Surveillance of invasive pneumococcal disease in Spain exploring the impact of the COVID-19 pandemic (2019-2023).

OBJECTIVES: Dynamic trends of invasive pneumococcal disease (IPD) including the evolution of prevalent serotypes are very useful to evaluate the impact of current and future pneumococcal conjugate vaccines (PCVs) and the rise of non-vaccine serotypes. In this study, we include epidemiological patterns of S. pneumoniae before and after COVID-19 pandemic. METHODS: We characterized all national IPD isolates from children and adults received at the Spanish Pneumococcal Reference Laboratory during 2019-2023. RESULTS: In the first pandemic year 2020, we found a general reduction in IPD cases across all age groups, followed by a partial resurgence in children in 2021 but not in adults. By 2022, IPD cases in children had returned to pre-pandemic levels, and partially in adults. In 2023, IPD rates surpassed those of the last pre-pandemic year. Notably, the emergence of serotype 3 is of significant concern, becoming the leading cause of IPD in both pediatric and adult populations over the last two years (2022-2023). Increase of serotype 4 in young adults occurred in the last epidemiological years. CONCLUSIONS: The COVID-19 pandemic led to a temporary decline in all IPD cases during 2020 attributable to non-pharmaceutical interventions followed by a subsequent rise. Employing PCVs with broader coverage and/or enhanced immunogenicity may be critical to mitigate the marked increase of IPD.

Effectiveness of Modified Vaccinia Ankara-Bavaria Nordic Vaccination in a Population at High Risk of Mpox: A Spanish Cohort Study.

BACKGROUND: With more than 7500 cases reported since April 2022, Spain has experienced the highest incidence of mpox in Europe. From 12 July onward, the modified vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine was offered as pre-exposure prophylaxis for those receiving pre-exposure prophylaxis for human immunodeficiency virus (HIV-PrEP). Our aim was to assess the effectiveness of 1 dose of MVA-BN vaccine as pre-exposure prophylaxis against mpox virus (MPXV) infection in persons on HIV-PrEP. METHODS: National retrospective cohort study between 12 July and 12 December 2022. Individuals aged ≥18 years receiving HIV-PrEP as of 12 July with no previous MPXV infection or vaccination were eligible. Each day, we matched individuals receiving a first dose of vaccine and unvaccinated controls of the same age and region. We used a Kaplan-Meier estimator, calculated risk ratios (RR) and vaccine effectiveness (VE = [1 - RR]x100). RESULTS: We included 5660 matched pairs, with a median follow-up of 62 days (interquartile range, 24-97). Mpox cumulative incidence was 5.6 per 1000 (25 cases) in unvaccinated and 3.5 per 1000 (18 cases) in vaccinated. No effect was found during days 0-6 post-vaccination (VE, -38.3; 95% confidence interval [CI], -332.7 to 46.4), but VE was 65% at ≥7 days (95% CI, 22.9 to 88.0) and 79% at ≥14 days (95% CI, 33.3 to 100.0) post-vaccination. CONCLUSIONS: One dose of MVA-BN vaccine offered protection against mpox in most-at-risk population shortly after the vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.

Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children.

BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.

Effectiveness of a Second Dose of an mRNA Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in Individuals Previously Infected by Other Variants.

