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.

IV Spanish Consensus Conference on Helicobacter pylori infection treatment / IV Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori

Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended

La infección por Helicobacter pylori afecta aproximadamente al 50% de la población española y es causante de la gastritis crónica, la úlcera péptica y el cáncer gástrico. Se han llevado a cabo hasta el momento, en nuestro país, 3 reuniones de Consenso sobre el manejo de la infección por H. pylori (la última de ellas en 2012). Los cambios en los esquemas de tratamiento y la creciente evidencia disponible al respecto han justificado la organización de esta IV Conferencia Española de Consenso en marzo de 2016, centrada en el tratamiento de esta infección. Participaron 19 expertos sobre el tema, que realizaron una búsqueda sistemática de la evidencia científica y elaboraron una serie de recomendaciones que fueron sometidas a un proceso de interacción de votaciones anónimas seriadas mediante metodología Delphi. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Este consenso establece, como punto de partida, un aumento de la exigencia en la eficacia de los tratamientos recomendados, que deben alcanzar, o preferiblemente superar, el 90% de curación al ser administrados de forma empírica. De este modo, tanto en primera como en segunda línea se recomiendan tratamientos cuádruples con o sin bismuto, generalmente prescritos durante 14 días. El tratamiento cuádruple sin bismuto concomitante, que incluye un inhibidor de la bomba de protones, claritromicina, amoxicilina y metronidazol, se recomienda como primera línea. En el presente consenso se revisan también con detalle otras alternativas de tratamiento tanto de primera línea como de rescate.

Streptococcus pneumoniae ocular infections, prominent role of unencapsulated isolates in conjunctivitis.

The aim of this study was to determine the characteristics and shifts in serotype distribution of pneumococcal isolates causing ocular infections in a region of northern Spain in two periods: 1999-2010 for episodes of conjunctivitis (n = 612) and 1980-2010 for uncommon and more severe non-conjunctival ocular infections (n = 36). All isolates were serotyped and non-typeable isolates were confirmed as unencapsulated by multiplex-PCR of the lytA, ply and cpsA genes. Genotyping was done by pulsed-field gel electrophoresis and multi-locus sequence typing. Most conjunctivitis cases occurred in children under 5 years old (89.5%), and more severe non-conjunctival ocular infections occurred in patients older than 25 years (86.1%). Unencapsulated isolates were detected in 213 conjunctivitis episodes (34.8%) and one non-conjunctival infection (2.8%). Rates of unencapsulated isolates were similar throughout the study. Among 399 conjunctival encapsulated isolates, the most prevalent were serotypes 19A (n = 53), 15B (n = 30), 6A (n = 27), 19F (n = 25), 23F (n = 21) and 6B (n = 17). The most prevalent serotypes in non-conjunctival infections were serotype 3 (n = 4), 23F (n = 4), 6B (n = 3) and 19A (n = 3). Conjunctivitis caused by serotypes included in the hepta-valent pneumococcal conjugate vaccine steadily decreased, accounting for 34.9% (22/63) in 1999-2001, 19.7% (23/117) in 2002-04, 13.6% (33/242) in 2005-07 and 3.2% (6/190) in 2008-10. Among the 213 unencapsulated isolates, 31 different pulsed-field gel electrophoresis patterns were identified. The main clonal complexes (CC) were CC941 (ST941, ST942), CC448 (ST448) and CC344 (ST344, ST3097). CC941 was the predominant CC in 1999-2001, 2002-04 and 2005-07, being replaced by CC448 in 2008-10. The multidrug-resistant CC344 was present throughout the study.

Outbreak of Streptococcus pyogenes infection in healthcare workers in a paediatric intensive care unit: transmission from a single patient.

A 15-h stay in a paediatric intensive care unit by a girl with generalized dermal lesions superinfected with Streptococcus pyogenes led to four streptococcal infections in healthcare workers. Phenotypic and molecular analyses of the strains revealed that four isolates, characterized as emm87/ST62/T28, were identical to the isolate obtained from the index case. The occurrence of this outbreak, despite of the girl's brief hospital stay and appropriate patient management, highlights the high transmissibility of this pathogen.

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.

Molecular characterization of Streptococcus pneumoniae invasive serotype 19A isolates from adults in two Spanish regions (1994-2009).

From 1994 to 2009, the incidence of invasive serotype 19A pneumococci isolated from adults in Barcelona and San Sebastian almost doubled every 4 years. Genotyping of the 167 invasive isolates studied showed serotype 19A to be highly heterogeneous, with 35 different sequence types (STs) and a different clonal structure in each region and time period. Multiresistance, defined as non-susceptibility to three or more antimicrobials, was found in 86 (51.5%) isolates. The most frequent ST was the multidrug-resistant ST276 (n = 28), which is a single-locus variant of the Denmark(14)-ST230 global clone. The ST276 clone, only present in San Sebastian before 2001, was successfully disseminated from 2002 in both cities and was the main contributor to the overall increase of serotype 19A infections.

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.

Epidemiological and molecular analysis of Streptococcus pyogenes isolates causing invasive disease in Spain (1998-2009): comparison with non-invasive isolates.

