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Despite use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in England, disease burden among at-risk adults remains high. We evaluated the public health and budgetary impact of 20-valent pneumococcal conjugate vaccine (PCV20) compared to the current adult pneumococcal vaccination program.Five-year outcomes and costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65-99 years and adults aged 18-64 years with underlying conditions in England were projected using a deterministic cohort model. Hypothetical vaccination with PCV20 versus PPV23 was compared from the National Health Service (NHS) perspective.Replacing PPV23 with PCV20 would prevent 785 IPD hospitalizations, 11,751 CAP hospitalizations, and 1,414 deaths over 5 years, and would reduce medical care costs by £48.5 M. With vaccination costs higher by £107.2 M, projected net budgetary impact is £58.7 M. The budgetary impact would be greatest in year 1 (£26.3 M), and would decrease over time (to £1.6 M by year 5). The average budget increase (£11.7 M/year) represents0.01% of the Department of Health and Social Care total budget and3% of the vaccine budget.Use of PCV20 among adults currently eligible for PPV23 in England would substantially reduce the burden of pneumococcal disease, with modest budgetary impact.

Currently, the 13-valent pneumococcal conjugate vaccine (PCV13) is administered under a 1+1 (1 primary dose) pediatric schedule in the United Kingdom (UK). Higher-valency PCVs, 15-valent PCV (PCV15), or 20-valent PCV (PCV20) might be considered to expand serotype coverage. We evaluated the cost-effectiveness of PCV20 or PCV15 using either a 2+1 (2 primary doses) or 1+1 schedule for pediatric immunization in the UK. Using a dynamic transmission model, we simulated future disease incidence and costs under PCV13 1+1, PCV20 2+1, PCV20 1+1, PCV15 2+1, and PCV15 1+1 schedules from the UK National Health Service perspective. We prospectively estimated disease cases, direct costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Scenario analyses were performed to estimate the impact of model assumptions and parameter uncertainty. Over a five-year period, PCV20 2+1 averted the most disease cases and gained the most additional QALYs. PCV20 2+1 and 1+1 were dominant (cost-saving and more QALYs gained) compared with PCV15 (2+1 or 1+1) and PCV13 1+1. PCV20 2+1 was cost-effective (GBP 8110/QALY) compared with PCV20 1+1. PCV20 was found cost-saving compared with PCV13 1+1, and PCV20 2+1 was cost-effective compared with PCV20 1+1. Policymakers should consider the reduction in disease cases with PCV20, which may offset vaccination costs.

Background Lyme borreliosis (LB), a tick-borne disease caused by Borrelia burgdorferi sensu lato, has been subject to mandatory public health surveillance since 1996 in Poland. Here, the incidence, temporal trends, and geographical distribution of LB and its manifestations in Poland are described for the period 2015-2019. Methods This retrospective incidence study of LB and its manifestations in Poland was based on the data sent to the National Institute of Public Health (NIPH-NIH–NRI) by district sanitary-epidemiological stations using the electronic Epidemiological Records Registration System and data from the National Database on Hospitalization. LB and its manifestations were reported in two categories- probable and confirmed (through laboratory tests). Incidence rates were calculated using the population data from the Central Statistical Office of Poland. Results In Poland, a total of 94,715 cases of LB with an overall mean incidence of 49.3 cases per 100,000 population were reported between 2015-2019. Cases increased from 2015 (11,945) to 2016 (20,857), and then remained stable through 2019. LB was more common among women (55.7%). The highest incidence rates occurred among >50-year-olds, with a peak in 65-69-year-olds. 48,717 persons with LB were hospitalized in the 5-year period, with higher number of hospitalizations in age groups 55-69 years old. Erythema migrans and Lyme arthritis were the most common manifestations of LB with incidence rates of 36.2 and 15.8 per 100,000 population, respectively. EM accounted for approximately 74% of all manifestations of LB. The highest number of cases were recorded in the 3rd and 4th quarters of the year (July – December). Incidence rates in the East and Northeastern regions (Podlaskie, Lubelskie, and Warmińsko-Mazurskie voivodeships) of the country were higher than the national average. These regions correspond to greater forest cover and/or agricultural areas. Time trend of LB cases and incidence in Poland, 2015-2019. Conclusion LB is endemic in all regions of Poland, and many regions reported high incidence rates. LB is reported year-round in Poland. Thus, large variations in temporal and spatially granular incidence rates highlight the need for targeted prevention strategies, such as vaccines. Disclosures Jozica Skufca, Epidemiologist, p95: Paid by Pfizer to perform the study Archana Nagarajan, Ph.D., P95: Paid by Pfizer to perform the study Andreas Pilz, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Andrew Vyse, Ph.D., Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds Mendwas Dzingina, Ph.D., Pfizer: Stocks/Bonds Maxim Blum, Ph.D., P95: Paid by Pfizer to perform the study Margarita Riera, MD, MPH, P95: Paid by Pfizer to perform the study Bradford Gessner, MD, MPH, Pfizer: Stocks/Bonds James Stark, Ph.D., Pfizer: Stocks/Bonds.

