Epidemiología molecular del virus de la hepatitis B en el área sanitaria de Santiago de Compostela (España)

La epidemiología molecular de los genotipos y subtipos del VHB en Galicia adolece de datos recientes. En la presente tesis doctoral se analizaron la prevalencia y distribución de los genotipos y subtipos del VHB y su asociación con otros factores epidemiológicos, clínicos y virológicos en 320 pacientes con hepatitis B crónica a seguimiento en el AS de Santiago de Compostela. Este estudio confirma que en Galicia la distribución de genotipos y subgenotipos del VHB varía con la edad, el sexo, la procedencia, en las diferentes fases de la historia natural de la HBC, en la respuesta al tratamiento y en la coinfección con el VIH y/o VHC y también dentro de las diferentes áreas geográficas y grupos epidemiológicos

Evolution of the Quorum network and the mobilome (plasmids and bacteriophages) in clinical strains of Acinetobacter baumannii during a decade

In this study, we compared eighteen clinical strains of A. baumannii belonging to the ST-2 clone and isolated from patients in the same intensive care unit (ICU) in 2000 (9 strains referred to collectively as Ab_GEIH-2000) and 2010 (9 strains referred to collectively as Ab_GEIH-2010), during the GEIH-REIPI project (Umbrella BioProject PRJNA422585). We observed two main molecular differences between the Ab_GEIH-2010 and the Ab_GEIH-2000 collections, acquired over the course of the decade long sampling interval and involving the mobilome: i) a plasmid harbouring genes for blaOXA 24/40 ss-lactamase and abKA/abkB proteins of a toxin-antitoxin system; and ii) two temperate bacteriophages, Ab105-1varphi (63 proteins) and Ab105-2varphi (93 proteins), containing important viral defence proteins. Moreover, all Ab_GEIH-2010 strains contained a Quorum functional network of Quorum Sensing (QS) and Quorum Quenching (QQ) mechanisms, including a new QQ enzyme, AidA, which acts as a bacterial defence mechanism against the exogenous 3-oxo-C12-HSL. Interestingly, the infective capacity of the bacteriophages isolated in this study (Ab105-1varphi and Ab105-2varphi) was higher in the Ab_GEIH-2010 strains (carrying a functional Quorum network) than in the Ab_GEIH-2000 strains (carrying a deficient Quorum network), in which the bacteriophages showed little or no infectivity. This is the first study about the evolution of the Quorum network and the mobilome in clinical strains of Acinetobacter baumannii during a decade

Combined Use of the Ab105-2φΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multi-Resistant Acinetobacter baumannii

Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phi∆CI) that displayed antimicrobial activity against A. baumannii clinical strain Ab177_GEIH-2000 (isolated in the GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585, and for which meropenem and imipenem MICs of respectively, 32 μg/mL, and 16 μg/mL were obtained). We observed an in vitro synergistic antimicrobial effect (reduction of 4 log–7 log CFU/mL) between meropenem and the lytic phage in all combinations analyzed (Ab105-2phi∆CI mutant at 0.1, 1 and 10 MOI and meropenem at 1/4 and 1/8 MIC). Moreover, bacterial growth was reduced by 8 log CFU/mL for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phi∆CI mutant) and by 4 log CFU/mL for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phi∆CI mutant) at both MOI 1 and 10. These results were confirmed in an in vivo model (G. mellonella), and the combination of imipenem and mutant Ab105-2phi∆CI was most effective (p < 0.05). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to antibiotics used to combat multi-resistant strains of Acinetobacter baumannii

GEHEP 010 study: Prevalence and distribution of hepatitis B virus genotypes in Spain (2000–2016)

[Objective] To study the prevalence and distribution of HBV genotypes in Spain for the period 2000–2016.[Methods] Retrospective study recruiting 2559 patients from 17 hospitals. Distribution of HBV genotypes, as well as sex, age, geographical origin, mode of transmission, HDV-, HIV- and/or HCV-coinfection, and treatment were recorded.[Results] 1924 chronically HBV native Spanish patients have been recruited. Median age was 54 years (IQR: 41–62), 69.6% male, 6.3% HIV-coinfected, 3.1% were HCV-coinfected, 1.7% HDV-co/superinfected. Genotype distribution was: 55.9% D, 33.5% A, 5.6% F, 0.8% G, and 1.9% other genotypes (E, B, H and C). HBV genotype A was closely associated with male sex, sexual transmission, and HIV-coinfection. In contrast, HBV genotype D was associated with female sex and vertical transmission. Different patterns of genotype distribution and diversity were found between different geographical regions. In addition, HBV epidemiological patterns are evolving in Spain, mainly because of immigration. Finally, similar overall rates of treatment success across all HBV genotypes were found.[Conclusions] We present here the most recent data on molecular epidemiology of HBV in Spain (GEHEP010 Study). This study confirms that the HBV genotype distribution in Spain varies based on age, sex, origin, HIV-coinfection, geographical regions and epidemiological groups.This study has been funded in part by the funds of the research project GEHEP-2018-010, granted by the Hepatitis Group of the Spanish Society of Infectious Diseases and Clinical Microbiology (Grupo de Hepatitis de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, GEHEP/SEIMC)

