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Issue 13, April 4, 2017

CDC Science Clips: Volume 9, Issue 13, April 4, 2017

Each Tuesday, to enhance awareness of emerging scientific knowledge, selected science clips will be posted here for the public health community. The focus is applied public health research and prevention science that has the capacity to improve health now.

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

  1. CDC Vital Signs
    • Zoonotic and Vectorborne Diseases – Zika Virus RSS Word feed
      1. *Population-based pregnancy and birth defects surveillance in the era of Zika virus
        Gilboa SM, Mai CT, Shapiro-Mendoza CK, Cragan JD, Moore CA, Meaney-Delman DM, Jamieson DJ, Honein MA, Boyle CA.
        Birth Defects Research. 2017 ;109(5):372-378.
        Background: Zika virus is a newly recognized human teratogen; monitoring its impact on the birth prevalence of microcephaly and other adverse pregnancy outcomes will continue to be an urgent need in the United States and worldwide. Methods: When the Centers for Disease Control and Prevention (CDC) activated the Emergency Operations Center for the Zika virus outbreak response in January of 2016, public health leadership recognized that a joint, coordinated effort was required between activities focused on the effects of the infection among pregnant women and those focused on birth defects in fetuses and infants. Before the introduction of Zika virus in the Americas, population-based birth defects surveillance occurred independently of pregnancy surveillance activities. Results: The coordination of pregnancy surveillance and birth defects surveillance implemented through the CDC Zika virus response represents a paradigm shift. Conclusion: Coordination of these surveillance systems provides an opportunity to capture information from both a prospective and retrospective approach. This relatively modest investment in the public health infrastructure can continue to protect pregnant women and their infants during the ongoing response to Zika virus and in the next emergent threat to maternal and child health.

      2. *Zika Virus
        Petersen LR, Jamieson DJ, Powers AM, Honein MA.
        N Engl J Med. 2016 Apr 21;374(16):1552-63.
        [No abstract]
      3. Zika virus RNA replication and persistence in brain and placental tissue
        Bhatnagar J, Rabeneck DB, Martines RB, Reagan-Steiner S, Ermias Y, Estetter LB, Suzuki T, et al .
        Emerg Infect Dis. 2017 Mar;23(3):405-414.
        Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

      4. Baseline prevalence of birth defects associated with congenital Zika virus infection – Massachusetts, North Carolina, and Atlanta, Georgia, 2013-2014
        Cragan JD, Mai CT, Petersen EE, Liberman RF, Forestieri NE, Stevens AC, Delaney A, et al .
        MMWR Morb Mortal Wkly Rep. 2017 Mar 03;66(8):219-222.
        Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown. To better understand the impact of birth defects resulting from Zika virus infection, the CDC surveillance case definition established in 2016 for birth defects potentially related to Zika virus infection was retrospectively applied to population-based birth defects surveillance data collected during 2013-2014 in three areas before the introduction of Zika virus (the pre-Zika years) into the World Health Organization’s Region of the Americas (Americas). These data, from Massachusetts (2013), North Carolina (2013), and Atlanta, Georgia (2013-2014), included 747 infants and fetuses with one or more of the birth defects meeting the case definition (pre-Zika prevalence = 2.86 per 1,000 live births). Brain abnormalities or microcephaly were the most frequently recorded (1.50 per 1,000), followed by neural tube defects and other early brain malformationsdagger (0.88), eye abnormalities without mention of a brain abnormality (0.31), and other consequences of central nervous system (CNS) dysfunction without mention of brain or eye abnormalities (0.17). During January 15-September 22, 2016, the U.S. Zika Pregnancy Registry (USZPR) reported 26 infants and fetuses with these same defects among 442 completed pregnancies (58.8 per 1,000) born to mothers with laboratory evidence of possible Zika virus infection during pregnancy. Although the ascertainment methods differed, this finding was approximately 20 times higher than the proportion of one or more of the same birth defects among pregnancies during the pre-Zika years. These data demonstrate the importance of population-based surveillance for interpreting data about birth defects potentially related to Zika virus infection.

      5. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy
        Honein MA, Dawson AL, Petersen EE, Jones AM, Lee EH, Yazdy MM, Ahmad N, et al .
        Jama. 2017 Jan 03;317(1):59-68.
        Importance: Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10000 live births. Objective: To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. Design, Setting, and Participants: Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. Exposures: Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. Main Outcomes and Measures: Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. Results: Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. Conclusions and Relevance: Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.

      6. Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians
        Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, Fonseca EB, Ribeiro EM, Ventura LO, Neto NN, Arena JF, Rasmussen SA.
        JAMA Pediatr. 2017 Mar 01;171(3):288-295.
        Importance: Zika virus infection can be prenatally passed from a pregnant woman to her fetus. There is sufficient evidence to conclude that intrauterine Zika virus infection is a cause of microcephaly and serious brain anomalies, but the full spectrum of anomalies has not been delineated. To inform pediatric clinicians who may be called on to evaluate and treat affected infants and children, we review the most recent evidence to better characterize congenital Zika syndrome. Observations: We reviewed published reports of congenital anomalies occurring in fetuses or infants with presumed or laboratory-confirmed intrauterine Zika virus infection. We conducted a comprehensive search of the English literature using Medline and EMBASE for Zika from inception through September 30, 2016. Congenital anomalies were considered in the context of the presumed pathogenetic mechanism related to the neurotropic properties of the virus. We conclude that congenital Zika syndrome is a recognizable pattern of structural anomalies and functional disabilities secondary to central and, perhaps, peripheral nervous system damage. Although many of the components of this syndrome, such as cognitive, sensory, and motor disabilities, are shared by other congenital infections, there are 5 features that are rarely seen with other congenital infections or are unique to congenital Zika virus infection: (1) severe microcephaly with partially collapsed skull; (2) thin cerebral cortices with subcortical calcifications; (3) macular scarring and focal pigmentary retinal mottling; (4) congenital contractures; and (5) marked early hypertonia and symptoms of extrapyramidal involvement. Conclusions and Relevance: Although the full spectrum of adverse reproductive outcomes caused by Zika virus infection is not yet determined, a distinctive phenotype-the congenital Zika syndrome-has emerged. Recognition of this phenotype by clinicians for infants and children can help ensure appropriate etiologic evaluation and comprehensive clinical investigation to define the range of anomalies in an affected infant as well as determine essential follow-up and ongoing care.

      7. Update: Interim guidance for health care providers caring for pregnant women with possible Zika virus exposure – United States, July 2016
        Oduyebo T, Igbinosa I, Petersen EE, Polen KN, Pillai SK, Ailes EC, Villanueva JM, et al .
        MMWR Morb Mortal Wkly Rep. 2016 Jul 25;65(29):739-44.
        CDC has updated its interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure, to include the emerging data indicating that Zika virus RNA can be detected for prolonged periods in some pregnant women. To increase the proportion of pregnant women with Zika virus infection who receive a definitive diagnosis, CDC recommends expanding real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. Possible exposures to Zika virus include travel to or residence in an area with active Zika virus transmission, or sex* with a partner who has traveled to or resides in an area with active Zika virus transmission without using condoms or other barrier methods to prevent infection.(dagger) Testing recommendations for pregnant women with possible Zika virus exposure who report clinical illness consistent with Zika virus disease( section sign) (symptomatic pregnant women) are the same, regardless of their level of exposure (i.e., women with ongoing risk for possible exposure, including residence in or frequent travel to an area with active Zika virus transmission, as well as women living in areas without Zika virus transmission who travel to an area with active Zika virus transmission, or have unprotected sex with a partner who traveled to or resides in an area with active Zika virus transmission). Symptomatic pregnant women who are evaluated <2 weeks after symptom onset should receive serum and urine Zika virus rRT-PCR testing. Symptomatic pregnant women who are evaluated 2-12 weeks after symptom onset should first receive a Zika virus immunoglobulin (IgM) antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR testing should be performed. Testing recommendations for pregnant women with possible Zika virus exposure who do not report clinical illness consistent with Zika virus disease (asymptomatic pregnant women) differ based on the circumstances of possible exposure. For asymptomatic pregnant women who live in areas without active Zika virus transmission and who are evaluated <2 weeks after last possible exposure, rRT-PCR testing should be performed. If the rRT-PCR result is negative, a Zika virus IgM antibody test should be performed 2-12 weeks after the exposure. Asymptomatic pregnant women who do not live in an area with active Zika virus transmission, who are first evaluated 2-12 weeks after their last possible exposure should first receive a Zika virus IgM antibody test; if the IgM antibody test result is positive or equivocal, serum and urine rRT-PCR should be performed. Asymptomatic pregnant women with ongoing risk for exposure to Zika virus should receive Zika virus IgM antibody testing as part of routine obstetric care during the first and second trimesters; immediate rRT-PCR testing should be performed when IgM antibody test results are positive or equivocal. This guidance also provides updated recommendations for the clinical management of pregnant women with confirmed or possible Zika virus infection. These recommendations will be updated when additional data become available.

      8. Update: Interim guidance for the evaluation and management of infants with possible congenital Zika virus infection – United States, August 2016
        Russell K, Oliver SE, Lewis L, Barfield WD, Cragan J, Meaney-Delman D, Staples JE, et al .
        MMWR Morb Mortal Wkly Rep. 2016 Aug 26;65(33):870-878.
        CDC has updated its interim guidance for U.S. health care providers caring for infants born to mothers with possible Zika virus infection during pregnancy. Laboratory testing is recommended for 1) infants born to mothers with laboratory evidence of Zika virus infection during pregnancy and 2) infants who have abnormal clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission, regardless of maternal Zika virus test results. Congenital Zika syndrome is a recently recognized pattern of congenital anomalies associated with Zika virus infection during pregnancy that includes microcephaly, intracranial calcifications or other brain anomalies, or eye anomalies, among others (2). Recommended infant laboratory evaluation includes both molecular (real-time reverse transcription-polymerase chain reaction [rRT-PCR]) and serologic (immunoglobulin M [IgM]) testing. Initial samples should be collected directly from the infant in the first 2 days of life, if possible; testing of cord blood is not recommended. A positive infant serum or urine rRT-PCR test result confirms congenital Zika virus infection. Positive Zika virus IgM testing, with a negative rRT-PCR result, indicates probable congenital Zika virus infection. In addition to infant Zika virus testing, initial evaluation of all infants born to mothers with laboratory evidence of Zika virus infection during pregnancy should include a comprehensive physical examination, including a neurologic examination, postnatal head ultrasound, and standard newborn hearing screen. Infants with laboratory evidence of congenital Zika virus infection should have a comprehensive ophthalmologic exam and hearing assessment by auditory brainstem response (ABR) testing before 1 month of age. Recommendations for follow-up of infants with laboratory evidence of congenital Zika virus infection depend on whether abnormalities consistent with congenital Zika syndrome are present. Infants with abnormalities consistent with congenital Zika syndrome should have a coordinated evaluation by multiple specialists within the first month of life; additional evaluations will be needed within the first year of life, including assessments of vision, hearing, feeding, growth, and neurodevelopmental and endocrine function. Families and caregivers will also need ongoing psychosocial support and assistance with coordination of care. Infants with laboratory evidence of congenital Zika virus infection without apparent abnormalities should have ongoing developmental monitoring and screening by the primary care provider; repeat hearing testing is recommended. This guidance will be updated when additional information becomes available.

      9. Possible Zika virus infection among pregnant women – United States and Territories, May 2016
        Simeone RM, Shapiro-Mendoza CK, Meaney-Delman D, Petersen EE, Galang RR, Oduyebo T, Rivera-Garcia B, Valencia-Prado M, Newsome KB, Perez-Padilla J, Williams TR, Biggerstaff M, Jamieson DJ, Honein MA.
        MMWR Morb Mortal Wkly Rep. 2016 May 27;65(20):514-9.
        Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC’s national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(dagger) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),( section sign) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women residing in Puerto Rico. As of May 12, 2016, the surveillance systems were monitoring 157 and 122 pregnant women with laboratory evidence of possible Zika virus infection from participating U.S. states and territories, respectively. Tracking and monitoring clinical presentation of Zika virus infection, all prenatal testing, and adverse consequences of Zika virus infection during pregnancy are critical to better characterize the risk for congenital infection, the performance of prenatal diagnostic testing, and the spectrum of adverse congenital outcomes. These data will improve clinical guidance, inform counseling messages for pregnant women, and facilitate planning for clinical and public health services for affected families.

