In 2022, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), U.S. state and local partners, the Public Health Agency of Canada (PHAC), and the Canadian Food Inspection Agency (CFIA), conducted a bi-national sample-initiated retrospective outbreak investigation (SIROI) of Listeria monocytogenes illnesses linked to enoki mushrooms. The FDA and CDC investigated the first known L. monocytogenes outbreak linked to enoki mushrooms from 2016-2020, making the 2022 outbreak the second time this pathogen-commodity pair was investigated by FDA and CDC. The 2022 outbreak included six ill people, all of whom were hospitalized. Epidemiologic, laboratory, and traceback evidence led to multiple public health actions, including voluntary recalls by firms, public communications about the outbreak, and FDA's country-wide Import Alert for enoki mushrooms from China. This SIROI illustrates the importance of surveillance sampling, national and international coordination of efforts, and rapid information sharing to identify and stop foodborne outbreaks on a global scale. To reduce the risk of listeriosis illnesses linked to contaminated enoki mushrooms, public health and regulatory agencies in the United States and Canada remain committed to conducting comprehensive surveillance for Listeria in foods and in people, efficiently investigating identified outbreaks, and implementing control measures to potentially minimize the impact of future outbreaks.

Antimicrobial resistance (AR) spread is a worldwide health challenge, stemming in large part, from the ability of microbes to share their genetic material through horizontal gene transfer (HGT). Overuse and misuse of antibiotics in clinical settings and in food production have been linked to this increased prevalence and spread of AR. Consequently, public health and consumer concerns have resulted in a remarkable recent reduction in antibiotics used for food animal production. This is driven by the assumption that removing this selective pressure will favor the recovery of antibiotic susceptible taxa and will limit AR sharing through HGT, allowing the currently available antibiotic arsenal to be effective for a longer period. In this study we used broiler chicks raised antibiotic-free and Salmonella enterica serovar Heidelberg (SH), as a model food pathogen, to test this hypothesis. Our results show that neonatal broiler chicks challenged with an antibiotic susceptible SH strain and raised without antibiotics carried susceptible and multidrug resistance SH strains 14 days after challenge. SH infection perturbed the microbiota of broiler chicks and gavaged chicks acquired antibiotic resistant SH at a higher rate. We determined that the acquisition of a plasmid from commensal Escherichia coli population conferred multidrug resistance phenotype to SH recipients and carriage of this plasmid increased the fitness of SH under acidic selection pressure. These results suggest that HGT of AR shaped the evolution of SH and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria to Salmonella.Importance The reported increase in antibiotic resistant bacteria in humans have resulted in a major shift away from antibiotics use in food animal production. This has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, and this in turn will allow the currently available antibiotic arsenal to be more effective. This shift in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic susceptible Salmonella Heidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggests that simply removing antibiotics from food-animal production might not be sufficient to limit the spread of antimicrobial resistance.Competing Interest StatementThe authors have declared no competing interest.

As of August 2022, clusters of acute severe hepatitis of unknown etiology in children have been reported from 35 countries, including the United States(1,2). Previous studies have found human adenoviruses (HAdVs) in the blood from cases in Europe and the United States(3-7), although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment based sequencing, and agnostic metagenomic sequencing to analyze samples from 16 HAdV-positive cases from October 1, 2021 to May 22, 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P<0.001) and to 0 of 30 patients with hepatitis of defined etiology (P<0.001). In controls, HAdV-41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P<0.001). Co-infections by Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and/or enterovirus A71 (EV-A71) were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P<0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses.

The National Center for Health Statistics (NCHS) disseminates information on a broad range of health topics through diverse publications. These publications must rely on clear and transparent presentation standards that can be broadly and efficiently applied. Standards are particularly important for large, cross-cutting reports where estimates cannot be individually evaluated and indicators of precision cannot be included alongside the estimates. This report describes the NCHS Data Presentation Standards for Proportions. The multistep NCHS Data Presentation Standards for Proportions are based on a minimum denominator sample size and on the absolute and relative widths of a confidence interval calculated using the Clopper-Pearson method. Proportions (usually multiplied by 100 and expressed as percentages) are the most commonly reported estimates in NCHS reports.