Background Lyme borreliosis (LB) is a tick-borne zoonotic disease endemic in many European countries, including Finland. We describe the incidence, time trends and geographical distribution of LB in Finland for the period 2015–2020. The data generated can help inform public health policy, including prevention strategies. Methods We retrieved online available LB cases and incidence from two Finnish national databases. Microbiologically confirmed disseminated LB cases were identified from The National Infectious Disease Register (NIDR) and clinically diagnosed LB cases, from the National Register of Primary Health Care Visits (Avohilmo), with the total LB cases equal to the sum from these two sources. Both registers contain data from the entire country and by hospital districts (HDs) and municipalities. Total LB incidence was calculated as the sum of microbiologically confirmed and clinically diagnosed LB cases divided by the population size. Results A total of 33,185 LB cases were reported over the 2015-2020 period, of which 12,590 (38%) were microbiologically confirmed and 20,595 (62%), clinically diagnosed. The average annual national incidence for total, microbiologically confirmed and clinically diagnosed LB were, respectively, 99.6, 38.1, and 61.4 per 100,000 population. The overall LB incidence was highest in the south to southwestern coastal areas by the Baltic Sea and in eastern areas, with average annual incidences of 109.0 to 207.3/100,000. The Ahvenanmaa Island was a hyperendemic region with an average annual incidence of 2,473.9/100,000 and the only HD to report more microbiologically confirmed cases (69%) as compared to clinically diagnosed cases. The highest incidence rates were among persons aged over 60 years, peaking at age 70–74 years. Below 40 years, the highest incidence rates were observed among 5-9-year-olds. Most cases were reported between May and October, with a peak in July and August. Average annual incidence (per 100,000 residents) by the Finnish hospital districts (HD) from 2015-2020. A) Clinically diagnosed LB; B) Microbiologically confirmed LB; C) Both combined, clinically diagnosed, and microbiologically confirmed LB. Conclusion The incidence of LB in Finland is among the highest in Europe but varied substantially by HD and many regions reported incidence much higher than the national average. These regions also corresponded to high population density areas, suggesting preventive measures such as vaccines may be an efficient use of resources. Disclosures Jozica Skufca, Epidemiologist, p95: Paid by Pfizer to perform the study Nick DeSmedt, Masters in Computer Engineering, P95: P95 was paid by Pfizer to perform the study Andreas Pilz, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Andrew Vyse, Ph.D., Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds Margarita Riera, MD, MPH, P95: Paid by Pfizer to perform the study Maxim Blum, Ph.D., P95: Paid by Pfizer to perform the study Bradford Gessner, MD, MPH, Pfizer: Stocks/Bonds James Stark, Ph.D., Pfizer: Stocks/Bonds.

Background Lyme borreliosis (LB) is an infectious, vector-borne disease caused by the spirochete Borrelia burgdorferi sensu lato and mainly transmitted by the Ixodes species ticks. Public surveillance of LB occurs in 9 of 16 federal states of Germany and remains a critical facet of disease epidemiology and trends. We describe the incidence, time trends, seasonality, and geographic distribution of LB in Germany using publicly reported surveillance data. Methods We obtained LB cases and incidence (2016-2020) from the online platform SurvStat@RKI 2.0, maintained by the Robert Koch Institute (RKI). Cases and incidence of LB were extracted by year, geographic area, week of notification, sex, age and by 2 case definition categories (clinically diagnosed LB, clinically diagnosed and laboratory-confirmed LB) reported by 9 states where LB notification is mandatory. The nine states include Bavaria, Berlin, Brandenburg, Mecklenburg-Vorpommern, Saxony, Saxony-Anhalt, Thuringia, Rhineland-Palatinate, and Saarland. Results During 2016-2020, the 9 federal states reported 63,940 LB cases, of which 60,570 (94.7%) were clinically diagnosed, and 3,370 (5.3%) also had laboratory confirmation, with an average of 12,789 cases annually. LB incidence rates were mostly stable over time. The average annual LB incidence was 37.2/100,000 person-years, ranging from 22.9 to 64.6/100,000 person-years among 9 states; from 16.8 to 85.6/100,000 person-years among 19 regions; and from 2.9 to 172.8/100,000 person-years among 158 counties. Incidence was lowest among persons 20‒24 years old (16.1/100,000 person-years) and highest among those aged 65‒69 years old (60.9/100,000 person-years). Most cases were reported between June and September, with a peak in July of every year. Annual incidence (per 100,000 person-years) of overall Lyme borreliosis notified in 158 counties (NUTS3), 2016-2020 Conclusion The risk of LB varied substantially at the smallest geographic unit and to a lesser degree by age group. Our results underscore the importance of presenting LB data at the most spatially granular unit and by age to allow implementation of efficient preventive interventions and reduction strategies. Disclosures Jozica Skufca, Epidemiologist, p95: Paid by Pfizer to perform the study Thao Mai Phuong Tran, Ph.D., P95: P95 was paid by Pfizer to perform the study Gordon Brestrich, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Andreas Pilz, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Andrew Vyse, Ph.D., Pfizer: Stocks/Bonds Claudius Malerczyk, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Mendwas Dzingina, Ph.D., Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds Maxim Blum, Ph.D., P95: Paid by Pfizer to perform the study Margarita Riera, MD, MPH, P95: Paid by Pfizer to perform the study Bradford Gessner, MD, MPH, Pfizer: Stocks/Bonds James Stark, Ph.D., Pfizer: Stocks/Bonds.

