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Volume 12, Issue 12, April 14, 2020

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CDC Science Clips: Volume 12, Issue 12, April 14, 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 is pleased to feature articles on sexually transmitted diseases (STDs) in conjunction with STD Awareness Week. Featured articles highlight recent research on STDs, including studies that identify the often severe consequences of STDs, including congenital syphilis and disseminated gonococcal infection, as well as strategies to prevent STDs and their consequences in populations most affected including men who have sex with men, women, and persons at risk for HIV.

STD Awareness Week, observed April 12-18, 2020, provides an opportunity to raise awareness about STDs and how they impact our lives; reduce STD-related stigma, fear, and discrimination; and ensure people have the tools and knowledge to prevent, test for, and treat STDs.  Because local prevention needs vary with the communities, CDC has provided diverse campaigns to choose from with different prevention focuses and audiences:

  • Get Yourself Tested (GYT) – Encourages young people to get tested and treated for STDs and HIV
  • Talk. Test. Treat. – Focuses on three simple actions individuals and healthcare providers can take to protect their health/their patient’s health: Talk, Test, Treat
  • Syphilis Strikes Back – Highlights the resurgence of syphilis and the specific threat against gay and bisexual men, pregnant women, and newborn babies
  • Treat Me Right – Underscores the need for strong patient-provider relationships to overcome the rising STD burden

The report consists of these components:

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    • Communicable Diseases - Sexually Transmitted Diseases Awareness
      1. BACKGROUND: Ceftriaxone is the only consistently active antimicrobial agent recommended for the treatment of Neisseria gonorrhoeae. Although some new antimicrobials are in development, the necessity to expand treatment options in the near term may require using older drugs that have not been widely used to treat gonorrhoea. METHODS: We conducted a literature review of clinical trials and case series, published from 1983 to 2017, reporting treatment efficacy results following administration of 1 g aztreonam intramuscularly or IV for uncomplicated gonococcal infections. We summed trial data, stratified by anatomical site of infection, and calculated summary efficacy estimates and 95% CI for each site of infection. RESULTS: The 10 identified clinical trials enrolled 678, 38 and 16 individuals with urogenital, rectal and pharyngeal gonorrhoea, respectively. Aztreonam had an efficacy of 98.6% (95% CI: 97.5%-99.4%) for urogenital, 94.7% (95% CI: 82.3%-99.4%) for rectal and 81.3% (95% CI: 54.4%-96.0%) for pharyngeal gonococcal infections. CONCLUSIONS: Although most clinical trials included in this meta-analysis were conducted >30 years ago, aztreonam appears to have excellent efficacy for urogenital gonorrhoea; its efficacy at extragenital sites remains uncertain.

      2. Disseminated gonococcal infections in patients receiving eculizumab: A case seriesexternal icon
        Crew PE, Abara WE, McCulley L, Waldron PE, Kirkcaldy RD, Weston EJ, Bernstein KT, Jones SC, Bersoff-Matcha SJ.
        Clin Infect Dis. 2019 Aug 1;69(4):596-600.
        BACKGROUND: Gonorrhea is the second most commonly reported notifiable condition in the United States. Infrequently, Neisseria gonorrhoeae can cause disseminated gonococcal infection (DGI). Eculizumab, a monoclonal antibody, inhibits terminal complement activation, which impairs the ability of the immune system to respond effectively to Neisseria infections. This series describes cases of N. gonorrhoeae infection among patients receiving eculizumab. METHODS: Pre- and postmarketing safety reports of N. gonorrhoeae infection in patients receiving eculizumab worldwide were obtained from US Food and Drug Administration safety databases and the medical literature, including reports from the start of pivotal clinical trials in 2004 through 31 December 2017. Included patients had at least 1 eculizumab dose within the 3 months prior to N. gonorrhoeae infection. RESULTS: Nine cases of N. gonorrhoeae infection were identified; 8 were classified as disseminated (89%). Of the disseminated cases, 8 patients required hospitalization, 7 had positive blood cultures, and 2 required vasopressor support. One patient required mechanical ventilation. Neisseria gonorrhoeae may have contributed to complications prior to death in 1 patient; however, the fatality was attributed to underlying disease per the reporter. CONCLUSIONS: Patients receiving eculizumab may be at higher risk for DGI than the general population. Prescribers are encouraged to educate patients receiving eculizumab on their risk for serious gonococcal infections and perform screening for sexually transmitted diseases (STDs) per the Centers for Disease Control and Prevention STD treatment guidelines or in suspected cases. If antimicrobial prophylaxis is used during eculizumab therapy, prescribers should consider trends in gonococcal antimicrobial susceptibility due to emerging resistance concerns.

      3. Identification of United States counties at elevated risk for congenital syphilis using predictive modeling and a risk scoring systemexternal icon
        Cuffe KM, Kang JD, Dorji T, Bowen VB, Leichliter JS, Torrone E, Bernstein KT.
        Sex Transm Dis. 2020 Feb 7.
        BACKGROUND: Although preventable through timely screening and treatment, congenital syphilis (CS) rates are increasing in the United States (US), occurring in 5% of counties in 2015. Although individual-level factors are important predictors of CS, given the geographic focus of CS, it is also imperative to understand what county-level factors are associated with CS. METHODS: This is a secondary analysis of reported county CS cases to the National Notifiable Disease Surveillance System (NNDSS) during 2014-15 and 2016-17. We developed a predictive model to identify county-level factors associated with CS and use these to predict counties at elevated risk for future CS. RESULTS: Our final model identified 973 (31.0% of all US counties) counties at elevated risk for CS (sensitivity: 88.1%; specificity: 74.0%). County factors that were predictive of CS included metropolitan area, income inequality, P&S syphilis rates among women and MSM, and population proportions of those who are non-Hispanic Black, Hispanic, living in urban areas, and uninsured. The predictive model using 2014-2015 CS outcome data was predictive of 2016-2017 CS cases (area under the curve value = 89.2%) CONCLUSIONS: Given the dire consequences of CS, increasing prevention efforts remains important. The ability to predict counties at most elevated risk for CS based on county factors may help target CS resources where they are needed most.

      4. The modern epidemic of syphilisexternal icon
        Ghanem KG, Ram S, Rice PA.
        N Engl J Med. 2020 Feb 27;382(9):845-854.

      5. Extragenital chlamydia and gonorrhea among community venue-attending men who have sex with men - five cities, United States, 2017external icon
        Johnson Jones ML, Chapin-Bardales J, Bizune D, Papp JR, Phillips C, Kirkcaldy RD, Wejnert C, Bernstein KT.
        MMWR Morb Mortal Wkly Rep. 2019 Apr 12;68(14):321-325.
        Sexually transmitted diseases (STDs) disproportionately affect gay, bisexual, and other men who have sex with men (MSM) in the United States (1). Because chlamydia and gonorrhea at extragenital (rectal and pharyngeal) anatomic sites are often asymptomatic, these anatomic sites serve as a reservoir of infection, which might contribute to gonococcal antimicrobial resistance (2) and increased risk for human immunodeficiency virus (HIV) transmission and acquisition (3). To ascertain prevalence of extragenital STDs, MSM attending community venues were recruited in five U.S. cities to provide self-collected swabs for chlamydia and gonorrhea screening as part of National HIV Behavioral Surveillance (NHBS). Overall, 2,075 MSM provided specimens with valid results, and 13.3% of participants were infected with at least one of the two pathogens in at least one of these two extragenital anatomic sites. Approximately one third of participating MSM had not been screened for STDs in the previous 12 months. MSM attending community venues had a high prevalence of asymptomatic extragenital STDs. The findings underscore the importance of sexually active MSM following current recommendations for STD screening at all exposed anatomic sites at least annually (4).

      6. Proportion of incident human immunodeficiency virus cases among men who have sex with men attributable to gonorrhea and chlamydia: A modeling analysisexternal icon
        Jones J, Weiss K, Mermin J, Dietz P, Rosenberg ES, Gift TL, Chesson H, Sullivan PS, Lyles C, Bernstein KT, Jenness SM.
        Sex Transm Dis. 2019 Jun;46(6):357-363.
        BACKGROUND: Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) acquisition and transmission. We estimated the proportion of HIV incidence among men who have sex with men attributable to infection with the 2 most common bacterial STIs, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). METHODS: We used a stochastic, agent-based model of a sexual network of MSM with cocirculating HIV, NG, and CT infections. Relative risk (RR) multipliers, specific to anatomic site of infection, modified the risk of HIV transmission and acquisition based on STI status. We estimated the effect of NG and CT on HIV incidence overall and on HIV acquisition and HIV transmission separately. Each scenario was simulated for 10 years. The population attributable fraction (PAF) was determined for each combination of RRs by comparing the incidence in the final year of a scenario to a scenario in which the RRs associated with NG and CT were set to 1.0. RESULTS: Overall, 10.2% (interquartile range [IQR], 7.9-12.4) of HIV infections were attributable to NG/CT infection. Then in sensitivity analyses, the PAF for HIV transmission ranged from 3.1% (IQR, 0.5-5.2) to 20.4% (IQR, 17.8-22.5) and the PAF for HIV acquisition ranged from 2.0% (IQR, -0.7 to 4.3) to 13.8% (IQR, 11.7-16.0). CONCLUSIONS: Despite challenges in estimating the causal impact of NG/CT on HIV risk, modeling is an alternative approach to quantifying plausible ranges of effects given uncertainty in the biological cofactors. Our estimates represent idealized public health interventions in which STI could be maximally prevented, setting targets for real-world STI interventions that seek to reduce HIV incidence.

      7. STD partner services to monitor and promote HIV pre-exposure prophylaxis use among men who have sex with menexternal icon
        Katz DA, Dombrowski JC, Barry M, Spellman D, Bell TR, Golden MR.
        J Acquir Immune Defic Syndr. 2019 Apr 15;80(5):533-541.
        BACKGROUND: Men who have sex with men (MSM) with bacterial sexually transmitted diseases (STDs) are at elevated risk of HIV. We evaluated the integration of pre-exposure prophylaxis (PrEP) referrals into STD partner services (PS) for MSM. SETTING: King County, Washington. METHODS: Disease Intervention Specialists (DIS) in King County attempt to provide PS to all MSM with early syphilis and, as resources allow, MSM with gonorrhea or chlamydia. Our health department defines MSM with any of the following as at high HIV risk: early syphilis, rectal gonorrhea, methamphetamine/poppers use, sex work, or an HIV-unsuppressed partner. DIS offer high-risk MSM referral to our STD Clinic for PrEP and other MSM referral to community providers. In 2017, we interviewed a random sample of MSM offered referrals in 2016 to assess PrEP initiation after PS. RESULTS: From August 2014 to August 2017, 7546 cases of bacterial STDs were reported among HIV-negative MSM. DIS provided PS to 3739 MSM, of whom 2055 (55%) were at high risk. DIS assessed PrEP use in 1840 (90%) of these men, 895 (49%) of whom reported already using PrEP. DIS offered referrals to 693 (73%) of 945 MSM not on PrEP; 372 (54%) accepted. Among 132 interviewed for the random sample, men who accepted referrals at initial interview were more likely to report using PrEP at follow-up (32/68 = 47%) than those who did not (12/64 = 19%) (P = 0.0006). An estimated 10.4% of all interviewed MSM initiated PrEP following PS-based referral. CONCLUSIONS: Integrating PrEP referrals into STD PS is an effective population-based strategy to link MSM at high HIV risk to PrEP.

      8. Expanding U.S. laboratory capacity for Neisseria gonorrhoeae antimicrobial susceptibility testing and whole-genome sequencing through the CDC's Antibiotic Resistance Laboratory Networkexternal icon
        Kersh EN, Pham CD, Papp JR, Myers R, Steece R, Kubin G, Gautom R, Nash EE, Sharpe S, Gernert KM, Schmerer M, Raphael BH, Henning T, Gaynor AM, Soge O, Schlanger K, Kirkcaldy RD, St Cyr SB, Torrone EA, Bernstein K, Weinstock H.
        J Clin Microbiol. 2020 Mar 25;58(4).
        U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. In 2016, the CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up the national capacity for detecting several resistance threats including N. gonorrhoeae AR-Ng testing, a subactivity of the CDC's AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in Maryland, Tennessee, Texas, and Washington), and the CDC's national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and the program Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole-genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 N. gonorrhoeae isolates, respectively, and the CDC received 531 and 646 concerning isolates and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported the laboratory capacity for N. gonorrhoeae AST and associated genetic marker detection, expanding preexisting notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.

      9. High prevalence of vaginal and rectal Mycoplasma genitalium macrolide resistance among female STD clinic patients in Seattle, Washingtonexternal icon
        Khosropour CM, Jensen JS, Soge OO, Leipertz G, Unutzer A, Pascual R, Barbee LA, Dombrowski JC, Golden MR, Manhart LE.
        Sex Transm Dis. 2020 Feb 18.
        BACKGROUND: Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are increasingly recognized as common infections among women. Little is known about the prevalence of rectal Mycoplasma genitalium (MG), rectal MG/CT/GC co-infection, or MG antimicrobial resistance patterns among women. METHODS: In 2017-2018 we recruited women at high risk for CT from Seattle's municipal STD clinic. Participants self-collected vaginal and rectal specimens for CT/GC nucleic acid amplification testing (NAAT). We retrospectively tested samples for vaginal and rectal MG using NAAT, and tested MG-positive specimens for macrolide resistance-mediating mutations (MRM) and ParC quinolone resistance-associated mutations (QRAMs). RESULTS: Of 50 enrolled women, 13 (26%) tested positive for MG, including 10 (20%) with vaginal MG and 11 (22%) with rectal MG; 8 (62%) had concurrent vaginal/rectal MG. Five (38%) were co-infected with CT; none with GC. Only 2 of 11 women with rectal MG reported anal sex in the prior year. Of MG-positive specimens, 100% of rectal and 89% of vaginal specimens had a MRM. There were no vaginal or rectal MG-positive specimens with ParC QRAMs previously associated with quinolone failure. Five MG-infected women received azithromycin for vaginal CT, four of whom had a MG MRM detected in their vaginal and/or rectal specimens. CONCLUSIONS: We observed a high prevalence of macrolide-resistant vaginal and rectal MG among a population of women at high risk for CT. This study highlights how the use of antimicrobials designed to treat an identified infection - in this case CT - could influence treatment outcomes and antimicrobial susceptibility in other unidentified infections.

      10. During 2013-2017, the national annual rate of reported primary and secondary (P&S) syphilis cases in the United States increased 72.7%, from 5.5 to 9.5 cases per 100,000 population (1). The highest rates of P&S syphilis are seen among gay, bisexual, and other men who have sex with men (collectively referred to as MSM) (2), and MSM continued to account for the majority of cases in 2017 (1). However, during 2013-2017, the P&S syphilis rate among women increased 155.6% (from 0.9 to 2.3 cases per 100,000 women), and the rate among all men increased 65.7% (from 10.2 to 16.9 cases per 100,000 men), indicating increasing transmission between men and women in addition to increasing transmission between men (1). To further understand these trends, CDC analyzed national P&S syphilis surveillance data for 2013-2017 and assessed the percentage of cases among women, men who have sex with women only (MSW), and MSM who reported drug-related risk behaviors during the past 12 months. Among women and MSW with P&S syphilis, reported use of methamphetamine, injection drugs, and heroin more than doubled during 2013-2017. In 2017, 16.6% of women with P&S syphilis used methamphetamine, 10.5% used injection drugs, and 5.8% used heroin during the preceding 12 months. Similar trends were seen among MSW, but not among MSM. These findings indicate that a substantial percentage of heterosexual syphilis transmission is occurring among persons who use these drugs, particularly methamphetamine. Collaboration between sexually transmitted disease (STD) control programs and partners that provide substance use disorder services will be important to address recent increases in heterosexual syphilis.

      11. Lymphogranuloma venereum: An increasingly common anorectal infection among men who have sex with men attending New York city sexual health clinicsexternal icon
        Pathela P, Jamison K, Kornblum J, Quinlan T, Halse TA, Schillinger JA.
        Sex Transm Dis. 2019 Feb;46(2):e14-e17.
        Using Chlamydia trachomatis anorectal specimens routinely tested for lymphogranuloma venereum (LGV) (2008-2011) and samples of archived specimens tested for LGV (2012-2015), we observed increased LGV positivity among men who have sex with men attending NYC Sexual Health Clinics. Using clinical data, we determined predictors of anorectal LGV that may guide clinical management.