On September 1, 2022, CDC recommended an updated (bivalent) COVID-19 vaccine booster to help restore waning protection conferred by previous vaccination and broaden protection against emerging variants for persons aged ≥12 years (subsequently extended to persons aged ≥6 months).* To assess the impact of original (monovalent) COVID-19 vaccines and bivalent boosters, case and mortality rate ratios (RRs) were estimated comparing unvaccinated and vaccinated persons aged ≥12 years by overall receipt of and by time since booster vaccination (monovalent or bivalent) during Delta variant and Omicron sublineage (BA.1, BA.2, early BA.4/BA.5, and late BA.4/BA.5) predominance.(†) During the late BA.4/BA.5 period, unvaccinated persons had higher COVID-19 mortality and infection rates than persons receiving bivalent doses (mortality RR = 14.1 and infection RR = 2.8) and to a lesser extent persons vaccinated with only monovalent doses (mortality RR = 5.4 and infection RR = 2.5). Among older adults, mortality rates among unvaccinated persons were significantly higher than among those who had received a bivalent booster (65-79 years; RR = 23.7 and ≥80 years; 10.3) or a monovalent booster (65-79 years; 8.3 and ≥80 years; 4.2). In a second analysis stratified by time since booster vaccination, there was a progressive decline from the Delta period (RR = 50.7) to the early BA.4/BA.5 period (7.4) in relative COVID-19 mortality rates among unvaccinated persons compared with persons receiving who had received a monovalent booster within 2 weeks-2 months. During the early BA.4/BA.5 period, declines in relative mortality rates were observed at 6-8 (RR = 4.6), 9-11 (4.5), and ≥12 (2.5) months after receiving a monovalent booster. In contrast, bivalent boosters received during the preceding 2 weeks-2 months improved protection against death (RR = 15.2) during the late BA.4/BA.5 period. In both analyses, when compared with unvaccinated persons, persons who had received bivalent boosters were provided additional protection against death over monovalent doses or monovalent boosters. Restored protection was highest in older adults. All persons should stay up to date with COVID-19 vaccination, including receipt of a bivalent booster by eligible persons, to reduce the risk for severe COVID-19.

Using family systems theory, this longitudinal study of middle school youth examined the effects of abuse, family conflict, and sibling aggression on sexual harassment perpetration (N = 1563; M(age) 11.2, 51% boys; 39% Hispanic, 29% Black, and 19% White). Boys reported more sexual harassment than girls; perpetration increased for both. The association between a hostile home environment and sexual harassment perpetration was moderated by school experiences. School belonging buffered effects of hostile home environment on baseline sexual harassment perpetration for boys who experienced abuse and White adolescents with high sibling aggression. Academic grades moderated change in perpetration over time, but effects differed by sex and race. It is important to understand how early violence exposures relate to sexual violence perpetration during early adolescence.

OBJECTIVES: Early in the COVID-19 pandemic, several outbreaks were linked with facilities employing essential workers, such as long-term care facilities and meat and poultry processing facilities. However, timely national data on which workplace settings were experiencing COVID-19 outbreaks were unavailable through routine surveillance systems. We estimated the number of US workplace outbreaks of COVID-19 and identified the types of workplace settings in which they occurred during August-October 2021. METHODS: The Centers for Disease Control and Prevention collected data from health departments on workplace COVID-19 outbreaks from August through October 2021: the number of workplace outbreaks, by workplace setting, and the total number of cases among workers linked to these outbreaks. Health departments also reported the number of workplaces they assisted for outbreak response, COVID-19 testing, vaccine distribution, or consultation on mitigation strategies. RESULTS: Twenty-three health departments reported a total of 12 660 workplace COVID-19 outbreaks. Among the 12 470 workplace types that were documented, 35.9% (n = 4474) of outbreaks occurred in health care settings, 33.4% (n = 4170) in educational settings, and 30.7% (n = 3826) in other work settings, including non-food manufacturing, correctional facilities, social services, retail trade, and food and beverage stores. Eleven health departments that reported 3859 workplace outbreaks provided information about workplace assistance: 3090 (80.1%) instances of assistance involved consultation on COVID-19 mitigation strategies, 1912 (49.5%) involved outbreak response, 436 (11.3%) involved COVID-19 testing, and 185 (4.8%) involved COVID-19 vaccine distribution. CONCLUSIONS: These findings underscore the continued impact of COVID-19 among workers, the potential for work-related transmission, and the need to apply layered prevention strategies recommended by public health officials.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