Background Lyme neuroborreliosis (LNB) is a potentially severe manifestation of Lyme borreliosis (LB), a spirochetal tick-borne infectious disease caused by Borrelia burgdorferi. We describe the incidence, time trends and geographic distribution of LNB in Denmark, with the aim to inform public health policy, including the potential use of new vaccines under development. Methods Based on the case definition for LNB (clinical diagnosis of LB plus detection of antibodies in blood and cerebral spinal fluid [confirmed case], OR clinical symptoms compatible with LNB and detection of antibodies in blood [probable case]), we obtained cases reported by laboratories and physicians (2015–2019) from the online platform maintained by the Statens Serum Institut (SSI). The LNB incidence (per 100,000 persons) was calculated by dividing LNB cases by the population data (denominator) obtained from Statistics Denmark. Results Between 2015 and 2019, laboratories reported annually 162 to 200 LNB cases, while physicians reported 48 to 68 cases (Figure). The annual LNB incidence notified by laboratories ranged from 2.8 (95% CI: 2.4‒3.3) to 3.4 (95% CI: 3.0‒4.0) per 100,000 persons for the 5 study years. The average annual LNB incidence per 100,000 persons for 5 Danish regions ranged from 2.3 to 3.3; for 11 provinces, from 1.9 to 7.6; and for 98 municipalities, from 0 to 22.1. Incidence peaks occurred in persons 5‒14 and 65‒74 years of age. Higher incidences were observed among males versus females in all age groups. LNB cases were reported throughout the year, with peaks in July to September. Number of LNB cases and annual incidence (per 100,000 population) notified by (A)physicians and (B) laboratories Conclusion LNB incidence in Denmark is moderate with no evidence of decline. Cases occurred across all regions but were focally concentrated among residents of some municipalities. By analyzing and reporting spatially granular data, we could identify areas with the highest LNB incidence. This may assist policy makers with assessing the efficiency of geographically targeted versus national prevention interventions, including vaccines should these be licensed. To this end, expanding the current surveillance system to include other manifestations of LB would be valuable to better understand geographic endemicity. Disclosures Jozica Skufca, Epidemiologist, p95: Paid by Pfizer to perform the study Nick DeSmedt, Masters in Computer Engineering, P95: P95 was paid by Pfizer to perform the study Andreas Pilz, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Andrew Vyse, Ph.D., Pfizer: Stocks/Bonds Elizabeth Begier, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds Maxim Blum, Ph.D., P95: Paid by Pfizer to perform the study Margarita Riera, MD, MPH, P95: Paid by Pfizer to perform the study Bradford Gessner, MD, MPH, Pfizer: Stocks/Bonds Mette Skovdal, Ph.D., Pfizer Denmark: Stocks/Bonds James Stark, Ph.D., Pfizer: Stocks/Bonds.

Despite the current pneumococcal vaccination program in England for older adults and adults with underlying conditions, disease burden remains high. We evaluated cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to current pneumococcal recommendations for adults in England.Lifetime outcomes/costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65-99 years and adults aged 18-64 years with underlying conditions in England were projected using a deterministic cohort model. Vaccination with PCV20 was compared with 23-valent pneumococcal polysaccharide vaccine (PPV23) from the National Health Service perspective.PCV20 was cost saving compared with PPV23 in base case and most sensitivity analyses. In the base case, replacing PPV23 with PCV20 prevented 7,789 and 140,046 cases of IPD and hospitalized CAP, respectively, and 22,199 associated deaths, resulting in incremental gain of 91,375 quality-adjusted life-years (QALYs) and incremental savings of £160M. In probabilistic sensitivity analyses, PCV20 (vs. PPV23) was cost saving in 85% of simulations; incremental cost per QALY was below £30,000 in 99% of simulations.PCV20 vaccination in adults aged 65-99 years and those aged 18-64 years with underlying comorbidities in England is expected to prevent more hospitalizations, save more lives, and yield lower overall costs than current recommendations for PPV23.

Accurate and up-to-date figures of the cost of community-acquired pneumonia (CAP) hospitalization are needed to understand the associated economic burden for public health decision-makers. Recent estimates are lacking, and previously published estimates differ markedly. Our objective was to estimate the current mean cost to the UK National Health Service (NHS) for adult hospitalized CAP. All CAP hospitalizations in 2019 for those aged ≥18 years were identified from English Hospital Episode Statistics (HES). Each hospitalization was mapped to the tariff cost paid to the care provider within the NHS, including critical care costs and accounting for length of stay and complexity of the case. Mean hospitalization costs were estimated in total and in individuals with defined underlying comorbidities. A mean cost of £3,904 was estimated for 187,251 CAP admissions providing a total cost of approximately £731 million per annum. The mean cost was £3,402, excluding critical care costs, and £11,654 for critical care episodes in the 4.4% of admissions receiving this care. Groups at high risk of CAP had higher mean costs, ranging from £4,458 for people with diabetes to £5,215 for those with heart disease aged 65 years who comprised 74.3% of admissions overall. This estimate of the cost of hospitalization for CAP from the total population and in those with certain underlying comorbidities will allow a valid understanding of the cost-benefit of vaccination and evidence-based prioritization of pneumococcal vaccination to those at highest risk. Community-acquired pneumonia (CAP) is a disease that is most commonly caused in England by the bacterium Streptococcus pneumoniae, which infects patients outside of a hospital. Patients who suffer from CAP often require hospitalization, which incurs a cost to the UK National Health Service (NHS). The goal of this study was to establish the annual cost of hospitalized CAP.The researchers used England’s national healthcare database, known as Hospital Episodes Statistics (HES), to select all adults in England who were hospitalized for CAP in 2019. For the 187,251 patients hospitalized, an average cost of £3,904 per person was estimated, amounting to a total cost of £731 million per year to the NHS. Most people admitted to hospital with CAP were at risk for the disease (due to factors such as increased age or presence of another disease) and the cost of treatment for this subgroup was disproportionately larger than that for treatment of patients not at risk. Furthermore, while approximately 5% of patients admitted for CAP received critical care during treatment, the average cost for these patients was over £8,000 higher than for those outside this subsection.The costs of hospitalization reported in this analysis were higher than previously estimated. The researchers highlighted weaknesses in other studies and limitations of the current study which could explain the difference. This work provides up-to-date figures for the cost of treating CAP in hospital in England. Public health decision-makers can use these estimates to determine the cost-benefit of vaccines that can help protect against important causes of CAP, particularly vaccines that target S. pneumoniae. Community-acquired pneumonia (CAP) is a disease that is most commonly caused in England by the bacterium Streptococcus pneumoniae, which infects patients outside of a hospital. Patients who suffer from CAP often require hospitalization, which incurs a cost to the UK National Health Service (NHS). The goal of this study was to establish the annual cost of hospitalized CAP. The researchers used England’s national healthcare database, known as Hospital Episodes Statistics (HES), to select all adults in England who were hospitalized for CAP in 2019. For the 187,251 patients hospitalized, an average cost of £3,904 per person was estimated, amounting to a total cost of £731 million per year to the NHS. Most people admitted to hospital with CAP were at risk for the disease (due to factors such as increased age or presence of another disease) and the cost of treatment for this subgroup was disproportionately larger than that for treatment of patients not at risk. Furthermore, while approximately 5% of patients admitted for CAP received critical care during treatment, the average cost for these patients was over £8,000 higher than for those outside this subsection. The costs of hospitalization reported in this analysis were higher than previously estimated. The researchers highlighted weaknesses in other studies and limitations of the current study which could explain the difference. This work provides up-to-date figures for the cost of treating CAP in hospital in England. Public health decision-makers can use these estimates to determine the cost-benefit of vaccines that can help protect against important causes of CAP, particularly vaccines that target S. pneumoniae.

