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Issue 39, October 26, 2021

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CDC Science Clips: Volume 13, Issue 39, October 26, 2021

This week, CDC Science Clips is pleased to feature the winners of the 2021 Charles C. Shepard Science Awards.

This award is presented to the best manuscript on original research published by a CDC or ATSDR scientist in a reputable, peer-reviewed journal. The purpose of the award is: 

  • To recognize excellence in scientific achievement by CDC and ATSDR authors of outstanding scientific papers 
  • To honor the memory of Charles C. Shepard whose career was marked by the pursuit of scientific excellence 
The program for the 2021 Shepard Awards ceremony and a complete list of nominees may be found herepdf icon.

The report consists of these components:

  1. 2021 Charles C. Shepard Science Awards
    • Assessment
      1. Given recent slowing of declines in national all-cause, heart disease, and stroke mortality, examining spatiotemporal distributions of coronary heart disease (CHD) death rates and trends can provide data critical to improving the cardiovascular health of populations. This paper documents county-level CHD death rates and trends by age group, race, and gender from 1979 through 2017. Using data from the National Vital Statistics System and a Bayesian multivariate space-time conditional autoregressive model, we estimated county-level age-standardized annual CHD death rates for 1979 through 2017 by age group (35-64 years, 65 years and older), race (white, black, other), and gender (men, women). We then estimated county-level total percent change in CHD death rates during four intervals (1979-1990, 1990-2000, 2000-2010, 2010-2017) using log-linear regression models. For all intervals, national CHD death rates declined for all groups. Prior to 2010, although most counties across age, race, and gender experienced declines, pockets of increasing CHD death rates were observed in the Mississippi Delta, Oklahoma, East Texas, and New Mexico across age groups and gender, and were more prominent among non-white populations than whites. Since 2010, across age, race, and gender, county-level declines in CHD death rates have slowed, with a marked increase in the percent of counties with increasing CHD death rates (e.g. 4.4% and 19.9% for ages 35 and older during 1979-1990 and 2010-2017, respectively). Recent increases were especially prevalent and geographically widespread among ages 35-64 years, with 40.5% of counties (95% CI: 38.4, 43.1) experiencing increases. Spatiotemporal differences in these long term, county-level results can inform responses by the public health community, medical providers, researchers, and communities to address troubling recent trends.

    • Data Methods and Study
      1. Risk scores for predicting early antiretroviral therapy mortality in sub-Saharan Africa to inform who needs intensification of care: a derivation and external validation cohort studyexternal icon
        Auld AF, Fielding K, Agizew T, Maida A, Mathoma A, Boyd R, Date A, Pals SL, Bicego G, Liu Y, Shiraishi RW, Ehrenkranz P, Serumola C, Mathebula U, Alexander H, Charalambous S, Emerson C, Rankgoane-Pono G, Pono P, Finlay A, Shepherd JC, Holmes C, Ellerbrock TV, Grant AD.
        BMC Med. 2020 Nov 9;18(1):311.
        BACKGROUND: Clinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4 < 200/μL or WHO stage III/IV. METHODS: We used Botswana XPRES trial data for adult ART enrollees to develop CD4-independent and CD4-dependent multivariable prognostic models for 6-month mortality. Scores were derived by rescaling coefficients. Scores were developed using the first 50% of XPRES ART enrollees, and their accuracy validated internally and externally using South African TB Fast Track (TBFT) trial data. Predictive accuracy was compared between scores and WHO EC. RESULTS: Among 5553 XPRES enrollees, 2838 were included in the derivation dataset; 68% were female and 83 (3%) died by 6 months. Among 1077 TBFT ART enrollees, 55% were female and 6% died by 6 months. Factors predictive of 6-month mortality in the derivation dataset at p < 0.01 and selected for the CD4-independent score included male gender (2 points), ≥ 1 WHO tuberculosis symptom (2 points), WHO stage III/IV (2 points), severe anemia (hemoglobin < 8 g/dL) (3 points), and temperature > 37.5 °C (2 points). The same variables plus CD4 < 200/μL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4-6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. CONCLUSIONS: Sensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA.

    • Health Equity Science
      1. Association of smoke-free laws with preterm or low birth weight deliveries-A multistate analysisexternal icon
        Ji X, Cox S, Grosse SD, Barfield WD, Armour BS, Courtney-Long EA, Li R.
        Health Serv Res. 2021 Feb;56(1):61-72.
        OBJECTIVE: To assess the association between the change in statewide smoke-free laws and the rate of preterm or low birth weight delivery hospitalizations. DATA SOURCE: 2002-2013 Healthcare Cost and Utilization Project State Inpatient Databases. STUDY DESIGN: Quasi-experimental difference-in-differences design. We used multivariate logistic models to estimate the association between the change in state smoke-free laws and preterm or low birth weight delivery hospitalizations. The analyses were also stratified by maternal race/ethnicity to examine the differential effects by racial/ethnic groups. DATA COLLECTION/EXTRACTION METHODS: Delivery hospitalizations among women aged 15-49 years were extracted using the International Classification of Diseases, Ninth Revision, and Diagnosis-Related Group codes. PRINCIPAL FINDINGS: Non-Hispanic black mothers had a higher rate of preterm or low birth weight delivery hospitalization than other racial/ethnic groups. Overall, there was no association between the change in smoke-free laws and preterm or low birth weight delivery rate. Among non-Hispanic black mothers, the change in statewide smoke-free laws was associated with a 0.9-1.9 percentage point (P < .05) reduction in preterm or low birth weight delivery rate beginning in the third year after the laws took effect. There was no association among non-Hispanic white mothers. A decline in the black-white disparity of 0.6-1.6 percentage points (P < .05) in preterm or low birth weight delivery rates was associated with the change in state smoke-free laws. CONCLUSION: The change in state smoke-free laws was associated with a reduction in racial/ethnic disparities in preterm or low birth weight delivery hospitalizations in selected US states.

    • Laboratory Science
      1. Development of a new oral poliovirus vaccine for the eradication end game using codon deoptimizationexternal icon
        Konopka-Anstadt JL, Campagnoli R, Vincent A, Shaw J, Wei L, Wynn NT, Smithee SE, Bujaki E, Te Yeh M, Laassri M, Zagorodnyaya T, Weiner AJ, Chumakov K, Andino R, Macadam A, Kew O, Burns CC.
        NPJ Vaccines. 2020 ;5(1):26.
        Enormous progress has been made in global efforts to eradicate poliovirus, using live-attenuated Sabin oral poliovirus vaccine (OPV). However, as the incidence of disease due to wild poliovirus has declined, vaccine-derived poliovirus (VDPV) has emerged in areas of low-vaccine coverage. Coordinated global cessation of routine, type 2 Sabin OPV (OPV2) use has not resulted in fewer VDPV outbreaks, and continued OPV use in outbreak-response campaigns has seeded new emergences in low-coverage areas. The limitations of existing vaccines and current eradication challenges warranted development of more genetically stable OPV strains, most urgently for OPV2. Here, we report using codon deoptimization to further attenuate Sabin OPV2 by changing preferred codons across the capsid to non-preferred, synonymous codons. Additional modifications to the 5' untranslated region stabilized known virulence determinants. Testing of this codon-deoptimized new OPV2 candidate (nOPV2-CD) in cell and animal models demonstrated that nOPV2-CD is highly attenuated, grows sufficiently for vaccine manufacture, is antigenically indistinguishable from Sabin OPV2, induces neutralizing antibodies as effectively as Sabin OPV2, and unlike Sabin OPV2 is genetically stable and maintains an attenuation phenotype. In-human clinical trials of nOPV2-CD are ongoing, with potential for nOPV strains to serve as critical vaccine tools for achieving and maintaining polio eradication.

    • Prevention and Control
      1. Effect of tuberculosis screening and retention interventions on early antiretroviral therapy mortality in Botswana: a stepped-wedge cluster randomized trialexternal icon
        Auld AF, Agizew T, Mathoma A, Boyd R, Date A, Pals SL, Serumola C, Mathebula U, Alexander H, Ellerbrock TV, Rankgoane-Pono G, Pono P, Shepherd JC, Fielding K, Grant AD, Finlay A.
        BMC Med. 2020 Feb 11;18(1):19.
        BACKGROUND: Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality. METHODS: At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation. RESULTS: We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61-0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees. CONCLUSIONS: Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed. TRIAL REGISTRATION: Retrospectively registered: ClinicalTrials.gov (NCT02538952).


