Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children.

BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.

Meningococcal carriage in men who have sex with men presenting at a sexual health unit in Spain.

Neisseria meningitidis (Nm) is asymptomatically carried in the nasopharynx of 5-10% adults, although certain populations, such as men who have sex with men (MSM), exhibit a higher colonisation rate. Interest in Nm carriage has been renewed, owed to meningitis outbreaks within populations of MSM. The aim of this study was to characterise Nm isolates and risk factors for its carriage among MSM attending a sexual health unit. A retrospective cross-sectional study was undertaken between June 2018 and December 2021. We took anal, oropharyngeal, urethral, and blood samples as part of the sexually transmitted infection screening procedures routinely implemented. Nm isolates were subjected to antimicrobial susceptibility testing; the serogroup and genogroup were determined by multi-locus sequence typing. A total of 399 subjects were recruited, and the Nm oropharyngeal carriage rate was 29%, similar among both people living with HIV (PLWH) and uninfected individuals. Nm carriage was less common in vaccinated individuals, especially those who had received the tetravalent vaccine (2.6% vs. 10.6%, p = 0.008). The most frequent serogroups were B (40%) and non-groupable (45%). Most of the isolates were susceptible to ciprofloxacin (96%) and ceftriaxone (100%). However, we identified 21 strains (20%) belonging to hyperinvasive lineages (CC11, CC4821, CC32, CC41/44, CC213, and CC269), most of which belonged to serogroup B. Given that vaccination with MenACWY was associated with a low Nm carriage, we encourage routine vaccination of all MSM. Moreover, the administration of the meningitis B vaccine should also be assessed considering that several invasive lines included in serogroup B are circulating among MSM.

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018.

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.

Listeriosis outbreak caused by contaminated stuffed pork, Andalusia, Spain, July to October 2019.

Between 1 July and 26 October 2019 in Andalusia, Spain, a large outbreak with 207 confirmed cases of listeriosis was identified. Confirmed cases had a median age of 44 years (range: 0-94) and 114 were women (55.1%). Most cases (n = 154) had mild gastroenteritis, 141 (68.1%) required hospitalisation and three died; five of 34 pregnant women had a miscarriage. The median incubation period was 1 day (range: 0-30), and was significantly shorter in cases presenting with gastroenteritis compared to those presenting without gastroenteritis (1 day vs. 3 days, respectively, p value < 0.001). Stuffed pork, a ready-to-eat product consumed unheated, from a single producer contaminated with Listeria monocytogenes ST388 was identified as the source of infection. The outbreak strain was identified in 189 human samples and 87 non-human (82 food and 5 environmental) samples. Notification of new cases declined abruptly after control measures were implemented. These included contaminated food recall, protocols for clinical management of suspected cases and for post-exposure prophylaxis in pregnant women and communication campaigns with concise messages to the population through social media. Given that there were 3,059 probable cases, this was the largest L. monocytogenes outbreak ever reported in Europe.

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data.

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.

Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017.

BackgroundThe total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries.AimThe aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe.MethodsIn this observational, retrospective study, IMD surveillance data collected from 2013-17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics.ResultsThe overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children (< 15 years) was lower than in other age groups. Of the culture-confirmed MenW IMD cases, 80% (615/767) were caused by hypervirulent cc11.ConclusionDuring the years 2013-17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.

Two Cases of Neisseria meningitidis Proctitis in HIV-Positive Men Who Have Sex with Men.

We report 2 cases from Spain of infectious proctitis caused by Neisseria meningitidis in HIV-positive men who have sex with men. Genetic characterization of the isolates showed that they are unusual strains not found in other more frequent meningococcal locations. This finding suggests an association between specific strains and anogenital tract colonization.

WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014.

OBJECTIVES: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms. METHODS: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS. RESULTS: Thirty-six N. gonorrhoeae multi-antigen sequence typing STs and five phylogenomic clades, including 4-22 isolates from several countries per clade, were identified. The azithromycin target mutation A2059G (Escherichia coli numbering) was found in all four alleles of the 23S rRNA gene in all isolates with high-level azithromycin resistance (n = 4; MIC ≥256 mg/L). The C2611T mutation was identified in two to four alleles of the 23S rRNA gene in the remaining 71 isolates. Mutations in mtrR and its promoter were identified in 43 isolates, comprising isolates within the whole azithromycin MIC range. No mutations associated with azithromycin resistance were found in the rplD gene or the rplV gene and none of the macrolide resistance-associated genes [mef(A/E), ere(A), ere(B), erm(A), erm(B), erm(C) and erm(F)] were identified in any isolate. CONCLUSIONS: Clonal spread of relatively few N. gonorrhoeae strains accounts for the majority of the azithromycin resistance (MIC >2 mg/L) in Europe. The four isolates with high-level resistance to azithromycin (MIC ≥256 mg/L) were widely separated in the phylogenomic tree and did not belong to any of the main clades. The main azithromycin resistance mechanisms were the A2059G mutation (high-level resistance) and the C2611T mutation (low- and moderate-level resistance) in the 23S rRNA gene.

