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Wastewater monitoring has been used to identify SARS-CoV-2 outbreaks and track new variants. This sentinel system should be expanded to monitor other pathogens and boost public health preparedness.

Tissue-resident memory T (T RM ) cells constitute a subpopulation of memory cells that reside in tissues instead of recirculating. CD8 + epithelial TRM (eT RM ) cells, which occupy the epithelium of sites like the skin, require transforming growth factor–β (TGF-β) for their development. Mani et al. found that α V integrin–expressing dendritic cells, which activate and present TGF-β, are key (see the Perspective by Farber). Surprisingly, this interplay did not occur in the skin or draining lymph nodes during T cell priming. Rather, resting naïve CD8 + T cells interacted with α V integrin–expressing migratory dendritic cells during immune homeostasis, reversibly preconditioning them to become eT RM cells upon activation. A potent cytokine is thus controlled in a context-dependent manner and preimmune T cell repertoires may be less uniform than previously presumed. Science , this issue p. eaav5728 ; see also p. 188 Resting naïve immunological T cells are poised to become tissue-resident memory cells after encounters with TGF-β–bearing dendritic cells. Epithelial resident memory T (eT RM ) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eT RM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8 + T cells and prepares them for the formation of eT RM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I–dependent interactions with peripheral tissue–derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β–activating α V integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.

While many pregnant individuals use prescription medications, evidence supporting product safety during pregnancy is often inadequate. Existing electronic healthcare data sources provide large, diverse samples of health plan members to allow for the study of medical product utilization during pregnancy, as well as pregnancy, maternal, and infant outcomes. The Sentinel System is a national medical product surveillance system that includes administrative claims and electronic health record databases from large national and regional health insurers. In addition to these data sources, Sentinel develops and maintains a sizeable selection of analytic tools to facilitate epidemiologic analyses in a way that protects patient privacy and health system autonomy. In this article, we provide an overview of Sentinel System infrastructure, including the Mother–Infant Linkage Table, parameterizable analytic tools, and algorithms to estimate gestational age and identify pregnancy outcomes. We also describe past and future Sentinel work that contributes to our understanding of the way medical products are used and the safety of these products during pregnancy.

Background Surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years. Methods Antimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134  N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs). Results In 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC ≥ 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (~11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2–3.5, p  < 0.01). Conclusions The 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono- or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

Monitoring environmental DNA can track the presence of organisms, from viruses to animals, but requires continuous sampling of transient sequences from a complex milieu. Here we designed living sentinels using Bacillus subtilis to report the uptake of a DNA sequence after matching it to a preencoded target. Overexpression of ComK increased DNA uptake 3,000-fold, allowing for femtomolar detection in samples dominated by background DNA. This capability was demonstrated using human sequences containing single-nucleotide polymorphisms (SNPs) associated with facial features. Sequences were recorded with high efficiency and were protected from nucleases for weeks. The SNP could be determined by sequencing or in vivo using CRISPR interference to turn on reporter expression in response to a specific base. Multiple SNPs were recorded by one cell or through a consortium in which each member recorded a different sequence. Sentinel cells could surveil for specific sequences over long periods of time for applications spanning forensics, ecology and epidemiology. Nou et al. engineered Bacillus subtilis cells into a living sentinel system, which can take up environmental DNA and fluoresce when a matching sequence is detected. This system enables recording of SNPs for facial features and has broad applications spanning forensics to agriculture.

Current models predict increases in High Arctic temperatures and precipitation that will have profound impacts on the Arctic hydrological cycle, including enhanced glacial melt and thawing of active layer soils. However, it remains uncertain how these changes will impact the structure of downstream resident freshwater microbial communities and ensuing microbially driven freshwater ecosystem services. Using the Lake Hazen watershed (Nunavut, Canada; 82°N, 71°W) as a sentinel system, we related microbial community composition (16S rRNA gene sequencing) to physicochemical parameters (e.g. dissolved oxygen and nutrients) over an annual hydrological cycle in three freshwater compartments within the watershed: (i) glacial rivers; (ii) active layer thaw-fed streams and waterbodies and (iii) Lake Hazen, into which (i) and (ii) drain. Microbial communities throughout these freshwater compartments were strongly interconnected, hydrologically, and often correlated with the presence of melt-sourced chemicals (e.g. dissolved inorganic carbon) as the melt season progressed. Within Lake Hazen itself, water column microbial communities were generally stable over spring and summer, despite fluctuating lake physicochemistry, indicating that these communities and the potential ecosystem services they provide therein may be resilient to environmental change. This work helps to establish a baseline understanding of how microbial communities and the ecosystem services they provide in Arctic watersheds might respond to future climate change.

