Volume 10, Issue 8, March 6, 2018

CDC Science Clips: Volume 10, Issue 8, March 6, 2018

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

This week, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue (www.cdc.gov/vitalsigns). The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Substance Use and Abuse – Prescription Drug Overdose
      1. *The prescription opioid and heroin crisis: a public health approach to an epidemic of addictionExternal
        Kolodny A, Courtwright DT, Hwang CS, Kreiner P, Eadie JL, Clark TW, Alexander GC.
        Annu Rev Public Health. 2015 Mar 18;36:559-74.

        Public health authorities have described, with growing alarm, an unprecedented increase in morbidity and mortality associated with use of opioid pain relievers (OPRs). Efforts to address the opioid crisis have focused mainly on reducing nonmedical OPR use. Too often overlooked, however, is the need for preventing and treating opioid addiction, which occurs in both medical and nonmedical OPR users. Overprescribing of OPRs has led to a sharp increase in the prevalence of opioid addiction, which in turn has been associated with a rise in overdose deaths and heroin use. A multifaceted public health approach that utilizes primary, secondary, and tertiary opioid addiction prevention strategies is required to effectively reduce opioid-related morbidity and mortality. We describe the scope of this public health crisis, its historical context, contributing factors, and lines of evidence indicating the role of addiction in exacerbating morbidity and mortality, and we provide a framework for interventions to address the epidemic of opioid addiction.

      2. The purpose of this first annual surveillance report is to summarize the latest information available on the national level for various health outcomes, health behaviors, and prescribing patterns related to the drug problem in the United States. The most recent year of information available is different for different outcomes. The emphasis is on national information, but some state information is also presented. This document is intended to serve as a resource for persons charged with addressing this ongoing national problem. It will be updated annually.

      3. Prevalence and treatment of pain in EDs in the United States, 2000 to 2010External
        Chang HY, Daubresse M, Kruszewski SP, Alexander GC.
        Am J Emerg Med. 2014 May;32(5):421-31.

        OBJECTIVES: To describe changes in the prevalence and severity of pain and prescribing of non-opioid analgesics in US emergency departments (EDs) from 2000 to 2010. METHODS: Analysis of serial cross-sectional data regarding ED visits from the National Hospital Ambulatory Medical Care Survey. Visits were limited to patients >/=18 years old without malignancy. Outcome measures included annual volume of visits among adults with a primary symptom or diagnosis of pain, annual rates of patient-reported pain severity, and predictors of non-opioid receipt for non-malignant pain. RESULTS: Rates of pain remained stable, representing approximately 45% of visits from 2000 through 2010. Patients reported pain as their primary symptom twice as often as providers reported a primary pain diagnosis (40% vs 20%). The percentage of patients reporting severe pain increased from 25% (95% confidence intervals [CI] 22%-27%) in 2003 to 40% (CI 37%-42%) in 2008. From 2000 to 2010, the proportion of pain visits treated with pharmacotherapies increased from 56% (CI 53%-58%) to 71% (CI 69%-72%), although visits treated exclusively with non-opioids decreased 21% from 28% (CI 27%-30%) to 22% (CI 20%-23%). The adjusted odds of non-opioid rather than opioid receipt were greater among visits for patients 18 to 24 years old (odds ratio [OR] 1.35, CI 1.24-1.46), receiving fewer medicines (OR 2.91, CI 2.70-3.15) and those with a diagnosis of mental illness (OR 2.24, CI 1.99-2.52). CONCLUSIONS: Large increases in opioid utilization in EDs have coincided with reductions in the use of non-opioid analgesics and an unchanging prevalence of pain among patients.

      4. Relationship between nonmedical prescription-opioid use and heroin useExternal
        Compton WM, Jones CM, Baldwin GT.
        N Engl J Med. 2016 Jan 14;374(2):154-63.

        [No abstract]

      5. CDC Guideline for Prescribing Opioids for Chronic Pain – United States, 2016External
        Dowell D, Haegerich TM, Chou R.
        MMWR Recomm Rep. 2016 Mar 18;65(1):1-49.

        This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations.

      6. Vital Signs: Demographic and substance use trends among heroin users – United States, 2002-2013External
        Jones CM, Logan J, Gladden RM, Bohm MK.
        MMWR Morb Mortal Wkly Rep. 2015 Jul 10;64(26):719-25.

        BACKGROUND: Heroin use and overdose deaths have increased significantly in the United States. Assessing trends in heroin use among demographic and particular substance-using groups can inform prevention efforts. METHODS: FDA and CDC analyzed data from the National Survey on Drug Use and Health and National Vital Statistics System reported during 2002-2013. Trends in heroin use among demographic and substance using groups were compared for 2002-2004, 2005-2007, 2008-2010, and 2011-2013. A multivariable logistic regression model was used to identify characteristics associated with heroin abuse or dependence. RESULTS: Annual average rates of past-year heroin use increased from 1.6 per 1,000 persons aged >/= 12 years in 2002-2004 to 2.6 per 1,000 in 2011-2013. Rates of heroin abuse or dependence were strongly positively correlated with rates of heroin-related overdose deaths over time. For the combined data years 2011-2013, the odds of past-year heroin abuse or dependence were highest among those with past-year cocaine or opioid pain reliever abuse or dependence. CONCLUSIONS: Heroin use has increased significantly across most demographic groups. The increase in heroin abuse or dependence parallels the increase in heroin-related overdose deaths. Heroin use is occurring in the context of broader poly-substance use. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Further implementation of a comprehensive response that targets the wider range of demographic groups using heroin and addresses the key risk factors for heroin abuse and dependence is needed. Specific response needs include reducing inappropriate prescribing and use of opioids through early identification of persons demonstrating problematic use, stronger prescription drug monitoring programs, and other clinical measures; improving access to, and insurance coverage for, evidence-based substance abuse treatment, including medication-assisted treatment for opioid use disorders; and expanding overdose recognition and response training and access to naloxone to treat opioid pain reliever and heroin overdoses.

      7. Opioid overdose deaths quadrupled from 8,050 in 1999 to 33,091 in 2015 and accounted for 63% of drug overdose deaths in the United States in 2015. During 2010-2015, heroin overdose deaths quadrupled from 3,036 to 12,989 (1). Sharp increases in the supply of heroin and illicitly manufactured fentanyl (IMF) are likely contributing to increased deaths (2-6). CDC examined trends in unintentional and undetermined deaths involving heroin or synthetic opioids excluding methadone (i.e., synthetic opioids)* by the four U.S. Census regions during 2006-2015. Drug exhibits (i.e., drug products) obtained by law enforcement and reported to the Drug Enforcement Administration’s (DEA’s) National Forensic Laboratory Information System (NFLIS) that tested positive for heroin or fentanyl (i.e., drug reports) also were examined. All U.S. Census regions experienced substantial increases in deaths involving heroin from 2006 to 2015. Since 2010, the South and West experienced increases in heroin drug reports, whereas the Northeast and Midwest experienced steady increases during 2006-2015.(dagger) In the Northeast, Midwest, and South, deaths involving synthetic opioids and fentanyl drug reports increased considerably after 2013. These broad changes in the U.S. illicit drug market highlight the urgent need to track illicit drugs and enhance public health interventions targeting persons using or at high risk for using heroin or IMF.

      8. Deaths involving fentanyl, fentanyl analogs, and U-47700 – 10 states, July-December 2016External
        O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM.
        MMWR Morb Mortal Wkly Rep. 2017 Nov 3;66(43):1197-1202.

        Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4). In addition, fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (5,6) and the illicit opioid drug supply (7). Carfentanil is estimated to be 10,000 times more potent than morphine (8). Estimates of the potency of acetylfentanyl and furanylfentanyl vary but suggest that they are less potent than fentanyl (9). Estimates of relative potency have some uncertainty because illicit fentanyl analog potency has not been evaluated in humans. This report describes opioid overdose deaths during July-December 2016 that tested positive for fentanyl, fentanyl analogs, or U-47700, an illicit synthetic opioid, in 10 states participating in CDC’s Enhanced State Opioid Overdose Surveillance (ESOOS) program.* Fentanyl analogs are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required. Fentanyl was detected in at least half of opioid overdose deaths in seven of 10 states, and 57% of fentanyl-involved deaths also tested positive for other illicit drugs, such as heroin. Fentanyl analogs were present in >10% of opioid overdose deaths in four states, with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently. Expanded surveillance for opioid overdoses, including testing for fentanyl and fentanyl analogs, assists in tracking the rapidly changing illicit opioid market and informing innovative interventions designed to reduce opioid overdose deaths.

      9. Increases in drug and opioid-involved overdose deaths – United States, 2010-2015External
        Rudd RA, Seth P, David F, Scholl L.
        MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1445-1452.

        The U.S. opioid epidemic is continuing, and drug overdose deaths nearly tripled during 1999-2014. Among 47,055 drug overdose deaths that occurred in 2014 in the United States, 28,647 (60.9%) involved an opioid (1). Illicit opioids are contributing to the increase in opioid overdose deaths (2,3). In an effort to target prevention strategies to address the rapidly changing epidemic, CDC examined overall drug overdose death rates during 2010-2015 and opioid overdose death rates during 2014-2015 by subcategories (natural/semisynthetic opioids, methadone, heroin, and synthetic opioids other than methadone).* Rates were stratified by demographics, region, and by 28 states with high quality reporting on death certificates of specific drugs involved in overdose deaths. During 2015, drug overdoses accounted for 52,404 U.S. deaths, including 33,091 (63.1%) that involved an opioid. There has been progress in preventing methadone deaths, and death rates declined by 9.1%. However, rates of deaths involving other opioids, specifically heroin and synthetic opioids other than methadone (likely driven primarily by illicitly manufactured fentanyl) (2,3), increased sharply overall and across many states. A multifaceted, collaborative public health and law enforcement approach is urgently needed. Response efforts include implementing the CDC Guideline for Prescribing Opioids for Chronic Pain (4), improving access to and use of prescription drug monitoring programs, enhancing naloxone distribution and other harm reduction approaches, increasing opioid use disorder treatment capacity, improving linkage into treatment, and supporting law enforcement strategies to reduce the illicit opioid supply.

      10. Drugs most frequently involved in drug overdose deaths: United States, 2010-2014External
        Warner M, Trinidad JP, Bastian BA, Minino AM, Hedegaard H.
        Natl Vital Stat Rep. 2016 Dec;65(10):1-15.

        Objectives-This report identifies the specific drugs most frequently involved in drug overdose deaths in the United States from 2010 through 2014. Methods-The 2010-2014 National Vital Statistics System mortality files were linked to electronic files containing literal text information from death certificates. Drug overdose was defined using the International Classification of Diseases, Tenth Revision underlying cause-of-death codes X40-X44 (unintentional), X60-X64 (suicide), X85 (homicide), and Y10-Y14 (undetermined intent). Among deaths with an underlying cause of death of drug overdose, the literal text in three fields of the death certificate (i.e., the cause of death from Part I, significant conditions contributing to death from Part II, and a description of how the injury occurred from Box 43) were searched to identify drug mentions. Search term lists were developed using existing drug classification systems as well as from manual review of the literal text. The search term list was then used to identify the specific drugs involved in overdose deaths. Descriptive statistics were reported for drug overdose deaths involving the 10 most frequently mentioned drugs on death certificates. Tables and figures presenting information on the specific drugs involved in deaths are based on deaths with mention of at least one specific drug on the death certificate. Results-From 2010 through 2014, the number of drug overdose deaths per year increased 23%, from 38,329 in 2010 to 47,055 in 2014. During this time period, the percentage of drug overdose deaths involving at least one specific drug increased, from 67% in 2010 to 78% in 2014. Among drug overdose deaths with at least one drug specified on the death certificate, the 10 drugs most frequently involved in overdose deaths included the following opioids: heroin, oxycodone, methadone, morphine, hydrocodone, and fentanyl; the following benzodiazepines: alprazolam and diazepam; and the following stimulants: cocaine and methamphetamine. During this 5-year period, the age-adjusted rate of drug overdose deaths involving heroin more than tripled, and the rate of drug overdose deaths involving methamphetamine more than doubled. The rate of drug overdose deaths involving fentanyl more than doubled in a single year (from 2013 to 2014). In 2014, of the 36,667 drug overdose deaths involving at least one specific drug, 52% of these deaths specified one drug, 38% specified two or three drugs, and 11% specified four or more drugs. Conclusions-Analysis of the literal text from death certificates can be used to identify patterns in the specific drugs most frequently involved in drug overdose deaths. From 2010 through 2014, the top 10 drugs involved were the same, but the relative ranking and age-adjusted rates for deaths involving these drugs changed. Literal text analysis also revealed that many drug overdose deaths involved multiple drugs. Findings should be interpreted in light of the improvement in the quality of the data that resulted from better reporting of specific drugs on death certificates from 2010 through 2014. Relative increases in the death rates involving specific drugs and the rankings of these drugs may be affected by improvements in reporting, real increases in the numbers of death, or both.

  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. Healthcare experiences of low-income women with prior gestational diabetesExternal
        Oza-Frank R, Conrey E, Bouchard J, Shellhaas C, Weber MB.
        Matern Child Health J. 2018 Feb 17.

        Introduction An important yet understudied component of postpartum type 2 diabetes risk reduction among high risk women is experiences with the healthcare system. Our objective was to describe the healthcare experiences of a diverse, low-income sample of women with prior GDM, including their suggestions for improving care. Methods Focus groups were conducted among African American, Hispanic, and Appalachian women who were diagnosed with GDM within the past 10 years. Participants were recruited from community and medical resources. Twelve focus groups were conducted, four within each race-ethnic group. Results Three broad themes were identified around barriers to GDM care, management, and follow-up: (1) communication issues; (2) personal and environmental barriers; and (3) type and quality of healthcare. Many women felt communication with their provider could be improved, including more education on the severity of GDM, streamlining information to be less overwhelming, and providing additional support through referrals to community resources. Although women expressed interest in receiving more actionable advice for managing GDM during pregnancy and for preventing type 2 diabetes postpartum, few women reported changing behaviors. Barriers to behavior change were related to cost, transportation, and competing demands. Several opportunities for improved care were elucidated. Discussion Our findings suggest that across all racial and ethnic representations in our sample, low-income women with GDM experience similar communication, personal, and environmental barriers related to the healthcare they receive for their GDM. Considering the increased exposure to the health care system during a GDM-affected pregnancy, there are opportunities to address barriers among women with GDM across different race-ethnic groups.

      2. Background: /Purpose: Little is known about primary care physicians’ (PCPs) beliefs about prostate cancer screening efficacy, evidence uncertainty, and their actual screening behaviors. We examined factors associated with PCP beliefs about screening efficacy and uncertainty and whether beliefs were associated with prostate specific-antigen (PSA) test use. Methods: The 2008 National Survey of Primary Care Physicians’ Practices Regarding Prostate Cancer Screening collected information on physicians’ attitudes, beliefs, and practices related to prostate cancer and screening (n=1,256). Two factors were constructed that measured belief in certainty of evidence for PSA testing and belief in screening efficacy. These factors, along with PCP sociodemographic and practice-related factors, were used to examine associations with offering the PSA test. Results: Most PCPs were male (70%), Caucasian (76%), under age 50 (56%), and practiced in communities with more than 50,000 residents (54%). In bivariate analysis, variables associated with PCP belief in evidence uncertainty included female gender, younger age, and lower patient volume. Variables associated with belief in screening efficacy included older age and general and family practice specialty. After adjustment, PCPs with high belief in evidence uncertainty were less likely (OR=0.19, 95% CI=0.06, 0.62) to offer PSA and more likely to practice shared decision making (OR=1.80, 95% CI=1.22-2.67). PCPs with high belief in screening efficacy were more likely (OR=2.99, 95% CI=1.15, 7.77) to offer PSA and less likely to practice shared decision making (OR=0.47, 95% CI=0.32-0.70). Conclusion: Our data indicate that belief patterns about evidence uncertainty and the efficacy of using PSA may play a role in whether PCPs offer PSA.

    • Communicable Diseases
      1. Background: There are no data on the prevalence of cytomegalovirus (CMV) shedding from a representative sample of the US population. This information is critical for understanding and preventing CMV. Methods: We tested urine specimens from CMV IgG-positive participants aged 6-49 years in three racial/ethnic groups from the National Health and Nutrition Examination Surveys (NHANES) 1999-2004 for the presence of CMV DNA with real-time polymerase chain reaction (PCR) assay. We examined the association of sociodemographic characteristics with shedding prevalence and viral loads. Results: Among 6,828 CMV IgG-positive subjects tested, 537 had CMV DNA detected in urine-a shedding prevalence of 9.70%. Among persons 6-49 years, shedding prevalence was 3.83%. The prevalence of urinary shedding was inversely associated with increasing age (26.60%, 6.50%, and 3.45% in CMV IgG-positive subjects aged 6-11, 12-19, and 20-49 years, respectively; P 0.001 for trend test and pairwise comparisons). Urinary viral load also decreased significantly with age (mean: 2.97, 2.69, and 2.43 log10 copies/mL in those age groups, respectively; P 0.001 for trend test and pairwise comparisons). Conclusions: Urinary CMV shedding and viral loads decreased dramatically by age, likely reflecting higher rates of primary CMV infection and longer duration of shedding in younger individuals. The findings demonstrate that children 6-11 years of age continue to shed CMV at higher rates and viral loads than adolescents and adults and thus may still be an important source for CMV transmission.

