Current Issue

CDC Science Clips: Volume 12, Issue 32, September 16, 2020

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!

This week's Science Clips issue features winning articles in the CDC's Charles C. Shepard Awards. The preeminent science awards of CDC/ATSDR, inaugurated in 1986, are named in honor of Charles C. Shepard, MD, the internationally recognized microbiologist who was chief of the Leprosy and Rickettsia Branch at CDC for more than 30 years, until his death on February 18, 1985. The Charles C. Shepard Science Awards recognize excellence in science at CDC and ATSDR. For scientific publications, the award is presented to the best manuscript on original research published by a CDC or ATSDR scientist in a reputable, peer-reviewed journal.

  1. CDC Shepard Awards - 2020
    • Assessment (co-winners)
      1. Syndromic Surveillance for E-Cigarette, or Vaping, Product Use-Associated Lung Injuryexternal icon
        Hartnett KP, Kite-Powell A, Patel MT, Haag BL, Sheppard MJ, Dias TP, King BA, Melstrom PC, Ritchey MD, Stein Z, Idaikkadar N, Vivolo-Kantor AM, Rose DA, Briss PA, Layden JE, Rodgers L, Adjemian J.
        N Engl J Med. 2020 Feb 20;382(8):766-772.

      2. Trends and Patterns of Geographic Variation in Opioid Prescribing Practices by State, United States, 2006-2017external icon
        Schieber LZ, Guy GP, Seth P, Young R, Mattson CL, Mikosz CA, Schieber RA.
        JAMA Netw Open. 2019 Mar 1;2(3):e190665.
        IMPORTANCE: Risk of opioid use disorder, overdose, and death from prescription opioids increases as dosage, duration, and use of extended-release and long-acting formulations increase. States are well suited to respond to the opioid crisis through legislation, regulations, enforcement, surveillance, and other interventions. OBJECTIVE: To estimate temporal trends and geographic variations in 6 key opioid prescribing measures in 50 US states and the District of Columbia. DESIGN, SETTING, AND PARTICIPANTS: Population-based cross-sectional analysis of opioid prescriptions filled nationwide at US retail pharmacies between January 1, 2006, and December 31, 2017. Data were obtained from the IQVIA Xponent database. All US residents who had an opioid prescription filled at a US retail pharmacy were included. MAIN OUTCOMES AND MEASURES: Primary outcomes were annual amount of opioids prescribed in morphine milligram equivalents (MME) per person; mean duration per prescription in days; and 4 separate prescribing rates-for prescriptions 3 or fewer days, those 30 days or longer, those with a high daily dosage (≥90 MME), and those with extended-release and long-acting formulations. RESULTS: Between 2006 and 2017, an estimated 233.7 million opioid prescriptions were filled in retail pharmacies in the United States each year. For all states combined, 4 measures decreased: (1) mean (SD) amount of opioids prescribed (mean [SD] decrease, 12.8% [12.6%]) from 628.4 (178.0) to 543.4 (158.6) MME per person, a statistically significant decrease in 23 states; (2) high daily dosage (mean [SD] decrease, 53.1% [13.6%]) from 12.3 (3.4) to 5.6 (1.7) per 100 persons, a statistically significant decrease in 49 states; (3) short-term (≤3 days) duration (mean [SD] decrease, 43.1% [9.4%]) from 18.0 (5.4) to 10.0 (2.5) per 100 persons, a statistically significant decrease in 48 states; and (4) extended-release and long-acting formulations (mean [SD] decrease, 14.7% [13.7%]) from 7.2 (1.9) to 6.0 (1.7) per 100 persons, a statistically significant decrease in 27 states. Two measures increased, each associated with the duration of prescription dispensed: (1) mean (SD) prescription duration (mean [SD] increase, 37.6% [6.9%]) from 13.0 (1.2) to 17.9 (1.4) days, a statistically significant increase in every state; and (2) prescriptions for a term of 30 days or longer (mean [SD] increase, 37.7% [28.9%]) from 18.3 (7.7) to 24.9 (10.7) per 100 persons, a statistically significant increase in 39 states. Two- to 3-fold geographic differences were observed across states, measured by comparing the ratio of each state's 90th to 10th percentile for each measure. CONCLUSIONS AND RELEVANCE: In this study, across 12 years, the mean duration and prescribing rate for long-term prescriptions of opioids increased, whereas the amount of opioids prescribed per person and prescribing rate for high-dosage prescriptions, short-term prescriptions, and extended-release and long-acting formulations decreased. Some decreases were significant, but results were still high. Two- to 3-fold state variation in 5 measures occurred in most states. This information may help when state-specific intervention programs are being designed.

    • Data Methods and Study Design
      1. Entropy of mitochondrial DNA circulating in blood is associated with hepatocellular carcinomaexternal icon
        Campo DS, Nayak V, Srinivasamoorthy G, Khudyakov Y.
        BMC Med Genomics. 2019 Jun 6;12(Suppl 4):74.
        BACKGROUND: Ultra-Deep Sequencing (UDS) enabled identification of specific changes in human genome occurring in malignant tumors, with current approaches calling for the detection of specific mutations associated with certain cancers. However, such associations are frequently idiosyncratic and cannot be generalized for diagnostics. Mitochondrial DNA (mtDNA) has been shown to be functionally associated with several cancer types. Here, we study the association of intra-host mtDNA diversity with Hepatocellular Carcinoma (HCC). RESULTS: UDS mtDNA exome data from blood of patients with HCC (n = 293) and non-cancer controls (NC, n = 391) were used to: (i) measure the genetic heterogeneity of nucleotide sites from the entire population of intra-host mtDNA variants rather than to detect specific mutations, and (ii) apply machine learning algorithms to develop a classifier for HCC detection. Average total entropy of HCC mtDNA is 1.24-times lower than of NC mtDNA (p = 2.84E-47). Among all polymorphic sites, 2.09% had a significantly different mean entropy between HCC and NC, with 0.32% of the HCC mtDNA sites having greater (p < 0.05) and 1.77% of the sites having lower mean entropy (p < 0.05) as compared to NC. The entropy profile of each sample was used to further explore the association between mtDNA heterogeneity and HCC by means of a Random Forest (RF) classifier The RF-classifier separated 232 HCC and 232 NC patients with accuracy of up to 99.78% and average accuracy of 92.23% in the 10-fold cross-validation. The classifier accurately separated 93.08% of HCC (n = 61) and NC (n = 159) patients in a validation dataset that was not used for the RF parameter optimization. CONCLUSIONS: Polymorphic sites contributing most to the mtDNA association with HCC are scattered along the mitochondrial genome, affecting all mitochondrial genes. The findings suggest that application of heterogeneity profiles of intra-host mtDNA variants from blood may help overcome barriers associated with the complex association of specific mutations with cancer, enabling the development of accurate, rapid, inexpensive and minimally invasive diagnostic detection of cancer.

    • Laboratory Science
      1. Insights into the antigenic advancement of influenza A(H3N2) viruses, 2011-2018external icon
        Jorquera PA, Mishin VP, Chesnokov A, Nguyen HT, Mann B, Garten R, Barnes J, Hodges E, De La Cruz J, Xu X, Katz J, Wentworth DE, Gubareva LV.
        Sci Rep. 2019 Feb 25;9(1):2676.
        Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011-2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo, and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection.

    • Prevention and Control
      1. BACKGROUND: For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE: The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS: We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS: Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS: The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at as NCT00207558.

  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.
    • Chronic Diseases and Conditions
      1. Opioid dispensing among adult Medicaid enrollees by diabetes statusexternal icon
        Ng BP, Rabold E, Guy GP, Park C, Zhang P, Smith BD.
        Curr Med Res Opin. 2020 Aug 27:1.
        Objective: Diabetes disproportionately affects low income individuals, many of whom are covered by Medicaid. Comorbidities and complications of diabetes can lead to chronic pain; however, little is known about opioid use patterns among Medicaid enrollees with diabetes. This study examined opioid dispensing among Medicaid enrollees by diabetes status.Methods: Medicaid claims data from 2014 were used to examine opioid dispensing by diabetes status among 622,992 adult enrollees aged 19-64 years. A logistic model adjusting for demographics and comorbidities was used to examine the association between diabetes and opioid dispensing among enrollees. Analyses were completed in 2019.Results: Overall, 61.6% of enrollees with diabetes filled at least one opioid prescription compared to 31.8% of enrollees without diabetes. A higher proportion of enrollees with diabetes had long-term opioid prescriptions (>90 days' supply) (with diabetes: 51.0% vs. without: 32.1%, p < 0.001). Characteristics of individual prescriptions, including daily morphine milligram equivalents (45.9 vs. 49.4), formulation (percent short-acting: 91.5% vs. 90.7%), and type of opioids (i.e. percent hydrocodone: 46.7 vs. 45.3), were similar for those with and without diabetes. After adjustment, enrollees with diabetes were 1.43 times more likely to receive an opioid prescription compared to those without (OR 1.43, 95% CI =1.40-1.46).Conclusions: Medicaid enrollees with diabetes were prescribed opioids more frequently and were more likely to have longer opioid supply than enrollees without diabetes. For practitioners who care for patients with diabetes, aligning pain management approaches with evidence-based resources, like the CDC Guideline for Prescribing Opioids for Chronic Pain, can encourage safer opioid prescribing practices.

      2. Trends in obesity prevalence by race and Hispanic origin - 1999-2000 to 2017-2018external icon
        Ogden CL, Fryar CD, Martin CB, Freedman DS, Carroll MD, Gu Q, Hales CM.
        Jama. 2020 Aug 28.

      3. The Million Hearts Initiative: Catalyzing utilization of cardiac rehabilitation and accelerating implementation of new care modelsexternal icon
        Wall HK, Stolp H, Wright JS, Ritchey MD, Thomas RJ, Ades PA, Sperling LS.
        J Cardiopulm Rehabil Prev. 2020 Sep;40(5):290-293.
        Million Hearts and partners have been committed to raising national cardiac rehabilitation participation rates to a goal of 70%. Quality improvement tools, resources, and surveillance models have been developed in support. Efforts to enhance research programs and collaborative initiatives have created momentum to accelerate implementation of new care models.

    • Communicable Diseases
      1. Seroprevalence of antibodies against Chlamydia trachomatis and enteropathogens and distance to the nearest water source among young children in the Amhara Region of Ethiopiaexternal icon
        Aiemjoy K, Aragie S, Wittberg DM, Tadesse Z, Callahan EK, Gwyn S, Martin D, Keenan JD, Arnold BF.
        PLoS Negl Trop Dis. 2020 Sep 2;14(9):e0008647.
        The transmission of trachoma, caused by repeat infections with Chlamydia trachomatis, and many enteropathogens are linked to water quantity. We hypothesized that children living further from a water source would have higher exposure to C. trachomatis and enteric pathogens as determined by antibody responses. We used a multiplex bead assay to measure IgG antibody responses to C. trachomatis, Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae in eluted dried blood spots collected from 2267 children ages 0-9 years in 40 communities in rural Ethiopia in 2016. Linear distance from the child's house to the nearest water source was calculated. We derived seroprevalence cutoffs using external negative control populations, if available, or by fitting finite mixture models. We used targeted maximum likelihood estimation to estimate differences in seroprevalence according to distance to the nearest water source. Seroprevalence among 1-9-year-olds was 43% for C. trachomatis, 28% for S. enterica, 70% for E. histolytica, 54% for G. intestinalis, 96% for C. jejuni, 76% for ETEC and 94% for C. parvum. Seroprevalence increased with age for all pathogens. Median distance to the nearest water source was 473 meters (IQR 268, 719). Children living furthest from a water source had a 12% (95% CI: 2.6, 21.6) higher seroprevalence of S. enterica and a 12.7% (95% CI: 2.9, 22.6) higher seroprevalence of G. intestinalis compared to children living nearest. Seroprevalence for C. trachomatis and enteropathogens was high, with marked increases for most enteropathogens in the first two years of life. Children living further from a water source had higher seroprevalence of S. enterica and G. intestinalis indicating that improving access to water in the Ethiopia's Amhara region may reduce exposure to these enteropathogens in young children.

      2. Early use of the palliative approach to improve patient outcomes in HIV disease: Insights and findings from the Care and Support Access (CASA) Study 2013-2019external icon
        Alexander CS, Raveis VH, Karus D, Carrero-Tagle M, Lee MC, Pappas G, Lockman K, Brotemarkle R, Memiah P, Mulasi I, Hossain BM, Welsh C, Henley Y, Piet L, N'Diaye S, Murray R, Haltiwanger D, Smith CR, Flynn C, Redfield R, Silva CL, Amoroso A, Selwyn P.
        Am J Hosp Palliat Care. 2020 Aug 27.
        Young men of color who have sex with men (yMSM) living with human immunodeficiency virus (HIV) in syndemic environments have been difficult-to-retain in care resulting in their being at-risk for poor health outcomes despite availability of effective once-daily antiretroviral treatment (ART). Multiple methods have been implemented to improve outcomes for this cohort; none with sustainable results. Outpatient HIV staff themselves may be a contributing factor. We introduced multidisciplinary staff to the concept of using a palliative approach early (ePA) in outpatient HIV care management to enable them to consider the patient-level complexity of these young men. Young MSM (18-35 years of age) enrolled in and cared for at the intervention site of the Care and Support Access Study (CASA), completed serial surveys over 18 months. Patients' Global and Summary quality of life (QoL) increased during the study at the intervention site (IS) where staff learned about ePA, compared with patients attending the control site (CS) (p=.021 and p=.018, respectively). Using serial surveys of staff members, we found that in the era of HIV disease control, outpatient staff are stressed more by environmental factors than by patients' disease status seen historically in the HIV epidemic. A Community Advisory Panel of HIV stakeholders contributed to all phases of this study and altered language used in educational activities with staff members to describe the patient cohort.

