Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies. METHODS: For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011-2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 - IRR)*100. RESULTS: After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI -4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI -8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20-29% and 32-53% of IPD cases in PCV13 and PCV10 sites, respectively. CONCLUSION: Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.

Prevalence of asymptomatic Leishmania infection and associated risk factors, after an outbreak in the south-western Madrid region, Spain, 2015.

BackgroundA large outbreak of leishmaniasis with 758 cutaneous and visceral leishmaniasis cases occurred in 2009 in Fuenlabrada, in the south-west of the Madrid region of Spain.AimWe aimed to determine the prevalence of asymptomatic Leishmania infection after this outbreak, and its associated risk factors.MethodsA cross-sectional study of 804 healthy individuals living in Fuenlabrada who had no history of leishmaniasis, was conducted between January and July 2015. Asymptomatic infections were sought by either a combination of PCR, immunofluorescent antibody titre, and direct agglutination tests, or by whole blood stimulation assay (WBA) with interleukin-2 (IL-2) quantification.ResultsUsing the first approach, prevalence of asymptomatic individuals was 1.1% (9/804), while the second returned a value of 20.7% (143/804). Older age, being male, proximity to the park where the focus of infection was identified, and living in a detached house, were all strongly associated with the prevalence of asymptomatic infection.ConclusionsThe true number of infected individuals may be underestimated if only serological methods are used. The combination of WBA with IL-2 quantification may allow to better determine the prevalence of asymptomatic Leishmania infection, which would be useful in establishing control measures and in quantifying their impact. In our study, the use of WBA with IL-2 quantification also helped establish the risk factors that influence exposure to and infection by Leishmania.

[Population study of seroprevalence of antibodies against hepatitis A virus in the Community of Madrid, 2008-2009]. / Estudio poblacional de seroprevalencia de anticuerpos frente al virus de la hepatitis A en la Comunidad de Madrid, 2008-2009.

INTRODUCTION: Seroprevalence surveys enable the level of endemicity of hepatitis A (HAV) to be assessed. The aim of this study was to estimate the seroprevalence (SP) antibody against HAV by age group, and compare it with those obtained in previous surveys. METHODS: Observational cross-sectional study. The target population consists of residents from 2 to 60 years old in the Community of Madrid. Two-stage cluster sampling was performed with stratification of first stage units. After signing the informed consent, a serum sample was extracted from each participant and sociodemographic data were collected by a questionnaire. RESULTS: SP antibodies to hepatitis A is 46.8% (95% CI 44.6 to 49.0). The SP increases with age. It is higher in the population from more endemic countries and people with less education and lower social class. In relation to the previous survey, SP increased in the population under 30 years old, and a decline after that age is observed. If only the autochthonous population and from countries with very low endemicity is observed, the increase is statistically significant in the 2-5 years age group. CONCLUSIONS: Our region has a very low level of endemicity thus, following the recommendations of WHO, vaccination should be targeted at specific risk groups.

Prevalence of undiagnosed HIV infection in the general population having blood tests within primary care in Madrid, Spain.

OBJECTIVE: To estimate the prevalence of undiagnosed HIV infection in men and women aged 16-80 years, having blood tests within primary care in Madrid, Spain. METHODS: A serosurvey to monitor vaccine-preventable diseases in the general population aged 16-80 years was conducted in 2008-2009. Eligible individuals were those having blood tests. The blood extraction centres, the primary sampling units, were chosen in proportion to the size and socio-economic characteristics of the target population, aiming for a sample size of 5355 subjects with equal sex distribution within five age bands. Migrants aged 16-40 years were oversampled. Previous HIV diagnoses were excluded. Prevalence rates of HIV infection with 95% CIs were estimated allocating weights inverse to their probability of selection. RESULTS: Overall, 3695 subjects agreed to participate, yielding a response rate of 69%, similar for men (66%) and women (73%); individuals recruited at healthcare centres or by telephone; and for all age groups except those aged ≥60 (57%) years. HIV infection was diagnosed in 12 subjects (0.35%; 95% CI 0.13 to 0.57); prevalence, higher in men (0.51%; 95% CI 0.12 to 0.89) than in women (0.20%; 95% CI 0.00 to 0.44); participants from other countries (0.61%; 95% CI 0.03 to 1.18) as compared with Spanish born (0.30%; 95% CI 0.06 to 0.53) and aged 21-30 years (0.65%; 95% CI 0.01 to 1.29), or 31-40 years (0.71%; 95% CI 0.02 to 1.41). None of the differences were statistically significant. Most of the 12 subjects were under follow-up for medical conditions; 11 had visited the primary care clinic in the preceding month. CONCLUSION: The prevalence of undiagnosed HIV infection is very high and calls for strategies to unveil occult HIV infection.

