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Volume 14, Issue 11, March 15, 2022

CDC Science Clips: Volume 14, Issue 11, March 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. Sentinel surveillance reveals emerging daptomycin-resistant ST736 enterococcus faecium and multiple mechanisms of linezolid resistance in enterococci in the United Statesexternal icon
        Gargis AS, Spicer LM, Kent AG, Zhu W, Campbell D, McAllister G, Ewing TO, Albrecht V, Stevens VA, Sheth M, Padilla J, Batra D, Johnson JK, Halpin AL, Rasheed JK, Elkins CA, Karlsson M, Lutgring JD.
        Front Microbiol. 2021 ;12:807398.
        Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013-2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA-encoding multiresistance plasmids of animal origin. The optrA-encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance.

      2. HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswanaexternal icon
        Bareng OT, Moyo S, Zahralban-Steele M, Maruapula D, Ditlhako T, Mokaleng B, Mokgethi P, Choga WT, Moraka NO, Pretorius-Holme M, Mine MO, Raizes E, Molebatsi K, Motswaledi MS, Gobe I, Mohammed T, Gaolathe T, Shapiro R, Mmalane M, Makhema JM, Lockman S, Essex M, Novitsky V, Gaseitsiwe S.
        J Antimicrob Chemother. 2022 Mar 1.
        OBJECTIVES: To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project. METHODS: A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51-999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL. RESULTS: Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group. CONCLUSIONS: A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.

    • Chronic Diseases and Conditions
      1. Localized prostate cancer: An analysis of the CDC Breast and Prostate Cancer Data Quality and Patterns of Care study (CDC PoC-BP)external icon
        Celtik K, Wallis CJ, Lo M, Lim K, Lipscomb J, Fleming S, Wu XC, Anderson RT, Thompson TD, Farach A, Hamilton AS, Miles BJ, Satkunasivam R.
        Can Urol Assoc J. 2022 Feb 28.
        INTRODUCTION: Limited evidence exists on the comparative effectiveness of local treatments for prostate cancer (PCa) due to the lack of generalizability. Using granular national data, we sought to examine the association between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) treatment and survival. METHODS: Records were abstracted for localized PCa cases diagnosed in 2004 across seven state registries to identify patients undergoing RP (n=3019) or IMRT (n=667). Comorbidity was assessed by the Adult Comorbidity Evaluation-27 (ACE-27). Propensity score matching (PSM) was used to balance covariates between treatment groups. All-cause and PCa-specific mortality were primary endpoints. A subgroup analysis of patients with high-risk PCa (RP, n=89; IMRT, n=95) was conducted. RESULTS: Following PSM, matched patients (n=502 pairs) treated with either RP or IMRT were well-balanced with respect to covariates. With a median followup of 10.5 years (interquartile range [IQR] 9.9-11.0), the 11-year overall survival (OS) was 71.2% (95% confidence interval [CI] 66.9-75.8) for RP and 62.3% (95% CI 57.4-67.6) for IMRT. IMRT was associated with a 41% increased risk of all-cause mortality (hazard ratio [HR] 1.41, 95% CI 1.13-1.76) but not PCa-specific mortality (HR 1.75, 95% CI 0.84-3.64), as compared to RP. In patients with high-risk PCa, IMRT, as compared to RP, was not associated with statistically significant difference in all-cause (HR 1.53, 95% CI 0.97-2.42) or PCa-specific mortality (HR 1.92, 95% CI 0.69-5.36). CONCLUSIONS: Despite a low mortality rate at 10 years and possible residual confounding, we found a significantly increased risk of all-cause mortality, but no PCa-specific mortality associated with IMRT as compared to RP in this population-based study.

      2. Trends in cirrhosis and mortality by age, sex, race, and antiviral treatment status among US chronic hepatitis B patients (2006-2016)external icon
        Lu M, Li J, Zhou Y, Rupp LB, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Daida YG, Schmidt MA, Trudeau S, Gordon SC.
        J Clin Gastroenterol. 2022 Mar 1;56(3):273-279.
        BACKGROUND: Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS: Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS: Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS: From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.

      3. Major ambulatory surgery among US adults with inflammatory bowel disease, 2017external icon
        Xu F, Wheaton AG, Liu Y, Greenlund KJ.
        PLoS One. 2022 ;17(2):e0264372.
        BACKGROUND: Patients with inflammatory bowel disease (IBD) have higher health services use than those without IBD. We investigated patient and hospital characteristics of major ambulatory surgery encounters for Crohn's disease (CD) or ulcerative colitis (UC) vs non-IBD patients. METHODS: We conducted a cross-sectional study using 2017 Nationwide Ambulatory Surgery Sample. Major ambulatory surgery encounters among patients aged ≥18 years with CD (n = 20,635) or UC (n = 9,894) were compared to 9.4 million encounters among non-IBD patients. Weighted percentages of patient characteristics (age, sex, median household income, primary payers, patient location, selected comorbidities, discharge destination, type of surgeries) and hospital-related characteristics (hospital size, ownership, location and teaching status, region) were compared by IBD status (CD, UC, and no IBD). Linear regression was used to estimate mean total charges, controlling for these characteristics. RESULTS: Compared with non-IBD patients, IBD patients were more likely to have private insurance, reside in urban areas and higher income zip codes, and undergo surgeries in hospitals that were private not-for-profit, urban teaching, and in the Northeast. Gastrointestinal surgeries were more common among IBD patients. Some comorbidities associated with increased risk of surgical complications were more prevalent among IBD patients. Total charges were 9% lower for CD patients aged <65 years (Median: $16,462 vs $18,106) and 6% higher for UC patients aged ≥65 years (Median: $16,909 vs $15,218) compared to their non-IBD patient counterparts. CONCLUSIONS: Differences in characteristics of major ambulatory surgery encounters by IBD status may identify opportunities for efficient resource allocation and positive surgical outcomes among IBD patients.

    • Communicable Diseases
      1. Reported Legionnaires' disease (LD) cases began increasing in the United States in 2003 after relatively stable numbers for >10 years; reasons for the rise are unclear. We compared epidemiologic patterns associated with cases reported to the Centers for Disease Control and Prevention before and during the rise. The age-standardized average incidence was 0.48 cases/100,000 population during 1992-2002 compared with 2.71 cases/100,000 in 2018. Reported LD incidence increased in nearly every demographic, but increases tended to be larger in demographic groups with higher incidence. During both periods, the largest number of cases occurred among White persons, but the highest incidence was in Black or African American persons. Incidence and increases in incidence were generally largest in the East North Central, Middle Atlantic, and New England divisions. Seasonality was more pronounced during 2003-2018, especially in the Northeast and Midwest. Rising incidence was most notably associated with increasing racial disparities, geographic focus, and seasonality.

      2. Neisseria meningitidis serogroup C clonal complex 10217 outbreak in West Kpendjal Prefecture, Togo 2019external icon
        Feagins AR, Sadji AY, Topaz N, Itsko M, Halatoko JW, Dzoka A, Labite J, Kata Y, Gomez S, Kossi K, Assane H, Nikiema-Pessinaba C, Novak R, Marjuki H, Wang X.
        Microbiol Spectr. 2022 Mar 2:e0192321.
        Togo has reported seasonal meningitis outbreaks caused by non-Neisseria meningitidis serogroup A (NmA) pathogens since the introduction of meningococcal serogroup A conjugate vaccine (MACV, MenAfriVac) in 2014. From 2016 to 2017, NmW caused several outbreaks. In early 2019, a NmC outbreak was detected in the Savanes region of Togo and its investigation is described here. Under case-based surveillance, epidemiological and clinical data, and cerebrospinal fluid specimens were collected for every suspected case of meningitis. Specimens were tested for meningitis pathogens using confirmatory microbiological and molecular methods. During epidemic weeks 9 to 15, 199 cases were reported, with 179 specimens being available for testing and 174 specimens (97.2%) were tested by at least one confirmatory method. The NmC was the predominant pathogen confirmed (93.9%), belonging to sequence type (ST)-9367 of clonal complex (CC) 10217. All NmC cases were localized to the West Kpendjal district of the Savanes region with attack rates ranging from 4.1 to 18.8 per 100,000 population and case fatality rates ranging up to 2.2% during weeks 9 to 15. Of the 93 NmC confirmed cases, 63.4% were males and 88.2% were in the 5 to 29 age group. This is the first report of a NmC meningitis outbreak in Togo. The changing epidemiology of bacterial meningitis in the meningitis belt post-MACV highlights the importance of monitoring of emerging strain and country preparedness for outbreaks in the region. IMPORTANCE The recent emergence of an invasive NmC strain in Togo is an example of the changing bacterial meningitis epidemiology in the meningitis belt post-MACV. The current epidemiology includes the regional circulation of various non-NmA serogroups, which emphasizes the need for effective molecular surveillance, laboratory diagnosis, and a multivalent vaccine that is effective against all serogroups in circulation.

      3. Interim guidance: 4-month rifapentine-moxifloxacin regimen for the treatment of drug-susceptible pulmonary tuberculosis - United States, 2022external icon
        Carr W, Kurbatova E, Starks A, Goswami N, Allen L, Winston C.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):285-289.
        On May 5, 2021, CDC's Tuberculosis Trials Consortium and the National Institutes of Health (NIH)-sponsored AIDS Clinical Trials Group (ACTG) published results from a randomized controlled trial indicating that a 4-month regimen containing rifapentine (RPT), moxifloxacin (MOX), isoniazid (INH), and pyrazinamide (PZA) was as effective as the standard 6-month regimen for tuberculosis (TB) treatment (1). On the basis of these findings, CDC recommends the 4-month regimen as a treatment option for U.S. patients aged ≥12 years with drug-susceptible pulmonary TB and provides implementation considerations for this treatment regimen.

      4. Antigen test positivity after COVID-19 isolation - Yukon-Kuskokwim Delta region, Alaska, January-February 2022external icon
        Lefferts B, Blake I, Bruden D, Hagen MB, Hodges E, Kirking HL, Bates E, Hoeldt A, Lamont B, Saydah S, MacNeil A, Bruce MG, Plumb ID.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):293-298.
        Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for ≥24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR] = 6.39) or after symptomatic infection (aOR = 9.63), and less likely after previous infection (aOR = 0.30), receipt of a primary COVID-19 vaccination series (aOR = 0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR = 0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days.

      5. Multistate outbreak of melioidosis associated with imported aromatherapy sprayexternal icon
        Gee JE, Bower WA, Kunkel A, Petras J, Gettings J, Bye M, Firestone M, Elrod MG, Liu L, Blaney DD, Zaldivar A, Raybern C, Ahmed FS, Honza H, Stonecipher S, O'Sullivan BJ, Lynfield R, Hunter M, Brennan S, Pavlick J, Gabel J, Drenzek C, Geller R, Lee C, Ritter JM, Zaki SR, Gulvik CA, Wilson WW, Beshearse E, Currie BJ, Webb JR, Weiner ZP, Negrón ME, Hoffmaster AR.
        N Engl J Med. 2022 Mar 3;386(9):861-868.
        Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.

