Development of broad-spectrum antiviral therapies is critical for outbreak and pandemic preparedness against emerging and reemerging viruses. Viruses inducing hemorrhagic fevers cause high morbidity and mortality in humans and are associated with several recent international outbreaks, but approved therapies for treating most of these pathogens are lacking. Here, we show that 4'-fluorouridine (4'-FlU; EIDD-2749), an orally available ribonucleoside analog, has antiviral activity against multiple hemorrhagic fever viruses in cell culture, including Nipah virus, Crimean-Congo hemorrhagic fever virus, orthohantaviruses, and arenaviruses. We performed preclinical in vivo evaluation of oral 4'-FlU against two arenaviruses, Old World Lassa virus (LASV) and New World Junín virus (JUNV), in guinea pig models of lethal disease. 4'-FlU demonstrated both advantageous pharmacokinetic characteristics and high efficacy in both of these lethal disease guinea pig models. Additional experiments supported protection of the infected animals even when 4'-FlU delivery was reduced to a low dose of 0.5 milligram per kilogram. To demonstrate clinical utility, 4'-FlU treatment was evaluated when initiated late in the course of infection (12 or 9 days after infection for LASV and JUNV, respectively). Delayed treatment resulted in rapid resolution of clinical signs, demonstrating an extended window for therapeutic intervention. These data support the use of 4'-FlU as a potent and efficacious treatment against highly pathogenic arenaviruses of public health concern with a virus inhibition profile suggesting broad-spectrum utility as an orally available antiviral drug against a wide variety of viral pathogens.

BACKGROUND: Tuberculosis infection (TBI) and chronic hepatitis B virus (HBV) infection disproportionately affect non-US-born persons. Early identification and treatment are critical to reduce transmission, morbidity, and mortality, but little is known about screening in the United States. METHODS: We conducted a cross-sectional study in a large integrated California health system in September 2022 assessing TBI and HBV screening among persons aged ≥18 years who were born in countries with high TB burden (TB disease incidence rates ≥20/100 000 population) and/or HBV burden (hepatitis B surface antigen seroprevalence >2%). RESULTS: Of 510 361 non-US-born persons born in countries with high TB burden, 322 027 (63.1%) were born in countries with high HBV burden and 188 334 (36.9%) in countries with only high TB burden. Among persons born in countries with high TB and HBV burden, 29.6% were screened for TBI, 64.5% for HBV, and 23.4% for TBI and HBV; 9.9% had TBI and 3.1% had HBV infection. Among persons born in countries with high TB burden only, 27.9% were screened for TBI and 7.5% had TBI. CONCLUSIONS: Among non-US-born persons from countries with high TB and HBV burden, we found low screening rates and elevated prevalence of TBI and chronic HBV infection. Cotesting for TBI and HBV infection in non-US-born persons from countries with high TB and HBV burden might improve outcomes by identifying persons who warrant TBI treatment, HBV treatment, or HBV vaccination. Increased screening is the first step in reducing health inequities and overall disease burden.

The SARS-CoV-2 main protease (M(pro)) has been proven to be a highly effective target for therapeutic intervention, yet only one drug currently holds FDA approval status for this target. We were inspired by a series of publications emanating from the Jorgensen and Anderson groups describing the design of potent, non-peptidic, competitive SARS-CoV-2 M(pro) inhibitors, and we saw an opportunity to make several design modifications to improve the overall pharmacokinetic profile of these compounds without losing potency. To this end, we created a focused virtual library using reaction-based enumeration tools in the Schrödinger suite. These compounds were docked into the M(pro) active site and subsequently prioritized for synthesis based upon relative binding affinity values calculated by FEP+. Fourteen compounds were selected, synthesized, and evaluated both biochemically and in cell culture. Several of the synthesized compounds proved to be potent, competitive M(pro) inhibitors with improved metabolic stability profiles.

