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MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary. [ABSTRACT FROM AUTHOR]

Objective: Comparison of statistical methods and measurement scales to identify nosocomial infection risk factors in intensive care units (ICU).Design: Prospective study in 558 patients admitted to the ICU of a referral hospital between February and November 1994.Methods: Analysis using three logistic regression models, three standard Cox regression models, and two Cox regression models with time-dependent extrinsic factors. Different scales were used to measure exposures to risk factors (dichotomous, ordinal, quantitative, and time-dependent variables).Results: The most appropriate models were those that measured exposure using dichotomous variables. Models using ordinal or quantitative variables estimated biased coefficients and/or failed to comply with the statistical assumptions underlying the analyses. The Cox regression model with quantitative time-dependent variables met all the statistical assumptions, obtained a precise assessment of risk by exposure time, and estimated unbiased coefficients.Conclusions: The Cox regression analysis with quantitative time-dependent variables is the most valid alternative for assessing the risk of nosocomial infection per day of exposure to an extrinsic risk factor in the ICU. [ABSTRACT FROM AUTHOR]

Contact tracing of individual exposed to any infectious measles case deserves special attention when in the country the disease is mostly imported. We present the coordinated public health actions triggered after reporting a suspected measles case in an aircraft. Spanish public health authorities and airlines responded promptly to allow a rapid contact tracing. Even one secondary measles case was reported no further transmission was identified, revealing that giving PEP and appropriate information help to avoid transmission and to maintain measles elimination in Spain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS)., Methods: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines., Results: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections., Conclusion: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings., (© 2024. The Author(s).)

Background: Maternal pertussis vaccination during the third trimester of pregnancy was implemented in 2015 in Spain, reaching a national coverage of 84% in 2019. In this ecological study, we investigated whether there was a change in the disease severity for pertussis in infants upon introduction of prenatal pertussis vaccination., Methods: We performed a time-trend analysis of infant pertussis hospitalizations during 2005-2019 in Spain using national register data. Annual hospitalization rates per 100,000 population and the mean length of hospitalization were calculated for infants < 3 months of age (target group benefiting from the prenatal vaccination) and a reference group aged 3-11 months. We compared overall rates and annual percent changes of the above variables in both groups for the time period before (2005-2014) and after vaccination introduction (2015-2019), using segmented Poisson regression., Results: During the pre-vaccination period, infants aged 0-2 months had a 5-times higher rate of pertussis hospitalization and spent on average 50 % longer in hospital than the reference group. After the maternal vaccination introduction, the hospitalization rate decreased more rapidly in infants aged 0-2 months than in infants aged 3-11 months: annual reduction of 34 % (95 % CI: 31-38) versus 26 % (95 % CI: 21-31) in the hospitalization rate and 13 % (95 % CI: 11-15) versus 6 % (95 % CI: 2-9) in the mean hospital stay, respectively. In 2019, the mean hospital stay for pertussis was about 4.5 days in both groups., Conclusions: Maternal pertussis vaccination in Spain led to a reduction in disease severity in the target group as compared to older infants, highlighting the need for increased efforts on educating healthcare professionals on the importance of maternal vaccinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Mumps is a vaccine-preventable disease caused by the mumps virus (MuV). However, MuV has re-emerged in many countries with high vaccine coverage. The World Health Organization (WHO) recommends molecular surveillance based on sequencing of the small hydrophobic (SH) gene. Additionally, the combined use of SH and non-coding regions (NCR) has been described in different studies, proving to be a useful complement marker to discriminate general patterns of circulation at national and international levels. The aim of this work is to test local-level usefulness of the combination of SH and MF-NCR sequencing in tracing hidden transmission clusters and chains during the last epidemic wave (2015-2020) in Spain. A database with 903 cases from the Autonomous Community of Madrid was generated by the integration of microbiological and epidemiological data. Of these, 453 representative cases were genotyped. Eight different SH variants and thirty-four SH haplotypes were detected. Local MuV circulation showed the same temporal pattern previously described at a national level. Only two of the thirteen previously identified outbreaks were caused by more than one variant/haplotype. Geographical representation of SH variants allowed the identification of several previously undetected clusters, which were analysed phylogenetically by the combination of SH and MF-NCR, in a total of 90 cases. MF-NCR was not able to improve the discrimination of geographical clusters based on SH sequencing, showing limited resolution for outbreak investigations.

