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SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96–100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.

Background The implementation of digital disease surveillance systems at national levels in Africa have been challenged by many factors. These include user applicability, utility of IT features but also stable financial support. Funding closely intertwines with implementations in terms of geographical reach, disease focus, and sustainability. However, the practice of evidence sharing on geographical and disease coverage, costs, and funding sources for improving the implementation of these systems on the continent is unclear. Objectives To analyse the key characteristics and availability of evidence for implementing digital infectious disease surveillance systems in Africa namely their disease focus, geographical reach, cost reporting, and external funding support. Methods We conducted a systematic review of peer-reviewed and grey literature for the period 2003 to 2022 (PROSPERO registration number: CRD42022300849). We searched five databases (PubMed, MEDLINE over Ovid, EMBASE, Web of Science, and Google Scholar) and websites of WHO, Africa CDC, and public health institutes of African countries. We mapped the distribution of projects by country; identified reported implementation cost components; categorised the availability of data on cost components; and identified supporting funding institutions outside Africa. Results A total of 29 reports from 2,033 search results were eligible for analysis. We identified 27 projects implemented in 13 countries, across 32 sites. Of these, 24 (75%) were pilot projects with a median duration of 16 months, (IQR: 5–40). Of the 27 projects, 5 (19%) were implemented for HIV/AIDs and tuberculosis, 4 (15%) for malaria, 4 (15%) for all notifiable diseases, and 4 (15%) for One Health. We identified 17 cost components across the 29 reports. Of these, 11 (38%) reported quantified costs for start-up capital, 10 (34%) for health personnel compensation, 9 (31%) for training and capacity building, 8 (28%) for software maintenance, and 7(24%) for surveillance data transmission. Of 65 counts of external funding sources, 35 (54%) were governmental agencies, 15 (23%) foundations, and 7 (11%) UN agencies. Conclusions The evidence on costing data for the digitalisation of surveillance and outbreak response in the published literature is sparse in quantity, limited in detail, and without a standardised reporting format. Most initial direct project costs are substantially donor dependent, short lived, and thus unsustainable.

Background Contact behaviour is crucial to assess and predict transmission of respiratory pathogens like SARS-CoV-2. Contact behaviour has traditionally been assessed in cross-sectional surveys and not as part of longitudinal population-based studies which simultaneously measure infection frequency and vaccination coverage. During the COVID-19 pandemic, several studies assessed contact behaviour over longer periods and correlated this to data on immunity. This can inform future dynamic modelling. Here, we assess how contact behaviour varied based on SARS-CoV-2 infection or vaccination status in two large population-based studies in Germany during 2021. Methods We assessed direct encounters, separated into household and non-household contacts, in participants of MuSPAD ( n  = 12,641), a population-based cohort study, and COVIMOD ( n  = 31,260), a longitudinal contact survey. We calculated mean numbers of reported contacts and fitted negative binomial mixed-effects models to estimate the impact of immunity status, defined by vaccination or previous infection, on contact numbers; logistic mixed-effects models were used to examine the relationship between contact behaviour and seropositivity due to infection. Results Contact numbers varied over the course of the pandemic from 7.6 to 10.8 per 24 h in MuSPAD and 2.1 to 3.1 per 24 h in COVIMOD. The number of non-household contacts was higher in participants who reported previous infections and vaccinations (contact ratio (CR) MuSPAD: 1.22 (95%CI 0.94–1.60); COVIMOD: 1.35 (CI 1.12–1.62)) compared to unvaccinated and uninfected individuals. Non-household contact numbers were also higher in fully vaccinated participants (MUSPAD: CR 1.15 (CI 1.05–1.26); COVIMOD: 1.43 (CI 1.32–1.56)) compared to unvaccinated individuals. Compared to individuals without household contacts, the odds for seropositivity due to infection were higher among MuSPAD individuals with three or more household contacts (odds ratio (OR) 1.54 (CI 1.12–2.13)) and eleven or more non-household contacts (OR 1.29 (CI 1.01–1.65)). Conclusions Different contact behaviours based on infection and/or vaccination status suggest that public health policies targeting immunity status may influence the contact behaviour of those affected. A combined assessment of self-reported contacts, infections, and vaccinations as well as laboratory-confirmed serostatus in the population can support modelling of the spread of infections. This could help target containment policies and evaluate the impact of public health measures.