      10. Description of 13 infants born during October 2015-January 2016 with congenital Zika virus infection without microcephaly at birth – Brazil
        van der Linden V, Pessoa A, Dobyns W, Barkovich AJ, Junior HV, Filho EL, Ribeiro EM, et al .
        MMWR Morb Mortal Wkly Rep. 2016 Dec 02;65(47):1343-1348.
        Congenital Zika virus infection can cause microcephaly and severe brain abnormalities. Congenital Zika syndrome comprises a spectrum of clinical features; however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly. To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceara with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference.

  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 RSS Word feed
      1. Depressive states among adults with diabetes: Findings from the National Health and Nutrition Examination Survey, 2007-2012
        Albertorio-Diaz JR, Eberhardt MS, Oquendo M, Mesa-Frias M, He Y, Jonas B, Kang K.
        Diabetes Res Clin Pract. 2017 Feb 27;127:80-88.
        AIMS: To determine (1) the prevalence of SubD states among adults with diabetes, and (2) whether evidence exists of an independent association between diabetes status and SubD, controlling for selected confounders. METHODS: Data from the 2007-2012 National Health and Nutrition Examination Surveys were combined to estimates of depressive states by diabetes status among the noninstitutionalized U.S. adult population, and to assess the association of diabetes status and depressive states using a polytomous logistic regression model. RESULTS: An estimated 17%, or 3.7 million, of U.S. adults with diabetes (diagnosed and undiagnosed) met criteria for either mD or ssD. The majority of SubD cases with diabetes were found to be ssD (10.1%) compared with mD (6.9%). After controlling for the effects of age, sex, race and ethnicity, education, body mass index, and poverty as covariates, an independent association persists between diagnosed diabetes and each SubD grouping (ssD: OR=1.82, CIs 1.33, 2.47; mD: OR=1.95, CIs 1.39, 2.74) compared with respondents having no diabetes. No association was found between depression and undiagnosed diabetes or prediabetes compared with those having no diabetes. CONCLUSION: Milder forms of depression such as ssD and mD are more extant than major depressive episodes among adults with diabetes. The odds that an adult with diagnosed diabetes meets the criteria for ssD or mD are higher by 80% and 95%, respectively, after controlling for age, sex, race and ethnicity, education, body mass index, and poverty factors when compared against adults with no diabetes.

      2. The association between beliefs about vitamin D and skin cancer risk-related behaviors
        Holman DM, Berkowitz Z, Guy GP, Lunsford NB, Coups EJ.
        Prev Med. 2017 Mar 17.
        Major health organizations recommend obtaining most of one’s vitamin D through dietary sources rather than from sun exposure, given the link between sun exposure and increased skin cancer risk. The purpose of this study is to examine the association between beliefs about vitamin D and skin cancer risk-related behaviors, a topic on which research is limited. We analyzed cross-sectional online survey data collected in the summer of 2015 from 4127U.S. adults aged 18years and older. Overall, 19.7% of adults believed that sun protection would put them at risk of not getting enough vitamin D. However, less than half (43.1%) thought they could get enough vitamin D from dietary sources. Individuals with this belief were more likely to protect their skin when spending time outdoors (71.3%) compared with those who were neutral or disagreed (56.5%; P<0.001). Only 5.1% of adults believed that indoor tanning is an effective way to get vitamin D. Compared to those who disagreed or were neutral, those who thought it was effective were more likely to be outdoor tanners (45.1% vs. 28.5%; P<0.001) and indoor tanners (13.8% vs 1.9%; P<0.001). Beliefs about vitamin D were associated with skin cancer risk-related behaviors. Including information about vitamin D in skin cancer prevention messages may be beneficial.

      3. Trends in osteoporosis and low bone mass in older US adults, 2005-2006 through 2013-2014
        Looker AC, Sarafrazi Isfahani N, Fan B, Shepherd JA.
        Osteoporos Int. 2017 Mar 18.
        This study examined trends in osteoporosis and low bone mass in older US adults between 2005 and 2014 using bone mineral density (BMD) data from the National Health and Nutrition Examination Survey (NHANES). Osteoporosis and low bone mass appear to have increased at the femur neck but not at the lumbar spine during this period. INTRODUCTION: Recent preliminary data from Medicare suggest that the decline in hip fracture incidence among older US adults may have plateaued in 2013-2014, but comparable data on BMD trends for this time period are currently lacking. This study examined trends in the prevalence of osteoporosis and low bone mass since 2005 using BMD data from NHANES. The present study also updated prevalence estimates to 2013-2014 and included estimates for non-Hispanic Asians. METHODS: Femur neck and lumbar spine BMD by DXA were available for 7954 adults aged 50 years and older from four NHANES survey cycles between 2005-2006 and 2013-2014. RESULTS: Significant trends (quadratic or linear) were observed for the femur neck (mean T-score and osteoporosis in both sexes; low bone mass in women) but not for the lumbar spine. The trend in femur neck status was somewhat U-shaped, with prevalences being most consistently significantly higher (by 1.1-6.6 percentage points) in 2013-2014 than 2007-2008. Adjusting for changes in body mass index, smoking, milk intake, and physician’s diagnosis of osteoporosis between surveys did not change femur neck trends. In 2013-2014, the percent of older adults with osteoporosis was 6% at the femur neck, 8% at the lumbar spine, and 11% at either site. CONCLUSIONS: There was some evidence of a decline in femur neck BMD between 2005-2006 and 2013-2014, but not in lumbar spine BMD. Changes in the risk factors that could be examined did not explain the femur neck BMD trends.

      4. Indoor tanning initiation among tanners in the United States
        Watson M, Shoemaker M, Baker K.
        JAMA Dermatol. 2017 Mar 22.
        [No abstract]
    • Communicable Diseases RSS Word feed
      1. Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters
        Cavanaugh JS, Jou R, Wu MH, Dalton T, Kurbatova E, Ershova J, Cegielski JP.
        J Antimicrob Chemother. 2017 Feb 20.
        Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation.

      2. Correlates of county-level nonviral sexually transmitted infection hot spots in the US: application of hot spot analysis and spatial logistic regression
        Chang BA, Pearson WS, Owusu-Edusei K.
        Ann Epidemiol. 2017 Feb 21.
        PURPOSE: We used a combination of hot spot analysis (HSA) and spatial regression to examine county-level hot spot correlates for the most commonly reported nonviral sexually transmitted infections (STIs) in the 48 contiguous states in the United States (US). METHODS: We obtained reported county-level total case rates of chlamydia, gonorrhea, and primary and secondary (P&S) syphilis in all counties in the 48 contiguous states from national surveillance data and computed temporally smoothed rates using 2008-2012 data. Covariates were obtained from county-level multiyear (2008-2012) American Community Surveys from the US census. We conducted HSA to identify hot spot counties for all three STIs. We then applied spatial logistic regression with the spatial error model to determine the association between the identified hot spots and the covariates. RESULTS: HSA indicated that >/=84% of hot spots for each STI were in the South. Spatial regression results indicated that, a 10-unit increase in the percentage of Black non-Hispanics was associated with approximately 42% (P < 0.01) [ approximately 22% (P < 0.01), for Hispanics] increase in the odds of being a hot spot county for chlamydia and gonorrhea, and approximately 27% (P < 0.01) [ approximately 11% (P < 0.01) for Hispanics] for P&S syphilis. Compared with the other regions (West, Midwest, and Northeast), counties in the South were 6.5 (P < 0.01; chlamydia), 9.6 (P < 0.01; gonorrhea), and 4.7 (P < 0.01; P&S syphilis) times more likely to be hot spots. CONCLUSION: Our study provides important information on hot spot clusters of nonviral STIs in the entire United States, including associations between hot spot counties and sociodemographic factors.

      3. Identifying gaps in HIV service delivery across the diagnosis-to-treatment cascade: Findings from health facility surveys in six sub-Saharan countries
        Church K, Machiyama K, Todd J, Njamwea B, Mwangome M, Hosegood V, Michel J, Oti S, Nyamukapa C, Crampin A, Amek N, Nakigozi G, Michael D, Gomez-Olive FX, Nakiyingi-Miiro J, Zaba B, Wringe A.
        J Int AIDS Soc. 2017 ;20(1).
        Introduction: Despite the rollout of antiretroviral therapy (ART), challenges remain in ensuring timely access to care and treatment for people living with HIV. As part of a multi-country study to investigate HIV mortality, we conducted health facility surveys within 10 health and demographic surveillance system sites across six countries in Eastern and Southern Africa to investigate clinic-level factors influencing (i) use of HIV testing services, (ii) use of HIV care and treatment and (iii) patient retention on ART. Methods: Health facilities (n = 156) were sampled within 10 surveillance sites: Nairobi and Kisumu (Kenya), Karonga (Malawi), Agincourt and uMkhanyakude (South Africa), Ifakara and Kisesa (Tanzania), Kyamulibwa and Rakai (Uganda) and Manicaland (Zimbabwe). Structured questionnaires were administered to in-charge staff members of HIV testing, prevention of mother-to-child transmission (PMTCT) and ART units within the facilities. Forty-one indicators influencing uptake and patient retention along the continuum of HIV care were compared across sites using descriptive statistics. Results: The number of facilities surveyed ranged from six in Malawi to 36 in Zimbabwe. Eighty percent were governmentrun; 73% were lower-level facilities and 17% were district/referral hospitals. Client load varied widely, from less than one up to 65 HIV testing clients per provider per week. Most facilities (>80%) delivered services or interventions that would support patient retention in care such as delivering free services, offering PMTCT within antenatal care, pre-ART monitoring and adherence counselling. Many facilities under-delivered in several areas, however, such as targeted testing for high-risk groups (21%) and mobile testing (36%). There were also intra-site and inter-site differences, including in the delivery of Option B+ (ranging from 6% in Kisumu to 93% in Kyamulibwa), and nurse-led ART initiation (ranging from 50% in Kisesa to 100% in Karonga and Agincourt). Only facilities in Malawi did not require additional lab tests for ART initiation. Stock-outs of HIV test kits and antiretroviral drugs were particularly common in Tanzania. Conclusions: We identified a high standard of health facility performance in delivering strategies that may support progression through the continuum of HIV care. HIV testing policy and practice was particularly weak. Inter- and intracountry differences in quality and coverage represent opportunities to improve the delivery of comprehensive services to people living with HIV.

      4. Cross-resistance to lincosamides, streptogramins A and pleuromutilins in Streptococcus agalactiae isolates from the USA
        Hawkins PA, Law CS, Metcalf BJ, Chochua S, Jackson DM, Westblade LF, Jerris R, Beall BW, McGee L.
        J Antimicrob Chemother. 2017 Mar 13.
        Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of meningitis, sepsis and pneumonia in neonates in the United States. GBS also causes invasive disease in older infants, pregnant women, children and young adults with underlying medical conditions, and older adults. Resistance to lincosamides in the absence of erythromycin resistance is rare in GBS, but has been previously reported in clinical isolates, both on its own or in combination with resistance to streptogramins A and pleuromutilins (L/LSA/LSAP phenotypes). Objectives: To retrospectively screen the Active Bacterial Core surveillance (ABCs) GBS isolate collection for these phenotypes in order to identify the causal genetic determinants and determine whether their frequency is increasing. Methods: Based on MIC data, 65 (0.31%) isolates susceptible to erythromycin (MIC </=0.25 mg/L) and non-susceptible to clindamycin (MIC >/=0.5 mg/L) were identified among 21186 GBS isolates. Genomic DNA was extracted and WGS was performed. The presence of 10 genes previously associated with LSA resistance was investigated by read mapping. Results: Forty-nine (75%) isolates carried the lsa (C) gene and expressed the LSAP phenotype, and 12 (18%) carried both the lnu (B) and lsa (E) genes and expressed the LSAP phenotype. The four remaining isolates were negative for all determinants investigated. Conclusions: While the overall observed frequency of these phenotypes among our GBS isolates was quite low (0.31%), this frequency has increased in recent years. To the best of our knowledge, this is the first time the LSAP phenotype has been reported among GBS isolates from the USA.

      5. Lifetime risk of a diagnosis of HIV infection in the United States
        Hess KL, Hu X, Lansky A, Mermin J, Hall HI.
        Ann Epidemiol. 2017 Feb 21.
        PURPOSE: To estimate lifetime risk of receiving an HIV diagnosis in the United States if existing infection rates continue. METHODS: We used mortality, census, and HIV surveillance data for 2010 to 2014 to calculate age-specific probabilities of an HIV diagnosis. The probabilities were applied to a hypothetical cohort of 10 million live births to estimate lifetime risk. RESULTS: Lifetime risk was 1 in 68 for males and 1 in 253 for females. Lifetime risk for men was 1 in 22 for blacks, 1 in 51 for Hispanic/Latinos, and 1 in 140 for whites; and for women was 1 in 54 for blacks, 1 in 256 for Hispanic/Latinas, and 1 in 941 for whites. By risk group, the highest risk was among men who have sex with men (1 in 6) and the lowest was among male heterosexuals (1 in 524). Most of the states with the highest lifetime risk were in the South. CONCLUSIONS: The estimates highlight different risks across populations and the need for continued improvements in prevention and treatment. They can also be used to communicate the risk of HIV infection and increase public awareness of HIV.