Background: Mumps is a viral infection mainly characterized by inflammation of the parotid glands. Despite of vaccination programs, infections among fully vaccinated populations were reported. The World Health Organization (WHO) recommends molecular surveillance of mumps based on sequencing of the small hydrophobic (SH) gene. The use of hypervariable non-coding regions (NCR) as additional molecular markers was proposed in multiple studies. Circulation of mumps virus (MuV) genotypes and variants in different European countries were described in the literature. From 2010 to 2020, mumps outbreaks caused by genotype G were described. However, this issue has not been analyzed from a wider geographical perspective. In the present study, sequence data from MuV detected in Spain and in The Netherlands during a period of 5  years (2015- March 2020) were analyzed to gain insights in the spatiotemporal spread of MuV at a larger geographical scale than in previous local studies., Methods: A total of 1,121 SH and 262 NCR between the Matrix and Fusion protein genes (MF-NCR) sequences from both countries were included in this study. Analysis of SH revealed 106 different haplotypes (set of identical sequences)., Results: Of them, seven showing extensive circulation were considered variants. All seven were detected in both countries in coincident temporal periods. A single MF-NCR haplotype was detected in 156 sequences (59.3% of total), and was shared by five of the seven SH variants, as well as three minor MF-NCR haplotypes. All SH variants and MF-NCR haplotypes shared by both countries were detected first in Spain., Discussion: Our results suggest a transmission way from south to north Europe. The higher incidence rate of mumps in Spain in spite of similar immunization coverage in both countries, could be associated with higher risk of MuV exportation. In conclusion, the present study provided novel insights into the circulation of MuV variants and haplotypes beyond the borders of single countries. In fact, the use of MF-NCR molecular tool allowed to reveal MuV transmission flows between The Netherlands and Spain. Similar studies including other (European) countries are needed to provide a broader view of the data presented in this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gavilán, van de Nes-Reijnen, Castellanos, Woudenberg, López-Perea, Masa-Calles, Echevarría, Fernández-García and Bodewes.)

Background: In countries entering the post-elimination phase for measles, the study of variants by sequencing of 450 nucleotides of the N gene (N450) does not always allow the tracing of chains of transmission. Indeed, between 2017 and 2020, most measles virus sequences belonged to either the MVs/Dublin.IRL/8.16 (B3-Dublin) or the MVs/Gir Somnath.IND/42.16 (D8-Gir Somnath) variants. We evaluated the additional use of a non-coding region (MF-NCR) as a tool to enhance resolution and infer case origin, chains of transmission and characterize outbreaks., Methods: We obtained 115 high-quality MF-NCR sequences from strains collected from Spanish patients infected with either B3-Dublin or D8-Gir Somnath variants between 2017 and 2020, performed epidemiological, phylogenetic and phylodynamic analyses and applied a mathematical model to determine relatedness among identified clades., Results: Applying this model allowed us to identify phylogenetic clades potentially derived from concomitant importations of the virus rather than single chain of transmission, inferred based on only N450 and epidemiology data. In a third outbreak, we found two related clades that corresponded to two chains of transmission., Discussion: Our results show the ability of the proposed method to improve identification of simultaneous importations in the same region which could trigger enhanced contact tracing. Moreover, the identification of further transmission chains indicates that the size of import-related outbreaks was smaller than previously found, supporting the interpretation that endemic measles transmission was absent in Spain between 2017 and 2020. We suggest considering the use of the MF-NCR region in conjunction with the study of N450 variants in future WHO recommendations for measles surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jacqueline, Gavilán, López-Perea, Penedos, Masa-Calles, Echevarría, Fernández-García and on behalf of the MMR Study Group.)

Given sustained high vaccination coverage and enhanced surveillance for measles, Spain has been free of endemic measles transmission since 2014, achieving elimination certification from the World Health Organization in 2017. In November 2017, measles was introduced through an imported case travelling to the Valencian Community, causing an interregional outbreak. Here, we describe the outbreak using data reported to the national epidemiological surveillance network. The outbreak involved 154 cases (67 males, 87 females) notified in four regions; 148 were laboratory-confirmed and six epidemiologically linked. Most cases were adults aged 30-39 (n = 62, 40.3%) years. Sixty-two cases were hospitalised (40.3%) and 35 presented complications (22.7%). Two thirds of the cases (n = 102) were unvaccinated including 11 infants (≤ 1 year) not yet eligible for vaccination. The main route of transmission was nosocomial; at least six healthcare facilities and 41 healthcare workers and support personnel were affected. Sequencing of the viral nucleoprotein C-terminus (N450) identified genotype B3, belonging to the circulating MVs/Dublin.IRL/8.16-variant. Control measures were implemented, and the outbreak was contained in July 2018. The outbreak highlighted that raising awareness about measles and improving the vaccination coverage in under-vaccinated subgroups and personnel of healthcare facilities are key measures for prevention of future outbreaks.

