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Volume 11, Issue 29 July 23, 2019

Related Pages

CDC Science Clips: Volume 11, Issue 29, July 23, 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!

The report consists of these components:

  1. CDC Public Health Grand Rounds
    • Zoonotic and Vectorborne Diseases – Emerging Tickborne Diseases
      1. Tickborne diseases – confronting a growing threatexternal icon
        Paules CI, Marston HD, Bloom ME, Fauci AS.
        N Engl J Med. 2018 Aug 23;379(8):701-703.

        [No abstract]

      2. Multistate infestation with the exotic disease-vector tick Haemaphysalis longicornis – United States, August 2017-September 2018external icon
        Beard CB, Occi J, Bonilla DL, Egizi AM, Fonseca DM, Mertins JW, Backenson BP, Bajwa WI, Barbarin AM, Bertone MA, Brown J, Connally NP, Connell ND, Eisen RJ, Falco RC, James AM, Krell RK, Lahmers K, Lewis N, Little SE, Neault M, Perez de Leon AA, Randall AR, Ruder MG, Saleh MN, Schappach BL, Schroeder BA, Seraphin LL, Wehtje M, Wormser GP, Yabsley MJ, Halperin W.
        MMWR Morb Mortal Wkly Rep. 2018 Nov 30;67(47):1310-1313.
        Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six species of domestic animals, six species of wildlife, and humans. To forestall adverse consequences in humans, pets, livestock, and wildlife, several critical actions are indicated, including expanded surveillance to determine the evolving distribution of H. longicornis, detection of pathogens that H. longicornis currently harbors, determination of the capacity of H. longicornis to serve as a vector for a range of potential pathogens, and evaluation of effective agents and methods for the control of H. longicornis.

      3. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis – United Statesexternal icon
        Biggs HM, Behravesh CB, Bradley KK, Dahlgren FS, Drexler NA, Dumler JS, Folk SM, Kato CY, Lash RR, Levin ML, Massung RF, Nadelman RB, Nicholson WL, Paddock CD, Pritt BS, Traeger MS.
        MMWR Recomm Rep. 2016 May 13;65(2):1-44.
        Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

      4. Impact of wearing and washing/drying of permethrin-treated clothing on their contact irritancy and toxicity for nymphal Ixodes scapularis (Acari: Ixodidae) ticksexternal icon
        Connally NP, Rose DA, Breuner NE, Prose R, Fleshman AC, Thompson K, Wolfe L, Broeckling CD, Eisen L.
        J Med Entomol. 2019 Jan 8;56(1):199-214.
        Permethrin-treated clothing is available as consumer products to prevent bites by tick and insect pests. We used bioassays to examine the impact of wearing and washing/drying of permethrin-treated shirts, pants, and socks, and wearing of treated shoes, on their contact irritancy and toxicity for nymphal Ixodes scapularis Say (Acari: Ixodidae) ticks, the primary vectors in the eastern United States of the causative agents of Lyme disease, human anaplasmosis, and human babesiosis. Pristine permethrin-treated clothing displayed strong contact irritancy and toxicity toward I. scapularis nymphs, with 0-30% of ticks across clothing types and tick sources displaying normal movement 1 h after forced contact for 30-120 s with treated textile. Following 16 d of wear and 16 rounds of machine washing and drying, we recorded reduced concentrations (by 50-90%) of permethrin, compared with pristine treated clothing, from shirts, pants, and socks. This loss of permethrin was associated with reduced contact irritancy and toxicity for ticks after forced contact with worn and washed/dried treated clothing: 31-67% of ticks displayed normal movement 1 h after contact. Nevertheless, the worn and washed/dried treated clothing was still superior to nontreated textile, for which 90-100% of ticks displayed normal movement. Treated shoes, which were worn but not washed, remained as toxic to the ticks as pristine treated shoes. We caution that these laboratory bioassay results should not be interpreted as being directly indicative of the outcome of using washed/worn permethrin-treated clothing in daily life. Although wear and washing/drying did reduce the irritancy and toxicity of permethrin-treated clothing for I. scapularis nymphs more than we had expected, the remaining effect might still reduce the risk of tick bites in a real-life scenario.

      5. Rocky Mountain spotted fever from an unexpected tick vector in Arizonaexternal icon
        Demma LJ, Traeger MS, Nicholson WL, Paddock CD, Blau DM, Eremeeva ME, Dasch GA, Levin ML, Singleton J, Zaki SR, Cheek JE, Swerdlow DL, McQuiston JH.
        N Engl J Med. 2005 Aug 11;353(6):587-94.
        BACKGROUND: Rocky Mountain spotted fever is a life-threatening, tick-borne disease caused by Rickettsia rickettsii. This disease is rarely reported in Arizona, and the principal vectors, Dermacentor species ticks, are uncommon in the state. From 2002 through 2004, a focus of Rocky Mountain spotted fever was investigated in rural eastern Arizona. METHODS: We obtained blood and tissue specimens from patients with suspected Rocky Mountain spotted fever and ticks from patients’ homesites. Serologic, molecular, immunohistochemical, and culture assays were performed to identify the causative agent. On the basis of specific laboratory criteria, patients were classified as having confirmed or probable Rocky Mountain spotted fever infection. RESULTS: A total of 16 patients with Rocky Mountain spotted fever infection (11 with confirmed and 5 with probable infection) were identified. Of these patients, 13 (81 percent) were children 12 years of age or younger, 15 (94 percent) were hospitalized, and 2 (12 percent) died. Dense populations of Rhipicephalus sanguineus ticks were found on dogs and in the yards of patients’ homesites. All patients with confirmed Rocky Mountain spotted fever had contact with tick-infested dogs, and four had a reported history of tick bite preceding the illness. R. rickettsii DNA was detected in nonengorged R. sanguineus ticks collected at one home, and R. rickettsii isolates were cultured from these ticks. CONCLUSIONS: This investigation documents the presence of Rocky Mountain spotted fever in eastern Arizona, with common brown dog ticks (R. sanguineus) implicated as a vector of R. rickettsii. The broad distribution of this common tick raises concern about its potential to transmit R. rickettsii in other settings.

      6. In the 1980s, the blacklegged tick, Ixodes scapularis Say, and rodents were recognized as the principal vector and reservoir hosts of the Lyme disease spirochete Borrelia burgdorferi in the eastern United States, and deer were incriminated as principal hosts for I. scapularis adults. These realizations led to pioneering studies aiming to reduce the risk for transmission of B. burgdorferi to humans by attacking host-seeking ticks with acaricides, interrupting the enzootic transmission cycle by killing immatures infesting rodent reservoirs by means of acaricide-treated nesting material, or reducing deer abundance to suppress tick numbers. We review the progress over the past three decades in the fields of: 1) prevention of human-tick contact with repellents and permethrin-treated clothing, and 2) suppression of I. scapularis and disruption of enzootic B. burgdorferi transmission with environmentally based control methods. Personal protective measures include synthetic and natural product-based repellents that can be applied to skin and clothing, permethrin sprays for clothing and gear, and permethrin-treated clothing. A wide variety of approaches and products to suppress I. scapularis or disrupt enzootic B. burgdorferi transmission have emerged and been evaluated in field trials. Application of synthetic chemical acaricides is a robust method to suppress host-seeking I. scapularis ticks within a treated area for at least 6-8 wk. Natural product-based acaricides or entomopathogenic fungi have emerged as alternatives to kill host-seeking ticks for homeowners who are unwilling to use synthetic chemical acaricides. However, as compared with synthetic chemical acaricides, these approaches appear less robust in terms of both their killing efficacy and persistence. Use of rodent-targeted topical acaricides represents an alternative for homeowners opposed to open distribution of acaricides to the ground and vegetation on their properties. This host-targeted approach also provides the benefit of the intervention impacting the entire rodent home range. Rodent-targeted oral vaccines against B. burgdorferi and a rodent-targeted antibiotic bait have been evaluated in laboratory and field trials but are not yet commercially available. Targeting of deer-via deer reduction or treatment of deer with topical acaricides-can provide area-wide suppression of host-seeking I. scapularis These two deer-targeted approaches combine great potential for protection that impacts the entire landscape with severe problems relating to public acceptance or implementation logistics. Integrated use of two or more methods has unfortunately been evaluated in very few published studies, but additional field evaluations of integrated tick and pathogen strategies are underway.

      7. The blacklegged tick, Ixodes scapularis Say, is the primary vector to humans in the eastern United States of the Lyme disease spirochete Borrelia burgdorferi, as well as causative agents of anaplasmosis and babesiosis. Its close relative in the far western United States, the western blacklegged tick Ixodes pacificus Cooley and Kohls, is the primary vector to humans in that region of the Lyme disease and anaplasmosis agents. Since 1991, when standardized surveillance and reporting began, Lyme disease case counts have increased steadily in number and in geographical distribution in the eastern United States. Similar trends have been observed for anaplasmosis and babesiosis. To better understand the changing landscape of risk of human exposure to disease agents transmitted by I. scapularis and I. pacificus, and to document changes in their recorded distribution over the past two decades, we updated the distribution of these species from a map published in 1998. The presence of I. scapularis has now been documented from 1,420 (45.7%) of the 3,110 continental United States counties, as compared with 111 (3.6%) counties for I. pacificus. Combined, these vectors of B. burgdorferi and other disease agents now have been identified in a total of 1,531 (49.2%) counties spread across 43 states. This marks a 44.7% increase in the number of counties that have recorded the presence of these ticks since the previous map was presented in 1998, when 1,058 counties in 41 states reported the ticks to be present. Notably, the number of counties in which I. scapularis is considered established (six or more individuals or one or more life stages identified in a single year) has more than doubled since the previous national distribution map was published nearly two decades ago. The majority of county status changes occurred in the North-Central and Northeastern states, whereas the distribution in the South remained fairly stable. Two previously distinct foci for I. scapularis in the Northeast and North-Central states appear to be merging in the Ohio River Valley to form a single contiguous focus. Here we document a shifting landscape of risk for human exposure to medically important ticks and point to areas of re-emergence where enhanced vector surveillance and control may be warranted.

      8. Tick-borne zoonoses in the United States: Persistent and emerging threats to human healthexternal icon
        Eisen RJ, Kugeler KJ, Eisen L, Beard CB, Paddock CD.
        Ilar j. 2017 Dec 15;58(3):319-335.
        In the United States, ticks transmit the greatest diversity of arthropod-borne pathogens and are responsible for the most cases of all vector-borne diseases. In recent decades, the number of reported cases of notifiable tick-borne diseases has steadily increased, geographic distributions of many ticks and tick-borne diseases have expanded, and new tick-borne disease agents have been recognized. In this review, we (1) describe the known disease agents associated with the most commonly human-biting ixodid ticks, (2) review the natural histories of these ticks and their associated pathogens, (3) highlight spatial and temporal changes in vector tick distributions and tick-borne disease occurrence in recent decades, and (4) identify knowledge gaps and barriers to more effective prevention of tick-borne diseases. We describe 12 major tick-borne diseases caused by 15 distinct disease agents that are transmitted by the 8 most commonly human-biting ixodid ticks in the United States. Notably, 40% of these pathogens were described within the last two decades. Our assessment highlights the importance of animal studies to elucidate how tick-borne pathogens are maintained in nature, as well as advances in molecular detection of pathogens which has led to the discovery of several new tick-borne disease agents.

      9. Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United Statesexternal icon
        Paddock CD, Sumner JW, Comer JA, Zaki SR, Goldsmith CS, Goddard J, McLellan SL, Tamminga CL, Ohl CA.
        Clin Infect Dis. 2004 Mar 15;38(6):805-11.
        Ticks, including many that bite humans, are hosts to several obligate intracellular bacteria in the spotted fever group (SFG) of the genus Rickettsia. Only Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, has been definitively associated with disease in humans in the United States. Herein we describe disease in a human caused by Rickettsia parkeri, an SFG rickettsia first identified >60 years ago in Gulf Coast ticks (Amblyomma maculatum) collected from the southern United States. Confirmation of the infection was accomplished using serological testing, immunohistochemical staining, cell culture isolation, and molecular methods. Application of specific laboratory assays to clinical specimens obtained from patients with febrile, eschar-associated illnesses following a tick bite may identify additional cases of R. parkeri rickettsiosis and possibly other novel SFG rickettsioses in the United States.

      10. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive studyexternal icon
        Pritt BS, Mead PS, Johnson DK, Neitzel DF, Respicio-Kingry LB, Davis JP, Schiffman E, Sloan LM, Schriefer ME, Replogle AJ, Paskewitz SM, Ray JA, Bjork J, Steward CR, Deedon A, Lee X, Kingry LC, Miller TK, Feist MA, Theel ES, Patel R, Irish CL, Petersen JM.
        Lancet Infect Dis. 2016 May;16(5):556-564.
        BACKGROUND: Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is a multisystem disease caused by Borrelia burgdorferi sensu lato genospecies and characterised by tissue localisation and low spirochaetaemia. In this study we aimed to describe a novel Borrelia species causing Lyme borreliosis in the USA. METHODS: At the Mayo clinic, from 2003 to 2014, we tested routine clinical diagnostic specimens from patients in the USA with PCR targeting the oppA1 gene of B burgdorferi sensu lato. We identified positive specimens with an atypical PCR result (melting temperature outside of the expected range) by sequencing, microscopy, or culture. We collected Ixodes scapularis ticks from regions of suspected patient tick exposure and tested them by oppA1 PCR. FINDINGS: 100 545 specimens were submitted by physicians for routine PCR from Jan 1, 2003 to Sept 30, 2014. From these samples, six clinical specimens (five blood, one synovial fluid) yielded an atypical oppA1 PCR product, but no atypical results were detected before 2012. Five of the six patients with atypical PCR results had presented with fever, four had diffuse or focal rash, three had symptoms suggestive of neurological inclusion, and two were admitted to hospital. The sixth patient presented with knee pain and swelling. Motile spirochaetes were seen in blood samples from one patient and cultured from blood samples from two patients. Among the five blood specimens, the median oppA1 copy number was 180 times higher than that in 13 specimens that tested positive for B burgdorferi sensu stricto during the same time period. Multigene sequencing identified the spirochaete as a novel B burgdorferi sensu lato genospecies. This same genospecies was detected in ticks collected at a probable patient exposure site. INTERPRETATION: We describe a new pathogenic Borrelia burgdorferi sensu lato genospecies (candidatus Borrelia mayonii) in the upper midwestern USA, which causes Lyme borreliosis with unusually high spirochaetaemia. Clinicians should be aware of this new B burgdorferi sensu lato genospecies, its distinct clinical features, and the usefulness of oppA1 PCR for diagnosis. FUNDING: US Centers for Disease Control and Prevention Epidemiology and Laboratory Capacity for Infectious Diseases (ELC) Cooperative Agreement and Mayo Clinic Small Grant programme.

