Volume 11, Issue 23 June 11, 2019

CDC Science Clips: Volume 11, Issue 23, June 11, 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 collaborate with CDC Vital Signs by featuring scientific articles from the latest issue on rabies. The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Zoonotic and Vectorborne Diseases – Rabies
      1. *Management and modeling approaches for controlling raccoon rabies: The road to eliminationexternal icon
        Elmore SA, Chipman RB, Slate D, Huyvaert KP, VerCauteren KC, Gilbert AT.
        PLoS Negl Trop Dis. 2017 Mar;11(3):e0005249.
        Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (PEP) annually. Previous rabies variant elimination in raccoons (Canada), foxes (Europe), and dogs and coyotes (United States) demonstrates that elimination of the raccoon variant from the eastern US is feasible, given an understanding of rabies control costs and benefits and the availability of proper tools. Also critical is a cooperatively produced strategic plan that emphasizes collaborative rabies management among agencies and organizations at the landscape scale. Common management strategies, alone or as part of an integrated approach, include the following: oral rabies vaccination (ORV), trap-vaccinate-release (TVR), and local population reduction. As a complement, mathematical and statistical modeling approaches can guide intervention planning, such as through contact networks, circuit theory, individual-based modeling, and others, which can be used to better understand and predict rabies dynamics through simulated interactions among the host, virus, environment, and control strategy. Strategies derived from this ecological lens can then be optimized to produce a management plan that balances the ecological needs and program financial resources. This paper discusses the management and modeling strategies that are currently used, or have been used in the past, and provides a platform of options for consideration while developing raccoon rabies virus elimination strategies in the US.

      2. *Rabies in North America and Europeexternal icon
        Finnegan CJ, Brookes SM, Johnson N, Smith J, Mansfield KL, Keene VL, McElhinney LM, Fooks AR.
        J R Soc Med. 2002 Jan;95(1):9-13.

        [No abstract]

      3. Cost-effectiveness of dog rabies vaccination programs in East Africaexternal icon
        Borse RH, Atkins CY, Gambhir M, Undurraga EA, Blanton JD, Kahn EB, Dyer JL, Rupprecht CE, Meltzer MI.
        PLoS Negl Trop Dis. 2018 May;12(5):e0006490.
        BACKGROUND: Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. METHODS: RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). RESULTS: Without dog vaccination, over 10 years there would a total of be approximately 44,000-65,000 rabid dogs and 2,100-2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000-1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000-1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). CONCLUSIONS: Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs.

      4. Workshop summary: prioritizing zoonotic diseases for multisectoral, One Health collaboration in the United States
        Centers for Disease Control and Prevention, US Department of Agriculture, US Department of the Interior.
        Atlanta, GA: US Department of Health and Human Services, CDC. 2019.
        The CDC, the U.S. Department of Agriculture (USDA), and the U.S. Department of the Interior (DOI) organized a One Health Zoonotic Disease Prioritization (OHZDP) workshop to further joint efforts to address zoonotic disease challenges in the United States. The workshop was held December 5-7, 2017, at the Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR) headquarters in Washington, DC. During the workshop, participants identified a list of zoonotic diseases (or zoonoses) relevant for the United States, defined the criteria for prioritization, and determined questions and weights relevant to each criterion. Participants identified eight zoonotic diseases as priorities using a semi-quantitative selection tool, the One Health Zoonotic Disease Prioritization (OHZDP) tool, developed by CDC. Participants then used components of the One Health Systems Mapping and Analysis Resource Toolkit (OH-SMARTTM), co-developed by USDA and the University of Minnesota, to review and visualize the One Health system currently in place to address the priority zoonotic diseases in the United States among relevant federal agencies. The One Health system includes the procedures and processes for transdisciplinary and multisectoral coordination. Next, participants developed specific steps to address the newly prioritized diseases following the workshop. The specific workshop goals were:
        (1) To use a multisectoral, One Health approach to identify and prioritize endemic and emerging zoonotic diseases of greatest national concern for the United States that should be jointly addressed by human, animal, and environmental health sectors responsible for federal zoonotic disease programs in HHS, USDA, and DOI; and (2) to develop plans for implementing and strengthening multisectoral, One Health approaches to address these diseases in the United States. This workshop was a critical step towards a unique U.S. approach to One Health, ensuring that all stakeholders have a shared vision and roadmap for implementing One Health strategies for disease surveillance, response, preparedness, workforce, and prevention and control activities in their current and future areas of focus. The workshop summary describes the process used to prioritize the top zoonotic diseases of concern for the United States and the key themes surrounding priority next steps to address these diseases using a multisectoral, One Health approach that includes relevant human, animal, and environmental health sectors and other relevant partners.

      5. Epidemiology of rabies post-exposure prophylaxis–United States of America, 2006-2008external icon
        Christian KA, Blanton JD, Auslander M, Rupprecht CE.
        Vaccine. 2009 Nov 27;27(51):7156-61.
        BACKGROUND: The United States of America (USA) does not have a national reporting system for rabies post-exposure prophylaxis (PEP). We describe the epidemiology of PEP in the USA so recommendations can be made during a PEP shortage. METHODS: A two-part questionnaire designed to evaluate PEP distribution practices and estimate PEP use was administered to state health department representatives. RESULTS: Seventy-five percent of participants responded that no public health guidance was needed to make a recommendation for PEP. The annual national average PEP use is 23,415 courses of PEP (range: 10,645-35,845). CONCLUSION: PEP is loosely monitored and a precise estimate of PEP use is unknown. Improved national surveillance for PEP is needed.

      6. WHO recommends that 70% of dogs in a population should be immunized to eliminate or prevent outbreaks of rabies. This critical percentage (pc) has been established empirically from observations on the relationship between vaccination coverage and rabies incidence in dog populations around the world. Here, by contrast, we estimate pc by using epidemic theory, together with data available from four outbreaks in urban and rural areas of the USA, Mexico, Malaysia and Indonesia. From the rate of increase of cases at the beginning of these epidemics, we obtain estimates of the basic case reproduction number of infection, R0, in the range 1.62-2.33, implying that pc lies between 39% and 57%. The errors attached to these estimates of pc suggest that the recommended coverage of 70% would prevent a major outbreak of rabies on no fewer than 96.5% of occasions.

      7. In the United States and Canada, the most recent documented cases of rabies have been attributed to bat rabies viruses (RABV). We undertook this systematic review in an effort to summarize and enhance understanding of the risk of infection for individuals who have been potentially exposed to a suspect or confirmed rabid bat. United States rabies surveillance summaries documented a total of 41 human bat-rabies virus variant verified non-transplant cases between 1990 and 2015. All cases were fatal. Seven (17.1%) of 41 cases reported a bite from a bat. Ten (24.3%) cases had unprotected physical contact (UPC); these included seven cases that had a bat land or crawl on them (contact with claws) and one case that touched a bat’s teeth. Seven (17.1%) cases had probable UPC. Insectivorous bat teeth are extremely sharp and highly efficient for predation upon arthropod prey. Bats also have sharp claws on the end of their thumbs and feet. One of the most common bat RABV variants has an ability to replicate in non-neural cells. Questioning individuals about unprotected contact with bat teeth and claws (including a bat landing or crawling on a person) may help identify additional exposures.

      8. Perceptions and Practices of Mass Bat Exposure Events in the Setting of Rabies Among U.S. Public Health Agenciesexternal icon
        Hsu CH, Brown CM, Murphy JM, Haskell MG, Williams C, Feldman K, Mitchell K, Blanton JD, Petersen BW, Wallace RM.
        Zoonoses Public Health. 2017 Mar;64(2):127-136.
        Current guidelines in the setting of exposures to potentially rabid bats established by the Advisory Committee on Immunization Practices (ACIP) address post-exposure prophylaxis (PEP) administration in situations where a person may not be aware that a bite or direct contact has occurred and the bat is not available for diagnostic testing. These include instances when a bat is discovered in a room where a person awakens from sleep, is a child without an adult witness, has a mental disability or is intoxicated. The current ACIP guidelines, however, do not address PEP in the setting of multiple persons exposed to a bat or a bat colony, otherwise known as mass bat exposure (MBE) events. Due to a dearth of recommendations for response to these events, the reported reactions by public health agencies have varied widely. To address this perceived limitation, a survey of 45 state public health agencies was conducted to characterize prior experiences with MBE and practices to mitigate the public health risks. In general, most states (69% of the respondents) felt current ACIP guidelines were unclear in MBE scenarios. Thirty-three of the 45 states reported prior experience with MBE, receiving an average of 16.9 MBE calls per year and an investment of 106.7 person-hours annually on MBE investigations. PEP criteria, investigation methods and the experts recruited in MBE investigations varied between states. These dissimilarities could reflect differences in experience, scenario and resources. The lack of consistency in state responses to potential mass exposures to a highly fatal disease along with the large contingent of states dissatisfied with current ACIP guidance warrants the development of national guidelines in MBE settings.

      9. Rabies surveillance in the United States during 2017external icon
        Ma X, Monroe BP, Cleaton JM, Orciari LA, Li Y, Kirby JD, Chipman RB, Petersen BW, Wallace RM, Blanton JD.
        J Am Vet Med Assoc. 2018 Dec 15;253(12):1555-1568.
        OBJECTIVE To describe rabies and rabies-related events occurring during 2017 in the United States. DESIGN Cross-sectional analysis of passive surveillance data. ANIMALS All animals submitted for laboratory diagnosis of rabies in the United States during 2017. PROCEDURES State and territorial public health departments provided data on animals submitted for rabies testing in 2017. Data were analyzed temporally and geographically to assess trends in domestic and sylvatic animal rabies cases. RESULTS During 2017, 52 jurisdictions reported 4,454 rabid animals to the CDC, representing a 9.3% decrease from the 4,910 rabid animals reported in 2016. Of the 4,454 cases of animal rabies, 4,055 (91.0%) involved wildlife species. Relative contributions by the major animal groups were as follows: 1,433 (32.2%) bats, 1,275 (28.6%) raccoons, 939 (21.1%) skunks, 314 (7.0%) foxes, 276 (6.2%) cats, 62 (1.4%) dogs, and 36 (0.8%) cattle. There was a 0.4% increase in the number of samples submitted for testing in 2017, compared with the number submitted in 2016. Two human rabies deaths were reported in 2017, compared with none in 2016. CONCLUSIONS AND CLINICAL RELEVANCE The overall number of reported cases of animal rabies has decreased over time. Laboratory testing of animals suspected to be rabid remains a critical public health function and continues to be a cost-effective method to directly influence human rabies postexposure prophylaxis recommendations.

