The consumption of alcohol and other substances during pregnancy can impair prenatal development. While scientifically informed public health measures have raised awareness of the risks of harmful prenatal substance exposures, the use of alcohol and other substances during pregnancy continues to rise. The successful dissemination of consistent messaging, health care professional education and training, and universal implementation of clinical interventions may help reduce drinking in pregnancy and prevent fetal alcohol spectrum disorders (FASDs), a constellation of developmental disabilities and birth defects caused by alcohol use during pregnancy. Alcohol screening and brief intervention (alcohol SBI) is an evidence-based preventive practice that enables early identification of excessive drinking and intervention prior to serious consequences. Routine clinical implementation of alcohol SBI has been shown to effectively reduce excessive alcohol consumption among adults, including pregnant people. Many barriers prevent widespread implementation of the practice: a lack of health care professional knowledge of the prevalence and implications of prenatal alcohol exposure, stigma surrounding individuals who use substances potentially harmful to their pregnancy, resistance to public health messages encouraging alcohol avoidance during pregnancy, and discomfort and hesitancy with alcohol SBI procedures among practitioners. The Centers for Disease Control and Prevention (CDC) leads the public health effort to prevent alcohol use during pregnancy and improve identification of and care for children living with FASDs. CDC partners with health systems, health care professional associations, universities, and community-based networks to promote alcohol SBI as an effective but underused preventive health service. This special section consisting of 6 articles including this introductory commentary represents the efforts of 11 CDC projects and their partners to demonstrate the rationale for FASD prevention and intervention, engage health care disciplines to expand prevention messaging and education for providers, develop practical approaches for implementing alcohol SBI in diverse clinical settings, and prevent alcohol use in pregnancy and FASDs.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Bartonella quintana infection can lead to bacillary angiomatosis, peliosis hepatis, chronic bacteremia, and culture-negative endocarditis. Transmitted by the human body louse (Pediculus humanus humanus), B. quintana infection has become an emerging disease in recent decades among persons experiencing homelessness. By using retrospective laboratory surveillance, we identified 5 cases of left-sided, culture-negative B. quintana endocarditis among persons in New York, New York, USA, during January 1, 2020-November 23, 2023. Identifications were made by using molecular assays. All patients experienced unsheltered homelessness in the year before hospitalization. Of those patients, 4 experienced heart failure, 3 renal failure, and 2 embolic strokes; 2 died. Aortic valve replacement occurred in 4 cases. A history of possible body louse infestation was found in 4 cases. Clinicians should consider housing status and history of lice exposure in patients with suspected bartonellosis and have a low threshold for diagnostic testing and empiric treatment in patients experiencing homelessness.

Beyond its physical health impact, the COVID-19 pandemic also resulted in grief from loss of loved ones, isolation due to social distancing, stress, fear, and economic distress-all of which impacted mental health. How Right Now/Qué Hacer Ahora (HRN) is an award-winning, national campaign that provides emotional support to people disproportionately affected by COVID-19. We conducted a theory-based, culturally responsive evaluation to assess the campaign's effect on coping behaviors and resiliency between summer 2020 and spring 2021. We surveyed HRN's priority audiences (older adults/caregivers and those with preexisting health conditions, experiencing violence, or economic distress) in English and Spanish using NORC's national probability panel, AmeriSpeak, over three waves. We also analyzed social media data and monitored HRN website traffic and triangulated these data to understand the campaign's full impact. Campaign exposure was associated with people who were experiencing higher levels of stress and were more likely to seek information to support their emotional well-being. Campaign exposure was also positively associated with increased feelings of resilience and confidence in using coping strategies, especially for people experiencing violence or economic distress and people from racial and ethnic groups. Findings demonstrate the campaign's success in reaching its intended audiences with the mental health support they needed. Additionally, the HRN evaluation's design illustrates how the use of multiple data sources can elucidate a deeper understanding of campaign impact. Findings underscore that culturally responsive health communication interventions-like HRN-can provide needed mental health support and resources to disproportionately affected communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

BACKGROUND: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. METHODS: We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. FINDINGS: Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. INTERPRETATION: Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. FUNDING: The Centers for Disease Control and Prevention.

