií nepřináší vyšší dávka BLV (10 mg) žádný benefit oproti dávce 2 mg jednou denně. V červenci 2020 dostal BLV od Evropské lékové agentury (EMA) podmíněné oprávnění k použití pro léčbu CHD s kompenzovaným jaterním onemocněním, s doporučením pokračovat v léčbě BLV v dávce 2 mg denně, dokud je patrný klinický benefit. Podmíněná registrace byla změněna na standardní registraci v červenci 2023.

For the first time, this is a separate Czech recommended practice that focuses only on HDV infection. Until now, HDV infection has been mentioned only in the guidelines on hepatitis B virus (HBV) infection, in the HBV/HDV co-infection chapters. The European Association for the Study of the Liver (EASL) clinical practice guidelines from July 2023 were the basis for writing this guideline. HDV can co-infect a susceptible host with HBV (co-infection) or superinfect a person chronically infected with HBV. HBV/HDV coinfection usually leads to acute hepatitis with a wide clinical spectrum ranging from an asymptomatic course, to mild hepatitis, to acute liver failure. However, only a small proportion of cases (around 2 %) progress to chronicity. In contrast, superinfection with HDV on chronic HBV infection very often leads to severe acute hepatitis, which progresses to chronic hepatitis D (CHD) in up to 90 % of cases and is associated with more severe chronic outcomes than HBV monoinfection. CHD has been shown to progress more frequently and more rapidly to liver cirrhosis than HBV monoinfection. Globally, an estimate of 4.5-13 % of HBsAg-positive persons are infected with HDV, representing 12-72 million persons infected with HDV in absolute numbers. HDV infection is still rare in the Czech Republic, with a maximum of a few dozen patients, almost exclusively foreigners coming from endemic areas, mainly from Mongolia and other Asian countries. With the increasing migration of people from endemic areas, the incidence and prevalence of hepatitis D in our country may increase rapidly. Experts estimate that the prevalence of HDV among HBsAg positive patients in the Czech Republic is around 1 %. Until 2020, interferon (IFN)α-based therapy was the only treatment option for CHD. Gradually, pegylated interferon (PEG-IFN)α treatment proved to be more effective than treatment with conventional (standard) IFNα - 25 vs. 17 % virological response at the end of 48 weeks of treatment. Subsequently, however, more than half of the patients successfully treated so far experienced virological relapse after treatment. Extending the duration of PEG-IFNα treatment to 2 years did not increase treatment success according to the results of most clinical trials. Bulevirtide (BLV) is a synthetic lipopeptide consisting of 47 amino acids from the preS1 domain of the large HBsAg protein, which binds to NTCP, thereby preventing HDV from entering the hepatocyte. Clinical trials have tested the efficacy and safety of BLV treatment at doses of 2, 5 and 10 mg once daily subcutaneously, alone or in combination with PEG-IFNα. As the optimal duration of BLV treatment has not yet been established, it has not yet been possible to assess the sustained virological response, as BLV treatment was not discontinued in the studies. According to the results of clinical trials, a higher dose of BLV (10 mg) provides no benefit compared to a dose of 2 mg once daily. In July 2020, BLV received conditional marketing authorisation from the European Medicines Agency (EMA) for the treatment of CHD and compensated liver disease, with a recommendation to continue BLV treatment at a dose of 2 mg daily until clinical benefit is seen. The conditional marketing authorisation was switched to a standard marketing autho

• Keywords
• pegylovaný interferon alfa,
• MeSH
• Hepatitis D, Chronic * drug therapy   MeSH
• Interferon-alpha pharmacology   therapeutic use   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH

Vaccine-induced protection against tick-borne encephalitis virus (TBEV) is mediated by antibodies to the viral particle/envelope protein. The detection of non-structural protein 1 (NS1) specific antibodies has been suggested as a marker indicative of natural infections. However, recent work has shown that TBEV vaccines contain traces of NS1, and immunization of mice induced low amounts of NS1-specific antibodies. In this study, we investigated if vaccination induces TBEV NS1-specific antibodies in humans. Healthy army members (n = 898) were asked to fill in a questionnaire relating to flavivirus vaccination or infection, and blood samples were collected. In addition, samples of 71 suspected acute TBE cases were included. All samples were screened for the presence of TBEV NS1-specific IgG antibodies using an in-house developed ELISA. Antibodies were quantified as percent positivity in reference to a positive control. For qualitative evaluation, cut-off for positivity was defined based on the mean OD of the lower 95% of the vaccinated individuals + 3 SD. We found significantly higher NS1-specific IgG antibody titers (i.e., quantitative evaluation) in individuals having received 2, 3, or 4 or more vaccine doses than in non-vaccinated individuals. Similarly, the percentage of individuals with a positive test result (i.e., qualitative evaluation) was higher in individuals vaccinated against tick-borne encephalitis than in unvaccinated study participants. Although NS1-specific IgG titers remained at a relatively low level when compared to TBE patients, a clear distinction was not always possible. Establishing a clear cut-off point in detection systems is critical for NS1-specific antibodies to serve as a marker for distinguishing the immune response after vaccination and infection.