      3. Cost of pediatric hospitalizations in Burkina Faso: A cross-sectional study of children aged <5 years enrolled through an acute gastroenteritis surveillance programexternal icon
        Aliabadi N, Bonkoungou IJ, Pindyck T, Nikièma M, Leshem E, Seini E, Kam M, Konaté S, Ouattara M, Ouédraogo B, Gue E, Nezien D, Ouedraogo I, Parashar U, Medah I, Mwenda JM, Tate JE.
        Vaccine. 2020 Aug 28.
        INTRODUCTION: Diarrheal illness is a leading cause of hospitalizations among children <5 years. We estimated the costs of inpatient care for rotavirus and all-cause acute gastroenteritis (AGE) in two Burkina Faso hospitals. METHODS: We conducted a cross-sectional study among children <5 years from December 2017 to June 2018 in one urban and one rural pediatric hospital. Costs were ascertained through caregiver interview and chart abstraction. Direct medical, non-medical, and indirect costs per child incurred are reported. Costs were stratified by rotavirus results. RESULTS: 211 children <5 years were included. AGE hospitalizations cost 161USD (IQR 117-239); 180USD (IQR 121-242) at the urban and 154USD (IQR 116-235) at the rural site. Direct medical costs were higher in the urban compared to the rural site (140USD (IQR 102-182) vs. 90USD (IQR 71-108), respectively). Direct non-medical costs were higher at the rural versus urban site (15USD (IQR 10, 15) vs. 11USD (IQR 5-20), respectively). Indirect costs were higher at the rural versus urban site (35USD (IQR 8-91) vs. 0USD (IQR 0-26), respectively). Rotavirus hospitalizations incurred less direct medical costs as compared to non-rotavirus hospitalizations at the rural site (79USD (IQR 64-103) vs. 95USD (IQR 80-118)). No other differences by rotavirus testing status were observed. The total median cost of a hospitalization incurred by households was 24USD (IQR 12-49) compared to 75USD for government (IQR 59-97). Direct medical costs for households were higher in the urban site (median 49USD (IQR 31-81) versus rural (median 14USD (IQR 8-25)). Households in the lowest wealth quintiles at the urban site expended 149% of their monthly income on the child's hospitalization, compared to 96% at the rural site. CONCLUSIONS: AGE hospitalization costs differed between the urban and rural hospitals and were most burdensome to the lowest income households. Rotavirus positivity was not associated with greater household costs.

      4. Human immunodeficiency virus testing among people who inject drugs in rural West Virginiaexternal icon
        Allen ST, Grieb SM, White RH, O'Rourke A, Kilkenny ME, Jones CM, Latkin C, Sherman SG.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S346-s353.
        BACKGROUND: Limited research exists on factors associated with human immunodeficiency virus (HIV) testing among people who inject drugs (PWID) in rural America. The purpose of this research is to identify factors associated with rural PWID in Appalachia having not been tested for HIV in the past year. METHODS: Cross-sectional data (n = 408) from a 2018 PWID population estimation study in West Virginia were used to examine factors associated with PWID having not been tested for HIV in the past year. RESULTS: Most participants identified as male (61%), white, non-Hispanic (84%), and reported having recently injected heroin (81%) and/or crystal methamphetamine (71%). Most (64%) reported having been tested for HIV in the past year, 17% reported having been tested but not in the past year, and 19% reported never having been tested. In multivariable analysis, not having been in a drug treatment program in the past year was associated with PWID not having been tested for HIV in the past year (adjusted prevalence ratio, 1.430; 95% confidence interval, 1.080-1.894). CONCLUSIONS: Drug treatment programs may be important venues for rural PWID to access HIV testing; however, testing services should be offered at multiple venues as most PWID had not engaged in drug treatment in the past year.

      5. Implementation and evaluation of a Project ECHO telementoring program for the Namibian HIV workforceexternal icon
        Bikinesi L, O'Bryan G, Roscoe C, Mekonen T, Shoopala N, Mengistu AT, Sawadogo S, Agolory S, Mutandi G, Garises V, Pati R, Tison L, Igboh L, Johnson C, Rodriguez EM, Ellerbrock T, Menzies H, Baughman AL, Brandt L, Forster N, Scott J, Wood B, Unruh KT, Arora S, Iandiorio M, Kalishman S, Zalud-Cerrato S, Lehmer J, Lee S, Mahdi MA, Spedoske S, Zuber A, Reilley B, Ramers CB, Hamunime N, O'Malley G, Struminger B.
        Hum Resour Health. 2020 Sep 1;18(1):61.
        BACKGROUND: The Namibian Ministry of Health and Social Services (MoHSS) piloted the first HIV Project ECHO (Extension for Community Health Outcomes) in Africa at 10 clinical sites between 2015 and 2016. Goals of Project ECHO implementation included strengthening clinical capacity, improving professional satisfaction, and reducing isolation while addressing HIV service challenges during decentralization of antiretroviral therapy. METHODS: MoHSS conducted a mixed-methods evaluation to assess the pilot. Methods included pre/post program assessments of healthcare worker knowledge, self-efficacy, and professional satisfaction; assessment of continuing professional development (CPD) credit acquisition; and focus group discussions and in-depth interviews. Analysis compared the differences between pre/post scores descriptively. Qualitative transcripts were analyzed to extract themes and representative quotes. RESULTS: Knowledge of clinical HIV improved 17.8% overall (95% confidence interval 12.2-23.5%) and 22.3% (95% confidence interval 13.2-31.5%) for nurses. Professional satisfaction increased 30 percentage points. Most participants experienced reduced professional isolation (66%) and improved CPD credit access (57%). Qualitative findings reinforced quantitative results. Following the pilot, the Namibia MoHSS Project ECHO expanded to over 40 clinical sites by May 2019 serving more than 140 000 people living with HIV. CONCLUSIONS: Similar to other Project ECHO evaluation results in the United States of America, Namibia's Project ECHO led to the development of ongoing virtual communities of practice. The evaluation demonstrated the ability of the Namibia HIV Project ECHO to improve healthcare worker knowledge and satisfaction and decrease professional isolation.

      6. Enhanced contact investigations for nine early travel-related cases of SARS-CoV-2 in the United Statesexternal icon
        Burke RM, Balter S, Barnes E, Barry V, Bartlett K, Beer KD, Benowitz I, Biggs HM, Bruce H, Bryant-Genevier J, Cates J, Chatham-Stephens K, Chea N, Chiou H, Christiansen D, Chu VT, Clark S, Cody SH, Cohen M, Conners EE, Dasari V, Dawson P, DeSalvo T, Donahue M, Dratch A, Duca L, Duchin J, Dyal JW, Feldstein LR, Fenstersheib M, Fischer M, Fisher R, Foo C, Freeman-Ponder B, Fry AM, Gant J, Gautom R, Ghinai I, Gounder P, Grigg CT, Gunzenhauser J, Hall AJ, Han GS, Haupt T, Holshue M, Hunter J, Ibrahim MB, Jacobs MW, Jarashow MC, Joshi K, Kamali T, Kawakami V, Kim M, Kirking HL, Kita-Yarbro A, Klos R, Kobayashi M, Kocharian A, Lang M, Layden J, Leidman E, Lindquist S, Lindstrom S, Link-Gelles R, Marlow M, Mattison CP, McClung N, McPherson TD, Mello L, Midgley CM, Novosad S, Patel MT, Pettrone K, Pillai SK, Pray IW, Reese HE, Rhodes H, Robinson S, Rolfes M, Routh J, Rubin R, Rudman SL, Russell D, Scott S, Shetty V, Smith-Jeffcoat SE, Soda EA, Spitters C, Stierman B, Sunenshine R, Terashita D, Traub E, Vahey GM, Verani JR, Wallace M, Westercamp M, Wortham J, Xie A, Yousaf A, Zahn M.
        PLoS One. 2020 ;15(9):e0238342.
        Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19.

      7. Epidemiology of enterotoxigenic Escherichia coli infection in Minnesota, 2016-2017external icon
        Buuck S, Smith K, Fowler RC, Cebelinski E, Lappi V, Boxrud D, Medus C.
        Epidemiol Infect. 2020 Sep 1:1-26.

      8. Delay or avoidance of medical care because of COVID-19-related concerns - United States, June 2020external icon
        Czeisler M, Marynak K, Clarke KE, Salah Z, Shakya I, Thierry JM, Ali N, McMillan H, Wiley JF, Weaver MD, Czeisler CA, Rajaratnam SM, Howard ME.
        MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1250-1257.
        Temporary disruptions in routine and nonemergency medical care access and delivery have been observed during periods of considerable community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). However, medical care delay or avoidance might increase morbidity and mortality risk associated with treatable and preventable health conditions and might contribute to reported excess deaths directly or indirectly related to COVID-19 (2). To assess delay or avoidance of urgent or emergency and routine medical care because of concerns about COVID-19, a web-based survey was administered by Qualtrics, LLC, during June 24-30, 2020, to a nationwide representative sample of U.S. adults aged ≥18 years. Overall, an estimated 40.9% of U.S. adults have avoided medical care during the pandemic because of concerns about COVID-19, including 12.0% who avoided urgent or emergency care and 31.5% who avoided routine care. The estimated prevalence of urgent or emergency care avoidance was significantly higher among the following groups: unpaid caregivers for adults* versus noncaregivers (adjusted prevalence ratio [aPR] = 2.9); persons with two or more selected underlying medical conditions(†) versus those without those conditions (aPR = 1.9); persons with health insurance versus those without health insurance (aPR = 1.8); non-Hispanic Black (Black) adults (aPR = 1.6) and Hispanic or Latino (Hispanic) adults (aPR = 1.5) versus non-Hispanic White (White) adults; young adults aged 18-24 years versus adults aged 25-44 years (aPR = 1.5); and persons with disabilities(§) versus those without disabilities (aPR = 1.3). Given this widespread reporting of medical care avoidance because of COVID-19 concerns, especially among persons at increased risk for severe COVID-19, urgent efforts are warranted to ensure delivery of services that, if deferred, could result in patient harm. Even during the COVID-19 pandemic, persons experiencing a medical emergency should seek and be provided care without delay (3).

      9. Improved ascertainment of modes of HIV transmission in Ukraine indicates importance of drug injecting and homosexual riskexternal icon
        Dumchev K, Kornilova M, Kulchynska R, Azarskova M, Vitek C.
        BMC Public Health. 2020 Aug 26;20(1):1288.
        BACKGROUND: It is important to understand how HIV infection is transmitted in the population in order to guide prevention activities and properly allocate limited resources. In Ukraine and other countries where injecting drug use and homosexuality are stigmatized, the information about mode of transmission in case registration systems is often biased. METHODS: We conducted a cross-sectional survey in a random sample of patients registered at HIV clinics in seven regions of Ukraine in 2013-2015. The survey assessed behavioral risk factors and serological markers of viral hepatitis B and C. We analyzed the discrepancies between the registered mode of transmission and the survey data, and evaluated trends over 3 years. RESULTS: Of 2285 participants, 1032 (45.2%) were females. The proportion of new HIV cases likely caused by injecting drug use based on the survey data was 59.7% compared to 33.2% in official reporting, and proportion of cases likely acquired through homosexual transmission was 3.8% compared to 2.8%. We found a significant decrease from 63.2 to 57.5% in the proportion of injecting drug use-related cases and a steep increase from 2.5 to 5.2% in homosexual transmission over 3 years. CONCLUSIONS: The study confirmed the significant degree of misclassification of HIV mode of transmission among registered cases. The role of injecting drug use in HIV transmission is gradually decreasing, but remains high. The proportion of cases related to homosexual transmission is relatively modest, but is rapidly increasing, especially in younger men. Improvements in ascertaining the risk factor information are essential to monitor the epidemic and to guide programmatic response.

      10. A model for bringing TB expertise to HIV providers: Medical consultations to the CDC-funded Regional Tuberculosis Training and Medical Consultation Centers, 2013-2017external icon
        Fernando R, McDowell AC, Bhavaraju R, Fraimow H, Wilson JW, Armitige L, Haley C, Goswami ND.
        PLoS One. 2020 ;15(8):e0236933.
        BACKGROUND: Persons living with human immunodeficiency virus (HIV) are at a greater risk of developing tuberculosis (TB) compared to people without HIV and of developing complications due to the complexity of TB/HIV coinfection management. METHODS: During 2013-2017, the Centers for Disease Control and Prevention (CDC) funded 5 TB Regional Training and Medical Consultation Centers (RTMCCs) (now known as TB Centers of Excellence or COEs) to provide medical consultation to providers for TB disease and latent TB infection (LTBI), with data entered into a Medical Consultation Database (MCD). Descriptive analyses of TB/HIV-related consultations were conducted using SAS® software, version [9.4] to determine the distribution of year of consultation, medical setting and provider type, frequency of consultations regarding a pediatric (<18 years) patient, and to categorize key concepts and themes arising within consultation queries and medical consultant responses. RESULTS: Of 14,586 consultations captured by the MCD in 2013-2017, 544 (4%) were categorized as TB/HIV-related, with 100 (18%) received in 2013, 129 (24%) in 2014, 104 (19%) in 2015, 117 (22%) in 2016, and 94 (17%) in 2017. Most TB/HIV consultations came from nurses (54%) or physicians (43%) and from local (65%) or state health departments (10%). Only 17 (3%) of HIV-related consultations involved pediatric cases. Off the 544 TB/HIV consultations, 347 (64%) concerned the appropriate treatment regimen for TB/HIV or LTBI/HIV for a patient on or not on antiretroviral therapy (ART). CONCLUSIONS: The data support a clear and ongoing gap in areas of specialized HIV knowledge by TB experts that could be supplemented with proactive educational outreach. The specific categories of TB/HIV inquiries captured by this analysis are strategically informing future targeted training and educational activities planned by the CDC TB Centers of Excellence, as well as guiding HIV educational efforts at regional and national TB meetings.

      11. Community and close contact exposures associated with COVID-19 among symptomatic adults >/= 18 years in 11 outpatient health care facilities - United States, July 2020external icon
        Fisher KA, Tenforde MW, Feldstein LR, Lindsell CJ, Shapiro NI, Files DC, Gibbs KW, Erickson HL, Prekker ME, Steingrub JS, Exline MC, Henning DJ, Wilson JG, Brown SM, Peltan ID, Rice TW, Hager DN, Ginde AA, Talbot HK, Casey JD, Grijalva CG, Flannery B, Patel MM, Self WH.
        MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1258-1264.
        Community and close contact exposures continue to drive the coronavirus disease 2019 (COVID-19) pandemic. CDC and other public health authorities recommend community mitigation strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). Characterization of community exposures can be difficult to assess when widespread transmission is occurring, especially from asymptomatic persons within inherently interconnected communities. Potential exposures, such as close contact with a person with confirmed COVID-19, have primarily been assessed among COVID-19 cases, without a non-COVID-19 comparison group (3,4). To assess community and close contact exposures associated with COVID-19, exposures reported by case-patients (154) were compared with exposures reported by control-participants (160). Case-patients were symptomatic adults (persons aged ≥18 years) with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing. Control-participants were symptomatic outpatient adults from the same health care facilities who had negative SARS-CoV-2 test results. Close contact with a person with known COVID-19 was more commonly reported among case-patients (42%) than among control-participants (14%). Case-patients were more likely to have reported dining at a restaurant (any area designated by the restaurant, including indoor, patio, and outdoor seating) in the 2 weeks preceding illness onset than were control-participants (adjusted odds ratio [aOR] = 2.4; 95% confidence interval [CI] = 1.5-3.8). Restricting the analysis to participants without known close contact with a person with confirmed COVID-19, case-patients were more likely to report dining at a restaurant (aOR = 2.8, 95% CI = 1.9-4.3) or going to a bar/coffee shop (aOR = 3.9, 95% CI = 1.5-10.1) than were control-participants. Exposures and activities where mask use and social distancing are difficult to maintain, including going to places that offer on-site eating or drinking, might be important risk factors for acquiring COVID-19. As communities reopen, efforts to reduce possible exposures at locations that offer on-site eating and drinking options should be considered to protect customers, employees, and communities.

