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Issue 7, February 15, 2022

CDC Science Clips: Volume 14, Issue 7, February 15, 2022

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreexternal icon to track social and mainstream media mentions.

  1. 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. Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolatesexternal icon
        Kaniga K, Hasan R, Jou R, Vasiliauskienė E, Chuchottaworn C, Ismail N, Metchock B, Miliauskas S, Viet Nhung N, Rodrigues C, Shin S, Simsek H, Smithtikarn S, Ngoc AL, Boonyasopun J, Kazi M, Kim S, Kamolwat P, Musteikiene G, Sacopon CA, Tahseen S, Vasiliauskaitė L, Wu MH, Vally Omar S.
        J Clin Microbiol. 2022 Jan 19;60(1):e0291920.
        Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 μg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 μg/ml by BMD and 0.25 μg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 μg/ml and 0.5 μg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

      2. Correlation between phenotypic and in silico detection of antimicrobial resistance in Salmonella enterica in Canada using Staramrexternal icon
        Bharat A, Petkau A, Avery BP, Chen J, Folster J, Carson CA, Kearney A, Nadon C, Mabon P, Thiessen J, Alexander DC, Allen V, El Bailey S, Bekal S, German GJ, Haldane D, Hoang L, Chui L, Minion J, Zahariadis G, Van Domselaar G, Reid-Smith RJ, Mulvey MR.
        Microorganisms. 2022 ;10(2).
        Whole genome sequencing (WGS) of Salmonella supports both molecular typing and detection of antimicrobial resistance (AMR). Here, we evaluated the correlation between phenotypic antimicrobial susceptibility testing (AST) and in silico prediction of AMR from WGS in Salmonella enterica (n = 1321) isolated from human infections in Canada. Phenotypic AMR results from broth microdilution testing were used as the gold standard. To facilitate high-throughput prediction of AMR from genome assemblies, we created a tool called Staramr, which incorporates the ResFinder and PointFinder databases and a custom gene-drug key for antibiogram prediction. Overall, there was 99% concordance between phenotypic and genotypic detection of categorical resistance for 14 antimicrobials in 1321 isolates (18,305 of 18,494 results in agreement). We observed an average sensitivity of 91.2% (range 80.5–100%), a specificity of 99.7% (98.6–100%), a positive predictive value of 95.4% (68.2–100%), and a negative predictive value of 99.1% (95.6–100%). The positive predictive value of gentamicin was 68%, due to seven isolates that carried aac(3)-IVa, which conferred MICs just below the breakpoint of resistance. Genetic mechanisms of resistance in these 1321 isolates included 64 unique acquired alleles and mutations in three chromosomal genes. In general, in silico prediction of AMR in Salmonella was reliable compared to the gold standard of broth microdilution. WGS can provide higher-resolution data on the epidemiology of resistance mechanisms and the emergence of new resistance alleles. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

    • Chronic Diseases and Conditions
      1. Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate dataexternal icon
        Magliano DJ, Chen L, Carstensen B, Gregg EW, Pavkov ME, Salim A, Andes LJ, Balicer R, Baviera M, Chan JC, Cheng YJ, Gardiner H, Gulseth HL, Gurevicius R, Ha KH, Jermendy G, Kim DJ, Kiss Z, Leventer-Roberts M, Lin CY, Luk AO, Ma S, Mata-Cases M, Mauricio D, Nichols GA, Pildava S, Porath A, Read SH, Robitaille C, Roncaglioni MC, Lopez-Doriga Ruiz P, Wang KL, Wild SH, Yekutiel N, Shaw JE.
        Lancet Diabetes Endocrinol. 2022 Feb;10(2):112-119.
        BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

    • Communicable Diseases
      1. Surveillance for disseminated gonococcal infections, Active Bacterial Core surveillance (ABCs) - United States, 2015-2019external icon
        Weston EJ, Heidenga BL, Farley MM, Tunali A, D'Angelo MT, Moore A, Workowski K, Raphael BH, Weinstock H, Torrone E.
        Clin Infect Dis. 2022 Jan 28.
        BACKGROUND: Disseminated gonococcal infections (DGI) are thought to be uncommon; surveillance is limited and case reports are analyzed retrospectively or in case clusters. We describe the population-level burden of culture-confirmed DGI through the Active Bacterial Core surveillance (ABCs) system. METHODS: During 2015-2016, retrospective surveillance was conducted among residents in two ABCs areas and prospectively in three ABCs areas during 2017-2019. A DGI case was defined as isolation of Neisseria gonorrhoeae (Ng) from a normally sterile site. A case report form was completed for each case and antimicrobial susceptibility testing (AST) was performed on available isolates. RESULTS: During 2015-2019, 77 DGI cases were identified (~a rate of 0.13 cases per 100,000 population) and accounted for 0.06% of all reported gonorrhea cases in the three surveillance areas. Most DGI cases were male (64%), non-Hispanic Black (68%), and ranged from 16-67 years; blood (55%) and joint (40%) were the most common sterile sites. Among 29 isolates with AST results during 2017-2019, all were susceptible to ceftriaxone. CONCLUSIONS: DGI is an infrequent complication of Ng; since Ng can quickly develop antimicrobial resistance, continued DGI surveillance, including monitoring trends in antimicrobial susceptibility, could help inform DGI treatment recommendations.

      2. Disengagement from HIV care and failure of second-line therapy in Nigeria: a retrospective cohort study, 2005-2017external icon
        El Bouzidi K, Murtala-Ibrahim F, Kwaghe V, Datir RP, Ogbanufe O, Crowell TA, Charurat M, Dakum P, Gupta RK, Ndembi N, Sabin CA.
        J Acquir Immune Defic Syndr. 2022 Jan 26.
        BACKGROUND: Understanding the correlates of disengagement from HIV care and treatment failure during second-line antiretroviral therapy (ART) could inform interventions to improve clinical outcomes among people living with HIV (PLHIV). METHODS: We conducted a retrospective cohort study of PLHIV aged >15 years who started second-line ART at a tertiary centre in Nigeria between 2005 and 2017. Participants were considered to have disengaged from care if they had not returned within a year after each clinic visit. Cox proportional hazards models were used to investigate factors associated with: i) viral failure (HIV-1 RNA >1,000 copies/mL), ii) immunologic failure (CD4 count decrease or <100 cells/mm3), and iii) severe weight loss (>10% of bodyweight), after >6 months of second-line ART. RESULTS: Among 1031 participants, 33% (341) disengaged from care during a median follow-up of 6.9 years (IQR 3.7-8.5). Of these, 26% (89/341) subsequently re-entered care. Disengagement was associated with male gender, age <30, lower education level and low CD4 count at second-line ART initiation. Among participants with endpoint assessments available, 20% (112/565) experienced viral failure, 32% (257/809) experienced immunologic failure, and 23% (190/831) experienced weight loss. A lower risk of viral failure was associated with professional occupations compared to elementary: adjusted hazard ratio 0.17 (95% confidence interval 0.04-0.70). CONCLUSION: Adverse outcomes were common during second-line ART. However, re-engagement is possible and resources should be allocated to focus on retaining PLHIV in care and providing services to trace and re-engage those who have disengaged from care.

      3. Prevalence of human papillomavirus among women older than recommended age for vaccination by birth cohort, United States 2003‒2016external icon
        Vahle K, Gargano JW, Lewis RM, Querec TD, Unger ER, Bednarczyk RA, Markowitz LE.
        J Infect Dis. 2022 Jan 5;225(1):94-104.
        BACKGROUND: Apparent associations between human papillomavirus (HPV) prevalence and age observed in cross-sectional studies could be misleading if cohort effects influence HPV detection. METHODS: Using data from 2003-2016 National Health and Nutrition Examination Surveys, we evaluated overall and 10-year birth cohort-specific cervicovaginal HPV prevalence estimates (any, high-risk [HR], and non-HR) by 3-year age group among 27 to 59-year-old women born in 1950-1979. Average percent changes (APC) in HPV prevalence by 3-year age were calculated. RESULTS: Overall, prevalence of any HPV declined from 49.9% in 27-29 year olds to 33.8% in 57-59 year olds (APC, -2.82% per 3-year age group; 95% confidence interval [CI], -4.02% to -1.60%) as did prevalence of HR-HPV (APC, -6.19%; 95% CI, -8.09% to -4.26%) and non-HR-HPV (APC, -2.00%; 95% CI, -3.48% to -.51%). By birth cohort, declines by age group were seen in prevalences of any HPV, HR-HPV, and non-HR-HPV for those born in the 1950s and 1970s and in any HPV and HR-HPV for those born in the 1960s (APC range, -14.08% to 0.06%). CONCLUSIONS: Declines in HPV prevalence with age in these cross-sectional surveys cannot be explained by birth cohort differences alone, as associations were observed across all birth cohorts.

      4. Mucocutaneous manifestations among adults hospitalized with multisystem inflammatory syndrome following SARS-cov-2 infectionexternal icon
        Tannenbaum R, Rekhtman S, Strunk A, Birabaharan M, Shaigany S, Burshtein J, Grbic N, Nazir Z, Norden A, Godfred-Cato S, Belay E, Patel P, Garg A.
        JAAD Int. 2022 Jan 24.
        Among adults hospitalized for severe illness with probable MIS-A, 6 patients with hyperinflammation had mucocutaneous involvement, most commonly with purpura.

