Usefulness of serological studies for the early diagnosis of Lyme disease in Primary Health Care Centres

Objetivo: Determinar la utilidad del diagnóstico precoz de la enfermedad de Lyme (EL) en los Centros de Atención Primaria (CAP) empleando el ELISA como técnica de cribado serológico. Métodos: Se realiza un estudio retrospectivo (2006-2013) consistente en la determinación mediante ELISA de la seropositividad a Borrelia de 2.842 personas consideradas en riesgo de padecer EL. Se estudia la relación entre el hábitat y la zona de residencia de las personas con seropositividad a Borrelia, según la procedencia de las muestras (CAP/Hospital). Resultados: El 15,2% de los sueros resultaron positivos frente a Borrelia spp. La seropositividad fue significativamente superior en las muestras remitidas desde los CAP que desde el Hospital y en los habitantes del rural y la montana˜ frente al área urbana y la meseta. El porcentaje de seropositividad se incrementó con el transcurso de los anos. ˜ Los médicos de Atención Primaria detectaron mayor porcentaje de enfermos de Lyme en Fase I y tras la instauración del tratamiento no se observaron secuelas. Conclusiones: El papel del médico de atención primaria es primordial en el diagnóstico precoz de la EL, constatándose un mayor porcentaje de seropositivos entre las muestras remitidas desde los CAP con predominio del diagnóstico en Fase I de enfermedad y la resolución sin secuelas. La detección de anticuerpos específicos frente a Borrelia, mediante ELISA, es una prueba útil para el cribado de pacientes en riesgo de ELObjective: The main aim of this study was to determine the usefulness of an early diagnosis of Lyme disease (LD) in Primary Health Care Centres (PHCC) using the ELISA test as serological screening technique. Methods: A retrospective study (2006-2013) was performed in order to determine the antiBorrelia seropositivity in 2,842 people at risk of having LD. The possible relationship between the environment and the area of residence with anti-Borrelia seropositivity was also studied according to the origin of the specimens (PHCC/Hospital). Results: Overall, 15.2% of samples were positive to Borrelia spp. Seropositivity was significantly higher in samples sent by PHCC doctors than those sent by Hospital doctors. Seropositivity was significantly higher in rural than in urban populations and in those who live in mountainous or flat areas. The percentage of seropositivity has increased over the years. Conclusions: The role of the PHCC doctor is essential for achieving an early diagnosis of Lyme disease, as a higher percentage of seropositives was detected in samples submitted from PHCC. Furthermore, most early localised LD patients were diagnosed in PHCC, avoiding the appearance of sequelae. Therefore, detection of Borrelia specific antibodies using an ELISA assay is a useful screening test for patients at risk of LD.Secretaría General de Universidades por la concesión de una ayuda para la estructuración de Grupos de Investigación Competitiva, modalidad de Grupos de Referencia Competitiva (GRC2015/003, Xunta de Galicia)S

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

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.This work was funded by grant EPICOVIGAL FONDO SUPERA-COVID19 from Banco Santander-CSIC-CRUE and grant CT850A-2 from ACIS SERGAS from the Consellería de Sanidade Xunta de Galicia. PGG was supported by grant ED481A-2021/345 from the Consellería de Cultura, Educación e Universidade Xunta de Galicia. SD acknowledges support from the Fonds National de la Recherche (F.R.S.-FNRS, Belgium; grant no. F.4515.22). SD and GB acknowledge support from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, FWO, Belgium; grant no. G098321N) and from the European Union Horizon RIA 2023 project LEAPS (grant no. 101094685). GB acknowledges support from the Internal Funds KU Leuven (Grant No. C14/18/094), from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, FWO, Belgium; grant no. G0E1420N) and from the DURABLE EU4Health project 02/2023-01/2027, which is co-funded by the European Union (call EU4H-2021-PJ4; grant no. 101102733). SD and PL acknowledge support from the European Union Horizon 2020 project MOOD (grant agreement no. 874850). PL and MAS acknowledge support from the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422 - ReservoirDOCS), from the Wellcome Trust through project 206298/Z/17/Z and from the National Institutes of Health grants R01 AI153044, R01 AI162611 and U19 AI135995. PL also acknowledges support from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, G0D5117N, and G051322N); MIV, JCS and NSO acknowledge support from the Foundation for Science and Technology (FCT) (project UIDB/50026/2020, UIDP/50026/2020).N

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

13 páginas, 4 figurasThe dynamics of severe acute respiratory syndrome coronavirus 2 (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-BA.1 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 United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. 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.This work was funded by grant EPICOVIGAL FONDO SUPERA-COVID19 from Banco Santander-CSIC-CRUE and grant CT850A-2 from ACIS SERGAS from the Consellería de Sanidade Xunta de Galicia. PGG was supported by grant ED481A-2021/345 from the Consellería de Cultura, Educación e Universidade Xunta de Galicia. SD acknowledges support from the Fonds National de la Recherche (F.R.S.-FNRS, Belgium; grant no. F.4515.22). SD and GB acknowledge support from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, FWO, Belgium; grant no. G098321N) and from the European Union Horizon RIA 2023 project LEAPS (grant no. 101094685). GB acknowledges support from the Internal Funds KU Leuven (Grant No. C14/18/094), from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, FWO, Belgium; grant no. G0E1420N) and from the DURABLE EU4Health project 02/2023-01/2027, which is co-funded by the European Union (call EU4H-2021-PJ4; grant no. 101102733). SD and PL acknowledge support from the European Union Horizon 2020 project MOOD (grant agreement no. 874850). PL and MAS acknowledge support from the European Union's Horizon 2020 research and innovation programme (grant agreement no. 725422 - ReservoirDOCS), from the Wellcome Trust through project 206298/Z/17/Z and from the National Institutes of Health grants R01 AI153044, R01 AI162611 and U19 AI135995. PL also acknowledges support from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, G0D5117N, and G051322N); MIV, JCS and NSO acknowledge support from the Foundation for Science and Technology (FCT) (project UIDB/50026/2020, UIDP/50026/2020).Peer reviewe

Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3