      6. Severe acute respiratory syndrome coronavirus 2 seroprevalence and reported coronavirus disease 2019 cases in US children, August 2020-May 2021external icon
        Couture A, Lyons BC, Mehrotra ML, Sosa L, Ezike N, Ahmed FS, Brown CM, Yendell S, Azzam IA, Katić BJ, Cope A, Dickerson K, Stone J, Traxler LB, Dunn JR, Davis LB, Reed C, Clarke KE, Flannery B, Charles MD.
        Open Forum Infect Dis. 2022 Mar;9(3):ofac044.
        BACKGROUND: Case-based surveillance of pediatric coronavirus disease 2019 (COVID-19) cases underestimates the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children and adolescents. Our objectives were to estimate monthly SARS-CoV-2 antibody seroprevalence and calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 8 US states. METHODS: Using data from the Nationwide Commercial Laboratory Seroprevalence Survey, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. We calculated and compared cumulative incidence of SARS-CoV-2 infection extrapolated from population-standardized seroprevalence of antibodies to SARS-CoV-2, cumulative COVID-19 case reports since March 2020, and infection-to-case ratios among persons of all ages and children aged 0-17 years for each state. RESULTS: Of 41 583 residual serum specimens tested, children aged 0-4, 5-11, and 12-17 years accounted for 1619 (3.9%), 10 507 (25.3%), and 29 457 (70.8%), respectively. Median SARS-CoV-2 antibody seroprevalence among children increased from 8% (range, 6%-20%) in August 2020 to 37% (range, 26%-44%) in May 2021. Estimated ratios of SARS-CoV-2 infections to reported COVID-19 cases in May 2021 ranged by state from 4.7-8.9 among children and adolescents to 2.2-3.9 for all ages combined. CONCLUSIONS: Through May 2021 in selected states, the majority of children with serum specimens included in serosurveys did not have evidence of prior SARS-CoV-2 infection. Case-based surveillance underestimated the number of children infected with SARS-CoV-2 more than among all ages. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.

      7. Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison)external icon
        Ritter JM, Wilson TM, Gary JM, Seixas JN, Martines RB, Bhatnagar J, Bollweg BC, Lee E, Estetter L, Silva-Flannery L, Bullock HA, Towner JS, Cossaboom CM, Wendling NM, Amman BR, Harvey RR, Taylor D, Rettler H, Barton Behravesh C, Zaki SR.
        Vet Pathol. 2022 Mar 1:3009858221079665.
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.

    • Community Health Services
      1. Expanded access to HIV treatment services has improved outcomes for children and adolescents living with HIV in Kenya. Minimal data are available on these outcomes. We describe temporal trends in outcomes for children and adolescents initiating antiretroviral therapy (ART) from 2004 to 2014 at sites supported by Centre for Health Solutions - Kenya in central Kenya. We retrospectively analysed data from children aged 0-9 years (n=3519) and adolescents aged 10-19 years (n=1663) living with HIV who newly initiated ART at 47 health facilities in central Kenya. Year cohorts were analysed from the Comprehensive Patient Application Database (CPAD) and International Quality Care (IQCare) electronic medical databases including temporal trends in outcomes and associated factors using multivariable competing risks regression analysis. There were more girls (2453 [52.7%]) than boys, with most enrolled at World Health Organisation (WHO) stage II (1813 [37.7%]) or III disease (1694 [35.1%]). Most of the children and adolescents (4,431 [96.4%]) did not have tuberculosis (TB) symptoms. Cumulative LTFU incidence at 6, 12, 24, and 36 months were 5.0%, 9.9%, 22.9%, and 33.1%, respectively. Cumulative mortality incidence at 6, 12, 24, and 36 months were 0.7%, 1.0%, 1.2%, and 1.5%, respectively. LTFU was higher among female children and adolescents, those initiated on tenofovir-based regimens, and those with presumptive TB symptoms. Mortality risk was higher among those with WHO stage III or IV disease, and children and adolescents on TB treatment or who had presumptive TB. Enrolment occurred at a young age and pediatric friendly ART regimens initiated at earlier WHO stages implying effective early infant diagnosis and treatment for all strategies resulting in improved treatment outcomes. The higher retention rates in recent years as well as the lower retention after many years of follow-up underscores the importance of implementing longitudinal follow-up strategies targeting this population.

      2. Reaching 95-95-95 targets: The role of private sector health facilities in closing the HIV detection gap-Kisumu Kenya, 2018external icon
        Onyango D, McHembere W, Agaya J, Wang A, Cain KP, Grobbee DE, van der Sande MA, Baker B, Yuen CM.
        Int J STD AIDS. 2022 Feb 28:9564624221076953.
        BACKGROUND: HIV testing efficiency could be improved by focusing on high yield populations and identifying types of health facilities where people with undiagnosed HIV infection are more likely to attend. METHODS: A retrospective cohort analysis of data collected during an integrated TB/HIV active case-finding intervention in Western Kenya. Data were analyzed from health facilities' registers on individuals who reported TB-suggestive symptoms between 1 July and 31 December 2018 and who had an HIV test result within one month following symptom screening. We used logistic regression with general estimating equations adjusting for sub-county level data to identify health facility-level predictors of new HIV diagnoses. RESULTS: Of 11,376 adults with presumptive TB identified in 143 health facilities, 1038 (9%) tested HIV positive. The median HIV positivity per health facility was 6% (IQR = 2-15%). Patients with TB symptoms were over three times as likely to have a new HIV diagnosis in private not-for-profit facilities compared to those in government facilities (adjusted odds ratio (aOR) 3.40; 95% CI = 1.96-5.90). Patients tested in hospitals were over two times as likely to have a new HIV diagnosis as those tested in smaller facilities (i.e., health centers and dispensaries) (aOR 2.26; 95% CI = 1.60-3.21). CONCLUSION: Individuals with presumptive TB who attended larger health facilities and private not-for-profit facilities had a higher likelihood of being newly diagnosed with HIV. Strengthening HIV services at these facilities and outreach to populations that use them could help to close the HIV diagnosis gap.

    • Environmental Health
      1. Reduction of exposure to simulated respiratory aerosols using ventilation, physical distancing, and universal maskingexternal icon
        Coyle JP, Derk RC, Lindsley WG, Boots T, Blachere FM, Reynolds JS, McKinney WG, Sinsel EW, Lemons AR, Beezhold DH, Noti JD.
        Indoor Air. 2022 Feb;32(2):e12987.
        To limit community spread of SARS-CoV-2, CDC recommends universal masking indoors, maintaining 1.8 m of physical distancing, adequate ventilation, and avoiding crowded indoor spaces. Several studies have examined the independent influence of each control strategy in mitigating transmission in isolation, yet controls are often implemented concomitantly within an indoor environment. To address the influence of physical distancing, universal masking, and ventilation on very fine respiratory droplets and aerosol particle exposure, a simulator that coughed and exhaled aerosols (the source) and a second breathing simulator (the recipient) were placed in an exposure chamber. When controlling for the other two mitigation strategies, universal masking with 3-ply cotton masks reduced exposure to 0.3-3 µm coughed and exhaled aerosol particles by >77% compared to unmasked tests, whereas physical distancing (0.9 or 1.8 m) significantly changed exposure to cough but not exhaled aerosols. The effectiveness of ventilation depended upon the respiratory activity, that is, coughing or breathing, as well as the duration of exposure time. Our results demonstrate that a layered mitigation strategy approach of administrative and engineering controls can reduce personal inhalation exposure to potentially infectious very fine respiratory droplets and aerosol particles within an indoor environment.

      2. Understanding the role of persistent organic pollutants and stress in the association between proximity to the World Trade Center disaster and birth outcomesexternal icon
        Spratlen MJ, Perera FP, Sjodin A, Wang Y, Herbstman JB, Trasande L.
        Int J Environ Res Public Health. 2022 Feb 11;19(4).
        Fetal growth is affected by exposure to both prenatal stress and environmental contaminants. The attacks on the World Trade Center (WTC) resulted in exposure to chemicals and psychological stress amongst New York City residents. We measured prenatal maternal stress and exposure to persistent organic pollutants (polybrominated diphenyl ethers, polychlorinated biphenyls, and polychlorinated dibenzo-p-dioxins (PCDDs)) in 108 participants from a Columbia University WTC birth cohort. Principal component (PC) analyses were conducted to characterize the mixture of exposure to the three groups of chemicals. We evaluated the associations between geographical exposures (proximity to the WTC disaster) and both chemical exposures (PCs) and stress (demoralization). We then evaluated the effect these exposures (PCs and stress) had on previously reported associations between geographical WTC exposure and birth outcomes (birth weight and birth length) in this study population to understand their individual roles in the observed associations. Geographical exposure via proximity to the WTC was associated with the PC reflecting higher PCDD exposure (PC3) (β = 0.60, 95% CI: 0.03, 1.18 for living/working within 2 miles of the WTC; and β = 0.73, 95% CI = 0.08, 1.38 for living within 2 miles of WTC). Previously reported reductions in birth weight and length associated with WTC proximity (β = -215.2, 95% CI: -416.2, -14.3 and β = -1.47, 95% CI: -2.6, -0.34, respectively) were attenuated and no longer significant for birth weight (β = -156.4, 95% CI: -358.2, 45.4) after adjusting for PC3, suggesting that PCDDs may act as partial mediators in this previously observed association. The results of this study can help focus future research on the long-term health effects of these prenatally exposed populations.

      3. Hexavalent chromium [Cr(VI)] is a common environmental carcinogen causing lung cancer in humans. This study investigates the mechanism of Cr(VI) carcinogenesis focusing on the role of the epitranscriptomic dysregulation. The epitranscriptomic effect of Cr(VI) was determined in Cr(VI)-transformed human bronchial epithelial cells, chromate-exposed mouse and human lungs. The epitranscriptomic effect and its role in Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like property and tumorigenesis were determined by microarray analysis, soft agar colony formation, suspension spheroid formation and mouse xenograft tumorigenesis assays. It was found that chronic Cr(VI) exposure causes epitranscriptomic dysregulations as evidenced by the increased levels of total RNA N6-methyladenosine (m6A) modification and the RNA m6A methyltransferase METTL3 in Cr(VI)-transformed cells and chromate exposure-caused mouse and human lung tumors. Knockdown of METTL3 expression in Cr(VI)-transformed cells significantly reduces their m6A levels and transformed phenotypes and tumorigenicity in mice. Moreover, knockdown of METTL3 expression in parental non-transformed cells significantly reduces the capability of chronic Cr(VI) exposure to induce cell transformation and CSC-like property. Together, this study reveals that chronic Cr(VI) exposure is capable of altering cellular epitranscriptome by increasing the m6A RNA modification via upregulating the RNA methyltransferase METTL3 expression, which plays an important role in Cr(VI)-induced cell transformation, CSC-like property and tumorigenesis.