BackgroundHerpes zoster (HZ) affects 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age and the presence of immunocompromising conditions. In Spain, vaccination guidelines were recently updated to include the recommendation of the new recombinant zoster vaccine (RZV) for certain risk groups.AimTo describe the epidemiology of HZ-related hospitalisations in Spain in order to prioritise vaccination recommendations and define a baseline to monitor the effectiveness of vaccination policies.MethodsRetrospective study using the National Health System's Hospital Discharge Records Database, including all HZ-related hospitalisations from 1998 to 2018.ResultsThe 65,401 HZ-related hospitalisations, corresponded to an annual mean hospitalisation rate of 6.75 per 100,000 population. There was an increasing trend of HZ hospitalisations over the study period. This rate was higher in males and older age groups, particularly over 65 years. Comorbidities with higher risk of readmission were leukaemia/lymphoma (RR 2.4; 95% CI: 2.3-2.6) and solid malignant neoplasm (RR 2.2; 95% CI: 2.1-2.4). Comorbidities associated with higher risk of mortality were leukaemia/lymphoma (RR 2.9; 95% CI: 2.7-3.2), solid malignant neoplasm (RR 2.9; 95% CI: 2.7-3.1) and HIV infection (RR 2.2; 95% CI: 1.8-2.7).ConclusionOf all patients hospitalised with HZ, those with greater risk of mortality or readmission belonged to the groups prioritised by the current vaccination recommendations of the Spanish Ministry of Health. Our study provided relevant information on clinical aspects of HZ and established the base for future assessments of vaccination policies.

The monthly retrospective search for unreported acute flaccid paralysis (AFP) cases conducted as a complementary component of the Spanish AFP surveillance system identified a case of AFP in a child admitted in Spain from Senegal during August 2021. Vaccine-derived poliovirus 2 was identified in the stool in September 2021. We present public health implications and response undertaken within the framework of the National Action Plan for Polio Eradication and the Public Health Emergency of International Concern.

The MMR vaccination program was introduced in Spain in 1981. Consistently high vaccination coverage has led to Spain being declared free of endemic measles transmission since 2014. A few imported and import-related cases were reported during the post-elimination phase (2014 to 2020), with very low incidence: three cases per million of inhabitants a year, 70% in adults. In the post-elimination phase an increasing proportion of measles appeared in two-dose vaccinated individuals (up to 14%), posing a challenge to surveillance and laboratory investigations. Severity and clinical presentation were milder among the vaccinated. The IgM response varied and the viral load decreased, making the virus more difficult to detect. A valid set of samples (serum, urine and throat swab) is strongly recommended for accurate case classification. One third of measles in fully vaccinated people was contracted in healthcare settings, mainly in doctors and nurses, consistent with the important role of high intensity exposure in measles breakthrough cases. Surveillance protocols and laboratory algorithms should be adapted in advanced elimination settings. Reinforcing the immunity of people working in high exposure environments, such as healthcare settings, and implementing additional infection control measures, such as masking and social distancing, are becoming crucial for the global aim of measles eradication.

Objective: Herpes Zoster (HZ) results from reactivation of latent varicella-zoster virus infection and is associated with immunosuppression and ageing. HZ is of increasing importance in advanced societies. Vaccination appears as a powerful tool to reduce HZ as well as postherpetic neuralgia, the main zoster complication. This study aims to describe the temporal trend, the age and sex distribution of cases, hospitalisations and deaths by zoster occurred in Spain between 1998 and 2018., Methods: The available information for zoster in Spain were used: cases from National Surveillance System (2014-2018), registries from Spanish hospitalisation database (1998-2018) and deaths from the Spanish mortality statistics (1999-2018). Incidence, hospitalization (HR) and mortality (MR) rates per year and period were calculated. Rates by age group and sex as well as percentage and cumulative percentage for cases and hospitalisations by age group, were also calculated., Results: The global HZ incidence was 351.6/100,000 inhabitants and 625.5/100,000 among population aged 50 and over. The incidence increases with age, especially from the age of 50-54 years (41% increase over the 45-49 age group) and is always higher in women. The global HR was 6.75/100,000 and 15.7/100,000 in persons aged 50 and over; HR increases with age, especially from 60-64 years onwards (50% increase over 54-59 age group) and is always higher in men. The 68.8% of cases and 80.2% of hospitalisations for HZ occurred from the age of 50., Conclusions: In Spain HZ is a frequent and severe entity in adults and elderly people requiring public health interventions. The demographic changes and the introduction of vaccination require continued monitoring of HZ behaviour in terms of incidence and severity., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