      12. Clinical validation of the Aptima bacterial vaginosis and Aptima candida/trichomonas vaginitis assays: Results from a prospective multicenter clinical studyexternal icon
        Schwebke JR, Taylor SN, Ackerman R, Schlaberg R, Quigley NB, Gaydos CA, Chavoustie SE, Nyirjesy P, Remillard CV, Estes P, McKinney B, Getman DK, Clark C.
        J Clin Microbiol. 2020 Jan 28;58(2).
        Infectious vaginitis due to bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and Trichomonas vaginalis accounts for a significant proportion of all gynecologic visits in the United States. A prospective multicenter clinical study was conducted to validate the performance of two new in vitro diagnostic transcription-mediated amplification nucleic acid amplification tests (NAATs) for diagnosis of BV, VVC, and trichomoniasis. Patient- and clinician-collected vaginal-swab samples obtained from women with symptoms of vaginitis were tested with the Aptima BV and Aptima Candida/Trichomonas vaginitis (CV/TV) assays. The results were compared to Nugent (plus Amsel for intermediate Nugent) scores for BV, Candida cultures and DNA sequencing for VVC, and a composite of NAAT and culture for T. vaginalis The prevalences of infection were similar for clinician- and patient-collected samples: 49% for BV, 29% for VVC due to the Candida species group, 4% for VVC due to Candida glabrata, and 10% for T. vaginalis Sensitivity and specificity estimates for the investigational tests in clinician-collected samples were 95.0% and 89.6%, respectively, for BV; 91.7% and 94.9% for the Candida species group; 84.7% and 99.1% for C. glabrata; and 96.5% and 95.1% for T. vaginalis Sensitivities and specificities were similar in patient-collected samples. In a secondary analysis, clinicians' diagnoses, in-clinic assessments, and investigational-assay results were compared to gold standard reference methods. Overall, the investigational assays had higher sensitivity and specificity than clinicians' diagnoses and in-clinic assessments, indicating that the investigational assays were more predictive of infection than traditional diagnostic methods. These results provide clinical-efficacy evidence for two in vitro diagnostic NAATs that can detect the main causes of vaginitis.

      13. Ending congenital syphilisexternal icon
        Stafford IA, Sanchez PJ, Stoll BJ.
        Jama. 2019 Nov 11.

      14. Quarterly screening optimizes detection of sexually transmitted infections when prescribing HIV pre-exposure prophylaxisexternal icon
        Tang EC, Vittinghoff E, Philip SS, Doblecki-Lewis S, Bacon O, Chege W, Coleman ME, Elion R, Buchbinder S, Kolber MA, Liu AY, Cohen SE.
        Aids. 2020 Mar 19.
        OBJECTIVE: The optimal screening frequency of sexually transmitted infections (STIs) for men who have sex with men (MSM) and transgender women (TGW) on HIV pre-exposure prophylaxis (PrEP) is unclear, with current guidelines recommending screening every three to six months. We aimed to determine the number of STIs for which treatment would have been delayed without quarterly screening. DESIGN: The United States PrEP Demonstration Project was a prospective, open-label cohort study that evaluated PrEP delivery in STI clinics in San Francisco and Miami and a community health center in Washington, DC. 557 HIV-uninfected MSM and TGW were offered up to 48 weeks of PrEP and screened quarterly for STIs. METHODS: The proportion of gonorrhea, chlamydia, and syphilis infections for which treatment would have been delayed had screening been conducted every six versus every three months was determined by taking the number of asymptomatic STIs at weeks 12 and 36 divided by the total number of infections during the study follow-up period for each STI. RESULTS: 50.9% of participants had an STI during follow-up. If screening had been conducted only semiannually or based on symptoms, identification of 34.3% of gonorrhea, 40.0% of chlamydia, and 20.4% of syphilis infections would have been delayed by up to three months. The vast majority of participants (89.2%) with asymptomatic STIs reported condomless anal sex and had a mean of 8.1 partners between quarterly visits. CONCLUSIONS: Quarterly STI screening among MSM on PrEP could prevent a substantial number of partners from being exposed to asymptomatic STIs and decrease transmission. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT# 01632995.

      15. BACKGROUND: The rise of gonococcal antimicrobial resistance highlights the need for strategies that extend the clinically useful life span of antibiotics. Because there is limited evidence to support the current practice of switching empiric first-line antibiotic when resistance exceeds 5% in the population, our objective was to compare the impact of alternative strategies on the effective life spans of antibiotics and the overall burden of gonorrhea. METHODS AND FINDINGS: We developed and calibrated a mathematical model of gonorrhea transmission among men who have sex with men (MSM) in the United States. We calibrated the model to the estimated prevalence of gonorrhea, the rate of gonorrhea cases, and the proportion of cases presenting symptoms among MSM in the US. We used this model to project the effective life span of antibiotics and the number of gonorrhea cases expected under current and alternative surveillance strategies over a 50-year simulation period. We demonstrate that compared to the current practice, a strategy that uses quarterly (as opposed to yearly) surveillance estimates and incorporates both the estimated prevalence of resistance and the trend in the prevalence of resistance to determine treatment guidelines could extend the effective life span of antibiotics by 0.83 years. This is equivalent to successfully treating an additional 80.1 (95% uncertainty interval: [47.7, 111.9]) gonorrhea cases per 100,000 MSM population each year with the first-line antibiotics without worsening the burden of gonorrhea. If the annual number of isolates tested for drug susceptibility is doubled, this strategy could increase the effective life span of antibiotics by 0.94 years, which is equivalent to successfully treating an additional 91.1 (54.3, 127.3) gonorrhea cases per 100,000 MSM population each year without increasing the incidence of gonorrhea. Study limitations include that our conclusions might not be generalizable to other settings because our model describes the transmission of gonorrhea among the US MSM population, and, to better capture uncertainty in the characteristics of current and future antibiotics, we chose to model hypothetical drugs with characteristics similar to the antibiotics commonly used in gonorrhea treatment. CONCLUSIONS: Our results suggest that use of data from surveillance programs could be expanded to prolong the clinical effectiveness of antibiotics without increasing the burden of the disease. This highlights the importance of maintaining effective surveillance systems and the engagement of policy makers to turn surveillance findings into timely and effective decisions.


  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. Are uninsured women in a national screening program having longer intervals between cervical cancer screening tests?external icon
        Bartley SJ, Benard V, Tai E, Rockwell T, Kenney K, Richardson LC.
        Prev Med. 2020 Apr 1:106078.
        With increased understanding of the natural history of cervical cancer, cervical cancer screening recommendations have evolved (Schiffman & Wentzensen, 2013). As research better quantified the balance of benefits and harms of screening, new recommendations called for longer intervals between screening tests. Adherence to longer screening intervals detects similar numbers of abnormalities and decreases harms associated with overscreening/overtreatment. In this descriptive study, we examined the cervical cancer screening intervals from 2010 to 2018 in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). There were 1,397,899 women aged 21-64 who were screened for cervical cancer from 2010 to 2018 and 556,743 rescreenings of average risk women were performed. The median cervical screening interval increased from 2.02years in 2010 to 3.88years in 2018. Providers serving uninsured women in a national screening program are following the recommendations of longer intervals between cervical cancer screenings.

      2. Reporting and assessing the quality of diagnostic accuracy studies for cervical cancer screening and managementexternal icon
        Clarke MA, Darragh TM, Nelson E, Unger ER, Zuna R, Cremer M, Stockdale CK, Einstein MH, Wentzensen N.
        J Low Genit Tract Dis. 2020 Apr;24(2):157-166.
        OBJECTIVE: We adapted the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool for studies of cervical cancer screening and management and used the adapted tool to evaluate the quality of studies included in a systematic review supporting the 2019 Risk-Based Management Consensus Guidelines. METHODS: We evaluated the quality of all studies included in our systematic review for postcolposcopy (n = 5) and posttreatment (n = 23) surveillance using QUADAS-2 criteria. Subsequently, we adapted signaling questions to indications of cervical cancer screening and management. An iterative process was carried out to evaluate interrater agreement between 2 study authors (M.A.C. and N.W.). Discrepant ratings were discussed, and criteria were adapted accordingly. We also evaluated the influence of study quality on risk estimates and between study variation using stratified subgroup meta-analyses. RESULTS: Twelve signaling questions for bias assessment that were adapted to or newly developed for cervical cancer screening and management are described here. Interrater agreement on bias assessment increased from 70% to 83% during the adaptation process. Detailed assessment of bias and applicability showed that all studies on postcolposcopy management and 90% of studies on posttreatment management had high risk of bias in at least 1 domain. Most commonly, high risk of bias was observed for the patient selection domain, indicating the heterogeneity of study designs and clinical practice in reported studies. CONCLUSIONS: The adapted QUADAS-2 will have broad application for researchers, evidence evaluators, and journals who are interested in designing, conducting, evaluating, and publishing studies for cervical cancer screening and management.

      3. A systematic review of tests for postcolposcopy and posttreatment surveillanceexternal icon
        Clarke MA, Unger ER, Zuna R, Nelson E, Darragh TM, Cremer M, Stockdale CK, Einstein MH, Wentzensen N.
        J Low Genit Tract Dis. 2020 Apr;24(2):148-156.
        OBJECTIVE: For the 2019 ASCCP Risk-Based Management Consensus Guidelines, we conducted a systematic review of diagnostic assays for postcolposcopy and posttreatment management. MATERIALS AND METHODS: A literature search was conducted to identify articles reporting on tests/assays for cervical cancer screening, triage, postcolposcopy surveillance, and posttreatment surveillance published between 2012 and 2019 in PubMed and Embase. Titles and abstracts were evaluated by co-authors for inclusion. Included articles underwent full-text review, data abstraction, and quality assessment. Pooled absolute pretest and posttest risk estimates were calculated for studies evaluating management of patients after treatment. RESULTS: A total of 2,862 articles were identified through the search. Of 50 articles on postcolposcopy, 5 were included for data abstraction. Of 66 articles on posttreatment, 23 were included for data abstraction and were summarized in the meta-analysis. The pooled posttreatment risk of cervical intraepithelial neoplasia (CIN) 2+ in all studies was 4.8% (95% CI = 3.4%-6.8%), ranging from 0.4%-19.5% (tau = 0.57) in individual studies. Among individuals testing negative for human papillomavirus (HPV) posttreatment, the risk of CIN 2+ was 0.69% (95% CI = 0.3%-1.5%); among individuals testing positive for HPV posttreatment, the risk of CIN 2+ was 18.3% (95% CI = 12.1%-26.6%) in all studies. All risk estimates were substantially higher for liquid-based cytology. The HPV-cytology co-testing provided slightly better reassurance compared with HPV alone at the cost of much higher positivity. CONCLUSIONS: Despite a large number of published studies on postcolposcopy and posttreatment surveillance, only few met criteria for abstraction and were included in the meta-analysis. More high-quality studies are needed to evaluate assays and approaches that can improve management of patients with abnormal screening.

      4. Incorporating stakeholder feedback in guidelines development for the management of abnormal cervical cancer screening testsexternal icon
        Perkins RB, Fuzzell LN, Lake P, McIntyre M, Nayar R, Saraiya M, Loukissas J, Felder T, Guido RS, Vadaparampil ST.
        J Low Genit Tract Dis. 2020 Apr;24(2):167-177.
        OBJECTIVE: The 2019 ASCCP Risk-Based Management Consensus Guidelines present a paradigm shift from results- to risk-based management. Patient and provider factors can affect guideline adoption. We sought feedback from stakeholders to inform guideline development. MATERIALS AND METHODS: To solicit provider feedback, we surveyed attendees at the 2019 ASCCP annual meeting regarding readiness to adopt proposed changes and used a web-based public comment period to gauge agreement/disagreement with preliminary guidelines. We elicited patient feedback via a brief survey on preferences around proposed recommendations for treatment without biopsy. Surveys and public comment included both closed-ended and free-text items. Quantitative results were analyzed using descriptive statistics; qualitative results were analyzed using content analysis. Results were incorporated into guideline development in real time. RESULTS: Surveys indicated that 98% of providers currently evaluate their patients' past results to determine management; 88% felt formally incorporating history into management would represent an improvement in care. Most providers supported expedited treatment without biopsy: 22% currently perform expedited treatment and 60% were willing to do so. Among patients, 41% preferred expedited treatment, 32% preferred biopsy before treatment, and the remainder were undecided. Responses from the public comment period included agreement/disagreement with preliminary guidelines, reasons for disagreement, and suggestions for improvement. CONCLUSIONS: Stakeholder feedback was incorporated into the development of the 2019 ASCCP Risk-Based Management Consensus Guidelines. Proposed recommendations with less than two-thirds agreement in the public comment period were considered for revision. Findings underscore the importance of stakeholder feedback in developing guidelines that meet the needs of patients and providers.

      5. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursorsexternal icon
        Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, Huh WK, Kim JJ, Moscicki AB, Nayar R, Saraiya M, Sawaya GF, Wentzensen N, Schiffman M.
        J Low Genit Tract Dis. 2020 Apr;24(2):102-131.

      6. Prevalence of self-reported hypertension and antihypertensive medication use among adults - United States, 2017external icon
        Samanic CM, Barbour KE, Liu Y, Fang J, Lu H, Schieb L, Greenlund KJ.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):393-398.
        Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke (1). The prevalence of hypertension is higher among men than among women, increases with age, is highest among non-Hispanic blacks (blacks) (2), and has been consistently highest in the Southeastern region of the United States (1). To update prevalence estimates for self-reported hypertension and use of antihypertensive medication, CDC analyzed data from the 2017 Behavioral Risk Factor Surveillance System (BRFSS). The overall (unadjusted) prevalence of self-reported hypertension was 32.4% (95% confidence interval [CI] = 32.1%-32.7%). The age-standardized, median state-specific prevalence of self-reported hypertension was 29.7% (range = 24.3%-38.6%). Overall age-standardized hypertension prevalence was higher among men (32.9%) than among women (27.0%), highest among blacks (40.0%), decreased with increasing levels of education and household income, and was generally highest in the Southeastern and Appalachian states.* Among persons reporting hypertension, the overall unadjusted prevalence of self-reported antihypertensive medication use was 76.0% (95% CI = 75.5%-76.4%). The age-standardized, median state-specific prevalence of antihypertensive medication use among persons with reported hypertension was 59.4% (range = 50.2%-71.2%). Prevalence was higher among women than men, highest among blacks compared with other racial/ethnic groups, and highest among states in the Southeast, Appalachia, and the Dakotas. These findings can help inform CDC's initiatives to enhance hypertension awareness, treatment, and control across all states.

      7. Bridging the gap among clinical practice guidelines for pain management in cancer and sickle cell diseaseexternal icon
        Schatz AA, Oliver TK, Swarm RA, Paice JA, Darbari DS, Dowell D, Meghani SH, Winckworth-Prejsnar K, Bruera E, Plovnick RM, Richardson L, Vapiwala N, Wollins D, Hudis CA, Carlson RW.
        JCO Oncol Pract. 2020 Apr 7:Jop1900675.
        Opioids are a critical component of pain relief strategies for the management of patients with cancer and sickle cell disease. The escalation of opioid addiction and overdose in the United States has led to increased scrutiny of opioid prescribing practices. Multiple reports have revealed that regulatory and coverage policies, intended to curb inappropriate opioid use, have created significant barriers for many patients. The Centers for Disease Control and Prevention, National Comprehensive Cancer Network, and ASCO each publish clinical practice guidelines for the management of chronic pain. A recent JAMA Oncology article highlighted perceived variability in recommendations among these guidelines. In response, leadership from guideline organizations, government representatives, and authors of the original article met to discuss challenges and solutions. The meeting featured remarks by the Commissioner of Food and Drugs, presentations on each clinical practice guideline, an overview of the pain management needs of patients with sickle cell disease, an overview of perceived differences among guidelines, and a discussion of differences and commonalities among the guidelines. The meeting revealed that although each guideline varies in the intended patient population, target audience, and methodology, there is no disagreement among recommendations when applied to the appropriate patient and clinical situation. It was determined that clarification and education are needed regarding the intent, patient population, and scope of each clinical practice guideline, rather than harmonization of guideline recommendations. Clinical practice guidelines can serve as a resource for policymakers and payers to inform policy and coverage determinations.

