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Volume 11, Issue 45 November 12, 2019

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CDC Science Clips: Volume 10, Issue 45, November 12, 2019

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

This week Science Clips is pleased to feature articles from a Journal of Infectious Diseases supplement on MenAfriNet, a consortium that works to strengthen meningitis surveillance in sub-Saharan Africa. CDC leads the international consortium in collaboration with World Health Organization, Agence Médecine Préventive, African ministries of health, and other partners.

The full supplement, MenAfriNet: A Network Supporting Case-Based Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Africa, may be found at https://academic.oup.com/jid/issue/220/Supplement_4external icon

For additional information on MenAfriNet, please visit http://www.menafrinet.org/en-us/external icon and https://www.cdc.gov/meningococcal/global.html

The report consists of these components:

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs).
    The names of CDC authors are indicated in bold text.
    • Epidemiology and Surveillance – Meningitis
      1. Development and implementation of a cloud-based meningitis surveillance and specimen tracking system in Burkina Faso, 2018external icon
        Diallo AO, Kiemtore T, Bicaba BW, Medah I, Tarbangdo TF, Sanou S, Soeters HM, Novak RT, Ake HF.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S198-s205.
        Nationwide case-based meningitis surveillance was established in Burkina Faso following the introduction of meningococcal serogroup A conjugate vaccine in 2010. However, timely tracking and arrival of cerebrospinal fluid specimens for confirmation at national reference laboratories remained suboptimal. To better understand this gap and identify bottlenecks, the Burkina Faso Ministry of Health, along with key partners, developed and implemented a cloud-based System for Tracking Epidemiological Data and Laboratory Specimens (STELAB), allowing for timely nationwide data reporting and specimen tracking using barcodes. STELAB was adapted to Burkina Faso’s infrastructure to ensure suitability, functionality, flexibility, and sustainability. We describe the design, development, and implementation of STELAB. In addition, we discuss strategies used to promote sustainability, lessons learned during the first year of implementation, and future directions. STELAB’s novel design and country-driven approach has the potential to achieve sustainable real-time data reporting and specimen tracking for the first time in sub-Saharan Africa.

      2. The strengthening of laboratory systems in the meningitis belt to improve meningitis surveillance, 2008-2018: A partners’ perspectiveexternal icon
        Feagins AR, Vuong J, Fernandez K, Njanpop-Lafourcade BM, Mwenda JM, Sanogo YO, Paye MF, Payamps SK, Mayer L, Wang X.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S175-s181.
        Laboratories play critical roles in bacterial meningitis disease surveillance in the African meningitis belt, where the highest global burden of meningitis exists. Reinforcement of laboratory capacity ensures rapid detection of meningitis cases and outbreaks and a public health response that is timely, specific, and appropriate. Since 2008, joint efforts to strengthen laboratory capacity by multiple partners, including MenAfriNet, beginning in 2014, have been made in countries within and beyond the meningitis belt. Over the course of 10 years, national reference laboratories were supported in 5 strategically targeted areas: specimen transport systems, laboratory procurement systems, laboratory diagnosis, quality management, and laboratory workforce with substantial gains made in each of these areas. To support the initiative to eliminate meningitis by 2030, continued efforts are needed to strengthen laboratory systems.

      3. Improving case-based meningitis surveillance in 5 countries in the meningitis belt of sub-Saharan Africa, 2015-2017external icon
        Mbaeyi SA, Lingani C, Diallo AO, Bicaba B, Ouedraogo-Traore R, Acyl M, Gamougame K, Coulibaly O, Coulibaly S, Zaneidou M, Sidikou F, Nikiema C, Sadji AY, Ake F, Tarbangdo F, Sakande S, Tall H, Njanpop-Lafourcade BM, Moisi J, N’Diaye A, Bwaka A, Bita A, Fernandez K, Poy A, Soeters HM, Vuong J, Novak R, Ronveaux O.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S155-s164.
        BACKGROUND: The MenAfriNet consortium was established in 2014 to support implementation of case-based meningitis surveillance in 5 countries in the meningitis belt of sub-Saharan Africa: Burkina Faso, Chad, Mali, Niger, and Togo. Assessing surveillance performance is critical for interpretation of the collected data and implementation of future surveillance-strengthening initiatives. METHODS: Detailed epidemiologic and laboratory data were collected on suspected meningitis cases through case-based meningitis surveillance in participating districts in 5 countries. Performance of case-based surveillance was evaluated through sensitivity of case ascertainment in case-based versus aggregate meningitis surveillance and an analysis of surveillance indicators. RESULTS: From 2015 to 2017, 18 262 suspected meningitis cases were identified through case-based surveillance and 16 262 were identified through aggregate surveillance, for a case ascertainment sensitivity of 112.3%. Among suspected cases, 16 885 (92.5%) had a cerebrospinal fluid (CSF) specimen collected, 13 625 (80.7%) of which were received at a national reference laboratory. Among these, 13 439 (98.6%) underwent confirmatory testing, and, of those tested, 4371 (32.5%) were confirmed for a bacterial pathogen. CONCLUSIONS: Overall strong performance for case ascertainment, CSF collection, and laboratory confirmation provide evidence for the quality of MenAfriNet case-based surveillance in evaluating epidemiologic trends and informing future vaccination strategies.

      4. Neisseria meningitidis serogroup W meningitis epidemic in Togo, 2016external icon
        Mounkoro D, Nikiema CS, Maman I, Sakande S, Bozio CH, Tall H, Sadji AY, Njanpop-Lafourcade BM, Sibabe A, Landoh DE, Abodji EO, Kodjo A, Tamekloe TA, Essoh TA, Maba DW, Gessner BD, Moisi JC.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S216-s224.
        BACKGROUND: During 2014, 4 regions in Togo within the African meningitis belt implemented vaccination campaigns with meningococcal serogroup A conjugate vaccine (MACV). From January to July 2016, Togo experienced its first major Neisseria meningitidis serogroup W (NmW) outbreak. We describe the epidemiology, response, and management of the outbreak. METHODS: Suspected, probable, and confirmed cases were identified using World Health Organization case definitions. Through case-based surveillance, epidemiologic and laboratory data were collected for each case. Cerebrospinal fluid specimens were analyzed by polymerase chain reaction, culture, or latex agglutination. Vaccination campaigns were conducted in affected districts. RESULTS: From January 11 to July 5, 2016, 1995 suspected meningitis cases were reported, with 128 deaths. Among them, 479 (24.0%) were confirmed by laboratory testing, and 94 (4.7%) and 1422 (71.3%) remained as probable and suspected cases, respectively. Seven epidemic districts had cumulative attack rates greater than 100 per 100 000 population. Of the confirmed cases, 91.5% were NmW; 39 of 40 available NmW isolates were sequence type-11/clonal complex-11. CONCLUSIONS: This outbreak demonstrates that, although high coverage with MACV has reduced serogroup A outbreaks, large meningococcal meningitis outbreaks due to other serogroups may continue to occur; effective multivalent meningococcal conjugate vaccines could improve meningococcal disease prevention within meningitis belt populations.

      5. Country data for action: The MenAfriNet experience in strengthening meningitis surveillance in Africaexternal icon
        Novak RT, Moisi JC, Tall H, Preziosi MP, Hadler SC, Messonnier NE, Mihigo R.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S137-s139.

        [No abstract]

      6. Future directions for meningitis surveillance and vaccine evaluation in the meningitis belt of sub-Saharan Africaexternal icon
        Novak RT, Ronveaux O, Bita AF, Ake HF, Lessa FC, Wang X, Bwaka AM, Fox LM.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S279-s285.
        In sub-Saharan Africa, bacterial meningitis remains a significant public health problem, especially in the countries of the meningitis belt, where Neisseria meningitidis serogroup A historically caused large-scale epidemics. In 2014, MenAfriNet was established as a consortium of partners supporting strategic implementation of case-based meningitis surveillance to monitor meningitis epidemiology and impact of meningococcal serogroup A conjugate vaccine (MACV). MenAfriNet improved data quality through use of standardized tools, procedures, and laboratory diagnostics. MenAfriNet surveillance and study data provided evidence of ongoing MACV impact, characterized the burden of non-serogroup A meningococcal disease (including the emergence of a new epidemic clone of serogroup C), and documented the impact of pneumococcal conjugate vaccine. New vaccines and schedules have been proposed for future implementation to address the remaining burden of meningitis. To support the goals of “Defeating Meningitis by 2030,” MenAfriNet will continue to strengthen surveillance and support research and modeling to monitor the impact of these programs on meningitis burden in sub-Saharan Africa.

      7. MenAfriNet: A network supporting case-based meningitis surveillance and vaccine evaluation in the meningitis belt of Africaexternal icon
        Patel JC, Soeters HM, Diallo AO, Bicaba BW, Kadade G, Dembele AY, Acyl MA, Nikiema C, Lingani C, Hatcher C, Acosta AM, Thomas JD, Diomande F, Martin S, Clark TA, Mihigo R, Hajjeh RA, Zilber CH, Ake F, Mbaeyi SA, Wang X, Moisi JC, Ronveaux O, Mwenda JM, Novak RT.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S148-s154.
        Meningococcal meningitis remains a significant public health threat, especially in the African meningitis belt where Neisseria meningitidis serogroup A historically caused large-scale epidemics. With the rollout of a novel meningococcal serogroup A conjugate vaccine (MACV) in the belt, the World Health Organization recommended case-based meningitis surveillance to monitor MACV impact and meningitis epidemiology. In 2014, the MenAfriNet consortium was established to support strategic implementation of case-based meningitis surveillance in 5 key countries: Burkina Faso, Chad, Mali, Niger, and Togo. MenAfriNet aimed to develop a high-quality surveillance network using standardized laboratory and data collection protocols, develop sustainable systems for data management and analysis to monitor MACV impact, and leverage the surveillance platform to perform special studies. We describe the MenAfriNet consortium, its history, strategy, implementation, accomplishments, and challenges.

      8. Implementation of case-based surveillance and real-time polymerase chain reaction to monitor bacterial meningitis pathogens in Chadexternal icon
        Paye MF, Gamougame K, Payamps SK, Feagins AR, Moto DD, Moyengar R, Naibei N, Vuong J, Diallo AO, Tate A, Soeters HM, Wang X, Acyl MA.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S182-s189.
        BACKGROUND: Meningococcal serogroup A conjugate vaccine (MACV) was introduced in Chad during 2011-2012. Meningitis surveillance has been conducted nationwide since 2003, with case-based surveillance (CBS) in select districts from 2012. In 2016, the MenAfriNet consortium supported Chad to implement CBS in 4 additional districts and real-time polymerase chain reaction (rt-PCR) at the national reference laboratory (NRL) to improve pathogen detection. We describe analysis of bacterial meningitis cases during 3 periods: pre-MACV (2010-2012), pre-MenAfriNet (2013-2015), and post-MenAfriNet (2016-2018). METHODS: National surveillance targeted meningitis cases caused by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae. Cerebrospinal fluid specimens, inoculated trans-isolate media, and/or isolates from suspected meningitis cases were tested via culture, latex, and/or rt-PCR; confirmed bacterial meningitis was defined by a positive result on any test. We calculated proportion of suspected cases with a specimen received by period, and proportion of specimens with a bacterial meningitis pathogen identified, by period, pathogen, and test. RESULTS: The NRL received specimens for 6.8% (876/12813), 46.4% (316/681), and 79.1% (787/995) of suspected meningitis cases in 2010-2012, 2013-2015, and 2016-2018, respectively, with a bacterial meningitis pathogen detected in 33.6% (294/876), 27.8% (88/316), and 33.2% (261/787) of tested specimens. The number of N. meningitidis serogroup A (NmA) among confirmed bacterial meningitis cases decreased from 254 (86.4%) during 2010-2012 to 2 (2.3%) during 2013-2015, with zero NmA cases detected after 2014. In contrast, proportional and absolute increases were seen between 2010-2012, 2013-2015, and 2016-2018 in cases caused by S. pneumoniae (5.1% [15/294], 65.9% [58/88], and 52.1% [136/261]), NmX (0.7% [2/294], 1.1% [1/88], and 22.2% [58/261]), and Hib (0.3% [1/294], 11.4% [10/88], and 14.9% [39/261]). Of specimens received at the NRL, proportions tested during the 3 periods were 47.7% (418), 53.2% (168), and 9.0% (71) by latex; 81.4% (713), 98.4% (311), and 93.9% (739) by culture; and 0.0% (0), 0.0% (0), and 90.5% (712) by rt-PCR, respectively. During the post-MenAfriNet period (2016-2018), 86.1% (678) of confirmed cases were tested by both culture and rt-PCR, with 12.5% (85) and 32.4% (220) positive by culture and rt-PCR, respectively. CONCLUSIONS: CBS implementation was associated with increased specimen referral. Increased detection of non-NmA cases could reflect changes in incidence or increased sensitivity of case detection with rt-PCR. Continued surveillance with the use of rt-PCR to monitor changing epidemiology could inform the development of effective vaccination strategies.

      9. Invasive meningococcal disease in Africa’s meningitis belt: More than just meningitis?external icon
        Reese HE, Ronveaux O, Mwenda JM, Bita A, Cohen AL, Novak RT, Fox LM, Soeters HM.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S263-s265.
        Since the progressive introduction of the meningococcal serogroup A conjugate vaccine within Africa’s meningitis belt beginning in 2010, the burden of meningitis due to Neisseria meningitidis serogroup A (NmA) has substantially decreased. Non-A serogroups C/W/X are now the most prevalent. Surveillance within the belt has historically focused on the clinical syndrome of meningitis, the classic presentation for NmA, and may not adequately capture other presentations of invasive meningococcal disease (IMD). The clinical presentation of infection due to serogroups C/W/X includes nonmeningeal IMD, and there is a higher case-fatality ratio associated with these non-A serogroups; however, data on the nonmeningeal IMD burden within the belt are scarce. Expanding surveillance to capture all cases of IMD, in accordance with the World Health Organization’s updated vaccine-preventable disease surveillance standards and in preparation for the anticipated introduction of a multivalent meningococcal conjugate vaccine within Africa’s meningitis belt, will enhance meningococcal disease prevention across the belt.

      10. Toward a global genomic epidemiology of meningococcal diseaseexternal icon
        Retchless AC, Fox LM, Maiden MC, Smith V, Harrison LH, Glennie L, Harrison OB, Wang X.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S266-s273.
        Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.