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain.

BACKGROUND: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. METHODS: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. RESULTS: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. CONCLUSIONS: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).

Clonal spread of levofloxacin-resistant streptococcus pneumoniae invasive isolates in Madrid, Spain, 2007 to 2009.

Among 1,349 Streptococcus pneumoniae invasive isolates, 45 (3.3%) were levofloxacin resistant. Serotype distribution was as follows: 8 (n=32 isolates), 19A (n=4 isolates), 7F (n=3 isolates), 9V (n=2 isolates), 10A (n=1 isolate), 19F (n=1 isolate), 6B (n=1 isolate), and nontypeable (n=1 isolate). Levofloxacin-resistant isolates had dual mutations in the gyrA and parC genes. Serotype 8 strains corresponded to a capsular switching of the Sweden(15A)-25 clone. Levofloxacin resistance was also detected among multiresistant (ST276(19A), Spain9V-ST156, ST88(19F), and ST1542(6B)) and among usually antibiotic-susceptible (Netherlands7F-ST191, ST1201(19A), and ST2639(10A)) clones.

Evolution of the distribution of Streptococcus pneumoniae serotypes isolated in pleural fluid in the Madrid Autonomous Community between the years 2007-2018. / Evolución de la distribución de serotipos de Streptococcus pneumoniae aislados en líquido pleural en la Comunidad de Madrid entre los años 2007 y 2018.

INTRODUCTION: The aim of this study was to describe the distribution of Streptococcus pneumoniae serotypes in isolates from pleural fluid in the Madrid Autonomous Community between the years 2007-2018. METHODS: Invasive pneumococcal disease strains isolated during the period 2007-2018 were studied. The frequency of serotypes from pleural fluid was compared with that observed in other samples. RESULTS: A total of 6,115 pneumococcal invasive isolates were processed. Of them, 182 (3%) were isolated from pleural fluid. A total of 70.9% of isolates belonged to some of the following 6serotypes: 1, 3, 19A, 8, 7F and 5. The serotypes 3 and 8 increased significantly from 9.6% to 30.8%, and from 5.3% to 20.5%, respectively, over the periods 2007-2010 to 2015-2018. CONCLUSIONS: Pneumococcal serotypes 3 and 8 are currently significant causes of infection of pleural fluid in our region.

Age-Dependent Serotype-Associated Case-Fatality Rate in Invasive Pneumococcal Disease in the Autonomous Community of Madrid between 2007 and 2020.

The aim of this study was to investigate the serotype-associated fatality rate in cases of invasive pneumococcal disease (IPD) in the Spanish region of Madrid between 2007 and 2020. Serotyping was performed by Pneumotest Latex and the Quellung reaction using commercial antisera. Case-fatality rate was estimated as the ratio between the number of deaths at hospital discharge and the number of cases attributable to each serotype. To evaluate the association measures, the odds ratios with a 95% confidence interval were calculated. Twenty five pneumococcal serotypes were associated to mortality and comprised 87.8% of the total number of isolates characterized. Serotypes 8, 3, 19A, 1, 7F, 22F, 12F, and 11A were the most prevalent (≥3% each). Serotypes 31, 11A, and 19F were significantly associated to high case-fatality rates (>20% each). The lower significantly associated case-fatality rate (<10% each) was found in serotypes 5, 1, 12B, 7F, 12F, 8, 33, and 10A. The serotypes with higher mortality levels (≥0.04 per 100,000 population) were 11A (fatality 24.0%), 3 (fatality 18.7%), 19A (fatality 12.5%), and 8 (fatality 7.2%). Serotype 3 was worrisome because it is associated with important fatality levels combined with very high incidence and mortality rates. Serotype 11A also showed a high fatality with marked incidence and mortality levels. Some few frequent serotypes as 31, 19F, and 15A despite its high fatality had low levels of mortality. By contrast other serotypes as 8 showing low fatality had high mortality ranges because it shows a wide extended distribution. Finally, common serotypes, such as 1 and 5, presented small mortality length, due to their low case-fatality rates.

