Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007-2014).

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.

Thirty years of human infections caused by Yersinia enterocolitica in northern Spain: 1985-2014.

Yersinia enterocolitica infection is a zoonosis with worldwide distribution, gastroenteritis being by far the most common clinical manifestation of human infection. In Gipuzkoa, northern Spain, human Y. enterocolitica infections increased from the mid-1980s to the beginning of the 21st century (from 7·9 to 23·2 annual episodes per 100 000 population) to decrease to 7·2 annual episodes per 100 000 population in the last years of the study. The hospital admission rate due to yersiniosis during the last 15 years of the study was 7·3%. More than 99% of isolates were serotype O:3. Infection affected mainly children under 5 years of age (average rate: 140 episodes per 100 000 population). The incidence in adults was low but hospitalisation increased with age, exceeding 50% in people over 64 years old.

Minimum spread of the new Swedish variant of Chlamydia trachomatis and distribution of C. trachomatis ompA genotypes in three geographically distant areas of Spain, 2011-2012.

PURPOSE: The aim of this study was to determine the presence of the new Swedish Chlamydia trachomatis (C. trachomatis) variant (nvCT) and the distribution of C. trachomatis ompA genotypes in three geographically distant regions of Spain. METHODS: The genotypes of strains causing 624 episodes of infection (January 2011-September 2012) were studied using a nested PCR that amplifies a fragment of the ompA gene, followed by sequencing. To detect nvCT, a real-time PCR was used that amplifies a fragment of the cryptic plasmid with a 377 base pair deletion, which identifies the nvCT. RESULTS AND CONCLUSION: The ompA genotype was identified in 565 (90.5%) episodes. Eleven genotypes were detected, of which nine were found in all three regions. Only one nvCT strain was detected (0.4%), despite the predominance of genotype E (41%). Other frequent genotypes were genotypes D (19%), F (13%), G (11 %), and J (7%). Genotype L2b, causing lymphogranuloma venereum, was detected in men who have sex with men (MSM) in all three regions. Genotypes E and F were more frequent in women and heterosexual men, and genotypes D, G, J and L2b in MSM. In men, the main factor causing differences in the distribution of C. trachomatis was sexual behavior (MSM versus heterosexual men), while the distribution of C. trachomatis genotypes was similar in women and heterosexual men.

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.

Rotavirus genotypes in children in the Basque Country (North of Spain): rapid and intense emergence of the G12[P8] genotype.

Between July 2009 and June 2011, rotavirus was detected in 507 of 4597 episodes of acute gastroenteritis in children aged <3 years in Gipuzkoa (Basque Country, Spain), of which the G-type was determined in 458 (90·3%). During the annual seasonal epidemic of 2010-2011, the unusual G-type 12 was predominant, causing 65% (145/223) of cases of rotavirus gastroenteritis. All the G12 strains were clustered in lineage III and were preferentially associated with P-type 8. This epidemic was characterized by broad geographical distribution (rural and urban) and, over 7 months, affected both infants and children, the most frequently affected being children between 4 and 24 months. Of children with rotavirus G12, 16% required hospital admission, the admission rate in children aged <2 years being 20·7 cases/10 000 children. The sudden emergence and predominance of G12 rotaviruses documented in this winter outbreak suggest that they may soon become a major human rotavirus genotype.

Measles genotypes D4 and G3 reintroduced by multiple foci after 15 years without measles virus circulation, Gipuzkoa, the Basque Country, Spain, March to June 2011.

During a three-month period in spring 2011, 23 cases of measles occurred in seven independent outbreaks in a region in Spain with around 700,000 inhabitants, where the disease had been eliminated since 1997. High vaccination coverage and rapid diagnosis allowed implementation of containment measures and this prevented spread of the disease. Except for the first outbreak which affected 10 cases, each of the other six outbreaks caused a maximum of three secondary cases.

Human parechoviruses in infants with systemic infection.