BACKGROUND: Single-dose vaccination was widely recommended in the pre-Omicron era for persons with previous SARS-CoV-2 infection. The effectiveness of a second vaccine dose in this group in the Omicron era is unknown. METHODS: We linked nationwide population registries in Spain to identify community-dwelling individuals aged 18-64, with a positive SARS-CoV-2 test before single-dose mRNA vaccination (mRNA-1273 or BNT162b2). Every day between 3 January and 6 February 2022 we matched 1:1 individuals receiving a second mRNA vaccine dose and controls on sex, age, province, first dose type and time, month of primary infection, and number of previous tests. We then estimated Kaplan-Meier risks of confirmed SARS-CoV-2 reinfection. We performed a similar analysis in a Delta-dominant period, between 19 July and 30 November 2021. RESULTS: In the Omicron period, estimated effectiveness (95% CI) of a second dose was 62.2% (58.2-66.4%) 7-34 days after administration, similar across groups defined by age, sex, type of first vaccine, and time since the first dose. Estimated effectiveness was 65.4% (61.1-69.9%) for mRNA-1273 and 52.0% (41.8-63.1%) for BNT162b2. Estimated effectiveness was 78.5% (67.4-89.9%), 66.1% (54.9-77.5%), and 60.2% (55.5-64.8%) when primary infection had occurred in the Delta, Alpha, and pre-Alpha periods, respectively. In the Delta period, the estimated effectiveness of a second dose was 8.8% (-55.3% to 81.1%). CONCLUSIONS: Our results suggest that, over 1 month after administration, a second dose of mRNA vaccine increases protection against SARS-CoV-2 reinfection with the Omicron variant among individuals with single-dose vaccination and previously infected with another variant.

[Effectiveness of vaccines against SARS-CoV-2 used in Spain: infection, hospitalization and mortality in people aged fifty/fifty-nine.] / Efectividad de las vacunas frente a SARS-CoV-2 utilizadas en España: infección, hospitalización y mortalidad en personas de cincuenta a cincuenta y nueve años.

In this paper we compared brand-specific COVID-19 vaccine effectiveness (VE) during August 2021 in persons born 1962-1971 and vaccinated during June. For SARS-CoV-2 symptomatic infection, protection was lower for Janssen (56%; CI95%: 53-59) or AstraZeneca [Vaxzevria] (68%; CI95%: 65-70), compared to Pfizer-BioNTech [Comirnaty] (78%; CI95%: 77-78), AstraZeneca/Pfizer (86%; CI95%: 80-90) or Moderna [Spikevax] (89%; CI95%: 88-90). VE against hospitalization was ranged 86% for Janssen to 97%-98% for other vaccines.

En este trabajo se comparó la efectividad de la vacuna contra la COVID-19 (EV) durante agosto de 2021, en personas nacidas entre 1962 y 1971 y vacunadas durante junio, según la marca utilizada. La protección frente a infección por SARS-CoV-2 sintomática fue menor para la vacuna de Janssen (56%; IC95%: 53-59) y AstraZeneca [Vaxzevria] (68%; IC95%: 65-70), en comparación con Pfizer [Comirnaty] (78%; IC95%: 77-78), AZ/Pfizer (86%; IC95%: 80-90) y Moderna [Spikevax] (89%; IC95%: 88-90). La EV contra la hospitalización osciló entre el 86% de Janssen y el 97%-98% de las demás vacunas.

Efectividad de las vacunas frente aSARS-CoV-2 utilizadas en España: infección, hospitalización y mortalidaden personas de cincuenta a cincuentay nueve años / Effectiveness of vaccines against SARS-CoV-2 used in Spain: infection, hospitalization and mortality in people aged fifty/fifty-nine

En este trabajo se comparó la efectividad de la vacuna contra la COVID-19 (EV) durante agosto de 2021, en personas nacidas entre 1962y 1971 y vacunadas durante junio, según la marca utilizada. La protección frente a infección por SARS-CoV-2 sintomática fue menorpara la vacuna de Janssen (56%; IC95%: 53-59) y AstraZeneca [Vaxzevria] (68%; IC95%: 65-70), en comparación con Pfizer [Comir-naty] (78%; IC95%: 77-78), AZ/Pfizer (86%; IC95%: 80-90) y Moderna [Spikevax] (89%; IC95%: 88-90). La EV contra la hospitalizaciónosciló entre el 86% de Janssen y el 97%-98% de las demás vacunas.(AU)

In this paper we compared brand-specific COVID-19 vaccine effectiveness (VE) during August 2021 in persons born 1962-1971 and vaccina-ted during June. For SARS-CoV-2 symptomatic infection, protection was lower for Janssen (56%; CI95%: 53-59) or AstraZeneca [Vaxzevria](68%; CI95%: 65-70), compared to Pfizer-BioNTech [Comirnaty] (78%; CI95%: 77-78), AstraZeneca/Pfizer (86%; CI95%: 80-90) or Moderna[Spikevax] (89%; CI95%: 88-90). VE against hospitalization was ranged 86% for Janssen to 97%-98% for other vaccines

Effectiveness of mRNA vaccine boosters against infection with the SARS-CoV-2 omicron (B.1.1.529) variant in Spain: a nationwide cohort study.