      10. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practicesexternal icon
        Rupprecht CE, Briggs D, Brown CM, Franka R, Katz SL, Kerr HD, Lett SM, Levis R, Meltzer MI, Schaffner W, Cieslak PR.
        MMWR Recomm Rep. 2010 Mar 19;59(Rr-2):1-9.
        This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention—United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre-exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies.

  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. Application of geographic information systems to address chronic disease priorities: Experiences in state and local health departmentsexternal icon
        Brissette I, Casper M, Huston SL, Jordan M, Karns B, Kippes C, Kramer MR, Peacock JM, Vaughan AS.
        Prev Chronic Dis. 2019 May 23;16:E65.

        [No abstract]

      2. Awareness of heart attack symptoms and response among adults – United States, 2008, 2014, and 2017
        Fang J, Luncheon C, Ayala C, Odom E, Loustalot F.
        MMWR Morb Mortal Wkly Rep. 2019 ;68(5).

        [No abstract]

      3. Clinical characteristics of a large cohort of US participants enrolled in the National Amyotrophic Lateral Sclerosis (ALS) Registry, 2010-2015external icon
        Raymond J, Oskarsson B, Mehta P, Horton K.
        Amyotroph Lateral Scler Frontotemporal Degener. 2019 May 26:1-8.
        Background: Amyotrophic lateral sclerosis (ALS) is a progressive fatal disease with a varying range of clinical characteristics. Objective: To describe the clinical characteristics in a large cohort of ALS participants enrolled in the National ALS Registry. Methods: Data from ALS participants who completed the Registry’s online clinical survey module during 2010-2015 were analyzed to determine characteristics, such as site of onset, associated symptoms, time of symptom onset to diagnosis, time of diagnosis to hospice referral, and pharmacological and non-pharmacological interventions. Results: Of the 1758 participants who completed the survey, 60.9% were male, 62.1% were 50-69 years old, and 95.5% white. Approximately, 72.0% reported initial limb weakness onset of disease, followed by bulbar (22.1%), and trunk/global onset (6.1%). Other symptoms ever experienced included cramps (56.7%), fasciculations (56.3%), and dysarthria (33.0%). The median time between an increase of muscle cramps until an ALS diagnosis was 12 months; limb onset participants had cramps longer preceding diagnosis versus those with bulbar onset. The most frequent interventions used included riluzole (48.3% currently using), wheelchairs/scooters (32.8%), and noninvasive breathing equipment (30.0%). Participants with trunk/global onset were referred to hospice almost four times earlier than others. Conclusions: These data show how ALS clinical characteristics differ widely in a large cohort of participants preceding diagnosis and reflect variations in disease onset, progression, and prognosis. Better characterization of symptom onset may assist clinicians in diagnosing ALS sooner, which could lead to earlier therapeutic interventions.

      4. CE: Understanding the complications of sickle cell diseaseexternal icon
        Tanabe P, Spratling R, Smith D, Grissom P, Hulihan M.
        Am J Nurs. 2019 Jun;119(6):26-35.
        : Sickle cell disease (SCD) is an autosomal recessive genetic condition that alters the shape and function of the hemoglobin molecule in red blood cells. While the overall survival rate among children with SCD has improved in recent years, pediatric rates of hospitalization, ED use, and mortality from complications of SCD remain high. Among patients ages 18 and older, hospital admission and ED usage are even greater-and the median age at death of people with SCD is considerably lower than that of the general population. Nurses who care for patients with SCD have an opportunity to improve health outcomes and quality of life for these patients by recognizing the major SCD-associated complications and providing patients and their caregivers with appropriate educational information. The authors discuss the genetic, hematologic, and clinical features of SCD and describe the major associated health complications. In addition, they review the nursing implications of each complication and provide online links to resources for clinicians, patients, and caregivers.

    • Communicable Diseases
      1. Hepatocellular carcinoma surveillance in a cohort of chronic hepatitis C virus-infected patients with cirrhosisexternal icon
        Abara WE, Spradling P, Zhong Y, Moorman A, Teshale EH, Rupp L, Gordon SC, Schmidt M, Boscarino JA, Daida YG, Holmberg SD.
        J Gastrointest Cancer. 2019 May 23.
        BACKGROUND: Six-monthly hepatocellular carcinoma (HCC) screening in cirrhotic patients has been recommended since 2011. HCC prognosis is associated with diagnosis at an early stage. We examined the prevalence and correlates of 6-monthly HCC surveillance in a cohort of HCV-infected cirrhotic patients. METHODS: Data were obtained from the medical records of patients receiving care from four hospitals between January 2011 and December 2016. Frequencies and logistic regression were conducted. RESULTS: Of 2,933 HCV-infected cirrhotic patients, most were >/= 60 years old (68.5%), male (62.2%), White (65.8%), and had compensated cirrhosis (74.2%). The median follow-up period was 3.5 years. Among these patients, 10.9% were consistently screened 6 monthly and 21.4% were never screened. Patients with a longer history of cirrhosis (AOR = 0.86, 95% CI = 0.80-0.93) were less likely to be screened 6 monthly while decompensated cirrhotic patients (AOR = 1.39, 95% CI = 1.06-1.81) and cirrhotic patients between 18 and 44 years (AOR = 2.01, 95% CI = 1.07-3.74) were more likely to be screened 6 monthly compared to compensated cirrhotic patients and patients 60 years and older respectively. There were no significant differences by race, gender, or insurance type. CONCLUSION: The prevalence of consistent HCC surveillance remains low despite formalized recommendations. One in five patients was never surveilled. Patients with a longer history of cirrhosis were less likely to be surveilled consistently despite their greater HCC risk. Improving providers’ knowledge about current HCC surveillance guidelines, educating patients about the benefits of consistent HCC surveillance, and systemic interventions like clinical reminders and standing HCC surveillance protocols can improve guideline-concordant surveillance in clinical practice.

      2. Ghana’s HIV epidemic and PEPFAR’s contribution towards epidemic controlexternal icon
        Ali H, Amoyaw F, Baden D, Durand L, Bronson M, Kim A, Grant-Greene Y, Imtiaz R, Swaminathan M.
        Ghana Med J. 2019 Mar;53(1):59-62.
        Background: The aim of this review was to summarize the data on HIV/AIDS epidemiology and affected populations in Ghana and to describe the United States President’s Emergency Plan for Emergency Relief’s (PEPFAR) response to the epidemic. Design: We conducted a literature review focusing on PEPFAR’s contribution to the HIV response in Ghana. Additionally, we summarized the epidemiology of HIV. We searched both peer-reviewed and grey literature. Setting: Ghana. Results: Overall, HIV prevalence in Ghana is 1.6% with regional variation. Key populations (KPs) are disproportionately affected by HIV in the country. FSW and their clients, and MSM, account for 28% of all new infections. PEPFAR provides technical assistance (TA) to Ghana to maximize the quality, coverage and impact of the national HIV/AIDS response. To ensure adequate supply of antiretrovirals (ARVs), in 2016-2017, PEPFAR invested $23.7 million as a onetime supplemental funding to support Ghana’s ARV treatment program. In addition, the National AIDS Control Programme in collaboration with PEPFAR is implementing a scale up of viral load testing. PEPFAR is also implementing a comprehensive package of prevention services in five regions to help reach MSM and FSW and to expand HIV testing services for KPs. Conclusions: Ghana is making changes at both policy and program level in the fight against HIV/AIDS and is working towards achieving the UNAIDS’ 90-90-90 targets. PEPFAR is providing TA to ensure these goals can be achieved. Funding: This manuscript has been supported by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC).

      3. Evaluation of diarrheal disease surveillance in the Minawao refugee camp, Cameroon, 2016external icon
        Amabo FC, Seukap EC, Mathieu E, Etoundi GA.
        Int J Infect Dis. 2019 May;82:9-14.
        BACKGROUND: Between 2013 and 2015, the Minawao refugee camp in Cameroon received about 51000 refugees fleeing Boko Haram. A rapid increase in population and inadequate sanitary installations increase the risk of diarrheal disease. This study was performed to assess the structure and attributes of the surveillance system in Minawao. METHODS: Updated US Centers for Disease Control and Prevention guidelines were used to evaluate the public health surveillance system. Information sources included health registers, surveillance reports, and key informant interviews. Scorecards were used to assess the simplicity, flexibility, data quality, acceptability, sensitivity, timeliness, stability, and usefulness of the system. RESULTS: Surveillance in Minawao is both passive and active, integrating four diseases reported weekly/immediately. All key informants agreed that surveillance was part of their routine work. Of 138 surveillance reports reviewed, all were complete; 91 (66%) were timely. Overall, 143 (100%) cases of diarrheal disease identified in health registers were reported to the next level. Only two (20%) surveillance personnel could correctly state standardized case definitions (SCD); three (30%) were unable to identify cases of diarrheal disease based on SCD. CONCLUSIONS: In Minawao, diarrheal disease surveillance is acceptable, flexible, sensitive, and useful. To improve timeliness and the use of SCD, we recommend the use of mobile phones to report and display SCD in health facilities.

