OBJECTIVES: The aim of the study was to evaluate the efficiency of molecular diagnostics of tick-borne encephalitis (TBE) and to correlate viral RNA (vRNA) detection with the clinical and laboratory data. METHODS: Clinical samples from 1125 patients from South Bohemia, Czech Republic, a highly endemic TBE region, were screened for TBE virus (TBEV) RNA by RT-qPCR. Samples included blood, serum, cerebrospinal fluid (CSF), and urine. RESULTS: TBEV RNA was detected in 14 patients with clinically proven TBE. TBEV RNA was most frequently detected in sera during early infection (11/37 patients tested, 29.7%) but decreased with rising IgG antibody response (3/228, 1.3%). Detection in CSF and urine was infrequent (1/30, 3.3% and 1/52, 1.9%, respectively). Additionally, five patients initially not diagnosed with TBE were retrospectively found to have TBEV RNA in serum, indicating possible underdiagnosis, particularly in mild or atypical presentations. The study also highlighted the diagnostic challenge of an immunocompromised patient whose delayed antibody response hindered timely diagnosis. In such cases, RT-qPCR could significantly shorten the diagnostic timeline. CONCLUSIONS: These findings underscore the value of early RNA detection in improving the diagnosis of TBE and may in the future facilitate the early administration of potential treatment, thereby improving patient outcomes.
- MeSH
- Molecular Diagnostic Techniques methods MeSH
- Child MeSH
- Adult MeSH
- Immunoglobulin G blood MeSH
- Encephalitis, Tick-Borne * diagnosis virology MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Child, Preschool MeSH
- Antibodies, Viral blood MeSH
- RNA, Viral * blood cerebrospinal fluid isolation & purification MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Encephalitis Viruses, Tick-Borne * isolation & purification genetics MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with significant cardiovascular complications, including myocardial infection and pulmonary embolism. This study aims to elucidate the relationship between the presence of SARS-CoV-2 RNA in the myocardium of the left ventricle and the levels of IgG and IgM antibodies against the SARS-CoV-2 virus in deceased COVID-19 patients. We conducted a post-mortem examination on 91 individuals who succumbed to COVID-19-related complications. The presence of SARS-CoV-2 RNA in the myocardium of the left ventricle was analyzed reverse transcription real time PCR (RT-qPCR) (EliGene® COVID19 UKV/SAV RT kit, Elisabeth Pharmacon), and antibody levels in serum were analyzed by serological assays (VIDAS SARS-COV-2 IgM and VIDAS SARS-COV-2 IgG II tests, BioMérieux). Of the heart tissue samples, 44 % tested positive for SARS-CoV-2 RNA. Our findings indicate that any detectable level of IgG antibodies against SARS-CoV-2 reduces the risk of viral penetration into the myocardium by more than fourfold. Specifically, individuals with detectable levels of IgG and IgM antibodies exhibited a significantly reduced presence of SARS-CoV-2 RNA in cardiac tissues (p<0.0001 for IgG and p<0.001 for IgM). Notably, all patients who died from pulmonary embolism had elevated levels of IgG antibodies. The study underscores the protective role of IgG and IgM antibodies in preventing SARS-CoV-2 penetration into cardiac tissues. However, high antibody titers were associated with fatal outcomes such as pulmonary embolism, pointing to the intricate balance of immune response in COVID-19 pathology. Key words SARS-CoV-2, Antibody, IgG, IgM, Cardiac damage, qPCR, Pneumonia, Pulmonary embolism, Heart failure.
- MeSH
- COVID-19 * immunology virology MeSH
- Adult MeSH
- Immunoglobulin G * blood MeSH
- Immunoglobulin M * blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Myocardium * immunology metabolism MeSH
- Antibodies, Viral * blood MeSH
- RNA, Viral blood MeSH
- SARS-CoV-2 * immunology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.
