An Overview of Foodborne Sample-Initiated Retrospective Outbreak Investigations and Interagency Collaboration in the United States.

Foodborne outbreak investigations have traditionally included the detection of a cluster of illnesses first, followed by an epidemiologic investigation to identify a food of interest. The increasing use of whole genome sequencing (WGS) subtyping technology for clinical, environmental, and food isolates of foodborne pathogens, and the ability to share and compare the data on public platforms, present new opportunities to identify earlier links between illnesses and their potential sources. We describe a process called sample-initiated retrospective outbreak investigations (SIROIs) used by federal public health and regulatory partners in the United States. SIROIs begin with an evaluation of the genomic similarity between bacterial isolates recovered from food or environmental samples and clusters of clinical isolates while subsequent and parallel epidemiologic and traceback investigations are initiated to corroborate their connection. SIROIs allow for earlier hypothesis generation, followed by targeted collection of information about food exposures and the foods and manufacturer of interest, to confirm a link between the illnesses and their source. This often leads to earlier action that could reduce the breadth and burden of foodborne illness outbreaks. We describe two case studies of recent SIROIs and present the benefits and challenges. Benefits include insight into foodborne illness attribution, international collaboration, and opportunities for enhanced food safety efforts in the food industry. Challenges include resource intensiveness, variability of epidemiologic and traceback data, and an increasingly complex food supply chain. SIROIs are valuable in identifying connections among small numbers of illnesses that may span significant time periods; detecting early signals for larger outbreaks or food safety issues associated with manufacturers; improving our understanding of the scope of contamination of foods; and identifying novel pathogen/commodity pairs.

ASL Phonological Fluency: How Do Deaf Signers Retrieve and Produce Signs?

Researchers have focused on how deaf signing children acquire and use American Sign Language (ASL). One sub-skill of ASL proficiency is ASL phonology. This includes the ability to isolate and manipulate parameters within signs (i.e., handshape, location, and movement). Expressively, signed language phonological fluency tasks have investigated signers' abilities to produce signs given handshape constraints. We expanded the handshape task with the addition of sign production for two given locations with deaf adults and students. We also investigated how adjacent signs were recalled and produced within semantic and phonological clusters. Deaf adults frequently recalled signs with semantic connections and shared location. Students did the same, although shared handshape also facilitated their sign production. Finally, we present implications for ASL instruction with deaf students.

Four American Sign Language Learner Groups: Are They Really Different?

We investigated the receptive American Sign Language (ASL) skills of four separate groups using the 42-item ASL-Receptive Skills Test: Deaf high school-aged students who attended a residential school; deaf incoming college students who preferred signed language; deaf incoming college students who preferred spoken language; and typically hearing college-aged second language-second modality learners (M2L2) of ASL. Many deaf students learn ASL as a delayed first language due to a lack of sign language models within their home environments. In contrast, M2L2 students likely engage in some transfer between their first (spoken) and second (signed) language when learning ASL. All four groups scored similarly overall on the ASL-RST (~77% correct), and all four groups scored the lowest for number-distribution, spatial verbs location, size-and-shape-specifiers, and role shift. We present instructional implications that include incorporation of ASL standards and evidence-based instructional strategies for all four groups.

Use of Whole Genome Sequencing by the Federal Interagency Collaboration for Genomics for Food and Feed Safety in the United States.

ABSTRACT: This multiagency report developed by the Interagency Collaboration for Genomics for Food and Feed Safety provides an overview of the use of and transition to whole genome sequencing (WGS) technology for detection and characterization of pathogens transmitted commonly by food and for identification of their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among the following federal agencies: National Institutes of Health; Department of Health and Human Services, Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration (FDA); and the U.S. Department of Agriculture, Food Safety and Inspection Service, Agricultural Research Service, and Animal and Plant Health Inspection Service. We describe single nucleotide polymorphism, core-genome, and whole genome multilocus sequence typing data analysis methods as used in the PulseNet (CDC) and GenomeTrakr (FDA) networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Interagency Collaboration partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles) and source attribution efforts and increase transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information. We also highlight the impact of current trends in the use of culture-independent diagnostic tests for human diagnostic testing on analytical approaches related to food safety and what is next for the use of WGS in the area of food safety.

