Laboratory Surveillance Research Articles

EP484: Scaling a high throughput next generation sequencing laboratory for community surveillance of SARS-CoV-2 viral variants during the public health crisis

As threats to global health evolve, it is imperative that clinical laboratories are prepared to quickly respond through rapid method validation and laboratory scaling for diagnostics and surveillance of emerging infectious diseases. Here we report an optimized workflow using the Illumina COVIDSeq RUO Kits and the NovaSeq 6000 sequencer for high throughput sequencing of SARS-CoV-2 positive patient specimens. Sample preparation for high quality next-generation sequencing (NGS) includes multiple, time-consuming steps to reverse transcribe cDNA, to amplify and index the genome targets, and to pool, quantify, and normalize sequencing libraries.

Impact of the COVID-19 pandemic on gastrointestinal infection trends in England, February–July 2020

ObjectiveTo establish the impact of the first 6 months of the COVID-19 outbreak response on gastrointestinal (GI) infection trends in England.DesignRetrospective ecological study using routinely collected national and regional surveillance...

Coccidioidomycosis: A Contemporary Review.

Coccidioidomycosis, colloquially known as Valley Fever, is an invasive dimorphic fungal infection caused by Coccidioides immitis and C. posadasii. The fungi are found in the arid desert soils of the southwestern US, as well as in parts of Mexico and Central and South America. Acquisition is typically via inhalation of arthroconidia which become airborne after both natural (e.g., earthquakes, dust storms, and fires) and human-related events (e.g., military maneuvers, recreational activities, agriculture, and construction). The incidence of infection in increasing likely a result of both climatic and populational changes. Further, the recognized geographic distribution of Coccidioides spp. is expanding, as cases are being diagnosed in new areas (e.g., eastern Washington, Oregon, and Utah). Most coccidioidal infections are asymptomatic (60%); however, approximately one-third develop a pulmonary illness which is a leading cause of community-acquired pneumonia in highly endemic areas. Uncommonly (0.5–2% of cases), the infection disseminates to extrapulmonary locations (e.g., skin, bones/joints, and the central nervous system), and is most commonly seen among persons with cellular immunodeficiencies (e.g., transplant recipients, HIV, and pregnancy) and non-Caucasian races (especially African Americans and Filipinos). The diagnosis of coccidioidomycosis requires astute clinical suspicion and laboratory findings, including positive serology, cultures, and/or histopathology results. Treatment is warranted among persons with pneumonia who have risk factors for complicated disease and among those with extrapulmonary disease. Novel antifungals with improved fungicidal activity and rapidity of action with fewer side effects and drug interactions are needed. Preventive strategies (e.g., education regarding the disease, dust avoidance, mask wearing, including among select groups, antifungal prophylaxis, and surveillance laboratory testing) are advised for residents and travelers to endemic areas. Currently, no preventive vaccine is available. Coccidioidomycosis has been recognized for over a century, and an expanding wealth of knowledge has been gained regarding this emerging infectious disease which will be reviewed here.

COVID-19 Surveillance Enhanced by an Integrated Electronic Infectious Diseases Information System in Albania

PurposeThe objective of this paper is to showcase how COVID -19 control has been enhanced by interrelating syndromic surveillance, case based surveillance and laboratory surveillance and outbreak investigation into an integrated electronic Infectious Diseases Information System (IDIS).Methods & MaterialsDevelopment of IDIS began in December 2016 with the goal to modernize the Albanian surveillance system by developing a user-friendly, comprehensive database for case investigation, contact tracing, and laboratory data focusing on the improvement of the timeliness indicators of disease detection and response. The platform is based on open-source software solutions featuring (1) integration of data from different surveillance systems such as indicator, syndromic and event base; (2) better investigation and management of outbreaks and reduced data-entry time and errors (3) generation of line listing and contact-tracing and workflows to appropriately follow-up of cases and contacts; (4) integration with the national vaccination registry for retrieving vaccination history and prospectively apply ring vaccinations during outbreak control; (5) integration with laboratory information system public and private to retrieve diagnostic information; and (6) repository with qualitative and quantitative cache of epidemiological information and data;ResultsThe IDIS system has assisted public health surveillance to document COVID-19 cases and to take disease control actions such as case isolation, contact tracing and contact isolation, and more recently vaccination. To date 400.000 potential cases of COVID -19 have been notified in the system has been notified 273.000 have been individually investigated. About 487.000 laboratory results have been linked with case based information and respective contacts. The system has proved useful for data analysis as a series of epidemiological indicators have been calculated to inform evidence based decision making in controlling COVID-19 epidemic in Albania.ConclusionIDIS implementation has improved the consistency, communication, and effective use of public health data. In particular integration of different surveillance systems and workflows which are developed within IDIS provide an array of instruments to epidemiologists to detect cases faster, make better decisions based on multiple data sources and more effectively plan response measures.

