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Issue 6, February 7, 2023

CDC Science Clips: Volume 15, Issue 6, February 7, 2023

Welcome to CDC Science Clips, CDC’s weekly publications digest.

This week, Science Clips is pleased to feature articles related to the new CDC Vital Signs on Preventing Bloodstream Infections in People on Dialysis.

More than 800,000 people in the U.S. live with end-stage kidney disease, and more than half of them belong to a racial or ethnic minority group. Some people with end-stage kidney disease have a kidney transplant, but most receive dialysis treatments.

Dialysis treatment puts patients at higher risk for serious infections that may lead to sepsis and even death. Many germs can cause dialysis bloodstream infections. The most common is a group of germs called Staphylococcus aureus (staph).

More than 14,000 bloodstream infections occurred in patients on dialysis in the U.S. in 2020, and more than one in three were caused by staph. Staph bloodstream infections happen more often in Black and Hispanic patients on dialysis than White patients on dialysis. There are more staph bloodstream infections in areas of the U.S. with higher poverty, more household crowding, and lower education levels.

Preventing infections among patients receiving dialysis requires a broad and equitable approach to prevention and care of kidney disease for people from all racial, ethnic, and socioeconomic groups.

The names of CDC authors are indicated in bold text.

  1. CDC Vital Signs
    • Preventing Bloodstream Infections in People on Dialysis



      1. CKD and ESRD in US Hispanics
        Desai N, Lora CM, Lash JP, Ricardo AC.
        Am J Kidney Dis. 2019 Jan;73(1):102-111.
        Hispanics are the largest racial/ethnic minority group in the United States, and they experience a substantial burden of kidney disease. Although the prevalence of chronic kidney disease (CKD) is similar or slightly lower in Hispanics than non-Hispanic whites, the age- and sex-adjusted prevalence rate of end-stage renal disease is almost 50% higher in Hispanics compared with non-Hispanic whites. This has been attributed in part to faster CKD progression among Hispanics. Furthermore, Hispanic ethnicity has been associated with a greater prevalence of cardiovascular disease risk factors, including obesity and diabetes, as well as CKD-related complications. Despite their less favorable socioeconomic status, which often leads to limited access to quality health care, and their high comorbid condition burden, the risk for mortality among Hispanics appears to be lower than for non-Hispanic whites. This survival paradox has been attributed to a complex interplay between sociocultural and psychosocial factors, as well as other factors. Future research should focus on evaluating the long-term impact of these factors on patient-centered and clinical outcomes. National policies are needed to improve access to and quality of health care among Hispanics with CKD.

      2. Impact of poverty and health care insurance on arteriovenous fistula use among incident hemodialysis patients
        Nee R, Moon DS, Jindal RM, Hurst FP, Yuan CM, Agodoa LY, Abbott KC.
        Am J Nephrol. 2015 ;42(4):328-36.
        BACKGROUND: The impact of socioeconomic factors on arteriovenous fistula (AVF) creation in hemodialysis (HD) patients is not well understood. We assessed the association of area and individual-level indicators of poverty and health care insurance on AVF use among incident end-stage renal disease (ESRD) patients initiated on HD. METHODS: In this retrospective cohort study using the United States Renal Data System database, we identified 669,206 patients initiated on maintenance HD from January 1, 2007 through December 31, 2012. We assessed the Medicare-Medicaid dual-eligibility status as an indicator of individual-level poverty and ZIP code-level median household income (MHI) data obtained from the 2010 United States Census. We conducted logistic regression of AVF use at start of dialysis as the outcome variable. RESULTS: The proportions of dual-eligible and non-dual-eligible patients who initiated HD with an AVF were 12.53 and 16.17%, respectively (p<0.001). Dual eligibility was associated with significantly lower likelihood of AVF use upon initiation of HD (adjusted odds ratio (aOR) 0.91; 95% CI 0.90-0.93). Patients in the lowest area-level MHI quintile had an aOR of 0.97 (95% CI 0.95-0.99) compared to those in higher quintile levels. However, dual eligibility and area-level MHI were not significant in patients with Veterans Affairs (VA) coverage. CONCLUSIONS: Individual- and area-level measures of poverty were independently associated with a lower likelihood of AVF use at the start of HD, the only exception being patients with VA health care benefits. Efforts to improve incident AVF use may require focusing on pre-ESRD care to be successful.

      3. Racial disparities in invasive methicillin-resistant staphylococcus aureus infections, 2005-2014
        Gualandi N, Mu Y, Bamberg WM, Dumyati G, Harrison LH, Lesher L, Nadle J, Petit S, Ray SM, Schaffner W, Townes J, McDonald M, See I.
        Clin Infect Dis. 2018 Sep 28;67(8):1175-1181.
        BACKGROUND: Despite substantial attention to the individual topics, little is known about the relationship between racial disparities and antimicrobial-resistant and/or healthcare-associated infection trends, such as for methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We analyzed Emerging Infections Program 2005-2014 surveillance data (9 US states) to determine whether reductions in invasive MRSA incidence (isolated from normally sterile body sites) affected racial disparities in rates. Case classification included hospital-onset (HO, culture >3 days after admission), healthcare-associated community onset (HACO, culture ≤3 days after admission and dialysis, hospitalization, surgery, or long-term care residence within 1 year prior), or community-associated (CA, all others). Negative binomial regression models were used to evaluate the adjusted rate ratio (aRR) of MRSA in black patients (vs in white patients) controlling for age, sex, and temporal trends. RESULTS: During 2005-2014, invasive HO and HACO (but not CA) MRSA rates decreased. Despite this, blacks had higher rates for HO (aRR, 3.20; 95% confidence interval [CI], 2.35-4.35), HACO (aRR, 3.84; 95% CI, 2.94-5.01), and CA (aRR, 2.78; 95% CI, 2.30-3.37) MRSA. Limiting the analysis to chronic dialysis patients reduced, but did not eliminate, the higher HACO MRSA rates among blacks (aRR, 1.83; 95% CI, 1.72-1.96), even though invasive MRSA rates among dialysis patients decreased during 2005-2014. These racial differences did not change over time. CONCLUSIONS: Previous reductions in healthcare-associated MRSA infections have not affected racial disparities in MRSA rates. Improved understanding of the underlying causes of these differences is needed to develop effective prevention interventions that reduce racial disparities in MRSA infections.

      4. National Healthcare Safety Network (NHSN) dialysis event surveillance report for 2014
        Nguyen DB, Shugart A, Lines C, Shah AB, Edwards J, Pollock D, Sievert D, Patel PR.
        Clin J Am Soc Nephrol. 2017 Jul 7;12(7):1139-1146.
        BACKGROUND AND OBJECTIVES: Persons receiving outpatient hemodialysis are at risk for bloodstream and vascular access infections. The Centers for Disease Control and Prevention conducts surveillance for these infections through the National Healthcare Safety Network. We summarize 2014 data submitted to National Healthcare Safety Network Dialysis Event Surveillance. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dialysis facilities report three types of dialysis events (bloodstream infections; intravenous antimicrobial starts; and pus, redness, or increased swelling at the hemodialysis vascular access site). Denominator data consist of the number of hemodialysis outpatients treated at the facility during the first 2 working days of each month. We calculated dialysis event rates stratified by vascular access type (e.g., arteriovenous fistula, arteriovenous graft, or central venous catheter) and standardized infection ratios (comparing individual facility observed with predicted numbers of infections) for bloodstream infections. We described pathogens identified among bloodstream infections. RESULTS: A total of 6005 outpatient hemodialysis facilities reported dialysis event data for 2014 to the National Healthcare Safety Network. These facilities reported 160,971 dialysis events, including 29,516 bloodstream infections, 149,722 intravenous antimicrobial starts, and 38,310 pus, redness, or increased swelling at the hemodialysis vascular access site events; 22,576 (76.5%) bloodstream infections were considered vascular access related. Most bloodstream infections (63.0%) and access-related bloodstream infections (69.8%) occurred in patients with a central venous catheter. The rate of bloodstream infections per 100 patient-months was 0.64 (0.26 for arteriovenous fistula, 0.39 for arteriovenous graft, and 2.16 for central venous catheter). Other dialysis event rates were also highest among patients with a central venous catheter. Facility bloodstream infection standardized infection ratio distribution was positively skewed with a median of 0.84. Staphylococcus aureus was the most commonly isolated bloodstream infection pathogen (30.6%), and 39.5% of S. aureus isolates tested were resistant to methicillin. CONCLUSIONS: The 2014 National Healthcare Safety Network Dialysis Event data represent nearly all United States outpatient dialysis facilities. Rates of infection and other dialysis events were highest among patients with a central venous catheter compared with other vascular access types. Surveillance data can help define the epidemiology of important infections in this patient population.

      5. Race/ethnicity, age, and risk of hospital admission and length of stay during the first year of maintenance hemodialysis
        Yan G, Norris KC, Greene T, Yu AJ, Ma JZ, Yu W, Cheung AK.
        Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1402-9.
        BACKGROUND AND OBJECTIVES: Although patients undergoing maintenance hemodialysis have exceptionally high hospitalization rates, the risk factors for hospitalizations are unclear. This study sought to examine hospitalization rates among hemodialysis patients in the United States according to both race/ethnicity and age. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: US Renal Data System data on 563,281 patients beginning maintenance hemodialysis between 1995 and 2009 were analyzed. Rates of hospital admission and number of hospital days for all-cause and cause-specific hospitalizations during the first year of dialysis were compared among blacks, whites, and Hispanics in the entire cohort and subgroups stratified by age. RESULTS: After multiple adjustments, compared with whites, Hispanics overall had lower rates of both all-cause hospital days (adjusted rate ratio [aRR], 0.91; 95% confidence interval [95% CI], 0.90 to 0.93; P<0.001) and hospital admissions (aRR, 0.89; 95% CI, 0.88 to 0.90; P<0.001), whereas blacks had a lower rate of all-cause admissions (aRR, 0.95; 95% CI, 0.94 to 0.96; P<0.001). The racial/ethnic differences, however, varied by age. Hispanics exhibited the lowest rates of hospital days and admissions for all age groups≤70 years, but those >80 years had higher rates than their white counterparts. The adjusted black-to-white rate ratios exhibited a U-shaped pattern with age, with higher rates for blacks in the younger and older age groups. Hospitalization rates for dialysis-related infections were markedly higher in blacks and Hispanics than whites, which were consistent in all age groups for blacks (aRRs for hospital days ranged from 1.09 to 1.36) and all ages>60 years for Hispanics (aRRs ranged from 1.20 to 1.38). CONCLUSIONS: There are significant racial/ethnic differences in hospitalization rates within first year of dialysis, which are not consistent across the age groups and also differ by causes of hospitalization. Overall, blacks and Hispanics had lower rates of all-cause hospital admissions than whites. However, younger and older blacks and older Hispanics were at greatest risk.

      6. Impact of poverty and race on pre-end-stage renal disease care among dialysis patients in the United States
        Nee R, Yuan CM, Hurst FP, Jindal RM, Agodoa LY, Abbott KC.
        Clin Kidney J. 2017 Feb;10(1):55-61.
        BACKGROUND: Access to nephrology care prior to end-stage renal disease (ESRD) is significantly associated with lower rates of morbidity and mortality. We assessed the association of area-level and individual-level indicators of poverty and race/ethnicity on pre-ESRD care provided by nephrologists. METHODS: In this retrospective cohort study using the US Renal Data System database, we identified 739 537 patients initiated on maintenance dialysis from 1 January 2007 through 31 December 2012. We assessed the Medicare-Medicaid dual eligibility status as an indicator of individual-level poverty and ZIP code-level median household income (MHI) data obtained from the 2010 US census. We conducted multivariable logistic regression of pre-ESRD nephrology care as the outcome variable. RESULTS: Among patients in the lowest area-level MHI quintile, 61.28% received pre-ESRD nephrology care versus 67.68% among those in higher quintiles (P < 0.001). Similarly, the proportions of dual-eligible and nondual-eligible patients who had pre-ESRD nephrology care were 61.49 and 69.84%, respectively (P < 0.001). Patients in the lowest area-level MHI quintile were associated with significantly lower likelihood of pre-ESRD nephrology care (adjusted odds ratio [aOR] 0.86 [95% confidence interval (CI) 0.85-0.87]) compared with those in higher quintiles. Both African American (AA) and Hispanic patients were significantly less likely to have received pre-ESRD nephrology care [aOR 0.85 (95% CI 0.84-0.86) and aOR 0.72 (95% CI 0.71-0.74), respectively]. CONCLUSIONS: Individual- and area-level measures of poverty, AA race and Hispanic ethnicity were independently associated with a lower likelihood of pre-ESRD nephrology care. Efforts to improve pre-ESRD nephrology care may require focusing on the poor and minority groups.

      7. Racial and sex disparities in catheter use and dialysis access in the United States Medicare population
        Arya S, Melanson TA, George EL, Rothenberg KA, Kurella Tamura M, Patzer RE, Hockenberry JM.
        J Am Soc Nephrol. 2020 Mar;31(3):625-636.
        BACKGROUND: Despite efforts to increase arteriovenous fistula and graft use, 80% of patients in the United States start hemodialysis on a central venous catheter (CVC). METHODS: To better understand in incident hemodialysis patients how sex and race/ethnicity are associated with time on a central venous catheter and transition to an arteriovenous fistula and graft, our observational cohort study analyzed US Renal Data System data for patients with incident ESKD aged ≥66 years who started hemodialysis on a CVC in July 2010 through 2013. RESULTS: At 1 year, 32.7% of 74,194 patients transitioned to an arteriovenous fistula, 10.8% transitioned to an arteriovenous graft, 32.1% stayed on a CVC, and 24.5% died. Women spent a significantly longer time on a CVC than men. Compared with white patients, patients who were black, Hispanic, or of another racial/ethnicity minority spent significantly more days on a CVC. In competing risk regression, women were significantly less likely than men to transition to a fistula and more likely to transition to a graft. Compared with white patients, blacks were significantly less likely to transition to a fistula but more likely to transition to a graft, Hispanics were significantly more likely to transition to a fistula, and other races/ethnicities were significantly more likely to transition to either a fistula or a graft. CONCLUSIONS: Female patients spend a longer time on a CVC and are less likely to transition to permanent access. Compared with white patients, minorities also spend longer time on a CVC, but are more likely to eventually transition to permanent access. Strategies to speed transition to permanent access should target groups that currently lag in this area.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Antimicrobial Resistance and Antibiotic Stewardship
      1. Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey
        Kamori D, Barabona G, Rugemalila J, Maokola W, Masoud SS, Mizinduko M, Sabasaba A, Ruhago G, Sambu V, Mushi J, Mgomella GS, McOllogi JJ, Msafiri F, Mugusi S, Boniface J, Mutagonda R, Mlunde L, Amani D, Mboya E, Mahiti M, Rwebembera A, Ueno T, Pembe A, Njau P, Mutayoba B, Sunguya B.
        J Antimicrob Chemother. 2023.
        BACKGROUND: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. OBJECTIVES: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. METHODS: A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. RESULTS: HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. CONCLUSIONS: More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

        Mgomella, G. S.