      11. Emergence of a new pathogenic Ehrlichia species, Wisconsin and Minnesota, 2009external icon
        Pritt BS, Sloan LM, Johnson DK, Munderloh UG, Paskewitz SM, McElroy KM, McFadden JD, Binnicker MJ, Neitzel DF, Liu G, Nicholson WL, Nelson CM, Franson JJ, Martin SA, Cunningham SA, Steward CR, Bogumill K, Bjorgaard ME, Davis JP, McQuiston JH, Warshauer DM, Wilhelm MP, Patel R, Trivedi VA, Eremeeva ME.
        N Engl J Med. 2011 Aug 4;365(5):422-9.
        BACKGROUND: Ehrlichiosis is a clinically important, emerging zoonosis. Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Patients with suspected ehrlichiosis routinely undergo testing to ensure proper diagnosis and to ascertain the cause. METHODS: We used molecular methods, culturing, and serologic testing to diagnose and ascertain the cause of cases of ehrlichiosis. RESULTS: On testing, four cases of ehrlichiosis in Minnesota or Wisconsin were found not to be from E. chaffeensis or E. ewingii and instead to be caused by a newly discovered ehrlichia species. All patients had fever, malaise, headache, and lymphopenia; three had thrombocytopenia; and two had elevated liver-enzyme levels. All recovered after receiving doxycycline treatment. At least 17 of 697 Ixodes scapularis ticks collected in Minnesota or Wisconsin were positive for the same ehrlichia species on polymerase-chain-reaction testing. Genetic analyses revealed that this new ehrlichia species is closely related to E. muris. CONCLUSIONS: We report a new ehrlichia species in Minnesota and Wisconsin and provide supportive clinical, epidemiologic, culture, DNA-sequence, and vector data. Physicians need to be aware of this newly discovered close relative of E. muris to ensure appropriate testing, treatment, and regional surveillance. (Funded by the National Institutes of Health and the Centers for Disease Control and Prevention.).

      12. We report the discovery of large numbers of Haemaphysalis longicornis Neumann (Ixodida: Ixodidae) infesting a sheep in Hunterdon County, New Jersey, United States. All life stages were found on the sheep, which had no history of travel outside the country. H. longicornis is native to East Asia, and there are invasive populations in Australia, New Zealand and several Pacific islands, where this tick is a major livestock pest. It is currently unknown whether the New Jersey collections represent a limited or established population, but because this species could present a significant threat to human and animal health in the United States, vigilance is encouraged.

      13. The Lone star tick (Amblyomma americanum L.) is the primary vector for pathogens of significant public health importance in North America, yet relatively little is known about its current and potential future distribution. Building on a published summary of tick collection records, we used an ensemble modeling approach to predict the present-day and future distribution of climatically suitable habitat for establishment of the Lone star tick within the continental United States. Of the nine climatic predictor variables included in our five present-day models, average vapor pressure in July was by far the most important determinant of suitable habitat. The present-day ensemble model predicted an essentially contiguous distribution of suitable habitat extending to the Atlantic coast east of the 100th western meridian and south of the 40th northern parallel, but excluding a high elevation region associated with the Appalachian Mountains. Future ensemble predictions for 2061-2080 forecasted a stable western range limit, northward expansion of suitable habitat into the Upper Midwest and western Pennsylvania, and range contraction along portions of the Gulf coast and the lower Mississippi river valley. These findings are informative for raising awareness of A. americanum-transmitted pathogens in areas where the Lone Star tick has recently or may become established.

      14. The alpha-gal story: lessons learned from connecting the dotsexternal icon
        Steinke JW, Platts-Mills TA, Commins SP.
        J Allergy Clin Immunol. 2015 Mar;135(3):589-96; quiz 597.
        Anaphylaxis is a severe allergic reaction that can be rapidly progressing and fatal, and therefore establishing its cause is pivotal to long-term risk management. Our recent work has identified a novel IgE antibody response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal). IgE to alpha-gal has been associated with 2 distinct forms of anaphylaxis: (1) immediate-onset anaphylaxis during first exposure to intravenous cetuximab and (2) delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products (eg, beef and pork). Results of our studies and those of others strongly suggest that tick bites are a cause, if not the only significant cause, of IgE antibody responses to alpha-gal in the southern, eastern, and central United States; Europe; Australia; and parts of Asia. Typical immune responses to carbohydrates are considered to be T-cell independent, whereas IgE antibody production is thought to involve sequential class-switching that requires input from T cells. Therefore, establishing the mechanism of the specific IgE antibody response to alpha-gal will be an important aspect to address as this area of research continues.

      15. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Feverexternal icon
        Todd SR, Dahlgren FS, Traeger MS, Beltran-Aguilar ED, Marianos DW, Hamilton C, McQuiston JH, Regan JJ.
        J Pediatr. 2015 May;166(5):1246-51.
        OBJECTIVE: To evaluate whether cosmetically relevant dental effects occurred among children who had received doxycycline for treatment of suspected Rocky Mountain spotted fever (RMSF). STUDY DESIGN: Children who lived on an American Indian reservation with high incidence of RMSF were classified as exposed or unexposed to doxycycline, based on medical and pharmacy record abstraction. Licensed, trained dentists examined each child’s teeth and evaluated visible staining patterns and enamel hypoplasia. Objective tooth color was evaluated with a spectrophotometer. RESULTS: Fifty-eight children who received an average of 1.8 courses of doxycycline before 8 years of age and who now had exposed permanent teeth erupted were compared with 213 children who had never received doxycycline. No tetracycline-like staining was observed in any of the exposed children’s teeth (0/58, 95% CI 0%-5%), and no significant difference in tooth shade (P=.20) or hypoplasia (P=1.0) was found between the 2 groups. CONCLUSIONS: This study failed to demonstrate dental staining, enamel hypoplasia, or tooth color differences among children who received short-term courses of doxycycline at <8 years of age. Healthcare provider confidence in use of doxycycline for suspected RMSF in children may be improved by modifying the drug’s label.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Trends in high-grade cervical lesions and cervical cancer screening in 5 states, 2008-2015external icon
        Gargano JW, Park IU, Griffin MR, Niccolai LM, Powell M, Bennett NM, Johnson Jones ML, Whitney E, Pemmaraju M, Brackney M, Abdullah N, Scahill M, Dahl RM, Cleveland AA, Unger ER, Markowitz LE.
        Clin Infect Dis. 2019 Apr 8;68(8):1282-1291.
        BACKGROUND: We describe changes in rates of cervical intraepithelial neoplasia grades 2, 3 and adenocarcinoma in situ (CIN2+) during a period of human papillomavirus (HPV) vaccine uptake and changing cervical cancer screening recommendations. METHODS: We conducted population-based laboratory surveillance for CIN2+ in catchment areas in 5 states, 2008-2015. We calculated age-specific CIN2+ rates per 100000 women by age groups. We estimated incidence rate ratios (IRR) of CIN2+ for 2-year periods among all women and among screened women to evaluate changes over time. RESULTS: A total of 16572 CIN2+ cases were reported. Among women aged 18-20 and 21-24 years, CIN2+ rates declined in all sites, whereas in women aged 25-29, 30-34, and 35-39 years, trends differed across sites. The percent of women screened annually declined in all sites and age groups. Compared to 2008-2009, rates among screened women were significantly lower for all 3 periods in women aged 18-20 years (2010-2011: IRR 0.82, 95% confidence interval [CI] 0.67-0.99; 2012-2013: IRR 0.63, 95% CI 0.47-0.85; 2014-2015: IRR 0.44, 95% CI 0.28-0.68) and lower for the latter 2 time periods in women aged 21-24 years (2012-2013: IRR 0.86, 95% CI 0.79-0.94; 2014-2015: IRR 0.61, 95% CI 0.55-0.67). CONCLUSIONS: From 2008-2015, both CIN2+ rates and cervical cancer screening declined in women aged 18-24 years. The significant decreases in CIN2+ rates among screened women aged 18-24 years are consistent with a population-level impact of HPV vaccination.

    • Communicable Diseases
      1. Antibiotic and antifungal treatment among persons with confirmed coccidioidomycosis – Southern California, 2011external icon
        Chi GC, Benedict K, Beer KD, Jackson BR, McCotter O, Xie F, Lawrence JM, Tartof SY.
        Med Mycol. 2019 Jul 9.
        We investigated coccidioidomycosis testing and treatment patterns among persons in an integrated healthcare delivery system to identify gaps in diagnosis and treatment. Coccidioidomycosis diagnosis delays were common. Among persons who tested positive, 70% were prescribed antibiotics before positive coccidioidomycosis tests. Antibiotic treatment decreased and antifungal treatment increased after positive testing.

      2. We examined 2016 United States market research to understand the demographics and sexual health testing behaviors of dating app users. Internet/app users were more likely to be young adults, male, nonwhite, of Hispanic ethnicity, and unmarried. Users also reported greater testing for sexually transmitted disease, human immunodeficiency virus, and pregnancy.

      3. Burden of pneumonia-associated hospitalizations: United States, 2001-2014external icon
        Hayes BH, Haberling DL, Kennedy JL, Varma JK, Fry AM, Vora NM.
        Chest. 2018 Feb;153(2):427-437.
        BACKGROUND: The epidemiology of pneumonia has likely evolved in recent years, reflecting an aging population, changes in population immunity, and socioeconomic disparities. METHODS: Using the National (Nationwide) Inpatient Sample, estimated numbers and rates of pneumonia-associated hospitalizations for 2001-2014 were calculated. A pneumonia-associated hospitalization was defined as one in which the discharge record listed a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia if the principal diagnosis was respiratory failure or sepsis. RESULTS: There were an estimated 20,361,181 (SE, 95,601) pneumonia-associated hospitalizations in the United States during 2001-2014 (average annual age-adjusted pneumonia-associated hospitalization rate of 464.8 per 100,000 population [95% CI, 462.5-467.1]). The average annual age-adjusted pneumonia-associated hospitalization rate decreased over the study period (P < .0001). In-hospital death occurred in 7.4% (SE, 0.03) of pneumonia-associated hospitalizations. Non-Hispanic American Indian/Alaskan Natives and non-Hispanic blacks had the highest average annual age-adjusted rates of pneumonia-associated hospitalization of all race/ethnicities at 439.2 (95% CI, 415.9-462.5) and 438.6 (95% CI, 432.5-444.7) per 100,000 population, respectively. During 2001-2014, the proportion of pneumonia-associated hospitalizations colisting an immunocompromising condition increased from 18.7% (SE, 0.2) in 2001 to 29.9% (SE, 0.2) in 2014. Total charges for pneumonia-associated hospitalizations in 2014 were over $84 billion. CONCLUSIONS: Pneumonia is a major cause of morbidity and mortality in the United States. Differences in rates and outcomes of pneumonia-associated hospitalizations between sociodemographic groups warrant further investigation. The immunocompromised population has emerged as a group experiencing a disproportionate burden of pneumonia-associated hospitalizations.

      4. Infectious disease hospitalizations: United States, 2001 to 2014external icon
        Kennedy JL, Haberling DL, Huang CC, Lessa FC, Lucero DE, Daskalakis DC, Vora NM.
        Chest. 2019 Apr 29.
        BACKGROUND: Infectious disease epidemiology has changed over time, reflecting improved clinical interventions and emergence of threats such as antimicrobial resistance. This study investigated infectious disease hospitalizations in the United States from 2001 to 2014. METHODS: Estimated rates of infectious disease hospitalizations were calculated by using the National (Nationwide) Inpatient Sample. Infectious disease hospitalizations were defined as hospitalizations with a principal discharge diagnosis of an infectious disease. Diagnoses according to site of infection and sepsis were examined, as was occurrence of in-hospital death. The leading nonsepsis infectious disease secondary diagnoses for hospitalizations with a principal diagnosis of sepsis were identified. RESULTS: The mean annual age-adjusted infectious disease hospitalization rate was 1,468.2 (95% CI, 1,459.9-1,476.4) per 100,000 population; in-hospital death occurred in 4.22% (95% CI, 4.18-4.25) of infectious disease hospitalizations. The mean annual age-adjusted infectious disease hospitalization rate increased from 2001-2003 to 2012-2014 (rate ratio, 1.05; 95% CI, 1.01-1.09), as did the percentage of in-hospital death (4.21% [95% CI, 4.13-4.29] to 4.30% [95% CI, 4.26-4.35]; P = .049). The diagnoses with the highest hospitalization rates among all sites of infection and sepsis diagnoses were the lower respiratory tract followed by sepsis. The most common nonsepsis infectious disease secondary diagnoses among sepsis hospitalizations were “urinary tract infection,” “pneumonia, organism unspecified,” and “intestinal infection due to Clostridium [Clostridioides] difficile.” CONCLUSIONS: Although hospital discharge data are subject to limitations, particularly for tracking sepsis, lower respiratory tract infections and sepsis seem to be important contributors to infectious disease hospitalizations. Prevention of infections that lead to sepsis and improvements in sepsis management would decrease the burden of infectious disease hospitalizations and improve outcomes, respectively.