      4. The national and provincial burden of medically attended influenza-associated influenza-like illness and severe acute respiratory illness in the Democratic Republic of Congo, 2013-2015external icon
        Babakazo P, Lubula L, Disasuani W, Manya LK, Nkwembe E, Mitongo N, Kavunga-Membo H, Changachanga JC, Muhemedi S, Ilunga BK, Wemakoy EO, Tamfum JM, Kabamba-Tshilobo J, Tempia S.
        Influenza Other Respir Viruses. 2018 Nov;12(6):695-705.
        BACKGROUND: Estimates of influenza-associated outpatient consultations and hospitalizations are severely limited in low- and middle-income countries, especially in Africa. METHODS: We conducted active prospective surveillance for influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 5 healthcare facilities situated in Kinshasa Province during 2013-2015. We tested upper respiratory tract samples for influenza viruses using a reverse transcription-polymerase chain reaction assay. We estimated age-specific numbers and rates of influenza-associated ILI outpatient consultations and SARI hospitalizations for Kinshasa Province using a combination of administrative and influenza surveillance data. These estimates were extrapolated to each of the remaining 10 provinces accounting for provincial differences in prevalence of risk factors for pneumonia and healthcare-seeking behavior. Rates were reported per 100 000 population. RESULTS: During 2013-2015, the mean annual national number of influenza-associated ILI outpatient consultations was 1 003 212 (95% Confidence Incidence [CI]: 719 335-1 338 050 – Rate: 1205.3; 95% CI: 864.2-1607.5); 199 839 (95% CI: 153 563-254 759 – Rate: 1464.0; 95% CI: 1125.0-1866.3) among children aged <5 years and 803 374 (95% CI: 567 772-1 083 291 – Rate: 1154.5; 95% CI: 813.1-1556.8) among individuals aged >/=5 years. The mean annual national number of influenza-associated SARI hospitalizations was 40 361 (95% CI: 24 014-60 514 – Rate: 48.5; 95% CI: 28.9-72.7); 25 452 (95% CI: 19 146-32 944 – Rate: 186.5; 95% CI: 140.3-241.3) among children aged <5 years and 14 909 (95% CI: 4868-27 570 – Rate: 21.4; 95% CI: 28.9-72.7) among individuals aged >/=5 years. CONCLUSIONS: The burden of influenza-associated ILI outpatient consultations and SARI hospitalizations was substantial and was highest among hospitalized children aged <5 years.

      5. Systematic monitoring of retention in care in U.S.-based HIV care facilitiesexternal icon
        Dasgupta S, Weiser J, Craw J, Tie Y, Beer L.
        AIDS Care. 2019 May 25:1-6.
        National guidelines recommend that HIV providers systematically monitor retention in care to identify and re-engage persons suboptimally in care. We described (1) U.S.-based outpatient HIV care facilities that systematically monitor retention in care, and (2) characteristics of patients attending facilities that monitored retention in care. We used data collected during 6/2014-5/2015 from the Medical Monitoring Project, an annual, cross-sectional survey that produces nationally representative estimates of characteristics of HIV-positive persons in medical care. We described systematic monitoring of retention in care among facilities and patients attending facilities providing this service using weighted percentages and 95% confidence intervals, and used Rao-Scott chi-square tests (p < .05) to assess differences by selected characteristics. Overall, 67% of facilities systematically monitored retention in care, and 81% of patients attended these facilities. Federally qualified health centers, community-based organizations, health departments, non-private practices, and Ryan White HIV/AIDS Program (RWHAP)-funded facilities were more likely to systematically monitor retention in care. Persons living in poverty, and those who were homeless or incarcerated, or injected drugs were more likely to attend facilities with this service. Although systematic monitoring of retention in care is accessible for many patients, improvements at other, non-RWHAP-funded facilities may help in reaching national prevention goals.

      6. Bedaquiline microheteroresistance after cessation of tuberculosis treatmentexternal icon
        de Vos M, Ley SD, Wiggins KB, Derendinger B, Dippenaar A, Grobbelaar M, Reuter A, Dolby T, Burns S, Schito M, Engelthaler DM, Metcalfe J, Theron G, van Rie A, Posey J, Warren R, Cox H.
        N Engl J Med. 2019 May 30;380(22):2178-2180.

        [No abstract]

      7. Mapping the study topics and characteristics of HIV pre-exposure prophylaxis research literature: a protocol for a scoping reviewexternal icon
        Kamitani E, Johnson AH, Wichser M, Mizuno Y, DeLuca JB, Higa DH.
        BMJ Open. 2019 May 24;9(5):e024212.
        INTRODUCTION: The research literature addressing pre-exposure prophylaxis (PrEP) has increased considerably over the last decade. To better understand the research areas and explore research gaps, we will conduct a scoping review to map study topics and describe study characteristics and populations in publications focused on PrEP. The purpose of this protocol is to describe planned methods for the scoping review. METHODS AND ANALYSIS: We will implement a comprehensive systematic literature search to identify PrEP citations in the United States Centres for Disease Control and Prevention HIV/AIDS Prevention Research Synthesis Project database that is unique and extensively focuses on HIV/sexually transmitted infections/hepatitis. We will screen and include studies that are (1) focused on HIV PrEP, (2) primary research with human participants and (3) published in English. Two reviewers will independently abstract data on authors’ names, study years, countries, population characteristics and design. To describe and summarise study topics, we will use 19 codes and five categories that were developed from a preliminary study. The five categories are category 1: potential PrEP user/prescriber (behaviours/issues for potential PrEP takers/healthcare professionals), category 2: considerations while on PrEP (experiences of and problems related to staying on or prescribing PrEP), category 3: PrEP efficacy and safety (biomedical aspects and medication efficacy), category 4: methods of and experiences with PrEP clinical trials (possesses/experiences of clinical trials) and category 5: cost-effectiveness or economic evaluation (cost studies). Data will be analysed with descriptive statistics. ETHICS AND DISSEMINATION: The findings will be presented at HIV-related conferences and published in peer-review journals.

      8. Epidemiology of viral acute lower respiratory infections in a community-based cohort of rural north Indian childrenexternal icon
        Krishnan A, Kumar R, Broor S, Gopal G, Saha S, Amarchand R, Choudekar A, Purkayastha DR, Whitaker B, Pandey B, Narayan VV, Kabra SK, Sreenivas V, Widdowson MA, Lindstrom S, Lafond KE, Jain S.
        J Glob Health. 2019 Jun;9(1):010433.
        Background: In India, community-based acute lower respiratory infections (ALRI) burden studies are limited, hampering development of prevention and control strategies. Methods: We surveyed children <10 years old at home weekly from August 2012-August 2014, for cough, sore throat, rhinorrhoea, ear discharge, and shortness of breath. Symptomatic children were assessed for ALRI using World Health Organization definitions. Nasal and throat swabs were obtained from all ALRI cases and asymptomatic controls and tested using polymerase chain reaction for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza viruses (PIV), and influenza viruses (IV). We estimated adjusted odds ratios (aOR) using logistic regression to calculate etiologic fractions (EF). We multiplied agent-specific ALRI incidence rates by EF to calculate the adjusted incidence as episodes per child-year. Results: ALRI incidence was 0.19 (95% confidence interval (CI) = 0.18-0.20) episode per child-year. Association between virus and ALRI was strongest for RSV (aOR = 15.9; 95% CI = 7.3-34.7; EF = 94%) and least for IV (aOR = 4.6; 95% CI = 2.0-10.6; EF = 78%). Adjusted agent-specific ALRI incidences were RSV (0.03, 95% CI = 0.02-0.03), hMPV (0.02, 95% CI = 0.01-0.02), PIV (0.02, 95% CI = 0.01-0.02), and IV (0.01, 95% CI = 0.01-0.01) episode per child-year. Conclusions: ALRI among children in rural India was high; RSV was a significant contributor.

      9. Invasive meningococcal disease due to nongroupable Neisseria meningitidis – Active Bacterial Core Surveillance Sites, 2011-2016external icon
        McNamara LA, Potts CC, Blain A, Topaz N, Apostol M, Alden NB, Petit S, Farley MM, Harrison LH, Triden L, Muse A, Poissant T, Wang X, MacNeil JR.
        Open Forum Infect Dis. 2019 May;6(5):ofz190.
        We characterized 22 meningococcal disease cases due to nongroupable Neisseria meningitidis, a rare cause of invasive disease. Disease presentation and severity were similar to those for serogroupable meningococcal disease. However, 7 (32%) patients had complement deficiency or abnormal complement testing results, highlighting the importance of complement testing for nongroupable cases.

      10. Risk factors for tuberculosis and effect of preventive therapy among close contacts of persons with infectious tuberculosisexternal icon
        Reichler MR, Khan A, Sterling TR, Zhao H, Chen B, Yuan Y, Moran J, McAuley J, Mangura B.
        Clin Infect Dis. 2019 May 24.
        BACKGROUND: Close contacts of persons with pulmonary tuberculosis (TB) have high rates of TB disease. METHODS: We prospectively enrolled adult TB patients and their close contacts at nine United States and Canadian sites. TB patients and contacts were interviewed to identify potential index patient, contact, and exposure risk factors for TB. Contacts were evaluated for latent TB infection (LTBI) and TB, and the effectiveness of LTBI treatment for preventing contact TB was examined. RESULTS: Among 4490 close contacts, multivariable risk factors for TB were age < 5 years, US/Canadian birth, human immunodeficiency virus infection, skin test induration > 10 mm, shared bedroom with an index patient, exposure to more than one index patient, and index patient weight loss (P<.05 for each). Of 1406 skin test-positive contacts, TB developed in 49 (9.8%) of 446 who did not initiate treatment, 8 (1.8%) of 443 who received partial treatment, and 1 (0.2%) of 517 who completed treatment (1951, 290, and 31 cases/100,000 person years, respectively; P<.001). TB was diagnosed in 4.2% of US/Canadian-born compared with 2.3% of foreign-born contacts (P=.002), and rates of TB for US/Canadian-born and foreign-born contacts who did not initiate treatment were 3592 and 811 per 100,000 person years, respectively (P<.001). CONCLUSIONS: Treatment for LTBI was highly effective in preventing TB among close contacts of infectious TB patients. A number of index patient, contact, and exposure characteristics associated with increased risk of contact TB were identified. These findings help inform contact investigation, LTBI treatment, and other public health prevention efforts.