      8. OBJECTIVES: Adults with multiple chronic conditions (MCCs; >/=2 chronic conditions) account for a substantial number of visits to health care providers. The complexity of a patient's care, including the number of chronic conditions, may differ by physician specialty. The objectives of this study were to (1) examine differences in physician office visits among adults with MCCs by physician specialty and (2) identify the types of MCC dyads (combinations of 2 chronic conditions) most common among visits to office-based physicians. METHODS: We used data from the 2014-2015 National Ambulatory Medical Care Survey (unweighted analytic sample, n = 61 682), a nationally representative survey of physician office-based ambulatory visits, to examine differences in physician office visits among adults with MCCs by physician specialty. We also identified the most commonly observed MCC dyads among these visits. RESULTS: During 2014-2015, 40.0% of physician office visits were made by adults with MCCs. Compared with visits for all specialties combined (40.0%), a significantly higher percentage of physician office visits among adults with MCCs were to specialists in cardiovascular disease (74.7%) and internal medicine (57.6%). For all physician specialties except psychiatry, the MCC dyads of hyperlipidemia and hypertension and diabetes and hypertension were among the most commonly observed MCC dyads among visits made by adults with MCCs. CONCLUSIONS: Awareness of these findings may help specialists improve care for adults with MCCs. The recognition among physicians of common MCC dyads is relevant to the care management of persons with MCCs.

    • Communicable Diseases
      1. Rotavirus and type 1 diabetes - is there a connection? A synthesis of the evidenceexternal icon
        Burke RM, Tate JE, Jiang B, Parashar UD.
        J Infect Dis. 2020 Apr 6.
        Though the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences. Further, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to-date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear.

      2. OBJECTIVES: The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) depends on reporting by health care facilities and laboratories for disease surveillance. Our objective was to evaluate the completeness of DOHMH surveillance to identify births to hepatitis B virus (HBV)-positive women to prevent perinatal transmission. METHODS: We identified infants born to HBV-positive women by matching mothers of all infants born in NYC during May 1, 2013-May 1, 2014, identified from the Citywide Immunization Registry (CIR) to persons with HBV-positive laboratory reports in the Electronic Laboratory Reporting (ELR) system. We then matched infants born to mothers identified in the CIR/ELR match to infants born to HBV-positive women from the DOHMH perinatal HBV surveillance database. We performed capture-recapture analysis to evaluate completeness of DOHMH case identification. We compared the proportion of infants born to HBV-positive mothers reported to DOHMH with the proportion of infants identified only through the CIR/ELR match for receipt of postexposure prophylaxis (PEP) and completion of the HBV vaccination series and post-vaccination serology testing. RESULTS: Of 1662 infants identified from the CIR/ELR match and 1554 infants in the DOHMH database, 1493 infants matched. Of 169 infants only in the CIR/ELR data set, 55 were born to HBV-positive women residing in NYC. Sixty-one infants were only in the DOHMH database. An estimated 2 infants were not identified by either method. The CIR/ELR match increased infant identification by 3.5%, from 1554 to 1609 infants. The proportion of infants who received PEP was significantly higher among infants whose mothers were reported to DOHMH (vs not reported to DOHMH). PRACTICAL IMPLICATIONS: Use of the CIR/ELR match may further improve DOHMH identification of infants born to HBV-positive women and receipt of infant PEP.

      3. Longitudinal analysis of depressive symptoms, perceived social support, and alcohol use among HIV-infected men who inject drugs in Northern Vietnamexternal icon
        Hershow RB, Gottfredson NC, Ha TV, Chu VA, Lancaster KE, Quan VM, Levintow SN, Sripaipan T, Gaynes BN, Pence BW, Go VF.
        Subst Use Misuse. 2020 Apr 8:1-9.
        Background: Limited research examines depressive symptoms, alcohol use, and social support among HIV-infected people who inject drugs. Objectives: Using longitudinal data, we investigated whether perceived social support moderates the relationship between depressive symptoms and alcohol use among HIV-infected men who inject drugs in Vietnam. Methods: Data were collected from participants (N = 455; mean age 35 years) in a four-arm randomized controlled trial in Thai Nguyen, Vietnam. Data were collected at baseline, 6, 12, 18, and 24 months with 94% retention excluding dead (N = 103) or incarcerated (N = 37) participants. Multilevel growth models were used to assess whether: (1) depressive symptoms predict when risk of alcohol use is elevated (within-person effects); (2) depressive symptoms predict who is at risk for alcohol use (between-person effects); and (3) within- and between-person perceived social support moderates the depressive symptoms-alcohol relationship. Results: Participants reported high but declining levels of depressive symptoms and alcohol use. Participants with higher depressive symptoms drank less on average (B = -0.0819, 95% CI -0.133, -0.0307), but within-person, a given individual was more likely to drink when they were feeling more depressed than usual (B = 0.136, 95% CI 0.0880, 0.185). The positive relationship between within-person depressive symptoms and alcohol use grew stronger at higher levels of within-person perceived social support. Conclusions: HIV-infected men who inject drugs have increased alcohol use when they are experiencing higher depressive symptoms than usual, while those with higher average depressive symptoms over time report less alcohol use. Social support strengthens the positive relationship between within-person depressive symptoms and alcohol use.

      4. In the past two decades, major advances in biomedical intervention approaches to prevent HIV and many sexually transmissible infections (STIs) have shown great promise. However, challenges to prevention remain in the area of achieving population-level impact for biomedical prevention approaches. In this paper we address what social and behavioural research approaches can contribute beyond well-known behaviour change and counselling interventions. We organise work into five areas. Adherence and disinhibition research is primarily into individual-level constructs pertaining to maximising intervention effectiveness. Coverage research represents a population-level construct germane to maximising efficient prioritisation for prevention. Research covering social determinants, a second population-level construct, contributes to both prioritisation and effectiveness. Finally, disparities and social inequities need to be incorporated into prevention, given the pervasive and persistent disparities found in rates of HIV and STIs and in their antecedents.

      5. Fifty years of influenza A(H3N2) following the pandemic of 1968external icon
        Jester BJ, Uyeki TM, Jernigan DB.
        Am J Public Health. 2020 May;110(5):669-676.
        In 2018, the world commemorated the centennial of the 1918 influenza A(H1N1) pandemic, the deadliest pandemic in recorded history; however, little mention was made of the 50th anniversary of the 1968 A(H3N2) pandemic. Although pandemic morbidity and mortality were much lower in 1968 than in 1918, influenza A(H3N2) virus infections have become the leading cause of seasonal influenza illness and death over the last 50 years, with more than twice the number of hospitalizations from A(H3N2) as from A(H1N1) during the past six seasons. We review the emergence, progression, clinical course, etiology, epidemiology, and treatment of the 1968 pandemic and highlight the short- and long-term impact associated with A(H3N2) viruses. The 1968 H3N2 pandemic and its ongoing sequelae underscore the need for improved seasonal and pandemic influenza prevention, control, preparedness, and response efforts.

      6. The HIV continuum of care for adolescents and young adults attending 13 urban US HIV Care Centers of the NICHD-ATN-CDC-HRSA SMILE Collaborativeexternal icon
        Kapogiannis BG, Koenig LJ, Xu J, Mayer KH, Loeb J, Greenberg L, Monte D, Banks-Shields M, Fortenberry JD.
        J Acquir Immune Defic Syndr. 2020 May 1;84(1):92-100.
        BACKGROUND: Almost one-quarter of all new HIV diagnoses in the United States occur among persons aged 13-24 years. These youths have the poorest HIV care continuum (HCC) outcomes, yet few empirical youth-specific data are available. METHODS: The Strategic Multisite Initiative for the Identification, Linkage, and Engagement in Care of HIV-infected youth (SMILE) helped HIV-infected (mostly newly diagnosed) youth, aged 12-24 years, link to youth-friendly care, and evaluated each milestone of the HCC (October 2012-September 2014). Numbers of HIV-infected youth referred, linked, engaged, and retained in care were recorded, along with sociodemographics. Viral suppression (VS) was defined as >/=1 HIV viral load (VL) below the level of detection on study. Correlates of VS were examined using Cox proportional hazards models. RESULTS: Among 1411 HIV-infected youth, 1053 (75%) were linked, 839 (59%) engaged, and 473 (34%) retained in care at adolescent health care sites. Antiretroviral therapy was initiated among 474 (34%), and 166 (12%) achieved VS. Predictors of VS included lower VL at baseline [aHR 1.56 (95% CI: 1.32-1.89), P < 0.0001], recent antiretroviral therapy receipt [aHR 3.10 (95% CI: 1.86-5.18), P < 0.0001], and shorter time from HIV testing until referral to linkage coordinator [aHR 2.52 (95% CI: 1.50-4.23), P = 0.0005 for 7 days to 6 weeks and aHR 2.08 (95% CI: 1.08-4.04), P = 0.0294 for 6 weeks to 3 months compared with >3 months]. CONCLUSIONS: Although this large national sample of predominately newly diagnosed youths linked to care at similar rates as adults, they achieved disproportionately lower rates of VS. Prompt referral to youth-friendly linkage services was an independent predictor of VS. Youth-focused interventions are urgently needed to improve their HCC outcomes.

      7. Pre-treatment loss to follow-up among children with multidrug-resistant tuberculosis in South Africa, 2008-2010external icon
        Moore BK, Erasmus L, Ershova J, Smith SE, Ndjeka N, Podewils LJ.
        PLoS One. 2020 ;15(4):e0230504.
        Multidrug-resistant (MDR) TB is more difficult to diagnose and treat compared with drug-susceptible TB. Young children are at greater risk of severe TB disease and death when treatment is delayed compared to adults. We sought to describe characteristics of children (<13 years) diagnosed with MDR TB between 2008-2010 in three South African provinces and assess factors associated with pre-treatment loss to follow-up. We matched laboratory and medical records at treatment facilities to identify pre-treatment loss and examined demographic and clinical characteristics for association with loss. Categorical variables were examined for association using Pearson's x2 or Fisher's exact test, employing Bonferroni correction for multiple pairwise comparisons. Between 2008-2010, 156 children were diagnosed with laboratory-confirmed MDR TB. Only 44% (n = 69) were documented as having received treatment. Young children (<2 years) (47/59, 80%), children with extrapulmonary (EP) TB (27/34, 79%), and children diagnosed at general hospitals (60/97, 62%) were most likely to be lost before treatment. Children most vulnerable to death from TB are most likely to be lost before treatment, possibly leading to underestimates of disease burden, case notifications, and poor outcomes among this population. Point-of-care diagnosis and robust follow-up may reduce pre-treatment loss in this population.

      8. Modeling missing cases and transmission links in networks of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africaexternal icon
        Nelson KN, Gandhi NR, Mathema B, Lopman BA, Brust JC, Auld SC, Ismail N, Omar SV, Brown TS, Allana S, Campbell A, Moodley P, Mlisana K, Shah NS, Jenness SM.
        Am J Epidemiol. 2020 Apr 3.
        Transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa diagnosed in 2011-2014. We tested scenarios in which cases were missing at random, differentially by clinical characteristics or by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing randomly, the mean number of transmissions per case in the complete network needed to be larger than 20, far higher than expected, to reproduce the observed network. Instead, the most likely scenario involved undersampling of high-transmitting cases and models provided evidence for superspreading. This is the first study to assess support for different mechanisms of missingness in a TB transmission study, but our results are subject to the distributional assumptions of the network models we used. Transmission studies should consider the potential biases introduced by incomplete sampling and identify host, pathogen, or environmental factors driving superspreading.

      9. Suspected locally acquired coccidioidomycosis in human, Spokane, Washington, USAexternal icon
        Oltean HN, Springer M, Bowers JR, Barnes R, Reid G, Valentine M, Engelthaler DM, Toda M, McCotter OZ.
        Emerg Infect Dis. 2020 Mar;26(3):606-609.
        The full geographic range of coccidioidomycosis is unknown, although it is most likely expanding with environmental change. We report an apparently autochthonous coccidioidomycosis patient from Spokane, Washington, USA, a location to which Coccidioides spp. are not known to be endemic.

      10. Notes from the field: Seasonal human influenza A(H3N2) and influenza A(H1N1)pdm09 reassortant infection - Idaho, 2019external icon
        Pedersen R, Barton V, Tripp J, Blanton L, Barnes J, Hahn C.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):427-428.

      11. Vital Signs: Newly reported acute and chronic hepatitis C cases - United States, 2009-2018external icon
        Ryerson AB, Schillie S, Barker LK, Kupronis BA, Wester C.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):399-404.
        INTRODUCTION: Hepatitis C is a leading cause of death from liver disease in the United States. Acute hepatitis C infection is often asymptomatic, and >50% of cases will progress to chronic infection, which can be life-threatening. Hepatitis C can be diagnosed with a blood test and is curable, yet new cases of this preventable disease are increasing. METHODS: National Notifiable Diseases Surveillance System data were analyzed to determine the rate of acute hepatitis C cases reported to CDC by age group and year during 2009-2018 and the number and rate of newly reported chronic cases in 2018 by sex and age. The proportion of adults aged >/=20 years with hepatitis C who reported having ever been told that they had hepatitis C was estimated with 2015-2018 National Health and Nutrition Examination Survey data. RESULTS: During 2018, a total of 3,621 cases of acute hepatitis C were reported, representing an estimated 50,300 cases (95% confidence interval [CI] = 39,800-171,600). The annual rate of reported acute hepatitis C cases per 100,000 population increased threefold, from 0.3 in 2009 to 1.2 in 2018, and was highest among persons aged 20-29 (3.1) and 30-39 years (2.6) in 2018. A bimodal distribution of newly reported chronic hepatitis C cases in 2018 was observed, with the highest proportions among persons aged 20-39 years and 50-69 years. Only 60.6% (95% CI = 46.1%-73.9%) of adults with hepatitis C reported having been told that they were infected. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Increasing rates of acute hepatitis C among young adults, including reproductive-aged persons, have put multiple generations at risk for chronic hepatitis C. The number of newly reported chronic infections was approximately equal among younger and older adults in 2018. The new CDC hepatitis C testing recommendations advise screening all adults and pregnant women, not just persons born during 1945-1965, and those with risk factors.

      12. CDC recommendations for hepatitis C screening among adults - United States, 2020external icon
        Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB.
        MMWR Recomm Rep. 2020 Apr 10;69(2):1-17.
        Hepatitis C virus (HCV) infection is a major source of morbidity and mortality in the United States. HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use. No vaccine against hepatitis C exists and no effective pre- or postexposure prophylaxis is available. More than half of persons who become infected with HCV will develop chronic infection. Direct-acting antiviral treatment can result in a virologic cure in most persons with 8-12 weeks of all-oral medication regimens. This report augments (i.e., updates and summarizes) previously published recommendations from CDC regarding testing for HCV infection in the United States (Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rec 2012;61[No. RR-4]). CDC is augmenting previous guidance with two new recommendations: 1) hepatitis C screening at least once in a lifetime for all adults aged >/=18 years, except in settings where the prevalence of HCV infection is <0.1% and 2) hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1%. The recommendation for HCV testing that remains unchanged is regardless of age or setting prevalence, all persons with risk factors should be tested for hepatitis C, with periodic testing while risk factors persist. Any person who requests hepatitis C testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.

      13. Low uptake of direct-acting antiviral therapy among hepatitis C patients with advanced liver disease and access to care, 2014-2017external icon
        Spradling PR, Xing J, Rupp LB, Moorman AC, Gordon SC, Lu M, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Holmberg SD.
        J Clin Gastroenterol. 2020 Apr 3.
        GOALS: To determine the proportion and characteristics of adults with hepatitis C at health care organizations in 4 US states who initiated direct-acting antivirals (DAAs). BACKGROUND: There are almost no data to assess the penetrance of treatment of the hepatitis C population in general US health care settings. STUDY: We conducted a prospective observational study using electronic clinical, pharmacy, and mortality data to determine the fraction of patients who initiated DAAs between January 2014 and December 2017, by start date and regimen. We used stepwise multivariate logistic regression analysis to identify sociodemographic and clinical characteristics associated with receipt of DAAs. RESULTS: Of 8823 patients, 2887 (32.7%) received DAAs. Quarterly (Q) uptake ranged from 1.1% in Q3 2014 to a high of 5.6% in Q2 2015. Characteristics associated with receipt of DAAs included age 51 to 70 years, higher income, pre-2014 treatment failure, and higher noninvasive fibrosis score (FIB4); however, over one half of patients with FIB4 scores >3.25, consistent with severe liver disease, were not treated. A lower likelihood of initiation was associated with Medicaid coverage. Of 5936 patients who did not initiate treatment, 911 (15.3%) had died and 2774 (46.7%) had not had a clinical encounter in >/=12 months by the end of the study. Fewer than 1% of DAA prescriptions originated from nonspecialty providers. CONCLUSIONS: During 4 calendar years of follow-up, one third of patients initiated DAAs. Large fractions of untreated patients had advanced liver disease, died, or were lost to follow-up. Even among patients in integrated health care systems, receipt of DAAs was limited.