Adult-onset asthma, notably prevalent among healthcare professionals, especially nurses, is often attributed to occupational factors such as exposure to cleaning agents. Studies consistently underscore the substantial role of such exposure in work-related asthma among hospital staff. We aimed to (a) identify and characterize current practices in cleaning and aerosolized medication administration; (b) assess changes in practices since a similar 2003 study of Texas healthcare workers; and (c) identify factors contributing to diverse exposures within healthcare job categories. We conducted focus groups with 38 participants in 6 healthcare settings, analyzing current practices, changes since 2003, and factors contributing to exposure diversity. We used a three-step approach for data analysis, including sociodemographic characterization, a scissor-and-sort technique for exposure description, and qualitative content analysis. Participants were primarily healthcare providers (76%) and housekeepers/cleaners (11%) who reported exposure to aerosolized medications, cleaning products, adhesives, and solvents. Participants reported transitioning from cleaning practices to new formulas with reduced odors and shifting from spray cleansers to wipes. Personal protective equipment (PPE) used during cleaning tasks varied, with training differing among job categories. Aerosolized medication administration varied among facilities, with reported medication types and protocol changes over time. The results emphasized the significance of maintaining uniform protection, disseminating knowledge, and consistently adhering to PPE protocols in the healthcare environment. Addressing the identified gaps in comprehension and potential sources of exposure variability requires additional focus on occupational health and safety initiatives.

INTRODUCTION: Envenomation after a North American rattlesnake (Crotalus spp. and Sistrusus spp.) bite is associated with substantial morbidity. Arizona reports the highest number of rattlesnake envenomations annually in the United States. We evaluated the performance of poison and drug information centers for snakebite surveillance, compared with the hospital and emergency department discharge database. We used both datasets to improve the characterization of epidemiology, healthcare costs, and clinical effects of snakebite envenomations in Arizona. METHODS: We identified patients with a snakebite during 2017-2021 using Arizona hospital and emergency department discharge data and snakebite consults with two regional Arizona poison centers. Patients were matched using name and birthdate. The performance of poison center data for snakebite surveillance was evaluated using the percentage of snakebite patients in hospital and emergency department discharge data that consulted with poison centers. Patient demographics, healthcare characteristics, clinical effects, and context of snakebite events were described using both datasets. RESULTS: In total, 1,288 patients with a snakebite were identified using the Arizona hospital and emergency department discharge data, which resulted in 953 (74%) consultations with poison centers. The median age of patients was 48 years (IQR 28-62 years), and they were predominantly male (66%), White (90%), and non-Hispanic (84%). The median billed charges were US$ 84,880 (IQR US$ 13,286-US$ 168,043); the median duration of a healthcare stay was 34 h (IQR 13-48 h), and 29% of patients were transferred between healthcare facilities. Among 953 consulted poison center calls for a snakebite, a median of 14 vials of antivenom was administered per patient; 375 (60%) bites occurred near the home, and 345 (43%) patients were bitten on a lower extremity. One death was identified. DISCUSSION: Snakebites in Arizona can cause severe morbidity and require extensive healthcare resources for treatment. Poison centers are valuable for monitoring venomous snakebites in Arizona. CONCLUSIONS: Using hospital and emergency department discharge data with poison center records can improve public health surveillance data regarding snakebite epidemiology and human-snake interaction information and be used to tailor interventions to increase awareness of snake encounters and prevent snakebites.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection(1,2), yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) needs leaders at all levels who can address technical and adaptive challenges in a changing public health landscape. We assessed the feasibility of implementing an enterprise-wide leadership development model. METHODS: In June 2023, we launched a pilot program, Learn and Lead, for nonsupervisory staff in early and mid-career levels. One hundred sixty-nine participants registered, and 149 completed at least 6 weeks of the 8-week program. We gathered quantitative and qualitative data through weekly electronic surveys and in-depth interviews. We calculated frequencies for closed-ended Likert-scale items and performed content analysis of open-ended items to assess most frequently mentioned themes. We based the pilot's design on CDC's leadership development framework to assess application of the framework and alignment of curriculum to the framework. RESULTS: Three themes emerged: logistics and facilitation, leadership development curriculum, and making connections with self and others. Findings for logistics and facilitation highlighted preferences for course length, small breakout groups, mixed weeks, and value of staff support. Findings for the leadership development curriculum underscored the relevance of the US Office of Personnel Management's fundamental competencies to leadership development. Findings for making connections with self and others supported the cohort model and the importance of networking. CONCLUSIONS: The pilot curriculum aligned well with the CDC leadership development framework. Feedback provided by pilot participants is being used to help shape CDC's ongoing leadership development efforts.