      11. A new sequence type of Neisseria meningitidis serogroup C associated with a 2016 meningitis outbreak in Maliexternal icon
        Sanogo YO, Guindo I, Diarra S, Retchless AC, Abdou M, Coulibaly S, Maiga MF, Coumare M, Diarra B, Chen A, Chang HY, Vuong JT, Acosta AM, Sow S, Novak RT, Wang X.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S190-s197.
        In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouelessebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

      12. Epidemiology of bacterial meningitis in the nine years since meningococcal serogroup A conjugate vaccine introduction, Niger, 2010-2018external icon
        Sidikou F, Potts CC, Zaneidou M, Mbaeyi S, Kadade G, Paye MF, Ousmane S, Issaka B, Chen A, Chang HY, Issifou D, Lingani C, Sakande S, Bienvenu B, Mahamane AE, Diallo AO, Moussa A, Seidou I, Abdou M, Sidiki A, Garba O, Haladou S, Testa J, Obama Nse R, Mainassara HB, Wang X.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S206-s215.
        BACKGROUND: In 2010, Niger and other meningitis belt countries introduced a meningococcal serogroup A conjugate vaccine (MACV). We describe the epidemiology of bacterial meningitis in Niger from 2010 to 2018. METHODS: Suspected and confirmed meningitis cases from January 1, 2010 to July 15, 2018 were obtained from national aggregate and laboratory surveillance. Cerebrospinal fluid specimens were analyzed by culture and/or polymerase chain reaction. Annual incidence was calculated as cases per 100 000 population. Selected isolates obtained during 2016-2017 were characterized by whole-genome sequencing. RESULTS: Of the 21 142 suspected cases of meningitis, 5590 were confirmed: Neisseria meningitidis ([Nm] 85%), Streptococcus pneumoniae ([Sp] 13%), and Haemophilus influenzae ([Hi] 2%). No NmA cases occurred after 2011. Annual incidence per 100 000 population was more dynamic for Nm (0.06-7.71) than for Sp (0.18-0.70) and Hi (0.01-0.23). The predominant Nm serogroups varied over time (NmW in 2010-2011, NmC in 2015-2018, and both NmC and NmX in 2017-2018). Meningococcal meningitis incidence was highest in the regions of Niamey, Tillabery, Dosso, Tahoua, and Maradi. The NmW isolates were clonal complex (CC)11, NmX were CC181, and NmC were CC10217. CONCLUSIONS: After MACV introduction, we observed an absence of NmA, the emergence and continuing burden of NmC, and an increase in NmX. Niger’s dynamic Nm serogroup distribution highlights the need for strong surveillance programs to inform vaccine policy.

      13. Bacterial meningitis epidemiology in five countries in the meningitis belt of sub-Saharan Africa, 2015-2017external icon
        Soeters HM, Diallo AO, Bicaba BW, Kadade G, Dembele AY, Acyl MA, Nikiema C, Sadji AY, Poy AN, Lingani C, Tall H, Sakande S, Tarbangdo F, Ake F, Mbaeyi SA, Moisi J, Paye MF, Sanogo YO, Vuong JT, Wang X, Ronveaux O, Novak RT.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S165-s174.
        BACKGROUND: The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo. We describe bacterial meningitis epidemiology in these 5 countries in 2015-2017. METHODS: Case-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae cases were confirmed and N. meningitidis/H. influenzae were serogrouped/serotyped by real-time polymerase chain reaction, culture, or latex agglutination. We calculated annual incidence in participating districts in each country in cases/100 000 population. RESULTS: From 2015-2017, 18 262 suspected meningitis cases were reported; 92% had a CSF specimen available, of which 26% were confirmed as N. meningitidis (n = 2433; 56%), S. pneumoniae (n = 1758; 40%), or H. influenzae (n = 180; 4%). Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3. N. meningitidis incidence was 1.5 in Burkina Faso, 2.7 in Chad, 0.4 in Mali, 14.7 in Niger, and 12.5 in Togo. Several outbreaks occurred: NmC in Niger in 2015-2017, NmC in Mali in 2016, and NmW in Togo in 2016-2017. Of N. meningitidis cases, 53% were NmC, 30% NmW, and 13% NmX. Five NmA cases were reported (Burkina Faso, 2015). NmX increased from 0.6% of N. meningitidis cases in 2015 to 27% in 2017. CONCLUSIONS: Although bacterial meningitis epidemiology varied widely by country, NmC and NmW caused several outbreaks, NmX increased although was not associated with outbreaks, and overall NmA incidence remained low. An effective low-cost multivalent meningococcal conjugate vaccine could help further control meningococcal meningitis in the region.

      14. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis, Burkina Faso, 2016-2017external icon
        Soeters HM, Kambire D, Sawadogo G, Ouedraogo-Traore R, Bicaba B, Medah I, Sangare L, Ouedraogo AS, Ouangraoua S, Yameogo I, Congo-Ouedraogo M, Ky Ba A, Ake F, Srinivasan V, Novak RT, McGee L, Whitney CG, Van Beneden C.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S253-s262.
        BACKGROUND: In 2013, Burkina Faso introduced 13-valent pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization program, to be administered to children at 8, 12, and 16 weeks of age. We evaluated the impact of PCV13 on pneumococcal meningitis. METHODS: Using nationwide surveillance, we gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination; strains were serotyped using PCR. We compared annual incidence (cases per 100 000) 4 years after PCV13’s introduction (2017) to average pre-PCV13 incidence (2011-2013). We adjusted incidence for age and proportion of cases with CSF tested at national laboratories. RESULTS: In 2017, pneumococcal meningitis incidence was 2.7 overall and 10.5 (<1 year), 3.8 (1-4 years), 3.5 (5-14 years), and 1.4 (>/=15 years) by age group. Compared to 2011-2013, PCV13-serotype incidence was significantly lower among all age groups, with the greatest decline among children aged <1 year (77%; 95% confidence interval [CI], 65%-84%). Among all ages, the drop in incidence was larger for PCV13 serotypes excluding serotype 1 (79%; 95% CI, 72%-84%) than for serotype 1 (52%; 95% CI, 44%-59%); incidence of non-PCV13 serotypes also declined (53%; 95% CI, 37%-65%). In 2017, 45% of serotyped cases among all ages were serotype 1 and 12% were other PCV13 serotypes. CONCLUSIONS: In Burkina Faso, meningitis caused by PCV13 serotypes continues to decrease, especially among young children. However, the concurrent decline in non-PCV13 serotypes and short pre-PCV13 observation period complicate evaluation of PCV13’s impact. Efforts to improve control of serotype 1, such as switching from a 3 + 0 schedule to a 2 + 1 schedule, may improve overall control of pneumococcal meningitis in this setting.

      15. Evaluation of the impact of meningococcal serogroup A conjugate vaccine introduction on second-year-of-life vaccination coverage in Burkina Fasoexternal icon
        Zoma RL, Walldorf JA, Tarbangdo F, Patel JC, Diallo AO, Nkwenkeu SF, Kambou L, Nikiema M, Ouedraogo A, Bationo AB, Ouili R, Badolo H, Sawadogo G, Krishnaswamy A, Hatcher C, Hyde TB, Ake F, Novak RT, Wannemuehler K, Mirza I, Medah I, Soeters HM.
        J Infect Dis. 2019 Oct 31;220(Supplement_4):S233-s243.
        BACKGROUND: After successful meningococcal serogroup A conjugate vaccine (MACV) campaigns since 2010, Burkina Faso introduced MACV in March 2017 into the routine Expanded Programme for Immunization schedule at age 15-18 months, concomitantly with second-dose measles-containing vaccine (MCV2). We examined MCV2 coverage in pre- and post-MACV introduction cohorts to describe observed changes regionally and nationally. METHODS: A nationwide household cluster survey of children 18-41 months of age was conducted 1 year after MACV introduction. Coverage was assessed by verification of vaccination cards or recall. Two age groups were included to compare MCV2 coverage pre-MACV introduction (30-41 months) versus post-MACV introduction (18-26 months). RESULTS: In total, 15 925 households were surveyed; 7796 children were enrolled, including 3684 30-41 months of age and 3091 18-26 months of age. Vaccination documentation was observed for 86% of children. The MACV routine coverage was 58% (95% confidence interval [CI], 56%-61%) with variation by region (41%-76%). The MCV2 coverage was 62% (95% CI, 59%-65%) pre-MACV introduction and 67% (95% CI, 64%-69%) post-MACV introduction, an increase of 4.5% (95% CI, 1.3%-7.7%). Among children who received routine MACV and MCV2, 93% (95% CI, 91%-94%) received both at the same visit. Lack of caregiver awareness about the 15- to 18-month visit and vaccine unavailability were common reported barriers to vaccination. CONCLUSIONS: A small yet significant increase in national MCV2 coverage was observed 1 year post-MACV introduction. The MACV/MCV2 coadministration was common. Findings will help inform strategies to strengthen second-year-of-life immunization coverage, including to address the communication and vaccine availability barriers identified.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Diabetes prevalence and incidence among Medicare beneficiaries – United States, 2001-2015external icon
        Andes LJ, Li Y, Srinivasan M, Benoit SR, Gregg E, Rolka DB.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 1;68(43):961-966.
        Diabetes affects approximately 12% of the U.S. adult population and approximately 25% of adults aged >/=65 years. From 2009 to 2017, there was no significant change in diabetes prevalence overall or among persons aged 65-79 years (1). However, these estimates were based on survey data with <5,000 older adults. Medicare administrative data sets, which contain claims for millions of older adults, afford an opportunity to explore both trends over time and heterogeneity within an older population. Previous studies have shown that claims data can be used to identify persons with diagnosed diabetes (2). This study estimated annual prevalence and incidence of diabetes during 2001-2015 using Medicare claims data for beneficiaries aged >/=68 years and found that prevalence plateaued after 2012 and incidence decreased after 2006. In 2015 (the most recent year estimated) prevalence was 31.6%, and incidence was 3.0%. Medicare claims can serve as an important source of data for diabetes surveillance for the older population, which can inform prevention and treatment strategies.

      2. Current trends in the acute treatment of ischemic stroke: analysis from the Paul Coverdell National Acute Stroke Programexternal icon
        Asaithambi G, Tong X, Lakshminarayan K, Coleman King SM, George MG.
        J Neurointerv Surg. 2019 Oct 25.
        BACKGROUND: The intra-arterial treatment (IAT) of acute ischemic stroke (AIS) is now evidence-based and given the highest level of recommendation among eligible patients. Using a multi-state stroke registry, we studied the trend in IAT among patients with AIS over 11 years and its impact on the utilization of intravenous thrombolysis (IVT) within the same 11 years. METHODS: Using data from the Paul Coverdell National Acute Stroke Program (PCNASP), we studied trends in IVT and IAT for patients with AIS between 2008 and 2018. Trends over time were examined for rates of IVT only, IAT only, or a combination of IVT and IAT (IVT+IAT). Favorable outcome was defined as discharge to home. RESULTS: During the study period there were 595 677 patients (mean age 70.4 years, 50.4% women) from 646 participating hospitals with a clinical diagnosis of AIS in the PCNASP. Trends for IVT only, IAT only, and IVT+IAT all significantly increased over time (P<0.001). Total use of IVT and IAT increased from 7% in 2008 to 19.1% in 2018. The rate of patients discharged to home increased significantly over time among all treatment groups (P<0.001). CONCLUSION: In our large registry-based analysis, we observed a significant increase in the use of IAT for the treatment of AIS, with continued increases in the use of IVT. Concurrently, the percent of patients with favorable outcomes continued to increase.

      3. Hypertension and diabetes in non-pregnant women of reproductive age in the United Statesexternal icon
        Azeez O, Kulkarni A, Kuklina EV, Kim SY, Cox S.
        Prev Chronic Dis. 2019 Oct 24;16:E146.
        INTRODUCTION: Diagnosis and control of chronic conditions have implications for women’s health and are major contributing factors to maternal and infant morbidity and mortality. This study estimated the prevalence of hypertension and diabetes in non-pregnant women of reproductive age in the United States, the proportion who were unaware of their condition or whose condition was not controlled, and differences in the prevalence of these conditions by selected characteristics. METHODS: We used data from the 2011-2016 National Health and Nutrition Examination Survey to estimate overall prevalence of hypertension and diabetes among women of reproductive age (aged 20-44 y), the proportion who were unaware of having hypertension or diabetes, and the proportion whose diabetes or hypertension was not controlled. We used logistic regression models to calculate adjusted prevalence ratios to assess differences by selected characteristics. RESULTS: The estimated prevalence of hypertension was 9.3% overall. Among those with hypertension, 16.9% were unaware of their hypertension status and 40.7% had uncontrolled hypertension. Among women with diabetes, almost 30% had undiagnosed diabetes, and among those with diagnosed diabetes, the condition was not controlled in 51.5%. CONCLUSION: This analysis improves our understanding of the prevalence of hypertension and diabetes among women of reproductive age and may facilitate opportunities to improve awareness and control of these conditions, reduce disparities in women’s health, and improve birth outcomes.

      4. Patient navigator reported patient barriers and delivered activities in two large federally-funded cancer screening programsexternal icon
        Barrington WE, DeGroff A, Melillo S, Vu T, Cole A, Escoffery C, Askelson N, Seegmiller L, Gonzalez SK, Hannon P.
        Prev Med. 2019 Oct 21:105858.
        Few data are available on patient navigators (PNs) across diverse roles and organizational settings that could inform optimization of patient navigation models for cancer prevention. The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and the Colorectal Cancer and Control Program (CRCCP) are two federally-funded screening programs that support clinical- and community-based PNs who serve low-income and un- or underinsured populations across the United States. An online survey assessing PN characteristics, delivered activities, and patient barriers to screening was completed by 437 of 1002 identified PNs (44%). Responding PNs were racially and ethnically diverse, had varied professional backgrounds and practice-settings, worked with diverse populations, and were located within rural and urban/suburban locations across the U.S. More PNs reported working to promote screening for breast/cervical cancers (BCC, 94%) compared to colorectal cancer (CRC, 39%). BCC and CRC PNs reported similar frequencies of individual- (e.g., knowledge, motivation, fear) and community-level patient barriers (e.g., beliefs about healthcare and screening). Despite reporting significant patient structural barriers (e.g., transportation, work and clinic hours), most BCC and CRC PNs delivered individual-level navigation activities (e.g., education, appointment reminders). PN training to identify and champion timely and patient-centered adjustments to organizational policies, practices, and norms of the NBCCEDP, CRCCP, and partner organizations may be beneficial. More research is needed to determine whether multilevel interventions that support this approach could reduce structural barriers and increase screening and diagnostic follow-up among the marginalized communities served by these two important cancer-screening programs.

      5. Direct-to-member mailed colorectal cancer screening outreach for Medicaid and Medicare enrollees: Implementation and effectiveness outcomes from the BeneFIT studyexternal icon
        Coronado GD, Green BB, West , Schwartz MR, Coury JK, Vollmer WM, Shapiro JA, Petrik AF, Baldwin LM.
        Cancer. 2019 Oct 28.
        BACKGROUND: Colorectal cancer screening uptake is low, particularly among individuals enrolled in Medicaid. To the authors’ knowledge, little is known regarding the effectiveness of direct-to-member outreach by Medicaid health insurance plans to raise colorectal cancer screening use, nor how best to deliver such outreach. METHODS: BeneFIT is a hybrid implementation-effectiveness study of 2 program models that health plans developed for a mailed fecal immunochemical test (FIT) intervention. The programs differed with regard to whether they used a centralized approach (Health Plan Washington) or collaborated with health centers (Health Plan Oregon). The primary implementation outcome of the current study was the percentage of eligible enrollees to whom the plans delivered each intervention component. The primary effectiveness outcome was the rate of FIT completion within 6 months of mailing of the introductory letter. RESULTS: The health plans identified 12,000 eligible enrollees (8551 in Health Plan Washington and 3449 in Health Plan Oregon). Health Plan Washington mailed an introductory letter and FIT kit to 8551 enrollees (100%) and delivered a reminder call to 839 (10.3% of the 8132 attempted). Health Plan Oregon mailed an introductory letter, and a letter and FIT kit plus a reminder postcard to 2812 enrollees (81.5%) and 2650 enrollees (76.8%), respectively. FIT completion rates were 18.2% (1557 of 8551 enrollees) in Health Plan Washington. In Health Plan Oregon, completion rates were 17.4% (488 of 2812 enrollees) among enrollees who were mailed an introductory letter and 18.3% (484 of 2650 enrollees) among enrollees who also were mailed a FIT kit plus reminder postcard. CONCLUSIONS: The implementation of mailed FIT outreach by health plans may be effective and could reach many individuals at risk of developing colorectal cancer.

