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Volume 12, Issue 24, July 21, 2020

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CDC Science Clips: Volume 12, Issue 24, July 21, 2020

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

This week, CDC Science Clips is pleased to feature items related to the July CDC Public Health Grand Rounds: Acute Flaccid Myelitis: Answering Questions Through National Collaboration. Acute flaccid myelitis (AFM) is an uncommon but serious neurologic condition. It affects the nervous system and causes the muscles and reflexes in the body to become weak. Most AFM cases have been in young children. Cases have been increasing every other year in the United States since 2014. During this session of Public Health Grand Rounds, national AFM experts will discuss the epidemiology of AFM, along with the clinical presentation, diagnosis, treatment, rehabilitation, and prevention research updates. Grand Rounds also will present a parent’s perspective on building an AFM support network in the United States.

The report consists of these components:

  1. CDC Public Health Grand Rounds
    • Acute Flaccid Myelitis
      1. Enterovirus D68 infection in children with acute flaccid myelitis, Colorado, USA, 2014external icon
        Aliabadi N, Messacar K, Pastula DM, Robinson CC, Leshem E, Sejvar JJ, Nix WA, Oberste MS, Feikin DR, Dominguez SR.
        Emerg Infect Dis. 2016 Aug;22(8):1387-94.
        During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.

      2. Acute flaccid myelitis in the United States: 2015-2017external icon
        Ayers T, Lopez A, Lee A, Kambhampati A, Nix WA, Henderson E, Rogers S, Weldon WC, Oberste MS, Sejvar J, Hopkins SE, Pallansch MA, Routh JA, Patel M.
        Pediatrics. 2019 Nov;144(5).
        BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count >5 cells per mm(3) in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age ≤21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition.

      3. Understanding enterovirus d68-induced neurologic disease: A basic science reviewexternal icon
        Hixon AM, Frost J, Rudy MJ, Messacar K, Clarke P, Tyler KL.
        Viruses. 2019 Sep 4;11(9).
        In 2014, the United States (US) experienced an unprecedented epidemic of enterovirus D68 (EV-D68)-induced respiratory disease that was temporally associated with the emergence of acute flaccid myelitis (AFM), a paralytic disease occurring predominantly in children, that has a striking resemblance to poliomyelitis. Although a definitive causal link between EV-D68 infection and AFM has not been unequivocally established, rapidly accumulating clinical, immunological, and epidemiological evidence points to EV-D68 as the major causative agent of recent seasonal childhood AFM outbreaks in the US. This review summarizes evidence, gained from in vivo and in vitro models of EV-D68-induced disease, which demonstrates that contemporary EV-D68 strains isolated during and since the 2014 outbreak differ from historical EV-D68 in several factors influencing neurovirulence, including their genomic sequence, their receptor utilization, their ability to infect neurons, and their neuropathogenicity in mice. These findings provide biological plausibility that EV-D68 is a causal agent of AFM and provide important experimental models for studies of pathogenesis and treatment that are likely to be difficult or impossible in humans.

      4. PURPOSE OF REVIEW: Purpose of review Acute flaccid myelitis is a polio-like illness defined by the acute onset of flaccid paralysis in the setting spinal MRI demonstrating a longitudinal lesion in the gray matter of the cord. This paper aims to review the current state of knowledge and key clinical points for the diagnosis and management of acute flaccid myelitis. RECENT FINDINGS: Recent findings There were clusters of AFM noted in California and Colorado in 2014, with additional cases across the USA that year, and another spike in cases in 2016. Patients have been managed with classic treatments for transverse myelitis, but in general without benefit, although some colleagues have noted anecdotal improvement in individual patients. Our current practice at the Children's Hospital of Philadelphia is to initiate therapy with intravenous immunoglobulin (IVIG) upon recognition of acute flaccid myelitis in hopes of boosting humoral immunity, and to provide an emphasis on rehabilitation services, including physical and occupational therapy. There is some data that suggests a connection to the virus enterovirus D68 (EV D68), but there has been no definitive link. Publications regarding longer-term outcomes in these patients are early in development and, thus far, only provide data for 6 to 12 months from onset. Summary AFM is a serious illness with long-term consequences, and we have much to learn. Key areas in need of further investigation involve etiology, host susceptibilities, treatment options, and long-term outcome. Individual clinicians can assist in these efforts by the prompt reporting of cases of AFM to the US Centers for Disease Control and Prevention.