Evaluating the Quality of Federal SARS-CoV-2 Diagnostic Testing Data

PurposeIn April 2020, the US Department of Health and Human Services (HHS) and the US Centers for Disease Control and Prevention established the COVID-19 Electronic Laboratory Reporting program (CELR) to collect data on SARS-CoV-2 laboratory tests. Over the course of the following year, the federal government, partnering with the Association for Public Health Laboratories, onboarded every state to submit laboratory results to this system—the first of its kind in the US. We set out to evaluate the quality of data collected by CELR.Methods & MaterialsWe compared jurisdiction-level data collected through CELR and published by HHS to the testing data published by jurisdictions on their health department webpages. Because jurisdictions define their testing data differently, we anticipated some differences from federal testing data. However, jurisdictions also tend to prioritize their dashboard reporting—since it is what is used for policy decisions like reopening—so we hypothesized that differences from federal data absent a definitional explanation could point to problems with federal data. Where we found differences between jurisdictional and federal data, we conducted interviews with public health officials to understand their cause.ResultsOf the 56 states and territories, as of April 2021 (the first month when all states were onboarded to CELR), 38 had federal total data that diverges from state data by more than 5%. Of those states, the differences of 27 could not be explained by definitional factors. Based on our interviews, we identified three problems: non-electronic reporting streams, out-of-date surveillance systems, and deduplication of laboratory data.ConclusionThe federal testing dataset displays major unresolved quality problems, and because states present testing data so differently, state-published data forms a poor alternative to federal datasets. The federal government, which is uniquely positioned to provide testing data on infectious diseases, must work to improve the quality of laboratory data submissions by states. To support better national laboratory data, the United States should invest in updating state and laboratory data surveillance infrastructure—including updates to state surveillance systems and laboratory system updates to eliminate outdated reporting methods like faxes—and in creating more national laboratory data infrastructure.

Implementation and Extended Evaluation of the Euroimmun Anti-SARS-CoV-2 IgG Assay and Its Contribution to the United Kingdom's COVID-19 Public Health Response.

ABSTRACTIn March 2020, the Rare and Imported Pathogens Laboratory at the UK Health Security Agency (UKHSA) (formerly Public Health England [PHE]) Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing UKHSA, DHSC, and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved overall sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and interassay precision, correlation to neutralization, and assay linearity.IMPORTANCE Serology assays have been useful in determining those with previous SARS-CoV-2 infection in a wide range of research and serosurveillance projects. However, assays vary in their sensitivity at detecting SARS-CoV-2 antibodies. Here, we detail an extended evaluation and characterization of the Euroimmun anti-SARS-CoV-2 IgG assay, one that has been widely used within the United Kingdom on over 160,000 samples to date.

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy.

ObjectiveTo provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real‐world practice, in a broad population of infants with spinal muscular atrophy (SMA).MethodsA prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations. Efficacy assessments included World Health Organisation (WHO) motor milestones, oral and swallowing abilities, and requirements for respiratory support. The implementation of a model of care for onasemnogene abeparvovec administration in health practice is described.Results21 children were treated (age range, 0.65–24 months; body weight range, 2.5–12.5 kg) and 19/21 (90.4%) had previous nusinersen. Transient treatment‐related side effects occurred in all children; vomiting (100%), transaminitis (57%) and thrombocytopaenia (33%). Incidence of moderate/severe transaminitis was significantly greater in infants weighing ≥8 kg compared with <8 kg (p < 0.05). Duration of prednisolone following treatment was prolonged (mean 87.5 days, range 57–274 days). 16/21 (76%) children gained at least one WHO motor milestone. Stabilisation or improvement in bulbar or respiratory function was observed in 20/21 (95.2%) patients. Implementation challenges were mitigated by developing standard operating procedures and facilitating exchange of knowledge.InterpretationThis study provides real‐world evidence to inform treatment decisions and guide therapeutic expectations for onasemnogene abeparvovec and combination therapy for SMA in health practice, especially for children weighing ≥8 kg receiving higher vector loads. Proactive clinical and laboratory surveillance is essential to facilitate individualised management of risks.