Antimicrobial resistance (AMR) is a world-wide public health threat that is projected to lead to 10 million annual deaths globally by 2050. The AMR public health issue has led to the development of action plans to combat AMR, including improved antimicrobial stewardship, development of new antimicrobials, and advanced monitoring. The National Antimicrobial Resistance Monitoring System (NARMS) led by the United States (U.S) Food and Drug Administration along with the U.S. Centers for Disease Control and U.S. Department of Agriculture has monitored antimicrobial resistant bacteria in retail meats, humans, and food animals since the mid 1990's. NARMS is currently exploring an integrated One Health monitoring model recognizing that human, animal, plant, and environmental systems are linked to public health. Since 2020, the U.S. Environmental Protection Agency has led an interagency NARMS environmental working group (EWG) to implement a surface water AMR monitoring program (SWAM) at watershed and national scales. The NARMS EWG divided the development of the environmental monitoring effort into five areas: (i) defining objectives and questions, (ii) designing study/sampling design, (iii) selecting AMR indicators, (iv) establishing analytical methods, and (v) developing data management/analytics/metadata plans. For each of these areas, the consensus among the scientific community and literature was reviewed and carefully considered prior to the development of this environmental monitoring program. The data produced from the SWAM effort will help develop robust surface water monitoring programs with the goal of assessing public health risks associated with AMR pathogens in surface water (e.g., recreational water exposures), provide a comprehensive picture of how resistant strains are related spatially and temporally within a watershed, and help assess how anthropogenic drivers and intervention strategies impact the transmission of AMR within human, animal, and environmental systems.

Malaria is a severe and potentially fatal mosquitoborne disease caused by infection with Plasmodium spp. parasites. Although malaria is no longer endemic in the United States, imported infections are reported annually; the primary risk group has been U.S. residents traveling to areas where malaria is endemic (1). In 2023, sporadic locally acquired mosquito-transmitted malaria cases were reported in several U.S. states (2,3). This report describes increases in imported malaria cases in 2023 compared with 2022 in three public health jurisdictions along the U.S. southern border.

Pre-exposure prophylaxis (PrEP) with a weekly oral regimen of antiretroviral drugs could be a suitable preventative option for individuals who struggle with daily PrEP or prefer not to use long-acting injectables. We assessed in macaques the efficacy of weekly oral tenofovir alafenamide (TAF) at doses of 13.7 or 27.4 mg/kg. Macaques received weekly oral TAF for six weeks and were exposed twice-weekly to SHIV vaginally or rectally on day 3 and 6 after each dose. Median TFV-DP levels in PBMCs following the 13.7 mg/kg dose were 3110 and 1137 fmols/10(6) cells on day 3 and 6, respectively. With the 27.4 mg/kg dose, TFV-DP levels were increased (~2-fold) on day 3 and 6 (6095 and 3290 fmols/10(6) cells, respectively). Both TAF doses (13.7 and 27.4 mg/kg) conferred high efficacy (94.1% and 93.9%, respectively) against vaginal SHIV infection. Efficacy of the 27.4 mg/kg dose against rectal SHIV infection was 80.7%. We estimate that macaque doses of 13.7 and 27.4 mg/kg are equivalent to approximately 230 and 450 mg of TAF in humans, respectively. Our findings demonstrate the effectiveness of a weekly oral PrEP regimen and suggest that a clinically achievable oral TAF dose could be a promising option for non-daily PrEP.

BACKGROUND: In 2014, UNAIDS set a goal to end the AIDS epidemic by achieving targets for the percentage of people living with HIV who were aware of their status, on antiretroviral therapy (ART), and virally suppressed. In 2020, these targets were revised to 95% for each measure (known as 95-95-95), to be reached among people living with HIV by 2025. We used data from the Fifth Botswana AIDS Impact Survey (BAIS V) to measure progress towards these testing and treatment targets in Botswana. METHODS: BAIS V used a two-stage cluster design to obtain a nationally representative sample of people aged 15-64 years in Botswana. During March-August, 2021, 14 763 consenting participants were interviewed and tested for HIV in their households by survey teams. HIV-positive specimens were tested for viral load, presence of antiretroviral drugs, and recency of infection using the HIV-1 limiting antigen avidity enzyme immunoassay. Estimates of HIV-positive status and use of ART were based on self-report and the analysis of blood specimens for antiretroviral drugs. Viral load suppression was defined as an HIV RNA concentration of less than 1000 copies per mL. HIV incidence was calculated using the recent infection testing algorithm. Data were weighted to account for the complex survey design. FINDINGS: The national HIV prevalence in Botswana among people aged 15-64 years was 20·8% and the annual incidence of HIV infection was 0·2%. 95·1% (men 93·0%, women 96·4%) of people living with HIV aged 15-64 years were aware of their status, 98·0% (men 97·2%, women 98·4%) of those aware were on ART, and 97·9% (men 96·6%, women 98·6%) of those on ART had viral load suppression. Among young people (aged 15-24 years) living with HIV, 84·5% were aware of their status, 98·5% of those aware were on ART, and 91·6% of those on ART had viral load suppression. The prevalance of viral load suppression among all people living with HIV was 91·8%, and varied by district-ranging from 85·3% in Gaborone to 100·0% in Selibe Phikwe. INTERPRETATION: BAIS V is the first population-based survey worldwide to report the achievement of the UNAIDS 95-95-95 goals, both overall and among women. Strategies to reach undiagnosed men and young people, including young women, are needed. FUNDING: US President's Emergency Plan for AIDS Relief.