      12. Human immunodeficiency virus prevention for people who use drugs: Overview of reviews and the ICOS of PICOSexternal icon
        Johnson WD, Rivadeneira N, Adegbite AH, Neumann MS, Mullins MM, Rooks-Peck C, Wichser ME, McDonald CM, Higa DH, Sipe TA.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S278-s300.
        BACKGROUND: This article summarizes the results from systematic reviews of human immunodeficiency virus (HIV) prevention interventions for people who use drugs (PWUD). We performed an overview of reviews, meta-analysis, meta-epidemiology, and PROSPERO Registration CRD42017070117. METHODS: We conducted a comprehensive systematic literature search using the Centers for Disease Control and Prevention HIV/AIDS Prevention Research Synthesis Project database to identify quantitative systematic reviews of HIV public heath interventions with PWUD published during 2002-2017. We recombined results of US studies across reviews to quantify effects on HIV infections, continuum of HIV care, sexual risk, and 5 drug-related outcomes (sharing injection equipment, injection frequency, opioid use, general drug use, and participation in drug treatment). We conducted summary meta-analyses separately for reviews of randomized controlled trials (RCTs) and quasi-experiments. We stratified effects by 5 intervention types: behavioral-psychosocial (BPS), syringe service programs (SSP), opioid agonist therapy (OAT), financial and scheduling incentives (FSI), and case management (CM). RESULTS: We identified 16 eligible reviews including >140 US studies with >55 000 participants. Summary effects among US studies were significant and favorable for 4 of 5 outcomes measured under RCT (eg, reduced opioid use; odds ratio [OR] = 0.70, confidence interval [CI] = 0.56-0.89) and all 6 outcomes under quasi-experiments (eg, reduced HIV infection [OR = 0.42, CI = 0.27-0.63]; favorable continuum of HIV care [OR = 0.68, CI = 0.53-0.88]). Each intervention type showed effectiveness on 1-6 outcomes. Heterogeneity was moderate to none for RCT but moderate to high for quasi-experiments. CONCLUSIONS: Behavioral-psychosocial, SSP, OAT, FSI, and CM interventions are effective in reducing risk of HIV and sequelae of injection and other drug use, and they have a continuing role in addressing the opioid crisis and Ending the HIV Epidemic.

      13. BACKGROUND AND AIMS: Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy frequently preceded by an infection with Campylobacter jejuni or non-specific infections, and rarely by a vaccination. Due to a lack of a pathognomonic finding or biomarker, its diagnosis is based on a typical constellation of clinical and paraclinical symptoms and findings. The Brighton Collaboration GBS Working Group published in 2011 GBS case definitions and guidelines for diagnosis to improve the registration of GBS cases occurring in conjunction with vaccination programs world-wide. METHODS: We applied these criteria to two historical studies on GBS in children and adolescents performed retrospectively from 1989 to 1994 and prospectively from 1998 to 2002. RESULTS: The clinical criteria were met in 91% of the retrospective and all of the prospective cases. CSF investigations were conducted in all patients and revealed cytoalbuminologic dissociation in 80% of the retrospective and 75% of the prospective cohort. Nerve conduction studies were performed in 61% and 69% of the cohorts, respectively, and were pathological in 92% each. INTERPRETATION: The Brighton criteria are well-suited to capture GBS in retro- and prospective studies. However, because they are designed to diagnose classical symmetric and ascending GBS and Fisher syndrome, very rare topographical variants of GBS such as the pharyngo-cervico-brachial variant and others could be missed.

      14. Outcome of HIV testing among family members of index cases across 36 facilities in Abidjan, Côte d'Ivoireexternal icon
        Lasry A, Danho NK, Hulland EN, Diokouri AD, Kingbo MH, Doumatey NI, Ekra AK, Ebah LG, Kouamé H, Hedje J, Jean-Baptiste AE.
        AIDS Behav. 2020 Sep 1.
        In Côte d'Ivoire, the Family Approach to Counseling and Testing (FACT) program began in 2015 and provides facility-based HIV testing to the sexual partners, children and other household family members of HIV-positive index cases. We evaluated whether the FACT program is an effective approach to HIV case finding. We reviewed 1762 index patient charts to evaluate outcomes of the FACT program, held across 36 facilities in Abidjan. Index cases enumerated a total of 644 partners, 2301 children and 508 other family members including parents and siblings. Among the partners tested for HIV, the positivity rate was 21%; for children the positivity rate was 5% and for all other family members the positivity rate was 11%. Offering HIV testing services to the family members of HIV positive index cases is an effective approach to case finding in Côte d'Ivoire. Particularly, offering HIV testing to the partners of positive women index cases can be key to identifying previously undiagnosed men and linking them to treatment.

      15. Infectious diseases and injection drug use: Public health burden and responseexternal icon
        Levitt A, Mermin J, Jones CM, See I, Butler JC.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S213-s217.

      16. Healthcare access and utilization among persons who inject drugs in Medicaid expansion and nonexpansion states: 22 United States cities, 2018external icon
        Lewis R, Baugher AR, Finlayson T, Wejnert C, Sionean C.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S420-s428.
        BACKGROUND: Medicaid expansion under the Affordable Care Act increased insurance coverage, access to healthcare, and substance use disorder treatment, for many Americans. We assessed differences in healthcare access and utilization among persons who inject drugs (PWID) by state Medicaid expansion status. METHODS: In 2018, PWID were interviewed in 22 US cities for National HIV Behavioral Surveillance. We analyzed data from PWID aged 18-64 years who reported illicit use of opioids (n = 9957) in the past 12 months. Poisson regression models with robust standard errors were used to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were used to examine differences by Medicaid expansion status in indicators of healthcare access and utilization. RESULTS: Persons who inject drugs in Medicaid expansion states were more likely to have insurance (87% vs 36%; aPR, 2.3; 95% CI, 2.0-2.6), a usual source of healthcare (53% vs 34%; aPR, 1.5; 95% CI, 1.3-1.9), and have used medication-assisted treatment (61% vs 36%; aPR, 1.4; 95% CI, 1.1-1.7), and they were less likely to have an unmet need for care (21% vs 39%; aPR, 0.6; 95% CI, 0.4-0.7) than those in nonexpansion states. CONCLUSIONS: Low insurance coverage, healthcare access, and medication-assisted treatment utilization among PWID in some areas could hinder efforts to end the intertwined human immunodeficiency virus and opioid overdose epidemics.

      17. In 2015, a large human immunodeficiency virus (HIV) outbreak occurred among persons who inject drugs (PWID) in Indiana. During 2016-2019, additional outbreaks among PWID occurred across the United States. Based on information disseminated by responding health departments and Centers for Disease Control and Prevention (CDC) involvement, we offer perspectives about characteristics of and public health responses to 6 such outbreaks. Across outbreaks, injection of opioids (including fentanyl) or methamphetamine predominated; many PWID concurrently used opioids and methamphetamine or cocaine. Commonalities included homelessness or unstable housing, previous incarceration, and hepatitis C virus exposure. All outbreaks occurred in metropolitan areas, including some with substantial harm reduction and medical programs targeted to PWID. Health departments experienced challenges locating case patients and contacts, linking and retaining persons in care, building support to strengthen harm-reduction programs, and leveraging resources. Expanding the concept of vulnerability to HIV outbreaks and other lessons learned can be considered for preventing, detecting, and responding to future outbreaks among PWID.

      18. Digital auscultation in PERCH: Associations with chest radiography and pneumonia mortality in childrenexternal icon
        McCollum ED, Park DE, Watson NL, Fancourt NS, Focht C, Baggett HC, Abdullah Brooks W, Howie SR, Kotloff KL, Levine OS, Madhi SA, Murdoch DR, Scott JA, Thea DM, Awori JO, Chipeta J, Chuananon S, DeLuca AN, Driscoll AJ, Ebruke BE, Elhilal M, Emmanouilidou D, Githua LP, Higdon MM, Hossain L, Jahan Y, Karron RA, Kyalo J, Moore DP, Mulindwa JM, Naorat S, Prosperi C, Verwey C, West JE, Knoll MD, Brien KL, Feikin DR, Hammitt LL.
        Pediatr Pulmonol. 2020 Aug 27.
        BACKGROUND: Whether digitally recorded lung sounds are associated with radiographic pneumonia or clinical outcomes among children in low-income and middle-income countries is unknown. We sought to address these knowledge gaps. METHODS: We enrolled 1-59 month old children hospitalized with pneumonia at eight African and Asian Pneumonia Etiology Research for Child Health sites in six countries, recorded digital stethoscope lung sounds, obtained chest radiographs, and collected clinical outcomes. Recordings were processed and reclassified into binary categories positive or negative for adventitial lung sounds. Listening and reading panels classified recordings and radiographs. Recording classification associations with chest radiographs with World Health Organization (WHO)-defined primary endpoint pneumonia (radiographic pneumonia) or mortality were evaluated. We also examined case fatality among risk strata. RESULTS: Among children without WHO danger signs, wheezing (without crackles) had a lower adjusted odds ratio (aOR) for radiographic pneumonia (0.35, 95% confidence interval (CI) 0.15, 0.82), compared to children with normal recordings. Neither crackle only (no wheeze) (aOR 2.13, 95%CI 0.91, 4.96) or any wheeze (with or without crackle) (aOR 0.63, 95%CI 0.34, 1.15) were associated with radiographic pneumonia. Among children with WHO danger signs no lung recording classification was independently associated with radiographic pneumonia, although trends towards greater odds of radiographic pneumonia were observed among children classified with crackle only (no wheeze) or any wheeze (with or without crackle). Among children without WHO danger signs, those with recorded wheezing had a lower case fatality than those without wheezing (3.8% vs 9.1%, p=0.03). CONCLUSIONS: Among lower risk children without WHO danger signs digitally recorded wheezing is associated with a lower odds for radiographic pneumonia and with lower mortality. Although further research is needed, these data indicate that with further development digital auscultation may eventually contribute to child pneumonia care. This article is protected by copyright. All rights reserved.

      19. Analysis of MarketScan data for immunosuppressive conditions and hospitalizations for acute respiratory illness, United Statesexternal icon
        Patel M, Chen J, Kim S, Garg S, Flannery B, Haddadin Z, Rankin D, Halasa N, Talbot HK, Reed C.
        Emerg Infect Dis. 2020 Aug;26(8):1720-1730.
        Increasing use of immunosuppressive biologic therapies poses a challenge for infectious diseases. Immunosuppressed patients have a high risk for influenza complications and an impaired immune response to vaccines. The total burden of immunosuppressive conditions in the United States, including those receiving emerging biologic therapies, remains unknown. We used the national claims database MarketScan to estimate the prevalence of immunosuppressive conditions and risk for acute respiratory illnesses (ARIs). We studied 47.2 million unique enrollees, representing 115 million person-years of observation during 2012-2017, and identified immunosuppressive conditions in 6.2% adults 18-64 years of age and 2.6% of children <18 years of age. Among 542,105 ARI hospitalizations, 32% of patients had immunosuppressive conditions. The risk for ARI hospitalizations was higher among enrollees with immunosuppression than among nonimmunosuppressed enrollees. Future efforts should focus on developing improved strategies, including vaccines, for preventing influenza in immunosuppressed patients, who are an increasing population in the United States.

      20. Human immunodeficiency virus testing, diagnosis, linkage to care, and prevention services among persons who inject drugs, United States, 2012-2017external icon
        Rao S, Song W, Mulatu MS, Seena E, Essuon A, Heitgerd J.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S268-s277.
        BACKGROUND: Human immunodeficiency virus (HIV) testing and early diagnosis is associated with effective disease management and reduction in HIV transmission among persons who inject drugs (PWID). We examined trends in HIV testing outcomes among PWID during 2012-2017. METHODS: Centers for Disease Control and Prevention (CDC)-funded HIV testing data submitted by 61 health departments and 150 directly-funded community-based organizations during 2012-2017 were analyzed. We calculated estimated annual percentage changes (EAPC) to assess trends for HIV testing and testing outcomes. RESULTS: A total of 19 739 857 CDC-funded HIV tests were conducted during 2012-2017. Of these, 529 349 (2.7%) were among PWID. The percentage of newly diagnosed HIV increased from .7% in 2012 to .8% in 2017 (EAPC, 4.15%). The percentage interviewed for partner services increased from 46.7% in 2012 to 66.3% in 2017 (EAPC, 1.81%). No significant change was identified in trends for linkage to HIV medical care ≤90 days after diagnosis (EAPC, 0.52%) or referral to HIV prevention services (EAPC, 0.98%). CONCLUSIONS: Human immunodeficiency virus testing data revealed an increasing trend in newly diagnosed HIV among PWID but not linkage to HIV medical care or referral to prevention services. Expanding efforts to increase HIV testing and enhance linkage to services can lead to reductions in HIV transmission and improved health outcomes.

      21. Employing molecular phylodynamic methods to identify and forecast HIV transmission clusters in public health settings: A qualitative studyexternal icon
        Rich SN, Richards VL, Mavian CN, Switzer WM, Rife Magalis B, Poschman K, Geary S, Broadway SE, Bennett SB, Blanton J, Leitner T, Boatwright JL, Stetten NE, Cook RL, Spencer EC, Salemi M, Prosperi M.
        Viruses. 2020 Aug 22;12(9).
        Molecular HIV surveillance is a promising public health strategy for curbing the HIV epidemic. Clustering technologies used by health departments to date are limited in their ability to infer/forecast cluster growth trajectories. Resolution of the spatiotemporal dynamics of clusters, through phylodynamic and phylogeographic modelling, is one potential strategy to develop a forecasting tool; however, the projected utility of this approach needs assessment. Prior to incorporating novel phylodynamic-based molecular surveillance tools, we sought to identify possible issues related to their feasibility, acceptability, interpretation, and utility. Qualitative data were collected via focus groups among field experts (n = 17, 52.9% female) using semi-structured, open-ended questions. Data were coded using an iterative process, first through the development of provisional themes and subthemes, followed by independent line-by-line coding by two coders. Most participants routinely used molecular methods for HIV surveillance. All agreed that linking molecular sequences to epidemiological data is important for improving HIV surveillance. We found that, in addition to methodological challenges, a variety of implementation barriers are expected in relation to the uptake of phylodynamic methods for HIV surveillance. The participants identified several opportunities to enhance current methods, as well as increase the usability and utility of promising works-in-progress.