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Communicable Diseases

      2. Incidence Rates, Household Infection Risk, and Clinical Characteristics of SARS-CoV-2 Infection Among Children and Adults in Utah and New York City, New Yorkexternal icon
        Dawood FS, Porucznik CA, Veguilla V, Stanford JB, Duque J, Rolfes MA, Dixon A, Thind P, Hacker E, Castro MJ, Jeddy Z, Daugherty M, Altunkaynak K, Hunt DR, Kattel U, Meece J, Stockwell MS.
        JAMA Pediatr. 2021 Oct 8.
        IMPORTANCE: Data about the risk of SARS-CoV-2 infection among children compared with adults are needed to inform COVID-19 risk communication and prevention strategies, including COVID-19 vaccination policies for children. OBJECTIVE: To compare incidence rates and clinical characteristics of SARS-CoV-2 infection among adults and children and estimated household infection risks within a prospective household cohort. DESIGN, SETTING, AND PARTICIPANTS: Households with at least 1 child aged 0 to 17 years in selected counties in Utah and New York City, New York, were eligible for enrollment. From September 2020 through April 2021, participants self-collected midturbinate nasal swabs for reverse transcription-polymerase chain reaction testing for SARS-CoV-2 and responded to symptom questionnaires each week. Participants also self-collected additional respiratory specimens with onset of COVID-19-like illness. For children unable to self-collect respiratory specimens, an adult caregiver collected the specimens. MAIN OUTCOMES AND MEASURES: The primary outcome was incident cases of any SARS-CoV-2 infection, including asymptomatic and symptomatic infections. Additional measures were the asymptomatic fraction of infection calculated by dividing incidence rates of asymptomatic infection by rates of any infection, clinical characteristics of infection, and household infection risks. Primary outcomes were compared by participant age group. RESULTS: A total of 1236 participants in 310 households participated in surveillance, including 176 participants (14%) who were aged 0 to 4 years, 313 (25%) aged 5 to 11 years, 163 (13%) aged 12 to 17 years, and 584 (47%) 18 years or older. Overall incidence rates of SARS-CoV-2 infection were 3.8 (95% CI, 2.4-5.9) and 7.7 (95% CI, 4.1-14.5) per 1000 person-weeks among the Utah and New York City cohorts, respectively. Site-adjusted incidence rates per 1000 person-weeks were similar by age group: 6.3 (95% CI, 3.6-11.0) for children 0 to 4 years, 4.4 (95% CI, 2.5-7.5) for children 5 to 11 years, 6.0 (95% CI, 3.0-11.7) for children 12 to 17 years, and 5.1 (95% CI, 3.3-7.8) for adults (≥18 years). The asymptomatic fractions of infection by age group were 52%, 50%, 45%, and 12% among individuals aged 0 to 4 years, 5 to 11 years, 12 to 17 years, and 18 years or older, respectively. Among 40 households with 1 or more SARS-CoV-2 infections, the mean risk of SARS-CoV-2 infection among all enrolled household members was 52% (range, 11%-100%), with higher risks in New York City compared with Utah (80% [95% CI, 64%-91%] vs 44% [95% CI, 36%-53%]; P < .001). CONCLUSIONS AND RELEVANCE: In this study, children had similar incidence rates of SARS-CoV-2 infection compared with adults, but a larger proportion of infections among children were asymptomatic.

      3. COVID-19-Associated Orphanhood and Caregiver Death in the United Statesexternal icon
        Hillis SD, Blenkinsop A, Villaveces A, Annor FB, Liburd L, Massetti GM, Demissie Z, Mercy JA, Nelson CA, Cluver L, Flaxman S, Sherr L, Donnelly CA, Ratmann O, Unwin HJ.
        Pediatrics. 2021 Oct 7.

      4. Cohort profile: Indian Network of Population-Based Surveillance Platforms for Influenza and Other Respiratory Viruses among the Elderly (INSPIRE)external icon
        Krishnan A, Dar L, Amarchand R, Prabhakaran AO, Kumar R, Rajkumar P, Kanungo S, Bhardwaj SD, Choudekar A, Potdar V, Chakrabarti AK, Kumar CG, Parameswaran GG, Dhakad S, Manna B, Choudhary A, Lafond KE, Azziz-Baumgartner E, Saha S.
        BMJ Open. 2021 Oct 7;11(10):e052473.
        PURPOSE: We describe here a multicentric community-dwelling cohort of older adults (>60 years of age) established to estimate incidence, study risk factors, healthcare utilisation and economic burden associated with influenza and respiratory syncytial virus (RSV) in India. PARTICIPANTS: The four sites of this cohort are in northern (Ballabgarh), southern (Chennai), eastern (Kolkata) and western (Pune) parts of India. We enrolled 5336 participants across 4220 households and began surveillance in July 2018 for viral respiratory infections with additional participants enrolled annually. Trained field workers collected data about individual-level and household-level risk factors at enrolment and quarterly assessed frailty and grip strength. Trained nurses surveilled weekly to identify acute respiratory infections (ARI) and clinically assessed individuals to diagnose acute lower respiratory infection (ALRI) as per protocol. Nasal and oropharyngeal swabs are collected from all ALRI cases and one-fifth of the other ARI cases for laboratory testing. Cost data of the episode are collected using the WHO approach for estimating the economic burden of seasonal influenza. Handheld tablets with Open Data Kit platform were used for data collection. FINDINGS TO DATE: The attrition of 352 participants due to migration and deaths was offset by enrolling 680 new entrants in the second year. All four sites reported negligible influenza vaccination uptake (0.1%-0.4%), low health insurance coverage (0.4%-22%) and high tobacco use (19%-52%). Ballabgarh had the highest proportion (54.4%) of households in the richest wealth quintile, but reported high solid fuel use (92%). Frailty levels were highest in Kolkata (11.3%) and lowest in Pune (6.8%). The Chennai cohort had highest self-reported morbidity (90.1%). FUTURE PLANS: The findings of this cohort will be used to inform prioritisation of strategies for influenza and RSV control for older adults in India. We also plan to conduct epidemiological studies of SARS-CoV-2 using this platform.

      5. Household Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 in the United Statesexternal icon
        Lewis NM, Chu VT, Ye D, Conners EE, Gharpure R, Laws RL, Reses HE, Freeman BD, Fajans M, Rabold EM, Dawson P, Buono S, Yin S, Owusu D, Wadhwa A, Pomeroy M, Yousaf A, Pevzner E, Njuguna H, Battey KA, Tran CH, Fields VL, Salvatore P, O'Hegarty M, Vuong J, Chancey R, Gregory C, Banks M, Rispens JR, Dietrich E, Marcenac P, Matanock AM, Duca L, Binder A, Fox G, Lester S, Mills L, Gerber SI, Watson J, Schumacher A, Pawloski L, Thornburg NJ, Hall AJ, Kiphibane T, Willardson S, Christensen K, Page L, Bhattacharyya S, Dasu T, Christiansen A, Pray IW, Westergaard RP, Dunn AC, Tate JE, Nabity SA, Kirking HL.
        Clin Infect Dis. 2021 Oct 5;73(7):1805-1813.
        BACKGROUND: The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. METHODS: We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020-25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. RESULTS: Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%-36%) overall, 42% among children (aged <18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4-106.9) and 7.1 (95% CI: 1.2-42.5), respectively. CONCLUSIONS: We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.

      6. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS): Rationale, objectives, and designexternal icon
        Temte JL, Barlow S, Goss M, Temte E, Bell C, He C, Hamer C, Schemmel A, Maerz B, Comp L, Arnold M, Breunig K, Clifford S, Reisdorf E, Shult P, Wedig M, Haupt T, Conway J, Gangnon R, Fowlkes A, Uzicanin A.
        Influenza Other Respir Viruses. 2021 Oct 8.
        BACKGROUND: Influenza viruses pose significant disease burdens through seasonal outbreaks and unpredictable pandemics. Existing surveillance programs rely heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness-specific student absenteeism (a-ILI) in kindergarten through Grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. METHODS: Starting in September 2014, ORCHARDS combines automated reporting of daily absenteeism within six schools and home visits to school children with acute respiratory infection (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing and highly effective influenza surveillance program, based on MAI at five family medicine clinics in the same geographical area. RESULTS: Over the first 5 years, a-ILI occurred on 6634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of 1728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. CONCLUSION: ORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.

    • Environmental Health
      1. Concurrent urinary organophosphate metabolites and acetylcholinesterase activity in Ecuadorian adolescentsexternal icon
        Skomal AE, Zhang J, Yang K, Yen J, Tu X, Suarez-Torres J, Lopez-Paredes D, Calafat AM, Ospina M, Martinez D, Suarez-Lopez JR.
        Environ Res. 2021 Oct 7:112163.
        BACKGROUND: Organophosphates are insecticides that inhibit the enzymatic activity of acetylcholinesterase (AChE). Because of this, AChE is considered a physiological marker of organophosphate exposure in agricultural settings. However, limited research exists on the associations between urinary organophosphate metabolites and AChE activity in children. METHODS: This study included 526 participants from 2 exams (April and July-October 2016) of ages 12-17 years living in agricultural communities in Ecuador. AChE activity was measured at both examinations, and organophosphate metabolites, including para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), and malathion dicarboxylic acid (MDA) were measured in urine collected in July-October. We used generalized estimating equation generalized linear model (GEEGLM), adjusting for hemoglobin, creatinine, and other demographic and anthropometric covariates, to estimate associations of urinary metabolite concentrations with AChE activity (July-October) and AChE % change between April and July-October. RESULTS: The mean (SD) of AChE and AChE % change (April vs July-October) were 3.67 U/mL (0.54) and -2.5 % (15.4 %), respectively. AChE activity was inversely associated with PNP concentration, whereas AChE % change was inversely associated with PNP and MDA. There was evidence of a threshold: difference was only significant above the 80th percentile of PNP concentration (AChE difference per SD increase of metabolite = -0.12 U/mL [95 %CI: 0.20, -0.04]). Likewise, associations with AChE % change were significant only above the 80th percentile of TCPy (AChE % change per SD increase of metabolite = -1.38 % [95 %CI: 2.43 %, -0.32 %]) and PNP -2.47 % [95 %CI: 4.45 %, -0.50 %]). PNP concentration at ≥80th percentile was associated with elevated ORs for low AChE activity of 2.9 (95 % CI: 1.5, 5.7) and for AChE inhibition of ≤ -10 % of 3.7 (95 % CI: 1.4, 9.8). CONCLUSIONS: Urinary organophosphate metabolites, including PNP, TCPy and MDA, particularly at concentrations above the 80th percentile, were associated with lower AChE activity among adolescents. These findings bring attention to the value of using multiple constructs of pesticide exposure in epidemiologic studies.