Viral pathogenesis and therapeutic screening studies that utilize small mammalian models rely on the accurate quantification and interpretation of morbidity measurements, such as weight and body temperature, which can vary depending on the model, agent and/or experimental design used. As a result, morbidity-related data are frequently normalized within and across screening studies to aid with their interpretation. However, such data normalization can be performed in a variety of ways, leading to differences in conclusions drawn and making comparisons between studies challenging. Here, we discuss variability in the normalization, interpretation, and presentation of morbidity measurements for four model species frequently used to study a diverse range of human viral pathogens - mice, hamsters, guinea pigs and ferrets. We also analyze findings aggregated from influenza A virus-infected ferrets to contextualize this discussion. We focus on serially collected weight and temperature data to illustrate how the conclusions drawn from this information can vary depending on how raw data are collected, normalized and measured. Taken together, this work supports continued efforts in understanding how normalization affects the interpretation of morbidity data and highlights best practices to improve the interpretation and utility of these findings for extrapolation to public health contexts.

In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state and local health and regulatory partners investigated an outbreak of Salmonella enterica serovar Oranienburg infections linked to bulb onions from Mexico, resulting in 1040 illnesses and 260 hospitalizations across 39 states, the District of Columbia, and Puerto Rico. The Kansas Department of Agriculture recovered the outbreak strain of Salmonella Oranienburg from a sample of condiment collected from an ill person's home. The condiment was made with cilantro, lime, and onions, but, at the time of collection, there were no onions remaining in it. FDA conducted traceback investigations for white, yellow, and red bulb onions, cilantro, limes, tomatoes, and jalapeño peppers. Growers in the state of Chihuahua, Mexico, were identified as supplying the implicated onions that could account for exposure to onions for all illnesses included in the traceback investigation, but investigators could not determine a single source or route of contamination. FDA collected product and environmental samples across the domestic supply chain but did not recover the outbreak strain of Salmonella. Binational collaboration and information sharing supported Mexican authorities in collecting environmental samples from two packing plants and onion, water, and environmental samples from 15 farms and firms in Chihuahua, Mexico identified through FDA's traceback investigation, but did not recover the outbreak strain. Distributors of the implicated onions issued voluntary recalls of red, yellow, and white whole, fresh onions imported from the state of Chihuahua, Mexico. This outbreak showcased how investigators overcame significant traceback and epidemiologic challenges, the need for strengthening the ongoing collaboration between U.S. and Mexican authorities and highlighted the need for identifying practices across the supply chain that can help improve the safety of onions. © 2024

New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 μmol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 μmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.

BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

INTRODUCTION: From January 2021 to June 2022, the United States Centers for Disease Control and Prevention required predeparture SARS-CoV-2 testing for all air passengers arriving into the United States from a foreign country. METHODS: Using data collected during a surveillance project, we described predeparture testing behavior among a convenience sample of international air passengers entering the United States from July to September 2021 at six US ports of entry. We analyzed pairwise relationships between self-reported test type, test timing, demographic and travel characteristics, and COVID-19 vaccination status using chi-square and Fisher's exact tests. RESULTS: Participants were more likely to get a NAAT versus antigen test if they identified as non-Hispanic Asian or Pacific Islander (68.2%, n = 173), non-Hispanic Black (62.6%, n = 147), or if they preferred not to report race and ethnicity (60.8%, n = 209) when compared to those who identified as non-Hispanic White (47.1%, n = 1086, all p < 0.05). Those who identified as Hispanic or Latino (n = 671) were less likely to get a NAAT than the non-Hispanic White group (39.5% vs. 47.1%, p < 0.05). Participants arriving in the US from the Americas were less likely to get a NAAT (38.5%, n = 871) compared to those arriving from Europe (45.5%, n = 1165, p < 0.05). Participants who reported receiving their predeparture test 2 days or 3 or more days before departure were more likely to report receiving a NAAT (52.2%, n = 879, and 60.2%, n = 410, respectively) than those who reported testing within 1 day (41.4%, n = 1040, all p < 0.001) of departure. DISCUSSION: Test type was significantly associated with race and ethnicity, departure region, and test timing. Differences likely reflected regional disparities in the availability of tests at the time of the activity. Discrepancies in predeparture test timing and type worldwide may have consequences for the effectiveness and equity of travel requirements in future pandemics.