Population structure analysis and laboratory monitoring of Shigella by core-genome multilocus sequence typing

The laboratory surveillance of bacillary dysentery is based on a standardised Shigella typing scheme that classifies Shigella strains into four serogroups and more than 50 serotypes on the basis of biochemical tests and lipopolysaccharide O-antigen serotyping. Real-time genomic surveillance of Shigella infections has been implemented in several countries, but without the use of a standardised typing scheme. Here, we study over 4000 reference strains and clinical isolates of Shigella, covering all serotypes, with both the current serotyping scheme and the standardised EnteroBase core-genome multilocus sequence typing scheme (cgMLST). The Shigella genomes are grouped into eight phylogenetically distinct clusters, within the E. coli species. The cgMLST hierarchical clustering (HC) analysis at different levels of resolution (HC2000 to HC400) recognises the natural population structure of Shigella. By contrast, the serotyping scheme is affected by horizontal gene transfer, leading to a conflation of genetically unrelated Shigella strains and a separation of genetically related strains. The use of this cgMLST scheme will facilitate the transition from traditional phenotypic typing to routine whole-genome sequencing for the laboratory surveillance of Shigella infections.

Surveillance of Fluoroquinolone Resistance in Wisconsin: Geographic Variation and Impact of Revised CLSI Breakpoints

Objective: Many clinical microbiology laboratories procure antimicrobial susceptibility testing data using guidelines established by Clinical and Laboratory Standards Institute (CLSI). When necessary, CLSI revises interpretive breakpoints in efforts to improve clinical correlation, with two revisions relative to fluoroquinolone agents occurring in 2019. The purpose of this investigation was to determine the impact of fluoroquinolone breakpoint revisions on Wisconsin clinical isolates of Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa. Design: Multi-center laboratory surveillance, with testing at a single location utilizing standardized media and susceptibility testing protocols.Methods: From the Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) program, levofloxacin and ciprofloxacin minimum inhibitory concentration (MIC) values for 1911, 1521, and 1463 Wisconsin isolates of E. coli, P. mirabilis, and P. aeruginosa, respectively, were determined by broth microdilution testing. In separate data analyses, all MIC data were interpreted using CLSI breakpoints published prior to 2019, then secondarily by using CLSI breakpoints published since 2019 (which reflect lower breakpoints for both levofloxacin and ciprofloxacin resistance). Findings were further stratified by Wisconsin Department of Health Services region.Results: Up to 3.2% decreased statewide fluoroquinolone susceptibility was observed for E. coli isolates, while 5.1% and 6.3% decreases in levofloxacin susceptibility were noted for P. aeruginosa and P. mirabilis isolates, respectively, when revised breakpoints were applied. E. coli isolates from the Western region and P. mirabilis isolates from the Southeastern region demonstrated significant shifts toward decreased fluoroquinolone susceptibility upon application of revised breakpoints. Northern region P. mirabilis isolates exhibited consistently decreased fluoroquinolone susceptibility.Conclusions: Fluoroquinolone resistance has been underreported in Wisconsin as a whole, yet geographic variability continues to exist. Targeted annual surveillance is important to identify and monitor resistance trending. Compilations of SWOTARE surveillance data can be utilized to predict the impact of future CLSI interpretive breakpoint revisions in Wisconsin.

Is clinical primary care surveillance for tularaemia a useful addition to laboratory surveillance? An analysis of notification data for Finland, 2013 to 2019.

