Increase of Diversity of Mumps Virus Genotype G SH Variants Circulating Among a Highly Immunized Population: Spain, 2007-2019.

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.

Seroepidemiology of varicella zoster virus infection in Vojvodina, Serbia.

The present cross-sectional serosurvey constitutes the first effort to describe the varicella zoster virus (VZV) seroepidemiology in Serbia. An age-stratified serum bank of 3570 residual samples collected between 2015 and 2016 in each of the seven districts of the Vojvodina Province was tested for IgG anti-VZV antibodies with an enzyme immunoassay. Results were standardised into common units according to the European Sero-Epidemiology Network (ESEN2) methodology. Univariable and multivariable analyses were used to examine the relationships between standardised anti-VZV positivity or logarithmically transformed antibody titres and demographic features of study subjects. Seropositivity (85% overall) increased with age, in parallel with geometric mean titres. By the time of school entry, 68% of children were immune. The slower subsequent acquisition of immunity leaves epidemiologically relevant proportions of adolescents (7%), young adults (6%) and especially females of reproductive age (6%) prone to more severe forms of varicella. In the ongoing pre-vaccine era, natural infection provides a high level of collective immunity, with the highest VZV transmission in children of preschool age. The detected gaps in VZV immunity of the Serbian population support the adoption of the official recommendations for varicella immunisation of non-immune adolescents and young adults, including non-pregnant women of childbearing age.

Prevalence of anti-rubella, anti-measles and anti-mumps IgG antibodies in neonates and pregnant women in Catalonia (Spain) in 2013: susceptibility to measles increased from 2003 to 2013.

Non-immune neonates and non-immune pregnant women are at risk of developing rubella, measles and mumps infections, including congenital rubella syndrome. We describe the seroepidemiology of measles, mumps and rubella (MMR) in neonates and pregnant women in Catalonia (Spain). Anti-rubella, anti-measles and anti-mumps serum IgG titres were assessed using enzyme-linked immunosorbent assay (ELISA) tests in 353 cord blood samples from neonates of a representative sample of pregnant women obtained in 2013. The prevalence of protective antibody titres in neonates was 96 % for rubella IgG (≥8 IU/ml), 90 % for measles IgG (>300 IU/ml) and 84 % for mumps IgG (>460 EU/ml). Slightly lower prevalences of protective IgG titres, as estimated from the cord blood titres, were found in pregnant women: 95 % for rubella IgG, 89 % for measles IgG and 81 % for mumps IgG. The anti-measles and anti-mumps IgG titres and the prevalences of protective IgG titres against measles and mumps increased significantly (p < 0.001) with maternal age. The prevalence of protective anti-measles IgG titres decreased by 7 % [odds ratio (OR) = 0.15, p < 0.001), the prevalence of protective anti-rubella IgG titres increased by 3 % (OR = 1.80, p < 0.05) and the MMR vaccination coverage (during childhood) in pregnant women increased by 54 % (OR = 2.09, p < 0.001) from 2003 to 2013. We recommend to develop an MMR prevention programme in women of childbearing age based on mass MMR vaccination or MMR screening and vaccination of susceptible women to increase immunity levels against MMR.

Estimating seroprevalence of vaccine-preventable infections: is it worth standardizing the serological outcomes to adjust for different assays and laboratories?

The aim of the European Sero-Epidemiology Network 2 (ESEN2) project was to estimate age-specific seroprevalence for a number of vaccine-preventable diseases in Europe. To achieve this serosurveys were collected by 22 national laboratories. To adjust for a variety of laboratory methods and assays, all quantitative results were transformed to a reference laboratory's units and were then classified as positive or negative to obtain age-specific seroprevalence. The aim of this study was to assess the value of standardization by comparing the crude and standardized seroprevalence estimates. Seroprevalence was estimated for measles, mumps, rubella, diphtheria, varicella zoster and hepatitis A virus (HAV) and compared before and after serological results had been standardized. The results showed that if no such adjustment had taken place, seroprevalence would have differed by an average of 3·2% (95% bootstrap interval 2·9-3·6) although this percentage varied substantially by antigen. These differences were as high as 16% for some serosurveys (HAV) which means that standardization could have a considerable impact on seroprevalence estimates and should be considered when comparing serosurveys performed in different laboratories using different assay methods.

