Volume 10, Issue 43, November 13, 2018

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CDC Science Clips: Volume 10, Issue 43, November 13, 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!

The report consists of these components:

  1. CDC Public Health Grand Rounds
    • Chronic Diseases and Conditions – Diabetes

      1. How effective were lifestyle interventions in real-world settings that were modeled on the Diabetes Prevention Program?External
        Ali MK, Echouffo-Tcheugui J, Williamson DF.
        Health Aff (Millwood). 2012 Jan;31(1):67-75.

        We conducted a systematic review and meta-analysis of twenty-eight US-based studies applying the findings of the Diabetes Prevention Program, a clinical trial that tested the effects of a lifestyle intervention for people at high risk for diabetes, in real-world settings. The average weight change at twelve months after the intervention was a loss of about 4 percent from participants’ baseline weight. Change in weight was similar regardless of whether the intervention was delivered by clinically trained professionals or lay educators. Additional analyses limited to seventeen studies with a nine-month or greater follow-up assessment showed similar weight change. With every additional lifestyle session attended, weight loss increased by 0.26 percentage point. We conclude that costs associated with diabetes prevention can be lowered without sacrificing effectiveness, using nonmedical personnel and motivating higher attendance at program sessions.

      2. Lifestyle interventions to prevent type 2 diabetes: A systematic review of economic evaluation studiesExternal
        Alouki K, Delisle H, Bermudez-Tamayo C, Johri M.
        J Diabetes Res. 2016 ;2016:2159890.

        Objective. To summarize key findings of economic evaluations of lifestyle interventions for the primary prevention of type 2 diabetes (T2D) in high-risk subjects. Methods. We conducted a systematic review of peer-reviewed original studies published since January 2009 in English, French, and Spanish. Eligible studies were identified through relevant databases including PubMed, Medline, National Health Services Economic Evaluation, CINHAL, EconLit, Web of sciences, EMBASE, and the Latin American and Caribbean Health Sciences Literature. Studies targeting obesity were also included. Data were extracted using a standardized method. The BMJ checklist was used to assess study quality. The heterogeneity of lifestyle interventions precluded a meta-analysis. Results. Overall, 20 studies were retained, including six focusing on obesity control. Seven were conducted within trials and 13 using modeling techniques. T2D prevention by physical activity or diet or both proved cost-effective according to accepted thresholds, except for five inconclusive studies, three on diabetes prevention and two on obesity control. Most studies exhibited limitations in reporting results, primarily with regard to generalizability and justification of selected sensitivity parameters. Conclusion. This confirms that lifestyle interventions for the primary prevention of diabetes are cost-effective. Such interventions should be further promoted as sound investment in the fight against diabetes.

      3. Impact of the YMCA of the USA Diabetes Prevention Program on Medicare spending and utilizationExternal
        Alva ML, Hoerger TJ, Jeyaraman R, Amico P, Rojas-Smith L.
        Health Aff (Millwood). 2017 Mar 1;36(3):417-424.

        The YMCA of the USA received a Health Care Innovation Award from the Centers for Medicare and Medicaid Services to provide a diabetes prevention program to Medicare beneficiaries with prediabetes in seventeen regional networks of participating YMCAs nationwide. The goal of the program is to help participants lose weight and increase physical activity. We tested whether the program reduced medical spending and utilization in the Medicare population. Using claims data to compute total medical costs for fee-for-service Medicare participants and a matched comparison group of nonparticipants, we found that the overall weighted average savings per member per quarter during the first three years of the intervention period was $278. Total decreases in inpatient admissions and emergency department (ED) visits were significant, with nine fewer inpatient stays and nine fewer ED visits per 1,000 participants per quarter. These results justify continued support of the model.

      4. Diabetes: Combined Diet and Physical Activity Promotion Programs to Prevent Type 2 Diabetes Among People at Increased RiskExternal
        Community Preventive Services Task Force .
        Available from: https://www.thecommunityguide.org/findings/diabetes-combined-diet-and-physical-activity-promotion-programs-prevent-type-2-diabetes. 2014 .

        The Community Preventive Services Task Force (CPSTF) recommends combined diet and physical activity promotion programs for people at increased risk of type 2 diabetes to reduce new-onset diabetes. Combined diet and physical activity promotion programs also increase the likelihood of reverting to normoglycemia (normal blood sugar) and improve diabetes and cardiovascular disease risk factors, including overweight, high blood glucose, high blood pressure, and abnormal lipid profile. Based on the evidence, combined diet and physical activity promotion programs are effective across a range of counseling intensities, settings, and implementers. Programs commonly include a weight loss goal, individual or group sessions (or both) about diet and exercise, meetings with a trained diet or exercise counselor (or both), and individually tailored diet or exercise plans (or both). Higher intensity programs lead to greater weight loss and reduction in new-onset diabetes. Economic evidence indicates that these interventions are cost-effective.

      5. PURPOSE: The purpose of this report is (1) to describe the use of the American Association of Diabetes Educators’ (AADE’s) model of implementation of the National Diabetes Prevention Program through nationally certified diabetes self-management education (DSME) programs and (2) to report the aggregated program outcomes as defined by the Diabetes Prevention and Recognition Program standards of the Centers for Disease Control and Prevention (CDC). METHODS: In 2012, the AADE worked with the CDC to select 30 certified DSME programs for National Diabetes Prevention Program delivery. For the following 3 years, the AADE continued to work with 25 of the 30 original programs. Results for all CDC recognition standards have been collected from these 25 programs and analyzed as aggregated data over the course of 36 months. RESULTS: At the end of the full-year program, average percentage body weight loss for participants across all 25 programs exceeded the CDC’s minimum requirement of 5% weight loss. All programs on average met the CDC requirements for program attendance. CONCLUSION: Increasing access to the National Diabetes Prevention Program, through an array of networks, including certified DSME programs, will better ensure that people are able to engage in an effective approach to reducing their risk of diabetes.

      6. OBJECTIVE To summarize the evidence on effectiveness of translational diabetes prevention programs, based on promoting lifestyle change to prevent type 2 diabetes in real-world settings and to examine whether adherence to international guideline recommendations is associated with effectiveness. RESEARCH DESIGN AND METHODS Bibliographic databases were searched up to July 2012. Included studies had a follow-up of >/=12 months and outcomes comparing change in body composition, glycemic control, or progression to diabetes. Lifestyle interventions aimed to translate evidence from previous efficacy trials of diabetes prevention into real-world intervention programs. Data were combined using random-effects meta-analysis and meta-regression considering the relationship between intervention effectiveness and adherence to guidelines. RESULTS Twenty-five studies met the inclusion criteria. The primary meta-analysis included 22 studies (24 study groups) with outcome data for weight loss at 12 months. The pooled result of the direct pairwise meta-analysis shows that lifestyle interventions resulted in a mean weight loss of 2.12 kg (95% CI -2.61 to -1.63; I(2) = 91.4%). Adherence to guidelines was significantly associated with a greater weight loss (an increase of 0.3 kg per point increase on a 12-point guideline-adherence scale). CONCLUSIONS Evidence suggests that pragmatic diabetes prevention programs are effective. Effectiveness varies substantially between programs but can be improved by maximizing guideline adherence. However, more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects.

      7. A national effort to prevent type 2 diabetes: Participant-level evaluation of CDC’s National Diabetes Prevention ProgramExternal
        Ely EK, Gruss SM, Luman ET, Gregg EW, Ali MK, Nhim K, Rolka DB, Albright AL.
        Diabetes Care. 2017 Oct;40(10):1331-1341.

        OBJECTIVE: To assess participant-level results from the first 4 years of implementation of the National Diabetes Prevention Program (National DPP), a national effort to prevent type 2 diabetes in those at risk through structured lifestyle change programs. RESEARCH DESIGN AND METHODS: Descriptive analysis was performed on data from 14,747 adults enrolled in year-long type 2 diabetes prevention programs during the period February 2012 through January 2016. Data on attendance, weight, and physical activity minutes were summarized and predictors of weight loss were examined using a mixed linear model. All analyses were performed using SAS 9.3. RESULTS: Participants attended a median of 14 sessions over an average of 172 days in the program (median 134 days). Overall, 35.5% achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%). Participants reported a weekly average of 152 min of physical activity (median 128 min), with 41.8% meeting the physical activity goal of 150 min per week. For every additional session attended and every 30 min of activity reported, participants lost 0.3% of body weight (P < 0.0001). CONCLUSIONS: During the first 4 years, the National DPP has achieved widespread implementation of the lifestyle change program to prevent type 2 diabetes, with promising early results. Greater duration and intensity of session attendance resulted in a higher percent of body weight loss overall and for subgroups. Focusing on retention may reduce disparities and improve overall program results. Further program expansion and investigation is needed to continue lowering the burden of type 2 diabetes nationally.

      8. In type 2 diabetes (T2D) prevention research, evidence for maintenance of risk factor reduction after three years of follow-up is needed. The objective of this study was to evaluate the long-term effectiveness of a combined lifestyle intervention aiming at controlling body weight (BW) and waist circumference (WC) in non-diabetic, overweight/obese adults living in a low socio-economic community. On Reunion Island, 445 adults living in deprived areas, aged 18-40 and at high-risk for T2D, were included in an intervention versus control trial for primary prevention (2001-2002). The intervention promoted a healthy diet and moderate regular physical activity, through actions strengthening individuals or community and improving living conditions. The control group received a one-shot medical information and nutritional advices. After the end of the trial (2003), 259 of the subjects participated in a follow-up study (2010-2011). The outcomes were the nine-year changes from baseline in BW, body mass index (BMI) and WC measurements, separately. Statistical analyses were performed on an intention-to-treat basis, using available and imputed datasets. At inclusion, T2D risk factors were prevalent: family history of diabetes in first-degree relatives (42%), women with a personal history of gestational diabetes (11%), total obesity (43%, median BMI 29.1 kg/m(2)) and central obesity (71%). At follow-up, the adjusted effect on imputed dataset was significant for WC -2.4 cm (95% confidence interval: -4.7 to -0.0 cm, p = 0.046), non-significant for BW -2.2 kg (-4.6 to +0.2 kg, p = 0.073) and BMI -0.81 kg/m(2) (-1.69 to +0.08 kg/m(2), p = 0.074). A specific long-term effect was the increased likelihood of reduction in adiposity: BW loss, BMI reduction, and WC reduction were more frequent in the intervention group. In the context of low socio-economic communities, our data support the assumption of long-term effect of lifestyle interventions targeting total obesity and central obesity two major drivers of T2D.

      9. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metforminExternal
        Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM.
        N Engl J Med. 2002 Feb 7;346(6):393-403.

        BACKGROUND: Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors–elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle–are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. METHODS: We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. RESULTS: The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. CONCLUSIONS: Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.

      10. Effective translation of an intensive lifestyle intervention for Hispanic women with prediabetes in a community health center settingExternal
        Van Name MA, Camp AW, Magenheimer EA, Li F, Dziura JD, Montosa A, Patel A, Tamborlane WV.
        Diabetes Care. 2016 Apr;39(4):525-31.

        OBJECTIVE: The Diabetes Prevention Program (DPP) demonstrated that weight loss from intensive lifestyle intervention (ILI) in adults with prediabetes could decrease progression to type 2 diabetes. Inner-city, low-income Hispanic women are at high risk for developing type 2 diabetes; however, this type of intervention is not well established in this group. We hypothesized that a DPP intervention modified for a community health center (CHC) setting would decrease weight and improve metabolic measures in Hispanic women with prediabetes. RESEARCH DESIGN AND METHODS: Women diagnosed with prediabetes on a screening oral glucose tolerance test were recruited from a CHC. Participants (90% of whom were Hispanic) were randomized to either usual care (age 43 +/- 9.7 years, BMI 35.2 +/- 7.3 kg/m(2)) or ILI (age 43.8 +/- 10.8 years, BMI 35.4 +/- 8.5 kg/m(2)), structured as 14 weeks of group sessions focused on food choices, behavior change, physical activity, and weight loss. One year after enrollment, 122 women repeated baseline measures. RESULTS: Groups had similar baseline weight, BMI, and fasting and 2-h glucose. One year later, the ILI group had lost 3.8 kg (4.4%), while the usual care group had gained 1.4 kg (1.6%, P < 0.0001). Two-hour glucose excursion decreased 15 mg/dL (0.85 mmol/L) in the ILI and 1 mg/dL (0.07 mmol/L) in the usual care group (P = 0.03). Significant decreases favoring the ILI group were noted in BMI, percent body fat, waist circumference, and fasting insulin. CONCLUSIONS: A 14-week ILI program based on the DPP can effectively be translated into a predominantly Hispanic CHC setting, resulting in decreased weight, improved fasting insulin, and smaller glucose excursions 1 year after enrolling in the program.

      11. A nationwide community-based lifestyle program could delay or prevent type 2 diabetes cases and save $5.7 billion in 25 yearsExternal
        Zhuo X, Zhang P, Gregg EW, Barker L, Hoerger TJ, Tony P, Albright A.
        Health Aff (Millwood). 2012 Jan;31(1):50-60.

        The increasing health and economic burden of diabetes has made preventing the disease a public health priority. But investing in such chronic disease prevention programs requires a long-term horizon because many years may be required for the downstream savings to fully offset the up-front intervention cost. Using a simulation model, we projected the costs and benefits of a nationwide community-based lifestyle intervention program for preventing type 2 diabetes. Accounting for all costs to the US health care system, our results indicate that the program would break even in fourteen years. Within twenty-five years, the program would prevent or delay about 885,000 cases of type 2 diabetes in the United States and produce savings of $5.7 billion nationwide. If restricted to people ages 65-84, the program would save $2.4 billion. Thus, implementing such a program nationwide would be an efficient use of health care resources, although it might be necessary for all health insurers to participate to share prevention costs. Our results also indicate that although a prevention program would lead to cost savings in both younger and older people, it would achieve greater health and economic gains if it were directed at people under age sixty-five.

  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. Trends and disparities in cardiovascular mortality among U.S. adults with and without self-reported diabetes, 1988-2015External
        Cheng YJ, Imperatore G, Geiss LS, Saydah SH, Albright AL, Ali MK, Gregg EW.
        Diabetes Care. 2018 Nov;41(11):2306-2315.

        OBJECTIVE: Cardiovascular disease (CVD) mortality has declined substantially in the U.S. The aims of this study were to examine trends and demographic disparities in mortality due to CVD and CVD subtypes among adults with and without self-reported diabetes. RESEARCH DESIGN AND METHODS: We used the National Health Interview Survey (NHIS) (1985-2014) with mortality follow-up data through the end of 2015 to estimate nationally representative trends and disparities in major CVD, ischemic heart disease (IHD), stroke, heart failure, and arrhythmia mortality among adults >/=20 years of age by diabetes status. RESULTS: Over a mean follow-up period of 11.8 years from 1988 to 2015 of 677,051 adults, there were significant decreases in major CVD death (all P values <0.05) in adults with and without diabetes except adults 20-54 years of age. Among adults with diabetes, 10-year relative changes in mortality were significant for major CVD (-32.7% [95% CI -37.2, -27.9]), IHD (-40.3% [-44.7, -35.6]), and stroke (-29.2% [-40.0, -16.5]), but not heart failure (-0.5% [-20.7, 24.7]), and arrhythmia (-12.0% [-29.4, 77.5]); the absolute decrease of major CVD among adults with diabetes was higher than among adults without diabetes (P < 0.001). Men with diabetes had larger decreases in CVD death than women with diabetes (P < 0.001). CONCLUSIONS: Major CVD mortality in adults with diabetes has declined, especially in men. Large reductions were observed for IHD and stroke mortality, although heart failure and arrhythmia deaths did not change. All race and education groups benefitted to a similar degree, but significant gaps remained across groups.

      2. Prevalence and changes in preexisting diabetes and gestational diabetes among women who had a live birth – United States, 2012-2016External
        Deputy NP, Kim SY, Conrey EJ, Bullard KM.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 2;67(43):1201-1207.

        Diabetes during pregnancy increases the risk for adverse maternal and infant health outcomes. Type 1 or type 2 diabetes diagnosed before pregnancy (preexisting diabetes) increases infants’ risk for congenital anomalies, stillbirth, and being large for gestational age (1). Diabetes that develops and is diagnosed during the second half of pregnancy (gestational diabetes) increases infants’ risk for being large for gestational age (1) and might increase the risk for childhood obesity (2); for mothers, gestational diabetes increases the risk for future type 2 diabetes (3). In the United States, prevalence of both preexisting and gestational diabetes increased from 2000 to 2010 (4,5). Recent state-specific trends have not been reported; therefore, CDC analyzed 2012-2016 National Vital Statistics System (NVSS) birth data. In 2016, the crude national prevalence of preexisting diabetes among women with live births was 0.9%, and prevalence of gestational diabetes was 6.0%. Among 40 jurisdictions with continuously available data from 2012 through 2016, the age- and race/ethnicity-standardized prevalence of preexisting diabetes was stable at 0.8% and increased slightly from 5.2% to 5.6% for gestational diabetes. Preconception care and lifestyle interventions before, during, and after pregnancy might provide opportunities to control, prevent, or mitigate health risks associated with diabetes during pregnancy.