      5. High burden of active syphilis and human immunodeficiency virus/syphilis coinfection among men who have sex with men, transwomen, and genderqueer individuals in Zimbabweexternal icon
        Parmley LE, Chingombe I, Wu Y, Mapingure M, Mugurungi O, Samba C, Rogers JH, Hakim AJ, Gozhora P, Miller SS, Musuka G, Harris TG.
        Sex Transm Dis. 2022 Feb 1;49(2):111-116.
        BACKGROUND: Syphilis increases human immunodeficiency virus (HIV) acquisition risk and impacts the immunologic and virologic response among people living with HIV (PLHIV). We assessed the prevalence of active or current syphilis and HIV/syphilis and their correlates among men who have sex with men (MSM), transwomen, and genderqueer (TGW/GQ) individuals in Zimbabwe. METHODS: Among a respondent-driven sample of MSM and TGW/GQ who were tested for HIV and syphilis in Harare and Bulawayo, Zimbabwe in 2019 (n = 1511), multiple logistic regression was used to assess correlates of active syphilis. Unadjusted logistic regression was used among PLHIV (n = 340) due to small sample size. All analyses were unweighted as data did not reach convergence for HIV. RESULTS: Prevalence of active syphilis overall and among PLHIV was 5.5% and 10.1%, respectively, in Harare, and 5.6% and 11.0%, respectively, in Bulawayo. Participants were more likely to have active syphilis if they were PLHIV (adjusted odds ratio [aOR], 2.2; 95% confidence interval [CI], 1.4-3.6), aged 25-34 years (aOR, 2.2 years; 95% CI, 1.3-3.8 years; reference, 18-24 years), or self-report sexually transmitted infection symptoms (aOR, 1.8; 95% CI, 1.1-3.0). Compared with Bulawayo TGW/GQ, MSM in Harare (aOR, 0.2; 95% CI, 0.1-0.5) and Bulawayo (aOR, 0.2; 95% CI, 0.1-0.4), and TGW/GQ in Harare (aOR, 0.2; 95% CI, 0.1-0.6) were less likely to have active syphilis. Among PLHIV, coinfection was 13.0% among TGW/GQ and 9.7% among MSM. Odds of coinfection were higher for those aged 25 to 34 years (OR, 3.7 years; 95% CI, 1.2-11.1 years) and lower among Harare MSM (OR, 0.2; 95% CI, 0.1-0.7), Bulawayo MSM (OR, 0.1; 95% CI, 0.0-0.4), and Harare TGW/GQ (OR, 0.1; 95% CI, 0.0-0.4) compared with Bulawayo TGW/GQ. CONCLUSIONS: Findings highlight a high burden of syphilis among MSM and TGW/GQ and underscore the importance of HIV/syphilis detection and improved service delivery for these groups.

      6. Estimates of mortality associated with seasonal influenza for the European Union from the GLaMOR projectexternal icon
        Paget J, Iuliano A, Taylor RJ, Simonsen L, Viboud C, Spreeuwenberg P.
        Vaccine. 2022 Jan 28.
        BACKGROUND: The European Centres for Disease Prevention and Control (ECDC) estimates that seasonal influenzacauses 4-50 million symptomatic infections in the EU/EEA each year and 15,000-70,000 European citizens die of causes associated with influenza. We used modelling methods to estimate influenza-associated mortality for the European Union by age group and country. METHODS: We compiled influenza-associated respiratory mortality estimates for 31 countries around the world (11 countries in the EU) during 2002-2011 (excluding the 2009 pandemic). From these we extrapolated the influenza mortality burden for all 193 countries of the world, including the 28 countries of the EU, using a multiple imputation approach. To study the effect of vaccination programs, we obtained data from the EU-funded VENICE project regarding the percentage of persons over 65 who were vaccinated in each country; the data ranged from 2% to 82% between the 21 countries which provided estimates for the 2006/07 reference season. RESULTS: We estimated that an average of 27,600 (range 16,200-39,000) respiratory deaths were associated with seasonal influenza in the 28 EU countries per winter; 88% were among people 65 years and older, and the rates of mortality in this age group were roughly 35 times higher compared with those < 65 years. Estimates varied considerably across the EU; for example, rates in the elderly ranged from 21.6 (12.5-35.1) per 100,000 in Portugal to 36.5 (16.4-62.5) in Luxembourg, a difference of nearly 70%. We were unable to find a negative correlation between vaccination coverage rates and influenza-associated mortality estimates in the elderly. CONCLUSION: Our EU estimate of influenza-associated respiratory mortality is broadly consistent with the ECDC estimate. More research is needed to explain the observed variation in mortality across the EU, and on possible bias that could explain the unexpected lack of mortality benefits associated with European elderly influenza vaccination programs.

    • Community Health Services
      1. Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: a before-after cohort study using mixed effects regressionexternal icon
        Pry JM, Sikombe K, Mody A, Iyer S, Mutale J, Vlahakis N, Savory T, Wa Mwanza M, Mweebo K, Mwila A, Mwale C, Mukumbwa-Mwenechanya M, Kerkhoff AD, Sikazwe I, Bolton Moore C, Mwamba D, Geng EH, Herce ME.
        BMJ Glob Health. 2022 Jan;7(1).
        INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. METHODS: We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January-30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. RESULTS: A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation . CONCLUSIONS: Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency.

    • Disaster Preparedness and Emergency Services
      1. Five essential elements of immediate and mid-term mass trauma intervention: Empirical evidenceexternal icon
        Hobfoll SE, Watson P, Bell CC, Bryant RA, Brymer MJ, Friedman MJ, Friedman M, Gersons BP, de Jong J, Layne CM, Maguen S, Neria Y, Norwood AE, Pynoos RS, Reissman D, Ruzek JI, Shalev AY, Solomon Z, Steinberg AM, Ursano RJ.
        Psychiatry. 2021 Winter;84(4):311-346.
        Given the devastation caused by disasters and mass violence, it is critical that intervention policy be based on the most updated research findings. However, to date, no evidence-based consensus has been reached supporting a clear set of recommendations for intervention during the immediate and the mid-term post mass trauma phases. Because it is unlikely that there will be evidence in the near or mid-term future from clinical trials that cover the diversity of disaster and mass violence circumstances, we assembled a worldwide panel of experts on the study and treatment of those exposed to disaster and mass violence to extrapolate from related fields of research, and to gain consensus on intervention principles. We identified five empirically supported intervention principles that should be used to guide and inform intervention and prevention efforts at the early to mid-term stages. These are promoting: 1) a sense of safety, 2) calming, 3) a sense of self- and community efficacy, 4) connectedness, and 5) hope.

    • Environmental Health
      1. Water management programs are key to managing Legionella growth and spreadexternal icon
        Curtiss E, Hils J, Kunz J.
        J Environ Health. 2022 ;84(6):30-32.

      2. Air aware: Improving use of an existing air quality and health toolexternal icon
        Damon SA, Rupert DJ, Pryzby R.
        J Health Commun. 2022 Feb 1:1-7.
        Exposure to air pollutants is a significant health risk for individuals with asthma, cardiovascular disease, and chronic obstructive pulmonary disease. Measures such as limiting time outdoors or performing less strenuous tasks when air quality levels are better can mitigate these risks, but only if people are aware of both these recommendations and how to know when air quality is best, and worst. Formative audience assessment determined that applications developed for mobile devices are the optimal way to provide this information, but knowledge of the existing United States Environmental Protection Agency (EPA) and partners' AirNow tool was minimal. We developed, field-tested, adapted, and implemented pilot efforts at both the national and local levels to address this knowledge gap, and present findings suggesting a concentrated local effort can heighten use of AirNow, leading to more pro-healthy behavior.

      3. Indirect mediators of systemic health outcomes following nanoparticle inhalation exposureexternal icon
        Mostovenko E, Canal CG, Cho M, Sharma K, Erdely A, Campen MJ, Ottens AK.
        Pharmacol Ther. 2022 Jan 24:108120.
        The growing field of nanoscience has shed light on the wide diversity of natural and anthropogenic sources of nano-scale particulates, raising concern as to their impacts on human health. Inhalation is the most robust route of entry, with nanoparticles (NPs) evading mucociliary clearance and depositing deep into the alveolar region. Yet, impacts from inhaled NPs are evident far outside the lung, particularly on the cardiovascular system and highly vascularized organs like the brain. Peripheral effects are partly explained by the translocation of some NPs from the lung into the circulation; however, other NPs largely confined to the lung are still accompanied by systemic outcomes. Omic research has only just begun to inform on the complex myriad of molecules released from the lung to the blood as byproducts of pulmonary pathology. These indirect mediators are diverse in their molecular make-up and activity in the periphery. The present review examines systemic outcomes attributed to pulmonary NP exposure and what is known about indirect pathological mediators released from the lung into the circulation. Further focus was directed to outcomes in the brain, a highly vascularized region susceptible to acute and longer-term outcomes. Findings here support the need for big-data toxicological studies to understand what drives these health outcomes and better predict, circumvent, and treat the potential health impacts arising from NP exposure scenarios.