      5. Vital Signs: Surveillance for acute flaccid myelitis – United States, 2018external icon
        Lopez A, Lee A, Guo A, Konopka-Anstadt JL, Nisler A, Rogers SL, Emery B, Nix WA, Oberste S, Routh J, Patel M.
        MMWR Morb Mortal Wkly Rep. 2019 Jul 12;68(27):608-614.
        BACKGROUND: Acute flaccid myelitis (AFM), a serious paralytic illness, was first recognized as a distinct condition in 2014, when cases were reported concurrent with a large U.S. outbreak of severe respiratory illness caused by enterovirus D-68 (EV-D68). Since 2014, nationwide outbreaks of AFM have occurred every 2 years in the United States; the cause for the recent change in the epidemiology of AFM in the United States, including the occurrence of outbreaks and a biennial periodicity since 2014, is under investigation. This report updates clinical, laboratory, and outcome data for cases reported to CDC during 2018. METHODS: Clinical data and specimens from persons in the United States who met the clinical criterion for AFM (acute onset of flaccid limb weakness) with onset in 2018 were submitted to CDC for classification of the illnesses as confirmed, probable, or non-AFM cases. Enterovirus/rhinovirus (EV/RV) testing was performed on available specimens from persons meeting the clinical criterion. Descriptive analyses, laboratory results, and indicators of early recognition and reporting are summarized. RESULTS: From January through December 2018, among 374 reported cases of AFM, 233 (62%) (from 41 states) were classified as confirmed, 26 (7%) as probable, and 115 (31%) as non-AFM cases. Median ages of patients with confirmed, probable, and non-AFM cases were 5.3, 2.9, and 8.8 years, respectively. Laboratory testing identified multiple EV/RV types, primarily in respiratory and stool specimens, in 44% of confirmed cases. Among confirmed cases, the interval from onset of limb weakness until specimen collection ranged from 2 to 7 days, depending on specimen type. Interval from onset of limb weakness until reporting to CDC during 2018 ranged from 18 to 36 days, with confirmed and probable cases reported earlier than non-AFM cases. CONCLUSION: Identification of risk factors leading to outbreaks of AFM remains a public health priority. Prompt recognition of signs and symptoms, early specimen collection, and complete and rapid reporting will expedite public health investigations and research studies to elucidate the recent epidemiology of AFM and subsequently inform treatment and prevention recommendations.

      6. Evaluation of the clinical outcomes of the Test and Treat strategy to implement Treat All in Nigeria: Results from the Nigeria Multi-Center ART Studyexternal icon
        Stafford KA, Odafe SF, Lo J, Ibrahim R, Ehoche A, Niyang M, Aliyu GG, Gobir B, Onotu D, Oladipo A, Dalhatu I, Boyd AT, Ogorry O, Ismail L, Charurat M, Swaminathan M.
        PLoS One. 2019 ;14(7):e0218555.
        In December 2016, the Nigerian Federal Ministry of Health updated its HIV guidelines to a Treat All approach, expanding antiretroviral therapy (ART) eligibility to all individuals with HIV infection, regardless of CD4+ cell count, and recommending ART be initiated within two weeks of HIV diagnosis (i.e., the Test and Treat strategy). The Test and Treat policy was first piloted in 32 local government areas (LGAs). The primary objective of this study was to evaluate the clinical outcomes of adult patients initiated on ART within two weeks of HIV diagnosis during this pilot. We conducted a retrospective cohort analysis of patients who initiated ART within two weeks of new HIV diagnosis between October 2015 and September 2016 in eight randomly selected LGAs participating in the Test and Treat pilot study. 2,652 adults were newly diagnosed and initiated on ART within two weeks of HIV diagnosis. Of these patients, 8% had documentation of a 12-month viral load measurement, and 13% had documentation of a six-month viral load measurement. Among Test and Treat patients with a documented viral load, 79% were suppressed (</=400 copies/ml) at six months and 78% were suppressed at 12 months. By 12 months post-ART initiation, 34% of the patients who initiated ART under the Test and Treat strategy were lost to follow-up. The median CD4 cell count among patients initiating ART within two weeks of HIV diagnosis was 323 cells/mm3 (interquartile range, 161-518). While randomized controlled trials have demonstrated that Test and Treat strategies can improve patient retention and increase viral suppression compared to standard of care, these findings indicate that the effectiveness of Test and Treat in some settings may be far lower than the efficacy demonstrated in randomized controlled trials. Significant attention to the way Test and Treat strategies are implemented, monitored, and improved particularly related to early retention, can help expand access to ART for all patients.

      7. The National Network of Sexually Transmitted Disease Clinical Prevention Training Centers turns 40 – a look back, a look aheadexternal icon
        Stoner BP, Fraze J, Rietmeijer CA, Dyer J, Gandelman A, Hook EW, Johnston C, Neu NM, Rompalo AM, Bolan G.
        Sex Transm Dis. 2019 Aug;46(8):487-492.
        Since 1979, the National Network of Sexually Transmitted Disease (STD) Clinical Prevention Training Centers (NNPTC) has provided state-of-the-art clinical and laboratory training for STD prevention across the United States. This article provides an overview of the history and activities of the NNPTC from its inception to present day, and emphasizes the important role the network continues to play in maintaining a high-quality STD clinical workforce. Over time, the NNPTC has responded to changing STD epidemiological patterns, technological advances, and increasing private-sector care-seeking for STDs. Its current structure of integrated regional and national training centers allows NNPTC members to provide dynamic, tailored responses to STD training needs across the country.

      8. Excess heart age in adult outpatients in routine HIV careexternal icon
        Thompson-Paul AM, Palella FJ, Rayeed N, Ritchey MD, Lichtenstein KA, Patel D, Yang Q, Gillespie C, Loustalot F, Patel P, Buchacz K.
        Aids. 2019 Jul 3.
        OBJECTIVE: Cardiovascular disease (CVD) is a common cause of morbidity and mortality among persons living with HIV (PLWH). We used individual cardiovascular risk factor profiles to estimate heart age for PLWH in medical care in the U.S. DESIGN: Cross-sectional analyses of HIV Outpatient Study (HOPS) data METHODS:: Included in this analysis were participants aged 30-74 years, without prior CVD, >/= 2 HOPS clinic visits during 2010-2017, >/=1 year of follow-up, and available covariate data. We calculated age and race/ethnicity-adjusted heart age and excess heart age (chronological age minus heart age), using a Framingham risk score-based model. RESULTS: We analyzed data from 2467 men and 619 women (mean chronologic age 49.3 and 49.1 years, and 23.6% and 54.6% Non-Hispanic/Latino black, respectively). Adjusted excess heart age was 11.5 y (95% confidence interval, 11.1-12.0) among men and 13.1 y (12.0-14.1) among women. Excess heart age was seen among all age groups beginning with persons aged 30-39 y (men, 7.8 [6.9-8.8]; women, 7.7 [4.9-10.4]), with the highest excess heart age among participants aged 50-59 y (men, 13.7 y [13.0-14.4]; women, 16.4 y [14.8-18.0]). More than 50% of participants had an excess heart age of >/=10 years. CONCLUSIONS: Excess heart age is common among PLWH, begins in early adulthood, and impacts both women and men. Among PLWH, CVD risk factors should be addressed early and proactively. Routine use of the heart age calculator may help optimize CVD risk stratification and facilitate interventions for aging PLWH.

      9. Increase in invasive group A streptococcal disease and emergence of mucoid strains in a pediatric population: February-June 2017external icon
        Walker LW, Montoya L, Chochua S, Beall B, Green M.
        Open Forum Infect Dis. 2019 Jul;6(7):ofz275.
        Background: Infection with group A Streptococcus (GAS) can cause severe systemic and locally invasive disease. Invasive group A streptococcal (iGAS) disease incidence varies both seasonally and year-to-year, and it may exhibit clustered outbreaks. We observed an upswing in iGAS cases at a tertiary care Children’s Hospital, prompting further characterization of local iGAS disease. Methods: Cases of iGAS disease were abstracted from the medical record by manual chart review of all positive screening tests and cultures for GAS over a 4-year span. Incidence rates per 1000 hospital admissions and per 100 positive GAS tests were calculated and compared. Selected isolates were further characterized by whole-genome sequencing. Results: Significant year-to-year differences in per-admission iGAS incidence rate were observed in February and June, although per-positive test incidence rates were not significantly different. Whole-genome sequencing revealed 2 dominant serotypes-emm3 and emm6-with high rates of mucoid phenotype and systemic bacteremia. Conclusions: We document a significant but transient increase in iGAS disease incidence in 2 months of 2017. Genome sequencing revealed 2 dominant serotypes associated with mucoid phenotypes and severe disease, highlighting the dynamic nature of iGAS disease pattern.

    • Disaster Control and Emergency Services
      1. The COPEWELL Rubric: A self-assessment toolkit to strengthen community resilience to disastersexternal icon
        Schoch-Spana M, Gill K, Hosangadi D, Slemp C, Burhans R, Zeis J, Carbone EG, Links J.
        Int J Environ Res Public Health. 2019 Jul 4;16(13).
        Measurement is a community endeavor that can enhance the ability to anticipate, withstand, and recover from a disaster, as well as foster learning and adaptation. This project’s purpose was to develop a self-assessment toolkit-manifesting a bottom-up, participatory approach-that enables people to envision community resilience as a concrete, desirable, and obtainable goal; organize a cross-sector effort to evaluate and enhance factors that influence resilience; and spur adoption of interventions that, in a disaster, would lessen impacts, preserve community functioning, and prompt a more rapid recovery. In 2016-2018, we engaged in a process of literature review, instrument development, stakeholder engagement, and local field-testing, to produce a self-assessment toolkit (or “rubric”) built on the Composite of Post-Event Well-being (COPEWELL) model that predicts post-disaster community functioning and resilience. Co-developing the rubric with community-based users, we generated self-assessment instruments and process guides that localities can more readily absorb and adapt. Applied in three field tests, the Social Capital and Cohesion materials equip users to assess this domain at different geo-scales. Chronicling the rubric’s implementation, this account sheds further light on tensions between community resilience assessment research and practice, and potential reasons why few of the many current measurement systems have been applied.

    • Disease Reservoirs and Vectors
      1. Rabies outbreak in captive big brown bats (Eptesicus fuscus) used in a white-nose syndrome vaccine trialexternal icon
        Abbott RC, Saindon L, Falendysz EA, Greenberg L, Orciari L, Satheshkumar PS, Rocke TE.
        J Wildl Dis. 2019 Jul 11.
        An outbreak of rabies occurred in a captive colony of wild-caught big brown bats (Eptesicus fuscus). Five of 27 bats exhibited signs of rabies virus infection 22-51 d after capture or 18-22 d after contact with the index case. Rabid bats showed weight loss, aggression, increased vocalization, hypersalivation, and refusal of food. Antigenic typing and virus sequencing confirmed that all five bats were infected with an identical rabies virus variant that circulates in E. fuscus in the United States. Two bats with no signs of rabies virus infection were seropositive for rabies virus-neutralizing antibodies; the brains of these bats had no detectable viral proteins by the direct fluorescence antibody test. We suspect bat-to-bat transmission of rabies virus occurred among our bats because all rabies-infected bats were confined to the cage housing the index case and were infected with viruses having identical sequences of the entire rabies nucleoprotein gene. This outbreak illustrated the risk of rabies virus infection in captive bats and highlights the need for researchers using bats to assume that all wild bats could be infected with rabies virus.

      2. Evaluation of an adjuvanted hydrogel-based pDNA nanoparticulate vaccine for rabies prevention and immunocontraceptionexternal icon
        Bansal A, Gamal W, Wu X, Yang Y, Olson V, D’Souza MJ.
        Nanomedicine. 2019 Jul 3:102049.
        Immunocontraceptive vaccination is becoming an acceptable strategy in managing animal populations. Mass vaccination of dogs is the most cost-effective and efficient method to control rabies, and combination of rabies vaccination and animal population control will be an added advantage. In this study, we developed an adjuvanted hydrogel-based pDNA nanoparticulate vaccine for rabies protection and immunocontraception. In vivo, we observed an immune response skewed toward a Th2 type, in contrast to the Th1 type in our previous pDNA study. The observation was verified by the IgG2a/IgG1 ratio (<1), and cytokine expression profile of IL-4 and IFN-Upsilon. The humoral immune response is key for rabies protection and a GnRH antibody-based immunocontraception. In mice, anti-GnRH antibody titers were detected 4weeks after immunization and lasted for 12 weeks, post animal experiment was terminated. The adjuvanted pDNA nanoparticulate vaccine shows promise for future studies evaluating protection from rabies challenge and prevention of animal breeding.