Human parechoviruses (HPeVs) are RNA viruses related to neonatal sepsis, meningoencephalitis and other infections in young children. Little clinical and epidemiological information is available on these viruses. HPeVs were sought in cerebrospinal fluid from 397 infants aged less than 12 months from whom a sample was obtained to exclude meningitis or encephalitis from 2006 to 2009. HPeV infections were also tested in stool samples from 271 children aged less than 3 years old with gastroenteritis from November 2008 to March 2009. HPeV detection was by real-time polymerase chain reaction assay (region 5'UTR), followed by genotyping (region VP3/VP1). HPeVs were detected in the cerebrospinal fluid of nine infants (2.3%), one aged 6 months and eight aged 14-55 days old. All were admitted to hospital for febrile syndrome with abrupt clinical deterioration and suspected systemic infection without clear laboratory signs of meningeal inflammation. The same virus was detected in all the available nasopharyngeal aspirates, stool, and/or serum samples from each patient. At least eight of the nine cases were caused by HPeV3. HPeVs were detected in stool samples from 17 children (6.3%), the most prevalent types being types 1 and 3. In conclusion, HPeV infection is common in the Basque Country (Spain) and HPeV3 is a significant cause of hospital admission due to systemic infection in the first few months of life. In these patients, HPeVs should be investigated as part of routine tests for enterovirus.

Rotavirus genotypes in children in the Basque Country (northern Spain) over a 13-year period (July 1996-June 2009).

To describe the circulation dynamics of human rotavirus genotypes in a region of southern Europe over a 13-year period. The G- and P-types of rotavirus isolates of patients aged less than 5 years were analyzed using multiplex, reverse transcription polymerase-chain reaction. Of 1,538 isolates investigated, a combination of individual G- and P-types was obtained in 1,368. The most prevalent combination was G1[P8] (57.5% of the genotyped strains), which circulated in all seasons and predominated in nine out of 13 seasons. The strains G2[P4] (14.4%), G3[P8] (8.3%), G4[P8] (5.5%) and G9[P8] (13.4%) circulated intermittently. G4[P8] strains were frequently detected in the 1990s but only sporadically after 2000. G9[P8] strains emerged from 1997-1998 and became dominant in the winters of 2005-2007. G2[P4] strains were predominant in 2003-2004, before the rotavirus vaccines were commercialized. Unusual combinations of common G- and P-types and the presence of unusual G- and/or P-types (G6[P14], G8[P8], G8[P14] and G12[P8]) were rarely observed (<1%). We found no differences in hospitalization due to distinct genotypes. G-types G1-G4 and G9 represented >99% of circulating rotaviruses over a 13-year period. Therefore, vaccine efficacy in this region can be expected to be high.

Incidence of hospitalization due to community-acquired rotavirus infection: a 12-year study (1996-2008).

The incidence of hospitalization for acute gastroenteritis (AGE) is a useful parameter to assess the utility of the new rotavirus vaccines in high-income countries. Children hospitalized for AGE were identified by searching hospital discharge data and the records of the microbiology laboratory of Hospital Donostia. Rotavirus antigen was investigated in 96.1% of the 1114 children aged 1 month to <5 years hospitalized for AGE in the study period. Nearly 40% were rotavirus positive (44.9% of the 798 children aged 1 month to <2 years), with G1[P8] being the predominant genotype. The mean annual incidence rate of hospitalization due to rotavirus AGE was 29.8 and 63.7 cases/10 000 inhabitants in the <5 and <2 years age groups, respectively, in 1996-1999, decreasing to 13.6 and 27.4 cases/10 000 inhabitants in <5 and <2 years age groups, respectively, in 2002-2005 (P<0.001). This decrease coincided with a significant increase in the consumption of oral rehydration solutions.

A swimming pool-related outbreak of pharyngoconjunctival fever in children due to adenovirus type 4, Gipuzkoa, Spain, 2008.

An outbreak of pharyngoconjunctival fever affecting 59 children was detected in a municipality of northern Spain in July 2008. The outbreak was related to insufficient doses of water disinfectant in the municipal swimming pool.

Rapid spread of drug-resistant influenza A viruses in the Basque Country, northern Spain, 2000-1 to 2008-9.