      2. Multi-state syphilis outbreak among American Indians, 2013-2015External
        Bowen VB, Peterman TA, Calles DL, Thompson A, Kirkcaldy R, Taylor M.
        Sex Transm Dis. 2018 Feb 13.

        This article summarizes a multi-state outbreak of heterosexual syphilis, including 134 cases of syphilis in adults and adolescents and at least two cases of congenital syphilis, which occurred on an American Indian reservation in the United States during 2013-2015. In addition to providing salient details about the outbreak, the article seeks to document the case-finding and treatment activities undertaken, their relative success or failure, and the lessons learned from a coordinated, multiagency response. Of 134 adult cases of syphilis, 40% were identified by enhanced, interagency contact tracing and partner services; 26% through symptomatic testing; and 16% through screening of asymptomatic individuals as the result of an electronic medical record (EMR) screening prompt. A smaller proportion of cases were identified by community screening events in high-morbidity communities; high risk venue-based screening events; other screening, including screening upon request; and prenatal screening at first trimester, third trimester, and day-of-delivery. Future heterosexual syphilis outbreak responders should act quickly to coordinate a package of high-yield case-finding and treatment activities-potentially including activities that seek to do the following: 1) increase prenatal screening, 2) improve community awareness and symptomatic test-seeking, 3) educate providers and improve general screening for syphilis; 4) implement EMR reminders for providers; 5) screen high-morbidity communities and at high-risk venues; and 6) form novel partnerships to accomplish partner services work when the context does not allow for traditional, DIS-only partner services.

      3. Business travel-associated illness: a GeoSentinel analysisExternal
        Chen LH, Leder K, Barbre KA, Schlagenhauf P, Libman M, Keystone J, Mendelson M, Gautret P, Schwartz E, Shaw M, MacDonald S, McCarthy A, Connor BA, Esposito DH, Hamer D, Wilson ME.
        J Travel Med. 2018 Jan 1;25(1).

        Background: Analysis of a large cohort of business travelers will help clinicians focus on frequent and serious illnesses. We aimed to describe travel-related health problems in business travelers. Methods: GeoSentinel Surveillance Network consists of 64 travel and tropical medicine clinics in 29 countries; descriptive analysis was performed on ill business travelers, defined as persons traveling for work, evaluated after international travel 1 January 1997 through 31 December 2014. Results: Among 12 203 business travelers seen 1997-2014 (14 045 eligible diagnoses), the majority (97%) were adults aged 20-64 years; most (74%) reported from Western Europe or North America; two-thirds were male. Most (86%) were outpatients. Fewer than half (45%) reported a pre-travel healthcare encounter. Frequent regions of exposure were sub-Saharan Africa (37%), Southeast Asia (15%) and South Central Asia (14%). The most frequent diagnoses were malaria (9%), acute unspecified diarrhea (8%), viral syndrome (6%), acute bacterial diarrhea (5%) and chronic diarrhea (4%). Species was reported for 973 (90%) of 1079 patients with malaria, predominantly Plasmodium falciparum acquired in sub-Saharan Africa. Of 584 (54%) with malaria chemoprophylaxis information, 92% took none or incomplete courses. Thirteen deaths were reported, over half of which were due to malaria; others succumbed to pneumonia, typhoid fever, rabies, melioidosis and pyogenic abscess. Conclusions: Diarrheal illness was a major cause of morbidity. Malaria contributed substantial morbidity and mortality, particularly among business travelers to sub-Saharan Africa. Underuse or non-use of chemoprophylaxis contributed to malaria cases. Deaths in business travelers could be reduced by improving adherence to malaria chemoprophylaxis and targeted vaccination for vaccine-preventable diseases. Pre-travel advice is indicated for business travelers and is currently under-utilized and needs improvement.

      4. BACKGROUND: Improvements in resource allocation can increase the benefits of federally-funded sexually transmitted disease (STD) prevention activities. The purpose of this study was to illustrate how different strategies for allocating federal funds to sub-national districts for syphilis prevention might affect the incidence of syphilis at the national level. METHODS: We modeled syphilis rates by district and year using an equation based on a previous analysis of state-level syphilis elimination funding and syphilis case rates from 1998 to 2005 in the United States. We used the model to illustrate the potential impact of three different strategies for allocating supplemental federal funds to sub-national districts to support syphilis prevention activities a hypothetical country with 18 sub-national districts. The three strategies were based on each district’s (1) population size, (2) syphilis incidence rate, or (3) number of syphilis cases. The hypothetical country was similar to the United States in overall population and syphilis burden. RESULTS: Without the supplemental federal funds, there would be an estimated 48,600 incident infections annually in the hypothetical country. With the supplemental federal funds, the annual number of infections would be reduced to 27,800 with a population-based allocation of funding to each district, 26,700 with a rate-based allocation, and 24,400 with a case-based allocation of funding. CONCLUSIONS: Allocating federal STD prevention funds to districts based on burden of disease can be an efficient strategy, although this efficiency may be reduced or eliminated when high burden districts have less ability to provide adequate STD prevention services than lower burden districts.

      5. The etiology of vaginal discharge syndrome in Zimbabwe results from the Zimbabwe STI Etiology StudyExternal
        Chirenje ZM, Dhibi N, Handsfield HH, Gonese E, Barr BT, Gwanzura L, Latif AS, Maseko DV, Kularatne RS, Tshimanga M, Kilmarx PH, Machiha A, Mugurungi O, Rietmeijer CA.
        Sex Transm Dis. 2017 Nov 29.

        INTRODUCTION: Symptomatic vaginal discharge is a common gynecological condition managed syndromically in most developing countries. In Zimbabwe, women presenting with symptomatic vaginal discharge are treated with empirical regimens that commonly cover both sexually transmitted infections (STI) and reproductive tract infections, typically including a combination of an intramuscular injection of kanamycin, and oral doxycycline and metronidazole regimens. This study was conducted to determine the current etiology of symptomatic vaginal discharge and assess adequacy of current syndromic management guidelines. METHODS: We enrolled 200 women with symptomatic vaginal discharge presenting at 6 STI clinics in Zimbabwe. Microscopy was used to detect bacterial vaginosis and yeast infection. Nucleic acid amplifications tests were used to detect Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and Mycoplasma genitalium. In addition, serologic testing was performed to detect HIV infection. RESULTS: Of the 200 women, 146 (73%) had an etiology detected, including bacterial vaginosis (24.7%); N. gonorrhoeae (24.0%); yeast infection (20.7%); T. vaginalis (19.0%); C. trachomatis (14.0%) and M. genitalium (7.0%). Among women with STIs (N=90), 62 (68.9%) had a single infection, 18 (20.0%) had a dual infection and 10 (11.1%) had three infections.Of 158 women who consented to HIV testing, 64 (40.5%) were HIV infected.The syndromic management regimen covered 115 (57.5%) of the women in the sample who had gonorrhea, chlamydia, M. genitalium, or bacterial vaginosis, while 85 (42.5%) of women were treated without such diagnosis. CONCLUSION: Among women presenting with symptomatic vaginal discharge, bacterial vaginosis was the most common etiology and gonorrhea was the most frequently detected STI. The current syndromic management algorithm is suboptimal for coverage of women presenting with symptomatic vaginal discharge; addition of point of care testing could compliment the effectiveness of the syndromic approach.

      6. BACKGROUND: Health departments (HDs) cite state laws as barriers to billing third parties for sexually transmitted disease (STD) services, but the association between legal/policy barriers and third party HD billing has not been examined. This study investigates the relationship between laws that may limit HDs’ ability to bill, clinic perceptions of billing barriers, and billing practices. METHODS: Two surveys (1) clinic managers [N=246], 2) STD program managers [N=63]) conducted via a multi-regional needs assessment of federally funded HD clinics’ capacity to bill for STD services, billing/reimbursement practices, and perceived barriers were combined with an analysis of state laws regarding third party billing for STD services. Statistical analyses examined relationships between laws that may limit HDs’ ability to bill, clinic perceptions, and billing practices. RESULTS: Clinic managers reported clinics were less likely to bill Medicaid and other third parties in jurisdictions with a state law limiting their ability to bill compared to respondents who billed neither or one payer (OR=0.31, CI=0.10,0.97) and cited practical concerns as a primary barrier to billing (OR=2.83 CI=1.50,5.37). STD program managers’ reports that staff believed STD services should be free (OR=0.34, CI=0.13, 0.90) was associated with not billing (not sure versus no resistance to billing); confidentiality concerns was not a reported barrier to billing among either sample. CONCLUSIONS: Practical concerns and clinic staff beliefs that STD services should be free emerged as possible barriers to billing, and laws less so. Attempts to initiate HD billing for STD services may benefit from staff education as well as addressing perceived legal barriers and staff concerns.

      7. Assessing STD partner services in state and local health departmentsExternal
        Cuffe KM, Leichliter JS, Gift TL.
        Sex Transm Dis. 2018 Feb 7.

        State and local health department STD programs provide several partner services to reduce disease transmission. Budget cuts and temporary staff reassignments for public health emergencies may affect the provision of partner services. Determining the impact of staffing reductions on STD rates and public health response should be further assessed.

      8. Prevalence of rectal chlamydial and gonococcal infections: a systematic reviewExternal
        Dewart CM, Bernstein KT, DeGroote NP, Romaguera R, Turner AN.
        Sex Transm Dis. 2017 Nov 1.

        We undertook a systematic review to examine rectal Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng) infections in women and men who have sex with men (MSM). English-language publications measuring rectal Ct or Ng prevalence using nucleic acid amplification tests were eligible. Searching multiple electronic databases, we identified 115 eligible reports published between January 2000 and November 2016. Overall, the prevalence of rectal Ct (9.0%) was higher than rectal Ng (4.7%). Rectal Ct prevalence was similar in MSM (9%) and women (9.2%), while rectal Ng prevalence was higher in MSM (6.1%) than women (1.7%). Generally, rectal Ct prevalence was similar in STD clinics (9.1%) and non-sexual health clinics (8.6%), whereas rectal Ng prevalence was somewhat lower in STD clinics (4.5%) than non-sexual health clinics (6%). These infections appear to be relatively common across a range of populations and clinical settings, highlighting the need for additional research on these preventable, treatable conditions.

      9. BACKGROUND: Congenital syphilis occurs when a pregnant woman with syphilis is not diagnosed or treated and the infection is passed in utero, causing severe infant morbidity and mortality. Congenital syphilis is easily prevented if women receive timely and adequate prenatal care. Cases of congenital syphilis are considered indicators of problems in the safety net. However, maternal social and behavioral factors can impede women’s care, even when providers follow guidelines. METHODS: We reviewed case interviews and maternal records for 23 congenital syphilis cases reported to CDC from Indiana between 2014 and 2016. We used qualitative methods to analyze narrative notes from maternal interviews to learn more about factors that potentially contributed to CS cases. RESULTS: All providers followed CDC and state recommendations for screening and treatment of pregnant women with syphilis. Twenty-one of 23 women had health insurance. The number of prenatal care visits women had was suboptimal; more than one third of women had no prenatal care. Nearly one third of women’s only risk factor was sex with a primary male sex partner. The majority of women suffered social vulnerabilities, including homelessness, substance abuse, and incarceration. CONCLUSIONS: Despite provider adherence to guidelines and health insurance availability, some pregnant women with syphilis are unlikely to receive timely diagnosis and treatment. Pregnant women at high risk for syphilis may need additional social and material support to prevent a CS case. Additional efforts are needed to reach the male partners of vulnerable females with syphilis.

      10. OBJECTIVES: To examine variability in condom use trends by sexual risk behavior among US high school students. METHODS: Data were from the 2003-2015 national Youth Risk Behavior Surveys conducted biennially among a nationally representative sample of students in grades 9-12. We used logistic regression to examine variability in trends of condom use during last sexual intercourse among female and male students by four by four sexual risk behaviors: drank alcohol or used drugs before last sexual intercourse, first sexual intercourse before age 13 years, four or more sex partners during their life, and two or more sex partners during the past three months. RESULTS: Between 2003 and 2015 significant declines in self-reported condom use were observed among black female (63.6% in 2003 to 46.7% in 2015) and white male students (69.0% in 2003 to 58.1% in 2015). Among female students, declines in self-reported condom use were significant only among those who drank or use drugs before last sexual intercourse, had four or more sex partners during their life, or two or more sex partners during the past three months. There was a significant interaction between trends in condom use and first sexual intercourse before age 13 years, suggesting more pronounced declines among female students who initiated first sexual intercourse before age 13 years than their female peers. Trends did not vary by sexual risk behavior for males. CONCLUSIONS: Results suggest that declines in self-reported condom use have occurred among female students at greater risk for acquiring a sexually transmitted disease (STD).

      11. Burden of pneumonia-associated hospitalizations: United States, 2001-2014External
        Hayes BH, Haberling DL, Kennedy JL, Varma JK, Fry AM, Vora NM.
        Chest. 2018 Feb;153(2):427-437.

        BACKGROUND: The epidemiology of pneumonia has likely evolved in recent years, reflecting an aging population, changes in population immunity, and socioeconomic disparities. METHODS: Using the National (Nationwide) Inpatient Sample, estimated numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were calculated. A pneumonia-associated hospitalization was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis. RESULTS: There were an estimated 20,361,181 (SE, 95,601) pneumonia-associated hospitalizations in the United States during 2001-2014 (average annual age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000 population [95% CI, 462.5-467.1]). The average annual age-adjusted pneumonia-associated hospitalization rate decreased over the study period (P < .0001). In-hospital death occurred in 7.4% (SE, 0.03) of pneumonia-associated hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic blacks had the highest average annual age-adjusted rates of pneumonia-associated hospitalization of all race/ethnicities at 439.2 (95% CI, 415.9-462.5) and 438.6 (95% CI, 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the proportion of pneumonia-associated hospitalizations colisting an immunocompromising condition increased from 18.7% (SE, 0.2) in 2001 to 29.9% (SE, 0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014 were over $84 billion. CONCLUSIONS: Pneumonia is a major cause of morbidity and mortality in the United States. Differences in rates and outcomes of pneumonia-associated hospitalizations between sociodemographic groups warrant further investigation. The immunocompromised population has emerged as a group experiencing a disproportionate burden of pneumonia-associated hospitalizations.

      12. BACKGROUND: Annual screening for chlamydia and gonorrhea is recommended for sexually active men who have sex with men (MSM) at anatomical sites of contact, regardless of condom use. METHODS: We assessed differences in self-reported chlamydia and gonorrhea testing and diagnosis in the past 12 months among MSM using National HIV Behavioral Surveillance data from 2011 and 2014. MSM who had >/= 1 partner in the past 12 months were included in analyses. Analyses of chlamydia and gonorrhea diagnosis data were limited to participants who reported past 12 months chlamydia and gonorrhea testing, respectively. Differences in testing and diagnosis over time were assessed using Poisson regression models with robust standard errors separately for chlamydia and gonorrhea. RESULTS: Analyses included data from 18,896 MSM (2011: n=9,256; 2014: n=9,640). Testing for chlamydia was 37% in 2011 and 47% in 2014 (PR: 1.25, 95% CI: 1.20-1.30) and 38% and 47% for gonorrhea (PR: 1.24, 95% CI: 1.19-1.29). Testing was higher in 2014 among most demographic subgroups. Prevalence of chlamydia diagnoses was 8% in 2011 and 11% in 2014 (PR: 1.37, 95% CI: 1.18-1.59) and of gonorrhea diagnoses was 10% in 2011 and 14% in 2014 (adjusted PR: 1.40, 95% CI: 1.23-1.60). Larger changes in diagnoses were observed among MSM in the white and ‘other’ racial categories and those who disclosed same-sex behavior to their healthcare provider. CONCLUSIONS: Self-reported testing and diagnoses among MSM increased from 2011 to 2014. Increased efforts are needed to meet annual STD screening recommendations among MSM at high HIV risk.

      13. BACKGROUND: Recent increases in syphilis among men who have sex with men (MSM) are especially concerning, given the biologic and epidemiologic associations between syphilis and HIV infection. We sought to better describe the current epidemiology of primary and secondary (P&S) syphilis and the prevalence of HIV infection among reported P&S syphilis cases by demographic group, including sex of sex partner, in the United States in 2016. METHODS: We reviewed national P&S syphilis case report data from 2016, including available risk factor information such as sex of sex partner and HIV status. Data were extracted from the National Electronic Telecommunications System for Surveillance, the system through which CDC receives notifiable STD data from all 50 states and the District of Columbia. The proportion of cases with HIV co-infection was calculated using cases with known HIV status as the denominator. RESULTS: Of 27,814 P&S syphilis cases reported in 2016, 58.1% were among MSM, 13.9% were among men who have sex with women only (MSW), 11.0% were among women, and 16.9% were among men without data on sex of sex partners. Similar patterns were observed across geographic regions, race/ethnicity groups, and most age groups. Overall, 38.5% of reported P&S syphilis cases with known HIV status were co-infected with HIV. The prevalence of HIV co-infection was highest among MSM (47.0%) compared with MSW (10.7%) or women (4.1%). Among MSM with P&S syphilis, the prevalence of HIV co-infection was highest among black MSM, ranging from 33.8% among black MSM aged 15-19 years to 77.8% among black MSM aged 45-49 years. CONCLUSIONS: These data underscore the epidemiologic linkages between syphilis and HIV, particularly among MSM. P&S syphilis may represent an opportunity to prevent HIV infection among persons who are HIV-negative and identify and link to care persons living with HIV infection but not currently engaged in care.