BackgroundIn Finland, surveillance of tularaemia relies on laboratory-confirmed case notifications to the National infectious Diseases Register (NIDR).AimThe aim of the study was to assess the suitability and usefulness of clinical surveillance as an addition to laboratory notification to improve tularaemia surveillance in Finland.MethodsWe retrieved NIDR tularaemia surveillance and primary healthcare data on clinically diagnosed tularaemia cases in Finland between 2013 and 2019. We compared incidences, demographic distributions and seasonal trends between the two data sources.ResultsThe median annual incidence was 0.6 (range: 0.1–12.7) and 0.8 (range: 0.6–7.2) per 100,000 for NIDR notifications and primary healthcare notifications, respectively. Cases reported to NIDR were slightly older than cases reported to primary healthcare (median: 53 years vs 50 years, p = 0.04), but had similar sex distribution. Seasonal peaks differed between systems, both in magnitude and in timing. On average, primary healthcare notifications peaked 3 weeks before NIDR. However, peaks in NIDR were more pronounced, for example in 2017, monthly incidence per 100,000 of NIDR notifications peaked at 12.7 cases in September, while primary healthcare notifications peaked at 7.2 (1.8 ratio) in August.ConclusionsClinically diagnosed cases provide a valuable additional data source for surveillance of tularaemia in Finland. A primary healthcare-based system would allow for earlier detection of increasing incidences and thereby for early warning of outbreaks. This is crucial in order to implement targeted control and prevention measures as early as possible.

Low Neutralizing Antibody Titers against the Mu Variant of SARS-CoV-2 in 31 BNT162b2 Vaccinated Individuals in Colombia.

Global surveillance programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are showing the emergence of variants with mutations in the spike protein. Genomic and laboratory surveillance are important to determine if these variants may be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated: Mu, a variant of interest; Gamma, a variant of concern; B.1.111, which lacks genetic markers associated with greater virulence. Microneutralization assays were performed by incubating 120 mean tissue culture infectious doses (TCID50) of each SARS-CoV-2 isolate with five two-fold serial dilutions of sera from 31 BNT162b2-vaccinated volunteers. The mean neutralization titer (MN50) was calculated by the Reed–Muench method. At the end of August, Mu represented 49% of coronavirus disease 2019 (COVID-19) cases in Colombia, followed by 25% of Gamma. In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162b2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. This study shows the importance of continuing surveillance programs of emerging variants, as well as the need to evaluate the neutralizing antibody response induced by other vaccines.

Epidemiological and Molecular-Genetic Characteristics of the Measles Outbreak in Kazakhstan

Introduction: Genetic characterization of measles viruses (MVs) is an important component of laboratory surveillance of measles. In this study, a phylogenetic analysis was performed of the nucleoprotein gene sequences isolated in the Republic of Kazakhstan in 2018 year. Objective: To study the epidemiological characteristics of measles and identify the circulating strain in the Republic of Kazakhstan during the period of increasing incidence for 36 global efforts to eliminate measles among the population. Material and Methods: On the basis of the reference laboratory “Center for Sanitary and Epidemiological Expertise and Monitoring” of the RSE at the PEM “NCPH” genotyping of measles virus isolated from biological material (urine) from laboratory-confirmed cases was performed. Results: According to the results of the study, it was revealed that the genotypes of the measles virus circulating in the Republic of Kazakhstan belong to two genotypes, the majority of samples (n=16) belonged to the D8genotype and2 samplesto the B3 genotype/MVi/Harare.ZWE/38.09./.

Detection and control of an ongoing international outbreak of hepatitis A among the Irish Traveller community beginning September 2020.

Abstract Hepatitis A virus (HAV) infection is a notifiable disease in Ireland, with national coverage of clinical and laboratory surveillance. In December 2020, a cluster of 11 HAV cases among the Irish Traveller community was detected. The outbreak investigation identified 61 total HAV cases from September 2020 to November 2021. Sequenced isolates were sub-genotype IA with identical genome sequence. Case-patients were predominantly aged under 18 (77%), hospitalised (46%) and lived on communal residential sites. Mass onsite HAV vaccination was employed following failure of initial ring vaccination to contain the outbreak. This is the largest outbreak of HAV described in Ireland, involving spillover to the UK and Netherlands. We recommend mass HAV vaccination and tailored communication for outbreak control in migratory subpopulations.

