Prospective evaluation of indirect costs due to acute rotavirus gastroenteritis in Spain: the ROTACOST study.

BACKGROUND: The effect of rotavirus in developed countries is mainly economic. This study aimed to assess the indirect costs induced by rotavirus acute gastroenteritis (RVAGE) in Spain. METHODS: A prospective observational study was conducted from October 2008 to June 2009. It included 682 children up to 5 years of age with acute gastroenteritis (AGE) who attended primary care (n = 18) and emergency room/hospital settings (n = 10), covering the regions of Galicia and Asturias (North-west Spain). All non-medical expenses incurred throughout the episode were recorded in detail using personal interviews and telephone contact. RESULTS: Among the 682 enrolled children, 207 (30.4%) were rotavirus positive and 170 (25%) had received at least one dose of rotavirus vaccine. The mean (standard deviation) indirect cost caused by an episode of AGE was estimated at 135.17 (182.70) Euros. Costs were 1.74-fold higher when AGE was caused by rotavirus compared with other etiologies: 192.7 (219.8) Euros vs. 111.6 (163.5) Euros (p < .001). The costs for absenteeism were the most substantial with a mean of 91.41 (134.76) Euros per family, resulting in a loss of 2.45 (3.17) days of work. In RVAGE patients, the absenteeism cost was 120.4 (154) Euros compared with 75.8 (123) for the other etiologies (p = .002), because of loss of 3.5 (3.6) vs 1.9 (2.9) days of work (p < .001). Meals costs were 2-fold-higher (48.5 (55) vs 24.3 (46) Euros, p < .001) and travel costs were 2.6-fold-higher (32 (92) vs 12.5 (21.1) Euros, p = .005) in RVAGE patients compared with those with other etiologies. There were no differences between RVAGE and other etiologies groups regarding costs of hiring of caregivers or purchase of material. Patients with RVAGE were admitted to hospital more frequently than those with other etiologies (47.8% vs 14%, p < .001). CONCLUSIONS: Rotavirus generates a significant indirect economic burden. Our data should be considered in the decision-making process of the eventual inclusion of rotavirus vaccine in the national immunization schedule of well developed countries

Risk Analysis by Age on the Burden of Meningococcal Disease in Spain.

We conducted an age-based risk analysis of meningococcal disease in Spain to provide prospects on a rational vaccine schedule in pediatrics. We used the National Hospital Registry to estimate meningococcal hospitalization rate. Population census for each year was used as the denominator in computing the hospitalization rate. We computed the odds ratio of each age using 5-year-old children. There was a dramatic decline in risk in 1 year (OR 0.58) to 4 years of age (OR 0.21). The risk continued to decline until 13 years old. Afterward, it had a minimal upward trajectory observed at 14–17 years old (OR 0.08). Infants and adolescents are at continued risk of invasive meningococcal disease in Spain. The highest risk occurs in infants. Surveillance data, together with evidence on long-term immunogenicity and capacity for herd effect, should be considered for a more relevant immunization schedule

Changes in epigenetic profiles throughout early childhood and their relationship to the response to pneumococcal vaccination

Background: Pneumococcal infections are a major cause of morbidity and mortality in young children and immaturity of the immune system partly underlies poor vaccine responses seen in the young. Emerging evidence suggests a key role for epigenetics in the maturation and regulation of the immune system in health and disease. The study aimed to investigate epigenetic changes in early life and to understand the relationship between the epigenome and antigen-specific antibody responses to pneumococcal vaccination. Methods: The epigenetic profiles from 24 healthy children were analyzed at 12 months prior to a booster dose of the 13-valent pneumococcal conjugate vaccine (PCV-13), and at 24 months of age, using the Illumina Methylation 450 K assay and assessed for differences over time and between high and low vaccine responders. Results: Our analysis revealed 721 significantly differentially methylated positions between 12 and 24 months (FDR < 0.01), with significant enrichment in pathways involved in the regulation of cell-cell adhesion and T cell activation. Comparing high and low vaccine responders, we identified differentially methylated CpG sites (P value < 0.01) associated with HLA-DPB1 and IL6. Conclusion: These data imply that epigenetic changes that occur during early childhood may be associated with antigen-specific antibody responses to pneumococcal vaccines. Keywords: Childhood; DNA methylation; Epigenetics; Immune system; Pneumococcal vaccination; Vaccine response

Excess hospitalizations and mortality associated with seasonal influenza in Spain, 2008–2018