      3. Frequent prescribed fires can reduce risk of tick-borne diseasesexternal icon
        Gleim ER, Zemtsova GE, Berghaus RD, Levin ML, Conner M, Yabsley MJ.
        Sci Rep. 2019 Jul 10;9(1):9974.
        Recently, a two-year study found that long-term prescribed fire significantly reduced tick abundance at sites with varying burn regimes (burned surrounded by burned areas [BB], burned surrounded by unburned areas [BUB], and unburned surrounded by burned areas [UBB]). In the current study, these ticks were tested for pathogens to more directly investigate the impacts of long-term prescribed burning on human disease risk. A total of 5,103 ticks (4,607 Amblyomma americanum, 76 Amblyomma maculatum, 383 Ixodes scapularis, two Ixodes brunneus, and 35 Dermacentor variabilis) were tested for Borrelia spp., Rickettsia spp., Ehrlichia spp., and Anaplasma phagocytophilum. Long-term prescribed fire did not significantly impact pathogen prevalence except that A. americanum from burned habitats had significantly lower prevalence of Rickettsia (8.7% and 4.6% for BUB and UBB sites, respectively) compared to ticks from control sites (unburned, surrounded by unburned [UBUB])(14.6%). However, during the warm season (spring/summer), encounter rates with ticks infected with pathogenic bacteria was significantly lower (98%) at burned sites than at UBUB sites. Thus, despite there being no differences in pathogen prevalence between burned and UBUB sites, risk of pathogen transmission is lower at sites subjected to long-term burning due to lower encounter rates with infected ticks.

    • Environmental Health
      1. An educational intervention on the risk perception of pesticides exposure and organophosphate metabolites urinary concentrations in rural school children in Maule Region, Chileexternal icon
        Munoz-Quezada MT, Lucero B, Bradman A, Steenland K, Zuniga L, Calafat AM, Ospina M, Iglesias V, Munoz MP, Buralli RJ, Fredes C, Gutierrez JP.
        Environ Res. 2019 Jun 24;176:108554.
        BACKGROUND: Organophosphate (OP) pesticides can be hazardous to human health if not applied with appropriate precautions. There is evidence in the Maule region of Chile that rural schoolchildren are exposed to OP pesticides. OBJECTIVE: To evaluate the effectiveness of an educational intervention on OP exposure and understanding of pesticides and their hazards (risk perception) in two school communities in the Maule Region of Chile during 2016. METHOD: We conducted a quasi-experimental study about the effects on OP pesticide exposure of a community outreach and education program (COEP) administered in four 2-h sessions that’s included hands-on activities among 48 schoolchildren from two rural schools. The intervention was directed to groups of parents and school-children separately, and aimed to educate them about the risks of exposure to pesticides and their effects on health. We measured 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY), malathion dicarboxylic acid (MDA), p-nitrophenol (PNP), specific urinary metabolites of the OP pesticides chlorpyrifos, diazinon, malathion and parathion, respectively, as well as the non-specific diethylakylphosphates (DEAPs) and dimethylalkylphosphates (DMAPs) in 192 urine samples of schoolchildren collected before and after the intervention. The risk perception of school children and their parents was also assessed through a questionnaire before and after the intervention. Generalized Estimated Equations were used to account for each child’s repeated measures during four sessions, two in September 2016 (pre-intervention) and two in November 2016 (post-intervention). RESULTS: The intervention level had significant effect on the risk perception of adults and children, which increased after the intervention. However, the intervention was not associated with reduced of urinary metabolites levels, with no significant differences between the pre and post measures. The detection frequencies were 1.1% (MDA), 71.4% (TCPy), 43.3% (IMPY), 98.96% (PNP), and 100% (DEAPs and DMAPs). Higher DEAPs urine concentrations were associated with eating more fruit at school (p=0.03), a younger age (p=0.03), and being male (p=0.01). DMAPs showed no associations with potential predictor variables (e.g. OPs applied at home, fruit consumption at school, among others). Higher TCPy was associated with attending a school closer to farms (p=0.04) and living in a home closer to farm fields (p=0.01); higher PNP was marginally associated with children younger age (p=0.035). CONCLUSION: Environmental exposure to OP pesticides was unchanged even after behavior changes. It is possible that a longer time period is needed to observe changes in both behavior and urinary metabolites. The levels of DEP and DMP metabolites found here are above the reference population of the US, and our findings indicate exposure to a wide variety of OP pesticides. Given that individual-level interventions were not associated with lower exposures, efforts to reduce exposure must occur upstream and require stricter regulation and control of pesticide use by government agencies.

      2. Exposure to neonicotinoid insecticides in the U.S. general population: Data from the 2015-2016 national health and nutrition examination surveyexternal icon
        Ospina M, Wong LY, Baker SE, Serafim AB, Morales-Agudelo P, Calafat AM.
        Environ Res. 2019 Jun 24;176:108555.
        BACKGROUND: Neonicotinoids are used for insect control in agriculture, landscaping, and on household pets. Neonicotinoids have become popular replacements for organophosphate and carbamate insecticides, and use is on the rise. OBJECTIVES: To assess human exposure to neonicotinoid insecticides in a representative sample of the U.S. general population 3 years and older from the 2015-2016 National Health and Nutrition Examination Survey (NHANES). METHODS: We used online solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to quantify in 3038 samples the urinary concentrations of six neonicotinoid biomarkers: four parent compounds (acetamiprid, clothianidin, imidacloprid, thiacloprid) and two metabolites (N-desmethyl-acetamiprid, 5-hydroxy-imidacloprid). We calculated distribution percentiles, and used regression models to evaluate associations of various demographic parameters and fasting time with urinary concentrations above the 95th percentile (a value selected to represent higher than average concentrations) of neonicotinoid biomarkers. RESULTS: Weighted detection frequencies were 35% (N-desmethyl-acetamiprid), 19.7% (5-hydroxy imidacloprid), 7.7% (clothianidin), 4.3% (imidacloprid), and <0.5% (acetamiprid, thiacloprid). The weighted frequency of having detectable concentrations of at least one of the six biomarkers examined was 49.1%. The 95th percentile concentrations for N-desmethyl-acetamiprid, 5-hydroxy imidacloprid, and clothianidin were 1.29, 1.37, and 0.396mug/L, respectively. For people who fasted <8h, regardless of race/ethnicity and sex, 3-5 year old children were more likely to have N-desmethyl-acetamiprid concentrations above the 95th percentile than adolescents (adjusted odds ratio (OR)=3.12; 95% confidence interval [CI], (0.98-9.98)) and adults (adjusted OR=4.29; 95% CI, (2.04-9.0)); and children 6-11 years of age were more likely than adults to have N-desmethyl-acetamiprid concentrations above the 95th percentile (adjusted OR=2.65; 95% CI, (1.2-5.84)). Asians were more likely than non-Asians to have concentrations above the 95th percentile of N-desmethyl-acetamiprid (adjusted OR=1.94; 95% CI, (1.08-3.49)) and 5-hydroxy-imidacloprid (adjusted OR=2.25; 95% CI, (1.44-3.51)). Samples collected during the summer were more likely to have metabolite concentrations above the 95th percentile than those collected in the winter (adjusted OR 1.55 for N-desmethyl-acetamiprid, and 2.43 for 5-hydroxy-imidacloprid). CONCLUSIONS: The detection of neonicotinoid metabolites more frequently and at much higher concentrations than the corresponding parent compounds suggests that the metabolites may be suitable biomarkers to assess background exposures. About half of the U.S. general population 3 years of age and older was recently exposed to neonicotinoids. Compared to other age ranges and ethnicities, young children and Asians may experience higher exposures. At present, reasons for such differences remain unknown.

      3. Prenatal exposure to per- and polyfluoroalkyl substances and infant growth and adiposity: the Healthy Start Studyexternal icon
        Starling AP, Adgate JL, Hamman RF, Kechris K, Calafat AM, Dabelea D.
        Environ Int. 2019 Jul 5;131:104983.
        BACKGROUND: Prenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that faster growth in early infancy may be associated with maternal PFAS concentrations. METHODS: Among 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression. RESULTS: Associations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5-1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (-0.26 SD per ln-ng/mL PFOS, 95% CI -0.43, -0.10; -0.17 SD per ln-ng/mL PFHxS, 95% CI -0.33, -0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio [OR] 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations. DISCUSSION: We observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass.

      4. Predictors of plasma polychlorinated biphenyl concentrations among reproductive-aged black womenexternal icon
        Wesselink AK, Bethea TN, McClean M, Weuve J, Williams PL, Hauser R, Sjodin A, Brasky TM, Baird DD, Wise LA.
        Int J Hyg Environ Health. 2019 Jul 5.
        Polychlorinated biphenyls (PCBs) are a class of lipophilic endocrine-disrupting chemicals with wide industrial use in the U.S. from the 1930s through 1977. Due to their environmental and biological persistence, low levels of PCBs remain detected in wildlife and humans. Although U.S. studies have shown higher serum PCB concentrations among Black women compared with White women, studies of correlates of PCB exposure among Black women are scarce. We examined predictors of plasma PCB concentrations in a cross-sectional analysis of baseline data from a prospective cohort study of 1693 premenopausal Black women aged 23-35 years from Detroit, Michigan (2010-2012). We collected demographic, behavioral, dietary, and medical data via self-administered questionnaires, telephone interviews, and in-person clinic visits, as well as non-fasting blood samples. We measured concentrations of 24 PCB congeners in baseline plasma from a subset of 762 participants. We used linear regression for log-transformed lipid-adjusted PCB concentrations to calculate percentage differences across levels of selected predictors. We did this separately for individual PCBs, sum of total PCBs, and sum of PCBs by degree of chlorination and hormonal activity. PCB concentrations were positively associated with age, duration of urban residence, cigarette smoking, heavy alcohol intake, and being breastfed in infancy, and inversely associated with body mass index (BMI) and lactation duration. The strength of some associations varied by degree of chlorination. For example, a 5-kg/m(2) higher BMI corresponded to a 2.9% lower summed concentration of tri- and tetra-substituted PCBs (95% CI -4.6%, -1.2%), an 8.3% lower summed concentration of penta- and hexa-substituted PCBs (95% CI -10.0%, -6.5%), and a 12.1% lower summed concentration of hepta-, octa-, nona-, and deca-substituted PCBs (95% CI -13.7%, -10.4%). Likewise, associations for age and being breastfed in infancy were stronger for higher-chlorinated PCBs. Results agree with studies on predictors of PCB body burdens, few of which include large numbers of Black women.

    • Genetics and Genomics
      1. Background An increasing number of diagnostic evaluations incorporate genetic testing to facilitate accurate and timely diagnoses. The increasing number and complexity of genetic tests continue to pose challenges in deciding when to test, selecting the correct test(s), and using results to inform medical diagnoses, especially for medical professionals lacking genetic expertise. Careful consideration of a diagnostic workflow can be helpful in understanding the appropriate uses of genetic testing within a broader diagnostic workup. Content The diagnosis of long QT syndrome (LQTS), a life-threatening cardiac arrhythmia, provides an example for this approach. Electrocardiography is the preferred means for diagnosing LQTS but can be uninformative for some patients due to the variable presentation of the condition. Family history and genetic testing can augment physiological testing to inform a diagnosis and subsequent therapy. Clinical and laboratory professionals informed by peer- reviewed literature and professional recommendations constructed a generalized LQTS diagnostic workflow. This workflow served to explore decisions regarding the use of genetic testing for diagnosing LQTS. Summary and outlook Understanding the complexities and approaches to integrating genetic testing into a broader diagnostic evaluation is anticipated to support appropriate test utilization, optimize diagnostic evaluation, and facilitate a multidisciplinary approach essential for achieving accurate and timely diagnoses.

    • Global Health
      1. Factors influencing acceptance of post-mortem examination of children at a tertiary care hospital in Nairobi, Kenyaexternal icon
        Bunei M, Muturi P, Otiato F, Njuguna HN, Emukule GO, Otieno NA, Dawa J, Chaves SS.
        Ann Glob Health. 2019 Jul 3;85(1).
        BACKGROUND: Clinical autopsies are not often part of routine care, despite their role in clarifying cause of death. In fact, autopsy rates across the world have declined and are especially low in sub-Saharan Africa. OBJECTIVES: We set out to identify factors associated with acceptance of pediatric autopsies among parents of deceased children less than five years old, and examined local preferences for minimally invasive tissue sampling (MITS) procedures during post-mortem (PM) examinations. METHODS: From December 2016 to September 2017, we contacted 113 parents/next of kin who had been previously approached to consent to a PM examination of their deceased child as part of a Kenyan study on cause of death. Interviews occurred up to three years after the death of their child. FINDINGS: Seventy-three percent (83/113) of eligible study participants were enrolled, of whom 62/83 (75%) had previously consented to PM examination of their child. Those who previously consented to PM had higher levels of education, were more likely employed, and had more knowledge about certain aspects of autopsies than non-consenters. The majority (97%) of PM consenters did so because they wanted to know the cause of death of their child, and up to a third believed autopsy studies helped advance medical knowledge. Reasons for non-consent to PM examination included: parents felt there was no need for further examination (29%) or they were satisfied with the clinical diagnosis (24%). Overall, only 40% of study participants would have preferred MITS procedures to conventional autopsy. However, 81% of autopsy non-consenters would have accepted PM examination if it only involved MITS techniques. CONCLUSION: There is potential to increase autopsy rates by strengthening reasons for acceptance and addressing modifiable reasons for refusals. Although MITS procedures have the potential to improve autopsy acceptance rates, they were not significantly preferred over conventional autopsies in our study population.