    • Communicable Diseases

      1. Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communitiesExternal
        Auld SC, Shah NS, Mathema B, Brown TS, Ismail N, Omar SV, Brust JC, Nelson KN, Allana S, Campbell A, Mlisana K, Moodley P, Gandhi NR.
        Eur Respir J. 2018 Oct;52(4).

        Despite evidence that transmission is driving an extensively drug-resistant TB (XDR-TB) epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection.We conducted a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the 2011-2014 period. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections. We performed whole-genome sequencing (WGS) on the Mycobacterium tuberculosis isolates and determined pairwise single nucleotide polymorphism (SNP) differences.Among 404 participants, 123 (30%) had person-to-person or hospital-based links, leaving 281 (70%) epidemiologically unlinked. The median SNP difference between participants with person-to-person and hospital-based links was 10 (interquartile range (IQR) 8-24) and 16 (IQR 10-23), respectively. The median SNP difference between unlinked participants and their closest genomic link was 5 (IQR 3-9) and half of unlinked participants were within 7 SNPs of at least five participants.The majority of epidemiologically-unlinked XDR-TB patients had low pairwise SNP differences with at least one other participant, consistent with transmission. These data suggest that much of transmission may result from casual contact in community settings between individuals not known to one another.

      2. Tuberculosis incidence among populations at high risk in California, Florida, New York, and Texas, 2011-2015External
        Cherng ST, Shrestha S, Reynolds S, Hill AN, Marks SM, Kelly J, Dowdy DW.
        Am J Public Health. 2018 Nov;108(S4):S311-s314.

        OBJECTIVES: To illustrate the magnitude of between-state heterogeneities in tuberculosis (TB) incidence among US populations at high risk for TB that may help guide state-specific strategies for TB elimination. METHODS: We used data from the National Tuberculosis Surveillance System and other public sources from 2011 to 2015 to calculate TB incidence in every US state among people who were non-US-born, had diabetes, or were HIV-positive, homeless, or incarcerated. We then estimated the proportion of TB cases that reflected the difference between each state’s reported risk factor-specific TB incidence and the lowest incidence achieved among 4 states (California, Florida, New York, Texas). We reported these differences for the 4 states and also calculated and aggregated across all 50 states to quantify the total percentage of TB cases nationally that reflected between-state differences in risk factor-specific TB incidence. RESULTS: On average, 24% of recent TB incidence among high-risk US populations reflected heterogeneity at the state level. The populations that accounted for the greatest percentage of heterogeneity-reflective cases were non-US-born individuals (51%) and patients with diabetes (24%). CONCLUSIONS: State-level differences in TB incidence among key populations provide clues for targeting state-level interventions.

      3. Antimicrobial resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic MeetingExternal
        Cristillo AD, Bristow CC, Torrone E, Dillon JA, Kirkcaldy RD, Dong H, Grad YH, Nicholas RA, Rice PA, Lawrence K, Oldach D, Shafer WM, Zhou P, Wi TE, Morris SR, Klausner JD.
        Sex Transm Dis. 2018 Oct 22.

        The goal of the Sexually Transmitted Infection Clinical Trial Group’s (STI-CTG) Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, non-profit and industry to discuss the current state of research, gaps and challenges in research and technology as well as priorities and new directions to address the continued emergence of multi-drug resistant NG infections. Topics discussed at the meeting, that will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing (WGS) and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG. (ii) The US National Strategy for combating antimicrobial resistant bacteria. (iii) Surveillance needs, challenges and novel technologies. (iv) Plasmid- and chromosomally-mediated mechanisms of AMR in NG, (v) Novel therapeutic (e.g., sialic acid analogs, FH/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (e.g., peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives and collaborations across academic and commercial research and public health programs.

      4. Selling and buying sex in the city: men who have sex with men in the Bangkok Men Who Have Sex With Men Cohort StudyExternal
        Dunne EF, Pattanasin S, Chemnasiri T, Varangrat A, Raengsakulrach B, Wichuda S, Ungsedhapand C, Sirivongrangson P, Chitwarakorn A, Holtz TH.
        Int J STD AIDS. 2018 Oct 26:956462418796440.

        We describe participants in the Bangkok Men who have sex with men Cohort Study (BMCS) who sold or bought sex. Men who have sex with men (MSM) and transgender women aged >/=18 years had HIV testing and behavioral data collected at enrollment and every four months. We evaluated report of receiving money or goods for sex (selling sex) or giving money or goods for sex (buying sex) at enrollment using logistic regression models; we also describe sex work over time, and HIV and syphilis incidence among those who report sex work. At enrollment, 511 (29.3%) of 1744 participants reported buying or selling sex. Factors associated with selling sex were young age, lower education, living alone or living with a friend, being unemployed, higher HIV knowledge, binge drinking and club drug use, a higher number of casual male partners, meeting sex partners at specific venues, having a foreign sex partner, and being HSV-1 seropositive. MSM aged 18-21 years who sold sex had an HIV incidence of 11.1 per 100 person-years (95% CI: 6.7-17.4). Almost one-third of participants from BMCS reported sex work at enrollment. Young men who sold sex had high HIV incidence and HIV prevention interventions are needed for this at-risk population in Bangkok, Thailand.

      5. Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second-line switches in SwazilandExternal
        Etoori D, Ciglenecki I, Ndlangamandla M, Edwards CG, Jobanputra K, Pasipamire M, Maphalala G, Yang C, Zabsonre I, Kabore SM, Goiri J, Teck R, Kerschberger B.
        J Int AIDS Soc. 2018 Oct;21(10):e25194.

        INTRODUCTION: As antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource-constrained settings report significant shortfalls. METHODS: From a public sector HIV programme in rural Swaziland, we evaluated the VL cascade of adults (>/=18 years) on ART from the time of the first elevated VL (>1000 copies/mL) between January 2013 and June 2014 to treatment switching by December 2015. We additionally described HIV drug resistance for patients with virological failure. We used descriptive statistics and Kaplan-Meier estimates to describe the different steps along the cascade and regression models to determine factors associated with outcomes. RESULTS AND DISCUSSION: Of 828 patients with a first elevated VL, 252 (30.4%) did not receive any enhanced adherence counselling (EAC). Six hundred and ninety-six (84.1%) patients had a follow-up VL measurement, and the predictors of receiving a follow-up VL were being a second-line patient (adjusted hazard ratio (aHR): 0.72; p = 0.051), Hlathikhulu health zone (aHR: 0.79; p = 0.013) and having received two EAC sessions (aHR: 1.31; p = 0.023). Four hundred and ten patients (58.9%) achieved VL re-suppression. Predictors of re-suppression were age 50 to 64 (adjusted odds ratio (aOR): 2.02; p = 0.015) compared with age 18 to 34 years, being on second-line treatment (aOR: 3.29; p = 0.003) and two (aOR: 1.66; p = 0.045) or three (aOR: 1.86; p = 0.003) EAC sessions. Of 278 patients eligible to switch to second-line therapy, 120 (43.2%) had switched by the end of the study. Finally, of 155 successfully sequenced dried blood spots, 144 (92.9%) were from first-line patients. Of these, 133 (positive predictive value: 92.4%) had resistance patterns that necessitated treatment switching. CONCLUSIONS: Patients on ART with high VLs were more likely to re-suppress if they received EAC. Failure to re-suppress after counselling was predictive of genotypically confirmed resistance patterns requiring treatment switching. Delays in switching were significant despite the ability of the WHO algorithm to predict treatment failure. Despite significant progress in recent years, enhanced focus on quality care along the VL cascade in resource-limited settings is crucial.

      6. Predictors of perinatal HIV transmission among women without prior antiretroviral therapy in a resource-limited setting: The BAN StudyExternal
        Ewing AC, Ellington SR, Wiener JB, Chasela CS, Tegha G, Nelson JA, Jamieson DJ, van der Horst C, Kourtis AP.
        Pediatr Infect Dis J. 2018 Oct 30.

        OBJECTIVES: To investigate potential risk factors for perinatal (intrauterine and intrapartum) mother-to-child transmission of HIV (MTCT) in women unexposed to Antiretroviral Therapy (ART) during pregnancy. METHODS: We compared factors according to perinatal MTCT outcome among 2,275 ART-naive (until the onset of labor) HIV-infected women in the Breastfeeding, Antiretrovirals and Nutrition study (2004-2010) in Lilongwe, Malawi. Factors included HIV viral load during pregnancy, food security, demographic characteristics, hematologic and blood chemistry measures, medical history and physical factors. Associations with perinatal MTCT and interactions with maternal viral load were assessed using simple and multivariable logistic regression. RESULTS: There were 119 (115 intrauterine, 4 intrapartum) cases of perinatal MTCT; only one to a mother with <1,000 HIV copies/mL. Maternal viral loads >10,000 copies/mL were common (63.1%). Lower maternal viral load (<1,000 copies/mL and 1,000.1-10,000 copies/mL) was associated with reduced odds of perinatal MTCT [adjusted odds ratio (aOR), 0.1; 95% confidence interval (CI), 0.01-0.4 and aOR, 0.2; 95% CI, 0.1-0.4, respectively), compared with maternal viral load >10,000 copies/mL. Low CD4+ T cell count (</= 350 cells/microL) was only associated with perinatal MTCT in unadjusted models. Food shortage (aOR, 1.8; 95% CI; 1.2-2.6), sexually transmitted infection (past year) (aOR, 1.9; 95% CI; 1.0-3.7), histories of herpes zoster (aOR, 3.0; 95% CI; 1.6-5.6) and tuberculosis (aOR, 2.5; 95% CI; 1.1-5.7) were associated with increased odds of perinatal MTCT. CONCLUSIONS: These findings confirm that lowering maternal HIV viral load is most important in preventing perinatal MTCT, and support efforts to address food shortage, STD and TB prevention, while informing programs to improve ART coverage in pregnancy.

      7. Hepatitis A virus outbreaks associated with drug use and homelessness – California, Kentucky, Michigan, and Utah, 2017External
        Foster M, Ramachandran S, Myatt K, Donovan D, Bohm S, Fiedler J, Barbeau B, Collins J, Thoroughman D, McDonald E, Ballard J, Eason J, Jorgensen C.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 2;67(43):1208-1210.

        During 2017, CDC received 1,521 reports of acute hepatitis A virus (HAV) infections from California, Kentucky, Michigan, and Utah; the majority of infections were among persons reporting injection or noninjection drug use or homelessness. Investigations conducted by local and state health departments indicated that direct person-to-person transmission of HAV infections was occurring, differing from other recent, large HAV outbreaks attributed to consumption of contaminated commercial food products. Outbreaks with direct HAV transmission among persons reporting drug use or homelessness signals a shift in HAV infection epidemiology in the United States, and vaccination of these populations at high risk can prevent future outbreaks.

      8. Impact of public health responses during a measles outbreak in an Amish community in Ohio: Modeling the dynamics of transmissionExternal
        Gastanaduy PA, Funk S, Paul P, Tatham L, Fisher N, Budd J, Fowler B, de Fijter S, DiOrio M, Wallace GS, Grenfell B.
        Am J Epidemiol. 2018 Sep 1;187(9):2002-2010.

        We quantified measles transmissibility during a measles outbreak in Ohio in 2014 to evaluate the impact of public health responses. Case incidence and the serial interval (time between symptom onset in primary cases and secondary cases) were used to assess trends in the effective reproduction number R (the average number of secondary cases generated per case). A mathematical model was parameterized using early R values to determine the size and duration of the outbreak that would have occurred if containment measures had not been initiated, as well as the impact of vaccination. As containment started, we found a 4-fold decline in R (from approximately 4 to 1) over the course of 2 weeks and maintenance of R < 1 as control measures continued. Under a conservative scenario, the model estimated 8,472 cases (90% confidence interval (CI): 8,447, 8,489) over 195 days (90% CI: 179, 223) without control efforts and 715 cases (90% CI: 103, 1,338) over 128 days (90% CI: 117, 139) when vaccination was included; 7,757 fewer cases (90% CI: 7,130, 8,365) and 67 fewer outbreak days (90% CI: 48, 98) were attributed to vaccination. Vaccination may not account entirely for transmission reductions, suggesting that changes in community behavior (social distancing) and other control efforts (isolation, quarantining) are important. Our findings highlight the benefits of measles outbreak response and of understanding behavior change dynamics.

      9. Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with menExternal
        Haaland RE, Fountain J, Hu Y, Holder A, Dinh C, Hall L, Pescatore NA, Heeke S, Hart CE, Xu J, Hu YJ, Kelley CF.
        J Int AIDS Soc. 2018 Oct;21(10):e25199.

        INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is highly effective in preventing HIV infection among men who have sex with men (MSM). The effects of consistent personal lubricant use in the rectum on tissue PrEP drug concentrations and the rectal microbiota are unknown. We investigated rectal PrEP drug concentrations and the microbiota in MSM before and after repeated rectal application of a hyperosmolar lubricant. METHODS: We randomized 60 HIV-negative MSM to apply 4 mL of hyperosmolar rectal lubricant daily (n = 20), take daily oral TDF/FTC (n = 19), or both (n = 21) for seven days. Blood, rectal biopsies and rectal secretions were collected via rigid sigmoidoscopy before and on day 8 after product use. Tenofovir (TFV) and FTC as well as their intracellular metabolites tenofovir-diphosphate (TFV-DP), FTC-triphosphate (FTC-TP) were measured by HPLC-mass spectrometry. Rectal mucosal microbiota was sequenced with 16S rRNA sequencing using Illumina MiSeq. RESULTS: Seven days of lubricant application was not associated with differences in PrEP drug concentrations in rectal tissue or secretions. Lubricant use was associated with a decrease in the relative abundance of the Bacteroides genus (p = 0.01) and a non-significant increase in the Prevotella genus (p = 0.09) in the rectum. PrEP drug concentrations in rectal tissue and secretions were not associated with microbiota composition or diversity either before or after lubricant use. CONCLUSIONS: Repeated rectal application of a hyperosmolar lubricant does not affect mucosal PrEP drug concentrations but is associated with changes in the rectal microbiome.

      10. Potential impact of HIV preexposure prophylaxis among black and white adolescent sexual minority malesExternal
        Hamilton DT, Goodreau SM, Jenness SM, Sullivan PS, Wang LY, Dunville RL, Barrios LC, Rosenberg ES.
        Am J Public Health. 2018 Nov;108(S4):S284-s291.

        OBJECTIVES: To assess the potential impact of preexposure prophylaxis (PrEP) on the HIV epidemic among Black and White adolescent sexual minority males (ASMM). METHODS: We used a network model and race-specific data from recent trials to simulate HIV transmission among a population of Black and White 13- to 18-year-old ASMM over 20 years. We estimated the number of infections prevented (impact) and the number needed to treat to prevent an infection (efficiency) under multiple coverage and adherence scenarios. RESULTS: At modeled coverage and adherence, PrEP could avert 3% to 20% of infections among Black ASMM and 8% to 51% among White ASMM. A larger number, but smaller percentage, of infections were prevented in Black ASMM in all scenarios examined. PrEP was more efficient among Black ASMM (number needed to treat to avert an infection = 25-32) compared with White ASMM (146-237). CONCLUSIONS: PrEP can reduce HIV incidence among both Black and White ASMM but is far more efficient for Black ASMM because of higher incidence. Public Health Implications. Black ASMM communities suffer disproportionate HIV burden; despite imperfect adherence, PrEP programs could prevent HIV efficiently in these communities.

      11. Age-period-cohort analyses of tuberculosis incidence rates by nativity, United States, 1996-2016External
        Iqbal SA, Winston CA, Bardenheier BH, Armstrong LR, Navin TR.
        Am J Public Health. 2018 Nov;108(S4):S315-s320.

        OBJECTIVES: To assess changes in US tuberculosis (TB) incidence rates by age, period, and cohort effects, stratified according to race/ethnicity and nativity. METHODS: We used US National Tuberculosis Surveillance System data for 1996 to 2016 to estimate trends through age-period-cohort models. RESULTS: Controlling for cohort and period effects indicated that the highest rates of TB incidence occurred among those 0 to 5 and 20 to 30 years of age. The incidence decreased by age for successive birth cohorts. There were greater estimated annual percentage decreases among US-born individuals (-7.3%; 95% confidence interval [CI] = -7.5, -7.1) than among non-US-born individuals (-4.3%; 95% CI = -4.5, -4.1). US-born individuals older than 25 years exhibited the largest decreases, a pattern that was not reflected among non-US-born adults. In the case of race/ethnicity, the greatest decreases by nativity were among US-born Blacks (-9.3%; 95% CI = -9.6, -9.1) and non-US-born Hispanics (-5.7%; 95% CI = -6.0, -5.5). CONCLUSIONS: TB has been decreasing among all ages, races and ethnicities, and consecutive cohorts, although these decreases are less pronounced among non-US-born individuals.