Co-Localization of Sampling and Sequencing for Zoonotic Pathogen Identification in the Field Monitoring Using Mobile Laboratories.

IntroductionAccurate etiological detection is needed to evaluate the risk of zoonotic diseases. Metagenomic next-generation sequencing (mNGS) can be used to monitor pathogens in animal species and identify potential zoonotic threats. The current sampling model for zoonotic pathogen monitoring in wild animals requires samples to be transferred from the field to a laboratory for further detection.MethodsWe constructed a zoonotic pathogen survey model using a set of mobile laboratories.ResultsThe monitoring in this study was preplanned to detect Yersinia pestis, but the mNGS unexpectedly identified Bartonella spp. in the rodent samples, thus exposing the threat of bartonellosis to humans in this region. The co-localization of sampling and sequencing (CLOSS) model we tested required no long-distance transferring of samples and expands the regional coverage of zoonotic surveys by using a mobile laboratory. DiscussionUsing this mNGS technique will enable detection of more zoonotic pathogens beyond the preplanned monitoring targets. This may increase the surveillance efficiency compared with that of the previous workflow and expand the application of the mobile laboratories for infectious diseases identification and surveillance in the field.

The Epidemiology of Respiratory Syncytial Virus in Children Under Five Years-Old During the COVID-19 Pandemic Measured by Laboratory, Clinical and Syndromic Surveillance in England: A Retrospective Observational Study Including the 2020/21 Winter Season

The Epidemiology of Respiratory Syncytial Virus in Children Under Five Years-Old During the COVID-19 Pandemic Measured by Laboratory, Clinical and Syndromic Surveillance in England: A Retrospective Observational Study Including the 2020/21 Winter Season

Effects of Non-Pharmacological Interventions on Respiratory Viruses Other Than SARS-CoV-2: Analysis of Laboratory Surveillance and Literature Review From 2018 to 2021.

BackgroundSince the global coronavirus disease 2019 (COVID-19) pandemic, non-pharmacological interventions (NPIs) such as extensive and comprehensive hand hygiene, mask-wearing, and social distancing have been implemented globally. This study aimed to investigate changes in respiratory viruses other than severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that occurred following the implementation of these NPIs.MethodsFrom January 2018 to December 2021, influenza-like illness patient specimens and specimens from the Korea Influenza and Respiratory Viruses Surveillance System were analyzed at the Incheon Metropolitan City Institute of Public Health and Environment. Oropharyngeal or nasopharyngeal swab samples from respiratory infection patients were transferred in a virus transport medium at 4°C. After RNA or DNA extraction, respiratory virus-specific genes for human influenza virus (IFV), adenovirus (ADV), parainfluenza virus (PIV), respiratory syncytial virus (RSV), human rhinovirus (hRV), human coronavirus, human bocavirus, and human metapneumovirus were detected by individual real-time reverse transcription polymerase chain reaction.ResultsA total 3,334 samples were collected. After NPI was implemented, the detection of respiratory viruses other than SARS-CoV-2 decreased overall. The yearly detection rate of respiratory viruses was decreased from 69.5% (399/574) in 2018 and 73.3% (505/689) in 2019 to 19.8% (206/1,043) in 2020 and 34.9% (365/1,028) in 2021. The epidemic was more prominent in respiratory viruses such as IFV and RSV, which were considered dominant viruses, especially those with viral envelopes. Among viruses that were not considered dominant, hRV showed no clear change before and after NPI, while PIV showed a rapid increase compared to the existing dominant viruses between October–December 2021, after the increase in the number of gatherings started at the end of September and the “Relaxing COVID19 and mitigation policy,” which was implemented on November 1.ConclusionNPI seems to have influenced the isolation and transmission of respiratory viruses in South Korea. In the future, additional studies focusing on the isolation and transmission patterns of respiratory viruses following NPI are needed.

An outbreak of hepatitis A associated with salted clams in Busan, Korea.