Lyme neuroborreliosis (LNB) can be a serious manifestation of Lyme borreliosis. We describe the incidence, time trends and geographic distribution of LNB in Denmark. We obtained LNB cases reported by laboratories and physicians (2015-2019) from the online platform maintained by the Statens Serum Institut (SSI) (2021b). The LNB incidence (per 100,000 persons) was calculated by dividing LNB cases by the population data (denominator) obtained from Statistics Denmark (2021). Between 2015 and 2019, laboratories reported annually 162 to 200 LNB cases, while physicians reported 48 to 68 cases. The annual LNB incidence notified by laboratories ranged from 2.8 (95% CI: 2.4‒3.3) to 3.4 (95% CI: 3.0‒4.0) per 100,000 persons for the 5 study years. The average annual LNB incidence per 100,000 persons for 5 Danish regions ranged from 2.3 to 3.3; for 11 provinces, from 1.9 to 7.6; and for 98 municipalities, from 0 to 22.1. Incidence peaks occurred in persons 5‒14 and 65‒74 years of age. Higher incidences were observed among males versus females in all age groups. LNB cases were reported throughout the year, with peaks in July to September. Notified LNB incidence in Denmark was moderate with no evidence of decline. Cases occurred across all regions but were focally concentrated among residents of some municipalities. Expanding the current surveillance system to include other manifestations of LB would be valuable to better understand geographic endemicity to inform targeted preventive measures.

INTRODUCTION: : The burden of pneumococcal disease in older UK adults remains substantial. Higher valency pneumococcal conjugate vaccines (PCVs) are currently in development with adult formulations for two of these anticipated to become available in 2022. This article collates and reviews relevant candidate data now available that may be used to support cost effectiveness assessments of vaccinating immunocompetent UK adults aged ≥65-years with PCVs. AREAS COVERED: This article uses published data from surveillance systems, randomised controlled trials and observational studies. It focuses on local data from the UK but where these are either limited or not available relevant global data are considered. EXPERT OPINION: : The body of relevant data now available suggests the UK is well placed to assess the cost effectiveness of vaccinating immunocompetent ≥65-year olds with new generation higher valency PCVs. Recent contemporary data provide important new and robust insights into the epidemiology of pneumococcal disease in older UK adults and help to address much of the uncertainty and data gaps associated with previous analyses. Using these data to make informed decisions about use of new higher valency PCVs for routine use in older adults will be important for public health in the UK.

Palaeoenvironmental reconstructions with temporal coverages extending beyond Marine Isotope Stage (MIS) three are scarce within the data sparse region of Chukotka, Far East Russia. The objective of this work was to infer palaeoenvironmental variability from a 10.76 m long, radiocarbon and OSL dated sediment core from Lake Ilirney, Chukotka (67°21´N, 168°19´E). We performed acoustic sub-bottom profiling of the lake basin and analysed high-resolution elements (XRF), organic carbon (TC, TN, TOC), grain-size, mineralogy (XRD) and partly also diatoms and pollen from the core. Our results affirm the application of XRF-based sediment-geochemical proxies as effective tracers of palaeoenvironmental variability within arctic lake systems. Our work reveals that a lake formed during MIS 3 from ca. 51.8 ka BP, following an extensive MIS 4 glaciation in the Ilirney valley. Catchment palaeoenvironmental conditions during this time likely remained cold associated with the continued presence of a catchment glacier until ca. 36.2 ka BP. Partial amelioration reflected by increased diatom, catchment vegetation and lake organic productivity and clastic sediment input from mixed sources from ca. 36.2 ka BP potentially resulted in a lake high-stand ~15 m above the present level and may represent evidence of a more productive palaeoenvironment overlapping in timing with the MIS 3 interstadial optimum. A transitional period of deteriorating palaeoenvironmental conditions occurred ca. 30- 27.9 ka BP and was superseded by periglacial-glacial conditions from ca. 27.9 ka BP, during MIS 2. Deglaciation as marked by sediment-geochemical proxies commenced ca. 20.2 ka BP. Our findings are compared with lacustrine, Yedoma and river-bluff records from across Beringia and potentially yield limited support for a marked Younger Dryas cooling in the study area.