    • Genetics and Genomics
      1. Complete Genome Sequence of Neisseria gonorrhoeae Multilocus Sequence Type ST7363 Isolated from Thailandexternal icon
        Cherdtrakulkiat T, Wongsurawat T, Jenjaroenpun P, Sutheeworapong S, Leelawiwat W, Woodring JV, Dunne EF, Papp JR, Srifuengfung S, Tribuddharat C.
        Microbiol Resour Announc. 2021 Oct 14;10(41):e0057321.
        A Neisseria gonorrhoeae multilocus sequence type (MLST) ST7363 strain was isolated from a patient at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, in 2010 and completely sequenced. This strain is susceptible to ceftriaxone and cefixime. A complete circular chromosome and circular plasmids were assembled from combined Oxford Nanopore Technologies (ONT) and Illumina sequencing.

    • Health Communication and Education
      1. BACKGROUND: Recent evidence suggests that many adults with intellectual and developmental disabilities (IDD) do not adequately manage hypertension (HTN) medication. Known risk factors for insufficient prescription filling include age, residential placement, and lack of caregiver support. This is a first report of a randomized intervention trial designed to analyze the relationship of a brief educational intervention with increased knowledge about HTN and improvement in prescription filling for anti-hypertensive medication. OBJECTIVE/HYPOTHESIS: The objective was to test whether an educational flyer and regular messages about HTN and the importance of refilling medication would improve scores on knowledge surveys. Participants were Medicaid members with HTN and IDD (Member) or caregivers (Helpers) who chose to participate on behalf of a Member. METHODS: Recruitment letters explained that either the Member or their Helper could participate (not both). Participants were randomly assigned to the Case or Comparison group, and both were comprised of Members and Helpers. Only Case participants received a flyer and monthly HTN education messages for one year, but all participants completed knowledge surveys at baseline, six, and 12 months. Linear regression and log-binomial models were used to compare responses between groups. RESULTS: Case Helpers had statistically significant improvements on HTN knowledge from baseline through the first year, compared to Comparison Members and Comparison Helpers. Regardless of group assignment, Helpers scored better on surveys than did Members. CONCLUSIONS: This study suggests that it is beneficial to explicitly include Helpers in health care instruction and in management of chronic disease for adults with IDD.

    • Health Disparities
      1. Assessing the practicalities of joint snakebite and dog rabies control programs: Commonalities and potential pitfallsexternal icon
        Scott TP, Sharma SK, Wallace RM, Nel LH, Adhikari SK, Abela-Ridder B, Thumbi SM.
        Toxicon X. 2021 Nov;12:100084.
        Both rabies and snakebite primarily affect underserved and impoverished communities globally, with an estimated 200,000 people dying from these diseases annually, and the greatest burden being in Africa and Asia. Both diseases have been neglected and have thus been denied appropriate prioritization, support, and interventions, and face many of the challenges common to all neglected tropical diseases (NTDs). In line with the call for integrated approaches between NTDs in the recent NTD Roadmap, we sought to build upon previous conceptualizations for an integrated approach by identifying the commonalities between snakebite and rabies to explore the feasibility of an integrated approach. While multiple areas for potential integration are identified, we highlight the potential pitfalls to integrating rabies and snakebite programs, considering the nuances that make each disease and its intervention program unique. We conclude that health system strengthening, and capacity building should be the focus of any integrated approach among NTDs, and that by strengthening overall health systems, both rabies and snakebite can advocate for further support from governments and stakeholders.

      2. Disparities in Treatment with Direct-Acting Hepatitis C Virus Antivirals Persist Among Adults Coinfected with HIV and Hepatitis C Virus in US Clinics, 2010-2018external icon
        Simoncini GM, Hou Q, Carlson K, Buchacz K, Tedaldi E, Palella F , Durham M, Li J.
        AIDS Patient Care STDS. 2021 Oct;35(10):392-400.
        Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (p < 0.05). Of 127 (97%) participants with at least 1 follow-up HCV VL, 110 (87%) achieved SVR at 12 weeks. Of the total 131 participants, 123 (94%) eventually achieved SVR. Less than half of HIV/HCV coinfected patients in HOPS have been prescribed DAAs. Interventions are needed to address deficits in DAA prescription, including among patients with public or no health insurance, younger age, and lower CD4 cell count.

      3. INTRODUCTION: Adolescent sexual minority males (ASMM) are disproportionately affected by HIV relative to other youth within the United States. Social determinants of health have been explored among this population; however, economic determinants such as material hardship, remain understudied. We examined the relationship between material hardship and sexual behavior among ASMM ages 13-18 residing in 3 U.S. cities using 2015 data from CDC's National HIV Behavioral Surveillance among Young Men who have Sex with Men. METHODS: Young men ages 13-18 residing in 3 U.S. cities were recruited via venue-based, respondent-driven, or Facebook sampling. We estimated adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) for condomless anal intercourse (CAI) with a male sex partner in the past 12 months and with having 4 or more male sex partners in the past 12 months. RESULTS: Of 547 ASMM, 27% reported experiencing material hardship in the past 12 months. After adjusting for demographics, household characteristics, and city, ASMM who experienced material hardship were more likely to report CAI with a male partner in the past 12 months (aPR: 1.55, 95% CI: 1.25 - 1.93), and to have had 4 or more male sex partners in the past 12 months (aPR: 1.44, 95% CI: 1.08 - 1.91). DISCUSSION: More than a quarter of ASMM experienced material hardship which was associated with increased sexual risk behavior among ASMM. Incorporating services that address all unmet needs is important to consider for HIV prevention efforts for ASMM.

    • Immunity and Immunization
      1. Vaccination Coverage by Age 24 Months Among Children Born in 2017 and 2018 - National Immunization Survey-Child, United States, 2018-2020external icon
        Hill HA, Yankey D, Elam-Evans LD, Singleton JA, Sterrett N.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 15;70(41):1435-1440.
        Immunization is a safe and cost-effective means of preventing illness in young children and interrupting disease transmission within the community.* The Advisory Committee on Immunization Practices (ACIP) recommends vaccination of children against 14 diseases during the first 24 months of life (1). CDC uses National Immunization Survey-Child (NIS-Child) data to monitor routine coverage with ACIP-recommended vaccines in the United States at the national, regional, state, territorial, and selected local levels.(†) CDC assessed vaccination coverage by age 24 months among children born in 2017 and 2018, with comparisons to children born in 2015 and 2016. Nationally, coverage was highest for ≥3 doses of poliovirus vaccine (92.7%); ≥3 doses of hepatitis B vaccine (HepB) (91.9%); ≥1 dose of measles, mumps, and rubella vaccine (MMR) (91.6%); and ≥1 dose of varicella vaccine (VAR) (90.9%). Coverage was lowest for ≥2 doses of influenza vaccine (60.6%). Coverage among children born in 2017-2018 was 2.1-4.5 percentage points higher than it was among those born in 2015-2016 for rotavirus vaccine, ≥1 dose of hepatitis A vaccine (HepA), the HepB birth dose, and ≥2 doses of influenza vaccine. Only 1.0% of children had received no vaccinations by age 24 months. Disparities in coverage were seen for race/ethnicity, poverty status, and health insurance status. Coverage with most vaccines was lower among children who were not privately insured. The largest disparities between insurance categories were among uninsured children, especially for ≥2 doses of influenza vaccine, the combined 7-vaccine series, (§) and rotavirus vaccination. Reported estimates reflect vaccination opportunities that mostly occurred before disruptions resulting from the COVID-19 pandemic. Extra efforts are needed to ensure that children who missed vaccinations, including those attributable to the COVID-19 pandemic, receive them as soon as possible to maintain protection against vaccine-preventable illnesses.