Optimizing strategies for meningococcal C disease vaccination in Valencia (Spain).

BACKGROUND: Meningococcal C (MenC) conjugate vaccines have controlled invasive diseases associated with this serogroup in countries where they are included in National Immunization Programs and also in an extensive catch-up program involving subjects up to 20 years of age. Catch-up was important, not only because it prevented disease in adolescents and young adults at risk, but also because it decreased transmission of the bacteria, since it was in this age group where the organism was circulating. Our objective is to develop a new vaccination schedule to achieve maximum seroprotection in these groups. METHODS: A recent study has provided detailed age-structured information on the seroprotection levels against MenC in Valencia (Spain), where vaccination is routinely scheduled at 2 months and 6 months, with a booster dose at 18 months of age. A complementary catch-up campaign was also carried out in n for children from 12 months to 19 years of age. Statistical analyses of these data have provided an accurate picture on the evolution of seroprotection in the last few years. RESULTS: An agent-based model has been developed to study the future evolution of the seroprotection histogram. We have shown that the optimum strategy for achieving high protection levels in all infants, toddlers and adolescents is a change to a 2 months, 12 months and 12 years of age vaccination pattern. If the new schedule were implemented in January 2014, high-risk subjects between 15-19 years of age would have very low seroprotection for the next 6 years, thereby threatening the program. CONCLUSIONS: High protection levels and a low incidence of meningococcal C disease can be achieved in the future by means of a cost-free change in vaccination program. However, we recommend a new catch-up program simultaneous to the change in regular vaccination program.

Audio-visual perception system for a humanoid robotic head.

One of the main issues within the field of social robotics is to endow robots with the ability to direct attention to people with whom they are interacting. Different approaches follow bio-inspired mechanisms, merging audio and visual cues to localize a person using multiple sensors. However, most of these fusion mechanisms have been used in fixed systems, such as those used in video-conference rooms, and thus, they may incur difficulties when constrained to the sensors with which a robot can be equipped. Besides, within the scope of interactive autonomous robots, there is a lack in terms of evaluating the benefits of audio-visual attention mechanisms, compared to only audio or visual approaches, in real scenarios. Most of the tests conducted have been within controlled environments, at short distances and/or with off-line performance measurements. With the goal of demonstrating the benefit of fusing sensory information with a Bayes inference for interactive robotics, this paper presents a system for localizing a person by processing visual and audio data. Moreover, the performance of this system is evaluated and compared via considering the technical limitations of unimodal systems. The experiments show the promise of the proposed approach for the proactive detection and tracking of speakers in a human-robot interactive framework.

Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study.

BACKGROUND: Regular quality-assured whole-genome sequencing linked to antimicrobial resistance (AMR) and patient metadata is imperative to elucidate the shifting gonorrhoea epidemiology, both nationally and internationally. We aimed to examine the gonococcal population in the European Economic Area (EEA) in 2020, elucidate emerging and disappearing gonococcal lineages associated with AMR and patient metadata, compare with 2013 and 2018 whole-genome sequencing data, and explain changes in gonococcal AMR and gonorrhoea epidemiology. METHODS: In this retrospective genomic surveillance study, we analysed consecutive gonococcal isolates that were collected in EEA countries through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) in 2020, and made comparisons with Euro-GASP data from 2013 and 2018. All isolates had linked AMR data (based on minimum inhibitory concentration determination) and patient metadata. We performed whole-genome sequencing and molecular typing and AMR determinants were derived from quality-checked whole-genome sequencing data. Links between genomic lineages, AMR, and patient metadata were examined. FINDINGS: 1932 gonococcal isolates collected in 2020 in 21 EEA countries were included. The majority (81·2%, 147 of 181 isolates) of azithromycin resistance (present in 9·4%, 181 of 1932) was explained by the continued expansion of the Neisseria gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) clonal complexes (CCs) 63, 168, and 213 (with mtrD/mtrR promoter mosaic 2) and the novel NG-STAR CC1031 (semi-mosaic mtrD variant 13), associated with men who have sex with men and anorectal or oropharyngeal infections. The declining cefixime resistance (0·5%, nine of 1932) and negligible ceftriaxone resistance (0·1%, one of 1932) was largely because of the progressive disappearance of NG-STAR CC90 (with mosaic penA allele), which was predominant in 2013. No known resistance determinants for novel antimicrobials (zoliflodacin, gepotidacin, and lefamulin) were found. INTERPRETATION: Azithromycin-resistant clones, mainly with mtrD mosaic or semi-mosaic variants, appear to be stabilising at a relatively high level in the EEA. This mostly low-level azithromycin resistance might threaten the recommended ceftriaxone-azithromycin therapy, but the negligible ceftriaxone resistance is encouraging. The decreased genomic population diversity and increased clonality could be explained in part by the COVID-19 pandemic resulting in lower importation of novel strains into Europe. FUNDING: European Centre for Disease Prevention and Control and Örebro University Hospital.