Hospitalization; Influenza; MortalityHospitalització; Grip; MortalitatHospitalización; Gripe; MortalidadBackground Influenza may trigger complications, particularly in at-risk groups, potentially leading to hospitalization or death. However, due to lack of routine testing, influenza cases are infrequently coded with influenza-specific diagnosis. Statistical models using influenza activity as an explanatory variable can be used to estimate annual hospitalizations and deaths associated with influenza. Our study aimed to estimate the clinical and economic burden of severe influenza in Spain, considering such models. Methods The study comprised ten epidemic seasons (2008/2009–2017/2018) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487–488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480–488, 517.1; ICD-10: J09–J18), respiratory (ICD-9: 460–519; ICD-10: J00–J99), respiratory or cardiovascular (C&R, ICD-9: 390–459, 460–519; ICD-10: I00–I99, J00–J99), and all-cause. Means, excluding the H1N1pdm09 pandemic (2009/2010), are reported in this study. Results The mean number of hospitalizations with a diagnosis of influenza per season was 13,063, corresponding to 28.1 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €45.7 million, of which 65.7% was generated by patients with comorbidities. Mean annual influenza-associated C&R hospitalizations were estimated at 34,894 (min: 16,546; max: 52,861), corresponding to 75.0 cases per 100,000 (95% confidence interval [CI]: 63.3–86.3) for all ages and 335.3 (95% CI: 293.2–377.5) in patients aged ≥ 65 years. We estimate 3.8 influenza-associated excess C&R hospitalizations for each hospitalization coded with an influenza-specific diagnosis in patients aged ≥ 65 years. The mean direct annual cost of the estimated excess C&R hospitalizations was €142.9 million for all ages and €115.9 million for patients aged ≥ 65 years. Mean annual influenza-associated all-cause mortality per 100,000 people was estimated at 27.7 for all ages. Conclusions Results suggest a relevant under-detected burden of influenza mostly in the elderly population, but not neglectable in younger people.The BARI study was funded by Sanofi. Martinón-Torres F has received support for the present work from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud): Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540/PI1601569/PI1901090) del plan nacional de I + D + I and ‘fondos FEDER’ and Proyectos GAIN Rescata-Covid_IN845D 2020/23 (GAIN, Xunta de Galicia)

Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective roleThis work was supported by the Spanish Government (Research Program Health Research Fund (FIS; PI10/00540) National Plan I + D + I and FEDER funds), by Regional Galician funds (Promotion of Research Project 10 PXIB 918 184PR) (FMT), by Ministerio de Ciencia e Innovación (SAF2011-26983), and by the Plan Galego IDT, Xunta de Galicia (EM 2012/045) (AS). A grant was received from the Sistema Universitario Gallego -Modalidad REDES (2014-PG139) from the Xunta de Galicia (to AS and FMT). MCL research activities have been supported by grants from Instituto de Investigación Sanitaria de Santiago de Compostela. FMT research activities have been supported by grants from Instituto Carlos III (Intensificación de la actividad investigadora). Investigators received funding from the European Union’s seventh Framework program under ECGA no. 279185 (EUCLIDS) during the production of this paper. JH was supported by the Imperial College Comprehensive Biomedical Research Centre and the Wellcome Trust Centre for Respiratory Infection at Imperial College (DMPED P26077 to JH). Micropathology Ltd. provided support in the form of salaries for authors ES and CF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ sectionS

Addressing influenza’s underestimated burden – Iberian experts call to action

Hospitalization; Influenza; PreventionHospitalització; Grip; PrevencióHospitalización; Gripe; PrevenciónHaving a proper understanding of the impact of influenza is a fundamental step towards improved preventive action. This paper reviews findings from the Burden of Acute Respiratory Infections study on the burden of influenza in Iberia, and its potential underestimation, and proposes specific measures to lessen influenza’s impact.The BARI study was funded by Sanofi

Clinical and economic burden of respiratory syncytial virus in Spanish children: the BARI study

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in children. However, its disease burden remains poorly understood, particularly outside of the hospital setting. Our study aimed to estimate the burden of medically attended acute lower respiratory infection (ALRI) cases potentially related to RSV in Spanish children. Longitudinal data from September 2017 to June 2018 of 51,292 children aged < 5 years old from the National Health‑ care System (NHS) of two Spanish regions were used. Three case definitions were considered: (a) RSV‑specific; (b) RSV‑specific and unspecified acute bronchiolitis (RSV‑specific and Bronchiolitis), and; (c) RSV‑specific and unspecified ALRI (RSV‑specific and ALRI). A total of 3460 medically attended ALRI cases potentially due to RSV were identified, of which 257 (7.4%), 164 (4.7%), and 3039 (87.8%) coded with RSV‑specific, unspecific bronchiolitis, and unspecific ALRI codes, respectively. Medically attended RSV‑specific and ALRI cases per 1000 children was 134.4 in the first year of life, 119.4 in the second, and 35.3 between 2 and 5 years old. Most cases were observed in otherwise healthy children (93.1%). Mean direct healthcare cost per medically attended RSV‑specific and ALRI case was €1753 in the first year of life, €896 in the second, and €683 between 2 and 5 years old. Hospitalization was the main driver of these costs, accounting for 55.6%, 38.0% and 33.4%, in each respective age group. In RSV‑specific cases, mean direct healthcare cost per medically attended case was higher, mostly due to hospitalization: €3362 in the first year of life (72.9% from hospitalizations), €3252 in the second (72.1%), and €3514 between 2 and 5 years old (74.2%). These findings suggest that hospitalization data alone will underestimate the RSV infections requiring medical care, as will relying only on RSV‑specific codes. RSV testing and codification must be improved and preventive solutions adopted, to protect all infants, particularly during the first year of life.The BARI study was funded by Sanofi.Medicin

