Explore the vast range of titles available.

To evaluate the use of hepatitis C virus (HCV) NS3 sequencing as alternative to the comercially available Versant HCV 2.0 reverse hybridization line-probe assay (LiPA 2.0) to determine HCV genotype 1 (HCV-1) subtypes. A cohort of 104 patients infected by HCV-1 according to LiPA 2.0 was analyzed in a cross-sectional study conducted in patients seen from January 2012 to June 2016 at an outpatient clinic in Buenos Aires, Argentina. The samples were included within well supported subtype clades: 64 with HCV-1b and 39 with HCV-1a infection. Twenty of the HCV-1a infected patientes were included in a supported sub-clade \"1\" and 19 individuals were among the basal sub-clade \"2\". LiPA 2.0 failed to subtype HCV-1 in 20 (19.2%) individuals. Subtype classification determined by NS3 direct sequencing showed that 2/18 (11.1%) of the HCV-1a-infected patients as determined by LiPA 2.0 were in fact infected by HCV-1b. Of the HCV-1b-infected according to LiPA 2.0, 10/66 (15.2%) patients showed HCV-1a infection according to NS3 sequencing. Overall misclassification was 14.3% (κ-index for the concordance with NS3 sequencing = 0.635). One (1%) patient was erroneously genotyped as HCV-1 and was revealed as HCV genotype 4 infection. Genomic sequencing of the HCV NS3 region represents an adequate alternative since it provides reliable genetic information. It even distinguishes between HCV-1a clades related to resistance-associated substitutions to HCV protease inhibitors, it provides reliable genetic information for genotyping/subgenotyping and simultaneously allows to determine the presence of resistance-associated substitutions to currently recommended DAAs.

Hepatitis B virus (HBV) and Hepatitis C virus (HCV) remain major global health challenges, together accounting for approximately 1.1 million deaths annually and representing leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma. In Paraguay, the true burden remains poorly defined, hindering effective public health planning toward the WHO’s 2030 elimination goal. This cross-sectional study aimed to establish a comprehensive, nationally representative epidemiological baseline among blood donors. We prospectively analyzed 85,811 blood donor samples. Screening involved chemiluminescent immunoassays for anti-HBc, HBsAg, and anti-HCV, followed by confirmatory Nucleic Acid Amplification Testing (NAT) for HBV-DNA and HCV-RNA. The age-standardized seroprevalences were: 1.66% for anti-HBc, 0.079% for HBsAg, and 0.261% for anti-HCV. However, significant regional variations were noted, with anti-HBc prevalence ranging from 0.70% to 3.86% ( p  < 0.001). Anti-HBc also increased with age (0.27% in < 20 years to 3.10% in > 50 years). Critically, no HBV markers were detected in donors born after the national 2003 vaccination program. Only 1 of 229 anti-HCV reactive samples was HCV-RNA detectable. While low overall seroprevalence confirms blood safety standards, pronounced regional disparities require targeted public health interventions focused on specific epidemiological hotspots. The absence of HBV markers in the post-vaccination cohort provides strong evidence of the national immunization program’s success, offering an invaluable baseline for future elimination strategies.

The subtype diversity of the hepatitis C virus (HCV) genotypes is unknown in Venezuela. Partial sequencing of the NS5B region was performed in 310 isolates circulating in patients from 1995 to 2007. In the samples collected between 2005 and 2007, HCV genotype 1 (G1) was the most common genotype (63%), composed as expected of mainly G1a and G1b. G2 was the second most common genotype (33%), being G2a almost absent and G2j the most frequent subtype. Sequence analysis of the core region confirmed the subtype assignment performed within the NS5b region in 63 isolates. The complete genome sequence of G2j was obtained. G2j has been described in France, Canada and Burkina Fasso, but it was not found in Martinique, where several subtypes of G2 circulate in the general population. Bayesian coalescence analysis indicated a most recent common ancestor (MRCA) of G2j around 1785, before the introduction of G1b (1869) and G1a (1922). While HCV G1a and G1b experienced a growth reduction since 1990, coincident with the time when blood testing was implemented in Venezuela, HCV G2j did not seem to reach growth equilibrium during this period. Assuming the introduction of G2j from Africa during the slave trade, the high frequency of G2j found in Venezuela could suggest: 1- the introduction of African ethnic groups different from the ones introduced to Martinique or 2- the occurrence of a founder effect. This study represents an in-depth analysis of the subtype diversity of HCV in Venezuela, which is still unexplored in the Americas and deserves further studies.