      2. BACKGROUND: As vaccine supply and access remain limited in many parts of the world, understanding the duration of protection from reinfection after natural infection is important. METHODS: Distinct individuals testing positive and negative for SARS-CoV-2 between March 6, 2020, and August 31, 2020, in Kentucky, USA, were identified using the Kentucky National Electronic Disease Surveillance System. Individuals were followed for occurrence of a positive test for SARS-CoV-2 from 91 days after their initial test result through December 31, 2020. Protection from reinfection provided by a prior infection was calculated and additional analyses evaluated impact of age, sex, symptom status, long-term care facility connection, testing occurrence and frequency, and time from initial infection. RESULTS: Protective effect from prior infection was 80.3% (95% CI, 78.2% - 82.2%) for those aged 20-59 years and 67.4% (95% CI, 62.8% - 71.4%) for those 60 years and older. At 30-day time periods through 270 days (with limited exceptions), protection was estimated to be greater than 75% for those aged 20-59 years and greater than 65% for those 60 years and older. Factors associated with repeat positive testing included a connection to a long-term care facility, duration of potential exposure, and absence of symptoms during initial infection. CONCLUSIONS: Natural infection provides substantial and persistent immunologic protection for a period of several months for most individuals, although subpopulations may be at greater risk for repeat positive testing and potential poor outcomes associated with reinfection. These subgroups include individuals 60 years and older, residents and staff of long-term care facilities, and those who have mild or asymptomatic illness with initial infection. Continued emphasis on vaccination and infection prevention and control strategies remains critically important in reducing the risk for reinfection and associated severe outcomes for these groups.

    • Informatics
      1. Determining diagnosis date of diabetes using structured electronic health record (EHR) data: the SEARCH for Diabetes in Youth Studyexternal icon
        Lenoir KM, Wagenknecht LE, Divers J, Casanova R, Dabelea D, Saydah S, Pihoker C, Liese AD, Standiford D, Hamman R, Wells BJ.
        BMC Med Res Methodol. 2021 Oct 10;21(1):210.
        BACKGROUND: Disease surveillance of diabetes among youth has relied mainly upon manual chart review. However, increasingly available structured electronic health record (EHR) data have been shown to yield accurate determinations of diabetes status and type. Validated algorithms to determine date of diabetes diagnosis are lacking. The objective of this work is to validate two EHR-based algorithms to determine date of diagnosis of diabetes. METHODS: A rule-based ICD-10 algorithm identified youth with diabetes from structured EHR data over the period of 2009 through 2017 within three children's hospitals that participate in the SEARCH for Diabetes in Youth Study: Cincinnati Children's Hospital, Cincinnati, OH, Seattle Children's Hospital, Seattle, WA, and Children's Hospital Colorado, Denver, CO. Previous research and a multidisciplinary team informed the creation of two algorithms based upon structured EHR data to determine date of diagnosis among diabetes cases. An ICD-code algorithm was defined by the year of occurrence of a second ICD-9 or ICD-10 diabetes code. A multiple-criteria algorithm consisted of the year of first occurrence of any of the following: diabetes-related ICD code, elevated glucose, elevated HbA1c, or diabetes medication. We assessed algorithm performance by percent agreement with a gold standard date of diagnosis determined by chart review. RESULTS: Among 3777 cases, both algorithms demonstrated high agreement with true diagnosis year and differed in classification (p = 0.006): 86.5% agreement for the ICD code algorithm and 85.9% agreement for the multiple-criteria algorithm. Agreement was high for both type 1 and type 2 cases for the ICD code algorithm. Performance improved over time. CONCLUSIONS: Year of occurrence of the second ICD diabetes-related code in the EHR yields an accurate diagnosis date within these pediatric hospital systems. This may lead to increased efficiency and sustainability of surveillance methods for incidence of diabetes among youth.

      2. Building Capacity of Community Health Centers to Overcome Data Challenges with the Development of an Agile COVID-19 Public Health Registry: A Multi-State Quality Improvement Effortexternal icon
        Romero L, Carneiro PB, Riley C, Clark H, Uy R, Park M, Mawokomatanda T, Bombard JM, Hinckley A, Skapik J.
        J Am Med Inform Assoc. 2021 Oct 14.
        OBJECTIVE: During the COVID-19 pandemic, federally qualified health centers rapidly mobilized to provide SARS-CoV-2 testing, COVID-19 care, and vaccination to populations at increased risk for COVID-19 morbidity and mortality. We describe the development of a reusable public health data analytics system for reuse of clinical data to evaluate the health burden, disparities, and impact of COVID-19 on populations served by health centers. MATERIALS AND METHODS: The Multi-State Data Strategy engaged project partners to assess public health readiness and COVID-19 data challenges. An infrastructure for data capture and sharing procedures between health centers and public health agencies was developed to support existing capabilities and data capacities to respond to the pandemic. RESULTS: Between August 2020 - March 2021, project partners evaluated their data capture and sharing capabilities and reported challenges and preliminary data. Major interoperability challenges included poorly aligned federal, state, and local reporting requirements, lack of unique patient identifiers, lack of access to pharmacy, claims and laboratory data, missing data, and proprietary data standards and extraction methods. DISCUSSION: Efforts to access and align project partners' existing health systems data infrastructure in the context of the pandemic highlighted complex interoperability challenges. These challenges remain significant barriers to real-time data analytics and efforts to improve health outcomes and mitigate inequities through data-driven responses. CONCLUSION: The reusable public health data analytics system created in the Multi-State Data Strategy can be adapted and scaled for other health center networks to facilitate data aggregation and dashboards for public health, organizational planning and quality improvement and can inform local, state, and national COVID-19 response efforts.

    • Injury and Violence
      1. Traumatic brain injuries (TBIs) have contributed to approximately one million deaths in the United States over the last 2 decades (1). CDC analyzed National Vital Statistics System (NVSS) mortality data for a 3-year period (2016-2018) to examine numbers and rates of TBI-related deaths, the percentage difference between each state's rate and the overall U.S. TBI-related death rate, leading causes of TBI, and the association between TBI and a state's level of rurality. During 2016-2018, a total of 181,227 TBI-related deaths (17.3 per 100,000 population per year) occurred in the United States. The percentage difference between state TBI-related death rates and the overall U.S. rate during this period ranged from 46.2% below to 101.2% above the overall rate. By state, the lowest rate was in New Jersey (9.3 per 100,000 population per year); the states with the highest rates were Alaska (34.8), Wyoming (32.6), and Montana (29.5). States in the South and those with a higher proportion of residents living in rural areas had higher rates, whereas states in the Northeast and those with a lower proportion of residents living in rural areas had lower TBI-related death rates. In 43 states, suicide was the leading cause of TBI-related deaths; in other states, unintentional falls or unintentional motor vehicle crashes were responsible for the highest numbers and rates of TBI-related deaths. Consistent with previous studies (2), differences in TBI incidence and outcomes were observed across U.S. states; therefore, states can use these findings to develop and implement evidence-based prevention strategies, based on their leading causes of TBI-related deaths. Expanding evidence-based prevention strategies that address TBI-related deaths is warranted, especially among states with high rates due to suicide, unintentional falls, and motor vehicle crashes.

      2. Adverse childhood experiences and police mental healthexternal icon
        Violanti JM, Mnatsakanova A, Gu JK, Service S, Andrew ME.
        Policing. 2021 .
        Purpose: The purpose of this study is to examine cross-sectional associations between adverse childhood experiences (ACEs) and mental health among police officers. Design/methodology/approach: The sample was from the Buffalo Cardio-Metabolic Occupational Police Stress study data (132 male and 51 female officers). Standardized surveys were administered to participants. Regression coefficients were obtained from models adjusted for age, sex, race and alcohol intake. All statistical tests were performed using a statistical significance level at p < 0.05. Findings: Regression analyses showed significant positive associations between ACEs and mental health (Posttraumatic Stress Disorder [PTSD]: β = 1.70, p < 0.001 and depressive symptoms: β = 1.29, p < 0.001). Resiliency significantly modified the association between ACEs and PTSD. A positive and significant association was observed among officers with lower resiliency (β = 2.65, p < 0.001). The association between ACEs and PTSD was stronger among male officers compared to females (β = 2.66, p < 0.001 vs. β = 0.59, p ≤ 0.248, respectively). Research limitations/implications: Child abuse and development of PTSD or depression could not be traced through time as this was a cross-sectional study. Recall bias may affect results. Practical implications: PTSD and depression associated with ACEs can affect the interpretation of threat and can exacerbate emotional regulation in officers. An inquiry should be expanded regarding work assignments of victimized officers, such as child exploitation and pornography investigation. Originality/value: There are few studies on ACEs and the mental health of police officers. The present study is among the first to associate multiple police mental health issues with ACEs. © 2021, Emerald Publishing Limited.

    • Laboratory Sciences
      1. Gramineous plants protect their seeds from a variety of biotic stresses by producing toxic and deterrent secondary metabolites such as benzoxazinoids. It is unclear how the composition and abundance of these natural toxins has changed over the course of crop-plant domestication. To address this uncertainty, we characterized differences in metabolic levels of benzoxazinoids and their derivatives, between four lines of tetraploid wheat: wild emmer wheat (WEW), the direct progenitor of modern wheat; non-fragile domesticated emmer wheat (DEW), which was first domesticated about 11,000 years ago; the subsequently developed non-fragile and free-threshing durum landraces (LD); and modern durum (MD) varieties. Three-dimensional principal component analysis of mass spectrometry data of wheat metabolites showed with high resolution clear differences between metabolic profiles of WEW, DEW, and durum (LD + MD) and similarity in the metabolic profiles of the two durum lines (LD and MD) that is coherent with the phylogenetic relationship between the corresponding wheat lines. Moreover, our results indicated that some secondary metabolites involved in plant defense mechanisms became significantly more abundant during wheat domestication, while other defensive metabolites decreased or were lost. These metabolic changes reflect the beneficial or detrimental roles the corresponding metabolites might play during the domestication of three taxonomic subspecies of tetraploid wheat (Triticum turgidum).