Adolescent sexual violence (SV), which includes non-contact verbal sexual harassment (SH) and forced sexual contact (FSC), is a significant public health problem with long-term impacts on health and well-being. Understanding how sports participation is linked to SV can inform prevention efforts; however, the current literature is unclear about the nature of this association. Using data from 20 high schools, we investigate whether athletes in certain sports are at higher risk of SH and FSC perpetration than either other athletes or sports non-participants, and whether the risk is moderated by gender, dismissiveness of SV, or substance use intentions. We also utilize social network data to explore the role of relationships with peers and trusted adults to attenuate SH and FSC perpetration. Second, we incorporate characteristics of friends to further examine the role and composition of peer groups in the association between sports participation and perpetration of SH and FSC. Findings revealed a bivariate association between sport contact level and SH perpetration, but not FSC, and the association disappeared after adjusting for other covariates. Most prominently, dismissiveness of SV, intentions to use substances, and prior perpetration had the strongest association with perpetration regardless of sport contact level. Results also provided some support for the influence of peers and trusted adults in the sports context. Notably, the percentage of friends who perpetrated FSC and the percentage of friends who play a low-contact sport were positively associated with FSC perpetration, and the percentage of friends who play a high-contact sport was positively associated with SH perpetration. The paper concludes with a discussion of the sports context as an important venue for comprehensive prevention efforts, including a focus on changing norms around adolescent SV and substance use.

During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.

Sexual violence (SV) among adolescents continues to be a major public health concern with numerous consequences. Research, predominantly with male collegiate samples, has suggested an association between sports participation and SV perpetration, and has included other important risk factors such as substance use and attitudes. However, more research is needed in this area among adolescents. The current study uses latent class analysis (LCA) to examine data- driven classes of high school student athletes (N = 665) engaged in three risk factor areas for SV: sport contact level, likelihood of substance use, and attitudes dismissive of SV. Once classes were enumerated and fit separately for male and female samples, pairwise comparisons were conducted on scores on two forms of SV (perpetration of sexual harassment and unwanted sexual contact) as a function of class membership. A 5-class solution was retained for both males and females. In the female sample, regarding SV-harassment, those most likely to perpetrate sexual harassment were those characterized by high likelihood of use of cigarettes, marijuana, alcohol, vape products, and those who played any type of sport. Too few females endorsed perpetration of unwanted sexual contact for pairwise comparisons to be conducted. For males, the classes most likely to perpetrate both forms of SV were those who were likely to endorse high likelihood to use of cigarettes, marijuana, alcohol, vape products, endorse attitudes dismissive of SV, and play any type of sport but especially high contact sports. These findings implicate high school athletic spaces as important venues for sexual violence prevention efforts.

The overuse and misuse of antibiotics in clinical settings and in food production have been linked to the increased prevalence and spread of antimicrobial resistance (AR). Consequently, public health and consumer concerns have resulted in a remarkable reduction in antibiotics used for food animal production. However, there are no data on the effectiveness of antibiotic removal in reducing AR shared through horizontal gene transfer (HGT). In this study, we used neonatal broiler chicks and Salmonella enterica serovar Heidelberg, a model food pathogen, to test if chicks raised antibiotic free harbor transferable AR. We challenged chicks with an antibiotic-susceptible S. Heidelberg strain using various routes of inoculation and determined if S. Heidelberg isolates recovered carried plasmids conferring AR. We used antimicrobial susceptibility testing and whole-genome sequencing (WGS) to show that chicks grown without antibiotics harbored an antimicrobial resistant S. Heidelberg population at 14 days after challenge and chicks challenged orally acquired AR at a higher rate than chicks inoculated via the cloaca. Using 16S rRNA gene sequencing, we found that S. Heidelberg infection perturbed the microbiota of broiler chicks, and we used metagenomics and WGS to confirm that a commensal Escherichia coli population was the main reservoir of an IncI1 plasmid acquired by S. Heidelberg. The carriage of this IncI1 plasmid posed no fitness cost to S. Heidelberg but increased its fitness when exposed to acidic pH in vitro. These results suggest that HGT of plasmids carrying AR shaped the evolution of S. Heidelberg and that antibiotic use reduction alone is insufficient to limit antibiotic resistance transfer from commensal bacteria to Salmonella enterica. IMPORTANCE The reported increase in antibiotic-resistant bacteria in humans has resulted in a major shift away from antibiotic use in food animal production. This shift has been driven by the assumption that removing antibiotics will select for antibiotic susceptible bacterial taxa, which in turn will allow the currently available antibiotic arsenal to be more effective. This change in practice has highlighted new questions that need to be answered to assess the effectiveness of antibiotic removal in reducing the spread of antibiotic resistance bacteria. This research demonstrates that antibiotic-susceptible Salmonella enterica serovar Heidelberg strains can acquire multidrug resistance from commensal bacteria present in the gut of neonatal broiler chicks, even in the absence of antibiotic selection. We demonstrate that exposure to acidic pH drove the horizontal transfer of antimicrobial resistance plasmids and suggest that simply removing antibiotics from food animal production might not be sufficient to limit the spread of antimicrobial resistance.

Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced. Depending on the genotype, alpha-thalassemia results in moderate to profound anemia, hemolysis, growth delays, splenomegaly, and increased risk for thromboembolic events; certain patients might require chronic transfusions. Although alpha-thalassemia is not a core condition of the United States Recommended Uniform Screening Panel* for state newborn screening programs, methodologies used by some newborn screening programs to detect sickle cell disease, which is a core panel condition, also detect a quantitative marker of alpha-thalassemia, hemoglobin (Hb) Bart's, an abnormal type of hemoglobin. The percentage of Hb Bart's detected correlates with alpha-thalassemia severity. The Association of Public Health Laboratories' Hemoglobinopathy Workgroup conducted a survey of state newborn screening programs' alpha-thalassemia screening methodologies and reporting and follow-up practices. Survey findings indicated that 41 of 44 responding programs (93%) report some form of alpha-thalassemia results and 57% used a two-method screening protocol. However, the percentage of Hb Bart's used for thalassemia classification, the types of alpha-thalassemia reported, and the recipients of this information varied widely. These survey findings highlight the opportunity for newborn screening programs to revisit their policies as they reevaluate their practices in light of the recently released guideline from the Clinical and Laboratory Standards Institute (CLSI) on Newborn Screening for Hemoglobinopathies (1). Although deferring to local programs for policies, the report used a cutoff of 25% Hb Bart's in its decision tree, a value many programs do not use. Standardization of screening and reporting might lead to more timely diagnoses and health care services and improved outcomes for persons with a clinically significant alpha-thalassemia.

BACKGROUND: Persons who inject drugs (PWID) have frequent healthcare encounters related to their injection drug use (IDU) but are often not tested for human immunodeficiency virus (HIV). We sought to quantify missed opportunities for HIV testing during an HIV outbreak among PWID. METHODS: PWID with HIV diagnosed in 5 Cincinnati/Northern Kentucky counties during January 2017-September 2018 who had ≥1 encounter 12 months prior to HIV diagnosis in 1 of 2 Cincinnati/Northern Kentucky area healthcare systems were included in the analysis. HIV testing and encounter data were abstracted from electronic health records. A missed opportunity for HIV testing was defined as an encounter for an IDU-related condition where an HIV test was not performed and had not been performed in the prior 12 months. RESULTS: Among 109 PWID with HIV diagnosed who had ≥1 healthcare encounter, 75 (68.8%) had ≥1 IDU-related encounters in the 12 months before HIV diagnosis. These 75 PWID had 169 IDU-related encounters of which 86 (50.9%) were missed opportunities for HIV testing and occurred among 46 (42.2%) PWID. Most IDU-related encounters occurred in the emergency department (118/169; 69.8%). Using multivariable generalized estimating equations, HIV testing was more likely in inpatient compared with emergency department encounters (adjusted relative risk [RR], 2.72; 95% confidence interval [CI], 1.70-4.33) and at the healthcare system receiving funding for emergency department HIV testing (adjusted RR, 1.76; 95% CI, 1.10-2.82). CONCLUSIONS: PWID have frequent IDU-related encounters in emergency departments. Enhanced HIV screening of PWID in these settings can facilitate earlier diagnosis and improve outbreak response.

A number of studies have examined the association between male involvement in sports and sexual violence (SV) perpetration, especially among college-age males. Less is known about the association between sports involvement and SV perpetration for adolescent males and females. To address this gap, the current study examined sports involvement in middle school (no sports, no/low contact, and high contact) among 1,561 students, who were then followed into high school and asked about the frequency of SV perpetration. Results from logistic regression models indicated that, even after controlling for mother's education, race/ethnicity, SV perpetration in middle school, and traditional beliefs about masculinity and substance use, middle school sports participation was significantly associated with risk of SV perpetration in high school. Compared with youth who reported no sports involvement in middle school, youth categorized as no/low contact sports involvement had greater odds of SV perpetration in high school. Sex differences emerged, revealing that no/low contact sports involvement was associated with SV perpetration for females and high contact sports involvement was associated with SV perpetration for males, compared with no sports involvement. These findings suggest potential opportunities to intervene in middle school to improve coaching practices, enhance respectful relationships, and modify athletes' norms, attitudes, and behaviors to reduce risk for SV perpetration in high school.