      12. Background: Care and viral suppression national goals for HIV infection are not being met for many at-risk groups. Assessment of the trends in national outcomes for linkage to care, receipt of care, and viral suppression among these groups is necessary to reduce transmission. Methods: Data reported to the National HIV Surveillance System by December 2016 were used to identify cases of HIV infection among persons aged 13 years and older in one of 17 identified jurisdictions with complete laboratory reporting. We estimated national trends in HIV-related linkage to care, receipt of care and viral suppression using estimated annual percent change from 2012-2015 for various characteristics of interest, overall and stratified by sex and race/ethnicity. Results: Overall, trends in linkage to and receipt of care and viral suppression increased from 2012-2015. Generally, linkage to and receipt of care increased among young black and Hispanic/Latino males, those with infection attributed to male-to-male sexual contact, and those not in stage 3 [AIDS] at HIV diagnosis. All sub-groups showed improvement in viral suppression. Within years, there remains a substantial disparity in receipt of care and viral suppression among racial/ethnic groups. Conclusion: While trends are encouraging, scientifically proven prevention programs targeted to high-risk populations are the foundation for stopping transmission of HIV infection. Frequent testing to support early diagnosis and prompt linkage to medical care, particularly among young men who have male to male sexual contact, black and Hispanic/Latino populations, are key to reducing transmission at all stages of disease.

      13. A recent infection testing algorithm (RITA) that includes a test for recent HIV infection and a viral load (VL) test is the recommended strategy to estimate national HIV incidence, reducing false-recent misclassification to <1%. The inclusion of information on exposure to antiretroviral therapy (ART), as a supplement to VL testing, could improve RITA performance by further lowering false-recent misclassification of true long-term infection. In 2012, Kenya and South Africa conducted national population-based surveys that collected information on HIV recency (i.e., HIV antibody seroconversion, on average, in the past 130 days) using the Limiting Antigen avidity (LAg-Avidity) enzyme immunoassay, HIV RNA levels, and ART exposure among HIV-infected respondents aged 15-49 years. In Kenya, ART exposure was defined as testing positive for one or more antiretroviral (ARV) drugs using high-performance liquid chromatography coupled with tandem mass spectrometry, and, if not ARV-positive, self-reporting a history of ART exposure. In South Africa, ART exposure was defined as testing ARV-positive. Two RITA strategies were compared: RITA #1 defined recent infection as testing LAg-Avidity-recent with unsuppressed VL (HIV RNA >/=1,000 copies/ml), and RITA #2 defined recent infection as testing LAg-Avidity-recent with unsuppressed VL and, if unsuppressed, having no ART exposure. RITA-derived incidence among persons aged 15-49 years in Kenya was 0.9% on RITA #1 and 0.8% on RITA #2. In South Africa, RITA-derived incidence was 2.2% on RITA #1 and 1.7% on RITA #2. Among specimens testing recent with unsuppressed VL in Kenya and South Africa, 16.0% and 19.7% had evidence of ART exposure, respectively. Although the performance of a VL- and ART-based RITA was encouraging, additional research is needed across HIV-1 subtypes and subpopulations to calibrate and validate this algorithm.

      14. Seroepidemiology of hepatitis viruses and hepatitis B genotypes of female marriage immigrants in KoreaExternal
        Kwon JC, Chang HY, Kwon OY, Park JH, Oh IS, Kim HJ, Lee JH, Roh HJ, Lee HW.
        Yonsei Med J. 2018 Nov;59(9):1072-1078.

        PURPOSE: The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. MATERIALS AND METHODS: Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. RESULTS: Subjects’ median age was 33 years (20-40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). CONCLUSION: Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

      15. Evaluation of the impact of a sequencing assay for detection of drug resistance on the clinical management of tuberculosisExternal
        Lowenthal P, Lin SG, Desmond E, Shah N, Flood J, Barry PM.
        Clin Infect Dis. 2018 Nov 1.

        Background: In 2012, the California Department of Public Health began using pyrosequencing (PSQ) to detect mutations associated with resistance to isoniazid, rifampin, quinolones and injectable drugs in Mycobacterium tuberculosis complex. We evaluated the impact of the PSQ assay on the clinical management of tuberculosis (TB) in California. Methods: TB surveillance and laboratory data for specimens submitted 8/1/2012-12/31/2016 were analyzed to determine time to effective treatment initiation. A survey of clinicians was used to assess how PSQ results influenced clinical decision-making. Results: Of 1,957 specimens tested with PSQ, 52% were sediments and 46% were culture isolates, submitted 8 and 35 days (median) after collection, respectively. Among 36 patients with multidrug-resistant TB (MDR-TB) who had a sediment specimen submitted for PSQ, median time from specimen collection to MDR-TB treatment initiation was 12 days vs 51 days when PSQ was not used. Of 303 TB patients with a completed survey, 126 (42%) clinicians reported PSQ as a reason for treatment change. Twenty-one patients either had an MDR-TB risk factor and a smear positive sputum specimen, but had PSQ performed on a culture isolate (9 of 36; 25%); or, didn’t have PSQ used for MDR-TB diagnosis (12 of 38; 32%) and thus, had an opportunity for earlier MDR-TB diagnosis with PSQ on sediment. Conclusions: Patients with MDR-TB initiated effective treatment five weeks earlier when PSQ was used compared to those without PSQ. Survey data suggest clinicians use PSQ to devise effective TB drug regimens. To maximize the benefit of PSQ, earlier submission of specimens should be prioritized.

      16. Making the link: A pilot health navigation intervention to improve timely linkage to care for men who have sex with men and transgender women recently diagnosed with HIV in Guatemala CityExternal
        Loya-Montiel MI, Davis DA, Aguilar-Martinez JM, Paz Bailey OA, Morales-Miranda S, Alvis-Estrada JP, Northbrook S, Barrington C.
        AIDS Behav. 2018 Oct 30.

        We piloted a health navigation strategy to promote timely linkage to care among men who have sex with men (MSM) and transgender women (TW) recently diagnosed with HIV in Guatemala City. We used a mixed-methods approach, integrating quantitative data collected during clinic visits and qualitative data from in-depth interviews, to characterize acceptability of navigation and time to linkage, defined as having the first clinical care visit. Out of 54 participants who enrolled in the pilot (n = 52 MSM; n = 2 TW), 50 (92.6%) accepted navigation and all were linked to care. Median time to linkage was 3 days (Interquartile Range 2-5 days). In qualitative interviews, participants expressed feeling scared and alone following their diagnosis and appreciated the support of a navigator, especially when they did not feel they could access their existing support networks. Future research and evaluation should continue to assess how to best use health navigation to support key populations recently diagnosed with HIV.

      17. Using an email alert to improve identification of pregnancy status for women with syphilis – Florida, 2017-2018External
        Matthias JM, Keller G, George D, Wilson C, Peterman TA.
        Sex Transm Dis. 2018 Oct 22.

        BACKGROUND: Congenital syphilis can be prevented if syphilis is treated early in pregnancy. Identifying women with syphilis who are pregnant facilitates prioritization for follow-up. In 2016, Florida reported 1,062 female syphilis cases, aged 15-44 years, and 160 (15%) cases were missing pregnancy status. The Florida Department of Health developed a system-generated weekly email notification sent to local program staff for all female syphilis investigations with unknown pregnancy status. We describe the outcome of these efforts to reduce unknown pregnancy status among women with syphilis. METHODS: Review of the frequency and outcomes (reduction in investigations flagged and change in pregnancy status variable) of the first email notification (10/2/2017) were compared to subsequent notifications through 6/25/2018. In addition, we reviewed pregnancy status of reported female syphilis cases (aged 15-44 years) from 2013-2018. RESULTS: The first email notification listed 76 investigations with unknown pregnancy status. This number decreased to 40 in one week and to 22 by one month. The decreased volume continued through June 2018 (n=13). Of the original 76 investigations, 3 women were pregnant and 38 (50%) were determined to meet the syphilis case definition (including 1 who was pregnant). In 2017, pregnancy ascertainment for female syphilis cases reached 98%. CONCLUSIONS: Focused efforts using email notification to obtain pregnancy status improved ascertainment in large STD programs with minimal effort. Most but not all women with unknown pregnancy status were identified as not pregnant.

      18. Tuberculosis preventive treatment: the next chapter of tuberculosis elimination in IndiaExternal
        Moonan PK, Nair SA, Agarwal R, Chadha VK, Dewan PK, Gupta UD, Ho CS, Holtz TH, Kumar AM, Kumar N, Kumar P, Maloney SA, Mase SR, Oeltmann JE, Paramasivan CN, Parmar MM, Rade KK, Ramachandran R, Rao R, Salhorta VS, Sarin R, Sarin S, Sachdeva KS, Selvaraju S, Singla R, Surie D, Tonsing J, Tripathy SP, Khaparde SD.
        BMJ Glob Health. 2018 ;3(5):e001135.

        The End TB Strategy envisions a world free of tuberculosis-zero deaths, disease and suffering due to tuberculosis by 2035. This requires reducing the global tuberculosis incidence from >1250 cases per million people to <100 cases per million people within the next two decades. Expanding testing and treatment of tuberculosis infection is critical to achieving this goal. In high-burden countries, like India, the implementation of tuberculosis preventive treatment (TPT) remains a low priority. In this analysis article, we explore potential challenges and solutions of implementing TPT in India. The next chapter in tuberculosis elimination in India will require cost-effective and sustainable interventions aimed at tuberculosis infection. This will require constant innovation, locally driven solutions to address the diverse and dynamic tuberculosis epidemiology and persistent programme monitoring and evaluation. As new tools, regimens and approaches emerge, midcourse adjustments to policy and practice must be adopted. The development and implementation of new tools and strategies will call for close collaboration between local, national and international partners-both public and private-national health authorities, non-governmental organisations, research community and the diagnostic and pharmaceutical industry. Leading by example, India can contribute to global knowledge through operational research and programmatic implementation for combating tuberculosis infection.

      19. Compromise of second-line antiretroviral therapy due to high rates of human immunodeficiency virus drug resistance in Mozambican treatment-experienced children with virologic failureExternal
        Vaz P, Buck WC, Bhatt N, Bila D, Auld A, Houston J, Cossa L, Alfredo C, Jobarteh K, Sabatier J, Macassa E, Sousa A, DeVos J, Jani I, Yang C.
        J Pediatric Infect Dis Soc. 2018 Oct 25.

        Background: Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. Methods: Children aged 1 to 14 years on ART for >/=12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with >/=1000 copies/mL were genotyped. Results: Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. Conclusion: This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings.

      20. Trends in poliovirus seroprevalence in Kano State, Northern NigeriaExternal
        Verma H, Iliyasu Z, Craig KT, Molodecky NA, Urua U, Jibir BW, Gwarzo GD, Gajida AU, McDonald S, Weldon WC, Oberste MS, Braka F, Mkanda P, Sutter RW.
        Clin Infect Dis. 2018 Oct 30;67(suppl_1):S103-s109.

        Background: Kano state has been a protracted reservoir of poliovirus in Nigeria. Immunity trends have been monitored through seroprevalence surveys since 2011. The survey in 2015 was, in addition, intended to assess the impact of use of inactivated poliovirus vaccine (IPV). Methods: It was a health facility based seroprevalence survey. Eligible children aged 6-9, 12-15 and 19-22 months of age brought to the paediatrics outpatient department of Murtala Mohammad Specialist Hospital between 19 October and 6 November 2015, were screened for eligibility. Eligible children were enrolled after parental consent, history taken, physical examination conducted, and a blood sample collected to test for neutralizing antibody titres against the three poliovirus serotypes. Results: Overall, 365 results were available in the three age groups. In the 6-9-month-old age group, the seroprevalence was 73% (95% confidence interval [CI] 64-80%), 83% (95% CI 75-88%), and 66% (95% CI 57-73%) for serotypes 1, 2, and 3, respectively. In the 12-15- and 19-22-month-old age groups, seroprevalence was higher but still remained <90% across serotypes. Seroprevalence to serotypes 1 and 3 in 2015 was similar to 2014; however, for serotype 2 there was a significant improvement. IPV received in supplemental immunization activities was found to be a significant predictor of seropositivity among 6-9-month-old infants for serotypes 1 and 2. Conclusions: Seroprevalence for serotypes 1 and 3 remains low (<80%) in 6-9-month-olds. This poses a significant risk for poliovirus spread if reintroduced into the population. Efforts to strengthen immunization coverage are imperative to secure and sustain high population immunity.

      21. Influenza viral shedding in a prospective cohort of HIV-infected and uninfected children and adults in 2 provinces of South Africa, 2012-2014External
        von Mollendorf C, Hellferscee O, Valley-Omar Z, Treurnicht FK, Walaza S, Martinson NA, Lebina L, Mothlaoleng K, Mahlase G, Variava E, Cohen AL, Venter M, Cohen C, Tempia S.
        J Infect Dis. 2018 Sep 8;218(8):1228-1237.

        Background: Prolonged shedding of influenza viruses may be associated with increased transmissibility and resistance mutation acquisition due to therapy. We compared duration and magnitude of influenza shedding between human immunodeficiency virus (HIV)-infected and -uninfected individuals. Methods: A prospective cohort study during 3 influenza seasons enrolled patients with influenza-like illness and a positive influenza rapid test. Influenza viruses were detected by real-time reverse transcription polymerase chain reaction. Weibull accelerated failure time regression models were used to describe influenza virus shedding. Mann-Whitney U tests explored initial influenza viral loads (VL). Results: Influenza virus shedding duration was similar in 65 HIV-infected (6 days; interquartile range [IQR] 3-10) and 176 HIV-uninfected individuals (7 days; IQR 4-11; P = .97), as was initial influenza VL (HIV-uninfected 5.28 +/- 1.33 log10 copies/mL, HIV-infected 4.73 +/- 1.68 log10 copies/mL; P = .08). Adjusted for age, HIV-infected individuals with low CD4 counts shed influenza virus for longer than those with higher counts (adjusted hazard ratio 3.55; 95% confidence interval, 1.05-12.08). Discussion: A longer duration of influenza virus shedding in HIV-infected individuals with low CD4 counts may suggest a possible increased risk for transmission or viral evolution in severely immunocompromised individuals. HIV-infected individuals should be prioritized for annual influenza immunization.

      22. Whole genome sequencing for investigations of meningococcal outbreaks in the United States: a retrospective analysisExternal
        Whaley MJ, Joseph SJ, Retchless AC, Kretz CB, Blain A, Hu F, Chang HY, Mbaeyi SA, MacNeil JR, Read TD, Wang X.
        Sci Rep. 2018 Oct 25;8(1):15803.

        Although rare in the U.S., outbreaks due to Neisseria meningitidis do occur. Rapid, early outbreak detection is important for timely public health response. In this study, we characterized U.S. meningococcal isolates (N = 201) from 15 epidemiologically defined outbreaks (2009-2015) along with temporally and geographically matched sporadic isolates using multilocus sequence typing, pulsed-field gel electrophoresis (PFGE), and six whole genome sequencing (WGS) based methods. Recombination-corrected maximum likelihood (ML) and Bayesian phylogenies were reconstructed to identify genetically related outbreak isolates. All WGS analysis methods showed high degree of agreement and distinguished isolates with similar or indistinguishable PFGE patterns, or the same strain genotype. Ten outbreaks were caused by a single strain; 5 were due to multiple strains. Five sporadic isolates were phylogenetically related to 2 outbreaks. Analysis of 9 outbreaks using timed phylogenies identified the possible origin and estimated the approximate time that the most recent common ancestor emerged for outbreaks analyzed. U.S. meningococcal outbreaks were caused by single- or multiple-strain introduction, with organizational outbreaks mainly caused by a clonal strain and community outbreaks by divergent strains. WGS can infer linkage of meningococcal cases when epidemiological links are uncertain. Accurate identification of outbreak-associated cases requires both WGS typing and epidemiological data.

    • Disaster Control and Emergency Services
      1. ABSTRACTOn October 7, 2016, Hurricane Matthew traveled along the coasts of Florida, Georgia, and South Carolina causing flooding and power outages. The Georgia Department of Public Health (DPH) developed the Web-based Responder Safety, Tracking, and Resilience (R-STaR) system to monitor the health and safety of public health responders and to inform disaster response planning for Hurricane Matthew. Using R-STaR, responders (n = 126) were e-mailed a daily survey while deployed to document injuries or harmful exposures and a post-deployment survey on their post-deployment health and satisfaction with using R-STaR. DPH epidemiologists contacted responders reporting injuries or exposures to determine the need for medical care. Frequencies were tabulated for quantitative survey responses, and qualitative data were summarized into key themes. Five percent (6/126) of responders reported injuries, and 81% (43/53) found R-STaR easy to use. Suggestions for R-STaR improvement included improving accessibility using mobile platforms and conducting pre-event training of responders on R-STaR. Lessons learned from R-STaR development and evaluation can inform the development and improvement of responder health surveillance systems at other local and state health departments and disaster and emergency response agencies. (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

    • Disease Reservoirs and Vectors

      1. Molecular detection and genotyping of pathogenic protozoan parasites in raw and treated water samples from southwest ColombiaExternal
        Sanchez C, Lopez MC, Galeano LA, Qvarnstrom Y, Houghton K, Ramirez JD.
        Parasit Vectors. 2018 Oct 26;11(1):563.