      14. Considering the potential application of whole genome sequencing to gonorrhea prevention and controlExternal
        Kirkcaldy RD, Town K, Gernert KM, Bowen VB, Torrone EA, Kersh E, Bernstein KT.
        Sex Transm Dis. 2018 Feb 15.

        [No abstract]

      15. Background: Nonavalent (9v) human papilloma virus vaccine targets high-risk (HR)-HPV types 16, 18, 31, 33, 45, 52, 58, and low-risk 6, 11. We examined prevalence, incidence, and clearance of anal and cervical HR-HPV in HIV-infected women. Methods: From 2004-2006, the SUN Study enrolled 167 women from four US cities. Anal and cervical specimens were collected annually for cytology and identification of 37 HPV types; 14 HR include: 9v 16, 18, 31, 33, 45, 52, 58; non-9v 35, 39, 51, 56, 59, 66, 68. Results: Baseline characteristics of 126 women included: median age 38 years; 57% non-Hispanic black; 67% HIV RNA < 400 copies/mL; 90% CD4 counts >/= 200 cells/mm3. HPV prevalence at anus and cervix was 90% and 83%; for 9v HR-HPV types, 67% and 51%; non-9v HR-HPV, 54% and 29%, respectively. 9v and non-9v HR-HPV incidence rates/100 person-years were similar (10.4 vs 9.5: 8.5 vs 8.3, respectively); 9v clearance rates were 42% and 61%; non-9v 46% and 59%, in anus and cervix, respectively. Conclusions: Anal HR-HPV prevalence was higher than cervical with lower clearance; incidence was similar. Although prevalence of non-9v HR-HPV was substantial, 9v HR-HPV types were generally more prevalent. These findings support use of nonavalent vaccine in HIV-infected women.

      16. BACKGROUND: Congenital syphilis (CS) disproportionately affects racial and ethnic minority women, especially in the US South. While CS is relatively easy and inexpensive to prevent through screening and treatment of pregnant women, CS cases have continued to rise and are concentrated in relatively few US counties and states. In 2010, Louisiana had the highest case rate in the country for primary, secondary, and congenital syphilis, with the highest number of CS cases in northwest Louisiana, where Shreveport is located. METHODS: We conducted qualitative interviews with community members (women and frontline providers) living in Caddo Parish to obtain their views about factors that negatively impact CS prevention. RESULTS: Participants described impediments in the pathways for prevention of CS. Lack of sexual and reproductive health education, discontinuities and fragmentation in health care insurance coverage, a dearth of referral points for prenatal care, and difficulty finding prenatal care providers who accept Medicaid can delay timely and adequate care for pregnant women. Providers reported that low reimbursement for necessary injections, and difficulty obtaining required medication challenged efforts to screen and treat pregnant women according to guidelines. CONCLUSIONS: Although CS is easily prevented, health system and policy obstacles in pathways to CS prevention and care may need remediation at state and local levels.

      17. Chlamydia prevalence trends among women and men entering the National Job Training Program from 1990 through 2012External
        Learner ER, Torrone EA, Fine JP, Pence BW, Powers KA, Miller WC.
        Sex Transm Dis. 2018 Jan 26.

        BACKGROUND: Evaluating chlamydia prevalence trends from sentinel surveillance is important for understanding population disease burden over time. However, prevalence trend estimates from surveillance data may be misleading if they do not account for changes in risk profiles of individuals who are screened (case mix) and changing performance of the screening tests used. METHODS: We analyzed chlamydia screening data from a sentinel surveillance population of 389,555 young women (1990-2012) and 303,699 young men (2003-2012) entering the US National Job Training Program. This period follows the introduction of national chlamydia screening programs designed to prevent transmission and reduce population disease burden. After ruling out bias due to case mix, we used an expectation-maximization based maximum likelihood approach to account for measurement error from changing screening tests, and generated minimally-biased long-term chlamydia prevalence trend estimates among youth and young adults in this sentinel surveillance population. RESULTS: Adjusted chlamydia prevalence among women was high throughout the study period, but fell from 20% in 1990 to 12% in 2003, and remained between 12% and 14% through 2012. Adjusted prevalence among men was steady throughout the study period at approximately 7%. For both women and men, adjusted prevalence was highest among Black and American Indian youth and young adults, and in the Southern and Midwestern regions of the US throughout the study period. CONCLUSIONS: Our minimally-biased trend estimates provide support for an initial decrease in chlamydia prevalence among women soon after the introduction of national chlamydia screening programs. Constant chlamydia prevalence in more recent years suggests that screening may not be sufficient to further reduce chlamydia prevalence among high-risk youth and young adults.

      18. Advances in measuring influenza burden of diseaseExternal
        Lee VJ, Ho ZJ, Goh EH, Campbell H, Cohen C, Cozza V, Fitzner J, Jara J, Krishnan A, Bresee J.
        Influenza Other Respir Viruses. 2018 Jan;12(1):3-9.

        [No abstract]

      19. New human immunodeficiency virus diagnoses among men who have sex with men attending STD clinics, STD Surveillance Network, January 2010 to June 2013External
        Llata E, Braxton J, Asbel L, Kerani RP, Murphy R, Pugsley R, Pathela P, Schumacher C, Tabidze I, Weinstock HS.
        Sex Transm Dis. 2018 Feb 7.

        OBJECTIVE: To estimate new HIV diagnosis rates among HIV negative MSM who are repeatedly tested for HIV in sexually transmitted disease (STD) clinics, and assess the impact of demographic and disease-specific characteristics that are associated with higher HIV diagnosis rates. STUDY DESIGN: Retrospective analysis using 2010-2013 data from the STD Surveillance Network (SSuN), a sentinel surveillance system comprised of health departments in 12 cities conducting sentinel surveillance in 40 STD clinics. We analyzed data from all MSM repeatedly (>/=2 times) tested for HIV, with an initial negative HIV test required for staggered cohort entry. Follow-up time was accrued from the date of the first negative HIV test to the most recent negative test or the first positive HIV test. STD diagnoses during the follow-up period were reviewed. We estimated HIV diagnoses rates (number of HIV diagnoses/total number of person-years at risk) by demographic and clinical characteristics with 95% confidence intervals (CI) using an inverse variance weighted random effects model, adjusting for heterogeneity between SSuN jurisdictions. RESULTS: Overall, 640 HIV diagnoses occurred among 14,824 individuals and 20,951.6 person-years (PY) of observation, for an adjusted incidence of HIV diagnosis of 3.0 per 100 PY (95% CI 2.6, 3.4). Rates varied across race/ethnicity groups with the highest rate among Blacks (4.7/100 PY; 95% CI 4.1-5.3) followed by Hispanics, Whites and persons of other races/ethnicities. MSM having a diagnosis of P&S syphilis on or after the first negative HIV test had a higher new HIV diagnosis rate (7.2/100 PY; 95% CI 5.8-9.0) compared to MSM who did not have a P&S syphilis diagnosis (2.8/100 PY; 95% CI 2.6-3.1). MSM who tested positive for rectal gonorrhea (6.3/100 PY; 95% CI 5.7-6.9) or rectal chlamydia (5.6/100 PY; 95% CI 4.6-6.6) had higher rates of new HIV diagnosis when compared to those with negative test results. CONCLUSIONS: MSM attending SSuN STD clinics have high rates of new HIV diagnoses, particularly those with a previous diagnosis of P&S syphilis, rectal chlamydia and/or gonorrhea. STD clinics continue to be important clinical setting for diagnosing HIV among MSM populations.

      20. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)External
        McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH.
        Clin Infect Dis. 2018 Feb 15.

        A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

      21. Comparative efficacy of low-dose versus standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New GuineaExternal
        Mitja O, Bottomley C, Kwakye C, Houinei W, Bauri M, Adwere P, Abdulai AA, Dua F, Boateng L, Wangi J, Ohene SA, Wangnapi R, Simpson SV, Miag H, Addo KK, Basing LA, Danavall D, Chi KH, Pillay A, Ballard R, Solomon AW, Chen CY, Bieb SV, Adu-Sarkodie Y, Mabey DC, Asiedu K.
        Lancet Glob Health. 2018 Feb 15.

        BACKGROUND: A dose of 30 mg/kg of azithromycin is recommended for treatment of yaws, a disease targeted for global eradication. Treatment with 20 mg/kg of azithromycin is recommended for the elimination of trachoma as a public health problem. In some settings, these diseases are co-endemic. We aimed to determine the efficacy of 20 mg/kg of azithromycin compared with 30 mg/kg azithromycin for the treatment of active and latent yaws. METHODS: We did a non-inferiority, open-label, randomised controlled trial in children aged 6-15 years who were recruited from schools in Ghana and schools and the community in Papua New Guinea. Participants were enrolled based on the presence of a clinical lesion that was consistent with infectious primary or secondary yaws and a positive rapid diagnostic test for treponemal and non-treponemal antibodies. Participants were randomly assigned (1:1) to receive either standard-dose (30 mg/kg) or low-dose (20 mg/kg) azithromycin by a computer-generated random number sequence. Health-care workers assessing clinical outcomes in the field were not blinded to the patient’s treatment, but investigators involved in statistical or laboratory analyses and the participants were blinded to treatment group. We followed up participants at 4 weeks and 6 months. The primary outcome was cure at 6 months, defined as lesion healing at 4 weeks in patients with active yaws and at least a four-fold decrease in rapid plasma reagin titre from baseline to 6 months in patients with active and latent yaws. Active yaws was defined as a skin lesion that was positive for Treponema pallidum ssp pertenue in PCR testing. We used a non-inferiority margin of 10%. This trial was registered with ClinicalTrials.gov, number NCT02344628. FINDINGS: Between June 12, 2015, and July 2, 2016, 583 (65.1%) of 895 children screened were enrolled; 292 patients were assigned a low dose of azithromycin and 291 patients were assigned a standard dose of azithromycin. 191 participants had active yaws and 392 had presumed latent yaws. Complete follow-up to 6 months was available for 157 (82.2%) of 191 patients with active yaws. In cases of active yaws, cure was achieved in 61 (80.3%) of 76 patients in the low-dose group and in 68 (84.0%) of 81 patients in the standard-dose group (difference 3.7%; 95% CI -8.4 to 15.7%; this result did not meet the non-inferiority criterion). There were no serious adverse events reported in response to treatment in either group. The most commonly reported adverse event at 4 weeks was gastrointestinal upset, with eight (2.7%) participants in each group reporting this symptom. INTERPRETATION: In this study, low-dose azithromycin did not meet the prespecified non-inferiority margin compared with standard-dose azithromycin in achieving clinical and serological cure in PCR-confirmed active yaws. Only a single participant (with presumed latent yaws) had definitive serological failure. This work suggests that 20 mg/kg of azithromycin is probably effective against yaws, but further data are needed. FUNDING: Coalition for Operational Research on Neglected Tropical Diseases.

      22. BACKGROUND: The success of an intervention to prevent syphilis will depend on the context and the goal of the intervention. To help programs choose interventions, we reviewed major changes in context and types of interventions that may be effective. METHODS: We reviewed the literature on the changing context of syphilis in the United States and interventions to prevent syphilis, focusing on papers that included evidence of effectiveness. RESULTS: Populations acquiring syphilis are constantly changing. Currently, incidence is very high among men who have sex with men. Among adults, late disease caused by syphilis has become rare. Congenital syphilis incidence has been low but is increasing, and morbidity and mortality remain high when babies are infected. Congenital syphilis now causes more deaths than syphilis among adults.Routine screening of MSM can identify and treat infections before they progress to disease (secondary prevention). Screening rates are highest when done as part of routine standing orders. Partner notification effectiveness has decreased, partly because many partners are anonymous. Most congenital syphilis can be prevented by screening pregnant women; it has been eliminated in areas where intense primary prevention efforts eliminated syphilis among women. CONCLUSION: So far, no program has stopped the increasing rates of infection among MSM, but secondary prevention efforts have prevented most disability. Congenital syphilis is increasing, and can be decreased by screening pregnant women and stopped by intensive efforts to prevent infection among women.

      23. Syphilis is (still) here; how must STD public health programs adapt?External
        Philip SS, Bernstein KT.
        Sex Transm Dis. 2018 Jan 4.

        [No abstract]

      24. Prescription of pre-exposure prophylaxis to MSM diagnosed and reported with gonorrhea, STD Surveillance Network, 2016External
        Ramirez V, Han E, Stoltey J, Nguyen TQ, Pathela P, Tourdot L, Walters J, Bell T, Torrone E, Stenger M.
        Sex Transm Dis. 2018 Feb 15.

        Using a representative sample of gonorrhea cases in select jurisdictions, we estimated the proportion of eligible men who have sex with men (MSM) reporting being prescribed pre-exposure prophylaxis (PrEP) to prevent HIV infection. In 2016, half (51.3%) of the estimated 33,165 eligible MSM reported being prescribed PrEP by their healthcare provider.

      25. Guidance about integration of comprehensive hepatitis C virus (HCV)-related services in sexually transmitted disease (STD) clinics is limited. We evaluated a federally-funded HCV testing and linkage-to-care program at an STD clinic in Durham County, North Carolina. During December 10, 2012-March 31, 2015, the program tested 733 patients for HCV who reported >/=1 HCV risk factor; 81 (11%) were HCV-infected (i.e., HCV antibody-positive and HCV ribonucleic acid-positive). Fifty-one infected patients (63%) were linked to care. We concluded that essential program resources include reflex HCV ribonucleic acid testing; a dedicated bridge counselor to provide test results, health education, and linkage-to-care assistance; and referral relationships for local HCV management and treatment.

      26. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case seriesExternal
        Scheltema NM, Gentile A, Lucion F, Nokes DJ, Munywoki PK, Madhi SA, Groome MJ, Cohen C, Moyes J, Thorburn K, Thamthitiwat S, Oshitani H, Lupisan SP, Gordon A, Sanchez JF, O’Brien KL, Gessner BD, Sutanto A, Mejias A, Ramilo O, Khuri-Bulos N, Halasa N, de-Paris F, Pires MR, Spaeder MC, Paes BA, Simoes EA, Leung TF, da Costa Oliveira MT, de Freitas Lazaro Emediato CC, Bassat Q, Butt W, Chi H, Aamir UB, Ali A, Lucero MG, Fasce RA, Lopez O, Rath BA, Polack FP, Papenburg J, Roglic S, Ito H, Goka EA, Grobbee DE, Nair H, Bont LJ.
        Lancet Glob Health. 2017 Oct;5(10):e984-e991.

        BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. METHODS: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. FINDINGS: We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5.0 months (IQR 2.3-11.0) in low-income or lower middle-income countries, 4.0 years (2.0-10.0) in upper middle-income countries, and 7.0 years (3.6-16.8) in high-income countries. INTERPRETATION: This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

      27. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices
        Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, Nelson NP.
        MMWR Recommendations and Reports. 2018 ;67(1):1-31.

        Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged < 19 years who have not been vaccinated previously. ACIP recommends vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseases guidelines for maternal antiviral therapy to reduce perinatal HBV transmission.

      28. Optimizing the impact of expedited partner therapyExternal
        Schillinger JA.
        Sex Transm Dis. 2018 Feb 15.

        [No abstract]

      29. The epidemiology of syphilis in New York City; historic trends and the current outbreak among men who have sex with men, 2016External
        Schillinger JA, Slutsker JS, Pathela P, Klingler E, Hennessy RR, Toro B, Blank S.
        Sex Transm Dis. 2018 Jan 19.

        BACKGROUND: Male primary and secondary (P&S) and early latent (EL) syphilis cases have increased markedly in New York City (NYC) after a historic nadir in 1998. The majority of cases are among men-who-have-sex-with-men (MSM). We describe the epidemiology of syphilis among NYC males to provide a model of how one jurisdiction collects, analyzes, interprets, uses, and disseminates local data to guide programmatic activities directed at syphilis control. METHODS: We analyzed trends in reported infectious syphilis cases using routinely collected surveillance and case investigation data. HIV co-infection status was ascertained by routine deterministic match between sexually transmitted infection and HIV surveillance registries, and self-report. We mapped diagnosing facilities to display the relative contribution of different public/private facilities. Characteristics of male syphilis cases diagnosed in public sexual health (SH) clinics were compared to those diagnosed elsewhere. RESULTS: During 2012-2016, male P&S syphilis case rates increased 81%, from 24.8 to 44.8/100,000 (1832 cases); the highest rates were among black non-Hispanic men. Overall, 87.6% (902/1030) of interviewed men in 2016 disclosed >1 male partner. HIV co-infection rates are high among MSM with P&S syphilis (43.4%; 394/907 in 2016), but appear to be decreasing (from 54.1% in 2012). Maps highlighted SH clinics’ contribution to diagnosing P&S syphilis cases among men of color. HIV co-infection rates were lower among men with P&S syphilis diagnosed in SH clinics than among those diagnosed elsewhere (34%, SH clinics versus 49%, other settings, p<0.0001). CONCLUSIONS: Syphilis infections continue to increase among MSM in NYC. Novel interventions responsive to the drivers of the current outbreak are needed.