BACKGROUND: Invasive orthopaedic interventions (IOI) are often used to control recurrent haemarthrosis, pain and loss of joint function, in males with haemophilia (Factor VIII and Factor IX deficiency). AIM: Identify risk factors associated with IOIs in males with haemophilia enrolled in the Universal Data Collection (UDC) surveillance program from 2000 until 2010. METHODS: Data were collected on IOIs performed on patients receiving care in 130 haemophilia treatment centers in the United States annually by health care providers using standardized forms. IOIs included in this study are as follows: 1) synovectomy and 2) arthrodesis or arthroplasty (A/A). Information about potential risk factors was obtained from the preceding UDC visit if available, or from the same visit if not. Patients with no reported IOI at any of their UDC visits were the reference group for the analysis. Multivariate analyses were conducted to identify independent risk factors for synovectomies and arthrodesis/arthroplasty. RESULTS: Risk factors significantly associated with the two IOI categories were age, student status, haemophilia severity, number of joint bleeds within the last 6 months, HIV or hepatitis C (HCV) status. Multivariate analyses showed patients on continuous prophylaxis were 50% less likely to have had a synovectomy and were 40% less likely to have an A/A. CONCLUSIONS: This study shows modifiable risk factors, including management of bleeding episodes with a continuous prophylactic treatment schedule are associated with a decreased likelihood of IOIs in males with haemophilia.

Background: Influenza outbreaks can occur among passengers and crews during the Alaska summertime cruise season. Ill travellers represent a potential source for introduction of novel or antigenically drifted influenza virus strains to the United States. From May to September 2013-2015, the Alaska Division of Public Health, the Centers for Disease Control and Prevention (CDC), and two cruise lines implemented a laboratory-based public health surveillance project to detect influenza and other respiratory viruses among ill crew members and passengers on select cruise ships in Alaska. Methods: Cruise ship medical staff collected 2-3 nasopharyngeal swab specimens per week from passengers and crew members presenting to the ship infirmary with acute respiratory illness (ARI). Specimens were tested for respiratory viruses at the Alaska State Virology Laboratory (ASVL); a subset of specimens positive for influenza virus were sent to CDC for further antigenic characterization. Results: Of 410 nasopharyngeal specimens, 83% tested positive for at least one respiratory virus; 71% tested positive for influenza A or B virus. Antigenic characterization of pilot project specimens identified strains matching predominant circulating seasonal influenza virus strains, which were included in the northern or southern hemisphere influenza vaccines during those years. Results were relatively consistent across age groups, recent travel history, and influenza vaccination status. Onset dates of illness relative to date of boarding differed between northbound (occurring later in the voyage) and southbound (occurring within the first days of the voyage) cruises. Conclusions: The high yield of positive results indicated that influenza was common among passengers and crews sampled with ARI. This finding reinforces the need to bolster influenza prevention and control activities on cruise ships. Laboratory-based influenza surveillance on cruise ships may augment inland influenza surveillance and inform control activities. However, these benefits should be weighed against the costs and operational limitations of instituting laboratory-based surveillance programs on ships.

PROBLEM/CONDITION: Higher rates of death in nonmetropolitan areas (often referred to as rural areas) compared with metropolitan areas have been described but not systematically assessed. PERIOD COVERED: 1999-2014 DESCRIPTION OF SYSTEM: Mortality data for U.S. residents from the National Vital Statistics System were used to calculate age-adjusted death rates and potentially excess deaths for nonmetropolitan and metropolitan areas for the five leading causes of death. Age-adjusted death rates included all ages and were adjusted to the 2000 U.S. standard population by the direct method. Potentially excess deaths are defined as deaths among persons aged <80 years that exceed the numbers that would be expected if the death rates of states with the lowest rates (i.e., benchmark states) occurred across all states. (Benchmark states were the three states with the lowest rates for each cause during 2008-2010.) Potentially excess deaths were calculated separately for nonmetropolitan and metropolitan areas. Data are presented for the United States and the 10 U.S. Department of Health and Human Services public health regions. RESULTS: Across the United States, nonmetropolitan areas experienced higher age-adjusted death rates than metropolitan areas. The percentages of potentially excess deaths among persons aged <80 years from the five leading causes were higher in nonmetropolitan areas than in metropolitan areas. For example, approximately half of deaths from unintentional injury and chronic lower respiratory disease in nonmetropolitan areas were potentially excess deaths, compared with 39.2% and 30.9%, respectively, in metropolitan areas. Potentially excess deaths also differed among and within public health regions; within regions, nonmetropolitan areas tended to have higher percentages of potentially excess deaths than metropolitan areas. INTERPRETATION: Compared with metropolitan areas, nonmetropolitan areas have higher age-adjusted death rates and greater percentages of potentially excess deaths from the five leading causes of death, nationally and across public health regions. PUBLIC HEALTH ACTION: Routine tracking of potentially excess deaths in nonmetropolitan areas might help public health departments identify emerging health problems, monitor known problems, and focus interventions to reduce preventable deaths in these areas.