    • Epidemiology and Surveillance
      1. Temperature and oxygen saturation in skilled nursing facility residents positive for SARS-CoV-2 prior to symptom onsetexternal icon
        Lehnertz NB, Lifson A, Galloway E, Taylor J, Carter RJ, Kazazian L, Day K, Miller S, Mendez E, Lynfield R.
        J Am Geriatr Soc. 2022 Feb;70(2):363-369.
        BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spreads rapidly amongst residents of skilled nursing facilities (SNFs). The rapid transmission dynamics and high morbidity and mortality that occur in SNFs emphasize the need for early detection of cases. We hypothesized that residents of SNFs infected with SARS-CoV-2 would demonstrate an acute change in either temperature or oxygen saturation (SpO(2) ) prior to symptom onset. The Minnesota Department of Health (MDH) conducted a retrospective analysis of both temperature and SpO(2) at two separate SNFs to assess the utility of these quantitative markers to identify SARS-CoV-2 infection prior to the development of symptoms. METHODS: A retrospective analysis was conducted of 165 individuals positive for SARS-CoV-2 who were residents of SNFs that experienced coronavirus disease 2019 (COVID-19) outbreaks during April-June 2020 in a metropolitan area of Minnesota. Age, sex, symptomology, temperature and SpO(2) values, date of symptom onset, and date of positive SARS-CoV-2 test were analyzed. Temperature and SpO(2) values for the period 14 days before and after the date of initial positive test were included. Descriptive analyses evaluated changes in temperature and SpO(2) , defined as either exceeding a set threshold or demonstrating an acute change between consecutive measurements. RESULTS: Two (1%) residents had a temperature value ≥100°F, and 30 (18%) had at least one value ≥99°F within 14 days before symptom development. One hundred and sixteen residents (70%) had at least one SpO(2) value ≤94%, while 131 (80%) had an acute decrease in SpO(2) of ≥3% between consecutive values in the 14 days prior to symptom onset. CONCLUSIONS: Our results suggest that acute change in SpO(2) might be useful in the identification of SARS-CoV-2 infection prior to the development of symptoms among residents living in SNFs. Facilities may consider adding SpO(2) to daily temperature and symptom screening checklists to improve early detection of residents of SNFs infected with SARS-CoV-2.

      2. Active surveillance and early detection of community transmission of SARS-CoV-2 Mu variant (B.1.621) in the Brazilian Amazonexternal icon
        Oliveira GS, Silva-Flannery L, da Silva JF, Siza C, Esteves RJ, Marston BJ, Morgan J, Plucinski M, Roca TP, Silva A, Pereira SS, Salcedo JM, Pereira D, Naveca FG, Vieira Dall'Acqua DS.
        J Med Virol. 2022 Mar 2.
        Through active surveillance and contact tracing from outpatients, we aimed to identify and characterize SARS-CoV-2 variants circulating in Porto Velho, Rondônia a city in the Brazilian Amazon. As part of a prospective cohort, we gather information from 2,506 individuals among COVID-19 patients and household contacts. Epidemiological data, nasopharyngeal swabs, and blood samples were collected from all participants. Nasopharyngeal swabs were tested for antigen rapid diagnostic test and reverse transcription polymerase chain reaction (RT-PCR) followed by genomic sequencing. Blood samples underwent ELISA testing for IgA, IgG and IgM antibody levels. From 757 specimens sequenced, three were identified as Mu variant, none of the individuals carrying this variant had travel history in the previous 15 days before diagnosis. One case was asymptomatic and two presented mild symptoms. Two infected individuals from different household caring virus with additional amino acid substitutions ORF7a P45L and ORF1a T1055A compared to the Mu virus reference sequence. One patient presented IgG levels. Our results highlight that genomic surveillance for SARS-CoV-2 variants can assist in detecting the emergency of SARS-CoV-2 variants in the community, prior to its identification in other parts of the country. This article is protected by copyright. All rights reserved.

    • Food Safety
      1. Protecting retail food safety by strengthening partnerships and collaborationexternal icon
        Brown L, Smith C, Wildey L.
        J Environ Health. 2022 ;84(7):32-34.
        The article discusses the support being extended by the U.S. Centers for Disease Control and Prevention (CDC) to the Retail Food Safety Regulatory Association Collaborative. Topics explored include the commitment of the Collaborative to the reduction of foodborne illnesses associated with the retail food sector, the objectives set by the Collaborative to improve retail food safety, and the involvement of the CDC in foodborne outbreak investigations.

      2. GUEST COMMENTARY. Tools and techniques to promote proper food cooling in restaurantsexternal icon
        Hedeen N, Schaffner D, Green Brown L.
        J Environ Health. 2022 ;84(7):8-11.
        Slow cooling of hot foods is a common pathogen proliferation factor contributing to restaurant-related outbreaks. The Food and Drug Administration (FDA) model Food Code provides guidelines on the time and temperatures needed for proper cooling and recommends several methods to facilitate rapid food cooling. Restaurants continue to struggle with proper cooling even given these guidelines (Hedeen & Smith, 2020). Research summarized in this guest commentary indicates that portioning foods into containers with a depth of <3 in. and ventilating the containers during the cooling process promote rapid cooling. Restaurant operators and health department inspectors could use these cooling methods to maximize cooling efforts. Additionally, a simple method (using a mathematical equation) could help restaurant operators and inspectors to estimate the cooling rates of foods. This simple method uses only two food temperatures taken at any two points in the cooling process (using the equation [Log(T1 - Tdf) - Log(T2 - Tdf)]/δt) to estimate whether the food is expected to meet FDA cooling guidelines. This method allows operators and inspectors to identify foods unlikely to meet FDA guidelines and take corrective actions on those foods without having to monitor food temperatures for the entire cooling process, which typically takes 6 hr. More research is underway to further refine aspects of this method.

    • Genetics and Genomics
      1. VPipe: An automated bioinformatics platform for assembly and management of viral next-generation sequencing dataexternal icon
        Wagner DD, Marine RL, Ramos E, Ng TF, Castro CJ, Okomo-Adhiambo M, Harvey K, Doho G, Kelly R, Jain Y, Tatusov RL, Silva H, Rota PA, Khan AN, Oberste MS.
        Microbiol Spectr. 2022 Mar 2:e0256421.
        Next-generation sequencing (NGS) is a powerful tool for detecting and investigating viral pathogens; however, analysis and management of the enormous amounts of data generated from these technologies remains a challenge. Here, we present VPipe (the Viral NGS Analysis Pipeline and Data Management System), an automated bioinformatics pipeline optimized for whole-genome assembly of viral sequences and identification of diverse species. VPipe automates the data quality control, assembly, and contig identification steps typically performed when analyzing NGS data. Users access the pipeline through a secure web-based portal, which provides an easy-to-use interface with advanced search capabilities for reviewing results. In addition, VPipe provides a centralized system for storing and analyzing NGS data, eliminating common bottlenecks in bioinformatics analyses for public health laboratories with limited on-site computational infrastructure. The performance of VPipe was validated through the analysis of publicly available NGS data sets for viral pathogens, generating high-quality assemblies for 12 data sets. VPipe also generated assemblies with greater contiguity than similar pipelines for 41 human respiratory syncytial virus isolates and 23 SARS-CoV-2 specimens. IMPORTANCE Computational infrastructure and bioinformatics analysis are bottlenecks in the application of NGS to viral pathogens. As of September 2021, VPipe has been used by the U.S. Centers for Disease Control and Prevention (CDC) and 12 state public health laboratories to characterize >17,500 and 1,500 clinical specimens and isolates, respectively. VPipe automates genome assembly for a wide range of viruses, including high-consequence pathogens such as SARS-CoV-2. Such automated functionality expedites public health responses to viral outbreaks and pathogen surveillance.

    • Global Health
      1. Overseas treatment of latent tuberculosis infection in US-bound immigrantsexternal icon
        Khan A, Phares CR, Phuong HL, Trinh DT, Phan H, Merrifield C, Le PT, Lien QT, Lan SN, Thoa PT, Thu LT, Tran T, Tran C, Platt L, Maloney SA, Nhung NV, Nahid P, Oeltmann JE.
        Emerg Infect Dis. 2022 Mar;28(3):582-590.
        Seventy percent of tuberculosis (TB) cases in the United States occur among non-US-born persons; cases usually result from reactivation of latent TB infection (LTBI) likely acquired before the person's US arrival. We conducted a prospective study among US immigrant visa applicants undergoing the required overseas medical examination in Vietnam. Consenting applicants >15 years of age were offered an interferon-γ release assay (IGRA); those 12-14 years of age received an IGRA as part of the required examination. Eligible participants were offered LTBI treatment with 12 doses of weekly isoniazid and rifapentine. Of 5,311 immigrant visa applicants recruited, 2,438 (46%) consented to participate; 2,276 had an IGRA processed, and 484 (21%) tested positive. Among 452 participants eligible for treatment, 304 (67%) initiated treatment, and 268 (88%) completed treatment. We demonstrated that using the overseas medical examination to provide voluntary LTBI testing and treatment should be considered to advance US TB elimination efforts.

    • Health Behavior and Risk
      1. Pediatric emergency department visits before and during the COVID-19 pandemic - United States, January 2019-January 2022external icon
        Radhakrishnan L, Carey K, Hartnett KP, Kite-Powell A, Zwald M, Anderson KN, Leeb RT, Holland KM, Gates A, DeVies J, Smith AR, van Santen KL, Crossen S, Sheppard M, Wotiz S, Johnson AG, Winn A, Kirking HL, Lane RI, Njai R, Rodgers L, Thomas CW, Soetebier K, Adjemian J.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):313-318.
        Emergency departments (EDs) in the United States remain a frontline resource for pediatric health care emergencies during the COVID-19 pandemic; however, patterns of health-seeking behavior have changed during the pandemic (1,2). CDC examined changes in U.S. ED visit trends to assess the continued impact of the pandemic on visits among children and adolescents aged 0-17 years (pediatric ED visits). Compared with 2019, pediatric ED visits declined by 51% during 2020, 22% during 2021, and 23% during January 2022. Although visits for non-COVID-19 respiratory illnesses mostly declined, the proportion of visits for some respiratory conditions increased during January 2022 compared with 2019. Weekly number and proportion of ED visits increased for certain types of injuries (e.g., drug poisonings, self-harm, and firearm injuries) and some chronic diseases, with variation by pandemic year and age group. Visits related to behavioral concerns increased across pandemic years, particularly among older children and adolescents. Health care providers and families should remain vigilant for potential indirect impacts of the COVID-19 pandemic, including health conditions resulting from delayed care, and increasing emotional distress and behavioral health concerns among children and adolescents.