In the context of COVID-19 pandemic in Catalonia (Spain), the present study analyses respiratory samples collected by the primary care network using Acute Respiratory Infections Sentinel Surveillance System (PIDIRAC) during the 2019-2020 season to complement the pandemic surveillance system in place to detect SARS-CoV-2. The aim of the study is to describe whether SARS-CoV-2 was circulating before the first confirmed case was detected in Catalonia, on February 25th, 2020. The study sample was made up of all samples collected by the PIDIRAC primary care network as part of the Influenza and Acute Respiratory Infections (ARI) surveillance system activities. The study on respiratory virus included coronavirus using multiple RT-PCR assays. All positive samples for human coronavirus were subsequently typed for HKU1, OC43, NL63, 229E. Every respiratory sample was frozen at-80°C and retrospectively studied for SARS-CoV-2 detection. A descriptive study was performed, analysing significant differences among variables related to SARS-CoV- 2 cases comparing with rest of coronaviruses cases through a bivariate study with Chi-squared test and statistical significance at 95%. Between October 2019 and April 2020, 878 respiratory samples from patients with acute respiratory infection or influenza syndrome obtained by PIDIRAC were analysed. 51.9% tested positive for influenza virus, 48.1% for other respiratory viruses. SARS-CoV-2 was present in 6 samples. The first positive SARS-CoV-2 case had symptom onset on 2 March 2020. These 6 cases were 3 men and 3 women, aged between 25 and 50 years old. 67% had risk factors, none had previous travel history nor presented viral coinfection. All of them recovered favourably. Sentinel Surveillance PIDIRAC enhances global epidemiological surveillance by allowing confirmation of viral circulation and describes the epidemiology of generalized community respiratory viruses' transmission in Catalonia. The system can provide an alert signal when identification of a virus is not achieved in order to take adequate preparedness measures.

Background Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. Methods Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. Results The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. Conclusions In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.

Background In Germany, general childhood varicella vaccination has been recommended since 2004. A feared effect of low vaccination coverage is a possible shift in incidence from children to teenagers and young adults who are at higher risk of severe outcomes. If true, this shift would possibly necessitate changes to the national immunization strategy. We aimed to evaluate the effects of the general vaccination recommendation on age-specific varicella incidences in Germany in general and examine specifically whether a shift from children to teenagers (15 to 19 years) has occurred. Methods Trends in age-specific incidences were evaluated using triangulation with the following datasets: national mandatory notification data ( N) (2014–2022), billing data of the statutory health insurance associations ( I ) (2009–2017) and data from a doctor's sentinel system ( S ) (2006–2017). Similar clinical case definitions were used in N and S , while I used ICD-10-codes. Age groups were stratified as available in all three systems. Incidences per year were calculated based on the total population ( N ), the number of statutory health insured ( I) , and extrapolated from S to the total population. Results During all years of observation, age-specific incidences have dropped significantly across all age-groups for S und I. The age groups (under 10 years) with initially highest incidences were the ones with the strongest reductions (under 1 year: -90%, 1–4 years: -95.5%, 5–9 years: -89.2% for S ; -67.7%, -78%, -79.3% for I ). A single 53.1% increase in the low incidence in S among 15–19-year olds observed in 2017 compared to 2016 could not be confirmed in N or I . Increases in incidences during the first two years of N are probably due to improved notification behaviour over these years. In 2019, all age-specific incidences increased ( N ), with 15 to 19-year olds showing the highest relative increase (28.2%). Conclusions Since the introduction of the general vaccine recommendation against varicella, incidences across all age-groups have declined significantly. Available data indicate no evidence for a shift in disease incidence to older age groups. Every incidence increase beyond childhood age should however be followed up closely. So far, children and adolescents have both benefitted from the current vaccination strategy.

Background Chlamydia trachomatis (chlamydia) is a common, frequently asymptomatic, sexually transmitted infection. It can result in severe sequelae, such as ectopic pregnancy and infertility. In Germany, chlamydia is not notifiable. An opportunistic screening program for women < 25 years was introduced in 2008. The aim of this research was to triangulate different data sources to describe the epidemiological situation of chlamydia in Germany and to investigate whether the current target group of the chlamydia screening program aligns with these findings. Methods Urine specimens from participants from population-based health examination surveys of children (2014–17) and adults (2008–11) were tested for chlamydia, using nucleic acid amplification testing. These data were used to generate weighted chlamydia prevalence estimates by age group and sex. Data from a nationwide chlamydia laboratory sentinel system (2014–16) were used to calculate the positive proportion among individuals tested for chlamydia by age, sex and test reason. Results Using data from the population-based surveys, we found a chlamydia prevalence estimate of 2.8% (95% confidence interval (CI) 1.0–7.5%) among all 15- to 17-year-old girls and of 9.6% (95% CI 0.0–23) among those reporting to be sexually active. In adult women, we found the highest prevalence among 18- to 24-year-olds (all: 2.3%; 95% CI 1.0–5.3%; sexually active: 3.1%; 95% CI 1.3–7.0%). In adult men, we found the highest prevalence among 25- to 29-year-olds (all: 3.5%; 95% CI 1.6–7.7%; sexually active: 3.3%; 95% CI 1.3–7.8%). Data from the chlamydia laboratory sentinel showed the highest positive proportion among those opportunistically screened in 19-year-old women (6.1%; 95%- CI 5.9–6.4%), among those screened due to pregnancy in 15-year-old girls (10%; 95% CI 8.5–12%), and among those tested due to symptoms or a positive partner in 19-year-old women (10%; 95% CI 9.8–11%) and 19-year-old men (24%; 95% CI 22–26%). Conclusions Chlamydia seems to mainly affect adolescents and young adults in Germany, with similar overall prevalence in men and women, but with slightly different age distributions. Women at highest risk of chlamydia are covered by the current screening program but given the on-going discussions in high-income countries on cost-effectiveness and benefit-to-harm ratio of these programs, the program-aim needs reconsideration.