This study examines the microbiological and epidemiological characteristics of toxigenic and nontoxigenic Corynebacterium isolates submitted to the national reference laboratory in Spain, between 2014 and 2019, in order to describe the current situation and improve our knowledge regarding these emerging pathogens. Epidemiological information was extracted from the Spanish Surveillance System. Microbiological and molecular characterization was carried out using phenotypic methods, multilocus sequence typing (MLST), whole-genome sequencing (WGS), and core genome MLST (cgMLST). Thirty-nine isolates were analyzed. Twenty-one isolates were identified as Corynebacterium diphtheriae (6 toxigenic), 14 as C. belfantii , 4 as C. ulcerans (3 toxigenic), and 1 as C. rouxii One C. diphtheriae isolate was identified as nontoxigenic tox gene bearing (NTTB). Ages of patients ranged from 1 to 89 years, with 10% (3/30) of nontoxigenic and 22% (2/9) of toxigenic isolates collected from children less than 15 years. Twenty-five of the patients were males (17/30 in nontoxigenic; 8/9 in toxigenic). MLST identified 28 sequence types (STs), of which 7 were described for the first time in Spain. WGS analysis showed that 10 isolates, including 3 toxigenic isolates, harbored a variety of antibiotic resistance genes in addition to the high prevalence of penicillin resistance phenotypically demonstrated. Phylogenetic analysis revealed one cluster of isolates from family members. Risk information was available for toxigenic isolates (9/39); 3 patients reported recent travels to countries of endemicity and 3 had contact with cats/dogs. One unvaccinated child with respiratory diphtheria had a fatal outcome. Including nontoxigenic Corynebacterium infections in disease surveillance and using WGS could further improve current surveillance., (Copyright © 2021 American Society for Microbiology.)

With a highly immunized population, rubella infection in Spain is so low that the WHO has declared the elimination of rubella. Rubella in pregnant women is also very rare. The objective of this study is to describe the last cases of congenital rubella syndrome reported and recommend actions to maintain the status of the disease as eliminated. The CRS cases reported to the Spanish National Epidemiological Surveillance Network between 1997 and 2016 were studied, and the epidemiological, clinical, diagnostic and maternal characteristics of newborns with CRS described. The incidence of CRS was calculated using Birth Statistics from the Spanish National Statistics Agency (INE). Twenty-three cases of CRS were reported, 70% of which were associated with rubella outbreaks. The most common clinical conditions were heart disease (52.2%), deafness (39.1%) and cataracts (30.4%); 91.3% of cases were confirmed by laboratory testing. 70.0% were born from a non-vaccinated foreign mother, resident in Spain (cumulative rate incidence (CR): 1.1/100,000 births), with mothers coming from Africa (36.0%), Latin America (29.0%), Eastern Europe (21.0%) and Asia (14.0%). Six were born to Spanish mothers (CR: 0.08/ 100,000 births), the last of which were in 2005. The majority of CRS cases were born to unvaccinated immigrant women infected in Spain during rubella outbreaks. Universal vaccination in childhood is the most efficient strategy to prevent rubella. The limited circulation of the virus will, however, quickly lead to a loss of awareness about rubella among clinicians and epidemiologists. It is necessary to maintain protocols capable of identifying signs consistent with rubella in pregnant women and signs suggestive of congenital rubella in newborns., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Acute flaccid paralysis (AFP) surveillance is key for global polio eradication. It allows detecting poliovirus (PV) reintroductions from endemic countries. This study describes AFP surveillance in Spain from 1998 to 2015. During this time, 678 AFP cases were reported to the Spanish National Surveillance Network. The mean notification rate was 0.58 AFP cases/100,000 population under 15 years old (range: 0.45/100,000-0.78/100,000). Two periods (P) are described: P1 (1998-2006) with the AFP notification rate ranging from 0.66/100,000 to 0.78/100,000, peaking in 2001 (0.84/100,000); and P2 (2007-2015) when the AFP rate ranged from 0.43/100,000 to 0.57/100,000, with the lowest rate in 2009 (0.31/100,000). No poliomyelitis cases were caused by wild PV infections, although two Sabin-like PVs and one imported vaccine-derived PV-2 were detected. Overall, 23 (3.4%) cases met the hot case definition. Most cases were clinically diagnosed with Guillain-Barré syndrome (76.9%; 504/655). The adequate stool collection rate ranged from 33.3% (7/21) to 72.5% (29/40). The annual proportion of AFP cases with non-polio enterovirus findings varied widely across the study period. AFP surveillance with laboratory testing for non-polio enteroviruses must be maintained and enhanced both to monitor polio eradication and to establish sensitive surveillance for prompt detection of other enteroviruses causing serious symptoms.