      11. The role of the primary romantic relationship in HIV care engagement outcomes among young HIV-positive black men who have sex with menexternal icon
        Tan JY, Pollack L, Rebchook G, Peterson J, Huebner D, Eke A, Johnson W, Kegeles S.
        AIDS Behav. 2018 Mar;22(3):774-790.
        The primary romantic relationship plays a fundamental role in health maintenance, but little is known about its role in HIV care engagement among young Black men who have sex with men (MSM) living with HIV. We examined how HIV care engagement outcomes (i.e., having a primary healthcare provider, receiving HIV treatment, taking antiretroviral medication, and medication adherence) vary by partnership status (single vs. concordant-positive vs. discordant) in a sample of young Black MSM living with HIV. Results showed mixed findings. Partnership status was significantly associated with HIV care engagement, even after adjusting for individual, social, and structural factors. While partnered men were consistently more likely than their single counterparts to have a regular healthcare provider, to receive recent treatment, and to have ever taken antiretroviral medication, they were less likely to report currently receiving antiretroviral therapy. Moreover, men with a discordant partner reported better adherence compared to men with a concordant or no partner. The association between partnership status and HIV care engagement outcomes was not consistent across the stages of the HIV Care Continuum, highlighting the complexity in how and why young Black men living with HIV engage in HIV healthcare. Given the social context of HIV disease management, more research is needed to explicate underlying mechanisms involved in HIV care and treatment that differ by relational factors for young Black MSM living with HIV.

    • Environmental Health
      1. Association of perfluoroalkyl substances exposure with cardiometabolic traits in an island population of the eastern Adriatic coast of Croatiaexternal icon
        Chen A, Jandarov R, Zhou L, Calafat AM, Zhang G, Urbina EM, Sarac J, Augustin DH, Caric T, Bockor L, Petranovic MZ, Novokmet N, Missoni S, Rudan P, Deka R.
        Sci Total Environ. 2019 May 20;683:29-36.
        BACKGROUND: Exposure to perfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, may be related to cardiometabolic diseases in adults. Studies in European populations to examine the association of PFAS exposure and comprehensive cardiometabolic traits and metabolic syndrome (MetS) are limited. METHODS: In this pilot cross-sectional study of a well-characterized adult population of the island of Hvar, situated off the eastern Adriatic coast of Croatia, we measured PFAS concentrations in plasma samples collected during 2007-2008 and examined their cross-sectional associations with cardiometabolic traits and MetS after adjustment of covariates (n=122). PFAS investigated in this study included perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). RESULTS: The geometric mean (range) was 8.91 (2.36, 33.67) ng/mL for PFOS, 2.87 (1.03, 8.02) ng/mL for PFOA, 0.77 (0.25, 2.40) ng/mL for PFHxS, and 1.29 (0.48, 3.46) ng/mL for PFNA, with frequency of detection at 100%, 100%, 95.9%, and 100%, respectively. PFOS, PFOA, and PFNA concentrations were positively associated with the risk of MetS as defined by the Adult Treatment Panel III (ATP III) criteria, with estimated odds ratios and 95% confidence intervals at 1.89 (0.93, 3.86), 2.19 (0.88, 5.44), and 2.95 (1.12, 7.80), respectively, with only PFNA reaching statistical significance. PFNA concentrations were associated with increased risk of overweight or obesity. CONCLUSIONS: Background exposure to PFOS, PFOA, and PFNA was marginally associated with increased risk of MetS in this small study, and these results should be confirmed with a larger sample size and longitudinal follow-up.

      2. Eleven polybrominated diphenyl ether (tri- to deca-BDE) congeners and 2,2′,4,4′,5,5′-hexabromobiphenyl (BB153) have been measured in pooled serum samples from the National Health and Nutrition Examination Survey (NHANES) for one decade (from survey years 2005/06 through 2013/14). The pools, which are representative of the general noninstitutionalized population of the United States, encompassed thirty-two demographic groups defined by sex, race/ethnicity (Mexican American, non-Hispanic black, non-Hispanic white, and all other race/ethnicities), and age (12-19, >20-39, >40-59, and >/=60 years). The adjusted geometric means were determined in a multiple linear regression model for the six congeners (BDE28, BDE47, BDE99, BDE100, BDE153, and BB153) with detectable concentrations in at least 60% of pools in each of the thirty-two demographic groups; the level of significance for all statistical comparisons thereof were determined. BDE154 and BDE209 were detected in 60% of the NHANES 2011/12 and 2013/14 pools; only these two survey periods were evaluated for these congeners. The percent change in concentration by a 2-year survey period was calculated. All examined PBDEs reported in five survey periods decreased in concentration, except BDE153, for which concentrations increased by 12.0% (95% CI 7.1-16.4) and 8.4% (95% CI 2.9-14.1) for the age groups 40-59 and >/=60 years, respectively; no significant change was observed in younger age groups. Excluding BDE153, we observed larger percentage decreases by a 2-year survey period for the age groups 12-19, 20-39, and >/=60 years compared with the age group 40-59 years. The percentage decrease by a two-year survey period ranged between -19.6% (BDE99, 20-39 years old) and -4.5% (BDE100, 40-59 years old). Although five polybrominated diphenyl ether (PDBE) congeners and BB153 are still frequently detected in the U.S. general population, PBDE concentrations have decreased since 2005-2006, likely, because of changes in manufacturing practices that started in the mid-2000s.

    • Health Behavior and Risk
      1. HIV testing is a critical strategy for prevention of HIV yet testing among sexually experienced adolescents is sub-optimal. The purpose of this study is to examine associations between risk behaviors and experiences related to substance use, violence, and mental health and suicide and receipt of testing. We analyzed cross-sectional data from the 2017 national Youth Risk Behavior Survey, a nationally representative sample of U.S. high school students in grades 9-12. Analyses were limited to sexually experienced participants (n = 5192). Measures included nine indicators related to substance use, violence, and mental health and suicide. Unadjusted and adjusted prevalence ratios were calculated for each indicator to examine associations with testing. Adjusted models controlled for same-sex sexual behavior, sexual risk, and demographic characteristics. Prevalence of HIV testing was 17.2%. In adjusted models, forced sexual intercourse, injection drug use, other illicit drug use, and persistent feelings of sadness or hopelessness were associated with a higher likelihood of testing. Prevalence of HIV testing in this sexually experienced sample was low. Some behaviors and experiences that may be indicative of HIV risk, including sexual dating violence and prescription opioid misuse, were not associated with testing.

    • Health Economics
      1. Background: ME/CFS is a complex and disabling illness with substantial economic burden and functional impairment comparable to heart disease and multiple sclerosis. Many patients with ME/CFS do not receive appropriate healthcare, partially due to lack of diagnostic tests, and knowledge/attitudes/beliefs about ME/CFS. This study was to assess the utility of US ambulatory healthcare data in profiling demographics, co-morbidities, and healthcare in ME/CFS. Methods: Data came from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) in the U.S. Weighted analysis was performed. We examined 9.06 billion adult visits from 2000 to 2009 NAMCS/NHAMCS data. ME/CFS-related visits were identified by ICD-9-CM code, 780.71, up to tertiary diagnosis. Results: We estimated 2.9 million (95% CI: 1.8-3.9 million) ME/CFS-related visits during 2000-2009, with no statistical evidence (p-trend = 0.31) for a decline or increase in ME/CFS-related visits. Internists, general and family practitioners combined provided 52.12% of these visits. Patients with ME/CFS-related visits were mostly in their 40 and 50 s (47.76%), female (66.07%), white (86.95%), metropolitan/urban residents (92.05%), and insured (87.26%). About 71% of ME/CFS patients had co-morbidities, including depression (35.79%), hypertension (31.14%), diabetes (20.30%), and arthritis (14.11%). As one quality indicator, physicians spent more time on ME/CFS-related visits than non-ME/CFS visits (23.62 vs. 19.38 min, p = 0.065). As additional quality indicators, the top three preventive counseling services provided to patients with ME/CFS-related visits were diet/nutrition (8.33%), exercise (8.21%), and smoking cessation (7.24%). Compared to non-ME/CFS visits, fewer ME/CFS-related visits included counseling for stress management (0.75 vs. 3.14%, p = 0.010), weight reduction (0.88 vs. 4.02%, p = 0.002), injury prevention (0.04 vs. 1.64%, p < 0.001), and family planning/contraception (0.17 vs. 1.45%, p = 0.037). Conclusions: Visits coded with ME/CFS did not increase from 2000 to 2009. Almost three quarters of ME/CFS-related visits were made by ME/CFS patients with other co-morbid conditions, further adding to complexity in ME/CFS healthcare. While physicians spent more time with ME/CFS patients, a lower proportion of ME/CFS patients received preventive counseling for weight reduction, stress management, and injury prevention than other patients despite the complexity of ME/CFS. NAMCS/NHAMCS data are useful in evaluating co-morbidities, healthcare utilization, and quality indicators for healthcare in ME/CFS.

      2. The social and economic toll of cancer survivorship: a complex web of financial sacrificeexternal icon
        Banegas MP, Schneider JL, Firemark AJ, Dickerson JF, Kent EE, de Moor JS, Virgo KS, Guy GP, Ekwueme DU, Zheng Z, Varga AM, Waiwaiole LA, Nutt SM, Narayan A, Yabroff KR.
        J Cancer Surviv. 2019 May 23.
        PURPOSE: To assess the financial outcomes and associated social and economic effects on cancer survivors and their families. METHODS: We assessed the responses of 1656 cancer survivors to a survey with both closed- and open-ended questions about cancer-related financial sacrifices they and their family experienced and evaluated differences in financial sacrifice by reported levels of cancer-related debt. RESULTS: The most commonly reported financial sacrifices included cutbacks on household budgets, challenges with health care insurance and costs, career/self-advancement constraints, reduction/depletion of assets, and inability to pay bills. Survivors who incurred $10,000 or more in debt were significantly more likely to report social and economic impacts, including housing concerns and strained relationships. CONCLUSIONS: Our analysis demonstrates both the frequency with which cancer survivors and families must make financial sacrifices as a result of their cancer, and the variety of forms that this sacrifice can take, even for individuals who have health insurance. The many types of financial hardship create challenges that are unique to each survivor and family. IMPLICATIONS FOR CANCER SURVIVORS: Interventions that allow for personalized assistance with the specific financial and social needs of cancer survivors and their families have the potential to address a critical aspect of the long-term wellbeing of this important population.