Interpretative Labor and the Bane of Nonstandardized Metadata in Public Health Surveillance and Food Safety.

Open-source DNA sequence databases have long been touted as beneficial to public health, including the facilitation of earlier detection and response to infectious disease outbreaks. Of critical importance to harnessing these benefits is the metadata that describe general and other domain-specific attributes (eg, collection location, isolate type) of a sample. Unlike the sequence data, metadata are often incomplete and lack adherence to an international standard. Here, we describe the problem posed by such variable and incomplete metadata in terms of interpretative labor costs (the time and energy necessary to make sense of the signal in the genetic data) and the impact such metadata have on foodborne outbreak detection and response. Improving the quality of sequence-associated metadata would allow for earlier detection of emerging food safety hazards and allow faster response to foodborne outbreaks.

Goodnight Gorilla: Deaf Student American Sign Language Narrative Renditions After Viewing a Model.

The present study used an observational learning framework to investigate changes in non-native signing deaf children's narrative renditions before (Time 1) and after (Time 2) a single viewing of a signing adult's rendition of the same story. The deaf adult model rendered the picture book Goodnight Gorilla in American Sign Language (ASL) with the pages of the book displayed behind her. We analyzed the details children aged 6-13 years included within their narratives and how they rendered those details. Specifically, we compared their use of depicting constructions (DCs), constructed action (CA), simultaneous use of both DCs and CA, and only lexical signs before and after viewing the model. The deaf adult predominantly and equally used CA and constructed actin paired with DCs and rarely used lexical signs alone during her rendition. After watching the adult rendition, children's renditions were longer and they included more details. Children increased their use of DCs, CA, and to a lesser extent, combinations of DCs and CA. However, half of the children never used DCs paired with CA. Suggestions for pairing ASL content standards with viewings of deaf adult sign language models are discussed.

Partnering with Local Hospitals and Public Health to Manage COVID-19 Outbreaks in Nursing Homes.

BACKGROUND/OBJECTIVES: Almost half of deaths related to COVID-19 in the United States are linked to nursing homes (NHs). We describe among short-term and long-term residents at three NHs in Michigan the outbreak identification process, universal testing, point prevalence of COVID-19, and subsequent containment efforts, outcomes, and challenges. DESIGN: Outbreak investigation. SETTING: Three NHs in southeast Michigan. PARTICIPANTS: All residents (N = 215) at three NHs (total beds = 356) affiliated with a large academic healthcare system. METHODS: Upon detection of confirmed cases within the facility, each NH in collaboration and consultation with local hospital, public health officials, and parent corporation implemented immediate facility-wide testing and the following intervention measures: cohorting of COVID-19 positive residents; communication regarding testing and results with residents, healthcare professionals, and families; personal protective equipment reeducation and use throughout facilities; and dedicated staffing for infected patients cohorted in a dedicated COVID-19 wing. We collected patient data regarding demographics, symptoms, comorbidities, hospitalization, and 14-day outcomes. RESULTS: A total of 29 cases of COVID-19 were identified at three participating NHs. Nineteen cases of COVID-19 were identified through symptom-triggered testing from March 23 to April 23, 2020; 10 (4.7%) additional cases were identified through universal testing of 215 residents conducted from April 7 to 15, 2020. The hospitalization rate was 37.9%. The case fatality rate was 20.7% (6/29); these patients had multiple comorbidities. No residents who tested positive through the point-prevalence survey required hospitalization, and five were discharged home within 14 days. CONCLUSION: Proactive and coordinated steps between NH medical directors and administrators, referral hospitals including their laboratories, and local public health officials are necessary to rapidly respond to an outbreak and limit the transmission of COVID-19. This coordinated public health approach may save lives, minimize the burden to the healthcare system, and reduce healthcare costs.

Multistate Outbreak of Listeriosis Associated with Packaged Leafy Green Salads, United States and Canada, 2015-2016.