    • Epidemiology and Surveillance
      1. Severe acute respiratory syndrome coronavirus 2 transmission in a Georgia school district-United States, December 2020-January 2021external icon
        Gettings JR, Gold JA, Kimball A, Forsberg K, Scott C, Uehara A, Tong S, Hast M, Swanson MR, Morris E, Oraka E, Almendares O, Thomas ES, Mehari L, McCloud J, Roberts G, Crosby D, Balajee A, Burnett E, Chancey RJ, Cook P, Donadel M, Espinosa C, Evans ME, Fleming-Dutra KE, Forero C, Kukielka EA, Li Y, Marcet PL, Mitruka K, Nakayama JY, Nakazawa Y, O'Hegarty M, Pratt C, Rice ME, Rodriguez Stewart RM, Sabogal R, Sanchez E, Velasco-Villa A, Weng MK, Zhang J, Rivera G, Parrott T, Franklin R, Memark J, Drenzek C, Hall AJ, Kirking HL, Tate JE, Vallabhaneni S.
        Clin Infect Dis. 2022 Jan 29;74(2):319-326.
        BACKGROUND: To inform prevention strategies, we assessed the extent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During 1 December 2020-22 January 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (eg, sports, elementary school classroom), index case role (ie, staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1119 contacts, 688 (61.5%) of whom received testing. Fifty-nine of 679 (8.7%) contacts tested positive; 15 of 86 (17.4%) index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SARs were in indoor, high-contact sports settings (23.8% [95% confidence interval {CI}, 12.7%-33.3%]), staff meetings/lunches (18.2% [95% CI, 4.5%-31.8%]), and elementary school classrooms (9.5% [95% CI, 6.5%-12.5%]). The SAR was higher for staff (13.1% [95% CI, 9.0%-17.2%]) vs student index cases (5.8% [95% CI, 3.6%-8.0%]) and for symptomatic (10.9% [95% CI, 8.1%-13.9%]) vs asymptomatic index cases (3.0% [95% CI, 1.0%-5.5%]). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include coronavirus disease 2019 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

    • Genetics and Genomics
      1. Mutation of mycobacterium tuberculosis and implications for using whole-genome sequencing for investigating recent tuberculosis transmissionexternal icon
        Nelson KN, Talarico S, Poonja S, McDaniel CJ, Cilnis M, Chang AH, Raz K, Noboa WS, Cowan L, Shaw T, Posey J, Silk BJ.
        Front Public Health. 2021 ;9:790544.
        Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.

      2. Genomic analysis of clostridioides difficile in 2 regions of the United States reveals a diversity of strains and limited transmissionexternal icon
        Pecora N, Holzbauer S, Wang X, Gu Y, Taffner S, Hatwar T, Hardy D, Dziejman M, D'Heilly P, Pung K, Guh A, Qiu X, Gill S, Dumyati G.
        J Infect Dis. 2022 Jan 5;225(1):121-129.
        BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole-genome sequencing across 2 Centers for Disease Control and Prevention Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community-associated (CA) and healthcare-associated (HCA) disease and assess transmission. METHODS: Whole-genome sequencing was performed on C. difficile isolates from patients with CDI over 3 months between 2016 and 2017. Patients were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. CDI cases were epidemiologically classified as HCA or CA. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were sequence type (ST) 42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), and ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%) and ST41 (77.8%). ST1 was more frequent in New York than in Minnesota (10.8% vs 3.1%). Thirty-three pairs were closely related genomically, 14 of which had potential patient-to-patient transmission supported by record review. CONCLUSIONS: The genomic epidemiology of C. difficile across 2 regions of the United States indicates the presence of a diverse strain profile and limited direct transmission.

    • Health Communication and Education
      1. BACKGROUND: On 1 February 2016, the World Health Organization declared Zika transmission a public health emergency of international concern. Monitoring and responding to community awareness, concern, and possible knowledge gaps are critical during public health emergencies. Here, we describe the review and analysis of micro-blogs posted on Sina-Weibo, China's largest social media platform, to develop and disseminate a Zika virus education campaign. METHODS: We used CYYUN Voice Express' Weibo Spider tool and the search terms of "Zhaika" OR "Zika" OR "Zikv" to capture microblogs about Zika virus retrospectively from February 1 to December 31, 2016 and prospectively from June 1 to November 15, 2017. We described microblogs meeting our inclusion criteria by month and Zika virus outbreaks in Asia and by source (e.g., government agency, individual, or other). We identified common misleading or inaccurate content authored by individual micro-bloggers (i.e., not supported by available scientific evidence) through a qualitative review. We used this information to develop and disseminate health awareness material about the Zika virus through China CDC's 12320 Health Hotline Weibo account. An online survey was conducted to obtain feedback on the material. RESULTS: We captured 15,888 microblogs meeting our inclusion criteria. Zika-related microblogs peaked in September 2016, corresponding to news reports about the Zika outbreak in Singapore (August to November 2016). Most microblogs (12,994 [82%]) were authored by individual users, followed by media agencies (842 [5%]), businesses (829 [5%]), international organizations (370 [2%]), and Chinese government agencies (235 [1%]). Relevant microblogs primarily focused on clinical symptoms and health risks, modes of transmission, and actions taken by individuals to prevent infection and seek health care. Incorrect and/or mis-leading information from individual users concentrated on modes of transmission and possible treatments. The microblog "#Zika is that far and this close" health campaign was posted on Sina-Weibo and Baidu (Internet search engine in China) on September 18, 2016. Younger respondents (p-value = 0.01), and those with at least a college education (p-value = 0.03), were more likely than other respondents to consider the online campaign reliable and trustworthy. CONCLUSION: Routine review of Sina-Weibo and other social media platforms could enhance the ability of public health staff to effectively respond to community concerns and awareness during public health emergencies. Advancements of social media monitoring tools and staff training could help to promote health awareness during emergencies by directly addressing public perceptions and concerns. Various approaches may be needed to reach different at-risk populations, particularly older and less educated populations who may prefer more traditional modes of communication.

    • Health Economics
      1. Cost-effectiveness of long-acting injectable HIV preexposure prophylaxis in the United States : A cost-effectiveness analysisexternal icon
        Neilan AM, Landovitz RJ, Le MH, Grinsztejn B, Freedberg KA, McCauley M, Wattananimitgul N, Cohen MS, Ciaranello AL, Clement ME, Reddy KP, Hyle EP, Paltiel AD, Walensky RP.
        Ann Intern Med. 2022 Feb 1.
        BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP). OBJECTIVE: To identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States. DESIGN: Simulation, cost-effectiveness analysis. DATA SOURCES: Trial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed. TARGET POPULATION: 476 700 MSM/TGW at very high risk for HIV (VHR). TIME HORIZON: 10 years. PERSPECTIVE: Health care system. INTERVENTION: CAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP. OUTCOME MEASURES: Primary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP. RESULTS OF BASE-CASE ANALYSIS: Compared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year). RESULTS OF SENSITIVITY ANALYSIS: In a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year). LIMITATION: Uncertain clinical and economic benefits of averting future transmissions. CONCLUSION: Effective oral PrEP limits the additional price society should be willing to pay for CAB-LA. PRIMARY FUNDING SOURCE: FHI 360; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.

      2. Cost-effectiveness of 1-time universal screening for chronic hepatitis b infection in adults in the United Statesexternal icon
        Toy M, Hutton D, Harris AM, Nelson N, Salomon JA, So S.
        Clin Infect Dis. 2022 Jan 29;74(2):210-217.
        BACKGROUND: An estimated 862 000 to 2.4 million people have chronic hepatitis B infection (CHB). Hepatitis B screening is recommended for pregnant women and populations with increased CHB risk. However, diagnosis rates remain low, with only 33% of people with CHB aware of their infection. This study aimed to assess the cost-effectiveness of universal adult screening for CHB. METHODS: We used a Markov model to calculate the costs, population health impact, and cost-effectiveness of 1-time universal screening and CHB monitoring and treatment compared with current practice. Sensitivity analysis was performed on model parameters to identify thresholds for cost-saving or cost-effectiveness based on a willingness to pay of $50 000/quality-adjusted life-year. The analysis assumed testing would be performed during routine healthcare visits and that generic tenofovir or entecavir would be dispensed for treatment. Testing costs were based on Medicare reimbursement rates. RESULTS: At an estimated 0.24% prevalence of undiagnosed CHB, universal hepatitis B surface antigen (HBsAg) screening in adults aged 18-69 years is cost-saving compared with current practice if antiviral treatment drug costs remain below $894/year. Compared with current practice, universal screening would avert an additional 7.4 cases of compensated cirrhosis, 3.3 cases of decompensated cirrhosis, 5.5 cases of hepatocellular carcinoma, 1.9 liver transplants, and 10.3 hepatitis B virus-related deaths at a saving of $263 000/100 000 adults screened. CONCLUSIONS: Universal HBsAg screening of adults in the US general population for CHB is cost-effective and likely cost-saving compared with current CHB screening recommendations.

      3. Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101-200 cells/µL in Botswanaexternal icon
        Tenforde MW, Muthoga C, Ponatshego P, Ngidi J, Mine M, Greene G, Jordan A, Chiller T, Larson BA, Jarvis JN.
        Wellcome Open Res. 2021 ;6:55.
        Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101-200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101-200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101-200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved).  While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101-200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.

    • Health Equity and Health Disparities
      1. Neighborhood socioeconomic environment and risk of type 2 diabetes: Associations and mediation through food environment pathways in three independent study samplesexternal icon
        Thorpe LE, Adhikari S, Lopez P, Kanchi R, McClure LA, Hirsch AG, Howell CR, Zhu A, Alemi F, Rummo P, Ogburn EL, Algur Y, Nordberg CM, Poulsen MN, Long L, Carson AP, DeSilva SA, Meeker M, Schwartz BS, Lee DC, Siegel KR, Imperatore G, Elbel B.
        Diabetes Care. 2022 Feb 1.
        OBJECTIVE: We examined whether relative availability of fast-food restaurants and supermarkets mediates the association between worse neighborhood socioeconomic conditions and risk of developing type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: As part of the Diabetes Location, Environmental Attributes, and Disparities Network, three academic institutions used harmonized environmental data sources and analytic methods in three distinct study samples: (1) the Veterans Administration Diabetes Risk (VADR) cohort, a national administrative cohort of 4.1 million diabetes-free veterans developed using electronic health records (EHRs); (2) Reasons for Geographic and Racial Differences in Stroke (REGARDS), a longitudinal, epidemiologic cohort with Stroke Belt region oversampling (N = 11,208); and (3) Geisinger/Johns Hopkins University (G/JHU), an EHR-based, nested case-control study of 15,888 patients with new-onset T2D and of matched control participants in Pennsylvania. A census tract-level measure of neighborhood socioeconomic environment (NSEE) was developed as a community type-specific z-score sum. Baseline food-environment mediators included percentages of (1) fast-food restaurants and (2) food retail establishments that are supermarkets. Natural direct and indirect mediating effects were modeled; results were stratified across four community types: higher-density urban, lower-density urban, suburban/small town, and rural. RESULTS: Across studies, worse NSEE was associated with higher T2D risk. In VADR, relative availability of fast-food restaurants and supermarkets was positively and negatively associated with T2D, respectively, whereas associations in REGARDS and G/JHU geographies were mixed. Mediation results suggested that little to none of the NSEE-diabetes associations were mediated through food-environment pathways. CONCLUSIONS: Worse neighborhood socioeconomic conditions were associated with higher T2D risk, yet associations are likely not mediated through food-environment pathways.

