Application of the screening method to monitor influenza vaccine effectiveness among the elderly in Germany

Background: Elderly people are at increased risk for severe influenza illness and constitute therefore a major target-group for seasonal influenza vaccination in most industrialized countries. The aim of this study was to estimate influenza vaccine effectiveness (VE) among individuals aged 60+ years over three seasons and to assess if the screening method is a suitable tool to monitor influenza VE in this particular target-group in Germany. Methods: We identified laboratory-confirmed influenza cases aged 60+ years through the national communicable disease reporting system for seasons 2010/11, 2011/12 and 2012/13. Vaccination coverage (VC) data were retrieved from a database of health insurance claims representing ~85% of the total German population. We applied the screening method to calculate influenza subtype-specific VE and compared our results with VE estimates from other observational studies in Europe. Results: In total, 7,156 laboratory-confirmed influenza cases were included. VE against all influenza types ranged between 49% (95% confidence interval [CI]: 39–56) in 2011/12 and 80% (95% CI: 76-83%) in 2010/11. In 2010/11 subtype-specific VE against influenza A(H1N1)pdm and B was 76% and 84%, respectively. In the following seasons, VE against influenza A(H1N1)pdm, A(H3N2) and B was 87%, -9% , 74% (2011/12), and 74%, 39%, 73% (2012/13). VE was higher among hospitalized compared to non-hospitalized influenza A cases. Seventeen observational studies from Europe reporting subtype-specific VE among the elderly were identified for the respective seasons (all applying the test-negative design) and showed comparable subtype-specific VE estimates. Conclusions: According to our study, influenza vaccination provided moderate protection against laboratory-confirmed influenza A(H1N1)pdm and B in individuals aged 60+ but no or only little protection against A(H3N2). Higher VE among hospitalized cases might indicate higher protection against severe influenza disease. Based on the available data, the screening method allowed us to assess subtype-specific VE in hospitalized and non-hospitalized elderly persons. Since controlling for several important confounders was not possible, the applied method only provided crude VE estimates. However, given the precise VC-data and the large number of cases, the screening method provided results being in line with VE estimates from other observational studies in Europe that applied a different study design

Determinants of physician attitudes towards the new selective measles vaccine mandate in Germany

Background In Germany, a mandatory policy on measles vaccination came into effect in March 2020. Physicians, as the main vaccine providers, have a crucial role in implementing it. Mandatory vaccination changes the preconditions under which patient-provider communication on vaccines occurs. Physicians might or might not favor vaccine mandates depending on, among other factors, their attitudes towards vaccines and capabilities as vaccine providers. The aim of this study was to investigate in different subgroups of physicians the association between various factors and their attitudes towards a mandatory policy. Methods In total, 2229 physicians participated in a mixed-mode online/paper-pencil survey. Respondents were general practitioners, pediatricians, gynecologists, and internists. Primary determinants were the 5C psychological antecedents of vaccination, communication self-efficacy, patient clientele, projected consequences of the mandate and sociodemographic characteristics. Associations between outcomes and determinants were examined using linear regression analysis. Results Approximately 86% of physicians were in favor of the measles vaccine mandate for children. Regarding the 5C model, physicians were more in favor of vaccine mandates when they scored higher on confidence and collective responsibility, and lower on complacency and calculation. They were more in favor of vaccine mandates when they had higher communication self-efficacy and a more vaccine-positive patient clientele. Pediatricians were less in favor of mandates for children (80.0%) than other physician subgroups (87.1%). They were also less convinced that a mandate would result in more children getting vaccinated (59.3%) than other physician subgroups (78.3%). When controlled for these expected consequences, being a pediatrician no longer lowered the attitude towards the mandate. Conclusions Physicians in Germany are predominantly in favor of a measles vaccine mandate. Whether or not physicians believe the mandate to be effective in increasing vaccine coverage affects their attitude towards the mandate. In pediatricians, this belief explains their less positive attitude towards the mandate. In addition, physicians need adequate support to communicate well with patients, especially those who are hesitant, to booster their communication self-efficacy. To increase acceptance of vaccine mandates, the 5C model can be used, e.g., collective responsibility can be communicated, to avoid anger stemming from a negative attitude to mandates.Peer Reviewe

Impfen im Kontext globaler Herausforderungen

Peer Reviewe

Marked Underreporting of Pertussis Requiring Hospitalization in Infants as Estimated by Capture-Recapture Methodology, Germany, 2013-2015