• MeSH
• Immunoglobulin G MeSH
• Flavivirus Infections * MeSH
• Encephalitis, Tick-Borne * prevention & control   MeSH
• Humans MeSH
• Antibodies, Viral MeSH
• Antibody Formation MeSH
• Vaccination MeSH
• Viral Vaccines * MeSH
• Encephalitis Viruses, Tick-Borne * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Hepatitis B virus (HBV) is one of the most dangerous human pathogenic viruses found in all corners of the world. Recent sequencing of ancient HBV viruses revealed that these viruses have accompanied humanity for several millenia. As G-quadruplexes are considered to be potential therapeutic targets in virology, we examined G-quadruplex-forming sequences (PQS) in modern and ancient HBV genomes. Our analyses showed the presence of PQS in all 232 tested HBV genomes, with a total number of 1258 motifs and an average frequency of 1.69 PQS per kbp. Notably, the PQS with the highest G4Hunter score in the reference genome is the most highly conserved. Interestingly, the density of PQS motifs is lower in ancient HBV genomes than in their modern counterparts (1.5 and 1.9/kb, respectively). This modern frequency of 1.90 is very close to the PQS frequency of the human genome (1.93) using identical parameters. This indicates that the PQS content in HBV increased over time to become closer to the PQS frequency in the human genome. No statistically significant differences were found between PQS densities in HBV lineages found in different continents. These results, which constitute the first paleogenomics analysis of G4 propensity, are in agreement with our hypothesis that, for viruses causing chronic infections, their PQS frequencies tend to converge evolutionarily with those of their hosts, as a kind of 'genetic camouflage' to both hijack host cell transcriptional regulatory systems and to avoid recognition as foreign material.

• MeSH
• Biological Evolution MeSH
• G-Quadruplexes * MeSH
• Genome, Human MeSH
• Genomics MeSH
• Humans MeSH
• Paleontology MeSH
• Hepatitis B virus * genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

One consequence of the ongoing coronavirus disease pandemic was the rapid development of both in-house and commercial serological assays detecting anti-SARS-CoV-2 antibodies, in an effort to reliably detect acute and past SARS-CoV-2 infections. It is crucial to evaluate the quality of these serological tests and consequently the sero-epidemiological studies that are performed with the respective tests. Here, we describe the set-up and results of a comparative study, in which a laboratory contracted by the European Centre for Disease Prevention and Control offered a centralised service to EU/EEA Member and pre-accession Member States to test representative serum specimens with known serological results, with the gold standard technique (virus neutralisation tests) to determine the presence of neutralising antibodies. Laboratories from 12 European countries shared 719 serum specimens with the contractor laboratory. We found that in-house serological tests detecting neutralising antibodies showed the highest percent agreement, both positive and negative, with the virus neutralisation test results. Despite extensive differences in virus neutralisation protocols neutralisation titres showed a strong correlation. From the commercial assays, the best positive percent agreement was found for SARS-CoV-2 IgG (sCOVG) (Siemens - Atellica IM Analyzer). Despite lower positive percent agreement of LIAISON SARS-CoV-2 TrimericS IgG kit (Diasorin Inc.), the obtained results showed relatively good correlation with neutralisation titres. The set-up of this study allowed for high comparability between laboratories and enabled laboratories that do not have the capacity or capability to perform VNTs themselves. Given the variety of in-house protocols detecting SARS-CoV-2 specific neutralising antibodies, including the virus strain, it could be of interest to select reference isolates for SARS-CoV-2 diagnostic to be made available for interested EU Member States and pre-accession countries.

• MeSH
• COVID-19 * diagnosis   MeSH
• Immunoglobulin G MeSH
• Clinical Laboratory Techniques methods   MeSH
• Humans MeSH
• Antibodies, Neutralizing MeSH
• Antibodies, Viral MeSH
• SARS-CoV-2 MeSH
• COVID-19 Testing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

The global effort to eliminate HCV infection requires new approaches to accessing and testing the affected population in a setting with as low of a threshold as possible. The focus should be on socially marginalized people who inject drugs (PWIDs) and who are not willing or able to visit standard medical services. With this vision, we established an outreach service-a testing point in an ambulance in the park in front of the Main Railway Station of the capital city of Prague-to provide bloodborne disease testing and treatment. The service was available every week on Wednesday afternoon. Over the initial two years of our experience, 168 unique people were tested. Of them, 82 (49%) were diagnosed with chronic HCV infection and were eligible for treatment with antivirals. Of these, 24 (29%) initiated antiviral treatment over the study period, and 17 (71%) of these individuals achieved a documented sustained virological response. Offering medical services in PWIDs' neighborhoods helps overcome barriers and increase the chances that they will become patients and begin HCV treatment. The described outcomes appear promising for reaching the vision of linkage to the care of such a hard-to-reach population and can serve as a feasible model of care for further expansion.

• MeSH
• Antiviral Agents therapeutic use   MeSH
• Hepacivirus MeSH
• Hepatitis C * drug therapy   epidemiology   prevention & control   MeSH
• Substance Abuse, Intravenous * epidemiology   MeSH
• Humans MeSH
• Drug Users * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Recovered COVID-19 patients may test positive for SARS-CoV-2 for a long time from intermittent shedding of viral fragments. A 36-year-old man who tested positive for SARS-CoV-2 in the Czech Republic and recovered tested positive again in Bhutan, 105 days beyond his first positive test. He experienced minimal symptoms and recovered without complications. Although no virological test was conducted to rule out reinfection, the repeat positive test after initial recovery likely resulted from prolonged shedding of dead viral particles than a reinfection.

• MeSH
• COVID-19 * MeSH
• Adult MeSH
• Humans MeSH
• Reinfection MeSH
• SARS-CoV-2 * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Geographicals
• Czech Republic MeSH