    • Health Economics
      1. Assessment of economic burden of concurrent measles and rubella outbreaks, Romania, 2011-2012external icon
        Njau J, Janta D, Stanescu A, Pallas SS, Pistol A, Khetsuriani N, Reef S, Ciurea D, Butu C, Wallace AS, Zimmerman L.
        Emerg Infect Dis. 2019 Jun;25(6):1101-1109.
        We estimated the economic impact of concurrent measles and rubella outbreaks in Romania during 2011-2012. We collected costs from surveys of 428 case-patients and caretakers, government records, and health staff interviews. We then estimated financial and opportunity costs. During the study period, 12,427 measles cases and 24,627 rubella cases were recorded; 27 infants had congenital rubella syndrome (CRS). The cost of the outbreaks was US $9.9 million. Cost per case was US $439 for measles, US $132 for rubella, and US $44,051 for CRS. Up to 36% of households needed to borrow money to pay for illness treatment. Approximately 17% of patients continued to work while ill to pay their treatment expenses. Our key study findings were that households incurred a high economic burden compared with their incomes, the health sector bore most costs, and CRS costs were substantial and relevant to include in rubella outbreak cost studies.

      2. INTRODUCTION: Public health focuses on a range of evidence-based approaches for addressing chronic conditions, from individual-level clinical interventions to broader changes in policies and environments that protect people’s health and make healthy living easier. This study examined the potential long-term impact of clinical and community interventions as they were implemented by Community Transformation Grant (CTG) program awardees. METHODS: We used the Prevention Impacts Simulation Model, a system dynamics model of cardiovascular disease prevention, to simulate the potential 10-year and 25-year impact of clinical and community interventions implemented by 32 communities receiving a CTG program award, assuming that program interventions were sustained during these periods. RESULTS: Sustained clinical interventions implemented by CTG awardees could potentially avert more than 36,000 premature deaths and $3.2 billion in discounted direct medical costs (2017 US dollars) over 10 years and 109,000 premature deaths and $8.1 billion in discounted medical costs over 25 years. Sustained community interventions could avert more than 24,000 premature deaths and $3.4 billion in discounted direct medical costs over 10 years and 88,000 premature deaths and $9.1 billion in discounted direct medical costs over 25 years. CTG clinical activities had cost-effectiveness of $302,000 per death averted at the 10-year mark and $188,000 per death averted at the 25-year mark. Community interventions had cost-effectiveness of $169,000 and $57,000 per death averted at the 10- and 25-year marks, respectively. CONCLUSION: Clinical interventions have the potential to avert more premature deaths than community interventions. However, community interventions, if sustained over the long term, have better cost-effectiveness.

    • Healthcare Associated Infections
      1. Collaborative solutions to antibiotic stewardship in small community and critical access hospitalsexternal icon
        Bhatt J, Smith B, Neuhauser MM, Srinivasan A, Moore P, Hyun DY.
        Acad Med. 2019 Jul 2.
        The overuse and misuse of antibiotics affects patients in many ways, including by driving antibiotic resistance, a serious public health threat in the United States and around the world. To improve patient safety and address rising rates of resistance, an increasing number of health care facilities have created antibiotic stewardship programs (ASPs). ASPs have been successful in slowing the emergence of resistance and improving patient outcomes. However, there are serious geographic and resource barriers to ASP adoption in small community hospitals and critical access hospitals. Fortunately, many barriers can be overcome by using collaborative models to bring together key stakeholders, including large hospitals and health systems and academic medical centers; hospital associations; federal, state, and local public health organizations; and federal and state offices of rural health. These stakeholders are ideally positioned to assist with stewardship efforts in small community and critical access hospitals and, in doing so, can improve patient safety while stemming the spread of resistant bacteria.

      2. On the origins of a species: What might explain the rise of Candida auris?external icon
        Jackson BR, Chow N, Forsberg K, Litvintseva AP, Lockhart SR, Welsh R, Vallabhaneni S, Chiller T.
        J Fungi (Basel). 2019 Jul 6;5(3).
        Candida auris is an emerging multidrug-resistant yeast first described in 2009 that has since caused healthcare-associated outbreaks of severe human infections around the world. In some hospitals, it has become a leading cause of invasive candidiasis. C. auris is markedly different from most other pathogenic Candida species in its genetics, antifungal resistance, and ability to spread between patients. The reasons why this fungus began spreading widely in the last decade remain a mystery. We examine available data on C. auris and related species, including genomic epidemiology, phenotypic characteristics, and sites of detection, to put forth hypotheses on its possible origins. C. auris has not been detected in the natural environment; related species have been detected in in plants, insects, and aquatic environments, as well as from human body sites. It can tolerate hypersaline environments and higher temperatures than most Candida species. We explore hypotheses about the pre-emergence niche of C. auris, whether in the environmental or human microbiome, and speculate on factors that might have led to its spread, including the possible roles of healthcare, antifungal use, and environmental changes, including human activities that might have expanded its presence in the environment or caused increased human contact.

      3. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: A multihospital cohort studyexternal icon
        Vaughn VM, Flanders SA, Snyder A, Conlon A, Rogers MA, Malani AN, McLaughlin E, Bloemers S, Srinivasan A, Nagel J, Kaatz S, Osterholzer D, Thyagarajan R, Hsaiky L, Chopra V, Gandhi TN.
        Ann Intern Med. 2019 Jul 9.
        Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient’s shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results: Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation: Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion: Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary Funding Source: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.

    • Immunity and Immunization
      1. The partnership for influenza vaccine introduction (PIVI): Supporting influenza vaccine program development in low and middle-income countries through public-private partnershipsexternal icon
        Bresee JS, Lafond KE, McCarron M, Azziz-Baumgartner E, Chu SY, Ebama M, Hinman AR, Xeuatvongsa A, Bino S, Richardson D, Porter RM, Moen A, McKinlay M.
        Vaccine. 2019 Jul 6.
        Influenza vaccination remains the most effective tool for reducing seasonal influenza disease burden. Few Low and Middle-Income Countries (LMICs) have robust, sustainable annual influenza national vaccination programs. The Partnership for Influenza Vaccine Introduction (PIVI) was developed as a public-private partnership to support LMICs to develop and sustain national vaccination programs through time-limited vaccine donations and technical support. We review the first 5years of experience with PIVI, including the concept, country progress toward sustainability, and lesson learned. Between 2013 and 2018, PIVI worked with Ministries of Health in 17 countries. Eight countries have received donated vaccines and technical support; of these, two have transitioned to sustained national support of influenza vaccination and six are increasing national support of the vaccine programs towards full transition to local vaccine program support by 2023. Nine additional countries have received technical support for building the evidence base for national policy development and/or program evaluation. PIVI has resulted in increased use of vaccines in partner countries, and early countries have demonstrated progress towards sustainability, suggesting that a model of vaccine and technical support can work in LMICs. PIVI expects to add new country partners as current countries transition to self-reliance.

      2. Distribution of rotavirus genotypes in the post-vaccine introduction era in Ashaiman, Greater Accra Region, Ghana, 2014-2016external icon
        Letsa V, Damanka S, Dennis F, Lartey B, Armah GE, Betrapally N, Gautam R, Esona MD, Bowen MD, Quaye O.
        J Med Virol. 2019 Jul 9.
        Group A Rotaviruses (RVAs) are the most important etiological agents of acute gastroenteritis (AGE) in children less than 5 years of age. Mortality resulting from RVA gastroenteritis is higher in developing countries than in developed ones, causing a huge public health burden in global regions like Africa and South-East Asia. This study reports RVA genotypes detected in Ashaiman, Greater Accra Region, Ghana, in the post vaccine introduction era for the period 2014-16. Stool samples were collected from children less than 5 years of age who visited Ashaiman Polyclinic with acute gastroenteritis from November 2014 to May 2015 and from December 2015 to June 2016. The samples were tested by enzyme immunoassay (EIA), and One-Step multiplex RT-PCR was performed on the EIA positive samples for gel based binomial genotyping. Of 369 stool samples collected from children with AGE, 145 (39%) tested positive by EIA. Five VP7 (G1, G3, G9, G10 and G12) and three VP4 (P[4], P[6] and P[8]) genotypes were detected. Eight G/P combinations were identified of which, G3P[6], G12P[8], G1P[8] and G9P[4] were the most prevalent and responsible for 93 (68%) of the AGE cases, and 7 mixed-types were detected which represented 8% of the RVA cases. High prevalence, diversity and mixed-types of RVAs were detected from Ashaiman with the emergence of unusual genotypes. This article is protected by copyright. All rights reserved.

      3. Hepatitis B surface antigen seroprevalence among pre- and post-vaccine cohorts in Cambodia, 2017external icon
        Ork V, Woodring J, Shafiqul Hossain M, Wasley A, Nagashima S, Yamamoto C, Chuon C, Sugiyama A, Ohisa M, Akita T, Ko K, Mao B, Tanaka J.
        Vaccine. 2019 Jul 5.
        BACKGROUND: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children. METHODS: A cross-sectional multi-stage cluster survey was conducted among children born during 2010-2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24h) vaccination were analysed by multivariate logistic analysis. FINDINGS: A total of 2,520 children 5-7years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered</=24h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%-5.45%) among mothers and 0.56% (95%CI: 0.32%-0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%-14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%-18.11%). INTERPRETATION: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030. FUNDING: As per sources of funding.

    • Injury and Violence
      1. Addressing gaps in global data on violence against children and adolescentsexternal icon
        Massetti GM, Dahlberg LL.
        Lancet Child Adolesc Health. 2019 Jul 2.

        [No abstract]

      2. Sex and age effects in past-year experiences of violence amongst adolescents in five countriesexternal icon
        Stark L, Seff I, Hoover A, Gordon R, Ligiero D, Massetti G.
        PLoS One. 2019 ;14(7):e0219073.
        PURPOSE: To date, there has been insufficient focus on age and sex differences in studies of violence amongst adolescents and young adults in low- and middle-income countries. As adolescence is a formative period during which experiencing violence can have both short- and long-term consequences, we aim to investigate experiences of violence by age and sex across five countries. METHODS: Incidences of past-year violence victimization were estimated by sex across two-year age bands (13-24 years) using Violence Against Children Survey datasets from Cambodia, Haiti, Kenya, Malawi, and Tanzania. Analyses were conducted separately for each country. The presence of an association with age and each type of violence was identified using logistic regressions separately by sex. Sex was then added to the models as an interaction term and adjusted Wald tests were used to assess differences between males and females in age effects. RESULTS: Risk of physical violence by both an adult caregiver and a community member decreased with age for both sexes in all countries. In contrast, risk of IPV increased with age for both sexes in all countries. Although some countries displayed a steeper increase in risk of IPV and sexual violence with age for males, females face higher overall levels of risk for these forms of violence. CONCLUSION: Findings highlight how adolescents’ and young adults’ risk of violence changes with age and type of violence. The analysis underscores the importance of collecting violence data disaggregated by age and sex to best inform policies and programming. IMPLICATIONS AND CONTRIBUTIONS: We analyzed five Violence Against Children Surveys (VACS) and found age effects for physical, sexual, and intimate partner violence for adolescents 13-24 years old. Age effects for sexual violence are stronger among females than males. Future policies targeting adolescents should consider how age and gender influence risk of violence.

    • Laboratory Sciences
      1. Influenza passaging annotations: what they tell us and why we should listenexternal icon
        DuPai CD, McWhite CD, Smith CB, Garten R, Maurer-Stroh S, Wilke CO.
        Virus Evol. 2019 Jan;5(1):vez016.
        Influenza databases now contain over 100,000 worldwide sequence records for strains influenza A(H3N2) and A(H1N1). Although these data facilitate global research efforts and vaccine development practices, they also represent a stumbling block for researchers because of their confusing and heterogeneous annotation. Unclear passaging annotations are particularly concerning given the recent work highlighting the presence and risk of false adaptation signals introduced by cell passaging of viral isolates. With this in mind, we aim to provide a concise outline of why viruses are passaged, a clear overview of passaging annotation nomenclature currently in use, and suggestions for a standardized nomenclature going forward. Our hope is that this summary will empower researchers and clinicians alike to more easily understand a virus sample’s passage history when analyzing influenza sequences.

      2. Proposed BoNT/A and /B peptide substrates cannot detect multiple subtypes in the Endopep-MS Assayexternal icon
        Kalb SR, Baudys J, Kiernan K, Wang D, Becher F, Barr JR.
        J Anal Toxicol. 2019 Jul 9.
        Botulinum neurotoxins (BoNTs) are a family of protein toxins consisting of seven known serotypes (BoNT/A-BoNT/G) and multiple subtypes within the serotypes, and all of which cause the disease botulism-a disease of great public health concern. Accurate detection of BoNTs in human clinical samples is therefore an important public health goal. To achieve this goal, our laboratory developed a mass spectrometry-based assay detecting the presence of BoNT via its enzymatic activity on a peptide substrate. Recently, publications reported the use of new peptide substrates to detect BoNT/A and /B with improved results over other peptide substrates. However, the authors did not provide results of their peptide substrate on multiple subtypes of BoNT. In this work, we describe the results of testing the new substrates with multiple BoNT/A and /B subtypes and find that the substrates cannot detect many subtypes of BoNT/A and /B.