We investigated an outbreak of listeriosis detected by whole-genome multilocus sequence typing and associated with packaged leafy green salads. Nineteen cases were identified in the United States during July 5, 2015-January 31, 2016; isolates from case-patients were closely related (median difference 3 alleles, range 0-16 alleles). Of 16 case-patients interviewed, all reported salad consumption. Of 9 case-patients who recalled brand information, all reported brands processed at a common US facility. The Public Health Agency of Canada simultaneously investigated 14 cases of listeriosis associated with this outbreak. Isolates from the processing facility, packaged leafy green salads, and 9 case-patients from Canada were closely related to US clinical isolates (median difference 3 alleles, range 0-16 alleles). This investigation led to a recall of packaged leafy green salads made at the processing facility. Additional research is needed to identify best practices and effective policies to reduce the likelihood of Listeria monocytogenes contamination of fresh produce.

Shiga Toxin-Producing E. coli Infections Associated with Flour.

BACKGROUND: In 2016, a multijurisdictional team investigated an outbreak of Shiga toxin-producing Escherichia coli (STEC) serogroup O121 and O26 infections linked to contaminated flour from a large domestic producer. METHODS: A case was defined as infection with an outbreak strain in which illness onset was between December 21, 2015, and September 5, 2016. To identify exposures associated with the outbreak, outbreak cases were compared with non-STEC enteric illness cases, matched according to age group, sex, and state of residence. Products suspected to be related to the outbreak were collected for STEC testing, and a common point of contamination was sought. Whole-genome sequencing was performed on isolates from clinical and food samples. RESULTS: A total of 56 cases were identified in 24 states. Univariable exact conditional logistic-regression models of 22 matched sets showed that infection was significantly associated with the use of one brand of flour (odds ratio, 21.04; 95% confidence interval [CI], 4.69 to 94.37) and with tasting unbaked homemade dough or batter (odds ratio, 36.02; 95% CI, 4.63 to 280.17). Laboratory testing isolated the outbreak strains from flour samples, and whole-genome sequencing revealed that the isolates from clinical and food samples were closely related to one another genetically. Trace-back investigation identified a common flour-production facility. CONCLUSIONS: This investigation implicated raw flour as the source of an outbreak of STEC infections. Although it is a low-moisture food, raw flour can be a vehicle for foodborne pathogens.

Notes from the Field: Outbreak of Listeriosis Associated with Consumption of Packaged Salad - United States and Canada, 2015-2016.

In September 2015, PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified a cluster of Listeria monocytogenes (Listeria) clinical isolates indistinguishable by two-enzyme pulsed-field gel electrophoresis (PFGE) pattern combination and highly related by whole-genome multilocus sequence typing (wgMLST). A case was defined as isolation of Listeria with the outbreak PFGE pattern and highly related by wgMLST with an isolation date on or after July 5, 2015, the isolate date of the earliest case in this cluster.

Loperamide-Related Deaths in North Carolina.

Loperamide (Imodium®) has been accepted as a safe, effective, over-the-counter anti-diarrheal drug with low potential for abuse. It is a synthetic opioid that lacks central nervous system activity at prescribed doses, rendering it ineffective for abuse. Since 2012, however, the North Carolina Office of the Chief Medical Examiner has seen cases involving loperamide at supratherapeutic levels that indicate abuse. The recommended dose associated with loperamide should not exceed 16 mg per day, although users seeking an opioid-like high reportedly take it in excess of 100 mg per dose. When taken as directed, the laboratory organic base extraction screening method with gas chromatography-mass spectrometry/nitrogen phosphorus detector lacks the sensitivity to detect loperamide. When taken in excess, the screening method identifies loperamide followed by a separate technique to confirm and quantify the drug by liquid chromatography-tandem mass spectrometry. Of the 21 cases involving loperamide, the pathologist implicated the drug as either additive or primary to the cause of death in 19 cases. The mean and median peripheral blood concentrations for the drug overdose cases were 0.27 and 0.23 mg/L, respectively. Furthermore, an extensive review of the pharmacology associated with loperamide and its interaction with P-glycoprotein will be examined as it relates to the mechanism of toxicity.

