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Introduction Invasive meningococcal disease (IMD) is a severe infectious disease, mainly affecting children under 5 years, associated with long-term physical, neurological and psychological sequelae. In Spain, most IMD cases are caused by meningococcal serogroup B (MenB). This study estimates its economic burden from a societal perspective in Spain. Methods A previously published bottom-up, model-based incidence costing approach by Scholz et al. (2019) to estimate the economic burden of MenB in Germany was adapted to the Spanish setting. Diagnosis and age-related costs for a hypothetical Spanish cohort were calculated over a lifetime horizon. Official Spanish databases, literature and expert opinion were used as data sources. The costs were updated to 2019 prices, and a 3% discount rate was applied. Direct costs related to the acute IMD phase, long-term sequelae, rehabilitation and public health response were considered. Indirect costs included productivity losses and premature mortality and were calculated using the human-capital approach (HCA) and friction-cost approach (FCA). Deterministic and probabilistic sensitivity analyses were also performed. Result At base-case, the total cost for a cohort of 142 patients (2017–2018 period) was €4.74 million (€33,484/case) using the FCA and €13.14 million (€92,768/case) using the HCA. Direct costs amounted to €4.65 million (€32,765/case). Sequelae costs represented 62.46% of the total cost using the FCA and 77.63% using the HCA. Deterministic sensitivity analysis showed that variation of ± 20% in the input parameter values (population, epidemiology, productivity, costs) had the greatest influence on the base-case results, and the probabilistic sensitivity analysis showed the probability of fitting base-case estimates was > 99%, both for FCA and HCA. Discussion MenB IMD is an uncommon but severe disease, with a high economic burden for Spanish society. The elevated costs per IMD case reflect its severity in each patient suffering this disease, especially due to the development of sequelae.

Abstract: Introduction: Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis that is characterized by a chronic, severe cough. The optimum immunization schedule for pertussis is unclear, so these vary by countries. Aim: To estimate the seroprevalence of pertussis in adults in Hungary. Method: Serum anti-pertussis toxin immunoglobulin G (anti-PT IgG) antibody levels were analyzed using enzyme-linked immunosorbent assay in adults in general practitioners’ practices during one year. Sera were classified following manufacturer’s instructions as: strongly indicative of current/recent infection (≥1.5 optical density [OD] units); indicative of current/recent infection (≥1.0 OD units); seropositive (>0.3 OD units); or seronegative (≤0.3 OD units). Results: 1999 adults (60.6% female; mean age 47.4 ± 17.7 years) were included. 14.8% were seropositive, 1.1% were indicative of current/recent infection, and 0.1% were strongly indicative of current/recent infection. Conclusions: 85.2% of the subjects were seronegative and therefore susceptible to pertussis infection. Approximately 1% was suspicious of current/recent pertussis infection, potentially transmissible to susceptible young infants. Vaccination of adults is a key way to indirectly protect infants. Orv Hetil. 2018; 159(13): 503–510.

Resumen: Introducción: El estudio se llevó a cabo para estimar la carga de enfermedad de la gripe confirmada por laboratorio en niños menores de 15 años. Pacientes y métodos: Los niños que acudieron al Hospital Universitario de Basurto con síntomas de infección respiratoria aguda y/o fiebre aislada entre noviembre de 2010 y mayo de 2011 fueron incluidos en el estudio (NCT01592799). Se tomaron 2 muestras de secreción nasofaríngea: una para un test de diagnóstico rápido en el Servicio de Urgencias y otra para análisis en laboratorio con reacción en cadena de la polimerasa en tiempo real y cultivo viral. Resultados: Se seleccionó a un total de 501 niños, de los que 91 fueron hospitalizados. El diagnóstico de gripe se confirmó en 131 (26,1%); 120/410 (29,3%) fueron tratados ambulatoriamente y 11/91 (12,1%), hospitalizados. En 370/501 niños (73,9%) el resultado no fue positivo. La proporción de otros virus respiratorios fue 145/501 (28,9%) casos y de coinfección con otro virus respiratorio además de gripe de 7/501 (1,4%). Los tipos de virus de gripe fueron: A (H1N1 y H3N2) 53,2% (67/126); B (Victoria y Yamagata) 46,0% (58/126); A + B 0,8% (1/126). El coste médico directo medio asociado con cada caso de gripe confirmada fue de 177,00 € (N = 131). No se observaron diferencias estadísticamente significativas entre el coste asociado con gripe A o B. Conclusión: Casi la mitad de los casos fueron virus de gripe B. La administración de una vacuna que incluya tipos A y B de gripe debería reducir la carga de la enfermedad. Abstract: Introduction: This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age. Patients and methods: Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture. Results: A total of 501 children were recruited, of whom 91 were hospitalized. Influenza diagnosis was confirmed in 131 children (26.1%); 120 of 410 (29.3%) treated as outpatients and 11 of 91 (12.1%) hospitalized children. A total of 370 of 501 children (73.9%) had no laboratory test positive for influenza. The proportion of subjects with other respiratory viruses was 145/501 (28.9%) cases and co-infection with the influenza virus plus another respiratory virus was detected in 7/501 (1.4%) cases. Influenza virus types were: A (H1N1 and H3N2) 53.2% (67/126); B (Victoria and Yamagata) 46.0% (58/126); A + B 0.8% (1/126). The median direct medical costs associated with each case of laboratory-confirmed influenza was €177.00 (N = 131). No significant differences were observed between the medical costs associated with influenza A and B. Conclusion: Almost half of the cases were influenza virus B type. The administration of a vaccine containing influenza A and B types to children below 15 years of age might reduce the overall burden of the illness.