BACKGROUND: The omicron (B.1.1.529) variant of SARS-CoV-2 has increased capacity to elude immunity and cause breakthrough infections. The aim of this study was to estimate the effectiveness of mRNA-based vaccine boosters (third dose) against infection with the omicron variant by age, sex, time since complete vaccination, type of primary vaccine, and type of booster. METHODS: In this nationwide cohort study, we linked data from three nationwide population registries in Spain (Vaccination Registry, Laboratory Results Registry, and National Health System registry) to select community-dwelling individuals aged 40 years or older, who completed their primary vaccine schedule at least 3 months before the start of follow-up, and had not tested positive for SARS-CoV-2 since the start of the pandemic. On each day between Jan 3, and Feb 6, 2022, we matched individuals who received a booster mRNA vaccine and controls of the same sex, age group, postal code, type of vaccine, time since primary vaccination, and number of previous tests. We estimated risk of laboratory-confirmed SARS-CoV-2 infection using the Kaplan-Meier method and compared groups using risk ratios (RR) and risk differences. Vaccine effectiveness was calculated as one minus RR. FINDINGS: Between Jan 3, and Feb 6, 2022, 3 111 159 matched pairs were included in our study. Overall, the estimated effectiveness from day 7 to 34 after a booster was 51·3% (95% CI 50·2-52·4). Estimated effectiveness was 52·5% (51·3-53·7) for an mRNA-1273 booster and 46·2% (43·5-48·7) for a BNT162b2 booster. Effectiveness was 58·6% (55·5-61·6) if primary vaccination had been with ChAdOx1 nCoV-19 (Oxford-AstraZeneca), 55·3% (52·3-58·2) with mRNA-1273 (Moderna), 49·7% (48·3-51·1) with BNT162b2 (Pfizer-BioNTech), and 48·0% (42·5-53·7) with Ad26.COV2.S (Janssen). Estimated effectiveness was 43·6% (40·0-47·1) when the booster was administered between 151 days and 180 days after complete vaccination and 52·2% (51·0-53·3) if administered more than 180 days after primary scheduled completion. INTERPRETATION: Booster mRNA vaccine-doses were moderately effective in preventing infection with the omicron variant of SARS-CoV-2 for over a month after administration, which indicates their suitability as a strategy to limit the health effects of COVID-19 in periods of omicron variant domination. Estimated effectiveness was higher for mRNA-1273 compared with BNT162b2 and increased with time between completed primary vaccination and booster. FUNDING: None.

Prevalence and undiagnosed fraction of hepatitis C infection in 2018 in Spain: results from a national population-based survey.

BACKGROUND: A national strategy against hepatitis C virus (HCV) was implemented in Spain in 2015 with the aim of reducing associated morbidity and mortality. In order to improve our understanding of the epidemiology of HCV, we analysed the prevalence of HCV antibodies and active infection overall and by age and sex in the general population aged 20-80 years. We also aimed to report the undiagnosed fraction. METHODS: A national population-based seroprevalence survey was conducted in 2017-2018. A representative sample from the general population was selected using two-stage sampling. The prevalence of total HCV antibodies and of HCV RNA was calculated using inverse probability weighting based on bootstrapping. RESULTS: Overall, we approached 17 496 persons; 9103 agreed to participate and met the eligibility criteria and 7675 were aged 20-80. We obtained a prevalence of HCV antibodies of 0.85% [95% confidence interval (CI): 0.64-1.08%] and of active infection of 0.22% (95% CI: 0.12-0.32%). The prevalence of active HCV infection was highest in men aged 50-59 (0.86%; 95% CI: 0.28-1.57%) and in men aged 60-69 years (0.72%; 95% CI: 0.27-1.28%). Prevalence was below 0.20% in the remaining age groups. The undiagnosed fraction for active HCV infection was 29.4%. CONCLUSION: This study shows that prevalence of HCV in the general population in Spain is low and reflects the impact of scaling up treatment with direct acting antivirals, together with other prevention strategies, from 2015 onwards. The data reported can guide subsequent public health actions.