Palaeoenvironmental reconstructions with temporal coverages extending beyond Marine Isotope Stage (MIS) three are scarce within the data sparse region of Chukotka, Far East Russia. The objective of this paper is to infer palaeoenvironmental variability from a 10.76 m long, OSL- and 14C- dated sediment core from Lake Ilirney, Chukotka (67°21′N, 168°19′E). We analysed high-resolution sediment-geochemistry (XRF), sedimentology (TC, TN, TOC, grain-size), mineralogy (XRD) and preliminary micropalaeontological data (diatoms and pollen) from the core as well as acoustic sub-bottom profiling data from the lake basin. Our results affirm the application of XRF-based sediment-geochemical proxies as effective tracers of palaeoenvironmental variability within arctic lake systems. Our study reveals that a lake formed during MIS3 from 51.8 (±4.1) ka BP, following extensive MIS4 glaciation. Catchment palaeoenvironmental conditions during this time remained harsh associated with the continued presence of a catchment glacier until 36.2 (±2.6) ka BP. Partial amelioration reflected by increased diatom, catchment vegetation and lake organic productivity and clastic sediment input from mixed sources from 36.2 (±2.6) ka BP resulted in a lake high-stand ∼15 m above present and is interpreted as evidence of a more productive palaeoenvironment coincident with the MIS3 interstadial optimum. A transitional period of deteriorating palaeoenvironmental conditions occurred ∼30–27.9 ka BP and was superseded by periglacial-glacial conditions from 27.9 (±0.8) ka BP, during the last glacial maximum. Deglaciation as marked by sediment-geochemical proxies commenced at 20.2 (±0.8) ka BP. Our findings are compared with lacustrine, Yedoma and river-bluff records from across Beringia and potentially yield limited support for a marked Younger Dryas cooling in the study area.

Recent large-scale fire events in Siberia have drawn increased attention to boreal forest fire history. Boreal forests contain about 25% of all global biomass and act as an enormous carbon storage. Fire events are important ecological disturbances connected to the overarching environmental changes that face the Arctic and Subarctic, like vegetation dynamics, permafrost degradation, changes in soil nutrient cycling and global warming, and act as the dominant driver behind boreal forest’s landscape carbon balance. By looking into past fire regimes we can learn about fire frequency and potential linkages to other environmental factors, e.g. fuel types, reconstructed temperature/humidity or geomorphologic landscape dynamics. Unfortunately, fire history data is still very sparse in large parts of Siberia, a region strongly influenced by climate change. The Global Charcoal Database (www.paleofire.org) lists only a handful of continuous charcoal records for all of Siberia, with only three of those featuring published data from macroscopic charcoal as opposed to microscopic charcoal from pollen slides.We aim to reconstruct the late Holocene fire history using lacustrine sediments of Lake Khamra (SW Yakutia at N 59.99°, E 112.98°). It covers an area of c. 4.6 km² with about 22 m maximum water depth, located within the zone of transition from summer-green and larch-dominated to evergreen boreal forest. We present the first continuous, high-resolution (c. 10 years/sample) macroscopic charcoal record (> 150 μm) including information on particle size and morphology for the past c. 2200 years. We compare this to complementary information from microscopic charcoal in pollen slides, a pollen and non-pollen palynomorph record as well as μXRF data. This multi-proxy approach adds valuable data about fire activity in the region and allows a comparison of different prevalent fire reconstruction methods. As the first record of its kind from Siberia, it provides a long-term context for current fire activity in central Siberian boreal forests and enables a better understanding of the environmental interactions occurring in the changing subarctic landscape.

BackgroundHospitalised pneumonia may have long-term clinical and financial impact in adult patients with underlying comorbidities.MethodsWe conducted a retrospective cohort study using the Hospital Episode Statistics (HES) database to determine the clinical and financial burden over 3 years of hospitalised community-acquired pneumonia (CAP) to England’s National Health Service (NHS). Subjects were adults with six underlying comorbidities (chronic heart disease (CHD); chronic kidney disease (CKD); chronic liver disease (CLD); chronic respiratory disease (CRD); diabetes mellitus (DM) and post bone marrow transplant (post-BMT)) with an inpatient admission in 2012/2013. Patients with CAP in 2013/2014 were followed for 3 years and compared with similarly aged, propensity score-matched adults with the same comorbidity without CAP.FindingsThe RR of hospital admissions increased after CAP, ranging from 1.08 (95% CI 1.04 to 1.12) for CKD to 1.38 (95% CI 1.35 to 1.40) for CRD. This increase was maintained for at least 2 years. Mean difference in hospital healthcare costs (£) was higher for CAP patients in 2013/2014; ranging from £1115 for DM to £8444 for BMT, and remained higher for 4/6 groups for 2 more years, ranging from £1907 (95% CI £1573 to £2240) for DM to £11 167 (95% CI £10 847 to £11 486) for CRD.) The OR for mortality was significantly higher for at least 3 years after CAP, ranging from 4.76 (95% CI 4.12 to 5.51, pInterpretationFor patients with selected underlying comorbidities, healthcare utilisation, costs and mortality increase for at least 3 years after being hospitalised CAP.