    • Communicable Diseases
      1. Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africaexternal icon
        Brown TS, Challagundla L, Baugh EH, Omar SV, Mustaev A, Auld SC, Shah NS, Kreiswirth BN, Brust JC, Nelson KN, Narechania A, Kurepina N, Mlisana K, Bonneau R, Eldholm V, Ismail N, Kolokotronis SO, Robinson DA, Gandhi NR, Mathema B.
        Proc Natl Acad Sci U S A. 2019 Oct 28.
        Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal approximately 400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.

      2. A localized sanitation status index as a proxy for fecal contamination in urban Maputo, Mozambiqueexternal icon
        Capone D, Adriano Z, Berendes D, Cumming O, Dreibelbis R, Holcomb DA, Knee J, Ross I, Brown J.
        PLoS One. 2019 ;14(10):e0224333.
        Sanitary surveys are used in low- and middle-income countries to assess water, sanitation, and hygiene conditions, but have rarely been compared with direct measures of environmental fecal contamination. We conducted a cross-sectional assessment of sanitary conditions and E. coli counts in soils and on surfaces of compounds (household clusters) in low-income neighborhoods of Maputo, Mozambique. We adapted the World Bank’s Urban Sanitation Status Index to implement a sanitary survey tool specifically for compounds: a Localized Sanitation Status Index (LSSI) ranging from zero (poor sanitary conditions) to one (better sanitary conditions) calculated from 20 variables that characterized local sanitary conditions. We measured the variation in the LSSI with E. coli counts in soil (nine locations/compound) and surface swabs (seven locations/compound) in 80 compounds to assess reliability. Multivariable regression indicated that a ten-percentage point increase in LSSI was associated with 0.05 (95% CI: 0.00, 0.11) log10 fewer E. coli/dry gram in courtyard soil. Overall, the LSSI may be associated with fecal contamination in compound soil; however, the differences detected may not be meaningful in terms of public health hazards.

      3. Antibiotic resistant Salmonella in swine wastes and farm surface watersexternal icon
        Casanova LM, Hill VR, Sobsey MD.
        Lett Appl Microbiol. 2019 Oct 24.
        Hog production takes place mostly in large concentrated animal feeding operations (CAFOs) where waste is managed by storing in lagoons prior to land application of lagoon liquid. Salmonella, including antibiotic resistant Salmonella, have been found in the farm environment and lagoons. The objective of this research was to determine whether Salmonella resistant to clinically relevant antibiotics were present in wastewaters and surface waters from hog CAFOs. Samples of hog waste and on farm environmental waters were analysed for Salmonella, which were tested for antimicrobial susceptibility. The highest percentage of resistant isolates were found in raw waste flushed from hog houses and in lagoon wastewater; few resistant isolates were found in on-farm surface water. Resistance to sulfamethoxazole was most common, mostly in waste samples and less commonly in surface water, followed by chloramphenicol and ampicillin. No resistance to cephalosporin or fluoroquinolones was found. Resistance to clinically relevant antibiotics was commonly found in Salmonella from hog waste but was less extensive in farm surface waters. Management of wastes from hog CAFOs should be designed to further reduce the risk of human exposures resulting from environmental contamination with Salmonella.

      4. [No abstract]

      5. Impact of home-based HIV testing services on progress toward the UNAIDS 90-90-90 targets in a hyperendemic area of South Africaexternal icon
        Lewis L, Maughan-Brown B, Grobler A, Cawood C, Khanyile D, Glenshaw M, Kharsany AB.
        J Acquir Immune Defic Syndr. 2019 Feb 1;80(2):135-144.
        BACKGROUND: In several subgroups of South Africa, the percentage of HIV-positive individuals aware of their status falls well below the UNAIDS 90% target. This study examined the impact that home-based HIV testing services (HBHTS) had on knowledge of status in a hyperendemic area of South Africa. METHODS: We analysed data from the second cross-sectional HIV Incidence Provincial Surveillance System survey (2015/2016), a representative sample (n = 10,236) of individuals aged 15-49 years. Participants completed a questionnaire, provided blood samples for laboratory testing (used to estimate HIV prevalence), and were offered HBHTS. The proportion of people living with HIV (n = 3870) made aware of their status through HBHTS was measured, and factors associated with HBHTS uptake were identified. RESULTS: Knowledge of HIV-positive status at the time of the survey was 62.9% among men and 73.4% among women. Through HBHTS, the percentage of HIV-positive men and women who knew their status rose to 74.2% and 80.5%, respectively. The largest impact was observed among youth (15-24 years). Knowledge of status increased from 36.6% to 59.3% and from 50.8% to 64.8% among young men and women, respectively. In addition, 51.4% of those who had previously never tested received their first test. Key reasons for declining HBHTS among undiagnosed HIV-positive individuals included fear and self-report of an HIV-negative status. CONCLUSIONS: HBHTS was effective in increasing awareness of HIV-positive status, particularly among youth, men, and those who had never tested. HBHTS could have a marked impact on progress toward the UNAIDS 90-90-90 targets within these subgroups.

      6. Pharyngeal gonococcal infections: A cross-sectional study in a network of sexually transmitted disease clinics; STD Surveillance Network (SSuN)-January 2016 to June 2018external icon
        Llata E, Braxton J, Asbel L, Huspeni D, Hsu K, Kerani RP, Nguyen TQ, Pathela P, Schumacher C, Toevs K, Torrone E.
        Sex Transm Dis. 2019 Oct 28.
        We conducted a cross-sectional analysis using STD clinic data to determine test of cure (TOC) rates among persons diagnosed with pharyngeal gonococcal infections who were treated with a non-ceftriaxone, non-azithromycin therapy. Less than 10% returned for a TOC, highlighting the need to understand factors that can lead to improved compliance.

      7. Homelessness is a challenge to retention in HIV care and adherence to antiretroviral therapy. We describe the sociodemographic and behavioral characteristics of HIV-positive adults who reported recent homelessness. The Medical Monitoring Project is a complex sample survey of HIV-positive adults receiving medical care in the United States. We used weighted interview and medical record data collected from June 2009 to May 2015 to estimate the prevalence of depression, substance use, and HIV risk behaviors among adults experiencing recent homelessness. From 2009 to 2015, 8.3% of HIV-positive adults experienced recent homelessness. Homeless adults were more likely than housed adults to have major depression, to binge drink, use non-injection drugs, use injection drugs, and smoke. Over 60% of homeless adults were sexually active during the past year, with homeless adults reporting more condomless sex with an HIV-negative or unknown status sex partner than housed adults. Programs attempting to improve the health outcomes of HIV-positive homeless persons and reduce ongoing HIV transmission can focus on providing basic needs, such as housing, and ancillary services, such as mental health counseling or substance abuse treatment and counseling.

      8. The Severe Typhoid Fever in Africa Program: Study design and methodology to assess disease severity, host immunity, and carriage associated with invasive salmonellosisexternal icon
        Park SE, Toy T, Cruz Espinoza LM, Panzner U, Mogeni OD, Im J, Poudyal N, Pak GD, Seo H, Chon Y, Schutt-Gerowitt H, Mogasale V, Ramani E, Dey A, Park JY, Kim JH, Seo HJ, Jeon HJ, Haselbeck A, Conway Roy K, MacWright W, Adu-Sarkodie Y, Owusu-Dabo E, Osei I, Owusu M, Rakotozandrindrainy R, Soura AB, Kabore LP, Teferi M, Okeke IN, Kehinde A, Popoola O, Jacobs J, Lunguya Metila O, Meyer CG, Crump JA, Elias S, Maclennan CA, Parry CM, Baker S, Mintz ED, Breiman RF, Clemens JD, Marks F.
        Clin Infect Dis. 2019 Oct 30;69(Supplement_6):S422-s434.
        BACKGROUND: Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. METHODS: A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. RESULTS: Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. CONCLUSIONS: SETA supports public health policy on typhoid immunization strategy in Africa.

      9. Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficienciesexternal icon
        Perelygina L, Chen MH, Suppiah S, Adebayo A, Abernathy E, Dorsey M, Bercovitch L, Paris K, White KP, Krol A, Dhossche J, Torshin IY, Saini N, Klimczak LJ, Gordenin DA, Zharkikh A, Plotkin S, Sullivan KE, Icenogle J.
        PLoS Pathog. 2019 Oct 28;15(10):e1008080.
        Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10-3 subs/site/year and 8.9 x 10-4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.

      10. Domestically acquired Seoul virus causing hemophagocytic lymphohistiocytosis – Washington, DC, 2018external icon
        Shastri B, Kofman A, Hennenfent A, Klena JD, Nicol S, Graziano JC, Morales-Betoulle M, Cannon D, Maradiaga A, Tran A, Ramdeen SK.
        Open Forum Infect Dis. 2019 Oct;6(10):ofz404.
        Seoul orthohantavirus (SEOV) infections, uncommonly reported in the United States, often result in mild illness. We report a case of hemophagocytic lymphohistiocytosis secondary to SEOV infection that was domestically acquired in Washington, DC.

      11. Multicountry distribution and characterization of extended-spectrum beta-lactamase-associated gram-negative bacteria from bloodstream infections in sub-Saharan Africaexternal icon
        Toy T, Pak GD, Duc TP, Campbell JI, El Tayeb MA, Von Kalckreuth V, Im J, Panzner U, Cruz Espinoza LM, Eibach D, Dekker DM, Park SE, Jeon HJ, Konings F, Mogeni OD, Cosmas L, Bjerregaard-Andersen M, Gasmelseed N, Hertz JT, Jaeger A, Krumkamp R, Ley B, Thriemer K, Kabore LP, Niang A, Raminosoa TM, Sampo E, Sarpong N, Soura A, Owusu-Dabo E, Teferi M, Yeshitela B, Poppert S, May J, Kim JH, Chon Y, Park JK, Aseffa A, Breiman RF, Schutt-Gerowitt H, Aaby P, Adu-Sarkodie Y, Crump JA, Rakotozandrindrainy R, Meyer CG, Sow AG, Clemens JD, Wierzba TF, Baker S, Marks F.
        Clin Infect Dis. 2019 Oct 30;69(Supplement_6):S449-s458.
        BACKGROUND: Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum beta-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. METHODS: Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for beta-lactamase were performed on all pathogens. RESULTS: Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. CONCLUSIONS: Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.

      12. [No abstract]

      13. Optimizing coverage vs frequency for sexually transmitted infection screening of men who have sex with menexternal icon
        Weiss KM, Jones JS, Anderson EJ, Gift T, Chesson H, Bernstein K, Workowski K, Tuite A, Rosenberg ES, Sullivan PS, Jenness SM.
        Open Forum Infect Dis. 2019 Oct;6(10):ofz405.
        Background: The incidence of bacterial sexually transmitted infections (STIs) in men who have sex with men (MSM) has increased substantially despite availability of effective antibiotics. The US Centers for Disease Control and Prevention (CDC) recommends annual screening for all sexually active (SA) MSM and more frequent screening for high-risk (HR) MSM. The population-level benefits of improved coverage vs increased frequency of STI screening among SA vs HR MSM are unknown. Methods: We used a network transmission model of gonorrhea (NG) and chlamydia (CT) among MSM to simulate the implementation of STI screening across different scenarios, starting with the CDC guidelines at current coverage levels. Counterfactual model scenarios varied screening coverage and frequency for SA MSM and HR MSM (MSM with multiple recent partners). We estimated infections averted and the number needed to screen to prevent 1 new infection. Results: Compared with current recommendations, increasing the frequency of screening to biannually for all SA MSM and adding some HR screening could avert 72% of NG and 78% of CT infections over 10 years. Biannual screening of 30% of HR MSM at empirical coverage levels for annual SA screening could avert 76% of NG and 84% of CT infections. Other scenarios, including higher coverage among SA MSM and increasing frequency for HR MSM, averted fewer infections but did so at a lower number needed to screen. Conclusions: The optimal screening scenarios in this model to reduce STI incidence among MSM included more frequent screening for all sexually active MSM and higher coverage of screening for HR men with multiple partners.

    • Disaster Control and Emergency Services
      1. Enhancing community preparedness: an inventory and analysis of disaster citizen science activitiesexternal icon
        Chari R, Petrun Sayers EL, Amiri S, Leinhos M, Kotzias V, Madrigano J, Thomas EV, Carbone EG, Uscher-Pines L.
        BMC Public Health. 2019 Oct 23;19(1):1356.
        BACKGROUND: Disaster citizen science, or the use of scientific principles and methods by “non-professional” scientists or volunteers, may be a promising way to enhance public health emergency preparedness (PHEP) and build community resilience. However, little research has focused on understanding this emerging field and its implications for PHEP. To address research gaps, this paper: (1) assesses the state of disaster citizen science by developing an inventory of disaster citizen science projects; (2) identifies different models of disaster citizen science; and (3) assesses their relevance for PHEP. METHODS: We searched the English-language peer-reviewed and grey literature for disaster citizen science projects with no time period specified. Following searches, a team of three reviewers applied inclusion/exclusion criteria that defined eligible disasters and citizen science activities. Reviewers extracted the following elements from each project: project name and description; lead and partner entities; geographic setting; start and end dates; type of disaster; disaster phase; citizen science model; and technologies used. RESULTS: A final set of 209 projects, covering the time period 1953-2017, were included in the inventory. Projects were classified across five citizen science models: distributed or volunteer sensing (n = 19; 9%); contributory (n = 98; 47%); distributed intelligence (n = 52; 25%); collaborative research (n = 32; 15%); and collegial research (n = 8; 4%). Overall, projects were conducted across all disaster phases and most frequently for earthquakes, floods, and hurricanes. Although activities occurred globally, 40% of projects were set in the U.S. Academic, government, technology, and advocacy organizations were the most prevalent lead entities. Although a range of technologies were used, 77% of projects (n = 161) required an internet-connected device. These characteristics varied across citizen science models revealing important implications for applications of disaster citizen science, enhancement of disaster response capabilities, and sustainability of activities over time. CONCLUSIONS: By increasing engagement in research, disaster citizen science may empower communities to take collective action, improve system response capabilities, and generate relevant data to mitigate adverse health impacts. The project inventory established a baseline for future research to capitalize on opportunities, address limitations, and help disaster citizen science achieve its potential.

