Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Human T-lymphotropic virus-1 infection among Latin American pregnant women living in Spain.

Objectives: Human T-lymphotropic virus (HTLV) antenatal screening is not mandatory in Spain. Surveys conducted decades ago reported HTLV-1 seroprevalence rates of 0.2% among foreign pregnant women in Spain. The migrant flow to Spain from HTLV-1 endemic regions in Latin America and sub-Saharan Africa has increased during the last decade. Currently, 25% of pregnant women in Spain are foreigners. Methods: From January 2021 to October 2023 a cross-sectional study was carried out in all consecutive pregnant women attended at eleven Spanish clinics. A commercial enzyme immunoassay (EIA) was used for screening of serum HTLV-1/2 antibodies. Reactive samples were confirmed by immunoblot. Results: A total of 9813 pregnant women with a median age of 34 years-old were examined. Native Spaniards were 6977 (76.5%). Of 2147 foreigners (23.5%), 903566 (9.9%) were Latin Americans, 416 (4.5%) North Africans, 293 (3.2%) from Romania, and 196 (2.1%) from sub-Saharan Africa. A total of 47 samples were EIA reactive but only five were confirmed as HTLV-1 positive using immunoblot. Infected women came from Paraguay, Colombia, the Dominican Republic, Venezuela and Peru. All but one were primigravida, with ages ranging from 20 to 33 years-old. One was HIV-1 positive, and another was infected with Chlamydia trachomatis. Conclusion: The overall seroprevalence for HTLV-1 among pregnant women in Spain is 0.05% but rises ten-fold (0.55%) among Latin Americans. This rate is higher than in surveys conducted decades ago. Our results support that anti-HTLV testing should be part of antenatal screening in Spain in pregnant women coming from Latin America, as it is already done with Chagas disease.

Detección y cuantificación de VHB y VHC en muestras de plasma mediante la utilización de diferentes ensayos moleculares: estudio comparativo / Detection and quantification of HBV and HCV in plasma samples by means of different molecular assays: Comparative study

Introducción: La carga viral es un marcador muy útil para realizar el seguimiento de los pacientes infectados por VHB y VHC. Este trabajo compara ensayos basados en amplificación mediada por transcripción y en PCR a tiempo real con el objetivo de comprobar si pueden ser intercambiables. Material y métodos: Estudio bicéntrico en el que se analizó la carga viral de 147 muestras de plasma de pacientes infectados por VHB y 229 por VHC, mediante ensayos basados en amplificación mediada por transcripción (Aptima® HBV Quant y Aptima® HCV Quant Dx, que utilizan el sistema Panther (Hologic®)) y PCR a tiempo real (COBAS® AmpliPrep / COBAS® TaqMan® y COBAS® 6800), calculando el grado de concordancia entre ellos. Resultados: Se detectó carga viral en ambos equipos en 60 (40,82%) muestras de VHB (mediana del log de la carga viral: COBAS®: 2,51UI/mL (RIC 2,20-3,17), Panther: 2,71UI/mL (RIC 2,21-3,22)) y en 39 (16,96%) muestras de VHC (mediana del log de la carga viral: COBAS®: 3,93UI/mL (RIC 2,24-6,01), Panther: 3,80UI/mL (RIC 1,99-6,14)). La concordancia entre ambos equipos fue de κ=0,943 para VHB y κ=0,925 para VHC. La comparación de las muestras con carga viral detectada mediante los 2 ensayos mostró una correlación alta tanto para VHB (R2=0,86) como para VHC (R2=0,97). Conclusiones: Los ensayos basados tanto en amplificación mediada por transcripción como en PCR a tiempo real pueden ser intercambiables para el manejo de pacientes infectados con VHB y VHC.(AU)