      3. Mouse pulmonary response to dust from sawing Corian(R), a solid-surface composite materialexternal icon
        Mandler WK, Qi C, Orandle MS, Sarkisian K, Mercer RR, Stefaniak AB, Knepp AK, Bowers LN, Battelli LA, Shaffer J, Friend SA, Qian Y, Sisler JD.
        J Toxicol Environ Health A. 2019 Jul 10:1-19.
        Corian(R), a solid-surface composite (SSC), is composed of alumina trihydrate and acrylic polymer. The aim of the present study was to examine the pulmonary toxicity attributed to exposure to SSC sawing dust. Male mice were exposed to either phosphate buffer saline (PBS, control), 62.5, 125, 250, 500, or 1000 microg of SSC dust, or 1000 microg silica (positive control) via oropharyngeal aspiration. Body weights were measured for the duration of the study. Bronchoalveolar lavage fluid (BALF) and tissues were collected for analysis at 1 and 14 days post-exposure. Enhanced-darkfield and histopathologic analysis was performed to assess particle distribution and inflammatory responses. BALF cells and inflammatory cytokines were measured. The geometric mean diameter of SSC sawing dust following suspension in PBS was 1.25 microm. BALF analysis indicated that lactate dehydrogenase (LDH) activity, inflammatory cells, and pro-inflammatory cytokines were significantly elevated in the 500 and 1000 microg SSC exposure groups at days 1 and 14, suggesting that exposure to these concentrations of SSC induced inflammatory responses, in some cases to a greater degree than the silica positive control. Histopathology indicated the presence of acute alveolitis at all doses at day 1, which was largely resolved by day 14. Alveolar particle deposition and granulomatous mass formation were observed in all exposure groups at day 14. The SSC particles were poorly cleared, with 81% remaining at the end of the observation period. These findings demonstrate that SSC sawing dust exposure induces pulmonary inflammation and damage that warrants further investigation. Abbreviations: ANOVA: Analysis of Variance; ATH: Alumina Trihydrate; BALF: Bronchoalveolar Lavage Fluid; Dpg: Geometric Mean Diameter; FE-SEM: Field Emission Scanning Electron Microscopy; IACUC: Institutional Animal Care and Use Committee; IFN-gamma: Interferon Gamma; IL-1 Beta: Interleukin-1 Beta; IL-10: Interleukin-10; IL-12: Interleukin-12; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-5: Interleukin-5; IL-6: Interleukin-6; KC/GRO: Neutrophil-Activating Protein 3; MMAD: Mass Median Aerodynamic Diameter; PBS: Phosphate-Buffered Saline; PEL: Permissible Exposure Limit; PM: Polymorphonuclear Leukocytes; PNOR: Particles Not Otherwise Regulated; SEM/EDX: Scanning Electron Microscope/Energy-Dispersive X-Ray; SSA: Specific Surface Area; SSC: Solid Surface Composite; TNFalpha: Tumor Necrosis Factor-Alpha; VOC: Volatile Organic Compounds; sigmag: Geometric Standard Deviation.

      4. Performance of cepheid GeneXpert HIV-1 viral load plasma assay to accurately detect treatment failure: a clinical meta-analysisexternal icon
        Sacks JA, Fong Y, Gonzalez MP, Andreotti M, Baliga S, Garrett N, Jordan J, Karita E, Kulkarni S, Mor O, Mosha F, Ndlovu Z, Plantier JC, Saravanan S, Scott L, Peter T, Doherty M, Alexander H, Vojnov L.
        Aids. 2019 Jul 2.
        BACKGROUND: Coverage of viral load testing remains low with only half of the patients in need having adequate access. Alternative technologies to high throughput centralized machines can be used to support viral load scale-up; however, clinical performance data are lacking. We conducted a meta-analysis comparing the Cepheid Xpert HIV-1 viral load plasma assay to traditional laboratory-based technologies. METHODS: Cepheid Xpert HIV-1 and comparator laboratory technology plasma viral load results were provided from 13 of the 19 eligible studies, which accounted for a total of 3790 paired data points. We used random effects models to determine the accuracy and misclassification at various treatment failure thresholds (detectable, 200, 400, 500, 600, 800 and 1000 copies/ml). RESULTS: Thirty percent of viral load test results were undetectable, while 45% were between detectable and 10 000 copies/ml and the remaining 25% were above 10 000 copies/ml. The median Xpert viral load was 119 copies/ml and the median comparator viral load was 157 copies/ml, while the log10 bias was 0.04 (0.02-0.07). The sensitivity and specificity to detect treatment failure were above 95% at all treatment failure thresholds, except for detectable, at which the sensitivity was 93.33% (95% confidence interval: 88.2-96.3) and specificity was 80.56% (95% CI: 64.6-90.4). CONCLUSION: The Cepheid Xpert HIV-1 viral load plasma assay results were highly comparable to laboratory-based technologies with limited bias and high sensitivity and specificity to detect treatment failure. Alternative specimen types and technologies that enable decentralized testing services can be considered to expand access to viral load.

      5. Foamy viruses (FVs) are complex retroviruses present in many mammals, including nonhuman primates, where they are called simian foamy viruses (SFVs). SFVs can zoonotically infect humans, but very few complete SFV genomes are available, hampering the design of diagnostic assays. Gibbons are lesser apes widespread across Southeast Asia that can be infected with SFV, but only two partial SFV sequences are currently available. We used a metagenomics approach with next-generation sequencing of nucleic acid extracted from the cell culture of a blood specimen from a lesser ape, the pileated gibbon (Hylobates pileatus), to obtain the complete SFVhpi_SAM106 genome. We used Bayesian analysis to co-infer phylogenetic relationships and divergence dates. SFVhpi_SAM106 is ancestral to other ape SFVs with a divergence date of ~20.6 million years ago, reflecting ancient co-evolution of the host and SFVhpi_SAM106. Analysis of the complete SFVhpi_SAM106 genome shows that it has the same genetic architecture as other SFVs but has the longest recorded genome (13,885-nt) due to a longer long terminal repeat region (2,071 bp). The complete sequence of the SFVhpi_SAM106 genome fills an important knowledge gap in SFV genetics and will facilitate future studies of FV infection, transmission, and evolutionary history.

      6. Simultaneous detection of four protozoan parasites on leafy greens using a novel multiplex PCR assayexternal icon
        Shapiro K, Kim M, Rajal VB, Arrowood MJ, Packham A, Aguilar B, Wuertz S.
        Food Microbiology. 2019 ;84.
        Pathogen contamination of fresh produce presents a health risk for consumers; however, the produce industry still lacks adequate tools for simultaneous detection of protozoan parasites. Here, a simple multiplex PCR (mPCR) assay was developed for detection of protozoan (oo)cysts and compared with previously published real-time PCR assays and microscopy methods. The assay was evaluated for simultaneous detection of Cryptosporidium, Giardia, Cyclospora cayetanensis, and Toxoplasma gondii followed by parasite differentiation via either a nested specific PCR or a restriction fragment length polymorphism (RFLP) assay. Spiking experiments using spinach as a model leafy green were performed for assay validation. Leaf-washing yielded higher recoveries and more consistent detection of parasites as compared with stomacher processing. Lowest limits of detection using the nested mPCR assay were 1?10 (oo)cysts/g spinach (in 10 g samples processed), and this method proved more sensitive than qPCR for parasite detection. Microscopy methods were more reliable for visual detection of parasites in lower spiking concentrations, but are more costly and laborious, require additional expertise, and lack molecular confirmation essential for accurate risk assessment. Overall, the nested mPCR assay provides a rapid (<24 h), inexpensive ($10 USD/sample), and simple approach for simultaneous detection of protozoan pathogens on fresh produce.

      7. Evaluation of A(H1N1)pdm09 LAIV vaccine candidates stability and replication efficiency in primary human nasal epithelial cellsexternal icon
        Shcherbik S, Pearce N, Carney P, Bazhenova E, Larionova N, Kiseleva I, Rudenko L, Kumar A, Goldsmith CS, Dugan V, Stevens J, Wentworth DE, Bousse T.
        Vaccine: X. 2019 9 August;2 .
        The recent reduction of live attenuated influenza vaccine (LAIV) effectiveness in multivalent formulations was particularly associated with the A(H1N1)pdm09 component. In the 2017 the WHO vaccine composition committee changed its recommendations for the A(H1N1)pdm09 component to include an A/Michigan/45/2015-like virus. We evaluated effectiveness and quality of newly developed and previous A(H1N1)pdm09 LAIV reassortants through assessment of their thermal and pH stability, receptor binding specificity and replication fitness in primary human airway epithelial cells of nasal origin (hAECN). Our analysis showed that LAIV expressed hemagglutinin (HA) and neuraminidase (NA) from an A/Michigan/45/2015-like strain A/New York/61/2015 (A/New York/61/2015-CDC-LV16A, NY-LV16A), exhibit higher thermal and pH stability compared to the previous vaccine candidates expressing HA and NA from A/California/07/2009 and A/Bolivia/559/2013 (A17/Cal09 and A17/Bol13). Reassortants A/South Africa/3626/2013-CDC-LV14A (SA-LV14A) and NY-LV16A showed preferential binding to alpha2,6 sialic acid (SA) receptors and replicated at higher titers and more extensively in hAECN compared to A17/Cal09 and A17/Bol13, which had an alpha2,3 SA receptor binding preference. Our data analysis supports selection of A/New York/61/2015-CDC-LV16A for LAIV formulation and the introduction of new assays for LAIV characterization.

      8. Multi-walled carbon nanotube-induced gene expression biomarkers for medical and occupational surveillanceexternal icon
        Snyder-Talkington BN, Dong C, Singh S, Raese R, Qian Y, Porter DW, Wolfarth MG, Guo NL.
        Int J Mol Sci. 2019 May 29;20(11).
        As the demand for multi-walled carbon nanotube (MWCNT) incorporation into industrial and biomedical applications increases, so does the potential for unintentional pulmonary MWCNT exposure, particularly among workers during manufacturing. Pulmonary exposure to MWCNTs raises the potential for development of lung inflammation, fibrosis, and cancer among those exposed; however, there are currently no effective biomarkers for detecting lung fibrosis or predicting the risk of lung cancer resulting from MWCNT exposure. To uncover potential mRNAs and miRNAs that could be used as markers of exposure, this study compared in vivo mRNA and miRNA expression in lung tissue and blood of mice exposed to MWCNTs with in vitro mRNA and miRNA expression from a co-culture model of human lung epithelial and microvascular cells, a system previously shown to have a higher overall genome-scale correlation with mRNA expression in mouse lungs than either cell type grown separately. Concordant mRNAs and miRNAs identified by this study could be used to drive future studies confirming human biomarkers of MWCNT exposure. These potential biomarkers could be used to assess overall worker health and predict the occurrence of MWCNT-induced diseases.

      9. Suboptimal handling of Piccolo samples or reagent discs for consideration in Ebola responseexternal icon
        Spengler JR, Welch SR, Genzer SC, Coleman-McCray J, Harmon JR, Nichol ST, Spiropoulou CF.
        Emerg Infect Dis. 2019 Jun;25(6):1238-1240.
        Operating clinical analyzers within recommended parameters can be challenging during outbreak response. Using the Piccolo Xpress point-of-care blood chemistry analyzer on guinea pig blood, we found that values of many analytes are still readily comparable when samples and reagent discs are handled at various conditions outside of manufacturer recommendations.

      10. A nonhuman primate model for rectally transmitted syphilisexternal icon
        Tansey C, Zhao C, Hopkins A, Ritter JM, Fakile YF, Pillay A, Katz SS, Pereira L, Mitchell J, Deyounks F, Kersh EN, McNicholl JM, Vishwanathan SA.
        J Infect Dis. 2018 Mar 13;217(7):1139-1144.
        Among men who have sex with men (MSM), those with a diagnosis of syphilis or other rectal sexually transmitted infections (STIs) are at a higher risk for human immunodeficiency virus acquisition, which is concerning given the large increase in recently reported syphilis cases in the United States. We have developed the first nonhuman primate model for rectally transmitted syphilis by exposing simian/human immunodeficiency virus-infected and naive rhesus macaques to Treponema pallidum in the rectum. All animals showed mucosal lesions, systemic dissemination, and seroconversion (treponemal antibodies). This model would be valuable for studying the manifestations of and interventions for T. pallidum infection, with and without human immunodeficiency virus coinfection.

      11. Characterization of novel reoviruses Wad Medani virus (Orbivirus) and Kundal virus (Coltivirus) collected from Hyalomma anatolicum ticks in India during surveillance for Crimean Congo hemorrhagic feverexternal icon
        Yadav PD, Whitmer SL, Sarkale P, Fei Fan Ng T, Goldsmith CS, Nyayanit DA, Esona MD, Shrivastava-Ranjan P, Lakra R, Pardeshi P, Majumdar TD, Francis A, Klena JD, Nichol ST, Stroher U, Mourya D.
        J Virol. 2019 Jul 1;93(13).
        In 2011, ticks were collected from livestock following an outbreak of Crimean Congo hemorrhagic fever (CCHF) in Gujarat state, India. CCHF-negative Hyalomma anatolicum tick pools were passaged for virus isolation, and two virus isolates were obtained, designated Karyana virus (KARYV) and Kundal virus (KUNDV), respectively. Traditional reverse transcription-PCR (RT-PCR) identification of known viruses was unsuccessful, but a next-generation sequencing (NGS) approach identified KARYV and KUNDV as viruses in the Reoviridae family, Orbivirus and Coltivirus genera, respectively. Viral genomes were de novo assembled, yielding 10 complete segments of KARYV and 12 nearly complete segments of KUNDV. The VP1 gene of KARYV shared a most recent common ancestor with Wad Medani virus (WMV), strain Ar495, and based on nucleotide identity we demonstrate that it is a novel WMV strain. The VP1 segment of KUNDV shares a common ancestor with Colorado tick fever virus, Eyach virus, Tai Forest reovirus, and Tarumizu tick virus from the Coltivirus genus. Based on VP1, VP6, VP7, and VP12 nucleotide and amino acid identities, KUNDV is proposed to be a new species of Coltivirus Electron microscopy supported the classification of KARYV and KUNDV as reoviruses and identified replication morphology consistent with other orbi- and coltiviruses. The identification of novel tick-borne viruses carried by the CCHF vector is an important step in the characterization of their potential role in human and animal pathogenesis.IMPORTANCE Ticks and mosquitoes, as well Culicoides, can transmit viruses in the Reoviridae family. With the help of next-generation sequencing (NGS), previously unreported reoviruses such as equine encephalosis virus, Wad Medani virus (WMV), Kammavanpettai virus (KVPTV), and, with this report, KARYV and KUNDV have been discovered and characterized in India. The isolation of KUNDV and KARYV from Hyalomma anatolicum, which is a known vector for zoonotic pathogens, such as Crimean Congo hemorrhagic fever virus, Babesia, Theileria, and Anaplasma species, identifies arboviruses with the potential to transmit to humans. Characterization of KUNDV and KARYV isolated from Hyalomma ticks is critical for the development of specific serological and molecular assays that can be used to determine the association of these viruses with disease in humans and livestock.