      30. BACKGROUND: Increased HIV testing efforts have resulted in re-testing previously diagnosed persons. This study examined CDC-funded HIV testing programs to evaluate how the needs of previously diagnosed persons are being addressed. METHODS: CDC-funded HIV testing, previously diagnosed HIV positivity, current care status, and linkage to care were examined by demographic and test setting among previously diagnosed HIV-positive persons in 2015. Additionally, trends of HIV positivity and previously diagnosed HIV-positivity were examined from 2011-2015. RESULTS: In 2015, CDC funded 3,026,074 HIV tests, and 27,729 were HIV-positive tests. Of those, 13,528 (48.8%) were previously diagnosed persons. Only 11.6% of previously diagnosed persons reported already being in HIV care; after excluding them, 62.1% of previously diagnosed persons were linked within 90 days. Additionally, the percentage of previously diagnosed persons steadily increased from 2011 (25.9%) to 2015 (34.1%), p<.001. CONCLUSIONS: Almost half of all HIV-positive tests were among previously diagnosed persons, but only 11.6% were already in HIV care. Linkage is necessary among persons who already know their HIV status because they were either never linked or need to be re-engaged into care. Barriers in linkage and retention among this group also need to be addressed.

      31. Using a hospital admission survey to estimate the burden of influenza-associated severe acute respiratory infection in one province of Cambodia – methods used and lessons learnedExternal
        Stewart RJ, Ly S, Sar B, Ieng V, Heng S, Sim K, Machingaidze C, Roguski K, Dueger E, Moen A, Tsuyuoka R, Iuliano AD.
        Influenza Other Respir Viruses. 2018 Jan;12(1):104-112.

        BACKGROUND: Understanding the burden of influenza-associated severe acute respiratory infection (SARI) is important for setting national influenza surveillance and vaccine priorities. Estimating influenza-associated SARI rates requires hospital-based surveillance data and a population-based denominator, which can be challenging to determine. OBJECTIVES: We present an application of the World Health Organization’s recently developed manual (WHO Manual) including hospital admission survey (HAS) methods for estimating the burden of influenza-associated SARI, with lessons learned to help others calculate similar estimates. METHODS: Using an existing SARI surveillance platform in Cambodia, we counted influenza-associated SARI cases during 2015 at one sentinel surveillance site in Svay Rieng Province. We applied WHO Manual-derived methods to count respiratory hospitalizations at all hospitals within the catchment area, where 95% of the sentinel site case-patients resided. We used HAS methods to adjust the district-level population denominator for the sentinel site and calculated the incidence rate of influenza-associated SARI by dividing the number of influenza-positive SARI infections by the adjusted population denominator and multiplying by 100 000. We extrapolated the rate to the provincial population to derive a case count for 2015. We evaluated data sources, detailed steps of implementation, and identified lessons learned. RESULTS: We estimated an adjusted influenza-associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay Rieng Hospital and 77 influenza-associated SARI cases in Svay Rieng Province after extrapolation. CONCLUSIONS: Methods detailed in the WHO Manual and operationalized successfully in Cambodia can be used in other settings to estimate rates of influenza-associated SARI.

      32. To assess trends in Neisseria gonorrhoeae among gay, bisexual, and other men who have sex with men (MSM), we reviewed existing and published gonorrhea surveillance data in the United States (U.S.). Data identified in this review include: national gonorrhea case report data and data from three other surveillance programs, the Gonococcal Isolate Surveillance Project (GISP), the STD Surveillance Network (SSuN), and National HIV Behavioral Surveillance (NHBS).Rates of reported cases of gonorrhea among men increased 54.8% during 2006-2015 compared to a 2.6% increase among women. Since 2012, the rate of reported gonorrhea cases among men surpassed the rate among women; the male-to-female case rate ratio increased from 0.97 in 2012 to 1.31 in 2015. The proportion of gonococcal urethral isolates collected in GISP that were collected from MSM increased from 21.5% to 38.1% during 2006-2015. During 2009-2015, the percent of MSM who tested positive for rectal and oropharyngeal gonorrhea in STD clinics increased by 73.4% and 12.6%, respectively. Estimated rates of gonorrhea among MSM increased 151% during 2010-2015 in jurisdictions participating in SSuN. Data from NHBS demonstrate that testing for gonorrhea among MSM increased 23.1% between 2011 and 2014.Together, surveillance data suggest a disproportionate burden of gonorrhea among MSM in the U.S. and suggest increases in both screening and disease in recent years. Since each data source has inherent limitations and biases, examining these data from different systems together strengthens this conclusion.

      33. BACKGROUND: Homelessness significantly affects health and well-being. Homeless adults often experience co-occurring and debilitating physical, psychological, and social conditions. These determinants are associated with disproportionate rates of infectious disease among homeless adults, including tuberculosis, HIV, and hepatitis. Less is known about sexually transmitted infection (STI) prevalence among homeless adults. METHODS: We systematically searched three databases, and reviewed the 2000-2016 literature on STI prevalence among homeless adults in the U.S. We found 59 articles of US studies on STIs that included homeless adults. Of the 59 articles, eight met the inclusion criteria of US-based, English-language, peer-reviewed articles, published 2000-2016, with homeless adults in the sample. Descriptive and qualitative analyses were used to report STI prevalence rates and associated risk factors. RESULTS: Overall, STI prevalence ranged from 2.1% to 52.5%. A composite STI prevalence was most often reported (n=7) with rates ranging from 7.3% to 39.9%. Reported prevalence of chlamydia/gonorrhea (7.8%) was highest among younger homeless adult women. Highest reported STI prevalence was hepatitis C (52.5%) among older homeless men. Intimate partner violence, injection and non-injection substance use, incarceration history, and homelessness severity are associated with higher STI prevalence. CONCLUSION: Homeless adults are a vulnerable population. Factors found to be associated with sexual risk were concurrently associated with housing instability and homelessness severity. Addressing STI prevention needs of homeless adults can be enhanced by integrating sexual health, and other health services where homeless adults seek or receive housing and other support services.

    • Disease Reservoirs and Vectors
      1. Impoundments formed by microdams in rural areas of Africa are important sources of water for people, but they provide potential larval habitats for Anopheles (Diptera: Culicidae) mosquitoes that are vectors of malaria. To study this association, the perimeters of 31 microdam impoundments in western Kenya were sampled for Anopheles larvae in three zones (patches of floating and emergent vegetation, shorelines of open water, and aggregations of cattle hoofprints) across dry and rainy seasons. Of 3,169 larvae collected, most (86.8%) were collected in the rainy season. Of 2,403 larvae successfully reared to fourth instar or adult, nine species were identified; most (80.2%) were Anopheles arabiensis Patton, sampled from hoofprint zones in the rainy season. Other species collected were Anopheles coustani Laveran, Anopheles gambiae s.s. Giles, Anopheles funestus Giles, and Anopheles rivulorum Leeson, Anopheles pharoensis Theobald, Anopheles squamosus Theobald, Anopheles rufipes (Gough), and Anopheles ardensis (Theobald). Larvae of An. funestus were uncommon (1.5%) in both dry and rainy seasons and were confined to vegetated zones, suggesting that microdam impoundments are not primary habitats for this important vector species, although microdams may provide a dry season refuge habitat for malaria vectors, contributing to population persistence through the dry season. In this study, microdam impoundments clearly provided habitat for the malaria vector An. arabiensis in the rainy season, most of which was within the shallow apron side of the impoundments where people brought cattle for watering, resulting in compacted soil with aggregations of water-filled hoofprints. This observation suggests a potential conflict between public health concerns about malaria and people’s need for stable and reliable sources of water.

    • Environmental Health
      1. Hazardous chemical releases occurring in school settings, 14 states, 2008-2013External
        Anderson AR, Eure TR, Orr MF, Kolbe LJ, Woolf A.
        J Environ Health. 2017 Nov;80(4):E1-e7.

        Children are considered to be a vulnerabletion when it comes to exposures to hazardous substances. Schools, where children spend about one third of their day, are expected to be a safe environment. Yet, there are many hazardous substances in schools that can be inadvertently or intentionally released and harm the health of students and teachers alike. The purpose of this analysis is to characterize acute chemical release incidents in school settings and identify prevention practices. The acute chemical incident surveillance programs of the Agency for Toxic Substances and Disease Registry (ATSDR) captured 24,748 acute chemical release incidents from 14 states that participated during 2008-2013. We examined 335 of these incidents that occurred at schools. While only 1.3% (n = 335) of all chemical incidents reported to ATSDR occurred in schools, these incidents represented a larger part of the total impacts, including 8.5% of incidents with persons injured, 5.7% of evacuations ordered, and 31.1% of people evacuated. Natural gas (21.8%) and mercury (18.2%) were the chemicals most frequently released. Collecting and analyzing data on acute school chemical releases allows stakeholders to target prevention initiatives and provide a school environment safe from these chemical exposures.

      2. Evaluating effects of prenatal exposure to phthalate mixtures on birth weight: A comparison of three statistical approachesExternal
        Chiu YH, Bellavia A, James-Todd T, Correia KF, Valeri L, Messerlian C, Ford JB, Minguez-Alarcon L, Calafat AM, Hauser R, Williams PL.
        Environ Int. 2018 Feb 13;113:231-239.

        OBJECTIVES: We applied three statistical approaches for evaluating associations between prenatal urinary concentrations of a mixture of phthalate metabolites and birth weight. METHODS: We included 300 women who provided 732 urine samples during pregnancy and delivered a singleton infant. We measured urinary concentrations of metabolites of di(2-ethylhexyl)-phthalate, di-isobutyl-, di-n-butyl-, butylbenzyl-, and diethyl phthalates. We applied 1) linear regressions; 2) classification methods [principal component analysis (PCA) and structural equation models (SEM)]; and 3) Bayesian kernel machine regression (BKMR), to evaluate associations between phthalate metabolite mixtures and birth weight adjusting for potential confounders. Data were presented as mean differences (95% CI) in birth weight (grams) as each phthalate increased from the 10th to the 90th percentile. RESULTS: When analyzing individual phthalate metabolites using linear regressions, each metabolite demonstrated a modest inverse association with birth weight [from -93 (-206, 21) to -49 (-164, 65)]. When simultaneously including all metabolites in a multivariable model, inflation of the estimates and standard errors were noted. PCA identified two principal components, both inversely associated with birth weight [-23 (-68, 22), -27 (-71, 17), respectively]. These inverse associations were confirmed when applying SEM. BKMR further identified that monoethyl and mono(2-ethylhexyl) phthalate and phthalate concentrations were linearly related to lower birth weight [-51(-164, 63) and -122 (-311, 67), respectively], and suggested no evidence of interaction between metabolites. CONCLUSIONS: While none of the methods produced significant results, we demonstrated the potential issues arising using linear regression models in the context of correlated exposures. Among the other selected approaches, classification techniques identified common sources of exposures with implications for interventions, while BKMR further identified specific contributions of individual metabolites.

      3. Cumulative exposure to environmental pollutants during early pregnancy and reduced fetal growth: the Project Viva cohortExternal
        Rokoff LB, Rifas-Shiman SL, Coull BA, Cardenas A, Calafat AM, Ye X, Gryparis A, Schwartz J, Sagiv SK, Gold DR, Oken E, Fleisch AF.
        Environ Health. 2018 Feb 20;17(1):19.

        BACKGROUND: Reduced fetal growth is associated with perinatal and later morbidity. Prenatal exposure to environmental pollutants is linked to reduced fetal growth at birth, but the impact of concomitant exposure to multiple pollutants is unclear. The purpose of this study was to examine interactions between early pregnancy exposure to cigarette smoke, traffic pollution, and select perfluoroalkyl substances (PFASs) on birth weight-for-gestational age (BW/GA). METHODS: Among 1597 Project Viva mother-infant pairs, we assessed maternal cigarette smoking by questionnaire, traffic pollution at residential address by black carbon land use regression model, and plasma concentration of select PFASs in early pregnancy. We calculated sex-specific BW/GA z-scores, an index of fetal growth, from national reference data. We fit covariate-adjusted multi-pollutant linear regression models and examined interactions between exposures, using a likelihood-ratio test to identify a best-fit model. RESULTS: Two hundred six (13%) mothers smoked during pregnancy. Mean [standard deviation (SD)] for black carbon was 0.8 (0.3) mug/m(3), perfluorooctane sulfonate (PFOS) was 29.1 (16.5) ng/mL, and BW/GA z-score was 0.19 (0.96). In the best-fit model, BW/GA z-score was lower in infants of mothers exposed to greater black carbon [- 0.08 (95% CI: -0.15, – 0.01) per interquartile range (IQR)]. BW/GA z-score (95% CI) was also lower in infants of mothers who smoked [- 0.09 (- 0.23, 0.06)] or were exposed to greater PFOS [- 0.03 (- 0.07, 0.02) per IQR], although confidence intervals crossed the null. There were no interactions between exposures. In secondary analyses, instead of PFOS, we examined perfluorononanoate (PFNA) [mean (SD): 0.7 (0.4) ng/mL], a PFAS more closely linked to lower BW/GA in our cohort. The best-fit multi-pollutant model included positive two-way interactions between PFNA and both black carbon and smoking (p-interactions = 0.03). CONCLUSIONS: Concurrent prenatal exposures to maternal smoking, black carbon, and PFOS are additively associated with lower fetal growth, whereas PFNA may attenuate associations of smoking and black carbon with lower fetal growth. It is important to examine interactions between multiple exposures in relation to health outcomes, as effects may not always be additive and may shed light on biological pathways.

    • Epidemiology and Surveillance
      1. Trends in secondary schools’ practices to support lesbian, gay, bisexual, transgender, and questioning students, 2008-2014External
        Demissie Z, Rasberry CN, Steiner RJ, Brener N, McManus T.
        Am J Public Health. 2018 Feb 22:e1-e8.

        OBJECTIVES: To examine trends in the percentage of US secondary schools that implemented practices related to the support of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) students. METHODS: This analysis used data from 4 cycles (2008-2014) of School Health Profiles, a surveillance system that provides results representative of secondary schools in each state. Each school completed 2 self-administered questionnaires (principal and teacher) per cycle. We used logistic regression models to examine linear trends. RESULTS: Of 8 examined practices to support LGBTQ youths, only 1-identifying safe spaces for LGBTQ youths-increased in most states (72%) from 2010 to 2014. Among the remaining 7, only 1-prohibiting harassment based on a student’s perceived or actual sexual orientation or gender identity-had relatively high rates of adoption (a median of 90.3% of schools in 2014) across states. CONCLUSIONS: Many states have seen no change in the implementation of school practices associated with LGBTQ students’ health and well-being. (Am J Public Health. Published online ahead of print February 22, 2018: e1-e8. doi:10.2105/AJPH.2017.304296).

    • Food Safety
      1. A multistate outbreak of human Salmonella agona infections associated with consumption of fresh, whole papayas imported from Mexico – United States, 2011External
        Mba-Jonas A, Culpepper W, Hill T, Cantu V, Loera J, Borders J, Saathoff-Huber L, Nsubuga J, Zambrana I, Dalton S, Williams I, Neil KP.
        Clin Infect Dis. 2018 Feb 19.

        Background: Nontyphoidal Salmonella causes ~1 million food-borne infections annually in the United States. We began investigating a multistate outbreak of Salmonella serotype Agona infections in April 2011. Methods: A case was defined as infection with the outbreak strain of Salmonella Agona occurring between 1 January and 25 August 2011. We developed hypotheses through iterative interviews. Product distribution analyses and traceback investigations were conducted. The Food and Drug Administration (FDA) tested papayas from Mexico for Salmonella. Results: We identified 106 case patients from 25 states. Their median age was 21 years (range, 1-91). Thirty-nine of 61 case patients (64%) reported Hispanic/Latino ethnicity; 11 of 65 (17%) travelled to Mexico before illness. Thirty-two of 56 case patients (57%) reported papaya consumption. Distribution analyses revealed that three firms, including Distributor A, distributed papaya to geographic areas that aligned with both the location and timing of illnesses. Traceback of papayas purchased by ill persons in four states identified Distributor A as the common supplier. FDA testing isolated the outbreak strain from a papaya sample collected at distributor A and from another sample collected at the US-Mexico border, destined for distributor A. FDA isolated Salmonella species from 62 of 388 papaya import samples (16%). The investigation led to a recall of fresh, whole papayas from Distributor A and an FDA import alert for all papayas from Mexico. Conclusions: This is the first reported Salmonella outbreak in the United States linked to fresh, whole papayas. The outbreak highlights important issues regarding the safety of imported produce.

    • Genetics and Genomics
      1. Draft reference genome sequence of Corynebacterium mastitidis 16-1433, isolated from a mouseExternal
        Cheleuitte-Nieves C, Gulvik CA, Humrighouse BW, Bell ME, Villarma A, Westblade LF, Lipman NS, Fischetti VA, McQuiston JR.
        Genome Announc. 2018 Feb 15;6(7).