      3. Medicaid coverage of sexually transmitted disease service visitsexternal icon
        Pearson WS, Spicknall IH, Cramer R, Jenkins WD.
        Am J Prev Med. 2019 May 16.
        INTRODUCTION: Chlamydia and gonorrhea are the most commonly reported notifiable infections in the U.S., with direct medical costs for the treatment of these infections exceeding $700 million annually. Medicaid currently covers approximately 80 million low-income Americans, including a high percentage of racial and ethnic minorities. Studies have shown that racial and ethnic minority populations, particularly those with low SES, are at an increased risk of acquiring a sexually transmitted disease. Therefore, as Medicaid expands, there will likely be a greater demand for sexually transmitted disease services in community-based physician offices. To determine demand for these services among Medicaid enrollees, this study examined how often Medicaid was used to pay for sexually transmitted disease services received in this setting. METHODS: This study combined 2014 and 2015 data from the National Ambulatory Medical Care Survey and tested for differences in the proportion of visits with an expected payment source of Medicaid when sexually transmitted disease services were and were not provided. All analyses were conducted in October 2018. RESULTS: During 2014-2015, an estimated 25 million visits received a sexually transmitted disease service. Medicaid paid for a greater percentage of sexually transmitted disease visits (35.5%, 95% CI=22.5%, 51.1%) compared with non-sexually transmitted disease visits (12.1%, 95% CI=10.8%, 13.6%). Logistic regression modeling, controlling for age, sex, and race of the patient, showed that visits covered by Medicaid had increased odds of paying for a sexually transmitted disease service visit (OR=1.97, 95% CI=1.12, 3.46), compared with other expected payment sources. CONCLUSIONS: Focusing sexually transmitted disease prevention in Medicaid populations could reduce sexually transmitted disease incidence and resulting morbidity and costs.

    • Healthcare Associated Infections
      1. Total duration of antimicrobial therapy resulting from inpatient hospitalizationexternal icon
        Dyer AP, Dodds Ashley E, Anderson DJ, Sarubbi C, Wrenn R, Hicks LA, Srinivasan A, Moehring RW.
        Infect Control Hosp Epidemiol. 2019 May 28:1-8.
        OBJECTIVE: To assess the feasibility of electronic data capture of postdischarge durations and evaluate total durations of antimicrobial exposure related to inpatient hospital stays. DESIGN: Multicenter, retrospective cohort study. SETTING: Two community hospitals and 1 academic medical center. PATIENTS: Hospitalized patients who received >/=1 dose of a systemic antimicrobial agent. METHODS: We collected and reviewed electronic data on inpatient and discharge antimicrobial prescribing from April to September 2016 in 3 pilot hospitals. Inpatient antimicrobial use was obtained from electronic medication administration records. Postdischarge antimicrobial use was calculated from electronic discharge prescriptions. We completed a manual validation to evaluate the ability of electronic prescriptions to capture intended postdischarge antibiotics. Inpatient, postdischarge, and total lengths of therapy (LOT) per admission were calculated to assess durations of antimicrobial therapy attributed to hospitalization. RESULTS: A total of 45,693 inpatient admissions were evaluated. Antimicrobials were given during 23,447 admissions (51%), and electronic discharge prescriptions were captured in 7,442 admissions (16%). Manual validation revealed incomplete data capture in scenarios in which prescribers avoided the electronic system. The postdischarge LOT among admissions with discharge antimicrobials was median 8 days (range, 1-360) with peaks at 5, 7, 10, and 14 days. Postdischarge days accounted for 38% of antimicrobial exposure days. CONCLUSION: Discharge antimicrobial therapy accounted for a large portion of antimicrobial exposure related to inpatient hospital stays. Discharge prescription data can feasibly be captured through electronic prescribing records and may aid in designing stewardship interventions at transitions of care.

      2. OBJECTIVE: To evaluate the Orange County Clostridium difficile infection (CDI) prevention collaborative’s effect on rates of CDI in acute-care hospitals (ACHs) in Orange County, California. DESIGN: Controlled interrupted time series. METHODS: We convened a CDI prevention collaborative with healthcare facilities in Orange County to reduce CDI incidence in the region. Collaborative participants received onsite infection control and antimicrobial stewardship assessments, interactive learning and discussion sessions, and an interfacility transfer communication improvement initiative during June 2015-June 2016. We used segmented regression to evaluate changes in monthly hospital-onset (HO) and community-onset (CO) CDI rates for ACHs. The baseline period comprised 17 months (January 2014-June 2015) and the follow-up period comprised 28 months (September 2015-December 2017). All 25 Orange County ACHs were included in the CO-CDI model to account for direct and indirect effects of the collaborative. For comparison, we assessed HO-CDI and CO-CDI rates among 27 ACHs in 3 San Francisco Bay Area counties. RESULTS: HO-CDI rates in the 15 participating Orange County ACHs decreased 4% per month (incidence rate ratio [IRR], 0.96; 95% CI, 0.95-0.97; P &lt; .0001) during the follow-up period compared with the baseline period and 3% (IRR, 0.97; 95% CI, 0.95-0.99; P = .002) per month compared to the San Francisco Bay Area nonparticipant ACHs. Orange County CO-CDI rates declined 2% per month (IRR, 0.98; 95% CI, 0.96-1.00; P = .03) between the baseline and follow-up periods. This decline was not statistically different from the San Francisco Bay Area ACHs (IRR, 0.97; 95% CI, 0.95-1.00; P = .09). CONCLUSIONS: Our analysis of ACHs in Orange County provides evidence that coordinated, regional multifacility initiatives can reduce CDI incidence.

      3. Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2)external icon
        Zingg W, Park BJ, Storr J, Ahmad R, Tarrant C, Castro-Sanchez E, Perencevich E, Widmer A, Krause KH, Kilpatrick C, Tomczyk S, Allegranzi B, Cardo D, Pittet D.
        Antimicrob Resist Infect Control. 2019 ;8:83.
        Background: The high burden of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) is partially due to excessive antimicrobial use both in human and animal medicine worldwide. How can technology help to overcome challenges in infection prevention and control (IPC) and to prevent HAI and emerging AMR? Methods: In June 2017, 42 international experts convened in Geneva, Switzerland to discuss four potential domains of technology in IPC and AMR: 1) role and potential contribution of microbiome research; 2) whole genome sequencing; 3) effectiveness and benefit of antimicrobial environmental surfaces; and 4) future research in hand hygiene. Results: Research on the microbiome could expand understanding of antimicrobial use and also the role of probiotics or even faecal transplantation for therapeutic purposes. Whole genome sequencing will provide new insights in modes of transmission of infectious diseases. Although it is a powerful tool for public health epidemiology, some challenges with interpretation and costs still need to be addressed. The effectiveness and cost-effectiveness of antimicrobially coated or treated environmental high-touch surfaces requires further research before they can be recommended for routine use. Hand hygiene implementation can be advanced, where technological enhancement of surveillance, technique and compliance are coupled with reminders for healthcare professionals. Conclusions: The four domains of technological innovation contribute to the prevention of HAI and AMR at different levels. Microbiome research may offer innovative concepts for future prevention, whole genome sequencing could detect new modes of transmission and become an additional tool for effective public health epidemiology, antimicrobial surfaces might help to decrease the environment as source of transmission but continue to raise more questions than answers, and technological innovation may have a role in improving surveillance approaches and supporting best practice in hand hygiene.

    • Immunity and Immunization
      1. National Immunization Technical Advisory Groups (NITAGs) are multidisciplinary national experts who provide independent, evidence-informed vaccine policy recommendations to national health authorities. An essential NITAG function is to ensure that these decisions are grounded in the best available evidence generated through a systematic, transparent process. However, in many low- and middle-income countries (LMICs), experience with this decision making method is limited. The Task Force for Global Health manages the Partnership for Influenza Vaccine Introduction (PIVI) program in collaboration with the Centers for Disease Control and Prevention, Ministries of Health, corporate partners and others. During 2017, PIVI worked with its country partners and the World Health Organization regional and local offices to assess NITAG strengthening needs and to provide technical assistance in 7 LMIC countries (Laos Peoples Democratic Republic, Mongolia, Vietnam, Armenia, Cote d’Ivoire; Moldova and the Republic of Georgia). Our workshops supported general NITAG capacity building and the evidence-based review process using vaccines of interest to the country. For NITAGs reviewing evidence on seasonal influenza, we developed an influenza resource package to support their review and provide country-relevant information in an easy to use format. Of the seven NITAGs trained, six have applied some of the concepts learnt: revision or development of formal transparent, systematic procedures for their operations; preparation of recommendations on seasonal influenza vaccination using quality-assessed data from systematic searches and local data; and have applied the principles learned for making other new vaccine recommendations. Our experience confirms that LMIC NITAGs are considerably under-resourced without adequate technical support or access to global peer-reviewed literature. Ongoing support from NITAG partners must be secured and creative approaches might be needed to help countries achieve the GVAP 2020 target and support development of sustainable vaccine policies and programs.

      2. Genotypes of clinical varicella-zoster virus isolates from Manaus, Brazilexternal icon
        Bastos MS, Folster J, Alvarenga OP, Sampaio DA, Rabelo RM, Joao GA, Lacerda MV, Schmid DS.
        Rev Soc Bras Med Trop. 2019 May 16;52:e20180166.
        INTRODUCTION: Vaccination against varicella-zoster virus (VZV) has been effective and safe in countries that routinely administer the vaccine. Brazil began universal VZV vaccination in 2013. This study aimed to identify VZV genotypes present in Manaus, Brazil prior to widespread immunization. METHODS: Vesicular lesions or cerebral-spinal-fluid samples were collected from patients diagnosed with VZV, herpes zoster, or meningitis/encephalitis. DNA was extracted, amplified, and sequenced. RESULTS: Half the isolates were clade-5 viruses and the remaining were divided between the European clades 1 and 3. CONCLUSIONS: This study provides insights into the circulating VZV genotypes in Manaus prior to widespread vaccination.