      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. Outcomes of Colorado children with acute flaccid myelitis at 1 yearexternal icon
        Martin JA, Messacar K, Yang ML, Maloney JA, Lindwall J, Carry T, Kenyon P, Sillau SH, Oleszek J, Tyler KL, Dominguez SR, Schreiner TL.
        Neurology. 2017 Jul 11;89(2):129-137.
        OBJECTIVE: We describe long-term functional, neurodiagnostic, and psychosocial outcomes of a cohort of 12 children from Colorado diagnosed with acute flaccid myelitis (AFM) in 2014. METHODS: Children were assessed every 3 months for 1 year or until clinical resolution. Assessments included neurologic examination, MRI, EMG/nerve conduction studies (NCS), functional measures (Assisting Hand Assessment, Hammersmith Functional Motor Scale), and Patient-Reported Outcomes Measurement Information System questionnaires. RESULTS: Eight of 12 children completed the study. Six of 8 had persistent motor deficits at 1 year; 2 demonstrated full recovery. Four were not enrolled, 2 of whom reported full recovery. The 6 affected were weakest in proximal muscles, showing minimal to no improvement and significant atrophy at 1 year. All patients improved in distal muscle groups. Cranial nerve dysfunction resolved in 2 of 5 and improved in all. Four of 5 showed progressive functional improvement at 6 and 12 months. Two of 8 reported pain at 1 year. Three of 8 reported depressive symptoms. Repeat MRI was performed in 7 of 8 children a median of 7 months after onset and showed significant improvement or normalization in all but one child. Repeat EMG/NCS was performed on 4 children a median of 8 months after onset and showed ongoing denervation and chronic reinnervation in 3 children with persistent deficits. CONCLUSIONS: At 1 year, children with AFM demonstrated functional gains but weakness persisted. EMG changes correlated with persistent deficits better than imaging. Despite improvements, AFM had substantial long-term functional effects on affected children.

      7. Characteristics of patients with acute flaccid myelitis, United States, 2015-2018external icon
        McLaren N, Lopez A, Kidd S, Zhang JX, Nix WA, Link-Gelles R, Lee A, Routh JA.
        Emerg Infect Dis. 2020 Feb;26(2):212-9.
        Observed peaks of acute flaccid myelitis (AFM) cases have occurred biennially since 2014 in the United States. We aimed to determine if AFM etiology differed between peak and nonpeak years, considering that clinical features of AFM differ by virus etiology. We compared clinical and laboratory characteristics of AFM cases that occurred during peak (2016 and 2018, n = 366) and nonpeak (2015 and 2017, n = 50) years. AFM patients in peak years were younger (5.2 years) than those in nonpeak years (8.3 years). A higher percentage of patients in peak years than nonpeak years had pleocytosis (86% vs. 60%), upper extremity involvement (33% vs. 16%), and an illness preceding limb weakness (90% vs. 62%) and were positive for enterovirus or rhinovirus RNA (38% vs. 16%). Enterovirus D68 infection was associated with AFM only in peak years. Our findings suggest AFM etiology differs between peak and nonpeak years.

      8. Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causalityexternal icon
        Messacar K, Asturias EJ, Hixon AM, Van Leer-Buter C, Niesters HG, Tyler KL, Abzug MJ, Dominguez SR.
        Lancet Infect Dis. 2018 Aug;18(8):e239-e247.
        Increased circulation of enterovirus D68 in 2014 and 2016 temporally and geographically coincided with increases in cases of acute flaccid myelitis, an uncommon condition of paralysis due to lesions in the anterior horn of the spinal cord. The identification of enterovirus D68 in respiratory specimens from cases of acute flaccid myelitis worldwide further supports an association, yet the absence of direct virus isolation from affected tissues, infrequent detection in cerebrospinal fluid, and the absence, until recently, of an animal model has left the causal nature of the relationship unproven. In this Personal View we evaluate epidemiological and biological evidence linking enterovirus D68 and acute flaccid myelitis. We applied the Bradford Hill criteria to investigate the evidence for a causal relationship and highlight the importance of comprehensive surveillance and research to further characterise the role of enterovirus D68 in acute flaccid myelitis and pursue effective therapies and prevention strategies.