        We report here a nearly complete draft genome sequence for a Corynebacterium mastitidis isolate from a mouse. The total read coverage is 198x, and the genome size is 2,264,319 bp with a 69.04% GC content. This genome complements the only other genome available for C. mastitidis, which was obtained from a sheep.

      2. Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signalExternal
        Delgado DA, Zhang C, Chen LS, Gao J, Roy S, Shinkle J, Sabarinathan M, Argos M, Tong L, Ahmed A, Islam T, Rakibuz-Zaman M, Sarwar G, Shahriar H, Rahman M, Yunus M, Jasmine F, Kibriya MG, Ahsan H, Pierce BL.
        J Med Genet. 2018 Jan;55(1):64-71.

        BACKGROUND: Leucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry. OBJECTIVE: This study aims to enhance our understanding of genetic determinants of TL across populations. METHODS: We performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes. RESULTS: Our results replicate previously reported associations in the TERC and TERT regions (P=2.2×10(-8) and P=6.4×10(-6), respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10(-7)) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (>/=0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only. CONCLUSIONS: In this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.

      3. Enterocytozoon bieneusi genotypes in Tibetan sheep and yaksExternal
        Zhang Q, Cai J, Li P, Wang L, Guo Y, Li C, Lei M, Feng Y, Xiao L.
        Parasitol Res. 2018 Jan 14.

        Few studies have been conducted on the distribution of Enterocytozoon bieneusi genotypes in Tibetan sheep and yaks, which live outdoors in extreme climate with high altitude. In this study, fecal specimens from 312 Tibetan sheep and 554 yaks in Qinghai, China, were collected and examined for E. bieneusi by PCR-sequence analysis of the ribosomal internal transcribed spacer. Among them, 73 (23.4%) specimens from Tibetan sheep and 40 (7.2%) from yaks were positive for E. bieneusi. There were eight E. bieneusi genotypes in Tibetan sheep, including three known ones (BEB6, COS-I, and NESH5) and five novel ones (named as CHS13-CHS17). Similarly, seven E. bieneusi genotypes were found in yaks, including five known ones (J, BEB4, BEB6, COS-I, and NESH5) and two novel ones (named as CHN13 and CHN14). Most of the E. bieneusi genotypes and all frequent ones identified in the study belonged to group 2. One new subgroup of genotypes was identified within group 1. The distribution of E. bieneusi genotypes was different between Tibetan sheep and yaks, with BEB6 as the dominant one (42.5%) in Tibetan sheep and J as the dominant one (47.5%) in yaks. These data support the occurrence of host adaptation among E. bieneusi genotypes within group 2.

    • Healthcare Associated Infections
      1. Outbreak of bacterial endocarditis associated with an oral surgery practice: New Jersey public health surveillance, 2013 to 2014External
        Ross KM, Mehr JS, Greeley RD, Montoya LA, Kulkarni PA, Frontin S, Weigle TJ, Giles H, Montana BE.
        J Am Dent Assoc. 2018 Feb 2.

        BACKGROUND: In October 2014, the New Jersey Department of Health received reports of 3 patients who developed Enterococcus faecalis endocarditis after undergoing surgical procedures at the same oral surgery practice in New Jersey. Bacterial endocarditis is an uncommon but life-threatening condition; 3 patients with enterococcal endocarditis associated with a single oral surgery practice is unusual. An investigation was initiated because of the potential ongoing public health risk. METHODS: Public health officials conducted retrospective surveillance to identify additional patients with endocarditis associated with the practice. They interviewed patients using a standardized questionnaire. An investigative public health team inspected the office environment, interviewed staff, and reviewed medical records. RESULTS: Public health officials identified 15 confirmed patients with enterococcal endocarditis of those patients who underwent procedures from December 2012 through August 2014. Among these patients, 12 (80%) underwent cardiac surgery. One (7%) patient died from complications of endocarditis and subsequent cardiac surgery. Breaches of recommended infection prevention practices were identified that might have resulted in transmission of enterococci during the administration of intravenous sedation, including failure to perform hand hygiene and failure to maintain aseptic technique when performing procedures and handling medications. CONCLUSIONS: This investigation highlights the importance of adhering to infection prevention recommendations in dental care settings. No additional patients with endocarditis were identified after infection prevention and control recommendations were implemented. PRACTICAL IMPLICATIONS: Infection prevention training should be emphasized at all levels of professional dental training. All dental health care personnel establishing intravenous treatment and administering intravenous medications should be trained in safe injection practices.

      2. This case study is part of a series centered on the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) health care-associated infection (HAI) surveillance definitions. This specific case study focuses on appropriately mapping locations within an NHSN-enrolled facility. The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions among IPs and encourage accurate determination of HAI events. An online survey link is provided where participants may confidentially answer questions related to the case study and receive immediate feedback in the form of correct answers and explanations and rationales. Details of the case study, answers, and explanations have been reviewed and approved by NHSN staff. We hope that participants take advantage of this educational offering and thereby gain a greater understanding of NHSN HAI surveillance definitions.

    • Immunity and Immunization
      1. Estimated impact of rotavirus vaccine on hospitalizations and deaths from rotavirus diarrhea among children <5 in AsiaExternal
        Burnett E, Tate JE, Kirkwood CD, Nelson EA, Santosham M, Steele AD, Parashar UD.
        Expert Rev Vaccines. 2018 Feb 21.

        OBJECTIVES: Of the 215,000 global deaths from rotavirus estimated in 2013, 41% occur in Asian countries. However, despite a recommendation for global rotavirus vaccination since 2009, only eight countries in Asia have introduced the rotavirus vaccine into their national immunization program as of September 2017. To help policy makers assess the potential value of vaccination, we projected the reduction in rotavirus hospitalizations and deaths following a hypothetical national introduction of rotavirus vaccines in all countries in Asia using data on national-level rotavirus mortality, <5 population, rotavirus hospitalizations rates, routine vaccination coverage, and vaccine effectiveness. METHODS: To quantify uncertainty, we generated 1,000 simulations of these inputs. RESULTS: Our model predicted 710,000 fewer rotavirus hospitalizations, a 49% decrease from the 1,452,000 baseline hospitalizations and 35,000 fewer rotavirus deaths, a 40% decrease from the 88,000 baseline deaths if all 43 Asian countries had introduced rotavirus vaccine. Similar reductions were projected in subanalyses by vaccine introduction status, subregion, and birth cohort size. CONCLUSION: Rotavirus vaccines will substantially reduce morbidity and mortality due to rotavirus infections in Asia.

      2. Development and pilot testing of a text message vaccine reminder system for use during an influenza pandemicExternal
        Lehnert JD, Shevach A, Walker S, Wang R, Fitzgerald TJ, Graitcer SB.
        Hum Vaccin Immunother. 2018 Feb 16:1-19.

        In an influenza pandemic, two vaccine doses administered 21 days apart may be needed for individuals of all ages to achieve seroprotection. Achieving dose-series completion can be challenging even for routinely recommended vaccines. To prepare for a two-dose influenza pandemic vaccine campaign and promote dose-series completion and correct dosing intervals, CDC and its partners developed a text message-based vaccine reminder system to remind persons who receive a first dose of pandemic influenza vaccine to receive the second dose. Taking advantage of the high prevalence of cell phones in the United States, the system sent second-dose text message reminders and hyperlinks to educational information. The system was pilot tested from November 2015 to April 2016 among graduate public health students enrolled at four United States universities. Universities were selected based on convenience, and each university used a different recruitment method. Among 59 volunteers who pilot tested the system and completed a survey, 57 (92%) felt the system would be helpful during a pandemic. Forty (68%) respondents felt the information included in the messages was informative. Volunteers recommended including actionable ways to stay healthy during a pandemic, though specific suggestions varied. With further development, text reminder systems could be used to promote adherence to a two-dose regimen in a future pandemic, although audience-specific messaging and other complementary systems will likely be needed. Public and private partners can adapt and implement this tool in conjunction with their routine patient information systems to improve dose-series completion and ensure optimal protection during an influenza pandemic.

      3. Reporting of adverse events following immunization (AEFI) is a key component for functional vaccine safety monitoring system. The aim of our study is to document trends in the AEFI reporting ratio globally and across the six World Health Organization (WHO) regions. We describe the number of AEFI reports communicated each year through the World Health Organization/United Nations Children’s Fund Joint Reporting Form on Immunization from 2000 to 2015. The AEFI reporting ratios (annual AEFI reports per 100,000 surviving infants) were calculated to identify WHO countries (n=191 in 2000 and n=194 by 2015) that met a minimal reporting ratio of 10, a target set by the Global Vaccine Action Plan for vaccine safety monitoring as a proxy measure for a functional AEFI reporting system. The number of countries reporting any AEFI fluctuated over time but with progress from 32 (17%) in 2000 to 124 (64%) in 2015. In 2015, the global average AEFI reporting ratio was 549 AEFI reports per 100,000 surviving infants. The number of countries with AEFI reporting ratiosgreater than10 increased from 8 (4%) in 2000 to 81 (42%) in 2015. In 2015, 60% of countries in the WHO Region of the Americas reported at least 10 AEFI per 100,000 surviving infants, followed by 55% in European Region, 43% in Eastern Mediterranean Region, 33% in Western Pacific Region, 27% in South-East Asia Region and 21% in African Region. Overall, AEFI reporting has increased over the past sixteen years worldwide, but requires strengthening in a majority of low- and middle- income countries. The AEFI reporting ratio is useful for benchmarking and following trends over time; but does not provide information on the quality of the reporting system and does not guarantee capacity to detect and manage a vaccine safety problem at a national level. Additional efforts are required to ensure and improve data quality, AEFI reporting and surveillance of immunization safety in every country.

      4. Hospital, maternal, and birth factors associated with hepatitis B vaccination at birth – West Virginia, 2015External
        Massey J, Nair A, Dietz S, Snaman D, Bixler D.
        Pediatr Infect Dis J. 2018 Feb 16.

        BACKGROUND: Hepatitis B virus (HBV) is a bloodborne pathogen typically transmitted through sexual contact, injection drug use, or perinatally. A hepatitis B vaccine (HepB) is available; the first dose is recommended at birth. We sought to identify hospital policy, maternal characteristics, and birth factors associated with HepB receipt at birth in West Virginia (WV). METHODS: We conducted a retrospective cohort study of WV live births in 2015 using vital records matched to immunization registry records to determine frequency of HepB birth dose receipt (<3 days postdelivery). We surveyed all WV birthing facilities in 2015 (N = 26) about perinatal HBV prevention policies. We examined associations of hospital policy, maternal characteristics, and birth factors with HepB receipt at birth by using a mixed-effects regression model to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs). RESULTS: Of 17,458 births, 14,006 (80.2%) infants received a HepB birth dose. Hospital use of preprinted newborn routine admission vaccination orders was associated with HepB birth dose receipt (aPR 10.60; 95% CI, 2.12-52.72). Not using illicit drugs during pregnancy, maternal age <35 years, and weekday births were associated with HepB birth dose receipt (aPR 1.81, 95% CI, 1.54-2.13; aPR 1.34, 95% CI, 1.17-1.54; and aPR 1.15, 95% CI, 1.03-1.28, respectively). CONCLUSIONS: Hospitals using preprinted admission orders had higher frequencies of HepB birth dose receipt. Additional study is needed to identify HepB birth dose receipt barriers among infants with maternal illicit drug use, maternal age >/=35 years, or deliveries during a weekend.

      5. Hepatitis A vaccination coverage among adolescents (13-17 years) in the United States, 2008-2016External
        Nelson NP, Yankey D, Singleton JA, Elam-Evans LD.
        Vaccine. 2018 Feb 12.

        BACKGROUND: The hepatitis A (HepA) vaccine was recommended by the Advisory Committee on Immunization Practices (ACIP) incrementally from 1996 to 1999. In 2006, HepA vaccine was recommended (1) universally for children aged 12-23months, (2) for persons who are at increased risk for infection, or (3) for any person wishing to obtain immunity. Catch-up vaccination can be considered. OBJECTIVE: To assess HepA vaccine coverage among adolescents and factors independently associated with vaccination administration in the US. METHODS: The 2008-2016 National Immunization Survey-Teen was utilized to determine 1 and >/=2 dose HepA vaccination coverage among adolescents aged 13-17years. Factors associated with HepA vaccine series initiation (1 dose) were determined by bivariate and multivariable analyses. Data were stratified by state groups based on ACIP recommendation: universal child vaccination recommended since 1999 (group 1); child vaccination considered since 1999 (group 2); universal child vaccination recommendation since 2006 (group 3). RESULTS: In 2016, national vaccination coverage for 1 and >/=2 doses of HepA vaccine among adolescents was 73.9% and 64.4%, respectively. Nationally, a 40 percentage point increase in vaccination coverage occurred among adolescents born in 1995 compared to adolescents born in 2003. Nationally, the independent factors associated with increased vaccine initiation was race/ethnicity (Hispanic, American Indian/Alaskan Native, Asian), military payment source and provider recommendation for HepA vaccination (2008-2013). Living in a suburban or rural region, living in poverty (level <1.33-5.03), and absence of state daycare or school HepA requirement were common factors associated with decreased likelihood of vaccine initiation. CONCLUSIONS: Efforts to increase HepA vaccine coverage in adolescents in all regions of the country would strengthen population protection from hepatitis A virus (HAV).

      6. Infant hospitalizations and mortality after maternal vaccinationExternal
        Sukumaran L, McCarthy NL, Kharbanda EO, Vazquez-Benitez G, Lipkind HS, Jackson L, Klein NP, Naleway AL, McClure DL, Hechter RC, Kawai AT, Glanz JM, Weintraub ES.
        Pediatrics. 2018 Feb 20.

        BACKGROUND: The Advisory Committee on Immunization Practices currently recommends pregnant women receive influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. There are limited studies of the long-term safety in infants for vaccines administered during pregnancy. We evaluate whether maternal receipt of influenza and Tdap vaccines increases the risk of infant hospitalization or death in the first 6 months of life. METHODS: We included singleton, live birth pregnancies in the Vaccine Safety Datalink between 2004 and 2014. Outcomes were infant hospitalizations and mortality in the first 6 months of life. We performed a case-control study matching case patients and controls 1:1 and used conditional logistic regression to estimate odds ratios for maternal exposure to influenza and/or Tdap vaccines in pregnancy. RESULTS: There were 413 034 live births in our population. Of these, 25 222 infants had hospitalizations and 157 infants died in the first 6 months of life. We found no association between infant hospitalization and maternal influenza (adjusted odds ratio: 1.00; 95% confidence interval [CI]: 0.96-1.04) or Tdap (adjusted odds ratio: 0.94; 95% CI: 0.88-1.01) vaccinations. We found no association between infant mortality and maternal influenza (adjusted odds ratio: 0.96; 95% CI: 0.54-1.69) or Tdap (adjusted odds ratio: 0.44; 95% CI: 0.17-1.13) vaccinations. CONCLUSIONS: We found no association between vaccination during pregnancy and risk of infant hospitalization or death in the first 6 months of life. These findings support the safety of current recommendations for influenza and Tdap vaccination during pregnancy.

      7. [No abstract]

    • Injury and Violence
      1. Sexual orientation discordance and nonfatal suicidal behaviors in U.S. high school studentsExternal
        Annor FB, Clayton HB, Gilbert LK, Ivey-Stephenson AZ, Irving SM, David-Ferdon C, Kann LK.
        Am J Prev Med. 2018 Feb 8.

        INTRODUCTION: Studies among adults have documented association between sexual orientation discordance and some suicide risk factors. However, studies examining sexual orientation discordance and nonfatal suicidal behaviors in youth are rare. This study examines the association between sexual orientation discordance and suicidal ideation/suicide attempts among a nationally representative sample of U.S. high school students. METHODS: Using sexual identity and sex of sexual contact measures from the 2015 national Youth Risk Behavior Survey (n=6,790), a sexual orientation discordance variable was constructed describing concordance and discordance (agreement and disagreement, respectively, between sexual identity and sex of sexual contacts). Three suicide-related questions (seriously considered attempting suicide, making a plan about how they would attempt suicide, and attempting suicide) were combined to create a two-level nonfatal suicide risk variable. Analyses were restricted to students who identified as heterosexual or gay/lesbian, who had sexual contact, and who had no missing data for sex or suicide variables. The association between sexual orientation discordance and nonfatal suicide risk was assessed using logistic regression. Analyses were performed in 2017. RESULTS: Approximately 4.0% of students experienced sexual orientation discordance. High suicide risk was significantly more common among discordant students compared with concordant students (46.3% vs 22.4%, p<0.0001). In adjusted models, discordant students were 70% more likely to have had suicidal ideation/suicide attempts compared with concordant students (adjusted prevalence ratio=1.7, 95% CI=1.4, 2.0). CONCLUSIONS: Sexual orientation discordance was associated with increased likelihood of nonfatal suicidal behaviors. Discordant adolescents may experience unique stressors that should be considered when developing and implementing suicide prevention programs.

      2. Correlates of disclosure of sexual violence among Kenyan youthExternal
        Boudreau CL, Kress H, Rochat RW, Yount KM.
        Child Abuse Negl. 2018 Feb 16;79:164-172.