      22. INTRODUCTION: Most clinical trials for new antiretroviral (ARV) agents are conducted among narrowly defined adult populations. Only after safety and efficacy have been clearly demonstrated among adults living with HIV are trials including adolescents, children and infants conducted. This approach contributes to significant delays in the availability of optimal new ARV regimens for infants, children and adolescents. This commentary discusses issues related to the inclusion of adolescents aged 12 to 18 years in initial HIV clinical phase 3 trials of novel antiretrovirals (ARVs) or conducting parallel phase 3 clinical trials among adolescents. DISCUSSION: The absorption, metabolic and excretion or elimination pathways for drugs do not significantly differ between adolescents and adults. In fact, dosing recommendations for ARVs are the same for adults and adolescents who meet the age and weight criteria. Although conducting clinical trials among adolescents present special challenges (e.g. consenting minors and concerns about trial completion and contraception), these challenges can be addressed to obtain high-quality trial results. Importantly, new agents and optimized combinations have more favourable dosing schedules and side-effect profiles and are more effective ARV agents with higher HIV drug resistance thresholds, which would be extremely beneficial to improve outcomes among HIV-positive adolescents. CONCLUSIONS: Adolescents may not present with significantly different pharmacokinetic characteristics from those in adults. Including HIV-positive adolescents in phase 3 ARV clinical trials, either with adults or in specific adolescent studies conducted in parallel, would allow adolescents to access promising, more effective treatment for HIV years earlier than with the current stepwise approach.

      23. Injection drug use-associated candidemia: Incidence, clinical features, and outcomes, east Tennessee, 2014-2018external icon
        Rossow JA, Gharpure R, Brennan J, Relan P, Williams SR, Vallabhaneni S, Jackson BR, Graber CR, Hillis SR, Schaffner W, Dunn JR, Jones TF.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S442-s450.
        BACKGROUND: Injection drug use (IDU) is an established but uncommon risk factor for candidemia. Surveillance for candidemia is conducted in East Tennessee, an area heavily impacted by the opioid crisis and IDU. We evaluated IDU-associated candidemia to characterize the epidemiology and estimate the burden. METHODS: We assessed the proportion of candidemia cases related to IDU during January 1, 2014-September 30, 2018, estimated candidemia incidence in the overall population and among persons who inject drugs (PWID), and reviewed medical records to compare clinical features and outcomes among IDU-associated and non-IDU candidemia cases. RESULTS: The proportion of IDU-associated candidemia cases in East Tennessee increased from 6.1% in 2014 to 14.5% in 2018. Overall candidemia incidence in East Tennessee was 13.5/100 000, and incidence among PWID was 402-1895/100 000. Injection drug use-associated cases were younger (median age, 34.5 vs 60 years) and more frequently had endocarditis (39% vs 3%). All-cause 30-day mortality was 8% among IDU-associated cases versus 25% among non-IDU cases. CONCLUSIONS: A growing proportion of candidemia in East Tennessee is associated with IDU, posing an additional burden from the opioid crisis. The lower mortality among IDU-associated cases likely reflects in part the younger demographic; however, Candida endocarditis seen among approximately 40% underscores the seriousness of the infection and need for prevention.

      24. When used appropriately, pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition. Early implementation outcomes often suggest poor PrEP adherence and persistence; however, this intervention is time-limited and the need for PrEP fluctuates as risk behaviours change. In this Viewpoint we examine the current guidelines and early programmatic outcomes after starting, stopping, and restarting PrEP, and we review the implications of PrEP in relation to HIV testing algorithms. Guidelines suggest to discontinue PrEP when a person is no longer at risk for HIV, but effectively implementing this strategy requires support tools to make the decision of stopping and restarting PrEP that considers the complex relationship between risk perceptions and risk behaviours. Safely discontinuing PrEP also requires greater understanding of the daily dosing duration that is needed to protect the person after their last HIV exposure. Additionally, clear strategies are needed to re-engage a person as their HIV exposure risk changes over time.

      25. National public health burden estimates of endocarditis and skin and soft-tissue infections related to injection drug use: A reviewexternal icon
        See I, Gokhale RH, Geller A, Lovegrove M, Schranz A, Fleischauer A, McCarthy N, Baggs J, Fiore A.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S429-s436.
        BACKGROUND: Despite concerns about the burden of the bacterial and fungal infection syndromes related to injection drug use (IDU), robust estimates of the public health burden of these conditions are lacking. The current article reviews and compares data sources and national burden estimates for infective endocarditis (IE) and skin and soft-tissue infections related to IDU in the United States. METHODS: A literature review was conducted for estimates of skin and soft-tissue infection and endocarditis disease burden with related IDU or substance use disorder terms since 2011. A range of the burden is presented, based on different methods of obtaining national projections from available data sources or published data. RESULTS: Estimates using available data suggest the number of hospital admissions for IE related to IDU ranged from 2900 admissions in 2013 to more than 20 000 in 2017. The only source of data available to estimate the annual number of hospitalizations and emergency department visits for skin and soft-tissue infections related to IDU yielded a crude estimate of 98 000 such visits. Including people who are not hospitalized, a crude calculation suggests that 155 000-540 000 skin infections related to IDU occur annually. DISCUSSION: These estimates carry significant limitations. However, regardless of the source or method, the burden of disease appears substantial, with estimates of thousands of episodes of IE among persons with IDU and at least 100 000 persons who inject drugs (PWID) with skin and soft-tissue infections annually in the United States. Given the importance of these types of infections, more robust and reliable estimates are needed to better quantitate the occurrence and understand the impact of interventions.

      26. BACKGROUND: While increases in overdoses, viral hepatitis, and endocarditis associated with drug use have been well-documented in North Carolina, the full scope of invasive drug-related infections (IDRIs) has not. We characterized trends in IDRIs among hospitalized patients in North Carolina. METHODS: We compared invasive infections that were related or not related to drug use among hospitalized patients aged 18-55 years based on retrospective review of administrative records from 2010-2018. Hospitalizations for endocarditis, central nervous system/spine infections, osteomyelitis, and septic arthritis were labeled as IDRIs if discharge codes included opioid and/or amphetamine misuse. Trends, rates, and distributions were calculated. RESULTS: Among 44 851 hospitalizations for the specified infections, 2830 (6.3%) were IDRIs. The proportion of infections attributable to drug use increased from 1.5% (2010) to 13.1% (2018), and the rate grew from 1.2 to 15.1 per 100 000. Compared with those who had non-drug-related infections, patients with IDRIs were younger (median age, 35 vs 46 years), more likely to be non-Hispanic white (81% vs 56%), and had longer hospitalizations (median, 8 vs 6 days). 43% of hospitalizations for IDRIs involved infective endocarditis. CONCLUSIONS: The rate of IDRIs in North Carolina increased substantially during 2010-2018, indicating an urgent need for enhanced infection prevention, harm reduction, and addiction services aimed at community and inpatient settings.

      27. Characterizing norovirus transmission from outbreak data, United Statesexternal icon
        Steele MK, Wikswo ME, Hall AJ, Koelle K, Handel A, Levy K, Waller LA, Lopman BA.
        Emerg Infect Dis. 2020 Aug;26(8):1818-1825.
        Norovirus is the leading cause of acute gastroenteritis outbreaks in the United States. We estimated the basic (R(0)) and effective (R(e)) reproduction numbers for 7,094 norovirus outbreaks reported to the National Outbreak Reporting System (NORS) during 2009-2017 and used regression models to assess whether transmission varied by outbreak setting. The median R(0) was 2.75 (interquartile range [IQR] 2.38-3.65), and median R(e) was 1.29 (IQR 1.12-1.74). Long-term care and assisted living facilities had an R(0) of 3.35 (95% CI 3.26-3.45), but R(0) did not differ substantially for outbreaks in other settings, except for outbreaks in schools, colleges, and universities, which had an R(0) of 2.92 (95% CI 2.82-3.03). Seasonally, R(0) was lowest (3.11 [95% CI 2.97-3.25]) in summer and peaked in fall and winter. Overall, we saw little variability in transmission across different outbreaks settings in the United States.

      28. Three years of progress toward achieving hepatitis C elimination in the country of Georgia, April 2015-March 2018external icon
        Tsertsvadze T, Gamkrelidze A, Chkhartishvili N, Abutidze A, Sharvadze L, Kerashvili V, Butsashvili M, Metreveli D, Gvinjilia L, Shadaker S, Nasrullah M, Adamia E, Zeuzem S, Afdhal N, Arora S, Thornton K, Skaggs B, Kuchuloria T, Lagvilava M, Sergeenko D, Averhoff F.
        Clin Infect Dis. 2020 Aug 22;71(5):1263-1268.
        BACKGROUND: In April 2015, in collaboration with the US Centers for Disease Control and Prevention and Gilead Sciences, the country of Georgia embarked on the world's first hepatitis C elimination program. We aimed to assess progress toward elimination targets 3 years after the start of the elimination program. METHODS: We constructed a hepatitis C virus (HCV) care cascade for adults in Georgia, based on the estimated 150 000 persons aged ≥18 years with active HCV infection. All patients who were screened or entered the treatment program during April 2015-March 2018 were included in the analysis. Data on the number of persons screened for HCV were extracted from the national HCV screening database. For the treatment component, we utilized data from the Georgia National HCV treatment program database. Available treatment options included sofosbuvir and ledipasvir/sofosbuvir-based regimens. RESULTS: Since April 2015, a cumulative 974 817 adults were screened for HCV antibodies; 86 624 persons tested positive, of whom 61 925 underwent HCV confirmatory testing. Among the estimated 150 000 adults living with chronic hepatitis C in Georgia, 52 856 (35.1%) were diagnosed, 45 334 (30.2%) initiated treatment with direct-acting antivirals, and 29 090 (19.4%) achieved a sustained virologic response (SVR). Overall, 37 256 persons were eligible for SVR assessment; of these, only 29 620 (79.5%) returned for evaluation. The SVR rate was 98.2% (29 090/29 620) in the per-protocol analysis and 78.1% (29 090/37 256) in the intent-to-treat analysis. CONCLUSIONS: Georgia has made substantial progress in the path toward eliminating hepatitis C. Scaling up of testing and diagnosis, along with effective linkage to treatment services, is needed to achieve the goal of elimination.

      29. Human immunodeficiency virus (HIV) outbreak investigation among persons who inject drugs in Massachusetts enhanced by HIV sequence dataexternal icon
        Tumpney M, John B, Panneer N, McClung RP, Campbell EM, Roosevelt K, DeMaria A, Buchacz K, Switzer WM, Lyss S, Cranston K.
        J Infect Dis. 2020 Sep 2;222(Supplement_5):S259-s267.
        BACKGROUND: The Massachusetts Department of Public Health and the Centers for Disease Control and Prevention collaborated to characterize a human immunodeficiency virus (HIV) outbreak in northeastern Massachusetts and prevent further transmission. We determined the contributions of HIV sequence data to defining the outbreak. METHODS: Human immunodeficiency virus surveillance and partner services data were analyzed to understand social and molecular links within the outbreak. Cases were defined as HIV infections diagnosed during 2015-2018 among people who inject drugs with connections to northeastern Massachusetts or HIV infections among other persons named as partners of a case or whose HIV polymerase sequence linked to another case, regardless of diagnosis date or geography. RESULTS: Of 184 cases, 65 (35%) were first identified as part of the outbreak through molecular analysis. Twenty-nine cases outside of northeastern Massachusetts were molecularly linked to the outbreak. Large molecular clusters (75, 28, and 11 persons) were identified. Among 161 named partners, 106 had HIV; of those, 40 (38%) diagnoses occurred through partner services. CONCLUSIONS: Human immunodeficiency virus sequence data increased the case count by 55% and expanded the geographic scope of the outbreak. Human immunodeficiency virus sequence and partner services data each identified cases that the other method would not have, maximizing prevention and care opportunities for HIV-infected persons and their partners.

    • Disaster Control and Emergency Services
      1. Hurricane evacuation laws in eight southern U.S. coastal states - December 2018external icon
        Kruger J, Smith MJ, Chen B, Paetznick B, Bradley BM, Abraha R, Logan M, Chang ER, Sunshine G, Romero-Steiner S.
        MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1233-1237.
        National Preparedness month is observed every September as a public service reminder of the importance of personal and community preparedness for all events; it coincides with the peak of the hurricane season in the United States. Severe storms and hurricanes can have long-lasting effects at all community levels. Persons who are prepared and well-informed are often better able to protect themselves and others (1). Major hurricanes can devastate low-lying coastal areas and cause injury and loss of life from storm surge, flooding, and high winds (2). State and local government entities play a significant role in preparing communities for hurricanes and by evacuating coastal communities before landfall to reduce loss of life from flooding, wind, and power outages (3). Laws can further improve planning and outreach for catastrophic events by ensuring explicit statutory authority over evacuations of communities at risk (4). State evacuation laws vary widely and might not adequately address information and communication flows to reach populations living in disaster-prone areas who are at risk. To understand the range of evacuation laws in coastal communities that historically have been affected by hurricanes, a systematic policy scan of the existing laws supporting hurricane evacuation in eight southern coastal states (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, South Carolina, and Texas) was conducted. After conducting a thematic analysis, this report found that all eight states have laws to execute evacuation orders, traffic control (egress/ingress), and evacuation to shelters. However, only four of the states have laws related to community outreach, delivery of public education programs, and public notice requirements. The findings in this report suggest a need for authorities in hurricane-prone states to review how to execute evacuation policies, particularly with respect to community outreach and communication to populations at risk. Implementation of state evacuation laws and policies that support hurricane evacuation management can help affected persons avoid harm and enhance community resiliency (5). Newly emerging and re-emerging infectious diseases, such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have and will continue to additionally challenge hurricane evacuations.

    • Disease Reservoirs and Vectors
      1. The COVID-19 pandemic should not derail global vector control effortsexternal icon
        Seelig F, Bezerra H, Cameron M, Hii J, Hiscox A, Irish S, Jones RT, Lang T, Lindsay SW, Lowe R, Nyoni TM, Power GM, Quintero J, Stewart-Ibarra AM, Tusting LS, Tytheridge S, Logan JG.
        PLoS Negl Trop Dis. 2020 Aug;14(8):e0008606.