      9. Acute flaccid myelitis: A clinical review of US cases 2012-2015external icon
        Messacar K, Schreiner TL, Van Haren K, Yang M, Glaser CA, Tyler KL, Dominguez SR.
        Ann Neurol. 2016 Sep;80(3):326-38.
        This review highlights clinical features of the increasing cases of acute flaccid paralysis associated with anterior myelitis noted in the United States from 2012 to 2015. Acute flaccid myelitis refers to acute flaccid limb weakness with spinal cord gray matter lesions on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing. Although some individuals demonstrated improvement in motor weakness and functional deficits, most have residual weakness a year or more after onset. Epidemiological evidence and biological plausibility support an association between enterovirus D68 and the recent increase in acute flaccid myelitis cases in the United States. Ann Neurol 2016;80:326-338.

      10. Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort studyexternal icon
        Messacar K, Spence-Davizon E, Osborne C, Press C, Schreiner TL, Martin J, Messer R, Maloney J, Burakoff A, Barnes M, Rogers S, Lopez AS, Routh J, Gerber SI, Oberste MS, Nix WA, Abzug MJ, Tyler KL, Herlihy R, Dominguez SR.
        Lancet Infect Dis. 2020 Feb;20(2):230-239.
        BACKGROUND: In May, 2018, Children's Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak. METHODS: In this retrospective observational cohort study, children (younger than 18 years) who presented to Children's Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018. FINDINGS: Between March 10 and Nov 10, 2018, 74 children presenting to Children's Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0-31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1-2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover. INTERPRETATION: This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance. FUNDING: None.

      11. Antibodies to enteroviruses in cerebrospinal fluid of patients with acute flaccid myelitisexternal icon
        Mishra N, Ng TF, Marine RL, Jain K, Ng J, Thakkar R, Caciula A, Price A, Garcia JA, Burns JC, Thakur KT, Hetzler KL, Routh JA, Konopka-Anstadt JL, Nix WA, Tokarz R, Briese T, Oberste MS, Lipkin WI.
        mBio. 2019 Aug 13;10(4).
        Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.

      12. Pan-viral serology implicates enteroviruses in acute flaccid myelitisexternal icon
        Schubert RD, Hawes IA, Ramachandran PS, Ramesh A, Crawford ED, Pak JE, Wu W, Cheung CK, O'Donovan BD, Tato CM, Lyden A, Tan M, Sit R, Sowa GA, Sample HA, Zorn KC, Banerji D, Khan LM, Bove R, Hauser SL, Gelfand AA, Johnson-Kerner BL, Nash K, Krishnamoorthy KS, Chitnis T, Ding JZ, McMillan HJ, Chiu CY, Briggs B, Glaser CA, Yen C, Chu V, Wadford DA, Dominguez SR, Ng TF, Marine RL, Lopez AS, Nix WA, Soldatos A, Gorman MP, Benson L, Messacar K, Konopka-Anstadt JL, Oberste MS, DeRisi JL, Wilson MR.
        Nat Med. 2019 Nov;25(11):1748-1752.
        Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)(1-6). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)(2). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM.

      13. Acute flaccid myelitis in the United States, August-December 2014: Results of nationwide surveillanceexternal icon
        Sejvar JJ, Lopez AS, Cortese MM, Leshem E, Pastula DM, Miller L, Glaser C, Kambhampati A, Shioda K, Aliabadi N, Fischer M, Gregoricus N, Lanciotti R, Nix WA, Sakthivel SK, Schmid DS, Seward JF, Tong S, Oberste MS, Pallansch M, Feikin D.
        Clin Infect Dis. 2016 Sep 15;63(6):737-745.
        BACKGROUND: During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. METHODS: Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. RESULTS: From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/µL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/µL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. CONCLUSIONS: Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM.