A worldwide increase of adamantane-resistant influenza A(H3N2) and oseltamivir-resistant influenza A(H1N1) viruses has been observed in recent years. The aim of this study was to analyse the prevalence of antiviral drug-resistant influenza A in a region of northern Spain. Resistance to adamantanes was detected in 45.3% (68/150) of influenza AH3 viruses analysed for the period from 2000-1 to 2008-9. Adamantane-resistance was absent in our region during the 2000-1 to 2002-3 influenza seasons. However, after the first adamantane-resistant virus (characterised as A/Fujian/411/2002) was detected in the 2003-4 season, a rapid increase in the proportion of resistant strains was observed (4.9% [2/41], 80% [8/10] and 100% [53/53] in the 2004-5, 2006-7 and 2008-9 seasons, respectively). Four of the first five adamantane-resistant AH3 viruses detected were isolated from adult patients, but the subsequent spread was observed mainly among children. No resistance to adamantanes was detected among the 65 influenza AH1 viruses analysed throughout the study period. Among the 172 influenza A (76 AH1 and 96 AH3) viruses analysed, five strains (AH1 with mutation H274Y) showed oseltamivir resistance, and all were detected in the last season. Amantadine use was very scarce in our region, and oseltamivir was not used at all; therefore the increase of resistance was attributed to imported drug-resistant influenza viruses.

Residual immunity in older people against the influenza A(H1N1)--recent experience in northern Spain.

The 2009 pandemic influenza A(H1N1) virus has a higher incidence in children and young adults, a pattern that has also been reported in seasonal influenza caused by the influenza A(H1N1)virus. We analysed age at infection in symptomatic patients with influenza in the Basque Country (northern Spain), reported through the sentinel influenza surveillance system which monitors 2.2-2.5%of the population. Between September 1999 and August 2009,influenza A(H3N2) or seasonal influenza A(H1N1) was detected in 941 patients, and from April to August 2009, pandemic influenza A(H1N1) was detected in 112 patients. The H3/H1 seasonal influenza ratio was between 3.3 and 3.4 in the under 60 year olds,but 9.8 in older individuals, suggesting that people born before 1950 have residual immunity against the influenza A H1N1 subtype (both seasonal and pandemic).

A PCR-restriction fragment length polymorphism assay to genotype human metapneumovirus.

Human metapneumovirus (hMPV) genotypes A and B show epidemiological and probably clinical differences. This report describes a fast and simple PCR-restriction fragment length polymorphism (PCR-RFLP) assay, involving digestion of the fusion protein gene with Tsp509I, that allows lineages A1, A2, B1 and B2 to be distinguished. The assay should help in elucidating the epidemiology of hMPV, and possibly in predicting the severity of clinical infection.

Chlamydia trachomatis genotypes A and B from urogenital specimens of patients in Spain: molecular characterization.

OBJECTIVES: Chlamydia trachomatis ompA genotypes A and B, primarily associated with trachoma, were unexpectedly detected in urogenital samples of patients in Spain, a trachoma-free country. In this study, we aimed to explain this finding using analysis of organotropism-related genes and a multilocus sequence typing (MLST) technique. METHODS: C. trachomatis genotypes A or B were detected in 8/930 (0.9%) infection episodes between 2006 and 2012. In these strains, organotropism-related genes (polymorphic membrane protein gene H, tryptophan synthase gene A, CTA0934, and cytotoxin) were studied. Further, the strains were analysed by MLST, using a polymerase chain reaction that amplifies five highly variable genomic loci (hctB, CT058, CT144, CT172, and pbpB). Amplicons were sequenced and phylogenetic analysis was conducted. RESULTS: Seven strains were detected in the eight infection episodes (in one patient, an identical strain being found in two episodes). Analysis of organotropism-related genes showed that these strains shared genetic features characteristic of genitotropic genotypes but not of trachoma strains. Three strains of genotype A showed a unique and new MLST-sequence type (ST551, allele profile 8-8-2-27-69). The four strains of genotype B belonged to ST138. CONCLUSIONS: C. trachomatis ompA genotypes A and B associated with trachoma, but detected sporadically in urogenital samples in trachoma-free countries, may be the result of recombination between strains adapted to trachoma and strains adapted to sexual transmission.

Robustness of measles immunity in parturient women in Gipuzkoa, Basque Country, Spain, in the post-vaccination era.