    • Chronic Diseases and Conditions
      1. Risk factors for HPV-associated cancers among people living with HIV in Washington, DC
        Waters AV, Dorsey K, Allston A, Woods A, Furness B, Doshi R.
        AIDS Res Hum Retroviruses. 2023.
        DC has high rates of Human Immunodeficiency Virus (HIV) infection and Human Papillomavirus (HPV)-associated cancers. People living with HIV (PLWH) are at risk for developing HPV-associated cancers. Previous studies identified factors that may further increase the risk of HPV-associated cancer among PLWH such as: age, race/ethnicity, sex, risk factor for HIV transmission, stage of HIV infection, and age at HIV diagnosis. The extent to which PLWH in DC are affected by HPV-associated cancers has not previously been well-described, and to our knowledge, the relationship between bacterial sexually transmitted infections (STIs) and subsequent development of HPV-associated cancer among PLWH in DC has not been explored. This was a retrospective case-control analysis of surveillance data on cancer, STIs, and HIV in Washington, DC from 1996-2015. There were 20,744 PLWH included in this study, of whom 335 (1.6%) had been diagnosed with an HPV-associated cancer. Among males living with HIV (MLWH), for every additional STI per ten person-years, risk of developing an HPV-associated cancer increased by 11%. Exposure to STIs was not a significant risk factor for HPV-associated cancer among females. Ever being diagnosed with stage three HIV infection increased risk of HPV-associated cancers among males by 109% and females living with HIV by 111% . STI exposures were associated with HPV-associated cancers among MLWH in DC and ever being diagnosed with advanced HIV infection was associated with HPV-associated cancers among all PLWH. Clinicians treating MLWH should ensure their patients receive primary HPV infection prevention and HPV-associated cancer screenings.

        Furness, B.

      2. Statewide county-level autism spectrum disorder prevalence estimates - seven U.S. states, 2018
        Shaw KA, Williams S, Hughes MM, Warren Z, Bakian AV, Durkin MS, Esler A, Hall-Lande J, Salinas A, Vehorn A, Andrews JG, Baroud T, Bilder DA, Dimian A, Galindo M, Hudson A, Hallas L, Lopez M, Pokoski O, Pettygrove S, Rossow K, Shenouda J, Schwenk YD, Zahorodny W, Washington A, Maenner MJ.
        Ann Epidemiol. 2023.
        PURPOSE: Autism spectrum disorder (ASD) prevalence information is necessary for identifying community needs such as addressing disparities in identification and services. METHODS: Seven Autism and Developmental Disabilities Monitoring (ADDM) Network sites participated in a pilot project to link statewide health and education data to generate county-level prevalence estimates for a broader age range for their states for the first time. RESULTS: Statewide prevalence of ASD for ages 3-21 years in 2018 ranged from 1.5% in Tennessee and Wisconsin to 2.3% in Arizona. The median county-level prevalence of ASD was 1.4% of residents ages 3-21 years. More boys than girls had ASD at all sites, and prevalence was lower among non-Hispanic Black (Black), Hispanic, Asian/Pacific Islander (A/PI), and American Indian/Alaska Native (AI/AN) residents compared to non-Hispanic White (White) residents at most sites. ASD prevalence estimates for children aged 8 years were similar to 2018 ADDM Network estimates that used record review to provide more in-depth information, but showed greater variation for children aged 4 years. CONCLUSION: Linkage of statewide data sets provides less detailed but actionable local information when more resource-intensive methods are not possible.

        Shaw, K. A. Williams, S. Hughes, M. M. Washington, A. Maenner, M. J.

    • Communicable Diseases
      1. Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis
        Banc-Husu AM, Moulton EA, Shiau H, Gutierrez Sanchez LH, Desai MS, Cerminara D, Munoz FM, Buffaloe LM, Valencia-Deray KG, Galvan NT, Bhatnagar J, Estetter L, Rassaei N, Reagan-Steiner S, Wicker J, Dunn JJ, Allen CE, Patel KR, Harpavat S, Goss JA, Leung DH.
        Am J Transplant. 2023;23(1):93-100.
        Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

        Bhatnagar, J. Estetter, L. Rassaei, N. Reagan-Steiner, S.

      2. Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network
        Cohen AL, Platts-Mills JA, Nakamura T, Operario DJ, Antoni S, Mwenda JM, Weldegebriel G, Rey-Benito G, de Oliveira LH, Ortiz C, Daniels DS, Videbaek D, Singh S, Njambe E, Sharifuzzaman M, Grabovac V, Nyambat B, Logronio J, Armah G, Dennis FE, Seheri ML, Magagula N, Mphahlele J, Fumian TM, Maciel IT, Gagliardi Leite JP, Esona MD, Bowen MD, Samoilovich E, Semeiko G, Abraham D, Giri S, Praharaj I, Kang G, Thomas S, Bines J, Liu N, Kyu HH, Doxey M, Rogawski McQuade ET, McMurry TL, Liu J, Houpt ER, Tate JE, Parashar UD, Serhan F.
        BMJ Glob Health. 2022;7(9).
        INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

        Cohen, A. L. Esona, M. D. Bowen, M. D. Tate, J. E. Parashar, U. D.

      3. Prevalence and clinical outcomes of respiratory syncytial virus versus influenza in adults hospitalized with acute respiratory illness from a prospective multicenter study
        Begley KM, Monto AS, Lamerato LE, Malani AN, Lauring AS, Talbot HK, Gaglani M, McNeal T, Silveira FP, Zimmerman RK, Middleton DB, Ghamande S, Murthy K, Kim L, Ferdinands JM, Patel MM, Martin ET.
        Clin Infect Dis. 2023.
        BACKGROUND: Current understanding of severe RSV infections in adults is limited by clinical under-recognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across three respiratory seasons from hospitals participating across all sites of the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN, 2016-2019). All participants were tested for RSV and influenza by RT-PCR. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10,311 hospitalized adults, 6% tested positive for RSV (n=622), 18.8% positive for influenza (n=1,940), and 75.1% negative for RSV and influenza (n=7,749). Congestive Heart Failure (CHF) or Chronic Obstructive Pulmonary Disease (COPD) was more frequent among adults with RSV than influenza (CHF: 37.3% vs. 28.8%, p<0.0001; COPD: 47.6% vs. 35.8%, p<0.0001). Patients with RSV more frequently had longer admissions [OR=1.38 (95% CI: 1.06-1.80) for stays >one week] and mechanical ventilation [OR=1.45 (95% CI: 1.09-1.93)] compared with influenza, but not compared to the influenza negative group [OR=1.03 (95% CI: 0.82-1.28); OR=1.17 (0.91-1.49), respectively.]. CONCLUSIONS: The prevalence of RSV across three recent respiratory illness seasons was considerable. Our findings suggest those with RSV might incur worse outcomes than influenza in hospitalized adults and frequently have pre-existing cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults experiencing severe ARI.

        Kim, L. Ferdinands, J. M. Patel, M. M.

      4. Factors driving norovirus transmission in long-term care facilities: A case-level analysis of 107 outbreaks
        Chen Y, Lopman BA, Hall AJ, Kambhampati AK, Roberts L, Mason J, Vilen K, Salehi E, Fraser A, Adams C.
        Epidemics. 2023;42:100671.
        Norovirus is the most common cause of gastroenteritis outbreaks in long-term care facilities (LTCFs) in the United States, causing a high burden of disease in both residents and staff. Understanding how case symptoms and characteristics contribute to norovirus transmission can lead to more informed outbreak control measures in LTCFs. We examined line lists for 107 norovirus outbreaks that took place in LTCFs in five U.S. states from 2015 to 2019. We estimated the individual effective reproduction number, R(i), to quantify individual case infectiousness and examined the contribution of vomiting, diarrhea, and being a resident (vs. staff) to case infectiousness. The associations between case characteristics and R(i) were estimated using a multivariable, log-linear mixed model with inverse variance weighting. We found that cases with vomiting infected 1.28 (95 % CI: 1.11, 1.48) times the number of secondary cases compared to cases without vomiting, and LTCF residents infected 1.31 (95 % CI: 1.15, 1.50) times the number of secondary cases compared to staff. There was no difference in infectiousness between cases with and without diarrhea (1.07; 95 % CI: 0.90, 1.29). This suggests that vomiting, particularly by LTCF residents, was a primary driver of norovirus transmission. These results support control measures that limit exposure to vomitus during norovirus outbreaks in LTCFs.

        Hall, A. J. Kambhampati, A. K.

      5. Probable vertical transmission of Alpha variant of concern (B.1.1.7) with evidence of SARS-CoV-2 infection in the syncytiotrophoblast, a case report
        Bullock HA, Fuchs E, Martines RB, Lush M, Bollweg B, Rutan A, Nelson A, Brisso M, Owusu-Ansah A, Sitzman C, Ketterl L, Timmons T, Lopez P, Mitchell E, McCutchen E, Figliomeni J, Iwen P, Uyeki TM, Reagan-Steiner S, Donahue M.
        Front Med (Lausanne). 2022;9:1099408.
        INTRODUCTION: Definitive vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been rarely reported. We present a case of a third trimester pregnancy with fetal distress necessitating cesarean section that demonstrated maternal, placental, and infant infection with the SARS-CoV-2 Alpha variant/B.1.1.7. METHODS: CDC's Influenza SARS-CoV-2 Multiplex RT-PCR Assay was used to test for SARS-CoV-2 in a maternal NP swab, maternal plasma, infant NP swab, and formalin-fixed paraffin-embedded (FFPE) placental tissue specimens. Whole genome sequencing (WGS) was performed on maternal plasma, infant, and placental specimens to determine the SARS-CoV-2 genotype. Histopathological evaluation, SARS-CoV-2 immunohistochemistry testing (IHC), and electron microscopy (EM) analysis were performed on placenta, umbilical cord, and membrane FFPE blocks. RESULTS: All specimens tested positive for SARS-CoV-2 by RT-PCR. WGS further revealed identical SARS-CoV-2 sequences from clade 20I/501Y.V1 (lineage Alpha/B.1.1.7) in maternal plasma, infant, and placental specimens. Histopathologic evaluation of the placenta showed histiocytic and neutrophilic intervillositis with fibrin deposition and trophoblast necrosis with positive SARS-CoV-2 immunostaining in the syncytiotrophoblast and electron microscopy evidence of coronavirus. DISCUSSION: These findings suggest vertical transmission of SARS-CoV-2, supported by clinical course timing, identical SARS-CoV-2 genotypes from maternal, placental, and infant samples, and IHC and EM evidence of placental infection. However, determination of the timing or distinction between prepartum and peripartum SARS-CoV-2 transmission remains unclear.

        Bullock, H. A. Fuchs, E. Martines, R. B. Bollweg, B. Uyeki, T. M. Reagan-Steiner, S.

      6. Data about the prevalence, diagnosis, treatment, and public knowledge of superficial fungal infections in the United States are scarce. These infections are a growing concern given the emergence of antifungal drug resistance. We analyzed data from a national survey of nearly 6000 U.S. adults. Overall, 114 (2.7%) participants reported having ringworm and 415 (10.0%) reported a fungal nail infection in the past 12 months; 61.4% of participants with any superficial fungal infection were self-diagnosed. Most patients (55.5%) used over-the-counter antifungals. The common nature of superficial fungal infections and the high rates of self-diagnosis and treatment indicate that community education about these infections should be considered a public health priority.

        Benedict, K. Gold, J. A. W. Wu, K.

      7. Assessment of COVID-19 outbreaks in long-term care facilities
        Bennett CC, Welton M, Bos J, Moon G, Berkley A, Kavlak L, Pearson J, Turabelidze G, Frazier J, Fehrenbach N, Brown CK.
        J Hosp Infect. 2023.
        BACKGROUND: The B.1.167.2 (Delta) variant quickly became the predominant circulating SARS-CoV-2 strain in the United States during Summer 2021. Missouri identified a high number of outbreaks in long-term care facilities (LTCF) across the state with low vaccination rates among LTCF staff members and poor adherence to mitigation measures within local communities. AIM: This report aims to describe COVID-19 outbreaks that occurred in Missouri LTCFs impacting staff and residents during the surge of the Delta variant. METHODS: Outbreaks of COVID-19 in 178 LTCFs were identified by the Missouri Department of Health and Senior Services. Case data from LTCFs with the highest burden of disease were analyzed to assess disease transmission, vaccination status, and outcomes among residents and staff. Additional investigational measures included onsite visits to facilities with recent COVID-19 outbreaks in communities with substantial transmission to assess mitigation measures. FINDINGS: During 22(nd) April - 29(th) July 2021, 159 COVID-19 cases among 72 staff members and 87 residents, were identified in 10 LTCFs. Over 74.7% of resident cases were vaccinated compared to 23.6% of staff cases. Vaccinated residents had a lower proportion of hospitalizations and deaths reported compared to unvaccinated residents. Data analysis and contact tracing efforts from a sample of the facilities suggest staff members were likely a major factor in introducing SARS-CoV-2 virus into the facilities. Adherence to COVID-19 mitigation measures varied at the visited facilities. CONCLUSION: Data showed that vaccination rates varied between staff cases and resident cases in facilities with high burden outbreaks. Differences were identified in mitigation practices in at least two facilities.

        Bennett, C. C. Frazier, J. Fehrenbach, N. Brown, C. K.

      8. Epidemiology of human mpox - worldwide, 2018-2021
        McCollum AM, Shelus V, Hill A, Traore T, Onoja B, Nakazawa Y, Doty JB, Yinka-Ogunleye A, Petersen BW, Hutson CL, Lewis R.
        MMWR Morb Mortal Wkly Rep. 2023;72(3):68-72.
        Monkeypox (mpox) is a zoonotic disease caused by Monkeypox virus (MPXV), an Orthopoxvirus; the wild mammalian reservoir species is not known. There are two genetic clades of MPXV: clade I and clade II (historically found in central and west Africa, respectively), with only Cameroon reporting both clades (1). Human cases have historically been reported from 1) mostly rural, forested areas in some central and west African countries; 2) countries reporting cases related to population migration or travel of infected persons; and 3) exposure to imported infected mammals (2). The annual number of cases in Africa has risen since 2014 and cumulatively surpassed reports from the previous 40 years for most countries. This reemergence of mpox might be due to a combination of environmental and ecological changes, animal or human movement, the cessation of routine smallpox vaccination since its eradication in 1980, improvements in disease detection and diagnosis, and genetic changes in the virus (2). This report describes the epidemiology of mpox since 1970 and during 2018-2021, using data from national surveillance programs, World Health Organization (WHO) bulletins, and case reports, and addresses current diagnostic and treatment challenges in countries with endemic disease. During 2018-2021, human cases were recognized and confirmed in six African countries, with most detected in the Democratic Republic of the Congo (DRC) and Nigeria. The reemergence and increase in cases resulted in its being listed in 2019 as a priority disease for immediate and routine reporting through the Integrated Disease Surveillance and Response strategy in the WHO African region.* In eight instances, patients with mpox were identified in four countries outside of Africa after travel from Nigeria. Since 2018, introductory and intermediate training courses on prevention and control of mpox for public health and health care providers have been available online at OpenWHO.(†)(,)(§) The global outbreak that began in May 2022(¶) has further highlighted the need for improvements in laboratory-based surveillance and access to treatments and vaccines to prevent and contain the infection, including in areas of Africa with endemic mpox.