      6. ‘Once there is life, there is hope’ Ebola survivors’ experiences, behaviours and attitudes in Sierra Leone, 2015
        Karafillakis E, Jalloh MF, Nuriddin A, Larson HJ, Whitworth J, Lees S, Hageman KM, Sengeh P, Jalloh MB, Bunnell R, Carroll DD, Morgan O.
        BMJ Global Health. 2016 ;1(3).
        Background: In Sierra Leone, over 4000 individuals survived Ebola since the outbreak began in 2014. Because Ebola survivorship was largely unprecedented prior to this outbreak, little is known about survivor experiences during and post illness. Methods To assess survivors’ experiences and attitudes related to Ebola, 28 in-depth interviews and short quantitative surveys with survivors from all four geographic regions of Sierra Leone were conducted in May 2015. Results: Survivor experiences, emotions and attitudes changed over time as they moved from disease onset to treatment, discharge and life post-discharge. Survivors mentioned experiencing acute fear and depression when they fell ill. Only half reported positive experiences in holding centres but nearly all were positive about their treatment centre experiences. Survivor euphoria on discharge was followed by concerns about their financial situation and future. While all reported supportive attitudes from family members, about a third described discrimination and stigma from their communities. Over a third became unemployed, especially those previously engaged in petty trade. Survivor knowledge about sexual transmission risk reflected counselling messages. Many expressed altruistic motivations for abstinence or condom use. In addition, survivors were strongly motivated to help end Ebola and to improve the healthcare system. Key recommendations from survivors included improved counselling in holding centres and long-term government support for survivors, including opportunities for participation in Ebola response efforts. Conclusions: Survivors face myriad economic, social and health challenges. Addressing survivor concerns, including the discrimination they face, could facilitate their reintegration into communities and their contributions to future Ebola responses.

      7. Systematic review, meta-analysis, and cost effectiveness of treatment of latent tuberculosis infection to reduce progression to multidrug-resistant tuberculosis
        Marks SM, Mase SR, Bamrah Morris S.
        Clin Infect Dis. 2017 Mar 14.
        Background: Evidence-based recommendations for treating persons having presumed latent tuberculosis infection (LTBI) after contact to infectious multidrug-resistant tuberculosis (MDR TB) are lacking because published data consist of small observational studies. TB incidence in persons treated for latent multidrug-resistant-TB infection (MDR LTBI) is unknown. Methods: We conducted a systematic review of studies published (1/1/1994-12/31/2014) to analyze TB incidence, treatment completion and discontinuation, and cost effectiveness. We considered contacts with LTBI effectively treated if they were on >/= one medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment versus non-treatment outcomes and performed meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. Results: We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR LTBI; 10 presented outcomes only for treated contacts, and five presented outcomes only for untreated contacts. The estimated MDR TB incidence reduction was 90% (9%-99%) using data from five comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. Conclusions: Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR LTBI, suggesting effectiveness in prevention of progression to MDR TB, and confirmed cost effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.

      8. High HIV prevalence and risk among male clients of female sex workers in Hanoi and Ho Chi Minh City, Vietnam
        Nadol P, Hoang TV, Le LV, Nguyen TA, Kaldor J, Law M.
        AIDS Behav. 2017 Mar 21.
        In Vietnam’s concentrated HIV epidemic, female sex workers (FSWs) are at increased risk for acquiring and transmitting HIV, largely through their male clients. A high proportion of males in Vietnam report being clients of FSWs. Studying HIV-related risk factors and prevalence among male clients is important, particularly given the potential for male clients to be a ‘bridge’ of HIV transmission to the more general population or to sex workers. Time-location sampling was used to identify FSW in Hanoi and Ho Chi Minh City, Vietnam’s largest cities, in 2013-2014. Recruited FSWs were asked to refer one male client to the study. Demographic and risk behavior data were collected from FSWs and male clients by administered questionnaires. Biologic specimens collected from male clients were tested for HIV and opiates. Sampling weights, calculated based on the FSWs probability of being selected for enrolment, were applied to prevalence estimates for both FSWs and male clients. Logistic regression models were developed to obtain odds ratios for HIV infection among male clients. A total of 804 male clients were enrolled. Overall, HIV prevalence among male clients was 10.2%; HIV prevalence was 20.7% (95% confidence interval (CI) 15.0-27.9%) among those reporting a history of illegal drug use and 32.4% (95% CI 20.2-47.7%) among those with opioids detected in urine. HIV prevalence among male clients did not differ across ‘bridging’ categories defined by condom use with FSWs and regular partners over the previous 6 months. HIV among male clients was associated with a reported history of illegal drug use (OR 3.76; 95% CI 1.87-7.56), current opioid use (OR 2.55; 95% CI 1.02-6.36), and being referred by an FSW who self-reported as HIV-positive (OR 5.37; 95% CI 1.46-19.75). Self-reported HIV prevalence among enrolled FSWs was 2.8%. Based on HIV test results of male clients and self-reported status from FSWs, an estimated 12.1% of male client-FSW pairs were sero-discordant. These results indicate high HIV prevalence among male clients of FSWs, particularly among those with a history of drug use. Programs to expand HIV testing, drug-use harm reduction, and HIV treatment for HIV-infected male clients of FSWs should be considered as key interventions for controlling the HIV epidemic in Vietnam.

      9. Increasing HIV-1 subtype diversity in seven states, United States, 2006-2013
        Oster AM, Switzer WM, Hernandez AL, Saduvala N, Wertheim JO, Nwangwu-Ike N, Ocfemia MC, Campbell E, Hall HI.
        Ann Epidemiol. 2017 Feb 22.
        PURPOSE: The aim of the analysis was to explore HIV-1 subtype diversity in the United States and understand differences in prevalence of non-B subtypes and circulating recombinant forms (CRFs) between demographic/risk groups and over time. METHODS: We included HIV-1 polymerase sequences reported to the National HIV Surveillance System for HIV infections diagnosed during 2006-2013 in seven states. We assigned subtype or CRF using the automated subtyping tool COMET, assessed subtype/CRF prevalence by demographic characteristics and country of birth, and determined changes in subtype/CRF by HIV diagnosis year. RESULTS: Of 32,968 sequences, 30,757 (93.3%) were subtype B. The most common non-B subtypes and CRFs were C (1.6%), CRF02_AG (1.4%), A (0.6%), CRF01_AE (0.5%), and G (0.3%). Elevated percentages of non-B infections occurred among persons aged <13 years at diagnosis (40.9%), Asians (32.1%), persons born outside the United States (22.6%), and persons with infection attributable to heterosexual contact (12.0%-15.0%). Prevalence of non-B infections increased from 5.9% in 2006 to 8.5% in 2013. CONCLUSIONS: Subtype B continues to predominate in the United States. However, the percentage of non-B infections has grown in recent years, and numerous demographic subgroups have much higher prevalence. Subgroups and areas with high prevalence of non-B infections might represent sub-epidemics meriting further investigation.

      10. Tuberculosis – United States, 2016
        Schmit KM, Wansaula Z, Pratt R, Price SF, Langer AJ.
        MMWR Morb Mortal Wkly Rep. 2017 Mar 24;66(11):289-294.
        In 2016, a total of 9,287 new tuberculosis (TB) cases were reported in the United States; this provisional count represents the lowest number of U.S. TB cases on record and a 2.7% decrease from 2015. The 2016 TB incidence of 2.9 cases per 100,000 persons represents a slight decrease compared with 2015 (-3.4%). However, epidemiologic modeling demonstrates that if similar slow rates of decline continue, the goal of U.S. TB elimination will not be reached during this century. Although current programs to identify and treat active TB disease must be maintained and strengthened, increased measures to identify and treat latent TB infection (LTBI) among populations at high risk are also needed to accelerate progress toward TB elimination.

      11. Novel orthopoxvirus infection in an Alaska resident
        Springer YP, Hsu CH, Werle ZR, Olson LE, Cooper MP, Castrodale LJ, Fowler N, McCollum AM, Goldsmith CS, Emerson GL, Wilkins K, Doty JB, Burgado J, Gao J, Patel N, Mauldin MR, Reynolds MG, Satheshkumar PS, Davidson W, Li Y, McLaughlin JB.
        Clin Infect Dis. 2017 Mar 15.
        Background: Human infection by orthopoxviruses is being reported with increasing frequency, attributed in part to the cessation of smallpox vaccination and concomitant waning of population-level immunity. In July 2015, a female resident of interior Alaska, presented to an urgent care clinic with a dermal lesion consistent with poxvirus infection. Laboratory testing of a virus isolated from the lesion confirmed infection by an Orthopoxvirus. Methods: The virus isolate was characterized by using electron microscopy and nucleic acid sequencing. An epidemiologic investigation that included patient interviews, contact tracing and serum testing, as well as environmental and small mammal sampling was conducted to identify the infection source and possible additional cases. Results: Neither signs of active infection nor evidence of recent prior infection were observed in any of the 4 patient contacts identified. The patient’s infection source was not definitively identified. Potential routes of exposure included imported fomites from Azerbaijan by the patient’s cohabiting partner, or from wild small mammals in or around the patient’s residence. Phylogenetic analyses demonstrated that the virus represents a distinct and previously undescribed genetic lineage of Orthopoxvirus, which is most closely related to the Old World orthopoxviruses. Conclusions: Investigation findings point to infection of the patient following exposure in or near Fairbanks. This conclusion raises questions about the geographic origins (Old World versus North American) of the genus Orthopoxvirus. Clinicians should remain vigilant for signs of poxvirus infection and alert public health officials when cases are suspected.

      12. Estimated perinatal HIV infection among infants born in the United States, 2002-2013
        Taylor AW, Nesheim SR, Zhang X, Song R, FitzHarris LF, Lampe MA, Weidle PJ, Sweeney P.
        JAMA Pediatr. 2017 Mar 20.
        Importance: Perinatal transmission of human immunodeficiency virus (HIV) can be reduced through services including antiretroviral treatment and prophylaxis. Data on the national incidence of perinatal HIV transmission and missed prevention opportunities are needed to monitor progress toward elimination of mother-to-child HIV transmission. Objective: To estimate the number of perinatal HIV cases among infants born in the United States. Design, Setting, and Participants: Data were obtained from the National HIV Surveillance System on infants with HIV born in the United States (including the District of Columbia) and their mothers between 2002 and 2013 (reported through December 31, 2015). Estimates were adjusted for delay in diagnosis and reporting by weighting each reported case based on a model incorporating time from birth to diagnosis and report. Analysis was performed from April 1 to August 15, 2016. Exposures: Maternal HIV infection and antiretroviral medication, including maternal receipt prenatally or during labor/delivery and infant receipt postnatally. Main Outcomes and Measures: Diagnosis of perinatally acquired HIV infection in infants born in the United States. Infant and maternal characteristics, including receipt of perinatal HIV testing, treatment, and prophylaxis. Results: The estimated annual number of perinatally infected infants born in the United States decreased from 216 (95% CI, 206-230) in 2002 to 69 (95% CI, 60-83) in 2013. Among perinatally HIV-infected children born in 2002-2013, 836 (63.0%) of the mothers identified as black or African American and 243 (18.3%) as Hispanic or Latino. A total of 236 (37.5%) of the mothers had HIV infection diagnosed before pregnancy in 2002-2005 compared with 120 (51.5%) in 2010-2013; the proportion of mother-infant pairs receiving all 3 recommended arms of antiretroviral prophylaxis or treatment (prenatal, intrapartum, and postnatal) was 22.4% in 2002-2005 and 31.8% in 2010-2013, with approximately 179 (28.4%) (2002-2005) and 94 (40.3%) (2010-2013) receiving antiretroviral prophylaxis or treatment during pregnancy. Five Southern states (Florida, Texas, Georgia, Louisiana, and Maryland) accounted for 687 (38.0%) of infants born with HIV infection in the United States during the overall period. According to national data for live births, the incidence of perinatal HIV infection among infants born in the United States in 2013 was 1.75 per 100000 live births. Conclusions and Relevance: Despite reduced perinatal HIV infection in the United States, missed opportunities for prevention were common among infected infants and their mothers in recent years. As of 2013, the incidence of perinatal HIV infection remained 1.75 times the proposed Centers for Disease Control and Prevention elimination of mother-to-child HIV transmission goal of 1 per 100000 live births.