      14. The US Centers for Disease Control and Prevention recommends screening populations at increased risk for tuberculosis (TB), including persons born in countries with high TB rates. This approach assumes that TB risk for expatriates living in the United States is representative of TB risk in their countries of birth. We compared US TB rates by country of birth with corresponding country rates by calculating incidence rate ratios (IRRs) (World Health Organization rate/US rate). The median IRR was 5.4. The median IRR was 0.5 for persons who received a TB diagnosis <1 year after US entry, 4.9 at 1 to <10 years, and 10.0 at >10 years. Our analysis suggests that World Health Organization TB rates are not representative of TB risk among expatriates in the United States and that TB testing prioritization in the United States might better be based on US rates by country of birth and years in the United States.

      15. Infective endocarditis among persons aged 18-64 years with HIV, hepatitis C infection, or opioid use disorder - United States, 2007-2017external icon
        Wong CY, Zhu W, Aurigemma GP, Furukawa N, Teshale EH, Huang YA, Peters PJ, Hoover KW.
        Clin Infect Dis. 2020 Apr 9.
        BACKGROUND: Infective endocarditis (IE) is a life-threatening bacterial infection of the heart valves, most often diagnosed in older persons and persons with prior cardiac surgery. It is also associated with injection drug use, a behavior that has increased in recent years along with the U.S. opioid crisis. METHODS: We conducted a retrospective cohort analysis of commercial and Medicaid health insurance databases to estimate incident cases of IE in the United States in 2017, stratified by HIV, HCV infection and opioid use disorder (OUD). We also estimated annual percentage changes (EAPCs) in IE from 2007-2017 among persons with commercial insurance. RESULTS: The weighted incidence rate of IE was 13.8 cases per 100,000 persons among persons with commercial insurance, and 78.7 among those with Medicaid. The incidence rate of IE among commercially insured persons increased slightly from 2007-2017 (EAPC 1.0%). It decreased among commercially insured persons with HIV from 148.0 in 2007 to 112.1 in 2017 (EAPC -4.3%) and increased among those with HCV infection from 172.4 to 238.6 in 2017 (EAPC 3.2%). Among persons aged 18-29 years with HCV infection, IE increased from 337.6 in 2007 to 1028.7 in 2017 (EAPC 15.3%), and among those with OUD it increased from 156.4 in 2007 to 642.9 in 2017 (EAPC 13.8%). CONCLUSIONS: The incidence rate of IE increased markedly among young persons with HCV infection or OUD. This increase appears to parallel the ongoing national opioid crisis. Harm reduction with syringe services programs, medications for opioid use disorder, and safe injection practices can prevent HIV, HCV, and IE.

      16. BACKGROUND: The rise of gonococcal antimicrobial resistance highlights the need for strategies that extend the clinically useful life span of antibiotics. Because there is limited evidence to support the current practice of switching empiric first-line antibiotic when resistance exceeds 5% in the population, our objective was to compare the impact of alternative strategies on the effective life spans of antibiotics and the overall burden of gonorrhea. METHODS AND FINDINGS: We developed and calibrated a mathematical model of gonorrhea transmission among men who have sex with men (MSM) in the United States. We calibrated the model to the estimated prevalence of gonorrhea, the rate of gonorrhea cases, and the proportion of cases presenting symptoms among MSM in the US. We used this model to project the effective life span of antibiotics and the number of gonorrhea cases expected under current and alternative surveillance strategies over a 50-year simulation period. We demonstrate that compared to the current practice, a strategy that uses quarterly (as opposed to yearly) surveillance estimates and incorporates both the estimated prevalence of resistance and the trend in the prevalence of resistance to determine treatment guidelines could extend the effective life span of antibiotics by 0.83 years. This is equivalent to successfully treating an additional 80.1 (95% uncertainty interval: [47.7, 111.9]) gonorrhea cases per 100,000 MSM population each year with the first-line antibiotics without worsening the burden of gonorrhea. If the annual number of isolates tested for drug susceptibility is doubled, this strategy could increase the effective life span of antibiotics by 0.94 years, which is equivalent to successfully treating an additional 91.1 (54.3, 127.3) gonorrhea cases per 100,000 MSM population each year without increasing the incidence of gonorrhea. Study limitations include that our conclusions might not be generalizable to other settings because our model describes the transmission of gonorrhea among the US MSM population, and, to better capture uncertainty in the characteristics of current and future antibiotics, we chose to model hypothetical drugs with characteristics similar to the antibiotics commonly used in gonorrhea treatment. CONCLUSIONS: Our results suggest that use of data from surveillance programs could be expanded to prolong the clinical effectiveness of antibiotics without increasing the burden of the disease. This highlights the importance of maintaining effective surveillance systems and the engagement of policy makers to turn surveillance findings into timely and effective decisions.

    • Disease Reservoirs and Vectors
      1. Rickettsia parkeri (Rickettsiales: Rickettsiaceae) in the Sky Islands of West Texasexternal icon
        Paddock CD, Hecht JA, Green AN, Waldrup KA, Teel PD, Karpathy SE, Johnson TL.
        J Med Entomol. 2020 Apr 4.
        Rickettsia parkeri, a tick-borne pathogen distributed throughout several countries of the Americas, causes a mild to moderately severe, eschar-associated spotted fever rickettsiosis. Although most U.S. cases of R. parkeri rickettsiosis are reported from southeastern states, some have been reported recently from remote regions of southern Arizona. These cases are linked to R. parkeri-infected ticks of the Amblyomma maculatum (Acari: Ixodidae) group found in several isolated mountain ranges of southern Arizona and New Mexico, referred to as 'sky islands'. Archival records also document ticks of the A. maculatum group collected from domestic and wild animals in West Texas. We surveyed sites in two sky island chains of Jeff Davis and Brewster counties to document the off-host occurrence of these ticks and identify the presence of R. parkeri in the Trans-Pecos region of Texas. During August 2019, 43 adult A. maculatum group ticks were flagged from vegetation or removed from a road-killed, female mule deer. Of 39 samples evaluated by PCR, eight contained a partial sca0 sequence with complete identity to R. parkeri and two with complete identity to 'Candidatus Rickettsia andeanae', a species of undetermined pathogenicity. Four isolates of R. parkeri were obtained using cell culture. Persons at risk for R. parkeri rickettsiosis include those who work or recreate in these mountains, such as hikers, backpackers, research scientists, foresters, and border enforcement personnel. Additional investigations are needed to define the distribution of these medically important arthropods in other parts of the southwestern United States and northern Mexico.

    • Environmental Health
      1. Association of parental preconception exposure to phthalates and phthalate substitutes with preterm birthexternal icon
        Zhang Y, Mustieles V, Yland J, Braun JM, Williams PL, Attaman JA, Ford JB, Calafat AM, Hauser R, Messerlian C.
        JAMA Netw Open. 2020 Apr 1;3(4):e202159.
        Importance: Although phthalate exposure during pregnancy has been associated with preterm birth, the association of preconception exposure in either parent with preterm birth constitutes a knowledge gap. Objective: To examine the association of paternal and maternal preconception urinary concentrations of biomarkers of phthalates and phthalate substitutes with singleton preterm birth. Design, Setting, and Participants: This study, conducted at an academic fertility center in Boston, Massachusetts, included a prospective preconception cohort of subfertile couples comprising 419 mothers and 229 fathers and their 420 live-born singleton offspring born between January 1, 2005, and December 31, 2018. Statistical analysis was performed from August 1 to October 31, 2019. Exposures: Urinary concentrations of metabolites of phthalates and phthalate substitutes obtained before conception. Main Outcomes and Measures: Gestational age was abstracted from delivery records and validated using the American College of Obstetricians and Gynecologists guidelines for births after medically assisted reproduction. The risk ratio (RR) of preterm birth (live birth before 37 completed weeks' gestation) was estimated in association with urinary concentrations of 11 individual phthalate metabolites, the molar sum of 4 di-(2-ethylhexyl) phthalate (SigmaDEHP) metabolites, and 2 metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH, a nonphthalate plasticizer substitute) using modified Poisson regression models adjusted for covariates. Results: The mean (SD) age of the 419 mothers was 34.7 (4.0) years, the mean (SD) age of the 229 fathers was 36.0 (4.5) years, and the mean (SD) gestational age of the 420 singleton children (217 boys) was 39.3 (1.7) weeks, with 34 (8%) born preterm. In adjusted models, maternal preconception SigmaDEHP concentrations (RR, 1.50; 95% CI, 1.09-2.06; P = .01) and cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH, a metabolite of DINCH) concentrations (RR, 1.70; 95% CI, 0.89-3.24; P = .11) were associated with an increased risk of preterm birth. After additional adjustment for prenatal SigmaDEHP or MHiNCH concentrations, the association of maternal preconception exposure to SigmaDEHP and preterm birth remained robust (RR, 1.69; 95% CI, 1.17-2.44; P = .006), while the association of maternal preconception exposure to MHiNCH and preterm birth was attenuated (RR, 1.17; 95% CI, 0.49-2.81; P = .72). The remaining urinary metabolites examined in either parent showed no association with preterm birth. Conclusions and Relevance: In this prospective cohort of subfertile couples, maternal preconception exposure to SigmaDEHP metabolites was associated with an increased risk of preterm birth. The results suggest that female exposure to select phthalate plasticizers during the preconception period may be a potential risk factor for adverse pregnancy outcomes, which may need to be considered in preconception care strategies.

    • Epidemiology and Surveillance
      1. Nowcasting by Bayesian smoothing: A flexible, generalizable model for real-time epidemic trackingexternal icon
        McGough SF, Johansson MA, Lipsitch M, Menzies NA.
        PLoS Comput Biol. 2020 Apr 6;16(4):e1007735.
        Achieving accurate, real-time estimates of disease activity is challenged by delays in case reporting. "Nowcast" approaches attempt to estimate the complete case counts for a given reporting date, using a time series of case reports that is known to be incomplete due to reporting delays. Modeling the reporting delay distribution is a common feature of nowcast approaches. However, many nowcast approaches ignore a crucial feature of infectious disease transmission-that future cases are intrinsically linked to past reported cases-and are optimized to one or two applications, which may limit generalizability. Here, we present a Bayesian approach, NobBS (Nowcasting by Bayesian Smoothing) capable of producing smooth and accurate nowcasts in multiple disease settings. We test NobBS on dengue in Puerto Rico and influenza-like illness (ILI) in the United States to examine performance and robustness across settings exhibiting a range of common reporting delay characteristics (from stable to time-varying), and compare this approach with a published nowcasting software package while investigating the features of each approach that contribute to good or poor performance. We show that introducing a temporal relationship between cases considerably improves performance when the reporting delay distribution is time-varying, and we identify trade-offs in the role of moving windows to accurately capture changes in the delay. We present software implementing this new approach (R package "NobBS") for widespread application and provide practical guidance on implementation.

    • Genetics and Genomics
      1. A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosisexternal icon
        Justice CM, Cuellar A, Bala K, Sabourin JA, Cunningham ML, Crawford K, Phipps JM, Zhou Y, Cilliers D, Byren JC, Johnson D, Wall SA, Morton JE, Noons P, Sweeney E, Weber A, Rees KE, Wilson LC, Simeonov E, Kaneva R, Yaneva N, Georgiev K, Bussarsky A, Senders C, Zwienenberg M, Boggan J, Roscioli T, Tamburrini G, Barba M, Conway K, Sheffield VC, Brody L, Mills JL, Kay D, Sicko RJ, Langlois PH, Tittle RK, Botto LD, Jenkins MM, LaSalle JM, Lattanzi W, Wilkie AO, Wilson AF, Romitti PA, Boyadjiev SA.
        Hum Genet. 2020 Apr 7.
        Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P </= 5 x 10(-8)): rs781716 (P = 4.71 x 10(-9); odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 x 10(-8); OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 x 10(-9); OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 x 10(-8), OR = 0.45; P = 3.31 x 10(-8), OR = 0.45; P = 1.09 x 10(-8), OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 x 10(-8), OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 x 10(-6)). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

    • Health Communication and Education
      1. A public health systems view of risk communication about Zikaexternal icon
        Kirk Sell T, Ravi SJ, Watson C, Meyer D, Pechta LE, Rose DA, Lubell KM, Podgornik MN, Schoch-Spana M.
        Public Health Rep. 2020 Apr 3:33354920912215.
        OBJECTIVES: The spread of Zika virus throughout Latin America and parts of the United States in 2016 and 2017 presented a challenge to public health communicators. The objective of our study was to describe emergency risk communication practices during the 2016-2017 Zika outbreak to inform future infectious disease communication efforts. METHODS: We conducted semi-structured telephone interviews with 13 public health policy makers and practitioners, 10 public information officers, and 5 vector-control officials from May through August 2017. RESULTS: Within the public health macro-environment, extended outbreak timeframe, government trust, US residence status, and economic insecurity set the backdrop for Zika communication efforts. Limited resources, staffing, and partnerships negatively affected public health structural capacity for communication efforts. Public health communicators and practitioners used a range of processes and practices to engage in education and outreach, including fieldwork, community meetings, and contact with health care providers. Overall, public health agencies' primary goals were to prevent Zika infection, reduce transmission, and prevent adverse birth outcomes. CONCLUSIONS: Lessons learned from this disease response included understanding the macro-environment, developing partnerships across agencies and the community, and valuing diverse message platforms. These lessons can be used to improve communication approaches for health officials at the local, state, and federal levels during future infectious disease outbreaks.

    • Health Disparities
      1. The paper evaluates 11 measures of inequality d(p1,p2) between two proportions p1 and p2, some of which are new to the health disparities literature. These measures are selected because they are continuous, nonnegative, equal to zero if and only if |p1-p2|=0, and maximal when |p1-p2|=1. They are also symmetric [d(p1,p2)=d(p2,p1)] and complement-invariant [d(p1,p2)=d(1-p2,1-p1)]. To study inter-measure agreement, five of the 11 measures, including the absolute difference, are retained, because they remain finite and are maximal if and only if |p1-p2|=1. Even when the two proportions are assumed to be drawn at random from a shared distribution-interpreted as the absence of an avoidable difference-the expected value of d(p1,p2) depends on the shape of the distribution (and the choice of d) and can be quite large. To allow for direct comparisons among measures, a standard measurement unit akin to a z-score is proposed. For skewed underlying beta distributions, four of the five retained measures, once standardized, offer more conservative assessments of the magnitude of inequality than the absolute difference. The paper concludes that, even for measures that share the highlighted mathematical properties, magnitude comparisons are most usefully assessed relative to an elicited or estimated underlying distribution for the two proportions.

    • Healthcare Associated Infections
      1. Characterizing healthcare delivery in the United States using Census Bureau's County Business Patterns (2000-2016)external icon
        Astha KC, Schaefer MK, Stone ND, Perz J.
        Infect Control Hosp Epidemiol. 2020 Apr 7:1-6.
        BACKGROUND: The US Census Bureau's County Business Patterns (CBP) series provides a unique opportunity to describe the healthcare sector using a single, national data source. METHODS: We analyzed CBP data on business establishments in the healthcare industry for 2000-2016 for all 50 states and the District of Columbia. Setting and facility types were defined using the North American Industry Classification System. RESULTS: In 2016, CBP enumerated 707,634 US healthcare establishments (a 34% increase from 2000); 86.5% were outpatient facilities and services followed by long-term care facilities (12.5%) and acute-care facilities (1.0%). Between 2000 and 2016, traditional facilities such as general medical surgical and surgical hospitals (-0.4%) and skilled nursing facilities (+0.1%) decreased or remained flat, while other long-term care and outpatient providers grew rapidly. CONCLUSION: This analysis highlights the steady growth and increased specialization of the US healthcare sector, particularly in long-term care and outpatient settings.

      2. Multispecies outbreak of Verona integron-encoded metallo-beta-lactamase-producing multidrugresistant bacteria driven by a promiscuous incompatibility group A/C2external icon
        de Man TJ, Yaffee AQ, Zhu W, Batra D, Alyanak E, Rowe LA, McAllister G, Moulton-Meissner H, Boyd S, Flinchum A, Slayton RB, Hancock S, Spalding Walters M, Laufer Halpin A, Rasheed JK, Noble-Wang J, Kallen AJ, Limbago BM.
        Clin Infect Dis. 2020 Apr 7.
        BACKGROUND: Antibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation. METHODS: Electronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments. RESULTS: We identified 14 Verona integron-encoded metallo-ss-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment. CONCLUSIONS: This investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.