        McCollum, A. M. Shelus, V. Nakazawa, Y. Doty, J. B. Petersen, B. W. Hutson, C. L.

      9. Early and increased influenza activity among children - Tennessee, 2022-23 influenza season
        Thomas CM, White EB, Kojima N, Fill MA, Hanna S, Jones TF, Newhouse CN, Orejuela K, Roth E, Winders S, Chandler DR, Grijalva CG, Schaffner W, Schmitz JE, DaSilva J, Kirby MK, Mellis AM, Rolfes MA, Sumner KM, Flannery B, Talbot HK, Dunn JR.
        MMWR Morb Mortal Wkly Rep. 2023;72(3):49-54.
        Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed.

        Thomas, C. M. White, E. B. Kojima, N. DaSilva, J. Kirby, M. K. Mellis, A. M. Rolfes, M. A. Sumner, K. M. Flannery, B.

      10. Influenza antiviral use in patients hospitalized with laboratory-confirmed influenza in the United States, FluSurv-NET, 2015-2019
        Tenforde MW, Cummings CN, O'Halloran AC, Rothrock G, Kirley PD, Alden NB, Meek J, Yousey-Hindes K, Openo KP, Anderson EJ, Monroe ML, Kim S, Nunez VT, McMahon M, McMullen C, Khanlian SA, Spina NL, Muse A, Gaitán MA, Felsen CB, Lung K, Shiltz E, Sutton M, Thomas A, Talbot HK, Schaffner W, Price A, Chatelain R, Reed C, Garg S.
        Open Forum Infect Dis. 2023;10(1):ofac681.
        From surveillance data of patients hospitalized with laboratory-confirmed influenza in the United States during the 2015-2016 through 2018-2019 seasons, initiation of antiviral treatment increased from 86% to 94%, with increases seen across all age groups. However, 62% started therapy ≥3 days after illness onset, driven by late presentation to care.

        Tenforde, M. W. Cummings, C. N. O'Halloran, A. C. Reed, C. Garg, S.

      11. Retention and predictors of attrition among HIV-infected children on antiretroviral therapy in Côte d'Ivoire between 2012 and 2016
        Touré F, Etheredge GD, Brennan C, Parris K, Diallo MO, Ouffoue AF, Ekra A, Prao H, Assamoua NV, Gnongoue C, Kone F, Koffi C, Kamagaté F, Rivadeneira E, Carpenter D.
        Pediatr Infect Dis J. 2023.
        BACKGROUND: An estimated 21,000 children aged 0-14 years were living with HIV in Côte d'Ivoire in 2020, of whom only 49% have been diagnosed and are receiving antiretroviral therapy (ART). Retention in HIV care and treatment is key to optimize clinical outcomes. We evaluated pediatric retention in select care and treatment centers (CTCs) in Côte d'Ivoire. METHODS: We retrospectively reviewed medical records using 2-stage cluster sampling for children under 15 years initiated on ART between 2012 and 2016. Kaplan-Meier time-to-event analysis was done to estimate cumulative attrition rates per total person-years of observation. Cox proportional hazard regression was performed to identify factors associated with attrition. RESULTS: A total of 1198 patient records from 33 CTCs were reviewed. Retention at 12, 24, 36, 48 and 60 months after ART initiation was 91%, 84%, 74%, 72% and 70%, respectively. A total of 309 attrition events occurred over 3169 person-years of follow-up [266 children were lost to follow-up (LTFU), 29 transferred to another facility and 14 died]. LTFU determinants included attending a "public-private" CTC [adjusted hazard ratio (aHR) 6.05; 95% confidence interval (CI): 4.23-8.65], receiving care at a CTC without an on-site laboratory (aHR: 4.01; 95% CI: 1.70-9.46) or attending a CTC without an electronic medical record (EMR) system (aHR: 2.22; 95% CI: 1.59-3.12). CONCLUSIONS: In Cote d'Ivoire, patients attending a CTC that is public-private, does not have on-site laboratory or EMR system were likely to be LTFU. Decentralization of laboratory services and scaling use of EMR systems could help to improve pediatric retention.

        Brennan, C. Ekra, A. Prao, H. Kamagaté, F.

      12. Risk factors for melioidosis in Udupi district, Karnataka, India, January 2017-July 2018
        Akhileshwar S, Ashok T, Ramesh C, Anubhav S, Vasudeva U, Chiranjay M, Shyamsundar S, Deepak S, Suma N, Papanna M, Yadav R, Singh SK, Tanzin D.
        PLoS Glob Public Health. 2022;2(12).
        We initiated an epidemiological investigation following the death of a previously healthy 17 year-old boy with neuro-melioidosis. A case was defined as a culture-confirmed melioidosis patient from Udupi district admitted to hospital A from January 2013-July 2018. For the case control study, we enrolled a subset of cases admitted to hospital A from January 2017- July 2018. A control was resident of Udupi district admitted to hospital A in July 2018 with a non-infectious condition. Using a matched case-control design, we compared each case to 3 controls using age and sex groups. We assessed for risk factors related to water storage, activities of daily living, injuries and environmental exposures (three months prior to hospitalization), using conditional regression analysis. We identified 50 cases with case fatality rate 16%. Uncontrolled diabetes mellitus was present in 84% cases and 66% of cases occurred between May and October (rainy season). Percutaneous inoculation through exposure to stagnant water and injury leading to breakage in the skin were identified as an important mode of transmission. We used these findings to develop a surveillance case definition and initiated training of the district laboratory for melioidosis diagnosis.

        Papanna, M. Yadav, R.

    • Community Health Services
      1. BACKGROUND: In early 2020, following the start of the coronavirus disease 2019 (COVID-19) pandemic, institutions of higher education (IHEs) across the United States rapidly pivoted to online learning to reduce the risk of on-campus virus transmission. We explored IHEs' use of this and other nonpharmaceutical interventions (NPIs) during the subsequent pandemic-affected academic year 2020-2021. METHODS: From December 2020 to June 2021, we collected publicly available data from official webpages of 847 IHEs, including all public (n = 547) and a stratified random sample of private four-year institutions (n = 300). Abstracted data included NPIs deployed during the academic year such as changes to the calendar, learning environment, housing, common areas, and dining; COVID-19 testing; and facemask protocols. We performed weighted analysis to assess congruence with the October 29, 2020, US Centers for Disease Control and Prevention (CDC) guidance for IHEs. For IHEs offering ≥50% of courses in person, we used weighted multivariable linear regression to explore the association between IHE characteristics and the summated number of implemented NPIs. RESULTS: Overall, 20% of IHEs implemented all CDC-recommended NPIs. The most frequently utilized NPI was learning environment changes (91%), practiced as one or more of the following modalities: distance or hybrid learning opportunities (98%), 6-ft spacing (60%), and reduced class sizes (51%). Additionally, 88% of IHEs specified facemask protocols, 78% physically changed common areas, and 67% offered COVID-19 testing. Among the 33% of IHEs offering ≥50% of courses in person, having < 1000 students was associated with having implemented fewer NPIs than IHEs with ≥1000 students. CONCLUSIONS: Only 1 in 5 IHEs implemented all CDC recommendations, while a majority implemented a subset, most commonly changes to the classroom, facemask protocols, and COVID-19 testing. IHE enrollment size and location were associated with degree of NPI implementation. Additional research is needed to assess adherence to NPI implementation in IHE settings.

        Moreland, S. Zviedrite, N. Ahmed, F. Uzicanin, A.

      2. Community-based referral for tuberculosis preventive therapy is effective for treatment completion
        Shenoi SV, Kyriakides TC, Dokubo EK, Guddera V, Vranken P, Desai M, Friedland G, Moll AP.
        PLoS Glob Public Health. 2022;2(12).
        Expansion of tuberculous preventive therapy (TPT) is essential to curb TB incidence and mortality among people with HIV (PWH), yet implementation has been slow. Innovative strategies to operationalize TPT are urgently needed. Here we present an evaluation of community-based identification and referral of PWH on completion of a six-month course of isoniazid in a highly prevalent region in rural South Africa. Using a community-based TB/HIV intensive case finding strategy, a team of nurses and lay workers identified community members with HIV who were without fever, night sweats, weight loss, or cough and referred them to the government primary care clinics for daily oral isoniazid, the only available TPT regimen. We measured monthly adherence and six-month treatment completion in the community-based identification and referral (CBR) group compared to those already engaged in HIV care. Adherence was measured by self-report and urine isoniazid metabolite testing. A multivariable analysis was performed to identify independent predictors of TPT completion. Among 240 participants, 81.7% were female, median age 35 years (IQR 30-44), and 24.6% had previously been treated for TB. The median CD4 count in the CBR group was 457 (IQR 301-648), significantly higher than the clinic-based comparison group median CD4 of 344 (IQR 186-495, p<0.001). Independent predictors of treatment completion included being a woman (aOR 2.41, 95% 1.02-5.72) and community-based identification and referral for TPT (aOR 2.495, 95% 1.13-5.53). Among the CBR group, treatment completion was 90.0%, an absolute 10.8% higher than the clinic-based comparison group (79.2%, p = 0.02). Adherence was significantly greater in the CBR group than the clinic-based comparison group, as measured by self-report (p = 0.02) and urine isoniazid testing (p = 0.01). Among those not on ART at baseline, 10% of eligible PWH subsequently initiated ART. Community members living with HIV in TB endemic regions identified and referred for TPT demonstrated higher treatment completion and adherence compared to PWH engaged for TPT while receiving clinic-based care. Community-based identification and referral is an innovative adjunctive strategy to facilitate implementation of TB preventive therapy in people living with HIV.

        Dokubo, E. K. Vranken, P. Desai, M.

    • Disaster Preparedness and Emergency Services

    • Environmental Health
      1. Notes from the field: Follow-up assessment 1 year after a chemical exposure investigation - Winnebago County, Illinois, July-August 2022
        Sekkarie A, DeJonge P, Martell S, Patrick S, Caudill M, Horton DK, Orr M, Konkle S.
        MMWR Morb Mortal Wkly Rep. 2023;72(3):80-81.

      2. Outbreak of acute gastroenteritis associated with drinking water in rural Kazakhstan: a matched case-control study
        Orysbayeva M, Zhuman B, Turegeldiyeva D, Horth R, Zhakipbayeva B, Singer D, Smagul M, Nabirova D.
        PLoS Glob Public Health. 2022;2(12).
        We conducted an outbreak investigation from June 3 to 15th in a rural village in northern Kazakhstan, after surveillance showed an increase in gastroenteritis. Cases were residents who presented for medical treatment for diarrhea, fever (>37.5 degrees C), vomiting, or weakness from May 14 to June 15, 2021. Controls were residents matched by age +or-2 years at a ratio of two controls for every case. Cases and controls were interviewed using structured questionnaires. We abstracted clinical data from medical records. We mapped cases and assessed risk for disease using conditional multivariable logistic regression. We identified 154 cases of acute gastroenteritis (attack rate of ~26 per 1,000 inhabitants). Symptoms were diarrhea, fever, vomiting, weakness, and decreased appetite. Among cases that participated (n = 107), 74% reported having drank unboiled tap water vs 18% of controls (n = 219). This was the only risk factor associated with disease (adjusted odds ratio: 18; 95% CI 9-35). Drinking water from a dispenser or carbonated drinks was protective. The city has two water supply networks; cases were clustered (107 cases in 79 households) in one. The investigation found that monitoring of quality and safety of water according to national regulations had not been conducted since 2018. No fatalities occurred, and no associated cases were reported after our investigation. Results suggest that untreated tap water was the probable source of the outbreak. The water supply had been cleaned and disinfected twice by the facility 2 days before our investigation began. Recommendations were made for regular monitoring of water supply facilities with rapid public notification when issues are detected to reduce likelihood of future drinking water associated outbreaks.

        Horth, R. Zhakipbayeva, B. Singer, D. Nabirova, D.

      3. Harmful algal bloom exposures self-reported to poison centers in the United States, May-October 2019
        Lavery AM, Kieszak SM, Law R, Bronstein AC, Funk AR, Banerji S, Brown K, Backer LC.
        Public Health Rep. 2023:333549221146654.
        The National Poison Data System (NPDS) comprises self-reported information from people who call US poison center hotlines. NPDS data have proven to be important in identifying emerging public health threats. We used NPDS to examine records of people who had self-reported exposure to harmful algal blooms (HABs). Participating poison centers then contacted people who had called their centers from May through October 2019 about their HAB exposure to ask about exposure route, symptoms, health care follow-up, and awareness of possible risks of exposure. Of 55 callers who agreed to participate, 47 (85%) reported exposure to HABs while swimming or bathing in HAB-contaminated water. Nine callers reported health symptoms from being near waters contaminated with HABs, suggesting potential exposure via aerosolized toxins. Symptoms varied by the reported routes of exposure; the most commonly reported symptoms were gastrointestinal and respiratory. More public and health care provider education and outreach are needed to improve the understanding of HAB-related risks, to address ways to prevent HAB-related illnesses, and to describe appropriate support when exposures occur.

        Lavery, A. M. Kieszak, S. M. Law, R. Backer, L. C.

    • Epidemiology and Surveillance
      1. The V-safe after vaccination health checker: Active vaccine safety monitoring during CDC's COVID-19 pandemic response
        Myers TR, Marquez PL, Gee JM, Hause AM, Panagiotakopoulos L, Zhang B, McCullum I, Licata C, Olson CK, Rahman S, Kennedy SB, Cardozo M, Patel CR, Maxwell L, Kallman JR, Shay DK, Shimabukuro TT.
        Vaccine. 2023.
        The Centers for Disease Control and Prevention (CDC) developed and implemented the v-safe after vaccination health checker (v-safe) to monitor COVID-19 vaccine safety and as an active surveillance supplement to existing CDC vaccine safety monitoring programs. V-safe allows persons who received COVID-19 vaccines to report on post-vaccination experiences and how symptoms affected their health at daily, weekly, and monthly timepoints after vaccination. Text message reminders are sent linking to Internet-based health check-in surveys. Surveys include questions to identify v-safe participants who may be eligible to enroll in a separate pregnancy registry activity that evaluates maternal and infant outcomes in those pregnant at the time of vaccination or receiving vaccine in the periconception period. We describe the development of and enhancements to v-safe, data management, promotion and communication to vaccination sites and partners, publications, strengths and limitations, and implications for future systems. We also describe enrollment in v-safe over time and demographics of persons participating in v-safe during the first year of operation (December 14, 2020 - December 13, 2021). During this time, 9,342,582 persons submitted 131,543,087 v-safe surveys. The majority of participants were female (62.3 %) and non-Hispanic White (61.2 %); median age was 49.0 years. Most participants reported receiving an mRNA COVID-19 vaccine as their first recorded dose (95.0 %). V-safe contributed to CDC's vaccine safety assessments for FDA-authorized COVID-19 vaccines by enabling near real-time reporting of reactogenicity once the COVID-19 vaccination program began in the community, encouraging reports to the Vaccine Adverse Event Reporting System and facilitating enrollment in a large post-vaccination pregnancy registry. Given that v-safe is an integral component of the most comprehensive safety monitoring program in U.S. history, we believe that this approach has promise as a potential application for future pandemic response activities as well as rollout of novel vaccines in a non-pandemic context.