        BACKGROUND: Protozoan parasites such as Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis, Toxoplasma gondii and Entamoeba histolytica represent a great challenge to the systems producing water for human consumption because their cystic forms are persistent in the environment and resist to the disinfection methods conventionally used for their control. In this study, we investigated the presence of these protozoan pathogens in both raw and treated water samples used for the production of drinking water in Narino Department, southwest Colombia. We collected 110 water samples (10 lof each sample) and analyzed them with real-time PCR (qPCR). qPCR-positive samples were genotyped with PCR and DNA sequencing. RESULTS: Giardia duodenalis was detected in 35/110 (31.8%) of the samples and Cryptosporidium spp. in 9/110 (8.2%) of the samples; no sample was positive for T. gondii, E. histolytica or C. cayetanensis. Giardia duodenalis was detected in samples of both raw water (Drinking Water Treatment Plants (DWTP): 47.83%;Drinking Water Rural Plants (DWRP): 18.42%) and water collected either after conventional physicochemical treatment (26.09%) or after disinfection by chlorine (50%), whereas Cryptosporidium spp. were only detected in raw waters (DWTP: 17.39%; DWRP: 13.16%). The two pathogens were detected in both types of treatment plants supplying water to urban areas and to rural zones. Analysis of gdh and tpi markers identified assemblages AI, AII and H of G. duodenalis, while analysis of the small subunit rRNA and gp60 markers of Cryptosporidium-positive samples identified C. parvum (Subtype IIcA5G3c), C. galli, C. molnari, Cryptosporidium sp. genotype II of bats and Cryptosporidium sp. genotype VIII of birds. CONCLUSIONS: The results obtained demonstrate the presence of protozoan parasites in the water of the study region, and the need to improve the surveillance systems for these pathogens and identify the corresponding sources of contamination.

    • Environmental Health

      1. Urinary concentrations of parabens mixture and pregnancy glucose levels among women from a fertility clinicExternal
        Bellavia A, Chiu YH, Brown FM, Minguez-Alarcon L, Ford JB, Keller M, Petrozza J, Williams PL, Ye X, Calafat AM, Hauser R, James-Todd T.
        Environ Res. 2018 Oct 14;168:389-396.

        BACKGROUND: A number of endocrine disrupting chemicals (EDC) have been associated with gestational diabetes (GDM) risk factors. However, no human study has investigated the association between pregnancy exposure to parabens, a class of EDCs, and pregnancy glucose levels, a risk factor for GDM. Furthermore, little is known about this association in subfertile women-a group at high risk of GDM. METHODS: A total of 241 women from the Environment and Reproductive Health Study had data available on 1st and/or 2nd trimester urinary methylparaben, propylparaben, and butylparaben concentrations, and blood glucose levels after the glucose loading test (GLT), a non-fasting 50g glucose loading test taken at late 2nd trimester. Trimester-specific associations between specific gravity adjusted methylparaben, butylparaben, and propylparaben with adjusted mean of pregnancy glucose levels were evaluated in linear regression models, using quartiles of each paraben’s distribution, and as a paraben mixture, using mutual adjustment and Bayesian kernel machine regression (BKMR), a recently proposed method for investigating chemical mixtures that flexibly models the joint effect of chemicals. RESULTS: Investigating parabens one at the time did not provide any significant results. When investigating parabens as a chemical mixture with both multiple regression and BKMR, we observed positive associations of butylparaben (e.g comparing the 4th and 1st quartiles) with glucose levels, for both the 1st trimester (adjusted difference=12.5mg/dL; 95% CI: 0.9, 24.2) and 2nd trimester (adjusted difference=11.2mg/dL; 95% CI: 0.2, 22.3), and a negative association between 1st trimester propylparaben and glucose (adjusted difference=-22.3mg/dL; 95% CI: -43.2, -1.4). CONCLUSIONS: We found 1st trimester butylparaben and propylparaben urinary concentrations to be associated with glucose levels in a pregnancy cohort of women at high risk of GDM, even after adjusting for potential confounders. Because exposure to parabens is widespread, these findings may suggest further investigating the effects of this chemical class on pregnancy health.

      2. An algorithm for quantitatively estimating non-occupational pesticide exposure intensity for spouses in the Agricultural Health StudyExternal
        Deziel NC, Beane Freeman LE, Hoppin JA, Thomas K, Lerro CC, Jones RR, Hines CJ, Blair A, Graubard BI, Lubin JH, Sandler DP, Chen H, Andreotti G, Alavanja MC, Friesen MC.
        J Expo Sci Environ Epidemiol. 2018 Oct 30.

        Residents of agricultural areas experience pesticide exposures from sources other than direct agricultural work. We developed a quantitative, active ingredient-specific algorithm for cumulative (adult, married lifetime) non-occupational pesticide exposure intensity for spouses of farmers who applied pesticides in the Agricultural Health Study (AHS). The algorithm addressed three exposure pathways: take-home, agricultural drift, and residential pesticide use. Pathway-specific equations combined (i) weights derived from previous meta-analyses of published pesticide exposure data and (ii) information from the questionnaire on frequency and duration of pesticide use by applicators, home proximity to treated fields, residential pesticide usage (e.g., termite treatments), and spouse’s off-farm employment (proxy for time at home). The residential use equation also incorporated a published probability matrix that documented the likelihood active ingredients were used in home pest treatment products. We illustrate use of these equations by calculating exposure intensities for the insecticide chlorpyrifos and herbicide atrazine for 19,959 spouses. Non-zero estimates for >/=1 pathway were found for 78% and 77% of spouses for chlorpyrifos and atrazine, respectively. Variability in exposed spouses’ intensity estimates was observed for both pesticides, with 75th to 25th percentile ratios ranging from 7.1 to 7.3 for take-home, 6.5 to 8.5 for drift, 2.4 to 2.8 for residential use, and 3.8 to 7.0 for the summed pathways. Take-home and drift estimates were highly correlated (>/=0.98), but were not correlated with residential use (0.010.02). This algorithm represents an important advancement in quantifying non-occupational pesticide relative exposure differences and will facilitate improved etiologic analyses in the AHS spouses. The algorithm could be adapted to studies with similar information.

      3. Water, sanitation, pollution, and health in the ArcticExternal
        Jensen PE, Hennessy TW, Kallenborn R.
        Environ Sci Pollut Res Int. 2018 Oct 25.

        [No abstract]

    • Genetics and Genomics

      1. New insights into the evolutionary and genomic landscape of Molluscum contagiosum virus (MCV) based on nine MCV1 and six MCV2 complete genome sequencesExternal
        Zorec TM, Kutnjak D, Hosnjak L, Kusar B, Trcko K, Kocjan BJ, Li Y, Krizmaric M, Miljkovic J, Ravnikar M, Poljak M.
        Viruses. 2018 Oct 26;10(11).

        Molluscum contagiosum virus (MCV) is the sole member of the Molluscipoxvirus genus and the causative agent of molluscum contagiosum (MC), a common skin disease. Although it is an important and frequent human pathogen, its genetic landscape and evolutionary history remain largely unknown. In this study, ten novel complete MCV genome sequences of the two most common MCV genotypes were determined (five MCV1 and five MCV2 sequences) and analyzed together with all MCV complete genomes previously deposited in freely accessible sequence repositories (four MCV1 and a single MCV2). In comparison to MCV1, a higher degree of nucleotide sequence conservation was observed among MCV2 genomes. Large-scale recombination events were identified in two newly assembled MCV1 genomes and one MCV2 genome. One recombination event was located in a newly identified recombinant region of the viral genome, and all previously described recombinant regions were re-identified in at least one novel MCV genome. MCV genes comprising the identified recombinant segments have been previously associated with viral interference with host T-cell and NK-cell immune responses. In conclusion, the two most common MCV genotypes emerged along divergent evolutionary pathways from a common ancestor, and the differences in the heterogeneity of MCV1 and MCV2 populations may be attributed to the strictness of the constraints imposed by the host immune response.

    • Health Disparities

      1. Monitoring progress in reducing disparities in HIV, hepatitis, STDs, and tuberculosisExternal
        Dean HD, Truman BI, Mermin JH.
        Am J Public Health. 2018 Nov;108(S4):S236.

        [No abstract]

      2. Unequal declines in absolute and relative disparities in HIV diagnoses among black women, United States, 2008 to 2016External
        Demeke HB, Johnson AS, Wu B, Moonesinghe R, Dean HD.
        Am J Public Health. 2018 Nov;108(S4):S299-s303.

        OBJECTIVES: To assess changes in disparities of HIV diagnosis rates among Black women aged 18 years or older living in the United States. METHODS: We calculated estimated annual percent changes (EAPCs) in annual diagnosis rates, rate differences (absolute disparity), and rate ratios (relative disparity) for groups (total, US-born, and non-US-born) of Black women (referent was all White women) with diagnosed HIV infection, using data reported to the National HIV Surveillance System. RESULTS: Of 39 333 Black women who received an HIV diagnosis during 2008 to 2016, 21.4% were non-US-born. HIV diagnosis rates declined among all Black women, with the smallest decline among non-US-born groups (EAPC = -3.1; P </= .001). Absolute disparities declined for both US-born and non-US-born Black women; however, the relative disparity declined for Black women overall and US-born Black women, whereas it increased for non-US-born (including Caribbean- and Africa-born) Black women. CONCLUSIONS: Differences in disparities in HIV diagnoses exist between US-, and non-US-born (specifically Caribbean- and Africa-born) Black women. Accounting for the heterogeneity of the Black women’s population is crucial in measuring and monitoring progress toward eliminating health disparities among Black women.

      3. HIV infection-related care outcomes among U.S.-born and non-U.S.-born blacks with diagnosed HIV in 40 U.S. areas: The National HIV Surveillance System, 2016External
        Demeke HB, Johnson AS, Zhu H, Gant Z, Duffus WA, Dean HD.
        Int J Environ Res Public Health. 2018 Oct 30;15(11).

        HIV care outcomes must be improved to reduce new human immunodeficiency virus (HIV) infections and health disparities. HIV infection-related care outcome measures were examined for U.S.-born and non-U.S.-born black persons aged >/=13 years by using National HIV Surveillance System data from 40 U.S. areas. These measures include late-stage HIV diagnosis, timing of linkage to medical care after HIV diagnosis, retention in care, and viral suppression. Ninety-five percent of non-U.S.-born blacks had been born in Africa or the Caribbean. Compared with U.S.-born blacks, higher percentages of non-U.S.-born blacks with HIV infection diagnosed during 2016 received a late-stage diagnoses (28.3% versus 19.1%) and were linked to care in </=1 month after HIV infection diagnosis (76.8% versus 71.3%). Among persons with HIV diagnosed in 2014 and who were alive at year-end 2015, a higher percentage of non-U.S.-born blacks were retained in care (67.8% versus 61.1%) and achieved viral suppression (68.7% versus 57.8%). Care outcomes varied between African- and Caribbean-born blacks. Non-U.S.-born blacks achieved higher care outcomes than U.S.-born blacks, despite delayed entry to care. Possible explanations include a late-stage presentation that requires immediate linkage and optimal treatment and care provided through government-funded programs.

      4. Association of race and ethnicity with glycemic control and hemoglobin A1c levels in youth with type 1 diabetesExternal
        Kahkoska AR, Shay CM, Crandell J, Dabelea D, Imperatore G, Lawrence JM, Liese AD, Pihoker C, Reboussin BA, Agarwal S, Tooze JA, Wagenknecht LE, Zhong VW, Mayer-Davis EJ.
        JAMA Netw Open. 2018 Sep 7;1(5).

        IMPORTANCE: Health disparities in the clinical presentation and outcomes among youth with type 1 diabetes exist. Long-term glycemic control patterns in racially/ethnically diverse youth are not well described. OBJECTIVES: To model common trajectories of hemoglobin A1c (HbA1c) among youth with type 1 diabetes and test how trajectory group membership varies by race/ethnicity. DESIGN SETTING AND PARTICIPANTS: Longitudinal cohort study conducted in 5 US locations. The analysis included data from 1313 youths (aged <20 years) newly diagnosed in 2002 through 2005 with type 1 diabetes in the SEARCH for Diabetes in Youth study (mean [SD] age at diabetes onset, 8.9 [4.2] years) who had 3 or more HbA1c study measures during 6.1 to 13.3 years of follow-up. Data were analyzed in 2017. EXPOSURES: Self-reported race/ethnicity. MAIN OUTCOMES AND MEASURES: Hemoglobin A1c trajectories identified through group-based trajectory modeling over a mean (SD) of 9.0 (1.4) years of diabetes duration. Multinomial models studied the association of race/ethnicity with HbA1c trajectory group membership, adjusting for demographic characteristics, clinical factors, and socioeconomic position. RESULTS: The final study sample of 1313 patients was 49.3% female (647 patients) with mean (SD) age 9.7 (4.3) years and mean (SD) disease duration of 9.2 (6.3) months at baseline. The racial/ethnic composition was 77.0% non-Hispanic white (1011 patients), 10.7% Hispanic (140 patients), 9.8% non-Hispanic black (128 patients), and 2.6% other race/ethnicity (34 patients). Three HbA1c trajectories were identified: group 1, low baseline and mild increases (50.7% [666 patients]); group 2, moderate baseline and moderate increases (41.7% [548 patients]); and group 3, moderate baseline and major increases (7.5% [99 patients]). Group 3 was composed of 47.5% nonwhite youths (47 patients). Non-Hispanic black youth had 7.98 higher unadjusted odds (95% CI, 4.42-14.38) than non-Hispanic white youth of being in the highest HbA1c trajectory group relative to the lowest HbA1c trajectory group; the association remained significant after full adjustment (adjusted odds ratio of non-Hispanic black race in group 3 vs group 1, 4.54; 95% CI, 2.08-9.89). Hispanic youth had 3.29 higher unadjusted odds (95% CI, 1.78-6.08) than non-Hispanic white youth of being in the highest HbA1c trajectory group relative to the lowest HbA1c trajectory group; the association remained significant after adjustment (adjusted odds ratio of Hispanic ethnicity in group 3 vs group 1, 2.24; 95% CI, 1.02-4.92). In stratified analyses, the adjusted odds of nonwhite membership in the highest HbA1c trajectory remained significant among male patients and youth diagnosed at age 9 years or younger, but not female patients and youth who were older than 9 years when they were diagnosed (P for interaction = .04 [sex] and .02 [age at diagnosis]). CONCLUSIONS AND RELEVANCE: There are racial/ethnic differences in long-term glycemic control among youth with type 1 diabetes, particularly among nonwhite male patients and nonwhite youth diagnosed earlier in life.

      5. Changes in tuberculosis disparities at a time of decreasing tuberculosis incidence in the United States, 1994-2016External
        Khan A, Marks S, Katz D, Morris SB, Lambert L, Magee E, Bowman S, Grant G.
        Am J Public Health. 2018 Nov;108(S4):S321-s326.

        OBJECTIVES: To assess national progress in reducing disparities in rates of tuberculosis (TB) disease, which disproportionately affects minorities. METHODS: We used Centers for Disease Control and Prevention (CDC) surveillance data and US Census data to calculate TB rates for 1994 through 2016 by race/ethnicity, national origin, and other TB risk factors. We assessed progress in reducing disparities with rate ratios (RRs) and indexes of disparity, defined as the average of the differences between subpopulation and all-population TB rates divided by the all-population rate. RESULTS: Although TB rates decreased for all subpopulations, RRs increased or stayed the same for all minorities compared with Whites. For racial/ethnic groups, indexes of disparity decreased from 1998 to 2008 (P < .001) but increased thereafter (P = .33). The index of disparity by national origin increased an average of 1.5% per year. CONCLUSIONS: Although TB rates have decreased, disparities have persisted and even increased for some populations. To address the problem, the CDC’s Division of TB Elimination has focused on screening and treating latent TB infection, which is concentrated among minorities and is the precursor for more than 85% of TB cases in the United States.

      6. Patterns of racial/ethnic disparities and prevalence in HIV and syphilis diagnoses among men who have sex with men, 2016: A novel data visualizationExternal
        Sullivan PS, Purcell DW, Grey JA, Bernstein KT, Gift TL, Wimbly TA, Hall E, Rosenberg ES.
        Am J Public Health. 2018 Nov;108(S4):S266-s273.