      2. Phylogenomics of SARS-COV-2 in emergency shelters for people experiencing homelessnessexternal icon
        Casto AM, Rogers JH, Link AC, Boeckh M, Jackson ML, Uyeki TM, Englund JA, Starita LM, Chu HY.
        J Infect Dis. 2022 Jan 29.
        Residents and staff of emergency shelters for people experiencing homelessness (PEH) are at high risk of infection with SARS-CoV-2. The importance of shelter-related transmission of SARS-CoV-2 in this population remains unclear. It is also unknown whether there is significant spread of shelter-related viruses into surrounding communities. We analyzed genome sequence data for 28 SARS-CoV-2-positive specimens collected from 8 shelters in King County, Washington between March and October, 2020. We identified at least 12 separate SARS-CoV-2 introduction events into these 8 shelters and estimated that 57% (16 out of 28) of the examined cases of SARS-CoV-2 infection were the result of intra-shelter transmission. However, we identified just a few SARS-CoV-2 specimens from Washington that were possible descendants of shelter viruses. Our data suggest that SARS-CoV-2 spread in shelters is common, but we did not observe evidence of wide-spread transmission of shelter-related viruses into the general population.

      3. INTRODUCTION: Health-related behavioral risk factors and obesity are linked to high risk for multiple chronic diseases. We examined the prevalence of these risk factors among American Indians and Alaska Natives (AI/ANs) compared with that of non-Hispanic Whites and across Indian Health Service (IHS) regions. METHODS: We used 2017 Behavioral Risk Factor Surveillance System data from participants in 50 states and the District of Columbia to assess 4 behavioral risk factors (current cigarette smoking, heavy drinking, binge drinking, and physical inactivity) and obesity. We analyzed disparities in these risk factors between AI/AN and non-Hispanic White participants, nationwide and by IHS region, by conducting log-linear regression analyses while controlling for potential confounders. RESULTS: Nationwide, crude prevalence of current smoking, physical inactivity, and obesity were significantly higher among AI/AN than non-Hispanic White participants. After adjustment for sociodemographic characteristics, AI/AN participants were 11% more likely to report current smoking (P < .05) and 23% more likely to report obesity (P < .001) than non-Hispanic White participants. These patterns persisted in most IHS regions with some exceptions. In the Southwest region, AI/AN participants were 39% less likely to report current smoking than non-Hispanic White participants (P < .001). In the Pacific Coast region, compared with non-Hispanic White participants, AI/AN participants were 54% less likely to report heavy drinking (P < .01) but 34% more likely to report physical inactivity (P < .05). Across IHS regions, AI/AN participants residing in Alaska and the Northern Plains regions had the highest prevalence of current smoking and binge drinking, and those in the Southwest and Pacific Coast regions had the lowest prevalence of current smoking. AI/AN participants in the Southwest region had the lowest prevalence of physical inactivity, and those in the Southern Plains region had the highest prevalence of obesity. CONCLUSIONS: The findings of this study support the importance of public health efforts to address and improve behavioral risk factors related to chronic disease in AI/AN people, both nationwide and among IHS regions, through culturally appropriate interventions.

    • Healthcare Associated Infections
      1. Stopping Hospital Infections with Environmental Services (shine): A cluster-randomized trial of intensive monitoring methods for terminal room cleaning on rates of multidrug-resistant organisms in the intensive care unitexternal icon
        Ziegler MJ, Babcock HH, Welbel SF, Warren DK, Trick WE, Tolomeo P, Omorogbe J, Garcia D, Habrock-Bach T, Donceras O, Gaynes S, Cressman L, Burnham JP, Bilker W, Reddy SC, Pegues D, Lautenbach E, Kelly BJ, Fuchs B, Martin ND, Han JH.
        Clin Infect Dis. 2022 Feb 1.
        BACKGROUND: Multidrug-resistant organisms (MDROs) frequently contaminate hospital environments. We performed a multicenter, cluster-randomized, crossover trial of two methods for monitoring of terminal cleaning effectiveness. METHODS: Six intensive care units (ICUs) at three medical centers received both interventions sequentially, in randomized order. Ten surfaces were surveyed each in five rooms weekly, after terminal cleaning, with ATP monitoring or an ultraviolet fluorescent marker (UV/F). Results were delivered to environmental services staff in real-time with failing surfaces recleaned. We measured monthly rates of MDRO infection or colonization, including methicillin-resistant Staphylococcus aureus, Clostridioides difficile, vancomycin-resistant Enterococcus, and MDR gram-negative bacilli (MDR-GNB) during a 12-month baseline period and sequential 6-month intervention periods, separated by a 2-month washout. Primary analysis compared only the randomized intervention periods, while secondary analysis included the baseline. RESULTS: The ATP method was associated with a reduction in incidence rate of MDRO infection or colonization compared to the UV/F period (incidence rate ratio (IRR) 0.876, 95% confidence-interval (CI) 0.807 - 0.951, P=0.002). Including the baseline period, the ATP method was associated with reduced infection with MDROs (IRR 0.924, 95% CI 0.855 - 0.998, P=0.04), and MDR-GNB infection or colonization (IRR 0.856, 95% CI 0.825 - 0.887, P<0.001). The UV/F intervention was not associated with a statistically significant impact on these outcomes. Room turn-around time increased by a median of one minute with the ATP intervention and 4.5 minutes with UV/F compared to baseline. CONCLUSIONS: Intensive monitoring of ICU terminal room cleaning with an ATP modality is associated with a reduction of MDRO infection and colonization.

      2. Development and evaluation of a structured guide to assess the preventability of hospital-onset bacteremia and fungemiaexternal icon
        Schrank GM, Sick-Samuels A, Bleasdale SC, Jacob JT, Dantes R, Gokhale RH, Mayer J, Mehrotra P, Mehta SA, Mena Lora AJ, Ray SM, Rhee C, Salinas JL, Seo SK, Shane AL, Nadimpalli G, Milstone AM, Robinson G, Brown CH, Harris AD, Leekha S.
        Infect Control Hosp Epidemiol. 2022 Jan 28:1-7.
        OBJECTIVE: To assess preventability of hospital-onset bacteremia and fungemia (HOB), we developed and evaluated a structured rating guide accounting for intrinsic patient and extrinsic healthcare-related risks. DESIGN: HOB preventability rating guide was compared against a reference standard expert panel. PARTICIPANTS: A 10-member panel of clinical experts was assembled as the standard of preventability assessment, and 2 physician reviewers applied the rating guide for comparison. METHODS: The expert panel independently rated 82 hypothetical HOB scenarios using a 6-point Likert scale collapsed into 3 categories: preventable, uncertain, or not preventable. Consensus was defined as concurrence on the same category among ≥70% experts. Scenarios without consensus were deliberated and followed by a second round of rating.Two reviewers independently applied the rating guide to adjudicate the same 82 scenarios in 2 rounds, with interim revisions. Interrater reliability was evaluated using the κ (kappa) statistic. RESULTS: Expert panel consensus criteria were met for 52 scenarios (63%) after 2 rounds.After 2 rounds, guide-based rating matched expert panel consensus in 40 of 52 (77%) and 39 of 52 (75%) cases for reviewers 1 and 2, respectively. Agreement rates between the 2 reviewers were 84% overall (κ, 0.76; 95% confidence interval [CI], 0.64-0.88]) and 87% (κ, 0.79; 95% CI, 0.65-0.94) for the 52 scenarios with expert consensus. CONCLUSIONS: Preventability ratings of HOB scenarios by 2 reviewers using a rating guide matched expert consensus in most cases with moderately high interreviewer reliability. Although diversity of expert opinions and uncertainty of preventability merit further exploration, this is a step toward standardized assessment of HOB preventability.

      3. An epidemic of pediatric HIV from reuse of infusion equipment in Pakistanexternal icon
        Syed MA, Khan A, Chaudhry A, Baig MA, Memon NM, Kumar S, Bhurt SA, Qadri M, Vighio A, Baig ZI, Rabold EM, Ali H, Blanton C, Asghar RJ, Ikram A, Rahim M, Solangi M, Mahipala P, Fontaine RE.
        J Acquir Immune Defic Syndr. 2022 Feb 1;89(2):121-128.
        BACKGROUND: From April to June 2019, a total of 909 new HIV infections were identified in Larkana, Pakistan; 86% was children younger than 15 years. To identify the possible transmission links in this outbreak, a case-control study was conducted in June 2019. METHODS: For cases, we selected a systematic random sample of 100 HIV-positive children from the screening list. We chose 2 age-matched and sex-matched controls from the neighborhood of each HIV-positive case. All selected children were tested using the World Health Organization-approved rapid diagnosis test algorithm. We interviewed the parents of each selected child about previous exposures to parenteral treatment and compared exposures of case and control children using conditional logistic regression. RESULTS: The ages of the selected children ranged from 1 month to 10 years. More than 90% of both HIV+ and HIV- children had received outpatient health care from MBBS-qualified private physicians. Eighty-three percent of HIV+ children versus 46% of HIV- children had received health care from one private physician [adjusted odds ratio (aOR) = 29, 95% confidence interval (95% CI): 10 to 79]. Intravenous infusions during the last outpatient visit were reported by 29% of case versus 7% of controls (aOR 57, 95% CI: 2.9 to >1000), whereas no case children and 17% of control children had received only intramuscular injections (aOR 0, 95% CI: 0 to 41). Among cases, 94% had been given infusions through a drip set compared with 85% of control children (aOR = 7.7, 95% CI: 2.3 to 26). Infusions had been administered with reused IV drip sets in 70% of cases compared with 8% of controls (aOR = 197, 95% CI: 16 to 2400). DISCUSSION: Private physicians reusing intravenous drip sets to treat outpatients seen in private practice were responsible for this HIV epidemic. Mapping and regulation of private practitioners were suggested.