The first three SARS-CoV-2 phylogenetic lineages classified as variants of concern (VOCs) in the United States (U.S.) from December 15, 2020 to February 28, 2021, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1) lineages, were initially detected internationally. This investigation examined available travel history of coronavirus disease 2019 (COVID-19) cases reported in the U.S. in whom laboratory testing showed one of these initial VOCs. Travel history, demographics, and health outcomes for a convenience sample of persons infected with a SARS-CoV-2 VOC from December 15, 2020 through February 28, 2021 were provided by 35 state and city health departments, and proportion reporting travel was calculated. Of 1,761 confirmed VOC cases analyzed, 1,368 had available data on travel history. Of those with data on travel history, 1,168 (85%) reported no travel preceding laboratory confirmation of SARS-CoV-2 and only 105 (8%) reported international travel during the 30 days preceding a positive SARS-CoV-2 test or symptom onset. International travel was reported by 92/1,304 (7%) of persons infected with the Alpha variant, 7/55 (22%) with Beta, and 5/9 (56%) with Gamma. Of the first three SARS-CoV-2 lineages designated as VOCs in the U.S., international travel was common only among the few Gamma cases. Most persons infected with Alpha and Beta variant reported no travel history, therefore, community transmission of these VOCs was likely common in the U.S. by March 2021. These findings underscore the importance of global surveillance using whole genome sequencing to detect and inform mitigation strategies for emerging SARS-CoV-2 VOCs.

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: Tuberculosis (TB) elimination within the United States (US) will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), though gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the US. Data was abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23,885 participants tested by LHDs, 46% (11,009) were male with a median age of 31 (IQR 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16,689 (70%) received a tuberculin skin test (TST), 6,993 (29%) received a Quantiferon (QFT), and 1,934 (8%) received a T-SPOT.TB; 5% (1,190) had more than one test. Among those tested, 2,877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, p<0.01). Of 2,515 (11%) of the total participants diagnosed with LTBI, 1,073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.

BACKGROUND: The transportation and utilities industries include establishments engaged in the movement of passengers and freight, or the provision of public power, water, and other services. Along with the warehousing industry, they make up the US National Occupational Research Agenda's Transportation, Warehousing and Utilities (TWU) industry sector. In 2018 the sector composed 5% of the US workforce, with approximately 8 million workers. TWU workers experienced 19% of all fatalities among U.S. workers in 2018 and 7% of total occupational injuries and illnesses. METHODS: Around-the-clock operations, heavy workloads, long and irregular shifts, complicated schedules, and time pressures characterize work across the US TWU sector. However, there are considerable differences in worker priorities and concerns between TWU industries. Major areas of concern within the sector include disparities in work schedules; required training for employee fatigue awareness and prevention; physical and mental job demands; and safety culture. RESULTS: Strategies for fatigue mitigation are critical to reduce the prevalence of injuries, safety-critical events, and crashes in TWU workers. Further research on the incidence and characterization of fatigue among TWU workers will guide the development of effective mitigation strategies. The influence of work scheduling on missed sleep opportunities and disrupted circadian rhythms should be determined. Evaluation of fatigue mitigation strategies can lead to the adoption of the most effective ones for each TWU industry. CONCLUSION: Implementation of effective strategies is critical for the health, safety, wellbeing, and productivity of workers in the TWU sector.

During November 19-21, 2021, an indoor convention (event) in New York City (NYC), was attended by approximately 53,000 persons from 52 U.S. jurisdictions and 30 foreign countries. In-person registration for the event began on November 18, 2021. The venue was equipped with high efficiency particulate air (HEPA) filtration, and attendees were required to wear a mask indoors and have documented receipt of at least 1 dose of a COVID-19 vaccine.* On December 2, 2021, the Minnesota Department of Health reported the first case of community-acquired COVID-19 in the United States caused by the SARS-CoV-2 B.1.1.529 (Omicron) variant in a person who had attended the event (1). CDC collaborated with state and local health departments to assess event-associated COVID-19 cases and potential exposures among U.S.-based attendees using data from COVID-19 surveillance systems and an anonymous online attendee survey. Among 34,541 attendees with available contact information, surveillance data identified test results for 4,560, including 119 (2.6%) persons from 16 jurisdictions with positive SARS-CoV-2 test results. Most (4,041 [95.2%]), survey respondents reported always wearing a mask while indoors at the event. Compared with test-negative respondents, test-positive respondents were more likely to report attending bars, karaoke, or nightclubs, and eating or drinking indoors near others for at least 15 minutes. Among 4,560 attendees who received testing, evidence of widespread transmission during the event was not identified. Genomic sequencing of 20 specimens identified the SARS-CoV-2 B.1.617.2 (Delta) variant (AY.25 and AY.103 sublineages) in 15 (75%) cases, and the Omicron variant (BA.1 sublineage) in five (25%) cases. These findings reinforce the importance of implementing multiple, simultaneous prevention measures, such as ensuring up-to-date vaccination, mask use, physical distancing, and improved ventilation in limiting SARS-CoV-2 transmission, during large, indoor events.(†).