        INTRODUCTION: Sexual violence (SV) against children is a global health and human rights issue that can have short and long-term consequences for health and wellbeing. Disclosing SV increases the likelihood that children can access health and protective services and receive psychosocial support. Research in high-income countries has found that child SV survivors are more likely to disclose when they are girls/women, experience fewer SV events, and experience SV perpetrated by a stranger. No studies have examined correlates of SV disclosure in Kenya. OBJECTIVE: The objective of this research was to assess the correlates of disclosing SV among Kenyan youth ages 13-24 who reported an SV experience before age 18. METHODS: In 2010, the Kenya Ministry of Gender, Children and Social Development, the U.S. Centers for Disease Control and Prevention’s (CDC) Division of Violence Prevention, the UNICEF Kenya Country Office, and the Kenya National Bureau of Statistics (KNBS) conducted a national survey of violence against children. These data were used to conduct weighted logistic regression analyses to determine which factors were correlated with reporting SV disclosure. RESULTS: Among the 27.8% of girls/women and 14.5% of boys/men who reported SV before age 18, 44.6% of girls/women and 28.2% of boys/men reported to have disclosed the experience. In weighted logistic regression analysis, the odds of disclosure were lower among survivors who were boys/men and among survivors who reported more SV events, and higher when any perpetrator was a family member. CONCLUSION: More context-specific research on SV disclosure among young people is needed globally.

      3. Falls are the leading cause of fatal and non-fatal injuries among older adults. The American and British Geriatric Societies recommend a fall risk assessment to identify risk factors and guide interventions to prevent these falls. This study describes the self-reported discussion of fall prevention approaches used by primary care providers (PCPs)-family practitioners, internists and nurse practitioners-who treat older adults. Results are described overall and by PCP type. We analyzed a sample of 1210 U.S. PCPs who participated in the 2014 DocStyles survey. PCPs reported on their recommendation of fall prevention approaches including general exercise, Tai Chi, medication adjustments, home safety modifications, vitamin D supplements, assistive devices, alarm systems, and referral to physical therapy, foot specialist, or vision specialist. Frequencies and adjusted odds ratios for fall prevention approaches were assessed by provider and practice characteristics. Self-reported discussion of any fall prevention approaches was 89.3%. Controlling for provider and practice characteristics, there were significant differences for some approaches by provider type. Family practitioners were more likely to suggest home modification [adjusted Odds Ratio: 1.8 (1.32.4)], exercise [aOR: 2.0 (1.52.5)], and Tai Chi [aOR: 1.5 (1.02.2)] than internists. Nurse practitioners were more likely to suggest home modification [aOR: 2.1 (1.33.4)] and less likely to suggest vitamin D [aOR: 0.6 (0.41.0)] than internists. Fall prevention suggestions vary by type of PCP. Dissemination of geriatric guidelines should include all PCPs who routinely see older adults.

      4. Incidence of delayed intracranial hemorrhage in older patients after blunt head traumaExternal
        Chenoweth JA, Gaona SD, Faul M, Holmes JF, Nishijima DK.
        JAMA Surg. 2018 Feb 14.

        Importance: Current guidelines conflict on the management of older adults who have blunt head trauma taking anticoagulant and antiplatelet medications. This is partially due to the limited data comparing patients who are taking these medications with those who are not. Objective: To investigate the incidence of delayed traumatic intracranial hemorrhage in older adults with head trauma, including those taking anticoagulant and antiplatelet medications. Design, Setting, and Participants: This prospective observational cohort study included patients 55 years and older who had blunt head trauma and were transported via emergency medical services between August 1, 2015, and September 30, 2016. The setting was a multicenter study conducted at 11 hospitals in northern California. Patients were excluded if they had traumatic intracranial hemorrhage on the initial cranial computed tomographic scan, did not have a cranial computed tomographic scan performed at the initial emergency department visit, refused consent for a follow-up telephone call, or did not have reliable means of follow-up. Main Outcome and Measure: The primary outcome of this study was the incidence of delayed traumatic intracranial hemorrhage within 14 days of injury. Results: Among 859 patients enrolled in the study, the median age was 75 years (interquartile range, 64-85 years), and 389 (45.3%) were male. A total of 343 patients (39.9%) were taking an anticoagulant or antiplatelet medication. Three patients (0.3%; 95% CI, 0.1%-1.0%) had a delayed traumatic intracranial hemorrhage. Of the 3 patients, 1 of 75 patients (1.3%; 95% CI, 0.0%-7.2%) who were taking warfarin sodium alone and 2 of 516 patients (0.4%; 95% CI, 0.1%-1.4%) who were not taking any anticoagulant or antiplatelet medication had a delayed traumatic intracranial hemorrhage. Thirty-nine patients (4.5%; 95% CI, 3.2%-6.2%) were lost to follow-up. Conclusions and Relevance: Overall, the incidence of delayed intracranial hemorrhage in older adults who have blunt head trauma is low, including patients taking an anticoagulant or antiplatelet medication. These findings suggest that routine observation and serial cranial computed tomography may not be necessary in these patients.

      5. Characterizing sexual violence victimization in youth: 2012 National Intimate Partner and Sexual Violence SurveyExternal
        Merrick MT, Basile KC, Zhang X, Smith SG, Kresnow MJ.
        Am J Prev Med. 2018 Feb 12.

        INTRODUCTION: Youth sexual violence victimization is an urgent public health concern that can lead to a variety of health problems and increased risk for victimization during adulthood. Examining the characteristics of early victimization and their association with subsequent victimization during adulthood may help strengthen primary prevention efforts. METHODS: Data are from the 2012 National Intimate Partner and Sexual Violence Survey. Prevalence estimates were computed in 2017 for rape and made to sexually penetrate, their subtypes, as well as proportions among victims by type of perpetrator. Chi-square tests of association were conducted between youth sexual violence victimization and the same experiences in adulthood. RESULTS: Approximately 10 million U.S. females (8.4%) experienced completed or attempted rape and 1.9 million U.S. males (1.6%) were made to penetrate someone during youth. Most victims knew their perpetrators. Being raped or made to penetrate during youth was associated with increased likelihood of such victimization in adulthood. CONCLUSIONS: Females and males experience youth sexual violence victimization at alarming rates. Primary prevention efforts with youth are critical to prevent early victimization, subsequent victimization in adulthood, and the mental and physical health consequences associated with sexual violence victimization.

      6. Disclosure of sexual violence among girls and young women aged 13 to 24 years: Results from the Violence Against Children Surveys in Nigeria and MalawiExternal
        Nguyen KH, Kress H, Atuchukwu V, Onotu D, Swaminathan M, Ogbanufe O, Msungama W, Sumner SA.
        J Interpers Violence. 2018 Feb 1:886260518757225.

        Understanding factors that are associated with disclosure of sexual violence (SV) is important for the delivery of health services as well as developing strategies for prevention and response. The Violence Against Children Surveys were conducted in Malawi and Nigeria. We examined the prevalence of SV, help-seeking behaviors, and factors associated with disclosure among girls and young women aged 13 to 24. The self-reported prevalence of SV was similar in Nigeria (26%) and Malawi (27%). Among females who experienced SV, approximately one third (37%) in Nigeria and one half (55%) in Malawi ever disclosed their experience of SV. Females in Nigeria were significantly more likely to disclose to their parents (31.8%) than females in Malawi (9.5%). The most common reason for nondisclosure in Nigeria was not feeling a need or desire to tell anyone (34.9%) and in Malawi was embarrassment (29.3%). Very close relationships with one or both parents were significantly associated with disclosure among Nigerian females (odds ratio [OR] = 5.5, 95% confidence interval [CI] = [2.1, 14.6]) but were inversely associated with disclosure among Malawian females (OR = 0.05, 95% CI = [0.01, 0.33]). Reasons for nondisclosure of SV and factors associated with disclosure among females differ in the African nations studied. The stigma associated with shame of SV may prevent females from disclosing and thus receiving necessary support and health, social, and other services. This study demonstrates a need to reduce barriers for disclosure to improve the delivery of health, social, and other response services across African nations, as well as to develop culturally appropriate strategies for its response.

      7. Precollege sexual violence perpetration and associated risk and protective factors among male college freshmen in GeorgiaExternal
        Salazar LF, Swartout KM, Swahn MH, Bellis AL, Carney J, Vagi KJ, Lokey C.
        J Adolesc Health. 2018 Mar;62(3s):S51-s57.

        PURPOSE: Sexual violence (SV) perpetration on college campuses is a serious and prevalent public health issue in the U.S. In response, incoming male freshmen are mandated to receive SV prevention programming. To provide a more effective response, however, we need to understand the SV behaviors of male freshmen before they arrive on campus and the associated factors that contribute to risk and that afford protection, areas that have received limited attention. METHODS: Male freshmen (N = 1,133) across 30 selected 4-year colleges and universities throughout the state of Georgia were recruited for a longitudinal study on SV perpetration. Levels of precollege SV as well as a range of covariates were assessed at baseline. Self-reported SV perpetrators were compared with nonperpetrators on demographic and hypothesized covariates deemed either risk or protective; then risk and protective models were analyzed using binary logistic regression. RESULTS: Weighted analyses revealed that 19.3% self-reported perpetrating SV before college. Before starting college, young men who reported more sexual media consumption, heavy episodic drinking, hypermasculine beliefs, and peers who endorsed SV were more likely to have a history of SV perpetration at college matriculation. Alternatively, men with more knowledge of effective sexual consent and stronger family functioning were less likely to arrive to college with an SV perpetration history. CONCLUSIONS: A significant proportion of incoming male freshmen have perpetrated SV previously. Colleges and universities need to assess incoming freshmen for risk behaviors and negative beliefs and to offer both primary and secondary preventions to more effectively reduce further perpetration.

    • Laboratory Sciences
      1. Detection of TR34/L98H Cyp51A mutation through passive surveillance for azole-resistant Aspergillus fumigatus in the US, 2015-2017External
        Berkow EL, Nunnally NS, Bandea A, Kuykendall R, Beer K, Lockhart SR.
        Antimicrob Agents Chemother. 2018 Feb 20.

        Emergence of azole resistant Aspergillus fumigatus has become a clinical problem in many parts of the world. Several amino acid mutations in the azole target protein, Cyp51Ap, contribute to this resistance, with the most concerning being the environmentally-derived TR34/L98H and TR46/Y121F/T289A mutations. Here, we performed passive surveillance to assess a sample of the A. fumigatus population in the US for the presence of these mutations. We found 1.4% of those isolates to exhibit elevated MIC via broth microdilution and five of those isolates harbored the TR34/L98H mutation.

      2. INTRODUCTION: The use of pre-analytical heat treatment (PHT) with the Nijmegen-Bethesda assay (NBA) for inhibitors to factor VIII (FVIII) can remove/destroy infused or endogenous FVIII from patient plasma samples, allowing testing of recently infused patients with haemophilia. Two PHT methods have been described as follows: heating to 56 degrees C for 30 minutes and heating to 58 degrees C for 90 minutes. Data examining the effects of PHT on anti-FVIII IgG4 , the antibodies known to correlate most closely with the presence of FVIII inhibitors, are limited. AIM: To assess the effect of PHT on the levels of detectable anti-FVIII IgG4 . METHODS: Nijmegen-Bethesda assay-positive specimens were incubated at 56, 58 or 60 degrees C for 90 minutes, and anti-FVIII IgG4 was measured by fluorescence immunoassay (FLI) at 30-minute intervals. The effects of PHT on the ability of recombinant FVIII (rFVIII) to inhibit detection of patient antibodies by FLI was also examined to assess the stability of rFVIII under the various PHT conditions tested. RESULTS: Levels of anti-FVIII IgG4 showed little change following incubations at 56 degrees C (mean 101% of original value at 30 minutes and 100% at 60 minutes) but decreased upon exposure to 58 degrees C (mean 85% at 30 minutes and 66% at 60 minutes). In addition, heating to 56 degrees C effectively decreased the ability of rFVIII to block antibody binding compared to unheated rFVIII. CONCLUSION: The optimal temperature for PHT in the FVIII NBA is 56 degrees C. Higher temperatures may lead to loss of inhibitory antibodies.

      3. Digitizing medicines for remote capture of oral medication adherence using co-encapsulationExternal
        Browne SH, Peloquin C, Santillo F, Haubrich R, Muttera L, Moser K, Savage GM, Benson CA, Blaschke TF.
        Clin Pharmacol Ther. 2018 Mar;103(3):502-510.

        High-resolution measurement of medication adherence is essential to personalized drug therapy. A US Food and Drug Administration (FDA)-cleared device, using an edible ingestion sensor (IS), external wearable patch, and paired mobile device can detect and record ingestion events. Oral medications must be combined with an IS to generate precise “digitized-medication” ingestion records. We developed a Good Manufacturing Practice protocol to repackage oral medications with the IS within certified Capsugel capsules, termed co-encapsulation (CoE). A randomized bioequivalence study of CoE-IS-Rifamate (Isoniazid/Rifampin 150/300 mg) vs. native-Rifamate was conducted in 12 patients with active Mycobacterium tuberculosis and demonstrated bioequivalence using the population method ratio test (95% confidence interval). Subsequently, CoE-IS-medications across all biopharmaceutical classes underwent in vitro dissolution testing utilizing USP and FDA guidelines. CoE-IS medications tested met USP dissolution specifications and were equivalent to their native formulations. CoE combines oral medications with the IS without altering the quality of the native formulation, generating “digitized” medications for remote capture of dosing histories.

      4. Laboratory evaluation of commercially available platforms to detect West Nile and Zika viruses from honey cardsExternal
        Burkhalter KL, Wiggins K, Burkett-Cadena N, Alto BW.
        J Med Entomol. 2018 Feb 15.

        Commercially available assays utilizing antigen or nucleic acid detection chemistries provide options for mosquito control districts to screen their mosquito populations for arboviruses and make timely operational decisions regarding vector control. These assays may be utilized even more advantageously when combined with honey-soaked nucleic acid preservation substrate (‘honey card’) testing by reducing or replacing the time- and labor-intensive efforts of identifying and processing mosquito pools. We tested artificially inoculated honey cards and cards fed upon individually by West Nile virus (WNV) and Zika virus (ZIKV)-infected mosquitoes with three assays to compare detection rates and the limit of detection for each platform with respect to virus detection of a single infected mosquito and quantify the time interval of virus preservation on the cards. Assays evaluated included CDC protocols for real-time reverse transcriptase polymerase chain reaction (RT-PCR) for WNV and ZIKV, Pro-Lab Diagnostics ProAmpRT WNV loop-mediated amplification (LAMP) and ZIKV LAMP assays, and the Rapid Analyte Measurement Platform (RAMP) WNV assay. Real-time RT-PCR was the most sensitive assay and the most robust to viral RNA degradation over time. To maximize the detection of virus, honey cards should be left in the traps </=1 d if using LAMP assays and </=3 d if using real-time RT-PCR to detect viruses from field samples. The WNV RAMP assay, although effective for pool screening, lacks sensitivity required for honey card surveillance. Future studies may determine the minimum number of infectious mosquitoes required to feed on a honey card that would be reliably detected by the LAMP or RAMP assays.

      5. MicroRNA regulation of host immune responses following fungal exposureExternal
        Croston TL, Lemons AR, Beezhold DH, Green BJ.
        Front Immunol. 2018 ;9:170.

        Fungal bioaerosols are ubiquitous in the environment and human exposure can result in a variety of health effects ranging from systemic, subcutaneous, and cutaneous infections to respiratory morbidity including allergy, asthma, and hypersensitivity pneumonitis. Recent research has focused on the role of microRNAs (miRNAs) following fungal exposure and is overlooked, yet important, group of regulators capable of influencing fungal immune responses through a variety of cellular mechanisms. These small non-coding ribose nucleic acids function to regulate gene expression at the post-transcriptional level and have been shown to participate in multiple disease pathways including cancer, heart disease, apoptosis, as well as immune responses to microbial hazards and occupational allergens. Recent animal model studies have characterized miRNAs following the exposure to inflammatory stimuli. Studies focused on microbial exposure, including bacterial infections, as well as exposure to different allergens have shown miRNAs, such as miR-21, miR-146, miR-132, miR-155, and the let-7 family members, to be involved in immune and inflammatory responses. Interestingly, the few studies have assessed that the miRNA profiles following fungal exposure have identified the same critical miRNAs that have been characterized in other inflammatory-mediated and allergy-induced experimental models. Review of available in vitro, animal and human studies of exposures to Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Paracoccidioides brasiliensis, and Stachybotrys chartarum identified several miRNAs that were shared between responses to these species including miR-125 a/b (macrophage polarization/activation), miR-132 [toll-like receptor (TLR)2-mediated signaling], miR-146a (TLR mediated signaling, alternative macrophage activation), and miR-29a/b (natural killer cell function, C-leptin signaling, inhibition of Th1 immune response). Although these datasets provide preliminary insight into the role of miRNAs in fungal exposed models, interpretation of miRNA datasets can be challenging for researchers. To assist in navigating this rapidly evolving field, the aim of this review is to describe miRNAs in the framework of host recognition mechanisms and provide initial insight into the regulatory pathways in response to fungal exposure.