    • Immune System Disorders
      1. Association of tumor necrosis factor α inhibitor use with diagnostic features and mortality of tuberculosis in the United States, 2010-2017external icon
        Katrak SS, Li R, Reynolds S, Marks SM, Probst JR, Chorba T, Winthrop K, Castro KG, Goswami ND.
        Open Forum Infect Dis. 2022 Feb;9(2):ofab641.
        BACKGROUND: An elevated risk of tuberculosis (TB) disease in persons who have received tumor necrosis factor alpha inhibitor medications (TNF-α inhibitors) has been reported for nearly two decades, but clinical diagnostic features and outcomes of TB in this population remain poorly described. METHODS: We analyzed national surveillance data for TB cases among persons aged 15 years and older reported in the United States during 2010-2017 and associated mortality data reported through 2019 to describe the clinical characteristics of those receiving TNF-α inhibitors. RESULTS: Of 70 129 TB cases analyzed, 504 (0.7%) of the patients had TNF-α inhibitor use reported at TB diagnosis. Patients with TNF-α inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF-α inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P < .001). Patients receiving TNF-α inhibitors were less likely to have acid-fast bacilli noted on sputum smear microscopy (25.6% vs 39.1%, P = .04), and more likely to have drug-resistant disease (13.5% vs 10.0%, P < .001). TB-attributed deaths did not significantly differ between patients receiving and not receiving TNF-α inhibitors (adjusted odds ratio, 1.46 [95% confidence interval, .95-2.26]). CONCLUSIONS: Clinicians evaluating TNF-α inhibitor-treated patients should have a high index of suspicion for TB and be aware that extrapulmonary or sputum smear-negative TB disease is more common in these patients. No significantly diminished survival of TB patients treated with TNF-α inhibitor therapy before TB diagnosis was noted.

    • Immunity and Immunization
      1. Effectiveness of COVID-19 vaccines among incarcerated people in California state prisons: retrospective cohort studyexternal icon
        Chin ET, Leidner D, Zhang Y, Long E, Prince L, Schrag SJ, Verani JR, Wiegand RE, Alarid-Escudero F, Goldhaber-Fiebert JD, Studdert DM, Andrews JR, Salomon JA.
        Clin Infect Dis. 2022 Jan 27.
        BACKGROUND: Prisons and jails are high-risk settings for COVID-19. Vaccines may substantially reduce these risks, but evidence is needed on COVID-19 vaccine effectiveness for incarcerated people, who are confined in large, risky congregate settings. METHODS: We conducted a retrospective cohort study to estimate effectiveness of mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed SARS-CoV-2 infections among incarcerated people in California prisons from December 22, 2020 through March 1, 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates, adjusted for resident characteristics and infection rates across prisons. RESULTS: Among 60,707 cohort members, 49% received at least one BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable: 74% [95% CI, 62-82%] and 92% [95% CI, 74-98%] from 14 days after first and second doses, respectively. CONCLUSIONS: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination, and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population.

      2. Using an agent-based model, we examined the impact of community prevalence, the Delta variant, staff vaccination coverage, and boosters for residents on outbreak dynamics in nursing homes. Increased staff coverage and high booster vaccine effectiveness leads to fewer infections, but cumulative incidence is highly dependent on community transmission.

      3. Characteristics of reported deaths among fully vaccinated persons with COVID-19 -United States, January-April 2021external icon
        Watkins LK, Mitruka K, Dorough L, Bressler SS, Kugeler KJ, Sadigh KS, Birhane MG, Nolen LD, Fischer M.
        Clin Infect Dis. 2022 Jan 29.
        BACKGROUND: COVID-19 vaccines are highly efficacious, but SARS-CoV-2 infections post-vaccination occur. We characterized COVID-19 cases among fully vaccinated persons with an outcome of death. METHODS: We analyzed COVID-19 cases voluntarily reported to CDC by US health departments during January 1, 2021-April 30, 2021. We included cases among U.S. residents with a positive SARS-CoV-2 test ≥14 days after completion of an authorized primary vaccine series and who had a known outcome (alive or death) as of May 31, 2021. When available, specimens were sequenced for viral lineage and death certificates were reviewed for cause(s) of death. RESULTS: Of 8,084 reported COVID-19 cases among fully vaccinated persons during the surveillance period, 245 (3.0%) died. Compared with patients who remained alive, those who died were older (median age 82 years vs. 57 years, P <0.01), more likely to reside in a long-term care facility (51% vs. 18%, P <0.01), and more likely to have at least one underlying health condition associated with risk for severe disease (64% vs. 24%, P <0.01). Among 245 deaths, 191 (78%) were classified as COVID-19-related. Of 106 deaths with available death certificates, COVID-19 was listed on 81 (77%). There were no differences in the type of vaccine administered or the most common viral lineage (B.1.1.7). CONCLUSIONS: COVID-19 deaths are rare in fully vaccinated persons, occurring most commonly in those with risk factors for severe disease, including older age and underlying health conditions. All eligible persons should be fully vaccinated against COVID-19 and follow other prevention measures to mitigate exposure risk.

      4. Lassa virus replicon particle vaccine protects strain 13/N guinea pigs against challenge with geographically and genetically diverse viral strainsexternal icon
        Spengler JR, Kainulainen MH, Welch SR, Coleman-McCray JA, Harmon JR, Condrey JA, Scholte FE, Nichol ST, Montgomery JM, Albariño CG, Spiropoulou CF.
        J Infect Dis. 2022 Jan 31.
        Lassa virus (LASV) causes mild to severe hemorrhagic fever disease in humans. Strain 13/N guinea pigs are highly susceptible to infection with LASV strain Josiah (clade IV), providing a critical model system for therapeutics and vaccine development. To develop additional models of disease, we detail the clinical course in guinea pigs infected with 5 geographically and genetically diverse LASV strains. Two of the developed models (LASV clades II and III) were then used to evaluate efficacy of a virus replicon particle (VRP) vaccine against heterologous LASV challenge, demonstrating complete protection against clinical disease after a single vaccination dose.

      5. COVID-19 incidence and death rates among unvaccinated and fully vaccinated adults with and without booster doses during periods of Delta and Omicron variant emergence - 25 U.S. jurisdictions, April 4-December 25, 2021external icon
        Johnson AG, Amin AB, Ali AR, Hoots B, Cadwell BL, Arora S, Avoundjian T, Awofeso AO, Barnes J, Bayoumi NS, Busen K, Chang C, Cima M, Crockett M, Cronquist A, Davidson S, Davis E, Delgadillo J, Dorabawila V, Drenzek C, Eisenstein L, Fast HE, Gent A, Hand J, Hoefer D, Holtzman C, Jara A, Jones A, Kamal-Ahmed I, Kangas S, Kanishka F, Kaur R, Khan S, King J, Kirkendall S, Klioueva A, Kocharian A, Kwon FY, Logan J, Lyons BC, Lyons S, May A, McCormick D, Mendoza E, Milroy L, O'Donnell A, Pike M, Pogosjans S, Saupe A, Sell J, Smith E, Sosin DM, Stanislawski E, Steele MK, Stephenson M, Stout A, Strand K, Tilakaratne BP, Turner K, Vest H, Warner S, Wiedeman C, Zaldivar A, Silk BJ, Scobie HM.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 28;71(4):132-138.
        Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status(†) indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended(§) additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),(¶) case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.

      6. Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. Adults: Updated recommendations of the Advisory Committee on Immunization Practices - United States, 2022external icon
        Kobayashi M, Farrar JL, Gierke R, Britton A, Childs L, Leidner AJ, Campos-Outcalt D, Morgan RL, Long SS, Talbot HK, Poehling KA, Pilishvili T.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 28;71(4):109-117.
        In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme Corp.) were licensed by the Food and Drug Administration for adults aged ≥18 years, based on studies that compared antibody responses to PCV20 and PCV15 with those to 13-valent PCV (PCV13) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). Antibody responses to two additional serotypes included in PCV15 were compared to corresponding responses after PCV13 vaccination, and antibody responses to seven additional serotypes included in PCV20 were compared with those to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) (Merck Sharp & Dohme Corp.). On October 20, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years, and for adults aged 19-64 years with certain underlying medical conditions or other risk factors* who have not previously received a PCV or whose previous vaccination history is unknown. ACIP employed the Evidence to Recommendation (EtR) framework,(†) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)(§) approach to guide its deliberations regarding use of these vaccines. Before this, PCV13 and PPSV23 were recommended for use for U.S. adults and the recommendations varied by age and risk groups. This was simplified in the new recommendations.