Target gene sequencing to define the susceptibility of Neisseria meningitidis to ciprofloxacin.

Meningococcal gyrA gene sequence data, MICs, and mouse infection were used to define the ciprofloxacin breakpoint for Neisseria meningitidis. Residue T91 or D95 of GyrA was altered in all meningococcal isolates with MICs of ≥ 0.064 µg/ml but not among isolates with MICs of ≤ 0.032 µg/ml. Experimental infection of ciprofloxacin-treated mice showed slower bacterial clearance when GyrA was altered. These data suggest a MIC of ≥ 0.064 µg/ml as the ciprofloxacin breakpoint for meningococci and argue for the molecular detection of ciprofloxacin resistance.

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV.

BACKGROUND: Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. METHODS: A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. RESULTS: There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. CONCLUSIONS: CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.

Searching for new cell-penetrating agents: hybrid cyclobutane-proline γ,γ-peptides.

Two generations of hybrid γ,γ-peptides containing cyclobutane amino acids and cis-γ-amino-L-proline joined in alternation have been synthesized and their capacity to cross the eukaryotic cell membrane has been evaluated. The first generation consists of di-, tetra- and hexapeptides, and their properties have been analyzed as well as the influence of peptide length and chirality of the cyclobutane residues. Results have shown that the absolute configuration of the cyclobutane amino acid does not have a relevant influence. The second generation consists of hybrid γ,γ-hexapeptides with a common backbone and distinct side chains introduced with different linkage types through the α-amino group (N(α)) of the proline monomers. These peptides have been shown to be non-toxic towards HeLa cells and to internalize them effectively, the best results being obtained for the peptides with a spacer of five carbons between the N(α) atom and the guanidinium group. The introduction of cyclobutane residues inside the sequence affords a good balance between charge and hydrophobicity, reducing the number of positive charges. This results in lower toxicity and similar cell-uptake properties when compared to previously described peptide agents.

Large Increase in Azithromycin-Resistant Neisseria gonorrhoeae in Northern Spain.

The aim of this study was to characterize the evolution of gonorrhea in the general population by correlating epidemiological, genotypic, and antimicrobial resistance data of Neisseria gonorrhoeae isolates collected in northern Spain from 2014 to 2018. One hundred ninety-four strains underwent antimicrobial susceptibility testing and were genetically analyzed by N. gonorrhoeae multiantigen sequence typing. Increasing cases of gonococcal infections have been observed after 2015. Most occurred in male with urethritis. Sequence type (ST)-9972 and ST-1576, the predominant genotypes identified, have not been previously described as epidemic clones. Of great concern was the significant increase in azithromycin-resistant N. gonorrhoeae. More than 30% of these isolates were obtained from men who have sex with men (MSM). ST-12302 was the most prevalent clone among the azithromycin-resistant strains, and was also resistant to penicillin, ciprofloxacin, and tetracycline. This multidrug-resistant clone was exclusively isolated from MSM during 2018. The incidence rates of gonorrhea and azithromycin-resistant N. gonorrhoeae have significantly increased due to the emergence of new clones. ST-12302 has recently been recognized as an epidemic clone; therefore, its surveillance could be the key in controlling further dissemination of azithromycin resistance. These data highlight the need to perform local studies to update treatment guidelines and reinforce preventive measures against gonorrhea.

Recommendation document on rapid intravenous rehydration in acute gastroenteritis.

INTRODUCTION: The efficacy and safety of the Rapid Intravenous Rehydration (RIR) guidelines in children affected by dehydration secondary to acute gastroenteritis is supported by current scientific evidence, but there is also great variability in its use in clinical practice. OBJECTIVE: To prepare a document with evidence-based recommendations about RIR in paediatric population. METHODS: The project was developed based on GRADE methodology, according to the following work schedule: Working Group training; creation of a catalogue of questions about research and definition of "relevant outcomes"; score and selection criteria for each item; bibliographic review; scientific evidence evaluation and synthesis (GRADE); review, discussion and creation of recommendations. 10 clinical questions and 15 relevant outcomes were created (7 about efficacy and 8 about security). RESULTS: 16 recommendations were set up, from which we can highlight as the main ones: 1) RIR is safe for children affected by mild-moderate dehydration secondary to acute gastroenteritis, unless expressly contraindicated or acute severe comorbidity (strong recommendation, moderate evidence). 2) Its use is recommended in this situation when oral rehydration has failed or due to contraindication (strong, high). 3) Isotonic fluids are recommended (strong, high), suggesting saline fluid as the first option (light, low), supplemented by glucose (2.5%) in those patients showing normoglycemia and ketosis (strong, moderate). 4) A rhythm of 20cc/kg/h is recommended (strong, high) during 1-4 h (strong, moderate). CONCLUSIONS: This document establishes consensus recommendations, based on the available scientific evidence, which could contribute to the standardisation of the use of RIR in our setting.