        Myers, T. R. Marquez, P. L. Gee, J. M. Hause, A. M. Panagiotakopoulos, L. Zhang, B. McCullum, I. Licata, C. Olson, C. K. Shay, D. K. Shimabukuro, T. T.

    • Genetics and Genomics
      1. Genotypic investigation of a rotavirus cluster at a quaternary-care pediatric hospital
        Kitt EM, Yoon HW, Comar CE, Smith KP, Harris RM, Esona MD, Gautam R, Mijatovic-Rustempasic S, Hopkins AL, Jaimes J, Handy LK.
        Infect Control Hosp Epidemiol. 2023:1-3.
        Rotavirus (RV) was a common healthcare-associated infection prior to the introduction of the RV vaccine. Following widespread RV vaccination, healthcare-associated rotavirus cases are rare. We describe an investigation of a cluster of rotavirus infections in a pediatric hospital in which an uncommon genotype not typically circulating in the United States was detected.

        Esona, M. D. Gautam, R. Mijatovic-Rustempasic, S. Hopkins, A. L. Jaimes, J.

    • Health Behavior and Risk
      1. Characteristics of the moveable middle: Opportunities among adults open to COVID-19 vaccination
        Omari A, Boone KD, Zhou T, Lu PJ, Kriss JL, Hung MC, Carter RJ, Black C, Weiss D, Masters NB, Lee JT, Brewer NT, Szilagyi PG, Singleton JA.
        Am J Prev Med. 2022.
        INTRODUCTION: Focusing on subpopulations that express the intention to receive a COVID-19 vaccination but are unvaccinated may improve the yield of COVID-19 vaccination efforts. METHODS: A nationally representative sample of 789,658 U.S. adults aged ≥18 years participated in the National Immunization Survey Adult COVID Module from May 2021 to April 2022. The survey assessed respondents' COVID-19 vaccination status and intent by demographic characteristics (age, urbanicity, educational attainment, region, insurance, income, and race/ethnicity). This study compared composition and within-group estimates of those who responded that they definitely or probably will get vaccinated or are unsure (moveable middle) from the first and last month of data collection. RESULTS: Because vaccination uptake increased over the study period, the moveable middle declined among persons aged ≥18 years. Adults aged 18-39 years and suburban residents comprised most of the moveable middle in April 2022. Groups with the largest moveable middles in April 2022 included persons with no insurance (10%), those aged 18-29 years (8%), and those with incomes below poverty (8%), followed by non-Hispanic Native Hawaiian or other Pacific Islander (7%), non-Hispanic multiple or other race (6%), non-Hispanic American Indian or Alaska Native persons (6%), non-Hispanic Black or African American persons (6%), those with below high school education (6%), those with high school education (5%), and those aged 30-39 years (5%). CONCLUSIONS: A sizable percentage of adults open to receiving COVID-19 vaccination remain in several demographic groups. Emphasizing engagement of persons who are unvaccinated in some racial/ethnic groups, aged 18-39 years, without health insurance, or with lower income may reach more persons open to vaccination.

        Omari, A. Zhou, T. Lu, P. J. Kriss, J. L. Hung, M. C. Carter, R. J. Black, C. Weiss, D. Masters, N. B. Lee, J. T. Singleton, J. A.

    • Health Economics
      1. Costs and cost-effectiveness of a collaborative data-to-care intervention for HIV treatment and care in the United States
        Shrestha RK, Fanfair RN, Randall LM, Lucas C, Nichols L, Camp N, Brady KA, Jenkins H, Altice FL, DeMaria A, Villanueva M, Weidle PJ.
        J Int AIDS Soc. 2023;26(1):e26040.
        INTRODUCTION: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States. METHODS: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective. RESULTS: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL). CONCLUSIONS: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context.

        Shrestha, R. K. Fanfair, R. N. Camp, N. Weidle, P. J.

      2. Medical costs of substance use disorders in the US employer-sponsored insurance population
        Li M, Peterson C, Xu L, Mikosz CA, Luo F.
        JAMA Netw Open. 2023;6(1):e2252378.
        IMPORTANCE: Direct costs of substance use disorders (SUDs) in the United States are incurred primarily among the working-age population. Quantifying the medical cost of SUDs in the employer-sponsored insurance (ESI) population can improve understanding of how SUDs are affecting workplaces and inform decision-making on the value of prevention strategies. OBJECTIVE: To estimate the annual attributable medical cost of SUDs in the ESI population from the health care payer perspective. DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, Merative MarketScan 2018 databases were weighted to represent the non-Medicare eligible ESI population. Regression and mathematical modeling of medical expenditures controlled for insurance enrollee demographic, clinical, and insurance factors to compare enrollees with and without an SUD diagnosis to identify the annual attributable medical cost of SUDs. Data analysis was conducted from January to March 2022. EXPOSURES: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification SUD diagnoses on inpatient or outpatient medical records according to Clinical Classifications Software categories (alcohol-, cannabis-, hallucinogen-, inhalant-, opioid-, sedative-, stimulant-, and other substance-related disorders). MAIN OUTCOMES AND MEASURES: Annual SUD medical cost in the ESI population overall and by substance type (eg, alcohol). Number of enrollees with an SUD diagnosis and the annual mean cost per affected enrollee of SUD diagnosis (any and by substance type) are also reported. RESULTS: Among 162 million ESI enrollees, 2.3 million (1.4%) had an SUD diagnosis in 2018. The regression analysis sample included 21 225 individuals with an SUD diagnosis (121 357 [57.7%] male individuals; 68 325 [32.5%] aged 25-44 years) and 1 049 539 individuals with no SUD diagnosis. The mean annual medical cost attributable to SUD diagnosis per affected enrollee was $15 640 (95% CI, $15 340-$15 940), and the total annual medical cost in the ESI population was $35.3 billion (2018 USD). Alcohol use disorder ($10.2 billion) and opioid use disorder ($7.3 billion) were the most costly. CONCLUSIONS AND RELEVANCE: In this economic evaluation of medical expenditures in the ESI population, the per-person and total medical costs of SUDs were substantial. Strategies to support employees and their health insurance dependents to prevent and treat SUDs can be considered in terms of potentially offsetting the existing high medical cost of SUDs. Medical expenditures for SUDs represent the minimum direct cost that employers and health insurers face because not all people with SUDs have a diagnosis, and costs related to absenteeism, presenteeism, job retention, and mortality are not addressed.

        Li, M. Peterson, C. Xu, L. Mikosz, C. A. Luo, F.

    • Health Equity and Health Disparities
      1. Needs for shelter or housing assistance among people with diagnosed HIV by jurisdiction: United States, 2015-2020
        Dasgupta S, Beer L, Lu JF, Weiser J, Yuan X, Nair P, Banks L, Marcus R.
        AIDS. 2023;37(3):535-540.
        OBJECTIVE: To describe the landscape of needs for housing assistance among people with HIV (PWH) and availability of Housing Opportunities for People with AIDS (HOPWA) funding with respect to housing service needs, nationally and for 17 US jurisdictions. DESIGN: The CDC Medical Monitoring Project (MMP) is an annual, cross-sectional survey designed to report nationally and locally representative estimates of characteristics and outcomes among adults with diagnosed HIV in the United States. METHODS: We analyzed 2015-2020 data from MMP and 2019 funding data from HOPWA. Weighted percentages and 95% confidence intervals (CIs) for national and jurisdiction-level estimates were reported. RESULTS: Nationally, 1 in 4 (27.7%) PWH had shelter or housing service needs. Among those who needed housing services, 2 in 5 (40.4%) did not receive them (range: 21.3% in New York to 62.3% in Georgia). Reasons for unmet needs were multifactorial and varied by jurisdiction. Available 2019 HOPWA funding per person in need would cover up to 1.24 months of rent per person nationally (range: 0.53 months in Virginia to 9.54 months in Puerto Rico), and may not have matched housing assistance needs among PWH in certain jurisdictions. CONCLUSION: Addressing housing service needs necessitates a multipronged approach at the provider, jurisdiction, and national level. Locally, jurisdictions should work with their partners to understand and address housing service needs among PWH. Nationally, distribution of HOPWA funding for housing services should be aligned according to local needs; the funding formula could be modified to improve access to housing services among PWH.

        Dasgupta, S. Beer, L. Weiser, J. Marcus, R.

      2. BACKGROUND: Black and Hispanic/Latino men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV). In the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project, 7 community collaboratives were developed to provide comprehensive HIV prevention services for these populations. METHODS: We analyzed National HIV Surveillance System data to determine the number of HIV diagnoses for each year from 2014 to 2019 among Black, Hispanic/Latino, and White MSM in 7 THRIVE-eligible Metropolitan Statistical Areas (MSAs) that were awarded funding and 12 THRIVE-eligible MSAs that were not awarded funding. We used generalized linear Poisson regression models to estimate adjusted estimated annual percentage changes (EAPCs) with 95% confidence intervals for HIV diagnosis rates controlling for HIV prevalence, viral suppression, HIV testing rates, preexposure prophylaxis (PrEP) prescription rates, poverty, education, and insurance status. RESULTS: We found larger estimated decreases in HIV diagnosis rates in THRIVE jurisdictions compared with non-THRIVE jurisdictions. The adjusted EAPC among Black MSM was -8.2 (-11.7 to -4.6) in THRIVE MSAs compared with -4.2 (-7.8 to -0.4) in non-THRIVE MSAs. The adjusted EAPC among Hispanic/Latino MSM was -8.6 (-12.2 to -4.8) in THRIVE MSAs compared with -2.6 (-5.1 to -0.1)in non-THRIVE MSAs. The adjusted EAPC among White MSM was -7.6 (-12.0 to -3.1) in THRIVE MSAs compared with 5.9 (1.8-10.1) in non-THRIVE MSAs. CONCLUSIONS: The THRIVE community collaborative model was associated with a decrease in HIV diagnoses among Black and Hispanic/Latino MSM. To achieve the goals of the US Ending the HIV Epidemic initiative, effective interventions aimed to increase PrEP use need to be focused on Black and Hispanic/Latino MSM.

        Iqbal, K. Zhu, W. Wiener, J. Dominguez, K. L. Tanner, M. R. Kourtis, A. P. Singh, S. Hoover, K. W. Iqbal, K. Zhu, W. Wiener, J. Dominguez, K. L. Tanner, M. R. Kourtis, A. P. Singh, S. Hoover, K. W.

      3. Changes in racial and ethnic disparities in glucose-lowering drug utilization and glycated haemoglobin A1c in US adults with diabetes: 2005-2018
        Li P, Zhang P, Guan D, Guo J, Zhang Y, Pavkov ME, Bullard KM, Shao H.
        Diabetes Obes Metab. 2023;25(2):516-525.
        AIM: To examine changes in racial and ethnic disparities in glucose-lowering drugs (GLD) use and glycated haemoglobin A1c in US adults with diabetes from 2005 to 2018. METHODS: We conducted pooled cross-sectional analysis using data from the 2005-2018 Medical Expenditure Panel Surveys, and the 2005-2018 National Health and Nutrition Examination Survey. Individuals ≥18 years with diabetes were included. Racial and ethnic disparities were measured in (a) newer non-insulin GLD use; (b) insulin analogue use; (c) non-insulin GLDs adherence; (d) insulin adherence; and (e) glucose management, along with (f) the proportion of the disparities explained by potential contributing factors. RESULTS: From 2005 to 2018, racial and ethnic disparities persisted in newer GLD use, non-insulin GLDs adherence, insulin analogue use and glucose management. In 2018, compared with non-Hispanic white adults, non-Hispanic black, Hispanic and other race/ethnicity groups had lower rates of using newer GLDs (adjusted risk ratio: 0.44, 0.52, 0.64, respectively; p < .05 for all) and insulin analogues (adjusted risk ratio: 0.93, 0.89, 0.95, respectively; p < .05 for all except other groups), lower non-insulin GLD adherence (proportion of days covered: -4.5%, -5.6%, -4.3%, respectively; p < .05 for all), higher glycated haemoglobin A1c (0.29%, 0.32%, 0.02%, respectively; p < .05 for all except other group), and similar insulin adherences. Socioeconomic and health status were the main contributors to these disparities. CONCLUSIONS: Our findings provide evidence of racial and ethnic disparities in newer GLD use and quality of care in glucose management. Our study results can inform decision-makers of the status of racial and ethnic disparities and identify ways to reduce these disparities.

        Zhang, P. Pavkov, M. E. Bullard, K. M. Zhang, P. Pavkov, M. E. Bullard, K. M.

      4. Having health insurance is associated with better access to healthcare and lower rates of comorbidity in the general population, but data are limited on insurance's impact on adults with congenital heart disease (ACHD). The Congenital Heart Survey To Recognize Outcomes, Needs and well-beinG (CH STRONG) was conducted among ACHD in three locations from 2016 to 2019. We performed multivariable logistic regression to determine the associations between health insurance and both access to healthcare and presence of comorbidities. We also compared health insurance and comorbidities among ACHD to similarly-aged individuals in the Behavioral Risk Factor Surveillance System (BRFSS) as a proxy for the general population. Of 1354 CH STRONG respondents, the majority were ≤ 30 years old (83.5%), and 8.8% were uninsured versus 17.7% in the BRFSS (p < 0.01). Compared to insured ACHD, uninsured were less likely to report regular medical care (adjusted odds ratio [aOR] 0.2, 95% confidence interval [CI] 0.1-0.3) and visited an emergency room more often (aOR 1.6, CI 1.0-2.3). Among all ACHD reporting disability, uninsured individuals less frequently received benefits (aOR 0.1, CI 0.0-0.3). Depression was common among uninsured ACHD (22.5%), but insured ACHD had lower rates of depression than insured in the BRFSS (13.3% vs. 22.5%, p < 0.01). In conclusion, rates of insurance were higher among ACHD compared to the general population. Nonetheless, uninsured ACHD inconsistently accessed healthcare and benefits. Further studies are needed to determine if insurance ameliorates the risk of morbidity as ACHD age.

        Farr, S. L. Oster, M. E.

      5. It is not just the southeast-geographically pervasive racial disparities in Neisseria gonorrhoeae between non-Hispanic Black and White US women
        Rowlinson E, Stenger MR, Valentine JA, Hughes JP, Khosropour CM, Golden MR.
        Sex Transm Dis. 2023;50(2):98-103.
        Spatial analyses of gonorrhea morbidity among women often highlight the Southeastern United States but may not provide information on geographic variation in the magnitude of racial disparities; such maps also focus on geographic space, obscuring underlying population characteristics. We created a series of visualizations depicting both county-level racial disparities in female gonorrhea diagnoses and variations in population size. We calculated county- and region-level race-specific relative rates (RelR) and between-race rate differences (RDs) and rate ratios (RRs) comparing gonorrhea case rates in non-Hispanic Black (NHB) versus non-Hispanic White (NHW) women. We then created proportional symbol maps with color representing counties' RelR/RD/RR category and symbol size representing counties' female population. Gonorrhea rates among NHB women were highest in the Midwest (718.7/100,000) and West (504.8), rates among NHW women were highest in the West (74.1) and Southeast (72.1). The RDs were highest in the Midwest (654.6 excess cases/100,000) and West (430.7), whereas the RRs were highest in the Northeast (12.4) and Midwest (11.2). Nearly all US counties had NHB female rates ≥3× those in NHW women, with NHB women in most highly populated counties experiencing ≥9-fold difference in gonorrhea rates. Racial disparities in gonorrhea were not confined to the Southeast; both relative and absolute disparities were equivalent or larger in magnitude in areas of the Northeast, Midwest, and West. Our findings help counter damaging regional stereotypes, provide evidence to refocus prevention efforts to areas of highest disparities, and suggest a useful template for monitoring racial disparities as an actionable public health metric. eng

        Stenger, M. R. Valentine, J. A. Stenger, M. R. Valentine, J. A.