What have we learnt about rotavirus in Spain in the last 10 years?

En España, las vacunas frente a rotavirus (RV) están disponibles desde 2006 pero no están ni recomendadas ni financiadas por el Sistema Nacional de Salud. Sin embargo, a través de las recomendaciones de la Asociación Española de Pediatría se han alcanzado coberturas de vacunación intermedias. Se ha realizado una revisión sistemática de la literatura sobre los estudios realizados en España en los últimos 12 a˜nos (2006-2018) en relación con la infección y las vacunas frente a RV. Se identifican 43 estudios que cumplían los criterios de selección. La carga de enfermedad en población <5 a˜nos en atención primaria oscila entre 15 y 19 casos por 1.000 ni˜nos y en hospitalaria entre 120 y 480 casos por 100.000, lo que supone una importante repercusión económica y social. Las vacunas frente a RV han mostrado en España una efectividad de entre el 83 y el 96% y un impacto de hasta un 70% de reducción de hospitalizaciones, que es dependiente de la cobertura de vacunación alcanzada. Se identifican además nuevas líneas de investigación relacionadas con el papel de la vacuna del RV y la protección frente a convulsiones, o el papel del microbiota, entre otros. La información actualmente disponible refrenda la importante carga de enfermedad por RV en España y la elevada efectividad de las vacunas disponibles. Estas evidencias permiten una reevaluación de las recomendaciones nacionales sobre vacunación frente a RV.Vaccines against rotavirus (RV) have been available in Spain since 2006, but they are neither recommended nor financed by the National Health System. Nevertheless, through recommendations of the Spanish Association of Paediatrics vaccination has achieved interme- diate coverage. A systematic literature review was performed on studies carried out in Spain in the last 12 years (2006-2018) on RV infection and vaccination. Results: A total of 43 studies were identified that met the inclusion criteria. The disease burden in children less than 5 years in the Primary Care setting ranged from 15 to 19 cases per 1,000 children, and between 120 and 480 cases per 100,000 in the hospital setting, which has a significant economic and social impact. Vaccines against RV have shown an effectiveness of between 83% and 96%, and an impact of up to 70% in reducing hospital admissions, which is dependent on the achieved vaccine coverage. New research lines are identified, such as the role of the rotavirus vaccine and protection against seizures or the impact on the gut microbiota. The current available information supports the significant burden of rotavirus disease in Spain and the high effectiveness of the available vaccines. This evidence should allow for an updated re-evaluation of the national recommendations on rotavirus vaccination.La redacción de este artículo ha sido apoyada en parte a través de una beca de MSD España.Medicin

Real-world impact of rotavirus vaccination in European healthcare settings: a systematic literature review

Introduction: Rotavirus is one of the most common pathogens causing diarrhea in children <5 years and has a major impact on childhood morbidity and mortality. Since the implementation of rotavirus vaccines into childhood immunization programs across Europe, there has been a reduction in rotavirus burden, including hospitalizations, outpatient cases, costs, and deaths. Areas covered: A systematic literature review identified publications describing the clinical and economic impact of rotavirus vaccinations across Europe, from their introduction in 2006 to the end of 2020. A total of 3,137 articles were identified, of which 46 were included in the review. Included articles reported the impact of rotavirus vaccination on disease in any age group. Expert opinion: Rotavirus vaccination has resulted in substantial reductions in hospitalizations and rotavirus-associated costs across Europe, particularly in children <5 years. There is some evidence of herd protection afforded to older age groups where vaccine uptake is high among infants, highlighting the potential for vaccination to confer a greater societal benefit as programs become more established. Increasing vaccination coverage and continuing investment in widespread rotavirus vaccination programs across countries will likely increase the substantial public health benefits associated with vaccination and further reduce the clinical and economic burden of disease.This manuscript was funded by Merck & Co., Inc., Kenilworth, NJ, USA. The funder contributed to the design of the study, collection, analysis, and interpretation of data as well as the writing and revision of the manuscript.Medicin

Fever in high-risk paediatric patients presenting to European emergency departments : the perform experience

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