Similar severity of influenza primary and re-infections in pre-school children requiring outpatient treatment due to febrile acute respiratory illness: prospective, multicentre surveillance study (2013-2015).

BACKGROUND: Influenza virus infections in immunologically naïve children (primary infection) may be more severe than in children with re-infections who are already immunologically primed. We compared frequency and severity of influenza virus primary and re-infections in pre-school children requiring outpatient treatment. METHODS: Influenza-unvaccinated children 1-5 years of age presenting at pediatric practices with febrile acute respiratory infection < 48 h after symptom onset were enrolled in a prospective, cross-sectional, multicenter surveillance study (2013-2015). Influenza types/subtypes were PCR-confirmed from oropharyngeal swabs. Influenza type/subtype-specific IgG antibodies serving as surrogate markers for immunological priming were determined using ELISA/hemagglutination inhibition assays. The acute influenza disease was defined as primary infection/re-infection by the absence/presence of influenza type-specific immunoglobulin G (IgG) and, in a second approach, by the absence/presence of subtype-specific IgG. Socio-demographic and clinical data were also recorded. RESULTS: Of 217 influenza infections, 178 were due to influenza A (87 [49%] primary infections, 91 [51%] re-infections) and 39 were due to influenza B (38 [97%] primary infections, one [3%] re-infection). Children with "influenza A primary infections" showed fever with respiratory symptoms for a shorter period than children with "influenza A re-infections" (median 3 vs. 4 days; age-adjusted p = 0.03); other disease characteristics were similar. If primary infections and re-infections were defined based on influenza A subtypes, 122 (87%) primary infections (78 "A(H3N2) primary infections", 44 "A(H1N1)pdm09 primary infections") and 18 (13%) re-infections could be classified (14 "A(H3N2) re-infections" and 4 "A(H1N1)pdm09 re-infections"). Per subtype, primary infections and re-infections were of similar disease severity. Children with re-infections defined on the subtype level usually had non-protective IgG titers against the subtype of their acute infection (16 of 18; 89%). Some patients infected by one of the influenza A subtypes showed protective IgG titers (≥ 1:40) against the other influenza A subtype (32/140; 23%). CONCLUSIONS: Pre-school children with acute influenza A primary infections and re-infections presented with similar frequency in pediatric practices. Contrary to expectation, severity of acute "influenza A primary infections" and "influenza A re-infections" were similar. Most "influenza A re-infections" defined on the type level turned out to be primary infections when defined based on the subtype. On the subtype level, re-infections were rare and of similar disease severity as primary infections of the same subtype. Subtype level re-infections were usually associated with low IgG levels for the specific subtype of the acute infection, suggesting only short-time humoral immunity induced by previous infection by this subtype. Overall, the results indicated recurring influenza virus infections in this age group and no or only limited heterosubtypic antibody-mediated cross-protection.

Impact of herpes zoster and postherpetic neuralgia on the quality of life of Germans aged 50 or above.

BACKGROUND: Herpes zoster (HZ) is a painful dermatomal rash caused by reactivation of latent varicella zoster virus surviving in the patient's sensory ganglia after a previous episode of varicella. The incidence of HZ increases markedly with age as does the proportion of HZ patients who develop postherpetic neuralgia (PHN) with often severe and debilitating pain persisting for months and even years. This prospective study aimed to assess the impact of HZ and PHN on the quality of life (QoL) of individuals aged ≥ 50 years in Germany. METHODS: Patients were recruited when consulting primary care physicians for a first HZ episode. PHN was defined as a 'worst' pain score ≥ 3 on the Zoster Brief Pain Inventory (ZBPI) scale persisting or appearing 90 days or more after rash onset. PHN-cases were followed for up to nine months after rash onset. The interference of pain with patients' ability to carry out normal activities was assessed by the ZBPI activities of daily living (ADL) scale and QoL by the EuroQoL five-dimension scale (EQ-5D) utility score. RESULTS: Of 513 patients enrolled, 61 (11.9%) developed PHN. At HZ onset, the mean ZBPI worst pain score of all patients was 5.1, the least square (LS)means estimates of the ZBPI ADL and EQ-5D utility scores were 2.970 and 0.740, respectively. Over three months follow-up, the pain scores decreased and the QoL increased monotonically across all age groups. At Day 90, the mean ZBPI worst pain score of the PHN patients was 4.4, while the LSmeans estimates of the ZBPI ADL and EQ-5D utility scores were 2.899 and 0.826, respectively. For patients with PHN persisting at nine months, the pain scores and QoL remained unchanged over the six months following the development of PHN. CONCLUSION: HZ and PHN had a substantial impact on the patients' QoL and ability to function in their normal activities. There was a clear association in time between the evolution of pain and estimated QoL. The impact on ADL and QoL did not vary with age.