        OBJECTIVES: To describe disparities in HIV infection and syphilis among gay, bisexual, and other men who have sex with men (MSM) in US states through ratio-based measures and graphical depictions of disparities. METHODS: We used state-level surveillance data of reported HIV and syphilis cases in 2015 and 2016, and estimates of MSM population sizes to estimate HIV and syphilis prevalence by race/ethnicity and rate ratios (RRs) and to visually display patterns of disparity and prevalence among US states. RESULTS: State-specific rates of new HIV diagnoses were higher for Black than for White MSM (RR range = 2.35 [Rhode Island] to 10.12 [Wisconsin]) and for Hispanic than for White MSM (RR range = 1.50 [Tennessee] to 5.78 [Pennsylvania]). Rates of syphilis diagnoses were higher for Black than for White MSM in 42 of 44 states (state RR range = 0.89 [Hawaii] to 17.11 [Alaska]). Scatterplots of HIV diagnosis rates by race showed heterogeneity in epidemic scenarios, even in states with similar ratio-based disparity measures. CONCLUSIONS: There is a widely disparate impact of HIV and syphilis among Black and Hispanic MSM compared with White MSM. Between-state variation suggests that states should tailor and focus their prevention responses to best address state data.

      7. Disparities in hepatitis B virus infection and immunity among New York City Asian American patients, 1997 to 2017External
        Tang AS, Lyu J, Wang S, He Q, Pong P, Harris AM.
        Am J Public Health. 2018 Nov;108(S4):S327-s335.

        OBJECTIVES: To measure disparities in hepatitis B virus (HBV) infection and immunity among a high-risk patient population at a community health center in New York City. METHODS: We performed a retrospective chart review of 25 565 adults with HBV surface antigen, surface antibody, and total core antibody tests from 1997 to 2017. We categorized HBV test results by infection and immunity status and analyzed by demographic characteristics with chi(2) and logistic regression analysis. RESULTS: Of 25 565 adults, 13.4% were currently infected, 52.1% were ever infected, 33.4% were immune from vaccination, and 14.5% were susceptible. Significant factors associated with ever infection were age, male sex, being China-born, limited English proficiency, having Medicaid or no insurance, and family history of HBV (P < .01). CONCLUSIONS: Our study demonstrated a high burden of HBV infection among foreign-born Asian Americans seeking care at a community health center. Public Health Implications. It is important to test patients at high risk for HBV infection with all 3 tests to identify those with current infection, risk for reactivation, or need for vaccination, and to assess the effectiveness of public health interventions.

      8. [No abstract]

    • Health Economics

      1. Population-level outcomes and cost-effectiveness of expanding the recommendation for age-based hepatitis C testing in the United StatesExternal
        Barocas JA, Tasillo A, Eftekhari Yazdi G, Wang J, Vellozzi C, Hariri S, Isenhour C, Randall L, Ward JW, Mermin J, Salomon JA, Linas BP.
        Clin Infect Dis. 2018 Aug 1;67(4):549-556.

        Background: The US Centers for Disease Control and Prevention and the U.S. Preventive Services Task Force recommend one-time hepatitis C virus (HCV) testing for persons born 1945-1965 and targeted testing for high-risk persons. This strategy targets HCV testing to a prevalent population at high risk for HCV morbidity and mortality, but does not include younger populations with high incidence. To address this gap and improve access to HCV testing, age-based strategies should be considered. Methods: We used a simulation of HCV to estimate the effectiveness and cost-effectiveness of HCV testing strategies: 1) standard of care (SOC) – recommendation for one-time testing for all persons born 1945-1965, 2) recommendation for one-time testing for adults >/=40 years (>/=40 strategy), 3) >/=30 years (>/=30 strategy), and 4) >/=18 years (>/=18 strategy). All strategies assumed targeted testing of high-risk persons. Inputs were derived from national databases, observational cohorts and clinical trials. Outcomes included quality-adjusted life expectancy, costs, and cost-effectiveness. Results: Expanded age-based testing strategies increased US population lifetime case identification and cure rates. Greatest increases were observed in the >/=18 strategy. Compared to the SOC, this strategy resulted in an estimated 256,000 additional infected persons identified and 280,000 additional cures at the lowest cost per QALY gained (ICER = $28,000/QALY). Conclusions: In addition to risk-based testing, one-time HCV testing of persons 18 and older appears to be cost-effective, leads to improved clinical outcomes and identifies more persons with HCV than the current birth cohort recommendations. These findings could be considered for future recommendation revisions.

      2. Resources needed for US CDC’s support to the response to post-epidemic clusters of Ebola in West Africa, 2016External
        Carias C, Adhikari BB, Ravat F, Meltzer MI, Marston BJ.
        Infect Dis Poverty. 2018 Oct 12;7(1):113.

        BACKGROUND: West African countries Liberia, Sierra Leone, and Guinea experienced the largest and longest epidemic of Ebola virus disease from 2014 to 2016; after the epidemic was declared to be over, Liberia, Guinea, and Sierra Leone still experienced Ebola cases/clusters. The United States Centers for Disease Control and Prevention (US CDC) participated in the response efforts to the latter Ebola clusters, by assisting with case investigation, contact identification, and monitoring. This study aims to estimate the cost to the US CDC of responding to three different Ebola clusters after the end of the Ebola epidemic in 2015: i) Sierra Leone, Tonkolili (Jan 2016, 2 Ebola cases, 5 affected regions); ii) Guinea, Nzerekore (Mar-May 2016, 10 Ebola cases, 2 affected regions); iii) Liberia, Somali Drive (Mar 2016, 3 Ebola cases, 1 affected region). MAIN TEXT: After interviewing team members that had participated in the response, we estimated total costs (expressed in 2016 US Dollars [USD]), where total costs correspond to travel costs, deployed personnel costs, costs to prepare for deployment, procurement and interagency collaboration costs, among others. We also estimated cost per cluster case (corresponding to the total costs divided by the total number of cluster cases); and cost per case-affected-region (equal to the total costs divided by the product of the number of cases times the number of regions affected). We found that the response cost varied sixteenfold between USD 113 166 in Liberia and USD 1 764 271 in Guinea, where the main cost drivers were travel and personnel costs. The cost per cluster case varied tenfold between 37 722 in Liberia (three cases) and USD 347 226 in Sierra Leone, and the cost per case-affected-region varied threefold between USD 37 722 in Liberia and USD 88 214 in Guinea. CONCLUSIONS: Costs vary with the characteristics of each cluster, with those spanning more regions and cases requiring more resources for case investigation and contact identification and monitoring. These data will assist policy makers plan for similar post-epidemic responses.

      3. Healthcare expenditures for privately insured US patients with cystic fibrosis, 2010-2016External
        Grosse SD, Do TQ, Vu M, Feng LB, Berry JG, Sawicki GS.
        Pediatr Pulmonol. 2018 Oct 31.

        OBJECTIVES: Published cost estimates for cystic fibrosis (CF) are based on older data and do not reflect increased use of specialty drugs in recent years. We assessed recent trends in healthcare expenditures for CF patients in the United States (US) with employer-sponsored health insurance. METHODS: The study is a retrospective analysis of claims data for privately insured individuals aged 0-64 years who were continuously enrolled in non-capitated plans for at least 1 calendar year during 2010-2016. Mean annual expenditures during a calendar year were calculated for individuals who met a claims-based CF case definition. Average annual growth rates were calculated through linear regression of the natural logarithm of annual expenditures. RESULTS: The annual CF prevalence was 1.1-1.4 per 10 000 adults and 2.9-3.0 per 10 000 children. Average spending adjusted for inflation nearly doubled from roughly $67 000 per patient in 2010 and 2011 to approximately $131 000 per patient in 2016. Inflation-adjusted spending on outpatient and inpatient care increased by 0.5% and 2.5% per year, respectively, whereas pharmaceutical spending increased by 20.2% per year. Virtually all of the growth in pharmaceutical spending was accounted for by spending on specialty drugs; inflation-adjusted spending on other medications increased by 1.3% per year. The annual growth rate in pharmaceutical spending rose by 33.1% during 2014-2016, the years during which lumacaftor/ivacaftor was introduced. CONCLUSIONS: Per-patient expenditures for privately-insured patients with CF almost doubled during 2010-2016; specialty drugs were largely responsible for this increase, with a major contribution from new, genotype-targeted CFTR modulator medications.

      4. INTRODUCTION: Staying home when sick can reduce the spread of influenza. The objectives of this study were to quantify the percentage of workers who had paid sick leave (PSL) benefits, examine sociodemographic characteristics that may be associated with having these benefits, and examine the association between having PSL benefits and use of sick days and influenza vaccination status. METHODS: The public-use dataset from the 2009 National H1N1 Flu Survey (NHFS) were analyzed in 2017. Wald chi-square tests and t-tests were used to test for associations between having PSL benefits and sociodemographic characteristics and industry and occupation groups, the associations between having PSL benefits and seeking treatment when sick with influenza-like illness (ILI), and taking days off work when sick with ILI. Logistic regression was used to determine variables associated with having PSL benefits and the association between having PSL benefits and influenza vaccination status. RESULTS: Sixty-one percent of employed adults reported having PSL benefits during the 2009-10 influenza season. Being younger, female, Hispanic, less educated, or a farm/blue collar worker were associated with reduced likelihood of having PSL benefits. Not having PSL benefits was associated with a lower likelihood of receiving an influenza vaccination and visiting a health professional when sick with ILI. CONCLUSIONS: The percentage of workers who have PSL benefits differs by sociodemographic characteristics and industry/occupation groups. Offering PSL benefits along with promoting influenza vaccination and encouraging employees with ILI to stay home can increase influenza vaccination coverage and help control the spread of influenza.

    • Healthcare Associated Infections

      1. Environmental panels as a proxy for nursing facility patients with methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus colonizationExternal
        Cassone M, Mantey J, Perri MB, Gibson K, Lansing B, McNamara S, Patel PK, Cheng VC, Walters MS, Stone ND, Zervos MJ, Mody L.
        Clin Infect Dis. 2018 Aug 31;67(6):861-868.

        Background: Most nursing facilities (NFs) lack methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) surveillance programs due to limited resources and high costs. We investigated the utility of environmental screening of high-touch surfaces in patient rooms as a way to circumvent these challenges. Methods: We compared MRSA and VRE culture data from high-touch surfaces in patients’ rooms (14450 samples from 6 NFs) and ranked each site’s performance in predicting patient colonization (7413 samples). The best-performing sites were included in a MRSA- and a VRE-specific panel that functioned as a proxy for patient colonization. Molecular typing was performed to confirm available concordant patient-environment pairs. Results: We identified and validated a MRSA panel that consisted of the bed controls, nurse call button, bed rail, and TV remote control. The VRE panel included the toilet seat, bed controls, bed rail, TV remote control, and top of the side table. Panel colonization data tracked patient colonization. Negative predictive values were 89%-92% for MRSA and 82%-84% for VRE. Molecular typing confirmed a strong clonal type relationship in available concordant patient-environment pairs (98% for MRSA, 91% for VRE), pointing to common epidemiological patterns for environmental and patient isolates. Conclusions: Environmental panels used as a proxy for patient colonization and incorporated into facility surveillance protocols can guide decolonization strategies, improve awareness of MRSA and VRE burden, and inform efforts to reduce transmission. Targeted environmental screening may be a viable surveillance strategy for MRSA and VRE detection in NFs.

      2. Prevalence of Staphylococcus aureus and use of antistaphylococcal therapy in children hospitalized with pneumoniaExternal
        Frush JM, Zhu Y, Edwards KM, Grijalva CG, Thomsen IP, Self WH, Jain S, Anderson EJ, Ampofo K, Pavia AT, Arnold SR, McCullers JA, Williams DJ.
        J Hosp Med. 2018 Oct 31.

        Within a cohort of >2,000 children hospitalized with community-acquired pneumonia, staphylococcal pneumonia was rare (1%) but associated with adverse in-hospital outcomes. Despite this low prevalence, use of antistaphylococcal antibiotics was common (24%). Efforts are needed to minimize overuse of antistaphylococcal antibiotics while also ensuring adequate treatment for pathogen-specific diseases.

      3. Droplet rather than aerosol mediated dispersion is the primary mechanism of bacterial transmission from contaminated hand washing sink trapsExternal
        Kotay S, Donlan RM, Ganim C, Barry K, Christensen BE, Mathers AJ.
        Appl Environ Microbiol. 2018 Oct 26.

        An alarming rise in hospital outbreaks implicating hand-washing sinks has led to widespread acknowledgement that sinks are a major reservoir of antibiotic resistant pathogens in patient-care areas. An earlier study using a GFP-expressing Escherichia coli (GFP-E. coli) as a model organism demonstrated dispersal from drain biofilm in contaminated sinks. The present study further characterizes the dispersal of microorganisms from contaminated sinks. Replicate hand-washing sinks were inoculated with GFP-E. coli, and dispersion was measured using qualitative (settle plates) and quantitative (air sampling) methods. Dispersal caused by faucet water was captured with settle plates and air sampling methods when bacteria were present on the drain. In contrast, no dispersal was captured without or in between faucet events amending earlier theory that bacteria aerosolize from P-trap and disperse. Numbers of dispersed GFP-E. coli diminished substantially within 30 minutes after faucet usage, suggesting that the organisms were associated with larger droplet-sized particles that are not suspended in the air for long periods.IMPORTANCE Among the possible environmental reservoirs in a patient care environment, sink drains are increasingly recognized as potential reservoir of multidrug resistant healthcare-associated pathogens to hospitalized patients. With increasing antimicrobial resistance limiting therapeutic options for patients, better understanding of how pathogens disseminate from sink drains is urgently needed. Once this knowledge gap has decreased, interventions can be engineered to decrease or eliminate transmission from hospital sink drains to patients. The current study further defines the mechanisms of transmission for bacteria colonizing sink drains.

      4. Changes in prevalence of health care-associated infections in U.S. hospitalsExternal
        Magill SS, O’Leary E, Janelle SJ, Thompson DL, Dumyati G, Nadle J, Wilson LE, Kainer MA, Lynfield R, Greissman S, Ray SM, Beldavs Z, Gross C, Bamberg W, Sievers M, Concannon C, Buhr N, Warnke L, Maloney M, Ocampo V, Brooks J, Oyewumi T, Sharmin S, Richards K, Rainbow J, Samper M, Hancock EB, Leaptrot D, Scalise E, Badrun F, Phelps R, Edwards JR.
        N Engl J Med. 2018 Nov 1;379(18):1732-1744.

        BACKGROUND: A point-prevalence survey that was conducted in the United States in 2011 showed that 4% of hospitalized patients had a health care-associated infection. We repeated the survey in 2015 to assess changes in the prevalence of health care-associated infections during a period of national attention to the prevention of such infections. METHODS: At Emerging Infections Program sites in 10 states, we recruited up to 25 hospitals in each site area, prioritizing hospitals that had participated in the 2011 survey. Each hospital selected 1 day on which a random sample of patients was identified for assessment. Trained staff reviewed medical records using the 2011 definitions of health care-associated infections. We compared the percentages of patients with health care-associated infections and performed multivariable log-binomial regression modeling to evaluate the association of survey year with the risk of health care-associated infections. RESULTS: In 2015, a total of 12,299 patients in 199 hospitals were surveyed, as compared with 11,282 patients in 183 hospitals in 2011. Fewer patients had health care-associated infections in 2015 (394 patients [3.2%; 95% confidence interval {CI}, 2.9 to 3.5]) than in 2011 (452 [4.0%; 95% CI, 3.7 to 4.4]) (P<0.001), largely owing to reductions in the prevalence of surgical-site and urinary tract infections. Pneumonia, gastrointestinal infections (most of which were due to Clostridium difficile [now Clostridioides difficile]), and surgical-site infections were the most common health care-associated infections. Patients’ risk of having a health care-associated infection was 16% lower in 2015 than in 2011 (risk ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.005), after adjustment for age, presence of devices, days from admission to survey, and status of being in a large hospital. CONCLUSIONS: The prevalence of health care-associated infections was lower in 2015 than in 2011. To continue to make progress in the prevention of such infections, prevention strategies against C. difficile infection and pneumonia should be augmented. (Funded by the Centers for Disease Control and Prevention.).

      5. Carbapenem-nonsusceptible gram-negative pathogens in ICU and non-ICU settings in US hospitals in 2017: A multicenter studyExternal
        McCann E, Srinivasan A, DeRyke CA, Ye G, DePestel DD, Murray J, Gupta V.
        Open Forum Infect Dis. 2018 Oct;5(10):ofy241.

        Background: Infections caused by Gram-negative pathogens resistant to carbapenems have limited treatment options and are associated with increased morbidity and mortality. We evaluated the rates, infection sources, and pathogen types associated with carbapenem-nonsusceptible (Carb-NS) Gram-negative isolates in intensive care unit (ICU) and non-ICU settings in a large US hospital database. Methods: We conducted a retrospective cross-sectional analysis of carbapenem susceptibility of all nonduplicate isolates of Gram-negative pathogens collected from January 1, 2017, to December 31, 2017, at 358 US hospitals in the BD Insights Research Database. Carb-NS isolates included all pathogens reported at the institutional level as intermediate or resistant. Results: Of 312 075 nonduplicate Gram-negative isolates, 10 698 (3.4%) were Carb-NS. Respiratory samples were the most frequent source of Carb-NS isolates (35.2%); skin/wound accounted for 23.6%. Pseudomonas aeruginosa was the most common Carb-NS pathogen (58.5% of isolates), and about 30% were Enterobacteriaceae. The highest rates of Carb-NS were found in Acinetobacter spp. (35.6%) and P. aeruginosa (14.6%). The rate of Carb-NS was significantly higher in ICU (5.4%) vs non-ICU settings (2.7%; P < .0001 in univariate analysis). This difference remained significant in multivariable analysis after adjusting for infection and hospital characteristics (odds ratio, 1.35; 95% confidence interval, 1.17-1.56; P < .0001). Conclusions: Infections caused by Carb-NS isolates pose a significant clinical problem across different sources of infection, species of pathogen, and hospital settings. Widespread infection prevention and antimicrobial stewardship initiatives, in combination with new treatment options, may be required to reduce the burden of carbapenem resistance in health care settings.