      3. Trends in U.S. burden of Clostridioides difficile infection and outcomesexternal icon
        Guh AY, Mu Y, Winston LG, Johnston H, Olson D, Farley MM, Wilson LE, Holzbauer SM, Phipps EC, Dumyati GK, Beldavs ZG, Kainer MA, Karlsson M, Gerding DN, McDonald LC.
        N Engl J Med. 2020 Apr 2;382(14):1320-1330.
        BACKGROUND: Efforts to prevent Clostridioides difficile infection continue to expand across the health care spectrum in the United States. Whether these efforts are reducing the national burden of C. difficile infection is unclear. METHODS: The Emerging Infections Program identified cases of C. difficile infection (stool specimens positive for C. difficile in a person >/=1 year of age with no positive test in the previous 8 weeks) in 10 U.S. sites. We used case and census sampling weights to estimate the national burden of C. difficile infection, first recurrences, hospitalizations, and in-hospital deaths from 2011 through 2017. Health care-associated infections were defined as those with onset in a health care facility or associated with recent admission to a health care facility; all others were classified as community-associated infections. For trend analyses, we used weighted random-intercept models with negative binomial distribution and logistic-regression models to adjust for the higher sensitivity of nucleic acid amplification tests (NAATs) as compared with other test types. RESULTS: The number of cases of C. difficile infection in the 10 U.S. sites was 15,461 in 2011 (10,177 health care-associated and 5284 community-associated cases) and 15,512 in 2017 (7973 health care-associated and 7539 community-associated cases). The estimated national burden of C. difficile infection was 476,400 cases (95% confidence interval [CI], 419,900 to 532,900) in 2011 and 462,100 cases (95% CI, 428,600 to 495,600) in 2017. With accounting for NAAT use, the adjusted estimate of the total burden of C. difficile infection decreased by 24% (95% CI, 6 to 36) from 2011 through 2017; the adjusted estimate of the national burden of health care-associated C. difficile infection decreased by 36% (95% CI, 24 to 54), whereas the adjusted estimate of the national burden of community-associated C. difficile infection was unchanged. The adjusted estimate of the burden of hospitalizations for C. difficile infection decreased by 24% (95% CI, 0 to 48), whereas the adjusted estimates of the burden of first recurrences and in-hospital deaths did not change significantly. CONCLUSIONS: The estimated national burden of C. difficile infection and associated hospitalizations decreased from 2011 through 2017, owing to a decline in health care-associated infections. (Funded by the Centers for Disease Control and Prevention.).

      4. Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012-2017external icon
        Jernigan JA, Hatfield KM, Wolford H, Nelson RE, Olubajo B, Reddy SC, McCarthy N, Paul P, McDonald LC, Kallen A, Fiore A, Craig M, Baggs J.
        N Engl J Med. 2020 Apr 2;382(14):1309-1319.
        BACKGROUND: Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action. METHODS: Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012-2017, we generated national case counts for both hospital-onset and community-onset infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase (ESBL) production, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant acinetobacter species, and MDR Pseudomonas aeruginosa. RESULTS: The hospital cohort in the study accounted for 41.6 million hospitalizations (>20% of U.S. hospitalizations annually). The overall rate of clinical cultures was 292 cultures per 1000 patient-days and was stable throughout the time period. In 2017, these pathogens caused an estimated 622,390 infections (95% confidence interval [CI], 579,125 to 665,655) among hospitalized patients. Of these infections, 517,818 (83%) had their onset in the community, and 104,572 (17%) had their onset in the hospital. MRSA and ESBL infections accounted for the majority of the infections (52% and 32%, respectively). Between 2012 and 2017, the incidence decreased for MRSA infection (from 114.18 to 93.68 cases per 10,000 hospitalizations), VRE infection (from 24.15 to 15.76 per 10,000), carbapenem-resistant acinetobacter species infection (from 3.33 to 2.47 per 10,000), and MDR P. aeruginosa infection (from 13.10 to 9.43 per 10,000), with decreases ranging from -20.5% to -39.2%. The incidence of carbapenem-resistant Enterobacteriaceae infection did not change significantly (from 3.36 to 3.79 cases per 10,000 hospitalizations). The incidence of ESBL infection increased by 53.3% (from 37.55 to 57.12 cases per 10,000 hospitalizations), a change driven by an increase in community-onset cases. CONCLUSIONS: Health care-associated antimicrobial resistance places a substantial burden on patients in the United States. Further work is needed to identify improved interventions for both the inpatient and outpatient settings. (Funded by the Centers for Disease Control and Prevention.).

      5. Acquisition of antibiotic-resistant bacteria by U.S. international travelersexternal icon
        Mellon G, Turbett SE, Worby C, Oliver E, Walker AT, Walters M, Kelly P, Leung DT, Knouse M, Hagmann S, Earl A, Ryan ET, LaRocque RC.
        N Engl J Med. 2020 Apr 2;382(14):1372-1374.

      6. Multiple respiratory syncytial virus introductions into a neonatal intensive care unitexternal icon
        Rose EB, Washington EJ, Wang L, Benowitz I, Thornburg NJ, Gerber SI, Peret TC, Langley GE.
        J Pediatric Infect Dis Soc. 2020 Apr 4.
        BACKGROUND: Outbreaks of respiratory syncytial virus (RSV) in neonatal intensive care units (NICUs) are of concern because of the risk of severe disease in young infants. We describe an outbreak of RSV in a NICU and use whole genome sequencing (WGS) to better understand the relatedness of viruses among patients.SummaryUsing whole genome sequencing, we found 2 introductions of respiratory syncytial virus (RSV) into a neonatal intensive care unit causing 7 infections. This outbreak highlights the risk of healthcare-associated infections during RSV season; early recognition is critical to limit transmission. METHODS: An investigation was conducted to identify patients and describe their clinical course. Infection control measures were implemented to prevent further spread. Respiratory specimens from outbreak-related patients and the community were tested using WGS. Phylogenetic trees were constructed to understand relatedness of the viruses. RESULTS: Seven patients developed respiratory symptoms within an 11-day span in December 2017 and were diagnosed with RSV; 6 patients (86%) were preterm and 1 had chronic lung disease. Three patients required additional respiratory support after symptom onset, and none died. Six of 7 patients were part of the same cluster based on > 99.99% nucleotide agreement with each other and 3 unique single-nucleotide polymorphisms were identified in viruses sequenced from those patients. The seventh patient was admitted from the community with respiratory symptoms and had a genetically distinct virus that was not related to the other 6. Implementation of enhanced infection control measures likely limited the spread. CONCLUSIONS: Using WGS, we found 2 distinct introductions of RSV into a NICU, highlighting the risk of healthcare-associated infections during RSV season. Early recognition and infection control measures likely limited spread, emphasizing the importance of considering RSV in the differential diagnosis of respiratory infections in healthcare settings.

      7. Laboratory analysis of an outbreak of Candida auris in New York from 2016 to 2018: Impact and lessons learnedexternal icon
        Zhu Y, O'Brien B, Leach L, Clarke A, Bates M, Adams E, Ostrowsky B, Quinn M, Dufort E, Southwick K, Erazo R, Haley VB, Bucher C, Chaturvedi V, Limberger RJ, Blog D, Lutterloh E, Chaturvedi S.
        J Clin Microbiol. 2020 Mar 25;58(4).
        Candida auris is a multidrug-resistant yeast which has emerged in health care facilities worldwide; however, little is known about identification methods, patient colonization, environmental survival, spread, and drug resistance. Colonization on both biotic (patients) and abiotic (health care objects) surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in New York (NY) from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/nonselective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of the internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal gene for C. auris genotyping. Results included (a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates as well as identification of 277 clinical cases and 350 colonized cases from 151 health care facilities, including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, (b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, (c) demonstration of relatively heavier colonization of C. auris in nares than in the axilla/groin, and (d) predominance of the South Asia clade I with intrinsic resistance to fluconazole and elevated MIC to voriconazole (81%), amphotericin B (61%), flucytosine (5FC) (3%), and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

    • Immune System Disorders
      1. Prospective cohort study of influenza vaccine effectiveness among healthcare personnel in Lima, Peru: Estudio Vacuna de Influenza Peru, 2016-2018external icon
        Wesley MG, Soto G, Arriola CS, Gonzales M, Newes-Adeyi G, Romero C, Veguilla V, Levine MZ, Silva M, Ferdinands JM, Dawood FS, Reynolds SB, Hirsch A, Katz M, Matos E, Ticona E, Castro J, Castillo M, Bravo E, Cheung A, Phadnis R, Martin ET, Tinoco Y, Neyra Quijandria JM, Azziz-Baumgartner E, Thompson MG.
        Influenza Other Respir Viruses. 2020 Apr 5.
        BACKGROUND: The Estudio Vacuna de Influenza Peru (VIP) cohort aims to describe the frequency of influenza virus infection, identify predictors of vaccine acceptance, examine the effects of repeated influenza vaccination on immunogenicity, and evaluate influenza vaccine effectiveness among HCP. METHODS: The VIP cohort prospectively followed HCP in Lima, Peru, during the 2016-2018 influenza seasons; a fourth year is ongoing. Participants contribute blood samples before and after the influenza season and after influenza vaccination (for vaccinees). Weekly surveillance is conducted to identify acute respiratory or febrile illnesses (ARFI). When an ARFI is identified, participants self-collect nasal swabs that are tested for influenza viruses by real-time reverse transcriptase-polymerase chain reaction. Influenza vaccination status and 5-year vaccination history are ascertained. We analyzed recruitment and enrollment results for 2016-2018 and surveillance participation for 2016-2017. RESULTS: In the first 3 years of the cohort, VIP successfully contacted 92% of potential participants, enrolled 76% of eligible HCP, and retained >90% of participants across years. About half of participants are medical assistants (54%), and most provide "hands-on" medical care (76%). Sixty-nine percent and 52% of participants completed surveillance for >70% of weeks in years 1 and 2, respectively. Fewer weeks of completed surveillance was associated with older age (>/=50 years), being a medical assistant, self-rated health of fair or poor, and not receiving the influenza vaccine during the current season (P-values < .05). CONCLUSIONS: The VIP cohort provides an opportunity to address knowledge gaps about influenza virus infection, vaccination uptake, effectiveness and immunogenicity among HCP.

    • Immunity and Immunization
      1. Modeling the waning and boosting of immunity from infection or vaccinationexternal icon
        Carlsson RM, Childs LM, Feng Z, Glasser JW, Heffernan JM, Li J, Rost G.
        J Theor Biol. 2020 Apr 6:110265.
        Immunity following natural infection or immunization may wane, increasing susceptibility to infection with time since infection or vaccination. Symptoms, and concomitantly infectiousness, depend on residual immunity. We quantify these phenomena in a model population composed of individuals whose susceptibility, infectiousness, and symptoms all vary with immune status. We also model age, which affects contact, vaccination and possibly waning rates. The resurgences of pertussis that have been observed wherever effective vaccination programs have reduced typical disease among young children follow from these processes. As one example, we compare simulations with the experience of Sweden following resumption of pertussis vaccination after the hiatus from 1979 to 1996, reproducing the observations leading health authorities to introduce booster doses among school-aged children and adolescents in 2007 and 2014, respectively. Because pertussis comprises a spectrum of symptoms, only the most severe of which are medically attended, accurate models are needed to design optimal vaccination programs where surveillance is less effective.

      2. Insights on population structure and within-host genetic changes among meningococcal carriage isolates from U.S. universitiesexternal icon
        Joseph SJ, Topaz N, Chang HY, Whaley MJ, Vuong JT, Chen A, Hu F, Schmink SE, Jenkins LT, Rodriguez-Rivera LD, Thomas JD, Acosta AM, McNamara L, Soeters HM, Mbaeyi S, Wang X.
        mSphere. 2020 Apr 8;5(2).
        In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population.IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis, can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease.

      3. Pregnancy outcomes among women receiving rVSVDelta-ZEBOV-GP Ebola vaccine during the Sierra Leone Trial to introduce a vaccine against Ebolaexternal icon
        Legardy-Williams JK, Carter RJ, Goldstein ST, Jarrett OD, Szefer E, Fombah AE, Tinker SC, Samai M, Mahon BE.
        Emerg Infect Dis. 2020 Mar;26(3):541-548.
        Little information exists regarding Ebola vaccine rVSVDeltaG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.


      5. Influenza vaccine effectiveness in inpatient and outpatient settings in the United States, 2015 - 2018external icon
        Tenforde MW, Chung J, Smith ER, Talbot HK, Trabue CH, Zimmerman RK, Silveira FP, Gaglani M, Murthy K, Monto AS, Martin ET, McLean HQ, Belongia EA, Jackson LA, Jackson ML, Ferdinands JM, Flannery B, Patel MM.
        Clin Infect Dis. 2020 Apr 9.
        BACKGROUND: Demonstration of influenza vaccine effectiveness (VE) against hospitalization for severe illness in addition to milder outpatient illness may strengthen vaccination messaging and improve suboptimal uptake in the U.S. Our objective was to compare patient characteristics and VE between U.S. inpatient and outpatient VE networks. METHODS: We tested adults >/=18-years with acute respiratory illness (ARI) for influenza within two VE networks, one outpatient- and the other hospital-based, from 2015-2018. We compared age, sex, and chronic high-risk conditions between populations. The test-negative design was used to compare vaccination odds in influenza-positive cases versus influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time-to-testing from symptom-onset, season (overall VE) and underlying conditions. VE differences (DeltaVE) were assessed with 95% confidence intervals (CI) determined through bootstrapping with significance defined as excluding the null. RESULTS: The VE networks enrolled 14,573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median 62-years vs. 49-years) and had more high-risk conditions (median 4 vs. 1). Overall influenza VE across seasons was 31% (95%CI:26%-37%) among outpatients and 36% (27%-44%) among inpatients. Strain-specific VE among outpatients versus inpatients was 37% (25%-47%) vs. 53% (37%-64%) against H1N1pdm09, 19% (9%-27%) vs. 23% (8%-35%) against H3N2, and 46% (38%-53%) vs. 46% (31%-58%) against B-viruses. DeltaVE was not significant for any comparison across all sites. CONCLUSIONS: Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health status among inpatients, influenza vaccination was effective in preventing hospitalizations associated with influenza.

    • Injury and Violence
      1. Effects of the Dating Matters(R) comprehensive prevention model on health- and delinquency-related risk behaviors in middle school youth: A cluster-randomized controlled trialexternal icon
        Estefan LF, Vivolo-Kantor AM, Niolon PH, Le VD, Tracy AJ, Little TD, DeGue S, Latzman NE, Tharp A, Lang KM, McIntosh WL.
        Prev Sci. 2020 Apr 3.
        Teen dating violence (TDV) is associated with a variety of delinquent behaviors, such as theft, and health- and delinquency-related risk behaviors, including alcohol use, substance abuse, and weapon carrying. These behaviors may co-occur due to shared risk factors. Thus, comprehensive TDV-focused prevention programs may also impact these other risk behaviors. This study examined the effectiveness of CDC's Dating Matters(R): Strategies to Promote Healthy Teen Relationships (Dating Matters) comprehensive TDV prevention model compared to a standard-of-care condition on health- and delinquency-related risk behaviors among middle school students. Students (N = 3301; 53% female; 50% black, non-Hispanic; and 31% Hispanic) in 46 middle schools in four sites across the USA were surveyed twice yearly in 6th, 7th, and 8th grades. A structural equation modeling framework with multiple imputation to account for missing data was utilized. On average over time, students receiving Dating Matters scored 9% lower on a measure of weapon carrying, 9% lower on a measure of alcohol and substance abuse, and 8% lower on a measure of delinquency by the end of middle school than students receiving an evidence-based standard-of-care TDV prevention program. Dating Matters demonstrated protective effects for most groups of students through the end of middle school. These results suggest that this comprehensive model is successful at preventing risk behaviors associated with TDV. clinicaltrials.gov Identifier: NCT01672541.