During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3-17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3-August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non-fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.

Understanding the contribution of CDC-funded testing toward diagnosing HIV informs efforts to end the HIV epidemic. Due to differences in surveillance data and CDC program data, which sometimes rely on self-reported information, the number of new diagnoses cannot be directly compared. CDC recently asked grantees to check surveillance data to inform the identification of new diagnoses from CDC-funded tests. In this analysis, we use this newly available information to estimate the percent of all HIV diagnoses from 2010 to 2017 in the United States that result from CDC-funded tests. Among tests with surveillance information, correlates of correct categorization using self-report only were assessed. Weights were calculated from that analysis and used to estimate the total number of CDC-funded new diagnoses. Estimates are presented overall and by demographics/transmission risk group. We estimate that one third of all HIV diagnoses in the United States from 2010 to 2017 resulted from a CDC-funded test. The percent of diagnoses that resulted from CDC-funded tests was higher among some high-risk groups: 41% among 20-29-year-olds and 39% among blacks/African Americans. When compared to total diagnoses in the United States from 2010 to 2017, a large proportion resulted from CDC-funded tests, particularly among young individuals and blacks/African Americans. CDC's contribution to new HIV diagnoses was previously unknown. CDC-funded testing is an important part of the national effort to diagnose all people with HIV as early as possible after infection.

We describe coronavirus disease (COVID-19) among US food manufacturing and agriculture workers and provide updated information on meat and poultry processing workers. Among 742 food and agriculture workplaces in 30 states, 8,978 workers had confirmed COVID-19; 55 workers died. Racial and ethnic minority workers could be disproportionately affected by COVID-19.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is spread from person to person (1-3). Quarantine of exposed persons (contacts) for 14 days following their exposure reduces transmission (4-7). Contact tracing provides an opportunity to identify contacts, inform them of quarantine recommendations, and monitor their symptoms to promptly identify secondary COVID-19 cases (7,8). On March 12, 2020, Maine Center for Disease Control and Prevention (Maine CDC) identified the first case of COVID-19 in the state. Because of resource constraints, including staffing, Maine CDC could not consistently monitor contacts, and automated technological solutions for monitoring contacts were explored. On May 14, 2020, Maine CDC began enrolling contacts of patients with reported COVID-19 into Sara Alert (MITRE Corporation, 2020),* an automated, web-based, symptom monitoring tool. After initial communication with Maine CDC staff members, enrolled contacts automatically received daily symptom questionnaires via their choice of e-mailed weblink, text message, texted weblink, or telephone call until completion of their quarantine. Epidemiologic investigations were conducted for enrollees who reported symptoms or received a positive SARS-CoV-2 test result. During May 14-June 26, Maine CDC enrolled 1,622 contacts of 614 COVID-19 patients; 190 (11.7%) eventually developed COVID-19, highlighting the importance of identifying, quarantining, and monitoring contacts of COVID-19 patients to limit spread. In Maine, symptom monitoring was not feasible without the use of an automated symptom monitoring tool. Using a tool that permitted enrollees to specify a method of symptom monitoring was well received, because the majority of persons monitored (96.4%) agreed to report using this system.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts(dagger) across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry.

OBJECTIVES: HIV testing identifies persons living with HIV and can lead to treatment, decreased risk behaviors, and reduced transmission. The objective of our study was to describe state-level trends in HIV testing in the general US adult population aged 18-64 years, for both ever tested for HIV and tested for HIV in the previous 12 months. METHODS: Using 2011-2017 Behavioral Risk Factor Surveillance System data, we estimated the percentage of the state population, plus the District of Columbia, aged 18-64 years ever tested for HIV and tested for HIV in the previous 12 months. The 50 states and the District of Columbia were grouped according to the estimated prevalence of HIV in 2011. We used orthogonal contrasts to calculate P values for linear trends. RESULTS: The percentage of the population ever tested for HIV increased significantly in 23 states during 2011-2017, whereas the percentage tested for HIV in the previous 12 months increased significantly in 8 states. In 2017, the mean percentage ever tested for HIV in states with a high prevalence of HIV was 8.6 percentage points higher than the mean percentage in states with a low prevalence of HIV (48.5% vs 39.9%); the mean increase in the percentage ever tested was highest (11.4%) in states with a low prevalence of HIV. CONCLUSION: Enhanced efforts by states to make HIV testing simple, accessible, and routine are needed to reduce the number of persons who are not aware of their infection.