      2. Evaluating disaster damages and operational status of health-care facilities during the emergency response phase of Hurricane Maria in Puerto Ricoexternal icon
        Irvin-Barnwell EA, Cruz M, Maniglier-Poulet C, Cabrera J, Rivera Diaz J, De La Cruz Perez R, Forrester C, Shumate A, Mutter J, Graziano L, Rivera Gonzalez L, Malilay J, Raheem M.
        Disaster Med Public Health Prep. 2019 Oct 29:1-9.
        On September 20, 2017, Hurricane Maria made landfall on Puerto Rico as a category 4 storm, resulting in serious widespread impact across the island, including communication and power outages, water systems impairment, and damage to life-saving infrastructure. In collaboration with the Puerto Rico Department of Health, the Public Health Branch (PHB), operating under the Department of Health and Human Services Incident Response Coordination Team, was tasked with completing assessments of health-care facilities in Puerto Rico to determine infrastructure capabilities and post-hurricane capacity. Additionally, in response to significant data entry and presentation needs, the PHB leadership worked with the Puerto Rico Planning Board to develop and test a new app-based infrastructure capacity assessment tool. Assessments of hospitals were initiated September 28, 2017, and completed November 10, 2017 (n = 64 hospitals, 97%). Assessments of health-care centers were initiated on October 7, 2017, with 186 health-care centers (87%) assessed through November 18, 2017. All hospitals had working communications; however, 9% (n = 17) of health-care centers reported no communication capabilities. For the health-care centers, 114 (61%) reported they were operational but had sustainment needs. In conclusion, health-care facility assessments indicated structural damage issues and operational capacity decreases, while health-care centers reported loss of communication capabilities post-Hurricane Maria.

    • Disease Reservoirs and Vectors
      1. Outbreak of diarrhoea in piglets caused by novel rotavirus genotype G4P[49] in north-western district of Bangladesh, February 2014external icon
        Sarkar S, Esona MD, Gautam R, Castro CJ, Ng TF, Haque W, Khan SU, Hossain ME, Rahman MZ, Gurley ES, Kennedy ED, Bowen MD, Parashar UD, Rahman M.
        Transbound Emerg Dis. 2019 Aug 30.
        Group A rotavirus (RVA) associated diarrhoea in piglets represents one of the major causes of morbidity and mortality in pig farms worldwide. A diarrhoea outbreak occurred among nomadic piglets in north-western district of Bangladesh in February 2014. Outbreak investigation was performed to identify the cause, epidemiologic and clinical features of the outbreak. Rectal swabs and clinical information were collected from diarrhoeic piglets (n = 36). Rectal swabs were tested for RVA RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR) using NSP3-specific primers. The G (VP7) and P (VP4) genes were typed by conventional RT-PCR and sanger sequencing and full genome sequences were determined using next-generation sequencing. We found the attack rate was 61% (50/82) among piglets in the nomadic pig herd, and the case fatality rate was 20% (10/50) among piglets with diarrhoea. All study piglets cases had watery diarrhoea, lack of appetite or reluctance to move. A novel RVA strain with a new P[49] genotype combined with G4 was identified among all piglets with diarrhoea. The genome constellation of the novel RVA strains was determined to be G4-P[49]-I1-R1-C1-M1-A8-N1-T7-E1-H1. Genetic analysis shows that the novel G4P[49] strain is similar to Indian and Chinese porcine or porcine-like G4 human strains and is genetically distant from Bangladeshi human G4 strains. Identification of this novel RVA strain warrants further exploration for disease severity and zoonotic potential.

    • Drug Safety
      1. Emergency visits for oral anticoagulant bleedingexternal icon
        Geller AI, Shehab N, Lovegrove MC, Rose KO, Weidle NJ, Goring SK, Budnitz DS.
        J Gen Intern Med. 2019 Oct 29.

        [No abstract]

    • Environmental Health
      1. To provide guidance to clinicians, the Wilderness Medical Society convened experts to develop evidence-based guidelines for water disinfection in situations where the potability of available water is not ensured, including wilderness and international travel, areas affected by disaster, and other areas without adequate sanitation. The guidelines present the available methods for reducing or eliminating microbiologic contamination of water for individuals, groups, or households; evaluation of their effectiveness; and practical considerations. The evidence evaluation includes both laboratory and clinical publications. The panel graded the recommendations based on the quality of supporting evidence and the balance between benefits and risks or burdens, according to the criteria published by the American College of Chest Physicians.

      2. Estimated burden of disease from arsenic in drinking water supplied by domestic wells in the United Statesexternal icon
        Greco SL, Belova A, Haskell J, Backer L.
        J Water Health. 2019 Oct;17(5):801-812.
        Well water around the world can be contaminated with arsenic, a naturally occurring geological element that has been associated with myriad adverse health effects. Persons obtaining their drinking water from private wells are often responsible for well testing and water treatment. High levels of arsenic have been reported in well water-supplied areas of the United States. We quantified – in cases and dollars – the potential burden of disease associated with the ingestion of arsenic through private well drinking water supplies in the United States. To estimate cancer and cardiovascular disease burden, we developed a Monte Carlo model integrating three input streams: (1) regional concentrations of arsenic in drinking water wells across the United States; (2) dose-response relationships in the form of cancer slope factors and hazard ratios; and (3) economic cost estimates developed for morbidity endpoints using ‘cost-of-illness’ methods and for mortality using ‘value per statistical life’ estimates. Exposure to arsenic in drinking water from U.S. domestic wells is modeled to contribute 500 annual premature deaths from ischemic heart disease and 1,000 annual cancer cases (half of them fatal), monetized at $10.9 billion (2017 USD) annually. These considerable public health burden estimates can be compared with the burdens of other priority public health issues to assist in decision-making.

      3. Prenatal exposure to phthalates and neurodevelopment in the CHAMACOS cohortexternal icon
        Hyland C, Mora AM, Kogut K, Calafat AM, Harley K, Deardorff J, Holland N, Eskenazi B, Sagiv SK.
        Environ Health Perspect. 2019 Oct;127(10):107010.
        BACKGROUND: Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence. OBJECTIVE: We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. METHODS: We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort (n=334). We used age-specific linear regression models and generalized estimating equation models to assess longitudinal effects and examined differences by sex. RESULTS: Phthalate metabolites were detected in 88%-100% of samples, depending on the metabolite. Associations of phthalates with neurodevelopmental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates (SigmaLMW) were associated with more self-reported hyperactivity [beta=0.8, 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in SigmaLMW phthalates], attention problems (beta=1.5, 95% CI: 0.7, 2.2), and anxiety (beta=0.9, 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., beta for Full-Scale IQ for boys=-1.9, 95% CI: -4.1, 0.3 and -1.7, 95% CI: -3.8, 0.3, respectively; beta for girls=1.8, 95% CI: 0.1, 3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; p-int=0.01 for both). CONCLUSION: We found predominantly null associations of prenatal phthalates with neurodevelopment in CHAMACOS, and weak associations of SigmaLMW phthalates with internalizing and externalizing behaviors in adolescence. No previous studies have examined associations of prenatal phthalate exposure with neurodevelopment into adolescence, an important time for manifestations of effects. https://doi.org/10.1289/EHP5165.

    • Food Safety
      1. Low prevalence of viable Toxoplasma gondii in fresh, unfrozen, American pasture-raised pork and lamb from retail meat stores in the United Statesexternal icon
        Dubey JP, Hill DE, Fournet V, Hawkins-Cooper D, Cerqueira-Cezar CK, Murata FH, Verma SK, Kwok OC, Rani S, Fredericks J, Adams B, Jones JL, Wiegand RE, Ying Y, Guo M, Su C, Pradhan AK.
        Food Control. 2020 ;109.
        In a national survey of fresh, unfrozen, American pasture-raised lamb and pork, the prevalence of viable Toxoplasma gondii was determined in 1500 samples selected by random multistage sampling (750 pork, 750 lamb) obtained from 250 retail meat stores from 10 major geographic areas in the USA. Each sample consisted of a minimum of 500 g of meat purchased from the retail meat case. To detect viable T. gondii, 50 g meat samples of each of 1500 samples were bioassayed in mice. Viable T. gondii was isolated from 2 of 750 lamb samples (unweighted: 0.19%, 0.00-0.46%; weighted: 0.04%, 0.00-0.11%) and 1 of 750 pork samples (unweighted: 0.12%, 0.00-0.37%; weighted: 0.18%, 0.00-0.53%). Overall, the prevalence of viable T. gondii in these retail meats was very low. Nevertheless, consumers, especially pregnant women, should be aware that they can acquire T. gondii infection from ingestion of undercooked meat.

    • Health Communication and Education
      1. Developing and testing the Deten El Zika Campaign in Puerto Ricoexternal icon
        Poehlman JA, Sidibe T, Jimenez-Magdaleno KV, Vazquez N, Ray SE, Mitchell EW, Squiers L.
        J Health Commun. 2019 Oct 31:1-12.
        Responding to an emerging health threat often requires rapid deployment of behavior change communication. Health communication best practices include developing and testing draft messages and materials to ensure that they resonate with and inspire priority groups to act. However, when faced with an emergency health threat, the timeline for these activities can be compressed from months to weeks. This article discusses the rapid development and implementation of a Zika virus prevention campaign for pregnant women in Puerto Rico. The goal of the campaign was to increase knowledge among and motivate pregnant women, their partners and family members, and the community to follow Zika virus prevention recommendations. The steps in campaign development include environmental scanning, concept development and testing, and message testing to ensure development of campaign materials that resonated with and were well-received by key audience groups. The materials adhere to principles of behavior change communication, and offer our insights for development of future campaigns when under time constraints.

    • Health Economics
      1. Unsterile opioid injection increases risk for infection transmission, including HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). We assess prevalence of and risk factors associated with opioid overdose and infections with HIV, HBV, or HCV among Medicare beneficiaries with opioid-related fee-for-service claims during 2015. We conducted a cross-sectional analysis to estimate claims for opioid use and overdose and HIV, HBV, or HCV infections, using data from US Medicare fee-for-service claims. Beneficiaries with opioid-related claims had increased odds for HIV (2.3; 95% confidence interval (CI), 2.3-2.4), acute HBV (6.7; 95% CI, 6.3-7.1), chronic HBV (5.0; 95% CI, 4.7-5.4), acute HCV (9.6; 95% CI, 9.2-10.0), and chronic HCV (8.9; 95% CI, 8.7-9.1). Beneficiaries with opioid-related claims and for HIV, HBV, or HCV infection, respectively, had a 1.1-1.9-fold odds for having a claim for opioid overdose. Independent risk factors for opioid overdose and each selected infection outcome included age, sex, race/ethnicity, region, and residence in a high-vulnerability county. Having opioid-related claims and selected demographic attributes were independent, significant risk factors for having HIV, HBV, or HCV claims among US Medicare beneficiaries. These results might help guide interventions intended to reduce incidences of HIV, HCV, and HBV infections among beneficiaries with opioid-related claims.

      2. Medicare claims paid by the Federal Black Lung Benefits Program: U.S. Medicare Beneficiaries, 1999-2016external icon
        Kurth L, Casey M, Schleiff P, Halldin C, Mazurek J, Blackley D.
        J Occup Environ Med. 2019 Oct 22.
        OBJECTIVE: To establish the burden of totally disabling respiratory impairment among coal miners, we identified the healthcare utilization and cost for Medicare claims where the Federal Black Lung Program (FBLP) was the primary payer. METHODS: We extracted FBLP claims from 1999-2016 institutional Medicare data along with beneficiary, comorbidity, and claim cost information. Healthcare utilization was evaluated and compared to the 2016 Medicare population. RESULTS: The FBLP was the primary payer on 75,690 claims from 19,700 beneficiaries and paid an increasing percentage of the total paid to providers annually. Claims decreased from 1999-2016 but cost per claim increased. Beneficiaries were hospitalized and visited the ER for respiratory and cardiovascular conditions. CONCLUSIONS: Medicare beneficiaries with FBLP primary payer claims have higher healthcare utilization and comorbidities compared to Medicare enrollees, indicative of increased financial and healthcare burden.

      3. Program cost analysis of influenza vaccination of health care workers in Albaniaexternal icon
        Pallas SW, Ahmeti A, Morgan W, Preza I, Nelaj E, Ebama M, Levin A, Lafond KE, Bino S.
        Vaccine. 2019 Oct 25.
        BACKGROUND: Since 2012, WHO has recommended influenza vaccination for health care workers (HCWs), which has different costs than routine infant immunization; however, few cost estimates exist from low- and middle-income countries. Albania, a middle-income country, has self-procured influenza vaccine for some HCWs since 2014, supplemented by vaccine donations since 2016 through the Partnership for Influenza Vaccine Introduction (PIVI). We conducted a cost analysis of HCW influenza vaccination in Albania to inform scale-up and sustainability decisions. METHODS: We used the WHO’s Seasonal Influenza Immunization Costing Tool (SIICT) micro-costing approach to estimate incremental costs from the government perspective of facility-based vaccination of HCWs in Albania with trivalent inactivated influenza vaccine for the 2018-19 season based on 2016-17 season data from administrative records, key informant consultations, and a convenience sample of site visits. Scenario analyses varied coverage, vaccine presentation, and vaccine prices. RESULTS: In the baseline scenario, 13,377 HCWs (70% of eligible HCWs) would be vaccinated at an incremental financial cost of US$61,296 and economic cost of US$161,639. Vaccine and vaccination supplies represented the largest share of financial (89%) and economic costs (44%). Per vaccinated HCW financial cost was US$4.58 and economic cost was US$12.08 including vaccine and vaccination supplies (US$0.49 and US$6.76 respectively without vaccine and vaccination supplies). Scenarios with higher coverage, pre-filled syringes, and higher vaccine prices increased total economic and financial costs, although the economic cost per HCW vaccinated decreased with higher coverage as some costs were spread over more HCWs. Across all scenarios, economic costs were <0.07% of Albania’s estimated government health expenditure, and <5.07% of Albania’s estimated immunization program economic costs. CONCLUSIONS: Cost estimates can help inform decisions about scaling up influenza vaccination for HCWs and other risk groups.

    • Immunity and Immunization
      1. Biosafety risk assessment for production of candidate vaccine viruses to protect humans from zoonotic highly pathogenic avian influenza virusesexternal icon
        Chen LM, Donis RO, Suarez DL, Wentworth DE, Webby R, Engelhardt OG, Swayne DE.
        Influenza Other Respir Viruses. 2019 Oct 28.
        A major lesson learned from the public health response to the 2009 H1N1 pandemic was the need to shorten the vaccine delivery timeline to achieve the best pandemic mitigation results. A gap analysis of previous pre-pandemic vaccine development activities identified possible changes in the Select Agent exclusion process that would maintain safety and shorten the timeline to develop candidate vaccine viruses (CVVs) for use in pandemic vaccine manufacture. Here, we review the biosafety characteristics of CVVs developed in the past 15 years to support a shortened preparedness timeline for A(H5) and A(H7) subtype highly pathogenic avian influenza (HPAI) CVVs. Extensive biosafety experimental evidence supported recent changes in the implementation of Select Agent regulations that eliminated the mandatory chicken pathotype testing requirements and expedited distribution of CVVs to shorten pre-pandemic and pandemic vaccine manufacturing by up to 3 weeks.