Introduction: Viral load is a very useful marker for monitoring patients infected with HBV and HCV. This work compares assays based on transcription-mediated amplification and on real-time PCR to verify whether they can be interchangeable. Material and methods: a bicentric study, in which 147 plasma samples from patients infected with HBV and 229 with HCV were analyzed, was carried out. Transcription-mediated amplification-based assays (Aptima® HBV Quant and Aptima® HCV Quant Dx, employing Panther system (Hologic®)) and on real-time PCR (COBAS® AmpliPrep / COBAS® TaqMan® and COBAS® 6800) were used and the degree of concordance between them was calculated. Results: Viral load was detected in both systems in 60 (40.82%) HBV samples (median log viral load: COBAS®: 2.51IU/mL (IQR 2.20-3.17), Panther: 2.71IU/mL (IQR 2.21-3.22)) and in 39 (16.96%) HCV samples (median log viral load: COBAS®: 3.93IU/mL (IQR 2.24-6.01), Panther: 3.80IU/mL (IQR 1.99-6.14)). The agreement between both systems was κ=0.943 for HBV and κ=0.925 for HCV. Comparison of viral load samples detected by both assays showed a hight correlation for HBV (R2=0.86) and for HCV (R2=0.97). Conclusions: Both transcription-mediated amplification and on real-time PCR based assays may be interchangeable for the management of patients infected with HBV and HCV.(AU)

MRI-based Neuropathy Score Reporting And Data System (NS-RADS): multi-institutional wider-experience usability study of peripheral neuropathy conditions among 32 radiology readers.

OBJECTIVE: To determine the inter-reader reliability and diagnostic performance of classification and severity scales of Neuropathy Score Reporting And Data System (NS-RADS) among readers of differing experience levels after limited teaching of the scoring system. METHODS: This is a multi-institutional, cross-sectional, retrospective study of MRI cases of proven peripheral neuropathy (PN) conditions. Thirty-two radiology readers with varying experience levels were recruited from different institutions. Each reader attended and received a structured presentation that described the NS-RADS classification system containing examples and reviewed published articles on this subject. The readers were then asked to perform NS-RADS scoring with recording of category, subcategory, and most likely diagnosis. Inter-reader agreements were evaluated by Conger's kappa and diagnostic accuracy was calculated for each reader as percent correct diagnosis. A linear mixed model was used to estimate and compare accuracy between trainees and attendings. RESULTS: Across all readers, agreement was good for NS-RADS category and moderate for subcategory. Inter-reader agreement of trainees was comparable to attendings (0.65 vs 0.65). Reader accuracy for attendings was 75% (95% CI 73%, 77%), slightly higher than for trainees (71% (69%, 72%), p = 0.0006) for nerves and comparable for muscles (attendings, 87.5% (95% CI 86.1-88.8%) and trainees, 86.6% (95% CI 85.2-87.9%), p = 0.4). NS-RADS accuracy was also higher than average accuracy for the most plausible diagnosis for attending radiologists at 67% (95% CI 63%, 71%) and for trainees at 65% (95% CI 60%, 69%) (p = 0.036). CONCLUSION: Non-expert radiologists interpreted PN conditions with good accuracy and moderate-to-good inter-reader reliability using the NS-RADS scoring system. CLINICAL RELEVANCE STATEMENT: The Neuropathy Score Reporting And Data System (NS-RADS) is an accurate and reliable MRI-based image scoring system for practical use for the diagnosis and grading of severity of peripheral neuromuscular disorders by both experienced and general radiologists. KEY POINTS: • The Neuropathy Score Reporting And Data System (NS-RADS) can be used effectively by non-expert radiologists to categorize peripheral neuropathy. • Across 32 different experience-level readers, the agreement was good for NS-RADS category and moderate for NS-RADS subcategory. • NS-RADS accuracy was higher than the average accuracy for the most plausible diagnosis for both attending radiologists and trainees (at 75%, 71% and 65%, 65%, respectively).

Prevalence and phenotypic susceptibility to doravirine of the HIV-1 reverse transcriptase V106I polymorphism in B and non-B subtypes.

AIM: To evaluate the prevalence and in vitro susceptibility to doravirine of RT-V106I polymorphism detected in samples collected from drug-naïve subjects. METHODS: Doravirine susceptibility was measured in site-directed mutants (SDMs) containing V106I, V106A, V106 M and Y188L mutations in subtype B (NL4-3, HXB2) and CRF02_AG background and in recombinant viruses with RT harboring V106I alone derived from 50 PLWH. RESULTS: HIV-1 B subtype was detected in 1523/2705 cases. Prevalence of V106I was 3.2% in B and 2.5% in non-B subtypes, and was higher in subtype F (8.1%), and D (14.3%). Fold-changes (FC) in susceptibility for SDMs were below doravirine biological cutoff (3.0) for V106I, but not for V106A, V106 M, and Y188L. Clinically-derived viruses tested included 22 B (median FC 1.2 [IQR 0.9-1.6]) and 28 non-B subtypes (median FC 1.8 [IQR 0.9-3.0]). Nine (18%) viruses showed FC values equal or higher than the doravirine biological FC cutoff. CONCLUSIONS: The prevalence of the HIV-1 RT-V106I polymorphism in MeditRes HIV consortium remains low, but significantly more prevalent in subtypes D and F. V106I minimally decreased the susceptibility to doravirine in SDMs and most clinical isolates. Reduced susceptibility seems to occur at increased frequency in subtype F1, however the clinical impact remains to be investigated.