Forest fires are an important factor of the global carbon cycle and high latitude ecosystems. Eastern Siberian tundra, summergreen larch-dominated boreal forest on permafrost and evergreen spruce- and pine-dominated boreal forest have characteristic fire regimes with varying fire frequencies and intensities. However, it is unknown which role fire plays in climate-vegetation-permafrost feedbacks and how high-latitude fire regimes and ecosystems will change in a warmer world – questions that are crucial considering that boreal and permafrost regions have been identified as tipping elements in the climate system (Lenton et al., 2008, PNAS).Here, we investigate fire regime shifts during previous warmer-than-present interglacials, i.e. marine isotope stages (MIS) 5e and 11c, which were not influenced by human activity. We use specific biomass burning residues, i.e. monosaccharide anhydrides (anhydrosugars), that are a rather chemically reactive group of pyrogenic carbon. These molecules are mainly produced by low-temperature fires, but their pathways through the Earth system from source to sink and their stability in sedimentary deposits are very poorly constrained (Suciu et al. 2019, Biogeochemistry). A recent study (Dietze et al., 2020, ClimPastDisc) found anhydrosugars in up to 420 kyr old sediment of Lake El’gygytgyn (ICDP Site 5011-1), northeastern Siberia, and suggest that these molecular markers are suitable proxies for fires in Siberian summergreen boreal forests. Surprisingly, the ratios of the anhydrosugars levoglucosan to its isomers mannosan and galactosan were exceptionally low compared to published emission ratios from modern biomass burning, pointing to either a specific local biomass source and/or isomer-specific preservation.To understand what anhydrosugars from interglacial Arctic lake sediments tell us about fire regime changes, we studied modern sediment samples from Lake El’gygytgyn, its catchment and from other lakes located in East Siberian summergreen and evergreen boreal forest. The latter lake systems represent spatial analogues to the conditions at Lake El’gygytgyn during MIS 5e and 11c, respectively. We analyzed anhydrosugars using ultra high-performance liquid chromatography coupled to a high-resolution mass spectrometer. We discuss the modern anhydrosugar concentrations and isomer ratios in context of (1) well-explored modern lake and catchment configurations and (2) multiple late glacial to interglacial results of Lake El’gygytgyn sediment cores. By better constraining the sources and (degradation) pathways that determine the proxy meaning of sedimentary anhydrosugars in northeastern Siberia, we provide a step forward to understand the regional pyrogenic carbon cycle and long-term feedbacks that are crucial for model predictions of future fire regime shifts in the high northern latitudes.

Understanding the hydrologic connectivity between kettle holes and shallow groundwater, particularly in reaction to the highly variable local meteorological conditions, is of paramount importance for tracing water in a hydro(geo)logically complex landscape and thus for integrated water resource management. This article is aimed at identifying the dominant hydrological processes affecting the kettle holes' water balance and their interactions with the shallow groundwater domain in the Uckermark region, located in the north‐east of Germany. For this reason, based on the stable isotopes of oxygen (δ18O) and hydrogen (δ2H), an isotopic mass balance model was employed to compute the evaporative loss of water from the kettle holes from February to August 2017. Results demonstrated that shallow groundwater inflow may play the pivotal role in the processes taking part in the hydrology of the kettle holes in the Uckermark region. Based on the calculated evaporation/inflow (E/I) ratios, most of the kettle holes (86.7%) were ascertained to have a partially open, flow‐through‐dominated system. Moreover, we identified an inverse correlation between E/I ratios and the altitudes of the kettle holes. The same holds for electrical conductivity (EC) and the altitudes of the kettle holes. In accordance with the findings obtained from this study, a conceptual model explaining the interaction between the shallow groundwater and the kettle holes of Uckermark was developed. The model exhibited that across the highest altitudes, the recharge kettle holes are dominant, where a lower ratio of E/I and a lower EC was detected. By contrast, the lowest topographical depressions represent the discharge kettle holes, where a higher ratio of E/I and EC could be identified. The kettle holes existing in between were categorized as flow‐through kettle holes through which the recharge takes place from one side and discharge from the other side., The prevailing hydrological processes influencing the kettle holes in the Uckermark region in the north‐east of Germany were investigated using the stable isotopes of oxygen and hydrogen. The possible contribution of the groundwater inflow into the kettle holes was characterized via evaporation/inflow (E/I) ratios. A conceptual model portraying hydrologic connectivity between different types of kettle holes and in relation their adjacent shallow groundwater domain was provided. image

Meningococcal serogroup B disease (MenB) is endemic in the UK and continues to cause the majority of invasive meningococcal disease. Two broadly protective protein-based MenB vaccines are now licensed and available, both with wide age indications. Whilst the UK recently became the first country to routinely vaccinate infants against MenB, a recommendation has not yet been extended to older age groups who can also now benefit from these vaccines.This review summarizes the evidence supporting the rationale for adolescents and adults in the UK to consider MenB vaccination.Although MenB disease is rare, the UK reports one of the highest annual incidence rates within the European region, with over a third of cases occurring in those aged 10+ years. Overall, the case fatality rate following MenB disease in the UK is 4.2% but can be more than twice as high in teenagers and adults than in infants, and survivors are often left with life-changing disabling sequelae. MenB outbreaks are unpredictable and continue to occur in regions where it is endemic. These outbreaks often affect students attending school or university, with living on a campus being an important risk factor. Concerned individuals in this age group should consider MenB vaccination.