      13. Influenza and respiratory syncytial virus in infants study (IRIS) of hospitalized and non-ill infants aged <1 year in four countries: study design and methods
        Thompson MG, Hunt DR, Arbaji AK, Simaku A, Tallo VL, Biggs HM, Kulb C, Gordon A, Khader IA, Bino S, Lucero MG, Azziz-Baumgartner E, Shifflett P, Sanchez F, Marar BI, Bakalli I, Simoes EA, Levine MZ, Meece JK, Balmaseda A, Al-Sanouri TM, Dhimolea M, de Jesus JN, Thornburg NJ, Gerber SI, Gresh L.
        BMC Infect Dis. 2017 Mar 22;17(1):222.
        BACKGROUND: This multi-country prospective study of infants aged <1 year aims to assess the frequency of influenza virus and respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. METHODS/DESIGN: We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset </=10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. DISCUSSION: The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new vaccines and other prevention and treatment strategies.

      14. Tuberculosis among foreign-born persons diagnosed >/=10 years after arrival in the United States, 2010-2015
        Tsang CA, Langer AJ, Navin TR, Armstrong LR.
        MMWR Morb Mortal Wkly Rep. 2017 Mar 24;66(11):295-298.
        The majority of tuberculosis (TB) cases in the United States are attributable to reactivation of latent TB infection (LTBI). LTBI refers to the condition when a person is infected with Mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of TB disease. CDC and the U.S. Preventive Services Task Force (USPSTF) recommend screening populations at increased risk for LTBI, including persons who have lived in congregate settings at high risk and persons who were born in, or are former residents of countries with TB incidence >/=20 cases per 100,000 population. In 2015, foreign-born persons constituted 66.2% of U.S. TB cases. During the past 30 years, screening of persons from countries with high TB rates has focused on overseas screening for immigrants and refugees, and domestic screening for persons who have newly arrived in the United States. However, since 2007, an increasing number and proportion of foreign-born patients receiving a diagnosis of TB first arrived in the United States >/=10 years before the development and diagnosis of TB disease. To better understand how this group of patients differs from persons who developed TB disease and received a diagnosis <10 years after U.S. arrival, CDC analyzed data for all reported TB cases in the United States since 1993 in the National TB Surveillance System (NTSS). After adjusting for age and other characteristics, foreign-born persons who arrived in the United States >/=10 years before diagnosis were more likely to be residents of a long-term care facility or to have immunocompromising conditions other than human immunodeficiency virus (HIV) infection. These findings support using the existing CDC and USPSTF recommendations for TB screening of persons born in countries with high TB rates regardless of time since arrival in the United States.

      15. Detect to prevent: Evaluating testing and treatment practices for latent tuberculosis infection in long-term care facilities
        Winston CA, Stone ND.
        J Am Geriatr Soc. 2017 Mar 17.
        [No abstract]
    • Disaster Control and Emergency Services RSS Word feed
      1. Physiological evaluation of personal protective ensembles recommended for use in West Africa
        Coca A, Quinn T, Kim JH, Wu T, Powell J, Roberge R, Shaffer R.
        Disaster Med Public Health Prep. 2017 Mar 17:1-7.
        OBJECTIVE: Personal protective equipment (PPE) provides health care workers with a barrier to prevent human contact with viruses like Ebola and potential transmission of the disease. However, PPE can also introduce an additional physiological burden from potentially increased heat stress. This study evaluated the human physiological and subjective responses to continuous light exercise within environmental conditions similar to those in West Africa while wearing 3 different, commonly used PPE ensembles (E1, E2, and E3). METHODS: Six healthy individuals were tested in an environmental chamber (32 degrees C, 92% relative humidity) while walking (3 METs, 2.5 mph, 0% incline) on a treadmill for 60 minutes. All subjects wore medical scrubs and PPE items. E1 also had a face shield and fluid-resistant surgical gown; E2 additionally included goggles, coverall, and separate hood; and E3 also contained a highly impermeable coverall, separate hood, and surgical mask cover over the N95 respirator. RESULTS: Heart rate and core temperature at the end of the exercise were significantly higher for E2 and E3 than for E1. Subjective perceptions of heat and exertion were significantly higher for E2 and E3 than for E1. CONCLUSIONS: Heat stress and PPE training, as well as the implementation of a work-to-rest ratio that avoids dehydration and possible heat stress issues, are recommended. (Disaster Med Public Health Preparedness. 2017;page 1 of 7).

      2. Physiological evaluation of cooling devices in conjunction with personal protective ensembles recommended for use in West Africa
        Quinn T, Kim JH, Strauch A, Wu T, Powell J, Roberge R, Shaffer R, Coca A.
        Disaster Med Public Health Prep. 2017 Mar 17:1-7.
        OBJECTIVE: Cooling devices (CDs) worn under personal protective equipment (PPE) can alleviate some of the heat stress faced by health care workers responding to the Ebola outbreak in West Africa. METHODS: Six healthy, young individuals were tested while wearing 4 different CDs or no cooling (control) under PPE in an environmental chamber (32 degrees C/92% relative humidity) while walking (3 METs, 2.5 mph, 0% grade) on a treadmill for 60 minutes. Exercise was preceded by a 15-minute stabilization period and a 15-minute donning period. RESULTS: The control condition resulted in a significantly higher rectal temperature (Tre) at the end of the exercise than did all CD conditions (CD1, P=0.004; CD2, P=0.01; CD3, P=0.000; CD4, P=0.000) with CD1 and CD2 resulting in a higher Tre than CD3 and CD4 (P<0.05). The control condition resulted in a higher heart rate (HR) at the end of exercise than did the CD3 (P=0.01) and CD4 (P=0.009) conditions, whereas the HR of the CD1 and CD2 conditions was higher than that of the CD3 and CD4 conditions (P<0.05). Weight loss in the control condition was higher than in the CD3 (P=0.003) and CD4 (P=0.01) conditions. Significant differences in subjective measurements of thermal stress were found across conditions and time. CONCLUSIONS: Use of CDs can be advantageous in decreasing the negative physiological and subjective responses to the heat stress encountered by health care workers wearing PPE in hot and humid environments. (Disaster Med Public Health Preparedness. 2017;page 1 of 7).

      3. Identifying and prioritizing information needs and research priorities of public health emergency preparedness and response practitioners
        Siegfried AL, Carbone EG, Meit MB, Kennedy MJ, Yusuf H, Kahn EB.
        Disaster Med Public Health Prep. 2017 Mar 23:1-10.
        OBJECTIVE: This study describes findings from an assessment conducted to identify perceived knowledge gaps, information needs, and research priorities among state, territorial, and local public health preparedness directors and coordinators related to public health emergency preparedness and response (PHPR). The goal of the study was to gather information that would be useful for ensuring that future funding for research and evaluation targets areas most critical for advancing public health practice. METHODS: We implemented a mixed-methods approach to identify and prioritize PHPR research questions. A web survey was sent to all state, city, and territorial health agencies funded through the Public Health Emergency Preparedness (PHEP) Cooperative Agreement program and a sample of local health departments (LHDs). Three focus groups of state and local practitioners and subject matter experts from the Centers for Disease Control and Prevention (CDC) were subsequently conducted, followed by 3 meetings of an expert panel of PHPR practitioners and CDC experts to prioritize and refine the research questions. RESULTS: We identified a final list of 44 research questions that were deemed by study participants as priority topics where future research can inform PHPR programs and practice. We identified differences in perceived research priorities between PHEP awardees and LHD survey respondents; the number of research questions rated as important was greater among LHDs than among PHEP awardees (75%, n=33, compared to 24%, n=15). CONCLUSIONS: The research questions identified provide insight into public health practitioners’ perceived knowledge gaps and the types of information that would be most useful for informing and advancing PHPR practice. The study also points to a higher level of information need among LHDs than among PHEP awardees. These findings are important for CDC and the PHPR research community to ensure that future research studies are responsive to practitioners’ needs and provide the information required to enhance their capacity to meet the needs of the communities and jurisdictions they serve. (Disaster Med Public Health Preparedness. 2017;page 1 of 10).

    • Disease Reservoirs and Vectors RSS Word feed
      1. Seroprevalence of Rift Valley fever in cattle along the Akagera-Nyabarongo rivers, Rwanda
        Umuhoza T, Berkvens D, Gafarasi I, Rukelibuga J, Mushonga B, Biryomumaisho S.
        J S Afr Vet Assoc. 2017 Jan 20;88(0):e1-e5.
        Rift Valley fever (RVF) virus is caused by a zoonotic arbovirus that is endemic to eastern and southern Africa. It has also been reported in West and North Africa, Madagascar and the Arabian Peninsula. The virus is transmitted by mosquitoes, but people can also become infected while handling blood or other body fluids of animals and humans with RVF. In 2007, there was a large outbreak of RVF in Kenya, Tanzania, Sudan and Somalia. Outbreaks were also reported in South Africa in 2008-2011. The epidemiology of RVF and factors for disease occurrence in Rwanda are neither clear nor documented. Therefore, we conducted a crosssectional study from December 2012 to March 2013 to generate baseline information on RVF in cattle. Purposive sampling of cattle (n = 595) was done in six districts, and serum samples were screened with competitive enzyme-linked immunosorbent assay (ELISA). We performed a statistical analysis on the generated data, and risk factors associated with RVF seroprevalence were determined by a simple logistic regression. Overall, RVF seroprevalence was 16.8% (95% confidence interval [CI] [13.8% – 20.0%]). The highest seroprevalence was recorded in Kirehe district (36.9%) followed by Ngoma (22.3%), and the least was recorded in Nyagatare (7.9%). RVF was more likely to occur in adult cattle (19.9% [odds ratio {OR} = 1.88, 95% CI {0.98-3.61}]) compared to young cattle (10.5% [OR = 0.47, 95% CI {0.26-0.83}]). Pure exotic or cross-breeds were significantly exposed to RVF virus (seroprevalence 22.9% [OR = 4.26, 95% CI {1.82-9.99}]) in comparison to 14.1% (OR = 0.55, 95% CI [0.35-0.86]) in local breeds. Sex differences were not statistically significant. These findings indicated that cattle have been exposed to RVF virus in six districts in Rwanda with a significant risk in adult, exotic or cross-breeds in Kirehe district.

    • Environmental Health RSS Word feed
      1. Physical, mental, and financial impacts from drought in two California counties, 2015
        Barreau T, Conway D, Haught K, Jackson R, Kreutzer R, Lockman A, Minnick S, Roisman R, Rozell D, Smorodinsky S, Tafoya D, Wilken JA.
        Am J Public Health. 2017 Mar 21:e1-e8.
        OBJECTIVES: To evaluate health impacts of drought during the most severe drought in California’s recorded history with a rapid assessment method. METHODS: We conducted Community Assessments for Public Health Emergency Response during October through November 2015 in Tulare County and Mariposa County to evaluate household water access, acute stressors, exacerbations of chronic diseases and behavioral health issues, and financial impacts. We evaluated pairwise associations by logistic regression with pooled data. RESULTS: By assessment area, households reported not having running water (3%-12%); impacts on finances (25%-39%), property (39%-54%), health (10%-20%), and peace of mind (33%-61%); worsening of a chronic disease (16%-46%); acute stress (8%-26%); and considering moving (14%-34%). Impacts on finances or property were each associated with impacts on health and peace of mind, and acute stress. CONCLUSIONS: Drought-impacted households might perceive physical and mental health effects and might experience financial or property impacts related to the drought. Public Health Implications. Local jurisdictions should consider implementing drought assistance programs, including behavioral health, and consider rapid assessments to inform public health action. (Am J Public Health. Published online ahead of print March 21, 2017: e1-e8. doi:10.2105/AJPH.2017.303695).