Background: The National Asthma Education and Prevention Program guidelines emphasize environmental control as an integral part of asthma management; however, limited national-level data exist on how clinicians implement environmental control recommendations. Objective: We analyzed data on clinicians’ self-reported use of recommended environmental control practices in a nationally representative sample (n = 1645) of primary care physicians, asthma specialists, and advanced practice providers from the National Asthma Survey of Physicians, a supplemental questionnaire to the 2012 National Ambulatory Medical Care Survey. Methods: We examined clinician and practice characteristics as well as clinicians’ decisions and strategies regarding environmental trigger assessment and environmental control across provider groups. Regression modeling was used to identify clinician and practice characteristics associated with implementation of guideline recommendations. Results: A higher percentage of specialists assessed asthma triggers at home, school, and/or work than primary care or advanced practice providers (almost always: 53.6% vs 29.4% and 23.7%, respectively, P <.001). Almost all clinicians (>93%) recommended avoidance of secondhand tobacco smoke, whereas recommendations regarding cooking appliances (eg, proper ventilation) were infrequent. Although assessment and recommendation practices differed between clinician groups, modeling results showed that clinicians who reported almost always assessing asthma control were 5- to 6-fold more likely to assess environmental asthma triggers. Use of asthma action plans was also strongly associated with implementation of environmental control recommendations. Conclusions: Environmental assessment and recommendations to patients varied among asthma care providers. High adherence to other key guideline components, such as assessing asthma control, was associated with environmental assessment and recommendation practices on environmental control. © 2023

Vaginal inserts that can be used on demand before or after sex may be a desirable HIV prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF/20mg) and elvitegravir (EVG/16mg) were highly protective against repeated SHIV vaginal exposures when administered to macaques 4h before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8h or 24h after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.

The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

Bartonella quintana infection is a vectorborne disease transmitted by the human body louse (1). In the United States, homelessness is the principal risk factor for B. quintana infection (2), likely attributable to limited access to hygiene facilities (1). This infection is not nationally notifiable in the United States, and its incidence is unknown. Acute B. quintana infection can cause fever, headache, and bone pain; severe manifestations include chronic bacteremia, bacillary angiomatosis, and infective endocarditis (3). Because the bacterium requires special conditions to grow in culture, standard blood cultures are usually negative (4). Diagnosis by serology is most common; however, cross-reactivity with other Bartonella species (e.g., B. henselae) can hamper interpretation. Molecular assays specific for B. quintana have been developed (5), but availability is limited to a few laboratories. Once diagnosed, infection can be cured by several weeks to months of antibiotic therapy.

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.

OBJECTIVE: Healthcare workers (HCWs) are at risk for work-related asthma, which may be affected by changes in cleaning practices. We examined associations of cleaning tasks and products with work-related asthma in HCWs in 2016, comparing them to prior results from 2003. METHODS: We estimated asthma prevalence by professional group, and explored associations of self-reported asthma with job-exposure matrix-based cleaning tasks/products in a representative Texas sample of 9914 physicians, nurses, respiratory/occupational therapists, and nurse aides. RESULTS: Response rate was 34.8%(n = 2,421). The weighted prevalences of physician-diagnosed(15.3%), work-exacerbated (4.1%), and new-onset asthma(NOA) (6.7%), and bronchial hyperresponsiveness symptoms(31.1%) were similar to 2003. NOA was associated with building surface cleaning(OR = 1.91; 95%CI:1.10-3.33), use of orthophthalaldehyde(OR = 1.77; 95%CI:1.15-2.72), bleach/quaternary compounds(OR = 1.91; 95%CI:1.10-3.33), and sprays(OR = 1.97; 95%CI:1.12-3.47). CONCLUSION: Prevalence of asthma/BHR appears unchanged, whereas associations of NOA with exposures to surface cleaning remained, and decreased for instrument cleaning.