The infants of mothers with vaccine-induced immunity lose passive acquired measles antibodies earlier than infants of naturally infected mothers. This study included two cohorts of parturient women: one composed of women who gave birth in 1990 (end of the epidemic period), and another comprising women who gave birth in 2006 (after eight years without virus circulation). Immunoglobulin G (IgG) antibodies against measles (IgG-AM) were investigated by enzyme immunoassay in stored serum samples (-40 degrees C). Measles-IgG titres of >400 mIU/mL were found in all 185 parturient women who gave birth in 1990, all with natural immunity. Of 185 women who gave birth in 2006, most of whom had vaccine-induced protection, measles-IgG were undetectable in 4.9% (<150mIU/mL), values were borderline in 7% (150-299 mIU/mL), and the geometric mean titre was lower (p<0.001), being 3.4 to 3.8 times lower in women aged <28 years. The changing levels of maternal measles antibodies suggest that in Spain, the window of susceptibility to measles in infants is increasing. To protect susceptible infants against measles in countries with long-established vaccination programs where measles immunity in parturient women was artificially acquired, it is essential to ensure that both doses of the routine measles vaccine achieve a coverage of >95%, and that infants receive the first vaccination dose before 15 months of age (e.g. at 12 months).

Gipuzkoa, Basque Country, Spain (1984-2004): a hyperendemic area of Q fever.

Overall 1,261 cases of Q fever were diagnosed between 1984 and 2004 in Gipuzkoa (Basque Country, Spain). Most (75.5%) of the cases ocurred in subjects 15-45 years of age. A total of 79.5% of the cases (n = 1003) ocurred between January and June. The annual incidence for acute Q fever in Gipuzkoa was 7.7, 15.8, 9.6, and 5.7 for the periods 1984-1989, 1990-1994, 1995-1999, and 2000-2004, respectively. In 94% of the cases IgM titer was >/=1/256. The most frequent clinical manifestation was pneumonia (79%). Only two cases of chronic Q fever were detected during the 21 years studied.

[Clinical characteristics of children hospitalized for influenza virus infection]. / Características clínicas de los niños hospitalizados por infección por virus Influenza.

BACKGROUND: The clinical manifestations of influenza virus are fairly nonspecific and are similar to those of other viral infections, respiratory processes due to other causes and even septic disease in neonates. Few studies have been performed of the clinical characteristics of influenza virus infection in hospitalized children. OBJECTIVE: To evaluate the clinical characteristics of children hospitalized for influenza virus infection in four consecutive epidemic waves (2000-2004). MATERIAL AND METHODS: We retrospectively reviewed the medical records of children hospitalized for influenza A and B virus infection confirmed by cell culture and polymerase chain reaction. Age, sex, symptoms on admission, complementary investigations, diagnosis and outcome were evaluated. RESULTS: Eighty-four children were hospitalized, of which 74 had influenza virus type AH3, five had influenza virus type AH1 and five had influenza B virus. A total of 42.8 % were aged less than 6 months. The main symptoms were fever (75 patients), cough (56 patients) and ENT involvement (53 patients). The most frequent causes of admission were febrile syndrome (75 patients), bronchiolitis (19 patients), pneumonia (13 patients) and bronchitis (8 patients). In 21 patients viral or bacterial coinfection was found, the most frequent of which was respiratory syncytial virus (10 patients). Few differences were found among age groups except for pneumonia and prolonged fever (more frequent in children older than 6 months) and lymphocytosis (in children younger than 6 months). The greatest number of complementary investigations in younger children was performed for acute febrile syndrome in neonates aged less than 6 months. Risk factors for hospitalization were found in only three children, all of whom were older than 6 months. Outcome was favorable in all children. CONCLUSIONS: Influenza virus infection in hospitalized children is most frequent in previously healthy neonates with fever and nonspecific signs and symptoms that are similar to those of other infectious processes. Specific microbiological diagnostic techniques are required for an early diagnosis. Healthy infants aged less than 24 months are most at risk for hospitalization for influenza virus infection.

Molecular evidence of homosexual transmission of HIV type 2 in Spain.