      7. Effectiveness of a third dose of mRNA vaccines against COVID-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance - VISION Network, 10 states, August 2021-January 2022external icon
        Thompson MG, Natarajan K, Irving SA, Rowley EA, Griggs EP, Gaglani M, Klein NP, Grannis SJ, DeSilva MB, Stenehjem E, Reese SE, Dickerson M, Naleway AL, Han J, Konatham D, McEvoy C, Rao S, Dixon BE, Dascomb K, Lewis N, Levy ME, Patel P, Liao IC, Kharbanda AB, Barron MA, Fadel WF, Grisel N, Goddard K, Yang DH, Wondimu MH, Murthy K, Valvi NR, Arndorfer J, Fireman B, Dunne MM, Embi P, Azziz-Baumgartner E, Zerbo O, Bozio CH, Reynolds S, Ferdinands J, Williams J, Link-Gelles R, Schrag SJ, Verani JR, Ball S, Ong TC.
        MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(4):139-145.
        Estimates of COVID-19 mRNA vaccine effectiveness (VE) have declined in recent months (1,2) because of waning vaccine induced immunity over time,* possible increased immune evasion by SARS-CoV-2 variants (3), or a combination of these and other factors. CDC recommends that all persons aged ≥12 years receive a third dose (booster) of an mRNA vaccine ≥5 months after receipt of the second mRNA vaccine dose and that immunocompromised individuals receive a third primary dose.(†) A third dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine increases neutralizing antibody levels (4), and three recent studies from Israel have shown improved effectiveness of a third dose in preventing COVID-19 associated with infections with the SARS-CoV-2 B.1.617.2 (Delta) variant (5-7). Yet, data are limited on the real-world effectiveness of third doses of COVID-19 mRNA vaccine in the United States, especially since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in mid-December 2021. The VISION Network(§) examined VE by analyzing 222,772 encounters from 383 emergency departments (EDs) and urgent care (UC) clinics and 87,904 hospitalizations from 259 hospitals among adults aged ≥18 years across 10 states from August 26, 2021(¶) to January 5, 2022. Analyses were stratified by the period before and after the Omicron variant became the predominant strain (>50% of sequenced viruses) at each study site. During the period of Delta predominance across study sites in the United States (August-mid-December 2021), VE against laboratory-confirmed COVID-19-associated ED and UC encounters was 86% 14-179 days after dose 2, 76% ≥180 days after dose 2, and 94% ≥14 days after dose 3. Estimates of VE for the same intervals after vaccination during Omicron variant predominance were 52%, 38%, and 82%, respectively. During the period of Delta variant predominance, VE against laboratory-confirmed COVID-19-associated hospitalizations was 90% 14-179 days after dose 2, 81% ≥180 days after dose 2, and 94% ≥14 days after dose 3. During Omicron variant predominance, VE estimates for the same intervals after vaccination were 81%, 57%, and 90%, respectively. The highest estimates of VE against COVID-19-associated ED and UC encounters or hospitalizations during both Delta- and Omicron-predominant periods were among adults who received a third dose of mRNA vaccine. All unvaccinated persons should get vaccinated as soon as possible. All adults who have received mRNA vaccines during their primary COVID-19 vaccination series should receive a third dose when eligible, and eligible persons should stay up to date with COVID-19 vaccinations.

      8. COVID-19 vaccines in children and adolescentsexternal icon
        Maldonado YA, O'Leary ST, Ardura MI, Banerjee R, Bryant KA, Campbell JD, Caserta MT, John CC, Gerber JS, Kourtis AP, Ratner AJ, Romero JR, Shah SS, Zangwill KM, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, Bernstein HH, Cohn AC, Farizo KM, Halasa NB, Kafer LM, Kim D, López Medina E, Moore D, Panagiotakopoulos L, Sauvé L, Silverman NS, Starke JR, Tomashek KM, Frantz JM, Committee on Infectious D.
        Pediatrics. 2022 Jan 1;149(1).

      9. Measles susceptibility in maternal-infant dyads-Bamako, Maliexternal icon
        Dixon MG, Tapia MD, Wannemuehler K, Luce R, Papania M, Sow S, Levine MM, Pasetti MF.
        Vaccine. 2022 Jan 28.
        Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity. We investigated the relationship between maternal age and measles susceptibility in mother-infant pairs in Mali through six months of infancy. We measured serum measles antibodies in 340 mother-infant pairs by plaque reduction neutralization test (PRNT) and calculated the proportion of mothers with protective titers (>120 mIU/mL) at delivery and the proportion of infants with protective titers at birth, and at three and six months of age. We explored associations between maternal age and measles antibodies in mothers and infants at the timepoints noted. Ten percent of Malian newborns were susceptible to measles; by six months nearly all were. Maternal and infant antibody titers were highly correlated. At delivery, 11% of mothers and 10% of newborns were susceptible to measles. By three and six months, infant susceptibility increased to 72% and 98%, respectively. Infants born to younger mothers were most susceptible at birth and three months. Time to susceptibility was 6.6 weeks in infants born to mothers with measles titer >120-<430 mIU/mL versus 15.4 weeks when mothers had titers ≥430 mIU/mL. Maternal and newborn seroprotective status were positively correlated. Improved strategies are needed to protect susceptible infants from measles infection and death. Increasing measles immunization coverage in vaccine eligible populations, including nonimmune reproductive-aged women and older children should be considered.

    • Injury and Violence
      1. Surveillance for violent deaths - National Violent Death Reporting System, 39 states, the District of Columbia, and Puerto Rico, 2018external icon
        Sheats KJ, Wilson RF, Lyons BH, Jack SP, Betz CJ, Fowler KA.
        MMWR Surveill Summ. 2022 Jan 28;71(3):1-44.
        PROBLEM/CONDITION: In 2018, approximately 68,000 persons died of violence-related injuries in the United States. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 39 states the District of Columbia, and Puerto Rico in 2018. Results are reported by sex, age group, race and ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics. PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: NVDRS collects data regarding violent deaths obtained from death certificates, coroner and medical examiner reports, and law enforcement reports. This report includes data collected for violent deaths that occurred in 2018. Data were collected from 36 states with statewide data (Alabama, Alaska, Arizona, Colorado, Connecticut, Delaware, Georgia, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Vermont, Virginia, Washington, West Virginia, and Wisconsin), three states with data from counties representing a subset of their population (21 California counties, 28 Illinois counties, and 39 Pennsylvania counties), the District of Columbia, and Puerto Rico. NVDRS collates information for each death and links deaths that are related (e.g., multiple homicides, homicide followed by suicide, or multiple suicides) into a single incident. RESULTS: For 2018, NVDRS collected information on 52,773 fatal incidents involving 54,170 deaths that occurred in 39 states and the District of Columbia. In addition, information was collected on 880 fatal incidents involving 975 deaths in Puerto Rico. Data for Puerto Rico were analyzed separately. Of the 54,170 deaths, the majority (64.1%) were suicides, followed by homicides (24.8%), deaths of undetermined intent (9.0%), legal intervention deaths (1.4%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force acting in the line of duty, excluding legal executions), and unintentional firearm deaths (<1.0%). (The term "legal intervention" is a classification incorporated into the International Classification of Diseases, Tenth Revision, and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.) Demographic patterns and circumstances varied by manner of death. The suicide rate was higher among males than among females and was highest among adults aged 35-64 years and non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic White persons. The most common method of injury for suicide was a firearm among males and hanging, strangulation, or suffocation among females. Suicide was most often preceded by a mental health, intimate partner, or physical health problem, or a recent or impending crisis during the previous or upcoming 2 weeks. The homicide rate was highest among persons aged 20-24 years and was higher among males than females. Non-Hispanic Black males experienced the highest homicide rate of any racial or ethnic group. The most common method of injury for homicide was a firearm. When the relationship between a homicide victim and a suspect was known, the suspect was most frequently an acquaintance or friend for male victims and a current or former intimate partner for female victims. Homicides most often were precipitated by an argument or conflict, occurred in conjunction with another crime, or, for female victims, were related to intimate partner violence. Homicide suspects were primarily male and the highest proportion were aged 25-44 years. When race and ethnicity information was known, non-Hispanic Black persons comprised the largest group of suspects overall and among those aged ≤44 years, and non-Hispanic White persons comprised the largest group of suspects among those aged ≥45 years. Almost all legal intervention deaths were experienced by males, and the legal intervention death rate was highest among males aged 30-34 years. Non-Hispanic AI/AN males had the highest legal intervention death rate, followed by non-Hispanic Black males. A firearm was used in the majority of legal intervention deaths. When a specific type of crime was known to have precipitated a legal intervention death, the type of crime was most frequently assault or homicide. The most frequent circumstances reported for legal intervention deaths were use of a weapon by the victim in the incident and a mental health or perceived substance use problem (other than alcohol use). Law enforcement officers who inflicted fatal injuries in the context of legal intervention deaths were primarily males aged 25-44 years. Unintentional firearm deaths were most frequently experienced by males, non-Hispanic White persons, and persons aged 15-24 years. These deaths most often occurred while the shooter was playing with a firearm and most frequently were precipitated by a person unintentionally pulling the trigger or mistakenly thinking that the firearm was unloaded. The rate of deaths of undetermined intent was highest among males, particularly among non-Hispanic Black and non-Hispanic AI/AN males, and among persons aged 45-54 years. Poisoning was the most common method of injury in deaths of undetermined intent, and opioids were detected in approximately 80% of decedents tested for those substances. INTERPRETATION: This report provides a detailed summary of data from NVDRS on violent deaths that occurred in 2018. The suicide rate was highest among non-Hispanic AI/AN and non-Hispanic White males, and the homicide rate was highest among non-Hispanic Black males. Mental health problems, intimate partner problems, interpersonal conflicts, and acute life stressors were primary circumstances for multiple types of violent death. Circumstances for suspects of homicide varied by age group and included having prior contact with law enforcement and involvement in incidents that were precipitated by another crime, intimate partner violence, and drug dealing or substance use. PUBLIC HEALTH ACTION: NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in developing, implementing, and evaluating programs, policies, and practices to reduce and prevent violent deaths. For example, Arizona and Wisconsin used their state-level VDRS data to support suicide prevention efforts within their respective states. Wisconsin VDRS used multiple years of data (2013-2017) to identify important risk and protective factors and subsequently develop a comprehensive suicide prevention plan. Arizona VDRS partners with the Arizona Be Connected Initiative to provide customized community-level data on veteran suicide deaths in Arizona. Similarly, states participating in NVDRS have used their VDRS data to examine intimate partner violence-related deaths to support prevention efforts. For example, data from the South Carolina VDRS were used to examine intimate partner homicides that occurred in South Carolina during 2017. South Carolina VDRS found that 12% of all homicides that occurred in 2017 were intimate partner violence-related, with females accounting for 52% of intimate partner homicide-related victims. These data were shared with domestic violence prevention collaborators in South Carolina to bolster their efforts in reducing intimate partner violence-related deaths. In 2018, NVDRS data included four additional states compared with 2017, providing more comprehensive and actionable violent death information for public health efforts to reduce violent deaths.