Detection and quantification of HBV and HCV in plasma samples by means of different molecular assays: Comparative study.

INTRODUCTION: Viral load is a very useful marker for monitoring patients infected with HBV and HCV. This work compares assays based on transcription-mediated amplification (TMA) and on real-time PCR (RT-PCR) to verify whether they can be interchangeable. MATERIAL AND METHODS: A bicentric study, in which 147 plasma samples from patients infected with HBV and 229 with HCV were analyzed, was carried out. TMA-based assays (Aptima® HBV Quant and Aptima® HCV Quant Dx, employing Panther system (Hologic®)) and RT-PCR (COBAS® AmpliPrep/COBAS® TaqMan® and COBAS® 6800) were used and the degree of concordance between them was calculated. RESULTS: Viral load was detected in both systems in 60 (40.82%) HBV samples (median log viral load: COBAS: 2.51IU/mL (IQR 2.20-3.17), Panther: 2.71IU/mL (IQR 2.21-3.22)) and in 39 (16.96%) HCV samples (median log viral load: COBAS: 3.93IU/mL (IQR 2.24-6.01), Panther: 3.80IU/mL (IQR 1.99-6.14)). The agreement between both systems was κ=0.943 for HBV and κ=0.925 for HCV. Comparison of viral load samples detected by both assays showed a hight correlation for HBV (R2=0.86) and for HCV (R2=0.97). CONCLUSIONS: Both TMA and RT-PCR based assays may be interchangeable for the management of patients infected with HBV and HCV.

Transmitted drug resistance to antiretroviral drugs in Spain during the period 2019-2021.

To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.

HTLV infection in persons with sexually transmitted diseases in Spain.

Background: HTLV-1 infection is a neglected disease, despite estimates of 10 million people infected worldwide and producing life-threatening illnesses in 10% of carriers. Sexual transmission is the main route of contagion. However, HTLV-1 is not listed among sexually transmitted infections (STIs). Methods: Serum from all consecutive individuals who had attended six STI clinics across Spain during the last 12 months were tested for HTLV antibodies using a commercial enzyme immunoassay (EIA). Reactive samples were confirmed by immunoblot. Results: A total of 2,524 samples were examined. The majority (1,936; 76.7%) belonged to men, of whom 676 (34.9%) were men who have sex with men (MSM) receiving HIV pre-exposure prophylaxis. Although native Spaniards predominated (1,470; 58.2%), up to 593 (23.5%) came from Latin America and 139 (5.5%) were African. A total of 26 individuals were initially EIA reactive and immunoblot confirmed 5 as HTLV-1 and 7 as HTLV-2. All but one HTLV-1+ case came from Latin America. Three were men and two were women. Among Latin Americans, the HTLV-1 seroprevalence was 0.67%. In contrast, all seven HTLV-2+ were native Spaniards and former injection drug users, and all but one were HIV+. Conclusion: The rate of HTLV infection among individuals with STIs in Spain is 0.5%, which is greater than in the general population. These results support the introduction of universal HTLV screening in persons who attend clinics for STIs.

HTLV-1-associated myelopathy in Spain.

BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease. METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic. RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/104 PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence. CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.

Longitudinal study of patients with discrepant results in CLIFT and a solid-phase dsDNA antibody assay: does a gold standard dsDNA assay exist?