      2. Investigation of optimal dose of early intervention to prevent posttraumatic stress disorder: A multiarm randomized trial of one and three sessions of modified prolonged exposureexternal icon
        Maples-Keller JL, Post LM, Price M, Goodnight JM, Burton MS, Yasinski CW, Michopoulos V, Stevens JS, Hinrichs R, Rothbaum AO, Hudak L, Houry D, Jovanovic T, Ressler K, Rothbaum BO.
        Depress Anxiety. 2020 Apr 5.
        BACKGROUND: Posttraumatic stress disorder (PTSD) is linked to a specific event, providing the opportunity to intervene in the immediate aftermath of trauma to prevent the development of this disorder. A previous trial demonstrated that trauma survivors who received three sessions of modified prolonged exposure therapy demonstrated decreased PTSD and depression prospectively compared to assessment only. The present study investigated the optimal dosing of this early intervention to test one versus three sessions of exposure therapy in the immediate aftermath of trauma. METHODS: Participants (n = 95) recruited from a Level 1 Trauma Center were randomly assigned in a 1.5:1.5:1 ratio in a parallel-group design to the three conditions: one-session exposure therapy, three-session exposure therapy, and assessment only. Follow-up assessments were conducted by study assessors blind to study condition. RESULTS: Mixed-effects model results found no significant differences in PTSD or depression symptoms between the control condition and those who received one or three exposure therapy sessions across 1-12-month follow-up assessment. Results indicate that the intervention did not interfere with natural recovery. Receiver operating characteristic curve analyses on the screening measure used for study inclusion (Predicting PTSD Questionnaire; PPQ) in the larger sample from which the treatment sample was drawn (n = 481) found that the PPQ was a poor predictor of likely PTSD at all follow-up time points (Area under the curve's = 0.55-0.62). CONCLUSIONS: This likely impacted study results as many participants demonstrated natural recovery. Recommendations for future early intervention research are reviewed, including strategies to identify more accurately those at risk for PTSD and oversampling more severe trauma types.

      3. Perpetration of intimate partner violence and mental health outcomes: sex- and gender-disaggregated associations among adolescents and young adults in Nigeriaexternal icon
        Stark L, Seff I, Weber AM, Cislaghi B, Meinhart M, Bermudez LG, Atuchukwu V, Onotu D, Darmstadt GL.
        J Glob Health. 2020 Jun;10(1):010708.
        Background: The association between intimate partner violence (IPV) victimisation and poor mental health outcomes is well established. Less is known about the correlation between IPV perpetration and mental health, particularly among adolescents and young adults. Using data from the nationally representative Violence Against Children Survey, this analysis examines the association between IPV perpetration and mental health for male and female adolescents and young adults in Nigeria. Methods: Multivariate logistic regression models were used to examine associations between ever-perpetration of IPV and four self-reported mental health variables: severe sadness, feelings of worthlessness, suicide ideation, and alcohol use. Models were sex-disaggregated, controlled for age, marital status, and schooling, and tested with and without past exposure to violence. Standard errors were adjusted for sampling stratification and clustering. Observations were weighted to be representative of 13-24 year-olds in Nigeria. Results: Males were nearly twice as likely as females to perpetrate IPV (9% v. 5%, respectively; P < 0.001), while odds of perpetration for both sexes were higher for those ever experiencing IPV (adjusted odds ratio (aOR) = 4.60 for males; aOR = 2.71 for females). Female perpetrators had 2.73 higher odds of reporting severe sadness (95% confidence interval CI = 1.44, 5.17; P = 0.002) and 2.72 times greater odds of reporting suicide ideation (1.28, 5.79; P = 0.010) than non-perpetrating females, even when controlling for past-year violence victimisation. In contrast, male perpetrators had 2.65 times greater odds of feeling worthless (1.09, 6.43; P = 0.031), and 2.36 times greater odds of reporting alcohol use in the last 30 days (1.50, 3.73; P < 0.001), as compared to non-perpetrating males. Conclusions: Among adolescents and young adults in Nigeria, IPV perpetration and negative mental health outcomes are associated but differ for males and females. Mindful of the cross-sectional nature of the data, it is possible that socially determined gender norms may shape the ways in which distress from IPV perpetration is understood and expressed. Additional research is needed to clarify these associations and inform violence prevention efforts.

    • Laboratory Sciences
      1. Effect of a high-fat diet and occupational exposure in different rat strains on lung and systemic responses: Examination of the exposome in an animal modelexternal icon
        Antonini JM, Kodali V, Shoeb M, Kashon M, Roach KA, Boyce G, Meighan T, Stone S, McKinney W, Boots T, Roberts JR, Zeidler-Erdely PC, Erdely A.
        Toxicol Sci. 2020 Mar 1;174(1):100-111.
        The exposome is the measure of all exposures of an individual in a lifetime and how those exposures relate to health. The goal was to examine an experimental model integrating multiple aspects of the exposome by collecting biological samples during critical life stages of an exposed animal that are applicable to worker populations. Genetic contributions were assessed using strains of male rats with different genetic backgrounds (Fischer-344, Sprague Dawley, and Brown-Norway) maintained on a regular or high-fat diet for 24 weeks. At week 7 during diet maintenance, groups of rats from each strain were exposed to stainless steel welding fume (WF; 20 mg/m3 x 3 h/d x 4 days/week x 5 weeks) or air until week 12, at which time some animals were euthanized. A separate set of rats from each strain were allowed to recover from WF exposure until the end of the 24-week period. Bronchoalveolar lavage fluid and serum were collected at 7, 12, and 24 weeks to assess general health indices. Depending on animal strain, WF exposure and high-fat diet together worsened kidney toxicity as well as altered different serum enzymes and proteins. Diet had minimal interaction with WF exposure for pulmonary toxicity endpoints. Experimental factors of diet, exposure, and strain were all important, depending on the health outcome measured. Exposure had the most significant influence related to pulmonary responses. Strain was the most significant contributor regarding the other health indices examined, indicating that genetic differences possibly drive the exposome effect in each strain.

      2. Evaluation of commercial molecular diagnostic methods for the detection and determination of macrolide resistance in Mycoplasma pneumoniaeexternal icon
        Leal SM, Totten AH, Xiao L, Crabb DM, Ratliff A, Duffy LB, Fowler KB, Mixon E, Winchell JM, Diaz MH, Benitez AJ, Wolff BJ, Qin X, Tang YW, Gonzalez M, Selvarangan R, Hong T, Brooks E, Dallas S, Atkinson TP, Zheng X, Dien Bard J, Waites KB.
        J Clin Microbiol. 2020 Apr 8.
        We evaluated six commercial molecular tests targeting M. pneumoniae: the BioFire FilmArray Respiratory Panel (RP), the Meridian Alethia Mycoplasma Direct, the GenMark ePlex Respiratory Pathogen Panel (RPP), the Luminex NxTAG RPP, the ELITech ELITe InGenius Mycoplasma MGB Research Use Only Polymerase Chain Reaction (PCR), and the SpeeDx Resistance Plus MP. Laboratory-developed PCR assays at the University of Alabama at Birmingham and the Centers for Disease Control and Prevention were used as reference standards. Among 428 specimens, 212 were designated confirmed-positives for M. pneumoniae The highest clinical sensitivities were found with the InGenius (99.5%) and the FilmArray RP (98.1%). The Resistance Plus MP identified 93.3% of the confirmed-positive specimens, whereas 83.6%, 64.6%, and 55.7% were identified by the ePlex RPP, NxTAG RPP, and Mycoplasma Direct assays, respectively. There was no significant difference between the sensitivity of the reference methods and that of the FilmArray RP and InGenius assays, but the remaining four assays detected significantly fewer positive specimens (p < 0.05). Specificities of all assays were 99.5 - 100%. The Resistance Plus MP detected macrolide resistance in 27/33 specimens resulting in a sensitivity of 81.8%. This study provides the first large scale comparison of commercial molecular assays for detection of M. pneumoniae in the United States and identified clear differences among their performance. Additional studies are necessary to explore the impact of variable test performance on patient outcome.

      3. Identification of Mycobacterium tuberculosis peptides in serum extracellular vesicles from persons with latent tuberculosis infectionexternal icon
        Mehaffy C, Kruh-Garcia NA, Graham B, Jarlsberg LG, Willyerd CE, Borisov A, Sterling TR, Nahid P, Dobos KM.
        J Clin Microbiol. 2020 Apr 3.
        Identification of biomarkers for latent Mycobacterium tuberculosis infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) assays that detected M. tuberculosis (Mtb) peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40 M. tuberculosis peptides from 19 proteins that most commonly co-purify with serum vesicles of patients with TB. Here, we used this technology to evaluate if Mtb peptides can also be detected in individuals with latent TB infection (LTBI). Serum extracellular vesicles from 74 individuals presumed to have latent M. tuberculosis infection (LTBI) based on close contact with a household member with TB or a recent tuberculin skin test (TST) conversion were included in this study. Twenty-nine samples from individuals with no evidence of TB infection by TST and no known exposure to TB were used as controls to establish a threshold to account for non-specific/background signal. We identified at least one of the 40 M. tuberculosis peptides in 70 (95%) individuals with LTBI. A single peptide from the Glutamine synthetase (GlnA1) enzyme was identified in 61/74 (82%) individuals with LTBI, suggesting peptides from M. tuberculosis proteins involved in nitrogen metabolism as candidates for pathogen specific biomarkers for detection of LTBI. The detection of M. tuberculosis peptides in serum extracellular vesicles from persons with LTBI represents a potential advance in the diagnosis of LTBI.

      4. Comparison of a VLP-based and GST-L1-based multiplex immunoassay to detect vaccine-induced HPV-specific antibodies in first-void urineexternal icon
        Pattyn J, Panicker G, Willhauck-Fleckenstein M, Van Keer S, Teblick L, Pieters Z, Tjalma WA, Matheeussen V, Van Damme P, Waterboer T, Unger ER, Vorsters A.
        J Med Virol. 2020 Apr 8.
        BACKGROUND: Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). METHODS: We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bi- or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs ). FINDINGS: As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine p = 0.0003; serum p </= 0.0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, rs = 0.85/0.86/0.91/0.79, p </= 0.001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, rs = 0.86/0.83/0.89/0.53, p </= 0.0001; serum anti-HPV6/11/16/18, rs = 0.93/0.89/0.94/0.75, p </= 0.0001). CONCLUSION: FV urine HPV antibody detection is comparable with both assays, further supporting this non-invasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection. This article is protected by copyright. All rights reserved.

      5. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in miceexternal icon
        Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, Agostini ML, Leist SR, Schafer A, Dinnon KH, Stevens LJ, Chappell JD, Lu X, Hughes TM, George AS, Hill CS, Montgomery SA, Brown AJ, Bluemling GR, Natchus MG, Saindane M, Kolykhalov AA, Painter G, Harcourt J, Tamin A, Thornburg NJ, Swanstrom R, Denison MR, Baric RS.
        Sci Transl Med. 2020 Apr 6.
        Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog beta-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (beta-D-N(4)-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.

      6. Frequency of invasive fungal disease in adults: Experience of a specialized laboratory in Medellin, Colombia (2009-2015)external icon
        Valencia Y, Caceres DH, de Bedout C, Cano LE, Restrepo A.
        J Fungi (Basel). 2020 Mar 20;6(1).
        Invasive fungal diseases (IFD) contribute significantly to worldwide morbidity and mortality, but their frequency is not well-described in some countries. The present work describes the frequency of IFD in a specialized laboratory in Colombia. A retrospective, descriptive study was implemented between March 2009 and December 2015. Results: 13,071 patients with clinical suspicion of IFD were referred during the study period, from which 33,516 biological samples were processed and analyzed using 14 laboratory methods. Diagnosis was confirmed in 1425 patients (11%), distributed according to the mycoses of interest analyzed here: histoplasmosis in 641/11,756 patients (6%), aspergillosis in 331/10,985 patients (3%), cryptococcosis in 239/8172 patients (3%), pneumocystosis in 111/1651 patients (7%), paracoccidioidomycosis in 60/10,178 patients (0.6%), and invasive candidiasis in 48/7525 patients (0.6%). From the first year of the study period to the last year, there was a 53% increase in the number of cases of IFD diagnosed. Our laboratory experienced a high frequency of IFD diagnosis, possibly attributable to the availability of a greater range of diagnostic tools. Frequency of IFD in this study was atypical compared with other studies, probably as a result of the single laboratory-site analysis. This demonstrates that implementing educational strategies helps to create a high index of clinical suspicion, while the availability and utilization of appropriate diagnostic assays assure greater reliability in identification of these cases.

      7. Expanded sequential quadriplex real-time polymerase chain reaction (PCR) for identifying pneumococcal serotypes, penicillin susceptibility, and resistance markersexternal icon
        Velusamy S, Tran T, Mongkolrattanothai T, Walker H, McGee L, Beall B.
        Diagn Microbiol Infect Dis. 2020 Mar 12:115037.
        We expanded our current Centers for Disease Control and Prevention triplexed real-time polymerase chain reaction scheme identifying 11 individual serotypes and 10 serogroups to a quadriplex format identifying 34 individual serotypes and 13 small serogroups, 4 antibiotic resistance determinants, pilus targets, and penicillin susceptibility. Newly developed assays are specific for serotypes/serogroups, are sensitive (10 copies/reaction), and further discriminate larger serogroups into individual serotypes or smaller serogroups.

      8. Development of an RNA strand-specific hybridization assay to differentiate replicating versus non-replicating influenza A virusexternal icon
        Yang G, Hodges EN, Winter J, Zanders N, Shcherbik S, Bousse T, Murray JR, Muraduzzaman AK, Rahman M, Alamgir AS, Sabrina Flora M, Blanton L, Barnes JR, Wentworth DE, Davis CT.
        J Clin Microbiol. 2020 Apr 3.
        Replication of influenza A virus (IAV) from negative-sense viral RNA (vRNA) requires the generation of positive-sense RNA (+RNA). Most molecular assays, such as conventional real-time RT-PCR (rRT-PCR), detect total RNA in a sample without differentiating vRNA from +RNA. These assays are not designed to distinguish IAV infection versus exposure of an individual to an environment enriched with IAVs, but wherein no viral replication occurs. We, therefore, developed a strand-specific hybridization (SSH) assay that differentiates between vRNA and +RNA and quantifies relative levels of each RNA species. The SSH assay exhibited a linearity of 7 logs with a lower limit of detection of 6.0x10(2) copies of molecules per reaction. No signal was detected in samples with a high load of non-target template or influenza B virus, demonstrating assay specificity. IAV +RNA was detected at 2-4 hours post-inoculation of MDCK cells, whereas synthesis of cold-adapted IAV +RNA was significantly impaired at 37 degrees C. The SSH assay was then used to test IAV rRT-PCR positive nasopharyngeal specimens collected from individuals exposed to IAV at swine exhibitions (n=7) or while working at live bird markets (n=2). The SSH assay was able to differentiate vRNA and +RNA in samples collected from infected, symptomatic individuals versus individuals who were exposed to IAV in the environment, but had no active viral replication. Data generated with this technique, especially when coupled with clinical data and assessment of seroconversion, will facilitate differentiation of actual IAV infection with replicating virus versus individuals exposed to high levels of environmental contamination, but without virus infection.

    • Military Medicine and Health
      1. Gulf War Illness (GWI) is a chronic multi-symptom disorder, characterized by symptoms such as fatigue, pain, cognitive and memory impairment, respiratory, skin and gastrointestinal problems, that is experienced by approximately one-third of 1991 Gulf War veterans. Over the nearly three decades since the end of the war, investigators have worked to elucidate the initiating factors and underlying causes of GWI. A significant portion of this research has indicated a strong correlation between GWI and exposure to a number of different acetycholinesterase inhibitors (AChEIs) in theater, such as sarin and cyclosarin nerve agents, chlorpyrifos and dichlorvos pesticides, and the anti-nerve agent prophylactic pyridostigmine bromide. Through studying these exposures and their relationship to the symptoms presented by ill veterans, it has become increasingly apparent that GWI is the likely result of an underlying neuroimmune disorder. While evidence indicates that AChEIs are a key exposure in the development of GWI, particularly organophosphate AChEIs, the mechanism(s) by which these chemicals instigate illness appears to be related to "off-target", non-cholinergic effects. In this review, we will discuss the role of AChEI exposure in the development and persistence of GWI; in particular, how these chemicals, combined with other exposures, have led to a chronic neuroimmune disorder.