      3. Meeting report narcolepsy and pandemic influenza vaccination: What we know and what we need to know before the next pandemic? A report from the 2nd IABS meetingexternal icon
        Edwards K, Hanquet G, Black S, Mignot E, Jankosky C, Shimabukuro T, Miller E, Nohynek H, Neels P.
        Biologicals. 2019 May 23.
        A group of scientific and public health experts and key stakeholders convened to discuss the state of knowledge on the relationship between adjuvanted monovalent inactivated 2009 influenza A H1N1 vaccines used during the 2009 influenza pandemic and narcolepsy. There was consensus that an increased risk of narcolepsy was consistently observed after Pandemrix (AS03-adjuvanted) vaccine, but similar associations following Arepanrix (AS03-adjuvanted) or Focetria (MF59-adjuvanted) vaccines were not observed. Whether the differences are due to vaccine composition or other factors such as the timing of large-scale vaccination programs relative to H1N1pdm09 wild-type virus circulation in different geographic regions is not clear. The limitations of retrospective observational methodologies could also be contributing to some of the differences across studies. More basic and epidemiologic research is needed to further elucidate the association between adjuvanted influenza vaccine and narcolepsy and its mechanism and to inform planning and preparation for vaccination programs in advance of the next influenza pandemic.

      4. Evaluation of intussusception after oral monovalent rotavirus vaccination in South Africaexternal icon
        Groome MJ, Tate JE, Arnold M, Chitnis M, Cox S, de Vos C, Kirsten M, le Grange SM, Loveland J, Machaea S, Maharaj A, Andrews N, Madhi SA, Parashar UD.
        Clin Infect Dis. 2019 May 24.
        BACKGROUND: Post-licensure studies have shown an association between rotavirus vaccination and intussusception. We assessed the risk of intussusception associated with Rotarix(R) (RV1) administration, at six and 14 weeks of age, in an upper-middle income country, South Africa. METHODS: Active prospective surveillance for intussusception was conducted in eight hospitals from September 2013-December 2017. Retrospective case enrolment was done at one hospital from July 2012-August 2013. Demographic characteristics, symptom onset and rotavirus vaccine status were ascertained. Using the self-controlled case-series method, we estimated age-adjusted incidence-rate ratios within 1-7, 8-21, and 1-21 days of rotavirus vaccination in children aged 28-275 days at onset of symptoms. In addition, age-matched controls were enrolled for a subset of cases (n=169), and a secondary analysis performed. RESULTS: There were 346 cases included in the case-series analysis. Post-dose one, there were zero intussusception cases within 1-7 days, and five cases within 8-21 days of vaccination. Post-dose two, 15 cases occurred within 1-7 days, and 18 cases within 8-21 days of vaccination. There was no increased risk of intussusception 1-7 days after dose one (no cases observed) or dose two (relative incidence (RI): 1.71; 95% confidence interval (CI) 0.83-3.01). Similarly, there was no increased risk 8-21 days after the first (RI: 4.01; 95% CI 0.87-10.56) or second dose (RI: 0.96; 95% CI 0.52-1.60). Results were similar for the case-control analysis. CONCLUSIONS: The risk of intussusception in the 21 days after the first or second dose of RV1 was not higher than the background risk among South Africa infants.

      5. Sociodemographic and clinical correlates of human papillomavirus vaccine attitudes and receipt among Wisconsin adolescentsexternal icon
        Hanson KE, McLean HQ, Belongia EA, Stokley S, McNeil MM, Gee J, VanWormer JJ.
        Papillomavirus Res. 2019 May 25.
        Few studies have assessed adolescent human papillomavirus (HPV) vaccine attitudes and whether they are associated with vaccination uptake. This study characterized HPV vaccine attitudes among male and female adolescents, identified factors associated with attitude changes, and examined associations between attitudes and vaccination receipt. Surveys were administered to adolescents aged 15-16 years who had not completed the HPV vaccine series. A modified version of the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS) was employed to assess barriers, harms, ineffectiveness, and uncertainties scores. Surveys were available from 108 participants; 63% were male and 33% had initiated the HPV vaccine series at baseline. CHIAS scores significantly decreased (i.e., became more favorable) between baseline and follow up for barriers (p=0.01) and uncertainties (p<0.01). At least one sociodemographic/clinical factor was associated with changes in each score. Attitude changes were not associated with receipt of HPV vaccine, although adolescents with higher baseline harms scores were significantly less likely to receive an HPV vaccine dose (OR=0.67). Adolescents’ HPV vaccine attitudes slightly improved over a one year period during which an intervention was implemented. More research is needed to learn how parent and adolescent HPV vaccine attitudes form, and how best to address concerns about vaccine harms.

      6. Effectiveness of 10-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in Pakistanexternal icon
        Riaz A, Mohiuddin S, Husain S, Yousafzai MT, Sajid M, Kabir F, Rehman NU, Mirza W, Salam B, Nadeem N, Pardhan K, Khan KM, Raza SJ, Arif F, Iqbal K, Zuberi HK, Whitney CG, Omer SB, Zaidi AK, Ali A.
        Int J Infect Dis. 2019 Mar;80:28-33.
        OBJECTIVE: To assess the effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) against invasive pneumococcal disease (IPD) due to vaccine serotypes of Streptococcus pneumoniae post introduction of the vaccine into the routine immunization program in Pakistan. METHODS: A matched case-control study was conducted at 16 hospitals in Sindh Province, Pakistan. Children aged <5years (eligible to receive PCV10) who presented with radiographically confirmed pneumonia and/or meningitis were enrolled as cases. PCR for the lytA gene was conducted on blood (for radiographic pneumonia) and cerebrospinal fluid (for meningitis) samples to detect S. pneumoniae. The proportion of IPD due to vaccine serotypes (including vaccine-related serogroups) was determined through serial multiplex PCR. For each case, at least five controls were enrolled from children hospitalized at the same institution, matched for age, district, and season. RESULTS: Of 92 IPD patients enrolled during July 2013 to March 2017, 24 (26.0%) had disease caused by vaccine serotypes. Most case (87.5% of 24) and control (66.4% of 134) children had not received any PCV10 doses. The estimated effectiveness of PCV10 against vaccine-type IPD was 72.7% (95% confidence interval (CI) -7.2% to 92.6%) with at least one dose, 78.8% (95% CI -11.9% to 96.0%) for at least two doses, and 81.9% (95% CI -55.7% to 97.9%) for all three doses of vaccine. CONCLUSIONS: The vaccine effectiveness point estimates for PCV10 were high and increased with increasing number of doses. However, vaccine effectiveness estimates did not reach statistical significance, possibly due to low power. The findings indicate the likely impact of vaccine in reducing the burden of vaccine-type IPD if vaccine uptake can be improved.

    • Injury and Violence
      1. An RCT of Dating Matters: Effects on Teen Dating Violence and Relationship Behaviorsexternal icon
        Niolon PH, Vivolo-Kantor AM, Tracy AJ, Latzman NE, Little TD, DeGue S, Lang KM, Estefan LF, Ghazarian SR, McIntosh WL, Taylor B, Johnson LL, Kuoh H, Burton T, Fortson B, Mumford EA, Nelson SC, Joseph H, Valle LA, Tharp AT.
        Am J Prev Med. 2019 May 16.
        INTRODUCTION: Teen dating violence is a serious public health problem with few effective prevention strategies. This study examines whether the Dating Matters comprehensive prevention model, compared with a standard of care intervention, prevented negative relationship behaviors and promoted positive relationship behaviors. STUDY DESIGN: This longitudinal, cluster-RCT compared the effectiveness of Dating Matters with standard of care across middle school. Standard of care was an evidence-based teen dating violence prevention curriculum (Safe Dates) implemented in eighth grade. SETTING/PARTICIPANTS: Forty-six middle schools in high-risk urban neighborhoods in four U.S. cities were randomized. Schools lost to follow-up were replaced with new schools, which were independently randomized (71% school retention). Students were surveyed in fall and spring of sixth, seventh, and eighth grades (2012-2016). The analysis sample includes students from schools implementing Dating Matters or standard of care for >2 years who started sixth grade in the fall of 2012 or 2013 and had dated (N=2,349 students, mean age 12 years, 49% female, and 55% black, non-Hispanic, 28% Hispanic, 17% other). INTERVENTION: Dating Matters is a comprehensive, multicomponent prevention model including classroom-delivered programs for sixth to eighth graders, training for parents of sixth to eighth graders, educator training, a youth communications program, and local health department activities to assess capacity and track teen dating violence-related policy and data. MAIN OUTCOME MEASURES: Self-reported teen dating violence perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills were examined as outcomes. Imputation and analyses were conducted in 2017. RESULTS: Latent panel models demonstrated significant program effects for three of four outcomes; Dating Matters students reported 8.43% lower teen dating violence perpetration, 9.78% lower teen dating violence victimization, and 5.52% lower use of negative conflict resolution strategies, on average across time points and cohorts, than standard of care students. There were no significant effects on positive relationship behaviors. CONCLUSIONS: Dating Matters demonstrates comparative effectiveness, through middle school, for reducing unhealthy relationship behaviors, such as teen dating violence and use of negative conflict resolution strategies, relative to the standard of care intervention. TRIAL REGISTRATION: This study is registered at NCT01672541.

    • Laboratory Sciences
      1. The concordance of the limiting antigen and the Bio-Rad avidity assays in persons from Estonia infected mainly with HIV-1 CRF06_cpxexternal icon
        Huik K, Soodla P, Pauskar M, Owen SM, Luo W, Murphy G, Jogeda EL, Kallas E, Rajasaar H, Avi R, Masciotra S, Lutsar I.
        PLoS One. 2019 ;14(5):e0217048.
        BACKGROUND: Serological assays to determine HIV incidence have contributed to estimates of HIV incidence, monitoring of HIV spread, and evaluation of prevention strategies. Two frequently used incidence assays are the Sedia HIV-1 LAg-Avidity EIA (LAg) and the Bio-Rad avidity incidence (BRAI) assays with a mean duration of recent infection (MDRI) of 130 and 240 days for subtype B infections, respectively. Little is known about how these assays perform with recombinant HIV-1 strains. We evaluated the concordance of these assays in a population infected mainly with HIV-1 CRF06_cpx. MATERIAL/METHODS: Remnant serum samples (n = 288) collected from confirmed, newly-diagnosed HIV-positive persons from Estonia in 2013 were tested. Demographic and clinical data were extracted from clinical databases. LAg was performed according to the manufacturer’s protocol and BRAI testing was done using a validated protocol. Samples with LAg-pending or BRAI-invalid results were reclassified as recent if they were from persons with viral loads <1000 copies/mL or were reclassified as long-term if presenting with AIDS. RESULTS: In total 325 new HIV infections were diagnosed in 2013 in Estonia. Of those 276 persons were tested with both LAg and BRAI. Using assay results only, the recency rate was 44% and 70% by LAg and BRAI, respectively. The majority of samples (92%) recent by LAg were recent by BRAI. Similarly, 89% of samples long-term by BRAI were long-term by LAg. After clinical information was included in the analysis, the recency rate was 44% and 62% for LAg and BRAI, respectively. The majority of samples (86%) recent by LAg were recent by BRAI and 91% of long-term infections by BRAI were long-term by LAg. CONCLUSIONS: Comparison of LAg and BRAI results in this mostly CRF06_cpx-infected population showed good concordance for incidence classification. Our finding of a higher recency rate with BRAI in this population is likely related to the longer MDRI for this assay.