      2. The epidemiology and burden of influenza B/Victoria and B/Yamagata lineages in Kenya, 2012-2016external icon
        Emukule GO, Otiato F, Nyawanda BO, Otieno NA, Ochieng CA, Ndegwa LK, Muturi P, Bigogo G, Verani JR, Muthoka PM, Hunsperger E, Chaves SS.
        Open Forum Infect Dis. 2019 Oct;6(10):ofz421.
        Background: The impact of influenza B virus circulation in Sub-Saharan Africa is not well described. Methods: We analyzed data from acute respiratory illness (ARI) in Kenya. We assessed clinical features and age-specific hospitalization and outpatient visit rates by person-years for influenza B/Victoria and B/Yamagata and the extent to which circulating influenza B lineages in Kenya matched the vaccine strain component of the corresponding season (based on Northern Hemisphere [October-March] and Southern Hemisphere [April-September] vaccine availability). Results: From 2012 to 2016, influenza B represented 31% of all influenza-associated ARIs detected (annual range, 13-61%). Rates of influenza B hospitalization and outpatient visits were higher for <5 vs >/=5 years. Among <5 years, B/Victoria was associated with pneumonia hospitalization (64% vs 44%; P = .010) and in-hospital mortality (6% vs 0%; P = .042) compared with B/Yamagata, although the mean annual hospitalization rate for B/Victoria was comparable to that estimated for B/Yamagata. The 2 lineages co-circulated, and there were mismatches with available trivalent influenza vaccines in 2/9 seasons assessed. Conclusions: Influenza B causes substantial burden in Kenya, particularly among children aged <5 years, in whom B/Victoria may be associated with increased severity. Our findings suggest a benefit from including both lineages when considering influenza vaccination in Kenya.

      3. Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018-2019 seasonexternal icon
        Flannery B, Kondor RJ, Chung JR, Gaglani M, Reis M, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Belongia EA, McLean HQ, Kim SS, Blanton L, Kniss K, Budd AP, Brammer L, Stark TJ, Barnes JR, Wentworth DE, Fry AM, Patel M.
        J Infect Dis. 2019 Oct 30.
        BACKGROUND: Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness and vaccine strain selection. We used U.S. virologic surveillance and Influenza Vaccine Effectiveness (VE) Network data to evaluate consequences of this clade. METHODS: Distribution of influenza viruses was described using virologic surveillance data. The VE Network enrolled ambulatory patients aged >/=6 months with acute respiratory illness at five sites. Respiratory specimens were tested by RT-PCR for influenza and sequenced. Using a test-negative design, we estimated VE comparing odds of influenza among vaccinated versus unvaccinated participants. RESULTS: During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2,763 VE Network case patients, 1,325 (48%) were infected with A(H1N1)pdm09 and 1,350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1,054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval [CI], 37 to 51%) against A(H1N1)pdm09 and 9% (95% CI, -4 to 20%) against A(H3N2); effectiveness was 5% (95% CI, -10 to 19%) against A(H3N2) clade 3C.3a viruses. CONCLUSIONS: Predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased vaccine effectiveness, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines.

      4. Impact of maternal HIV infection and placental malaria on the transplacental transfer of influenza antibodies in mother-infant pairs in Malawi, 2013-2014external icon
        Ho A, Mapurisa G, Madanitsa M, Kalilani-Phiri L, Kamiza S, Makanani B, Ter Kuile FO, Buys A, Treurnicht F, Everett D, Mwapasa V, Widdowson MA, McMorrow M, Heyderman RS.
        Open Forum Infect Dis. 2019 Oct;6(10):ofz383.
        Background: Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection. Methods: We conducted a cross-sectional study of influenza vaccine-naive pregnant women recruited at delivery from Blantyre (urban, low malaria transmission) and Chikwawa (rural, high malaria transmission) in Southern Malawi. HIV-infected mothers were excluded in Chikwawa. Maternal and cord blood antibodies against circulating influenza strains A/California/7/2009, A/Victoria/361/2011, B/Brisbane/60/2008, and B/Wisconsin/1/2010 were measured by hemagglutination inhibition (HAI). We studied the impact of maternal HIV infection and placental malaria on influenza antibody levels in mother-infant pairs in Blantyre and Chikwawa, respectively. Results: We included 454 mother-infant pairs (Blantyre, n = 253; Chikwawa, n = 201). HIV-infected mothers and their infants had lower seropositivity (HAI titer >/=1:40) against influenza A(H1N1)pdm09 (mothers, 24.3 vs 45.4%; P = .02; infants, 24.3 vs 50.5%; P = .003) and A(H3N2) (mothers, 37.8% vs 63.9%; P = .003; infants, 43.2 vs 64.8%; P = .01), whereas placental malaria had an inconsistent effect on maternal and infant seropositivity. In multivariable analyses, maternal HIV infection was associated with reduced infant seropositivity (A(H1N1)pdm09: adjusted odds ratio [aOR], 0.34; 95% confidence interval [CI], 0.15-0.79; A(H3N2): aOR, 0.43; 95% CI, 0.21-0.89). Transplacental transfer was not impaired by maternal HIV or placental malaria. Conclusions: Maternal HIV infection influenced maternal antibody response to influenza A virus infection, and thereby antibody levels in newborns, but did not affect transplacental antibody transfer.

      5. Conditions and evidence continue to evolve related to the prediction of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus (iVDPV) excreters, which affect assumptions related to forecasting risks and evaluating potential risk management options. Multiple recent reviews provided information about individual iVDPV excreters, but inconsistencies among the reviews raise some challenges. This analysis revisits the available evidence related to iVDPV excreters and provides updated model estimates that can support future risk management decisions. The results suggest that the prevalence of iVDPV excreters remains highly uncertain and variable, but generally confirms the importance of managing the risks associated with iVDPV excreters throughout the polio endgame in the context of successful cessation of all oral poliovirus vaccine use.

      6. Patient and provider perspectives on how trust influences maternal vaccine acceptance among pregnant women in Kenyaexternal icon
        Nganga SW, Otieno NA, Adero M, Ouma D, Chaves SS, Verani JR, Widdowson MA, Wilson A, Bergenfeld I, Andrews C, Fenimore VL, Gonzalez-Casanova I, Frew PM, Omer SB, Malik FA.
        BMC Health Serv Res. 2019 Oct 24;19(1):747.
        BACKGROUND: Pregnant women and newborns are at high risk for infectious diseases. Altered immunity status during pregnancy and challenges fully vaccinating newborns contribute to this medical reality. Maternal immunization is a strategy to protect pregnant women and their newborns. This study aimed to find out how patient-provider relationships affect maternal vaccine uptake, particularly in the context of a lower middle- income country where limited research in this area exists. METHODS: We conducted semi-structured, in-depth narrative interviews of both providers and pregnant women from four sites in Kenya: Siaya, Nairobi, Mombasa, and Marsabit. Interviews were conducted in either English or one of the local regional languages. RESULTS: We found that patient trust in health care providers (HCPs) is integral to vaccine acceptance among pregnant women in Kenya. The HCP-patient relationship is a fiduciary one, whereby the patients’ trusts is primarily rooted in the provider’s social position as a person who is highly educated in matters of health. Furthermore, patient health education and provider attitudes are crucial for reinstating and fostering that trust, especially in cases where trust was impeded by rumors, community myths and misperceptions, and religious and cultural factors. CONCLUSION: Patient trust in providers is a strong facilitator contributing to vaccine acceptance among pregnant women in Kenya. To maintain and increase immunization trust, providers have a critical role in cultivating a positive environment that allows for favorable interactions and patient health education. This includes educating providers on maternal immunizations and enhancing knowledge of effective risk communication tactics in clinical encounters.

      7. Global routine vaccination coverage, 2018external icon
        Peck M, Gacic-Dobo M, Diallo MS, Nedelec Y, Sodha SS, Wallace AS.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 25;68(42):937-942.
        Endorsed by the World Health Assembly in 2012, the Global Vaccine Action Plan 2011-2020 (GVAP) (1) calls on all countries to reach >/=90% national coverage with all vaccines in the country’s national immunization schedule by 2020. Building on previous analyses (2) and using the World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) global vaccination coverage estimates as of 2018, this report presents global, regional, and national vaccination coverage estimates and trends, including vaccination dropout rates. According to these estimates, global coverage with the first dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP1) remained relatively unchanged from 2010 (89%) to 2018 (90%). Global coverage with the third DTP dose (DTP3) followed a similar global trend to that of DTP1, remaining relatively consistent from 2010 (84%) to 2018 (86%) (3). Globally, 19.4 million children (14%) were not fully vaccinated in 2018, and among them, 13.5 million (70%) did not receive any DTP doses. Overall, dropout rates from DTP1 to DTP3 decreased globally from 6% in 2010 to 4% in 2018. Global coverage with the first dose of measles-containing vaccine (MCV1) remained between 84% and 86% during 2010-2018. Among countries that offer a second MCV dose (MCV2) during the second year of life, coverage increased from 19% in 2007 to 54% in 2018; among countries offering MCV2 to older age groups (children aged 3-14 years), coverage also increased, from 36% in 2007 to 69% in 2018 (3). Globally, the estimated difference in coverage with MCV1 and MCV2 in 2018 was 17%. However, among new and underused vaccines, global coverage increased from 2007 to 2018 for completed series of rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b vaccine (Hib), and hepatitis B vaccine (HepB). To reach global vaccination coverage goals for vaccines recommended during childhood, adolescence, and adulthood, tailored strategies that address local determinants for incomplete vaccination are needed, including targeting hard-to-reach and hard-to-vaccinate populations.

      8. Tuberculosis vaccine development: Progress in clinical evaluationexternal icon
        Sable SB, Posey JE, Scriba TJ.
        Clin Microbiol Rev. 2019 Dec 18;33(1).
        Tuberculosis (TB) is the leading killer among all infectious diseases worldwide despite extensive use of the Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine. A safer and more effective vaccine than BCG is urgently required. More than a dozen TB vaccine candidates are under active evaluation in clinical trials aimed to prevent infection, disease, and recurrence. After decades of extensive research, renewed promise of an effective vaccine against this ancient airborne disease has recently emerged. In two innovative phase 2b vaccine clinical trials, one for the prevention of Mycobacterium tuberculosis infection in healthy adolescents and another for the prevention of TB disease in M. tuberculosis-infected adults, efficacy signals were observed. These breakthroughs, based on the greatly expanded knowledge of the M. tuberculosis infection spectrum, immunology of TB, and vaccine platforms, have reinvigorated the TB vaccine field. Here, we review our current understanding of natural immunity to TB, limitations in BCG immunity that are guiding vaccinologists to design novel TB vaccine candidates and concepts, and the desired attributes of a modern TB vaccine. We provide an overview of the progress of TB vaccine candidates in clinical evaluation, perspectives on the challenges faced by current vaccine concepts, and potential avenues to build on recent successes and accelerate the TB vaccine research-and-development trajectory.

      9. Disparities in HPV vaccination coverage by metropolitan statistical area (MSA) status were observed in the 2016 and 2017 National Immunization Survey – Teen (NIS-Teen). In 2017, HPV vaccination initiation (>/=1dose) coverage was 11 percentage points lower for adolescents living in non-MSAs (mostly rural areas) and 7 percentage points lower among those living in MSA, non-principal cities (suburban areas) compared to those living in MSA, principal cities (mostly urban areas). In order to understand how this disparity has changed over time, we examined trends in HPV vaccine initiation by MSA status from 2013 to 2017. Weighted linear regression by survey year was used to estimate annual percentage point changes in HPV vaccination initiation. The five-year average annual percentage point increases in HPV vaccination initiation coverage were 5.2 in mostly urban areas, 4.9 for suburban areas, and 5.2 for mostly rural areas. Despite increases in each MSA area, coverage in mostly rural areas was consistently and significantly lower than coverage in mostly urban areas. Coverage was significantly lower among teens living in mostly rural areas regardless of poverty status, sex, and race/ethnicity except among black, non-Hispanic adolescents. There was no significant change in the magnitude of the disparity between mostly urban areas and mostly rural areas over time (p = .98). A better understanding of the facilitators and barriers to HPV vaccination in mostly rural areas is needed to identify and implement targeted strategies to improve HPV vaccination coverage and reduce these disparities.

    • Injury and Violence
      1. US Centers for Disease Control and Prevention’s HEADS UP branding and evaluation processexternal icon
        Waltzman D, Hoffman R, Donnell Z, Bell E, Sarmiento K.
        Health Educ J. 2019 .
        Background: For 15 years, the US Centers for Disease Control and Prevention’s (CDC) HEADS UP education campaign has focused on increasing awareness of concussion among children to reduce adverse outcomes from this injury. Objective: To keep pace with the rapid expansion in media coverage, research, state laws and education efforts on concussion, the CDC embarked on a comprehensive evaluation effort to assess the campaign?s brand. Method: The CDC conducted a multi-step process to evaluate HEADS UP. This included surveying partner organisations and focus groups targeting key audiences. Results: The analysis demonstrated that most (70%) partner organisations have used the materials for 4 years or longer, and more than half (51%) found the materials very useful or extremely useful. Focus groups with the campaign’s target audiences yielded insights and opportunities to refresh the CDC HEADS UP brand. The need for more compelling images, prevention facts and use of eye-catching colours was signalled by all the campaign’s target audiences. Updates focused on the use of data visualisation, more emotionally compelling images and more engaging colours. The CDC also created a new tagline to focus on concussion prevention that encourages children and young people to think about protecting their brains from concussion so that they can have a safer future. Conclusion: This paper describes the process used to update the branding of an educational health promotion campaign in order to meet the needs of key audiences. Findings can help others working to keep their educational campaigns relevant and aligned with expanding and changing public health problems.

    • Laboratory Sciences
      1. A guide for the use of the ferret model for influenza virus infectionexternal icon
        Belser JA, Eckert AM, Huynh T, Gary JM, Ritter JM, Tumpey TM, Maines TR.
        Am J Pathol. 2019 Oct 22.
        As influenza viruses continue to jump species barriers to cause human infection, assessments of disease severity and viral replication kinetics in vivo provide crucial information for public health professionals. The ferret model is a valuable resource for evaluating influenza virus pathogenicity; thus, understanding the most effective sample collection and usage techniques, as well as the full spectrum of attainable data following experimental inoculation in this species, is paramount. This is especially true for scheduled necropsy of virus-infected ferrets, a standard component in evaluation of influenza virus pathogenicity, as necropsy findings can provide important information regarding disease severity and pathogenicity that is not otherwise available from the live animal. In this review, we describe the range of influenza viruses assessed in ferrets, the measures of experimental disease severity in this model, and optimal sample collection during necropsy of virus-infected ferrets. Collectively, this information is critical for assessing systemic involvement following influenza virus infection in mammals.