INTRODUCTION: Molecular subtyping of pathogens is critical for foodborne disease outbreak detection and investigation. Many clusters initially identified by pulsed-field gel electrophoresis (PFGE) are not confirmed as point-source outbreaks. We evaluated characteristics of clusters that can help prioritize investigations to maximize effective use of limited resources. MATERIALS AND METHODS: A multiagency collaboration (FoodNet) collected data on Salmonella and Escherichia coli O157 clusters for 3 years. Cluster size, timing, extent, and nature of epidemiologic investigations were analyzed to determine associations with whether the cluster was identified as a confirmed outbreak. RESULTS: During the 3-year study period, 948 PFGE clusters were identified; 849 (90%) were Salmonella and 99 (10%) were E. coli O157. Of those, 192 (20%) were ultimately identified as outbreaks (154 [18%] of Salmonella and 38 [38%] of E. coli O157 clusters). Successful investigation was significantly associated with larger cluster size, more rapid submission of isolates (e.g., for Salmonella, 6 days for outbreaks vs. 8 days for nonoutbreaks) and PFGE result reporting to investigators (16 days vs. 29 days, respectively), and performance of analytic studies (completed in 33% of Salmonella outbreaks vs. 1% of nonoutbreaks) and environmental investigations (40% and 1%, respectively). Intervals between first and second cases in a cluster did not differ significantly between outbreaks and nonoutbreaks. CONCLUSIONS: Molecular subtyping of pathogens is a rapidly advancing technology, and successfully identifying outbreaks will vary by pathogen and methods used. Understanding criteria for successfully investigating outbreaks is critical for efficiently using limited resources.

INTRODUCTION: Recurrent joint hemarthroses due to hemophilia (Factor VIII and Factor IX deficiency) often lead to invasive orthopedic interventions to decrease frequency of bleeding and/or to alleviate pain associated with end-stage hemophilic arthropathy. AIM: Identify trends in invasive orthopedic interventions among people with hemophilia who were enrolled in the Universal Data Collection (UDC) program during the period 2000-2010. METHODS: Data were collected from 130 hemophilia treatment centers in the United States annually during the period 2000-2010, in collaboration with the Centers for Disease Control and Prevention (CDC). The number of visits in which an invasive orthopedic intervention was reported was expressed as a proportion of the total visits in each year of the program. Invasive orthopedic interventions consisted of arthroplasty, arthrodesis, and synovectomy. Joints included in this study were the shoulder, elbow, hip, knee, and ankle. RESULTS: A 5.6% decrease in all invasive orthopedic interventions in all joints of people with hemophilia enrolled in the UDC program over the 11-year study period was observed. CONCLUSIONS: These data reflect a declining trend in invasive orthopedic interventions in people with hemophilia. Further research is needed to understand the characteristics that may influence invasive orthopedic interventions.

BACKGROUND: The term severe acute respiratory infection (SARI) encompasses a heterogeneous group of respiratory illnesses. Grading the severity of SARI is currently reliant on indirect disease severity measures such as respiratory and heart rate, and the need for oxygen or intensive care. With the lungs being the primary organ system involved in SARI, chest radiographs (CXRs) are potentially useful for describing disease severity. Our objective was to develop and validate a SARI CXR severity scoring system. METHODS: We completed validation within an active SARI surveillance project, with SARI defined using the World Health Organization case definition of an acute respiratory infection with a history of fever, or measured fever of ≥ 38 degrees C; and cough; and with onset within the last 10 days; and requiring hospital admission. We randomly selected 250 SARI cases. Admission CXR findings were categorized as: 1 = normal; 2 = patchy atelectasis and/or hyperinflation and/or bronchial wall thickening; 3 = focal consolidation; 4 = multifocal consolidation; and 5 = diffuse alveolar changes. Initially, four radiologists scored CXRs independently. Subsequently, a pediatrician, physician, two residents, two medical students, and a research nurse independently scored CXR reports. Inter-observer reliability was determined using a weighted Kappa (kappa) for comparisons between radiologists; radiologists and clinicians; and clinicians. Agreement was defined as moderate (kappa > 0.4-0.6), good (kappa > 0.6-0.8) and very good (kappa > 0.8-1.0). RESULTS: Agreement between the two pediatric radiologists was very good (kappa = 0.83, 95 % CI 0.65-1.00) and between the two adult radiologists was good (kappa = 0.75, 95 % CI 0.57-0. 93). Agreement of the clinicians with the radiologists was moderate-to-good (pediatrician:kappa = 0.65; pediatric resident:kappa = 0.69; physician:kappa = 0.68; resident:kappa = 0.67; research nurse:kappa = 0.49, medical students: kappa = 0.53 and kappa = 0.56). Agreement between clinicians was good-to-very good (pediatrician vs. physician:kappa = 0.85; vs. pediatric resident:kappa = 0.81; vs. medicine resident:kappa = 0.76; vs. research nurse:kappa = 0.75; vs. medical students:kappa = 0.63 and 0.66). Following review of discrepant CXR report scores by clinician pairs, kappa values for radiologist-clinician agreement ranged from 0.59 to 0.70 and for clinician-clinician agreement from 0.97 to 0.99. CONCLUSIONS: This five-point CXR scoring tool, suitable for use in poorly- and well-resourced settings and by clinicians of varying experience levels, reliably describes SARI severity. The resulting numerical data enables epidemiological comparisons of SARI severity between different countries and settings.