      2. Evaluation of mannose binding lectin gene variants in pediatric influenza virus-related critical illnessexternal icon
        Levy ER, Yip WK, Super M, Ferdinands JM, Mistry AJ, Newhams MM, Zhang Y, Su HC, McLaughlin GE, Sapru A, Loftis LL, Weiss SL, Hall MW, Cvijanovich N, Schwarz A, Tarquinio KM, Mourani PM, Randolph AG.
        Front Immunol. 2019 ;10:1005.
        Background: Mannose-binding lectin (MBL) is an innate immune protein with strong biologic plausibility for protecting against influenza virus-related sepsis and bacterial co-infection. In an autopsy cohort of 105 influenza-infected young people, carriage of the deleterious MBL gene MBL2_Gly54Asp(“B”) mutation was identified in 5 of 8 individuals that died from influenza-methicillin-resistant Staphylococcus aureus (MRSA) co-infection. We evaluated MBL2 variants known to influence MBL levels with pediatric influenza-related critical illness susceptibility and/or severity including with bacterial co-infections. Methods: We enrolled children and adolescents with laboratory-confirmed influenza infection across 38 pediatric intensive care units from November 2008 to June 2016. We sequenced MBL2 “low-producer” variants rs11003125(“H/L”), rs7096206(“Y/X”), rs1800450Gly54Asp(“B”), rs1800451Gly57Glu(“C”), rs5030737Arg52Cys(“D”) in patients and biologic parents. We measured serum levels and compared complement activity in low-producing homozygotes (“B/B,” “C/C”) to HYA/HYA controls. We used a population control of 1,142 healthy children and also analyzed family trios (PBAT/HBAT) to evaluate disease susceptibility, and nested case-control analyses to evaluate severity. Results: We genotyped 420 patients with confirmed influenza-related sepsis: 159 (38%) had acute lung injury (ALI), 165 (39%) septic shock, and 30 (7%) died. Although bacterial co-infection was diagnosed in 133 patients (32%), only MRSA co-infection (n = 33, 8% overall) was associated with death (p < 0.0001), present in 11 of 30 children that died (37%). MBL2 variants predicted serum levels and complement activation as expected. We found no association between influenza-related critical illness susceptibility and MBL2 variants using family trios (633 biologic parents) or compared to population controls. MBL2 variants were not associated with admission illness severity, septic shock, ALI, or bacterial co-infection diagnosis. Carriage of low-MBL producing MBL2 variants was not a risk factor for mortality, but children that died did have higher carriage of one or more B alleles (OR 2.3; p = 0.007), including 7 of 11 with influenza MRSA-related death (vs. 2 of 22 survivors: OR 14.5, p = 0.0002). Conclusions: MBL2 variants that decrease MBL levels were not associated with susceptibility to pediatric influenza-related critical illness or with multiple measures of critical illness severity. We confirmed a prior report of higher B allele carriage in a relatively small number of young individuals with influenza-MRSA associated death.

      3. Vagococcus bubulae sp. nov., isolated from ground beef, and Vagococcus vulneris sp. nov., isolated from a human foot woundexternal icon
        Shewmaker PL, Whitney AM, Gulvik CA, Humrighouse BW, Gartin J, Moura H, Barr JR, Moore ER, Karlsson R, Pinto TC, Teixeira LM.
        Int J Syst Evol Microbiol. 2019 May 24.
        Two unusual catalase-negative, Gram-stain-positive, Vagococcus-like isolates that were referred to the CDC Streptococcus Laboratory for identification are described. Strain SS1994(T) was isolated from ground beef and strain SS1995(T) was isolated from a human foot wound. Comparative 16S rRNA gene sequence analysis of isolates SS1994(T) and SS1995(T) against Vagococcus type strain sequences supported their inclusion in the genus Vagococcus. Strain SS1994(T) showed high sequence similarity (>97.0 %) to the two most recently proposed species, Vagococcus martis (99.2 %) and Vagococcus teuberi (99.0 %) followed by Vagococcus penaei (98.8 %), strain SS1995(T) (98.6 %), Vagococcus carniphilus (98.0 %), Vagococcus acidifermentans (98.0 %) and Vagococcus fluvialis (97.9 %). The 16S rRNA gene sequence of strain SS1995(T) was most similar to V. penaei (99.1 %), followed by SS1994(T) (98.6 %), V. martis (98.4 %), V. teuberi (98.1 %), V. acidifermentans (97.8 %), and both V. carniphilus and V. fluvialis (97.5 %). A polyphasic taxonomic study using conventional biochemical and the rapid ID 32 STREP system, MALDI-TOF MS, cell fatty acid analysis, pairwise sequence comparisons of the 16S rRNA, rpoA, rpoB, pheS and groL genes, and comparative core and whole genome sequence analyses revealed that strains SS1994(T) and SS1995(T) were two novel Vagococcus species. The novel taxonomic status of the two isolates was confirmed with core genome phylogeny, average nucleotide identity <84 % and in silico DNA-DNA hybridization <28 % to any other Vagococcus species. The names Vagococcusbubulae SS1994(T)=(CCUG 70831(T)=LMG 30164(T)) and Vagococcusvulneris SS1995(T)=(CCUG 70832(T)=LMG 30165(T)) are proposed.

      4. Fecal IgA against a sporozoite antigen at 12 months is associated with delayed time to subsequent cryptosporidiosis in urban Bangladesh: a prospective cohort studyexternal icon
        Steiner KL, Kabir M, Priest JW, Hossain B, Gilchrist CA, Cook H, Ma JZ, Korpe PS, Ahmed T, Faruque AS, Haque R, Petri WA.
        Clin Infect Dis. 2019 May 25.
        In this prospective cohort study of Bangladeshi children, greater fecal IgA, but not plasma IgG, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children.

      5. Redox (phospho)lipidomics of signaling in inflammation and programmed cell deathexternal icon
        Tyurina YY, St Croix CM, Watkins SC, Watson AM, Epperly MW, Anthonymuthu TS, Kisin ER, Vlasova , Krysko O, Krysko DV, Kapralov AA, Dar HH, Tyurin VA, Amoscato AA, Popova EN, Bolevich SB, Timashev PS, Kellum JA, Wenzel SE, Mallampalli RK, Greenberger JS, Bayir H, Shvedova AA, Kagan VE.
        J Leukoc Biol. 2019 May 9.
        In addition to the known prominent role of polyunsaturated (phospho)lipids as structural blocks of biomembranes, there is an emerging understanding of another important function of these molecules as a highly diversified signaling language utilized for intra- and extracellular communications. Technological developments in high-resolution mass spectrometry facilitated the development of a new branch of metabolomics, redox lipidomics. Analysis of lipid peroxidation reactions has already identified specific enzymatic mechanisms responsible for the biosynthesis of several unique signals in response to inflammation and regulated cell death programs. Obtaining comprehensive information about millions of signals encoded by oxidized phospholipids, represented by thousands of interactive reactions and pleiotropic (patho)physiological effects, is a daunting task. However, there is still reasonable hope that significant discoveries, of at least some of the important contributors to the overall overwhelmingly complex network of interactions triggered by inflammation, will lead to the discovery of new small molecule regulators and therapeutic modalities. For example, suppression of the production of AA-derived pro-inflammatory mediators, HXA3 and LTB4, by an iPLA2 gamma inhibitor, R-BEL, mitigated injury associated with the activation of pro-inflammatory processes in animals exposed to whole-body irradiation. Further, technological developments promise to make redox lipidomics a powerful approach in the arsenal of diagnostic and therapeutic instruments for personalized medicine of inflammatory diseases and conditions.

    • Maternal and Child Health
      1. Baseline urinary tract imaging in infants enrolled in the UMPIRE Protocol for Children with Spina Bifidaexternal icon
        Tanaka ST, Paramsothy P, Thibadeau J, Wiener JS, Joseph DB, Cheng EY, Tu D, Austin C, Koh CJ, Wallis MC, Walker WO, Smith KA, Routh JC, Baum MA.
        J Urol. 2019 Jun;201(6):1193-1198.
        PURPOSE: The lifetime risk of renal damage in children with spina bifida is high but only limited baseline imaging data are available for this population. We evaluated a large prospective cohort of infants with spina bifida to define their baseline imaging characteristics. MATERIALS AND METHODS: The UMPIRE Protocol for Young Children with Spina Bifida is an iterative quality improvement protocol that follows a cohort of newborns at 9 United States centers. Using descriptive statistics, we report the initial baseline imaging characteristics, specifically regarding renal bladder ultrasound, cystogram and dimercaptosuccinic acid nuclear medicine scan. RESULTS: Data on 193 infants from 2015 to 2018 were analyzed. Renal-bladder ultrasound was normal in 55.9% of infants, while 40.4% had Society for Fetal Urology grade 1 to 2 hydronephrosis in at least 1 kidney, 3.7% had grade 3 to 4 hydronephrosis in either kidney and 21.8% had grade 1 or higher bilateral hydronephrosis. There was no vesicoureteral reflux in 84.6% of infants. A third of enrolled infants underwent dimercaptosuccinic acid nuclear medicine renal scan, of whom 92.4% had no renal defects and 93.9% had a difference in differential function of less than 15%. CONCLUSIONS: The majority of infants born with spina bifida have normal baseline imaging characteristics and normal urinary tract anatomy at birth. This proactive protocol offers careful scheduled surveillance of the urinary tract with the goal of lifelong maintenance of normal renal function and healthy genitourinary development.