Direct serogrouping of Streptococcus pneumoniae strains in clinical samples by use of a latex agglutination test.

Pneumotest-Latex (Statens Seruminstitut) was evaluated for direct serogrouping of Streptococcus pneumoniae strains in clinical samples from patients with invasive disease. The technique was accurate to its level of discrimination for 62 of 67 clinical samples (92.5%). Pneumotest-Latex would be a useful alternative for direct serogrouping of pneumococci in clinical samples.

Streptococcus pneumoniae serotypes with meningeal tropism in cases of invasive pneumococcal disease. Community of Madrid, 2007-2018. / Serotipos de Streptococcus pneumoniae con tropismo meníngeo en casos de enfermedad neumocócica invasora. Comunidad de Madrid, 2007-2018.

INTRODUCTION: To describe the distribution of Streptococcus pneumoniae serotypes isolated in cerebrospinal fluid (CSF) between 2007-2018 in the Community of Madrid (CM) and to identify those with higher meningeal tropism. METHODS: Strains isolated from invasive pneumococcal disease were sent to the Regional Laboratory of Public Health by Microbiology laboratories of public and private hospitals of the CM. The frequency of serotypes from CSF was compared with that observed in other samples. RESULTS: A total of 6,115 strains were processed and 5% (n=304) were isolated from CSF. Seven serotypes (11A, 19F, 23B, 10A, 24F, 23A and 35F) showed a frequency significantly higher in CSF than in other usually sterile samples. Serotypes 24F, 11A and 23B showed high penicillin-resistance. CONCLUSION: The frequency and resistance of certain pneumococcal serotypes with high meningeal tropism could compromise the treatment of central nervous system infections.

Increase of serotype 8, ST53 clone, as the prevalent strain of Streptococcus pneumoniae causing invasive disease in Madrid, Spain (2012-2015).

INTRODUCTION: In recent years, Streptococcus pneumoniae serotype 8 has become the most prevalent cause of invasive pneumococcal disease (IPD) in Madrid, Spain. The objective of this study was to characterize the invasive clones of S. pneumoniae serotype 8 in Madrid over the 2012-2015 period. METHODS: From January 2012 to December 2015, a total of 1543 invasive isolates were studied. Serotyping was carried out by Pneumotest-Latex agglutination and Quellung reaction. Susceptibilities to penicillin, erythromycin and levofloxacin were determined by the Etest®. All serotype 8 strains were typed by multilocus sequence typing (MLST) and by pulsed-field gel electrophoresis (PFGE). RESULTS: Two hundred and forty-eight (248) serotype 8 strains were detected (16.1%) and 243 of them were available for molecular typing. Nine sequence types (STs) by MLST (8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 and 8-ST4301), and nine PFGE profiles were identified (one corresponding to each ST). The 8-ST53 clone was the most widespread, and increased from 53.8% among all serotype 8 isolates in 2012, to 90.1% in 2015. In contrast, the 8-ST63 clone, resistant to levofloxacin and erythromycin, decreased from 30.8%, among all serotype 8 strains in 2012, to 5.0% in 2015. CONCLUSIONS: The increase in our region of S. pneumoniae serotype 8, not included in conjugated vaccines, occurred at the expense of the 8-ST53 clone. On the contrary, the 8-ST63 clone decreased. Since clone 8-ST63 has the theoretical advantage of its levofloxacin-erythromycin resistance in comparison to 8-ST53, the predominance of 8-ST53 over 8-ST63 is striking.

Absence of IgG antibodies among high-risk contacts of two confirmed cases of Crimean-Congo haemorrhagic fever in the autonomous region of Madrid (Spain).