      12. Grouping of carbonaceous nanomaterials based on association of patterns of inflammatory markers in BAL fluid with adverse outcomes in lungsexternal icon
        Yanamala N, Desai I, Miller W, Kodali V, Syamlal G, Roberts JR, Erdely A.
        Nanotoxicology. 2019 Jul 8:1-38.
        Carbonaceous nanomaterials (CNMs) are universally being used to make commodities, as they present unique opportunities for development and innovation in the fields of engineering, biotechnology, etc. As technology advances to incorporate CNMs in industry, the potential exposures associated with these particles also increase. CNMs have been found to be associated with substantial pulmonary toxicity, including inflammation, fibrosis, and/or granuloma formation in animal models. This study attempts to categorize the toxicity profiles of various carbon allotropes, in particular, carbon black, different multi-walled carbon nanotubes, graphene-based materials and their derivatives. Statistical and machine learning based approaches were used to identify groups of CNMs with similar pulmonary toxicity responses from a panel of proteins measured in bronchoalveolar lavage (BAL) fluid samples and with similar pathological outcomes in the lungs. Thus, grouped particles, based on their pulmonary toxicity profiles, were used to select a small set of proteins that could potentially identify and discriminate between the toxicity profiles associated within each group. Specifically, MDC/CCL22 and MIP-3beta/CCL19 were identified as common protein markers associated with both toxicologically distinct groups of CNMs. In addition, the persistent expression of other selected protein markers in BAL fluid from each group suggested their ability to predict toxicity in the lungs, i.e., fibrosis and microgranuloma formation. The advantages of such approaches can have positive implications for further research in toxicity profiling.

    • Nutritional Sciences
      1. NIH workshop on human milk composition: summary and visionsexternal icon
        Casavale KO, Ahuja JK, Wu X, Li Y, Quam J, Olson R, Pehrsson P, Allen L, Balentine D, Hanspal M, Hayward D, Hines EP, McClung JP, Perrine CG, Belfort MB, Dallas D, German B, Kim J, McGuire M, McGuire M, Morrow AL, Neville M, Nommsen-Rivers L, Rasmussen KM, Zempleni J, Lynch CJ.
        Am J Clin Nutr. 2019 Jul 5.
        Nationally representative data from mother-child dyads that capture human milk composition (HMC) and associated health outcomes are important for advancing the evidence to inform federal nutrition and related health programs, policies, and consumer information across the governments in the United States and Canada as well as in nongovernment sectors. In response to identified gaps in knowledge, the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH sponsored the “Workshop on Human Milk Composition-Biological, Environmental, Nutritional, and Methodological Considerations” held 16-17 November 2017 in Bethesda, Maryland. Through presentations and discussions, the workshop aimed to 1) share knowledge on the scientific need for data on HMC; 2) explore the current understanding of factors affecting HMC; 3) identify methodological challenges in human milk (HM) collection, storage, and analysis; and 4) develop a vision for a research program to develop an HMC data repository and database. The 4 workshop sessions included 1) perspectives from both federal agencies and nonfederal academic experts, articulating scientific needs for data on HMC that could lead to new research findings and programmatic advances to support public health; 2) information about the factors that influence lactation and/or HMC; 3) considerations for data quality, including addressing sampling strategies and the complexities in standardizing collection, storage, and analyses of HM; and 4) insights on how existing research programs and databases can inform potential visions for HMC initiatives. The general consensus from the workshop is that the limited scope of HM research initiatives has led to a lack of robust estimates of the composition and volume of HM consumed and, consequently, missed opportunities to improve maternal and infant health.

      2. Integrating small-quantity lipid-based nutrient supplements (SQ-LNS) into infant and young child feeding (IYCF) programmes can increase consumption of essential nutrients among children in vulnerable populations; however, few studies have assessed the impact of integrated IYCF-SQ-LNS programmes on IYCF practices. A 2-year, enhanced IYCF intervention targeting pregnant women and infants (0-12 months) was implemented in a health zone in the Democratic Republic of Congo (DRC). The enhanced IYCF intervention included community- and facility-based counselling for mothers on handwashing, SQ-LNS, and IYCF practices, plus monthly SQ-LNS distributions for children 6-12 months; a control zone received the national IYCF programme (facility-based IYCF counselling with no SQ-LNS distributions). Cross-sectional preintervention and postintervention surveys (n = 650 and 638 in intervention and control areas at baseline; n = 654 and 653 in each area at endline, respectively) were conducted in mothers of children 6-18 months representative of both zones. Difference in differences (DiD) analyses used mixed linear regression models. There were significantly greater increases in the proportion of mothers in the intervention (vs. control) zone who reported: initiating breastfeeding within 1 hr of birth (Adj. DiD [95% CI]: +56.4% [49.3, 63.4], P < 0.001), waiting until 6 months to introduce water (+66.9% [60.6, 73.2], P < 0.001) and complementary foods (+56.4% [49.3, 63.4], P < 0.001), feeding the minimum meal frequency the previous day (+9.2% [2.7, 15.7], P = 0.005); feeding the child in a separate bowl (+9.7% [2.2, 17.2], P = 0.01); awareness of anaemia (+16.9% [10.4, 23.3], P < 0.001); owning soap (+14.9% [8.3, 21.5], P < 0.001); and washing hands after defecating and before cooking and feeding the child the previous day (+10.5% [5.8, 15.2], +12.5% [9.3, 15.6] and +15.0% [11.2, 18.8], respectively, P < 0.001 for all). The enhanced IYCF intervention in the DRC was associated with an improvement in several important IYCF practices but was not associated with a change in dietary diversity (minimum dietary diversity and minimum acceptable diet remained below 10% in both zones without significant differences between zones). The provision of fortified complementary foods, such as SQ-LNS, may be an important source of micronutrients and macronutrients for young children in areas with high rates of poverty and limited access to diverse foods. Future research should verify the potential of integrated IYCF-SQ-LNS to improve IYCF practices, and ultimately children’s nutritional status.

    • Occupational Safety and Health
      1. Firefighters’ and instructors’ absorption of PAHs and benzene during training exercisesexternal icon
        Fent KW, Toennis C, Sammons D, Robertson S, Bertke S, Calafat AM, Pleil JD, Geer Wallace MA, Kerber S, Smith DL, Horn GP.
        Int J Hyg Environ Health. 2019 Jul 2.
        INTRODUCTION: Training fires may constitute a major portion of some firefighters’ occupational exposures to smoke. However, the magnitude and composition of those exposures are not well understood and may vary by the type of training scenario and fuels. OBJECTIVES: To understand how structure fire training contributes to firefighters’ and instructors’ select chemical exposures, we conducted biological monitoring during exercises involving combustion of pallet and straw and oriented strand board (OSB) or the use of simulated smoke. METHODS: Urine was analyzed for metabolites of polycyclic aromatic hydrocarbons (PAHs) and breath was analyzed for volatile organic compounds (VOCs) including benzene. RESULTS: Median concentrations of nearly all PAH metabolites in urine increased from pre-to 3-hr post-training for each scenario and were highest for OSB, followed by pallet and straw, and then simulated smoke. For instructors who supervised three trainings per day, median concentrations increased at each collection. A single day of OSB exercises led to a 30-fold increase in 1-hydroxypyrene for instructors, culminating in a median end-of-shift concentration 3.5-fold greater than median levels measured from firefighters in a previous controlled-residential fire study. Breath concentrations of benzene increased 2 to 7-fold immediately after the training exercises (with the exception of simulated smoke training). Exposures were highest for the OSB scenario and instructors accumulated PAHs with repeated daily exercises. CONCLUSIONS: Dermal absorption likely contributed to the biological levels as the respiratory route was well protected. Training academies should consider exposure risks as well as instructional objectives when selecting training exercises.

      2. Ergonomics assessment methods used by ergonomics professionalsexternal icon
        Lowe BD, Dempsey PG, Jones EM.
        Applied Ergonomics. 2019 ;81.
        A web-based survey was conducted of ergonomics practitioners holding certifications in the U.S., Canada, Great Britain, Australia, and New Zealand. The survey follows 12 years after an earlier initial survey reported by Dempsey et al. (2005). Approximately 1221 eligible participants were invited by e-mail to participate, and 405 surveys were included in the final analysis. The survey queried use of basic instruments relevant to ergonomic practice as well as more specific analytical tools such as observational techniques for assessing postural demands of work and instrumentation for direct measurement of such demands. Some ergonomic assessment methods appear to have increased in their overall use by U.S. ergonomists compared to 2005 data. This was observed for: RULA, REBA, Psychophysical Upper Extremity Data, Strain Index, and ACGIH TLV for Hand Activity Level. There is minimal evidence of increased overall use of direct measurement approaches in the U.S. There appear to be geographic differences between countries/continents in terms of use of various methods. The use of mobile device/smart phone ?apps? by ergonomists was queried and these technologies presently appear to be in early adoption phase with 24?28% of practitioners reporting use of an app in their ergonomics practice.

      3. Child care stress and anxiety in police officers moderated by work factorsexternal icon
        McCanlies EC, Mnatsakanova A, Andrew ME, Violanti JM, Hartley TA.
        Policing. 2019 .
        Purpose: Balancing work and family in dual-earner households can be stressful. Research suggests that increased work-family conflict (WFC) significantly predicts poor psychological health and increased stress in police officers. The purpose of this paper is to assess whether child care stress was associated with anxiety symptoms and if stressful work events and shift work modified this relationship among 163 Buffalo, NY police officers. Design/methodology/approach: Participants indicated child care stress by reporting how much stress they felt (0 ? none to 10 ? high) when making child care/daily living arrangements. Shiftwork was assessed from pay-roll data (1994 to date of exam) and by asking, ?Do you work opposite shift from your spouse/partner to care for your children?? to assess partner?s shift. The Beck Anxiety Scale and Spielberger Police Stress Survey were used to assess anxiety and work stress, respectively. Effect modification was assessed by stratifying on police stress scores using their median values, and on partner?s shift. All models were adjusted for age, alcohol intake, sex and smoking status. Findings: Results suggest that child care stress was positively associated with anxiety symptoms and that this relationship was moderated by high (>median) work stress factors and afternoon/midnight shift-work, but not having a partner who works opposite shift. These results indicate that child care stress is associated with anxiety symptoms and that this relationship may be modified by work factors. Research limitations/implications: A number of limitations should be considered while interpreting the results. This study is cross-sectional, which prevents causal inferences; therefore, the temporal pattern between exposure and outcome cannot be determined. The independent, dependent and moderating variables are all self-report measures, which may introduce recall bias. Lastly, generalizability is limited to police departments of similar size and geographic area. Practical implications: Police experience high stress as part of their jobs, these results indicate that similar to other professions, WFC can also affect police officers, and is associated with higher levels of anxiety. Originality/value: Few research studies have evaluated the affects of family issues in police. Specifically, the relationship between child care stress and anxiety, and how this relationship may be modified by high work stress.

      4. Background: The seafood processing industry is critical to Alaska’s economy and hazardous to workers; however, limited research has addressed workers’ safety and health. Safety and health program management is a decisive factor in preventing fatalities, injuries, and illnesses. We interviewed managers to gain their views on their safety and health programs. Methods: Semi-structured interviews were conducted with 14 upper-level managers who oversaw programs for Alaskan worksites. Interviews were audio-recorded and transcribed. Qualitative content analysis techniques, including inductive coding, were utilized to explore participants’ experiences and views regarding: management and workers’ roles; hazard control systems; safety and health training; regulatory and economic factors; and programs’ challenges and successes. Results: The 14 participants represented 13 companies that operated 32 onshore plants and 30 vessels with processing capabilities. Participants reported managing programs for an estimated 68% of the Alaskan seafood processing industry’s workforce. Based on participants’ responses, we identified five factors that could be modified to improve safety and health industry-wide: manager training and knowledge sharing; worker training; organizational aspects related to safety culture; application of ergonomic principles; and work hours. Participants reported that fully engaging workers in programs was beneficial. Conclusions: Industry members should more widely share their best practices for protecting workers’ safety and health. Occupational safety and health practitioners and researchers should support the development and evaluation of (a) training for non/limited-English-speaking-workers, (b) ergonomic interventions, and (c) fatigue risk management systems. Future research should engage worksite managers and workers to characterize their safety and health experiences and needs.