In recent decades, vaccination has substantially reduced the number of measles cases to levels close to the elimination stage. However, major measles outbreaks occurred in Europe during 2010-2012, after the introduction of the D4-Enfield lineage. We have performed a molecular characterization of 75 measles virus genotype D4 strains from patients infected in Spain between 2004 and 2012 by sequencing the N-450 region and the M-F non-coding region (M-F NCR) in order to identify genetic features of these viruses. The analysis of the N-450 region confirmed that all samples obtained since 2008 belonged to variants or sets of identical sequences of the D4-Enfield lineage, including a new one named MVs/Madrid.ESP/46.10/. Analysis of the M-F NCR showed insertions and deletions associated with previously described, uncommon non-standard genome length measles viruses. This genetic feature was identified in the D4-Enfield lineage viruses, but not in the other D4 viruses that were circulating in Spain before 2008, suggesting that these non-standard length M-F NCR sequences are characteristic of the D4-Enfield lineage. The results of the phylogenetic analysis of Spanish M-F NCRs suggest higher resolution in discriminating strains than did the N-450 analysis. In addition, the results of the analysis of the M-F NCR on the MVs/Madrid.ESP/46.10/ sub-lineage seem to support the potential utility of this region as a tool for epidemiological surveillance complementary to the N-450 region, as previously suggested. Further investigation on this question, as well as the surveillance of new potentially emerging strains with non-standard length M-F NCR are strongly recommended as part of future strategies for measles elimination., Competing Interests: The authors have declared that no competing interests exist.

BackgroundSince mumps vaccination was introduced in 1981 in Spain, the incidence of the disease has dropped significantly. However, cyclic epidemic waves and outbreaks still occur, despite high vaccination coverage. The World Health Organization (WHO) recommends genotyping to trace the pattern of mumps virus (MuV) circulation. Genotype H was predominant in Spain, but was replaced in 2005 by genotype G which has subsequently remained dominant. Of the small hydrophobic protein gene sequences, 78% are identical and belong to the MuVi/ Sheffield.GBR.1.05/[G]-variant. Aim: Our study aimed to investigate whether the circulation of MuV strains in Spain was continuous after the emergence of genotype G in 2005. Method: We obtained 46 samples from Spanish patients infected with MuVi/Sheffield.GBR.1.05/[G] during two epidemic waves and analysed them using new molecular markers based on genomic non-coding regions (NCRs) that discriminate subvariants of this virus strain. Results: Phylogenetic analyses of the nucleoprotein-phosphoprotein and matrix protein-fusion protein NCR indicated strain replacement after a drop in incidence in 2009, which had not been detectable by SH sequencing. Clustering of sequences from patients epidemiologically linked in the same outbreak suggests a potential use for these NCRs in outbreak characterisation. Conclusion: We suggest to consider their use in conjunction with the SH gene in the future WHO recommendations for MuV epidemiological surveillance.

Enterovirus D68 was known to be the cause of mild to severe respiratory infections, but in the last few years, it has also been associated with myelitis and paralysis. This report describes the first Enterovirus D68 detections in acute flaccid paralysis cases occurring between December 2015 and March 2016 in Spain.

Introduction: During the final phase of measles elimination rigorous investigation of each individual case becomes fundamental to confirm or discard cases, particularly among vaccinated people, since they experience a milder disease, and laboratory diagnosis is more complex. Our study focused in the epidemiology of measles in vaccinated people., Methods: Longitudinal study on measles cases in two dose vaccinated people in Spain from 2003 to 2014., Results: We confirmed 138 measles cases (90 of them, laboratory confirmed) in people with two doses of vaccine. The median of time from last vaccination to rash onset showed a lineal trend (P<.001), in parallel with the number of doses of vaccine received (0, 1, 2 doses). Among confirmed cases, the hospitalization risk decreased inversely proportional to the number of administered vaccine doses (linear trend, P<.001). Only in 23.9% of confirmed cases and 50% of discarded cases the guidelines about sample taking were fulfilled. 50% of samples in two dose vaccinated people were taken without fulfilling time delay criteria. 16.7% (36/215) of discarded cases with a negative IgM result did correspond to samples taken early (first 72h after rash) and could represent false negatives., Conclusion: Our results highlight the importance of fulfilling properly the guidelines for laboratory diagnosis in order to confirm or discard every measles case, especially in two dose vaccinated people. When a negative IgM result is obtained in early samples a new IgM test should be practiced, as well as a PCR test, in order to avoid infra-detection of cases., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