Crimean-Congo haemorrhagic fever (CCHF) is a widely distributed tick-borne disease. In Spain, the disease has emerged as outbreak associated with high-risk exposures. Our goal was to evaluate the prevalence of antibodies against the CCHF virus (CCHFV) in high-risk contacts. A cross-sectional study was conducted. Three hundred eighty-six high-risk contacts were identified comprising family contacts and hospital workers who had attended the cases. Fifty-seven cases with closer exposure were selected. However, forty-nine cases participated in the study. IgG antibodies were detected by immunoenzymatic techniques. All determinations tested negative for anti-CCHFV IgG antibodies. Most of the responders were women (73.5%), and belong to the intensive care department (53.1%). In relation to other possible sources of exposures, 18.4% travelled to countries with CCHF transmission risk. No CCHF positivity was recorded among selected high-risk contacts. This highlights the importance of standard precautions which might have protected healthcare workers and care providers from CCHF infection.

A sampling design for a sentinel general practitioner network.

OBJECTIVE: To construct a design for probabilistic sampling of reporting physicians in sentinel networks. METHODS: We performed a multi-stage sample selection study. Data on primary care physicians and their patients were obtained from the Madrid Health Institute for 2005. The geographical unit of reference was the basic health area. A factorial analysis was performed on the basis of demographic, socio-cultural and socio-occupational variables. A cluster analysis was conducted to group the 247 basic health areas into homogeneous strata, which were then tested using a discriminant analysis. The general practitioners and pediatricians needed in each stratum were selected by simple random sampling. The representativeness of the population monitored by the selected physicians was studied with respect to the population of Madrid. RESULTS: Factorial analysis yielded five factors. Using these, 14 strata were obtained, which were shown to be homogeneous and mutually different by discriminant analysis. The minimum population that needed to be monitored consisted of 146,946 adults and 24,518 children, proportionally distributed among the respective strata. Eighty-eight general practitioners and 32 pediatricians were selected, who respectively covered populations of 154,610 and 31,336 persons representative of the general population. CONCLUSIONS: Obtaining samples through suitable designs improves the accuracy of the information gathered by health sentinel networks in epidemiologic surveillance. Ensuring the representativeness of the study population vis-à-vis the general population is essential; cluster analysis and simple random sampling are methods that meet this need. Selecting physicians by means of probabilistic methods enables the accuracy of estimates to be ascertained.

Impact of the MMR vaccine on the incidence of mumps in the Community of Madrid and evaluation of the effectiveness of the Jeryl-Lynn strain. Years 1998-2016. / Impacto de la vacuna triple vírica sobre la incidencia de la parotiditis en la Comunidad de Madrid y evaluación de la efectividad de la cepa Jeryl-Lynn entre 1998 y 2016.

INTRODUCTION: Mumps is characterised by parotid inflammation and fever and is preventable by vaccination with MMR vaccine. The objective of the study is to assess the impact and effectiveness of the vaccine. MATERIAL AND METHODS: Cases notified to the Notifiable Disease System between 1998 and 2016 were used for the study. The vaccine effectiveness (VE) was calculated in cohorts vaccinated with two doses of Jeryl-Lynn, and the impact was calculated by comparing incidences by age and by Rubini (1995-1998) and Jeryl-Lynn (1999-2002) cohorts during the periods 1998-2004, 2005-2009 and 2010-2015. The incidences for age group and period were compared with the previous period and the incidences for cohorts were compared within a period with incidence ratios (IR) using Poisson models. The VE was estimated using the screening method using logistic regression models. RESULTS: 13,816 cases were reported. The incidence in 2005-2009 was higher than in 1998-2004 (IR: 1.46, 95% CI: 1.40-1.53), and it remained stable in 2010-2015 (IR: 0.99, 95% CI: 0.95-1.03). The average incidence rate of the Rubini cohort was 69.43 and the Jeryl-Lynn cohort was 32.24. The IR was 0.25 (95% CI: 0.22-0.29), 0.55 (95% CI: 0.49-0.61) and 0.88 (95% CI: 0.76-1.00) for each period respectively. 2,574 cases were included in the VE study. EV decreased over time reaching not significant values after seven years of follow-up (VE: 55%, 95% CI: 82 to -12%). CONCLUSIONS: Parotiditis behavior is characterised by fluctuations, changes in presentation and a decrease in VE.