      2. Eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) can cause fatal encephalitis in humans and equids. Some MAbs to the E1 glycoprotein are known to be cross-reactive, weakly neutralizing in vitro but can protect from disease in animal models. We investigated the mechanism of neutralization of VEEV infection by the broadly cross-reactive E1-specific MAb 1A4B-6. 1A4B-6 protected 3-week-old Swiss Webster mice prophylactically from lethal VEEV challenge. Likewise, 1A4B-6 inhibited virus growth in vitro at a pre-attachment step after virions were incubated at 37 °C and inhibited virus-mediated cell fusion. Amino acid residue N100 in the fusion loop of E1 protein was identified as critical for binding. The potential to elicit broadly cross-reactive MAbs with limited virus neutralizing activity in vitro but that can inhibit virus entry and protect animals from infection merits further exploration for vaccine and therapeutic developmental research.

      3. Classification of measles breakthrough cases in an elimination setting using a comprehensive algorithm of laboratory results: why sensitive and specific IgM assays are importantexternal icon
        Mercader S, Dominguez A, Torner N, Costa J, Sowers SB, Martinez A, Bellini WJ, Hickman CJ.
        Int J Infect Dis. 2021 Sep 8;112:21-24.
        OBJECTIVE: In 2006, a measles outbreak occurred in Catalonia (Spain), six years after endemic measles was declared eliminated. This study aimed to classify 19 confirmed measles breakthrough cases (BC) using a high-performance avidity assay developed in 2010. METHODS: Serum specimens were tested by indirect IgG, indirect IgM, capture IgM enzyme immunoassay, an endpoint-titer IgG avidity assay, and a plaque reduction neutralization assay. Serology and RNA detection results were combined in an algorithm for measles confirmation and classification of breakthrough cases and analyzed with clinical and epidemiological data. RESULTS: Of 19 samples, thirteen (68%) were conclusive with the classification of BCs, and six (32%) had false-positive IgM results on an indirect-format assay; they were classified as rash and fever illness of undetermined etiology. BCs were primary vaccine failures (seven or 54%), secondary vaccine failures (four or 31%), and two (15%) could not be classified. CONCLUSIONS: In measles elimination settings, high-performing assays and a comprehensive algorithm of laboratory results (IgG, IgM, and RNA detection), including IgG avidity and PRN results when necessary, can assist in accurate laboratory confirmation and classification of suspected measles cases for surveillance. Highly specific IgM assays are required to minimize the number of false-positive results.

      4. Optimizing Available Tools for Achieving Result Standardization: Value Added by Joint Committee on Traceability in Laboratory Medicine (JCTLM)external icon
        Panteghini M, Braga F, Camara JE, Delatour V, Van Uytfanghe K, Vesper HW, Zhang T.
        Clin Chem. 2021 Oct 11.
        BACKGROUND: The JCTLM created a Task Force on Reference Measurement System Implementation (TF-RMSI) to provide guidance on metrological traceability implementation for the in vitro diagnostics (IVD) community. CONTENT: TF-RMSI investigated the reference measurement systems (RMS) for 13 common measurands by applying the following procedural steps: (a) extracting data from the JCTLM database of available certified reference materials (CRMs) and reference measurement procedures (RMPs); (b) describing the RMS to which each recruited CRM or RMP belongs; (c) identifying the intended use of the CRMs, and, if used as a common calibrator for IVD measuring systems and/or trueness assessment of field methods was included, checking the CRM's certificate for information about commutability with clinical samples; and (d) checking if the CRM or RMP measurement uncertainty (MU) has the potential to be small enough to avoid significantly affecting the analytical performance specifications (APS) for MU of clinical sample results when the MU from the IVD calibrator and from the end-user measuring system were combined. SUMMARY: We produced a synopsis of JCTLM-listed higher-order CRMs and RMPs for the selected measurands, including their main characteristics for implementing traceability and fulfilling (or not) the APS for suitable MU. Results showed that traceability to higher-order references can be established by IVD manufacturers within the defined APS for most of the 13 selected measurands. However, some measurands do not yet have suitable CRMs for use as common calibrators. For these measurands, splitting clinical samples with a laboratory performing the RMP may provide a practical alternative for establishing a calibration hierarchy.

      5. Clinical Influenza Testing Practices in Hospitalized Children at United States Medical Centers, 2015-2018external icon
        Tenforde MW, Campbell AP, Michaels MG, Harrison CJ, Klein EJ, Englund JA, Selvarangan R, Halasa NB, Stewart LS, Weinberg GA, Williams JV, Szilagyi PG, Staat MA, Boom JA, Sahni LC, Singer MN, Azimi PH, Zimmerman RK, McNeal MM, Talbot HK, Monto AS, Martin ET, Gaglani M, Silveira FP, Middleton DB, Ferdinands JM, Rolfes MA.
        J Pediatric Infect Dis Soc. 2021 Oct 13.
        At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

      6. A Low-Cost, High-Throughput Digital Image Analysis of Stain Patterns on Smoked Cigarette Filter Butts to Estimate Mainstream Smoke Exposureexternal icon
        Watson CH, Yan J, Stanfill S, Valentin-Blasini L, Bravo Cardenas R, Blount BC.
        Int J Environ Res Public Health. 2021 Oct 8;18(19).
        Standard machine smoking protocols provide useful information for examining the impact of design parameters, such as filter ventilation, on mainstream smoke delivery. Unfortunately, their results do not accurately reflect human smoke exposure. Clinical research and topography devices in human studies yield insights into how products are used, but a clinical setting or smoking a cigarette attached to such a device may alter smoking behavior. To better understand smokers' use of filtered cigarette products in a more natural environment, we developed a low-cost, high-throughput approach to estimate mainstream cigarette smoke exposure on a per-cigarette basis. This approach uses an inexpensive flatbed scanner to scan smoked cigarette filter butts and custom software to analyze tar-staining patterns. Total luminosity, or optical staining density, of the scanned images provides quantitative information proportional to mainstream smoke-constituent deliveries on a cigarette-by-cigarette basis. Duplicate sample analysis using this new approach and our laboratory's gold-standard liquid chromatography/tandem mass spectrometry (LC/MS/MS) solanesol method yielded comparable results (+7% bias) from the analysis of 20 commercial cigarettes brands (menthol and nonmentholated). The brands varied in design parameters such as length, filter ventilation, and diameter. Plots correlating the luminosity to mainstream smoked-nicotine deliveries on a per-cigarette basis for these cigarette brands were linear (average R(2) > 0.91 for nicotine and R(2) > 0.83 for the tobacco-specific nitrosamine NNK), on a per-brand basis, with linearity ranging from 0.15 to 3.00 mg nicotine/cigarette. Analysis of spent cigarette filters allows exposures to be characterized on a per-cigarette basis or a "daily dose" via summing across results from all filter butts collected over a 24 h period. This scanner method has a 100-fold lower initial capital cost for equipment than the LC/MS/MS solanesol method and provides high-throughput results (~200 samples per day). Thus, this new method is useful for characterizing exposure related to filtered tobacco-product use.

    • Nutritional Sciences
      1. Patterns of wasting among pregnant and lactating women in Uganda, 2015-2018: analysis of Nutrition surveillance dataexternal icon
        Kyamwine IB, Namukose S, Wibabara Y, Bulage L, Kwesiga B, Ario AR, Harris JR.
        BMC Nutr. 2021 Oct 14;7(1):59.
        BACKGROUND: Maternal nutrition is closely linked to the survival and development of children during the first 1000 days of life. Maternal wasting, a measure of malnutrition, is measured using the mid-upper arm circumference. However, in 2019, the rate and distribution of wasting among pregnant and lactating women was not known. We described annual trends and distribution of wasting among pregnant and lactating women (PLW), Uganda, 2015-2018, to inform programming on targeted nutritional interventions. METHODS: We analyzed nutrition surveillance data from the District Health Information System for all PLW from 2015 to 2018. We used the World Health Organization standard thresholds to determine wasting among PLW by year and region, drawing choropleth maps to demonstrate the geographic distribution of wasting among PLW. We used logistic regression to assess wasting trends. RESULTS: During 2015-2018, 268,636 PLW were wasted (prevalence = 5.5%). Of the 15 regions of Uganda, Karamoja (prevalence = 21%) and Lango (prevalence = 17%) registered the highest prevalence while Toro (prevalence = 2.7%) and Kigezi (prevalence = 2.0%) registered the lowest prevalence. The national annual prevalence of wasting among PLW declined by 31% from 2015 to 2018 (OR = 0.69, p < 0.001). Regions in the north had increasing trends of wasting over the period [Lango (OR = 1.6, p < 0.001) and Acholi (OR = 1.2, p < 0.001)], as did regions in the east [(Bugisu (OR = 3.4, p < 0.001), Bukedi (OR = 1.4, p < 0.001), and Busoga (OR = 1.3, p < 0.001)]. The other 11 regions showed declines. CONCLUSION: The trend of wasting among PLW nationally declined during the study period. Lango and Acholi regions, both of which were experiencing a nutrition state of emergency during this period, had both high and rising rates of wasting, as did the Karamoja region, which experienced the highest wasting rates. We recommended that the Ministry of Health increases its focus on nutrition monitoring for PLW and conduct an analysis to clearly identify the factors underlying malnutrition specific for PLW in these regions.