Influence of social contact patterns and demographic factors on influenza simulation results.

BACKGROUND: The demographic composition and the frequency and nature of social contacts may affect the spread of influenza virus in a population, resulting in distinct age-dependent immunity patterns. As demography and social contact rates differ strongly between European countries, this may impact infection incidence and vaccine effectiveness and thus limit the extent to which conclusions derived from observations in one country can be generalized to others. In the current study, we aimed to decipher the impact of social contact patterns and demographic factors on simulation results and, thus, to determine to what extent vaccination results can be generalized. METHODS: We simulated the transmission of four influenza strains (A(H1N1), A(H3N2), B/Victoria, B/Yamagata) in Belgium, Finland, Germany, GB, Italy, Luxembourg, Netherlands and Poland, using the simulation tool 4Flu. Individuals were connected in a dynamically evolving age-dependent contact network based on the POLYMOD study. RESULTS: When averaged over 20 years, simulation results without vaccination ranged from annually 20,984 (Germany) to 31,322 infections (Italy) per 100,000 individuals. QIV annually prevented 1758 (Poland) to 7720 infections (Germany) per 100,000. Variability of prevented cases remained high when the country-specific vaccination was replaced by unified coverage, but was reduced considerably if the same demography was used for all countries, or even more so when the same contact matrix was used. CONCLUSIONS: Contact matrix and demography strongly influence the age-dependent incidence of influenza and the success of vaccination. Projecting simulation results from one country to another can, therefore, lead to erroneous results.

4Flu - an individual based simulation tool to study the effects of quadrivalent vaccination on seasonal influenza in Germany.

BACKGROUND: Influenza vaccines contain Influenza A and B antigens and are adjusted annually to match the characteristics of circulating viruses. In Germany, Influenza B viruses belonged to the B/Yamagata lineage, but since 2001, the antigenically distinct B/Victoria lineage has been co-circulating. Trivalent influenza vaccines (TIV) contain antigens of the two A subtypes A(H3N2) and A(H1N1), yet of only one B lineage, resulting in frequent vaccine mismatches. Since 2012, the WHO has been recommending vaccine strains from both B lineages, paving the way for quadrivalent influenza vaccines (QIV). METHODS: Using an individual-based simulation tool, we simulate the concomitant transmission of four influenza strains, and compare the effects of TIV and QIV on the infection incidence. Individuals are connected in a dynamically evolving age-dependent contact network based on the POLYMOD matrix; their age-distribution reproduces German demographic data and predictions. The model considers maternal protection, boosting of existing immunity, loss of immunity, and cross-immunizing events between the B lineages. Calibration to the observed annual infection incidence of 10.6% among young adults yielded a basic reproduction number of 1.575. Vaccinations are performed annually in October and November, whereby coverage depends on the vaccinees' age, their risk status and previous vaccination status. New drift variants are introduced at random time points, leading to a sudden loss of protective immunity for part of the population and occasionally to reduced vaccine efficacy. Simulations run for 50 years, the first 30 of which are used for initialization. During the final 20 years, individuals receive TIV or QIV, using a mirrored simulation approach. RESULTS: Using QIV, the mean annual infection incidence can be reduced from 8,943,000 to 8,548,000, i.e. by 395,000 infections, preventing 11.2% of all Influenza B infections which still occur with TIV (95% CI: 10.7-11.8%). Using a lower B lineage cross protection than the baseline 60%, the number of Influenza B infections increases and the number additionally prevented by QIV can be 5.5 times as high. CONCLUSIONS: Vaccination with TIV substantially reduces the Influenza incidence compared to no vaccination. Depending on the assumed degree of B lineage cross protection, QIV further reduces Influenza B incidence by 11-33%.