      2. Inhalation of Stachybotrys chartarum fragments induces pulmonary arterial remodelingexternal icon
        Croston TL, Lemons AR, Barnes MA, Goldsmith WT, Orandle MS, Nayak AP, Germolec DR, Green BJ, Beezhold DH.
        Am J Respir Cell Mol Biol. 2019 Oct 31.
        Stachybotrys chartarum is a fungal contaminant within the built environment and a respiratory health concern in the United States. The objective of this study was to characterize the mechanisms influencing pulmonary immune responses to repeatedly inhaled S. chartarum. Groups of B6C3F1/N mice repeatedly inhaled viable trichothecene-producing S. chartarum conidia (Strain A or Strain B), heat-inactivated conidia, or HEPA-filtered air twice a week for 4 and 13 weeks. Strain A was found to produce higher amounts of respirable fragments compared to Strain B. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected at 24 and 48 hours following final exposure and processed for histology, flow cytometry, RNA, and proteomic analyses. At 4 weeks post-exposure, a Th2-mediated response was observed. After 13 weeks, a mixed T-cell response was observed following exposure to Strain A, compared to a Th2-mediated response following Strain B exposure. Following exposure, both strains induced pulmonary arterial remodeling at 13 weeks; however, Strain A-exposed mice progressed more quickly compared to Strain B-exposed mice. BALF was composed primarily of eosinophils, neutrophils, and macrophages. Both the immune response and the observed pulmonary arterial remodeling were supported by specific cellular, molecular, and proteomic profiles. The immunopathological responses occurred earlier in mice exposed to high fragment-producing Strain A. The rather striking induction of pulmonary remodeling by S. chartarum appears to be related to the presence of fungal fragments during exposure.

      3. Manufacturers of in vitro diagnostic medical devices, clinical laboratories, research laboratories and calibration laboratories require commutable reference materials that can be used in the calibration hierarchies of medical laboratory measurement procedures used for human specimens to establish metrological traceability to higher order reference systems. Commutable materials are also useful in external quality assessment surveys. In order to achieve these goals, matrix-based reference materials with long-term stability, appropriate measurand concentrations and commutability with individual human specimens are required. The Clinical and Laboratory Standards Institute (CLSI) guideline C37-A (now archived) provided guidance to prepare commutable pooled serum reference materials for use in the calibration hierarchies of cholesterol measurement procedures. Experience using the C37-A guideline has identified a number of technical enhancements as well as applications to measurands other than cholesterol. This experience is incorporated into this updated protocol to ensure the procedure will continue to meet the needs of the medical laboratory. The updated protocol describes a procedure for preparing frozen human serum units or pools with minimal matrix alterations that are likely to be commutable with individual human serum samples. The protocol provides step-by-step guidance for the planning phase, collection of individual serum units, processing the units, qualifying the units for use in a pool and frozen storage of aliquots of pooled sera to manufacture frozen serum pools. Guidance on how to perform quality control of the final product and suggestions on documentation are also provided.

      4. Proficiency testing of viral marker screening in African blood centers – seven African countries, 2017external icon
        Drammeh B, Laperche S, Hilton JF, Kaidarova Z, Ozeryansky L, De A, Kalou M, Benech I, Parekh B, Murphy EL.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 25;68(42):947-952.
        A 2014 report evaluating accuracy of serologic testing for transfusion-transmissible viruses at African blood center laboratories found sensitivities of 92%, 87%, and 90% for detecting infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), respectively (1). Following substantial investments in national blood transfusion service (NBTS) laboratories, in 2017 investigators tested proficiency at 84 blood center laboratories (29 NBTS and 55 non-NBTS) in seven African countries. A blinded panel of 25 plasma samples was shipped to each participating laboratory for testing with their usual protocols based on rapid diagnostic tests (RDTs) (2) and third and fourth generation enzyme immunoassays (EIA-3 and EIA-4). Sensitivity and specificity were estimated using separate regression models that clustered assays by laboratory and adjusted for assay type and NBTS laboratory status. Mean specificities were >/=95% for all three viruses; however, mean sensitivities were 97% for HIV-positive, 76% for HBV-positive, and 80% for HCV-positive samples. Testing sensitivities for all viruses were high when EIA-3 assays were used (>/=97%). Lower sensitivities for HBV-positive samples and HCV-positive samples were associated with assay types other than EIA-3, used primarily by non-NBTS laboratories. Proficiency for HIV testing has improved following international investments, but proficiency remains suboptimal for HBV and HCV testing. In sub-Saharan African blood centers, the quality of rapid tests used for HBV and HCV screening needs to be improved or their use discouraged in favor of EIA-3 tests.

      5. Changes in the receptor-binding properties of H3N2 viruses during long-term circulation in humansexternal icon
        Gambaryan AS, Balish A, Klimov AI, Tuzikov AB, Chinarev AA, Pazynina GV, Bovin NV.
        Biochemistry (Moscow). 2019 ;84(10):1177-1185.
        It was previously shown that hemagglutinin residues Thrl55, Glul58, and Ser228 are crucial for the recognition of Neu5Gc. In this study, we demonstrated that the ability to bind the Neu5Gc-terminated receptor is related to the amino acid 145: viruses of years 1972-1999 with Lysl45 bind to the receptor, whereas viruses with Asnl 45 do not. Sporadic appearance and disappearance of the ability to bind Neu5Gc oligosaccharides and the absence of Neu5Gc in the composition of human glycoconjugates indicate the non-adaptive nature of this ability. It was previously shown that unlike H1N1 viruses, H3N2 viruses of years 1968-1989 did not distinguish between Neu5Acalpha2-6Galbeta1-4Glc (6’SL) and Neu5Acalpha2-6Galbeta1-4GlcNAc (6’SLN). H3N2 viruses isolated after 1993 have acquired the ability to distinguish between 6?SL and 6?SLN, similarly to H1N1 viruses. We found that the affinity for 6’SLN has gradually increased from 1992 to 2003. After 2003, the viruses lost the ability to bind a number of sialosides, including 6’SL, that were good receptors for earlier H3N2 viruses, and retained high affinity for 6’SLN only, which correlated with the acquisition of new glycosylation sites at positions 122, 133, and 144, as well as Glul90Asp and Gly225Asp substitutions, in hemagglutinin. These substitutions are also responsible for the receptor-binding phenotype of human H1N1 viruses. We conclude that the convergent evolution of the receptor specificity of the H1N1 and H3N2 viruses indicates that 6’SLN is the optimal natural human receptor for influenza viruses.

      6. Flavorings-related lung disease: A brief review and new mechanistic dataexternal icon
        Hubbs AF, Kreiss K, Cummings KJ, Fluharty KL, O’Connell R, Cole A, Dodd TM, Clingerman SM, Flesher JR, Lee R, Pagel S, Battelli LA, Cumpston A, Jackson M, Kashon M, Orandle MS, Fedan JS, Sriram K.
        Toxicol Pathol. 2019 Oct 23:192623319879906.
        Flavorings-related lung disease is a potentially disabling and sometimes fatal lung disease of workers making or using flavorings. First identified almost 20 years ago in microwave popcorn workers exposed to butter-flavoring vapors, flavorings-related lung disease remains a concern today. In some cases, workers develop bronchiolitis obliterans, a severe form of fixed airways disease. Affected workers have been reported in microwave popcorn, flavorings, and coffee production workplaces. Volatile alpha-dicarbonyl compounds, particularly diacetyl (2,3-butanedione) and 2,3-pentanedione, are implicated in the etiology. Published studies on diacetyl and 2,3-pentanedione document their ability to cause airway epithelial necrosis, damage biological molecules, and perturb protein homeostasis. With chronic exposure in rats, they produce airway fibrosis resembling bronchiolitis obliterans. To add to this knowledge, we recently evaluated airway toxicity of the 3-carbon alpha-dicarbonyl compound, methylglyoxal. Methylglyoxal inhalation causes epithelial necrosis at even lower concentrations than diacetyl. In addition, we investigated airway toxicity of mixtures of diacetyl, acetoin, and acetic acid, common volatiles in butter flavoring. At ratios comparable to workplace scenarios, the mixtures or diacetyl alone, but not acetic acid or acetoin, cause airway epithelial necrosis. These new findings add to existing data to implicate alpha-dicarbonyl compounds in airway injury and flavorings-related lung disease.

      7. A novel TaqMan assay to detect Rickettsia 364D, the etiologic agent of Pacific Coast tick feverexternal icon
        Karpathy SE, Espinosa A, Yoshimizu MH, Hacker JK, Padgett KA, Paddock CD.
        J Clin Microbiol. 2019 Oct 30.
        Pacific Coast tick fever is a febrile illness associated with the bite of Dermacentor occidentalis and results from an infection due to the intracellular pathogen Rickettsia 364D (also known by the proposed name “Rickettsia philipii”). Current molecular methods for the detection of this pathogen rely on the amplification of a conserved spotted fever group rickettsial gene (ompA) followed by DNA sequencing of the amplicon to identify the species. This work describes the development of a Rickettsia 364D-specific TaqMan assay to simplify and accelerate the detection and identification processes. The assay demonstrated a sensitivity of 1 genomic copy per 4 mul sample and is highly specific for Rickettsia 364D. The utility of this assay for ecological and diagnostic samples was evaluated using single-blinded banked specimens and yielded a clinical sensitivity and specificity of 100%. In conclusion, we describe the development and evaluation of a novel TaqMan real-time PCR assay for the detection and identification of Rickettsia 364D suitable for ecological and diagnostic applications.

      8. Gene-edited vero cells as rotavirus vaccine substratesexternal icon
        Orr-Burks N, Murray J, Wu W, Kirkwood CD, Todd KV, Jones L, Bakre A, Wang H, Jiang B, Tripp RA.
        Vaccine X. 2019 Dec 10;3:100045.
        Background: Rotavirus (RV) is a leading cause of severe gastroenteritis globally and can cause substantial morbidity associated with gastroenteritis in children <5years of age. Orally administered live-attenuated RV vaccines offer protection against disease but vaccination efforts have been hampered by high manufacturing costs and the need to maintain a cold chain. Methods: A subset of Vero cell host genes was identified by siRNA that when knocked down increased RV replication and these anti-viral host genes were individually deleted using CRISPR-Cas9. Results: Fully-sequenced gene knockout Vero cell substrates were assessed for increased RV replication and RV vaccine antigen expression compared to wild type Vero cells. The results showed that RV replication and antigen production were logs higher in Vero cells having an EMX2 gene deletion compared to other Vero cell substrates tested. Conclusions: We used siRNAs to screen for host genes that negatively affected RV replication, then CRISPR-Cas9 gene editing to delete select genes. The gene editing led to the development of enhanced RV vaccine substrates supporting a potential path forward for improving RV vaccine production.

      9. The Biosafety Level 4 Zoonotic Laboratory Network (BSL4ZNet): Report of a workshop on live animal handlingexternal icon
        Pickering BS, Spengler JR, Shadabi E, Dalziel AE, Lautner EA, Silva P.
        Antiviral Res. 2019 Oct 25:104640.
        The Biosafety Level 4 Zoonotic Laboratory Network (BSL4ZNet) was established in 2016, to provide a means of communication and support for the global high-containment laboratory community. Its working groups focus on international response, institutional cooperation and knowledge sharing, scientific excellence and training. In the latter role, BSL4ZNet sponsored its first international workshop in February, 2018, held at the USDA National Centers for Animal Health, Ames, Iowa, USA, focused on necropsy procedures in high-containment laboratories. A second workshop, in November, 2018, was held at the National Microbiology Laboratories (CFIA/PHAC) in Winnipeg, Canada, and focused on decontamination. A third workshop, held at the Australian Animal Health Laboratory in Geelong, Australia, in February, 2019, was devoted to handling methods and ethical concerns for live animals in high-containment laboratories. The third workshop brought together 12 laboratorians from seven partner organizations in Australia, Canada, Germany, the United Kingdom and the United States. It included both discussion-based and hands-on training sessions on animal welfare, animal models, site-specific infrastructure constraints, health monitoring and humane endpoints, sampling procedures, and carcass disposal. This report summarizes the inception, development, and structure of the BSL4ZNet, and highlights the aims and results of the Geelong workshop.

      10. A 21-day sub-acute, whole-body inhalation exposure to printer-emitted engineered nanoparticles in rats: Exploring pulmonary and systemic effectsexternal icon
        Pirela SV, Bhattacharya K, Wang Y, Zhang Y, Wang G, Christophi CA, Godleski J, Thomas T, Qian Y, Orandle MS, Sisler JD, Bello D, Castranova V, Demokritou P.
        NanoImpact. 2019 ;15.
        Engineered nanomaterials (ENMs) used in toners to improve their performance are released in the air during laser printer use. ENMs play an important catalytic role in the breakdown of the toner polymer and subsequent rearrangement of organic compounds as well as in the formation of reactive oxygen species (ROS). Cellular, animal, and human occupational exposure studies have shown that such printer-emitted particles (PEPs) induce inflammation, systemic oxidative stress, and genotoxicity, as well as, increase frequency of coughing, wheezing, and upper airway symptoms, raising concerns about their long-term impact on human health. No safety thresholds or regulatory guidelines currently exist for PEPs. In this study, Sprague-Dawley rats were exposed (by whole-body inhalation) to PEPs 5 h/day for up to 21 days using an exposure platform previously developed by the authors. The control group comprised of an equal number of rats exposed to high-efficiency particulate air (HEPA) filtered air. The PEPs had a mean particle diameter of approximately 45 nm, and a total particle number concentration ranging from 4 to 21 x 105 #/cm3. The maximum total volatile organic compound (tVOCs) concentration was 363.2 +/- 162 ppb. The Multiple-Path Particle Dosimetry Model (MPPD) estimated the deposited fraction of PEPs to be around 7, 6 and 21% in the head, tracheobronchial (TB) and alveolar regions, respectively. Analysis of biochemical markers in the nasal and bronchoalveolar lavage fluids (NLF, BALF) of PEPs-exposed animals showed only mild oxidative stress and inflammation. No damage was detected in the histological and chemiluminescence analysis of lung and heart tissues of PEPs-exposed animals. Pro- and anti-inflammatory cytokines and chemokines, such as Interleukin (IL) 1beta, IL-12, IL-18, MIP-1alpha, MIP-2, GRO/KC, and Fractalkine were found to be up-/down-regulated in NLF and BALF of the PEPs-exposed animals. Also, serum biomarkers of oxidative stress and inflammation, such as 8-isoprostane, 4-hydroxynonemal, and Leukotriene B4 were elevated in PEPs-exposed animals. In conclusion, following exposure to PEPs, there was modest lung injury and inflammation in the respiratory tract. Specifically, changes in expression of certain cytokines and chemokines, along with serum levels of 8-isoprostane, were the most significant adverse effects reported following exposure to PEPs.