Molecular characterization of enteroviruses associated with neurological infections in Spain, 2008.

In order to investigate the etiology of viral neurological infections in Spain, a national study was performed in 2008. The results obtained have been published. Enteroviruses were the most frequent cause of the aseptic meningitis and infant febrile syndromes. The present report supplements the previous study with the genotyping of the detected enteroviruses. Typing was by amplification of partial VP1 region and sequencing in 70 (53%) of the 132 available cerebrospinal fluid samples positive for enteroviruses. Twelve different genotypes within the B species were identified. Echovirus 4 was predominant (24%), followed by echovirus 30 (19%), echovirus 9 (17%), and echovirus 6 (14%). In summary, a co-circulation of several enterovirus types associated with meningitis in children under 15 years old was observed. Although infrequently detected, echovirus 4 was the predominant genotype identified due to an aseptic meningitis outbreak which occurred in the Canary Islands in 2008.

Viral infections of the central nervous system in Spain: a prospective study.

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.

Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Circulation of mumps virus genotypes in Spain from 1996 to 2007.

Although the WHO recommends the use of genotyping as a tool for epidemiological surveillance for mumps, limited data on mumps virus (MV) genotype circulation that may be used to trace the patterns of virus spread are available. We describe the first complete series of data from Spain. The small hydrophobic region was sequenced from 237 MV-positive samples from several regions of Spain collected between 1996 and 2007. Six different genotypes were identified: A, C, D (D1), G (G1, G2), H (H1, H2), and J. Genotype H1 was predominant during the epidemic that occurred from 1999 to 2003 but was replaced by genotype G1 as the dominant genotype in the epidemic that occurred from 2005 to 2007. The same genotype G1 strain caused concomitant outbreaks in different parts of the world (the United States, Canada, and the United Kingdom). The remaining genotypes (genotypes A, C, D, and J) appeared in sporadic cases or small limited outbreaks. This pattern of circulation seems to reflect continuous viral circulation at the national level, despite the high rates of vaccine coverage.

Eliminating congenital rubella syndrome in Spain: does massive immigration have any influence?

In this short report we highlight the importance of implementing good immunization programs adapted to the epidemiological situation of rubella and congenital rubella syndrome (CRS), discuss the influence of massive immigration and stress the need to improve surveillance and control by implementing comprehensive national surveillance and promoting awareness among primary healthcare workers and midwives to find out any signs and symptoms compatible with rubella in pregnant women who have recently arrived from countries with high susceptibility to rubella infection.

Analysis of the surveillance situation for viral encephalitis and meningitis in Europe.

Infective processes in the brain, spinal cord and meninges are considered to be the main causes of encephalitis, myelitis and meningitis. However, most cases remain unexplained. The incidence of different viral aetiologies (zoonotic and non-zoonotic) is especially poorly estimated, due to the lack of a standard case definition and of agreed diagnostic algorithms, including harmonised diagnostic methods and sample collection. It is important to clarify the incidence of viral encephalitis/meningitis and to optimise the diagnosis of infectious neurological illness, particularly to ensure early recognition of outbreaks or emerging infectious such a West Nile encephalitis. The European Network for Diagnostics of 'Imported' Viral Diseases (ENIVD) has analysed the present surveillance situation for viral encephalitis/meningitis in Europe. Here we give an overview of the existing epidemiological sources of information in European Union (EU) Member States, mapping the laboratory capacity and identifying key requirements for a possible future surveillance study at European level. The data presented will help design a harmonised/standardised Europe-wide surveillance study investigating patients with encephalitis and/or meningitis in order to obtain more information on the role of infections in these rarely analysed syndromes, both from a clinical and an epidemiological perspective.