    • Environmental Health
      1. Association of exposure to endocrine-disrupting chemicals during adolescence with attention-deficit/hyperactivity disorder-related behaviorsexternal icon
        Shoaff JR, Coull B, Weuve J, Bellinger DC, Calafat AM, Schantz SL, Korrick SA.
        JAMA Netw Open. 2020 Aug 3;3(8):e2015041.
        IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurobehavioral disorder. Studies suggest that prenatal and early childhood exposure to endocrine-disrupting chemicals may be associated with ADHD, but the association during adolescence has not been studied to date. OBJECTIVE: To evaluate the association between exposure to select endocrine-disrupting chemicals during adolescence and ADHD-related behaviors. DESIGN, SETTING, AND PARTICIPANTS: For this cross-sectional analysis, data were collected from 205 adolescents in the New Bedford Cohort, an ongoing prospective birth cohort, between June 18, 2011, and June 10, 2014. The adolescents provided spot urine samples and underwent neurodevelopmental testing. Statistical analyses performed from January 15 to December 31, 2019, used a repeated-measures analysis with multivariate modified Poisson models to estimate the adjusted relative risk of ADHD-related behaviors associated with exposure to endocrine-disrupting chemicals. EXPOSURES: Urinary biomarker concentrations of endocrine-disrupting chemicals or their metabolites, including phthalates, parabens, phenols, and triclocarban, were quantified. Summary exposure measures were created, combining biomarker concentrations of chemicals with a shared mechanism of action, exposure pathway, or chemical class. MAIN OUTCOMES AND MEASURES: Behaviors related to ADHD were assessed with up to 14 indices from self-, parent-, and teacher-completed behavioral checklists using validated and standardized instruments; specifically, the Conners Attention Deficit Scale and the Behavior Assessment System for Children, Second Edition. Scores on each index were dichotomized to identify those with evidence of a significant behavioral problem, defined by each scale's interpretive guidelines. RESULTS: Among the 205 participants, the mean (SD) age at assessment was 15.3 (0.7) years, with 112 girls (55%) and 124 non-Hispanic White participants (61%). The median urine concentrations were 0.45 μmol/L of Σantiandrogenic phthalates, 0.13 μmol/L of ΣDEHP metabolites, 0.49 μmol/L of Σpersonal care product phthalates, 0.35 μmol/L of Σparabens, 0.02 μmol/L of Σbisphenols, and 0.02 μmol/L of Σdichlorophenols. A total of 82 (40%) had scores consistent with a significant behavioral problem, whereas 39 (19%) had an ADHD diagnosis. Each 2-fold increase in the sum of antiandrogenic phthalate concentrations was associated with a 1.34 (95% CI, 1.00-1.79) increase in the risk of significant ADHD-related behavior problems, whereas a 2-fold increase in the sum of dichlorophenols was associated with a 1.15 (95% CI, 1.01-1.32) increased risk. These associations tended to be stronger in male participants, but comparisons of sex-specific differences were imprecise. CONCLUSIONS AND RELEVANCE: Endocrine-disrupting chemicals are used in a wide variety of consumer products resulting in ubiquitous exposure. The study findings suggest that exposure to some of these chemicals, particularly certain phthalates, during adolescence may be associated with behaviors characteristic of ADHD.

    • Epidemiology and Surveillance
      1. Extrapolating sparse gold standard cause of death designations to characterize broader catchment areasexternal icon
        Lyles RH, Cunningham SA, Kundu S, Bassat Q, Mandomando I, Sacoor C, Akelo V, Onyango D, Zielinski-Gutierrez E, Taylor AW.
        Epidemiologic Methods. 2020 .
        The Child Health and Mortality Prevention Surveillance (CHAMPS) Network is designed to elucidate and track causes of under-5 child mortality and stillbirth in multiple sites in sub-Saharan Africa and South Asia using advanced surveillance, laboratory and pathology methods. Expert panels provide an arguable gold standard determination of underlying cause of death (CoD) on a subset of child deaths, in part through examining tissue obtained via minimally invasive tissue sampling (MITS) procedures. We consider estimating a population-level distribution of CoDs based on this sparse but precise data, in conjunction with data on subgrouping characteristics that are measured on the broader population of cases and are potentially associated with selection for MITS and with cause-specific mortality. We illustrate how estimation of each underlying CoD proportion using all available data can be addressed equivalently in terms of a Horvitz-Thompson adjustment or a direct standardization, uncovering insights relevant to the designation of appropriate subgroups to adjust for non-representative sampling. Taking advantage of the functional form of the result when expressed as a multinomial distribution-based maximum likelihood estimator, we propose small-sample adjustments to Bayesian credible intervals based on Jeffreys or related weakly informative Dirichlet prior distributions. Our analyses of early data from CHAMPS sites in Kenya and Mozambique and accompanying simulation studies demonstrate the validity of the adjustment approach under attendant assumptions, together with marked performance improvements associated with the proposed adjusted Bayesian credible intervals. Adjustment for non-representative sampling of those validated via gold standard diagnostic methods is a critical endeavor for epidemiologic studies like CHAMPS that seek extrapolation of CoD proportion estimates.

    • Health Economics
      1. Cost estimates of diarrhea hospitalizations among children <5 years old in Zimbabweexternal icon
        Mujuru HA, Burnett E, Nathoo KJ, Ticklay I, Gonah NA, Mukaratirwa A, Berejena C, Manangazira P, Rupfutse M, Chavers T, Weldegebriel GG, Mwenda JM, Parashar UD, Tate JE.
        Vaccine. 2020 Aug 29.
        INTRODUCTION: Diarrhoea is a leading killer of children <5 years old, accounting for 480,000 deaths in 2017. Zimbabwe introduced Rotarix into its vaccination program in 2014. In this evaluation, we estimate direct medical, direct non-medical, and indirect costs attributable to a diarrhea hospitalization in Zimbabwe after rotavirus vaccine introduction. METHODS: Children <5 years old admitted to Harare Central Hospital from June 2018 to April 2019 with acute watery diarrhea were eligible for this evaluation. A 3-part structured questionnaire was used to collect data by interview from the child's family and by review of the medical record. A stool specimen was also collected and tested for rotavirus. Direct medical costs were the sum of medications, consumables, diagnostic tests, and service delivery costs. Direct non-medical costs were the sum of transportation, meals and lodging for caregivers. Indirect costs are the lost income for household members. RESULTS: A total of 202 children were enrolled with a median age of 12 months (IQR: 7-21) and 48 (24%) had malnutrition. Children were sick for a median of 2 days and most had received outpatient medical care prior to admission. The median monthly household income was higher for well-nourished children compared to malnourished children (p < 0.001). The median total cost of a diarrhea illness resulting in hospitalization was $293.74 (IQR: 188.42, 427.89). Direct medical costs, with a median of $251.74 (IQR: 155.42, 390.96), comprised the majority of the total cost. Among children who tested positive for rotavirus, the median total illness cost was $243.78 (IQR: 160.92, 323.84). The median direct medical costs were higher for malnourished than well-nourished children (p < 0.001). CONCLUSION: Direct medical costs are the primary determinant of diarrhea illness costs in Zimbabwe. The descriptive findings from this evaluation are an important first step in calculating the cost effectiveness of rotavirus vaccine.

      2. Health utility estimates and their application to HIV prevention in the United States: Implications for cost-effectiveness modeling and future research needsexternal icon
        Whitham HK, Hutchinson AB, Shrestha RK, Kuppermann M, Grund B, Shouse RL, Sansom SL.
        MDM Policy Pract. 2020 Jul-Dec;5(2).
        Objectives. Health utility estimates from the current era of HIV treatment, critical for cost-effectiveness analyses (CEA) informing HIV health policy, are limited. We examined peer-reviewed literature to assess the appropriateness of commonly referenced utilities, present previously unreported quality-of-life data from two studies, and discuss future implications for HIV-related CEA. Methods. We searched a database of cost-effectiveness analyses specific to HIV prevention efforts from 1999 to 2016 to identify the most commonly referenced sources for health utilities and to examine practices around using and reporting health utility data. Additionally, we present new utility estimates from the Centers of Disease Control and Prevention's Medical Monitoring Project (MMP) and the INSIGHT Strategies for Management of Anti-Retroviral Therapy (SMART) trial. We compare data collection time frames, sample characteristics, assessment methods, and key estimates. Results. Data collection for the most frequently cited utility estimates ranged from 1985 to 1997, predating modern HIV treatment. Reporting practices around utility weights are poor and lack details on participant characteristics, which may be important stratifying factors for CEA. More recent utility estimates derived from MMP and SMART were similar across CD4+ count strata and had a narrower range than pre-antiretroviral therapy (ART) utilities. Conclusions. Despite the widespread use of ART, cost-effectiveness analysis of HIV prevention interventions frequently apply pre-ART health utility weights. Use of utility weights reflecting the current state of the US epidemic are needed to best inform HIV research and public policy decisions. Improved practices around the selection, application, and reporting of health utility data used in HIV prevention CEA are needed to improve transparency.

    • Healthcare Associated Infections
      1. Case-case comparison of Candida auris versus other Candida species bloodstream infections: Results of an outbreak investigation in Colombiaexternal icon
        Caceres DH, Rivera SM, Armstrong PA, Escandon P, Chow NA, Ovalle MV, Díaz J, Derado G, Salcedo S, Berrio I, Espinosa-Bode A, Varón C, Stuckey MJ, Mariño A, Villalobos N, Lockhart SR, Chiller TM, Prieto FE, Jackson BR.
        Mycopathologia. 2020 Aug 29.
        BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that causes outbreaks in healthcare settings around the world. In 2016, clinicians and public health officials identified patients with C. auris bloodstream infections (BSI) in Colombian healthcare facilities. To evaluate potential risk factors and outcomes for these infections, we investigated epidemiologic and clinical features of patients with C. auris and other Candida species BSI. METHODS: We performed a retrospective case-case investigation in four Colombian acute care hospitals, defining a case as Candida spp. isolated from blood culture during January 2015-September 2016. C. auris BSI cases were compared to other Candida species BSI cases. Odds ratio (OR), estimated using logistic regression, was used to assess the association between risk factors and outcomes. RESULTS: We analyzed 90 patients with BSI, including 40 with C. auris and 50 with other Candida species. All had been admitted to the intensive care unit (ICU). No significant demographic differences existed between the two groups. The following variables were independently associated with C. auris BSI: ≥ 15 days of pre-infection ICU stay (OR: 5.62, CI: 2.04-15.5), evidence of severe sepsis (OR: 3.70, CI 1.19-11.48), and diabetes mellitus (OR 5.69, CI 1.01-31.9). CONCLUSION: Patients with C. auris BSI had longer lengths of ICU stay than those with other candidemias, suggesting that infections are acquired during hospitalization. This is different from other Candida infections, which are usually thought to result from autoinfection with host flora.

      2. Ibrexafungerp: A novel oral triterpenoid antifungal in development for the treatment of Candida auris infectionsexternal icon
        Ghannoum M, Arendrup MC, Chaturvedi VP, Lockhart SR, McCormick TS, Chaturvedi S, Berkow EL, Juneja D, Tarai B, Azie N, Angulo D, Walsh TJ.
        Antibiotics (Basel). 2020 Aug 25;9(9).
        Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.

      3. Web-based interactive tool to identify facilities at risk of receiving patients with multidrug-resistant organismsexternal icon
        Octaria R, Chan A, Wolford H, Devasia R, Moon TD, Zhu Y, Slayton RB, Kainer MA.
        Emerg Infect Dis. 2020 Sep;26(9):2046-2053.
        To identify facilities at risk of receiving patients colonized or infected with multidrug-resistant organisms (MDROs), we developed an interactive web-based interface for visualization of patient-sharing networks among healthcare facilities in Tennessee, USA. Using hospital discharge data and the Centers for Medicare and Medicaid Services' claims and Minimum Data Set, we constructed networks among hospitals and skilled nursing facilities. Networks included direct and indirect transfers, which accounted for <365 days in the community outside of facility admissions. Authorized users can visualize a facility of interest and tailor visualizations by year, network dataset, length of time in the community, and minimum number of transfers. The interface visualizes the facility of interest with its connected facilities that receive or send patients, the number of interfacility transfers, and facilities at risk of receiving transfers from the facility of interest. This tool will help other health departments enhance their MDRO outbreak responses.

    • Immunity and Immunization
      1. Assessing reduced-dose pneumococcal vaccine schedules in South Africaexternal icon
        Dunne EM, Pilishvili T, Adegbola RA.
        Lancet Infect Dis. 2020 Aug 25.

      2. Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolutionexternal icon
        Huddleston J, Barnes JR, Rowe T, Xu X, Kondor R, Wentworth DE, Whittaker L, Ermetal B, Daniels RS, McCauley JW, Fujisaki S, Nakamura K, Kishida N, Watanabe S, Hasegawa H, Barr I, Subbarao K, Barrat-Charlaix P, Neher RA, Bedford T.
        Elife. 2020 Sep 2;9.
        Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence- only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.

      3. Hepatitis A vaccine immunogenicity 25 years after vaccination in Alaskaexternal icon
        Ramaswamy M, Bruden D, Nolen LD, Mosites E, Snowball M, Nelson NP, Bruce M, McMahon BJ.
        J Med Virol. 2020 .
        The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow-up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti-HAV) (>=20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti-HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti-HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti-HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti-HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series. Copyright This article is a U.S. Government work and in in the public domain in the USA.

    • Injury and Violence
      1. Effects of Dating Matters on sexual violence and sexual harassment outcomes among middle school youth: A cluster-randomized controlled trialexternal icon
        DeGue S, Niolon PH, Estefan LF, Tracy AJ, Le VD, Vivolo-Kantor AM, Little TD, Latzman NE, Tharp A, Lang KM, Taylor B.
        Prev Sci. 2020 Aug 26.
        Sexual violence (SV), including sexual harassment (SH), is a significant public health problem affecting adolescent health and well-being. This study extends prior research by evaluating the effectiveness of a comprehensive teen dating violence prevention model, Dating Matters, on SV and SH perpetration and victimization, inclusive of any victim-perpetrator relationship, among middle school students. Dating Matters includes classroom-delivered programs for youth in 6th, 7th, and 8th grades; community-based programs for parents; a youth communications program; training for educators; and community-level activities. Middle schools in four urban areas in the USA were randomly assigned to receive Dating Matters (DM, N = 22) or a standard-of-care intervention (SC, N = 24) over four consecutive school years (2012-2016). The analytic sample included two cohorts who entered the study in 6th grade and completed 8th grade by the end of the study allowing for full exposure to Dating Matters (DM: N = 1662; SC: N = 1639; 53% female; 50% black, non-Hispanic; 6 waves of data collection for each cohort). Structural equation modeling was employed with multiple imputation to account for missing data. Dating Matters was associated with significant reductions in SV and SH perpetration and victimization scores in most-but not all-sex/cohort groups by the end of 8th grade relative to an evidence-based TDV prevention program. On average, students receiving Dating Matters scored 6% lower on SV perpetration, 3% lower on SV victimization, 4% lower on SH perpetration, and 8% lower on SH victimization by the end of middle school than students receiving an evidence-based violence prevention program. Overall, Dating Matters shows promise for reducing SV and SH, occurring both within and outside dating relationships, through middle school. Identifier: NCT01672541.

