Reduced pertussis disease severity in infants following the introduction of pertussis vaccination of pregnant women in Spain, 2015-2019.

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.

Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis.

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.

Investigating Local Patterns of Mumps Virus Circulation, Using a Combination of Molecular Tools.

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.

Comparison of circulation patterns of mumps virus in the Netherlands and Spain (2015-2020).

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.

Utility of MF-non coding region for measles molecular surveillance during post-elimination phase, Spain, 2017-2020.

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.

An interregional measles outbreak in Spain with nosocomial transmission, November 2017 to July 2018.

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.

Epidemiology of Herpes Zoster in the pre-vaccination era: establishing the baseline for vaccination programme's impact in Spain.

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.

Meteorological conditions and Legionnaires' disease sporadic cases-a systematic review.

A number of studies suggest that meteorological conditions are related to the risk of Legionnaires' disease (LD) but the findings are not consistent. A systematic review was conducted to investigate the association of weather with sporadic LD and highlight the key meteorological conditions related to this outcome. PubMed, EMBASE, The Cochrane Library and OpenGrey were searched on 26-27 March 2020 without date, language or location restrictions. Key words included "legionellosis", "legionnaires' disease", combined with "meteorological conditions", "weather", "temperature", "humidity", "rain", "ultraviolet rays", "wind speed", etc. Studies were excluded if they did not examine the exposure of interest, the outcome of interest and their association or if they only reported LD outbreak cases. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and it was registered in PROSPERO (#CRD42020168869). There were 811 articles, of which 17 were included in the review. The studies investigated different meteorological variables and most of them examined the combined effect of several variables. The most commonly examined factors were precipitation and temperature, followed by relative humidity. The studies suggested that increased precipitation, temperature and relative humidity were positively associated with the incidence of LD. There was limited evidence that higher wind speed, pressure, visibility, UV radiation and longer sunshine duration were inversely linked with the occurrence of LD. A period of increased but not very high temperatures, followed by a period of increased precipitation, favour the occurrence of LD. Increased awareness of the association of temperature and precipitation and LD occurrence among clinicians and public health professionals can improve differential diagnosis for cases of sporadic community-acquired pneumonia and at the same time contribute to improving LD surveillance.

Considerations for COVID-19 management in reception centers for refugees, asylum seekers, and migrants, Spain 2020.

Shortly after the declaration of the COVID-19 pandemic, governments around the world were urged to leave no population behind. Following a COVID-19 risk evaluation in a refugee and asylum seekers reception center, in September 2020, we considered the priorities of managing COVID-19 in these settings. We encourage actions on the following four fronts to reduce the COVID-19-associated burden among these vulnerable populations based on our interviews, observations, and recommendations: (i) decongestion, (ii) facilitated testing, (iii) screening for symptoms, and (iv) targeted public health and risk communication.

An imported case of vaccine-derived poliovirus type 2, Spain in the context of the ongoing polio Public Health Emergency of International Concern, September 2021.

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.

Measles in Vaccinated People: Epidemiology and Challenges in Surveillance and Diagnosis in the Post-Elimination Phase. Spain, 2014-2020.

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.

[Surveillance and epidemiology of Herpes Zoster in Spain.] / Vigilancia y epidemiología del herpes zóster en España.

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.

OBJETIVO: El herpes zóster (HZ) aparece debido a la reactivación de la infección latente por el virus de la varicela-zóster y está asociado a la inmunosupresión y al envejecimiento. El HZ es de creciente importancia en las sociedades avanzadas. La vacunación se vislumbra como una potente herramienta para reducir el zóster y su principal complicación: la neuralgia postherpética. El objetivo de este estudio fue describir la tendencia temporal y la distribución por grupos de edad y sexo de los casos, hospitalizaciones y muertes por HZ en España entre 1998 y 2018. METODOS: Se analizaron los casos de HZ notificados a la Red Nacional de Vigilancia Epidemiológica entre 2014-2018, las hospitalizaciones por HZ del registro RAE-CMBD entre 1998-2018 y las muertes por HZ de la Estadística de Mortalidad del INE entre 1999-2018. Se calcularon: tasas de incidencia, hospitalización (TH) y mortalidad (TM) anual y de periodo; tasas globales y por grupos de edad y sexo, así como porcentaje y porcentaje acumulado de casos y hospitalizaciones por grupos de edad. RESULTADOS: La incidencia global de HZ se estimó en 351,6 por cada 100.000 habitantes y en 625,5 por cada 100.000 habitantes en personas de 50 años o más. La incidencia se incrementó con la edad, sobre todo a partir de los 50-54 años (incremento del 41% respecto al grupo de 45-49 años) y fue siempre más alta en mujeres. La TH global por HZ fue 6,75 por cada 100.000 habitantes y 15,7 por cada 100.000 habitantes en personas de 50 años o más. La TH fue creciendo con la edad, sobre todo a partir de los 60-64 años (incremento del 50% respecto al grupo de 54-59 años) y resultó siempre más alta en hombres. El 68,8% de casos y el 80,2% de hospitalizaciones por HZ ocurrieron a partir de los 50 años. CONCLUSIONES: En España, el HZ es una entidad frecuente y grave en adultos y personas mayores, que requiere intervenciones en Salud Pública. Los cambios demográficos y la incorporación de la vacunación exigen seguir monitorizando estrechamente el comportamiento del HZ en términos de incidencia y gravedad.

Molecular and Epidemiological Characterization of Toxigenic and Nontoxigenic Corynebacterium diphtheriae, Corynebacterium belfantii, Corynebacterium rouxii, and Corynebacterium ulcerans Isolates Identified in Spain from 2014 to 2019.

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.

Management of a COVID-19 outbreak in a hotel in Tenerife, Spain.

Since the first accounts of SARS-CoV-2, authorities have encountered numerous unprecedented situations threatening public health. This rapid communication addresses events that led to the quarantining of a hotel in Tenerife, Spain and the effectiveness of the rapidly implemented control measures. In total, eight cases have been associated with the hotel. Due to the international nature of the guests, had these timely precautions not been in place, a multinational cluster might have formed.

Last cases of rubella and congenital rubella syndrome in Spain, 1997-2016: The success of a vaccination program.

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.

Acute flaccid paralysis (AFP) surveillance: challenges and opportunities from 18 years' experience, Spain, 1998 to 2015.

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.

Genomic non-coding regions reveal hidden patterns of mumps virus circulation in Spain, 2005 to 2015.

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.

Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998-2014.

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.

Epidemiology of measles in vaccinated people, Spain 2003-2014. / Epidemiología del sarampión en personas vacunadas, España 2003-2014.

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.

[Epidemiologic Surveillance on Measles, Rubella and Congenital Rubella Syndrome. Spain].

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.