The incidence, clinical manifestations, and circulating clones involved in Streptococcus pyogenes invasive disease was analyzed in two regions of Spain between 1998 and 2009. The annual average incidence of invasive disease was 2 episodes per 100,000 inhabitants (3.1 for children and 1.9 for adults). The most frequent clinical manifestations were cellulitis (41.3%), bacteremia without focus (19.0%), streptococcal toxic shock syndrome (12.6%), and pneumonia (7.7%). Among 247 invasive isolates analyzed, the most prevalent clones were emm1/ST28 (27.9%), emm3/ST15-406 (9.8%), and emm4/ST39 (6.5%). The emm1/ST28 clone was the only clone detected each year throughout the study period and was associated with more than one third of all fatal outcomes. When invasive isolates were compared with 1,189 non-invasive isolates, the emm1/ST28 clone was significantly associated with invasive disease. The speA and ssa genes were more frequent among invasive emm1 and emm4 isolates, respectively. Forty-two (17%) invasive isolates were resistant to erythromycin (21 harbored the mef gene and 21 the ermB or ermA genes). Twenty-two (8.9%) isolates had reduced susceptibility to ciprofloxacin (minimum inhibitory concentration [MIC] 2-8 µg/mL) and 32 (13%) were tetracycline-resistant (tetM or tetO gene). In conclusion, the emm1 type was overrepresented among invasive cases and was associated with high mortality rates.

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.

Prevalence and molecular characterization of Streptococcus pneumoniae serotype 6C causing invasive disease in Gipuzkoa, northern Spain, 1990-2009.

The recently discovered pneumococcus serotype 6C was responsible for ten of the 1,530 invasive isolates studied between 1990 and 2009. These ten isolates belonged to seven sequence types (STs) and were isolated only from adult patients: six with bacteremia, three with meningitis, and one with peritonitis. All isolates but one were fully penicillin-susceptible.

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.

Antibody microarray typing, a novel technique for Streptococcus pneumoniae serotyping.

The use of antibody-based miniaturized devices for microbiological applications is a field poorly investigated in the era of more developed molecular amplification techniques. A novel antibody microarray for Streptococcus pneumoniae serotyping was developed, by printing nanolitre volumes of pneumococcal serotype-specific antibodies on multi-well slides. This microarray, which showed high specificity when tested against reference and clinical S. pneumoniae isolates, can be applicable as a faster, cost-effective and accurate serotyping technique for pneumococcal epidemiological studies.

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).

Clonal structure and 21-year evolution of Streptococcus pneumoniae serotype 1 isolates in northern Spain.

This study of 135 serotype 1 pneumococcal isolates (88 invasive and 47 non-invasive), collected between 1987 and 2007, gave eight sequence types (217, 227, 228, 304, 305, 306, 3860 and 3861) that group, using eBurst, into three different lineages and one singleton. The annual incidence of serotype 1 invasive episodes per million inhabitants increased from 1.8 in 1987-1993 to 4.0 in 1994-2000, and to 25.6 in 2001-2007. ST228 was the predominant clone until 1998. ST306 first appeared in 1998 and became the most prevalent sequence type (>80%) after the introduction, in June 2001, of the heptavalent pneumococcal conjugate vaccine.

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.

Invasive Streptococcus pneumoniae infections in children and older adults in the north of Spain before and after the introduction of the heptavalent pneumococcal conjugate vaccine.

In the last two decades, an increasing trend in the incidence of pneumococcal disease in Europe has been reported. We investigated the effect of the use of the heptavalent pneumococcal conjugate vaccine (PCV7) in an area of northern Spain, where all recorded cases of invasive pneumococcal diseases (IPD) were included (n = 450; 91 between 1996-2007 in children aged <5 years and 359 between 1998-2007 in adults aged >64 years). All isolates were serotyped. In children, the overall IPD incidence did not significantly decrease after the introduction, in late 2001, of PCV7. However, the incidence of PCV7 serotypes significantly decreased by 137.2% from 31.59 cases/100,000 population in 1996-2001 to 13.42 in 2002-2007 (95% confidence interval [CI] -27.2 to -342.4%), as did the overall rates of penicillin resistance (from 45.6 to 18.6%) and multiresistance (from 30.3 to 11%). In older adults, the overall IPD incidence showed a non-significant increase due to non-PCV7 serotypes, which seemed to continue a previous trend in our region.

Hospitalization rates for human metapneumovirus infection among 0- to 3-year-olds in Gipuzkoa (Basque Country), Spain.

Numerous studies have been published on human metapneumovirus (HMPV) infection, but few have been population based. The main aim of this study was to estimate the incidence rate of hospitalization for community-acquired HMPV infection in infants and children aged <3 years. Between July 2004 and June 2007, 796 episodes (742 patients) of community-acquired acute respiratory infection were hospitalized. HMPV was detected in 90 episodes (11.3%). Fifty-nine episodes occurred in infants aged <1 year. The mean length of hospital stay was 6.2 days (range 2-31 days). Thirteen children required admission to the intensive care unit. Viral co-infections were detected in 46 episodes (51.1%). The incidence rate of hospitalization per 1000 inhabitants was 2.6 (95% CI 2.1-3.2), lower than that for respiratory syncytial virus, but higher than that observed for the influenza and parainfluenza viruses. HMPV is a major respiratory pathogen that leads to a high hospitalization rate.

Factors impacting on length of stay and mortality of community-acquired pneumonia.

A 1-year retrospective multicentre study was performed to identify factors influencing hospital length of stay (LOS) and mortality of patients (n = 3233) admitted to hospital because of community-acquired pneumonia (CAP). Pneumonia severity index (PSI) high-risk classes (IV and V), positive blood culture, admission to an intensive care unit (ICU), multi-lobar involvement and alcohol consumption were associated independently with prolonged LOS. Tobacco smoking was associated with a reduced LOS. The LOS varied markedly among centres. Only PSI high-risk class, admission to ICU and multi-lobar involvement were associated with early, late and global mortality. Positive blood cultures, antimicrobial therapy according to treatment guidelines and the establishment of an aetiological diagnosis were linked to reduced late and global mortality. These data suggest that early mortality associated with CAP is highly dependent on the clinical status of the patient at presentation. Conversely, late mortality seems to be associated more closely with clinical management factors; hence, an aetiological diagnosis and compliance with appropriate therapeutic guidelines have a significant influence on outcome.

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.