    • Healthcare Associated Infections
      1. Transmission of Mycobacterium tuberculosis to healthcare personnel resulting from contaminated bone graft material, United States, June 2021- August 2022
        Li R, Deutsch-Feldman M, Adams T, Law M, Biak C, Pitcher E, Drees M, Hernandez-Romieu AC, Filardo TD, Cropper T, Martinez A, Wilson WW, Althomsons SP, Morris SB, Wortham JM, Benowitz I, Schwartz NG, White K, Haddad MB, Glowicz JB.
        Clin Infect Dis. 2023.
        A nationwide tuberculosis outbreak linked to a viable bone allograft product contaminated with Mycobacterium tuberculosis was identified in June 2021. Our subsequent investigation identified 73 healthcare personnel with new latent tuberculosis infection following exposure to the contaminated product, product recipients, surgical instruments, or medical waste.

        Li, R. Deutsch-Feldman, M. Hernandez-Romieu, A. C. Filardo, T. D. Cropper, T. Martinez, A. Wilson, W. W. Althomsons, S. P. Morris, S. B. Wortham, J. M. Benowitz, I. Schwartz, N. G. Haddad, M. B. Glowicz, J. B.

      2. Role of microbiota in the skin colonization of candida auris
        Tharp B, Zheng R, Bryak G, Litvintseva AP, Hayden MK, Chowdhary A, Thangamani S.
        mSphere. 2023:e0062322.
        Candida auris is an emerging multidrug-resistant fungal pathogen that can cause life-threatening infections in humans. Unlike other Candida species that colonize the gut, C. auris efficiently colonizes the skin and contaminates the patient's environment, resulting in rapid nosocomial transmission and outbreaks of systemic infections. As the largest organ of the body, the skin harbors beneficial microbiota that play a critical role to protect from invading pathogens. However, the role of skin microbiota in the colonization and pathogenesis of C. auris remains to be explored. With this perspective, we review and discuss recent insights into skin microbiota and their potential interactions with the immune system in the context of C. auris skin colonization. Understanding microbiota, C. auris, and host interactions in the skin is important to develop microbiome-based therapeutic approaches to prevent and treat this emerging fungal pathogen in humans.

        Litvintseva, A. P.

    • Immune System Disorders
      1. The epidemiology and clinical features of non-keratitis acanthamoeba infections in the United States, 1956-2020
        Haston JC, O'Laughlin K, Matteson K, Roy S, Qvarnstrom Y, Ali IK, Cope JR.
        Open Forum Infect Dis. 2023;10(1):ofac682.
        BACKGROUND: Acanthamoeba is a free-living ameba that can cause severe disease affecting the central nervous system, skin, sinuses, and other organs, particularly in immunocompromised individuals. These rare but severe infections are often fatal, yet incompletely described. METHODS: Cases included were either reported to the Centers for Disease Control and Prevention (CDC) Free-Living Ameba program or published in scientific literature. Characteristics of all patients in the United States with laboratory-confirmed non-keratitis Acanthamoeba infections were described using descriptive statistics, and associations with survival were determined using χ(2) and Fisher exact tests. RESULTS: Of 173 patients identified, 71% were male and the median age was 44 years (range, 0-87 years). Of these, 26 (15%) survived. Most patients (88%) had at least 1 immunocompromising condition, most commonly human immunodeficiency virus (39%), cancer (28%), and solid organ or hematopoietic stem cell transplant (28%). Granulomatous amebic encephalitis (GAE) was the most common disease presentation (71%). Skin (46%), sinuses (29%), lungs (13%), and bone (6%) were also involved. Nearly half of patients (47%) had involvement of >1 organ system. Survival was less frequent among those with GAE (3%, P < .001) compared with cutaneous disease, rhinosinusitis, or multiorgan disease not including GAE. Of 7 who received the currently recommended treatment regimen, 5 (71%) survived. CONCLUSIONS: Non-keratitis Acanthamoeba infections occur primarily in immunocompromised individuals and are usually fatal. Survival may be associated with disease presentation and treatment. Providers who care for at-risk patients should be aware of the various disease manifestations to improve early recognition and treatment.

        Haston, J. C. O'Laughlin, K. Matteson, K. Roy, S. Qvarnstrom, Y. Ali, I. K. M. Cope, J. R.

    • Immunity and Immunization
      1. Vaccine effectiveness against influenza-associated urgent care, emergency department, and hospital encounters during the 2021-2022 season, VISION Network
        Tenforde MW, Weber ZA, DeSilva MB, Stenehjem E, Yang DH, Fireman B, Gaglani M, Kojima N, Irving SA, Rao S, Grannis SJ, Naleway AL, Kirshner L, Kharbanda AB, Dascomb K, Lewis N, Dalton AF, Ball SW, Natarajan K, Ong TC, Hartmann E, Embi PJ, McEvoy CE, Grisel N, Zerbo O, Dunne MM, Arndorfer J, Goddard K, Dickerson M, Patel P, Timbol J, Griggs EP, Hansen J, Thompson MG, Flannery B, Klein NP.
        J Infect Dis. 2023.
        BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at three sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and SARS-CoV-2-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: 86,732 ED/UC ARI-associated encounters (7,696 [9%] cases) and 16,805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI): 20-29%) and 25% (95%CI: 11-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; CI: -5-17%) or with immunocompromising conditions (4%, CI:-45-36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.

        Tenforde, M. W. Kojima, N. Dickerson, M. Patel, P. Griggs, E. P. Thompson, M. G. Flannery, B.


      2. Absolute and relative vaccine effectiveness of primary and booster series of COVID-19 vaccines (mRNA and adenovirus vector) against COVID-19 hospitalizations in the United States, December 2021-April 2022
        Lewis NM, Murray N, Adams K, Surie D, Gaglani M, Ginde AA, McNeal T, Ghamande S, Douin DJ, Talbot HK, Casey JD, Mohr NM, Zepeski A, Shapiro NI, Gibbs KW, Files DC, Hager DN, Ali H, Prekker ME, Frosch AE, Exline MC, Gong MN, Mohamed A, Johnson NJ, Srinivasan V, Steingrub JS, Peltan ID, Brown SM, Martin ET, Monto AS, Lauring AS, Khan A, Hough CL, Busse LW, Bender W, Duggal A, Wilson JG, Gordon AJ, Qadir N, Chang SY, Mallow C, Rivas C, Babcock HM, Kwon JH, Chappell JD, Halasa N, Grijalva CG, Rice TW, Stubblefield WB, Baughman A, Lindsell CJ, Hart KW, Rhoads JP, McMorrow ML, Tenforde MW, Self WH, Patel MM.
        Open Forum Infect Dis. 2023;10(1):ofac698.
        BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines. METHODS: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE. RESULTS: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary. CONCLUSIONS: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

        Lewis, N. M. Murray, N. Adams, K. Surie, D. McMorrow, M. L. Tenforde, M. W. Patel, M. M.

      3. Understanding the host response to influenza A virus (IAV) infection is vital for developing intervention strategies. The primary barriers for invading respiratory pathogens are the respiratory tract epithelial cells and antimicrobial proteins generated by these cells. The antimicrobial peptide, β-defensin-1, has antiviral activity against both enveloped and non-enveloped viruses. Significant downregulation of β-defensin1 gene (DEFB1) expression was observed when human bronchial epithelial cells (HBEpCs) were exposed to IAV. HBEpCs overexpressing DEFB1 caused a significant reduction in IAV, that was confirmed by IAV matrix gene analysis, plaque assay, and confocal microscopy. DEFB1 expression after transfection with two micro RNAs (miRNAs), hsa-miR-186-5p and hsa-miR-340-5p, provided evidence that DEFB1 expression could be modulated by these miRNAs and hsa-miR-186-5p had a higher binding efficiency with DEFB1. Overexpression of DEFB1 in IAV-infected HBEpCs led to increased NF-κB expression. In a PCR array analysis of 84 transcription factors, either overexpressing DEFB1 or siRNA silencing of DEFB1 expression significantly modulated the expression of signal transducer and activator of transcription 3 (STAT3). In addition, Ingenuity Pathway Analysis (IPA) integrated with PCR array data showed that the JAK1/STAT3 pathway was significantly altered in cells overexpressing DEFB1, suggesting this to be one of the pathways by which defensin regulates IAV replication in HBEpCs. In conclusion, the reduction in IAV copy number in DEFB1 overexpressing cells suggests that β-defensin-1 plays a key role in regulating IAV survival through STAT3 and is a potential target for antiviral drug development.

        Othumpangat, S. Noti, J. D.

      4. BACKGROUND: COVID-19 vaccines may be co-administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines. OBJECTIVE: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of mRNA COVID-19 and seasonal influenza vaccines. METHODS: We searched the VAERS database for reports of adverse events (AEs) following co-administration of mRNA COVID-19 and seasonal influenza vaccines and following a first booster dose mRNA COVID-19 vaccine alone, during July 1, 2021-June 30, 2022. We assessed the characteristics of these reports and described the most frequently reported MedDRA preferred terms (PTs). Clinicians reviewed available medical records for serious reports and reports of adverse events of special interest (AESI) and categorized the main diagnosis by system organ class. RESULTS: From July 1, 2021 through June 30, 2022, VAERS received 2,449 reports of adverse events following co-administration of mRNA COVID-19 and seasonal influenza vaccines. Median age of vaccinees was 48 years (IQR: 31, 66); 387 (15.8%) were classified as serious. Most reports (1,713; 69.3%) described co-administration of a first booster dose of an mRNA COVID-19 vaccine with seasonal influenza vaccine. The most common AEs among non-serious reports were injection site reactions (193; 14.5%), headache (181; 13.6%), and pain (171; 12.8%). The most common AEs among reports classified as serious were dyspnea (38; 14.9%), COVID-19 infection (32; 12.6%), and chest pain (27; 10.6%). DISCUSSION: This review of reports to VAERS following co-administration of mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19 disease) was expected. CDC will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines, including co-administration involving bivalent mRNA COVID-19 booster vaccines that have been recommended for people ages ≥ 6 months in the United States.

        Moro, P. L. Zhang, B. Ennulat, C. Harris, M. McVey, R. Woody, G. Marquez, P. McNeil, M. M. Su, J. R.

    • Informatics
      1. Informative censoring-a cause of bias in estimating COVID-19 mortality using hospital data
        Lin HM, Liu ST, Levin MA, Williamson J, Bouvier NM, Aberg JA, Reich D, Egorova N.
        Life (Basel). 2023;13(1).
        (1) Background: Several retrospective observational analyzed treatment outcomes for COVID-19; (2) Methods: Inverse probability of censoring weighting (IPCW) was applied to correct for bias due to informative censoring in database of hospitalized patients who did and did not receive convalescent plasma; (3) Results: When compared with an IPCW analysis, overall mortality was overestimated using an unadjusted Kaplan-Meier curve, and hazard ratios for the older age group compared to the youngest were underestimated using the Cox proportional hazard models and 30-day mortality; (4) Conclusions: An IPCW analysis provided stabilizing weights by hospital admission.

        Williamson, J.

      2. Botulinum neurotoxin-producing species of Clostridium are highly diverse. Clostridium botulinum could represent at least four different species of Clostridium. In addition, strains that do not produce botulinum neurotoxin are closely related to toxigenic strains, probably representing the same species. Although reclassification of these organisms has been proposed in the past, their species names have remained unchanged, mainly because of the premise that changing names of medically relevant organisms might cause confusion in the healthcare and scientific community. In this review, we discuss the possible unintended consequences of reclassifying botulinum neurotoxin-producing species of Clostridium, which are of public health, medical, and biodefense interest.

        Lúquez, C. Halpin, J. L. Dykes, J.

    • Injury and Violence
      1. Associations of adverse childhood experiences with pregnancy and infant health
        Swedo EA, D'Angelo DV, Fasula AM, Clayton HB, Ports KA.
        Am J Prev Med. 2023.
        INTRODUCTION: Adverse childhood experiences are associated with a host of negative outcomes; however, few have studied cumulative adverse childhood experiences in the context of pregnancy and infant health. This study examines state-level prevalence of adverse childhood experiences and associations with pregnancy- and infant health‒related indicators. METHODS: The study used 2016-2018 Pregnancy Risk Assessment Monitoring System population-based data from 5 states. Analyses were conducted for individual states and grouped states using similar adverse childhood experience items. Thirteen adverse childhood experience measures were included across 3 domains: abuse, neglect, and household challenges. Adverse childhood experience scores were calculated for the number of adverse childhood experiences experienced (0, 1, 2, ≥3) on the basis of available state measures. Fourteen pregnancy- and infant health‒related indicators were examined, including unwanted pregnancy, adequate prenatal care, experiences during pregnancy (e.g., smoking, abuse, depression), gestational diabetes, hypertensive disorders of pregnancy, birth outcomes (e.g., preterm birth), and breastfeeding. Adjusting for demographics, parity, health insurance status, and educational attainment, prevalence ratios and 95% CIs were calculated to examine the associations between pregnancy- and infant health‒related indicators and adverse childhood experience scores. RESULTS: Over 50% of respondents reported at least 1 adverse childhood experience and 13%-31% reported ≥3 adverse childhood experiences, depending on the state. Significant associations were identified in all adjusted models between adverse childhood experiences and unwanted pregnancy, smoking, physical abuse, and depression during pregnancy. CONCLUSIONS: Adverse childhood experiences are associated with risk factors that impact pregnancy and infant health. Preventing and mitigating adverse childhood experiences is an important strategy to improve pregnancy- and infant health‒related indicators.

        Swedo, E. A. D'Angelo, D. V. Fasula, A. M. Clayton, H. B.