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

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

Prevalence and incidence of hepatitis delta in patients with chronic hepatitis B in Spain

Background Hepatitis delta virus (HDV) is a defective agent that only replicates in the presence of the hepatitis B virus. Accordingly, HDV acquisition may occur as superinfection of HBsAg+ carriers or following acute dual HDV and hepatitis B virus exposure. Herein, we examined the global and incident rates of HDV infections in Spain. Patients and methods The presence of anti-HDV antibody and new HDV superinfections was examined in all HBsAg+ patients who attended one large tertiary outclinic in Spain since year 2000. Anti-HDV antibodies were tested repeatedly every 5 years in those previously negative. Results During a median follow-up of 12 years, 478 individuals were diagnosed as HBsAg+. Overall, 64.4% were male, median age was 55 years, 88.1% were native Spaniards, 6.5% were coinfected with HIV, and 7.3% were reactive for hepatitis C virus (HCV) antibodies. A total of 19 (4%) patients had anti-HDV antibody at first diagnosis. There were no further HDV seroconversions. Most anti-HDV + patients were male (n = 12), former injection drug users (n= 13), and native Spaniards (n= 16). Coinfection with HIV was found in six, and 12 had HCV antibodies. Interestingly, three of seven women with delta hepatitis were foreigners (Asian or African), denied injection drug use, were younger than 40 years old, and negative for both HCV and HIV. Conclusion The prevalence of chronic hepatitis delta is currently very low (< 5%) among chronic HBsAg+ carriers in Spain, with lower rates in recent years. Moreover, new incident HDV infections were not seen in 478 chronic hepatitis B carriers since year 2000, following drastic declines in injection drug use

Effects of Maternal Stress on Breast Milk Production and the Microbiota of Very Premature Infants

Perinatal stress experienced by mothers of very premature newborns may influence the mother’s milk and the infant’s intestinal microbiota. This prospective study of mothers of very preterm infants fed with mother’s own milk (MOM) was carried out in a tertiary hospital over a 2-year period. The assessment of maternal stress in 45 mothers of 52 very preterm newborns using the parental stress scale (PSS:NICU) revealed an inverse relationship between stress and MOM production in the first days of life (p = 0.012). The greatest contributor to stress was the one related to the establishment of a mother–child bond. Maternal stress was lower in mothers in whom the kangaroo method was established early (p = 0.011) and in those with a higher educational level (p = 0.032). Levels of fecal calprotectin (FC) decreased with the passage of days and were directly correlated with birthweight (p = 0.044). FC levels 7 days post-delivery were lower in newborns that received postnatal antibiotics (p = 0.027). High levels of maternal stress resulted in progressive decreases and increases in the proportions of Firmicutes and Proteobacteria species, respectively, over 15 days post-delivery, both in MOM and in fecal samples from premature newborns. These findings underscore the importance of recognizing and appropriately managing maternal stress in neonatal units, given its marked influence on both the microbiota of maternal milk and the intestinal microbiota of premature newborns

Genomic analysis of 40 prophages located in the genomes of 16 carbapenemase-producing clinical strains of Klebsiella pneumoniae

Klebsiella pneumoniae is the clinically most important species within the genus Klebsiella and, as a result of the continuous emergence of multi-drug resistant (MDR) strains, the cause of severe nosocomial infections. The decline in the effectiveness of antibiotic treatments for infections caused by MDR bacteria has generated particular interest in the study of bacteriophages. In this study, we characterized a total of 40 temperate bacteriophages (prophages) with a genome range of 11.454-84.199 kb, predicted from 16 carbapenemase-producing clinical strains of K. pneumoniae belonging to different sequence types, previously identified by multilocus sequence typing. These prophages were grouped into the three families in the order Caudovirales (27 prophages belonging to the family Myoviridae, 10 prophages belonging to the family Siphoviridae and 3 prophages belonging to the family Podoviridae). Genomic comparison of the 40 prophage genomes led to the identification of four prophages isolated from different strains and of genome sizes of around 33.3, 36.1, 39.6 and 42.6 kb. These prophages showed sequence similarities (query cover >90 %, identity >99.9 %) with international Microbe Versus Phage (MVP) (http://mvp.medgenius.info/home) clusters 4762, 4901, 3499 and 4280, respectively. Phylogenetic analysis revealed the evolutionary proximity among the members of the four groups of the most frequently identified prophages in the bacterial genomes studied (33.3, 36.1, 39.6 and 42.6 kb), with bootstrap values of 100 %. This allowed the prophages to be classified into three clusters: A, B and C. Interestingly, these temperate bacteriophages did not infect the highest number of strains as indicated by a host-range assay, these results could be explained by the development of superinfection exclusion mechanisms. In addition, bioinformatic analysis of the 40 identified prophages revealed the presence of 2363 proteins. In total, 59.7 % of the proteins identified had a predicted function, mainly involving viral structure, transcription, replication and regulation (lysogenic/lysis). Interestingly, some proteins had putative functions associated with bacterial virulence (toxin expression and efflux pump regulators), phage defence profiles such as toxin-antitoxin modules, an anti-CRISPR/Cas9 protein, TerB protein (from terZABCDE operon) and methyltransferase proteins