    • Laboratory Sciences
      1. Distinguishing multisystem inflammatory syndrome in children from COVID-19, Kawasaki disease and toxic shock syndromeexternal icon
        Godfred-Cato S, Abrams JY, Balachandran N, Jaggi P, Jones K, Rostad CA, Lu AT, Fan L, Jabbar A, Anderson EJ, Kao CM, Hunstad DA, Rosenberg RB, Zafferani MJ, Ede KC, Ballan W, Laham FR, Beltran Y, Bryant B, Meng L, Hammett TA, Oster ME, Bamrah Morris S, Belay ED.
        Pediatr Infect Dis J. 2022 Jan 25.
        BACKGROUND: Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential. METHODS: Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis. RESULTS: A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97. CONCLUSIONS: Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS.

    • Maternal and Child Health
      1. Congenital syphilis-related stillbirths in the United States from 2015 to 2019external icon
        Machefsky A, Miele K, Kimball A, Thorpe P, Bachmann L, Bowen V.
        Am J Obstet Gynecol. 2022 ;226(2):303-304.

      2. Timing of first positive hepatitis c polymerase chain reaction test among pregnant women with hepatitis c infection – Surveillance for Emerging Threats to Mothers and Babies Networkexternal icon
        Woodworth K, Newton S, Sizemore L, Wingate H, Wills A, Thomas N, Reynolds B, Foster M, Gupta N, Wester C, Meaney-Delman D, Gilboa S, Tong V.
        Am J Obstet Gynecol. 2022 ;226(2):305-306.

      3. Periconceptional folic acid use prevents both rare and common neural tube defects in Chinaexternal icon
        Zhou Y, Crider KS, Yeung LF, Rose CE, Li Z, Berry RJ, Li S, Moore CA.
        Birth Defects Res. 2022 Jan 31.
        BACKGROUND: Neural tube defects (NTDs) encompass a variety of distinct types. We assessed if the preventive effect of folic acid (FA) varied by NTD type and infant sex. METHODS: We examined all pregnancies with NTD status confirmation from a pregnancy-monitoring system in selected locations in northern and southern regions of China between 1993 and 1996. Women who took 400 μg of FA daily during 42 days after last menstrual period were considered FA users. We analyzed NTD prevalence by FA use status, NTD type, geographic region, and infant sex. RESULTS: Among 626,042 pregnancies, 700 were affected by an NTD. Among FA nonusers, 65 pregnancies (8.8 per 10,000) in the north and 51 pregnancies (1.2 per 10,000) in the south were affected by one of the two rare NTDs, that is, craniorachischisis, iniencephaly. FA use prevented occurrence of these two rare NTDs and reduced the prevalence of spina bifida (SB) by 78% (from 17.9 to 3.9 per 10,000) in the north and 51% (from 2.4 to 1.2 per 10,000) in the south. Among FA users, SB prevalence, including SB with high lesion level, was significantly reduced in both geographic regions. FA use reduced prevalence of anencephaly and encephalocele by 85% and 50%, respectively in the north, while it did not reduce the prevalence of these two NTDs in the south. There was a greater reduction in NTD prevalence in female than in male infants and fetuses. CONCLUSIONS: This is the first study to show that FA prevents the entire spectrum of NTD types.

      4. Reasons for participation in a child development study: Are cases with developmental diagnoses different from controls?external icon
        Bradley CB, Tapia AL, DiGuiseppi CG, Kepner MW, Kloetzer JM, Schieve LA, Wiggins LD, Windham GC, Daniels JL.
        Paediatr Perinat Epidemiol. 2022 Feb 2.
        BACKGROUND: Current knowledge about parental reasons for allowing child participation in research comes mainly from clinical trials. Fewer data exist on parents' motivations to enrol children in observational studies. OBJECTIVES: Describe reasons parents of preschoolers gave for participating in the Study to Explore Early Development (SEED), a US multi-site study of autism spectrum disorder (ASD) and other developmental delays or disorders (DD), and explore reasons given by child diagnostic and behavioural characteristics at enrolment. METHODS: We included families of children, age 2-5 years, participating in SEED (n = 5696) during 2007-2016. We assigned children to groups based on characteristics at enrolment: previously diagnosed ASD; suspected ASD; non-ASD DD; and population controls (POP). During a study interview, we asked parents their reasons for participating. Two coders independently coded responses and resolved discrepancies via consensus. We fit binary mixed-effects models to evaluate associations of each reason with group and demographics, using POP as reference. RESULTS: Participants gave 1-5 reasons for participation (mean = 1.7, SD = 0.7). Altruism (48.3%), ASD research interest (47.4%) and perceived personal benefit (26.9%) were most common. Two novel reasons were knowing someone outside the household with the study conditions (peripheral relationship; 14.1%) and desire to contribute to a specified result (1.4%). Odds of reporting interest in ASD research were higher among diagnosed ASD participants (odds ratio [OR] 2.89, 95% confidence interval [CI] 2.49-3.35). Perceived personal benefit had higher odds among diagnosed (OR 1.92, 95% CI 1.61-2.29) or suspected ASD (OR 3.67, 95% CI 2.99-4.50) and non-ASD DD (OR 1.80, 95% CI 1.50-2.16) participants. Peripheral relationship with ASD/DD had lower odds among all case groups. CONCLUSIONS: We identified meaningful differences between groups in parent-reported reasons for participation. Differences demonstrate an opportunity for future studies to tailor recruitment materials and increase the perceived benefit for specific prospective participants.

      5. STORCH Infections among very low birth weight and preterm infants: 2018-2020external icon
        Edwards EM, Greenberg LT, Ehret DE, Soll RF, Lanzieri TM, Horbar JD.
        Pediatrics. 2022 Jan 1;149(1).

    • Nutritional Sciences
      1. Urinary phthalate and DINCH metabolite concentrations and gradations of maternal glucose intoleranceexternal icon
        James-Todd T, Ponzano M, Bellavia A, Williams PL, Cantonwine DE, Calafat AM, Hauser R, Quinn MR, Seely EW, McElrath TF.
        Environ Int. 2022 Jan 24;161:107099.
        BACKGROUND: Studies suggest a link between pregnancy phthalate exposures and gestational diabetes mellitus (GDM). Few studies have evaluated associations between phthalate biomarkers (individual or mixtures) with gradations of maternal glucose intolerance. METHODS: In a subset of 606 women participating in LIFECODES pregnancy cohort, a combination of 50-gram 1-h non-fasting glucose load test (GLT) and 100-gram 3-h fasting oral glucose tolerance test was used to determine pregnancy glycemic status (median: 27 weeks gestation): normoglycemia (n = 136), impaired glucose tolerance (IGT) (n = 296), and GDM (n = 174). Nineteen metabolites of phthalates and their replacements were measured during each trimester. We used multivariable logistic regression models to evaluate associations between biomarkers (in quartiles) and maternal glycemic status (GDM v. normoglycemia and IGT v. normoglycemia), adjusting for potential confounders. We also used principal component analysis to evaluate associations jointly accounting for metabolites as chemical mixtures. RESULTS: Higher 1st trimester mono-3-carboxypropyl phthalate (MCPP) was associated with decreased odds of GDM (Q4 v. Q1: 0.30; 95% CI: 0.13, 0.67) and IGT (Q4 v. Q1 OR: 0.37; 95% CI: 0.17, 0.79). Higher 2nd trimester mono-isobutyl phthalate (MiBP) was associated with increased IGT (Q4 v. Q1 OR: 2.07; 95% CI: 1.06, 4.07), and 2nd trimester mono-3-hydroxybutyl phthalate (MHBP) was non-monotonically associated with increased GDM (Q2 v. Q1 OR: 3.21; 95% CI: 1.54, 6.87). Mixture analyses showed similar associations (Q4 v. Q1 for 2nd trimester dibutyl phthalates metabotlites mixtures OR: 2.08; 95% CI: 1.04, 4.22). CONCLUSION: Some phthalate biomarkershad trimester-specific associations with glycemic outcomes, with long and short term health implications.

      2. Factors associated with anaemia among adolescent boys and girls 10-19 years old in Nepalexternal icon
        Ford ND, Bichha RP, Parajuli KR, Paudyal N, Joshi N, Whitehead RD, Chitekwe S, Mei Z, Flores-Ayala R, Adhikari DP, Rijal S, Jefferds ME.
        Matern Child Nutr. 2022 Jan;18 Suppl 1(Suppl 1):e13013.
        We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut-points using altitude- and smoking-adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10-19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex-specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (μg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (μmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [μmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation.