      6. Gastrointestinal microbiota disruption and risk of colonization with carbapenem-resistant Pseudomonas aeruginosa in ICU patientsExternal
        Pettigrew MM, Gent JF, Kong Y, Halpin AL, Pineles L, Harris AD, Johnson JK.
        Clin Infect Dis. 2018 Nov 1.

        Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) can colonize the gastrointestinal (GI) tract of intensive care unit (ICU) patients and CRPA colonization puts patients at increased risk of CRPA infection. Prior studies have not examined relationships between the microbiota, medications, and CRPA colonization-acquisition. Methods: Data and peri-rectal swabs were obtained from a cohort of ICU patients at the University of Maryland Medical Center. Patients (N=109) were classified into three groups by CRPA colonization-acquisition status and antimicrobial exposure. We conducted 16S rRNA gene sequencing of an ICU admission swab and >/= one additional swab and evaluated associations between patient characteristics, medications, the GI microbiota, and CRPA colonization-acquisition. Results: ICU patients had low levels of diversity and high relative abundance of pathobionts. Piperacillin-tazobactam was prescribed more frequently to patients with CRPA colonization-acquisition than those without. Piperacillin-tazobactam was associated with low abundance of potentially protective taxa (e.g., Lactobacillus and Clostridiales) and increased risk of Enterococcus domination [odds ratio (OR) 5.50; 95% confidence interval (CI) (2.03-14.92)]. Opioids were associated with dysbiosis in patients who did not receive antibiotics; potentially protective Blautia and Lactobacillus were higher in patients who did not receive opioids. A group of correlated taxa, identified at ICU admission, were associated with lower risk of CRPA colonization-acquisition [OR 0.58; 95% CI (0.38-0.87)]. Conclusions: Antibiotics differed in their impact on the microbiota with piperacillin-tazobactam being particularly damaging. Certain bacterial taxa (e.g., Clostridiales) were negatively associated with CRPA colonization-acquisition. These taxa may be markers of risk for CRPA colonization-acquisition and/or serve a protective role.

      7. Transmission of Eastern equine encephalitis virus from an organ donor to three transplant recipientsExternal
        Pouch SM, Katugaha SB, Shieh WJ, Annambhotla P, Walker WL, Basavaraju SV, Jones J, Huynh T, Reagan-Steiner S, Bhatnagar J, Grimm K, Stramer SL, Gabel J, Lyon GM, Mehta AK, Kandiah P, Neujahr DC, Javidfar J, Subramanian RM, Parekh SM, Shah P, Cooper L, Psotka MA, Radcliffe R, Williams C, Zaki SR, Staples JE, Fischer M, Panella AJ, Lanciotti RS, Laven JJ, Kosoy O, Rabe IB, Gould CV.
        Clin Infect Dis. 2018 Oct 29.

        Background: In fall 2017, three solid organ transplant recipients from a common donor developed encephalitis within one week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. Methods: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pre-transplant organ donor evaluation and local EEEV surveillance. Results: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the eight blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor’s county of residence. Neuroinvasive EEEV infection directly contributed to the death of one organ recipient and likely contributed to death in another. Conclusions: Our investigation demonstrated EEEV transmission through solid organ transplantation. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis.

    • Immunity and Immunization
      1. Background: Identifying polio vaccine regimens that can elicit robust intestinal mucosal immunity and interrupt viral transmission is a key priority of the polio endgame. Methods: In a 2013 Chilean clinical trial (NCT01841671) of trivalent inactivated polio vaccine (IPV) and bivalent oral polio vaccine (bOPV; targeting types 1 and 3), infants were randomized to receive IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV at 8, 16, and 24 weeks of age and challenged with monovalent oral polio vaccine type 2 (mOPV2) at 28 weeks. Using fecal samples collected from 152 participants, we investigated the extent to which IPV-bOPV and IPV-only immunization schedules induced intestinal neutralizing activity and immunoglobulin A against polio types 1 and 2. Results: Overall, 37% of infants in the IPV-bOPV groups and 26% in the IPV-only arm had detectable type 2-specific stool neutralization after the primary vaccine series. In contrast, 1 challenge dose of mOPV2 induced brisk intestinal immune responses in all vaccine groups, and significant rises in type 2-specific stool neutralization titers (P < .0001) and immunoglobulin A concentrations (P < 0.0001) were measured 2 weeks after the challenge. In subsidiary analyses, duration of breastfeeding also appeared to be associated with the magnitude of polio-specific mucosal immune parameters measured in infant fecal samples. Conclusions: Taken together, these results underscore the concept that mucosal and systemic immune responses to polio are separate in their induction, functionality, and potential impacts on transmission and, specifically, provide evidence that primary vaccine regimens lacking homologous live vaccine components are likely to induce only modest, type-specific intestinal immunity.

      2. INTRODUCTION: Latin American countries were among the first to adopt rotavirus vaccines into national immunization programs; we reviewed one decade of their experience with rotavirus vaccination. Areas covered: We systematically reviewed manuscripts published January 1990-January 2018 to assess rotavirus vaccine effectiveness (VE) via meta-analysis; describe trends in rotavirus and acute gastroenteritis (AGE)-associated hospitalizations and mortality before and after vaccine introduction; and estimate annual hospitalizations and deaths averted by rotavirus vaccination in Latin American and Caribbean children <5 years. Rotavirus vaccines demonstrated VE against rotavirus hospitalization of 76% (95% CI: 58-87) in low-mortality countries and 67% (95% CI: 54-76) in high-mortality countries for children <1 year of age. Reductions of 64.0% (IQR: 49.9-69.2) were observed in rotavirus hospitalizations, 32.8% (IQR 29.0-40.3) in AGE hospitalizations, and 53.5% (IQR: 40.4-57.1) in AGE-related mortalities in children <5 years. In 2015, an estimated 125,000 rotavirus-associated hospitalizations and 800 rotavirus-related deaths were prevented in countries that implemented rotavirus vaccines. Expert Commentary: Rotavirus vaccines remain an effective tool against diarrheal disease. The continued success of rotavirus vaccines provides evidence for adoption in Latin American and Caribbean countries that have not yet introduced it, and improvement within those with low coverage.

      3. Impact of maternal antibody on the immunogenicity of inactivated polio vaccine in infants immunized with bivalent oral polio vaccine: Implications for the polio eradication endgameExternal
        Gaensbauer JT, Gast C, Bandyopadhyay AS, O’Ryan M, Saez-Llorens X, Rivera L, Lopez-Medina E, Melgar M, Weldon WC, Oberste MS, Ruttimann R, Clemens R, Asturias EJ.
        Clin Infect Dis. 2018 Oct 30;67(suppl_1):S57-s65.

        Background: Quantifying interference of maternal antibodies with immune responses to varying dose schedules of inactivated polio vaccine (IPV) is important for the polio endgame as IPV replaces oral polio vaccine (OPV). Methods: Type 2 poliovirus humoral and intestinal responses were analyzed using pre-IPV type 2 seropositivity as proxy for maternal antibodies from 2 trials in Latin America. Infants received 1 or 2 doses of IPV in sequential IPV-bivalent oral polio vaccine (bOPV) or mixed bOPV-IPV schedules. Results: Among infants vaccinated with bOPV at age 6, 10, and 14 weeks of age and IPV at 14 weeks, those with type 2 pre-IPV seropositivity had lower seroprotection rates than seronegative infants at 4 weeks (92.7% vs 83.8%; difference, 8.9% [95% confidence interval, 0.6%-19.9%]; n = 260) and 22 weeks (82.7% vs 60.4%; difference, 22.3 [12.8%-32.4%]; n = 481) post-IPV. A second IPV at age 36 weeks resulted in 100% seroprotection in both groups. Among infants vaccinated with 1 IPV at age 8 weeks followed by 2 doses of bOPV, pre-IPV type 2-seropositive infants had lower seroprotection at age 28 weeks than those who were seronegative (93.0% vs 73.9%; difference, 19.6% [95% confidence interval, 7.3%-29.4%]; n = 168). A second dose of IPV at 16 weeks achieved >97% seroprotection at age 24 or 28 weeks, regardless of pre-IPV status. Poliovirus shedding after challenge with monovalent OPV, serotype 2, was higher in pre-IPV seropositive infants given sequential IPV-bOPV. No differences were observed in the mixed bOPV-IPV schedule. Conclusions: The presence of maternal antibody is associated with lower type 2 post-IPV seroprotection rates among infants who receive a single dose of IPV. This impact persists until late in infancy and is overcome by a second IPV dose.

      4. Influenza vaccine effectiveness and statin use among adults in the United States, 2011-2017External
        Havers FP, Chung JR, Belongia EA, McLean HQ, Gaglani M, Murthy K, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Petrie JG, Fry AM, Flannery B.
        Clin Infect Dis. 2018 Oct 27.

        Background: Statin medications have immunomodulatory effects. Several recent studies suggest that statins may reduce influenza vaccine response and reduce influenza vaccine effectiveness (VE). Methods: We compared influenza VE in statin users and nonusers aged >/=45 years enrolled in the US Vaccine Effectiveness Network study over 6 influenza seasons (2011-2012 through 2016-2017). All enrollees presented to outpatients clinics with acute respiratory illness and were tested for influenza. Information on vaccination status, medical history, and statin use at the time of vaccination were collected by medical and pharmacy records. Using a test-negative design, we estimated VE as (1 – OR) x 100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated vs unvaccinated participants. Results: Among 11692 eligible participants, 3359 (30%) were statin users and 2806 (24%) tested positive for influenza virus infection; 78% of statin users and 60% of nonusers had received influenza vaccine. After adjusting for potential confounders, influenza VE was 36% (95% confidence interval [CI], 22%-47%) among statin users and 39% (95% CI, 32%-45%) among nonusers. We observed no significant modification of VE by statin use. VE against influenza A(H1N1)pdm09, A(H3N2), and B viruses were similar among statin users and nonusers. Conclusions: In this large observational study, influenza VE against laboratory-confirmed influenza illness was not affected by current statin use among persons aged >/=45 years. Statin use did not modify the effect of vaccination on influenza when analyzed by type and subtype.

      5. Introduction of inactivated poliovirus vaccine in the Philippines: Effect on health care provider and infant caregiver attitudes and practicesCdc-pdfExternal
        Lopez AL, Harris JB, Raguindin PF, Aldaba J, Morales M, Sylim P, Wannemuehler K, Wallace A, Ehlman DC, Hyde TB, Fox KK, Nyambat B, Ducusin MJ, Hampton LM.
        Vaccine. 2018 .

        Background: The introduction of inactivated poliovirus vaccine (IPV) to the Philippines? national immunization schedule meant the addition of a third injectable vaccine at a child’s 14-week immunization visit. Although previous studies have shown that providing multiple vaccines at the same time affected neither the risk of severe adverse events nor vaccine efficacy, concerns were raised that providing three injections at a single visit, with two injections in one leg, might be unacceptable to health care providers (HCP) and infant caregivers. Methods: We conducted pre- and post-IPV introduction surveys on the acceptance and acceptability of the additional injectable vaccine in three of the Philippines? 17 administrative regions. Regions 3 and 6 were included in the pre-introduction phase and Regions 3, 6 and 10 were included in the post-introduction phase. Thirty public health centers (PHCs) were randomly sampled from each region. HCPs and infant caregivers were interviewed. In addition, vaccination records from a minimum of 20 eligible children pre-introduction and 10 children post-introduction per PHC were reviewed. Results and discussion: We interviewed 89 HCPs and 286 infant caregivers during the pre-introduction phase and 137 HCPs and 455 caregivers during the post-introduction phase. Among 986 vaccination records reviewed post-introduction, 84% (n = 826) of children received all three recommended injections at one visit, with a range from 61% (209/342) in Region 10 to 100% (328/328) in Region 3. The proportion of HCPs reporting that they had administered three or more injectable vaccines and the proportion of caregivers that would be comfortable with their child receiving three or more injectable vaccines at one visit increased from pre- to post-introduction (p < 0.0001 for both). Eighty-seven percent of HCPs that had administered three or more injectable vaccines post-introduction reported being comfortable or very comfortable with the number of vaccines they had administered.

      6. BACKGROUND: The Advisory Committee for Immunization Practices recommends that all pregnant women receive the seasonal influenza vaccine and the tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine during every pregnancy. However, vaccination coverage rates are suboptimal among pregnant women in the United States, leaving these women and their unborn children at risk of vaccine-preventable diseases and their complications. OBJECTIVES: We sought to understand the current landscape of published literature regarding maternal immunization, including barriers to and predictors of vaccine acceptance, and identify gaps in the research in order to inform strategies for future programmatic improvement. METHODS: We conducted a literature search using MEDLINE (OVID), PsychINFO, and CINAHL (Ebsco) databases. The search included published, English-language manuscripts that identified patient, provider, or system-level barriers to, predictors of, or interventions that improved uptake of maternal vaccines among pregnant women in the US. Studies were reviewed using an inductive thematic analysis approach. RESULTS: We included 75 studies in our review. Pregnant women identified 25 different barriers to accepting recommended maternal immunizations; barriers related to vaccine safety perceptions were the most common. Healthcare providers identified 24 different barriers to vaccinating their pregnant patients. The most commonly cited barriers among healthcare providers were financial concerns. Eighteen different predictors of vaccine acceptance were identified. Receipt of a healthcare provider’s recommendation was the factor most frequently reported as a reason for vaccination among pregnant women. CONCLUSIONS: We were able to identify gaps in the literature regarding maternal immunization and make recommendations for future research. Efforts to address the challenges of maternal immunization in the United States should include increasing the focus on Tdap, implementing more high-level assessments of safety perceptions and associated concerns, and determining most effective interventions.

      7. Update: Recommendations of the Advisory Committee on Immunization Practices for use of hepatitis A vaccine for postexposure prophylaxis and for preexposure prophylaxis for international travelExternal
        Nelson NP, Link-Gelles R, Hofmeister MG, Romero JR, Moore KL, Ward JW, Schillie SF.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 2;67(43):1216-1220.

        Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin (IG) effectively prevents infection with hepatitis A virus (HAV) when administered within 2 weeks of exposure. Preexposure prophylaxis against HAV infection through the administration of HepA vaccine or IG provides protection for unvaccinated persons traveling to or working in countries that have high or intermediate HAV endemicity. The Advisory Committee on Immunization Practices (ACIP) Hepatitis Vaccines Work Group conducted a systematic review of the evidence for administering vaccine for PEP to persons aged >40 years and reviewed the HepA vaccine efficacy and safety in infants and the benefits of protection against HAV before international travel. The February 21, 2018, ACIP recommendations update and supersede previous ACIP recommendations for HepA vaccine for PEP and for international travel. Current recommendations include that HepA vaccine should be administered to all persons aged >/=12 months for PEP. In addition to HepA vaccine, IG may be administered to persons aged >40 years depending on the provider’s risk assessment. ACIP also recommended that HepA vaccine be administered to infants aged 6-11 months traveling outside the United States when protection against HAV is recommended. The travel-related dose for infants aged 6-11 months should not be counted toward the routine 2-dose series. The dosage of IG has been updated where applicable (0.1 mL/kg). HepA vaccine for PEP provides advantages over IG, including induction of active immunity, longer duration of protection, ease of administration, and greater acceptability and availability.

    • Injury and Violence

      1. Rape-related pregnancy and association with reproductive coercion in the U.SExternal
        Basile KC, Smith SG, Liu Y, Kresnow MJ, Fasula AM, Gilbert L, Chen J.
        Am J Prev Med. 2018 Oct 17.

        INTRODUCTION: Rape-related pregnancy is a public health problem where sexual violence and reproductive health intersect; yet, there is a dearth of research to inform public health practice. The authors examined the prevalence and characteristics of rape-related pregnancy in U.S. women and its association with intimate partner reproductive coercion. METHODS: Data years 2010-2012 are pooled from the National Intimate Partner and Sexual Violence Survey, a telephone survey of U.S. adults. Accounting for complex survey design, in 2017, authors estimated the prevalence of vaginal rape-related pregnancy for U.S. women overall and by race/ethnicity. The authors also examined the proportion of rape-related pregnancy among victims of vaginal rape overall, by perpetrator type and by presence of reproductive coercion in the context of intimate partner rape. RESULTS: Almost 2.9 million U.S. women (2.4%) experienced rape-related pregnancy during their lifetime. Among rape victims, 77.3% reported a current/former intimate partner perpetrator, and 26.2% of intimate partner rape victims reported rape-related pregnancy compared with those raped by an acquaintance (5.2%) or stranger (6.9%). Women raped by an intimate partner and reporting rape-related pregnancy were significantly more likely to have experienced reproductive coercion compared with women who were raped by an intimate partner but did not become pregnant. CONCLUSIONS: This paper reports the first national prevalence of rape-related pregnancy by any perpetrator in two decades. The high proportion of rape-related pregnancy committed by intimate partner perpetrators and its association with reproductive coercion suggest the need for primary prevention of intimate partner violence and access to trauma-informed reproductive health services for rape/intimate partner violence victims.