    • Health Economics
      1. Unmet needs for HIV ancillary care services by health care coverage and Ryan White HIV/AIDS program assistanceexternal icon
        Dasgupta S, Crim SM, Dawson L, Kates J, Weiser J, Klein PW, Dempsey A, Hauck H, Lu JF, Shu F, Beer L.
        AIDS. 2022 Feb 24.
        OBJECTIVE: To investigate unmet needs for HIV ancillary care services by health care coverage type and Ryan White HIV/AIDS Program (RWHAP) assistance among adults with HIV. DESIGN: We analyzed data using the 2017-2019 cycles of the CDC Medical Monitoring Project, an annual, cross-sectional study designed to produce nationally representative estimates of characteristics among adults with diagnosed HIV. METHODS: Unmet need was defined as needing, but not receiving, ≥1 HIV ancillary care service. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) using predicted marginal means to examine associations between health care coverage type and unmet needs for HIV ancillary care services, adjusting for age. Associations were stratified by receipt of RWHAP assistance. RESULTS: Unmet needs for HIV ancillary care services were highest among uninsured persons (58.7%) and lowest among those with private insurance living ≥400% of the federal poverty level (FPL; 21.7%). Uninsured persons who received RWHAP assistance were less likely than those who did not receive RWHAP assistance to have unmet needs for HIV clinical support services (aPR: 0.21; 95% CI: 0.16-0.28) and other medical services (aPR: 0.75; 95% CI: 0.59-0.96), but not subsistence services (aPR: 0.97; 95% CI: 0.74-1.27). Unmet needs for other medical services and subsistence services did not differ by RWHAP assistance among those with Medicaid, Medicare, or other health care coverage. CONCLUSIONS: RWHAP helped reduce some needs for uninsured persons. However, with growing socioeconomic inequities following the COVID-19 pandemic, expanding access to needed services for all people with HIV could improve key outcomes.

      2. Healthcare utilization and costs associated with perinatal depression among Medicaid enrolleesexternal icon
        Pollack LM, Chen J, Cox S, Luo F, Robbins CL, Tevendale HD, Li R, Ko JY.
        Am J Prev Med. 2022 Feb 25.
        INTRODUCTION: Differences in healthcare utilization and medical expenditures associated with perinatal depression are estimated. METHODS: Using the MarketScan Multi-State Medicaid Database, the analytic cohort included individuals aged 15-44 years who had an inpatient live birth delivery hospitalization between January 1, 2017 and December 31, 2018. Multivariable negative binomial regression models were used to estimate the differences in utilization associated with perinatal depression, and multivariable generalized linear models were used to estimate the differences in expenditures associated with perinatal depression. Analyses were conducted in 2021. RESULTS: The cohort included 330,593 individuals. Nearly 17% had perinatal depression. Compared with individuals without perinatal depression individuals with perinatal depression had a larger number of inpatient admissions (0.19, 95% CI=0.18, 0.20), total inpatient days (0.95, 95% CI=0.92, 0.97), outpatient visits (14.02, 95% CI=13.81, 14.22), emergency department visits (1.70, 95% CI=1.66, 1.74), and weeks of drug therapy covered by a prescription (28.70, 95% CI=28.12, 29.28) and larger total expenditures ($5,078, 95% CI=$4,816, $5,340). Non-Hispanic Black individuals had larger differences in utilization and expenditures for inpatient services and outpatient visits but smaller differences in utilization for pharmaceutical services associated with perinatal depression than non-Hispanic White individuals. Hispanic individuals had larger differences in utilization for outpatient visits but smaller differences in utilization for pharmaceutical services associated with perinatal depression than non-Hispanic White individuals. CONCLUSIONS: Individuals with perinatal depression had more healthcare utilization and medical expenditures than individuals without perinatal depression, and differences varied by race/ethnicity. The findings highlight the need to ensure comprehensive and equitable mental health care to address perinatal depression.

      3. Optimizing HIV prevention efforts to achieve EHE incidence targetsexternal icon
        Jacobson EU, Hicks KA, Carrico J, Purcell DW, Green TA, Mermin JH, Farnham PG.
        J Acquir Immune Defic Syndr. 2022 Apr 1;89(4):374-380.
        BACKGROUND: A goal of the US Department of Health and Human Services' Ending the HIV Epidemic (EHE) in the United States initiative is to reduce the annual number of incident HIV infections in the United States by 75% within 5 years and by 90% within 10 years. We developed a resource allocation analysis to understand how these goals might be met. METHODS: We estimated the current annual societal funding [$2.8 billion (B)/yr] for 14 interventions to prevent HIV and facilitate treatment of infected persons. These interventions included HIV testing for different transmission groups, HIV care continuum interventions, pre-exposure prophylaxis, and syringe services programs. We developed scenarios optimizing or reallocating this funding to minimize new infections, and we analyzed the impact of additional EHE funding over the period 2021-2030. RESULTS: With constant current annual societal funding of $2.8 B/yr for 10 years starting in 2021, we estimated the annual incidence of 36,000 new cases in 2030. When we added annual EHE funding of $500 million (M)/yr for 2021-2022, $1.5 B/yr for 2023-2025, and $2.5 B/yr for 2026-2030, the annual incidence of infections decreased to 7600 cases (no optimization), 2900 cases (optimization beginning in 2026), and 2200 cases (optimization beginning in 2023) in 2030. CONCLUSIONS: Even without optimization, significant increases in resources could lead to an 80% decrease in the annual HIV incidence in 10 years. However, to reach both EHE targets, optimization of prevention funding early in the EHE period is necessary. Implementing these efficient allocations would require flexibility of funding across agencies, which might be difficult to achieve.

    • Health Equity and Health Disparities

      1. OBJECTIVES: To examine the extent to which lifelong neighborhood income modifies the generational association of teen birth among White and AA women in Cook County, IL. METHODS: Stratified and multilevel logistic regression analyses were conducted on the Illinois transgenerational dataset of singleton births (1989-1991) to non-Latina White and AA mothers (born 1956-1976) with appended U.S. census income information. We calculated rates and risks of teen births according to race, maternal age, and lifelong neighborhood economic environment. RESULTS: Teen birth occurred at a rate of 9.5% and 52.9% for White and AA women, respectively. White women whose mothers were teens when they were born had an over five-fold increased risk of becoming teen mothers themselves. For AA women, the risk was smaller, but statistically significant. For both races, women who experienced downward economic mobility had the highest risk of teen birth, while women with upward mobility had the lowest risk, even compared to women in lifelong high income neighborhoods. While White women exposed to lifelong low income had almost threefold increased risk of teen birth compared to those in lifelong high income neighborhoods, AA women in lifelong high and lifelong low income neighborhoods had similar risk of teen birth. CONCLUSIONS FOR PRACTICE: Understanding the racial differences in intergenerational patterns of teen birth is important for effective program planning and policy making, given that interventions targeted at daughters of teen mothers may differ in effectiveness for White and AA teens.

    • Healthcare Associated Infections
      1. Mathematical models are used to gauge the impact of interventions for healthcare-associated infections. As with any analytic method, such models require many assumptions. Two common assumptions are that asymptomatically colonized individuals are more likely to be hospitalized and that they spend longer in the hospital per admission because of their colonization status. These assumptions have no biological basis and could impact the estimated effects of interventions in unintended ways. Therefore, we developed a model of methicillin-resistant Staphylococcus aureus transmission to explicitly evaluate the impact of these assumptions. We found that assuming that asymptomatically colonized individuals were more likely to be admitted to the hospital or spend longer in the hospital than uncolonized individuals biased results compared to a more realistic model that did not make either assumption. Results were heavily biased when estimating the impact of an intervention that directly reduced transmission in a hospital. In contrast, results were moderately biased when estimating the impact of an intervention that decolonized hospital patients. Our findings can inform choices modelers face when constructing models of healthcare-associated infection interventions and thereby improve their validity.

    • Immunity and Immunization
      1. Neurological events reported after COVID-19 vaccines: An analysis of VAERSexternal icon
        Frontera JA, Tamborska AA, Doheim MF, Garcia-Azorin D, Gezegen H, Guekht A, Yusof Khan AH, Santacatterina M, Sejvar J, Thakur KT, Westenberg E, Winkler AS, Beghi E.
        Ann Neurol. 2022 Mar 2.
        OBJECTIVE: To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S.. METHODS: We utilized publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021-June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post-vaccination neurological event rates were compared between vaccine types and to age-matched baseline incidence rates in the U.S. and rates of neurological events following COVID. RESULTS: Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0-3) from inoculation. Guillain-Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer-BioNtech (BNT162b2) or Moderna (mRNA-1273; 0.15% versus 0.03% versus 0.03% of doses, respectively,P<0.0001). The observed-to-expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5-fold higher than background rates. However, the rate of neurological events after acute SARS-CoV-2 infection was up to 617-fold higher than after COVID vaccination. INTERPRETATION: Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS-CoV-2 infection are up to 617-fold higher than after COVID vaccination. This article is protected by copyright. All rights reserved.

      2. Disease eradication and elimination programs drive innovations based on progress toward measurable objectives, evaluations of new strategies and methods, programmatic experiences, and lessons learned from the field. Following progress toward global measles elimination, reducing measles mortality, and increasing introductions of measles and rubella vaccines to national programs, the measles and rubella immunization program has faced setbacks in recent years. Currently available vaccine delivery methods have complicated logistics and drawbacks that create barriers to vaccination; innovations for easier, more efficient, and safer vaccine delivery are needed. Progress can be accelerated by new technologies like microarray patches (MAPs) that are now widely recognized as a potential new tool for enhancing global immunizations efforts. Clinical trials of measles-rubella vaccine MAPs have begun, and several other vaccine MAPs are in the pre-clinical development pathway. MAPs could significantly contribute to Immunization Agenda 2030 priorities, including reaching zero-dose children; increasing vaccine access, demand, coverage, and equity; and achieving measles and rubella elimination. With strong partnerships between public health agencies and biotechnology companies, translational novel vaccine delivery systems can be developed to help solve public health problems and achieve global health priorities.