Background: In Germany, pertussis became notifiable in eastern federal states in 2002 and nationwide in March 2013. Infants are at greatest risk for severe disease, with a high proportion requiring hospitalization. We implemented enhanced hospital-based surveillance to estimate the incidence of pertussis requiring hospitalization among infants in Germany and to determine the proportion of infants hospitalized with pertussis too young to have been vaccinated. Methods: Enhanced surveillance was implemented within a nationwide hospital surveillance network (ESPED). We defined cases as children less than 1 year of age hospitalized due to laboratory-confirmed pertussis with disease onset from 01/07/2013-30/06/2015. We matched cases to those ascertained in the national statutory notification system, and estimated incidence using capture-recapture methodology. Results: The estimated annual incidence of pertussis requiring hospitalization in infants was 52/100,000 infants (95% confidence interval [CI] 48-57/100,000), with 39% under-reporting to the national notification system. During the two epidemiologic years under-reporting decreased from 46% to 32% and was lower in eastern than western federal states (21% vs. 40%). Within ESPED, 154 of 240 infants (64%) were younger than or still at the age recommended for the first vaccine dose;55 (23%) could have received one or more vaccine doses. Median length of hospitalization was 9 days (IQR 5-13 days) and 18% required intensive care treatment. Conclusions: Our study revealed a high burden of pertussis in infants with marked under-reporting, especially in western federal states where notification was only recently established. Strategies for the prevention of severe pertussis

How a generally well-accepted measles vaccine mandate may lead to inequities and decreased vaccine uptake: a preregistered survey study in Germany

Additional file 1: Supplementary Figure 1. Directed acyclic graph (DAG) on hypothesis 2: Higher reactance to the measles mandate among parents decreases uptake of other vaccines and the intention to vaccinate children against other diseases. Supplementary  Table 1. ANCOVA results for socio-economic status (income) and for knowledge about the measles vaccine mandate and the measles vaccine. Supplementary Table 2. ANCOVA results for socio-economic status (education) and for knowledge about the measles vaccine mandate and the measles vaccine. Supplementary  Table 3. Parental vaccination decisions for vaccines that had just become due or were soon to come. Supplementary  Table 4. Relationship between reactance and vaccination behavior. Results from multiple logistic regression model with hexavalent and pneumococcal vaccination status as outcomes, reactance as predictor and the 5C model, age, gender, region and institutional trust included as covariates. Supplementary  Table 5. Relationship between reactance and vaccination intention. Results from multiple linear regression models with intention to get vaccinated against HPV, Tdap, Men C as outcomes, reactance as predictor and the 5C model, age, gender, region and institutional trust included as covariates. Supplementary  Table 6. Mediation analyses: Effect of institutional trust (X) on attitude towards the mandate (Y) via reactance (M)

Risk of Guillain–Barré syndrome after vaccination against human papillomavirus: a systematic review and meta-analysis, 1 January 2000 to 4 April 2020

Background: Guillain–Barré syndrome (GBS) is a rare autoimmune disease that can follow viral infections and has in a few cases been linked to vaccinations. Pre-licensure clinical trials did not observe an association between human papillomavirus (HPV) vaccination and GBS, a post-marketing study from 2017 reported an increased relative risk. Aim: We assessed the risk of GBS after HPV vaccination through a systematic literature review and meta-analysis. Methods: We searched Embase, MEDLINE and Cochrane for studies reporting on the risk of GBS after HPV vaccination in individuals aged ≥ 9 years, published between 1 January 2000 and 4 April 2020, excluding studies without a comparator group. Seven studies reporting relative effect sizes were pooled using random-effects meta-analysis. We assessed quality of evidence using the GRADE approach. Study protocol was registered (PROSPERO No. #CRD42019123533). Results: Of 602 identified records, we included 25 studies. Based on over 10 million reports, cases of GBS were rare. In 22 studies no increased risk was observed, while in three studies a signal of increased risk of GBS after HPV vaccination was identified. Meta-analysis yielded a pooled random-effects ratio of 1.21 (95% CI: 0.60–2.43); I2 = 72% (95% CI: 36–88). This translates to a number needed to harm of one million to be vaccinated to generate one GBS case. Quality of evidence was very low. Conclusions: The absolute and relative risk of GBS after HPV vaccination is very low and lacks statistical significance. This is reassuring for the already implemented vaccination programmes and should be used in respective communication activities.Peer Reviewe