Background: Rotavirus (RV) is worldwide an important cause of acute gastroenteritis (AGE) in infants and young children. There is no specific treatment for AGE caused by RV (RVGE) but since 2006 two safe and effective vaccines have been available. RV vaccination was included in the national immunization program (NIP) of Latvia in 2015 with full reimbursement, and within the first year a coverage of 87% was achieved. This surveillance study was carried out to investigate the proportion of RVGE among AGE episodes in Latvia up to the inclusion of RV vaccination in the NIP to provide a basis for future assessments of the impact of RV vaccination. Methods: Prospective, one-year observational study of children younger than 5 years presenting with AGE in the primary care setting. At first primary care contact, a stool sample was collected and tested for RV using a rapid, visual immunochromatographic kit. The parents monitored their child’s symptoms over 2 weeks after the first contact and the investigator recorded these observations during a follow-up phone call. The proportion of RVGE among the AGE cases was estimated and the severity of each AGE case was assessed based on the recorded symptoms using the 20-point Vesikari scale. The seasonality of RVGE was also investigated. Results: Fifty-two primary care investigators collected data on 606 evaluable children with AGE. The proportion of RVGE was 38.1%. Severe AGE was experienced by 40.7% of the RV-positive and 19.5% of the RV-negative patients. The rate of hospitalization was 9.1% for the RV-positive and 4.8% for the RV-negative with no difference in the mean duration of hospital stays. AGE and RVGE both occurred all year round but with a clearly marked peak only for RVGE, from March to May. Conclusion: This study underlines that RV is an important cause of AGE in children under 5 years old in Latvia and that the burden of disease of RVGE in primary care was substantial before inclusion of RV vaccination in the NIP. Trial registration: NCT01733849

BACKGROUND Rotavirus (RV) causes a high proportion of acute gastroenteritis (AGE) cases, especially among children under the age of five years old. This surveillance study was undertaken to study the incidence and severity of rotavirus gastroenteritis (RVGE) in primary care settings in Bulgaria over a one-year period. METHODS In this prospective, observational study of AGE cases in children under five years of age presenting in the primary care setting over a one year period, stool samples were collected and tested for RV using a rapid visual immunochromatographic test kit. After the first visit, parents monitored their child for about two weeks and reported the symptoms experienced by the child during the follow-up period to the physician in a follow-up phone call. The percentage of RVGE cases among AGE was calculated and the severity of AGE (according to the 20-point Vesikari scale) was assessed by the physician based on the symptoms reported by the parents. The seasonality of RVGE was also studied. RESULTS The proportion of RVGE among the 624 AGE cases examined was 25.5%. Severe AGE was experienced by 81.8% RV-positive and 54.6% RV-negative children (p-value

This review was undertaken to consolidate information on the epidemiology and burden of influenza B, as well as the circulation patterns of influenza B lineage in 9 European countries. Following a comprehensive search of peer-reviewed and gray literature sources, we found that published data on influenza B epidemiology and burden are scarce. Surveillance data show frequent co-circulation of both influenza B lineages during influenza seasons, but little is known about its impact, especially in adults and the clinical burden of influenza B remains unknown. Mismatch between the circulating influenza B lineage and vaccine recommendations has been seen in at least one influenza season in every country. Such observations could impact the effectiveness of seasonal influenza vaccination programs using trivalent vaccines, which contain only one influenza B lineage (B/Yamagata or B/Victoria) and highlight the need for local studies to better understand the epidemiology and burden of influenza B in these countries.

Introduction This multi-center, hospital-based observational study determined the seroprevalence of pertussis antibodies amongst healthcare professionals from three different hospitals in Spain to ascertain the health status of professionals attending to susceptible groups who are at risk of contracting and transmitting pertussis. Methods Medical professionals from three hospitals in Spain were recruited for this study ( NCT01706224 ). Serum samples from subjects were assessed for anti-pertussis antibodies by ELISA. The percentage of subjects positive for anti-pertussis antibodies were determined by age-strata, gender, vaccination status, professional level (physicians, nurses, ancillary nurses and midwives), hospital department, number of working years, numbers of hours spent with the patient as well as number of children in the household. Results Overall, 31.2% of subjects were seropositive; 3.3% of these healthcare professionals had ELISA values indicative of current or recent infection. There were no significant differences in terms of pertussis prevalence with respect to age, gender, hospital department, profession, number of working years and number of hours spent with patients. These levels of seronegativity amongst healthcare workers further strengthen the rationale for vaccination amongst this specific population against pertussis.