The mumps vaccine (Jeryl-Lynn-strain) was introduced in Spain in 1981, and a vaccination policy which included a second dose was added in 1995. From 1992-1999, a Rubini-strain based vaccine was administered in many regions but later withdrawn due to lack of effectiveness. Despite high levels of vaccination coverage, epidemics have continued to appear. We characterized the three epidemic waves of mumps between 1998 and 2014, identifying major changes in susceptible populations using Poisson regression. For the period 1998-2003 (P1), the most affected group was from 1 to 4years old (y) [Incidence Rate (IR)=71.7 cases/100,000 population]; in the periods 2004-2009 (P2) and 2010-2014 (P3) IR ratio (IRR) increased among 15-24y (P2=1.46; P3=2.68) and 25-34y (P2=2.17; P3=4.05). Hospitalization rate (HR), complication rate (CR) and neurological complication rate (NR) among hospitalized subjects decreased across the epidemics, except for 25-34y which increased: HR ratio (HRR) (P2=2.18; P3=2.16), CRR (P3=2.48), NRR (P3=2.41). In Spain mumps incidence increased, while an overall decrease of hospitalizations and severe complications occurred across the epidemics. Cohorts born during periods of low vaccination coverage and those vaccinated with Rubini-strain were the most affected populations, leading to a shift in mumps cases from children to adolescents and young adults; this also reveals the waning immunity provided by the mumps vaccine. Despite not preventing all mumps cases, the vaccine appears to prevent serious forms of the disease., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pertussis is a re-emerging disease worldwide despite its high vaccination coverage. European and Latin-American countries have used different surveillance and vaccination policies against pertussis. We compared the epidemiology of this disease in two Ibero-American countries with different vaccination and surveillance policies., Methods: We compared the epidemiology of pertussis in Spain and the Dominican Republic (DR). We present a 10-year observational study of reported pertussis based on suspected and/or probable cases of pertussis identified by the national mandatory reporting system in both countries between 2005 and 2014. Both countries have a similar case definition for pertussis surveillance, although Spain applies laboratory testing, and uses real time PCR and/or culture for case confirmation while in DR only probable and/or suspected cases are reported. We analyzed incidence, hospitalization, case-fatality rates, mortality and vaccination coverage., Results: The average annual incidence in children aged <1 year was 3.40/100,000 population in Spain and 12.15/100,000 in DR (p = 0.01). While the incidence in DR was generally higher than in Spain, in 2011 it was six times higher in Spain than in DR. The highest infant mortality in Spain was 0.017/100,000 in 2011, and the highest in DR was 0.08/100,000 in 2014 (p = 0.01). The proportion of hospitalized cases per year among children <1 year varied between 22.0% and 93.7% in Spain, and between 1.1% and 29.4% in DR (p = 0.0002), while mortality varied from 0 to 0.017 and 0 to 0.08 per 100,000 population in Spain and DR, respectively (p = 0.001). Vaccination coverage was 96.5% in Spain and 82.2% in DR (p = 0.001)., Conclusions: Pertussis is a public health problem in both countries. Surveillance, prevention and control measures should be improved, especially in DR. Current vaccination programs are not sufficient for preventing continued pertussis transmission, even in Spain which has high vaccination coverage.

To achieve the goal of eliminating measles and rubella two key strategies have been defined: sustain very low level of population susceptibility and strengthen surveillance system by rigorous case investigation and rapid control measures implementation. Surveillance of measles, rubella and CRS are included into the Spanish Surveillance System (RENAVE); surveillance is mandatory, passive, nationwide and case-based with laboratory information integrated. Information flows from sub national to national level (National Centre for Epidemiology) and then, to the WHO-Europe through ECDC. In the final phase of elimination, good surveillance and documented evidences are keys. Information on epidemiology of measles, rubella and CRS cases and outbreaks, pattern of importation, genotypes circulating and performance of measles and rubella surveillance are required at national and international level. Also all investigated and discarded measles or rubella cases should be reported. Currently the system faces some challenges gathering needed information for documenting the elimination. As long as the disease incidence declines, increases difficulties in identifying clinical measles and rubella because of non-specific prodromal signs and atypical cases. Differential diagnosis for fever and rash including measles and rubella should be performed in all clinical settings. Three clinical specimens must be collected to confirm or discard cases and to allow the virus characterization in order to know the pattern of importation of measles and rubella.

In Spain, whole cell pertussis vaccination started in 1975, with three doses before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005. From 1998 to 2009, pertussis incidence rates remained ≤1.5 cases/100,000 inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998 to 2012 were analysed to assess disease trends and susceptible populations. We defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010-12. In 2002-05, the incidence rate increased in individuals aged 15-49 years (IRR: 1.41 (95% CI: 1.11-1.78)) and ≥50 years (IRR: 2.78 (95% CI: 1.78-4.33)) and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60-2.09)). In 2010-12, the incidence rate increased notably in all age groups, with IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI: 19.4-66.8) in 20-29 year-olds. These results, consistent with the country's vaccination history, suggest a progressive accumulation of susceptible individuals due to waning immunity after years of low incidence. Further vaccination strategies should be assessed and implemented to prevent pertussis in pre-vaccinated infants, in whom the disease is more severe.