      5. Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staffexternal icon
        Verbeek JH, Rajamaki B, Ijaz S, Tikka C, Ruotsalainen JH, Edmond MB, Sauni R, Kilinc Balci FS.
        Cochrane Database Syst Rev. 2019 Jul 1;7.
        BACKGROUND: In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or Severe Acute Respiratory Syndrome (SARS), healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients’ contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCW use PPE as instructed. OBJECTIVES: To evaluate which type of full body PPE and which method of donning or doffing PPE have the least risk of self-contamination or infection for HCW, and which training methods increase compliance with PPE protocols. SEARCH METHODS: We searched MEDLINE (PubMed up to 15 July 2018), Cochrane Central Register of Trials (CENTRAL up to 18 June 2019), Scopus (Scopus 18 June 2019), CINAHL (EBSCOhost 31 July 2018), and OSH-Update (up to 31 December 2018). We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. SELECTION CRITERIA: We included all controlled studies that compared the effects of PPE used by HCW exposed to highly infectious diseases with serious consequences, such as Ebola or SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that used simulated contamination with fluorescent markers or a non-pathogenic virus.We also included studies that compared the effect of various ways of donning or doffing PPE, and the effects of training in PPE use on the same outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We planned to perform meta-analyses but did not find sufficiently similar studies to combine their results. MAIN RESULTS: We included 17 studies with 1950 participants evaluating 21 interventions. Ten studies are Randomised Controlled Trials (RCTs), one is a quasi RCT and six have a non-randomised controlled design. Two studies are awaiting assessment.Ten studies compared types of PPE but only six of these reported sufficient data. Six studies compared different types of donning and doffing and three studies evaluated different types of training. Fifteen studies used simulated exposure with fluorescent markers or harmless viruses. In simulation studies, contamination rates varied from 10% to 100% of participants for all types of PPE. In one study HCW were exposed to Ebola and in another to SARS.Evidence for all outcomes is based on single studies and is very low quality.Different types of PPEPPE made of more breathable material may not lead to more contamination spots on the trunk (Mean Difference (MD) 1.60 (95% Confidence Interval (CI) -0.15 to 3.35) than more water repellent material but may have greater user satisfaction (MD -0.46; 95% CI -0.84 to -0.08, scale of 1 to 5).Gowns may protect better against contamination than aprons (MD large patches -1.36 95% CI -1.78 to -0.94).The use of a powered air-purifying respirator may protect better than a simple ensemble of PPE without such respirator (Relative Risk (RR) 0.27; 95% CI 0.17 to 0.43).Five different PPE ensembles (such as gown vs. coverall, boots with or without covers, hood vs. cap, length and number of gloves) were evaluated in one study, but there were no event data available for compared groups.Alterations to PPE design may lead to less contamination such as added tabs to grab masks (RR 0.33; 95% CI 0.14 to 0.80) or gloves (RR 0.22 95% CI 0.15 to 0.31), a sealed gown and glove combination (RR 0.27; 95% CI 0.09 to 0.78), or a better fitting gown around the neck, wrists and hands (RR 0.08; 95% CI 0.01 to 0.55) compared to standard PPE.Different methods of donning and doffing proceduresDouble gloving may lead to less contamination compared to single gloving (RR 0.36; 95% CI 0.16 to 0.78).Following CDC recommendations for doffing may lead to less contamination compared to no guidance (MD small patches -5.44; 95% CI -7.43 to -3.45).Alcohol-based hand rub used during the doffing process may not lead to less contamination than the use of a hypochlorite based solution (MD 4.00; 95% CI 0.47 to 34.24).Additional spoken instruction may lead to fewer errors in doffing (MD -0.9, 95% CI -1.4 to -0.4).Different types of trainingThe use of additional computer simulation may lead to fewer errors in doffing (MD -1.2, 95% CI -1.6 to -0.7).A video lecture on donning PPE may lead to better skills scores (MD 30.70; 95% CI 20.14,41.26) than a traditional lecture.Face to face instruction may reduce noncompliance with doffing guidance more (OR 0.45; 95% CI 0.21 to 0.98) than providing folders or videos only.There were no studies on effects of training in the long term or on resource use.The quality of the evidence is very low for all comparisons because of high risk of bias in all studies, indirectness of evidence, and small numbers of participants. AUTHORS’ CONCLUSIONS: We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. Alterations to PPE, such as tabs to grab may decrease contamination. Double gloving, following CDC doffing guidance, and spoken instructions during doffing may reduce contamination and increase compliance. Face-to-face training in PPE use may reduce errors more than video or folder based training. Because data come from single small studies with high risk of bias, we are uncertain about the estimates of effects.We still need randomised controlled trials to find out which training works best in the long term. We need better simulation studies conducted with several dozen participants to find out which PPE protects best, and what is the safest way to remove PPE. Consensus on the best way to conduct simulation of exposure and assessment of outcome is urgently needed. HCW exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection in the field.

    • Occupational Safety and Health – Mining
      1. Risk assessment of recordable occupational hearing loss in the mining industryexternal icon
        Sun K, Azman AS, Camargo HE, Dempsey PG.
        Int J Audiol. 2019 Jul 8:1-8.
        Objective: To evaluate the hearing loss risk in different sectors and subunits in the mining industry and to identify associated occupations, in an attempt to locate gaps between hearing conservation efforts and hearing loss risks.Design: Descriptive statistics and frequency tables were generated by commodity types, subunit operations, and/or occupations. Temporal trends of the incidences of hearing loss were reported by commodity types.Study Sample: The MSHA Accident/Injury/Illness and MSHA Address/Employment databases from 2000 to 2014 were used.Results: Incidence rate of OHL was reported highest in the coal sector compared to other commodity types. Those members of the workforce that entered the mining industry after the year 2000 accounted for 6.5% and 19.0% of the total hearing loss records for coal and non-coal, respectively. High-risk occupations found in all three commodity sectors (coal; stone, sand, and gravel; and metal/non-metal) were electrician/helper/wireman, mechanic/repairman/helper, bulldozer/tractor operator, and truck driver.Conclusion: Hearing loss risks were not uniform across mining sectors, subunit operations, and occupations. In addition to the continuous efforts of implementing engineering controls to reduce machinery sound level exposure for operators, a multi-level approach may benefit those occupations with a more dynamic exposure profile – e.g., labour/utilityman/bullgang, electrician/helper/wireman, and mechanic/repairman/helper.

    • Parasitic Diseases
      1. The public health control of scabies: priorities for research and actionexternal icon
        Engelman D, Cantey PT, Marks M, Solomon AW, Chang AY, Chosidow O, Enbiale W, Engels D, Hay RJ, Hendrickx D, Hotez PJ, Kaldor JM, Kama M, Mackenzie CD, McCarthy JS, Martin DL, Mengistu B, Maurer T, Negussu N, Romani L, Sokana O, Whitfeld MJ, Fuller LC, Steer AC.
        Lancet. 2019 Jul 6;394(10192):81-92.
        Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.

      2. Persistent hot spots in Schistosomiasis Consortium for Operational Research and Evaluation Studies for Gaining and Sustaining Control of Schistosomiasis after four years of mass drug administration of praziquantelexternal icon
        Kittur N, King CH, Campbell CH, Kinung’hi S, Mwinzi PN, Karanja DM, N’Goran EK, Phillips AE, Gazzinelli-Guimaraes PH, Olsen A, Magnussen P, Secor WE, Montgomery SP, Utzinger J, Walker JW, Binder S, Colley DG.
        Am J Trop Med Hyg. 2019 Jul 8.
        Control of schistosomiasis presently relies largely on preventive chemotherapy with praziquantel through mass drug administration (MDA) programs. The Schistosomiasis Consortium for Operational Research and Evaluation has concluded five studies in four countries (Cote d’Ivoire, Kenya, Mozambique, and Tanzania) to evaluate alternative approaches to MDA. Studies involved four intervention years, with final evaluation in the fifth year. Mass drug administration given annually or twice over 4 years reduced average prevalence and intensity of schistosome infections, but not all villages that were treated in the same way responded similarly. There are multiple ways by which responsiveness to MDA, or the lack thereof, could be measured. In the analyses presented here, we defined persistent hot spots (PHSs) as villages that achieved less than 35% reduction in prevalence and/or less than 50% reduction in infection intensity after 4 years of either school-based or community-wide MDA, either annually or twice in 4 years. By this definition, at least 30% of villages in each of the five studies were PHSs. We found no consistent relationship between PHSs and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. New research is warranted to identify PHSs after just one or a few rounds of MDA, and new adaptive strategies need to be advanced and validated for turning PHSs into responder villages.

    • Substance Use and Abuse
      1. Workplace secondhand tobacco smoke exposure among U.S. nonsmoking workers, 2015external icon
        Su CP, Syamlal G, Tamers S, Li J, Luckhaupt SE.
        MMWR Morb Mortal Wkly Rep. 2019 Jul 12;68(27):604-607.
        Secondhand tobacco smoke (SHS) exposure contributes to ill health and disease, including heart disease, lung cancer, and stroke (1). Although cigarette smoking has declined among U.S. workers, workplace exposure to SHS remains high, particularly among workers in certain industries, such as construction (2,3). Implementation of smoke-free laws has proven to be beneficial in reducing SHS exposure in general (1). CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement to assess the prevalence of self-reported workplace SHS exposure among nonsmoking workers by smoke-free policy status in the workers’ states of residence and in detailed industry categories and subcategories. In 2015, 19.9% of nonsmoking workers reported any exposure to SHS at work during the 12 months preceding the interview, and 10.1% reported frequent exposure (twice a week or more). Nonsmoking workers who resided in states with comprehensive smoke-free laws in all three categories of venues (private worksites, bars, and restaurants) were least likely to report frequent exposure to workplace SHS. Nonsmoking workers employed in the commercial and industrial machinery and equipment repair and maintenance industry reported the highest prevalences of any workplace SHS exposure (65.1%), whereas the construction industry had the highest reported number of exposed workers (2.9 million); these industry categories/subcategories include outdoor workplaces and other settings that are unlikely to be protected by smoke-free laws. Identifying specific at-risk workplaces and implementing targeted intervention strategies could help reduce SHS exposure at work and protect workers’ health.

    • Zoonotic and Vectorborne Diseases
      1. First reported human cases of leptospirosis in the United States Virgin Islands in the aftermath of Hurricanes Irma and Maria, September-November 2017external icon
        Marinova-Petkova A, Guendel I, Strysko JP, Ekpo LL, Galloway R, Yoder J, Kahler A, Artus A, Hoffmaster AR, Bower WA, Walke H, Ellis BR, Hunte-Ceasar T, Ellis EM, Schafer IJ.
        Open Forum Infect Dis. 2019 Jul;6(7):ofz261.
        Objective: Following Hurricanes Irma and Maria, the first case of human leptospirosis ever identified in the US Virgin Islands (USVI) was reported to the Virgin Islands Department of Health. Leptospirosis is a potentially fatal bacterial disease caused by Leptospira species found in animal urine and urine-contaminated water and soil. Outbreaks can occur following extreme weather events. Method: Additional cases of leptospirosis were identified in the 2.5 months post-hurricanes by reviewing emergency department (ED) records from territorial hospitals for patients demonstrating leptospirosis-consistent symptoms, testing symptomatic patients previously enrolled in the USVI arbovirus surveillance system (VIASS), and adding leptospirosis testing prospectively to VIASS. Available patient sera underwent local rapid diagnostic testing for anti-Leptospira IgM followed by confirmatory microscopic agglutination testing at the US Centers for Disease Control and Prevention. Water was collected from cisterns with epidemiologic links to confirmed cases and tested by real-time PCR (qPCR) for pathogenic Leptospira spp. Results: Sixteen retrospectively identified symptomatic patients were enrolled in VIASS; 15 with available samples tested negative. Based on review of 5226 ED charts, 6 patients were further investigated; of these, 5 were tested of which 1 was positive. Prospective leptospirosis surveillance tested 57 additional patients; of these, 1 was positive. Water from 1 of 5 tested cisterns was found positive by qPCR. Conclusions: This investigation documents the first 3 cases of leptospirosis reported in the USVI and demonstrates how VIASS successfully was adapted to establish leptospirosis surveillance. Contaminated cistern water was identified as a potential source for Leptospira spp. transmission, highlighting the need for additional post-hurricane remediation and disinfection guidance.

      2. Notes from the field: Conjunctivitis caused by toxigenic Corynebacterium ulcerans – Missouri, 2018external icon
        Weil LM, Butler C, Howell KR, Sharr S, Paley GL, Huang AJ, Maamari RN, Pawloski LC, Cassiday PK, Acosta AM, Hariri S, Tiwari TS.
        MMWR Morb Mortal Wkly Rep. 2019 Jul 12;68(27):615-616.

        [No abstract]

      3. Outbreak of human monkeypox in Nigeria in 2017-18: a clinical and epidemiological reportexternal icon
        Yinka-Ogunleye A, Aruna O, Dalhat M, Ogoina D, McCollum A, Disu Y, Mamadu I, Akinpelu A, Ahmad A, Burga J, Ndoreraho A, Nkunzimana E, Manneh L, Mohammed A, Adeoye O, Tom-Aba D, Silenou B, Ipadeola O, Saleh M, Adeyemo A, Nwadiutor I, Aworabhi N, Uke P, John D, Wakama P, Reynolds M, Mauldin MR, Doty J, Wilkins K, Musa J, Khalakdina A, Adedeji A, Mba N, Ojo O, Krause G, Ihekweazu C.
        Lancet Infect Dis. 2019 Jul 5.
        BACKGROUND: In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017-18 human monkeypox outbreak in Nigeria. METHODS: We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus. FINDINGS: 122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility. INTERPRETATION: This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria. FUNDING: None.

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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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Content source: Centers for Disease Control and Prevention