      3. Anti-SARS-CoV-2 IgG antibody levels among Thai healthcare providers receiving homologous and heterologous COVID-19 vaccination regimensexternal icon
        Kittikraisak W, Hunsawong T, Punjasamanvong S, Wongrapee T, Suttha P, Piyaraj P, Leepiyasakulchai C, Tanathitikorn C, Yoocharoen P, Jones AR, Mongkolsirichaikul D, Westercamp M, Azziz-Baumgartner E, Mott JA, Chottanapund S.
        Influenza Other Respir Viruses. 2022 Feb 24.
        BACKGROUND: We examined SARS-CoV-2 anti-spike 1 IgG antibody levels following COVID-19 vaccination (AstraZeneca [AZ], Sinovac [SV], Pfizer-BioNTech [PZ]) among Thai healthcare providers. METHODS: Blood specimens were tested using enzyme-linked immunosorbent assay. We analyzed seven vaccination regimens: (1) one dose of AZ or SV, (2) two doses of homologous (2AZ, 2SV) or heterologous (1AZ + 1PZ) vaccines, and (3) three doses of heterologous vaccines (2SV + 1AZ, 2SV + 1PZ). Differences in antibody levels were assessed using Kruskal-Wallis statistic, Mann-Whitney test, or Wilcoxon matched-pairs signed-rank test. Antibody kinetics were predicted using fractional polynomial regression. RESULTS: The 563 participants had median age of 39 years; 92% were female; 74% reported no underlying medical condition. Antibody levels peaked at 22-23 days in both 1AZ and 2SV vaccinees and dropped below assay's cutoff for positive (35.2 binding antibody units/ml [BAU/ml]) in 55 days among 1AZ vaccinees compared with 117 days among 2SV vaccinees. 1AZ + 1PZ vaccination regimen was highly immunogenic (median 2279 BAU/ml) 1-4 weeks post vaccination. 2SV + 1PZ vaccinees had significantly higher antibody levels than 2SV + 1AZ vaccinees 4 weeks post vaccination (3423 vs. 2105 BAU/ml; p-value < 0.01), and during weeks 5-8 (3656 vs. 1072 BAU/ml; p-value < 0.01). Antibodies peaked at 12-15 days in both 2SV + 1PZ and 2SV + 1AZ vaccinees, but those of 2SV + 1AZ declined more rapidly and dropped below assay's cutoff in 228 days while those of 2SV + 1PZ remained detectable. CONCLUSIONS: 1AZ + 1PZ, 2SV + 1AZ, and 2SV + 1PZ vaccinees had substantial IgG levels, suggesting that these individuals likely mounted sufficient anti-S1 IgG antibodies for possible protection against SARS-CoV-2 infection.

      4. Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigationexternal icon
        Yousaf AR, Cortese MM, Taylor AW, Broder KR, Oster ME, Wong JM, Guh AY, McCormick DW, Kamidani S, Schlaudecker EP, Edwards KM, Creech CB, Staat MA, Belay ED, Marquez P, Su JR, Salzman MB, Thompson D, Campbell AP.
        Lancet Child Adolesc Health. 2022 Feb 22.
        BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC). METHODS: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data. FINDINGS: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals. INTERPRETATION: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FUNDING: US Centers for Disease Control and Prevention.

      5. Use of Ebola vaccine: Expansion of recommendations of the Advisory Committee on Immunization Practices to include two additional populations - United States, 2021external icon
        Malenfant JH, Joyce A, Choi MJ, Cossaboom CM, Whitesell AN, Harcourt BH, Atmar RL, Villanueva JM, Bell BP, Hahn C, Loehr J, Davey RT, Sprecher A, Kraft CS, Shoemaker T, Montgomery JM, Helfand R, Damon IK, Frey SE, Chen WH.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):290-292.
        On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1).

      6. Microneedle patch as a new platform to effectively deliver inactivated polio vaccine and inactivated rotavirus vaccineexternal icon
        Moon SS, Richter-Roche M, Resch TK, Wang Y, Foytich KR, Wang H, Mainou BA, Pewin W, Lee J, Henry S, McAllister DV, Jiang B.
        NPJ Vaccines. 2022 Feb 28;7(1):26.
        We recently reported a lack of interference between inactivated rotavirus vaccine (IRV) and inactivated poliovirus vaccine (IPV) and their potential dose sparing when the two vaccines were administered intramuscularly either in combination or standalone in rats and guinea pigs. In the present study, we optimized the formulations of both vaccines and investigated the feasibility of manufacturing a combined IRV-IPV dissolving microneedle patch (dMNP), assessing its compatibility and immunogenicity in rats. Our results showed that IRV delivered by dMNP alone or in combination with IPV induced similar levels of RV-specific IgG and neutralizing antibody. Likewise, IPV delivered by dMNP alone or in combination with IRV induced comparable levels of neutralizing antibody of poliovirus types 1, 2, and 3. We further demonstrated high stability of IRV-dMNP at 5, 25, and 40 °C and IPV-dMNP at 5 and 25 °C, and found that three doses of IRV or IPV when co-administered at a quarter dose was as potent as a full target dose in inducing neutralizing antibodies against corresponding rotavirus or poliovirus. We conclude that IRV-IPV dMNP did not interfere with each other in triggering an immunologic response and were highly immunogenic in rats. Our findings support the further development of this innovative approach to deliver a novel combination vaccine against rotavirus and poliovirus in children throughout the world.

    • Injury and Violence
      1. Non-fatal injury data: characteristics to consider for surveillance and researchexternal icon
        Carmichael AE, Ballesteros MF, Qualters JR, Mack KA.
        Inj Prev. 2022 Feb 24.
        BACKGROUND: All data systems used for non-fatal injury surveillance and research have strengths and limitations that influence their utility in understanding non-fatal injury burden. The objective of this paper was to compare characteristics of major data systems that capture non-fatal injuries in the USA. METHODS: By applying specific inclusion criteria (eg, non-fatal and non-occupational) to well-referenced injury data systems, we created a list of commonly used non-fatal injury data systems for this study. Data system characteristics were compiled for 2018: institutional support, years of data available, access, format, sample, sampling method, injury definition/coding, geographical representation, demographic variables, timeliness (lag) and further considerations for analysis. RESULTS: Eighteen data systems ultimately fit the inclusion criteria. Most data systems were supported by a federal institution, produced national estimates and were available starting in 1999 or earlier. Data source and injury case coding varied between the data systems. Redesigns of sampling frameworks and the use of International Classification of Diseases, 9th Revision, Clinical Modification/International Classification of Diseases, 10th Revision, Clinical Modification coding for some data systems can make longitudinal analyses complicated for injury surveillance and research. Few data systems could produce state-level estimates. CONCLUSION: Thoughtful consideration of strengths and limitations should be exercised when selecting a data system to answer injury-related research questions. Comparisons between estimates of various data systems should be interpreted with caution, given fundamental system differences in purpose and population capture. This research provides the scientific community with an updated starting point to assist in matching the data system to surveillance and research questions and can improve the efficiency and quality of injury analyses.

      2. Changes in suicide rates - United States, 2019 and 2020external icon
        Ehlman DC, Yard E, Stone DM, Jones CM, Mack KA.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):306-312.
        Suicide was among the 10 leading causes of death in the United States in 2020 among persons aged 10-64 years, and the second leading cause of death among children and adolescents aged 10-14 and adults aged 25-34 years (1). During 1999-2020, nearly 840,000 lives were lost to suicide in the United States. During that period, the overall suicide rate peaked in 2018 and declined in 2019 and 2020 (1). Despite the recent decline in the suicide rate, factors such as social isolation, economic decline, family stressors, new or worsening mental health symptoms, and disruptions to work and school associated with the COVID-19 pandemic have raised concerns about suicide risk in the United States. During 2020, a total of 12.2 million U.S. adults reported serious thoughts of suicide and 1.2 million attempted suicide (2). To understand how changes in suicide death rates might have varied among subpopulations, CDC analyzed counts and age-adjusted suicide rates during 2019 and 2020 by demographic characteristics, mechanism of injury, county urbanization level, and state. From 2019 to 2020, the suicide rate declined by 3% overall, including 8% among females and 2% among males. Significant declines occurred in seven states but remained stable in the other states and the District of Columbia. Despite two consecutive years of declines, the overall suicide rate remains 30% higher compared with that in 2000 (1). A comprehensive approach to suicide prevention that uses data driven decision-making and implements prevention strategies with the best available evidence, especially among disproportionately affected populations (3), is critical to realizing further declines in suicide and reaching the national goal of reducing the suicide rate by 20% by 2025 (4).

    • Laboratory Sciences
      1. Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/ Ya Tsie trialexternal icon
        Magosi LE, Zhang Y, Golubchik T, DeGruttola V, Tchetgen Tchetgen E, Novitsky V, Moore J, Bachanas P, Segolodi T, Lebelonyane R, Pretorius Holme M, Moyo S, Makhema J, Lockman S, Fraser C, Essex MM, Lipsitch M.
        Elife. 2022 Mar 1;11.
        Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. Methods: To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana. We sequenced HIV viral whole genomes from 5,114 trial participants among the 30 trial communities. Results: Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 - 56.7] versus 3% [0.1 - 27.3]) than at baseline (7% [1.5 - 25.3] versus 5% [0.9 - 22.9]) compatible with a benefit from treatment-as-prevention. Conclusion: Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies. Funding: This study was supported by the National Institute of General Medical Sciences (U54GM088558); the Fogarty International Center (FIC) of the U.S. National Institutes of Health (D43 TW009610); and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention (CDC) (Cooperative agreements U01 GH000447 and U2G GH001911).

      2. Evaluation of commercially available high-throughput SARS-CoV-2 serologic assays for serosurveillance and related applicationsexternal icon
        Stone M, Grebe E, Sulaeman H, Di Germanio C, Dave H, Kelly K, Biggerstaff BJ, Crews BO, Tran N, Jerome KR, Denny TN, Hogema B, Destree M, Jones JM, Thornburg N, Simmons G, Krajden M, Kleinman S, Dumont LJ, Busch MP.
        Emerg Infect Dis. 2022 Mar;28(3):672-683.
        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.55-0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants.

      3. Use of serial testing to interrupt a SARS-CoV-2 outbreak on a hospital medical floor - Minnesota, October-December 2020external icon
        Prabhu RM, Firestone MJ, Bergman K, Beaudoin A, Hale T, Lorentz A, Garfin J, Wang X, Holzbauer S.
        Infect Control Hosp Epidemiol. 2022 Feb 28:1-16.
        OBJECTIVE: Describe a SARS-CoV-2 hospital outbreak and the role of serial testing of patients and healthcare personnel (HCP) in interrupting transmission. DESIGN: Outbreak investigation. SETTING: Medical floor of a tertiary care center in Minnesota. METHODS: Serial testing for SARS-CoV-2 and whole genome sequencing (WGS) of positive specimens from HCP and patients was used. An outbreak-associated case was defined as a positive SARS-CoV-2 molecular test in HCP who worked on the floor prior to testing positive or in a patient who was hospitalized on the medical floor during October 27-December 1, 2020. WGS was used to understand potential routes of transmission. RESULTS: The outbreak was detected after a patient hospitalized for 12 days tested positive for SARS-CoV-2. Serial testing of patients and HCP was conducted in response. Overall, 247 HCP and 41 patients participated in serial SARS-CoV-2 testing. Fifty-two (21%) HCP and 19 (46%) hospitalized patients tested positive. One additional HCP tested positive outside of serial testing. WGS of specimens from 27 (51%) HCP and 15 (79%) patients identified three distinct transmission clusters. WGS and epidemiologic evidence suggested intrafacility transmission. The proportion of asymptomatic and pre-symptomatic patients who tested positive (63%) and HCP who worked during their infectious period (75%) highlight the need for serial testing of asymptomatic patients and HCP during outbreaks. CONCLUSIONS: Coupled with preventive measures such as personal protective equipment use and physical distancing, serial testing of HCP and patients could help detect and prevent transmission within healthcare facilities during outbreaks and when nosocomial transmission is suspected.