Background: On the 4th of February 2008, 2 cases of measles, epidemiologically linked (2 members of the crew of the Fast-Ferry Jaime I from the company Balearia, which performs the route Algeciras-Tangier), were notified to the Epidemiological Surveillance Network in Andalusia (SVEA). The aim of this paper is to epidemiologically characterize this population level outbreak detected in the area of Campo de Gibraltar, the vaccine effectiveness and the control measures implemented., Methods: Descriptive observational study of reported cases. We have analysed the following variables: age, sex, municipality of residence, onset date, virus genotype, groups involved, previous immunization status, interventions, vaccine effectiveness. Information sources are SVEA records, vaccination program and individual digital story (Diraya). Rates 10(5) were calculated according to age group and frequency measurements. To compare vaccine effectiveness, the Chi(2) test was used., Results: We confirmed 155 cases of measles, 88.4% by laboratory techniques. Most affected age groups under 2 years (19%) and from 21 to 40 (51%). The 54.2% male. The 72,14% were not vaccinated. Virus was isolated from imported measles genotype D4. The vaccine efficacy was greater than 99%., Conclusions: The outbreak of the imported measles virus was confirmed. More than half of the cases were not vaccinated. The decrease in the incidence in vaccinated individuals recommends the necessity of carrying out Catch-Up campaigns to increase the coverage therefore avoiding the appearance of these outbreaks.

Objective: To evaluate the association between nosocomial infections (NI) and the mortality of Intensive Care Unit (ICU) patients, adjusting for the effect on mortality of other predictive variables., Methods: Prospective study on 944 concurrent patients admitted for at least 24 hours in the ICU of a tertiary level hospital between February and November of 1994. The association between NI (diagnosed using CDC criteria) and mortality was studied using multivariable logistic regression., Results: The cummulative incidence of mortality in the ICU was 11.2% (CI95% = 9.9-12.5). This incidence was significantly higher in infected patients with a crude mortality relative risk of 2.2 (CI95% = 1.5-3.1). In the multivariable analysis, the effect of NI (global, pneumonias, of the urinary tract and bacteriemias) on adjusted mortality depended on the patient's Acute Pysiology and Chronic Health Evaluation II (APACHE II) score. With low APACHE II scores, NI was associated with an increased mortality risk. Conversely, with higher APACHE II scores, the relevance of NI as a determinant of mortality decreased and prognosis was mainly associated with the patient's severity of illness., Conclusions: The association between NI and mortality, adjusting for other prognostic factors for mortality, is confirmed.

Objective: To identify risk factors predictive of nosocomial infection in an intensive-care unit (ICU) and to identify patients with a higher risk of nosocomial infection using a predictive model of nosocomial infection in our ICU., Design: Prospective study; daily concurrent surveillance of intensive-care-unit patients., Setting/patients: All patients admitted for at least 24 hours to the ICU of a tertiary-level hospital from February to November 1994 were followed daily., Methods: Variables measuring extrinsic and intrinsic risk factors for nosocomial infection were collected on each patient during their ICU stay, and the Cox Proportional Hazards multivariable technique was used to identify the variables significantly associated with infection., Results: The population studied consisted of 944 patients. The main risk factors identified were intrinsic; the significant extrinsic risk factors identified were head of the bed in a horizontal (< 30 degrees) position (this variable presented the highest increase of the infection hazard ratio) and the use of sedative medication. Patients presenting the highest risk scores using the predictive model are those with the highest risk of nosocomial infection., Conclusions: The important preventive measures derived from our results are that underlying conditions suffered by the patient at the ICU admission should be corrected promptly, the depression of the patient's level of consciousness with sedatives should be monitored carefully, and the horizontal position of the head of the bed should be avoided totally. Patients with a high risk of infection can be the target of special preventive measures.