Seroprevalence of antibodies to varicella-zoster virus in Madrid (Spain) in the absence of vaccination.

OBJECTIVE: to ascertain the seroprevalence of antibodies to varicella-zoster virus in the Madrid population prior to the introduction of vaccination. STUDY DESIGN: Cross-sectional antibody seroprevalence study. POPULATION: persons aged 2 to 40 years in Madrid. Field work: September 1999 to April 2000. Data were collected on demographic and socio-economic variables and on a number of exposures. IgG antibodies were determined using Enzyme Linked ImmunoSorbent Assay (ELISA), and antibody prevalence broken down by age group. Logistic regression was used to analyse the association between the presence of antibodies and the respective study variables. The results were compared against those of an earlier seroprevalence survey in Madrid (1993). RESULTS: A total of 2,131 subjects were included, with a non-response rate of 20.4%. Antibody prevalence was estimated at 90.2%; the 90% mark was reached at 11 years of age and almost 100% of adults presented with antibodies. In the case of children, school attendance associated with the presence of antibodies. No significant differences were observed vis-à-vis the results of the earlier survey. CONCLUSIONS: The seroprevalence profile coincides with those of other Spanish regions and European countries, and remains stable over time. Antibody presence rises sharply in children from aged 2 years to adolescence. Further seroprevalence studies are called for to study the disease trend and assess preventive measures.

Persistence and Variation in Overweight and Obesity Among the Pre-school Population of the Community of Madrid After 2 Years of Follow-up. The ELOIN Cohort.

INTRODUCTION AND OBJECTIVES: The childhood obesity epidemic is a worldwide public health problem which starts at very early ages. The aim of this study was to determine the persistence of and variation in overweight and obesity among a cohort of children followed up from 4 to 6 years of age. METHODS: The data were drawn from the ELOIN (Longitudinal Childhood Obesity Study), a population-based cohort in the Community of Madrid, Spain. A total of 2435 children were involved. Weight and height were objectively measured and standardised at 4 (2012-2013) and 6 years of age (2014-2015) by 31 purpose-trained pediatricians. Three reference criteria were used: the World Health Organization (WHO-2006), International Obesity Task Force (IOTF-2000), and Spanish tables of the Orbegozo Foundation 2004, were used to define "absence of excess weight", overweight and obesity. RESULTS: According to the above three classification criteria, between the ages of 4 and 6 years the prevalence of overweight increased from 5.7%-16.5% (range of the 3 criteria) to 8.9%-17.0%, and obesity increased from 3.0%-5.4% to 6.1%-10.1%. Three out of every 4 obese children at age 4 years persisted with obesity at age 6 years, whereas 20.6%-29.3% who were overweight became obese. A total of 8.0% to 16.1% of children maintained "excess weight" (overweight/obesity), 7.9% to 11% were new cases, and 2.2% to 5.9% showed remission. CONCLUSIONS: Excess weight increased between the ages of 4 and 6 years. Important variations were observed in weight status susceptible to intervention during well-child visits.

Varicella and herpes zoster in Madrid, based on the Sentinel General Practitioner Network: 1997-2004.

BACKGROUND: Varicella (chickenpox) is the primary disease caused by varicella-zoster virus. It is extremely contagious and is frequent in children. Indeed, in the absence of vaccination, a high proportion of the population is liable to contract it. Herpes zoster -more frequent among adults- is caused by reactivation of the latent virus. The objective of this study is to describe the status of and time trend for varicella and herpes zoster in the Madrid Autonomous Region prior to the introduction of the vaccine to the general population. DATA SOURCE: individualised varicella and herpes zoster case records kept by the Madrid Autonomous Region Sentinel General Practitioner Network for the period 1997-2004. Cumulative incidences, crude and standardised incidence rates, and age-specific rates of varicella and herpes zoster were calculated for each year. Kendall's Tau-b correlation coefficient was calculated to evaluate whether incidence displayed a time trend. Spectral density in the time series of weekly incidences was estimated using a periodogram. RESULTS: Standardised annual varicella incidence rates ranged from 742.5 (95% CI: 687.2-797.7) to 1239.6 (95% CI: 1164.5-1313.4) cases per 100 000 person-years. Most cases affected children, though complications were more frequent in adults. Varicella incidence displayed an annual periodicity but no trend over time. Most herpes zoster cases occurred at advanced ages, with incidence registering a rising annual trend but no seasonality factor. CONCLUSION: In the absence of vaccination, no significant changes in varicella incidence were in evidence recent years, though these were observed in the incidence of herpes zoster. Sentinel general practitioner networks are a valid instrument for surveillance of diseases such as varicella. Further varicella vaccination-coverage and vaccine-efficacy studies are called for.

Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study.

BACKGROUND: The Streptococcus pneumoniae Invasive Disease network (SpIDnet) actively monitors populations in nine sites in seven European countries for invasive pneumococcal disease. Five sites use 13-valent pneumococcal conjugate vaccine (PCV13) alone and four use the ten-valent PCV (PCV10) and PCV13. Vaccination uptake is greater than 90% in six sites and 67-78% in three sites. We measured the effects of introducing high-valency PCVs on the incidence of invasive pneumococcal disease in children younger than 5 years. METHODS: We compared the incidence of invasive pneumococcal disease in each of the 4 years after the introduction of PCV13 alone or PCV10 and PCV13 with the average incidence during the preceding period of heptavalent PCV (PCV7) use, overall and by serotype category. We calculated incidence rate ratios (IRRs) and 95% CIs for each year and pooled the values for all sites in a random effects meta-analysis. FINDINGS: 4 years after the introduction of PCV13 alone or PCV10 and PCV13, the pooled IRR was 0·53 (95% CI 0·43-0·65) for invasive pneumococcal disease in children younger than 5 years caused by any serotype, 0·16 (0·07-0·40) for disease caused by PCV7 serotypes, 0·17 (0·07-0·42) for disease caused by 1, 5, and 7F serotypes, and 0·41 (0·25-0·69) for that caused by 3, 6A and 19A serotypes. We saw a similar pattern when we restricted the analysis to sites where only PCV13 was used. The pooled IRR for invasive pneumococcal disease caused by non-PCV13 serotypes was 1·62 (1·09-2·42). INTERPRETATION: The incidence of invasive pneumococcal disease caused by all serotypes decreased due to a decline in the incidence of vaccine serotypes. By contrast, that of invasive pneumococcal disease caused by non-PCV13 serotypes increased, which suggests serotype replacement. Long-term surveillance will be crucial to monitor the further effects of PCV10 and PCV13 vaccination programmes in young children. FUNDING: European Centre for Disease Prevention and Control, Czech National Institute of Public Health, French National Agency for Public Health, Irish Health Services Executive, Norwegian Institute of Public Health, Public Health Agency of Catalonia, Public Health Department of Community of Madrid, Navarra Hospital Complex, Public Health Institute of Navarra, CIBER Epidemiology and Public Health, Institute of Health Carlos III, Public Health Agency of Sweden, and NHS Scotland.

Increase of serotype 8, ST53 clone, as the prevalent strain of Streptococcus pneumoniae causing invasive disease in Madrid, Spain (2012-2015) / Incremento del serotipo 8, clon ST53, como la cepa más prevalente causante de enfermedad neumocócica invasora en Madrid, España (2012-2015)

INTRODUCTION: In recent years, Streptococcus pneumoniae serotype 8 has become the most prevalent cause of invasive pneumococcal disease (IPD) in Madrid, Spain. The objective of this study was to characterize the invasive clones of S. pneumoniae serotype 8 in Madrid over the 2012-2015 period. METHODS: From January 2012 to December 2015, a total of 1543 invasive isolates were studied. Serotyping was carried out by Pneumotest-Latex agglutination and Quellung reaction. Susceptibilities to penicillin, erythromycin and levofloxacin were determined by the Etest®. All serotype 8 strains were typed by multilocus sequence typing (MLST) and by pulsed-field gel electrophoresis (PFGE). RESULTS: Two hundred and forty-eight (248) serotype 8 strains were detected (16.1%) and 243 of them were available for molecular typing. Nine sequence types (STs) by MLST (8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 and 8-ST4301), and nine PFGE profiles were identified (one corresponding to each ST). The 8-ST53 clone was the most widespread, and increased from 53.8% among all serotype 8 isolates in 2012, to 90.1% in 2015. In contrast, the 8-ST63 clone, resistant to levofloxacin and erythromycin, decreased from 30.8%, among all serotype 8 strains in 2012, to 5.0% in 2015. CONCLUSIONS: The increase in our region of S. pneumoniae serotype 8, not included in conjugated vaccines, occurred at the expense of the 8-ST53 clone. On the contrary, the 8-ST63 clone decreased. Since clone 8-ST63 has the theoretical advantage of its levofloxacin-erythromycin resistance in comparison to 8-ST53, the predominance of 8-ST53 over 8-ST63 is striking