      2. Trimester-specific urinary bisphenol A concentrations and blood glucose levels among pregnant women from a fertility clinic
        Chiu YH, Minguez-Alarcon L, Ford JB, Keller M, Seely EW, Messerlian C, Petrozza J, Williams PL, Ye X, Calafat AM, Hauser R, James-Todd T.
        J Clin Endocrinol Metab. 2017 Jan 12.
        Context: Women with a history of infertility are at increased risk of impaired glucose tolerance during pregnancy. Studies suggest higher urinary bisphenol A (BPA) concentrations are associated with diabetes in non-pregnant populations, but the association between BPA and glucose levels among pregnant women is unclear. Objective: To assess trimester-specific urinary BPA concentrations in relation to blood glucose levels among subfertile women. Design: Environment and Reproductive Health Study, an ongoing prospective cohort study. Setting: A fertility center in a teaching hospital. Patients: A total of 245 women contributed at least one urine sample during 1st and/or 2nd trimesters, delivered a singleton or twin pregnancy, and had available blood glucose data (2005-2015). Main Outcome Measure: Blood glucose levels after a non-fasting 50-gram glucose challenge test at 24-28 weeks of gestation. Results: The specific gravity-adjusted geometric mean urinary BPA concentrations during 1st and 2nd trimesters were 1.39 and 1.27 microg/L, respectively. Second trimester BPA concentrations were positively associated with blood glucose (P, trend=0.01). Specifically, the adjusted mean glucose levels (95%CI) for women in the highest quartile of 2nd trimester BPA concentrations was 119 (112, 126) mg/dL compared to 106 (100, 112) mg/dL for women in the lowest quartile. No associations were observed between 1st trimester BPA concentrations and blood glucose levels. Conclusions: BPA exposure during 2nd trimester may have adverse effect on blood glucose levels among subfertile women. As the findings represent the first report suggesting a potential etiologically relevant window for BPA and glucose in humans, further studies are needed.

      3. Exposure to di-2-ethylhexyl terephthalate in a convenience sample of U.S. adults from 2000 to 2016
        Silva MJ, Wong LY, Samandar E, Preau JL, Calafat AM, Ye X.
        Arch Toxicol. 2017 Mar 17.
        Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of di-2-ethylhexyl phthalate (DEHP), is a plasticizer used in a variety of commercial applications, but data on Americans’ exposure to DEHTP do not exist. We investigated the exposure to DEHTP in a convenience group of U.S. adults by analyzing urine collected anonymously in 2000 (N = 44), 2009 (N = 61), 2011 (N = 81), 2013 (N = 92), and 2016 (N = 149) for two major DEHTP oxidative metabolites: mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP). For comparison, we also quantified the analogous DEHP metabolites mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). We detected MECPTP, MEHHP, and MECPP in all samples collected in 2016 with geometric means of 13.1, 4.1, and 6.7 ng/mL, respectively; we detected MEHHTP in 91% of the samples (geometric mean = 3.1 ng/mL). Concentrations of MECPTP correlated well with those of MEHHTP (R 2 = 0.8, p < 0.001), but did not significantly correlate with those of MEHHP (p > 0.05) suggesting different sources of exposure to DEHP and DEHTP. We also evaluated the fraction of the metabolites eliminated in their free (i.e., unconjugated) form. The median percent of unconjugated species was lower for the DEHP metabolites (MECPP [45.5%], MEHHP [1.9%]) compared to the DEHTP metabolites (MECPTP [98.8%], MEHHTP [21.2%]). Contrary to the downward trend from 2000 to 2016 in urinary concentrations of MEHHP and MECPP, we observed an upward trend for MEHHTP and MECPTP. These preliminary data suggest that exposure to DEHTP may be on the rise. Nevertheless, general population exposure data using MEHHTP and MECPTP as exposure biomarkers would increase our understanding of exposure to DEHTP, one of the known DEHP alternatives.

      4. Toxicity of airborne dust as an indicator of moisture problems in school buildings
        Tirkkonen J, Taubel M, Leppanen H, Peltonen M, Lindsley W, Chen BT, Hyvarinen A, Hirvonen MR, Huttunen K.
        Inhal Toxicol. 2017 Feb;29(2):75-81.
        Moisture-damaged indoor environments are thought to increase the toxicity of indoor air particulate matter (PM), indicating that a toxicological assay could be used as a method for recognizing buildings with indoor air problems. We aimed to test if our approach of analyzing the toxicity of actively collected indoor air PM in vitro differentiates moisture-damaged from non-damaged school buildings. We collected active air samples with NIOSH Bioaerosol Cyclone Samplers from moisture-damaged (index) and non-damaged (reference) school buildings (4 + 4). The teachers and pupils of the schools were administered a symptom questionnaire. Five samples of two size fractions [Stage 1 (>1.9 mum) and Stage 2 (1-1.9 mum)] were collected from each school. Mouse RAW264.7 macrophages were exposed to the collected PM for 24 h and subsequently analyzed for changes in cell metabolic activity, production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. The teachers working in the moisture-damaged schools reported respiratory symptoms such as cough (p = 0.01) and shortness of breath (p = 0.01) more often than teachers from reference schools. Toxicity of the PM sample as such did not differentiate index from reference building,s but the toxicity adjusted for the amount of the particles tended to be higher in moisture-damaged schools. Further development of the method will require identification of other confounding factors in addition to the necessity to adjust for differences in particle counts between samples.

    • Food Safety RSS Word feed
      1. International outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder – USA and Canada, 2013-2014
        Harvey RR, Heiman Marshall KE, Burnworth L, Hamel M, Tataryn J, Cutler J, Meghnath K, Wellman A, Irvin K, Isaac L, Chau K, Locas A, Kohl J, Huth PA, Nicholas D, Traphagen E, Soto K, Mank L, Holmes-Talbot K, Needham M, Barnes A, Adcock B, Honish L, Chui L, Taylor M, Gaulin C, Bekal S, Warshawsky B, Hobbs L, Tschetter LR, Surin A, Lance S, Wise ME, Williams I, Gieraltowski L.
        Epidemiol Infect. 2017 Mar 20:1-10.
        Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013-2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

    • Genetics and Genomics RSS Word feed
      1. High-quality genome sequence of an Escherichia coli O157 strain carrying an mcr-1 resistance gene isolated from a patient in the United States
        Lindsey RL, Batra D, Rowe L, Loparev VN, Stripling D, Garcia-Toledo L, Knipe K, Juieng P, Sheth M, Martin H, Laufer Halpin A.
        Genome Announc. 2017 Mar 16;5(11).
        Enterobacteriaceae carrying plasmid-mediated colistin resistance have been found around the world. We report here the high-quality whole-genome sequence of an Escherichia coli O157:H48 isolate (2016C-3936C1) from Connecticut that carried the mcr-1 resistance gene on an IncX4-type plasmid.

      2. Genomic characterization of three melon necrotic spot viruses detected in human stool specimens
        Marine R, Castro C, Magana L, Ng TF, Aswath K, Collins N, Park GW, Vinje J, Oberste MS.
        Genome Announc. 2017 Mar 16;5(11).
        The complete coding sequences of three melon necrotic spot viruses (MNSVs) were obtained from viral metagenomics of stool samples from patients with acute gastroenteritis. These genomes were most similar to Spanish strains sequenced in 2003 and a novel MNSV watermelon strain in 2014.

    • Health Behavior and Risk RSS Word feed
      1. Spirituality/religiosity, substance use, and HIV testing among young black men who have sex with men
        Carrico AW, Storholm ED, Flentje A, Arnold EA, Pollack LM, Neilands TB, Rebchook GM, Peterson JL, Eke A, Johnson W, Kegeles SM.
        Drug Alcohol Depend. 2017 Mar 07;174:106-112.
        BACKGROUND: Spirituality and religiosity may serve as both a resource and a barrier to HIV prevention with young black men who have sex with men (YBMSM). We examined indices of spirituality/religiosity as correlates of binge drinking, stimulant use, and recent HIV testing in a sample of YBMSM. METHODS: From 2011-2013, annual venue-based surveys of sexually active YBMSM ages 18-29 were conducted in Dallas and Houston, Texas. Binge drinking and stimulant use were assessed in the past two months. Participants recently tested for HIV (i.e., within the past six months) were compared to those without recent HIV testing (i.e., never tested or tested more than six months ago). RESULTS: Among the 1565 HIV-negative or HIV-unknown YBMSM enrolled, more engagement in spiritual and religious activities was associated with greater odds of reporting stimulant use (Adjusted Odds Ratio [AOR]=1.20; 95% CI=1.04-1.40) while higher spiritual coping was associated with lower odds of reporting stimulant use (AOR=0.66; 95% CI=0.56-0.78). Binge drinking was independently associated with 29% lower odds of recent HIV testing (AOR=0.71; 95% CI=0.55-0.92), but lower odds of binge drinking did not mediate the association of engagement in spiritual and religious activities with 27% greater odds of recent HIV testing (AOR=1.27; 95% CI=1.11-1.46). CONCLUSIONS: Among YBMSM, culturally tailored approaches addressing spirituality/religiosity could support prevention of stimulant use and increase HIV testing. In particular, expanded efforts are needed to promote HIV testing in binge drinkers.

    • Immunity and Immunization RSS Word feed
      1. Secretor and salivary ABO blood group antigen status predict rotavirus vaccine-take in infants
        Kazi AM, Cortese MM, Yu Y, Lopman B, Morrow AL, Fleming JA, McNeal MM, Steele AD, Parashar UD, Zaidi AK, Ali A.
        J Infect Dis. 2017 Jan 18.
        Histo-blood group antigens (HBGA) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial that were seronegative at baseline, anti-rotavirus IgA seroconversion rates after 3 vaccine doses differed significantly by HBGA phenotype: lowest (19%) among infants who were non-secretors (ie, do not express the carbohydrate synthesized by FUT2 gene), intermediate among non-blood group O secretors (30%) and highest (51%) among O-blood group secretors. Differences in HBGA expression may be responsible for some of the discrepancy in level of protection detected for the current rotavirus vaccines in low- versus high-income settings.

      2. Evaluation of measles-mumps-rubella vaccination among newly arrived refugees
        Lee D, Weinberg M, Benoit S.
        Am J Public Health. 2017 Mar 21:e1-e3.
        OBJECTIVES: To assess US availability and use of measles-mumps-rubella (MMR) vaccination documentation for refugees vaccinated overseas. METHODS: We selected 1500 refugee records from 14 states from March 2013 through July 2015 to determine whether overseas vaccination records were available at the US postarrival health assessment and integrated into the Advisory Committee on Immunization Practices schedule. We assessed number of doses, dosing interval, and contraindications. RESULTS: Twelve of 14 (85.7%) states provided data on 1118 (74.5%) refugees. Overseas records for 972 (86.9%) refugees were available, most from the Centers for Disease Control and Prevention’s Electronic Disease Notification system (66.9%). Most refugees (829; 85.3%) were assessed appropriately for MMR vaccination; 37 (3.8%) should have received MMR vaccine but did not; 106 (10.9%) did not need the MMR vaccine but were vaccinated. CONCLUSIONS: Overseas documentation was available at most clinics, and MMR vaccinations typically were given when needed. Further collaboration between refugee health clinics and state immunization information systems would improve accessibility of vaccination documentation. (Am J Public Health. Published online ahead of print March 21, 2017: e1-e3. doi:10.2105/AJPH.2017.303698).

      3. Comparative effectiveness of high-dose versus standard-dose influenza vaccines among US medicare beneficiaries in preventing postinfluenza deaths during 2012-2013 and 2013-2014
        Shay DK, Chillarige Y, Kelman J, Forshee RA, Foppa IM, Wernecke M, Lu Y, Ferdinands JM, Iyengar A, Fry AM, Worrall C, Izurieta HS.
        J Infect Dis. 2017 Mar 02.
        Background: Recipients of high-dose vs standard-dose influenza vaccines have fewer influenza illnesses. We evaluated the comparative effectiveness of high-dose vaccine in preventing postinfluenza deaths during 2012-2013 and 2013-2014, when influenza viruses and vaccines were similar. Methods: We identified Medicare beneficiaries aged >/=65 years who received high-dose or standard-dose vaccines in community-located pharmacies offering both vaccines. The primary outcome was death in the 30 days following an inpatient or emergency department encounter listing an influenza International of Classification of Diseases, Ninth Revision, Clinical Modification code. Effectiveness was estimated by using multivariate Poisson regression models; effectiveness was allowed to vary by season. Results: We studied 1039645 recipients of high-dose and 1683264 recipients of standard-dose vaccines during 2012-2013, and 1508176 high-dose and 1877327 standard-dose recipients during 2013-2014. Vaccinees were well-balanced for medical conditions and indicators of frail health. Rates of postinfluenza death were 0.028 and 0.038/10000 person-weeks in high-dose and standard-dose recipients, respectively. Comparative effectiveness was 24.0% (95% confidence interval [CI], .6%-42%); there was evidence of variation by season (P = .12). In 2012-2013, high-dose was 36.4% (95% CI, 9.0%-56%) more effective in reducing mortality; in 2013-2014, it was 2.5% (95% CI, -47% to 35%). Conclusions: High-dose vaccine was significantly more effective in preventing postinfluenza deaths in 2012-2013, when A(H3N2) circulation was common, but not in 2013-2014.