In 2006, Centers for Disease Control and Prevention (CDC) recommended HIV screening in healthcare or clinical settings for all persons aged 13-64 years and annual rescreening for populations at high risk for HIV. We used the Behavioral Risk Factor Surveillance System to describe the prevalence and trends of ever tested for HIV and tested for HIV in the past 12 months among US adults. The percentage of ever tested increased from 42.9% in 2011 to 45.9% in 2017; testing in the past 12 months increased from 13.2% in 2011 to 14.8% in 2017. Despite these increases, less than half of US adults have ever been tested for HIV over ten years after CDC's recommendations. Increasing the prevalence of routine HIV screening and rescreening among individuals at high risk will reduce the number of undiagnosed persons with HIV infection and thus prevent new HIV infections-a key strategy in the Ending the HIV Epidemic initiative.

Objectives. To examine state-level factors associated with late-stage HIV diagnoses in the United States.Methods. We examined state-level factors associated with late-stage diagnoses by estimating negative binomial regression models. We used 2013 to 2016 data from the National HIV Surveillance System (late-stage diagnoses), the Behavioral Risk Factor Surveillance System (HIV testing), and the American Community Survey (sociodemographics).Results. Among individuals 25 to 44 years old, a 5% increase in the percentage of the state population tested for HIV in the preceding 12 months was associated with a 3% decrease in late-stage diagnoses. Among both individuals 25 to 44 years of age and those aged 45 years and older, a 5% increase in the percentage of the population living in a rural area was associated with a 2% to 3% increase in late-stage diagnoses.Conclusions. Increasing HIV testing may lower late-stage HIV diagnoses among younger individuals. Increasing HIV-related services may benefit both younger and older people in rural areas. (Am J Public Health. Published online ahead of print September 19, 2019: e1-e7. doi:10.2105/AJPH.2019.305273).

In the United States, the all-cause mortality rate among persons living with diagnosed HIV infection (PLWH) is almost twice as high as among the general population. We aimed to identify amendable factors that state public health programs can influence to reduce mortality among PLWH. Using generalized estimating equations (GEE), we estimated age-group-specific models (24-34, 35-54, >/= 55 years) to assess the association between state-level mortality rates among PLWH during 2010-2014 (National HIV Surveillance System) and amendable factors (percentage of Ryan White HIV/AIDS Program (RWHAP) clients with viral suppression, percentage of residents with healthcare coverage, state-enacted anti-discrimination laws index) while controlling for sociodemographic nonamendable factors. Controlling for nonamendable factors, states with 5% higher viral suppression among RWHAP clients had a 3-5% lower mortality rates across all age groups [adjusted Risk Ratio (aRR): 0.95, 95% Confidence Interval (CI): 0.92-0.99 for 24-34 years, aRR: 0.97, 95%CI: 0.94-0.99 for 35-54 years, aRR: 0.96, 95%CI: 0.94-0.99 for >/= 55 years]; states with 5% higher health care coverage had 4-11% lower mortality rate among older age groups (aRR: 0.96, 95%CI: 0.93-0.99 for 34-54 years; aRR: 0.89, 95%CI: 0.81-0.97 for >/= 55 years); and having laws that address one additional area of anti-discrimination was associated with a 2-3% lower mortality rate among older age groups (aRR: 0.98, 95%CI: 0.95-1.00 for 34-54 years; aRR: 0.97, 95%CI: 0.94-0.99 for >/= 55 years). The mortality rate among PLWH was lower in states with higher levels of residents with healthcare coverage, anti-discrimination laws, and viral suppression among RWHAP clients. States can influence these factors through programs and policies.