Cost-utility analysis of increasing uptake of universal seasonal quadrivalent influenza vaccine (QIV) in children aged 6 months and older in Germany.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.

What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death.While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease.Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases).What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population.We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old;vaccinating 40% of all (healthy and high-risk) children under 18 years old;vaccinating 90% of high-risk children under 18 years old.What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation.The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients.Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Safety, immunogenicity and immediate pain of intramuscular versus subcutaneous administration of a measles-mumps-rubella-varicella vaccine to children aged 11-21 months.

This study compared intramuscular and subcutaneous administration of two doses of measles-mumps-rubella-varicella (MMRV) combination vaccine (Priorix-Tetra, GlaxoSmithKline Biologicals) in children. Healthy children (N = 328) were randomised to receive MMRV either intramuscularly or subcutaneously. Reactogenicity was similar between treatment groups for immediate vaccination pain, vaccination site pain, redness and incidence of fever and rashes. Slightly less vaccination site swelling occurred during days 0-3 of the post-vaccination period after intramuscular administration. Seroconversion rates for all components, 42-56 days post-dose 2, ranged from 99.3% to 100% in the intramuscular group and from 98.6% to 100% in the subcutaneous. Cell-mediated immunity data supported the humoral immunogenicity findings. In summary, the MMRV vaccine is well tolerated and highly immunogenic when administered either subcutaneously or intramuscularly to children in the second year of life.

Assessing direct and indirect effects of pediatric influenza vaccination in Germany by individual-based simulations.

Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997-2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017-2036). Pediatric vaccination coverage of 10-60% annually prevented 218-1,732 (6.3-50.5%) infections in children, 204-1,961 (2.9-28.2%) in young adults and 95-868 (3.1-28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4-4.6 vaccinations were needed to prevent one infection among children; 1.7-1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.

Subtype-specific Clinical Presentation, Medical Treatment and Family Impact of Influenza in Children 1-5 Years of Age Treated in Outpatient Practices in Germany During Three Postpandemic Years, 2013-2015.

BACKGROUND: Limited data on the influenza burden in pediatric outpatients are available, especially regarding direct comparison of the cocirculating (sub)types A(H1N1)pdm09, A(H3N2) and B. METHODS: Children 1-5 years of age, unvaccinated against influenza and presenting with febrile acute respiratory infections (ARIs), were enrolled in 33 pediatric practices in Germany from 2013 to 2015 (January-May). Influenza was confirmed by multiplex polymerase chain reaction from pharyngeal swabs and (sub)typed. RESULTS: In 805 children with ARI, influenza was the most frequently detected respiratory virus (n = 305; 37.9%). Of 217 influenza patients included, 122 (56.2%) were infected with A(H3N2), 56 (25.8%) with A(H1N1)pdm09 and 39 (18.0%) with B. Median age was 3.7 years [interquartile range (IQR), 2.1-4.8]; 11% had underlying conditions. Median fever duration was 4 days (IQR, 3-5), and the disease duration was 9 days (IQR, 7-12). Most frequent diagnoses were pharyngitis (26%), bronchitis (18%) and acute otitis media (10%). Children received mainly antipyretics (86%) and adrenergic nasal drops/spray (53%); 9% received antibiotics and 3% oseltamivir. Thirty-six percent required at least 1 additional practice visit; 1% was hospitalized. Median absences from childcare were 5 days (IQR, 3-7); parents lost 4 workdays (IQR, 2-6). Symptoms, severity and impact on the family were largely unrelated to (sub)type. However, patients with A(H1N1)pdm09 had fewer underlying conditions (P = 0.017), whereas patients with B more often had pharyngitis (P = 0.022), acute otitis media (P = 0.012) and stenosing laryngotracheitis (P = 0.007). CONCLUSIONS: Influenza was the most frequently detected viral pathogen in outpatient children with febrile, mostly uncomplicated ARI. In this setting, clinical manifestations and severity were similar across the (sub)types prevalent during the postpandemic seasons.