Background Disease incidence is a key indicator for the assessment of population health and to guide public health policies. Defining accurate population denominators is challenging for incidence studies of hospital-based events, for which hospital catchment areas depend on patient choice and geographic proximity and often do not match established town or city boundaries. We describe a new method to accurately define a hospital's population denominator, which we developed for a study designed to estimate the incidence of hospitalisation for adult acute lower respiratory tract disease in Bristol, UK. Methods We examined hospital data for adult acute lower respiratory tract disease to identify general practitioner (GP) practices (n=82) whose patients were treated for adult acute lower respiratory tract disease at study hospitals and confirmed that nearly all patients (9230 [94·5%] of 9764) were registered with practices within the National Health Service's Bristol, North Somerset, and South Gloucestershire Clinical Commissioning Group (CCG). Hospital admission data were linked to aggregated GP practice patient registration data within this CCG for April 1, 2017, to March 31, 2020. The proportion of GP practices' patients who were hospitalised for adult acute lower respiratory tract disease that occurred at a specific study hospital was multiplied by their patient registration count for six age groups to obtain the practices' contribution to that hospital's denominator (eg, if 50% of GP practice admissions were at a specific study hospital among patients aged 50–64 years, the practice contributed half of their patients aged 50–64 years to the denominator). Alternate denominators were calculated using population census data matched to 20-minute drivetime estimates for study hospitals (the method used to define hospital catchment for local health service purposes). Findings The percentage of admissions at study hospitals varied substantially by GP practice (0–100%). 231 342 (86·3%) of 268 093 of the CCG's GP practice registrants aged 18–34 years received treatment at study hospitals (compared with 19 229 [80%] of 23 938 registrants aged or older than 85 years); some received treatment at another local hospital to the south. With 20-minute drivetime as an estimate measure, hospital catchment would be 550 155 (66·5%) of 827 304 individuals in the CCG population. Interpretation Using health-care data stratified by local CCG enables the estimation of local population denominators to support accurate incidence ascertainment within hospital-based surveillance studies. Funding This work was funded by Pfizer.

Background UK specific data on the risk of developing hospitalised CAP for patients with underlying comorbidities is lacking. This study compared the likelihood of hospitalised all-cause community acquired pneumonia (CAP) in patients with certain high-risk comorbidities and a comparator group with no known risk factors for pneumococcal disease. Methods This retrospective cohort study interrogated data in the Hospital Episodes Statistics (HES) dataset between financial years 2012/13 and 2016/17. In total 3,078,623 patients in England (aged ≥18 years) were linked to their hospitalisation records. This included 2,950,910 individuals with defined risk groups and a comparator group of 127,713 people who had undergone tooth extraction with none of the risk group diagnoses. Risk groups studied were chronic respiratory disease (CRD), chronic heart disease (CHD), chronic liver disease (CLD), chronic kidney disease (CKD), diabetes (DM) and post bone marrow transplant (BMT). The patients were tracked forward from year 0 (2012/13) to Year 3 (2016/17) and all diagnoses of hospitalised CAP were recorded. A Logistic regression model compared odds of developing hospitalised CAP for patients in risk groups compared to healthy controls. The model was simultaneously adjusted for age, sex, strategic heath authority (SHA), index of multiple deprivation (IMD), ethnicity, and comorbidity. To account for differing comorbidity profiles between populations the Charlson Comorbidity Index (CCI) was applied. The model estimated odds ratios (OR) with 95% confidence intervals of developing hospitalised CAP for each specified clinical risk group. Results Patients within all the risk groups studied were more likely to develop hospitalised CAP than patients in the comparator group. The odds ratios varied between underlying conditions ranging from 1.18 (95% CI 1.13, 1.23) for those with DM to 5.48 (95% CI 5.28, 5.70) for those with CRD. Conclusions Individuals with any of 6 pre-defined underlying comorbidities are at significantly increased risk of developing hospitalised CAP compared to those with no underlying comorbid condition. Since the likelihood varies by risk group it should be possible to target patients with each of these underlying comorbidities with the most appropriate preventative measures, including immunisations.

Pneumococcal colonization is rarely studied in adults, except as part of family surveys. We report the outcomes of colonization screening in healthy adults (all were nonsmokers without major comorbidities or contact with children aged, We detected pneumococcal colonization in 52 of 795 subjects, using nasal wash culture. The majority of pneumococci were nonvaccine serotypes, but we identified persistent circulation of serotypes 3, 19A, and 19F and the emergence of antimicrobial resistance in the latter years of the study.

Adolescents have the highest rates of meningococcal carriage and transmission. Interrupting the adolescent habitat in order to reduce carriage and transmission within adolescents and to other age groups could help to control meningococcal disease at a population level. Compared to immunization strategies restricted to young children, a strategy focused on adolescents may have more profound and long-lasting indirect impacts, and may be more cost effective. Despite challenges in reaching this age-group, experience with other vaccines show that high vaccine coverage of adolescents is attainable.