      2. Randomized evaluation of CDC HEADS UP concussion education materials for youth sport coaches
        Kroshus E, Zhou H, Ledsky R, Sarmiento K, DePadilla L.
        J Neurotrauma. 2023.
        The Centers for Disease Control and Prevention (CDC) HEADS UP youth sports coach materials are the most widely adopted form of concussion education for coaches across the United States-reaching millions of youth sports coaches over the last decade. These materials focus on concussion symptom identification, response, and management (e.g., return to school and sports), while also addressing the importance of communicating to athletes and their families about concussion safety. The purpose of this study was to assess the effectiveness of CDC HEADS UP materials on coach knowledge and communication with youth athletes about concussion safety. This is the first randomized control study of the CDC HEADS UP materials in real world youth sport conditions. Participants were 764 unique coaches at 15 YMCA associations. Cluster randomization was used to assign branches within associations to the intervention (CDC HEADS UP) and control (treatment as usual) conditions. Coaches completed surveys prior to and at the end of the competitive season. Communication with athletes about concussion increased among coaches in the intervention group (aRR=1.24, 95% CI=1.14, 1.36) but not the control group (aRR=1.09, 95% CI=0.90, 1.31), in multivariate analyses controlling for coach demographic characteristics and baseline communication practices. Concussion symptom knowledge and communication intentions also significantly increased in the intervention group but not in the control group. This study provides evidence that CDC HEADS UP materials increase the likelihood that youth sport coaches communicate with their athletes about concussion safety. As youth sports organizations increasingly mandate concussion education for coaches, CDC HEADS UP materials may be considered a leading resource for adoption and setting-relevant implementation.

        Zhou, H. Sarmiento, K. DePadilla, L.

    • Laboratory Sciences
      1. Kinetics and magnitude of viral RNA shedding as indicators for Influenza A virus transmissibility in ferrets
        Pulit-Penaloza JA, Brock N, Belser JA, Sun X, Pappas C, Tumpey TM, Maines TR.
        Commun Biol. 2023;6(1):90.
        The ferret transmission model is routinely used to evaluate the pandemic potential of newly emerging influenza A viruses. However, concurrent measurement of viral load in the air is typically not a component of such studies. To address this knowledge gap, we measured the levels of virus in ferret nasal washes as well as viral RNA emitted into the air for 14 diverse influenza viruses, encompassing human-, swine-, and avian-origin strains. Here we show that transmissible viruses display robust replication and fast release into the air. In contrast, poorly- and non-transmissible viruses show significantly reduced or delayed replication along with lower detection of airborne viral RNA at early time points post inoculation. These findings indicate that efficient ferret-to-ferret transmission via the air is directly associated with fast emission of virus-laden particles; as such, quantification of viral RNA in the air represents a useful addition to established assessments of new influenza virus strains.

        Pulit-Penaloza, J. A. Brock, N. Belser, J. A. Sun, X. Pappas, C. Tumpey, T. M. Maines, T. R.

      2. Comparison of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in Nigeria
        Iriemenam NC, Ige FA, Greby SM, Okunoye OO, Uwandu M, Aniedobe M, Nwaiwu SO, Mba N, Okoli M, William NE, Ehoche A, Mpamugo A, Mitchell A, Stafford KA, Thomas AN, Olaleye T, Akinmulero OO, Agala NP, Abubakar AG, Owens A, Gwyn SE, Rogier E, Udhayakumar V, Steinhardt LC, Martin DL, Okoye MI, Audu R.
        J Clin Virol Plus. 2023;3(1):100139.
        OBJECTIVES: Determining an accurate estimate of SARS-CoV-2 seroprevalence has been challenging in African countries where malaria and other pathogens are endemic. We compared the performance of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in a Nigerian population endemic for malaria. METHODS: De-identified plasma specimens from SARS-CoV-2 RT-PCR positive, dried blood spot (DBS) SARS-CoV-2 RT-PCR positive, and pre-pandemic negatives were used to evaluate the performance of the four SARS-CoV-2 assays (Tetracore, SARS2MBA, RightSign, xMAP). RESULTS: Results showed higher sensitivity with the multi-antigen (81% (Tetracore), 96% (SARS2MBA), 85% (xMAP)) versus the single-antigen (RightSign (64%)) SARS-CoV-2 assay. The overall specificities were 98% (Tetracore), 100% (SARS2MBA and RightSign), and 99% (xMAP). When stratified based on <15 days to ≥15 days post-RT-PCR confirmation, the sensitivities increased from 75% to 88.2% for Tetracore; from 93% to 100% for the SARS2MBA; from 58% to 73% for RightSign; and from 83% to 88% for xMAP. With DBS, there was no positive increase after 15-28 days for the three assays (Tetracore, SARS2MBA, and xMAP). CONCLUSION: Multi-antigen assays performed well in Nigeria, even with samples with known malaria reactivity, and might provide more accurate measures of COVID-19 seroprevalence and vaccine efficacy.

        Iriemenam, N. C. Greby, S. M. Okunoye, O. O. Owens, A. Gwyn, S. E. Rogier, E. Udhayakumar, V. Steinhardt, L. C. Martin, D. L.

      3. Prophylactic human papillomavirus (HPV) vaccines are recommended for prevention of HPV-associated cancers. Type-specific detection of HPV in formalin-fixed paraffin-embedded (FFPE) tissues retrieved from diagnostic pathology laboratories is important in monitoring the impact of HPV vaccines. However, few typing assays have been validated for testing FFPE samples. We compared results of the Novaplex II HPV28 Detection (Novaplex) assay with those from our reference assay (Linear Array with reflex Line Probe Assay) on 708 FFPE samples from cervical lesions. Novaplex showed high type-specific concordance with the reference method for HPV16/18, 9 types targeted by the Gardasil 9 vaccine, 14 high-risk types, and 21 types covered by comparison assays. The rate of inadequate samples was low in both approaches (3.4% reference and 1.7% Novaplex). The proportion of discrepant types was less than 3.5% and positive concordance was greater than 75.0%. Furthermore, the type-specific positive agreement (92.0% to 98.0%), negative agreement (96.0% to 99.0%), and accuracy (97.0% to 99.0%) was high. Cohen's kappa ranged from 0.86 to 0.89, indicating excellent agreement between Novaplex and reference assays. Our results show that Novaplex is a suitable method for detection of HPV in FFPE tissues.

        Thapa, H. R. Unger, E. R. Querec, T. D.

      4. The nucleotide-binding, oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multi-protein complex that combines sensing, regulation, and effector functions to regulate inflammation in health and disease. NLRP3 is activated by a diverse range of inflammation-instigating signals known as pathogen associated molecular patterns and danger associated molecular patterns. Upon activation, NLRP3 oligomerizes and recruits partner proteins to form a supramolecular platform to process the maturation and release of interleukin (IL)-1β, IL-18, and gasdermin D, major mediators of inflammation and inflammatory cell death termed pyroptosis. The NLRP3 inflammasome has been implicated in the pathogenesis of a wide range of disease conditions, including chronic inflammatory disease that are associated with lifestyle and dietary changes, aging, and environmental exposures and have become the leading cause of death worldwide. Pharmacological targeting of NLRP3 and signaling demonstrated promising efficacy in ameliorating a list of disease conditions in animal models. These findings underscore the potential and importance of NLRP3 as a druggable target for treating a range of diseases. In this review, recent progress in understanding the structure and mechanism of action of the NLRP3 inflammasome is discussed with focus on pharmacological inhibition of NLRP3 by small molecule inhibitors. New structural and mechanistic insights into NLRP3 activation and inhibitor-NLRP3 interactions would aid in the rational design and pharmacological evaluation of NLRP3 inhibitors for treatment of human disease. Significance Statement The NLRP3 inflammasome plays central role in innate immune sensing and control of inflammation. Pharmacological inhibition of NLRP3 demonstrated promising efficacy in a range of diseases in animal models. Recent elucidation of the structure and inhibitor binding of NLRP3 generated new insights into its mode of action and inhibitor-NLRP3 interaction at molecular levels, providing new framework for developing small chemical inhibitors of NLRP3 with improved efficacy and specificity against chronic disease that has become major health concerns worldwide.

        Ma, Q.

      5. Diagnostic accuracy of the Panbio COVID-19 antigen rapid test device for SARS-CoV-2 detection in Kenya, 2021: A field evaluation
        Irungu JK, Munyua P, Ochieng C, Juma B, Amoth P, Kuria F, Kiiru J, Makayotto L, Abade A, Bulterys M, Hunsperger E, Emukule GO, Onyango C, Samandari T, Barr BA, Akelo V, Weyenga H, Munywoki PK, Bigogo G, Otieno NA, Kisivuli JA, Ochieng E, Nyaga R, Hull N, Herman-Roloff A, Aman R.
        PLoS One. 2023;18(1):e0277657.
        BACKGROUND: Accurate and timely diagnosis is essential in limiting the spread of SARS-CoV-2 infection. The reference standard, rRT-PCR, requires specialized laboratories, costly reagents, and a long turnaround time. Antigen RDTs provide a feasible alternative to rRT-PCR since they are quick, relatively inexpensive, and do not require a laboratory. The WHO requires that Ag RDTs have a sensitivity ≥80% and specificity ≥97%. METHODS: This evaluation was conducted at 11 health facilities in Kenya between March and July 2021. We enrolled persons of any age with respiratory symptoms and asymptomatic contacts of confirmed COVID-19 cases. We collected demographic and clinical information and two nasopharyngeal specimens from each participant for Ag RDT testing and rRT-PCR. We calculated the diagnostic performance of the Panbio™ Ag RDT against the US Centers for Disease Control and Prevention's (CDC) rRT-PCR test. RESULTS: We evaluated the Ag RDT in 2,245 individuals where 551 (24.5%, 95% CI: 22.8-26.3%) tested positive by rRT-PCR. Overall sensitivity of the Ag RDT was 46.6% (95% CI: 42.4-50.9%), specificity 98.5% (95% CI: 97.8-99.0%), PPV 90.8% (95% CI: 86.8-93.9%) and NPV 85.0% (95% CI: 83.4-86.6%). Among symptomatic individuals, sensitivity was 60.6% (95% CI: 54.3-66.7%) and specificity was 98.1% (95% CI: 96.7-99.0%). Among asymptomatic individuals, sensitivity was 34.7% (95% CI 29.3-40.4%) and specificity was 98.7% (95% CI: 97.8-99.3%). In persons with onset of symptoms <5 days (594/876, 67.8%), sensitivity was 67.1% (95% CI: 59.2-74.3%), and 53.3% (95% CI: 40.0-66.3%) among those with onset of symptoms >7 days (157/876, 17.9%). The highest sensitivity was 87.0% (95% CI: 80.9-91.8%) in symptomatic individuals with cycle threshold (Ct) values ≤30. CONCLUSION: The overall sensitivity and NPV of the Panbio™ Ag RDT were much lower than expected. The specificity of the Ag RDT was high and satisfactory; therefore, a positive result may not require confirmation by rRT-PCR. The kit may be useful as a rapid screening tool only for symptomatic patients in high-risk settings with limited access to rRT-PCR. A negative result should be interpreted based on clinical and epidemiological information and may require retesting by rRT-PCR.

        Munyua, P. Juma, B. Bulterys, M. Hunsperger, E. Emukule, G. O. Onyango, C. Samandari, T. Barr, B. A. T. Akelo, V. Weyenga, H. Munywoki, P. K. Herman-Roloff, A.

    • Maternal and Child Health
      1. Gut microbiome composition and metabolic capacity differ by FUT2 secretor status in exclusively breastfed infants
        Thorman AW, Adkins G, Conrey SC, Burrell AR, Yu Y, White B, Burke R, Haslam D, Payne DC, Staat MA, Morrow AL, Newburg DS.
        Nutrients. 2023;15(2).
        A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme ("secretors"), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother's fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p &lt; 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant-but not maternal-secretor status is associated with infant microbial colonization and metabolic capacity.

        Burke, R. Payne, D. C.

      2. Considering antiviral treatment to preserve hearing in congenital CMV
        Lanzieri TM, Pesch MH, Grosse SD.
        Pediatrics. 2023.

      3. Vertical transfer of humoral immunity against Nipah virus: A novel evidence from Bangladesh
        Satter SM, Nazneen A, Aquib WR, Sultana S, Rahman MZ, Klena JD, Montgomery JM, Shirin T.
        Trop Med Infect Dis. 2022;8(1).
        A major obstacle to in-depth investigation of the immune response against Nipah virus (NiV) infection is its rapid progression and high mortality rate. This paper described novel information on the vertical transfer of immune properties. In January 2020, a female aged below five years and her mother from Faridpur district of Bangladesh were infected. Both had a history of raw date palm sap consumption and were diagnosed as confirmed NiV cases. The daughter passed away, and the mother survived with significant residual neurological impairment. She conceived one and a half year later and was under thorough antenatal follow-up by the surveillance authority. A healthy male baby was born. As part of routine survivor follow-up, specimens were collected from the newborn and tested for NiV infection at the reference laboratory to exclude vertical transmission. Although testing negative for anti-Nipah IgM and PCR for NiV, a high titre of anti-Nipah IgG was observed. The transfer of humoral immunity against NiV from mother to neonate was confirmed for the first time. The article will serve as a reference for further exploration regarding NiV-specific antibodies that are transferred through the placenta, their potential to protect newborns, and how this may influence vaccine recommendations.

        Klena, J. D. Montgomery, J. M.

    • Nutritional Sciences
      1. PURPOSE: The high intake of added sugars from foods or beverages increases the risk of obesity, hypertension, dyslipidemia, and cardiovascular disease. Because state-level data are lacking, we estimated dietary intake of added sugars by state and factors associated with intake among US adults. DESIGN: Nationally representative, cross-sectional, in-person, household survey. SETTING: 50 states and DC. SAMPLE: 52,279 US adults from pooled data from 2010 and 2015 National Health Interview Surveys. MEASURES: Estimated total added sugars intake (tsp/day) using the National Cancer Institute's scoring algorithm that converts responses from the Dietary Survey Questionnaire screener to estimated total added sugars intake (tsp/day). ANALYSIS: Mean dietary-added sugars intake estimates and standard error were calculated for adults' characteristics and by state for all 50 states and the District of Columbia. Differences by adult's characteristics were assessed by pairwise t-tests (p &lt; 0.05). All analyses accounted for complex survey design and sampling weights. RESULTS: Overall, US adults consumed 17.0 tsp of added sugars/day (range: 14.8 tsp/day in Alaska to 1.2 tsp/day in Kentucky). Added sugars intake varied by states and sociodemographic characteristics. CONCLUSION: Findings may inform efforts to reduce added sugars intake to lower the high burden of chronic disease.

        Lee, S. H. Park, S. Blanck, H. M.

      2. High added sugars intake among US adults: Characteristics, eating occasions, and top sources, 2015-2018
        Lee SH, Zhao L, Park S, Moore LV, Hamner HC, Galuska DA, Blanck HM.
        Nutrients. 2023;15(2).
        The 2020-2025 Dietary Guidelines for Americans (DGA) recommends less than 10% of total daily calories come from added sugars. However, many adults overconsume added sugars putting them at risk for poor health outcomes. We examined characteristics of high added sugars consumers among US adults (≥20 years) and described their top 10 sources of added sugars intake using National Health and Nutrition Examination Survey 2015-2018 data (n = 9647). We defined high consumers as consuming &gt;15% of daily calories from added sugars (1.5 times higher than the DGA). We used the National Cancer Institute method to estimate usual intake of energy and percent of calories from added sugars. Top 10 sources were identified based on their percentage contribution to total added sugars intake on a given day. T-tests were used to examine differences by age, sex, race/ethnicity, education, income, marital status, and weight status. Overall, mean usual total energy intake and added sugars intake was 2068 kcal/day and 264 kcal/day, respectively, and 30% of adults were classified as high consumers. The prevalence of high added sugars consumers was significantly higher among 20-30-year-olds (29%), 31-50-year-olds (33%), and 51-70-year-olds (29%) than those aged ≥70 years (22%); non-Hispanic Black (39%) and non-Hispanic White (31%) adults than Hispanics (26%); adults with &lt;high school (37%), high school/GED (38%), or some college (34%) than adults with college or higher (15%); adults living in lower-income households (39% for federal poverty income ratio &lt; 130% and 35% for 130%-&lt;350%) than high-income households (21%). The prevalence of high consumers did not differ by sex or weight status. Top sources of added sugars were sweetened beverages (42%), tea (12%), sweet bakery products (11%), and jams/syrups/sugars (7%). Our findings can inform intervention efforts to decrease added sugars intake to support health.