BACKGROUND: Human-capital based lifetime productivity estimates are frequently used in cost-of-illness (COI) analyses and, less commonly, in cost-effectiveness analyses (CEAs). Previous US estimates assumed that labor productivity and real earnings both grow by 1% per year. OBJECTIVES: We present estimates of annual and lifetime productivity for 2016 using data from the American Community Survey, the American Time Use Survey, and the Current Population Survey and with varying assumptions about real earnings growth. METHODS: We estimated the sum of market productivity (gross annual personal labor earnings adjusted for employer-paid benefits) and the imputed value of non-market time spent in household, caring, and volunteer services. The present value of lifetime productivity at various ages was calculated for synthetic cohorts using annual productivity estimates, life tables, discount rates, and assumptions about future earnings growth rates. RESULTS: Mean annual productivity was $57,324 for US adults in 2016, including $36,935 in market and $20,389 in non-market productivity. Lifetime productivity at birth, using a 3% discount rate, is roughly $1.5 million if earnings grow by 1% per year and $1.2 million if future earnings growth averages 0.5% per year. CONCLUSIONS: Inclusion of avoidable productivity losses in societal-perspective CEAs of health interventions is recommended in new US cost-effectiveness guidelines. However, estimates vary depending on whether analysts choose to estimate total productivity or just market productivity and on assumptions made about growth in future productivity and earnings.

To determine whether CDC-funded HIV testing programs are reaching persons disproportionately affected by HIV infection. The percentage distribution for HIV testing and diagnoses by demographics and transmission risk group (diagnoses only) were calculated using 2013 data from CDC's National HIV Surveillance System and CDC's national HIV testing program data. In 2013, nearly 3.2 million CDC-funded tests were provided to persons aged 13 years and older. Among persons who received a CDC-funded test, 41.1 % were aged 20-29 years; 49.2 % were male, 46.2 % were black/African American, and 56.2 % of the tests were conducted in the South. Compared with the characteristics of all persons diagnosed with HIV in the United States in 2013, among persons diagnosed as a result of CDC-funded tests, a higher percentage were aged 20-29 years (40.3 vs 33.7 %) and black/African American (55.3 vs 46.0 %). CDC-funded HIV testing programs are reaching young people and blacks/African Americans.

OBJECTIVE: The Enhanced Comprehensive HIV Prevention Planning project was the first initiative of the Centers for Disease Control and Prevention (CDC) to address the goals of the National HIV/AIDS Strategy (NHAS). Health departments in 12 U.S. cities with a high prevalence of AIDS conducted comprehensive program planning and implemented cost-effective, scalable HIV prevention interventions that targeted high-risk populations. We examined trends in health department HIV prevention programs in these cities during the project. METHODS: We analyzed the number of people who received partner services, condoms distributed, and people tested for HIV, as well as funding allocations for selected HIV prevention programs by year and by site from October 2010 through September 2013. We assessed trends in the proportional change in services and allocations during the project period using generalized estimating equations. We also conducted thematic coding of program activities that targeted people living with HIV infection (PLWH). RESULTS: We found significant increases in funding allocations for HIV testing and condom distribution. All HIV partner services indicators, condom distribution, and HIV testing of African American and Hispanic/Latino populations significantly increased. HIV tests associated with a new diagnosis increased significantly among those self-identifying as Hispanic/Latino but significantly decreased among African Americans. For programs targeting PLWH, health department activities included implementing new program models, improving local data use, and building local capacity to enhance linkage to HIV medical care, retention in care, and treatment adherence. CONCLUSIONS: Overall, these findings indicate that health departments in areas with a high burden of AIDS successfully shifted their HIV prevention resources to scale up important HIV programs and make progress toward NHAS goals. © 2016 Association of Schools and Programs of Public Health.

HIV prevalence and socio-demographic data were analyzed to assess the alignment of CDC-funded HIV testing activity in 2012 with its high-impact prevention approach. CDC-funded HIV-testing was conducted in counties with high HIV prevalence and in places potentially more affected by HIV as measured by urbanicity, percent black, percent poverty, and percent uninsured. The percent Hispanic/Latino was associated with a lower probability of HIV testing activity. Higher percentages of black and Hispanic/Latino in the population was positively associated with new HIV diagnoses. Analyzing county-level data confirmed the appropriateness of CDC-funded HIV testing activities under a high-impact prevention approach but also suggested areas for possible improvement.