      2. Like other cultures, measures to accurately and sensitively assess and treat disruptive behaviors in Taiwanese children are necessary. This research provides normative and psychometric data (i.e., item-total correlations, split-half coefficients, internal consistency, and internal validity) on the Eyberg Child Behavior Inventory (ECBI), including clinical cut-off scores, with a Taiwanese community sample. The results suggest that the ECBI may be helpful in screening for disruptive behaviors in Taiwanese children, which may allow for appropriate prevention and intervention efforts. Although results are comparable to other research, cultural differences do exist, thereby highlighting the importance of cultural considerations in assessing child behavior, irrespective of country of treatment.

      3. Sexual teen dating violence victimization: Associations with sexual risk behaviors among U.S. high school studentsExternal
        Demissie Z, Clayton HB, Vivolo-Kantor AM, Estefan LF.
        Violence Vict. 2018 ;33(5):964-980.

        Adolescent dating violence may lead to adverse health behaviors. We examined associations between sexual teen dating violence victimization (TDVV) and sexual risk behaviors among U.S. high school students using 2013 and 2015 National Youth Risk Behavior Survey data (combined n = 29,346). Sex-stratified logistic regression models were used to estimate these associations among students who had dated or gone out with someone during the past 12 months (n = 20,093). Among these students, 10.5% experienced sexual TDVV. Sexual TDVV was positively associated with sexual intercourse before age 13, four or more lifetime sexual partners, current sexual activity, alcohol or drug use before last sexual intercourse, and no pregnancy prevention during last sexual intercourse. Given significant findings among both sexes, it is valuable for dating violence prevention efforts to target both female and male students.

      4. Violence victimization, substance use, and suicide risk among sexual minority high school students – United States, 2015-2017External
        Johns MM, Lowry R, Rasberry CN, Dunville R, Robin L, Pampati S, Stone DM, Mercer Kollar LM.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 2;67(43):1211-1215.

        Youths identifying as lesbian, gay, bisexual, or another nonheterosexual identity (sexual minority youths) report more violence victimization, substance use, and suicide risk than do heterosexual youths (1). These disparities are generally attributed to minority stress (the process through which stigma directed toward sexual minorities influences health outcomes) (2,3). Sexual minority youths might experience negative outcomes associated with minority stress differently across sexual identities, but to date, no nationally representative study has examined differences in victimization, substance use, and suicide risk within sexual minority youth. Using pooled data from the 2015 and 2017 national Youth Risk Behavior Surveys (YRBS), relationships between sexual identity groups and victimization, substance use, and suicide risk were evaluated with sex-stratified logistic regression models. Compared with heterosexual students, bisexual females and all sexual minority males reported more victimization; lesbian and bisexual females reported more use of alcohol, cigarettes, and marijuana; and all sexual minority youths reported elevated high-risk substance use and suicide risk. Programmatic efforts to reduce and prevent victimization, substance use, and suicide risk among sexual minority youths might benefit from consideration of issues within group differences.

      5. Circumstances preceding suicide in U.S. soldiers: A qualitative analysis of narrative dataExternal
        Skopp NA, Holland KM, Logan JE, Alexander CL, Floyd CF.
        Psychol Serv. 2018 Oct 29.

        To gain a better understanding of military suicide, we examined suicide narratives for 135 Soldiers extracted from two large-scale surveillance systems: the Department of Defense Suicide Event Report (DoDSER) and the Centers for Disease Control and Prevention’s (CDC) National Violent Death Reporting System (NVDRS). Using coroner/medical examiner and law enforcement narratives captured in the NVDRS and mental health provider narrative data collected across multiple domains from the DoDSER, we examined circumstances surrounding military suicides using a qualitative content analysis approach. We identified five common proximal circumstances: (1) intimate partner relationship problems (63.0%); (2) mental health/substance abuse (51.9%); (3) military job-related (46.7%); (4) financial (17.8%); and (5) criminal/legal activity (16.3%). Evidence of premeditation was present in 37.0% of suicides. Decedents frequently struggled with multiple, high-stress problems and exhibited symptoms of coping and emotion regulation difficulties. Findings demonstrate potential points of intervention for suicide prevention strategies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

      6. Concussion knowledge and experience among a sample of American adultsExternal
        Waltzman D, Daugherty J.
        J Concussion. 2018 Jan 1;2:1-11.

        Background: Recently, there has been a strong emphasis on educating athletes, parents, coaches, and health care providers about concussions. However, not much is known about whether these efforts are affecting the general public’s level of concussion knowledge. Purpose: To determine what is currently known among the public about concussions and where education campaigns may be targeted in order to fill in the gaps. Methods: In order to achieve the project’s objective, CDC analyzed self-reported data from Porter Novelli’s 2017 SummerStyles survey, an annual survey of American adults aged 18 and older across the United States. The questions focused on personal concussion experiences, basic concussion knowledge, knowledge of prevention strategies, and perceived best sources of information about concussion. Results: Analysis of the data showed that approximately 18% of respondents reported that they had personally experienced a concussion in their lifetime, and about two-thirds of these respondents were evaluated by a health care provider after their injury. In terms of concussion knowledge, the majority were aware of common causes of concussion. While 94% knew that headache was a symptom of concussion, just over half were aware that sleep problems were as well. Most respondents (>78%) correctly identified that wearing seat-belts, preventing falls, and reducing participation in contact sports were ways to prevent a concussion, while installing baby-gates across stairs was less frequently known (65.5%) as a prevention technique. Nearly all of the respondents believed that a doctor or other health professional was a good source of information about concussions. These results varied by age, sex, race/ethnicity, and education. Conclusion: The results demonstrate that even though the public has a relatively high knowledge level of concussion, targeted education is needed to teach American adults about the symptoms and ways of getting a concussion.

    • Laboratory Sciences

      1. Multiplex TaqMan qPCR assay for specific identification of encapsulated Trichinella species prevalent in North AmericaExternal
        Almeida M, Bishop H, Nascimento FS, Mathison B, Bradbury RS, Silva AD.
        Mem Inst Oswaldo Cruz. 2018 Oct 29;113(11):e180305.

        BACKGROUND Human trichinellosis is a foodborne parasitic zoonotic disease caused by ingestion of raw or undercooked meat infected with nematode larvae of the genus Trichinella. In the USA, sporadic cases and outbreaks caused by the consumption of wild game meat infected with Trichinella have been reported. The current methods for diagnosis such as serology and microscopy are not specific, may result in false negative results, and cannot differentiate encapsulated Trichinella larvae to species level. The molecular protocols currently available for the differentiation of all encapsulate Trichinella species prevalent in North America have some limitations such as the inability to identify and resolve the presence of several Trichinella species in a single test. OBJECTIVES/METHODS In this study we developed and evaluated a multiplex TaqMan quantitative real-time polymerase chain reaction (qPCR) assay, which can simultaneously detect, identify and differentiate all species of encapsulated Trichinella occurring in North America i.e., T. nativa, T. spiralis, T. murrelli and Trichinella T6, even in cases of multiple infection in a single sample. We investigated two human biopsies and 35 wild animal meat samples considered as having a high likelihood of harboring Trichinella larvae obtained from the United States during 2009-2017. FINDINGS Using the multiplex assay describe here, 22 (59%) samples that tested positive contained Trichinella spp., were identified as: T. nativa (n = 7, including a human biopsy), T. spiralis (n = 9, including a human biopsy), T. murrelli (n = 3), Trichinella T6 (n = 1). Results also included two rare mixed infection cases in bears, a T. nativa/T. spiralis from Alaska and a T. spiralis/Trichinella T6 from California. The species identifications were confirmed using a conventional PCR targeting the rRNA ITS1-ITS2 region, followed by DNA sequencing analysis. The estimated limit of detection (LOD) was approximately seven larvae per gram of meat. MAIN CONCLUSIONS Differentiation of Trichinella spp. is needed to improve efforts on identification of case, optimize food safety control and better understand the geographic distribution of Trichinella species. The Trichinella qPCR multiplex proved to be a robust, easy to perform assay and is presented as an improved technique for identification of all known encapsulated species occurring in North America continent.

      2. Immune priming and long-term persistence of memory B cells after inactivated poliovirus vaccine in macaque models: Support for at least 2 dosesExternal
        Bhaumik SK, Kulkarni RR, Weldon WC, Silveira EL, Ahmed H, Gunisetty S, Chandele A, Antia R, Verma H, Sutter R, Pallansch MA, Oberste MS, Villinger F, Orenstein W, Murali-Krishna K.
        Clin Infect Dis. 2018 Oct 30;67(suppl_1):S66-s77.

        Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.

      3. A logic model of neuronal-glial interaction suggests altered homeostatic regulation in the perpetuation of neuroinflammationExternal
        Craddock TJ, Michalovicz LT, Kelly KA, Rice MA, Miller DB, Klimas NG, Morris M, O’Callaghan JP, Broderick G.
        Front Cell Neurosci. 2018 ;12:336.

        Aberrant inflammatory signaling between neuronal and glial cells can develop into a persistent sickness behavior-related disorders, negatively impacting learning, memory, and neurogenesis. While there is an abundance of literature describing these interactions, there still lacks a comprehensive mathematical model describing the complex feed-forward and feedback mechanisms of neural-glial interaction. Here we compile molecular and cellular signaling information from various studies and reviews in the literature to create a logically-consistent, theoretical model of neural-glial interaction in the brain to explore the role of neuron-glia homeostatic regulation in the perpetuation of neuroinflammation. Logic rules are applied to this connectivity diagram to predict the system’s homeostatic behavior. We validate our model predicted homeostatic profiles against RNAseq gene expression profiles in a mouse model of stress primed neuroinflammation. A meta-analysis was used to calculate the significance of similarity between the inflammatory profiles of mice exposed to diisopropyl fluorophostphate (DFP) [with and without prior priming by the glucocorticoid stress hormone corticosterone (CORT)], with the equilibrium states predicted by the model, and to provide estimates of the degree of the neuroinflammatory response. Beyond normal homeostatic regulation, our model predicts an alternate self-perpetuating condition consistent with chronic neuroinflammation. RNAseq gene expression profiles from the cortex of mice exposed to DFP and CORT+DFP align with this predicted state of neuroinflammation, whereas the alignment to CORT alone was negligible. Simulations of putative treatment strategies post-exposure were shown to be theoretically capable of returning the system to a state of typically healthy regulation with broad-acting anti-inflammatory agents showing the highest probability of success. The results support a role for the brain’s own homeostatic drive in perpetuating the chronic neuroinflammation associated with exposure to the organophosphate DFP, with and without CORT priming. The deviation of illness profiles from exact model predictions suggests the presence of additional factors or of lasting changes to the brain’s regulatory circuitry specific to each exposure.

      4. Evaluation of a temperature-restricted, mucosal tuberculosis vaccine in guinea pigsCdc-pdfExternal
        Gupta T, LaGatta M, Helms S, Pavlicek RL, Owino SO, Sakamoto K, Nagy T, Harvey SB, Papania M, Ledden S, Schultz KT, McCombs C, Quinn FD, Karls RK.
        Tuberculosis. 2018 ;113:179-188.

        Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Gu?rin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.

      5. Notes from the field: Intestinal colonization and possible iatrogenic botulism in mouse bioassay-negative serum specimens – Los Angeles County, California, November 2017External
        Halai UA, Terashita D, Kim M, Green N, Kalb SR, Chatham-Stephens K, Balter S.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 2;67(43):1221-1222.

        [No abstract]

      6. Hepatitis B vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaquesExternal
        Perez Cuevas MB, Kodani M, Choi Y, Joyce J, O’Connor SM, Kamili S, Prausnitz MR.
        Bioeng Transl Med. 2018 Sep;3(3):186-196.

        Chronic Hepatitis B virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. Perinatal and early childhood infections are strongly associated with developing chronic hepatitis B. Adding a birth dose of the hepatitis B vaccine (HepB BD) to routine childhood vaccination can prevent over 85% of these infections. However, HepB BD coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited HepB BD supply at birth. To address the challenges, we developed coated metal microneedle patches (cMNPs) and dissolvable microneedle patches (dMNPs) that deliver adjuvant-free hepatitis B vaccine to the skin in a simple-to-administer manner. The dMNP contains micron-scale, solid needles encapsulating vaccine antigen and dissolve in the skin, generating no sharps waste. We delivered HepB BD via cMNP to BALB/c mice and via dMNP to both mice and rhesus macaques. Both cMNP and dMNP were immunogenic, generating hepatitis B surface antibody levels similar to human seroprotection. Biomechanical analysis showed that at high forces the microneedles failed mechanically by yielding but microneedles partially blunted by axial compression were still able to penetrate skin. Overall, this study indicates that with further development, dMNPs could offer a method of vaccination to increase HepB BD access and reduce needle waste in developing countries.

      7. Increased discrimination of Treponema pallidum strains by subtyping with a four-component system incorporating a mononucleotide tandem repeat in rspAExternal
        Pillay A, Lee MK, Slezak T, Katz SS, Sun Y, Chi KH, Morshed M, Philip S, Ballard RC, Chen CY.
        Sex Transm Dis. 2018 Oct 25.

        A guanine mononucleotide repeat (MNR) in the rpsA (tp0279) gene was evaluated for improved strain discrimination using 72 Treponema pallidum-positive specimens. The tandem repeat combined with the enhanced CDC typing system (ECDCT) resulted in increased discrimination and should be useful for molecular epidemiologic studies on syphilis especially in outbreaks and among MSM.

      8. Skin sensitization testing needs and data uses by US regulatory and research agenciesExternal
        Strickland J, Daniel AB, Allen D, Aguila C, Ahir S, Bancos S, Craig E, Germolec D, Ghosh C, Hudson NL, Jacobs A, Lehmann DM, Matheson J, Reinke EN, Sadrieh N, Vukmanovic S, Kleinstreuer N.
        Arch Toxicol. 2018 Oct 30.

        United States regulatory and research agencies may rely upon skin sensitization test data to assess the sensitization hazards associated with dermal exposure to chemicals and products. These data are evaluated to ensure that such substances will not cause unreasonable adverse effects to human health when used appropriately. The US Consumer Product Safety Commission, the US Environmental Protection Agency, the US Food and Drug Administration, the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, and the US Department of Defense are member agencies of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). ICCVAM seeks to identify opportunities for the use of non-animal replacements to satisfy these testing needs and requirements. This review identifies the standards, test guidelines, or guidance documents that are applicable to satisfy each of these agency’s needs; the current use of animal testing and flexibility for using alternative methodologies; information needed from alternative tests to fulfill the needs for skin sensitization data; and whether data from non-animal alternative approaches are accepted by these US federal agencies.

      9. Antibiotic-resistant Escherichia coli and class 1 integrons in humans, domestic animals, and wild primates in rural UgandaExternal
        Weiss D, Wallace RM, Rwego IB, Gillespie TR, Chapman CA, Singer RS, Goldberg TL.
        Appl Environ Microbiol. 2018 Nov 1;84(21).

        Antibiotic resistance is a global concern, although it has been studied most extensively in developed countries. We studied Escherichia coli and class 1 integrons in western Uganda by analyzing 1,685 isolates from people, domestic animals, and wild nonhuman primates near two national parks. Overall, 499 isolates (29.6%) were resistant to at least one of 11 antibiotics tested. The frequency of resistance reached 20.3% of isolates for trimethoprim-sulfamethoxazole but was nearly zero for the less commonly available antibiotics ciprofloxacin (0.4%), gentamicin (0.2%), and ceftiofur (0.1%). The frequency of resistance was 57.4% in isolates from people, 19.5% in isolates from domestic animals, and 16.3% in isolates from wild nonhuman primates. Isolates of livestock and primate origin displayed multidrug resistance patterns identical to those of human-origin isolates. The percentage of resistant isolates in people was higher near Kibale National Park (64.3%) than near Bwindi Impenetrable National Park (34.6%), perhaps reflecting local socioeconomic or ecological conditions. Across antibiotics, resistance correlated negatively with the local price of the antibiotic, with the most expensive antibiotics (nalidixic acid and ciprofloxacin) showing near-zero resistance. Among phenotypically resistant isolates, 33.2% harbored class 1 integrons containing 11 common resistance genes arranged into nine distinct gene cassettes, five of which were present in isolates from multiple host species. Overall, these results show that phenotypic resistance and class 1 integrons are distributed broadly among E. coli isolates from different host species in this region, where local socioeconomic and ecological conditions may facilitate widespread diffusion of bacteria or resistance-conferring genetic elements.IMPORTANCE Antibiotic resistance is a global problem. This study, conducted in rural western Uganda, describes antibiotic resistance patterns in Escherichia coli bacteria near two forested national parks. Resistance was present not only in people, but also in their livestock and in nearby wild nonhuman primates. Multidrug resistance and class 1 integrons containing genes that confer resistance were common and were similar in people and animals. The percentage of resistant isolates decreased with increasing local price of the antibiotic. Antibiotic resistance in this setting likely reflects environmental diffusion of bacteria or their genes, perhaps facilitated by local ecological and socioeconomic conditions.