      2. Prevalence and Disparities in Folate and Vitamin B12 Deficiency Among Preschool Children in Guatemalaexternal icon
        Wong E, Molina-Cruz R, Rose C, Bailey L, Kauwell GP, Rosenthal J.
        Matern Child Health J. 2021 Oct 12.
        BACKGROUND AND OBJECTIVE: Folate and vitamin B12 deficiencies can impair proper growth and brain development in children. Data on the folate and vitamin B12 status of children aged 6-59 months in Guatemala are scarce. Identification of factors associated with higher prevalence of these micronutrient deficiencies within the population is needed for national and regional policymakers. OBJECTIVE: To describe national and regional post-fortification folate and vitamin B12 status of children aged 6-59 months in Guatemala. METHODS: A multistage, cluster probability study was carried out with national and regional representation of children aged 6-59 months. Demographic and health information was collected for 1246 preschool children, but blood samples for red blood cell (RBC) folate and vitamin B12 were collected and analyzed for 1,245 and 1143 preschool children, respectively. We used the following deficiency criteria as cutoff points for the analyses: < 305 nmol/L for RBC folate, < 148 pmol/L for vitamin B12 deficiency, and 148-221 pmol/L for marginal vitamin B12 deficiency. Prevalence of RBC folate deficiency and vitamin B12 deficiency and marginal deficiency were estimated. Prevalence risk ratios of RBC folate and vitamin B12 deficiency were estimated comparing subpopulations of interest. RESULTS: The national prevalence estimates of RBC folate deficiency among children was 33.5% [95% CI 29.1, 38.3]. The prevalence of RBC folate deficiency showed wide variation by age (20.3-46.6%) and was significantly higher among children 6-11 months and 12-23 months (46.6 and 37.0%, respectively), compared to older children aged 48-59 months (20.3%). RBC folate deficiency also varied widely by household wealth index (22.6-42.0%) and geographic region (27.2-46.7%) though the differences were not statistically significant. The national geometric mean for RBC folate concentrations was 354.2 nmol/L. The national prevalences of vitamin B12 deficiency and marginal deficiency among children were 22.5% [95% CI 18.2, 27.5] and 27.5% [95% CI 23.7, 31.7], respectively. The prevalence of vitamin B12 deficiency was significantly higher among indigenous children than among non-indigenous children (34.5% vs. 13.1%, aPRR 2.1 95% CI 1.4, 3.0). The prevalence of vitamin B12 deficiency also significantly varied between the highest and lowest household wealth index (34.3 and 6.0%, respectively). The national geometric mean for vitamin B12 concentrations was 235.1 pmol/L. The geometric means of folate and B12 concentrations were significantly lower among children who were younger, had a lower household wealth index, and were indigenous (for vitamin B12 only). Folate and vitamin B12 concentrations showed wide variation by region (not statistically significant), and the Petén and Norte regions showed the lowest RBC folate and vitamin B12 concentrations, respectively. CONCLUSIONS: In this study, a third of all children had RBC folate deficiency and half were vitamin B12 deficient. Folate deficiency was more common in younger children and vitamin B12 deficiency was more common in indigenous children and those from the poorest families. These findings suggest gaps in the coverage of fortification and the need for additional implementation strategies to address these gaps in coverage to help safeguard the health of Guatemalan children.

    • Occupational Safety and Health
      1. Intermediary Perspectives on Total Worker Health in Small Businessesexternal icon
        Cunningham T, Jacklitsch B, Richards R.
        Int J Environ Res Public Health. 2021 Oct 2;18(19).
        The future of work will include not only more small business employment, but also a need for greater consideration of more holistic approaches to addressing worker well-being. Previous research has suggested smaller firms need external assistance to add new or improve existing workplace health and safety activities. A Total Worker Health(®) (TWH) approach is potentially appealing to small employers as it is intended to identify and support comprehensive practices and policies that take into account the work environment (both physical and organizational) while also addressing the personal health risks of individuals, thus being more effective in preventing disease and promoting health and safety than each approach taken separately. NIOSH researchers applied the NIOSH Small Business Intervention Diffusion Model to conduct parallel community-based TWH activities in two geographically distinct communities in a large metropolitan area. Data were collected from intermediary organizations that work with or serve small businesses about their perceptions of the TWH approach as a potential service for them to offer small firms. Intermediary organizations engaged in implementation of TWH approaches with small businesses in the respective geographic areas for approximately one year. Results indicated intermediary organizations find value in providing TWH assistance to small employers, but several challenges for intermediaries implementing TWH among small employers remain.

      2. Notes from the Field: Fatal Anthrax Pneumonia in Welders and Other Metalworkers Caused by Bacillus cereus Group Bacteria Containing Anthrax Toxin Genes - U.S. Gulf Coast States, 1994-2020external icon
        Dawson P, Schrodt CA, Feldmann K, Traxler RM, Gee JE, Kolton CB, Marston CK, Gulvik CA, Antonini JM, Negrón ME, McQuiston JR, Hendricks K, Weiner Z, Balsamo GA, Sokol T, Byers P, Taylor K, Zaheer S, Long S, O'Sullivan B, de Perio MA, Hoffmaster AR, Salzer JS, Bower WA.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 15;70(41):1453-1454.

      3. Advanced sensor technologies and the future of workexternal icon
        Howard J, Murashov V, Cauda E, Snawder J.
        Am J Ind Med. 2021 Oct 13.
        Exposure science is fundamental to the field of occupational safety and health. The measurement of worker exposures to hazardous agents informs effective workplace risk mitigation strategies. The modern era of occupational exposure measurement began with the invention of the personal sampling device, which is still widely used today in the practice of occupational hygiene. Newer direct-reading sensor devices are incorporating recent advances in transducers, nanomaterials, electronics miniaturization, portability, batteries with high-power density, wireless communication, energy-efficient microprocessing, and display technology to usher in a new era in exposure science. Commercial applications of new sensor technologies have led to a variety of health and lifestyle management devices for everyday life. These applications are also being investigated as tools to measure occupational and environmental exposures. As the next-generation placeable, wearable, and implantable sensor technologies move from the research laboratory to the workplace, their role in the future of work will be of increasing importance to employers, workers, and occupational safety and health researchers and practitioners. This commentary discusses some of the benefits and challenges of placeable, wearable, and implantable sensor technologies in the future of work.

      4. Understanding of how Total Worker Health(®) (TWH) guidelines are implemented in employment organizations in the USA is not well understood. The purpose of this study is to explore how the principles of the Hierarchy of Controls Applied to NIOSH Total Worker Health (TWH HoC), have been implemented among organizations featured as Promising Practices for TWH between 2012-2019, with special focus on the work-related issues of fatigue, stress, sedentary work, and tobacco control. We also sought to identify benefits, obstacles, and lessons learned in the implementation of the TWH HoC. Eighteen organizations were identified to be included in the study. Using a qualitative cross-sectional design and purposive sampling, seven in-depth interviews were conducted with thirteen key informants. The Consolidated Framework for Implementation Research was used to guide the thematic analysis and interpretation of qualitative data. Four themes identified include recognition of the TWH approach and TWH HoC, implementation of the TWH HoC, barriers and facilitators in addressing specific work-related issues, and implementation climate primes benefits, obstacles, and lessons learned. The inner setting (i.e., culture, implementation climate, readiness for implementation) of organizations was a prominent determinant of the implementation of integrated worker safety, health, and well-being interventions.

      5. Oxidized carbon black nanoparticles induce endothelial damage through C-X-C chemokine receptor 3-mediated pathwayexternal icon
        Majumder N, Velayutham M, Bitounis D, Kodali VK, Hasan Mazumder MH, Amedro J, Khramtsov VV, Erdely A, Nurkiewicz T, Demokritou P, Kelley EE, Hussain S.
        Redox Biol. 2021 Oct 4;47:102161.
        Oxidation of engineered nanomaterials during application in various industrial sectors can alter their toxicity. Oxidized nanomaterials also have widespread industrial and biomedical applications. In this study, we evaluated the cardiopulmonary hazard posed by these nanomaterials using oxidized carbon black (CB) nanoparticles (CB(ox)) as a model particle. Particle surface chemistry was characterized by X-ray photo electron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR). Colloidal characterization and in vitro dosimetry modeling (particle kinetics, fate and transport modeling) were performed. Lung inflammation was assessed following oropharyngeal aspiration of CB or oxidized CB(ox) particles (20 μg per mouse) in C57BL/6J mice. Toxicity and functional assays were also performed on murine macrophage (RAW 264.7) and endothelial cell lines (C166) with and without pharmacological inhibitors. Oxidant generation was assessed by electron paramagnetic resonance spectroscopy (EPR) and via flow cytometry. Endothelial toxicity was evaluated by quantifying pro-inflammatory mRNA expression, monolayer permeability, and wound closure. XPS and FTIR spectra indicated surface modifications, the appearance of new functionalities, and greater oxidative potential (both acellular and in vitro) of CB(ox) particles. Treatment with CB(ox) demonstrated greater in vivo inflammatory potentials (lavage neutrophil counts, secreted cytokine, and lung tissue mRNA expression) and air-blood barrier disruption (lavage proteins). Oxidant-dependent pro-inflammatory signaling in macrophages led to the production of CXCR3 ligands (CXCL9,10,11). Conditioned medium from CB(ox)-treated macrophages induced significant elevation in endothelial cell pro-inflammatory mRNA expression, enhanced monolayer permeability and impairment of scratch healing in CXCR3 dependent manner. In summary, this study mechanistically demonstrated an increased biological potency of CB(ox) particles and established the role of macrophage-released chemical mediators in endothelial damage.