The estimated prevalence of HCV infection in Argentina is around 2%. However, higher rates of infection have been described in population studies of small urban and rural communities. The aim of this work was to compare the origin and diversification of HCV-1b in samples from two different epidemiological scenarios: Buenos Aires, a large cosmopolitan city, and O'Brien, a small rural town with a high prevalence of HCV infection. The E1/E2 and NS5B regions of the viral genome from 83 patients infected with HCV-1b were sequenced. Phylogenetic analysis and Bayesian Coalescent methods were used to study the origin and diversification of HCV-1b in both patient populations. Samples from Buenos Aires showed a polyphyletic behavior with a tMRCA around 1887-1900 and a time of spread of infection approximately 60 years ago. In contrast, samples from ÓBrien showed a monophyletic behavior with a tMRCA around 1950-1960 and a time of spread of infection more recent than in Buenos Aires, around 20-30 years ago. Phylogenetic and coalescence analysis revealed a different behavior in the epidemiological histories of Buenos Aires and ÓBrien. HCV infection in Buenos Aires shows a polyphyletic behavior and an exponential growth in two phases, whereas that in O'Brien shows a monophyletic cluster and an exponential growth in one single step with a more recent tMRCA. The polyphyletic origin and the probability of encountering susceptible individuals in a large cosmopolitan city like Buenos Aires are in agreement with a longer period of expansion. In contrast, in less populated areas such as O'Brien, the chances of HCV transmission are strongly restricted. Furthermore, the monophyletic character and the most recent time of emergence suggest that different HCV-1b ancestors (variants) that were in expansion in Buenos Aires had the opportunity to colonize and expand in O'Brien.

This study investigates the kinetics of interleukine-6 (IL-6) and interleukine-10 (IL-10) levels in dengue virus (DENV) infections during the febrile stage. Viremic patients were categorized into two phases based on anti-DENV IgM presence. Among 259 patients, 71% were in Phase I and 29% in Phase II. Secondary infections, accounting for 38.2% of cases, exhibited earlier elevations of IL-6 and IL-10 than primary infections, suggesting that pre-existing immune memory primes faster cytokine release. Thrombocytopenia and elevated aspartate transaminase (AST) levels were associated with Phase II, secondary infections, and hospitalization. Elevated IL-6 and IL-10 levels correlated with low platelet counts, linking them to clinical manifestations. The key finding is that IL-6 and IL-10 levels rise earlier in secondary infections compared to primary infections, whereas elevated cytokine levels typically occur later in the febrile phase. This study highlights the importance of cytokine dynamics in DENV infections, particularly during the early stages. The observation of cytokine concentration changes, especially in viremic samples, provides insights into the progression of dengue disease. Further research with broader cytokine panels is warranted to validate and expand these findings.

The adaptive immune response plays a crucial role in resolution of viral infections; however, there is limited data on the T cell response to SARS-CoV-2 vaccines such as BBIBP-CorV, Gam-COVID-Vac, and especially for the heterologous combination Gam-COVID-Vac/mRNA-1273 scheme. Furthermore, emerging variants may compromise the adaptive immune response established in the population. To evaluate the T cell immune response induced by the BBIBP-CorV, Gam-COVID-Vac and Gam-COVID-Vac/mRNA-1273, against the ancestral wild type (WT) virus and the Gamma and Omicron variants. Serum levels of IgG antibodies were assessed by CMIA (Abbott Diagnostics, Abbott Park, Illinois). T cell responses against WT virus, Gamma and Omicron were evaluated through an activation-induced marker assay. Sixty individuals, evenly distributed across the BBIBP-CorV, Gam-COVID-Vac, and Gam-COVID-Vac/mRNA-1273 groups, were included. The median age of participants was 48 years (IQR: 34–56), with 58.3 % (n = 35) being female. Seventeen (28.3 %) individuals had a prior confirmed COVID-19 infection. Gam-COVID-Vac/mRNA-1273 scheme elicited significantly higher humoral responses (p < 0.001). However, the three vaccination platforms showed consistent T cell responses across the three stimuli tested. Particularly, all three schemes induced stronger CD8+ responses against the WT virus. In addition, more responders to WT were observed in the BBIBP-CorV and Gam-COVID-Vac groups, while the Gam-COVID-Vac/mRNA-1273 group showed a greater proportion of responders to Omicron. This study provides new data on effective humoral and cellular immune responses against the ancestral WT virus as well as the Gamma and Omicron variants. Moreover, memory CD4+ and CD8+ T cell responses remain protective, and the heterologous scheme may elicit stronger T cell responses against emerging variants. •Strong adaptive T cell responses were observed across all vaccination schemes and stimuli tested.•Higher frequency of activated CD8+ lymphocytes was detected compared to CD4+ in response to SARS-CoV-2•BBIBP-CorV and Gam-COVID-Vac showed a response biased toward wild type virus.•Gam-COVID-Vac / mRNA-1273 recipients showed higher T cell responses to Omicron.•The Gam-COVID-Vac /mRNA-1273 vaccination scheme induced significantly enhanced humoral immune responses.

Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina).A total of 89 out of 1814 blood samples collected from people living in Wheelwright, were positive for HCV infection. The highest prevalence (4.9%) was observed in people older than 50 years, with the highest level for the group aged between 70-79 years (22%). The RFLP analyses showed that 91% of the positive samples belonged to the HCV-1b genotype. The E1/E2 and NS5B genes were sequenced, and their phylogenetic analysis showed that the HCV-1b sequences from Wheelwright were monophyletic. Bayesian coalescent-based methods were used to estimate substitution rates and time of the most recent common ancestor (tMRCA). The mean estimated substitution rates and the tMRCA for E1/E2 with and without HVR1 and NS5B were 7.41E-03 s/s/y and 61 years, 5.05E-03 s/s/y and 58 years and 3.24E-03 s/s/y and 53 years, respectively. In summary, the tMRCA values, the demographic model with constant population size, and the fact that the highest prevalence of infection was observed in elder people support the hypothesis that the HCV-1b introduction in Wheelwright initially occurred at least five decades ago and that the early epidemic was characterized by a fast rate of virus transmission. The epidemic seems to have been controlled later on down to the standard transmission rates observed elsewhere.

•Protective levels of aHBs were lower than the expected ones (45.9%).•Protective levels of aHBs in vaccinated children at birth were low (56.1%).•Protective levels of aHBs in vaccinated children at 11 years were higher (75.2%).•Vaccination campaigns against HBV should focus on people born in 1992 or before. Universal vaccination is the most effective strategy to control hepatitis B virus (HBV) infection. In Argentina, vaccination against HBV was incorporated in year 2000 for newborns and in 2003 for 11 years old children. However, there is a paucity of data about protection levels against HBV infection. The aim of this work was to determine the prevalence of seroprotective anti-HBs antibodies (aHBs) in Argentina. Serum samples negative for HBsAg and anti-HBc from 132 children born after year 2000 and 762 blood donors, older than 18 years, from five centers across the country, were analyzed for aHBs. Titers ≥10 mIU/mL were observed in 74/132 children (56.1%) and 336/762 (44.1%) in blood donors. The median age for blood donors was 33.9 (23–43); from them, 210 (27.6%) were born after 1992 and, therefore, were catch-up by vaccine implementation at 11 years old age. Donors born in 1992 or before showed a significantly lower frequency of protection (32.2%) compared to donors born after 1992 (75.2%), p < 0.0001. In addition, significant differences were observed in the status of seroprotection between different participating centers (p = 0.024). Implementation of HBV vaccine in 2000 and 2003 implied an overall increase of the aHBs seroprotective rates, with a particularly adequate response in children vaccinated at 11 years old age. The observed results suggest that population born in 1992 or before is currently the most susceptible. Consequently, it would be advisable to become aware of the risk of transmission in this age group and to stress this population vaccination campaigns.

During the first months of SARS-CoV-2 evolution in a new host, contrasting hypotheses have been proposed about the way the virus has evolved and diversified worldwide. The aim of this study was to perform a comprehensive evolutionary analysis to describe the human outbreak and the evolutionary rate of different genomic regions of SARS-CoV-2. The molecular evolution in nine genomic regions of SARS-CoV-2 was analyzed using three different approaches: phylogenetic signal assessment, emergence of amino acid substitutions, and Bayesian evolutionary rate estimation in eight successive fortnights since the virus emergence. All observed phylogenetic signals were very low and trees topologies were in agreement with those signals. However, after four months of evolution, it was possible to identify regions revealing an incipient viral lineages formation despite the low phylogenetic signal, since fortnight 3. Finally, the SARS-CoV-2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated to values of 1.37 x 10-3 and 2.19 x 10-3 substitution/site/year, respectively. In conclusion, results obtained in this work about the variable diversity of crucial viral regions and the determination of the evolutionary rate are consequently decisive to understand essential feature of viral emergence. In turn, findings may allow characterizing for the first time, the evolutionary rate of S protein that is crucial for vaccines development. Competing Interest Statement The authors have declared no competing interest.

Abstract Objective The spike protein of SARS-CoV-2 has become the main target for antiviral and vaccine development. Despite its relevance, there is scarce information about its evolutionary traces. The aim of this study was to investigate the diversification patterns of the spike for each clade of SARS-CoV-2 through different approaches. Methods Two thousand and one hundred sequences representing the seven clades of the SARS-CoV-2 were included. Patterns of genetic diversifications and nucleotide evolutionary rate were estimated for the spike genomic region. Results The haplotype networks showed a star shape, where multiple haplotypes with few nucleotide differences diverge from a common ancestor. Four hundred seventy nine different haplotypes were defined in the seven analyzed clades. The main haplotype, named Hap-1, was the most frequent for clades G (54%), GH (54%), and GR (56%) and a different haplotype (named Hap-252) was the most important for clades L (63.3%), O (39.7%), S (51.7%), and V (70%). The evolutionary rate for the spike protein was estimated as 1.08 x 10−3 nucleotide substitutions/site/year. Moreover, the nucleotide evolutionary rate after nine months of pandemic was similar for each clade. Conclusions In conclusion, the present evolutionary analysis is relevant since the spike protein of SARS-CoV-2 is the target for most therapeutic candidates; besides, changes in this protein could have consequences on viral transmission, response to antivirals and efficacy of vaccines. Moreover, the evolutionary characterization of clades improves knowledge of SARS-CoV-2 and deserves to be assessed in more detail since re-infection by different phylogenetic clades has been reported. Competing Interest Statement The authors have declared no competing interest.