    • Nutritional Sciences
      1. Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutritionexternal icon
        Kangas ST, Salpeteur C, Nikiema V, Talley L, Briend A, Ritz C, Friis H, Kaestel P.
        Clin Nutr. 2020 Mar 24.
        BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 mumol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 mug/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 mumol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 mug/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

      2. Adjusting plasma or serum zinc concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) projectexternal icon
        McDonald CM, Suchdev PS, Krebs NF, Hess SY, Wessells KR, Ismaily S, Rahman S, Wieringa FT, Williams AM, Brown KH, King JC.
        Am J Clin Nutr. 2020 Apr 1;111(4):927-937.
        BACKGROUND: The accurate estimation of zinc deficiency at the population level is important, as it guides the design, targeting, and evaluation of nutrition interventions. Plasma or serum zinc concentration (PZC) is recommended to estimate zinc nutritional status; however, concentrations may decrease in the presence of inflammation. OBJECTIVES: We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age (WRA; 15-49 y), and to compare different inflammation adjustment approaches, if adjustment is warranted. METHODS: Cross-sectional data from 13 nationally representative surveys (18,859 PSC, 22,695 WRA) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed. Correlation and decile analyses were conducted, and the following 3 adjustment methods were compared if a consistent negative association between PZC and C-reactive protein (CRP) or alpha-1-acid glycoprotein (AGP) was observed: 1) exclude individuals with CRP > 5 mg/L or AGP > 1 g/L; 2) apply arithmetic correction factors; and 3) use the BRINDA regression correction (RC) approach. RESULTS: In 6 of 12 PSC surveys, the estimated prevalence of zinc deficiency increased with increasing CRP deciles, and to a lesser extent, with increasing AGP deciles. In WRA, the association of PZC with CRP and AGP was weak and inconsistent. In the 6 PSC surveys in which adjustment methods were compared, application of RC reduced the estimated prevalence of zinc deficiency by a median of 11 (range: 4-18) percentage points, compared with the unadjusted prevalence. CONCLUSIONS: Relations between PZC and inflammatory markers were inconsistent, suggesting that correlation and decile analyses should be conducted before applying any inflammation adjustments. In populations of PSC that exhibit a significant negative association between PZC and CRP or AGP, application of the RC approach is supported. At this time, there is insufficient evidence to warrant inflammation adjustment in WRA.

      3. The co-occurrence of overweight and micronutrient deficiencies or anemia among women of reproductive age in Malawiexternal icon
        Rhodes EC, Suchdev PS, Narayan KM, Cunningham S, Weber MB, Tripp K, Mapango C, Ramakrishnan U, Hennink M, Williams AM.
        J Nutr. 2020 Apr 9.
        BACKGROUND: In low-resource settings, urbanization may contribute to the individual-level double burden of malnutrition (DBM), whereby under- and overnutrition co-occur within the same individuals. OBJECTIVE: We described DBM prevalence among Malawian women by urban-rural residence, examined whether urban residence was associated with DBM, and assessed whether DBM prevalence was greater than the prevalence expected by chance given population levels of under- and overnutrition, which would suggest DBM is a distinct phenomenon associated with specific factors. METHODS: We analyzed nationally representative data of 723 nonpregnant women aged 15-49 y from the 2015-2016 Malawi Micronutrient Survey. DBM was defined as co-occurring overweight or obesity (OWOB) and >/=1 micronutrient deficiency or anemia. We used Poisson regression models to examine the association between urban residence and DBM and its components. The Rao-Scott modified chi-square test compared the observed and expected DBM prevalence. RESULTS: Nationally, 10.8% (95% CI: 7.0, 14.5) of women had co-occurring OWOB and any micronutrient deficiency and 3.4% (95% CI: 1.3, 5.5) had co-occurring OWOB and anemia. The prevalence of co-occurring OWOB and any micronutrient deficiency was 2 times higher among urban women than rural women [urban 32.6 (24.1, 41.2) compared with rural 8.6 (5.2, 11.9), adjusted prevalence ratio: 2.0 (1.1, 3.5)]. Co-occurring OWOB and anemia prevalence did not significantly differ by residence [urban 6.9 (0.6, 13.2) compared with rural 3.0 (0.8, 5.3)]. There were no statistically significant differences in observed and expected prevalence estimates of DBM. CONCLUSIONS: This analysis shows that co-occurring OWOB and any micronutrient deficiency was higher among women in urban Malawi compared with rural areas. However, our finding that co-occurring OWOB and any micronutrient deficiency or anemia may be due to chance suggests that there may not be common causes driving DBM in Malawian women. Thus, there may not be a need to design and target interventions specifically for women with DBM.

      4. BACKGROUND: Vitamin B-12 and folate deficiencies in women and children have important public health implications. However, the evidence is conflicting and limited on whether the influence of inflammation on biomarker concentrations may be sufficiently and consistently influenced by inflammation to require adjustment for interpreting concentrations or estimating population prevalence of deficiencies. OBJECTIVE: We examined correlations between concentrations of the inflammation biomarkers C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) and serum vitamin B-12 and serum and RBC folate among nonpregnant women of reproductive age (WRA; 15-49 yr) and preschool children (PSC; 6-59 mo). METHODS: We analyzed cross-sectional data from 16 nationally representative nutrition surveys conducted in WRA (n = 32,588) and PSC (n = 8,256) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Spearman correlations between CRP or AGP and vitamin B-12 or folate concentrations were examined, taking into account complex survey design effects. RESULTS: Correlations between inflammation and vitamin B-12 or folate were weak, with no clear pattern of association in either WRA or PSC. Correlation coefficients between CRP and vitamin B-12 for WRA and PSC ranged from -0.25 to 0.16, and correlations between AGP and vitamin B-12 ranged between -0.07 and 0.14. Similarly, correlations between CRP and serum folate ranged from -0.13 to 0.08, and correlations between AGP and serum folate between -0.21 and 0.02. Only 3 surveys measured RBC folate, and among them, correlations for WRA ranged from -0.07 to 0.08 for CRP and -0.04 for AGP (1 country). CONCLUSIONS: Based on the weak and inconsistent correlations between CRP or AGP and vitamin B-12 or folate biomarkers, there is no rationale to adjust for inflammation when estimating population prevalence of vitamin B-12 or folate deficiencies in WRA or PSC.

    • Occupational Safety and Health
      1. BACKGROUND: Respirable crystalline silica (RCS) can potentially cause silicosis, lung cancer, and renal failure. The current study estimates the percentages of workers potentially overexposed to concentrations of RCS dust and silicosis proportional mortality rates (PMRs) by industry. METHODS: Occupational Safety and Health Administration compliance inspection sampling data for RCS collected during 1979 to 2015 were used to estimate percentages of workers exposed. The results were used in combination with US Census Bureau estimates to produce industry specific worker population estimates for 2014. Estimates of the numbers and percentages of workers exposed to RCS concentrations at least 1, 2, 5, and 10 times the National Institute for Occupational Safety and Health recommended exposure limit (REL) were calculated by industry using the 2002 North American Industry Classification System. Silicosis PMRs by industry were estimated using National Center for Health Statistics multiple cause of death data. RESULTS: RCS concentrations/workers exposed were highest in the poured concrete foundation and structure contractors; commercial and institutional building construction; and masonry contractors. Approximately 100 000 workers were exposed above the RCS REL, and most (79%) worked in the construction industry. Tile and terrazzo contractors (12%); brick, stone, and related construction merchant wholesalers (10%); masonry contractors (6%) and poured concrete foundation and structure contractors (6%) were the highest percentages of workers potentially overexposed. PMRs were highest for the structural clay product manufacturing and the foundries industries. CONCLUSION: Percentages of workers exposed to RCS varied by industry and in some industries workers are exposed over 10 times the REL. Exposures can be reduced below the REL by implementing the hierarchy of controls.

      2. Interest from Congress, executive branch leadership, and various other stakeholders for greater accountability in government continues to gain momentum today with government-wide efforts. However, measuring the impact of research programs has proven particularly difficult. Cause and effect linkages between research findings and changes to morbidity and mortality are difficult to prove. To address this challenge, the National Institute for Occupational Safety and Health program evaluators used a modified version of contribution analysis (CA) to evaluate two research programs. CA proved to be a useful framework for assessing research impact, and both programs received valuable, actionable feedback. Although there is room to further refine our approach, this was a promising step toward moving beyond bibiliometrics to more robust assessment of research impact.

      3. NIOSH: A short historyexternal icon
        Howard J.
        Am J Public Health. 2020 May;110(5):629-630.

      4. Background: Surgical N95 respirators are devices certified by the National Institute for Occupational Safety and Health (NIOSH) and also cleared by the Food and Drug Administration (FDA) as a medical device. They are commonly used in healthcare settings to provide protection from infectious aerosols, as well as, bodily fluid sprays and splashes. It is hypothesized based on design, some models may change their shape significantly (i.e., collapse) during heavy breathing, which may allow the device to touch the wearer's face. Concerns have been raised that droplets of infectious biological fluids may reach the inner layer of surgical N95 respirators leading to the transfer of microorganisms to the oronasal facial region upon collapse. Unfortunately, little data currently exists on respirator rigidity testing or its relation to efficacy. The objective of this study was to develop and optimize a manikin-based test system to evaluate respirator rigidity. Methods: Six surgical N95 models of three different designs (cup-shaped, flat fold and trifold) were tested at two different environmental conditions on the NIOSH medium headform. Rigidity evaluation was performed at 50% relative humidity (RH) and 22 degrees C, and at ~100% RH and 33 degrees C at 40, 50, and 60 L/min breathing flow rates. Facial contact secondary to shape change was assessed by coating the inner layer of the surgical N95 respirators with a fluorescent tracer and its transfer to the manikin face. Results: The results showed that the cup-shaped models were rigid and resistant to shape change at both environmental conditions and all flow rates. In contrast, the flat fold models and trifold models showed significant changes with rigidity, at higher breathing flow rates and higher RH and temperature conditions. The flat fold models showed transfer of the fluorescent tracer to the manikin face at higher RH and breathing rates, confirming a change in rigidity. Conclusions: The results from the study suggest that the manikin-based test system designed for the purposes of this study can be used to evaluate respirator rigidity.

      5. Generalizability of a biomathematical model of fatigue's sleep predictionsexternal icon
        Riedy SM, Fekedulegn D, Andrew M, Vila B, Dawson D, Violanti J.
        Chronobiol Int. 2020 Apr 2:1-9.
        Introduction: Biomathematical models of fatigue (BMMF) predict fatigue during a work-rest schedule on the basis of sleep-wake histories. In the absence of actual sleep-wake histories, sleep-wake histories are predicted directly from work-rest schedules. The predicted sleep-wake histories are then used to predict fatigue. It remains to be determined whether workers organize their sleep similarly across operations and thus whether sleep predictions generalize.Methods: Officers (n = 173) enrolled in the Buffalo Cardio-Metabolic Occupational Police Stress study were studied. Officers' sleep-wake behaviors were measured using wrist-actigraphy and predicted using a BMMF (FAID Quantum) parameterized in aviation and rail. Sleepiness (i.e. Karolinska Sleepiness Scale (KSS) ratings) was predicted using actual and predicted sleep-wake data. Data were analyzed using sensitivity analyses.Results: During officers' 16.0 +/- 1.9 days of study participation, they worked 8.6 +/- 3.1 shifts and primarily worked day shifts and afternoon shifts. Across shifts, 7.0 h +/- 1.9 h of actual sleep were obtained in the prior 24 h and associated peak KSS ratings were 5.7 +/- 1.3. Across shifts, 7.2 h +/- 1.1 h of sleep were predicted in the prior 24 h and associated peak KSS ratings were 5.5 +/- 1.2. The minute-by-minute predicted and actual sleep-wake data demonstrated high sensitivity (80.4%). However, sleep was observed at all hours-of-the-day, but sleep was rarely predicted during the daytime hours.Discussion: The sleep-wake behaviors predicted by a BMMF parameterized in aviation and rail demonstrated high sensitivity with police officers' actual sleep-wake behaviors. Additional night shift data are needed to conclude whether BMMF sleep predictions generalize across operations.

      6. The validity of the Canadian clinical scores for occupational asthma in European populationsexternal icon
        Suarthana E, Taghiakbari M, Saha-Chaudhuri P, Rifflart C, Suojalehto H, Holtta P, Walusiak-Skorupa J, Wiszniewska M, Munoz X, Romero-Mesones C, Sastre J, Rial MJ, Henneberger PK, Vandenplas O.
        Allergy. 2020 Apr 3.

      7. PURPOSE: Assess the effect of non-pharmaceutical interventions at work on noise exposure or occupational hearing loss compared to no or alternative interventions. RESEARCH STRATEGIES: Pubmed, Embase, Web of Science, OSHupdate, Cochrane Central and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched. SELECTION CRITERIA: Randomized Controlled Trials (RCT), Controlled Before-After studies (CBA) and Interrupted Time-Series studies (ITS) evaluating engineering controls, administrative controls, personal hearing protection devices, and hearing surveillance were included. Case studies of engineering controls were collected. DATA ANALYSIS: Cochrane methods for systematic reviews, including meta-analysis, were followed. RESULTS: 29 studies were included. Stricter legislation can reduce noise levels by 4.5 dB(A) (very low-quality evidence). Engineering controls can immediately reduce noise (107 cases). Eleven RCTs and CBA studies (3725 participants) were evaluated through Hearing Protection Devices (HPDs). Training of earplug insertion reduces noise exposure at short term follow-up (moderate quality evidence). Earmuffs might perform better than earplugs in high noise levels but worse in low noise levels (very low-quality evidence). HPDs might reduce hearing loss at very long-term follow-up (very low-quality evidence). Seventeen studies (84028 participants) evaluated hearing loss prevention programs. Better use of HPDs might reduce hearing loss but other components not (very low-quality evidence). CONCLUSION: Hearing loss prevention and interventions modestly reduce noise exposure and hearing loss. Better quality studies and better implementation of noise control measures and HPDs is needed.

      8. The aim of this study was to develop a new method to measure respirator protection factors for aerosol particles using portable instruments while workers conduct their normal work. The portable instruments, including a set of two handheld condensation particle counters (CPCs) and two portable aerosol mobility spectrometers (PAMSs), were evaluated with a set of two reference scanning mobility particle sizers (SMPSs). The portable instruments were mounted to a tactical load-bearing vest or backpack and worn by the test subject while conducting their simulated workplace activities. Simulated workplace protection factors (SWPFs) were measured using human subjects exposed to sodium chloride aerosols at three different steady state concentration levels: low (8x10(3) particles/cm(3)), medium (5x10(4) particles/cm(3)), and high (1x10(5) particles/cm(3)). Eight subjects were required to pass a quantitative fit test before beginning a SWPF test for the respirators. Each SWPF test was performed using a protocol of five exercises for 3 min each: (1) normal breathing while standing; (2) bending at the waist; (3) a simulated laboratory-vessel cleaning motion; (4) slow walking in place; and (5) deep breathing. Two instrument sets (one portable instrument {CPC or PAMS} and one reference SMPS for each set) were used to simultaneously measure the aerosol concentrations outside and inside the respirator. The SWPF was calculated as a ratio of the outside and inside particles. Generally, the overall SWPFs measured with the handheld CPCs had a relatively good agreement with those measured with the reference SMPSs, followed by the PAMSs. Under simulated workplace activities, all handheld CPCs, PAMSs, and the reference SMPSs showed a similar GM SWPF trend, and their GM SWPFs decreased when simulated workplace movements increased. This study demonstrated that the new design of mounting two handheld CPCs in the tactical load-bearing vest or mounting one PAMS unit in the backpack permitted subjects to wear it while performing the simulated workplace activities. The CPC shows potential for measuring SWPFs based on its light weight and lack of major instrument malfunctions.

    • Occupational Safety and Health - Mining
      1. Performance comparison of four portable FTIR instruments for direct-on-filter measurement of respirable crystalline silicaexternal icon
        Ashley EL, Cauda E, Chubb LG, Tuchman DP, Rubinstein EN.
        Ann Work Expo Health. 2020 Apr 8.
        Exposure to dusts containing respirable crystalline silica is a recognized hazard affecting various occupational groups such as miners. Inhalation of respirable crystalline silica can lead to silicosis, which is a potentially fatal lung disease. Currently, miners' exposure to respirable crystalline silica is assessed by collecting filter samples that are sent for laboratory analysis. A more timely field-based silica monitoring method using direct-on-filter (DoF) analysis is being developed by researchers at the National Institute for Occupational Safety and Health (NIOSH) to provide mine operators with the option to evaluate miners' exposure at the mine. This field-based silica monitoring technique involves the use of portable Fourier transform infrared (FTIR) instruments. As a step in the development of this new analytical technique, four commercially available portable FTIR instruments were evaluated for their ability to provide reproducible measurements from filter samples containing respirable crystalline silica. Reported testing indicates that measurements varied within +/-4.1% between instruments for filter samples that contained high-purity respirable crystalline silica. Measurements varied within +/-3.0% between instruments for filter samples that contained varying mineral composition. Filter samples were repeatedly analyzed by the same instrument over short and extended periods of time, and mean coefficients of variation did not exceed +/-1.6 and +/-2.4%, respectively. Mixed model analysis revealed that there was no statistically significant (P < 0.05) change in average measurements made over an extended period of time for all instruments. Results suggest that each of the four FTIR instruments evaluated in this study were able to generate precise and reproducible DoF analysis results of respirable dust samples.