Lessons Learned from an Outbreak in Germany, 2012-2013

Background We undertook investigations in response to an invasive meningococcal disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012–2013 to better understand meningococcal transmission and IMD risk in MSM. Methods We retrospectively searched for further IMD cases in MSM in Germany through local health departments and undertook exploratory interviews. We performed antigen sequence typing, characterized fHbp and aniA genes of strains with the outbreak finetype and reviewed epidemiologically or spatiotemporally linked cases from 2002–2014. Results Among the 148 IMD-cases notified from 01.01.2012–30.09.2013 in 18–59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C (MenC, all finetype C:P1.5–1,10–8:F3-6), 2 MenB. Interviews with 7 MSM revealed frequent meeting of multiple partners online or via mobile apps and illicit drug use as potential risk factors. MenC incidence was 13-fold higher in MSM than non-MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5–1,10–8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p = 0.04). Although definitive evidence for transmission among MSM in epidemiological or spatiotemporal clusters in 2002–2014 was lacking, clusters were more frequent in men aged 20–49 years. Molecular analysis of C:P1.5–1,10–8:F3-6 strains revealed cases with intact aniA since 2007, mainly associated with fHbp361, fHbp766 and fHbp813, all involving one or more MSM. Conclusions MenC incidence was elevated in MSM during the study period. Multiple casual sexual contacts and illicit drug use were common in affected MSM. In all strains from MSM we detected an intact aniA gene coding for a nitrite reductase, which permits survival in microanaerobic environments and could play a role in meningococcal transmission in MSM through urogenital colonization. Furthermore, meningococcal transmission among MSM may be sustained over large areas and thus require modified spatiotemporal scanning algorithms for timely detection and control

Epidemiology and cost of seasonal influenza in Germany - a claims data analysis

Background Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. Methods Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. Results Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (€251.91) and persons over 60 years of age (€131.59). Conclusion The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age.Peer Reviewe

Herpes zoster in Germany: Quantifying the burden of disease

Background: Herpes zoster (HZ) is caused by a reactivation of the varicella-zoster-virus (VZV) and mainly affects individuals aged ≥ 50 years. Vaccines have been licensed or are under development that can protect against HZ and its main complication postherpetic neuralgia (PHN). In Germany, the burden of disease caused by HZ is not well known. To support the decision making process related to a potential vaccination recommendation, we estimated annual HZ disease burden in people aged ≥ 50 years in Germany by utilizing various data sources. Methods: We assessed for 2007 and 2008 HZ-outpatient incidence (number of cases per 1,000 person-years, PY) by utilizing the Association of Statutory Health Insurance Physicians (ASHIP) database, which contains nationwide routine outpatient data. For the same time period annual number of HZ-inpatients and HZ-associated deaths were identified by using the Federal Health Monitoring System (FHM). PHN-incidence and loss of quality-adjusted life years (QALYs) caused by HZ were calculated by multiplying number of identified HZ-patients with upper and lower limit estimates for proportion of HZ-cases developing PHN and HZ-related QALY, respectively. Results: For the study period we identified an annual average of 306,511 HZ-outpatients aged 50+, resulting in a HZ-incidence of 9.6/1,000 PY. A total 14,249 HZ-associated inpatients and 66 deaths were reported in both years on average. HZ-incidence increased by age from 6.21 in people 50-54 years to 13.19 per 1,000 PY in people aged ≥ 90 years. Females were significantly more frequently affected than males in terms of outpatient HZ-incidence (11.12 vs. 7.8 per 1,000 PY), inpatient HZ-incidence (0.51 vs. 0.38 per 1,000 PY) and mortality (0.29 vs. 0.10 per 100,000 PY). PHN-incidence was estimated to range between 0.43 and 1.33 per 1,000 PY. Based on these figures, there were between 3,065 to 24,094 QALYs lost due to HZ in persons aged ≥ 50 years in Germany per annum. Conclusion: Our study provides important baseline estimates for HZ-related disease burden in Germany. HZ poses a considerable burden on the health care system in Germany both in terms of outpatient and inpatient services. Follow-up assessments of HZ disease burden are needed to monitor the impact of VZV-vaccinations in Germany

Malarone treatment failure not associated with previously described mutations in the cytochrome b gene

Malarone(® )(atovaquone-proguanil) is an effective drug for the treatment and prophylaxis of multidrug-resistant falciparum malaria. However, first cases of resistance have been reported, which are associated with mutations at codon 268 of the parasite's cytochrome b gene. We report the first case of Malarone(® )treatment failure from Central Africa. Drug concentration was well within curative range. Pre- and post-treatment Plasmodium falciparum isolates revealed codon 268 wild-type alleles, and no other mutations of the putative atovaquone-binding domain. These findings illustrate the spread of atovaquone-proguanil-resistance in Africa and question the usefulness of codon 268 as the only target for the surveillance of its emergence