Eight HIV-2-infected Caucasian men living in the same geographical area in Gipuzkoa (northern Spain) have been identified in the last 5 years. HIV-2 infection in this area is uncommon, and no other cases of HIV-2 infection have been found after extensive testing for HIV-1/2 antibodies. Epidemiological data suggested a possible link among the identified subjects, with homosexual contact being the most likely way of transmission. A genetic analysis of four of the subjects, from whom specimens were available, was conducted. Phylogenetic and signature pattern studies of the reverse transcriptase (RT) and env genes supported a single source of infection. Interindividual nucleotide variability ranged from 2.4 to 4.8% in the RT region and from 5.2 to 6.1% in the env gene, whereas the mean divergence between patient and control strains was 9.8 and 18.3%, respectively. The nucleotide and amino acid signature patterns were closely related in viruses from the four examined individuals. This is the first report of a cluster of HIV-2 infections with genetic sequence data support. The singularity of this cluster should alert clinicians on the possibility of HIV-2 outside endemic areas.

High seroprevalence of Coxiella burnetii infection in Eastern Cantabria (Spain).

BACKGROUND: Coxiella burnetii is the causative agent of Q fever, a worldwide zoonosis which shows a wide diversity of clinical manifestations. The objective of this seroepidemiological study was to estimate the prevalence of antibodies to C. burnetii in a representative population of the Eastern area of the Cantabrian Community (Northern Spain). METHODS: A cross-sectional study was conducted in 595 subjects from Eastern Cantabria. Four different zones (one urban and three rural zones) were defined according to the geographical characteristics of the area and the economic activities of the population. The population sample for this study was collected between December 1994 and March 1995, and was stratified by age, sex and municipality of residence. IgG and IgM antibodies against C. burnetii were assayed by an indirect immunofluorescence technique. RESULTS: The prevalence of anti-phase II Coxiella IgG (titre > or = 1:16) was 48.6% (95% confidence interval: 44.6-52.6%), with 81.3% havinga titre of > or = 1:64. The prevalence of IgG increased with age, ranging from 12.0% in people < 15 years to 70.3% in those > 65 years (P < 0.001). The antibody detection rate was higher in males (53.6%) than in females (43.3%) (P < 0.01). The prevalence of anti-phase II Coxiella IgG was less among subjects living in the urban zone (32.8%) than in those living in the other three rural zones: the two situated on the coast (54.0% and 54.9% respectively) and the inner mountainous zone (82.3%) (P < 0.001). CONCLUSIONS: The prevalence of C. burnetii infection observed in this study is one of the highest reported in Europe. The eastern area of Cantabria is a hyperendemic area for Q fever.

HTLV-I/II infections in Spain. The HTLV-I/II Spanish Study Group.

Antibodies to HTLV-I/II were investigated in sera from 7521 individuals living in Spain. They were classified in four major groups: a) subjects at high risk of retroviral infections e.g. parenteral drug addicts, homosexuals, prostitutes, and multiple-transfused individuals; b) patients suffering illness associated with HTLV-I in endemic regions; c) immigrants from endemic areas; and d) blood donors. Sera were collected from 1984 to December 1991. Repeatedly reactive ELISA was found in 211 samples (2.8%), but Western blot only confirmed the presence of HTLV-I/II antibodies in 23 samples (0.30%), corresponding to eight (0.25%) out of 3207 drug abusers, six (0.72%) out of 894 immigrants (five Africans and one South American), three (0.41%) out of 727 patients with HTLV-related diseases (one woman with HTLV-I associated myelopathy had received blood transfusions in an endemic area), four (0.54%) out of 793 prostitutes, one multiple-transfused native woman, and one (0.16%) out of 603 native seamen. The Western blot antibody pattern confirmed HTLV-II infection instead of HTLV-I in nine (39%) subjects. The remaining 14 (61%) HTLV-reactive samples were interpreted as HTLV-I seropositive, most of which were from immigrants. None of 857 blood donors analysed was reactive for HTLV antibody. These results suggest that both HTLV-I and HTLV-II are present in Spain, although at a low rate and mostly restricted to individuals coming from endemic areas, drug addicts, and prostitutes. Furthermore, diseases related to HTLV-I (particularly lymphoproliferative disorders, and subacute myelopathies) seem to be rarely associated with these viruses in Spain, a non-endemic area.