      4. Evaluation of the performance of Oraquick Rapid HIV-1/2 test among decedents in Kisumu, Kenyaexternal icon
        Opollo V, Nyakeriga E, Kingwara L, Sila A, Oguta M, Oyaro B, Onyango D, Mboya FO, Waruru A, Musingila P, Mwangome M, Nyagah LM, Ngugi C, Sava S, Waruiru W, Young PW, Junghae M.
        J Acquir Immune Defic Syndr. 2022 Mar 1;89(3):282-287.
        BACKGROUND: Estimating cause-related mortality among the dead is not common, yet for clinical and public health purposes, a lot can be learnt from the dead. HIV/AIDS accounted for the third most frequent cause of deaths in Kenya; 39.7 deaths per 100,000 population in 2019. OraQuick Rapid HIV-1/2 has previously been validated on oral fluid and implemented as a screening assay for HIV self-testing in Kenya among living subjects. We assessed the feasibility and diagnostic accuracy of OraQuick Rapid HIV-1/2 for HIV screening among decedents. METHODS: Trained morticians collected oral fluid from 132 preembalmed and postembalmed decedents aged >18 months at Jaramogi Oginga Odinga Teaching and Referral Hospital mortuary in western Kenya and tested for HIV using OraQuick Rapid HIV-1/2. Test results were compared with those obtained using the national HIV Testing Services algorithm on matched preembalming whole blood specimens as a gold standard (Determine HIV and First Response HIV 1-2-O). We calculated positive predictive values, negative predictive values, area under the curve, and sensitivity and specificity of OraQuick Rapid HIV-1/2 compared with the national HTS algorithm. RESULTS: OraQuick Rapid HIV-1/2 had similar sensitivity of 92.6% [95% confidence interval (CI): 75.7 to 99.1] on preembalmed and postembalmed samples compared with the gold standard. Specificity was 97.1% (95% CI: 91.9 to 99.4) and 95.2% (95% CI: 89.2 to 98.4) preembalming and postembalming, respectively. Preembalming and postembalming positive predictive value was 89.3% (95% CI: 71.8 to 97.7) and 83.3% (95% CI: 65.3 to 94.4), respectively. The area under the curve preembalming and postembalming was 94.9% (95% CI: 89.6 to 100) and 93.9% (95% CI: 88.5 to 99.4), respectively. CONCLUSIONS: The study showed a relatively high-performance sensitivity and specificity of OraQuick Rapid HIV-1/2 test among decedents, similar to those observed among living subjects. OraQuick Rapid HIV-1/2 presents a convenient and less invasive screening test for surveillance of HIV among decedents within a mortuary setting.

      5. Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgGexternal icon
        Costantini VP, Nguyen K, Lyski Z, Novosad S, Bardossy AC, Lyons AK, Gable P, Kutty PK, Lutgring JD, Brunton A, Thornburg NJ, Brown AC, McDonald LC, Messer W, Vinjé J.
        J Immunol. 2022 Feb 28.
        Oral fluids offer a noninvasive sampling method for the detection of Abs. Quantification of IgA and IgG Abs in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG Abs against the prefusion-stabilized form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein expressed in suspension-adapted HEK-293 cells. Normalization against total Ab isotype was performed to account for specimen differences, such as collection time and sample volume. Saliva samples collected from 187 SARS-CoV-2 confirmed cases enrolled in 2 cohorts and 373 prepandemic saliva samples were tested. The sensitivity of both EIAs was high (IgA, 95.5%; IgG, 89.7%) without compromising specificity (IgA, 99%; IgG, 97%). No cross-reactivity with endemic coronaviruses was observed. The limit of detection for SARS-CoV-2 salivary IgA and IgG assays were 1.98 ng/ml and 0.30 ng/ml, respectively. Salivary IgA and IgG Abs were detected earlier in patients with mild COVID-19 symptoms than in severe cases. However, severe cases showed higher salivary Ab titers than those with a mild infection. Salivary IgA titers quickly decreased after 6 wk in mild cases but remained detectable until at least week 10 in severe cases. Salivary IgG titers remained high for all patients, regardless of disease severity. In conclusion, EIAs for both IgA and IgG had high specificity and sensitivity for the confirmation of current or recent SARS-CoV-2 infections and evaluation of the IgA and IgG immune response.

      6. Results from a test-to-release from isolation strategy among fully vaccinated National Football League players and staff members with COVID-19 - United States, December 14-19, 2021external icon
        Mack CD, Wasserman EB, Killerby ME, Soelaeman RH, Hall AJ, MacNeil A, Anderson DJ, Walton P, Pasha S, Myers E, O'Neal CS, Hostler CJ, Singh N, Mayer T, Sills A.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):299-305.
        During December 2021, the United States experienced a surge in COVID-19 cases, coinciding with predominance of the SARS-CoV-2 B.1.1.529 (Omicron) variant (1). During this surge, the National Football League (NFL) and NFL Players Association (NFLPA) adjusted their protocols for test-to-release from COVID-19 isolation on December 16, 2021, based on analytic assessments of their 2021 test-to-release data. Fully vaccinated* persons with COVID-19 were permitted to return to work once they were asymptomatic or fever-free and experiencing improving symptoms for ≥24 hours, and after two negative or high cycle-threshold (Ct) results (Ct≥35) from either of two reverse transcription-polymerase chain reaction (RT-PCR) tests(†) (2). This report describes data from NFL's SARS-CoV-2 testing program (3) and time to first negative or Ct≥35 result based on serial COVID-19 patient testing during isolation. Among this occupational cohort of 173 fully vaccinated adults with confirmed COVID-19 during December 14-19, 2021, a period of Omicron variant predominance, 46% received negative test results or had a subsequent RT-PCR test result with a Ct≥35 by day 6 postdiagnosis (i.e., concluding 5 days of isolation) and 84% before day 10. The proportion of persons with positive test results decreased with time, with approximately one half receiving positive RT-PCR test results after postdiagnosis day 5. Although this test result does not necessarily mean these persons are infectious (RT-PCR tests might continue to return positive results long after an initial positive result) (4), these findings indicate that persons with COVID-19 should continue taking precautions, including correct and consistent mask use, for a full 10 days after symptom onset or initial positive test result if they are asymptomatic.

    • Maternal and Child Health
      1. Patterns of special education eligibility and age of first autism spectrum disorder (ASD) identification among US children with ASDexternal icon
        Esler AN, Sample J, Hall-Lande J, Harris B, Rice C, Poynter J, Kirby RS, Wiggins L.
        J Autism Dev Disord. 2022 Feb 25.
        The study examined timing of autism spectrum disorder (ASD) identification in education versus health settings for 8-year-old children with ASD identified through records-based surveillance. The study also examined type of ASD symptoms noted within special education evaluations. Results indicated that children with records from only education sources had a median time to identification of ASD over a year later than children with records from health sources. Black children were more likely than White children to have records from only education sources. Restricted and repetitive behaviors were less frequently documented in educational evaluations resulting in developmental delay eligibility compared to specific ASD eligibility among children with ASD. Future research could explore strategies reduce age of identification in educational settings and increase equitable access to health evaluations.

      2. Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling studyexternal icon
        Unwin HJ, Hillis S, Cluver L, Flaxman S, Goldman PS, Butchart A, Bachman G, Rawlings L, Donnelly CA, Ratmann O, Green P, Nelson CA, Blenkinsop A, Bhatt S, Desmond C, Villaveces A, Sherr L.
        Lancet Child Adolesc Health. 2022 Feb 24.
        BACKGROUND: In the 6 months following our estimates from March 1, 2020, to April 30, 2021, the proliferation of new coronavirus variants, updated mortality data, and disparities in vaccine access increased the amount of children experiencing COVID-19-associated orphanhood. To inform responses, we aimed to model the increases in numbers of children affected by COVID-19-associated orphanhood and caregiver death, as well as the cumulative orphanhood age-group distribution and circumstance (maternal or paternal orphanhood). METHODS: We used updated excess mortality and fertility data to model increases in minimum estimates of COVID-19-associated orphanhood and caregiver deaths from our original study period of March 1, 2020-April 30, 2021, to include the new period of May 1-Oct 31, 2021, for 21 countries. Orphanhood was defined as the death of one or both parents; primary caregiver loss included parental death or the death of one or both custodial grandparents; and secondary caregiver loss included co-residing grandparents or kin. We used logistic regression and further incorporated a fixed effect for western European countries into our previous model to avoid over-predicting caregiver loss in that region. For the entire 20-month period, we grouped children by age (0-4 years, 5-9 years, and 10-17 years) and maternal or paternal orphanhood, using fertility contributions, and we modelled global and regional extrapolations of numbers of orphans. 95% credible intervals (CrIs) are given for all estimates. FINDINGS: The number of children affected by COVID-19-associated orphanhood and caregiver death is estimated to have increased by 90·0% (95% CrI 89·7-90·4) from April 30 to Oct 31, 2021, from 2 737 300 (95% CrI 1 976 100-2 987 000) to 5 200 300 (3 619 400-5 731 400). Between March 1, 2020, and Oct 31, 2021, 491 300 (95% CrI 485 100-497 900) children aged 0-4 years, 736 800 (726 900-746 500) children aged 5-9 years, and 2 146 700 (2 120 900-2 174 200) children aged 10-17 years are estimated to have experienced COVID-19-associated orphanhood. Globally, 76·5% (95% CrI 76·3-76·7) of children were paternal orphans, whereas 23·5% (23·3-23·7) were maternal orphans. In each age group and region, the prevalence of paternal orphanhood exceeded that of maternal orphanhood. INTERPRETATION: Our findings show that numbers of children affected by COVID-19-associated orphanhood and caregiver death almost doubled in 6 months compared with the amount after the first 14 months of the pandemic. Over the entire 20-month period, 5·0 million COVID-19 deaths meant that 5·2 million children lost a parent or caregiver. Our data on children's ages and circumstances should support pandemic response planning for children globally. FUNDING: UK Research and Innovation (Global Challenges Research Fund, Engineering and Physical Sciences Research Council, and Medical Research Council), Oak Foundation, UK National Institute for Health Research, US National Institutes of Health, and Imperial College London.