INTRODUCCIÓN: En los últimos años Streptococcus pneumoniae serotipo 8 ha sido la causa más prevalente de enfermedad neumocócica invasora (ENI) en la Comunidad de Madrid. El objetivo de este estudio fue caracterizar los clones invasores de S. pneumoniae serotipo 8 circulantes en Madrid ente los años 2012 y 2015. MÉTODOS: Se estudiaron 1.543 cepas causantes de ENI aisladas entre enero de 2012 y diciembre de 2015. El serotipado se realizó mediante aglutinación con Pneumotest-Latex y reacción de Quellung. La determinación de la sensibilidad frente a penicilina, eritromicina y levofloxacino se realizó mediante Etest(R). Las cepas del serotipo 8 se tipificaron por MLST (multi-locus sequence typing) y electroforesis en campo pulsado (PFGE). RESULTADOS: Se detectaron 248 cepas del serotipo 8 (16,1%) y 243 de ellas estuvieron disponibles para tipado molecular. Se identificaron 9 tipos de ST: 8-ST53, 8-ST63, 8-ST404, 8-ST1107, 8-ST989, 8-ST1110, 8-ST2231, 8-ST3544 y 8-ST4301, y 9 perfiles de PFGE (uno correspondiente a cada ST). El clon 8-ST53 fue el más prevalente dentro del serotipo 8 y aumentó del 53,8% en 2012 al 90,1% en 2015. Por el contrario el clon 8-ST63 asociado con resistencia a levofloxacino y eritromicina disminuyó del 30,8% en 2012 al 5,0% en 2015. CONCLUSIONES: El incremento del serotipo 8 en nuestra región, no cubierto por las actuales vacunas conjugadas, se produjo a expensas del clon 8-ST53. Inversamente, el clon 8-ST63 disminuyó. Dado que el clon 8-ST63 presenta sobre el 8-ST53 la ventaja teórica de su resistencia frente a levofloxacino y eritromicina, resulta llamativo el predominio de 8-ST53 sobre 8-ST63

Measles virus genetic evolution throughout an imported epidemic outbreak in a highly vaccinated population.

Measles virus circulates endemically in African and Asian large urban populations, causing outbreaks worldwide in populations with up-to-95% immune protection. We studied the natural genetic variability of genotype B3.1 in a population with 95% vaccine coverage throughout an imported six month measles outbreak. From first pass viral isolates of 47 patients we performed direct sequencing of genomic cDNA. Whilst no variation from index case sequence occurred in the Nucleocapsid gene hyper-variable carboxy end, in the Hemagglutinin gene, main target for neutralizing antibodies, we observed gradual nucleotide divergence from index case along the outbreak (0% to 0.380%, average 0.138%) with the emergence of transient and persistent non-synonymous and synonymous mutations. Little or no variation was observed between the index and last outbreak cases in Phosphoprotein, Nucleocapsid, Matrix and Fusion genes. Most of the H non-synonymous mutations were mapped on the protein surface near antigenic and receptors binding sites. We estimated a MV-Hemagglutinin nucleotide substitution rate of 7.28 × 10-6 substitutions/site/day by a Bayesian phylogenetic analysis. The dN/dS analysis did not suggest significant immune or other selective pressures on the H gene during the outbreak. These results emphasize the usefulness of MV-H sequence analysis in measles epidemiological surveillance and elimination programs, and in detection of potentially emergence of measles virus neutralization-resistant mutants.