      2. Youth suicide: An opportunity for preventionexternal icon
        Ertl A, Crosby AE, Blair JM.
        J Am Acad Child Adolesc Psychiatry. 2020 Sep;59(9):1019-1021.
        In the United States, youth suicide is a large and growing public health problem that contributes to health care costs, lost productivity, morbidity, and premature death. In 2017, an estimated 199,877 youths aged 10 to 24 years were treated in emergency departments in the United States for self-harm,(1) and 7.4% of high school students reported that they attempted suicide one or more times in the past year.(2) Suicide was the second leading cause of death among youths aged 10 to 24 years in 2017,(1) and the suicide rate increased significantly for both male and female youths from 1999 to 2017.(3).

      3. Shared correlates of prescription drug misuse and severe suicide ideation among clinical patients at risk for suicideexternal icon
        Logan JE, Ertl AM, Rostad WL, Herbst JH, Ashby Plant E.
        Suicide Life Threat Behav. 2020 Aug 28.
        OBJECTIVE: Unintentional drug overdose and suicide have emerged as public health problems. Prescription drug misuse can elevate risk of overdose. Severe suicidal ideation increases risk of suicide. We identified shared correlates of both risk factors to inform cross-cutting prevention efforts. METHODS: We conducted a cross-sectional study using the Military Suicide Research Consortium's Common Data Elements survey; 2012-2017 baseline data collected from 10 research sites were analyzed. The sample included 3962 clinical patients at risk of suicide. Factors examined in relation to the outcomes, prescription drug misuse and severe suicidal ideation, included demographic characteristics and symptoms of: hopelessness; anxiety; post-traumatic stress disorder; alcohol use; other substance use; prior head/neck injury; insomnia; and belongingness. Poisson regression models with robust estimates provided adjusted prevalence ratios (aPRs) and 97.5% confidence intervals (CIs). RESULTS: Medium and high (vs. low) levels of insomnia were positively associated with prescription drug misuse (aPRs p < 0.025). Medium (vs. low) level of insomnia was positively associated with severe suicidal ideation (aPR: 1.09; CI: 1.01-1.18). Medium and high (vs. low) levels of perceived belongingness were inversely associated with both outcomes (aPRs p < 0.025). CONCLUSIONS: Research should evaluate whether addressing sleep problems and improving belongingness can reduce prescription drug misuse and suicidal ideation simultaneously.

      4. The association between sports- or physical activity-related concussions and suicidality among US high school students, 2017external icon
        Miller GF, DePadilla L, Jones SE, Bartholow BN, Sarmiento K, Breiding MJ.
        Sports Health. 2020 Aug 26.
        BACKGROUND: This study examined the association between sports- or physical activity-related concussions and having seriously considered attempting suicide, made a suicide plan, or attempted suicide (ie, suicidality), and tested potential moderators of the association. HYPOTHESIS: Risk factors such as persistent feelings of sadness or hopelessness, low academic grades, few hours of sleep, and current alcohol or marijuana use will increase the odds of suicidality among those who self-reported sports- or physical activity-related concussions, while protective factors such as physical activity and having played on a sports team will decrease the odds. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: This study used data from the 2017 Youth Risk Behavior Survey, a biennial, school-based, nationally representative survey of US students in grade levels 9 to 12 (N = 14,765). Logistic regression models examined associations between self-reported sports- or physical activity-related concussions and suicidality among the students, and whether physical activity, having played on a sports team, persistent feelings of sadness or hopelessness, academic grades, hours of sleep, or current alcohol or marijuana use moderated those associations. RESULTS: Sports- or physical activity-related concussions were found to be associated with suicidality. The associations remained significant in models that adjusted for demographic characteristics, and they did not appear to be moderated by physical activity, having played on sports team, academic grades, or sleep. CONCLUSIONS: Given the findings of this study and others, health care providers are advised to ask students who have experienced a concussion about their emotional well-being as part of their symptom-based assessment, using validated, age- appropriate concussion symptom scales. Comprehensively assessing students who have experienced a sports- or physical activity-related concussion for persistent feelings of sadness or hopelessness may alert providers to thoughts of suicidal ideation and will allow for earlier intervention. CLINICAL RELEVANCE: If thoughts of suicide are discovered among adolescents with a concussion, or if other risk factors are observed, referrals to medical and mental health providers for a more comprehensive assessment may be warranted.

    • Laboratory Sciences
      1. Hepatitis E virus (HEV) genotype 1 (gt1) and gt3 infections have distinct epidemiologic characteristics and genotype-specific molecular mechanisms of pathogenesis are not well characterized. Previously, we showed differences in immune response-related gene expression profiles of HEV gt1 and gt3 infections using qPCR. We hypothesize that HEV gt1 and gt3 infections induce transcriptome modifications contributing to disease pathogenesis. RNAseq analysis was performed using liver biopsy samples of naïve (baseline), HEV gt1, or gt3-infected rhesus macaques, and nine anti-HEV positive rhesus macaques re-inoculated with HEV gt1. All 10 primary HEV gt1/gt3 infected animals exhibited the typical course of acute viral hepatitis and cleared the infection between 27 to 67 days after inoculation. Viremic stages of HEV infection were defined as early, peak, and decline based on HEV RNA titers in daily stool specimens. During early, peak, and decline phases of infection, HEV gt1 induced 415, 417, and 1769 differentially expressed genes, respectively, and 310, 678, and 388 genes were differentially expressed by HEV gt3, respectively (fold change ≥ 2.0, p-value ≤ 0.05). In the HEV gt1 infection, genes related to metabolic pathways were differentially expressed during the three phases of infection. In contrast, oxidative reduction (early phase), immune responses (peak phase), and T cell cytokine production (decline phase) were found to be regulated during HEV gt3 infection. In addition, FoxO and MAPK signaling pathways were differentially regulated in re-infected and protected animals against HEV gt1 reinfection, respectively. Significant differences of hepatic gene regulation exist between HEV gt1 and gt3 infections. These findings reveal a new link between molecular pathogenesis and epidemiological characteristics seen in HEV gt1 and gt3 infections.

      2. Limited tryptic digestion-isotope dilution mass spectrometry (LTD-IDMS): A reagent-free analytical assay to quantify hemagglutinin of A(H5N1) vaccine materialexternal icon
        Cooper HC, Xie Y, Palladino G, Barr JR, Settembre EC, Wen Y, Williams TL.
        Anal Chem. 2020 Sep 1;92(17):11879-11887.
        Avian influenza viruses, such as A(H5N1) and A(H7N9), are primary public health concerns due to their pandemic potential. Influenza vaccines represent the most effective response to this threat especially with timely provision. The current pandemic response timelines require a substantial period for strain-specific reference antigen and sera preparation for use with single-radial immunodiffusion (SRID), the accepted vaccine potency assay. To address this time lag, the isotope dilution mass spectrometry (IDMS) method was developed to quantify the absolute hemagglutinin (HA, the main influenza antigen) amount in the vaccine without the need for purified, inactivated, and calibrated virus reference antigens. However, an additional challenge in determining potency is to differentiate between vaccine antigens in their most potent form from other less potent, stressed antigen forms. The limited trypsin digestion (LTD) method has been developed and does not require strain-specific full-length reference antigens or antibodies; instead, stressed HA is selectively degraded, leaving the more potent form to be measured. LTD, followed by precipitation and IDMS, allows for efficient differentiation between potent and significantly less potent HA for vaccine release and potency testing across the vaccine's shelf life. In this study, we tested the LTD-IDMS assay on A(H5N1) vaccine material that had been stressed by low pH, heat, and multiple freeze-thaw cycles. The results showed that the LTD-IDMS method effectively quantified the potent HA in A(H5N1) vaccine material with results comparable to SRID. As such, it shows great promise to complement and potentially replace SRID in a pandemic when strain-specific reagents may not be readily available.

      3. Human monoclonal antibody derived from transchromosomic (Tc) cattle neutralizes multiple H1 clades of influenza A virus by recognizing a novel conformational epitope in the HA head domainexternal icon
        Gao R, Sreenivasan CC, Sheng Z, Hause BM, Zhou B, Wentworth DE, Clement T, Rausch D, Brunick C, Christopher-Hennings J, Wu H, Bausch CL, Sullivan EJ, Hoppe AD, Huber VC, Wang D, Li F.
        J Virol. 2020 Aug 26.
        Influenza remains a global health risk and challenge. Currently, NA inhibitors are extensively used to treat influenza, but their efficacy is compromised by the emergence of drug resistant variants. Neutralizing antibodies targeting influenza A virus surface glycoproteins are critical components of influenza therapeutic agents and may provide alternative strategies to the existing countermeasures. However, the major hurdle for the extensive application of antibody therapies lies in the difficulty of generating non-immunogenic antibodies in large quantities rapidly. Here, we report one human monoclonal antibody (mAb), 53C10, isolated from transchromosomic (Tc) cattle exhibits potent neutralization and hemagglutination inhibition titers against different clades of H1N1 subtype influenza A viruses. In vitro selection of antibody escape mutants reveals that 53C10 recognizes a novel non-continuous epitope in the HA head domain involving three amino acid residues, glycine (G), Serine (S) and glutamic acid (E) at positions172, 207 and 212, respectively. The results of our experiments supported a critical role for substitution of arginine at position 207 (S207R) in mediating resistance to 53C10, while substitutions at either G172E or E212A did not alter antibody recognition and neutralization. The E212A mutation may provide structural stability for the epitope, while the substitution G172E probably compensates for loss of fitness introduced by S207R. Our results offer novel insights into the mechanism of action of mAb 53C10 and indicate its potential role in therapeutic treatment of H1 influenza virus infection in humans.IMPORTANCE Respiratory diseases caused by influenza viruses still pose a serious concern to global health and neutralizing antibodies constitute a promising area of antiviral therapeutics. However, the potential application of antibodies is often hampered by the challenge in generating non-immunogenic antibodies in large scale. In the present study, the transchromosomic (Tc) cattle were used for the generation of non-immunogenic monoclonal antibodies (mAbs) and characterization of such mAbs revealed one monoclonal antibody 53C10, exhibiting a potent neutralization activity against H1N1 influenza viruses. Further characterization of the neutralization-escape mutant generated using this mAb, showed that three amino acid substitutions in the HA head domain contributed to the resistance. These findings emphasize the importance of Tc cattle in the production of non-immunogenic mAbs and highlight the potential of 53C10 mAb in the therapeutic application against H1 influenza virus infection in humans.

      4. Zika virus (ZIKV) can establish infection in immune privileged sites such as the testes, eye and placenta. Whether ZIKV infection of white blood cells is required for dissemination of the virus to immune privileged sites has not been definitively shown. To assess whether initial ZIKV replication in myeloid cell populations is critical for dissemination during acute infection, recombinant ZIKVs were generated that could not replicate in these specific cells. ZIKV was cell-restricted by insertion of a complementary sequence to a myeloid-specific microRNA in the 3'untranslated region. Following inoculation of a highly sensitive immunodeficient mouse model, crucial immune parameters, such as quantification of leukocyte cell subsets, cytokine and chemokine secretion, and viremia were assessed. Decreased neutrophil numbers in the spleen were observed during acute infection with myeloid-restricted ZIKV that precluded the generation of viremia and viral dissemination to peripheral organs. Mice inoculated with a non-target microRNA control ZIKV demonstrated increased expression of key cytokines and chemokines critical for neutrophil and monocyte recruitment and increased neutrophil influx in the spleen. In addition, ZIKV-infected Ly6C(hi) monocytes were identified in vivo in the spleen. Mice inoculated with myeloid-restricted ZIKV exhibited similar trends as PBS-sham inoculated mice, including a lack of inflammatory cytokine production and a decrease in Ly6C(hi) ZIKV RNA positive monocytes.ImportanceMyeloid cells, including monocytes, play a crucial role in immune responses to pathogens. Monocytes have also been implicated as "Trojan horses" during viral infections, carrying infectious virus particles to immune privileged sites and/or to sites protected by physical blood-tissue barriers, such as the blood-testis barrier and the blood-brain barrier. In this study, we found that myeloid cells are crucial to Zika virus (ZIKV) pathogenesis. By engineering ZIKV clones to encode myeloid-specific microRNA target sequences, viral replication was inhibited in myeloid cells by harnessing the RNAi pathway. Severely immunodeficient mice inoculated with myeloid-restricted ZIKV did not demonstrate clinical signs of disease and survived infection. Furthermore, viral dissemination to peripheral organs was not observed in these mice. Lastly, we identified Ly6C(mid/hi) murine monocytes as the major myeloid cell population that disseminates ZIKV.

      5. CrAssphage as a novel tool to detect human fecal contamination on environmental surfaces and handsexternal icon
        Park GW, Ng TF, Freeland AL, Marconi VC, Boom JA, Staat MA, Montmayeur AM, Browne H, Narayanan J, Payne DC, Cardemil CV, Treffiletti A, Vinjé J.
        Emerg Infect Dis. 2020 Aug;26(8):1731-1739.
        CrAssphage is a recently discovered human gut-associated bacteriophage. To validate the potential use of crAssphage for detecting human fecal contamination on environmental surfaces and hands, we tested stool samples (n = 60), hand samples (n = 30), and environmental swab samples (n = 201) from 17 norovirus outbreaks for crAssphage by real-time PCR. In addition, we tested stool samples from healthy persons (n = 173), respiratory samples (n = 113), and animal fecal specimens (n = 68) and further sequenced positive samples. Overall, we detected crAssphage in 71.4% of outbreak stool samples, 48%-68.5% of stool samples from healthy persons, 56.2% of environmental swabs, and 60% of hand rinse samples, but not in human respiratory samples or animal fecal samples. CrAssphage sequences could be grouped into 2 major genetic clusters. Our data suggest that crAssphage could be used to detect human fecal contamination on environmental surfaces and hands.

      6. A method for trace analysis of aerosol mineral components using quantum cascade laser (QCL) based infrared absorption spectroscopy is described. The measurement approach involves: (a) collection of aerosol on a particulate filter; (b) sample treatment using low-temperature oxygenated plasma to minimize the matrix interferences; (c) redeposition of the treated sample as a dried spot for direct-on-filter analysis; and (d) infrared transmittance measurement of the dried spot using the QCL and mercury-cadmium-telluride detector. The method was applied to quantification of trace α-quartz in workplace aerosols. Infrared absorbance spectra in the range 750–1030 cm−1 were obtained using the QCL instrument; the characteristic peak of α-quartz at 798 cm−1 was used to measure its content. A correction scheme was applied to account for spectral interference from kaolinite mineral for coal dust samples. The detection limit for α-quartz was estimated to be 0.12 μg for a dried spot diameter of 1 mm. This detection limit is an order-of-magnitude lower than those attainable by the current standard X-ray diffraction (XRD) or Fourier transform infrared spectroscopy (FTIR) methods involving similar sample preparation and treatment. The QCL method was extended to the measurement of respirable α-quartz concentrations in workplace aerosols released during cutting of fiber-reinforced cement and engineered stone products (used in building construction), as well as those from various coal mine dusts. The measurements compared well with those from the standard XRD method, even for samples with matrix and mineral interferences. The results show that QCL-based IR transmission spectroscopy can offer sensitive, trace-level measurement of aerosol mineral components.