Direct and Indirect Effectiveness of mRNA Vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 in Long-Term Care Facilities, Spain.

We conducted a registries-based cohort study of long-term care facility residents >65 years of age offered vaccination against severe acute respiratory syndrome coronavirus 2 before March 10, 2021, in Spain. Risk for infection in vaccinated and nonvaccinated persons was compared with risk in the same persons in a period before the vaccination campaign, adjusted by daily-varying incidence and reproduction number. We selected 299,209 persons; 99.0% had >1 dose, 92.6% had 2 doses, and 99.8% of vaccines were Pfizer/BioNTech (BNT162b2). For vaccinated persons with no previous infection, vaccine effectiveness was 81.8% (95% CI 81.0%-82.7%), and 11.6 (95% CI 11.3-11.9) cases were prevented per 10,000 vaccinated/day. In those with previous infection, effectiveness was 56.8% (95% CI 47.1%-67.7%). In nonvaccinated residents with no previous infection, risk decreased by up to 81.4% (95% CI 73.3%-90.3%). Our results confirm vaccine effectiveness in this population and suggest indirect protection in nonvaccinated persons.

Effectiveness of mRNA COVID-19 vaccines in preventing SARS-CoV-2 infections and COVID-19 hospitalisations and deaths in elderly long-term care facility residents, Spain, weeks 53 2020 to 13 2021.

Residents in long-term care facilities (LTCF) experienced a large morbidity and mortality during the COVID-19 pandemic in Spain and were prioritised for early COVID-19 vaccination. We used the screening method and population-based data sources to obtain estimates of mRNA COVID-19 vaccine effectiveness for elderly LTCF residents. The estimates were 71% (95% CI: 56-82%), 88% (95% CI: 75-95%), and 97% (95% CI: 92-99%), against SARS-CoV-2 infections (symptomatic and asymptomatic), and COVID-19 hospitalisations and deaths, respectively.

Vaccines for the prevention of infections in adults: an opinion paper on the situation in Spain / Vacunas para la prevención de infecciones en adultos: artículo de opinión sobre la situación en España

The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table

El calendario de vacunación infantil es bien conocido y generalmente bien implementado en los países desarrollados. Por varias razones, no ocurre lo mismo en el caso de las vacunas destinadas a prevenir las infecciones en adultos, en los que la cobertura vacunal es incompleta y generalmente muy deficiente. Con el fin de evaluar la situación de la vacunación de adultos en España, la Fundación de Ciencias de la Salud ha reunido a una serie de expertos en diferentes campos, incluyendo médicos, enfermeras, representantes de asociaciones de pacientes, gestores sanitarios, economistas, autoridades sanitarias y periodistas para discutir este asunto. El formato fue el de una mesa redonda en la que una serie de preguntas, formuladas previamente por los coordinadores, debían ser contestadas y debatidas. El documento presentado no es una revisión exhaustiva del tema, ni tiene por objeto hacer recomendaciones, simplemente pretende dar una opinión multidisciplinar sobre aspectos que pueden ser debatibles o controvertidos. El documento revisa las principales enfermedades de los adultos que pueden prevenirse con vacunas, su impacto clínico y económico, las posibilidades de reducirlos con los programas de vacunación y las dificultades para llevarlos a cabo. Se discutió el papel de la enfermería, la farmacia, los servicios de salud, las asociaciones de pacientes y la propia administración sanitaria para cambiar la situación actual. Se evaluaron las perspectivas para nuevas vacunas y se especuló sobre el futuro en este campo. Por último, se discutieron los aspectos éticos especialmente relevantes en la toma de decisiones con respecto a la vacunación, que deben ser afrontados tanto por los individuos como por los estados. Hemos intentado resumir, al final de la presentación de cada pregunta, la opinión que representaba el consenso de todos los miembros de la mesa