  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Diabetes mellitus among adults with tuberculosis in the USA, 2010-2017external icon
        Armstrong LR, Kammerer JS, Haddad MB.
        BMJ Open Diabetes Res Care. 2020 Jul;8(1).
        INTRODUCTION: To describe diabetes trends among adults with incident tuberculosis (TB) disease and examine diabetes-associated TB characteristics and patient outcomes in the USA. RESEARCH DESIGN AND METHODS: We examined all 71 855 persons aged >/=20 years with incident TB disease reported to the National Tuberculosis Surveillance System during 2010-2017. We performed multivariable logistic regression, comparing characteristics and outcomes among patients with TB reported to have diabetes and those whose diabetes status was unknown. RESULTS: An overall 18% (n=13 281) of the 71 855 adults with incident TB disease were reported as also having diabetes; the annual proportion increased from 15% in 2010 to 22% in 2017. Among patients aged >/=45 years with both TB and diabetes, the adjusted OR for cavitary or sputum smear-positive TB was 1.7 and 1.5, respectively (95% CIs 1.5 to 1.8 and 1.4 to 1.6). Patients with TB and diabetes had 30% greater odds of dying and took longer to achieve negative Mycobacterium tuberculosis cultures and complete treatment. CONCLUSIONS: The prevalence of reported diabetes among adults with TB disease has increased. Having diabetes as a comorbidity negatively affects patient outcomes. In accordance with national recommendations, all patients aged >/=45 years and all younger patients who have risk factors for diabetes should be screened for diabetes at the start of TB treatment.

      2. Retention among participants in the National Diabetes Prevention Program Lifestyle Change Program, 2012-2017external icon
        Cannon MJ, Masalovich S, Ng BP, Soler RE, Jabrah R, Ely EK, Smith BD.
        Diabetes Care. 2020 Jul 2.
        OBJECTIVE: To assess retention in the National Diabetes Prevention Program (DPP) lifestyle change program, which seeks to prevent type 2 diabetes in adults at high risk. RESEARCH DESIGN AND METHODS: We analyzed retention among 41,203 individuals who enrolled in Centers for Disease Control and Prevention (CDC)-recognized in-person lifestyle change programs at organizations that submitted data to CDC's Diabetes Prevention Recognition Program during January 2012-February 2017. RESULTS: Weekly attrition rates were typically <1-2% but were between 3.5% and 5% at week 2 and at weeks 17 and 18, where session frequency typically transitions from weekly to monthly. The percent of participants retained through 18 weeks varied by age (45.9% for 18-29 year olds, 53.4% for 30-44 year olds, 60.2% for 45-54 year olds, 66.7% for 55-64 year olds, and 67.6% for >/=65 year olds), race/ethnicity (70.5% for non-Hispanic whites, 60.5% for non-Hispanic blacks, 52.6% for Hispanics, and 50.6% for other), mean weekly percentage of body weight lost (41.0% for </=0% lost, 66.2% for >0 to <0.25% lost, 72.9% for 0.25 to <0.5% lost, and 73.9% for >/=0.5% lost), and mean weekly physical activity minutes (12.8% for 0 min, 56.1% for >0 to <60 min, 74.8% for 60 to <150 min, and 82.8% for >/=150 min) but not by sex (63.0% for men and 63.1% for women). CONCLUSIONS: Our results demonstrate the need to identify strategies to improve retention, especially among individuals who are younger or are members of racial/ethnic minority populations and among those who report less physical activity or less early weight loss. Strategies that address retention after the first session and during the transition from weekly to monthly sessions offer the greatest opportunity for impact.

      3. A systematic review of trends in all-cause mortality among people with diabetesexternal icon
        Chen L, Islam RM, Wang J, Hird TR, Pavkov ME, Gregg EW, Salim A, Tabesh M, Koye DN, Harding JL, Sacre JW, Barr EL, Magliano DJ, Shaw JE.
        Diabetologia. 2020 Jul 6.
        AIMS/HYPOTHESIS: We examined all-cause mortality trends in people with diabetes and compared them with trends among people without diabetes. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for observational studies published from 1980 to 2019 reporting all-cause mortality rates across >/=2 time periods in people with diabetes. Mortality trends were examined by ethnicity, age and sex within comparable calendar periods. RESULTS: Of 30,295 abstracts screened, 35 studies were included, providing data on 69 separate ethnic-specific or sex-specific populations with diabetes since 1970. Overall, 43% (3/7), 53% (10/19) and 74% (32/43) of the populations studied had decreasing trends in all-cause mortality rates in people with diabetes in 1970-1989, 1990-1999 and 2000-2016, respectively. In 1990-1999 and 2000-2016, mortality rates declined in 75% (9/12) and 78% (28/36) of predominantly Europid populations, and in 14% (1/7) and 57% (4/7) of non-Europid populations, respectively. In 2000-2016, mortality rates declined in 33% (4/12), 65% (11/17), 88% (7/8) and 76% (16/21) of populations aged <40, 40-54, 55-69 and >/=70 years, respectively. Among the 33 populations with separate mortality data for those with and without diabetes, 60% (6/10) of the populations with diabetes in 1990-1999 and 58% (11/19) in 2000-2016 had an annual reduction in mortality rates that was similar to or greater than in those without diabetes. CONCLUSIONS/INTERPRETATION: All-cause mortality has declined in the majority of predominantly Europid populations with diabetes since 2000, and the magnitude of annual mortality reduction matched or exceeded that observed in people without diabetes in nearly 60% of populations. Patterns of diabetes mortality remain uncertain in younger age groups and non-Europid populations. REGISTRATION: PROSPERO registration ID CRD42019095974. Graphical abstract.