Incidence and costs of herpes zoster and postherpetic neuralgia in German adults aged ≥50 years: A prospective study.

OBJECTIVES: Herpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged ≥50 years in Germany, the proportion of PHN and the economic burden. METHODS: From 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged ≥50 years. PHN was defined as "worst pain" rated ≥3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time. RESULTS: HZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in ≥80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients ≥80 years. Estimated total cost per HZ patient was €156 from the healthcare system perspective and €311 from the societal perspective. CONCLUSIONS: The study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN.

Vaccination programs for older adults in an era of demographic change.

OBJECTIVES: Populations are aging worldwide. This paper summarizes some of the challenges and opportunities due to the increasing burden of infectious diseases in an aging population. RESULTS: Older adults typically suffer elevated morbidity from infectious disease, leading to increased demand for healthcare resources and higher healthcare costs. Preventive medicine, including vaccination can potentially play a major role in preserving the health and independence of older adults. However, this potential of widespread vaccination is rarely realized. Here, we give a brief overview of the problem, discuss concrete obstacles and the potential for expanded vaccination programs to promote healthy aging. CONCLUSION: The increasing healthcare burden of infectious diseases expected in aging populations could, to a large extent, be reduced by achieving higher vaccination coverage among older adults. Vaccination can thus contribute to healthy aging, alongside healthy diet and physical exercise. The available evidence indicates that dedicated programs can achieve substantial improvements in vaccination coverage among older adults, but more research is required to assess the generalizability of the results achieved by specific interventions (see Additional file 1).

Role of the plasmid-encoded tet(O) gene in tetracycline-resistant clinical isolates of Campylobacter jejuni and Campylobacter coli.

The prevalence of tetracycline resistance, tetracycline MICs and tet(O) gene localization were investigated in 83 Campylobacter isolates from patients suffering from acute gastroenteritis in Germany. Combined biochemical and molecular markers identified 74 isolates (89 %) as Campylobacter jejuni, including seven atypical isolates that failed to hydrolyse hippurate, and nine isolates (11 %) as Campylobacter coli. Tetracycline resistance was detected in six out of nine Campylobacter coli isolates (67 %) and 13 out of 74 C. jejuni isolates (18 %). Low-level tetracycline resistance was observed for C. coli (MIC 16 microg ml(-1) for all strains), whereas C. jejuni showed high-level resistance (MIC >256 microg ml(-1) for all strains). Both low- and high-level tetracycline resistance was associated with the presence of the tet(O) gene. In C. jejuni, tet(O) was plasmid-encoded in 54 % of tetracycline-resistant isolates, whereas in C. coli, tet(O) appeared to be located on the chromosome.

Vaccination of special populations: Protecting the vulnerable.

One of the strategic objectives of the 2011-2020 Global Vaccine Action Plan is for the benefits of immunisation to be equitably extended to all people. This approach encompasses special groups at increased risk of vaccine-preventable diseases, such as preterm infants and pregnant women, as well as those with chronic and immune-compromising medical conditions or at increased risk of disease due to immunosenescence. Despite demonstrations of effectiveness and safety, vaccine uptake in these special groups is frequently lower than expected, even in developed countries with vaccination strategies in place. For example, uptake of the influenza vaccine in pregnancy rarely exceeds 50% in developed countries and, although data are scarce, it appears that only half of preterm infants are up-to-date with routine paediatric vaccinations. Many people with chronic medical conditions or who are immunocompromised due to disease or aging are also under-vaccinated. In the US, coverage among people aged 65years or older was 67% for the influenza vaccine in the 2014-2015 season and 55-60% for tetanus and pneumococcal vaccines in 2013, while the coverage rate for herpes zoster vaccination among those aged 60years or older was only 24%. In most other countries, rates are far lower. Reasons for under-vaccination of special groups include fear of adverse outcomes or illness caused by the vaccine, the inconvenience (and in some settings, cost) of vaccination and lack of awareness of the need for vaccination or national recommendations. There is also evidence that healthcare providers' attitudes towards vaccination are among the most important influences on the decision to vaccinate. It is clear that physicians' adherence to recommendations needs to be improved, particularly where patients receive care from multiple subspecialists and receive little or no care from primary care providers.