      3. Pediatric emergency department visits associated with mental health conditions before and during the COVID-19 pandemic - United States, January 2019-January 2022external icon
        Radhakrishnan L, Leeb RT, Bitsko RH, Carey K, Gates A, Holland KM, Hartnett KP, Kite-Powell A, DeVies J, Smith AR, van Santen KL, Crossen S, Sheppard M, Wotiz S, Lane RI, Njai R, Johnson AG, Winn A, Kirking HL, Rodgers L, Thomas CW, Soetebier K, Adjemian J, Anderson KN.
        MMWR Morb Mortal Wkly Rep. 2022 Feb 25;71(8):319-324.
        In 2021, a national emergency* for children's mental health was declared by several pediatric health organizations, and the U.S. Surgeon General released an advisory(†) on mental health among youths. These actions resulted from ongoing concerns about children's mental health in the United States, which was exacerbated by the COVID-19 pandemic (1,2). During March-October 2020, among all emergency department (ED) visits, the proportion of mental health-related visits increased by 24% among U.S. children aged 5-11 years and 31% among adolescents aged 12-17 years, compared with 2019 (2). CDC examined changes in U.S. pediatric ED visits for overall mental health conditions (MHCs) and ED visits associated with specific MHCs (depression; anxiety; disruptive behavioral and impulse-control disorders; attention-deficit/hyperactivity disorder; trauma and stressor-related disorders; bipolar disorders; eating disorders; tic disorders; and obsessive-compulsive disorders [OCD]) during 2019 through January 2022 among children and adolescents aged 0-17 years, overall and by sex and age. After declines in weekly visits associated with MHCs among those aged 0-17 years during 2020, weekly numbers of ED visits for MHCs overall and for specific MHCs varied by age and sex during 2021 and January 2022, when compared with corresponding weeks in 2019. Among adolescent females aged 12-17 years, weekly visits increased for two of nine MHCs during 2020 (eating disorders and tic disorders), for four of nine MHCs during 2021 (depression, eating disorders, tic disorders, and OCD), and for five of nine MHCs during January 2022 (anxiety, trauma and stressor-related disorders, eating disorders, tic disorders, and OCD), and overall MHC visits during January 2022, compared with 2019. Early identification and expanded evidence-based prevention and intervention strategies are critical to improving children's and adolescents' mental health (1-3), especially among adolescent females, who might have increased need.

    • Occupational Safety and Health - Mining
      1. The Mine Safety and Health Administration (MSHA) promulgated a rule in 2014 that required numerous changes in compliance dust sampling requirements for coal mine operators. Two key parts of this rule were the lowering of the respirable coal mine dust standard from 2.0 mg/m3 to 1.5 mg/m3 and requiring operators of underground coal mines to use a continuous personal dust monitor (CPDM) for compliance sampling. The CPDM currently approved for compliance sampling is equipped with a display that provides miners with in-shift information on their respirable dust exposure. The goal is to provide an indication of a potential overexposure and empower the miner and mine operator to implement changes in controls and/or operating practices to prevent an overexposure from occurring. Compliance sampling data for four occupations that have historically had elevated dust exposures were downloaded from the MSHA website and analyzed to assess the impact of the CPDM on overexposures. These occupations include continuous miner operator, roof bolter operator, tailgate-side shearer operator, and jacksetter. MSHA inspector and mine operator sampling data from five years before the rule became effective was compared to sampling results for five years after the dust standard was lowered and CPDM use was required. The analysis indicates that use of the CPDM has resulted in substantially lower percentages of samples exceeding the applicable respirable dust standard for these four occupations. A discussion of key dust rule changes, the CPDM, and compliance sampling results are provided. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

      2. The necessity for improved hand and finger protection in miningexternal icon
        Heberger JR, Nasarwanji MF, Pollard JP, Kocher LM.
        Min Metall Explor. 2022 .
        Injuries associated with hands and fingers are highly prevalent in mining and identifying factors associated with these injuries are critical in developing prevention efforts. This study identifies nonfatal injury incidence rates, nature of injury, work activities, glove usage, and sources of hand and finger injuries in the U.S. mining industry, as reported to the Mine Safety and Health Administration (MSHA) from 2011 - 2017. Hand and finger injuries occur at a rate of 6.53 per 1000 full-time employees, which is nearly double the rate of the next highest affected body part, the back. Most of the hand and finger injuries were classified as cuts/lacerations/punctures (53%) followed by bone fractures/chips (26%). Materials handling and maintenance/repair were common activities at the time of the incident with miscellaneous metals (pipe, wire, guarding) and hand tools as the primary sources of hand and finger injury. Although the information on glove use was limited, leather gloves were most often worn when an injury occurred. When worn, gloves were found to contribute to 20% of the injuries, indicating their potential to protect the hands, but also potentially put the hands at risk. Further research is necessary to determine performance requirements for gloves used in mining operations, specifically those offering cut and puncture resistance. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

      3. Field test of a canopy air curtain on a ramcar for dust control in an underground coal mineexternal icon
        Reed WR, Colinet JF, Klima SS, Mazzella A, Ross G, Workman M, Morson T, Driscoll J.
        Min Metall Explor. 2022 .
        The canopy air curtain (CAC) has been proven to reduce the respirable dust exposure of roof bolter operators in underground coal mining. This technology is being adapted for use with shuttle cars and ramcars. The plenum is mounted on the underside of the shuttle car canopy over the operator’s position. The blower providing filtered air to the operator is plumbed into the shuttle car’s existing hydraulic system. After the system was installed on a ramcar, field testing of the CAC’s ability to provide respirable dust control was conducted on a section using blowing face ventilation. Results showed that overall respirable dust reductions during the total time the operator was underneath the canopy ranged from 11 to 34%, demonstrating adequate performance. However, further analysis demonstrated that the CAC performance was exceptional when the ramcar was being loaded by the continuous miner. At this location, a position where the shuttle car operator has their highest potential for respirable dust exposure, the CAC provided dust reductions ranging from 57 to 65%. These results, especially during ramcar loading at the CM, demonstrate that the CAC can be an important dust control device to reduce shuttle car and ramcar operators’ exposure to respirable coal mine dust. © 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

    • Parasitic Diseases
      1. Investigating flubendazole as an anthelmintic treatment for Guinea worm (Dracunculus medinensis): Clinical trials in laboratory-reared ferrets and domestic dogs in Chadexternal icon
        Cleveland CA, Garrett KB, Box EK, Thompson AT, Haynes EK, Elder DL, Richards RL, Majewska AA, Guagliardo SA, Wiegand RE, Bryan Ii JA, Torres-Velez F, Unterwegner K, Romero M, Zirimwabagabo H, Sidouin M, Oaukou PT, Ada MM, Ngandolo BN, Mackenzie CD, Geary TG, Weiss AJ, Yabsley MJ.
        Am J Trop Med Hyg. 2022 Feb 28.
        Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in domestic dog GW infections highlight the need for novel approaches. We conducted two clinical trials evaluating the efficacy of subcutaneously injected flubendazole (FBZ) as a treatment of GW infection. The first trial was conducted administering FBZ to experimentally infected ferrets; the second trial involved administering FBZ or a placebo to domestic dogs in the Republic of Tchad (Chad). We found contrasting results between the two trials. When adult gravid female GW were recovered from ferrets treated with FBZ, larvae presented in poor condition, with low to no motility, and an inability to infect copepods. Histopathology results indicated a disruption to morulae development within uteri of worms from treated animals. Results from the trial in Chadian dogs failed to indicate significant treatment of or prevention against GW infection. However, the difference in treatment intervals (1 month for ferrets and 6 months for dogs) or the timing of treatment (ferrets were treated later in the GW life-cycle than dogs) could explain different responses to the subcutaneous FBZ injections. Both trials provided valuable data guiding the use of FBZ in future trials (such as decreasing treatment intervals or increasing the dose of FBZ in dogs to increase exposure), and highlighted important lessons learned during the implementation of a field-based, double-blinded randomized control trial in Chadian dogs.

      2. The positive effect of malaria IPTp-SP on birthweight is mediated by gestational weight gain but modifiable by maternal carriage of enteric pathogensexternal icon
        Waltmann A, McQuade ET, Chinkhumba J, Operario DJ, Mzembe E, Itoh M, Kayange M, Puerto-Meredith SM, Mathanga DP, Juliano JJ, Carroll I, Bartelt LA, Gutman JR, Meshnick SR.
        EBioMedicine. 2022 Feb 22;77:103871.
        BACKGROUND: Poor pregnancy and birth outcomes are common in sub-Saharan Africa and have complex aetiologies. Sulfadoxine-pyrimethamine (SP), given for intermittent preventive therapy of malaria in pregnancy (IPTp), is one of few existing interventions that improves outcomes of both mother and baby despite widespread SP-resistant malaria. Compelling evidence exists that malaria-independent pathways contribute to this protective effect, but the exact sources of non anti-malarial protection remained unknown. We hypothesized that the beneficial effect of SP on birthweight is mediated by SP activity on maternal factors, including increased gestational weight gain and antibiotic activity on pathogens in the maternal gut. METHODS: Expectant mothers from a larger randomized control trial comparing the efficacy of IPTp-SP to IPTp with dihydroartemisinin-piperaquine (DP) were also enrolled in this sub-study study at their first antenatal care visit before commencement of IPTp (n = 105). Participants were followed monthly until delivery. Weights and mid-to-upper-arm circumferences (MUAC) were recorded. Monthly stool samples were collected and screened for five Escherichia coli pathotypes, Shigella spp., Vibrio cholerae, Salmonella, Campylobacter coli/jejuni, and three protozoa (Giardia spp., Entameba histolytica, and Cryptosporidium spp.) using previously validated molecular assays. FINDINGS: IPTp-SP vs. IPTP-DP was associated with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). GWG was found to be a mediator of the birthweight and IPTp-SP relationship, as the birthweight of SP infants, but not DP infants, varied according to maternal GWG. The burden of maternal enteric infections was high. The three most commonly observed pathogens were enteroaggregative E. coli (EAEC), atypical enteropathogenic E.coli/enterohaemorrhagic E. coli (aEPEC/EHEC), and typical enteropathogenic E.coli (tEPEC). We found that SP reduced the prevalence of EAEC in a dose-dependent manner. After 3 or more doses, SP-recipients were 90% less likely to be infected with EAEC compared to DP-recipients (OR(adj) = 0.07, CI95 = 0.12, 0.39, p = 0.002). Compared to DP, this coincided with higher maternal gestational weight gain (GWG) and nutritional indicators (MUAC and body-mass index, BMI). The beneficial effect of SP on maternal GWG, MUAC and BMI, was lower if SP mothers had detectable EAEC, aEPEC/EHEC, tEPEC, and LT-ETEC at baseline. Maternal EAEC and tEPEC at baseline associated with lower birthweight for babies of both SP mothers and DP mothers. When comparing IPTp regimens, the positive effect of SP on birthweight compared to DP was only observed for infants of women who did not test positive for EAEC at baseline (adjusted mean birthweight difference SP vs. DP = 156.0 g, CI95 = -18.0 g, 336.9 g, p = 0.087), though confidence intervals crossed the null. INTERPRETATION: Our findings indicate that in pregnant Malawian women, IPTp-SP vs. IPTp-DP is consistently associated with higher MUAC, BMI, and GWG following the WHO-recommended regimen of at least 3 doses, but carriage of maternal gut pathogens before initiation of IPTp lessens this effect. Because GWG was a mediator of the association between birthweight and SP, we show that SP's previously proven positive effect on birthweight is by promoting maternal weight gain. Overall, our results present one plausible pathway SP exerts malaria-independent protection against poor birth outcomes in the context of its waning antimalarial activity and warrants further investigation. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

      3. Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions from persons with symptomatic malaria infection in Ethiopia, Kenya, Madagascar, and Rwandaexternal icon
        Rogier E, McCaffery JN, Nace D, Svigel SS, Assefa A, Hwang J, Kariuki S, Samuels AM, Westercamp N, Ratsimbasoa A, Randrianarivelojosia M, Uwimana A, Udhayakumar V, Halsey ES.
        Emerg Infect Dis. 2022 Mar;28(3):608-616.
        Histidine-rich protein 2 (HRP2)-based rapid diagnostic tests detect Plasmodium falciparum malaria and are used throughout sub-Saharan Africa. However, deletions in the pfhrp2 and related pfhrp3 (pfhrp2/3) genes threaten use of these tests. Therapeutic efficacy studies (TESs) enroll persons with symptomatic P. falciparum infection. We screened TES samples collected during 2016-2018 in Ethiopia, Kenya, Rwanda, and Madagascar for HRP2/3, pan-Plasmodium lactate dehydrogenase, and pan-Plasmodium aldolase antigen levels and selected samples with low levels of HRP2/3 for pfhrp2/3 genotyping. We observed deletion of pfhrp3 in samples from all countries except Kenya. Single-gene deletions in pfhrp2 were observed in 1.4% (95% CI 0.2%-4.8%) of Ethiopia samples and in 0.6% (95% CI 0.2%-1.6%) of Madagascar samples, and dual pfhrp2/3 deletions were noted in 2.0% (95% CI 0.4%-5.9%) of Ethiopia samples. Although this study was not powered for precise prevalence estimates, evaluating TES samples revealed a low prevalence of pfhrp2/3 deletions in most sites.