OBJECTIVE: Antidouble-stranded DNA (dsDNA) antibodies are essential for diagnosis and follow-up of systemic lupus erythematous (SLE). To ensure the best diagnostic approach, most healthcare laboratories opt for a combination of highly sensitive methods, such as solid-phase immunoassays, and highly specific methods, such as the Crithidia luciliae indirect immunofluorescence test (CLIFT). Even so, discordant results are common, thus hindering the diagnostic process. Therefore, this study aimed to characterise a cohort of patients with discrepant results for a dsDNA fluorescence enzyme immunoassay (FEIA) and CLIFT during 2016-2018 and to follow patients up until December 2021. METHODS: We performed an observational, longitudinal and retrospective study on 417 samples from 257 patients who had been referred for suspected connective tissue diseases or followed up after diagnosis. All of them were positive for antinuclear antibodies (ANAs) using an indirect immunofluorescence assay (IFA) on Hep-2 cells, the entry criterion in our laboratory, and positive for FEIA dsDNA. Samples were then tested with CLIFT according to our routine protocol, which includes CLIFT testing after FEIA dsDNA results ≥10 UI/ml. After the assessment of data quality, the final analysis was based on 222 patients. RESULTS: Eighty-three patients (37.4%) had positive results in both tests and met the diagnostic criteria for SLE. However, 139 patients (62.6%) had discrepant results (FEIA+, CLIFT-). Of these, 58 patients (41.7%) had a diagnosis of SLE, with 47 (33.8%) having been previously diagnosed and under treatment. The remaining 11 patients (7.9%) had a new diagnosis of SLE, which was made up within 4 years of the initial screening. A total of 81 of the 139 patients (57.5%) with discrepant results did not meet lupus criteria during the follow-up period. CONCLUSIONS: The study showed that CLIFT could be negative in both treated and newly diagnosed SLE, thus underlining the importance of follow-up of dsDNA-positive results using solid-phase tests. Therefore, quantitative tests such as FEIA could add value to the diagnosis and management of patients with suspected SLE.

The slowdown of new infections by human retroviruses has reached a plateau in Spain.

The 2022 annual meeting of the HTLV & HIV-2 Spanish Network was held in Madrid on December 14. We summarize here the main information presented and discussed at the workshop and review time trends for human retroviral infections in Spain. As transmissible agents, infections by human retroviruses are of obligatory declaration. Until the end of 2022, the Spanish national registry had recorded 451 cases of HTLV-1, 821 of HTLV-2, and 416 of HIV-2. For HIV-1, estimates are of 150 000 people currently living with HIV-1 and 60 000 cumulative deaths due to AIDS. During year 2022, new diagnoses in Spain were of 22 for HTLV-1, 6 for HTLV-2, and 7 for HIV-2. The last updated figures for HIV-1 are from 2021 and counted 2786 new diagnoses. The slowdown in yearly infections for HIV-1 in Spain points out that new strategies are needed to achieve the United Nations 95-95-95 targets by 2025. For the remaining neglected human retroviral infections, their control might be pushed throughout four interventions: (1) expanding testing; (2) improving education and interventions aimed to reduce risk behaviors; (3) facilitating access to antiretrovirals as treatment and prevention, including further development of long-acting formulations; and (4) increasing vaccine research efforts. Spain is a 47 million population country in South Europe with strong migration flows from HTLV-1 endemic regions in Latin America and Sub-Saharan Africa. At this time universal HTLV screening has been implemented only in the transplantation setting, following the report of 5 cases of HTLV-associated myelopathy shortly after transplantation of organs from HTLV-1 positive donors. There are four target populations for expanding testing and unveiling asymptomatic carriers responsible for silent HTLV-1 transmissions: (1) migrants; (2) individuals with sexually transmitted infections; (3) pregnant women; and (4) blood donors.

Optimization of the molecular diagnosis of the acute hepatitis E virus infection.

To evaluate the diagnostic value of the combination of two broad-range PCR assays targeting two different and conserved regions of the viral genome for the diagnosis of acute Hepatitis E virus (HEV) infection. Patients with acute hepatitis were prospectively recruited. In all, HEV-IgM antibodies were tested together with evaluation of HEV viraemia by two PCR assays (ORF3 and ORF1). The number of individuals exhibiting negative IgM antibody results but carrying viral RNA was calculated by each PCR assay. Four-hundred and seventy individuals were included, of whom 145 (30.8%) were diagnosed as having acute HEV. Of them, 122 (84.1%) exhibited HEV-IgM antibodies, and 81 (55.8%) had detectable viral RNA for at least one PCR. Using the ORF3 molecular assay, 70 (48.3%) individuals were identified with HEV infection. When the ORF1 molecular assay was applied, 49 (33.8%) individuals were identified. The ORF3 assay detected viral RNA in 32 patients not detected by the ORF1 assay. In contrast, the ORF1 assay could amplify viral RNA in 11 patients who were not detected by the ORF3 assay. The parallel use of two broad-range PCR assays significantly increased the performance of the molecular diagnosis of HEV.