      4. A national measurement framework to assess and improve sickle cell care in 4 US regionsexternal icon
        Faro EZ, Shook L, Treadwell MJ, King AA, Whiteman LN, Ivy ED, Hulihan M, Kavanagh PL, Selk S, Oyeku S, Berns SD.
        Public Health Rep. 2020 Jul 8.
        OBJECTIVES: Coordinated measurement strategies are needed to inform collaborative approaches to improve access to and quality of care for persons with sickle cell disease (SCD). The objective of our study was to develop a multilevel measurement strategy to assess improvements in access to and quality of care for persons with SCD in 4 US regions. METHODS: From 2014 through 2017, regional grantees in the Sickle Cell Disease Treatment Demonstration Program collected administrative and patient-level electronic health record (EHR) data to assess quality improvement initiatives. Four grantees-covering 29 US states and territories and an SCD population of 56 720-used a collective impact model to organize their work. The grantees collected administrative data from state Medicaid and Medicaid managed care organizations (MCOs) at multiple points during 2014-2017 to assess improvements at the population level, and local patient-level data were abstracted from site-level EHRs at regular intervals to track improvements over time. RESULTS: Administrative data were an important source of understanding population-level improvements but were delayed, whereas patient-level data were more sensitive to small-scale quality improvements. CONCLUSIONS: We established a shared measurement approach in partnership with Medicaid and Medicaid MCO stakeholders that can be leveraged to effectively support quality improvement initiatives for persons with SCD in the United States.

      5. OBJECTIVE: Several cross-sectional studies have shown that height in childhood is correlated with BMI and with body fatness, and two longitudinal studies have reported that childhood height is associated with adult BMI. This study explored this longitudinal association in an electronic health record database of 2.8 million children. METHODS: Children were initially examined between the ages of 2 and 13.9 years and, on average, were reexamined 4 years later. RESULTS: As expected, there was a cross-sectional correlation between height-for-age z score and BMI that increased from r = -0.06 (age of 2 years) to r = 0.37 (age of 9-10 years). In addition, height-for-age at the first visit was related to subsequent BMI and obesity, with the prevalence of subsequent obesity increasing about fourfold over six categories of height-for-age at the first visit. About 40% of this longitudinal association was independent of initial BMI, but its magnitude decreased with initial age. For example, the initial height-for-age of children who were 12 years of age or older was only weakly associated with subsequent BMI. CONCLUSIONS: Health professionals should recognize that greater childhood height-for-age before 12 years of age may be a marker for increased risk of subsequent obesity.

      6. Pain among cancer survivorsexternal icon
        Gallaway MS, Townsend JS, Shelby D, Puckett MC.
        Prev Chronic Dis. 2020 Jul 9;17:E54.
        INTRODUCTION: Pain is one of the most common symptoms that people with cancer experience. Identification of demographic, physiologic, and behavioral correlates of pain among cancer survivors could help identify subgroups most in need of pain management. METHODS: We analyzed data from the 2012, 2014, and 2016 Behavioral Risk Factor Surveillance System Cancer Survivorship Optional Module, which was completed by 18 states and territories, to describe demographic and physiologic characteristics of cancer survivors reporting physical pain caused by cancer or cancer treatment. Adjusted and unadjusted population-based estimates and 95% confidence intervals were calculated. RESULTS: Of 12,019 cancer survivor respondents, 9.5% reported current pain related to cancer or cancer treatment. Current pain differed significantly by sex, race/ethnicity, age, and cancer type. Current pain was reported most often among survivors with more than 3 chronic diseases (16.7%) compared with survivors with none (8.1%) or 1 or 2 (10.0%). Pain was higher among survivors reporting fair or poor general health (18.0%) than among survivors reporting otherwise, and higher among survivors reporting more than 14 days of poor physical health (16.6%) or poor mental health (14.8%) compared with less than 14 days (in the past 30 days). CONCLUSIONS: Our results suggest that approximately 10% of cancer survivors in the United States are experiencing pain that may have persisted for years after their initial diagnosis and may not be adequately controlled. Increasing knowledge of the most appropriate pain management planning and strategies for controlling short- and long-term chronic pain among cancer survivors could help reduce the prevalence of pain.