    • Maternal and Child Health
      1. Newborn screening practices and alpha-thalassemia detection - United States, 2016external icon
        Bender MA, Yusuf C, Davis T, Dorley MC, Del Pilar Aguinaga M, Ingram A, Chan MS, Ubaike JC, Hassell K, Ojodu J, Hulihan M.
        MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1269-1272.
        Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced. Depending on the genotype, alpha-thalassemia results in moderate to profound anemia, hemolysis, growth delays, splenomegaly, and increased risk for thromboembolic events; certain patients might require chronic transfusions. Although alpha-thalassemia is not a core condition of the United States Recommended Uniform Screening Panel* for state newborn screening programs, methodologies used by some newborn screening programs to detect sickle cell disease, which is a core panel condition, also detect a quantitative marker of alpha-thalassemia, hemoglobin (Hb) Bart's, an abnormal type of hemoglobin. The percentage of Hb Bart's detected correlates with alpha-thalassemia severity. The Association of Public Health Laboratories' Hemoglobinopathy Workgroup conducted a survey of state newborn screening programs' alpha-thalassemia screening methodologies and reporting and follow-up practices. Survey findings indicated that 41 of 44 responding programs (93%) report some form of alpha-thalassemia results and 57% used a two-method screening protocol. However, the percentage of Hb Bart's used for thalassemia classification, the types of alpha-thalassemia reported, and the recipients of this information varied widely. These survey findings highlight the opportunity for newborn screening programs to revisit their policies as they reevaluate their practices in light of the recently released guideline from the Clinical and Laboratory Standards Institute (CLSI) on Newborn Screening for Hemoglobinopathies (1). Although deferring to local programs for policies, the report used a cutoff of 25% Hb Bart's in its decision tree, a value many programs do not use. Standardization of screening and reporting might lead to more timely diagnoses and health care services and improved outcomes for persons with a clinically significant alpha-thalassemia.

      2. 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. 2020 Sep 2.
        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.

      3. Folic acid antagonist use before and during pregnancy and risk for selected birth defectsexternal icon
        Kerr SM, Parker SE, Mitchell AA, Tinker SC, Werler MM.
        Birth Defects Res. 2020 Sep 2.
        BACKGROUND: Maternal folic acid (FA) intake before and during early pregnancy reduces the risk for neural tube defects (NTDs); evidence suggests it may also reduce the risk for oral clefts, urinary defects, and cardiac defects. We sought to re-examine the use of drugs, which affect folate metabolism, dihydrofolate reductase inhibiting (DHFRI) medications, and anti-epileptic drugs (AEDs), in data collected in the post-FA fortification era (1998+) in the Slone Birth Defects Study. METHODS: We assessed maternal DHFRI and AED use and risk for NTDs, oral clefts, and urinary and cardiac defects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. We assessed daily average FA intake of ≥400 mcg as a potential effect modifier. RESULTS: We analyzed data from 10,209 control and 9,625 case mothers. Among controls, the prevalence of exposure to DHFRI medications was 0.3% and to AEDs was 0.5%. Maternal use of AEDs was associated with increased risks for NTDs (OR: 3.4; 95% CI: 1.5, 7.5), oral clefts (OR: 2.3; 95% CI: 1.3, 4.0), urinary defects (OR: 1.6; 95% CI: 1.0, 2.7), and cardiac defects (OR: 1.6; 95% CI: 1.1, 2.3); similar or further increased risks were found among those with FA intake ≥400 mcg per day. DHFRI use was rare and relative risk estimates were imprecise and consistent with the null. CONCLUSIONS: Similar to our previous analyses, we observed associations between AED use and these defects. For DHFRI exposure, we found no evidence for increased risk of these defects. Though statistical power to examine FA effect modification was low, we found no evidence of further protection among those with FA intake ≥400 mcg, with some associations somewhat stronger in this group.

      4. Infants with congenital disorders identified through newborn screening - United States, 2015-2017external icon
        Sontag MK, Yusuf C, Grosse SD, Edelman S, Miller JI, McKasson S, Kellar-Guenther Y, Gaffney M, Hinton CF, Cuthbert C, Singh S, Ojodu J, Shapira SK.
        MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1265-1268.
        Newborn screening (NBS) identifies infants at risk for congenital disorders for which early intervention has been shown to improve outcomes (1). State public health programs are encouraged to screen for disorders on the national Recommended Uniform Screening Panel (RUSP), which increased from 29 disorders in 2005 to 35 in 2018.* The RUSP includes hearing loss (HL) and critical congenital heart defects, which can be detected through point-of-care screening, and 33 disorders detected through laboratory screening of dried blood spot (DBS) specimens. Numbers of cases for 33 disorders on the RUSP (32 DBS disorders and HL) reported by 50 U.S. state programs were tabulated. The three subtypes of sickle cell disease (SCD) listed as separate disorders on the RUSP (S,S disease; S,beta-thalassemia; and S,C disease) were combined for the current analysis, and the frequencies of the resulting disorders were calculated relative to annual births. During 2015-2017, the overall prevalence was 34.0 per 10,000 live births. Applying that frequency to 3,791,712 live births in 2018,(†) approximately 12,900 infants are expected to be identified each year with one of the disorders included in the study. The most prevalent disorder is HL (16.5 per 10,000), and the most prevalent DBS disorders are primary congenital hypothyroidism (CH) (6.0 per 10,000), SCD (4.9 per 10,000), and cystic fibrosis (CF) (1.8 per 10,000). Notable changes in prevalence for each of these disorders have occurred since the previous estimates based on 2006 births (2). The number of infants identified at a national level highlights the effect that NBS programs are having on infant health through early detection, intervention, and potential improved health, regardless of geographic, racial/ethnic, or socioeconomic differences.

    • Nutritional Sciences
      1. Early formula supplementation trends by race/ethnicity among US children born from 2009 to 2015external icon
        Li R, Perrine CG, Anstey EH, Chen J, MacGowan CA, Elam-Evans LD, Galuska DA.
        JAMA Pediatr. 2020 Aug 31.

      2. Global mid-upper arm circumference cut-offs for adults: a call to actionexternal icon
        Maalouf-Manasseh Z, Remancus S, Milner E, Fenlason L, Quick T, Patsche CB, Bose K, Collins S, Ververs M, Walia S, Escobar-Alegria J, Chung M, Tang AM.
        Public Health Nutr. 2020 Aug 26:1-2.
        Since 2009, mid-upper arm circumference (MUAC) has become an accepted measure for screening children for acute malnutrition and determining eligibility for services to manage acute malnutrition. Use of MUAC has increased the reach and enhanced the quality of community-based management of acute malnutrition services. Increasingly, MUAC is also used to assess nutritional status and eligibility for nutrition support among adolescents and adults, including pregnant and lactating women and HIV and TB clients. However, globally recognised cut-offs have not been established to classify malnutrition among adults using MUAC. Therefore, different countries and programmes use different MUAC cut-offs to determine eligibility for programme services. Patient monitoring guidelines provided by WHO for country adaptation to support the integrated management of adult illness do not include MUAC, in part because guidance does not exist about what MUAC cut-off should trigger further action.

    • Occupational Safety and Health
      1. Transplantation for work-related lung disease in the USAexternal icon
        Blackley DJ, Halldin CN, Hayanga JW, Laney AS.
        Occup Environ Med. 2020 Aug 28.
        OBJECTIVES: Work-related lung diseases (WRLDs) are entirely preventable. To assess the impact of WRLDs on the US transplant system, we identified adult lung transplant recipients with a WRLD diagnosis specified at the time of transplant to describe demographic, payer and clinical characteristics of these patients and to assess post-transplant survival. METHODS: Using US registry data from 1991 to 2018, we identified lung transplant recipients with WRLDs including coal workers' pneumoconiosis, silicosis, asbestosis, metal pneumoconiosis and berylliosis. RESULTS: The frequency of WRLD-associated transplants has increased over time. Among 230 lung transplants for WRLD, a majority were performed since 2009; 79 were for coal workers' pneumoconiosis and 78 were for silicosis. Patients with coal workers' pneumoconiosis were predominantly from West Virginia (n=31), Kentucky (n=23) or Virginia (n=10). States with the highest number of patients with silicosis transplant were Pennsylvania (n=12) and West Virginia (n=8). Patients with metal pneumoconiosis and asbestosis had the lowest and highest mean age at transplant (48.8 and 62.1 years). Median post-transplant survival was 8.2 years for patients with asbestosis, 6.6 years for coal workers' pneumoconiosis and 7.8 years for silicosis. Risk of death among patients with silicosis, coal workers' pneumoconiosis and asbestosis did not differ when compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Lung transplants for WRLDs are increasingly common, indicating a need for primary prevention and surveillance in high-risk occupations. Collection of patient occupational history by the registry could enhance case identification and inform prevention strategies.

      2. Inclination angles during cross-slope roof walkingexternal icon
        Breloff SP, Carey RE, Wade C, Waddell DE.
        Safety Science. 2020 December;132.
        Residential roofers have the highest rate of falls in the construction sector with injuries and fatalities costing billions of dollars annually. The sloped roof surface is the most predominant component within the residential roof work environment. Postural stability on a sloped work environment is not well studied. Calculating inclination angles (IAs) using the lateral ankle marker could be a quality measure to determine how cross-slope roof walking will influence stability. Will cross-slope roof-walking effect anterior-posterior (AP) and medial-lateral (ML) IAs in adult males? Eleven adult males participated in two testing sessions-level and cross-slope roof gait session on a 6/12 pitched roof segment. Changes in AP and ML IAs between conditions were compared at: heel strike (HS) and toe off (TO). Legs were analyzed separately due to the cross-slope walking. The left foot was 'higher' on the sloped roof and the right was 'lower.' Significant increases (p <= 0.006) in IAs were observed due to the sloped roof in all conditions except the AP 'lower' leg (p = 0.136). Increases in IA suggest a decrease in postural stability as the body will result in greater sway compared to a natural posture. Increases in AP IAs may cause slipping in the anterior or posterior direction as the normal force will decrease during HS and TO. In the ML direction, fall risk is increased and more stress is placed on the hip abductors in order to reduce falling. Thus traversing a sloped roof surface reduces stability of healthy workers and escalates injury/fall risk factors.

      3. Progress in corrections worker health: The national corrections collaborative utilizing a Total Worker Health strategyexternal icon
        El Ghaziri M, Jaegers LA, Monteiro CE, Grubb PL, Cherniack MG.
        J Occup Environ Med. 2020 Aug 28.
        OBJECTIVE: To examine National Corrections Collaborative (NCC) activities, as an outreach initiative, to advance corrections workplace health and safety research, practice, and policy through a series of applied Research to Practice (r2p) meetings informed by the Total Worker Health (TWH) strategy. METHODS: We mapped the coalescence of correctional worker health concerns, federal and national professional organization initiatives, and research activities that formed the NCC in 2014. RESULTS: During the NCC's 5-years of TWH activities, attendance increased, partner composition expanded, and themes of concern evolved. Partners were motivated to participate and work together towards building evidence for health and safety r2p. CONCLUSIONS: A unified plea to the academic and federal research communities for assistance with better evaluation instruments, data linkages, and for adopting an integrated TWH approach to workforce health and wellbeing continue to drive NCC r2p activities.

      4. Certain underlying medical conditions are associated with higher risks for severe morbidity and mortality from coronavirus disease 2019 (COVID-19) (1). Prevalence of these underlying conditions among workers differs by industry and occupation. Many essential workers, who hold jobs critical to the continued function of infrastructure operations (2), have high potential for exposure to SARS-CoV-2, the virus that causes COVID-19, because their jobs require close contact with patients, the general public, or coworkers. To assess the baseline prevalence of underlying conditions among workers in six essential occupations and seven essential industries, CDC analyzed data from the 2017 and 2018 Behavioral Risk Factor Surveillance System (BRFSS) surveys, the most recent data available.* This report presents unadjusted prevalences and adjusted prevalence ratios (aPRs) for selected underlying conditions. Among workers in the home health aide occupation and the nursing home/rehabilitation industry, aPRs were significantly elevated for the largest number of conditions. Extra efforts to minimize exposure risk and prevent and treat underlying conditions are warranted to protect workers whose jobs increase their risk for exposure to SARS-CoV-2.

      5. Security cameras in taxicabs with three rows of seatingexternal icon
        Zeng S.
        Int J Occup Saf Ergon. 2020 Sep 2:1-28.
        Taxicab security cameras are widely used to deter crimes against taxicab-drivers in two-row-seating taxicabs. Some of these cameras have difficulty for use in three-row-seating taxicabs due to increased distance between the camera and the third-row seats. This project tested five sample taxicab security cameras with different image-sensor pixel counts to determine their utility for three-row-seating taxicabs. The cameras videotaped a normalized camera resolution test chart mounted in the third-row seat of a simulated three-row-seating taxicab in both daylight and dark (with infrared radiation) conditions. The camera resolution of each camera was measured and compared with the resolution threshold for customer facial identification. A dome-mounted camera with a standard-definition image-sensor is suggested as an effective camera in sustaining high camera resolution with small data file size for facial identification in the third-row seats. The image-sensors with at least 1280×720 pixels are suggested for windshield-mounted cameras in three-row-seating taxicabs for facial identification.

    • Occupational Safety and Health - Mining
      1. Dust collectors for roof bolting machines generally use a dry box to collect the roof bolting material. Recently, an underground mining operation converted a dry box dust collector to a wet box dust collector with a unique exception from MSHA for testing purposes. Water is routed to the roof bolter from the main water line of the continuous miner. The wet box utilizes a water spray to wet the incoming material. Testing was conducted comparing the two different collector types. Respirable dust concentrations surrounding the roof bolter with the different collection boxes were similar. The main difference in respirable dust concentrations occurred when cleaning the dust boxes. The average respirable dust concentration during cleaning of the wet box was 0.475 mg/m3, and during the cleaning of the dry box, the average respirable dust concentration was 1.188 mg/m3, a 60% reduction in respirable dust concentration. The quartz content of the roof material was high, ranging from 28.9 to 52.7% during this study. The results from this study indicate that using the wet box as a collector reduced exposure to respirable dust up to 60% when cleaning the collector boxes.