Background On 12 December 2024, the Standing Committee on Vaccination (STIKO) recommended universal polio catch-up vaccination for children and adolescents up to 16, urging parents to check their children’s immunization status following detections of vaccine-derived poliovirus in wastewater. The Robert Koch Institute (RKI) also advised healthcare professionals to ensure vaccination coverage in priority groups. Regional health authorities, called on all citizens to review their vaccination records to address any immunization gaps. We investigated vaccine uptake (documented / recalled) to improve estimates of immunity against poliovirus among the German population and gain insights into the proportion of undocumented vaccines. Methods We conducted a survey in December 2024 using the eResearch System PIA (Prospective Monitoring and Management—App) to collect data on self-reported vaccine uptake among a German cohort. We calculated the frequency of vaccinations that were documented and undocumented, as well as the types of vaccines and the number of doses received. Vaccination status was classified as received ≤ 2 doses versus ≥ 3 doses of any polio-containing vaccine. We applied survey weights to calculate frequencies according the general German population (by age, sex, region) and logistic regression to examine the relationships between the vaccinations that were not documented but recalled, and the factors associated with these undocumented vaccinations. Results Among 1,124 participants who completed the survey on vaccination uptake, 1,097 (96.9%) participants stated to have a vaccination record. A total of 823/1,124 (74.3%) reported having a vaccination record, where at least one poliomyelitis vaccine was documented, whereas 233 (19.0%) participants recalled at least one poliomyelitis vaccination without documentation or vaccination record. Of 1,124, 68 participants (6.7%) did not report any polio vaccination neither documented nor recalled without documentation. Among the 823 participants with documented vaccination and at least one vaccination, 592 (75.1%) received at least three doses of a poliomyelitis vaccine, with a decline in older age groups, less than three doses were reported by 164 (17.6%), and the remaining 7.3% ( n  = 67) did not have information on the number of doses administered. Of 2,768 documented vaccine doses, 898 (29.9%) were oral poliovirus vaccines (OPV) and 704 (26.2%) were inactivated poliovirus vaccines (IPV). In 1,166 vaccines (43.9%), the type could not be derived by the participants from the vaccination record. The odds of having a recalled vaccination (not documented) was higher in male and the older age groups compared to females and younger participants. Discussion We found similar poliomyelitis vaccination uptake compared to other data sources e.g., of the Robert Koch Institute (RKI). Vaccine-derived immunity to poliomyelitis may be underestimated based on vaccination records only. There is a need to address potential gaps in health literacy and vaccination documentation. Efforts should be made to conduct continuous seroprevalence surveys in the population in response to emerging public health threats and deduce parameters to inform modelling infection dynamics in specific outbreak scenarios. Trial registration The PCR-4-ALL cohort was registered in the German Clinical Trials Register on the 3rd of September 2024 (DRKS00034763).

Background Lyme borreliosis is the most prevalent vector-borne disease in Europe, and numbers might increase due to climate change. However, borreliosis is not notifiable in North Rhine-Westphalia (NRW), Germany. Hence, little is known about the current human seroprevalence in NRW. However, the proportion of Borrelia burgdorferi sensu lato-infected ticks has increased in a NRW nature reserve. The literature suggests increasing age and male sex as risk factors for seropositivity, whereas the influence of socioeconomic status is controversial. Thus, we aimed to determine regional seropositivity for Borrelia burgdorferi sensu lato ( B. burgdorferi s.l.) and its risk factors in the Rhineland Study population in Bonn, NRW, and to compare it with previous surveys to evaluate potential effects of climate change. Methods We assessed seropositivity in 2865 Rhineland Study participants by determining immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies for B. burgdorferi s.l. using a two-step algorithm combining enzyme-linked immunosorbent assay tests and line immunoblots. We calculated the odds of being classified as IgG or IgM positive as a function of age, sex, and educational level using binomial logistic regression models. We applied varying seropositivity classifications and weights considering age, sex and education to compensate for differences between the sample and regional population characteristics. Results IgG antibodies for B. burgdorferi s.l. were present in 2.4% and IgM antibodies in 0.6% of the participants (weighted: 2.2% [IgG], 0.6% [IgM]). The likelihood of IgG seropositivity increased by 3.0% (95% confidence interval [CI] 1.5–5.2%) per 1 year increase in age. Men had 1.65 times the odds for IgG seropositivity as women (95% CI 1.01–2.73), and highly educated participants had 1.83 times the odds (95% CI 1.10–3.14) as participants with an intermediate level of education. We found no statistically significant link between age, sex, or education and IgM seropositivity. Our weighted and age-standardized IgG seroprevalence was comparable to the preceding serosurvey German Health Interview and Examination Survey for Adults (DEGS) for NRW. Conclusions We confirmed that increasing age and male sex are associated with increased odds for IgG seropositivity and provide evidence for increased seropositivity in the highly educated group. B. burgdorferi s.l. seropositivity remained constant over the past decade in this regional German population. Graphical abstract