    • Medicine
      1. Preventive medicine physicians and the Centers for Disease Control and Prevention’s 6|18 Initiativeexternal icon
        Livingston CJ, Allison RD, Niebuhr DW, Sherin KM, Costales VC, Berenji M, Phares TM, Caplan LS, Nelkovski L, Seeff LC, Singleton CM.
        Am J Prev Med. 2019 May 23.

        [No abstract]

    • Nutritional Sciences
      1. Age-specific reference ranges are needed to interpret serum methylmalonic acid concentrations in the US populationexternal icon
        Mineva EM, Sternberg MR, Zhang M, Aoki Y, Storandt R, Bailey RL, Pfeiffer CM.
        Am J Clin Nutr. 2019 May 25.
        BACKGROUND: Serum vitamin B-12 is measured to evaluate vitamin B-12 status. Serum methylmalonic acid (MMA) is a specific functional indicator of vitamin B-12 status; however, concentrations increase with impaired renal function. OBJECTIVE: The aim of this study was to describe the distribution of serum vitamin B-12 and MMA in US adults, and estimate age-specific reference intervals for serum MMA in a healthy subpopulation with replete vitamin B-12 status and normal renal function. METHODS: We examined cross-sectional data for serum vitamin B-12 and MMA in adults participating in the NHANES from 2011 to 2014. Vitamin B-12 was measured by electrochemiluminescence assay and MMA by isotope-dilution liquid chromatography-tandem mass spectrometry. RESULTS: In both bivariate and multivariate analyses, age, race/Hispanic origin, and vitamin B-12 supplement use were generally significantly associated with serum vitamin B-12 and MMA concentrations. Serum MMA concentrations increased with age, particularly in persons aged >/=70 y. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations than non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were widest for persons aged >/=70 y compared with younger age groups. Compared with the overall population, the central 95% reference intervals for serum MMA concentrations were considerably narrower for a vitamin B-12-replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, whereas serum MMA showed notable, increases with impaired renal function. CONCLUSIONS: The higher serum MMA concentrations throughout the entire distribution in older persons (especially persons aged >/=70 y) who are vitamin B-12-replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret vitamin B-12 status in epidemiologic research.

      2. Evaluation of measurement error in 24-hour dietary recall for assessing sodium and potassium intake among US adults – National Health and Nutrition Examination Survey (NHANES), 2014external icon
        Va P, Dodd KW, Zhao L, Thompson-Paul AM, Mercado CI, Terry AL, Jackson SL, Wang CY, Loria CM, Moshfegh AJ, Rhodes DG, Cogswell ME.
        Am J Clin Nutr. 2019 Jun 1;109(6):1672-1682.
        BACKGROUND: Understanding measurement error in sodium and potassium intake is essential for assessing population intake and studying associations with health outcomes. OBJECTIVE: The aim of this study was to compare sodium and potassium intake derived from 24-h dietary recall (24HDR) with intake derived from 24-h urinary excretion (24HUE). DESIGN: Data were analyzed from 776 nonpregnant, noninstitutionalized US adults aged 20-69 y who completed 1-to-2 24HUE and 24HDR measures in the 2014 NHANES. A total of 1190 urine specimens and 1414 dietary recalls were analyzed. Mean bias was estimated as mean of the differences between individual mean 24HDR and 24HUE measurements. Correlations and attenuation factors were estimated using the Kipnis joint-mixed effects model accounting for within-person day-to-day variability in sodium excretion. The attenuation factor reflects the degree to which true associations between long-term intake (estimated using 24HUEs) and a hypothetical health outcome would be approximated using a single 24HDR: values near 1 indicate close approximation and near 0 indicate bias toward null. Estimates are reported for sodium, potassium, and the sodium: potassium (Na/K) ratio. Model parameters can be used to estimate correlations/attenuation factors when multiple 24HDRs are available. RESULTS: Overall, mean bias for sodium was -452 mg (95% CI: -646, -259), for potassium -315 mg (CI: -450, -179), and for the Na/K ratio -0.04 (CI: -0.15, 0.07, NS). Using 1 24HDR, the attenuation factor for sodium was 0.16 (CI: 0.09, 0.21), for potassium 0.25 (CI:0.16, 0.36), and for the Na/K ratio 0.20 (CI: 0.10, 0.25). The correlation for sodium was 0.27 (CI: 0.16, 0.37), for potassium 0.35 (CI: 0.26, 0.55), and for the Na/K ratio 0.27 (CI: 0.13, 0.32). CONCLUSIONS: Compared with 24HUE, using 24HDR underestimates mean sodium and potassium intake but is unbiased for the Na/K ratio. Additionally, using 24HDR as a measure of exposure in observational studies attenuates the true associations of sodium and potassium intake with health outcomes.

    • Occupational Safety and Health
      1. This study examined whether different combinations of ambient temperature and relative humidity for the effective wet bulb globe temperature, in conjunction with two different levels of clothing adjustment factors, elicit a similar level of heat strain consistent with the current threshold limit value guidelines. Twelve healthy, physically active men performed four 15-min sessions of cycling at a fixed rate of metabolic heat production of 350 watts. Each trial was separated by a 15-min recovery period under four conditions: (1) Cotton coveralls + dry condition (WD: 45.5 degrees C dry-bulb, 15% relative humidity); (2) Cotton coveralls + humid condition (WH: 31 degrees C dry-bulb, 84% relative humidity); (3) Protective clothing + dry condition (PD: 30 degrees C dry-bulb, 15% relative humidity); and (4) Protective clothing + humid condition (PH: 20 degrees C dry-bulb, 80% relative humidity). Gloves (mining or chemical) and headgear (helmet or powered air-purifying respirator) were removed during recovery with hydration ad libitum. Rectal temperature (Tre), skin temperature (Tsk), physiological heat strain (PSI), perceptual heat strain (PeSI), and body heat content were calculated. At the end of the 2-hr trials, Tre remained below 38 degrees C and the magnitude of Tre elevation was not greater than 1 degrees C in all conditions (WD: 0.9, WH: 0.8, WH: 0.7, and PD: 0.6 degrees C). However, Tsk was significantly increased by approximately 2.1 +/- 0.8 degrees C across all conditions (all p </= 0.001). The increase in Tsk was the highest in WD followed by PD, WH, and PH conditions (all p </= 0.001). Although PSI and PeSI did not indicate severe heat strain during the 2-hr intermittent work period, PSI and PeSI were significantly increased over time (p </= 0.001). This study showed that core temperature and heat strain indices (PSI and PeSI) increased similarly across the four conditions. However, given that core temperature increased continuously during the work session, it is likely that the American Conference of Governmental Industrial Hygienist’s TLV((R)) upper limit core temperature of 38.0 degrees C may be surpassed during extended work periods under all conditions.

    • Substance Use and Abuse
      1. Measuring Alcohol Outlet Density: An Overview of Strategies for Public Health Practitionersexternal icon
        Sacks JJ, Brewer RD, Mesnick J, Holt JB, Zhang X, Kanny D, Elder R, Gruenewald PJ.
        J Public Health Manag Pract. 2019 May 20.
        CONTEXT: Excessive alcohol use is responsible for 88 000 deaths in the United States annually and cost the United States $249 billion in 2010. There is strong scientific evidence that regulating alcohol outlet density is an effective intervention for reducing excessive alcohol consumption and related harms, but there is no standard method for measuring this exposure. PROGRAM: We overview the strategies available for measuring outlet density, discuss their advantages and disadvantages, and provide examples of how they can be applied in practice. IMPLEMENTATION: The 3 main approaches for measuring density are container-based (eg, number of outlets in a county), distance-based (eg, average distance between a college and outlets), and spatial access-based (eg, weighted distance between town center and outlets). EVALUATION: While container-based measures are the simplest to calculate and most intuitive, distance-based or spatial access-based measures are unconstrained by geopolitical boundaries and allow for assessment of clustering (an amplifier of certain alcohol-related harms). Spatial access-based measures can also be adjusted for population size/demographics but are the most resource-intensive to produce. DISCUSSION: Alcohol outlet density varies widely across and between locations and over time, which is why it is important to measure it. Routine public health surveillance of alcohol outlet density is important to identify problem areas and detect emerging ones. Distance- or spatial access-based measures of alcohol outlet density are more resource-intensive than container-based measures but provide a much more accurate assessment of exposure to alcohol outlets and can be used to assess clustering, which is particularly important when assessing the relationship between density and alcohol-related harms, such as violent crime.

    • Zoonotic and Vectorborne Diseases
      1. Historical and genomic data reveal the influencing factors on global transmission velocity of plague during the Third Pandemicexternal icon
        Xu L, Stige LC, Leirs H, Neerinckx S, Gage KL, Yang R, Liu Q, Bramanti B, Dean KR, Tang H, Sun Z, Stenseth NC, Zhang Z.
        Proc Natl Acad Sci U S A. 2019 May 28.
        Quantitative knowledge about which natural and anthropogenic factors influence the global spread of plague remains sparse. We estimated the worldwide spreading velocity of plague during the Third Pandemic, using more than 200 years of extensive human plague case records and genomic data, and analyzed the association of spatiotemporal environmental factors with spreading velocity. Here, we show that two lineages, 2.MED and 1.ORI3, spread significantly faster than others, possibly reflecting differences among strains in transmission mechanisms and virulence. Plague spread fastest in regions with low population density and high proportion of pasture- or forestland, findings that should be taken into account for effective plague monitoring and control. Temperature exhibited a nonlinear, U-shaped association with spread speed, with a minimum around 20 degrees C, while precipitation showed a positive association. Our results suggest that global warming may accelerate plague spread in warm, tropical regions and that the projected increased precipitation in the Northern Hemisphere may increase plague spread in relevant regions.

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

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