We describe multidrug-resistant (MDR) Salmonella Heidelberg infections associated with mechanically separated chicken (MSC) served at a county correctional facility. Twenty-three inmates met the case definition. All reported diarrhea, 19 (83%) reported fever, 16 (70%) reported vomiting, 4 (17%) had fever ≥103 degrees F, and 3 (13%) were hospitalized. A case-control study found no single food item significantly associated with illness. Salmonella Heidelberg with an indistinguishable pulsed-field gel electrophoresis pattern was isolated from nine stool specimens; two isolates displayed resistance to a total of five drug classes, including the third-generation cephalosporin, ceftriaxone. MDR Salmonella Heidelberg might have contributed to the severity of illness. Salmonella Heidelberg indistinguishable from the outbreak subtype was isolated from unopened MSC. The environmental health assessment identified cross-contamination through poor food-handling practices as a possible contributing factor. Proper hand-washing techniques and safe food-handling practices were reviewed with the kitchen supervisor.

Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) is the most commonly identified serotype of STEC in the United States. An estimated 63,000 STEC O157 infections occur annually. Infection typically results in diarrhea, bloody stool, abdominal cramps, and, in some cases, hemolytic uremic syndrome. Recent outbreaks of STEC O157 have increasingly been associated with consumption of leafy greens such as lettuce and spinach. We investigated an outbreak of STEC O157 associated with the consumption of bagged salad with cases clustered in various institutional settings. A case-control study was conducted among cases from selected schools with controls matched by school and grade. Seventeen cases from three U.S. states were identified. The median age of cases was 23 years (range: 3-88) and 13 (76%) were female. Six cases were hospitalized and two died. Onset dates ranged from April 29 to May 12, 2012. The matched case-control analysis identified a single significant food service exposure: consumption of lettuce provided by a school cafeteria (median odds ratio=9.4, 95% confidence interval: 1.4-infinity, p=0.0469). The implicated bagged salad product was traced back to a single production facility. Implicated growing areas were scheduled for heightened inspection for the upcoming growing season. A combination of analytical epidemiologic studies among subclusters of cases, surveillance, and traceback implicated bagged salad in this outbreak investigation.

This study prospectively compared the effect of secondary prophylaxis to episodic treatment on target joint (TJ) range of motion (ROM), number of joint haemorrhages and new TJ development in patients with moderate or severe haemophilia. Two-hundred and eighty-six males, 17% in prophylaxis, 83% in episodic treatment group, participating in the Centers for Disease Control and Prevention's Universal Data Collection project, fulfilled inclusion criteria: age >2 years at enrolment, free of TJs at enrolment, developed at least one TJ after enrolment, and received either prophylaxis or episodic treatment continuously for two follow-up visits after TJ development. The outcomes of interest - percentage change in TJ ROM, number of joint haemorrhages and new TJ development, were modelled using multivariate linear, Poisson and logistic regression techniques respectively. Individuals who received secondary prophylaxis in comparison to episodic treatment were younger at TJ development (P < 0.01); there was no difference in the decrease in TJ ROM between the two groups (P = 0.9). Factors significantly associated with a higher rate of haemarthroses included episodic treatment, severe haemophilia, age >5 years at TJ development, obesity and inhibitor negative status. Secondary prophylaxis significantly decreased haemarthroses but was not associated with a significant improvement in TJ ROM or with new TJ development.