      6. Analytical high-resolution electron microscopy reveals organ-specific nanoceria bioprocessingExternal
        Graham UM, Yokel RA, Dozier AK, Drummy L, Mahalingam K, Tseng MT, Birch E, Fernback J.
        Toxicol Pathol. 2018 Jan;46(1):47-61.

        This is the first utilization of advanced analytical electron microscopy methods, including high-resolution transmission electron microscopy, high-angle annular dark field scanning transmission electron microscopy, electron energy loss spectroscopy, and energy-dispersive X-ray spectroscopy mapping to characterize the organ-specific bioprocessing of a relatively inert nanomaterial (nanoceria). Liver and spleen samples from rats given a single intravenous infusion of nanoceria were obtained after prolonged (90 days) in vivo exposure. These advanced analytical electron microscopy methods were applied to elucidate the organ-specific cellular and subcellular fate of nanoceria after its uptake. Nanoceria is bioprocessed differently in the spleen than in the liver.

      7. Acetylation by Eis and deacetylation by Rv1151c of Mycobacterium tuberculosis HupB: Biochemical and structural insightExternal
        Green KD, Biswas T, Pang AH, Willby MJ, Reed MS, Stuchlik O, Pohl J, Posey JE, Tsodikov OV, Garneau-Tsodikova S.
        Biochemistry. 2018 Feb 6;57(5):781-790.

        Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity and chromosome maintenance. Post-translational modifications of bacterial NAPs appear to function similarly to their better studied mammalian counterparts. The histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously observed to be acetylated by the acetyltransferase Eis, leading to genome reorganization. We report biochemical and structural aspects of acetylation of HupB by Eis. We also found that the SirT-family NAD(+)-dependent deacetylase Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation kinetics. We propose that activities of Eis and Rv1151c could regulate the acetylation status of HupB to remodel the mycobacterial chromosome in response to environmental changes.

      8. Herein we present the results of measurements using wireless direct-reading photoionization detector-based gas sensors to quantify concentrations of vapors of volatile organic compounds (VOCs) in and around flammable storage cabinets containing common organic solvents, including acetone, dichloromethane, trichloroethylene, and benzene. Such cabinets are commonly employed in laboratories to contain flammable liquids. A sensor array was deployed in a series of flammable storage cabinets in working laboratories. Measurements in cabinets containing bottles of typical solvents demonstrate that vapor concentrations gradually increase upon closing the cabinet door. The results suggest that these storage units can be a source of vapors of VOCs in laboratories and the unnecessary exposure of laboratory workers to chemical vapors. Ventilation of cabinets tended to lower maximum concentrations of VOCs. However, the efficacy of this engineering control was found to depend on the quality of the cabinet door seal, as well as having debris-free flame arrestors. Opening cabinet doors resulted in release of vapors to the laboratory atmosphere, which represents an unnecessary exposure risk for workers. A countermeasure aimed at improving the seal of previously opened solvent bottles reduced measured concentrations of VOCs in cabinets below the detector’s limit of detection.

      9. Revisiting rabies virus neutralizing antibodies through infecting BALB/c mice with live rabies virusExternal
        Qin Y, Smith TG, Jackson F, Gallardo-Romero NF, Morgan CN, Olson V, Hutson CL, Wu X.
        Virus Res. 2018 Feb 19.

        This study investigates the production of rabies virus (RABV) neutralizing antibody after virus infection through a mouse model. The BALB/c mice from different age groups (three, five, seven week old) were intramuscularly inoculated with live rabies virus (TX coyote 323R). Without pre-exposure or post-exposure prophylaxis (PEP), we found there is a decreased fatality with increased age of animals, the mortalities are 60%, 50%, and 30%, respectively. Interestingly, through assay of rapid fluorescent focus inhibition test (RFFIT), direct fluorescent antibody (DFA) and quantitative Polymerase Chain Reaction (qPCR), the results showed that all the animals that succumbed to rabies challenge, except one, developed circulating neutralizing antibodies, and all the healthy animals, except two, did not generate virus neutralizing antibodies (VNA). Our animal study suggests that the induction of VNA was an indicator of infection progression in the central nervous system (CNS) and speculate that RABV neutralizing antibodies did not cross the blood-brain barrier of the CNS for those diseased animals. We hypothesize that early release of viral antigens from damaged nerve tissue might potentially be a benefit for survivors, and we also discuss several other aspects of the interaction of RABV and its neutralizing antibodies.

      10. Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B resistant isolatesExternal
        Reichert Lima F, Lyra L, Pontes L, Moretti ML, Pham CD, Lockhart SR, Schreiber AZ.
        Mycoses. 2018 Feb 22.

        Aspergillus spp. are the most common invasive mold infection and are responsible for high mortality. A. fumigatus is currently of interest because resistance to azole antifungals has emerged. The Campinas University Hospital (HC-UNICAMP) receives high-risk patients susceptible to opportunistic infections but there have been no reports of resistant A. fumigatus. This study aimed to assess the susceptibility profile of Aspergillus isolates, specifically looking for azole resistance. ITS and beta-tubulin DNA sequencing was performed on 228 sequential clinical isolates. Broth microdilution susceptibility testing was performed for all isolates. A. fumigatus represented 74% of the isolates followed by A. flavus (12%). Nine A. fumigatus isolates from 9 different patients showed high MIC values to at least one azole, but cyp51A polymorphisms were detected in only 6 isolates and none correlated with known resistance mutations. The most troubling observation was that the minimum inhibitory concentration for amphotericin B was elevated (>/=2 mg L(-1) ) in 87% of patients with A. flavus isolates and 43% with A. fumigatus isolates. Given that amphotericin B is used to treat azole resistant infections, these data highlight the need for continuous surveillance in Aspergillus for all antifungal resistance to implement correct treatment strategies for the management of these pathogens. This article is protected by copyright. All rights reserved.

      11. Effectiveness of practices to support appropriate laboratory test utilization: A laboratory medicine best practices systematic review and meta-analysisExternal
        Rubinstein M, Hirsch R, Bandyopadhyay K, Madison B, Taylor T, Ranne A, Linville M, Donaldson K, Lacbawan F, Cornish N.
        Am J Clin Pathol. 2018 Feb 17;149(3):197-221.

        Objectives: To evaluate the effectiveness of practices used to support appropriate clinical laboratory test utilization. Methods: This review followed the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practices A6 cycle method. Eligible studies assessed one of the following practices for effect on outcomes relating to over- or underutilization: computerized provider order entry (CPOE), clinical decision support systems/tools (CDSS/CDST), education, feedback, test review, reflex testing, laboratory test utilization (LTU) teams, and any combination of these practices. Eligible outcomes included intermediate, systems outcomes (eg, number of tests ordered/performed and cost of tests), as well as patient-related outcomes (eg, length of hospital stay, readmission rates, morbidity, and mortality). Results: Eighty-three studies met inclusion criteria. Fifty-one of these studies could be meta-analyzed. Strength of evidence ratings for each practice ranged from high to insufficient. Conclusion: Practice recommendations are made for CPOE (specifically, modifications to existing CPOE), reflex testing, and combined practices. No recommendation for or against could be made for CDSS/CDST, education, feedback, test review, and LTU. Findings from this review serve to inform guidance for future studies.

      12. Short-term pulmonary toxicity assessment of pre- and post-incinerated organomodified nanoclay in miceExternal
        Stueckle TA, Davidson DC, Derk R, Kornberg TG, Battelli L, Friend S, Orandle M, Wagner A, Dinu CZ, Sierros KA, Agarwal S, Gupta RK, Rojanasakul Y, Porter DW, Rojanasakul L.
        ACS Nano. 2018 Feb 22.

        Organomodified nanoclays (ONCs) are increasingly used as filler materials to improve nanocomposite strength, wettability, flammability, and durability. However, pulmonary risks associated with exposure along their chemical lifecycle are unknown. This study’s objective was to compare pre- and post-incinerated forms of uncoated and organomodified nanoclays for potential pulmonary inflammation, toxicity, and systemic blood response. Mice were exposed via aspiration to low (30 mug) and high (300 mug) doses of preincinerated uncoated montmorillonite nanoclay (CloisNa), ONC (Clois30B), their respective incinerated forms (I-CloisNa and I-Clois30B), and crystalline silica (CS). Lung and blood tissues were collected at days 1, 7, and 28 to compare toxicity and inflammation indices. Well-dispersed CloisNa caused a robust inflammatory response characterized by neutrophils, macrophages, and particle-laden granulomas. Alternatively, Clois30B, I-Clois30B, and CS high-dose exposures elicited a low grade, persistent inflammatory response. High-dose Clois30B exposure exhibited moderate increases in lung damage markers and a delayed macrophage recruitment cytokine signature peaking at day 7 followed by a fibrotic tissue signature at day 28, similar to CloisNa. I-CloisNa exhibited acute, transient inflammation with quick recovery. Conversely, high-dose I-Clois30B caused a weak initial inflammatory signal but showed comparable pro-inflammatory signaling to CS at day 28. The data demonstrate that ONC pulmonary toxicity and inflammatory potential relies on coating presence and incineration status in that coated and incinerated nanoclay exhibited less inflammation and granuloma formation than pristine montmorillonite. High doses of both pre- and post-incinerated ONC, with different surface morphologies, may harbor potential pulmonary health hazards over long-term occupational exposures.

      13. Elevated plasma moxifloxacin concentrations and SLCO1B1 g.-11187G>A polymorphism in adults with pulmonary tuberculosisExternal
        Weiner M, Gelfond J, Johnson-Pais TL, Engle M, Peloquin CA, Johnson JL, Sizemore EE, Mac Kenzie WR.
        Antimicrob Agents Chemother. 2018 Feb 20.

        Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity against Mycobacterium tuberculosis However, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United State s enrolled in two treatment trials of moxifloxacin as part of multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental techniques. Human single-nucleotide polymorphisms of transporter genes were evaluated with analysis of covariance on moxifloxacin exposure and peak concentration (Cmax). Moxifloxacin area under the concentration-time curve from 0 to 24 h (AUC0-24) and Cmax were significantly increased by drug mg/kg dosage and genotype of variant g.-11187G>A in the SLCO1B1 gene (rs4149015), but not by geographic region. Median moxifloxacin AUC0-24 was 46% higher and Cmax 30% higher in 4 (8% of) participants who had the SLCO1B1 g.-11187 AG genotype compared with 45 participants who had the wild type GG genotype (median from model, AUC0-24 34.4 vs. 23.6 mug*h/mL, P =.005; Cmax 3.5 vs. 2.7 mug/mL, P =.009, ANCOVA). Because moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals, and prolonged QTc intervals are associated with cardiac arrhythmia, further study is needed to evaluate risk associated with the SLCO1B1 g.-11187G>A variant.

      14. Defining the sizes of airborne particles that mediate influenza transmission in ferretsExternal
        Zhou J, Wei J, Choy KT, Sia SF, Rowlands DK, Yu D, Wu CY, Lindsley WG, Cowling BJ, McDevitt J, Peiris M, Li Y, Yen HL.
        Proc Natl Acad Sci U S A. 2018 Feb 20.

        Epidemics and pandemics of influenza are characterized by rapid global spread mediated by non-mutually exclusive transmission modes. The relative significance between contact, droplet, and airborne transmission is yet to be defined, a knowledge gap for implementing evidence-based infection control measures. We devised a transmission chamber that separates virus-laden particles by size and determined the particle sizes mediating transmission of influenza among ferrets through the air. Ferret-to-ferret transmission was mediated by airborne particles larger than 1.5 microm, consistent with the quantity and size of virus-laden particles released by the donors. Onward transmission by donors was most efficient before fever onset and may continue for 5 days after inoculation. Multiple virus gene segments enhanced the transmissibility of a swine influenza virus among ferrets by increasing the release of virus-laden particles into the air. We provide direct experimental evidence of influenza transmission via droplets and fine droplet nuclei, albeit at different efficiency.

    • Maternal and Child Health
      1. BACKGROUND: Widely recommended developmental surveillance methods include developmental monitoring (DM) and development screening (DS). Much research has been done on DS, but very little research has compared the effectiveness of DM and DS together. OBJECTIVES: To investigate the relationship between DM and DS in Part C early intervention (EI) service receipt. METHODS: Authors used data from the 2007/2008 and 2011/2012 National Survey of Children’s Health (NSCH). Authors report the prevalence of children aged 10 months to 3 years who received (a) DM only, (b) DS only, (c) both DM and DS, and (c) no DM or DS across survey years. Authors compare the odds of EI receipt across these groups. RESULTS: During both periods, estimated EI receipt prevalence was higher for children receiving both DM and DS (8.38% in 2007/2008; 6.47% in 2011/2012) compared to children receiving no DM or DS (1.31% in 2007/2008; 1.92% in 2011/2012), DM alone (2.74% in 2007/2008; 2.70% in 2011/2012), or DS alone (3.59% in 2007/2008; 3.09% in 2011/2012) (for both time frames, p<.05). From 2007/2008 to 2011/2012, the proportion of children receiving DS only and both DM and DS increased, while children receiving DM only and no DM or DS decreased. CONCLUSIONS: Children receiving DM and DS together were more likely to receive EI compared to children receiving DM alone, DS alone, or neither DM nor DS. These findings support the AAP recommendations indicating that DM and DS are complementary strategies for improving early identification and linkage to EI for young children.

      2. Autism spectrum disorder (ASD) is a prevalent developmental disorder. Studies indicate that while ASD etiology has a genetic component, the risk is polygenic, with gene-environment interactions being likely. The prenatal period is a critical exposure window for nongenetic risk factors. Previous studies have found positive associations between congenital malformations (all types) and ASD; a few also found specific associations between genitourinary system malformations and ASD; and one study found an association between hypospadias and ASD. In the accompanying article, Rotem et al. (Am J Epidemiol. 2018;000(00):000-000) describe how they conducted a comprehensive analysis focusing on the shared risk of ASD with hypospadias or cryptorchidism, using existing data from a large Israeli health services system, which afforded several advantages because of the large sample size and low attrition of the patient population. The authors conducted a careful analysis, including sensitivity analyses, to account for risk factor and case misclassifications that might have occurred had they relied solely on preexisting diagnostic codes to define exposures and outcome. They observed positive associations between both hypospadias and cryptorchidism and ASD that were independent of numerous sociodemographic and pregnancy health factors. This study advances our understanding of ASD etiology and illustrates how existing data might be used to assess some ASD risk factors.

      3. The ratio of the index (2nd) finger to ring (4th) finger lengths (2D:4D) is a proxy for fetal testosterone and estradiol. Studies suggesting 2D:4D is inversely associated with autism spectrum disorder (ASD) in males were limited by lack of confounder and subgroup assessments. Studies of females are sparse. We examined associations between ASD and 2D:4D among children in the Study to Explore Early Development; we considered case subgroups and numerous potential demographic and maternal-perinatal health confounders. We observed a modest inverse association between ASD and right-hand 2D:4D in males; subgroup analyses indicated associations were limited to ASD cases with birth defects/genetic syndromes or dysmorphic features. We observed a positive association between ASD and left-hand 2D:4D in females, overall and within most case subgroups.

    • Mining
      1. Some relevant parameters for assessing fire hazards of combustible mine materials using laboratory scale experimentsExternal
        Litton CD, Perera IE, Harteis SP, Teacoach KA, DeRosa MI, Thomas RA, Smith AC.
        Fuel. 2018 ;218:306-315.

        When combustible materials ignite and burn, the potential for fire growth and flame spread represents an obvious hazard, but during these processes of ignition and flaming, other life hazards present themselves and should be included to ensure an effective overall analysis of the relevant fire hazards. In particular, the gases and smoke produced both during the smoldering stages of fires leading to ignition and during the advanced flaming stages of a developing fire serve to contaminate the surrounding atmosphere, potentially producing elevated levels of toxicity and high levels of smoke obscuration that render the environment untenable. In underground mines, these hazards may be exacerbated by the existing forced ventilation that can carry the gases and smoke to locations far-removed from the fire location. Clearly, materials that require high temperatures (above 1400 K) and that exhibit low mass loss during thermal decomposition, or that require high heat fluxes or heat transfer rates to ignite represent less of a hazard than materials that decompose at low temperatures or ignite at low levels of heat flux. In order to define and quantify some possible parameters that can be used to assess these hazards, small-scale laboratory experiments were conducted in a number of configurations to measure: 1) the toxic gases and smoke produced both during non-flaming and flaming combustion; 2) mass loss rates as a function of temperature to determine ease of thermal decomposition; and 3) mass loss rates and times to ignition as a function of incident heat flux. This paper describes the experiments that were conducted, their results, and the development of a set of parameters that could possibly be used to assess the overall fire hazard of combustible materials using small scale laboratory experiments.

    • Occupational Safety and Health – Mining
      1. This paper provides a suitability determination of international standards for evaluating electrical and electronic systems and line powered apparatus as an alternative to the Mine Safety and Health Administration (MSHA) criteria for two-fault intrinsic safety (IS) approval. The primary issue is to demonstrate that international equipment evaluation standards will provide at least the same level of protection for miners as the MSHA requirements. The secondary issue is to identify additional benefits that may be derived from the use of the “entity concept” in the approval process, such as potential cost savings and an easier and quicker path for the introduction of new technology.