BACKGROUND: Nontyphoidal Salmonella causes an estimated 1.2 million infections, 23,000 hospitalizations, and 450 deaths annually in the United States. Most illnesses are self-limited; however, treatment with antimicrobial agents can be life-saving for invasive infections. METHODS: The Foodborne Diseases Active Surveillance Network and the National Antimicrobial Resistance Monitoring System collaborated on a prospective cohort study of patients with nontyphoidal Salmonella bloodstream and gastrointestinal infections to determine differences in the clinical outcomes of resistant compared with pansusceptible infections. Interviews were conducted within 85 days of specimen collection date. RESULTS: Of 875 nontyphoidal Salmonella isolates, 705 (81%) were pansusceptible, 165 (19%) were resistant to at least 1 agent, and 5 (0.6%) had only intermediate resistance. The most common pattern, found in 51 (31%) of resistant isolates, was resistance to at least ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline (ACSSuT); 88% of isolates with this pattern were serotype Typhimurium or Newport. Fourteen (52%) of the 27 ceftriaxone-resistant isolates were also ACSSuT resistant. Adjusted for age and serotype, bloodstream infection was significantly more common among patients infected with strains resistant to only two, only three, or only five antimicrobial classes, to ACSSuT with or without other agents, to ACSSuT only, or to nalidixic acid with or without other agents than among patients with pansusceptible isolates. Adjusted for age, serotype, and bloodstream infection, hospitalization was significantly more common among patients infected with strains resistant to only three agents or to ceftriaxone (all ceftriaxone-resistant isolates were resistant to other agents) than among patients with pansusceptible isolates. CONCLUSION: This study extends evidence that patients with antimicrobial-resistant nontyphoidal Salmonella infections have more severe outcomes. Prevention efforts are needed to reduce unnecessary antimicrobial use in patient care settings and in food animals to help prevent the emergence of resistance and infections with resistant nontyphoidal Salmonella.

BACKGROUND: Salmonella is a major bacterial pathogen transmitted commonly through food. Increasing resistance to antimicrobial agents (e.g., ceftriaxone, ciprofloxacin) used to treat serious Salmonella infections threatens the utility of these agents. Infection with antimicrobial-resistant Salmonella has been associated with increased risk of severe infection, hospitalization, and death. We describe changes in antimicrobial resistance among nontyphoidal Salmonella in the United States from 1996 through 2009. METHODS: The Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System conducts surveillance of resistance among Salmonella isolated from humans. From 1996 through 2009, public health laboratories submitted isolates for antimicrobial susceptibility testing. We used interpretive criteria from the Clinical and Laboratory Standards Institute and defined isolates with ciprofloxacin resistance or intermediate susceptibility as nonsusceptible to ciprofloxacin. Using logistic regression, we modeled annual data to assess changes in antimicrobial resistance. RESULTS: From 1996 through 2009, the percentage of nontyphoidal Salmonella isolates resistant to ceftriaxone increased from 0.2% to 3.4% (odds ratio [OR]=20, 95% confidence interval [CI] 6.3-64), and the percentage with nonsusceptibility to ciprofloxacin increased from 0.4% to 2.4% (OR=8.3, 95% CI 3.3-21). The percentage of isolates that were multidrug resistant (resistant to ≥3 antimicrobial classes) decreased from 17% to 9.6% (OR=0.6, 95% CI 0.5-0.7), which was driven mainly by a decline among serotype Typhimurium. However, multidrug resistance increased from 5.9% in 1996 to a peak of 31% in 2001 among serotype Newport and increased from 12% in 1996 to 26% in 2009 (OR=2.6, 95% CI 1.1-6.2) among serotype Heidelberg. CONCLUSIONS: We describe an increase in resistance to ceftriaxone and nonsusceptibility to ciprofloxacin and an overall decline in multidrug resistance. Trends varied by serotype. Because of evidence that antimicrobial resistance among Salmonella is predominantly a consequence of antimicrobial use in food animals, efforts are needed to reduce unnecessary use, especially of critically important agents.

Results of an environmental assessment conducted in a newly emergent focus of murine typhus in southern California are described. Opossums, Didelphis virginiana Kerr, infested with cat fleas, Ctenocephalides felis Buche, in the suburban area were abundant. Animal and flea specimens were tested for the DNA of two flea-borne rickettsiae, Rickettsia typhi and Rickettsia felis. R. felis was commonly detected in fleas collected throughout this area while R. typhi was found at a much lower prevalence in the vicinity of just 7 of 14 case-patient homes identified. DNA of R. felis, but not R. typhi, was detected in renal, hepatic, and pulmonary tissues of opossums. In contrast, there were no hematologic polymerase chain reaction findings of R. felis or R. typhi in opossums, rats, and cats within the endemic area studied. Our data suggest a significant probability of human exposure to R. felis in the area studied; however, disease caused by this agent is not recognized by the medical community and may be misdiagnosed as murine typhus using nondiscriminatory serologic methods.