      7. Sustained lower incidence of diabetes-related end-stage kidney disease among American Indians and Alaska Natives, Blacks, and Hispanics in the U.S., 2000-2016external icon
        Rios Burrows N, Zhang Y, Hora I, Pavkov ME, Sheff K, Imperatore G, Bullock AK, Albright AL.
        Diabetes Care. 2020 Jul 2.
        OBJECTIVE: Diabetes-related end-stage kidney disease (ESKD-D) disproportionately affects U.S. racial/ethnic minority populations compared with whites. However, from 1996 to 2013, ESKD-D incidence among American Indians and Alaska Natives (AIANs) and blacks declined. We assessed recent ESKD-D incidence data to determine whether trends by race/ethnicity have changed since 2013. RESEARCH DESIGN AND METHODS: U.S. Renal Data System data from 2000 to 2016 were used to determine the number of whites, blacks, AIANs, Asians, and Hispanics aged >/=18 years with newly treated ESKD-D (with diabetes listed as primary cause). Using census population estimates as denominators, annual ESKD-D incidence rates were calculated and age adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and estimate an average annual percent change (AAPC) in incidence rates. RESULTS: For adults overall, from 2000 to 2016, age-adjusted ESKD-D incidence rates decreased by 53% for AIANs (66.7-31.2 per 100,000, AAPC -4.5%, P < 0.001), by 33% for Hispanics (50.0-33.3, -2.1%, P < 0.001), and by 20% for blacks (56.2-44.7, -1.6%, P < 0.001). However, during the study period, age-adjusted ESKD-D incidence rates did not change significantly for Asians and increased by 10% for whites (15.4-17.0, 0.6%, P = 0.01). In 2016, ESKD-D incidence rates in AIANs, Hispanics, and blacks were approximately 2.0-2.5 times higher than whites. CONCLUSIONS: ESKD-D incidence declined for AIANs, Hispanics, and blacks and increased for whites. Continued efforts might be considered to reverse the trend in whites and sustain and lower ESKD-D incidence in the other populations.

      8. Given recent slowing of declines in national all-cause, heart disease, and stroke mortality, examining spatiotemporal distributions of coronary heart disease (CHD) death rates and trends can provide data critical to improving the cardiovascular health of populations. This paper documents county-level CHD death rates and trends by age group, race, and gender from 1979 through 2017. Using data from the National Vital Statistics System and a Bayesian multivariate space-time conditional autoregressive model, we estimated county-level age-standardized annual CHD death rates for 1979 through 2017 by age group (35-64 years, 65 years and older), race (white, black, other), and gender (men, women). We then estimated county-level total percent change in CHD death rates during four intervals (1979-1990, 1990-2000, 2000-2010, 2010-2017) using log-linear regression models. For all intervals, national CHD death rates declined for all groups. Prior to 2010, although most counties across age, race, and gender experienced declines, pockets of increasing CHD death rates were observed in the Mississippi Delta, Oklahoma, East Texas, and New Mexico across age groups and gender, and were more prominent among non-white populations than whites. Since 2010, across age, race, and gender, county-level declines in CHD death rates have slowed, with a marked increase in the percent of counties with increasing CHD death rates (e.g. 4.4% and 19.9% for ages 35 and older during 1979-1990 and 2010-2017, respectively). Recent increases were especially prevalent and geographically widespread among ages 35-64 years, with 40.5% of counties (95% CI: 38.4, 43.1) experiencing increases. Spatiotemporal differences in these long term, county-level results can inform responses by the public health community, medical providers, researchers, and communities to address troubling recent trends.