SUMMARY: Common sources of shiga toxin-producing Escherichia coli (STEC) O157 infection have been identified by investigating outbreaks and by case-control studies of sporadic infections. We conducted an analysis to attribute STEC O157 infections ascertained in 1996 and 1999 by the Foodborne Diseases Active Surveillance Network (FoodNet) to sources. Multivariable models from two case-control studies conducted in FoodNet and outbreak investigations that occurred during the study years were used to calculate the annual number of infections attributable to six sources. Using the results of the outbreak investigations alone, 27% and 15% of infections were attributed to a source in 1996 and 1999, respectively. Combining information from both data sources, 65% of infections in 1996 and 34% of infections in 1999 were attributed. The results suggest that methods to incorporate data from multiple surveillance systems and over several years are needed to improve estimation of the number of illnesses attributable to exposure sources.

BACKGROUND: Approximately 40% of US travelers to less developed countries experience diarrheal illness. Using data from the Foodborne Diseases Active Surveillance Network (FoodNet), we describe travel-associated enteric infections during 2004-2009, characterizing the patients, pathogens, and destinations involved. METHODS: FoodNet conducts active surveillance at 10 US sites for laboratory-confirmed infections with 9 pathogens transmitted commonly through food. Travel-associated infections are infections diagnosed in the United States but likely acquired abroad based on a pathogen-specific time window between return from international travel to diagnosis. We compare the demographic, clinical, and exposure-related characteristics of travelers with those of nontravelers and estimate the risk of travel-associated infections by destination, using US Department of Commerce data. RESULTS: Of 64,039 enteric infections reported to FoodNet with information about travel, 8270 (13%) were travel associated. The pathogens identified most commonly in travelers were Campylobacter (42%), nontyphoidal Salmonella (32%), and Shigella (13%). The most common travel destinations were Mexico, India, Peru, Dominican Republic, and Jamaica. Most travel-associated infections occurred in travelers returning from Latin America and the Caribbean (LAC). Risk was greatest after travel to Africa (75.9 cases per 100,000 population), followed by Asia (22.7 cases per 100,000), and LAC (20.0 cases per 100,000). CONCLUSIONS: The Latin America and Caribbean region accounts for most travel-associated enteric infections diagnosed in the United States, although travel to Africa carries the greatest risk. Although FoodNet surveillance does not cover enterotoxigenic Escherichia coli, a common travel-associated infection, this information about other key enteric pathogens can be used by travelers and clinicians in pre- and posttravel consultations.

INTRODUCTION: Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort. METHODS: HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months. RESULTS: From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40) and (26-39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/microL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease. CONCLUSIONS: Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245).

Two cases of pulmonary alveolar proteinosis, including one death, occurred in workers at a facility producing indium-tin oxide (ITO), a compound used in recent years to make flat panel displays. Both workers were exposed to airborne ITO dust and had indium in lung tissue specimens. One worker was tested for autoantibodies to granulocytemacrophage-colonystimulating factor (GM-CSF) and found to have an elevated level. These cases suggest that inhalational exposure to ITO causes pulmonary alveolar proteinosis, which may occur via an autoimmune mechanism.

OBJECTIVE: The aim of this longitudinal study is to examine the relationship between weight loss from maximum body weight, body mass index (BMI), and mortality in a nationally representative sample of men and women. DESIGN: Longitudinal cohort study. SUBJECTS: In all, 6117 whites, blacks, and Mexican-Americans 50 years and over at baseline who survived at least 3 years of follow-up, from the Third National Health and Nutrition Examination Survey Linked Mortality Files (1988-1994 with passive mortality follow-up through 2000), were included. MEASUREMENTS: Measured body weight and self-reported maximum body weight obtained at baseline. Weight loss (maximum body weight minus baseline weight) was categorized as <5%, 5-<15%, and ≥15%. Maximum BMI (reported maximum weight (kg)/measured baseline height (m)(2)) was categorized as healthy weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). RESULTS: In all, 1602 deaths were identified. After adjusting for age, race, smoking, health status, and preexisting illness, overweight men with weight loss of 15% or more, overweight women with weight loss of 5-<15%, and women in all BMI categories with weight loss of 15% or more were at increased risk of death from all causes compared with those in the same BMI category who lost <5%; hazard ratios ranged from 1.46 to 2.70. Weight loss of 5-<15% reduced risk of death from cardiovascular diseases among obese men. CONCLUSIONS: Weight loss of 15% or more from maximum body weight is associated with increased risk of death from all causes among overweight men and among women regardless of maximum BMI. International Journal of Obesity advance online publication, 9 March 2010; doi:10.1038/ijo.2010.41.