OBJECTIVESIn July 2019, there were multiple reports on patients with hepatitis A among the visitors of a restaurant in Busan. The current study presents the results of an epidemiological investigation and outlines the supplementary measures that would help with hepatitis A control.METHODSA cohort study was conducted for all 2,865 customers who visited restaurant A from June to July. Using a standardized questionnaire, participants reported the presence of hepatitis A symptoms and whether they had consumed any of 19 food items. As for participants who had visited public health centers, their specimens were collected.RESULTSFrom the study cohort, 155 participants (5.4%) had confirmed hepatitis A. The epidemic curve was unimodal, and the median number of days from the restaurant visit to symptom onset was 31 days. A genotype analysis indicated that 89 of 90 tested patients had hepatitis A virus (HAV) genotype 1A. The results of a multivariate logistic regression analysis indicated that the ingestion of salted clams increased the risk of hepatitis A by 68.12 times (95% confidence interval [CI], 9.22 to 510.87). In an unopened package of salted clams found and secured through traceback investigation, HAV genotype 1A was detected.CONCLUSIONSTo prevent people from ingesting uncooked clams, there needs to be more efforts to publicize the dangers of uncooked clams; the food sampling test standards for salted clams should also be expanded. Furthermore, a laboratory surveillance system based on molecular genetics should be established to detect outbreaks earlier.

Real-time laboratory surveillance of Dengue antigen(NS1) - Best proposed early warning and response system for Dengue in Sri Lanka? - Results from a pilot study.

During the recent past, dengue fever and associated complications have been the most important concern for health policy makers of Sri Lanka. The current notification system has considerable inevitable delays in preventive measures. Implementing a laboratory-based real-time antigen (NS1) surveillance system for notification coupled with a rapid preventive response within the Colombo district as a pilot project and compares the notifications with existing national surveillance systems. An online notification platform was established with a centralized database. Seven main laboratories of the private sector linked with the notification system, where they can create new notifications at the central database, whenever the NS1 test detected as positive. Relevant Medical Officers of Health should update action implemented to complete the response process. A dashboard was designed to visualize each notification and its status with a predefined colour code. Patients from 14 Medical Officer of Health (MOH) areas out of 15 were captured. The immediate preventive response was recorded from the field preventive staff for 90% of the reporting. All most all attended patients have given health advice on awareness, prevention, and source reduction through premise inspection by trained field staff with 24hrs of notification. Salient features of the novel system are notification of antigen-positive patients, the rapidity of notification (real-time) and response, user-friendliness, access to multiple stakeholders simultaneously without data duplication, early involvement of the field staff, the ability to trace the cases using checklists and a color-coding system from a dashboard.

Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study

The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.

Enhancing Response to Foodborne Disease Outbreaks: Findings of the Foodborne Diseases Centers for Outbreak Response Enhancement (FoodCORE), 2010-2019.

Each year, foodborne diseases cause an estimated 48 million illnesses resulting in 128000 hospitalizations and 3000 deaths in the United States. Fast and effective outbreak investigations are needed to identify and remove contaminated food from the market to reduce the number of additional illnesses that occur. Many state and local health departments have insufficient resources to identify, respond to, and control the increasing burden of foodborne illnesses. The Centers for Disease Control and Prevention (CDC) Foodborne Diseases Centers for Outbreak Response Enhancement (FoodCORE) program provides targeted resources to state and local health departments to improve completeness and timeliness of laboratory, epidemiology, and environmental health activities for foodborne disease surveillance and outbreak response. In 2009, pilot FoodCORE centers were selected through a competitive application process and then implemented work plans to achieve faster and more complete surveillance and outbreak response activities in their jurisdiction. By 2019, 10 centers participated in FoodCORE: Colorado, Connecticut, Minnesota, New York City, Ohio, Oregon, South Carolina, Tennessee, Utah, and Wisconsin. CDC and FoodCORE centers collaboratively developed performance metrics to evaluate the impact and effectiveness of FoodCORE activities. Centers used performance metrics to document successes, identify gaps, and set goals for their jurisdiction. CDC used performance metrics to evaluate the implementation of FoodCORE priorities and identify successful strategies to develop replicable model practices. This report provides a description of implementing the FoodCORE program during year 1 (October 2010 to September 2011) through year 9 (January 2019 to December 2019). FoodCORE centers address gaps in foodborne disease response through enhanced capacity to improve timeliness and completeness of surveillance and outbreak response activities. Strategies resulting in faster, more complete surveillance and response are documented as model practices and are shared with state and local foodborne disease programs across the country.