      4. Seroprevalence of poliovirus antibodies in the Kansas City metropolitan area, 2012-2013
        Wallace GS, Pahud BA, Weldon WC, Curns AT, Oberste MS, Harrison CJ.
        Hum Vaccin Immunother. 2017 Jan 06:1-8.
        No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012-2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants <18 y of age. We evaluated the prevalence of serum antibodies to all 3 poliovirus serotypes. Seroprevalence was evaluated by demographics as well as between polio serotypes. The overall seroprevalence to poliovirus was 90.7%, 94.4%, and 83.3%, for types 1, 2, and 3, respectively. Seroprevalence was high (88.6%-96.2%) for all 3 types of poliovirus for the 6-10 y old age group that was likely to have received a complete schedule of IPV-only vaccination. Children 2-3 y of age, who have not yet completed their full IPV series, had lower seroprevalence compared with all older age groups for types 1 and 2 (p-value <0. 05). Seroprevalence was high for all 3 types of poliovirus in the population surveyed. Seroprevalence for subjects aged 2-3 y was lower than all other age groups for serotypes 1 and 2 highlighting the importance of completing the recommended poliovirus vaccine series with a booster dose at age 4-6 y.

      5. Notes from the field: Obstetric tetanus in an unvaccinated woman after a home birth delivery – Kentucky, 2016
        Yaffee AQ, Day DL, Bastin G, Powell M, Melendez S, Allen N, Miracle J, Jones M, Brawley R.
        MMWR Morb Mortal Wkly Rep. 2017 Mar 24;66(11):307-308.
        [No abstract]
    • Injury and Violence RSS Word feed
      1. Adverse childhood experiences and health and wellness outcomes among black men who have sex with men
        Ports KA, Lee RD, Raiford J, Spikes P, Manago C, Wheeler DP.
        J Urban Health. 2017 Mar 20.
        Black men who have sex with men (BMSM) are a population at the intersection of two minority statuses-racial minority and sexual minority. Membership in either group, compared to white or heterosexual group membership, may increase one’s risk of negative childhood and adult experiences. Baseline data from an HIV intervention efficacy trial (the Black Men Evolving Study) were used to explore the prevalence of adverse childhood experiences (ACEs) among 536 BMSM and associations between ACEs and adult mental and physical health outcomes. Overall, the prevalence of ACEs was high among this sample of BMSM with almost 90% experiencing at least one ACE. Findings revealed that ACE score was significantly associated with adult mental health (AOR = 1.21, 95% CI [1.12, 1.30]), but not with adult physical health. All ACEs were significantly associated with mental health, but only physical neglect and household substance abuse were significantly associated with physical health (AOR = 1.69, 95% CI [1.02, 2.74] and AOR = 1.57, 95% CI [1.03, 2.40], respectively). The findings support the need for interventions targeting improved adult health outcomes, particularly for minority groups, to consider the impact of early adversity on health and wellness.

      2. The development of severe and chronic violence among youth: The role of psychopathic traits and reward processing
        Reidy DE, Krusemark E, Kosson DS, Kearns MC, Smith-Darden J, Kiehl KA.
        Child Psychiatry Hum Dev. 2017 Mar 18.
        Psychopathic traits are a manifestation of a personality pathology that comprises a core affective-interpersonal dysfunction (callous-unemotional traits) and an impulsive-antisocial behavioral component. Of particular importance, psychopathic traits are associated with the perpetration of some of the most severe acts of violence, and they appear to indicate a subset of youth at risk for earlier onset, greater frequency, and persistence of violent offending. Although these youth represent a minority of the population, they commit a significant proportion of the violence in the general community. In our review, we highlight evidence of a unique neurobiological predisposition that underlies the core affective deficits and describe contemporary accounts for the developmental processes leading to the antisocial behavior associated with psychopathy. Current evidence suggests that, for this subset of youth, the structure and function of neural circuitry supporting emotion processing, reward learning, decision making, and the development of emotion related to empathy may be crucial to understanding why they are at risk for violence. In particular, a reward dominant pattern of neurobehavioral conditioning may explain how these youth progress to some of the most severe and persistent forms of violence. However, this pattern of conditioning may also be essential to the primary prevention of such deleterious behavior. We suspect that effective strategies to prevent such violence may ultimately be informed by understanding these affective and motivational mechanisms.

    • Laboratory Sciences RSS Word feed
      1. Optical molecular fluorescence determination of ultra-trace beryllium in occupational and environmental samples using highly alkaline conditions
        Adams L, Agrawal A, Cronin JP, Ashley K.
        Int J Environ Anal Chem. 2017 :1-12.
        Exposures to beryllium (Be), even at extremely low levels, can cause severe health effects in a percentage of those exposed; consequently, occupational exposure limits (OELs) promulgated for this element are the lowest established for any element. This work describes the advantages of using highly alkaline dye solutions for determination of Be in occupational hygiene and environmental samples by means of an optical molecular fluorescence technique after sample extraction in 1-3% (w?w-1) aqueous ammonium bifluoride (NH4HF2). Improved attributes include the ability to further enhance the detection limits of Be in extraction solutions of high acidity with minimal dilution, which is particularly beneficial when NH4HF2 solutions of higher concentration are used for extraction of Be from soil samples. Significant improvements in Be method detection limits (MDLs) are obtained at levels manyfold below those reported previously for this methodology. Notably, MDLs for Be of <0.01 ng L-1 /0.1 ng per sample have been attained, which are superior to MDLs routinely reported for this element by means of the most widely used ultra-trace elemental measurement technique, inductively coupled plasma mass spectrometry (ICP-MS). Very low MDLs for Be are essential in consideration of reductions in OELs for this element in workplace air by health organisations and regulatory agencies in the USA and internationally. Applications of enhanced Be measurements to air filter samples, surface wipe samples, soils and newly designed occupational air sampler inserts are illustrated.

      2. Development and implementation of the Caribbean Laboratory Quality Management Systems Stepwise Improvement Process (LQMS-SIP) towards accreditation
        Alemnji G, Edghill L, Guevara G, Wallace-Sankarsingh S, Albalak R, Cognat S, Nkengasong J, Gabastou JM.
        Afr J Lab Med. 2017 ;6 (1) (a496).
        Background: Implementing quality management systems and accrediting laboratories in the Caribbean has been a challenge. Objectives: We report the development of a stepwise process for quality systems improvement in the Caribbean Region. Methods: The Caribbean Laboratory Stakeholders met under a joint Pan American Health Organization/US Centers for Disease Control and Prevention initiative and developed a userfriendly framework called ‘Laboratory Quality Management System – Stepwise Improvement Process (LQMS-SIP) Towards Accreditation’ to support countries in strengthening laboratory services through a stepwise approach toward fulfilling the ISO 15189: 2012 requirements. Results: This approach consists of a three-tiered framework. Tier 1 represents the minimum requirements corresponding to the mandatory criteria for obtaining a licence from the Ministry of Health of the participating country. The next two tiers are quality improvement milestones that are achieved through the implementation of specific quality management system requirements. Laboratories that meet the requirements of the three tiers will be encouraged to apply for accreditation. The Caribbean Regional Organisation for Standards and Quality hosts the LQMS-SIP Secretariat and will work with countries, including the Ministry of Health and stakeholders, including laboratory staff, to coordinate and implement LQMS-SIP activities. The Caribbean Public Health Agency will coordinate and advocate for the LQMS-SIP implementation. Conclusion: This article presents the Caribbean LQMS-SIP framework and describes how it will be implemented among various countries in the region to achieve quality improvement.

      3. Pharmacokinetic profiles of meloxicam and sustained-release buprenorphine in prairie dogs (Cynomys ludovicianus)
        Cary CD, Lukovsky-Akhsanov NL, Gallardo-Romero NF, Tansey CM, Ostergaard SD, Taylor WD, Morgan CN, Powell N, Lathrop GW, Hutson CL.
        J Am Assoc Lab Anim Sci. 2017 Mar 01;56(2):160-165.
        In this study, we evaluated the pharmacokinetic profiles of meloxicam and sustained-release (SR) buprenorphine in prairie dogs. The 4 treatment groups were: low-dose meloxicam (0.2 mg/kg SC), high-dose meloxicam (4 mg/kg SC), low-dose buprenorphine SR (0.9 mg/kg SC), and high-dose buprenorphine SR (1.2 mg/kg SC). The highest plasma concentrations occurred within 4 h of administration for both meloxicam treatment groups. The therapeutic range of meloxicam in prairie dogs is currently unknown. However, as compared with the therapeutic range documented in other species (0.39 – 0.91 microg/mL), the mean plasma concentration of meloxicam fell below the minimal therapeutic range prior to 24 h in the low-dose group but remained above therapeutic levels for more than 72 h in the high-dose group. These findings suggest that the current meloxicam dosing guidelines may be subtherapeutic for prairie dogs. The highest mean plasma concentration for buprenorphine SR occurred at the 24-h time point (0.0098 microg/mL) in the low-dose group and at the 8-h time point (0.015 microg/mL) for the high-dose group. Both dosages of buprenorphine SR maintained likely plasma therapeutic levels (0.001 microg/mL, based on previous rodent studies) beyond 72 h. Given the small scale of the study and sample size, statistical analysis was not performed. The only adverse reactions in this study were mild erythematous reactions at injection sites for buprenorphine SR.

      4. Development and validation of a high-throughput online solid-phase extraction-liquid chromatography-tandem mass spectrometry method for the detection of gonyautoxins 1&4 and gonyautoxins 2&3 in human urine
        Coleman R, Lemire SW, Bragg W, Garrett A, Ojeda-Torres G, Wharton R, Hamelin E, Thomas J, Johnson RC.
        Biomed Chromatogr. 2017 Feb 10.
        Paralytic shellfish toxins (PSTs), including gonyautoxins and saxitoxins, are produced by multiple species of microalgae and dinoflagellates, and are bioaccumulated by shellfish and other animals. Human exposure to PSTs typically occurs through ingestion of recreationally harvested contaminated shellfish and results in nonspecific symptomology. Confirmation of exposure to PSTs has often relied on the measurement of saxitoxin, the most toxic congener; however, gonyautoxins (GTXs), the sulfated carbamate derivatives of saxitoxin, may be present in shellfish at higher concentrations. To improve identification of PST exposures, our group has developed an online solid phase extraction hydrophilic interaction liquid chromatography method to identify GTX1-4 in human urine with tandem mass spectrometry. The reportable range varied for each analyte, with all falling within 0.899 and 250 ng/mL in urine with precision <15% and >85% accuracy as determined for all quality control samples. This new online method quantitates GTX1-4 following exposures to PSTs, supporting the work of public health authorities.

      5. Multi-center evaluation of one commercial and 12 in-house real-time PCR assays for detection of Mycoplasma pneumoniae
        Dumke R, Benitez AJ, Chalker V, Gullsby K, Henrich B, Hidalgo-Grass C, Hoogenboezem T, Kese D, Loens K, Maaskant J, Michael-Gayego A, Moses AE, Nir-Paz R, Pas SD, Pereyre S, Petersen RF, Rosenblatt M, van Rossum AM, Uldum SA, Unger WW, Ursi D, Winchell JM, Bebear C.
        Diagn Microbiol Infect Dis. 2017 Mar 08.
        Detection of Mycoplasma pneumoniae by real-time PCR is not yet standardized across laboratories. We have implemented a standardization protocol to compare the performance of thirteen commercial and in-house approaches. Despite differences on threshold values of samples, all assays were able to detect at least 20M. pneumoniae genomes per reaction.

      6. Principles and recommendations for standardizing the use of the next-generation sequencing variant file in clinical settings
        Lubin IM, Aziz N, Babb LJ, Ballinger D, Bisht H, Church DM, Cordes S, Eilbeck K, Hyland F, Kalman L, Landrum M, Lockhart ER, Maglott D, Marth G, Pfeifer JD, Rehm HL, Roy S, Tezak Z, Truty R, Ullman-Cullere M, Voelkerding KV, Worthey E, Zaranek AW, Zook JM.
        J Mol Diagn. 2017 Mar 15.
        A national workgroup convened by the Centers for Disease Control and Prevention identified principles and made recommendations for standardizing the description of sequence data contained within the variant file generated during the course of clinical next-generation sequence analysis for diagnosing human heritable conditions. The specifications for variant files were initially developed to be flexible with regard to content representation to support a variety of research applications. This flexibility permits variation with regard to how sequence findings are described and this depends, in part, on the conventions used. For clinical laboratory testing, this poses a problem because these differences can compromise the capability to compare sequence findings among laboratories to confirm results and to query databases to identify clinically relevant variants. To provide for a more consistent representation of sequence findings described within variant files, the workgroup made several recommendations that considered alignment to a common reference sequence, variant caller settings, use of genomic coordinates, and gene and variant naming conventions. These recommendations were considered with regard to the existing variant file specifications presently used in the clinical setting. Adoption of these recommendations is anticipated to reduce the potential for ambiguity in describing sequence findings and facilitate the sharing of genomic data among clinical laboratories and other entities.