Background The clinical and economic costs of an episode of hospitalised pneumonia are usually assumed to be short-lived with patients subsequently returning to their previous health-state. We hypothesised that a diagnosis of hospitalised pneumonia in an individual within a specific risk group would have clinical and economic implications that would go beyond the initial episode. Aim Determine, within the NHS context, the clinical and financial burden of hospitalised pneumonia in 6 risk groups over a 4 year period utilising the Hospital Episodes Statistics (HES) database, which incorporates the entire population of England that visit a hospital. Method We retrospectively analysed HES data on individuals≥18 years. Those with a specified risk group diagnosis were tracked from 2012 to 2015. Individuals developing hospitalised pneumonia in the year following their risk group diagnosis were matched through propensity scoring to an individual within that risk group who did not go on to develop hospitalised pneumonia. Hospital activity, costs and mortality were compared between the two groups over the next 3 years. Results Conclusion This study utilises an entire adult population to ascertain the impact of hospitalised pneumonia in patients with certain underlying comorbidities. Hospitalised pneumonia has a significant long term impact on those within specific risk groups, resulting in additional hospital admissions and associated costs, and the initial pneumonia episode appears to significantly increase the likelihood of mortality.

Introduction/background Specific risk groups are at increased risk of hospitalisation and death from non-invasive pneumococcal disease. Evidence showing the increased odds ratio in these risk groups for developing hospitalised pneumonia in England is missing. Aim To quantify the odds of developing hospitalised pneumonia for 6 key risk groups as defined by The Green Book (UK vaccination policy guide) compared to ‘healthy controls’, with no risk group diagnosis, using the Hospital Episodes Statistics (HES) database. Materials and methods We retrospectively analysed the Hospital Episodes Statistics database, which includes analysed data on the entire ≥18 years population of England for episodes of hospitalised pneumonia over a period of 3 years. Patients and controls were identified by ICD-10 codes. Healthy controls were in-patient admissions for tooth extraction. Odds ratios were calculated while simultaneously adjusting for gender, age, Charlson Comorbidity Index, ethnicity, geography and deprivation. Results Odds ratio of developing hospitalised pneumonia for specific risk groups compared to healthy controls. Conclusion This is the first study of an entire adult population quantifying the increased odds of hospitalised pneumonia among patients with these underlying risk factors. These individuals are at a significant increased risk of developing hospitalised pneumonia and that the odds are substantially higher for those with CRD, CLD and BMT. These data support the potential benefit of adopting a targeted prevention strategy among specific risk groups.

The 13-valent pneumococcal conjugate vaccine (PCV) has been part of routine immunisation in a 2 + 1 schedule (two primary infant doses and one booster during the second year of life) in the UK since 2010. Recently, the UK's Joint Committee on Vaccination and Immunisation recommended changing to a 1 + 1 schedule while conceding that this will increase disease burden; however, uncertainty remains on how much pneumococcal burden – including invasive pneumococcal disease (IPD) and non-invasive disease – will increase. We built a dynamic transmission model to investigate this question. The model predicted that a 1 + 1 schedule would incur 8777–27 807 additional cases of disease and 241–743 more deaths over 5 years. Serotype 19A caused 55–71% of incremental IPD cases. Scenario analyses showed that booster dose adherence, effectiveness against carriage and waning in a 1 + 1 schedule had the most influence on resurgence of disease. Based on the model assumptions, switching to a 1 + 1 schedule will substantially increase disease burden. The results likely are conservative since they are based on relatively low vaccine-type pneumococcal transmission, a paradigm that has been called into question by data demonstrating an increase of IPD due to several vaccine serotypes during the last surveillance year available.

Pregnancy and the postpartum period are associated with elevated risks to both mother and infant from infectious disease. Vaccination of pregnant women, also called maternal immunization, has the potential to protect pregnant women, foetuses and infants from several vaccine-preventable diseases. Maternal immunoglobulin G antibodies are actively transferred through the placenta to provide passive immunity to new-borns during the first months of life, until the time for infant vaccinations or until the period of greatest susceptibility has passed. Currently, inactivated influenza, tetanus, and pertussis vaccines are recommended during pregnancy in many countries, but other vaccines may also be administered to pregnant women when risk factors are present. Several new vaccines with a specific indication for use during pregnancy are under development (e.g. respiratory syncytial virus and group B streptococcus vaccines). Years of experience suggest that maternal immunization against influenza, tetanus or pertussis has an acceptable safety profile, is well tolerated, effective and confers significant benefits to pregnant women and their infants. This review describes the principles of maternal immunization and provides an update of the recent evidence regarding the use and timing of maternal immunization. Finally, the barriers preventing wider vaccination coverage and the current limitations in addressing these are also described (Supplementary Material).Key messagesMaternal immunization gives pregnant women greater protection against infectious diseases; induces high levels of maternal antibodies that can be transferred to the foetus; and helps protect new-borns during their first months of life, until they are old enough to be vaccinated.Pregnant women and new-borns are more vulnerable to infectious diseases than the overall population; nevertheless, vaccination rates are often low in pregnant women.This review provides an update of the recent evidence regarding the use and timing of maternal immunization and describes the barriers preventing wider vaccination uptake and the current limitations in addressing these. Maternal immunization gives pregnant women greater protection against infectious diseases; induces high levels of maternal antibodies that can be transferred to the foetus; and helps protect new-borns during their first months of life, until they are old enough to be vaccinated. Pregnant women and new-borns are more vulnerable to infectious diseases than the overall population; nevertheless, vaccination rates are often low in pregnant women. This review provides an update of the recent evidence regarding the use and timing of maternal immunization and describes the barriers preventing wider vaccination uptake and the current limitations in addressing these.

TO THE EDITOR—We read with interest the article by Kent et al [1]. The authors note that the burden of invasive pneumococcal disease (IPD) in UK infants aged