Implementation of Nationwide Real-time Whole-genome Sequencing to Enhance Listeriosis Outbreak Detection and Investigation.

Listeria monocytogenes (Lm) causes severe foodborne illness (listeriosis). Previous molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE), were critical in detecting outbreaks that led to food safety improvements and declining incidence, but PFGE provides limited genetic resolution. A multiagency collaboration began performing real-time, whole-genome sequencing (WGS) on all US Lm isolates from patients, food, and the environment in September 2013, posting sequencing data into a public repository. Compared with the year before the project began, WGS, combined with epidemiologic and product trace-back data, detected more listeriosis clusters and solved more outbreaks (2 outbreaks in pre-WGS year, 5 in WGS year 1, and 9 in year 2). Whole-genome multilocus sequence typing and single nucleotide polymorphism analyses provided equivalent phylogenetic relationships relevant to investigations; results were most useful when interpreted in context of epidemiological data. WGS has transformed listeriosis outbreak surveillance and is being implemented for other foodborne pathogens.

Laboratory, Environmental, and Epidemiologic Investigation and Regulatory Enforcement Actions in Response to an Outbreak of Salmonella Bredeney Infections Linked to Peanut Butter.

Background. In September 2012, the Centers for Disease Control and Prevention (CDC), U.S. Food and Drug Administration (FDA), and state and local partners investigated an outbreak of Salmonella enterica serovar Bredeney linked to peanut butter (PB). Methods. A case was defined as infection with the outbreak strain of Salmonella Bredeney between June 1, 2012 and October 31, 2012. Food exposure questionnaires were analyzed by the CDC to determine the food vehicle. The FDA reviewed production information from Retail Chain A's sole supplier of PB, Company A. The PB samples collected from case-patients and Company A were tested for Salmonella. Results. Forty-two case-patients from 20 states were identified. Of 33 case-patients from whom food exposure information was obtained, 25 (76%) shopped at Retail Chain A and 25 (100%) purchased Company A PB. Three state health departments isolated the outbreak strain from opened jars of PB collected from case-patients. The FDA investigators identified multiple deficiencies in current Good Manufacturing Practices (cGMPs) in Company A's manufacturing facility and determined that internal controls were insufficient to prevent shipment of contaminated product. The FDA isolated the outbreak strain of Salmonella Bredeney from implicated product collected at the firm and the environment of the firm's food production facility. Conclusions. Timely laboratory, investigational, and epidemiologic data led to the voluntary recall of PB by Company A. The FDA suspended Company A's food facility registration, prohibiting the firm from introducing food into interstate commerce. This outbreak underscores the need for effective preventive controls, including robust internal environmental monitoring programs, appropriate action in response to contamination findings, and an improved understanding of food safety at the managerial and corporate levels.

Outbreak of hepatitis A in the USA associated with frozen pomegranate arils imported from Turkey: an epidemiological case study.

BACKGROUND: In May, 2013, an outbreak of symptomatic hepatitis A virus infections occurred in the USA. Federal, state, and local public health officials investigated the cause of the outbreak and instituted actions to control its spread. We investigated the source of the outbreak and assessed the public health measures used. METHODS: We interviewed patients, obtained their shopping information, and did genetic analysis of hepatitis A virus recovered from patients' serum and stool samples. We tested products for the virus and traced supply chains. FINDINGS: Of 165 patients identified from ten states, 69 (42%) were admitted to hospital, two developed fulminant hepatitis, and one needed a liver transplant; none died. Illness onset occurred from March 31 to Aug 12, 2013. The median age of patients was 47 years (IQR 35-58) and 91 (55%) were women. 153 patients (93%) reported consuming product B from retailer A. 40 patients (24%) had product B in their freezers, and 113 (68%) bought it according to data from retailer A. Hepatitis A virus genotype IB, uncommon in the Americas, was recovered from specimens from 117 people with hepatitis A virus illness. Pomegranate arils that were imported from Turkey--where genotype IB is common--were identified in product B. No hepatitis A virus was detected in product B. INTERPRETATION: Imported frozen pomegranate arils were identified as the vehicle early in the investigation by combining epidemiology--with data from several sources--genetic analysis of patient samples, and product tracing. Product B was removed from store shelves, the public were warned not to eat product B, product recalls took place, and postexposure prophylaxis with both hepatitis A virus vaccine and immunoglobulin was provided. Our findings show that modern public health actions can help rapidly detect and control hepatitis A virus illness caused by imported food. Our findings show that postexposure prophylaxis can successfully prevent hepatitis A illness when a specific product is identified. Imported food products combined with waning immunity in some adult populations might make this type of intervention necessary in the future. FUNDING: US Centers for Disease Control and Prevention, US Food and Drug Administration, and US state and local public health departments.