      7. Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis
        Ma J, Bishoff B, Mercer RR, Barger M, Schwegler-Berry D, Castranova V.
        Toxicol Appl Pharmacol. 2017 Mar 15.
        The emission of cerium oxide nanoparticles (CeO2) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO2-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO2 (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28days after CeO2 (3.5mg/kg) exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO2-exposed rats at 28days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO2 exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as alpha-smooth muscle actin (SMA), in CeO2-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-beta or alpha-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO2 exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO2 nanoparticle exposure.

      8. Monkeypox virus host factor screen in haploid cells identifies essential role of GARP complex in extracellular virus formation
        Realegeno S, Puschnik AS, Kumar A, Goldsmith C, Burgado J, Sambhara S, Olson VA, Carroll D, Damon I, Hirata T, Kinoshita T, Carette JE, Satheshkumar PS.
        J Virol. 2017 Mar 22.
        Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. The screen revealed several candidate genes, including those involved in Golgi trafficking, glycosaminoglycan biosynthesis and glycosylphosphatidylinositol (GPI) – anchor biosynthesis. We validated the role of a set of vacuolar protein sorting (VPS) genes during infection, VPS51-54, which comprise the Golgi-associated retrograde protein (GARP) complex. The GARP complex is a tethering complex involved in retrograde transport of endosomes to the trans-Golgi apparatus. Our data demonstrate that VPS52 and VPS54 were dispensable for mature virus (MV) production but were required for extracellular virus (EV) formation. For comparison, a known antiviral compound, ST-246, was used in our experiments demonstrating that EV titers in VPS52 and VPS54 knockout (KO) cells were comparable to levels exhibited by ST-246 treated wildtype cells. Confocal microscopy was used to examine actin tail formation, one of the viral egress mechanisms for cell-to-cell dissemination, and revealed an absence of actin tails in VPS52KO or VPS54KO infected cells. Further evaluation of these cells by electron microscopy demonstrated a decrease in wrapped viruses (WV) compared to wild type control. Collectively, our data demonstrate the role of GARP complex genes in double-membrane wrapping of MV necessary for EV formation, implicating the host endosomal trafficking pathway in orthopoxvirus infection.IMPORTANCE Human monkeypox is an emerging zoonotic infectious disease caused by Monkeypox virus (MPXV). Of the two MPXV clades, the Congo Basin strain is associated with severe disease, higher mortality, and increased human-to-human transmission relative to the West African strain. Monkeypox is endemic to regions of western and central Africa but was introduced into the United States in 2003 from the importation of infected animals. The threat of MPXV and other orthopoxviruses is increasing due to the absence of routine smallpox vaccination leading to a higher proportion of naive populations. In this study, we have identified and validated candidate genes that are required for MPXV infection, specifically the Golgi-associated retrograde protein (GARP) complex. Identifying host targets required for infection that prevents extracellular virus formation such as the GARP complex or the retrograde pathway can provide a potential target for anti-viral therapy.

      9. Integration of in silico methods and computational systems biology to explore endocrine-disrupting chemical binding with nuclear hormone receptors
        Ruiz P, Sack A, Wampole M, Bobst S, Vracko M.
        Chemosphere. 2017 Mar 09;178:99-109.
        Thousands of potential endocrine-disrupting chemicals present difficult regulatory challenges. Endocrine-disrupting chemicals can interfere with several nuclear hormone receptors associated with a variety of adverse health effects. The U.S. Environmental Protection Agency (U.S. EPA) has released its reviews of Tier 1 screening assay results for a set of pesticides in the Endocrine Disruptor Screening Program (EDSP), and recently, the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) data. In this study, the predictive ability of QSAR and docking approaches is evaluated using these data sets. This study also presents a computational systems biology approach using carbaryl (1-naphthyl methylcarbamate) as a case study. For estrogen receptor and androgen receptor binding predictions, two commercial and two open source QSAR tools were used, as was the publicly available docking tool Endocrine Disruptome. For estrogen receptor binding predictions, the ADMET Predictor, VEGA, and OCHEM models (specificity: 0.88, 0.88, and 0.86, and accuracy: 0.81, 0.84, and 0.88, respectively) were each more reliable than the MetaDrug model (specificity 0.81 and accuracy 0.77). For androgen receptor binding predictions, the Endocrine Disruptome and ADMET Predictor models (specificity: 0.94 and 0.8, and accuracy: 0.78 and 0.71, respectively) were more reliable than the MetaDrug model (specificity 0.33 and accuracy 0.4). A consensus approach is proposed that reaches general agreement among the models (specificity 0.94 and accuracy 0.89). This study integrates QSAR, docking, and systems biology approaches as a virtual screening tool for use in risk assessment. As such, this systems biology pathways and network analysis approach provides a means to more critically assess the potential effects of endocrine-disrupting chemicals.

      10. Molecular mechanisms of pulmonary response progression in crystalline silica exposed rats
        Sellamuthu R, Umbright C, Roberts JR, Young SH, Richardson D, McKinney W, Chen BT, Li S, Kashon M, Joseph P.
        Inhal Toxicol. 2017 Feb;29(2):53-64.
        An understanding of the mechanisms underlying diseases is critical for their prevention. Excessive exposure to crystalline silica is a risk factor for silicosis, a potentially fatal pulmonary disease. Male Fischer 344 rats were exposed by inhalation to crystalline silica (15 mg/m3, six hours/day, five days) and pulmonary response was determined at 44 weeks following termination of silica exposure. Additionally, global gene expression profiling in lungs and BAL cells and bioinformatic analysis of the gene expression data were done to understand the molecular mechanisms underlying the progression of pulmonary response to silica. A significant increase in lactate dehydrogenase activity and albumin content in BAL fluid (BALF) suggested silica-induced pulmonary toxicity in the rats. A significant increase in the number of alveolar macrophages and infiltrating neutrophils in the lungs and elevation in monocyte chemoattractant protein-1 (MCP-1) in BALF suggested the induction of pulmonary inflammation in the silica exposed rats. Histological changes in the lungs included granuloma formation, type II pneumocyte hyperplasia, thickening of alveolar septa and positive response to Masson’s trichrome stain. Microarray analysis of global gene expression detected 94 and 225 significantly differentially expressed genes in the lungs and BAL cells, respectively. Bioinformatic analysis of the gene expression data identified significant enrichment of several disease and biological function categories and canonical pathways related to pulmonary toxicity, especially inflammation. Taken together, these data suggested the involvement of chronic inflammation as a mechanism underlying the progression of pulmonary response to exposure of rats to crystalline silica at 44 weeks following termination of exposure.

      11. Discovery and synthesis of a phosphoramidate prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the treatment of Ebola and emerging viruses
        Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL.
        J Med Chem. 2017 Mar 09;60(5):1648-1661.
        The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1′-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 – 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.

      12. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the USA and Europe
        Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S.
        J Clin Endocrinol Metab. 2017 Jan 10.
        Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating cohort-specific assays to a reference method and standard. Population: 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; Male Sibling Study of Osteoporosis. Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control. Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were employed to generate harmonized values, which were used to derive standardized, age-specific reference ranges. Results: Harmonization procedure reduced inter-cohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19-39 years, harmonized 2.5th, 5th, 50th, 95th and 97.5th percentile values were 264, 303, 531, 852 and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men. Conclusion: The harmonized normal range (2.5th-to-97.5th percentile) in nonobese, population of European and American men, 19-39 years, is 264-916 ng/dL. A substantial proportion of inter-cohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator.

    • Maternal and Child Health RSS Word feed
      1. Treated prevalence of attention-deficit/hyperactivity disorder increased from 2009 to 2015 among school-aged children and adolescents in the United States
        Nyarko KA, Grosse SD, Danielson ML, Holbrook JR, Visser SN, Shapira SK.
        J Child Adolesc Psychopharmacol. 2017 Mar 22.
        OBJECTIVES: The purpose of this brief is to describe changes in the treated prevalence of medically managed attention-deficit/hyperactivity disorder (ADHD) among insured school-aged children and adolescents in the United States from 2009 to 2015. We examine the differences between those with employer-sponsored insurance (ESI) and with Medicaid insurance. METHODS: We utilized two large longitudinal administrative datasets containing medical and drug claims data on individuals with ESI and Medicaid insurance from Truven Health MarketScan(R) Administrative Claims Databases. Treated prevalence was measured as the percentage of school-aged children and adolescents enrolled in a calendar year who met the criteria for medically managed ADHD in the same calendar year. Subjects were eligible for inclusion if they were aged 6-17 years and were continuously enrolled during a calendar year. RESULTS: The annual prevalence of treated ADHD among school-aged children and adolescents with ESI increased from 4.5% in 2009 to 6.7% in 2015. Among those with Medicaid it increased from 11.3% in 2009 to 13.3% in 2012, and fell after 2012, remaining steady from 2013 through 2015. CONCLUSION: Treated prevalence of ADHD increased continuously over time among school-aged children and adolescents with ESI, but declined slightly after 2012 among those in the Medicaid sample.

    • Mining RSS Word feed
      1. Reduction in diesel particulate matter through advanced filtration and monitoring techniques
        Pritchard C, Hill J, Volkwein J, Noll J, Miller A.
        Mining Engineering. 2017 ;69(3):31-36.
        Hecla Limited, Magee Scientific and the U.S. National Institute for Occupational Safety and Health (NIOSH) combined efforts to evaluate an in situ air filtration system for use in an underground mine environment. The purpose of the collaboration was to determine the efficacy of such a technology for reducing the concentration of airborne diesel particulate matter (DPM), with the aim of improving air quality in underground hardrock mines. A secondary goal was to evaluate the use of an aethalometer as a means of real-time measurement of black carbon as a surrogate for DPM. The evaluation included measuring the DPM-capture efficiency of the filter when it was preloaded with dust. Toward this end, rock dust was introduced at the filter inlet to create a dust layer on the filter surface, with the intent of providing improved capture of the much smaller DPM particles. The filtration efficiency for DPM was assessed by comparing measurements of DPM taken at the inlet and outlet of the system, using both realtime and time-weighted-average approaches. The real-time measurements were performed with a Model AE33 aethalometer, and filter samples analyzed by the NIOSH 5040 method were used to assess the effects of the system on time-weighted-average concentrations of total carbon. Results showed a reduction in DPM concentrations in the range of 82 to 89 percent. While the calculated efficiencies based on the two different measurement methods were similar, the DPM levels reported by the aethalometer were higher, possibly due to differences in the performance of the size selectors used for the two methods: impactors versus cyclones. More research is required to develop a robust correlation between the two methods to support the use of the aethalometer in future mining applications. The advantages of the aethalometer are that it can measure and record DPM levels for weeks at a time and can be directly connected to a mine monitoring system, potentially at multiple locations. Ideally, such data can be used to initiate the startup of the filtration system should DPM concentrations reach an action level. This work demonstrated that in situ filtration systems, modified to collect DPM and coupled with real-time monitoring, show promise in reducing DPM concentrations in the mine environment.

    • Occupational Safety and Health RSS Word feed
      1. Misclassification of occupational disease in lung transplant recipients
        Blackley DJ, Halldin CN, Cohen RA, Cummings KJ, Storey E, Laney AS.
        J Heart Lung Transplant. 2017 Feb 24.
        [No abstract]
      2. Occupational use of high-level disinfectants and fecundity among nurses
        Gaskins AJ, Chavarro JE, Rich-Edwards JW, Missmer SA, Laden F, Henn SA, Lawson CC.
        Scand J Work Environ Health. 2017 Mar 01;43(2):171-180.
        Objective This study aimed to examine the relationship between occupational use of high-level disinfectants (HLD) and fecundity among female nurses. Methods Women currently employed outside the home and trying to get pregnant (N=1739) in the Nurses’ Health Study 3 cohort (2010-2014) were included in this analysis. Occupational exposure to HLD used to disinfect medical instruments and use of protective equipment (PE) was self-reported on the baseline questionnaire. Every six months thereafter women reported the duration of their ongoing pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95% confidence intervals (95% CI). Results Nurses exposed to HLD prior to and at baseline had a 26% (95% CI 8-47%) and 12% (95% CI -2-28%) longer median duration of pregnancy attempt compared to nurses who were never exposed. Among nurses exposed at baseline to HLD, use of PE attenuated associations with fecundity impairments. Specifically, women using 0, 1, and >/=2 types of PE had 18% (95% CI -7-49%), 16% (95% -3-39%), and 0% (95% -22-28%) longer median durations of pregnancy attempt compared to women who were never exposed. While the use of PE varied greatly by type (9% for respiratory protection to 69% for protective gloves), use of each PE appeared to attenuate the associations of HLD exposure with reduced fecundity. Conclusion Occupational use of HLD is associated with reduced fecundity among nurses, but use of PE appears to attenuate this risk.