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract).

Yellow fever vaccine-associated viscerotropic disease and death in Spain.

Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a recently described severe adverse event after yellow fever vaccination, and some cases have been reported in different countries [Anonymous. Effects of yellow fever and vaccination. Lancet 2001;358(9296):1907-9]. Herein we describe a YEL-AVD case in a young woman, who died after vaccination with 17D-204 strain. Clinical, serological and immunochemical analysis as well as virus detection, quantification, sequence analysis and cytokine release, were performed. Further investigations on yellow fever vaccine adverse events, and carefully analysis of the immune response elicited are important tasks for the future.

Virological analysis in the diagnosis of sudden children death: a medico-legal approach.

Infections are considered to be an important cause of unexpected death in children. It has also been assumed that respiratory viruses are involved in the genesis of sudden infant death syndrome (SIDS). The Spanish National Institute of Toxicology and Forensic Sciences act as the forensic reference centre for Spain. We analyse the experience of this centre in the virological study of 64 cases of sudden children death where viral serology, virological cultures, herpesviruses polymerase chain reaction (PCR) and electron microscopy were performed. According to pathological findings, death could only be attributed to an adenovirus infection in one amygdalitis with upper airways stenosis and asphyxia. Human herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile, 85.9% of the cases yielded negative viral results. Twenty-eight infants were finally categorised as SIDS. Pathological findings of infection were detected in 12 patients despite the negativity of viral analyses. Although viral infection is an uncommon cause of sudden children death, a complete microbiological investigation will help to solve the puzzle of SIDS. Definitive guidelines for microbiological analyses need to be updated whilst new pathogens are discovered or new techniques are implemented in order to clarify unsolved cases.

A measles outbreak in children under 15 months of age in La Rioja, Spain, 2005-2006.

This paper describes a measles outbreak in La Rioja, Spain, which began in December 2005 and mainly affected children under 15 months of age who were not yet immunised with MMR vaccine. The measles cases were detected by the mandatory reporting system, under which laboratories must report every confirmed measles case. Cases were classified in accordance with the National Measles Elimination Plan: suspected and laboratory-confirmed. In the period 14 December 2005 to 19 February 2006, 29 suspected cases of measles were investigated, and 18 were confirmed. The mean incubation period was 13.8 days (range: 9 to 18). Of the 18 confirmed cases, only two were in adults. MMR vaccination was recommended for all household contacts, as well as for children aged 6 to 14 months who attended the daycare centres where the cases had appeared. At these centres, the second dose of MMR was administered ahead of schedule for children under three years of age. It was recommended that the first dose of MMR vaccine be administered ahead of schedule for all children aged 9 to 14 months. During an outbreak of measles, children aged 6 months or older, who have not previously been vaccinated against measles, mumps and rubella, should receive a first dose as soon as possible, and those who have had a first dose should receive a second dose as soon as possible, provided that a minimum of one month has elapsed between the two doses.

A measles outbreak in children under 15 months of age in La Rioja, Spain, 2005-2006.

This paper describes a measles outbreak in La Rioja, Spain, which began in December 2005 and mainly affected children under 15 months of age who were not yet immunised with MMR vaccine. The measles cases were detected by the mandatory reporting system, under which laboratories must report every confirmed measles case. Cases were classified in accordance with the National Measles Elimination Plan: suspected and laboratory-confirmed. In the period 14 December 2005 to 19 February 2006, 29 suspected cases of measles were investigated, and 18 were confirmed. The mean incubation period was 13.8 days (range: 9 to 18). Of the 18 confirmed cases, only two were in adults. MMR vaccination was recommended for all household contacts, as well as for children aged 6 to 14 months who attended the daycare centres where the cases had appeared. At these centres, the second dose of MMR was administered ahead of schedule for children under three years of age. It was recommended that the first dose of MMR vaccine be administered ahead of schedule for all children aged 9 to 14 months. During an outbreak of measles, children aged 6 months or older, who have not previously been vaccinated against measles, mumps and rubella, should receive a first dose as soon as possible, and those who have had a first dose should receive a second dose as soon as possible, provided that a minimum of one month has elapsed between the two doses.

Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain.

This study presents data from a prospective study of adult patients with community-acquired pneumonia (CAP). Of 493 patients included in the study, 223 (45.2%) were aged > or = 65 years, and 265 (53.7%) had one or more underlying diseases, mostly chronic obstructive pulmonary disease, diabetes mellitus or dementia. In total, 281 microorganisms were identified in 250 (50.7%) patients, with two or more pathogens detected in 28 (5.7%) cases. Microbial diagnosis varied according to age, severity, co-morbidity and site-of-care, but there was much overlap among groups. Streptococcus pneumoniae was the single most prevalent organism in outpatients, patients admitted to hospital, and patients who died, either as a single pathogen or combined with another organism. Infections caused by 'atypical' pathogens were seen across all groups, including the elderly and patients with co-morbidities. Mortality varied according to the pneumonia severity index (PSI) of the pneumonia patient outcomes research team. Shock (OR 34.48), an age of > 65 years (OR 25) and altered mental status (OR 9.92) were factors associated independently with 30-day mortality. Key findings from this study were the advanced age of the population with CAP, and the high prevalence of dementia as an underlying disease. The study also revealed that microbiological diagnosis of CAP remains problematic. Although certain epidemiological features may help to predict the microbial aetiology, the overlap among groups reduces the usefulness of this information in guiding therapeutic decisions. Greater effort should be made to improve identification methods for microbial pathogens causing CAP.

[Nephropathia caused by hantavirus puumala: a case report]. / Nefropatía por hantavirus puumala: a propósito de un caso.

We present a patient from Germany with Hantavirus infection, admitted in the Emergency room of our hospital, with fever, thrombocytopenia, acute renal failure, oliguria, mild proteinuria and hematuria. Percutaneous renal biopsy revealed an acute interstitial nephritis without medulla haemorrhages. The virus infection confirmation was made by detection of IgM against Hantavirus Puumala. This infection should be considered in patients with thrombocytopenia, fever and acute renal failure, over all if they are from North and Central Europe.

Persistent human herpesvirus 8 viremia before Kaposi's sarcoma development in a liver transplant recipient.

HHV8 DNA has been detected in essentially all Kaposi's sarcoma (KS) lesions investigated, including those associated with transplantation. However, the possibility of human herpesvirus 8 (HHV8) detection in serum before appearing in the tumor is unknown. We therefore studied the natural history of HHV8 infection in a liver transplant recipient who developed KS 9 months after receiving the hepatic allograft. The presence of HHV8 DNA was retrospectively analyzed by using polymerase chain reaction in frozen stored follow-up serum specimens and KS tissues (skin and lymph node biopsies). Although KS was diagnosed the day +279 posttransplant by histopathological examination of KS tissues, retrospective analysis showed that HHV8 DNA was present in all successive serum specimens taken from the day +119 onward. Accordingly, asymptomatic and persistent HHV8 viremia may precede the appearance of typical KS lesions. Monitoring transplant recipients for HHV8 could be useful for developing therapeutic and prophylactic strategies.

Screening of antibodies to varicella-zoster virus in leukemic patients: comparison of commercial methods of enzyme-immunoassay and fluoroimmunoassay.

Commercial methods of enzyme immunoassay and fluoroimmunoassay for the detection of varicella-zoster antibodies were compared using serum samples from individuals in a program of bone marrow transplantation. The correlation was 93.4%. Enzyme immunoassay showed to be more sensitive. Both methods are applicable to the detection of varicella-zoster antibodies. However, when fluoroimmunoassay is used, we recommend the confirmation of negative results by a sensitive enzyme immunoassay.