    • Parasitic Diseases
      1. Relationships between measures of malaria at delivery and adverse birth outcomes in a high-transmission area of Ugandaexternal icon
        Ategeka J, Kakuru A, Kajubi R, Wasswa R, Ochokoru H, Arinaitwe E, Adoke Y, Jagannathan P, R. Kamya M, Muehlenbachs A, Chico RM, Dorsey G.
        J Infect Dis. 2020 Apr 2.
        BACKGROUND: Clinical trials of interventions for preventing malaria in pregnancy often use measures of malaria at delivery as their primary outcome. Although the objective of these interventions is to improve birth outcomes, data on associations between different measures of malaria at delivery and adverse birth outcomes are limited. METHODS: Data came from 637 Ugandan women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy. Malaria at delivery was detected using peripheral and placental blood microscopy, placental blood loop mediated isothermal amplification (LAMP) and placental histopathology. Multivariate analyses were used to estimate associations between measures of malaria at delivery and risks of low birth weight (LBW), small-for-gestational age (SGA) and preterm birth (PTB). RESULTS: Detection of malaria parasites by microscopy or LAMP was not associated with adverse birth outcomes. Presence of malaria pigment detected by histopathology in > 30% of high-powered fields was strongly associated with LBW (aRR=3.42, p=0.02) and SGA (aRR=4.24, p<0.001), but not preterm birth (aRR=0.88, p=0.87). CONCLUSIONS: A semi-quantitative classification system based on histopathologically detected malaria pigment provided the best surrogate measure of adverse birth outcomes in a high transmission setting and should be considered for use in malaria in pregnancy intervention studies.

      2. First trimester use of artemisinin-based combination therapy and the risk of low birth weight and small for gestational ageexternal icon
        Augusto O, Stergachis A, Dellicour S, Tinto H, Vala A, Ruperez M, Macete E, Nakanabo-Diallo S, Kazienga A, Valea I, d'Alessandro U, Ter Kuile FO, Calip GS, Ouma P, Desai M, Sevene E.
        Malar J. 2020 Apr 8;19(1):144.
        BACKGROUND: While there is increasing evidence on the safety of artemisinin-based combination therapy (ACT) for the case management of malaria in early pregnancy, little is known about the association between exposure to ACT during the first trimester and the effect on fetal growth. METHODS: Data were analysed from prospective studies of pregnant women enrolled in Mozambique, Burkina Faso and Kenya designed to determine the association between anti-malarial drug exposure in the first trimester and pregnancy outcomes, including low birth weight (LBW) and small for gestational age (SGA). Exposure to anti-malarial drugs was ascertained retrospectively by record linkage using a combination of data collected from antenatal and adult outpatient clinic registries, prescription records and self-reported medication usage by the women. Site-level data synthesis (fixed effects and random effects) was conducted as well as individual-level analysis (fixed effects by site). RESULTS: Overall, 1915 newborns were included with 92 and 26 exposed to ACT (artemether-lumefantrine) and quinine, respectively. In Burkina Faso, Mozambique and Kenya at recruitment, the mean age (standard deviation) was 27.1 (6.6), 24.2 (6.2) and 25.7 (6.5) years, and the mean gestational age was 24.0 (6.2), 21.2 (5.7) and 17.9 (10.2) weeks, respectively. The LBW prevalence among newborns born to women exposed to ACT and quinine (QNN) during the first trimester was 10/92 (10.9%) and 7/26 (26.9%), respectively, compared to 9.5% (171/1797) among women unexposed to any anti-malarials during pregnancy. Compared to those unexposed to anti-malarials, ACT and QNN exposed women had the pooled LBW prevalence ratio (PR) of 1.13 (95% confidence interval (CI) 0.62-2.05, p-value 0.700) and 2.03 (95% CI 1.09-3.78, p-value 0.027), respectively. Compared to those unexposed to anti-malarials ACT and QNN-exposed women had the pooled SGA PR of 0.85 (95% CI 0.50-1.44, p-value 0.543) and 1.41 (95% CI 0.71-2.77, p-value 0.322), respectively. Whereas compared to ACT-exposed, the QNN-exposed had a PR of 2.14 (95% CI 0.78-5.89, p-value 0.142) for LBW and 8.60 (95% CI 1.29-57.6, p-value 0.027) for SGA. The level of between sites heterogeneity was moderate to high. CONCLUSION: ACT exposure during the first trimester was not associated with an increased occurrence of LBW or SGA. However, the data suggest a higher prevalence of LBW and SGA for children born to QNN-exposed pregnancies. The findings support the use of ACT (artemether-lumefantrine) for the treatment of uncomplicated malaria during the first trimester of pregnancy.

    • Public Health Leadership and Management
      1. Community-university partnership characteristics for translation: Evidence from CDC's Prevention Research Centersexternal icon
        Young BR, Leeks KD, Bish CL, Mihas P, Marcelin RA, Kline J, Ulin BF.
        Front Public Health. 2020 ;8:79.
        Background: The Centers for Disease Control and Prevention's Prevention Research Centers (PRC) Program supports community engagement and partnerships to translate health evidence into practice. Translation is dependent on the quality of partnerships. However, questions remain about the necessary characteristics to develop and maintain translation partnerships. Aim: To identify the characteristics that influence community-university partnerships and examine alignment with the Knowledge to Action (K2A) Framework. Methods: Final Progress Reports (N = 37) from PRCs funded from September 2009 to September 2014 were reviewed in 2016-2017 to determine eligibility. Eligible PRCs included those that translated an innovation following the applied research phase (2009-2014) of the PRC award (n = 12). The PRCs and the adopters (i.e., community organizations) were recruited and participated in qualitative interviews in 2017. Results: Ten PRCs (83.3% response rate) and four adopters participated. Twelve codes (i.e., elements) were found that impacted partnerships along the translation continuum (e.g., adequate communication, technical assistance). Each element aligned with the K2A Framework at multiple steps within the translation phase. The intersection between the element and step in the translation phase is termed a "characteristic." Using interview data, fifty-two unique partnership characteristics for translation were found. Discussion and Conclusion: The results suggest multiple characteristics that impact translation partnerships. The inclusion of these partnership characteristics in policies and practices that seek to move practice-based or research-based evidence into widespread use may impact the receptivity by partners and evidence uptake by communities. Using the K2A Framework to assess translation partnerships was helpful and could be considered in process evaluations to inform translation partnership improvement.

    • Reproductive Health
      1. School district-provided supports to enhance sexual health education among middle and high school health education teachersexternal icon
        Szucs LE, Rasberry CN, Jayne PE, Rose ID, Boyce L, Murray CC, Lesesne CA, Parker JT, Roberts G.
        Teach Teach Educ. 2020 ;92.
        Schools support teachers in their professional learning, just as teachers support students in their learning. To accomplish this, schools can provide support systems that enhance teachers’ knowledge, comfort, and instructional skills. This study examined the impact of two district-provided supports (curriculum and professional development) on sexual health instruction among middle and high school health education teachers. Data were abstracted and analyzed using inductive coding from 24 teacher interviews (2015–2016). Findings illustrate outcomes from both curriculum and PD on teachers’ self-reported knowledge, comfort, and skills. The district-provided supports appeared to contribute to improved teachers’ self-efficacy in delivering sexual health education.

      2. "U.S. Medical Eligibility Criteria for Contraceptive Use" (U.S. MEC) 2016 provides evidence-based guidance for the safe use of contraceptive methods among U.S. women with certain characteristics or medical conditions (1). The U.S. MEC is adapted from global guidance from the World Health Organization (WHO) and kept up to date through continual review of published literature (1). CDC recently evaluated the evidence and the updated WHO guidance on the risk for human immunodeficiency virus (HIV) acquisition among women using hormonal contraception and intrauterine devices (IUDs) (2). After careful review, CDC adopted WHO's 2019 updated guidance for inclusion in the U.S. MEC guidance; CDC's updated guidance states that progestin-only injectable contraception (including depot medroxyprogesterone acetate [DMPA]) and IUDs (including levonorgestrel-releasing and copper-bearing) are safe for use without restriction among women at high risk for HIV infection (U.S. MEC category 1 [previously U.S. MEC category 2, advantages outweigh risks]) (Box). CDC's guidance also adds an accompanying clarification for women who wish to use IUDs, which states "Many women at a high risk for HIV infection are also at risk for other sexually transmitted diseases (STDs). For these women, refer to the recommendations in the 'U.S. Medical Eligibility Criteria for Contraceptive Use' for women with other factors related to STDs, and the 'U.S. Selected Practice Recommendations for Contraceptive Use' on STD screening before IUD insertion" (1,3). Recommendations for other hormonal contraceptive methods (including combined hormonal methods, implants, and progestin-only pills) remain the same; there is also no restriction for their use among women at high risk for HIV infection (U.S. MEC category 1). Finally, CDC clarified that the U.S. MEC recommendations for concurrent use of hormonal contraceptives or IUDs and antiretroviral use for treatment of HIV infection also apply to use of antiretrovirals for prevention of HIV acquisition (preexposure prophylaxis [PrEP]).

    • Zoonotic and Vectorborne Diseases
      1. A hundred years of rabies in Kenya and the strategy for eliminating dog-mediated rabies by 2030 [version 2; peer review: 4 approved]external icon
        Bitek AO, Osoro E, Munyua PM, Nanyingi M, Muthiani Y, Kiambi S, Muturi M, Mwatondo A, Muriithi R, Cleaveland S, Hampson K, Njenga MK, Kitala PM, Thumbi SM.
        AAS Open Res. 2019 Jun 10;1:23.
        Background: Rabies causes an estimated 59,000 human deaths annually. In Kenya, rabies was first reported in a dog in 1912, with the first human case reported in 1928. Here we examine retrospective rabies data in Kenya for the period 1912 - 2017 and describe the spatial and temporal patterns of rabies occurrence in the country. Additionally, we detail Kenya's strategy for the elimination of dog-mediated human rabies by 2030. Methods: Data on submitted samples and confirmed cases in humans, domestic animals and wildlife were obtained from Kenya's Directorate of Veterinary Services. These data were associated with the geographical regions where the samples originated, and temporal and spatial trends examined. Results: Between 1912 and the mid 1970's, rabies spread across Kenya gradually, with fewer than 50 cases reported per year and less than half of the 47 counties affected. Following an outbreak in the mid 1970's, rabies spread rapidly to more than 85% of counties, with a 4 fold increase in the percent positivity of samples submitted and number of confirmed rabies cases. Since 1958, 7,584 samples from domestic animals (93%), wildlife (5%), and humans (2%) were tested. Over two-thirds of all rabies cases came from six counties, all in close proximity to veterinary diagnostic laboratories, highlighting a limitation of passive surveillance. Conclusions: Compulsory annual dog vaccinations between 1950's and the early 1970's slowed rabies spread. The rapid spread with peak rabies cases in the 1980's coincided with implementation of structural adjustment programs privatizing the veterinary sector leading to breakdown of rabies control programs. To eliminate human deaths from rabies by 2030, Kenya is implementing a 15-year step-wise strategy based on three pillars: a) mass dog vaccination, b) provision of post-exposure prophylaxis and public awareness and c) improved surveillance for rabies in dogs and humans with prompt responses to rabies outbreaks.

      2. Progressive vaccinia acquired through zoonotic transmission in a patient with HIV/AIDS, Colombiaexternal icon
        Laiton-Donato K, Avila-Robayo P, Paez-Martinez A, Benjumea-Nieto P, Usme-Ciro JA, Pinzon-Narino N, Giraldo I, Torres-Castellanos D, Nakazawa Y, Patel N, Wilkins K, Li Y, Davidson W, Burgado J, Satheshkumar PS, Styczynski A, Mauldin MR, Gracia-Romero M, Petersen BW.
        Emerg Infect Dis. 2020 Mar;26(3):601-605.
        In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery.

      3. Detection of SARS-CoV-2 among residents and staff members of an independent and assisted living community for older adults - Seattle, Washington, 2020external icon
        Roxby AC, Greninger AL, Hatfield KM, Lynch JB, Dellit TH, James A, Taylor J, Page LC, Kimball A, Arons M, Schieve LA, Munanga A, Stone N, Jernigan JA, Reddy SC, Lewis J, Cohen SA, Jerome KR, Duchin JS, Neme S.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):416-418.
        In the Seattle, Washington metropolitan area, where the first case of novel coronavirus 2019 disease (COVID-19) in the United States was reported (1), a community-level outbreak is ongoing with evidence of rapid spread and high morbidity and mortality among older adults in long-term care skilled nursing facilities (SNFs) (2,3). However, COVID-19 morbidity among residents of senior independent and assisted living communities, in which residents do not live as closely together as do residents in SNFs and do not require skilled nursing services, has not been described. During March 5-9, 2020, two residents of a senior independent and assisted living community in Seattle (facility 1) were hospitalized with confirmed COVID-19 infection; on March 6, social distancing and other preventive measures were implemented in the community. UW Medicine (the health system linked to the University of Washington), Public Health - Seattle & King County, and CDC conducted an investigation at the facility. On March 10, all residents and staff members at facility 1 were tested for SARS-CoV-2, the virus that causes COVID-19, and asked to complete a questionnaire about their symptoms; all residents were tested again 7 days later. Among 142 residents and staff members tested during the initial phase, three of 80 residents (3.8%) and two of 62 staff members (3.2%) had positive test results. The three residents had no symptoms at the time of testing, although one reported an earlier cough that had resolved. A fourth resident, who had negative test results in the initial phase, had positive test results 7 days later. This resident was asymptomatic on both days. Possible explanations for so few cases of COVID-19 in this residential community compared with those in several Seattle SNFs with high morbidity and mortality include more social distancing among residents and less contact with health care providers. In addition, early implementation of stringent isolation and protective measures after identification of two COVID-19 cases might have been effective in minimizing spread of the virus in this type of setting. When investigating a potential outbreak of COVID-19 in senior independent and assisted living communities, symptom screening is unlikely to be sufficient to identify all persons infected with SARS-CoV-2. Adherence to CDC guidance to prevent COVID-19 transmission in senior independent and assisted living communities (4) could be instrumental in preventing a facility outbreak.

      4. Comparison of characteristics of patients with West Nile virus or St. Louis encephalitis virus neuroinvasive disease during concurrent outbreaks, Maricopa County, Arizona, 2015external icon
        Venkat H, Krow-Lucal E, Kretschmer M, Sylvester T, Levy C, Adams L, Fitzpatrick K, Laven J, Kosoy O, Sunenshine R, Smith K, Townsend J, Chevinsky J, Hennessey M, Jones J, Komatsu K, Fischer M, Hills S.
        Vector Borne Zoonotic Dis. 2020 Apr 6.
        West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related mosquito-borne flaviviruses that can cause neuroinvasive disease. No concurrent WNV and SLEV disease outbreaks have previously been identified. When concurrent outbreaks occurred in 2015 in Maricopa County, Arizona, we collected data to describe the epidemiology, and to compare features of patients with WNV and SLEV neuroinvasive disease. We performed enhanced case finding, and gathered information from medical records and patient interviews. A case was defined as a clinically compatible illness and laboratory evidence of WNV, SLEV, or unspecified flavivirus infection in a person residing in Maricopa County in 2015. We compared demographic and clinical features of WNV and SLEV neuroinvasive cases; for this analysis, a case was defined as physician-documented encephalitis or meningitis and a white blood cell count >5 cells/mm(3) in cerebrospinal fluid. In total, we identified 82 cases, including 39 WNV, 21 SLEV, and 22 unspecified flavivirus cases. The comparative analysis included 21 WNV and 14 SLEV neuroinvasive cases. Among neuroinvasive cases, the median age of patients with SLEV (63 years) was higher than WNV (52 years). Patients had similar symptoms; rash was identified more frequently in WNV (33%) neuroinvasive cases than in SLEV (7%) cases, but this difference was not statistically significant (p = 0.11). In summary, during the first known concurrent WNV and SLEV disease outbreaks, no specific clinical features were identified that could differentiate between WNV and SLEV neuroinvasive cases. Health care providers should consider both infections in patients with aseptic meningitis or encephalitis.

      5. Rapid sentinel surveillance for COVID-19 - Santa Clara County, California, March 2020external icon
        Zwald ML, Lin W, Sondermeyer Cooksey GL, Weiss C, Suarez A, Fischer M, Bonin BJ, Jain S, Langley GE, Park BJ, Moulia D, Benedict R, Nguyen N, Han GS.
        MMWR Morb Mortal Wkly Rep. 2020 Apr 10;69(14):419-421.
        On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.


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

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