      11. SOX9-ALDH axis determines resistance to chemotherapy in non-small cell lung cancerexternal icon
        Voronkova MA, Rojanasakul LW, Kiratipaiboon C, Rojanasakul Y.
        Mol Cell Biol. 2019 Oct 28.
        Chemotherapy resistance and tumor relapse are the major contributors to low patient survival, and both have been largely attributed to cancer stem-like cells (CSCs) or tumor initiating cells (TICs). Moreover, most conventional therapies are not effective against CSCs, which necessitates the discovery of CSC-specific biomarkers and drug targets. Here, we demonstrated that the embryonic transcription factor SOX9 is an important regulator of acquired chemoresistance in non-small cell lung cancer (NSCLC). Our results show that SOX9 expression is elevated in NSCLC cells after treatment with the chemotherapeutic cisplatin and that overexpression of SOX9 correlates with worse overall survival in lung cancer patients. We further demonstrated that SOX9 knockdown increases cellular sensitivity to cisplatin, whereas its overexpression promotes drug resistance. Moreover, this transcription factor promotes stem-like properties of NSCLC cells and increases their ALDH activity, which was identified as the key mechanism of SOX9-induced chemoresistance. Finally, we showed that ALDH1A1 is a direct transcriptional target of SOX9 based on chromatin immunoprecipitation and luciferase reporter assays. Taken together, our novel findings on the role of SOX9-ALDH axis support the use of this CSC regulator as a prognostic marker of cancer chemoresistance and as a potential drug target for CSC therapy.

      12. In situ imaging of fluorescent Nipah virus respiratory and neurological tissue tropism in the Syrian hamster modelexternal icon
        Welch SR, Scholte FE, Harmon JR, Coleman-McCray JD, Lo MK, Montgomery JM, Nichol ST, Spiropoulou CF, Spengler JR.
        J Infect Dis. 2019 Oct 30.
        Using a recombinant Nipah virus expressing a fluorescent protein (ZsG), we visualized virus tropism in the Syrian hamster model. We found that anatomical localization of fluorescence correlated to clinical signs; signal was primarily visualized in the respiratory tract in animals with acute-onset terminal disease, whereas central nervous system localization was seen in animals that succumbed with delayed disease onset. While polymerase chain reaction (PCR) detection corresponded well to ZsG signal, virus was only isolated from some lung, brain, liver, and kidney samples that were ZsG and/or PCR positive, and only from animals euthanized on or before 15 days post infection.

      13. Novel treatment of a vaccinia virus infection from an occupational needlestick – San Diego, California, 2019external icon
        Whitehouse ER, Rao AK, Yu YC, Yu PA, Griffin M, Gorman S, Angel KA, McDonald EC, Manlutac AL, de Perio MA, McCollum AM, Davidson W, Wilkins K, Ortega E, Satheshkumar PS, Townsend MB, Isakari M, Petersen BW.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 25;68(42):943-946.
        Vaccinia virus (VACV) is an orthopoxvirus used in smallpox vaccines, as a vector for novel cancer treatments, and for experimental vaccine research (1). The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for laboratory workers who handle replication-competent VACV (1). For bioterrorism preparedness, the U.S. government stockpiles tecovirimat, the first Food and Drug Administration-approved antiviral for treatment of smallpox (caused by variola virus and globally eradicated in 1980*(,dagger)) (2). Tecovirimat has activity against other orthopoxviruses and can be administered under a CDC investigational new drug protocol. CDC was notified about an unvaccinated laboratory worker with a needlestick exposure to VACV, who developed a lesion on her left index finger. CDC and partners performed laboratory confirmation, contacted the study sponsor to identify the VACV strain, and provided oversight for the first case of laboratory-acquired VACV treated with tecovirimat plus intravenous vaccinia immunoglobulin (VIGIV). This investigation highlights 1) the misconception among laboratory workers about the virulence of VACV strains; 2) the importance of providing laboratorians with pathogen information and postexposure procedures; and 3) that although tecovirimat can be used to treat VACV infections, its therapeutic benefit remains unclear.

    • Maternal and Child Health
      1. Genome-wide association studies of structural birth defects: A review and commentaryexternal icon
        Lupo PJ, Mitchell LE, Jenkins MM.
        Birth Defects Res. 2019 Oct 25.
        BACKGROUND: While there is strong evidence that genetic risk factors play an important role in the etiologies of structural birth defects, compared to other diseases, there have been relatively few genome-wide association studies (GWAS) of these conditions. We reviewed the current landscape of GWAS conducted for birth defects, noting novel insights, and future directions. METHODS: This article reviews the literature with regard to GWAS of structural birth defects. Key defects included in this review include oral clefts, congenital heart defects (CHDs), biliary atresia, pyloric stenosis, hypospadias, craniosynostosis, and clubfoot. Additionally, other issues related to GWAS are considered, including the assessment of polygenic risk scores and issues related to genetic ancestry, as well as utilizing genome-wide single nucleotide polymorphism array data to evaluate gene-environment interactions and Mendelian randomization. RESULTS: For some birth defects, including oral clefts and CHDs, several novel susceptibility loci have been identified and replicated through GWAS, including 8q24 for oral clefts, DGKK for hypospadias, and 4p16 for CHDs. Relatively common birth defects for which there are currently no published GWAS include neural tube defects, anotia/microtia, anophthalmia/microphthalmia, gastroschisis, and omphalocele. CONCLUSIONS: Overall, GWAS have been successful in identifying several novel susceptibility genes and genomic regions for structural birth defects. These findings have provided new insights into the etiologies of these phenotypes. However, GWAS have been underutilized for understanding the genetic etiologies of several birth defects.

    • Medicine
      1. OBJECTIVE: To describe hospitalizations involving an intensive care unit (ICU) admission among patients aged 65 years and older within New York City (NYC) hospitals during 2000-2014. DESIGN: Observational study using an all-payer hospital discharge dataset. SETTING: The setting was in NYC hospitals. PATIENTS: Patients aged 65 years and older admitted to an ICU within a NYC hospital during 2000-2014. INTERVENTIONS: No interventions were carried out. MEASUREMENTS AND MAIN RESULTS: We calculated the mean annual number of hospitalizations involving an ICU admission. We also examined characteristics of hospitalizations, including the occurrence of in-hospital death and principal diagnosis. There were 5,338,577 hospitalizations of patients aged >/=65 years within NYC hospitals during 2000-2014, of which 765,084 (14.3%) involved an ICU admission. The mean annual number of hospitalizations involving an ICU admission for this age group decreased from 57,938 during 2000-2002 to 45,785 during 2012-2014. The proportion of hospitalizations involving an ICU admission in which in-hospital death occurred decreased from 15.9% during 2000-2002 to 14.5% during 2012-2014. During 2000-2002, 11.6% of hospitalizations involving an ICU admission listed an “infectious” principal diagnosis, increasing to 20.7% during 2012-2014. Listing of a “cardiovascular” principal diagnosis decreased from 46.4% to 33.4% between these time periods. “Infectious” principal diagnoses accounted for 31.0% of all hospitalizations involving an ICU admission in which in-hospital death occurred during the entire study period, while “cardiovascular” principal diagnoses accounted for 21.3%. CONCLUSIONS: This investigation provides a clearer understanding of ICU utilization among patients aged 65 years and older in NYC. Ongoing monitoring is warranted given projections that the proportion of New Yorkers aged 65 years and older will increase in coming years. In particular, in light of the observed increase of infectious principal diagnoses during the study period, further investigation is needed into the role of infectious disease in causing critical illness in NYC.

    • Nutritional Sciences
      1. BACKGROUND: The US Dietary Guidelines for Americans provide dietary recommendations for individuals aged >/=2 y and metrics exist to assess alignment. Nonfederal feeding recommendations exist for children <2 y, but limited metrics and assessment of dietary quality are available. OBJECTIVE: We aimed to assess dietary quality of children aged 6 mo-4 y using a modified Diet Quality Index Score (DQIS). METHODS: NHANES 2011-2016 dietary data were used to estimate the dietary quality of children 6 mo-4 y old using a modified DQIS. Differences in mean modified DQIS by demographics were assessed using linear regression. RESULTS: Mean modified DQIS +/- SE was 22.4 +/- 0.23 out of 45 possible points (50%) for children 6 mo-4 y of age on a given day. Modified DQIS scores on a given day decreased with age (27.7 +/- 0.27 for 6- to 11-mo-olds, 23.9 +/- 0.31 for 1-y-olds, 21.4 +/- 0.26 for 2- to 3-y-olds, and 20.6 +/- 0.49 for 4-y-olds; P < 0.0001 for trend). Children 6-11 mo old had 16% higher overall modified DQIS scores than 1-y-olds (P < 0.0001) and higher modified DQIS subcomponent scores for refined grains and protein, indicating higher age-appropriate intakes (P < 0.05). Similarly, children 6-11 mo old also had higher modified DQIS subcomponent scores, indicating no or limited intake, for 100% fruit juice, sugar-sweetened beverages, other added sugars, and salty snacks (P < 0.02). CONCLUSIONS: Dietary quality declines with age and may begin as early as 1 y. The modified DQIS tool could help assess the dietary quality of young children. This may be important when identifying programmatic and policy efforts aimed at establishing and maintaining healthy dietary patterns beginning at an early age.

    • Occupational Safety and Health
      1. Noise exposures and perceptions of hearing conservation programs among wildland firefightersexternal icon
        Broyles G, Kardous CA, Shaw PB, Krieg EF.
        J Occup Environ Hyg. 2019 Oct 28:1-10.
        Wildland firefighters are exposed to numerous noise sources that may be hazardous to their hearing. This study examined the noise exposure profiles for 264 wildland firefighters across 15 job categories. All 264 firefighters completed questionnaires to assess their use of hearing protection devices, enrollment in hearing conservation programs, and their overall perception of their noise exposure. Roughly 54% of firefighters’ noise exposures exceeded the National Institute for Occupational Safety and Health recommended exposure limit of 85 decibels, A-weighted, over 8 hr, and 32% exceeded the Occupational Safety and Health Administration permissible exposure limit of 90 decibels, A-weighted, over 8 hr. Questionnaire results indicated good agreement between noise exposures and firefighters’ perceptions of the noise hazard. Approximately 65% reported that they used some form of hearing protection; however, only 19% reported receiving any proper training regarding the use of hearing protection devices, with the majority of those firefighters relying on earplugs, including electronic and level-dependent earplugs, over earmuffs or other forms of hearing protectors. The results also suggest that improved communication and situational awareness play a greater role in the consistent use of hearing protection devices than other factors such as risk of developing noise-induced hearing loss. The study highlighted the challenges facing wildland firefighters and their management and the need for a comprehensive wildland fire agencies’ hearing conservation program especially for firefighters who were exempt based on their occupational designations.

      2. Carbon monoxide exposures among U.S. wildland firefighters by work, fire, and environmental characteristics and conditionsexternal icon
        Henn SA, Butler C, Li J, Sussell A, Hale C, Broyles G, Reinhardt T.
        J Occup Environ Hyg. 2019 Oct 28:1-11.
        Carbon monoxide (CO) exposure levels encountered by wildland firefighters (WLFs) throughout their work shift can change considerably within a few minutes due to the varied tasks that are performed and the changing environmental and fire conditions encountered throughout the day. In a U.S. Forest Service study during the 2009-2012 fire seasons, WLFs from 57 different fires across the U.S. were monitored for CO using CO data-logging detectors while an observer recorded worker tasks, fire characteristics, and environmental conditions at scheduled intervals. Exposures to CO for 735 WLF’s work shifts were analyzed to assess the effect of variations among work tasks, fire characteristics, and environmental conditions. Geometric mean full shift time-weighted averages were low at 2.4 parts per million (ppm) and average length of work shift was 11 hr and 15 min. The task with the highest mean CO exposure was sawyer/swamper at 6.8 ppm; workers performing that task had an estimated 9 times higher odds of a having a 1-min CO measurement exceeding 25 ppm than the referent pump task (OR = 8.89, 95% CI = 1.97, 40.24). After adjusting CO exposure limits for shift length, elevation, and work level, 2% and 4% of the WLF’s work shifts exceeded the National Institute for Occupational Safety and Health’s recommended exposure level and the American Conference of Governmental Industrial Hygienist’s threshold limit value, respectively. In regression modeling, variables that were significantly associated with elevated levels of CO exposure included: task, fuel model, wind orientation, crew type, relative humidity, type of attack, and wind speed. In the absence of instruments such as CO detectors that can determine and alert WLFs to elevated CO levels, recognition of the conditions that lead to elevated levels of CO exposure can assist WLFs to effectively use administrative controls, such as work rotations, to minimize exposures.

      3. [No abstract]

    • Occupational Safety and Health – Mining
      1. The sudden collapse of approximately 3?Ha of room-and-pillar workings at a limestone mine in southwestern Pennsylvania in 2015 resulted in an air blast that injured three mine workers. Subsequent investigations showed that an area encompassing 35 pillars had collapsed. The pillars were 9-10?m wide and up to 18?m high. A notable geologic feature is the through-going joints that dip at 50-80 degrees and can extend from the roof to the floor of the pillars. These structures are thought to have weakened the pillars well below the strength that is predicted by empirical equations for hard-rock pillar design. This paper presents the relevant geotechnical data related to the collapsed area and numerical model results that were used to estimate the pillar loading underneath the variable topography, and compares the pillar loads to some established hard-rock pillar strength equations. The outcome is also compared to a strength equation that was developed specifically for limestone mines in which the negative impact of large angular discontinuities is explicitly accounted for. The results show that established hard-rock pillar strength equations do not adequately account for the impact of large through-going discontinuities on the strength of slender pillars. The equations would have significantly overestimated the strength of the pillars at the case study mine. The critical state of the workings would have been predicted correctly by the limestone pillar strength equation that accounts for the large discontinuities.

    • Parasitic Diseases
      1. Pgp3 seroprevalence and associations with active trachoma and ocular Chlamydia trachomatis infection in Malawi: cross-sectional surveys in six evaluation unitsexternal icon
        Burr SE, Hart J, Samikwa L, Chaima D, Cooley G, Martin D, Masika M, Solomon AW, Bailey RL, Kalua K.
        PLoS Negl Trop Dis. 2019 Oct;13(10):e0007749.
        BACKGROUND: Following one to five years of antibiotic mass drug administration (MDA) for the elimination of trachoma as a public health problem, programmes must conduct impact surveys to inform decisions on whether MDA is still needed. These decisions are currently based on the prevalence of trachomatous inflammation-follicular (TF), which, after MDA, correlates poorly with prevalence of ocular Chlamydia trachomatis infection. METHODOLOGY/PRINCIPAL FINDINGS: Impact surveys in six evaluation units (EUs) of Malawi were used as a platform to explore associations between the prevalence of TF, ocular C. trachomatis infection and anti-Pgp3 antibodies one year after the third annual round of MDA. Participants were examined for trachoma using the World Health Organization simplified grading system. Ocular swabs and dried blood spots (DBS) were collected from children aged 1-9 years. Swabs were tested for C. trachomatis DNA using GeneXpert. DBS were assayed for anti-Pgp3 antibodies using ELISA. EU-level prevalence of TF in children aged 1-9 years ranged from 4.7% (95% CI 3.4-6.3) to 7.2% (95% CI 5.8-8.9). Prevalence of C. trachomatis infection in children ranged from 0.1% (95% CI 0.0-0.6) to 0.7% (95% CI 0.3-1.3) while Pgp3 seroprevalence ranged from 6.9% (95% CI 5.4-8.6) to 12.0% (95% CI 10.1-14.0) and increased with age. CONCLUSIONS/SIGNIFICANCE: Based on current global policy, the prevalence of TF indicates that a further year of antibiotic MDA is warranted in four of six EUs yet the very low levels of infection cast doubt on the universal applicability of TF-based cut-offs for antibiotic MDA. Pgp3 seroprevalence was similar to that reported following MDA in other settings that have reached the elimination target however the predictive value of any particular level of seropositivity with respect to risk of subsequent infection recrudescence is, as yet, unknown.