Riesgo epidémico de la enfermedad asociada a una nueva cepa de Clostridium difficile / Epidemic risk of disease associated with a new strain of Clostridium difficile

Clostridium difficile ha puesto en alerta a los profesionales sanitarios en los últimos años por el incremento de su incidencia en Norteamérica y Europa. En brotes nosocomiales y en casos adquiridos en la comunidad, se ha identificado una cepa de C. difficile caracterizada como tipo toxinogénico III, ribotipo por PCR 027 (C. difficile 027), que tiene una patogenicidad mayor debido a la hiperproducción de exotoxinas y presenta un perfil de resistencia a antibióticos característico. En Europa, desde 2003, varios países han notificado casos de enfermedad asociada a C. difficile 027, lo que demuestra su rápida diseminación. En este artículo se revisan los últimos brotes asociados a C. difficile 027, que indican la necesidad de establecer un sistema de vigilancia homogéneo para la detección temprana y la toma de medidas de control que permitan disminuir la extensión de los brotes desde su inicio (AU)

The incidence of Clostridium difficile infection in North America and Europe has increased in the last years, generating concern among health professionals. A new strain of C. difficile has been identified in recent nosocomial outbreaks and community-acquired infections. This new strain, characterized as toxigenic type III, PCR ribotype 027 (C. difficile 027), presents higher pathogenicity because of increased exotoxin production, and a characteristic antibiotic resistance profile. Since 2003, several European countries have notified cases of C. difficile 027-associated disease, a fact that demonstrates its rapid dissemination. In this article, we review the latest nosocomial outbreaks associated with this new strain, which illustrate the need for a standardized surveillance system for early detection and implementation of control measures aimed at reducing the spread of this microorganism (AU)

[Epidemic risk of disease associated with a new strain of Clostridium difficile]. / Riesgo epidémico de la enfermedad asociada a una nueva cepa de Clostridium difficile.

The incidence of Clostridium difficile infection in North America and Europe has increased in the last years, generating concern among health professionals. A new strain of C. difficile has been identified in recent nosocomial outbreaks and community-acquired infections. This new strain, characterized as toxigenic type III, PCR ribotype 027 (C. difficile 027), presents higher pathogenicity because of increased exotoxin production, and a characteristic antibiotic resistance profile. Since 2003, several European countries have notified cases of C. difficile 027-associated disease, a fact that demonstrates its rapid dissemination. In this article, we review the latest nosocomial outbreaks associated with this new strain, which illustrate the need for a standardized surveillance system for early detection and implementation of control measures aimed at reducing the spread of this microorganism.

[Laboratory diagnosis of pertussis. Role of serology]. / Diagnóstico de laboratorio de tos ferina. Papel de la serología.

Culture is the reference method for the diagnosis of infection by Bordetella pertussis. Nevertheless, delayed sample collection and previous antibiotic treatment can limit culture sensitivity. In principle, direct immunofluorescence provides immediate diagnosis. It is, however, a subjective procedure that shows low sensitivity and specificity. PCR techniques increase culture sensitivity while maintaining high specificity, but their performance decreases along the evolution of the disease. Serologic methods are the main alternative for cases in which diagnosis is delayed. Current recommendations center on ELISA techniques that include purified antigens, such as filamentous hemaglutinin, and particularly, pertussis toxin. Traditionally, serological diagnosis requires confirmation by demonstrated seroconversion, but now the possibility of diagnosis based on titration of a single serum sample is being evaluated.