Cost-Utility of Quadrivalent Versus Trivalent Influenza Vaccine in Germany, Using an Individual-Based Dynamic Transmission Model.

BACKGROUND: Seasonal influenza infection is primarily caused by circulation of two influenza A strain subtypes and strains from two B lineages that vary each year. Trivalent influenza vaccine (TIV) contains only one of the two B-lineage strains, resulting in mismatches between vaccine strains and the predominant circulating B lineage. Quadrivalent influenza vaccine (QIV) includes both B-lineage strains. The objective was to estimate the cost-utility of introducing QIV to replace TIV in Germany. METHODS: An individual-based dynamic transmission model (4Flu) using German data was used to provide realistic estimates of the impact of TIV and QIV on age-specific influenza infections. Cases were linked to health and economic outcomes to calculate the cost-utility of QIV versus TIV, from both a societal and payer perspective. Costs and effects were discounted at 3.0 and 1.5 % respectively, with 2014 as the base year. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: Using QIV instead of TIV resulted in additional quality-adjusted life-years (QALYs) and cost savings from the societal perspective (i.e. it represents the dominant strategy) and an incremental cost-utility ratio (ICUR) of €14,461 per QALY from a healthcare payer perspective. In all univariate analyses, QIV remained cost-effective (ICUR <€50,000). In probabilistic sensitivity analyses, QIV was cost-effective in >98 and >99 % of the simulations from the societal and payer perspective, respectively. CONCLUSION: This analysis suggests that QIV in Germany would provide additional health gains while being cost-saving to society or costing €14,461 per QALY gained from the healthcare payer perspective, compared with TIV.

Improved serodiagnosis of Campylobacter jejuni infections using recombinant antigens.

Campylobacter jejuni is a frequent cause of infectious diarrhoea and is increasingly recognized as a trigger for late-onset complications. The poor standardization of commonly used serological tests might explain the conflicting results regarding the frequency of antecedent C. jejuni infections in defined patient groups. In order to obtain reliable epidemiological data as to the role of C. jejuni in causing late-onset complications, a highly specific and sensitive diagnostic tool for the epidemiological investigation of C. jejuni-associated diseases was developed. It was shown that recombinant proteins encoded by the C. jejuni genes cj0017 (P39) and cj0113 (P18) are specifically recognized by antibodies in sera from patients with C. jejuni enteritis. An ELISA using recombinant P18 and P39 as antigens was 91.9% sensitive and 99.0% specific, with positive and negative predictive values of 97.1% and 97.0%, respectively, comparing favourably with the 27.0% sensitivity of a routinely used serological assay.

Identification and characterization of a major subgroup of conjugative Campylobacter jejuni plasmids.

OBJECTIVES: Enterocyte invasion of Campylobacter jejuni 81-176 has been reported to depend upon the virulence plasmid pVir. The objective of this study was to determine the prevalence of pVir in clinical C. jejuni isolates, to investigate DNA homologies between C. jejuni plasmids and the significance of plasmids for C. jejuni invasiveness. METHODS: DNA homologies between C. jejuni plasmids were studied by southern blot hybridization. C. jejuni invasion into human intestinal Caco-2 cells was assessed in a gentamicin exclusion assay. RESULTS: Twenty-nine percent of C. jejuni isolated from patients with bloody or watery diarrhoea harboured plasmids of various sizes. One plasmid (7%) was a pVir homologue whereas, the majority of the plasmids (53%) belonged to a subgroup distinct from pVir. The plasmids of this novel subgroup share extensive DNA sequence homology with each other, including homologues to so-called invasion-promoting genes. However, conjugative transfer of these plasmids clearly did not increase invasiveness of plasmidless recipient C. jejuni strains. CONCLUSION: This study indicates that only a small proportion of C. jejuni strains carry the virulence factor pVir and that at least one other distinctive group of plasmids in C. jejuni exists, which does not seem to be associated with invasiveness.

Sustaining Vaccine Confidence in the 21st Century.