      2. A recent study conducted by the National Institute for Occupational Safety and Health (NIOSH) evaluated the roof bolter canopy air curtain (CAC) system in a blowing face ventilation system, demonstrating its effectiveness and illustrating the CAC protection zones. This study evaluates the roof bolter machine CAC while operating in an exhausting face ventilation system. This study considers two similar locations to allow comparison with the previous blowing face ventilation (Zheng et al., Min Metal Explor 36(6):1115–1126, (2019)) study: (1) a roof bolter machine bolting the roof at 20 ft (6.1 m) from the face and (2) a roof bolting machine bolting at 4 ft (1.2 m) from the face. The environment introduces 6.0 mg/m3 of respirable dust to represent the roof bolting machine operating downstream of the continuous miner. However, the exhausting face ventilation uses an exhaust curtain with 9000 cfm (4.25 m3/s) of air. Two roof bolter machine working positions are simulated with the use of dual drill heads in the inward position for two inside bolts and in the outward position for two outside bolts. The influence of the CAC on airflows and dust dispersion is evaluated with the CAC operating at 250 cfm (0.12 m3/s) with dust reductions ranging from 39.5 to 82.8%. When the roof bolter machine operated close to the face, increasing CAC airflow was required for adequate protection since the dust reductions can be as low as 39.5%. Additional CAC airflows of 350 cfm (0.17 m3/s) and 450 cfm (0.21 m3/s) were evaluated and demonstrated that dust reductions increased to 59.7% (350 cfm) and 72.0% (450 cfm) for the worst location where the roof bolter operators located.

    • Parasitic Diseases
      1. Fine-scale heterogeneity in Schistosoma mansoni force of infection measured through antibody responseexternal icon
        Arnold BF, Kanyi H, Njenga SM, Rawago FO, Priest JW, Secor WE, Lammie PJ, Won KY, Odiere MR.
        Proc Natl Acad Sci U S A. 2020 Aug 31.
        Schistosomiasis is among the most common parasitic diseases in the world, with over 142 million people infected in low- and middle-income countries. Measuring population-level transmission is centrally important in guiding schistosomiasis control programs. Traditionally, human Schistosoma mansoni infections have been detected using stool microscopy, which is logistically difficult at program scale and has low sensitivity when people have low infection burdens. We compared serological measures of transmission based on antibody response to S. mansoni soluble egg antigen (SEA) with stool-based measures of infection among 3,663 preschool-age children in an area endemic for S. mansoni in western Kenya. We estimated force of infection among children using the seroconversion rate and examined how it varied geographically and by age. At the community level, serological measures of transmission aligned with stool-based measures of infection (ρ = 0.94), and serological measures provided more resolution for between-community differences at lower levels of infection. Force of infection showed a clear gradient of transmission with distance from Lake Victoria, with 94% of infections and 93% of seropositive children in communities <1.5 km from the lake. Force of infection increased through age 3 y, by which time 65% (95% CI: 53%, 75%) of children were SEA positive in high-transmission communities-2 y before they would be reached by school-based deworming programs. Our results show that serologic surveillance platforms represent an important opportunity to guide and monitor schistosomiasis control programs, and that in high-transmission settings preschool-age children represent a key population missed by school-based deworming programs.

      2. Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacityexternal icon
        Briet O, Koenker H, Norris L, Wiegand R, Vanden Eng J, Thackeray A, Williamson J, Gimnig JE, Fortes F, Akogbeto M, Yadouleton AW, Ombok M, Bayoh MN, Mzilahowa T, Abílio AP, Mabunda S, Cuamba N, Diouf E, Konaté L, Hamainza B, Katebe-Sakala C, Ponce de León G, Asamoa K, Wolkon A, Smith SC, Swamidoss I, Green M, Gueye S, Mihigo J, Morgan J, Dotson E, Craig AS, Tan KR, Wirtz RA, Smith T.
        Malar J. 2020 Aug 28;19(1):310.
        BACKGROUND: Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear. METHODS: Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels. RESULTS: There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss. CONCLUSIONS: There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household.

      3. Evaluation of an ensemble-based distance statistic for clustering MLST datasets using epidemiologically defined clusters of cyclosporiasisexternal icon
        Nascimento FS, Barratt J, Houghton K, Plucinski M, Kelley J, Casillas S, Bennett CC, Snider C, Tuladhar R, Zhang J, Clemons B, Madison-Antenucci S, Russell A, Cebelinski E, Haan J, Robinson T, Arrowood MJ, Talundzic E, Bradbury RS, Qvarnstrom Y.
        Epidemiol Infect. 2020 Aug 3;148:e172.
        Outbreaks of cyclosporiasis, a food-borne illness caused by the coccidian parasite Cyclospora cayetanensis have increased in the USA in recent years, with approximately 2300 laboratory-confirmed cases reported in 2018. Genotyping tools are needed to inform epidemiological investigations, yet genotyping Cyclospora has proven challenging due to its sexual reproductive cycle which produces complex infections characterized by high genetic heterogeneity. We used targeted amplicon deep sequencing and a recently described ensemble-based distance statistic that accommodates heterogeneous (mixed) genotypes and specimens with partial genotyping data, to genotype and cluster 648 C. cayetanensis samples submitted to CDC in 2018. The performance of the ensemble was assessed by comparing ensemble-identified genetic clusters to analogous clusters identified independently based on common food exposures. Using these epidemiologic clusters as a gold standard, the ensemble facilitated genetic clustering with 93.8% sensitivity and 99.7% specificity. Hence, we anticipate that this procedure will greatly complement epidemiologic investigations of cyclosporiasis.

    • Public Health Law
      1. How state scope-of-practice policies impact NP careexternal icon
        Taylor LN, Gilchrist S.
        Am J Nurs. 2020 Sep;120(9):21-22.
        Three projects examine the effect of NP practice acts on access to health care.

    • Reproductive Health
      1. OBJECTIVE: The Zika Contraception Access Network (Z-CAN) was a short-term emergency response intervention that used contraception to prevent unintended pregnancy to reduce Zika-related adverse birth outcomes during the 2016-2017 Zika virus outbreak in Puerto Rico. Strategies and safeguards were developed to ensure women who chose long-acting reversible contraception (LARC) had access to no-cost removal, if desired, after Z-CAN ended. Study Design We assessed the number of women who chose LARC at their initial Z-CAN visit who filed complaints regarding challenges with LARC removal within 30-months after the Z-CAN program ended. Complaints and program responses were categorized. RESULTS: Of the 29,221 women who received Z-CAN services, 20,381 chose a LARC method at their initial visit (IUD= 12,276 and implant= 8,105). Between September 2017-February 2020, 63 patient complaints were logged, mostly due to LARC removal charges (76.2%) which were generally (71.4%) determined to be inappropriate charges. All complaints filed were resolved allowing LARC removal within an average of 28 days. CONCLUSION: Safeguards to ensure prompt LARC removal when desired are critical to ensure women's reproductive autonomy. IMPLICATIONS: Strategies and safeguards used by Z-CAN to ensure women have access to LARC removal might be used by other contraception programs to prevent reproductive coercion and promote reproductive autonomy to best meet the reproductive needs of women.

    • Social and Behavioral Sciences
      1. Frequent mental distress among adults, by disability status, disability type, and selected characteristics - United States, 2018external icon
        Cree RA, Okoro CA, Zack MM, Carbone E.
        MMWR Morb Mortal Wkly Rep. 2020 Sep 11;69(36):1238-1243.
        Frequent mental distress, defined as 14 or more self-reported mentally unhealthy days in the past 30 days,* is associated with adverse health behaviors, increased use of health services, mental disorders (e.g., diagnosis of major depressive disorder), chronic diseases, and functional limitations (1). Adults with disabilities more often report depression and anxiety (2), reduced health care access (3), and health-related risk behaviors (4) than do adults without disabilities. CDC analyzed 2018 Behavioral Risk Factor Surveillance System (BRFSS) data to compare the prevalence of frequent mental distress among adults with disabilities with that among adults without disabilities and to identify factors associated with mental distress among those with disabilities. Nationwide, an estimated 17.4 million adults with disabilities reported frequent mental distress; the prevalence of reported mental distress among those with disabilities (32.9%) was 4.6 times that of those without disabilities (7.2%). Among adults with disabilities, those with both cognitive and mobility disabilities most frequently reported mental distress (55.6%). Adults with disabilities who reported adverse health-related characteristics (e.g., cigarette smoking, physical inactivity, insufficient sleep, obesity, or depressive disorders) or an unmet health care need because of cost also reported experiencing more mental distress than did those with disabilities who did not have these characteristics. Adults living below the federal poverty level reported mental distress 70% more often than did adults in higher income households. Among states, age-adjusted prevalence of mental distress among adults with disabilities ranged from 25.2% (Alaska) to 42.9% (New Hampshire). Understanding the prevalence of mental distress among adults with disabilities could help health care providers, public health professionals, and policy makers target interventions and inform programs and policies to ensure receipt of mental health screening, care, and support services to reduce mental distress among adults with disabilities.

    • Substance Use and Abuse
      1. Protecting youth from tobacco around the globe: Evidence to practiceexternal icon
        Ahluwalia IB, Wilson K, Gorzkowski J.
        Pediatrics. 2020 Sep 1.

      2. Delay discounting is the process by which a commodity loses value as the delay to its receipt increases. Rapid discounting predicts various maladaptive behaviors including tobacco use. Typically, delay discounting of different outcomes has been compared between cigarette smokers and nonsmokers. To better understand the relationship of delay discounting to different modes of tobacco use, we examined the differences in delay discounting of different outcomes between cigarette smokers, smokeless tobacco users, e-cigarette users, and non-tobacco users. In the present study, all participants completed 8 titrating delay-discounting tasks: $100 gain, $500 gain, $500 loss, alcohol, entertainment, food, a temporary health gain, and a temporary cure from a disease. Non-tobacco users discounted most outcomes less than tobacco users overall; however, there were no differences in discounting among the different types of tobacco users. These results suggest that nicotine consumption of any kind is associated with a higher degree of impulsivity compared to non-tobacco users. Adoption of tobacco products that have been perceived as less harmful (e.g., e-cigarettes) is not associated with a baseline difference or decrease in delay discounting if adopted after a history of cigarette use.

      3. Association between the Tips From Former Smokers Campaign and smoking cessation among adults, United States, 2012-2018external icon
        Murphy-Hoefer R, Davis KC, King BA, Beistle D, Rodes R, Graffunder C.
        Prev Chronic Dis. 2020 Aug 27;17:E97.
        In 2012, the Centers for Disease Control and Prevention (CDC) launched the national Tips From Former Smokers (Tips) campaign to encourage people who smoke to quit by showing real-life heath consequences of tobacco use and promoting evidence-based resources for quitting. To assess the campaign's impact on quit attempts and sustained-quit estimates (ie, quits lasting ≥6 mos), CDC analyzed data from a nationally representative longitudinal survey of US adults who smoke cigarettes, aged 18 years or older in 2012-2018. The Tips campaign was associated with an estimated 16.4 million quit attempts and 1,005,419 sustained quits. Continued implementation of cessation campaigns, including the Tips campaign, could accelerate progress toward reducing rates of smoking-related diseases and death.

    • Veterinary Medicine
      1. Leishmania infantum in US-born dogexternal icon
        de Almeida ME, Spann DR, Bradbury RS.
        Emerg Infect Dis. 2020 Aug;26(8):1882-1884.
        Leishmaniasis is a vectorborne disease that can infect humans, dogs, and other mammals. We identified one of its causative agents, Leishmania infantum, in a dog born in California, USA, demonstrating potential for autochthonous infections in this country. Our finding bolsters the need for improved leishmaniasis screening practices in the United States.

    • Zoonotic and Vectorborne Diseases
      1. No evidence of acute dengue virus infections at a rural site in western Kenya, 2011 and 2013external icon
        Matheson AI, Mogeni OD, Lacsina JR, Ochieng M, Audi A, Bigogo G, Neatherlin J, Margolis HS, Fields B, Ahenda P, Walson JL, Montgomery JM.
        Am J Trop Med Hyg. 2020 Aug 31.
        The incidence and spread of dengue virus (DENV) have increased rapidly in recent decades. Dengue is underreported in Africa, but recent outbreaks and seroprevalence data suggest that DENV is widespread there. A lack of ongoing surveillance limits knowledge about its spatial reach and hinders disease control planning. We sought to add data on dengue distribution in Kenya through diagnostic testing of serum specimens from persons with an acute febrile illness (AFI) attending an outpatient clinic in rural western Kenya (Asembo) during rainy seasons. Patients with symptoms not likely to be misclassified as dengue (e.g., diarrhea and anemia), those with a positive diagnostic laboratory results which explained their febrile illness, or those with serum collected more than 5 days after fever onset were excluded. However, febrile patients with a positive malaria smear were included in the study. We used reverse transcription polymerase chain reaction (RT-PCR) to test for DENV and IgM anti-DENV to test for recent infection. Of the 615 serum specimens available for testing, none were dengue positive by either RT-PCR or IgM anti-DENV testing. Dengue did not appear to be a cause of febrile illness in this area of western Kenya, although our relatively small sample size may not have identified DENV infections occurring at low incidence. A more widespread AFI surveillance system that includes dengue diagnostic testing by RT-PCR and antibody-based methods is required to more definitively gauge the size and geographic distribution of DENV infection in western Kenya.

      2. Atypical manifestations of cat-scratch disease, United States, 2005-2014external icon
        Nawrocki CC, Max RJ, Marzec NS, Nelson CA.
        Emerg Infect Dis. 2020 Jul;26(7):1438-1446.
        Atypical manifestations that can be severe and difficult to diagnosis develop in 5%-20% of patients with cat-scratch disease. To clarify the epidemiology of atypical cat-scratch disease in the United States, we analyzed data from the 2005-2014 MarketScan national health insurance claims databases by using the International Classification of Diseases, 9th Revision, Clinical Modification, codes for cat-scratch disease and selected atypical manifestations: retinitis/neuroretinitis, conjunctivitis, neuritis, encephalitis, hepatosplenic disease, osteomyelitis, erythema nodosum, and endocarditis. Atypical cat-scratch disease accounted for 1.5% of all cases, resulting in an average annual incidence of 0.7 cases/100,000 population. Atypical cat-scratch disease was associated with increased risk for hospitalization (risk ratios 8.77, 95% CI 6.56-11.72) and occurred most often in female patients 10-14 years of age. Ocular (48.7%), hepatosplenic (24.6%), and neurologic (13.8%) manifestations were most common among patients. A more comprehensive understanding of atypical cat-scratch disease can improve patient diagnosis and potentially elucidate pathophysiology of the disease.

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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.

Page last reviewed: September 16, 2020, 12:00 AM