        Lee, S. H. Zhao, L. Park, S. Moore, L. V. Hamner, H. C. Galuska, D. A. Blanck, H. M.

      3. BACKGROUND: High consumption of added sugars is related to adverse health consequences. OBJECTIVE: The objective of this study was to examine characteristics of US youth who report high intakes of added sugars, as well as the eating occasions and top sources of added sugars that contributed to intakes among consumers with high added sugars intake. Design and participants/setting: We conducted a cross-sectional study using 2015-2018 NHANES data among 5280 US youths (2-19 years). MAIN OUTCOME MEASURES: Outcome measure was usual percent of calories from added sugars using 2 days of dietary recall based on the National Cancer Institute method. High consumers were defined as consuming greater than 15% of total daily calorie intake from added sugars (1.5 times higher than the 2020-2025 Dietary Guidelines for Americans recommendation of &lt;10% of total daily calorie intake). Explanatory measures were selected sociodemographics (e.g., age, sex, race/ethnicity). Eating occasions were breakfast, lunch, dinner, and snack. STATISTICAL ANALYSES PERFORMED: We used t-tests to compare mean differences between sociodemographic groups. RESULTS: Overall, 34% of US youths were classified as high consumers of added sugars. The prevalence of high consumers of added sugars significantly varied by some sociodemographics (i.e., age, race/ethnicity, and head of household's education level). The prevalence of high added sugars consumers was significantly greater among 12-19-year-olds (41%) and 6-11-year-olds (37%) compared to 2-5-year-olds (19%), non-Hispanic Black (42%) and non-Hispanic White (42%) persons compared to Hispanic persons (19%), and those with a head of household's education level of high school/some college (40%) compared to households with college degree or higher (29%). The prevalence of high consumers did not differ by sex, income, or weight status. Of eating occasions, the amount of added sugars youths consumed was highest during snack occasions among high consumers. Top five sources of added sugars among high consumers on a given day were sweetened beverages, sweet bakery products, candy, other desserts, and ready-to-eat cereals. CONCLUSION: One in three US youths consumed more than 15% of total calories from added sugars. High added sugars intake was more prevalent among certain subgroups such as 12-19-year-olds and non-Hispanic Black or non-Hispanic White youth. Our findings can provide information for intervention efforts to decrease added sugars intake to promote child health.

        Park, S. Zhao, L. Lee, S. H. Hamner, H. C. Moore, L. V. Galuska, D. A. Blanck, H. M.

    • Occupational Safety and Health
      1. Work: A social determinant of health worth capturing
        Armenti K, Sweeney MH, Lingwall C, Yang L.
        Int J Environ Res Public Health. 2023;20(2).
        Work is a recognized social determinant of health. This became most apparent during the COVID-19 pandemic. Workers, particularly those in certain industries and occupations, were at risk due to interaction with the public and close proximity to co-workers. The purpose of this study was to assess how states collected work and employment data on COVID-19 cases, characterizing the need for systematic collection of case-based specific work and employment data, including industry and occupation, of COVID-19 cases. A survey was distributed among state occupational health contacts and epidemiologists in all 50 states to assess current practices in state public health surveillance systems. Twenty-seven states collected some kind of work and employment information from COVID-19 cases. Most states (93%) collected industry and/or occupation information. More than half used text-only fields, a predefined reference or dropdown list, or both. Use of work and employment data included identifying high risk populations, prioritizing vaccination efforts, and assisting with reopening plans. Reported barriers to collecting industry and occupation data were lack of staffing, technology issues, and funding. Scientific understanding of work-related COVID-19 risk requires the systematic, case-based collection of specific work and employment data, including industry and occupation. While this alone does not necessarily indicate a clear workplace exposure, collection of these data elements can help to determine and further prevent workplace outbreaks, thereby ensuring the viability of the nation's critical infrastructure.

        Armenti, K. Sweeney, M. H. Yang, L.

      2. Workplace injuries caused by commercial fishing winches-Alaska, 2000-2020
        Victoroff TM, Case SL, Robertson LD, Syron LN.
        J Agromedicine. 2023.
        OBJECTIVES: Deck machinery is a leading source of hospitalized injury for commercial fishing workers in Alaska. More detailed data are needed about the specific circumstances leading to injuries for developing targeted prevention efforts. METHODS: This study analyzed claims submitted to the Alaska Fisherman's Fund (AFF) to identify patterns among injuries in Alaska from commercial fishing winches. RESULTS: During January 1, 2000-November 1, 2020, 125 traumatic injuries from commercial fishing winches were identified, mainly occurring among males (94%), frequently among fishermen aged 30 years or younger (54%). Over 80% of winch injuries occurred in salmon fisheries. By gear type, 40% of injuries occurred on vessels using purse seine gear, 30% on vessels using drift gillnet gear, and 12% among set gillnet operators. Most injuries involved a fisherman having a body part caught in or compressed by a winch or cables attached to a winch (67%). Injuries mainly affected upper extremities including fingers (50% of cases) or hands/wrists (together 22% of cases). Injury severity was not formally assessed, but injuries ranged from contusions, sprains, and strains to finger or hand crushing injuries, upper limb amputation, skull fracture, spinal fracture, and chest trauma. Most cases involved fractures (23%), amputations (18%), lacerations (16%), and contusions (16%). Of all injuries, 51% were caused by anchor winches, 32% were caused by deck winches, 9% were caused by trailer winches, and 9% were caused by other types of winches. CONCLUSIONS: Practical solutions are needed for avoiding entanglement and struck-by hazards when operating fishing winches. Anchor winches warrant focused attention, having accounted for more than half of all winch injuries identified in this study. Engineering solutions, including emergency stop devices or other simple mechanical interventions depending on winch type, could help to avert potentially disabling injuries from winches. Administrative controls such as task-specific training for winches should be emphasized, especially for younger or less experienced commercial fishing crew, who may be at increased risk for injury.

        Victoroff, T. M. Case, S. L. Robertson, L. D. Syron, L. N.

      3. Feasibility of a selective epoxidation technique for use in quantification of peracetic acid in air samples collected on sorbent tubes
        Walsh CM, Jackson SR, Baughman NN, Ham JE, Wells JR.
        J Chem Health Saf. 2022;29(4):378-386.
        Peracetic acid is a disinfection agent used in medical and food processing facilities, and occupational exposures have been documented. To facilitate characterization of daily occupational exposures, the current work describes the development of a personal sampling technique to quantify the peracetic acid concentration in air samples. Peracetic acid atmospheres were generated in 100 L Teflon chambers, and samples were collected on 350 mg XAD-7 solid sorbent tubes for 4 h at a flow rate of 250 mL/min using a personal sampling pump. Indirect measurement of peracetic acid was achieved by desorption from the sorbent and subsequent treatment with cyclohexene to initiate an epoxidation reaction, formally known as the Prilezhaev reaction. The epoxidation product, cyclohexene oxide, was quantified by gas chromatography-mass spectrometry. The reaction enabled quantification of peracetic acid with high specificity over the common co-contaminants hydrogen peroxide and acetic acid, which were introduced in 10-fold and 100-fold excess to challenge the reaction. The technique also demonstrated an overall estimate of bias and precision of 11 and 8%, respectively, and a limit of detection of 60 ppbv was estimated. Preliminary storage experiments indicate that unreacted peracetic acid is stable on the sorbent tubes for 72 h when stored at -20 °C following collection. Overall, the specificity of the reaction and capability to sample for longer time periods than current methods, in addition to the use of safer personal sampling materials, demonstrate the utility of this technique for peracetic acid measurement in air. © 2022 Elsevier Inc.. All rights reserved.

        Walsh, C. M. Jackson, S. R. Baughman, N. N. Ham, J. E. Wells, J. R.

    • Parasitic Diseases
      1. Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
        Saito M, McGready R, Tinto H, Rouamba T, Mosha D, Rulisa S, Kariuki S, Desai M, Manyando C, Njunju EM, Sevene E, Vala A, Augusto O, Clerk C, Were E, Mrema S, Kisinza W, Byamugisha J, Kagawa M, Singlovic J, Yore M, van Eijk AM, Mehta U, Stergachis A, Hill J, Stepniewska K, Gomes M, Guérin PJ, Nosten F, Ter Kuile FO, Dellicour S.
        Lancet. 2023;401(10371):118-130.
        BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

        Desai, M.

      2. A new WHO bottle bioassay method to assess the susceptibility of mosquito vectors to public health insecticides: results from a WHO-coordinated multi-centre study
        Corbel V, Kont MD, Ahumada ML, Andréo L, Bayili B, Bayili K, Brooke B, Pinto Caballero JA, Lambert B, Churcher TS, Duchon S, Etang J, Flores AE, Gunasekaran K, Juntarajumnong W, Kirby M, Davies R, Lees RS, Lenhart A, Lima JB, Martins AJ, Müller P, N'Guessan R, Ngufor C, Praulins G, Quinones M, Raghavendra K, Verma V, Rus AC, Samuel M, Ying KS, Sungvornyothin S, Uragayala S, Velayudhan R, Yadav RS.
        Parasit Vectors. 2023;16(1):21.
        BACKGROUND: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both. METHODS: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC(50) and LC(99), respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI(50) and OI(99)), to measure mortality and the sterilizing effect, respectively. RESULTS: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC(50)/LC(99) or OI(50)/OI(99) values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were < 10% for most mosquito species-insecticide combinations. CONCLUSION: Our findings, based on the largest susceptibility dataset ever produced on mosquitoes, showed that the new WHO bottle bioassay is adequate for evaluating mosquito susceptibility to new and promising public health insecticides currently deployed for vector control. The datasets presented in this study have been used recently by the WHO to establish 17 new insecticide discriminating concentrations (DCs) for either Aedes spp. or Anopheles spp. The bottle bioassay and DCs can now be widely used to monitor baseline insecticide susceptibility of wild populations of vectors of malaria and Aedes-borne diseases worldwide.

        Lenhart, A.

    • Social and Behavioral Sciences
      1. A social-ecological approach to modeling Sense of Virtual Community (SOVC) in Livestreaming Communities
        Kairam SR, Mercado MC, Sumner SA.
        Proc ACM Hum Comput Interact. 2022;6.
        Participation in communities is essential to individual mental and physical health and can yield further benefits for members. With a growing amount of time spent participating in virtual communities, it's increasingly important that we understand how the community experience manifests in and varies across these online spaces. In this paper, we investigate Sense of Virtual Community (SOVC) in the context of live-streaming communities. Through a survey of 1,944 Twitch viewers, we identify that community experiences on Twitch vary along two primary dimensions: belonging, a feeling of membership and support within the group, and cohesion, a feeling that the group is a well-run collective with standards for behavior. Leveraging the Social-Ecological Model, we map behavioral trace data from usage logs to various levels of the social ecology surrounding an individual user's participation within a community, in order to identify which of these can be associated with lower or higher SOVC. We find that features describing activity at the individual and community levels, but not features describing the community member's dyadic relationships, aid in predicting the SOVC that community members feel within channels. We consider implications for the design of live-streaming communities and for fostering the well-being of their members, and we consider theoretical implications for the study of SOVC in modern, interactive online contexts, particularly those fostering large-scale or pseudonymized interactions. We also explore how the Social-Ecological Model can be leveraged in other contexts relevant to Computer-Supported Cooperative Work (CSCW), with implications for future work. © 2022 ACM.

        Mercado, M. C. Sumner, S. A.

    • Substance Use and Abuse
      1. A longitudinal analysis of respiratory illness and tobacco use transitions
        Mayer M, Shin YE, Baker L, Cordova J, Mayne RG, Reyes-Guzman CM, Pfeiffer RM, Choi K.
        Am J Prev Med. 2023;64(2):175-183.
        INTRODUCTION: Among individuals with chronic respiratory conditions, transitions between patterns of tobacco product use are not well understood. This study examines how transitions, including quitting altogether, differ over time between those who do and do not have chronic respiratory conditions. METHODS: Data from youth and adult participants of the longitudinal Population Assessment of Tobacco and Health Study (2013-2018) were analyzed. Youth aged 12-17 years were included if they had aged into the adult sample by Wave 4. Stratified polytomous regression models built under a first-order Markov assumption modeled the probability of transitioning between different states/patterns of tobacco product use (exclusive current E-cigarette use, exclusive current combustible tobacco product use, current dual use of combustible products and E-cigarettes, and no current tobacco product use) at each wave. Marginal transition probabilities were computed as a function of ever or past-year diagnosis of a respiratory condition (separately for asthma and a composite variable representing chronic bronchitis, emphysema, and/or chronic obstructive pulmonary disease). Analyses were conducted in 2020-2021. RESULTS: Most individuals, regardless of respiratory condition, maintained the same pattern of tobacco use between waves. Exclusive combustible tobacco product users, including those with or without a respiratory condition, were not likely to become exclusive E-cigarette users or to quit using tobacco entirely. CONCLUSIONS: Although combustible tobacco use negatively impacts the management and prognosis of respiratory illnesses, combustible tobacco users who were recently diagnosed with a chronic respiratory condition were not likely to quit using tobacco. Efforts to encourage and support cessation in this medically vulnerable population should be increased.

        Cordova, J.

      2. Trends in over-the-counter nicotine replacement therapy sales, U.S., 2017‒2020
        Trigger S, Xu X, Malarcher A, Salazar E, Shin H, Babb S.
        Am J Prev Med. 2023.
        INTRODUCTION: Few studies have examined trends in over-the-counter U.S. Food and Drug Administration‒approved nicotine replacement therapy sales data and consumer preferences for nicotine replacement therapy attributes (e.g., flavor). Examination of consumer preferences may inform both public health smoking cessation programs as well as subsequent research on consumer preferences for potentially reduced-risk tobacco products U.S. Food and Drug Administration may authorize. METHODS: NielsenIQ Retail Measurement Service data were used to examine national trends in over-the-counter nicotine replacement therapy dollar sales from 2017 to 2020 and dollar sales by retail channel and product attributes for the most recent year available at the time of analysis (2020). RESULTS: Over-the-counter nicotine replacement therapy sales totaled about $1 billion annually between 2017 and 2020. Across the 4-year period, sales of gum and patches decreased, whereas lozenge sales increased (p<0.05 for all). In 2020, gum accounted for 52.7% ($511 million), lozenges accounted for 33.3% ($322 million), and patches accounted for 14.1% ($137 million) of over-the-counter nicotine replacement therapy sales. Drug stores were the retail channel accounting for the largest percentage of total over-the-counter nicotine replacement therapy sales (42.9%). Three leading brands-private label or store brands (62.8%), Nicorette (30.7%,), and NicoDerm CQ (5.7%)-accounted for 99.2% of the total over-the-counter nicotine replacement therapy market. Mint was the most common flavor, representing 41.2% of total gum and 73.6% of total lozenge sales. CONCLUSIONS: This analysis of over-the-counter nicotine replacement therapy sales sheds light on consumer preferences for attributes that can inform efforts to facilitate smoking cessation and research on preferences related to potentially reduced-risk tobacco products.