Notes from the field: multistate outbreak of listeriosis linked to soft-ripened cheese--United States, 2013.

On June 27, 2013, the Minnesota Department of Health notified CDC of two patients with invasive Listeria monocytogenes infections (listeriosis) whose clinical isolates had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. A query of PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified clinical and environmental isolates from other states. On June 28, CDC learned from the Food and Drug Administration's Coordinated Outbreak Response and Evaluation Network that environmental isolates indistinguishable from those of the two patients had been collected from Crave Brothers Farmstead Cheese during 2010-2011. An outbreak-related case was defined as isolation of L. monocytogenes with the outbreak PFGE pattern from an anatomic site that is normally sterile (e.g., blood or cerebrospinal fluid), or from a product of conception, with an isolate upload date during May 20-June 28, 2013. As of June 28, five cases were identified in four states (Minnesota, two cases; Illinois, Indiana, and Ohio, one each). Median age of the five patients was 58 years (range: 31-67 years). Four patients were female, including one who was pregnant at the time of infection. All five were hospitalized. One death and one miscarriage were reported.

Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS.

We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. All macaques were primed with DNA plasmids expressing SIV gag, pol, env, and Retanef genes and were boosted with recombinant modified vaccinia Ankara virus (MVA) expressing the same genes, either once (1 × MVA) or twice (2 × MVA), or were boosted once with MVA followed by a single boost with replication-competent adenovirus (Ad) type 5 host range mutant (Ad5 h) expressing SIV gag and nef genes but not Retanef or env (1 × MVA/Ad5). While two of the vaccine regimens (1 × MVA and 1 × MVA/Ad5) protected from high levels of SIV replication only during the acute phase of infection, the 2 × MVA regimen, with the highest anti-SIV gp120 titers, protected during the acute phase and transiently during the chronic phase of infection. Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses.

More than just a simple swish and spit: implementation of oral care best practice in clinical neurosciences.

Suboptimal oral care is well documented in the literature and is linked to increased nosocomial pneumonia rates and prolonged hospitalization, negatively affecting patients' quality of life (Terezakis et al. 2011). A standardized approach to oral care can change these adverse outcomes. This project used best practice guidelines and evidence in the literature to guide the development of oral care best practice within an acute care inpatient unit. Based on the work of the interprofessional Clinical Neurological Sciences (CNS) Continuous Quality Improvement (CQI) Council at London Health Sciences Centre-University Hospital (LHSC-UH), an oral care policy and bedside assessment tool were implemented in line with Stroke Best Practice Recommendations (Heart and Stroke Foundation of Canada 2010). A validated, reliable and feasible oral health assessment tool (OHAT) was selected for implementation, and is now completed on every patient within 24 hours of admission to the CNS inpatient unit. Favourable outcomes to date include improved accessibility of oral health supplies, including regular and suction toothbrushes, toothpaste and bite blocks. Post-implementation audits indicate increased frequency and quality of oral care. This review provides a synopsis of how oral care best practice was implemented in an acute care neurology/neurosurgery setting.

Late onset necrotizing enterocolitis in infants following use of a xanthan gum-containing thickening agent.

Adverse event reports submitted to the US Food and Drug Administration suggested a possible association between necrotizing enterocolitis and ingestion of a commercial feed thickener by premature infants. Review in 2011 of 22 cases with exposure revealed a distinct illness pattern.