      3. Background: The COVID-19 pandemic has triggered stress, anxiety, and disruption to many individuals’ daily lives, which might impact eating habits. Objective: To examine changes in eating habits related to less healthy foods and beverages during the early phase of the COVID-19 pandemic among US adults. Design: Cross-sectional study. Participants/setting: Authors used SummerStyles data gathered in June 2020 among 3916 US adults (≥18 years). Main outcome measures: The outcome of interest was the reported frequency of consuming more (1) unhealthy snacks and desserts including chips, cookies, and ice cream and (2) sugar-sweetened beverages (SSBs) like regular soda, fruit drinks, sports/energy drinks, sweetened coffee/teas during the COVID-19 pandemic. Responses were categorized as Never/Rarely, Sometimes, or Often/Always. Explanatory variables were sociodemographics, weight status, and census regions. Statistical analyses performed: We used multinomial regressions to calculate adjusted odds ratios (AOR) for Sometimes or Often/Always consuming more unhealthy snacks/desserts (vs. Never/Rarely); and Sometimes or Often/Always more SSBs (vs. Never/Rarely). Results: Overall, 36% of adults reported sometimes consuming more unhealthy snacks/desserts; 16% did so often/always. Twenty-two percent of adults reported sometimes drinking more SSBs; 10% did so often/always. Factors significantly associated with higher odds of reporting often/always consuming more unhealthy snacks/desserts were younger adults (AOR range = 1.51–2.86 vs. adults ≥65 years), females (AOR = 1.58 vs. males), non-Hispanic Black (AOR = 1.89 vs. non-Hispanic White), lower household income (AOR = 2.01 for <USD 35,000 vs. ≥USD 100,000), and obesity (AOR = 1.56 vs. underweight/healthy weight). Factors significantly associated with odds of Often/Always drinking more SSBs were being younger (AOR range = 2.26–4.39 vs. adults ≥65 years), non-Hispanic Black (AOR = 3.25 vs. non-Hispanic White), Hispanic (AOR = 1.75 vs. non-Hispanic White), non-Hispanic Other race/ethnicity (AOR = 2.41 vs. non-Hispanic White), lower education (AOR = 2.03 for ≤high school; AOR = 1.80 for some college vs. college graduate), lower household income (AOR range = 1.64–3.15 vs. ≥USD 100,000), and obesity (AOR = 1.61 vs. underweight/healthy weight). Conclusions: Consuming more sugary foods and SSBs during the first phase of the pandemic was higher in younger adults, lower-income adults, people of racial/ethnic minority groups, and adults with obesity. Dietary shifts to less healthy foods and drinks may influence metabolic health if sustained long-term. Implementing strategies to support individual’s healthy eating habits during the ongoing pandemic and the pandemic recovery may benefit health and wellness. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

    • Occupational Safety and Health
      1. Understanding filtering facepiece respiratorsexternal icon
        Andrews AS, Kiederer M, Casey ML.
        Am J Nurs. 2022 Feb 1;122(2):21-23.
        How to ensure adequate protection.

      2. Study shows noisy restaurants pose health risksexternal icon
        Eichwald J, Murphy W, Scinicariello F.
        Hearing Journal. 2022 ;75(1):8,10,11,12-8,10,11,12.

    • Parasitic Diseases
      1. Simulating the effect of evaluation unit size on eligibility to stop mass drug administration for lymphatic filariasis in Haitiexternal icon
        Kostandova N, Desir L, Direny A, Knipes A, Lemoine JF, Fayette CR, Kirby A, Gass K.
        PLoS Negl Trop Dis. 2022 Jan 28;16(1):e0010150.
        BACKGROUND: The Transmission Assessment Survey (TAS) is a decision-making tool to determine when transmission of lymphatic filariasis is presumed to have reached a level low enough that it cannot be sustained even in the absence of mass drug administration. The survey is applied over geographic areas, called evaluation units (EUs); existing World Health Organization guidelines limit EU size to a population of no more than 2 million people. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, TASs were conducted in 14 small EUs in Haiti. Simulations, using the observed TAS results, were performed to understand the potential programmatic impact had Haiti chosen to form larger EUs. Nine "combination-EUs" were formed by grouping adjacent EUs, and bootstrapping was used to simulate the expected TAS results. When the combination-EUs were comprised of at least one "passing" and one "failing" EU, the majority of these combination-EU would pass the TAS 79% - 100% of the time. Even in the case when both component EUs had failed, the combination-EU was expected to "pass" 11% of the time. Simulations of mini-TAS, a strategy with smaller power and hence smaller sample size than TAS, resulted in more conservative "passing" and "failing" when implemented in original EUs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the high potential for misclassification when the average prevalence of lymphatic filariasis in the combined areas differs with regards to the TAS threshold. Of particular concern is the risk of "passing" larger EUs that include focal areas where prevalence is high enough to be potentially self-sustaining. Our results reaffirm the approach that Haiti took in forming smaller EUs. Where baseline or monitoring data show a high or heterogeneous prevalence, programs should leverage alternative strategies like mini-TAS in smaller EUs, or consider gathering additional data through spot check sites to advise EU formation.

    • Public Health Law
      1. Mapping nurse practitioners' scope of practice laws: A resource for evaluating pre-exposure prophylaxis prescriptionsexternal icon
        Salvant Valentine S, Carnes N, Caldwell J, Gelaude D, Taylor R.
        Health Equity. 2022 ;6(1):27-31.
        Context: Reducing the number of new HIV infections will require addressing barriers to HIV pre-exposure prophylaxis (PrEP) access and uptake. Nurse practitioners (NPs) may help increase PrEP access and uptake. State scope of practice laws determines NPs' ability to work independently and their authority to prescribe PrEP, a legend nonscheduled medication. Methods: This analysis applied legal epidemiology methods to analyze the laws of the 50 states and the District of Columbia that govern NPs' scope of practice as they may apply to prescribing legend nonscheduled medications. These laws were extracted from Westlaw Next between April and June 2019. Results: As of June 8, 2019, 17 states had laws that allowed NPs to both practice independently and prescribe legend nonscheduled drugs without restriction. Conclusion: The role that state scope of practice laws plays in potentially limiting NPs' ability to prescribe PrEP should be considered. Increasing PrEP access and uptake is essential in reaching national HIV prevention goals. This analysis can inform further studies and polices on barriers to PrEP access and uptake.

    • Substance Use and Abuse
      1. BACKGROUND: Medication for Opioid Use Disorder (MOUD) has been shown to be a safe, cost-effective intervention that successfully lowers risk of opioid overdose. However, access to and use of MOUD has been limited. Our objective was to explore attitudes, opinions, and beliefs regarding MOUD among healthcare and social service providers in a community highly impacted by the opioid overdose epidemic. METHODS: As part of a larger ethnographic study examining neighborhoods in Allegheny County, PA, with the highest opioid overdose death rates, semi-structured qualitative in-person and telephone interviews were conducted with forty-five providers treating persons with opioid use disorders in these communities. An open coding approach was used to code interview transcripts followed by thematic analysis. RESULTS: Three major themes were identified related to MOUD from the perspectives of our provider participants. Within a variety of health and substance use service roles and settings, provider reflections revealed: (1) different opinions about MOUD as a transition to abstinence or as a long-term treatment; (2) perceived lack of uniformity and dissemination of accurate information of MOUD care, permitting differences in care, and (3) observed barriers to entry and navigation of MOUD, including referrals as a "word-of-mouth insider system" and challenges of getting patients MOUD services when they need it. CONCLUSIONS: Even in communities hard hit by the opioid overdose epidemic, healthcare providers' disagreement about the standard of care for MOUD can be a relevant obstacle. These insights can inform efforts to improve MOUD treatment and access for people with opioid use disorders.

    • Telehealth and Telemedicine
      1. A virtual partner services technical assistance (TA) project was piloted with the Minnesota Department of Health to address an ongoing syphilis outbreak. The TA reduced the health department's disease intervention specialist workload, achieved partner services outcomes comparable with in-person methods, and identified lessons learned to replicate with other jurisdictions.

    • Zoonotic and Vectorborne Diseases
      1. Risk factors for Brucellosis and knowledge-attitude practice among pastoralists in Afar and Somali regions of Ethiopiaexternal icon
        Tschopp R, GebreGiorgis A, Abdulkadir O, Molla W, Hamid M, Tassachew Y, Andualem H, Osman M, Waqjira MW, Mohammed A, Negron M, Walke H, Kadzik M, Mamo G.
        Prev Vet Med. 2022 Feb;199:105557.
        BACKGROUND: Brucellosis is a neglected bacterial zoonotic disease with substantial economic impact on households. Pastoral communities are a potential risk group due to their way of life being closely interlinked with their large livestock herds. METHODOLOGY: A semi-structured questionnaire survey was conducted in households in the pastoral Afar and Somali (SRS) regions. All households had people and animals serologically tested for brucellosis. Questions were related to husbandry, consumption habits, and knowledge-attitude-practice towards the disease and zoonoses. Descriptive statistics and logistic analysis were performed to assess potential risk factors for having households with positive humans and/or animals. RESULT: 647 households were included in the survey. Herd brucellosis prevalence was 40.3 % (15.9-86.3 % in Afar; 4-72.2 % in SRS). Over half (56.3 %) of the households in Afar and 41.8 % in SRS had at least one human reactor. Nearly a quarter of the households (22.8 %), recalled abortions in goats in the last 12 months, whereas 52.5 % and 50.3 % recalled stillborn in all species and membrane retentions respectively. All respondents drank raw milk and discarded animal afterbirths in the direct surroundings with minimal protection. Risk factors for animal reactors were goat herd size, and goat abortion. There was no identified risk factor for having human reactors in households. None of the households knew about brucellosis. CONCLUSION: Although being endemic in Afar and SRS, Brucellosis is not known by the pastoralists. Brucellosis control programs will have to be tailored to the pastoral context, accounting for their mobility, large, multi-species herds and habits.


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