BACKGROUND: The epidemiology of COVID-19 continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of hospitalized COVID-19 and risk factors for critical outcomes over time. METHODS: We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023 when multiple SARS-CoV-2 variants or sub-lineages predominated. We evaluated changes in baseline demographic and clinical characteristics and critical outcomes (intensive care unit admission and/or death) and used regression models to evaluate critical outcomes risk factors (risk ratios) stratified by COVID-19 vaccination status. RESULTS: 60,488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, from Delta period (June-December 2021) to the Omicron post-BA.4/BA.5 period (September 2022-March 2023), median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, while critical outcomes declined from 24.8% to 19.4% (all p < 0.001). Compared to all hospitalization events, those with critical outcomes had a higher proportion of four or more categories of medical conditions categories assessed (32.8% critical versus 23.0% all hospitalized). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated aRR 2.27 [95% CI: 2.14-2.41]; vaccinated aRR 1.73 [95% CI: 1.56-1.92]) across periods. CONCLUSION: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time and median patient age increased with time. Multimorbidity was mostly strongly associated with critical outcomes.

American Indian and Alaska Native (AI/AN) communities draw strength from Tribal culture and traditional ways of life, but social determinants of health, such as poverty, racial discrimination, unemployment, poor housing, and inadequate access to health care, contribute to persistent health disparities.1-3 Despite their resilience, AI/AN communities have disproportionate rates of obesity, diabetes, and other chronic and infectious diseases, including influenza, pneumonia, and COVID-19.4-9 The public health infrastructure required to address these inequities, however, is under-resourced and underdeveloped.10-12 The COVID-19 pandemic compounded these long-standing health inequities, elevating the need to address gaps in the current public health infrastructure.13-21 | In national health initiatives, Healthy People 2030,22,23 Public Health 3.0,24 and the 10 Essential Public Health Services framework,25 strategies to address social determinants of health and health equity, are multifaceted and complex and require robust public health infrastructure. To address infrastructure needs in AI/AN communities, the Centers for Disease Control and Prevention (CDC) developed the Tribal Epidemiology Center Public Health Infrastructure (TECPHI) program, a 5-year investment (2017-2022) to address gaps in data and build public health capacity to promote health and prevent disease in AI/AN communities.26,27 The impetus for the TECPHI program came from recommendations from the CDC/Agency for Toxic Substances and Disease Registry Tribal Advisory Committee, which supports CDC’s government-to-government relationship with Tribes and allows for engagement with Tribal leaders on approaches to promote health in AI/AN communities.28

The COVID-19 pandemic sparked the development of novel anti-viral drugs that have shown to be effective in reducing both fatality and hospitalization rates in patients with elevated risk for COVID-19 related morbidity or mortality. Currently, nirmatrelvir/ritonavir (Paxlovid™) fixed-dose combination is recommended by the World Health Organization for treatment of COVID-19. The ritonavir component is an inhibitor of cytochrome P450 (CYP) 3A, which is used in this combination to achieve needed therapeutic concentrations of nirmatrelvir. Because of the critical pharmacokinetic effect of this mechanism of action for Paxlovid™, co-administration with needed medications that inhibit or induce CYP3A is contraindicated, reflecting concern for interactions with the potential to alter the efficacy or safety of co-administered drugs that are also metabolized by CYP3A. Some herbal medicines are known to interact with drug metabolizing enzymes and transporters, including but not limited to inhibition or induction of CYP3A and P-glycoprotein. As access to these COVID-19 medications has increased in low- and middle-income countries (LMICs), understanding the potential for herb-drug interactions within these regions is important. Many studies have evaluated the utility of herbal medicines for COVID-19 treatments, yet information on potential herb-drug interactions involving Paxlovid™, specifically with herbal medicines commonly used in LMICs, is lacking. This review presents data on regionally-relevant herbal medicine use (particularly those promoted as treatments for COVID-19) and mechanism of action data on herbal medicines to highlight the potential for herbal medicine interaction Herb-drug interaction mediated by ritonavir-boosted antiviral protease inhibitors This work highlights potential areas for future experimental studies and data collection, identifies herbal medicines for inclusion in future listings of regionally diverse potential HDIs and underscores areas for LMIC-focused provider-patient communication. This overview is presented to support governments and health protection entities as they prepare for an increase of availability and use of Paxlovid™.