    • Parasitic Diseases RSS Word feed
      1. Giardiasis and subsequent irritable bowel syndrome: A longitudinal cohort study using health insurance data
        Nakao JH, Collier SA, Gargano JW.
        J Infect Dis. 2017 Feb 23.
        Background.: Giardia intestinalis is the most commonly reported human intestinal parasite in the United States. Increased incidence of chronic gastrointestinal complaints has been reported after some giardiasis outbreaks. We examined the relationship between giardiasis diagnosis and irritable bowel syndrome (IBS) diagnosis. Methods.: We used the 2006-2010 MarketScan commercial insurance database. Persons with at least 1 giardiasis diagnosis were individually matched on age group, sex, and enrollment length in months to 5 persons without a giardiasis diagnosis. Persons diagnosed with IBS before the date of study entry were excluded. We calculated crude incidence rates (IRs) and developed Cox proportional hazards models. Results.: The matched cohort included 3935 persons with giardiasis and 19663 persons without giardiasis. One-year incidence of IBS was higher in persons with giardiasis (IR = 37.7/1000 person-years vs 4.4/1000 person-years). The unadjusted hazard ratio was 4.8 (95% confidence interval [CI] = 3.6-6.4), attenuated slightly to 3.9 (95% CI = 2.9-5.4) after adjusting for anxiety, depression, and healthcare utilization. Conclusions.: In a large insurance database, individuals diagnosed with giardiasis were more likely to have a subsequent IBS diagnosis, despite accounting for confounders. Future research on risk factors for IBS among giardiasis patients and the pathophysiology of postinfectious IBS is needed.

      2. Intermittent preventive treatment with dihydroartemisinin-piperaquine for the prevention of malaria among HIV-infected pregnant women
        Natureeba P, Kakuru A, Muhindo M, Littmann E, Ochieng T, Ategeka J, Koss CA, Plenty A, Charlebois ED, Clark TD, Nzarubara B, Nakalembe M, Cohan D, Rizzuto G, Muehlenbachs A, Ruel T, Jagannathan P, Havlir DV, Kamya MR, Dorsey G.
        J Infect Dis. 2017 Feb 22.
        Background.: Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide treated nets (ITNs) remain the main interventions for prevention of malaria in HIV-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these intervention and new ones are needed. Methods.: We conducted a double-blind randomized placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide (IRS) had recently been implemented. Participants were enrolled between 12-28 weeks gestation and provided an ITN. The primary outcome was placental malaria by histopathology (active or past infection). Secondary outcomes included incidence of malaria; parasite prevalence; and adverse birth outcomes. Results.: All 200 women enrolled were followed through delivery and the primary outcome was assessed in 194. There was no statistically significant difference in the risk of placental malaria by histopathology between the daily TMP-SMX plus DP and daily TMP-SMX alone arms (6.1 vs. 3.1%, RR=1.96, 95%CI 0.50-7.61, P=0.50). Similarly, there were no differences in secondary outcomes. Conclusions.: Among HIV-infected pregnant women in the setting of IRS, adding monthly DP to daily TMP-SMX did not reduce the risk of placental or maternal malaria or improve birth outcomes.

    • Substance Use and Abuse RSS Word feed
      1. Sales of nicotine-containing electronic cigarette products: United States, 2015
        Marynak KL, Gammon DG, Rogers T, Coats EM, Singh T, King BA.
        Am J Public Health. 2017 Mar 21:e1-e4.
        OBJECTIVES: To assess the proportion of electronic cigarette (e-cigarette) products sold in the United States that contain nicotine according to retail scanner data. METHODS: We obtained unit sales data from January 11, 2015, to December 12, 2015, from The Nielsen Company for convenience stores; supermarkets; mass merchandisers; drug, club, and dollar stores; and Department of Defense commissaries. The data did not include purchases from tobacco specialty shops, “vape shops,” or online sources. Nicotine content was assessed by product type (disposables, rechargeables, and refills), region, and flavor status based on nicotine strength listed in the Universal Product Codes. For the 36.7% of entries lacking nicotine content information, we conducted Internet searches by brand, product, and flavor. RESULTS: In 2015, 99.0% of e-cigarette products sold contained nicotine, including 99.0% of disposables, 99.7% of rechargeables, and 98.8% of refills. Overall, 98.7% of flavored e-cigarette products and 99.4% of nonflavored e-cigarette products contained nicotine. CONCLUSIONS: In 2015, almost all e-cigarette products sold in US convenience stores and other assessed channels contained nicotine. Public Health Implications. Findings reinforce the importance of warning labels for nicotine-containing products, ingredient reporting, and restrictions on sales to minors. (Am J Public Health. Published online ahead of print March 21, 2017: e1-e4. doi:10.2105/AJPH.2017.303660).

      2. Secondhand exposure to electronic cigarette aerosol among US youths
        Wang TW, Marynak KL, Agaku IT, King BA.
        JAMA Pediatr. 2017 Mar 20.
        [No abstract]
    • Vital Statistics RSS Word feed
      1. Integrating community-based verbal autopsy into civil registration and vital statistics (CRVS): system-level considerations
        de Savigny D, Riley I, Chandramohan D, Odhiambo F, Nichols E, Notzon S, AbouZahr C, Mitra R, Cobos Munoz D, Firth S, Maire N, Sankoh O, Bronson G, Setel P, Byass P, Jakob R, Boerma T, Lopez AD.
        Glob Health Action. 2017 ;10(1):1272882.
        BACKGROUND: Reliable and representative cause of death (COD) statistics are essential to inform public health policy, respond to emerging health needs, and document progress towards Sustainable Development Goals. However, less than one-third of deaths worldwide are assigned a cause. Civil registration and vital statistics (CRVS) systems in low- and lower-middle-income countries are failing to provide timely, complete and accurate vital statistics, and it will still be some time before they can provide physician-certified COD for every death. Proposals: Verbal autopsy (VA) is a method to ascertain the probable COD and, although imperfect, it is the best alternative in the absence of medical certification. There is extensive experience with VA in research settings but only a few examples of its use on a large scale. Data collection using electronic questionnaires on mobile devices and computer algorithms to analyse responses and estimate probable COD have increased the potential for VA to be routinely applied in CRVS systems. However, a number of CRVS and health system integration issues should be considered in planning, piloting and implementing a system-wide intervention such as VA. These include addressing the multiplicity of stakeholders and sub-systems involved, integration with existing CRVS work processes and information flows, linking VA results to civil registration records, information technology requirements and data quality assurance. CONCLUSIONS: Integrating VA within CRVS systems is not simply a technical undertaking. It will have profound system-wide effects that should be carefully considered when planning for an effective implementation. This paper identifies and discusses the major system-level issues and emerging practices, provides a planning checklist of system-level considerations and proposes an overview for how VA can be integrated into routine CRVS systems.

    • Zoonotic and Vectorborne Diseases RSS Word feed
      1. Establishing a timeline to discontinue routine testing of asymptomatic pregnant women for Zika virus infection – American Samoa, 2016-2017
        Hancock WT, Soeters HM, Hills SL, Link-Gelles R, Evans ME, Daley WR, Piercefield E, Anesi MS, Mataia MA, Uso AM, Sili B, Tufa AJ, Solaita J, Irvin-Barnwell E, Meaney-Delman D, Wilken J, Weidle P, Toews KE, Walker W, Talboy PM, Gallo WK, Krishna N, Laws RL, Reynolds MR, Koneru A, Gould CV.
        MMWR Morb Mortal Wkly Rep. 2017 Mar 24;66(11):299-301.
        The first patients with laboratory-confirmed cases of Zika virus disease in American Samoa had symptom onset in January 2016. In response, the American Samoa Department of Health (ASDoH) implemented mosquito control measures, strategies to protect pregnant women, syndromic surveillance based on electronic health record (EHR) reports, Zika virus testing of persons with one or more signs or symptoms of Zika virus disease (fever, rash, arthralgia, or conjunctivitis), and routine testing of all asymptomatic pregnant women in accordance with CDC guidance. All collected blood and urine specimens were shipped to the Hawaii Department of Health Laboratory for Zika virus testing and to CDC for confirmatory testing. Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity. The weekly numbers of suspected Zika virus disease cases declined from an average of six per week in January-February 2016 to one per week in May 2016. By August, the EHR-based syndromic surveillance indicated a return to pre-outbreak levels. The last Zika virus disease case detected by real-time, reverse transcription-polymerase chain reaction (rRT-PCR) occurred in a patient who had symptom onset on June 19, 2016. In August 2016, ASDoH requested CDC support in assessing whether local transmission had been reduced or interrupted and in proposing a timeline for discontinuation of routine testing of asymptomatic pregnant women. An end date (October 15, 2016) was determined for active mosquito-borne transmission of Zika virus and a timeline was developed for discontinuation of routine screening of asymptomatic pregnant women in American Samoa (conception after December 10, 2016, with permissive testing for asymptomatic women who conceive through April 15, 2017).

      2. Probable Zika virus-associated Guillain-Barre syndrome: Challenges with clinico-laboratory diagnosis
        Miller E, Becker Z, Shalev D, Lee CT, Cioroiu C, Thakur K.
        J Neurol Sci. 2017 Apr 15;375:367-370.
        A 55year old woman in New York City presented in May 2016 with progressive weakness, ataxia, paresthesia, and areflexia, shortly after returning from the Dominican Republic. Lumbar puncture revealed cytoalbuminological dissociation. Due to her recent travel, Zika-associated Guillain Barre syndrome (GBS) was suspected and she underwent evaluation for recent flavivirus exposure. Zika virus RNA was not detected in serum, but Zika virus immunoglobulin M (IgM) was detected in both serum and cerebrospinal fluid. Dengue virus IgM in serum was equivocal and dengue virus IgG was detected in the serum. Plaque-reduction neutralization testing showed elevated titers to both Zika virus and dengue virus, providing evidence of recent infection with a flavivirus. The patient was diagnosed with probable Zika virus-associated GBS based on clinical findings, ancillary testing, and laboratory assays according to current guidance from the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists. Zika virus transmission in the Americas is resulting in increasing numbers of patients presenting with Zika virus-associated neurological syndromes. Clinical and laboratory diagnosis in these cases can be challenging and may be aided by consultation with CDC, and state and local public health agencies.

      3. Evaluation of bioMerieux’s dissociated VIDAS Lyme IgM II (LYM) and IgG II (LYG) as a first-tier diagnostic assay for Lyme disease
        Molins CR, Delorey MJ, Replogle A, Sexton C, Schriefer ME.
        J Clin Microbiol. 2017 Mar 22.
        The recommended laboratory diagnostic approach for Lyme disease is a standard two-tiered testing (STTT) algorithm where the first-tier is typically an enzyme immunoassay (EIA) that if positive or equivocal is reflexed to Western immunoblotting as the second-tier. bioMerieux manufacturers one of the most commonly used first-tier EIAs in the U.S., the combined IgM/IgG VIDAS (LYT). Recently, bioMerieux launched its dissociated first-tier tests, the VIDAS Lyme IgM II (LYM) and IgG II (LYG) EIAs, which use purified recombinant test antigens and a different algorithm than STTT. The dissociated LYM/LYG EIAs were evaluated against the combined LYT EIA using samples from 471 well-characterized Lyme patients and controls. Statistical analyses were conducted to assess the performance of these EIAs as first-tier tests and when used in two-tiered algorithms, including a modified two-tiered testing (MTTT) approach, where the second-tier test was a C6 EIA. Similar sensitivities and specificities were obtained for the two testing strategies (LYT vs. LYM/LYG) when used as first-tier tests (sensitivity: 83 to 85%; specificity: 85 to 88%) with an observed agreement of 80%. Sensitivities of 68 to 69% and 76 to 77% and specificities of 97% and 98 to 99% resulted when the two EIA strategies were followed by Western immunoblotting and when used in a MTTT, respectively. The MTTT approach resulted in significantly higher sensitivities as compared to STTT. Overall, the LYM/LYG EIAs performed equivalently to the LYT EIA in test-to-test comparisons or as first-tier assays in STTT or MTTT with few exceptions.

      4. Preparing for emerging infectious diseases
        Saiman L, Arrington AS, Bell M.
        JAMA Pediatr. 2017 Mar 20.
        [No abstract]

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