Background Lyme borreliosis (LB) is the most common tick-borne infectious disease in the northern hemisphere. The diagnosis of LB is usually made by clinical symptoms and subsequently supported by serology. In Europe, a two-step testing consisting of an enzyme-linked immunosorbent assay (ELISA) and an immunoblot is recommended. However, due to the low sensitivity of the currently available tests, antibody detection is sometimes inaccurate, especially in the early phase of infection, leading to underdiagnoses. Methods To improve upon Borrelia diagnostics, we developed a multiplex Borrelia immunoassay (Borrelia multiplex), which utilizes the new INTELLIFLEX platform, enabling the simultaneous dual detection of IgG and IgM antibodies, saving further time and reducing the biosample material requirement. In order to enable correct classification, the Borrelia multiplex contains eight antigens from the five human pathogenic Borrelia species known in Europe. Six antigens are known to mainly induce an IgG response and two antigens are predominant for an IgM response. Results To validate the assay, we compared the Borrelia multiplex to a commercial bead-based immunoassay resulting in an overall assay sensitivity of 93.7% (95% CI 84.8–97.5%) and a specificity of 96.5% (95%CI 93.5–98.1%). To confirm the calculated sensitivity and specificity, a comparison with a conventional 2-step diagnostics was performed. With this comparison, we obtained a sensitivity of 95.2% (95% CI 84.2–99.2%) and a specificity of 93.0% (95% CI 90.6–94.7%). Conclusion Borrelia multiplex is a highly reproducible cost- and time-effective assay that enables the profiling of antibodies against several individual antigens simultaneously.

Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.

Lyme borreliosis is the leading tick-related illness in Europe, caused by Borrelia Burgdorferi s.l. Lower Saxony, Germany, including its capital, Hanover, has a higher proportion of infected ticks than central European countries, justifying a research focus on the potential human consequences. The current knowledge gap on human incident infections, particularly in Western Germany, demands serological insights, especially regarding a potentially changing climate-related tick abundance and activity. We determined the immunoglobulin G (IgG) and immunoglobulin M (IgM) serostatuses for 8009 German National Cohort (NAKO) participants from Hanover, examined in 2014–2018. We used an enzyme-linked immunosorbent assay (ELISA) as the screening and a line immunoblot as confirmation for the Borrelia Burgdorferi s.l. antibodies. We weighted the seropositivity proportions to estimate general population seropositivity and estimated the force of infection (FOI). Using logistic regression, we investigated risk factors for seropositivity. Seropositivity was 3.0% (IgG) and 0.9% (IgM). The FOI varied with age, sharply increasing in participants aged ≥40 years. We confirmed advancing age and male sex as risk factors. We reported reduced odds for seropositivity with increasing body mass index and depressive symptomatology, respectively, pointing to an impact of lifestyle-related behaviors. The local proportion of seropositive individuals is comparable to previous estimates for northern Germany, indicating a steady seroprevalence.

Current estimates of pandemic SARS-CoV-2 spread in Germany using infectious disease models often do not use age-specific infection parameters and are not always based on age-specific contact matrices of the population. They also do usually not include setting- or pandemic phase-based information from epidemiological studies of reported cases and do not account for age-specific underdetection of reported cases. Here, we report likely pandemic spread using an age-structured model to understand the age- and setting-specific contribution of contacts to transmission during different phases of the COVID-19 pandemic in Germany. We developed a deterministic SEIRS model using a pre-pandemic contact matrix. The model was optimized to fit age-specific SARS-CoV-2 incidences reported by the German National Public Health Institute (Robert Koch Institute), includes information on setting-specific reported cases in schools and integrates age- and pandemic period-specific parameters for underdetection of reported cases deduced from a large population-based seroprevalence studies. Taking age-specific underreporting into account, younger adults and teenagers were identified in the modeling study as relevant contributors to infections during the first three pandemic waves in Germany. For the fifth wave, the Delta to Omicron transition, only age-specific parametrization reproduces the observed relative and absolute increase in pediatric hospitalizations in Germany. Taking into account age-specific underdetection did not change considerably how much contacts in schools contributed to the total burden of infection in the population (up to 12% with open schools under hygiene measures in the third wave). Accounting for the pandemic phase and age-specific underreporting is important to correctly identify those groups of the population in which quarantine, testing, vaccination, and contact-reduction measures are likely to be most effective and efficient. Age-specific parametrization is also highly relevant to generate informative age-specific output for decision makers and resource planers.