Susceptibility to hepatitis B virus infection in adults living in Spain.

BACKGROUND: A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain. METHODS: HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years. RESULTS: From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible. CONCLUSION: Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection.

A Straightforward Cytometry-Based Protocol for the Comprehensive Analysis of the Inflammatory Valve Infiltrate in Aortic Stenosis.

Aortic stenosis (AS) is a frequent cardiac disease in old individuals, characterized by valvular calcification, fibrosis, and inflammation. Recent studies suggest that AS is an active inflammatory atherosclerotic-like process. Particularly, it has been suggested that several immune cell types, present in the valve infiltrate, contribute to its degeneration and to the progression toward stenosis. Furthermore, the infiltrating T cell subpopulations mainly consist of oligoclonal expansions, probably specific for persistent antigens. Thus, the characterization of the cells implicated in the aortic valve calcification and the analysis of the antigens to which those cells respond to is of utmost importance to develop new therapies alternative to the replacement of the valve itself. However, calcified aortic valves have been only studied so far by histological and immunohistochemical methods, unable to render an in-depth phenotypical and functional cell profiling. Here we present, for the first time, a simple and efficient cytometry-based protocol that allows the identification and quantification of infiltrating inflammatory leukocytes in aortic valve explants. Our cytometry protocol saves time and facilitates the simultaneous analysis of numerous surface and intracellular cell markers and may well be also applied to the study of other cardiac diseases with an inflammatory component.

Recommendations for the integral diagnosis of chronic viral hepatitis in a single analytical extraction. / Recomendaciones para el diagnóstico integral de las hepatitis virales crónicas en una única extracción analítica.

The Spanish Society of Digestive Pathology (SEPD), the Spanish Association for the Study of the Liver (AEEH), the Spanish Society of Infections and Clinical Microbiology (SEIMC) and its Viral Hepatitis Study Group (GEHEP), and with the endorsement of the Alliance for the Elimination of Viral Hepatitis in Spain (AEHVE), have agreed on a document to carry out a comprehensive diagnosis of viral hepatitis (B, C and D), from a single blood sample; that is, a comprehensive diagnosis, in the hospital and/or at the point of care of the patient. We propose an algorithm, so that the positive result in a viral hepatitis serology (B, C and D), as well as human immunodeficiency virus (HIV), would trigger the analysis of the rest of the virus, including the viral load when necessary, in the same blood draw. In addition, we make two additional recommendations. First, the need to rule out a previous hepatitis A virus (VHA) infection, to proceed with its vaccination in cases where IgG-type studies against this virus are negative and the vaccine is indicated. Second, the determination of the HIV serology. Finally, in case of a positive result for any of the viruses analyzed, there must be an automated alerts and initiate epidemiological monitoring.

Real-life validation of a sample pooling strategy for screening of hepatitis C.

OBJECTIVES: To test a real-life sample pooling screening strategy which contributes to increasing the diagnostic capacity of clinical laboratories and expanding access to massive screening of hepatitis C. METHODS: After evaluating the sensitivity of the pooling strategy for seven different commercial assays which are used to determine the concentration of hepatitis C virus (HCV)-RNA in the plasma or serum, consecutive samples submitted for HCV diagnosis during the first 3 weeks of November 2021 were tested for HCV antibodies and, in parallel and in a blinded way, were pooled into 100 samples and tested for HCV-RNA. When the result was positive, a strategy to un-mask the positive(s) pool(s), which needed up to 15 total HCV-RNA tests, was used. RESULTS: All platforms were able to detect the presence of HCV-RNA in a single sample from a patient with viremic HCV present in pools of up to at least 10 000 HCV-RNA-free samples. A total of 1700 samples (17 pools) were analysed, with an overall prevalence of anti-HCV and HCV-RNA of 0.24%. After pooling, we could detect all samples previously detected using standard diagnosis tests (reflex testing) with a specificity and sensitivity of 100% (CI, 99.78-100%). Given the median current prices of anti-HCV and HCV-RNA on the market in Spain as well as personnel costs, testing using the pooling strategy would have resulted in a save of 3320€. CONCLUSIONS: Here, we demonstrated that by improving cost effectiveness, with no loss of sensitivity and specificity, the strategy of pooling samples may serve as an appropriate tool for use in large-scale screening of HCV.