- MeSH
- Antiviral Agents administration & dosage adverse effects MeSH
- Benzimidazoles administration & dosage adverse effects MeSH
- Quinoxalines administration & dosage adverse effects MeSH
- Hepatitis C, Chronic blood complications drug therapy virology MeSH
- Cyclopropanes administration & dosage adverse effects MeSH
- Drug Combinations MeSH
- Genotype * MeSH
- Hepacivirus enzymology genetics MeSH
- Liver Cirrhosis complications drug therapy MeSH
- Aminoisobutyric Acids administration & dosage adverse effects MeSH
- Leucine administration & dosage adverse effects analogs & derivatives MeSH
- Middle Aged MeSH
- Humans MeSH
- Lactams, Macrocyclic administration & dosage adverse effects MeSH
- Polymorphism, Genetic MeSH
- Proline administration & dosage adverse effects analogs & derivatives MeSH
- Pyrrolidines administration & dosage adverse effects MeSH
- RNA, Viral blood genetics MeSH
- Aged MeSH
- Sustained Virologic Response MeSH
- Sulfonamides administration & dosage adverse effects MeSH
- Viral Nonstructural Proteins genetics MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
OBJECTIVES: The aim of this study was to detect the seroprevalence of Crimean-Congo haemorrhagic fever virus (CCHFV) in patients with fever of unknown origin (FUO) in endemic (Kyzylorda) and non-endemic (Almaty) oblasts of Kazakhstan. METHODS: Paired serum samples from 802 patients with FUO were collected. Serum samples were investigated by ELISA to detect IgG and IgM antibodies against CCHFV. Sera with suspected acute infection were further investigated by RT-PCR to detect the viral RNA. RESULTS: IgG antibodies were detected in 12.7% of the sera from both oblasts. Acute infection was shown by IgM ELISA in four patients from Kyzylorda, with only one developing severe CCHF. Viral RNA was found by RT-PCR in the other three patients' sera. Phylogenetic analysis of partial L and S segments revealed CCHFV genotype Asia 2 and a possible reassortment between the genotypes Asia 1/Asia 2. Animal husbandry, such as working with cattle and horses, was significantly associated with CCHFV seropositivity. CONCLUSIONS: The antibodies and viral RNA detected in sera indicate that mild or even asymptomatic CCHFV infections are presented in Kazakhstan. This study describes the circulation of CCHFV in the so far non-endemic Almaty oblast for the first time. In conclusion, physicians treating patients with FUO in Kazakhstan should be aware of mild CCHF.
- MeSH
- Adult MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Hemorrhagic Fever, Crimean complications epidemiology MeSH
- Fever of Unknown Origin etiology MeSH
- Horses MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Antibodies, Viral blood MeSH
- RNA, Viral blood MeSH
- Seroepidemiologic Studies MeSH
- Cattle MeSH
- Hemorrhagic Fever Virus, Crimean-Congo genetics immunology MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Cattle MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Kazakhstan MeSH
In tick-borne encephalitis (TBE) endemic areas, consumption of unpasteurized milk or milk products from grazing domestic ruminants (goats, cattle, and sheep) represents a risk of TBE virus (TBEV) infection for humans. In addition to vaccination of humans, human alimentary TBEV infections can be avoided by pasteurizing milk or by vaccination of the ruminants. However, there is presently no TBEV vaccine for veterinary use. Here, we developed a new veterinary TBE vaccine candidate based on cell culture-derived, purified, and formaldehyde-inactivated TBEV (strain Hypr). The safety and immunogenicity of the vaccine was evaluated in mice and sheep and was well-tolerated while eliciting the production of high levels of virus-neutralizing antibodies. Vaccination provided full protection against lethal TBE in mice, prevented development of viremia in sheep and presence of TBEV in milk of lactating ewes. This vaccine is a good candidate for immunization of ruminants to prevent alimentary milk-borne TBEV infections in humans.
- MeSH
- Cell Culture Techniques MeSH
- Formaldehyde pharmacology MeSH
- Immunogenicity, Vaccine MeSH
- Vaccines, Inactivated administration & dosage immunology MeSH
- Encephalitis, Tick-Borne prevention & control veterinary MeSH
- Lactation MeSH
- Milk virology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Antibodies, Neutralizing blood immunology MeSH
- Sheep MeSH
- Polymerase Chain Reaction MeSH
- Antibodies, Viral blood immunology MeSH
- RNA, Viral analysis blood MeSH
- Viral Vaccines administration & dosage immunology MeSH
- Encephalitis Viruses, Tick-Borne MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- DNA, Viral blood MeSH
- Hepacivirus genetics MeSH
- RNA, Viral blood MeSH
- Laboratory Proficiency Testing MeSH
- Hepatitis B virus genetics MeSH
- Publication type
- Tables MeSH
OBJECTIVES: The number of HIV-infected individuals from developed countries travelling to tropical and subtropical areas has increased as a result of the clinical and survival benefits of combination antiretroviral therapy. The aim of our study was to describe the traveler population in the SHCS and to determine the frequency of viral rebound in virologically suppressed individuals after a travel episode to the tropics compared to non-travelers. METHODS: Swiss HIV Cohort Study participants with at least one follow-up visit between 1 January 1989 and 28 February 2015 were eligible for inclusion in the study. The primary outcome was the occurrence of viral rebound (viral load > 200 HIV-1 RNA copies/mL) after a travel episode compared with a nontravel episode in previously suppressed individuals (≤ 200 copies/mL). All virologically suppressed patients contributed multiple travel or nontravel episodes to the analysis. Logistic regression was performed including factors associated with viral rebound. RESULTS: We included 16 635 patients in the study, of whom 6084 (36.5%) had ever travelled to the tropics. Travel frequency increased over time, with travellers showing better HIV parameters than nontravellers [less advanced Centers for Disease Control and Prevention (CDC) stage and higher CD4 count nadir]. Viral rebound was seen in 477 (3.9%) of 12 265 travel episodes and in 5121 (4.5%) of 114 884 nontravel episodes [unadjusted odds ratio (OR) 0.87; 95% confidence interval (CI) 0.78-0.97]. Among these 477 post-travel viral rebounds, 115 had a resistance test performed and 51 (44%) of these showed new resistance mutations. Compared with European and North American patients, the odds for viral rebound were significantly lower in Southeast Asian (OR 0.67; 95% CI 0.51-0.88) and higher in sub-Saharan African (SSA) patients (OR 1.41; 95% CI 1.22-1.62). Travel further increased the odds of viral rebound in SSA patients (OR 2.00; 95% CI 1.53-2.61). CONCLUSIONS: Region of origin is the main risk factor for viral rebound rather than travel per se. Pre-travel adherence counselling should focus on patients of SSA origin.