The development of diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b (Hib) conjugate vaccine combinations culminated with hexavalent vaccines, the largest, most complex vaccine combinations in the immunization calendar. Hexavalent vaccines are used widely in Europe and are co-administered with multiple other recommended vaccines. Hib immunogenicity may reduce when combined with acellular pertussis antigens, or in some co-administrations. We reviewed the epidemiology of H. influenzae disease in Europe aiming to evaluate the current level of Hib control and indirectly assess the effectiveness against Hib of GSK's hexavalent vaccine in 10 countries where it is/has been used almost exclusively. Areas covered: We reviewed surveillance data from the European Union Invasive Bacterial Infections Surveillance Network and the European Surveillance System database from 1999-2014 and extracted case and incidence/notification rates (per 100,000 population) of invasive H. influenzae disease. We included age and serotype/strains distribution among countries in the European Union/European Economic Area region that reported to the European Centre for Disease Prevention and Control surveillance system. Expert commentary: The impact of Hib vaccination in Europe is sustained, testifying to continued effectiveness against invasive Hib disease after the implementation of hexavalent vaccines into immunization programs, which, since 2006, has been almost exclusively GSK´s hexavalent DTPa-HBV-IPV/Hib vaccine.

Introduction: This study was undertaken to estimate the burden of morbidity associated with laboratory-confirmed influenza in children below 15 years of age. Patients and methods: Children presenting with acute respiratory infection and/or isolated fever at the Basurto University Hospital, Bilbao, Spain between November 2010 and May 2011 were included in this study (NCT01592799). Two nasopharyngeal secretion samples were taken from each; one for a rapid influenza diagnostic test in the emergency department, and the second for laboratory analysis using real-time polymerase chain reaction and viral culture. Results: A total of 501 children were recruited, of whom 91 were hospitalized. Influenza diagnosis was confirmed in 131 children (26.1%); 120 of 410 (29.3%) treated as outpatients and 11 of 91 (12.1%) hospitalized children. A total of 370 of 501 children (73.9%) had no laboratory test positive for influenza. The proportion of subjects with other respiratory viruses was 145/501 (28.9%) cases and co-infection with the influenza virus plus another respiratory virus was detected in 7/501 (1.4%) cases. Influenza virus types were: A (H1N1 and H3N2) 53.2% (67/126); B (Victoria and Yamagata) 46.0% (58/126); A + B 0.8% (1/126). The median direct medical costs associated with each case of laboratory-confirmed influenza was €177.00 (N = 131). No significant differences were observed between the medical costs associated with influenza A and B. Conclusion: Almost half of the cases were influenza virus B type. The administration of a vaccine containing influenza A and B types to children below 15 years of age might reduce the overall burden of the illness. Resumen: Introducción: El estudio se llevó a cabo para estimar la carga de enfermedad de la gripe confirmada por laboratorio en niños menores de 15 años. Pacientes y métodos: Los niños que acudieron al Hospital Universitario de Basurto con síntomas de infección respiratoria aguda y/o fiebre aislada entre noviembre de 2010 y mayo de 2011 fueron incluidos en el estudio (NCT01592799). Se tomaron 2 muestras de secreción nasofaríngea: una para un test de diagnóstico rápido en el Servicio de Urgencias y otra para análisis en laboratorio con reacción en cadena de la polimerasa en tiempo real y cultivo viral. Resultados: Se seleccionó a un total de 501 niños, de los que 91 fueron hospitalizados. El diagnóstico de gripe se confirmó en 131 (26,1%); 120/410 (29,3%) fueron tratados ambulatoriamente y 11/91 (12,1%), hospitalizados. En 370/501 niños (73,9%) el resultado no fue positivo. La proporción de otros virus respiratorios fue 145/501 (28,9%) casos y de coinfección con otro virus respiratorio además de gripe de 7/501 (1,4%). Los tipos de virus de gripe fueron: A (H1N1 y H3N2) 53,2% (67/126); B (Victoria y Yamagata) 46,0% (58/126); A + B 0,8% (1/126). El coste médico directo medio asociado con cada caso de gripe confirmada fue de 177,00 € (N = 131). No se observaron diferencias estadísticamente significativas entre el coste asociado con gripe A o B. Conclusión: Casi la mitad de los casos fueron virus de gripe B. La administración de una vacuna que incluya tipos A y B de gripe debería reducir la carga de la enfermedad.

Although acute otitis media (AOM) remains a major public health problem worldwide and brings economic burden on health care system and caregivers, little information is available about its epidemiology in Eastern Europe. We conducted an epidemiological, prospective, observational, multi-centre cohort study (NCT01365390) in five East European countries (Estonia, Lithuania, Poland, Romania and Slovenia) between June 2011 and January 2013 to determine the incidence and clinical characteristics of AOM among children aged