Synthesis and structural study of highly constrained hybrid cyclobutane-proline γ,γ-peptides.

Two diastereomeric series of hybrid γ,γ-peptides derived from conveniently protected derivatives of (1R,2S)- and (1S,2R)-3-amino-2,2-dimethylcyclobutane-1-carboxylic acid and cis-4-amino-L: -proline joined in alternation have efficiently been prepared through convergent synthesis. High-resolution NMR experiments show that these compounds present defined conformations in solution affording very compact structures as the result of intra and inter residue hydrogen-bonded ring formation. (R,S)-cyclobutane containing peptides adopt more twisted conformations than (S,R) diastereomers. In addition, all these γ-peptides have high tendency to aggregation providing vesicles of nanometric size, which were stable when allowed to stand for several days, as verified by transmission electron microscopy.

Molecular characterization of invasive serogroup B Neisseria meningitidis isolates from Spain during 2015-2018: Evolution of the vaccine antigen factor H binding protein (FHbp).

Studies of meningococcal genetic population structure, including the potential associations between surface proteins variants and clonal complexes, are important to understand how new protein MenB vaccines might impact in specific scenarios. With the aim to analyze the diversity of Spanish invasive MenB strains, and genetic variability of the fHbp vaccine antigen, all MenB isolates received at National Reference Laboratory (NRL) from 2015 to 2018 were molecularly characterized. MATERIAL AND METHODS: 108, 103, 87 and 112 invasive MenB strains isolated during 2015-2018, respectively, were received at NRL. The strains were whole genome sequenced, and porA, fetA, MLST and fHbp variability was analyzed. Potential impact on MenB vaccines coverage was also assessed. RESULTS: A total of 42, 38 and 3 different FHbp subfamily A, B and A/B hybrid peptides, respectively, were found. FHbp subfamily A peptides were harboured by most of the strains (65.9%), being the most prevalent peptide 45 which was associated with genosubtype 22,14 and cc213. FHbp subfamily B peptides were harboured by 32.4% of the strains, and 6 strains harbouring subfamily A/B hybrid peptides were also found. The 64.15% of the strains showed FHbp variants "exact-match" or "cross-reactive" to the FHbp variants included in rLP2086 vaccine according to hSBA assays in the rLP2086 clinical development, and 15.85% showed FHbp peptides defined as predictors of FHbp-coverage for 4CMenB vaccine by gMATS. CONCLUSIONS: Due to invasive meningococcal strains temporal variability (eg prevalence of the cc213 increased from 3.6% in 2007 to 33% in 2018) affecting to the presence and distribution of the vaccine antigens, continuous detailed meningococcal surveillance and monitoring of the vaccine antigens is needed to determine the degree and durability of coverage provided by these protein vaccine.

[Recommendation document on rapid intravenous rehydration in acute gastroenteritis]. / Documento de recomendaciones sobre la rehidratación intravenosa rápida en gastroenteritis aguda.

INTRODUCTION: The efficacy and safety of the rapid intravenous rehydration (RIR) guidelines in children affected by dehydration secondary to acute gastroenteritis is supported by current scientific evidence, but there is also great variability in its use in clinical practice. OBJECTIVE: To prepare a document with evidence-based recommendations about RIR in paediatric population. METHODS: The project was developed based on GRADE methodology, according to the following work schedule: Working Group training; creation of a catalogue of questions about research and definition of «relevant outcomes¼; score and selection criteria for each item; bibliographic review; scientific evidence evaluation and synthesis (GRADE); review, discussion and creation of recommendations. 10 clinical questions and 15 relevant outcomes were created (7 about efficacy and 8 about security). RESULTS: Sixteen recommendations were set up, from which we can highlight as the main ones: (1) RIR is safe for children affected by mild-moderate dehydration secondary to acute gastroenteritis, unless expressly contraindicated or acute severe comorbidity (strong recommendation and moderate evidence). (2) Its use is recommended in this situation when oral rehydration has failed or due to contraindication (strong and high). (3) Isotonic fluids are recommended (strong and high), suggesting saline fluid as the first option (light and low), supplemented by glucose (2.5%) in those patients showing normoglycemia and ketosis (strong and moderate). (4) A rhythm of 20 cc/kg/h is recommended (strong and high) during 1-4 h (strong and moderate). CONCLUSIONS: This document establishes consensus recommendations, based on the available scientific evidence, which could contribute to the standardisation of the use of RIR in our setting.