    • Parasitic Diseases
      1. Molecular surveillance for polymorphisms associated with artemisinin-based combination therapy resistance in Plasmodium falciparum isolates collected in Mozambique, 2018external icon
        Chidimatembue A, Svigel SS, Mayor A, Aíde P, Nhama A, Nhamussua L, Nhacolo A, Bassat Q, Salvador C, Enosse S, Saifodine A, De Carvalho E, Candrinho B, Zulliger R, Goldman I, Udhayakumar V, Lucchi NW, Halsey ES, Macete E.
        Malar J. 2021 Oct 12;20(1):398.
        BACKGROUND: Due to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and the prevalence of polymorphisms in the pfk13, pfcrt, and pfmdr1 genes associated with drug resistance was investigated. METHODS: Children aged 6-59 months were enrolled in four study sites. Blood was collected and dried on filter paper from participants who developed fever within 28 days of initial malaria treatment. All samples were first screened for Plasmodium falciparum using a multiplex real-time PCR assay, and polymorphisms in the pfk13, pfcrt, and pfmdr1 genes were investigated by Sanger sequencing. RESULTS: No pfk13 mutations, associated with artemisinin partial resistance, were observed. The only pfcrt haplotype observed was the wild type CVMNK (codons 72-76), associated with chloroquine sensitivity. Polymorphisms in pfmdr1 were only observed at codon 184, with the mutant 184F in 43/109 (39.4%) of the samples, wild type Y184 in 42/109 (38.5%), and mixed 184F/Y in 24/109 (22.0%). All samples possessed N86 and D1246 at these two codons. CONCLUSION: In 2018, no markers of artemisinin resistance were documented. Molecular surveillance should continue to monitor the prevalence of these markers to inform decisions on malaria treatment in Mozambique.

      2. Spatial distribution of Plasmodium falciparum and P. vivax in northern Ethiopia by microscopy, rapid diagnostic test, laboratory antibody and antigen dataexternal icon
        Leonard CM, Assefa A, Sime H, Mohammed H, Kebede A, Solomon H, Drakeley C, Murphy M, Hwang J, Rogier E.
        J Infect Dis. 2021 Oct 10.
        BACKGROUND: Determining malaria transmission within regions of low, heterogenous prevalence is difficult. A variety of malaria tests exist and range from identification of diagnostic infection to testing for prior exposure. This study describes concordance of multiple malaria tests using data from a 2015 household survey conducted in Ethiopia. METHODS: Blood samples (n= 2,279) from three regions in northern Ethiopia were assessed for Plasmodium falciparum and P. vivax by microscopy, rapid diagnostic test (RDT), multiplex antigen assay, and multiplex assay for IgG antibodies. Geospatial analysis was conducted with spatial scan statistics and kernel density estimation to identify hotspots of malaria by different test results. RESULTS: Prevalence of malaria infection was low (1.4% by RDT, 1.0% by microscopy, and 1.8% by laboratory antigen assay). For P. falciparum, overlapping spatial clusters for all tests and an additional five unique IgG clusters were identified. For P. vivax, clusters identified for bead antigen assay, microscopy, and IgG with partial overlap. CONCLUSIONS: Assessing the spatial distribution of malaria exposure using multiple metrics can improve the understanding of malaria transmission dynamics in a region. The relative abundance of antibody clusters indicates that in areas of low-transmission, IgG antibodies are a more useful marker to assess malaria exposure.

    • Physical Activity
      1. Physical Activity Types and Programs Recommended by Primary Care Providers Treating Adults With Arthritis, DocStyles 2018external icon
        Guglielmo D, Theis KA, Murphy LB, Boring MA, Helmick CG, Omura JD, Odom EL, Duca LM, Croft JB.
        Prev Chronic Dis. 2021 Oct 14;18:E92.
        Primary care providers (PCPs) can offer counseling to adults with arthritis on physical activity, which can reduce pain and improve physical function, mental health, and numerous other health outcomes. We analyzed cross-sectional 2018 DocStyles data for 1,366 PCPs who reported they always or sometimes recommend physical activity to adults with arthritis. Most PCPs sampled (88.2%) recommended walking, swimming, or cycling; 65.5% did not recommend any evidence-based, arthritis-appropriate physical activity programs recognized by the Centers for Disease Control and Prevention. Opportunities exist for public health awareness campaigns to educate PCPs about evidence-based physical activity programs proven to optimize health for adults with arthritis when more than counseling is needed.

      2. Accelerometer-Measured Daily Steps, Physical Function, and Subsequent Fall Risk in Older Women: The Objective Physical Activity and Cardiovascular Disease in Older Women Studyexternal icon
        Schumacher BT, Bellettiere J, LaMonte MJ, Evenson KR, Di C, Lee IM, Sleet DA, Eaton CB, Lewis CE, Margolis KL, Tinker LF, LaCroix AZ.
        J Aging Phys Act. 2021 Oct 9:1-11.
        Steps per day were measured by accelerometer for 7 days among 5,545 women aged 63-97 years between 2012 and 2014. Incident falls were ascertained from daily fall calendars for 13 months. Median steps per day were 3,216. There were 5,473 falls recorded over 61,564 fall calendar-months. The adjusted incidence rate ratio comparing women in the highest versus lowest step quartiles was 0.71 (95% confidence interval [0.54, 0.95]; ptrend across quartiles = .01). After further adjustment for physical function using the Short Physical Performance Battery, the incidence rate ratio was 0.86 ([0.64, 1.16]; ptrend = .27). Mediation analysis estimated that 63.7% of the association may be mediated by physical function (p = .03). In conclusion, higher steps per day were related to lower incident falls primarily through their beneficial association with physical functioning. Interventions that improve physical function, including those that involve stepping, could reduce falls in older adults.

    • Program Evaluation
      1. Introduction: The United States Centers for Disease Control and Prevention (CDC), through U.S. President's Emergency Plan for AIDS Relief (PEPFAR), supports a third of all people receiving HIV care globally. CDC works with local partners to improve methods to find, treat, and prevent HIV and tuberculosis. However, a shortage of trained medical professionals has impeded efforts to control the HIV epidemic in Sub-Saharan Africa and Asia. The Project Extension for Community Healthcare Outcomes (ECHO(TM)) model expands capacity to manage complex diseases, share knowledge, disseminate best practices, and build communities of practice. This manuscript describes a practical protocol for an evaluation framework and toolkit to assess ECHO implementation. Methods and Analysis: This mixed methods, developmental evaluation design uses an appreciative inquiry approach, and includes a survey, focus group discussion, semi-structured key informant interviews, and readiness assessments. In addition, ECHO session content will be objectively reviewed for accuracy, content validity, delivery, appropriateness, and consistency with current guidelines. Finally, we offer a mechanism to triangulate data sources to assess acceptability and feasibility of the evaluation framework and compendium of monitoring and evaluation tools. Expected impact of the study on public health: This protocol offers a unique approach to engage diverse group of stakeholders using an appreciative inquiry process to co-create a comprehensive evaluation framework and a compendium of assessment tools. This evaluation framework utilizes mixed methods (quantitative and qualitative data collection tools), was pilot tested in Tanzania, and has the potential for contextualized use in other countries who plan to evaluate their Project ECHO implementation.

    • Public Health Leadership and Management
      1. Innovations to maximise impact of a data for decision-making training programme in the Federated States of Micronesiaexternal icon
        Durand AM, Hancock WT, Cash HL, Rouse I, Chutaro E, Taulung L, Patel M.
        BMJ Glob Health. 2021 Oct;6(10).
        Accurate and timely health information is an essential foundation for strengthening health systems. Data for decision making (DDM) is a training curriculum designed to enhance capacity of health department staff to capture and use high-quality data to address priority health issues. In 2013, the Pacific Public Health Surveillance Network adapted and piloted the DDM curriculum as an 'at work, from work, for work' field epidemiology training programme component for low-income and middle-income Pacific Island jurisdictions. Based on lessons learned from the pilot, we made several innovations, including delivery on-site at each district (rather than bringing trainees to a central location), conducting pre-DDM consultations and ongoing contact with health leaders across the programme, taking more care in selecting trainees and enrolling a larger cohort of students from within each health department. The decentralised programme was delivered in-country at four sites (both at national and state levels) in the Federated States of Micronesia. Following delivery, we performed an external evaluation of the programme to assess student outcomes, benefits to the health department and general programme effectiveness. Of the 48 trainees who completed all four classroom modules, 40 trainees participated in the evaluation. Thirty-two of these trainees completed the programme's capstone field project. Eighteen of these projects directly contributed to changes in legislation, revised programme budgets, changes in programme strategy to augment outreach and to target disease and risk factor 'hot spots'.