    • Parasitic Diseases
      1. Transitioning from river blindness control to elimination: steps toward stopping treatmentExternal
        Cantey PT, Roy SL, Boakye D, Mwingira U, Ottesen EA, Hopkins AD, Sodahlon YK.
        Int Health. 2018 Mar 1;10(suppl_1):i7-i13.

        The transition from onchocerciasis control to elimination requires country programmes to rethink their approach to a variety of activities as they move from addressing morbidity to addressing transmission of the parasite. Although the 2016 WHO guidelines provide extensive recommendations, it was beyond the scope of the document to provide guidance on all aspects of the transition. This paper will discuss some of the important issues that programmes are grappling with as they transition to elimination and provide some potential approaches that programmes can use to address them. Although there are some data to support some aspects of the suggested approaches, operational research will be needed to generate data to support these approaches further and to determine how programmes could best tailor them to their own unique epidemiological challenges. Good communication between the national programmes and the broader global programme will facilitate the clear articulation of programmatic challenges and the development of the evidence to support programme decision-making.

      2. The role of national committees in eliminating onchocerciasisExternal
        Griswold E, Unnasch T, Eberhard M, Nwoke BE, Morales Z, Muheki Tukahebwa E, Kebede B, Anagbogu I, Katabarwa M, Habomugisha P, Tadesse Z, Miri ES, Evans D, Cohn D, Elhassan E, Richards F.
        Int Health. 2018 Mar 1;10(suppl_1):i60-i70.

        National onchocerciasis elimination committees (NOECs) serve to help ministries of health complete the pathway to successful verification of elimination of onchocerciasis (river blindness), as outlined in the 2016 World Health Organization guidelines. These guidelines, however, only take effect when the country believes it has reached a point that elimination can be demonstrated, and do not address the preceding milestones. Therefore, NOECs can be of great help with guiding and tailoring earlier planning, programming and assessments to empower national programs to aggressively move toward their countries’ elimination goals. In this article, we provide suggestions for organizing NOECs and examples of four such committees that have successfully operated in Africa and the Americas.

      3. The links between agriculture, Anopheles mosquitoes, and malaria risk in children younger than 5 years in the Democratic Republic of the Congo: a population-based, cross-sectional, spatial studyExternal
        Janko MM, Irish SR, Reich BJ, Peterson M, Doctor SM, Mwandagalirwa MK, Likwela JL, Tshefu AK, Meshnick SR, Emch ME.
        Lancet Planet Health. 2018 Feb;2(2):e74-e82.

        Background: The relationship between agriculture, Anopheles mosquitoes, and malaria in Africa is not fully understood, but it is important for malaria control as countries consider expanding agricultural projects to address population growth and food demand. Therefore, we aimed to assess the effect of agriculture on Anopheles biting behaviour and malaria risk in children in rural areas of the Democratic Republic of the Congo (DR Congo). Methods: We did a population-based, cross-sectional, spatial study of rural children (<5 years) in the DR Congo. We used information about the presence of malaria parasites in each child, as determined by PCR analysis of dried-blood spots from the 2013-14 DR Congo Demographic and Health Survey (DHS). We also used data from the DHS, a longitudinal entomological study, and available land cover and climate data to evaluate the relationships between agriculture, Anopheles biting behaviour, and malaria prevalence. Satellite imagery was used to measure the percentage of agricultural land cover around DHS villages and Anopheles sites. Anopheles biting behaviour was assessed by Human Landing Catch. We used probit regression to assess the relationship between agriculture and the probability of malaria infection, as well as the relationship between agriculture and the probability that a mosquito was caught biting indoors. Findings: Between Aug 13, 2013, and Feb 13, 2014, a total of 9790 dried-blood spots were obtained from the DHS, of which 4612 participants were included in this study. Falciparum malaria infection prevalence in rural children was 38.7% (95% uncertainty interval [UI] 37.3-40.0). Increasing exposure to agriculture was associated with increasing malaria risk with a high posterior probability (estimate 0.07, 95% UI -0.04 to 0.17; posterior probability [estimate >0]=0.89), with the probability of malaria infection increased between 0.2% (95% UI -0.1 to 3.4) and 2.6% (-1.5 to 6.6) given a 15% increase in agricultural cover, depending on other risk factors. The models predicted that large increases in agricultural cover (from 0% to 75%) increase the probability of infection by as much as 13.1% (95% UI -7.3 to 28.9). Increased risk might be due to Anopheles gambiae sensu lato, whose probability of biting indoors increased between 11.3% (95% UI -15.3 to 25.6) and 19.7% (-12.1 to 35.9) with a 15% increase in agriculture. Interpretation: Malaria control programmes must consider the possibility of increased risk due to expanding agriculture. Governments considering initiating large-scale agricultural projects should therefore also consider accompanying additional malaria control measures. Funding: National Institutes of Health, National Science Foundation, Bill & Melinda Gates Foundation, President’s Malaria Initiative, and Royster Society of Fellows at the University of North Carolina at Chapel Hill.

      4. Risk factors for severe malaria among hospitalized patients in the United States, 2000-2014External
        Khuu D, Eberhard ML, Bristow BN, Javanbakht M, Ash LR, Shafir SC, Sorvillo FJ.
        Infection, Disease and Health. 2018 .

        Background: Factors associated with the development of severe malaria have not been well described for cases occurring in the United States (US). Methods: Severe malaria hospitalizations data from the 2000-2014 Nationwide Inpatient Sample were analyzed. Frequencies were reported by demographic, clinical, species, financial, geographic, and institutional characteristics, and trends and disparities were identified. Logistic regression models were used to identify potential predictors for severe disease among those with malaria. Results: From 2000 to 2014, there were an estimated 4823 severe malaria cases, representing 21.9% of all malaria-related hospitalizations, including 182 severe malaria deaths. Severe malaria was most common among inpatients who were male, Black, aged 45-64 years, and hospitalized in the South Atlantic division of the US. Older age was associated with higher odds of severe malaria, cerebral malaria, ARDS, severe anemia, and renal failure. Males had higher odds of developing renal failure and jaundice, while females had higher odds of developing severe anemia. HIV infection was associated with increased odds of severe malaria, severe anemia, and renal failure. Conclusion: Primary and secondary prevention measures, such as pre-travel consultations, chemoprophylaxis, and early diagnosis and treatment, should be emphasized and improved among high-risk prospective travelers to malaria endemic countries.

      5. Prevalence of molecular markers of artemisinin and lumefantrine resistance among patients with uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2015External
        Ljolje D, Dimbu PR, Kelley J, Goldman I, Nace D, Macaia A, Halsey ES, Ringwald P, Fortes F, Udhayakumar V, Talundzic E, Lucchi NW, Plucinski MM.
        Malar J. 2018 Feb 20;17(1):84.

        BACKGROUND: Artemisinin-based combination therapy is the first-line anti-malarial treatment for uncomplicated Plasmodium falciparum infection in Angola. To date, the prevalence of polymorphisms in the pfk13 gene, associated with artemisinin resistance, and pfmdr1, associated with lumefantrine resistance, have not been systematically studied in Angola. METHODS: DNA was isolated from pretreatment and late treatment failure dried blood spots collected during the 2015 round of therapeutic efficacy studies in Benguela, Lunda Sul, and Zaire Provinces in Angola. The pfk13 propeller domain and pfmdr1 gene were sequenced and analysed for polymorphisms. Pfmdr1 copy number variation was assessed using a real-time PCR method. The association between pfmdr1 and pfk13 mutations and treatment failure was investigated. RESULTS: The majority of pretreatment (99%, 466/469) and all late treatment failure (100%, 50/50) samples were wild type for pfk13. Three of the pretreatment samples (1%) carried the A578S mutation commonly observed in Africa and not associated with artemisinin resistance. All 543 pretreatment and day of late treatment failure samples successfully analysed for pfmdr1 copy number variation carried one copy of pfmdr1. The NYD haplotype was the predominant pfmdr1 haplotype, present in 63% (308/491) of pretreatment samples, followed by NFD, which was present in 32% (157/491) of pretreatment samples. The pfmdr1 N86 allele was overrepresented in day of late treatment failure samples from participants receiving artemether-lumefantrine (p value 0.03). CONCLUSIONS: The pretreatment parasites in patients participating in therapeutic efficacy studies in 2015 in Angola’s three sentinel sites showed genetic evidence of susceptibility to artemisinins, consistent with clinical outcome data showing greater than 99% day 3 clearance rates. The lack of increased pfmdr1 copy number is consistent with previous reports from sub-Saharan Africa. Although pfmdr1 NYD and NFD haplotypes were overrepresented in artemether-lumefantrine late treatment failure samples, their role as markers of resistance was unclear given that these haplotypes were also present in the majority of successfully treated patients in the artemether-lumefantrine treatment arms.

      6. Diagnostics for onchocerciasis in the era of eliminationExternal
        Unnasch TR, Golden A, Cama V, Cantey PT.
        Int Health. 2018 Mar 1;10(suppl_1):i20-i26.

        In the past few years, efforts to eliminate onchocerciasis from Africa have intensified. These efforts are primarily based on the mass distribution of the anti-helminthic drug Mectizan (ivermectin). This program has led to the development of new guidelines by the World Health Organization for the verification that transmission has been suppressed and eventually eliminated. The requirements of diagnostic tools for this purpose differ in many ways from tests used to diagnose infection in individuals. In this review, we summarize the progress that has been made to identify diagnostics that meet the specialized requirements needed to verify onchocerciasis elimination, discuss why these tests were selected and summarize the needs that still exist to complete the arsenal of diagnostic tools that will be useful as the goal of elimination is achieved.

    • Program Evaluation
      1. Using predictive evaluation to design, evaluate, and improve training for polio volunteersExternal
        Traicoff DA, Basarab D, Ehrhardt DT, Brown S, Celaya M, Jarvis D, Howze EH.
        Pedagogy Health Promot. 2018 Mar;4(1):35-42.

        Background: Predictive Evaluation (PE) uses a four-step process to predict results then designs and evaluates a training intervention accordingly. In 2012, the Sustainable Management Development Program (SMDP) at the Centers for Disease Control and Prevention used PE to train Stop Transmission of Polio (STOP) program volunteers. Methods: Stakeholders defined specific beliefs and practices that volunteers should demonstrate. These predictions and adult learning practices were used to design a curriculum to train four cohorts. At the end of each workshop, volunteers completed a beliefs survey and wrote goals for intended actions. The goals were analyzed for acceptability based on four PE criteria. The percentage of acceptable goals and the beliefs survey results were used to define the quality of the workshop. A postassignment adoption evaluation was conducted for two cohorts, using an online survey and telephone or in-person structured interviews. The results were compared with the end of workshop findings. Results: The percentage of acceptable goals across the four cohorts ranged from 49% to 85%. In the adoption evaluation of two cohorts, 88% and 94% of respondents reported achieving or making significant progress toward their goal. A comparison of beliefs survey responses across the four cohorts indicated consistencies in beliefs that aligned with stakeholders’ predictions. Conclusions: Goal statements that participants write at the end of a workshop provide data to evaluate training quality. Beliefs surveys surface attitudes that could help or hinder workplace performance. The PE approach provides an innovative framework for health worker training and evaluation that emphasizes performance.

    • Reproductive Health
      1. Computer-assisted motivational interviewing intervention to facilitate teen pregnancy prevention and fitness behavior changes: A randomized trial for young menExternal
        Bell DL, Garbers S, Catallozzi M, Hum RS, Nechitilo M, McKeague IW, Koumans EH, House LD, Rosenthal SL, Gold MA.
        J Adolesc Health. 2018 Mar;62(3s):S72-s80.

        PURPOSE: Despite recent declines, teen unintended pregnancy and sexually transmitted infections in the United States remain at levels higher than comparable nations. Initiatives to prevent teen pregnancy have focused primarily on female adolescents; how to effectively engage young men to reduce their risk of fathering a teen pregnancy has not been well studied. We proposed to adapt an innovative computer-assisted motivational interviewing (CAMI) intervention, originally designed and tested with young women, for use with young men, aged 15-24 years, to reduce their risk of fathering a teen pregnancy. This manuscript describes the design of a CAMI intervention for young men aimed at preventing teen pregnancy and improving fitness. METHODS: This randomized controlled trial will recruit 945 sexually active young men between the ages of 15 and 24 years from three health centers in New York City. Participants will be assigned by permuted block randomization to two study arms: one aimed at reducing involvement in unintended teen pregnancy (CAMI-teen pregnancy prevention) and the other at improving overall fitness (CAMI-Fitness). Except for topic, both intervention arms will provide four sessions of Motivational Interviewing coaching and use a mobile app to track behavior and set goals. We will assess young men’s sexual and reproductive health behaviors and fitness at baseline, 12, 24, 36, and 64 weeks using a mobile device app created for the study. RESULTS: Pending ongoing study. CONCLUSIONS: Results from the study are expected to enhance our understanding of the efficacy of CAMI to enhance young men’s reproductive health and fitness behaviors.

    • Zoonotic and Vectorborne Diseases
      1. Knowledge, attitudes, and practices of women of childbearing age testing negative for Zika virus in Kentucky, 2016External
        Heitzinger K, Thoroughman DA, Porter KA.
        Preventive Medicine Reports. 2018 ;10:20-23.

        Because infection with Zika virus during pregnancy can cause microcephaly and other birth defects, women of childbearing age are an important population for targeting of Zika-related public health messaging. To improve Zika-related communication and outreach in Kentucky, we conducted a survey to assess Zika knowledge, attitudes, and practices among all women of childbearing age who received a negative Zika test result from the state public health laboratory during February to July 2016. Although >90% of the 55 respondents knew the virus could be transmitted by mosquitoes and caused birth defects, just 56% (31/55) knew the virus could be sexually transmitted. These findings underscore the importance of continued efforts by CDC and state and local health departments to educate female travelers of childbearing age about risks for and prevention of Zika virus infection, particularly emphasizing use of condoms and abstinence to prevent transmission.

      2. Public health response to an imported case of canine melioidosisExternal
        Ryan CW, Bishop K, Blaney DD, Britton SJ, Cantone F, Egan C, Elrod MG, Frye CW, Maxted AM, Perkins G.
        Zoonoses Public Health. 2018 Feb 16.

        Melioidosis in humans presents variably as fulminant sepsis, pneumonia, skin infection and solid organ abscesses. It is caused by Burkholderia pseudomallei, which in the United States is classified as a select agent, with “potential to pose a severe threat to both human and animal health, to plant health or to animal and plant products” (Federal Select Agent Program, http://www.selectagents.gov/, accessed 22 September 2016). Burkholderia pseudomallei is found in soil and surface water in the tropics, especially South-East Asia and northern Australia, where melioidosis is endemic. Human cases are rare in the United States and are usually associated with travel to endemic areas. Burkholderia pseudomallei can also infect animals. We describe a multijurisdictional public health response to a case of subclinical urinary B. pseudomallei infection in a dog that had been adopted into upstate New York from a shelter in Thailand. Investigation disclosed three human contacts with single, low-risk exposures to the dog’s urine at his residence, and 16 human contacts with possible exposure to his urine or culture isolates at a veterinary hospital. Contacts were offered various combinations of symptom/fever monitoring, baseline and repeat B. pseudomallei serologic testing, and antibiotic post-exposure prophylaxis, depending on the nature of their exposure and their personal medical histories. The dog’s owner accepted recommendations from public health authorities and veterinary clinicians for humane euthanasia. A number of animal rescue organizations actively facilitate adoptions into the United States of shelter dogs from South-East Asia. This may result in importation of B. pseudomallei into almost any community, with implications for human and animal health.

      3. A multiplex serologic platform for diagnosis of tick-borne diseasesExternal
        Tokarz R, Mishra N, Tagliafierro T, Sameroff S, Caciula A, Chauhan L, Patel J, Sullivan E, Gucwa A, Fallon B, Golightly M, Molins C, Schriefer M, Marques A, Briese T, Lipkin WI.
        Sci Rep. 2018 Feb 16;8(1):3158.

        Tick-borne diseases are the most common vector-borne diseases in the United States, with serology being the primary method of diagnosis. We developed the first multiplex, array-based assay for serodiagnosis of tick-borne diseases called the TBD-Serochip. The TBD-Serochip was designed to discriminate antibody responses to 8 major tick-borne pathogens present in the United States, including Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, Ehrlichia chaffeensis, Rickettsia rickettsii, Heartland virus and Powassan virus. Each assay contains approximately 170,000 12-mer linear peptides that tile along the protein sequence of the major antigens from each agent with 11 amino acid overlap. This permits accurate identification of a wide range of specific immunodominant IgG and IgM epitopes that can then be used to enhance diagnostic accuracy and integrate differential diagnosis into a single assay. To test the performance of the TBD-Serochip, we examined sera from patients with confirmed Lyme disease, babesiosis, anaplasmosis, and Powassan virus disease. We identified a wide range of specific discriminatory epitopes that facilitated accurate diagnosis of each disease. We also identified previously undiagnosed infections. Our results indicate that the TBD-Serochip is a promising tool for a differential diagnosis not available with currently employed serologic assays for TBDs.

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Page last reviewed: January 31, 2019