Transmitted Drug Resistance to Integrase-Based First-Line Human Immunodeficiency Virus Antiretroviral Regimens in Mediterranean Europe.

BACKGROUND: We evaluated the prevalence of transmitted drug resistance (TDR) to integrase strand-transfer inhibitors (INSTIs) and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and of clinically relevant resistance (CRR) in newly diagnosed people with human immunodeficiency virus (HIV; PWH) naive to antiretroviral therapy (ART) in Europe. METHODS: MeditRes is a consortium that includes ART-naive PWH newly diagnosed in France, Greece, Italy, Portugal, and Spain during 2018-2021. Reverse transcriptase and INSTI sequences were provided by participating centers. To evaluate the prevalence of surveillance drug resistance mutations (SDRM), we used the calibrated population resistance tools from the Stanford HIV website. To evaluate CRR, defined as any resistance level ≥3, we used the Stanford HIV Drug Resistance Database v.9.1 algorithm. RESULTS: We included 2705 PWH, 72% men, median age of 37 years (interquartile range, 30-48); 43.7% were infected by non-B subtypes. The prevalence of INSTI-SDRMs was 0.30% (T66I, T66A, E92Q, E138T, E138K, Y143R, S147G, R263K; all n=1) and the prevalence of NRTI-SDRMs was 5.77% (M184V: 0.85%; M184I: 0.18%; K65R/N: 0.11%; K70E: 0.07%; L74V/I: 0.18%; any thymidine analog mutations: 4.36%). INSTI-CRR was 2.33% (0.15% dolutegravir/bictegravir, 2.29% raltegravir/elvitegravir) and 1.74% to first-line NRTIs (0.89% tenofovir/tenofovir alafenamide, 1.74% abacavir, 1.07% lamivudine/emtricitabine). CONCLUSIONS: We present the most recent data on TDR to integrase-based first-line regimens in Europe. Given the low prevalence of CRR to second-generation integrase inhibitors and to first-line NRTIs during 2018-2021, it is unlikely that newly diagnosed PWH in MeditRes countries would present with baseline resistance to a first-line regimen based on second-generation integrase inhibitors.

Oportunistic diagnosis based on age and hepatitis C virus clearance: an essential step to improve the overall health of the liver.

Back in January 2022, an EASL-Lancet Commission on the impact of liver disorders in the European region commissioned by the WHO demonstrated that this condition is, actually, the second leading cause of loss of labor years in Europe after ischemic heart disease (1). This is a very relevant piece of information since this is something that is going to impact the new generations of Europeans unless a significant change is made in public health policies. Despite the advances made over the last few years in hepatitis C virus clearance-understood as a significant reduction of morbidity and mortality associated with Hepatitis B and C viruses-there are still challenges ahead to improve liver health due to the high use of alcohol, and the inseparable triad obesity / diabetes mellitus / metabolic associated fatty liver disease. Also, access to healthcare for several population groups at risk of presenting higher rates of liver disease has become a problem.

Diagnóstico oportunista basado en la edad y eliminación de la hepatitis C: un paso imprescindible para mejorar la salud hepática global / Opportunistic diagnosis based on age and elimination of hepatitis C: an essential step to improve global liver health

En enero de este 2022 una Comisión de EASL-Lancet sobre el impacto de las enfermedades hepáticas en la región europea de la OMS mostró que esta patología es actualmente la segunda causa de pérdida de años de vida laboral en Europa, después de la cardiopatía isquémica. Esto es un dato muy relevante ya que va a impactar en las nuevas generaciones europeas si no existe un cambio importante en las políticas de salud pública. A pesar de los avances de los últimos años en la eliminación de las hepatitis virales entendidas como una disminución importante en la morbimortalidad de la hepatitis B y C, aún quedan retos para mejorar la salud hepática debido al elevado consumo de alcohol, la inseparable tripleta de obesidad / diabetes mellitus / esteatosis hepática metabólica y las dificultades en el acceso a la salud de amplios colectivos de nuestra población, que característicamente están en riesgo de presentar tasas más elevadas de enfermedad hepática (AU)