    • Substance Use and Abuse
      1. Binge Drinking Among Adults, by Select Characteristics and State - United States, 2018external icon
        Bohm MK, Liu Y, Esser MB, Mesnick JB, Lu H, Pan Y, Greenlund KJ.
        MMWR Morb Mortal Wkly Rep. 2021 Oct 15;70(41):1441-1446.
        Excessive alcohol use* is associated with disease, injury, and poor pregnancy outcomes and is responsible for approximately 95,000 deaths in the United States each year (1). Binge drinking (five or more drinks on at least one occasion for men or four or more drinks for women) is the most common and costly pattern of excessive alcohol use (2). CDC analyzed data from the 2018 Behavioral Risk Factor Surveillance System (BRFSS) to estimate past 30-day binge drinking prevalence, frequency, and intensity (number of drinks per occasion), overall and by select characteristics and state. The overall unadjusted prevalence of binge drinking during the past 30 days was 16.6%, representing an estimated 38.5 million U.S. adults aged ≥18 years; prevalence was highest (26.0%) among those aged 25-34 years. The age-standardized binge drinking prevalence was higher among men (22.5%) than among women (12.6%), increased with income, and was highest among non-Hispanic White adults and adults in the Midwest Census region. State-level age-standardized binge drinking prevalence ranged from 10.5% (Utah) to 25.8% (Wisconsin). Among adults who reported binge drinking, 25.0% did so at least weekly, on average, and 25.0% consumed at least eight drinks on an occasion. To reduce binge drinking, the Community Preventive Services Task Force recommends increasing alcohol taxes and implementing strategies that strengthen regulations to reduce alcohol availability.(†) The U.S. Preventive Services Task Force recommends clinicians screen adults for alcohol misuse in primary care settings and provide counseling as needed.(§).

      2. BACKGROUND: In response to the opioid crisis, over the last 10 years substantial strides have been made to increase the availability of evidence-based treatments for opioid use disorder, in particular buprenorphine maintenance, in the United States. Despite these worthwhile efforts, uptake rates of evidence-based treatment remain relatively low. As part of a broader study of opioid misuse, we examined proximity to evidence-based treatment as a potential barrier to treatment access. METHODS: In 2017-2018, we surveyed 218 individuals misusing prescription opioids or using street opioids in three Southern Californian counties. The study calculated driving distance from place of residence to the closest treatment provider offering buprenorphine or methadone treatment for opioid use disorders. RESULTS: Median distance to providers was 3.8 km (2.4 miles). Seventy one (33%) participants had received some form of treatment in the last 3 months; however, only 26 (40%) of these had received buprenorphine or methadone maintenance treatment. Participants receiving treatment at the time of their interview were traveling an average 16.8 km (10.4 miles) to reach treatment, indicating that as a group this population was both willing and able to seek and engage with treatment. CONCLUSIONS: In the suburban and exurban communities in which our study was based, our findings suggest that simple physical proximity to providers of evidence-based treatment for opioid use disorder is no longer a critical barrier. Other barriers to uptake of buprenorphine or methadone maintenance treatment clearly remain and need to be addressed. DISCLAIMER: Findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

    • Zoonotic and Vectorborne Diseases
      1. Phylogenetic Differentiation of Rickettsia parkeri Reveals Broad Dispersal and Distinct Clustering within North American Strainsexternal icon
        Allerdice ME, Paddock CD, Hecht JA, Goddard J, Karpathy SE.
        Microbiol Spectr. 2021 Oct 13:e0141721.
        The tick-borne pathogen Rickettsia parkeri causes a mild rickettsiosis, with cases reported from several countries to its known distribution in the Americas. Molecular analyses have identified a clear distinction between strains of R. parkeri sensu stricto (s. s.) and R. parkeri sensu lato (s. l.) as well as separation between North American and South American R. parkeri s. s. strains. To expand on this previous work, we developed a multilocus sequence typing analysis with two aims: first, to investigate the genetic diversity within strains of North American R. parkeri s. s., and second, to further the understanding of the genetic relationships between R. parkeri s. s. and R. parkeri s. l. Sixty-four R. parkeri isolates and 12 R. parkeri-positive tick lysates were analyzed using a novel typing scheme consisting of four coding regions and two intergenic regions. A concatenated Bayesian phylogeny that identified eight clades was constructed: three represent the R. parkeri s. l. strains, and five represent the R. parkeri s. s. strains. The clades appear to be generally phylogeographically organized and associated with specific tick vectors. However, while one of the four R. parkeri s. s. North American clades appears to be limited to the southwestern United States, the other North American clades exhibit broad dispersal, most notably seen in the largest group, which includes representative samples extending from northern Mexico to Delaware. This work highlights the increasingly recognized geographic range of R. parkeri in the Americas and suggests a potential public health risk for these areas. IMPORTANCE Since 1937, when Rickettsia parkeri was originally identified in Amblyomma maculatum group ticks, the recognized range and associated vectors for this pathogen have expanded significantly. In recent years, R. parkeri has been identified in 12 tick species from seven countries in the Americas. Herein, we provide evidence that the greatest genetic diversity within R. parkeri exists in North America, where one R. parkeri sensu lato and four R. parkeri sensu stricto genotypes are present. While one distinct R. parkeri sensu stricto genotype exists only in the southwestern United States, three genotypes are broadly distributed in the eastern United States, with the largest of these found across the known range of R. parkeri in North America. In contrast, the South American R. parkeri sensu stricto samples represent a single genotype and are completely clonal at the loci analyzed, irrespective of their country of origin.

      2. Acute and chronic Q fever national surveillance - United States, 2008-2017external icon
        Cherry CC, Nichols Heitman K, Bestul NC, Kersh GJ.
        Zoonoses Public Health. 2021 Oct 8.
        Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii and can manifest in an acute or chronic form. Many persons with acute Q fever are asymptomatic, but some develop a febrile illness, pneumonia or hepatitis. Chronic infections are rare and occur in less than 5% of persons exposed. Forms of chronic Q fever include endocarditis, infection of vascular grafts or aneurysms, osteomyelitis and osteoarthritis. Acute and chronic Q fever are nationally notifiable diseases, and presented here are the incidence, demographics and distribution of acute and chronic Q fever in the United States during 2008-2017. We summarized passive surveillance data from the Centers for Disease Control and Prevention's (CDC) National Notifiable Diseases Surveillance System (NNDSS) and supplemental case report forms (CRFs). Health departments reported 1,109 cases of acute Q fever and 272 chronic Q fever cases to NNDSS during this period. The 10-year average annual incidence for acute Q fever was 0.36 cases per million persons, and the average annual incidence for chronic Q fever was 0.09. Males accounted for nearly 75% of both acute and chronic Q fever cases. Average annual incidence was highest among persons aged 60-69 years for both acute and chronic Q fever (0.70 cases per million persons and 0.25, respectively). As reported through CRFs, many Q fever cases did not have a known exposure to C. burnetii; 60% (n = 380) of acute Q fever cases did not report exposure to animals in the 2 months before symptom onset. Almost 90% (n = 558) did not report exposure to unpasteurized milk. Only 40% (n = 247) of persons with reported Q fever were employed in high-risk occupations. Even though Q fever is a rare disease in the United States, incidence doubled from 2008 to 2017.

      3. Hantavirus Disease and COVID-19external icon
        Joyce AK, Oliver TT, Kofman AD, Talker DL, Safaeian S, Peker Barclift D, Perricone AJ, D'Andrea SM, Whitesell AN, Yazzie D, Guarner J, Saleki M, Ingall GB, Choi MJ, Antone-Nez R.
        Am J Clin Pathol. 2021 Oct 13.
        OBJECTIVES: Navajo Nation is disproportionately affected by hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease that can quickly progress to respiratory failure and cardiogenic shock. The initial signs and symptoms of HCPS are indistinguishable from coronavirus disease 2019 (COVID-19). However, this distinction is critical, as the disease course differs greatly, with most patients with COVID-19 experiencing mild to moderate illness. We set out to determine if the evaluation of peripheral blood smears for five hematopathologic criteria previously identified as hallmarks of hantavirus infection, or "the hantavirus 5-point screen," could distinguish between COVID-19 and HCPS. METHODS: The hantavirus 5-point screen was performed on peripheral blood smears from 139 patients positive for COVID-19 seeking treatment from Tséhootsooí Medical Center and two Emory University hospitals. RESULTS: Of these 139 individuals, 136 (98%) received a score of 3/5 or below, indicating low suspicion for HCPS. While thrombocytopenia, one of the key signs of HCPS, was seen in the patients with COVID-19, it was generally mild and remained stable on repeat specimens collected 12 to 24 hours later. CONCLUSIONS: Given these findings, the 5-point screen remains a useful rapid screening tool for potential HCPS cases and may be useful to distinguish early HCPS from COVID-19 in HCPS endemic regions.


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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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