      4. Positive-case follow up for lymphatic filariasis after a transmission assessment survey in Haitiexternal icon
        Hast MA, Javel A, Denis E, Barbre K, Rigodon J, Robinson K, Brant TA, Wiegand R, Gass K, Telfort MA, Dubray C.
        PLoS Negl Trop Dis. 2022 Feb 25;16(2):e0010231.
        BACKGROUND: Lymphatic filariasis (LF) has been targeted for global elimination as a public health problem since 1997. The primary strategy to interrupt transmission is annual mass drug administration (MDA) for ≥5 years. The transmission assessment survey (TAS) was developed as a decision-making tool to measure LF antigenemia in children to determine when MDA in a region can be stopped. The objective of this study was to investigate potential sampling strategies for follow-up of LF-positive children identified in TAS to detect evidence of ongoing transmission. METHODOLOGY/PRINCIPLE FINDINGS: Nippes Department in Haiti passed TAS 1 with 2 positive cases and stopped MDA in 2015; however, 8 positive children were found during TAS 2 in 2017, which prompted a more thorough assessment of ongoing transmission. Purposive sampling was used to select the closest 50 households to each index case household, and systematic random sampling was used to select 20 households from each index case census enumeration area. All consenting household members aged ≥2 years were surveyed and tested for circulating filarial antigen (CFA) using the rapid filarial test strip and for Wb123-specific antibodies using the Filaria Detect IgG4 ELISA. Among 1,927 participants, 1.5% were CFA-positive and 4.5% were seropositive. CFA-positive individuals were identified for 6 of 8 index cases. Positivity ranged from 0.4-2.4%, with highest positivity in the urban commune Miragoane. Purposive sampling found the highest number of CFA-positives (17 vs. 9), and random sampling found a higher percent positive (2.4% vs. 1.4%). CONCLUSIONS/SIGNIFICANCE: Overall, both purposive and random sampling methods were reasonable and achievable methods of TAS follow-up in resource-limited settings. Both methods identified additional CFA-positives in close geographic proximity to LF-positive children found by TAS, and both identified strong signs of ongoing transmission in the large urban commune of Miragoane. These findings will help inform standardized guidelines for post-TAS surveillance.

    • Substance Use and Abuse
      1. Comorbid substance use and mental health disorders: Prior treatment/admission as a predictor of criminal arrest among American youthsexternal icon
        Nkemjika S, Olatunji E, Olwit C, Jegede O, Brown C, Olupona T, Okosun IS.
        Cureus. 2022 Jan;14(1):e21551.
        BACKGROUND: There is a dearth of literature with regards to substance use disorder (SUD) treatment outcomes and criminal arrest relationships. AIM: We aimed to examine the association between criminal arrest within a month prior to SUD treatment admissions among 12- to 24-year-old Americans and the role of recurrent or prior SUD treatment. METHODS: The 2017 United States Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episode Data Set - Admissions (TEDS-A; N = 333,322) was used for this analysis. Prevalence odds ratios from the multivariate logistic regression analyses were used to determine associations between recurrent or prior SUD treatment and criminal arrest one month before admission, adjusting for selected independent variables. RESULTS: Prior history of SUD treatment remained associated with past criminal arrest (adjusted OR = 0.972; 95% CI: 0.954-0.991; P = 0.004) after adjusting for gender, marital status, employment status, and source of income. Comorbid SUD-mental disorder was associated with past criminal arrest (adjusted OR = 1.046; 95% CI: 1.010-1.083; P = 0.012) after adjusting for gender, marital status, employment status, education, and source of income. CONCLUSION: Our study shows that there is a protective association between history of previous substance treatment re-admissions and its relationship with criminal arrest one month before admission.

      2. OBJECTIVE: Academic detailing is a clinical education technique characterized by targeted, one-on-one, interactive conversations between trained staff and the clinician. This study describes variations in implementing academic detailing among jurisdictions receiving funding from the U.S. Centers for Disease Control and Prevention (CDC) to prevent prescription drug overdoses. DESIGN: In 2015, CDC started the Prescription Drug Overdose Prevention for States (PfS) program. SUBJECTS: This study focuses on 11 of the 29 funded jurisdictions that implemented academic detailing as part of their PfS efforts. METHODS: Jurisdictions provided annual progress reports from 2016 to 2019. We conducted semi-structured interviews in 2017 and 2018 with all funded jurisdictions and conducted follow-up interviews with three jurisdictions in 2020 to obtain additional context. We used an analytic matrix display to identify themes from annual progress report data, the coding report from the 2017/2018 interviews, and the three follow-up interviews from 2020. RESULTS: Two academic detailing models emerged: 1) one-on-one detailing where centrally trained staff conducted all visits and 2) a train-the-trainer model. Jurisdictions also described a hybrid model, which they referred to as academic detailing despite not meeting the definition of academic detailing. We identified variations in delivery strategies, staffing, and curriculum development within and between models. Despite these differences, common themes included the need to use data to focus academic detailing and the importance of partnerships. CONCLUSIONS: Adoption of academic detailing as a strategy for improving opioid prescribing behaviors has increased. However, there is limited guidance and standardization to guide and evaluate implementation and outcomes.

      3. INTRODUCTION: Noticing health warnings on cigarette packages has been associated with thinking about quitting. This study examined sociodemographic characteristics associated with awareness of health warnings on cigarette packages and thinking about quitting because of health warning labels among adults who currently smoked tobacco. METHODS: We analyzed data from the 2017 Zambia WHO STEPS survey (STEPwise approach to surveillance) for noncommunicable disease risk factors. Descriptive analyses and logistic regression were performed to assess the association of select sociodemographic characteristics with awareness of health warnings and thinking about quitting because of health warnings. RESULTS: Adults who currently smoked tobacco who were aged 30-44 years, of Chewa ethnicity, or with a formal education, were more likely to be aware of health warnings than those aged 18-29 years (adjusted prevalence ratio, APR=1.26; 95% CI: 1.02-1.54), of Bemba ethnicity (APR=1.43; 95% CI: 1.17-1.74), or with no formal education (APR: 2.61-5.95). Among all adults who currently smoked, those of Chewa ethnicity (APR=1.55; 95% CI: 1.03-2.35), or with a formal education (APR:1.80-4.38), were more likely to report thinking about quitting because of health warnings than those who were of Bemba ethnicity or with less than primary school education level. Women who currently smoked were 49% less likely (APR=0.51; 95% CI: 0.23-0.84) to report thinking about quitting than men. Among a subset of adults who currently smoked who were aware of health warning labels, no sociodemographic characteristics were significantly associated with thinking about quitting in unadjusted or adjusted models. CONCLUSIONS: Sociodemographic characteristics such as sex, ethnicity, and education level were significantly associated with awareness of cigarette health warnings. Among cigarette smokers aware of health warnings, no sociodemographic differences in thinking about quitting were found. Tobacco control campaigns may need to target people of ethnicities with the highest smoking prevalence in the country.

    • Zoonotic and Vectorborne Diseases
      1. Zootherapy as a potential pathway for zoonotic spillover: a mixed-methods study of the use of animal products in medicinal and cultural practices in Nigeriaexternal icon
        Friant S, Bonwitt J, Ayambem WA, Ifebueme NM, Alobi AO, Otukpa OM, Bennett AJ, Shea C, Rothman JM, Goldberg TL, Jacka JK.
        One Health Outlook. 2022 Feb 26;4(1):5.
        BACKGROUND: Understanding how and why people interact with animals is important for the prevention and control of zoonoses. To date, studies have primarily focused on the most visible forms of human-animal contact (e.g., hunting and consumption), thereby blinding One Health researchers and practitioners to the broader range of human-animal interactions that can serve as cryptic sources of zoonotic diseases. Zootherapy, the use of animal products for traditional medicine and cultural practices, is widespread and can generate opportunities for human exposure to zoonoses. Existing research examining zootherapies omits details necessary to adequately assess potential zoonotic risks. METHODS: We used a mixed-methods approach, combining quantitative and qualitative data from questionnaires, key informant interviews, and field notes to examine the use of zootherapy in nine villages engaged in wildlife hunting, consumption, and trade in Cross River State, Nigeria. We analyzed medicinal and cultural practices involving animals from a zoonotic disease perspective, by including details of animal use that may generate pathways for zoonotic transmission. We also examined the sociodemographic, cultural, and environmental contexts of zootherapeutic practices that can further shape the nature and frequency of human-animal interactions. RESULTS: Within our study population, people reported using 44 different animal species for zootherapeutic practices, including taxonomic groups considered to be "high risk" for zoonoses and threatened with extinction. Variation in use of animal parts, preparation norms, and administration practices generated a highly diverse set of zootherapeutic practices (n = 292) and potential zoonotic exposure risks. Use of zootherapy was patterned by demographic and environmental contexts, with zootherapy more commonly practiced by hunting households (OR = 2.47, p < 0.01), and prescriptions that were gender and age specific (e.g., maternal and pediatric care) or highly seasonal (e.g., associated with annual festivals and seasonal illnesses). Specific practices were informed by species availability and theories of healing (i.e., "like cures like" and sympathetic healing and magic) that further shaped the nature of human-animal interactions via zootherapy. CONCLUSIONS: Epidemiological investigations of zoonoses and public health interventions that aim to reduce zoonotic exposures should explicitly consider zootherapy as a potential pathway for disease transmission and consider the sociocultural and environmental contexts of their use in health messaging and interventions.

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