Background: To identify nosocomial infection risk factors in an intensive care unit and construct a predictive model that will enable future risk-adjusted comparisons of infection incidences., Patients and Methods: Prospective surveillance of pneumonia, bacteremia and urinary tract infections in intensive care unit patients. All patients (n = 944) admitted to the intensive care unit for at least 24 h were followed daily in a tertiary level hospital. Variables measuring extrinsic as well as intrinsic risk factors for nosocomial infections were collected from each patient during their intensive care unit stay and the Cox proportional hazards multivariable technique was applied to identify the variables mostly associated with infection in our hospital., Results: The main risk factors identified for pneumonias were intrinsic. The hazard ratios (HR) of two extrinsic risk factors were noteworthy: mechanical ventilation (HR = 7.51; 95% CI = 2.95-19.13) and sedation (HR = 2.01; 95% CI = 1.14-3.56). The extrinsic factors associated with bacteremias were, the sum of extrinsic risk factors (HR = 1.52; 95% CI = 1.17-1.97) and having a tracheostomy (HR = 3.61; 95% CI = 1.99-6.56). The urinary tract infections were negatively associated with the administration of antibiotics prior to infection onset (HR = 0.41; 95% CI = 0.21-0.78) and the male sex (HR = 0.40; 95% CI = 0.22-0.75). Conversely, urinary tract infections were positively associated with the presence of cancer (HR = 2.70; 95% CI = 1.03-7.11) and the APACHE II index (for every 5 units of increase of the APACHE II index, HR = 1.39; 95% CI = 1.09-1.79)., Conclusions: The most important risk factors identified for pneumonias and urinary tract infections in intensive care unit patients were endogenous, whereas they were exogenous for bacteremias.

Background: Accidents resulting from percutaneous exposure account for approximately one third of all accidents suffered at work by health workers in hospitals. Their importance lies in the illnesses caused by pathogens that can be transmitted in this way (hepatitis B, hepatitis C, HIV virus). The aims are to describe accidents of this type notified in a tertiary level hospital, identify factors associated with these accidents in nursing staff and build a predictive model for the individual risk of having an accident., Methods: A descriptive study of a retrospective cohort made up of all the people who notified having suffered an accident between 1-1-93 and 30-6-96. A study of cases and controls in nursing staff during the period 1-1-95 to 30-6-96, analysed through multiple logistical regression., Results: The cumulative incidence of cases of accidents in one year was 0.078 for male and female nurses. In 57.3% of cases, disposable or pre-loaded syringes were involved. The cumulative incidence of cases in one year was greater for intravenous catheterisation (8.5% per 100,000). The risk of having an accident, adjusted on account of confusing variables, was greater for female and male nurses (OR = 3.22; I.C.95% = 1.96-5.27), or workers in the Haemodialysis Unit (OR = 35.21; I.C.95% = 3.74-331.16) and for those employed on a temporary contract (OR = 4.50; I.C.95% = 2.24-9.04)., Conclusions: Accidents resulting from percutaneous exposure at this hospital are more frequent among nursing staff and are basically caused by any type of hollow needles. Factors associated with these accidents were identified, allowing specific prevention programmes to be targeted at those workers at greater risk. The model obtained is valid to estimate the degree of individual accident probability for the subjects studied.

Background: The constant increase of pharmaceutical costs is of great concern to the administrators of the Spanish National Health Service. Antibiotics administered as prophilaxis prior to surgery, play an important role in this increase. The compliance of physicians with protocols for chemoprophylaxis is therefore an important factor in the control of these pharmaceutical costs. The degree of compliance with the pre-established protocols of prophylaxis prior to surgery are examined in a tertiary level hospital during 1992 and the extra costs due to the lack of compliance with these protocols are estimated using a sample of 371 subjects. The object of this study is to describe the degree of the fulfillment of the protocols of surgical chemoprophylaxis in a tertiary level hospital and to estimate the minimum additional cost due to the wrong chemoprophylaxis., Methods: A descriptive study was made of the surgical prophylaxis using a sample of 371 subjects. The cost was estimated from the price of the antibiotics administered., Results: A total of 267 (71.9% IC95% = 67.3-76.5) subjects had received incorrect prophylaxis. The most important causes of incorrect prophylaxis were the wrong antibiotic choice and the excessive duration of their administration. The incorrect prophylaxis was responsible for an additional cost of 1,117,287 ptas. The application of these estimates to the entire 1992 surgical population, at our center, would yield an estimated additional cost of 39,409,965 pesetas., Conclusions: Our health services would have substantial savings if protocols for prophylaxis prior to surgery were strictly followed by physicians.

The interregional variation coefficient (VC) has been considered as an accurate measure of the dispersion of regional infant, neonatal, postneonatal and perinatal mortality rates. Thus, trends of annual VC have been analyzed, for each rate, from 1940 to 1986, to identify the evolution in time of the regional differences with respect to these mortality rates. None of the four mortality rates showed a decreasing trend in their respective VCs. This may indicate that interregional differences do not change along time. The postneonatal mortality rate has been shown to have the highest VCs during the study period (ranging from 23 to 40%), with an independent evolution with respect to neonatal mortality rate, probably because the factors that influence both rates are clearly different.