Predictors of Severity of Influenza-Related Hospitalizations: Results From the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS: The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Vaccine coverage estimation using a computerized vaccination registry with potential underreporting and a seroprevalence study.

OBJECTIVE: To develop a method to estimate vaccination coverage using both a computerized vaccine registry with an unknown underreporting rate and a seroprevalence study. A real example of a meningococcal C conjugate vaccine (MCCV) coverage estimation is studied to illustrate the proposed methodology. METHODS: We reviewed the Vaccine Information System of Valencia (Sistema de Información Vacunal, SIV) for the MCCV status of 1430 subjects aged 3-29 years as part of a seroprevalence study. When MCCV was not registered in SIV, subjects were classified into three groups (MCCV non-registered, no vaccination records and missing information) depending on the registry of other vaccines. A Bayesian model was developed to ascertain the percentage of MCCV-vaccinated subjects based on the meningococcal C seroprotection levels from the seroprevalence study. RESULTS: The seroprotection levels in subjects with no MCCV registered in SIV (358) were similar to those in subjects with MCCV registered (1072). This indicated a large proportion of vaccinated subjects with no MCCV registered. The estimated vaccine coverage was over 80% in all age groups, except >22 years, where it was 67.6% (95% CI: [54.0-80.4]), which corresponded to those aged over 13 years at the time of the catch-up campaign. An underreporting rate of 23.5-73.4%, depending on the age group, was estimated in those vaccinated in the 2002 catch-up campaign. CONCLUSION: The Bayesian model allowed for a more realistic estimation of MCCV uptake. In this example, we quantified the underreporting of a vaccine registry, especially occurring during a catch-up campaign that occurred at the establishment of the registry.

Antibiotic therapy for pediatric community-acquired pneumonia: do we know when, what and for how long to treat?

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.

Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.

An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.

Rotavirus vaccines: considerations for successful implementation in Europe.

A group of European experts in infectious diseases and vaccinology has met on several occasions to assess the rationale for universal vaccination against rotavirus infection of infants in Europe. On the basis of the available data, we concluded that vaccination was the best approach to prevent severe rotavirus gastroenteritis, and that European countries should consider implementing rotavirus vaccination in their routine immunisation programmes. The main barrier to the implementation of rotavirus vaccination in Europe is a general lack of awareness of stakeholders, policymakers, health-care professionals, and parents about rotavirus disease and the advantages of vaccination. Further studies on the cost of the disease and the benefit of vaccination, together with raising awareness are necessary steps to ensure successful implementation of rotavirus vaccination in Europe.