        Babb, S.

      3. Decrease in secondhand smoke exposure in work and public places among adults in the Philippines: An Analysis of the Global Adult Tobacco Survey, 2009 and 2015
        Kress AC, Mbulo L, Stadnik C, Hemedez-Gonzalez R, Twentyman E, Dorotheo EU, Pan L.
        Int J Environ Res Public Health. 2023;20(2).
        The implementation of several tobacco control policies in the Philippines may have contributed to a decrease in secondhand smoke (SHS) exposure. We examined changes in SHS exposure at work and in public places between 2009 and 2015 among adults aged ≥15 years and interpreted these results within the tobacco policy landscape in the Philippines. We analyzed the Philippines Global Adult Tobacco Survey 2009 and 2015 data. We examined marginal effects in logistic regression to get the adjusted prevalence of SHS exposure at five work and public places, controlling for selected characteristics. We calculated adjusted prevalence ratios and adjusted prevalence differences between 2009 and 2015. Adjusted prevalence of SHS exposure decreased from 2009 to 2015 by 19% (5.7 percentage points) at work, 45% (11.2 percentage points) in government buildings, 48% (3.2 percentage points) in healthcare facilities, 29% (8.2 percentage points) in restaurants, and 33% (19.9 percentage points) on public transportation. Although the prevalence of SHS exposure at work and in public places decreased significantly between 2009 and 2015, a substantial proportion of adults remain exposed to SHS. This study highlights the importance of continued implementation, enforcement, monitoring, and evaluation of tobacco control and prevention measures in the Philippines.

        Kress, A. C. Mbulo, L. Twentyman, E. Pan, L.

      4. Trends and characteristics of buprenorphine-involved overdose deaths prior to and during the COVID-19 pandemic
        Tanz LJ, Jones CM, Davis NL, Compton WM, Baldwin GT, Han B, Volkow ND.
        JAMA Netw Open. 2023;6(1):e2251856.
        IMPORTANCE: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access. OBJECTIVE: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022. MAIN OUTCOMES AND MEASURES: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group. RESULTS: During July 2019 to June 2021, 32 jurisdictions reported 8 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%]). CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

        Tanz, L. J. Jones, C. M. Davis, N. L. Baldwin, G. T.

      5. Substance use among persons with syphilis during pregnancy - Arizona and Georgia, 2018-2021
        Carlson JM, Tannis A, Woodworth KR, Reynolds MR, Shinde N, Anderson B, Hobeheidar K, Praag A, Campbell K, Carpentieri C, Willabus T, Burkhardt E, Torrone E, O'Callaghan KP, Miele K, Meaney-Delman D, Gilboa SM, Olsen EO, Tong VT.
        MMWR Morb Mortal Wkly Rep. 2023;72(3):63-67.
        Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined as delivery of a stillborn or live-born infant meeting the surveillance case definition for probable or confirmed congenital syphilis). The prevalence of substance use (e.g., tobacco, alcohol, cannabis, illicit use of opioids, and other illicit, nonprescription substances) in persons with a congenital syphilis pregnancy outcome (48.1%) was nearly double that among those with a noncongenital syphilis pregnancy outcome (24.6%). Persons with a congenital syphilis pregnancy outcome were six times as likely to report illicit use of opioids and four times as likely to report using other illicit, nonprescription substances during pregnancy than were persons with a noncongenital syphilis pregnancy outcome. Approximately one half of persons who used substances during pregnancy and had a congenital syphilis pregnancy outcome had late or no prenatal care. Tailored interventions should address barriers and facilitators to accessing screening and treatment for syphilis among persons who use substances. The need for syphilis screening and treatment should be addressed at any health care encounter during pregnancy, especially among persons who use substances.

        Woodworth, K. R. Reynolds, M. R. Anderson, B. Torrone, E. O'Callaghan, K. P. Miele, K. Meaney-Delman, D. Gilboa, S. M. Olsen, E. O. Tong, V. T.

      6. Alcohol use, screening, and brief intervention among pregnant persons - 24 U.S. Jurisdictions, 2017 and 2019
        Luong J, Board A, Gosdin L, Dunkley J, Thierry JM, Pitasi M, Kim SY.
        MMWR Morb Mortal Wkly Rep. 2023;72(3):55-62.
        Alcohol use during pregnancy is a major preventable cause of adverse alcohol-related outcomes, including birth defects and developmental disabilities.* Alcohol screening and brief intervention (ASBI) is an evidence-based primary care tool that has been shown to prevent or reduce alcohol consumption during pregnancy; interventions have resulted in an increase in the proportion of pregnant women reporting abstinence (odds ratio = 2.26; 95% CI = 1.43-3.56) (1). Previous national estimates have not characterized ASBI in populations of pregnant persons. Using 2017 and 2019 Behavioral Risk Factor Surveillance System (BRFSS) data, CDC examined prevalence of ASBI and characteristics of pregnant persons and nonpregnant women aged 18-49 years (reproductive-aged women) residing in jurisdictions that participated in the BRFSS ASBI module. During their most recent health care visit within the past 2 years, approximately 80% of pregnant persons reported being asked about their alcohol use; however, only 16% of pregnant persons who self-reported current drinking at the time of the survey (at least one alcoholic beverage in the past 30 days) were advised by a health care provider to quit drinking or reduce their alcohol use. Further, the prevalence of screening among pregnant persons who did not graduate from high school was lower than that among those who did graduate from high school or had at least some college education. This gap between screening and brief intervention, along with disparities in screening based on educational level, indicate missed opportunities to reduce alcohol use during pregnancy. Strategies to enhance ASBI during pregnancy include integrating screenings into electronic health records, increasing reimbursement for ASBI services, developing additional tools, including electronic ASBI, that can be implemented in a variety of settings (2,3).

        Luong, J. Board, A. Gosdin, L. Dunkley, J. Thierry, J. M. Pitasi, M. Kim, S. Y.

      7. Strategies to reduce harm: An expert panel discussion on the fentanyl crisis
        Leitz SJ, Bagley SM, Cook AJ, Jones C, Lawrence D, Pearce P.
        Perm J. 2023:1-13.

      8. Estimated population size of the people who inject drugs in Thai Nguyen, Vietnam: a two survey capture-recapture study using respondent driven sampling
        Ly Thuy N, De AK, Kim Anh Ai L, Cuong Manh P, Le K, Van Thi Hai H, Abdul-Quader AS.
        PLoS Glob Public Health. 2022;2(12).
        To develop an appropriate programmatic response to the concentrated HIV epidemic, program managers require reliable estimates of the sizes of the key populations. This study attempts to estimate the population size of people who inject drugs (PWID) in Thai Nguyen-a province in the northern part of Vietnam. Two source capture-recapture population size estimates were calculated using data from two respondent driven sampling survey rounds conducted in 5 selected districts from May to August 2019. The population size of the PWID was calculated based on the number of PWID recruited in each survey and 'recaptured' during the first and the second survey. Additionally, personal network size data collected in the RDS was used to measure the population of PWID using the Successive Sampling Population Size Estimate (SS-PSE) method. The population of PWID estimated in five selected districts using the two capture-recapture method (CRC) (median = 5,396, 95% CI: 4,011-9,100) was slightly lower than estimated using SS-PSE with RDS survey 1 (median = 5,580, 95% CI: 3,024-9,272) and higher than when using SS-PSE with RDS survey 2 (median = 4,793; 95% CI: 2,310-8,618). The provincial PWID population estimates based on various approaches (e.g. extrapolation based on the prevalence of PWID in the districts) ranged from 6,498 (95% CI: 4,829-10,957) to around 6,807 (95% CI: 5,341-10,527). A provincial estimate of 6,782 PWID, with a confidence interval ranging from 5,312 to 10,527, will help guide planning and resource allocation to support appropriate levels of HIV prevention, care, and treatment services in the Thai Nguyen province.

        De, A. K. Abdul-Quader, A. S.

    • Veterinary Medicine
      1. Habitat connectivity and host relatedness influence virus spread across an urbanising landscape in a fragmentation-sensitive carnivore
        Kozakiewicz CP, Burridge CP, Lee JS, Kraberger SJ, Fountain-Jones NM, Fisher RN, Lyren LM, Jennings MK, Riley SP, Serieys LE, Craft ME, Funk WC, Crooks KR, VandeWoude S, Carver S.
        Virus Evol. 2023;9(1):veac122.
        Spatially heterogeneous landscape factors such as urbanisation can have substantial effects on the severity and spread of wildlife diseases. However, research linking patterns of pathogen transmission to landscape features remains rare. Using a combination of phylogeographic and machine learning approaches, we tested the influence of landscape and host factors on feline immunodeficiency virus (FIV(Lru)) genetic variation and spread among bobcats (Lynx rufus) sampled from coastal southern California. We found evidence for increased rates of FIV(Lru) lineage spread through areas of higher vegetation density. Furthermore, single-nucleotide polymorphism (SNP) variation among FIV(Lru) sequences was associated with host genetic distances and geographic location, with FIV(Lru) genetic discontinuities precisely correlating with known urban barriers to host dispersal. An effect of forest land cover on FIV(Lru) SNP variation was likely attributable to host population structure and differences in forest land cover between different populations. Taken together, these results suggest that the spread of FIV(Lru) is constrained by large-scale urban barriers to host movement. Although urbanisation at fine spatial scales did not appear to directly influence virus transmission or spread, we found evidence that viruses transmit and spread more quickly through areas containing higher proportions of natural habitat. These multiple lines of evidence demonstrate how urbanisation can change patterns of contact-dependent pathogen transmission and provide insights into how continued urban development may influence the incidence and management of wildlife disease.

        Lee, J. S.

    • Zoonotic and Vectorborne Diseases
      1. Identification of mosquito proteins that differentially interact with alphavirus nonstructural protein 3, a determinant of vector specificity
        Byers NM, Burns PL, Stuchlik O, Reed MS, Ledermann JP, Pohl J, Powers AM.
        PLoS Negl Trop Dis. 2023;17(1):e0011028.
        Chikungunya virus (CHIKV) and the closely related onyong-nyong virus (ONNV) are arthritogenic arboviruses that have caused significant, often debilitating, disease in millions of people. However, despite their kinship, they are vectored by different mosquito subfamilies that diverged 180 million years ago (anopheline versus culicine subfamilies). Previous work indicated that the nonstructural protein 3 (nsP3) of these alphaviruses was partially responsible for this vector specificity. To better understand the cellular components controlling alphavirus vector specificity, a cell culture model system of the anopheline restriction of CHIKV was developed along with a protein expression strategy. Mosquito proteins that differentially interacted with CHIKV nsP3 or ONNV nsP3 were identified. Six proteins were identified that specifically bound ONNV nsP3, ten that bound CHIKV nsP3 and eight that interacted with both. In addition to identifying novel factors that may play a role in virus/vector processing, these lists included host proteins that have been previously implicated as contributing to alphavirus replication.

        Byers, N. M. Burns, P. L. Ledermann, J. P. Powers, A. M.

      2. In the United States, rodents serve as important hosts of medically important Ixodes ticks, including Ixodes scapularis and Ixodes pacificus, as well as reservoirs for human pathogens, including Anaplasma phagocytophilum, Borrelia burgdorferi sensu stricto (s.s.), and Babesia microti. Over the last four decades, different methods to disrupt enzootic transmission of these pathogens between tick vectors and rodent reservoirs have been developed and evaluated. Early work focused on self-application of topical acaricide by rodents to kill infesting ticks; this resulted in two different types of commercial products based on (i) delivery of permethrin to rodents via impregnated cotton offered as nesting material or (ii) application of fipronil to rodents via an impregnated wick as they navigate through a bait box to reach a food source. More recent work has focused on approaches where acaricides, antibiotics, or a vaccine against Bo. burgdorferi s.s. are delivered orally via rodent food baits. Of these, the oral vaccine and oral acaricide are nearest to commercialization. Other approaches in early stages of development include anti-tick vaccines for rodents and use of heritable genome editing to engineer white-footed mice (Peromyscus leucopus) that are refractory to Bo. burgdorferi s.s. In this review, I first outline general benefits and drawbacks of rodent-targeted tick and pathogen control methods, and then describe the empirical evidence for different approaches to impact enzootic pathogen transmission and acarological risk of human exposure to pathogen-infected Ixodes ticks. Rodent-targeted methods remain promising components of integrated tick management approaches but there are concerns about the robustness of the impact of existing rodent-targeted products across habitats and variable tick host communities, and in some cases also for the implementation cost in relation to what homeowners in Lyme disease endemic areas say they are willing to pay for tick control.

        Eisen, L.

      3. One health investigation of SARS-CoV-2 in people and animals on multiple mink farms in Utah
        Cossaboom CM, Wendling NM, Lewis NM, Rettler H, Harvey RR, Amman BR, Towner JS, Spengler JR, Erickson R, Burnett C, Young EL, Oakeson K, Carpenter A, Kainulainen MH, Chatterjee P, Flint M, Uehara A, Li Y, Zhang J, Kelleher A, Lynch B, Retchless AC, Tong S, Ahmad A, Bunkley P, Godino C, Herzegh O, Drobeniuc J, Rooney J, Taylor D, Barton Behravesh C.
        Viruses. 2022;15(1).
        From July-November 2020, mink (Neogale vison) on 12 Utah farms experienced an increase in mortality rates due to confirmed SARS-CoV-2 infection. We conducted epidemiologic investigations on six farms to identify the source of virus introduction, track cross-species transmission, and assess viral evolution. Interviews were conducted and specimens were collected from persons living or working on participating farms and from multiple animal species. Swabs and sera were tested by SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and serological assays, respectively. Whole genome sequencing was attempted for specimens with cycle threshold values &lt;30. Evidence of SARS-CoV-2 infection was detected by rRT-PCR or serology in ≥1 person, farmed mink, dog, and/or feral cat on each farm. Sequence analysis showed high similarity between mink and human sequences on corresponding farms. On farms sampled at multiple time points, mink tested rRT-PCR positive up to 16 weeks post-onset of increased mortality. Workers likely introduced SARS-CoV-2 to mink, and mink transmitted SARS-CoV-2 to other animal species; mink-to-human transmission was not identified. Our findings provide critical evidence to support interventions to prevent and manage SARS-CoV-2 in people and animals on mink farms and emphasizes the importance of a One Health approach to address emerging zoonoses.

        Cossaboom, C. M. Wendling, N. M. Lewis, N. M. Harvey, R. R. Amman, B. R. Towner, J. S. Spengler, J. R. Carpenter, A. Kainulainen, M. H. Chatterjee, P. Flint, M. Ahmad, A. Bunkley, P. Godino, C. Herzegh, O. Drobeniuc, J. Barton Behravesh, C.


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