- MeSH
- Medication Adherence psychology MeSH
- Travel * MeSH
- Adult MeSH
- Ethnicity * MeSH
- HIV Infections drug therapy virology MeSH
- HIV-1 isolation & purification MeSH
- Cohort Studies MeSH
- Humans MeSH
- Prospective Studies MeSH
- RNA, Viral blood MeSH
- Viral Load * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Switzerland MeSH
OBJECTIVE: To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. DESIGN: Nested case-control study within the EuroSIDA cohort. METHODS: Cases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling. RESULTS: The study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, p<0.001). Baseline tropism was not associated with the risk of clinical progression or death. CD4+T-cell slopes did not differ within or between tropism groups. CONCLUSIONS: The predictive role of plasma tropism determined using 454 sequencing in the context of people receiving cART with detectable VL is not helpful to identify subjects at higher risk for clinical progression to AIDS or death.
- MeSH
- Acquired Immunodeficiency Syndrome blood genetics mortality virology MeSH
- CD4-Positive T-Lymphocytes virology MeSH
- Adult MeSH
- HIV-1 genetics pathogenicity MeSH
- Anti-HIV Agents therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- CD4 Lymphocyte Count MeSH
- Disease Progression MeSH
- RNA, Viral blood MeSH
- Viral Tropism genetics MeSH
- Viral Load genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Keywords
- directly acting antiviral (DAA), přímo působící virostatika (DAA), ledipasvir, dasabuvir, ombitasvir, daclatasvir, pegylovaný interferon,
- MeSH
- Anilides administration & dosage MeSH
- Antiviral Agents * administration & dosage adverse effects therapeutic use MeSH
- Benzimidazoles administration & dosage MeSH
- Hepatitis C, Chronic * diagnosis drug therapy complications MeSH
- Long-Term Care MeSH
- Drug Combinations MeSH
- Fluorenes administration & dosage MeSH
- Genotype MeSH
- Heterocyclic Compounds, 3-Ring administration & dosage MeSH
- Imidazoles administration & dosage MeSH
- Interferon-alpha administration & dosage MeSH
- Liver Cirrhosis diagnosis drug therapy complications MeSH
- Carbamates administration & dosage MeSH
- Clinical Laboratory Techniques MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Disease Management * MeSH
- Drug Monitoring MeSH
- Polyethylene Glycols administration & dosage MeSH
- Ribavirin administration & dosage MeSH
- Ritonavir administration & dosage MeSH
- RNA, Viral blood MeSH
- Simeprevir MeSH
- Sofosbuvir MeSH
- Severity of Illness Index MeSH
- Sulfonamides administration & dosage MeSH
- Uracil analogs & derivatives administration & dosage MeSH
- Uridine Monophosphate analogs & derivatives administration & dosage MeSH
- Check Tag
- Humans MeSH
- Publication type
- Practice Guideline MeSH
x
x
- Keywords
- ledipasvir, studie ION-1, studie ION-2, studie ION-3,
- MeSH
- Antiviral Agents administration & dosage adverse effects therapeutic use MeSH
- Benzimidazoles pharmacology adverse effects therapeutic use MeSH
- Hepatitis C, Chronic * drug therapy virology MeSH
- Drug Combinations * MeSH
- Fluorenes pharmacology adverse effects therapeutic use MeSH
- Hepacivirus genetics MeSH
- Clinical Trials, Phase III as Topic MeSH
- Humans MeSH
- RNA, Viral blood MeSH
- Sofosbuvir * pharmacology adverse effects therapeutic use MeSH
- Drug Resistance, Viral MeSH
- Viral Load MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