    • Maternal and Child Health

      1. Adherence to recommended care guidelines in the treatment of preschool-age Medicaid-enrolled children with a diagnosis of ADHDExternal
        Moran A, Serban N, Danielson ML, Grosse SD, Cuffe SP.
        Psychiatr Serv. 2018 Oct 30:appips201800204.

        OBJECTIVE:: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood. Clinical guidelines recommend behavior therapy as the first-line treatment for preschool-age children with ADHD. This study evaluated longitudinal patterns of services received by Medicaid-enrolled children ages 2 to 5 with ADHD in seven southeastern states (Alabama, Florida, Georgia, Louisiana, Mississippi, North Carolina, and South Carolina). METHODS:: A discrete sequence clustering analysis was used with 2005-2012 Medicaid Analytic eXtract data to profile patient-level utilization for each state, with a focus on receipt of psychological services and medication. The model output was used to assess utilization behaviors longitudinally relative to recommended care guidelines and to characterize sources of variation in utilization patterns by demographic and ecological factors. RESULTS:: Five states had a utilization profile with a high probability of receipt of psychological services before medication among children with ADHD, covering 16% of the total study population. Most young children’s ADHD care experience in the seven states (65%) fit utilization profiles characterized by a high probability of receiving any ADHD medication. Black race was significantly associated with higher utilization of psychological services in three states. CONCLUSIONS:: About 16% of Medicaid-enrolled preschool-age children with ADHD received care during 2005-2012 that appeared to be consistent with 2011 recommended care guidelines. State-level and subpopulation variations in utilization for ADHD-related clinical care were found. The findings indicate that there were major gaps in treatment for ADHD among young children and that the gaps are wider for some states and subpopulations of children.

    • Occupational Safety and Health

      1. Determination of crystalline silica in respirable dust upon occupational exposure for Egyptian workersExternal
        Mohamed SH, El-Ansary AL, El-Aziz EM.
        Ind Health. 2018 Jun 1;56(3):255-263.

        Crystalline free silica is considered as a lung carcinogen and the occupational exposure to its dust is a health hazard to workers employed in industries that involve ores of mineral dust. In Egypt, thousands of people work under conditions of silica dust exposure exceeding the occupational exposure limit, as a result the monitoring of this occupational exposure to crystalline silica dust is required by government legislation. The assessment of the later is a multi-phase process, depend on workplace measurements, quantitative analyses of samples, and comparison of results with the permissible limits. This study aims to investigate occupational exposure to crystalline silica dust at 22 factories in Egypt with different industrial activities like stone cutting, glass making, ceramic, and sand blasting. Dust samples were collected from work sites at the breathing zone using a personal sampling pump and a size-selective cyclone and analyzed using FTIR. The sampling period was 60-120 min. The results show that the exposure at each of the industrial sectors is very much higher than the current national and international limits, and that lead to a great risk of lung cancer and mortality to workers.

      2. Flammability of respirators and other head and facial personal protective equipmentExternal
        Rengasamy S, Niezgoda G, Shaffer R.
        J Int Soc Respir Prot. 2018 ;35(1):1-13.

        Background: Personal protective equipment (PPE) is worn by workers in surgical settings to protect them and patients. Food and Drug Administration (FDA) clears some PPE (e.g., surgical masks (SM)) as class II medical devices, and regulates some (e.g. surgical head cover) as class I exempt devices. For respiratory protection, National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering facepiece respirators (FFRs), and powered air-purifying respirators (PAPRs) are used. One type of PPE, “surgical N95 respirators”, is a NIOSH-approved FFR that is also cleared by the FDA for use in medical settings. The surgical environment poses unique risks such as the potential for surgical fires. As part of its substantial equivalence determination process, FDA requests testing of flammability and other parameters for SM and surgical N95 respirators. A lack of data regarding flammability of PPE used in healthcare exists. We hypothesize that commonly used PPE, regardless of whether regulated and/or cleared by FDA or not, will pass an industry standard such as the 16 CFR 1610 flammability test. Methods: Eleven N95 FFR models, eight surgical N95 respirator models, seven SM models, five surgical head cover models, and five PAPR hood models were evaluated for flammability with a 45 degree flammability tester using the 16 CFR 1610 method. Three common fabrics were included for comparison. Results: All of the PPE samples regulated/and or cleared by FDA or not, passed the flammability test at class 1 (normal flammability), meaning they are less likely to burn. Only one of the three common fabrics, a cotton fabric at the lowest basis weight, was class 3 (high flammability). Conclusions: The results obtained in the study suggest that NIOSH-approved N95 FFRs would likely pass the 16 CFR 1610 flammability standard. Moreover, results suggest that NIOSH is capable of undertaking flammability testing using the 16 CFR 1610 standard as the flammability results NIOSH obtained for N95 FFRs were comparable to the results obtained by a third party independent laboratory.

    • Parasitic Diseases

      1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide studyExternal
        Assefa A, Ali A, Deressa W, Tsegaye W, Abebe G, Sime H, Kebede A, Jima D, Kassa M, Abreha T, Teka H, Solomon H, Malone J, Shi YP, Zhou Z, Reithinger R, Hwang J.
        Malar J. 2018 Oct 26;17(1):388.

        BACKGROUND: Building on the declining trend of malaria in Ethiopia, the Federal Ministry of Health aims to eliminate malaria by 2030. As Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia, the use of primaquine is indicated for both transmission interruption and radical cure, respectively. However, the limited knowledge of the local prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its associated variants has hindered the use of primaquine. METHODS: Some 11,138 dried blood spot (DBS) samples were collected in 2011 as part of a national, household Malaria Indicator Survey, a multi-stage nationally representative survey of all malaria-endemic areas of Ethiopia. A randomly selected sub-set of 1414 DBS samples was successfully genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Considering the geographical position and ethnic mix of the country, three common variants: G6PD*A (A376G), G6PD*A- (G202A) and Mediterranean (C563T) were investigated. RESULTS: Of the 1998 randomly selected individuals, 1429 (71.5%) DBS samples were genotyped and merged to the database, of which 53.5% were from females. G6PD*A (A376G) was the only genotype detected. No sample was positive for either G6PD*A- (G202A) or Mediterranean (C563T) variants. The prevalence of G6PD*A (A376G) was 8.9% [95% confidence interval (CI) 6.7-11.2] ranging from 12.2% in the Southern Nations, Nationalities and Peoples’ (95% CI 5.7-18.7) to none in Dire Dawa/Harari Region. CONCLUSION: The common G6PD*A- (G202A) or Mediterranean (C563T) variants were not observed in this nationwide study. The observed G6PD*A (A376G) mutation has little or no clinical significance. These findings supported the adoption of primaquine for P. falciparum transmission interruption and radical cure of P. vivax in Ethiopia. As the presence of other clinically important, less common variants cannot be ruled out, the implementation of radical cure will be accompanied by active haematological and adverse events monitoring in Ethiopia.

    • Statistics as Topic
      1. Quantitative risk assessments for physical, chemical, biological, occupational, or environmental agents rely on scientific studies to support their conclusions. These studies often include relatively few observations, and, as a result, models used to characterize the risk may include large amounts of uncertainty. The motivation, development, and assessment of new methods for risk assessment is facilitated by the availability of a set of experimental studies that span a range of dose-response patterns that are observed in practice. We describe construction of such a historical database focusing on quantal data in chemical risk assessment, and we employ this database to develop priors in Bayesian analyses. The database is assembled from a variety of existing toxicological data sources and contains 733 separate quantal dose-response data sets. As an illustration of the database’s use, prior distributions for individual model parameters in Bayesian dose-response analysis are constructed. Results indicate that including prior information based on curated historical data in quantitative risk assessments may help stabilize eventual point estimates, producing dose-response functions that are more stable and precisely estimated. These in turn produce potency estimates that share the same benefit. We are confident that quantitative risk analysts will find many other applications and issues to explore using this database.

    • Substance Use and Abuse

      1. Surveillance for cancers associated with tobacco use – United States, 2010-2014External
        Gallaway MS, Henley SJ, Steele CB, Momin B, Thomas CC, Jamal A, Trivers KF, Singh SD, Stewart SL.
        MMWR Surveill Summ. 2018 Nov 2;67(12):1-42.

        PROBLEM/CONDITION: Tobacco use is the leading preventable cause of cancer, contributing to at least 12 types of cancer, including acute myeloid leukemia (AML) and cancers of the oral cavity and pharynx; esophagus; stomach; colon and rectum; liver; pancreas; larynx; lung, bronchus, and trachea; kidney and renal pelvis; urinary bladder; and cervix. This report provides a comprehensive assessment of recent tobacco-associated cancer incidence for each cancer type by sex, age, race/ethnicity, metropolitan county classification, tumor characteristics, U.S. census region, and state. These data are important for initiation, monitoring, and evaluation of tobacco prevention and control measures. PERIOD COVERED: 2010-2014. DESCRIPTION OF SYSTEM: Cancer incidence data from CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program were used to calculate average annual age-adjusted incidence rates for 2010-2014 and trends in annual age-adjusted incidence rates for 2010-2014. These cancer incidence data cover approximately 99% of the U.S. POPULATION: This report provides age-adjusted cancer incidence rates for each of the 12 cancer types known to be causally associated with tobacco use, including liver and colorectal cancer, which were deemed to be causally associated with tobacco use by the U.S. Surgeon General in 2014. Findings are reported by demographic and geographic characteristics, percentage distributions for tumor characteristics, and trends in cancer incidence by sex. RESULTS: During 2010-2014, approximately 3.3 million new tobacco-associated cancer cases were reported in the United States, approximately 667,000 per year. Age-adjusted incidence rates ranged from 4.2 AML cases per 100,000 persons to 61.3 lung cancer cases per 100,000 persons. By cancer type, incidence rates were higher among men than women (excluding cervical cancer), higher among non-Hispanics than Hispanics (for all cancers except stomach, liver, kidney, and cervical), higher among persons in nonmetropolitan counties than those in metropolitan counties (for all cancers except stomach, liver, pancreatic, and AML), and lower in the West than in other U.S. census regions (all except stomach, liver, bladder, and AML). Compared with other racial/ethnic groups, certain cancer rates were highest among whites (oral cavity and pharyngeal, esophageal, bladder, and AML), blacks (colon and rectal, pancreatic, laryngeal, lung and bronchial, cervical, and kidney), and Asians/Pacific Islanders (stomach and liver). During 2010-2014, the rate of all tobacco-associated cancers combined decreased 1.2% per year, influenced largely by decreases in cancers of the larynx (3.0%), lung (2.2%), colon and rectum (2.1%), and bladder (1.3%). INTERPRETATION: Although tobacco-associated cancer incidence decreased overall during 2010-2014, the incidence remains high in several states and subgroups, including among men, whites, blacks, non-Hispanics, and persons in nonmetropolitan counties. These disproportionately high rates of tobacco-related cancer incidence reflect overall demographic patterns of cancer incidence in the United States and also reflect patterns of tobacco use. PUBLIC HEALTH ACTION: Tobacco-associated cancer incidence can be reduced through prevention and control of tobacco use and comprehensive cancer-control efforts focused on reducing cancer risk, detecting cancer early, and better assisting communities disproportionately affected by cancer. Ongoing surveillance to monitor cancer incidence can identify populations with a high incidence of tobacco-associated cancers and evaluate the effectiveness of tobacco control programs and policies. Implementation research can be conducted to achieve wider adoption of existing evidence-based cancer prevention and screening programs and tobacco control measures, especially to reach groups with the largest disparities in cancer rates.

      2. Effect of proxy responses on tobacco use surveys in Thailand, 2011External
        Hsia J, Puckcharern H, Town M.
        Prev Chronic Dis. 2018 Oct 25;15:E129.

        Proxy responses are often allowed in household tobacco surveys when all household members are included in a sample. To assess the effect of proxy responses on prevalence estimates, we compared 2 surveys in 2011 that gauged tobacco use in Thailand: the Cigarette Smoking and Alcohol Drinking Survey (SADS) and the Global Adult Tobacco Survey (GATS). Both surveys had similar nonsampling errors and design, but SADS allowed proxy responses and GATS did not. When proxy responses were included in SADS, the prevalence estimate was 10% lower in GATS for men (41.69% in GATS vs 46.55% in SADS) and 18% lower in GATS for women (2.14% in GATS vs 2.61% in SADS). Eliminating proxy responses is recommended to increase accuracy of tobacco-use surveillance.

      3. Opioid misuse among HIV-positive adults in medical care: Results from the Medical Monitoring Project, 2009 – 2014External
        Lemons A, DeGroote N, Perez A, Craw J, Nyaku M, Broz D, Mattson CL, Beer L.
        J Acquir Immune Defic Syndr. 2018 Oct 23.

        BACKGROUND: People living with HIV are prescribed opioids more often and at higher doses than people who do not have HIV, and disproportionately experience risk factors for substance use disorder, which suggests they could be at increased risk for the misuse of opioids. Researchers also suggest that opioid misuse negatively affects various HIV clinical outcomes, increasing the risk of transmission to partners with an HIV-negative status. METHODS: We calculated weighted percentages and 95% confidence intervals to estimate substance use characteristics among a probability sample of 28,162 HIV-positive adults receiving medical care in the US who misused opioids (n=975). Then, we used Rao-Scott chi2 tests to assess bivariate associations between opioid misuse and selected characteristics. RESULTS: In all, 3.3% misused opioids. Misuse was more common among young adults, males, and non-Hispanic whites. Persons who misused opioids were less likely to: have been prescribed antiretroviral therapy (ART) (88.7%), report being adherent to ART medications in the past 3 days (78.1%), and have durable viral suppression (54.3%) than persons who did not misuse opioids (92.5%, 87.7%, and 64.7%, respectively). Persons who misused opioids were more likely to report condomless sex with partners of negative or unknown HIV status while not durably virally suppressed (11.7% vs. 3.4%) than persons who did not misuse opioids. CONCLUSIONS: Opioid misuse among adults receiving HIV medical care is associated with inadequate ART adherence, insufficient durable viral suppression, and higher risk of HIV transmission to sexual partners.

    • Zoonotic and Vectorborne Diseases

      1. Persistence of Zika virus in body fluids – final reportExternal
        Paz-Bailey G, Rosenberg ES, Doyle K, Munoz-Jordan J, Santiago GA, Klein L, Perez-Padilla J, Medina FA, Waterman SH, Adams LE, Lozier MJ, Bertran-Pasarell J, Gubern CG, Alvarado LI, Sharp TM.
        N Engl J Med. 2018 Sep 27;379(13):1234-1243.

        BACKGROUND: To estimate the frequency and duration of detectable Zika virus (ZIKV) RNA in human body fluids, we prospectively assessed a cohort of newly infected participants in Puerto Rico. METHODS: We evaluated samples obtained from 150 participants (including 55 men) in whom ZIKV RNA was detected on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay in urine or blood in an enhanced arboviral clinical surveillance site. We collected serum, urine, saliva, semen, and vaginal secretions weekly for the first month and then at 2, 4, and 6 months. All specimens were tested by means of RT-PCR, and serum was tested with the use of anti-ZIKV IgM enzyme-linked immunosorbent assay. Among the participants with ZIKV RNA in any specimen at week 4, biweekly collection continued until all specimens tested negative. We used parametric Weibull regression models to estimate the time until the loss of ZIKV RNA detection in each body fluid and reported the findings in medians and 95th percentiles. RESULTS: The medians and 95th percentiles for the time until the loss of ZIKV RNA detection were 14 days (95% confidence interval [CI], 11 to 17) and 54 days (95% CI, 43 to 64), respectively, in serum; 8 days (95% CI, 6 to 10) and 39 days (95% CI, 31 to 47) in urine; and 34 days (95% CI, 28 to 41) and 81 days (95% CI, 64 to 98) in semen. Few participants had detectable ZIKV RNA in saliva or vaginal secretions. CONCLUSIONS: The prolonged time until ZIKV RNA clearance in serum in this study may have implications for the diagnosis and prevention of ZIKV infection. Current sexual-prevention guidelines recommend that men use condoms or abstain from sex for 6 months after ZIKV exposure; in 95% of the men in this study, ZIKV RNA was cleared from semen after about 3 months. (Funded by the Centers for Disease Control and Prevention.).

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CDC Science Clips Production Staff

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

Page last reviewed: January 31, 2019
Content source: Centers for Disease Control and Prevention