Vaccination provides many health and economic benefits to individuals and society, and public support for immunization programs is generally high. However, the benefits of vaccines are often not fully valued when public discussions on vaccine safety, quality or efficacy arise, and the spread of misinformation via the internet and other media has the potential to undermine immunization programs. Factors associated with improved public confidence in vaccines include evidence-based decision-making procedures and recommendations, controlled processes for licensing and monitoring vaccine safety and effectiveness and disease surveillance. Community engagement with appropriate communication approaches for each audience is a key factor in building trust in vaccines. Vaccine safety/quality issues should be handled rapidly and transparently by informing and involving those most affected and those concerned with public health in effective ways. Openness and transparency in the exchange of information between industry and other stakeholders is also important. To maximize the safety of vaccines, and thus sustain trust in vaccines, partnerships are needed between public health sector stakeholders. Vaccine confidence can be improved through collaborations that ensure high vaccine uptake rates and that inform the public and other stakeholders of the benefits of vaccines and how vaccine safety is constantly assessed, assured and communicated.

Prevalence of influenza A and B antibodies in pregnant women and their offspring.

BACKGROUND: Influenza is associated with substantial morbidity and mortality in pregnant women and neonates, but few countries offer annual influenza vaccination with the inactivated vaccine to all women who are, or intend to become, pregnant. OBJECTIVES: To provide seroepidemiological information on influenza A and B antibodies in pregnant women and their offspring in Germany. STUDY DESIGN: Anti-influenza antibodies were determined using commercially available enzyme-linked immunosorbent assays (ELISA) on serum obtained from 209 women and their newborns at delivery. RESULTS: The prevalence of antibodies against influenza A virus was 93.8% [89.6-96.6%] in the mothers and 96.7% [93.2-98.6%] in the newborns. The prevalence of antibodies against influenza B virus was 42.1% [35.3-49.1%] in the mothers and 78.5% [72.3-83.8%] in their newborns, which was a significant difference. The antibody concentrations against both influenza A and influenza B viruses were significantly lower in mother than in their newborns. CONCLUSIONS: Because of active placental transport of IgG antibodies, neonates have higher prevalence and/or concentrations of influenza A and B virus-specific antibodies induced by natural infections than their mothers. Considering these serological findings, especially the lower prevalence of maternal antibody against influenza B virus, annual influenza vaccination may improve the protection of pregnant women and their offspring against influenza.

Immunogenicity and reactogenicity of a trivalent influenza split vaccine in previously unvaccinated children aged 6-9 and 10-13 years.

Children previously unvaccinated against influenza are recommended to receive two doses of trivalent inactivated influenza vaccine (TIV). This study assessed the age limit for a second dose of TIV in previously unvaccinated children. Two hundred and twenty-four children were immunized with TIV (Influsplit SSW/Fluarix; GlaxoSmithKline Biologicals). Subjects aged 6-9 years (n=110) received two doses of TIV 4 weeks apart; those aged 10-13 years (n=114) received a single dose. Serum haemagglutination inhibiting (HI) antibody titers were evaluated before and after each vaccination. CHMP criteria for HI antibody response were met for all three vaccine strains after one vaccine dose in children 10-13 years and after two doses in children 6-9 years. A marked benefit was observed in 8-year-old children after a second dose even though one dose would be sufficient against all strains. Our results provide additional evidence that Influsplit SSW/Fluarix is well tolerated and highly immunogenic in children and support recommendations that previously unvaccinated children aged <9 years should receive two doses of influenza vaccine.

Improved serological diagnosis stresses the major role of Campylobacter jejuni in triggering Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune polyradiculoneuropathy. The most frequent antecedent pathogen is Campylobacter jejuni, followed by cytomegalovirus. However, more than 40% of GBS cases currently cannot be attributed to triggering events. This might be due to the shortcomings of the serological assays used for diagnosing infections, in particular for C. jejuni. In our study investigating 36 patients with acute GBS, standard serological methods identified the triggering viral or bacterial etiology in only 25% of cases. However, using a highly specific enzyme-linked immunosorbent assay based on two recombinant outer antigens encoded by C. jejuni genes Cj0017 (P39) and Cj0113 (P18), we found serological evidence of a preceding C. jejuni infection in 80.6% of the patients but in only 3.5% of the controls. We conclude that the role of C. jejuni in triggering GBS has been greatly underestimated.