Within 5 months after the earliest detection of human influenza A(H1N1)pdm09 virus, we found molecular and culture evidence of the virus in healthy US show pigs. The mixing of humans and pigs at swine shows possibly could further the geographic and cross-species spread of influenza A viruses.

BACKGROUND: Treatment of shigellosis with appropriate antimicrobial agents shortens duration of illness and bacterial shedding, but resistance to commonly used agents is increasing. METHODS: We describe resistance patterns among Shigella isolates in the United States with use of linked data from the Foodborne Diseases Active Surveillance Network (FoodNet) and National Antimicrobial Resistance Monitoring System (NARMS). FoodNet sites send every 20th Shigella isolate to the NARMS laboratory for susceptibility testing. RESULTS: During 2000-2010, the NARMS laboratory tested 1376 Shigella isolates from FoodNet sites. Of 1118 isolates (81%) linked to FoodNet, 826 (74%) were resistant to ampicillin, 649 (58%) to streptomycin, 402 (36%) to trimethoprim-sulfamethoxazole (TMP-SMX), 355 (32%) to sulfamethoxazole-sulfisoxazole, 312 (28%) to tetracycline, 19 (2%) to nalidixic acid, and 6 (0.5%) to ciprofloxacin. The proportion of Shigella isolates with resistance to TMP-SMX was 40% among white persons, 58% among Hispanic persons, and 75% among persons with a history of international travel. Resistance to at least TMP-SMX and ampicillin was present in 25% of isolate, and 5% were resistant to ampicillin, TMP-SMX, and chloramphenicol. Overall, 5% of isolates showed multidrug resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole-sulfisoxazole, and tetracycline, including 49 Shigella flexneri (33%) and 3 Shigella sonnei (0.3%) isolates. Male individuals were more likely than female individuals to be infected with a multidrug-resistant strain (7% versus 3%; P < .01). CONCLUSIONS: Antimicrobial resistance differed by race, ethnicity, age, travel, and species. Resistance to commonly used antibiotics is high; therefore, it is important to look at the susceptibility pattern before starting treatment.

Nontyphoidal salmonellae (NTS) are important causes of community-acquired bloodstream infection. We describe patterns of antimicrobial resistance among invasive NTS in the United States. We compared bloodstream NTS isolates with those from stool submitted to the National Antimicrobial Resistance Monitoring System (NARMS) from 1996-2007. We described antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median age (range) of patients with and without bacteremia was 36 (0, 97) years and 20 (0, 105) years, respectively (p<0.001). Males (OR 1.21, 95% CI 1.06, 1.38) and those aged ≥65 years were at greater risk for invasive disease. Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; Dublin, Sandiego, and Schwarzengrund were associated with the greatest risk for bloodstream isolation. Of invasive isolates 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%) isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone. Antimicrobial resistance to traditional agents is common. However, the occurrence of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for clinical and public health vigilance.

CTX-M-type Beta-lactamases are increasing among US Enterobacteriaceae isolates. Of 2,165 non-Typhi Salmonella isolates submitted in 2007 to the National Antimicrobial Resistance Monitoring System, 100 (4.6%) displayed elevated MICs (≥2 mg/L) of ceftriaxone or ceftiofur. Three isolates (serotypes Typhimurium, Concord, and I 4,5,12:i:-) contained blaCTX-M-5, blaCTX-M-15, and blaCTX-M-55/57, respectively.

Classic murine typhus, caused by Rickettsia typhi, is endemic in the continental United States in areas of Texas and southern California. We conducted an environmental investigation in an urban area of Los Angeles identified as the probable exposure site for a case of murine typhus. Four Rattus norvegicus heavily infested with Xenopsylla cheopis (average 32.5 fleas per animal, range 20-42) were trapped, and fleas, blood, and tissues were collected. DNAs from all specimens were tested for R. typhi and Rickettsia felis using a TaqMan assay targeting the rickettsial citrate synthase gene. Although rickettsiemia was not detected, DNA of R. felis was detected in at least one tissue from each rat. Tissues from 3 rats were also positive for R. typhi DNA. R. typhi and R. felis DNAs were detected in fleas collected from each animal with average minimal infection rates of 10% and 32.3%, respectively. Although R. typhi still circulates in urban Los Angeles in the classic Oriental flea-rat cycle, R. felis is more prevalent, even in this association.