      2. Progress toward global eradication of dracunculiasis – January 2018-June 2019external icon
        Hopkins DR, Weiss AJ, Roy SL, Zingeser J, Guagliardo SA.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 1;68(43):979-984.
        Dracunculiasis (also known as Guinea worm disease) is caused by the parasite Dracunculus medinensis and is acquired by drinking water containing copepods (water fleas) infected with D. medinensis larvae. The worm typically emerges through the skin on a lower limb approximately 1 year after infection, resulting in pain and disability (1). There is no vaccine or medicine to treat the disease; eradication efforts rely on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, chemical treatment of unsafe water with temephos (an organophosphate larvicide to kill copepods), and provision of safe drinking water (1,2). In 1986, with an estimated 3.5 million cases(dagger) occurring each year in 20 African and Asian countries( section sign) (3), the World Health Assembly called for dracunculiasis elimination (4). The global Guinea Worm Eradication Program (GWEP), led by The Carter Center and supported by the World Health Organization (WHO), CDC, the United Nations Children’s Fund, and other partners, began assisting ministries of health in countries with dracunculiasis. This report, based on updated health ministry data, describes progress to eradicate dracunculiasis during January 2018-June 2019 and updates previous reports (2,4,5). With only five countries currently affected by dracunculiasis (Angola, Chad, Ethiopia, Mali, and South Sudan), achievement of eradication is within reach, but it is challenged by civil unrest, insecurity, and lingering epidemiologic and zoologic questions.

    • Substance Use and Abuse
      1. In November 2018, US Food and Drug Administration announced its intent to prohibit menthol in combustible tobacco products, prohibit flavored cigars, and prohibit flavored e-cigarettes unless they are sold in age-restricted, in-person locations. This study assessed adult attitudes toward prohibiting flavors in all tobacco products, including e-cigarettes. Data were from the 2016 Summer Styles survey of 4203 US adults aged >/=18years. Respondents were asked whether they favored or opposed prohibiting flavors (e.g., menthol, spicy, sweet, or fruity flavor) in all tobacco products. Prevalence and correlates of favorability were assessed using weighted percentages and adjusted prevalence ratios (aPR) respectively. Assessed correlates were: sex, age, race/ethnicity, income, US Census region, marital status, children <18years living in the home, perceptions toward e-cigarette advertising, and current (past 30-day) tobacco product use. Overall, 47.3% of adults reported favorable attitudes toward prohibiting flavors in all tobacco products. By tobacco product use status, prevalence was 52.0%, 48.4%, and 34.8% among never, former, and current users, respectively (p<.05). Among current tobacco product users, favorability was more likely among adults who believed e-cigarette ads exposure makes youth think about smoking (aPR=1.82; 95% CI=1.20-2.78) and those with any children aged <18years in their household (aPR=1.38; 95% CI=1.05-1.82). To conclude, nearly half of adults favored prohibiting flavors in all tobacco products, including e-cigarettes. Prohibiting flavors in tobacco products could benefit public health by reducing both individual-level and population-level harms, including tobacco use initiation especially among youth.

      2. OBJECTIVE: To measure the association of raising the minimum legal age of tobacco sales to 21 years (T21) statewide with monthly sales of cigarette packs in California and Hawaii, the first two states to implement T21 statewide. METHODS: State monthly cigarette tax revenues from state departments of taxation were analysed for 11 states from January 2014 through December 2018 (n=660). Monthly cigarette packs sold were constructed using cigarette tax revenue and cigarette tax rate in each state. A difference-in-differences regression method was used to estimate the association of statewide T21 policies with monthly cigarette packs sold in California and Hawaii, separately, compared to the western states that did not implement such policies. Both models were controlled for year-month fixed effects, cigarette tax rates, smoke-free air laws, Medicaid coverage of smoking cessation, minimum legal sales ages for e-cigarettes and state marijuana laws, in addition to state demographic characteristics (sex, age, education, race/ethnicity and population size). FINDINGS: Implementation of T21 statewide was associated with a reduction of 9.41 (95% CI=-15.52 to -3.30) million monthly packs sold in California and 0.57 (95% CI=-0.83 to -0.30) million monthly packs sold in Hawaii, compared to regional states. These translate to a reduction of 13.1%-18.2%, respectively, in monthly packs sold relative to mean values before the implementation of T21. CONCLUSIONS: Raising the minimum legal age for tobacco sales to 21 years could reduce cigarette sales as part of a comprehensive tobacco control strategy that complements and builds on proven approaches to achieve this goal.

      3. Obstetrician-gynecologists’ practices and attitudes on substance use screening during pregnancyexternal icon
        Ko JY, Tong VT, Haight SC, Terplan M, Stark L, Snead C, Schulkin J.
        J Perinatol. 2019 Oct 30.
        OBJECTIVE: To describe obstetrician-gynecologists’ practices and attitudes related to substance use screening in pregnant patients. STUDY DESIGN: A 2017 cross-sectional survey assessed US obstetrician-gynecologists’ (n = 462; response rate = 34%) practices (substance use screening frequency and methods) and attitudes (practice priority of screening, confidence in treating, and responsibility statements). Chi-squared tests and adjusted modified Poisson regression were used to estimate associations between practices and attitudes. RESULTS: Of 353 respondents with screening information, 79% frequently screen for substance use and 11% used a validated instrument. Confidence was the highest for treating pregnant patients using tobacco (81%). Respondents whose practices make it a high priority to screen for all substances were 1.2 times as likely to frequently screen as their counterparts (95% CI: 1.1-1.3). CONCLUSIONS: Four out of five obstetricians-gynecologists reported a high frequency of substance use screening in pregnant patients. Findings highlight the importance of increasing priority of substance use screening by obstetrician-gynecologists.

      4. E-cigarette use, or vaping, practices and characteristics among persons with associated lung injury – Utah, April-October 2019external icon
        Lewis N, McCaffrey K, Sage K, Cheng CJ, Green J, Goldstein L, Campbell H, Ferrell D, Malan N, LaCross N, Maldonado A, Board A, Hanchey A, Harris D, Callahan S, Aberegg S, Risk I, Willardson S, Carter A, Nakashima A, Duncan J, Burnett C, Atkinson-Dunn R, Dunn A.
        MMWR Morb Mortal Wkly Rep. 2019 Oct 25;68(42):953-956.
        In August 2019, the Utah Department of Health (UDOH) received reports from health care providers of several cases of lung injury in persons who reported use of electronic cigarette (e-cigarette), or vaping, products (1,2). To describe the characteristics of medical care, potentially related conditions, and exposures among 83 patients in Utah, detailed medical abstractions were completed for 79 (95%) patients. Among patients receiving chart abstractions, 70 (89%) were hospitalized, 39 (49%) required breathing assistance, and many reported preexisting respiratory and mental health conditions. Interviews were conducted by telephone or in person with 53 (64%) patients or their proxies, and product samples from eight (15%) of the interviewed patients or proxies were tested. Among 53 interviewed patients, all of whom reported using e-cigarette, or vaping, products within 3 months of acute lung injury, 49 (92%) reported using any products containing tetrohydrocannabinol (THC), the principal psychoactive component of cannabis; 35 (66%) reported using any nicotine-containing products, and 32 (60%) reported using both. As reported in Wisconsin and Illinois (1), most THC-containing products were acquired from informal sources such as friends or illicit in-person and online dealers. THC-containing products were most commonly used one to five times per day, whereas nicotine-containing products were most commonly used >25 times per day. Product sample testing at the Utah Public Health Laboratory (UPHL) showed evidence of vitamin E acetate in 17 of 20 (89%) THC-containing cartridges, which were provided by six of 53 interviewed patients. The cause or causes of this outbreak is currently unknown (2); however, the predominant use among patients of e-cigarette, or vaping, products with prefilled THC-containing cartridges suggests that the substances in these products or the way in which they are heated and aerosolized play an important role in the outbreak. At present, persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific cause or causes of lung injury are not yet known and while the investigation continues, persons should consider refraining from use of all e-cigarette, or vaping, products.

      5. Among the 47,600 opioid-involved overdose deaths in the United States in 2017, 59.8% (28,466) involved synthetic opioids (1). Since 2013, synthetic opioids, particularly illicitly manufactured fentanyl (IMF), including fentanyl analogs, have been fueling the U.S. overdose epidemic (1,2). Although initially mixed with heroin, IMF is increasingly being found in supplies of cocaine, methamphetamine, and counterfeit prescription pills, which increases the number of populations at risk for an opioid-involved overdose (3,4). With the proliferation of IMF, opioid-involved overdose deaths have increased among minority populations including non-Hispanic blacks (blacks) and Hispanics, groups that have historically had low opioid-involved overdose death rates (5). In addition, metropolitan areas have experienced sharp increases in drug and opioid-involved overdose deaths since 2013 (6,7). This study analyzed changes in overdose death rates involving any opioid and synthetic opioids among persons aged >/=18 years during 2015-2017, by age and race/ethnicity across metropolitan areas. Nearly all racial/ethnic groups and age groups experienced increases in opioid-involved and synthetic opioid-involved overdose death rates, particularly blacks aged 45-54 years (from 19.3 to 41.9 per 100,000) and 55-64 years (from 21.8 to 42.7) in large central metro areas and non-Hispanic whites (whites) aged 25-34 years (from 36.9 to 58.3) in large fringe metro areas. Comprehensive and culturally tailored interventions are needed to address the rise in drug overdose deaths in all populations, including prevention strategies that address the risk factors for substance use across each racial/ethnic group, public health messaging to increase awareness about synthetic opioids in the drug supply, expansion of naloxone distribution for overdose reversal, and increased access to medication-assisted treatment.

      6. Identifying co-exposure to opiates and gabapentin during pregnancyexternal icon
        Loudin S, Haas J, Payne M, Linz MF, Meaney-Delman D, Honein MA, Saunders A.
        J Pediatr. 2019 Oct 23.
        Neonatal withdrawal can be difficult to treat in infants with co-exposure to opiates and gabapentin. Because maternal self-report can underestimate exposures, we evaluated the effect of universal toxicology screening for gabapentin. Identification of co-exposure to opiates and gabapentin increased after implementation of toxicology screening, with implications for improved neonatal care.

      7. Update: Characteristics of patients in a national outbreak of e-cigarette, or vaping, product use-associated lung injuries – United States, October 2019external icon
        Moritz ED, Zapata LB, Lekiachvili A, Glidden E, Annor FB, Werner AK, Ussery EN, Hughes MM, Kimball A, DeSisto CL, Kenemer B, Shamout M, Garcia MC, Reagan-Steiner S, Petersen EE, Koumans EH, Ritchey MD, King BA, Jones CM, Briss PA, Delaney L, Patel A, Polen KD, Sives K, Meaney-Delman D, Chatham-Stephens K.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 1;68(43):985-989.
        CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products.

      8. Substances used in electronic vapor products among adults in the United States, 2017external icon
        Trivers KF, Gentzke AS, Phillips E, Tynan M, Marynak KL, Schauer GL.
        Addict Behav Rep. 2019 .
        Introduction: Electronic vapor products (EVPs), including e-cigarettes, can be used to aerosolize many substances. Examination of substances used in EVPs by US adults has been limited; we assessed past-year use of EVPs to deliver various substances. Methods: Data came from the 2017 SummerStyles Survey, a web-based survey of US adults (N = 4107). Ever EVP users were asked if they had used nicotine, marijuana, flavors or “something else” in an EVP during the past year. Weighted estimates for any, exclusive, and combined EVP substance use were calculated among ever (n = 586) and current (past 30-day; n = 121) EVP users. Results: Past-year use of nicotine, flavors, and marijuana in EVPs was 30.7%, 23.6%, and 12.5% among ever EVP users, respectively; and 72.3%, 54.6%, and 17.8% among current EVP users. Among ever EVP users, the most commonly used substances were nicotine only (29.6%), nicotine plus flavors (27.2%), flavors only (16.4%), and marijuana only (14.9%). Among current EVP users, the most common substances used were nicotine plus flavors (39.1%), nicotine only (29.6%), and flavors only (11.2%). Among ever users, males and 18-29 year olds were more likely to report use of flavors than females and respondents >/=30 years. Conclusions: Approximately 7 in 10 current EVP users reported nicotine use, about 1 in 2 used flavors, and nearly 1 in 6 used marijuana. These findings suggest that EVPs are used to consume a variety of substances and could guide efforts to address tobacco and non-tobacco substance use.

      9. Tobacco use in top-grossing movies – United States, 2010-2018external icon
        Tynan MA, Polansky JR, Driscoll D, Garcia C, Glantz SA.
        MMWR Morb Mortal Wkly Rep. 2019 Nov 1;68(43):974-978.
        The Surgeon General has concluded that there is a causal relationship between depictions of smoking in movies and initiation of smoking among young persons (1). Youths heavily exposed to onscreen smoking imagery are more likely to begin smoking than are those with minimal exposure (1,2). To assess tobacco-use imagery in top-grossing youth-rated movies (General Audiences [G], Parental Guidance [PG], and Parents Strongly Cautioned [PG-13]),* 2010-2018 data from the Breathe California Sacramento Region and University of California-San Francisco’s Onscreen Tobacco Database were analyzed.(dagger) The percentage of all top-grossing movies with tobacco incidents remained stable from 2010 (45%) to 2018 (46%), including youth-rated movies (31% both years). However, total tobacco incidents increased 57% from 2010 to 2018, with a 120% increase in PG-13 movies. Tobacco incidents in PG-13 fictional movies declined 57% from 511 in 2010 to an all-time low of 221 in 2018. Although the number of PG-13 fictional movies with tobacco incidents declined 40% during 2010-2018, the number of PG-13 biographical dramas with tobacco incidents increased 233%. In 2018, biographical dramas accounted for most tobacco incidents, including 82% of incidents in PG-13 movies; 73% of characters who used tobacco in these biographical dramas were fictional. Continued efforts could help reduce tobacco incidents in top-grossing movies, particularly in PG-13 biographical dramas, to help prevent youth smoking initiation.

    • Zoonotic and Vectorborne Diseases
      1. Novel avian influenza A virus infections of humansexternal icon
        Uyeki TM, Peiris M.
        Infect Dis Clin North Am. 2019 Dec;33(4):907-932.
        A high index of suspicion and early diagnosis of avian influenza A virus infection is essential reduce transmission risk. Clinical suspicion relies on eliciting a history of recent exposure to poultry or to sick persons. Diagnosis requires collection of appropriate respiratory specimens. Patients with suspected infection should be isolated immediately and patients with lower respiratory tract disease should be placed on airborne precautions if possible. Antiviral treatment should be started as soon as possible based upon clinical suspicion while awaiting specific viral diagnosis. Corticosteroids and salicylates should be avoided. Clinical management focuses on supportive care of complications.

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CDC Science Clips Production Staff

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Page last reviewed: November 18, 2019, 12:00 AM
Content source: Centers for Disease Control and Prevention