      9. Effect of herpes zoster vaccine and antiviral treatment on risk of ischemic strokeexternal icon
        Yang Q, George MG, Chang A, Tong X, Merritt R, Hong Y.
        Neurology. 2020 Jul 7.
        OBJECTIVE: To determine whether increased risk of acute ischemic stroke (AIS) following herpes zoster (HZ) might be modified by the status of Zoster Vaccine Live (ZVL) vaccination and antiviral treatment following HZ. METHODS: We included 87,405 Medicare fee-for-service beneficiaries aged >/=66 years diagnosed with HZ and AIS from 2008-2017. We used a self-controlled case series design to examine the association between HZ and AIS, and estimated incident rate ratios (IRR) by comparing incidence of AIS in risk periods vs. control periods. To examine effect modification by ZVL and antiviral treatment, beneficiaries were classified into four mutually exclusive groups: (1) no vaccination and no antiviral treatment; (2) vaccination only; (3) antiviral treatment only; and (4) both vaccination and antiviral treatment. We tested for interaction to examine changes in IRRs across 4-groups. RESULTS: Among 87,405 beneficiaries with HZ and AIS, 22.0%, 2.0%, 70.1% and 5.8% were in groups 1 to 4, respectively. IRRs in 0-14, 15-30, 31-90, and 91-180 days following HZ were 1.89 (95% confidence interval [CI],1.77-2.02), 1.58 (95% CI,1.47-1.69), 1.36 (95% CI,1.31-1.42), and 1.19 (95% CI,1.15-1.23), respectively. There was no evidence of effect modification by ZVL and antiviral treatment on AIS (p=0.067 for interaction). The pattern of association between HZ and risk for AIS was largely consistent across age group, sex, and race. CONCLUSIONS: Risk of AIS increased significantly following HZ, and this increased risk was not modified by ZVL and antiviral treatment. Our findings suggest the importance of following recommended HZ vaccination in prevention of HZ and HZ-associated AIS.

    • Communicable Diseases
      1. Tuberculosis preventive treatment opportunities at antiretroviral therapy initiation and follow-up visitsexternal icon
        Agizew T, Surie D, Oeltmann JE, Letebele M, Pals S, Mathebula U, Mathoma A, Kassa M, Hamda S, Pono P, Rankgoane-Pono G, Boyd R, Auld A, Finlay A.
        Public Health Action. 2020 Jun 21;10(2):64-69.
        Setting: Twenty-two clinics providing HIV care and treatment in Botswana where tuberculosis (TB) and HIV comorbidity is as high as 49%. Objectives: To assess eligibility of TB preventive treatment (TPT) at antiretroviral therapy (ART) initiation and at four follow-up visits (FUVs), and to describe the TB prevalence and associated factors at baseline and yield of TB diagnoses at each FUV. Design: A prospective study of routinely collected data on people living with HIV (PLHIV) enrolled into care for the Xpert((R)) MTB/RIF Package Rollout Evaluation Study between 2012 and 2015. Results: Of 6041 PLHIV initiating ART, eligibility for TPT was 69% (4177/6041) at baseline and 93% (5408/5815); 95% (5234/5514); 96% (4869/5079); and 97% (3925/4055) at FUV1, FUV2, FUV3, and FUV4, respectively. TB prevalence at baseline was 11% and 2%, 3%, 3% and 6% at each subsequent FUV. At baseline, independent risk factors for prevalent TB were CD4 <200 cells/mm(3) (aOR = 1.4, P = 0.030); anemia (aOR = 2.39, P < 0.001); cough (aOR = 11.21, P < 0.001); fever (aOR = 2.15, P = 0.001); and weight loss (aOR = 2.60, P = 0.002). Conclusion: Eligibility for TPT initiation is higher at visits post-ART initiation, while most cases of active TB were identified at ART initiation. Missed opportunities for TB further compromises TB control effort among PLHIV in Botswana.

      2. Symptom profiles of a convenience sample of patients with COVID-19 - United States, January-April 2020external icon
        Burke RM, Killerby ME, Newton S, Ashworth CE, Berns AL, Brennan S, Bressler JM, Bye E, Crawford R, Harduar Morano L, Lewis NM, Markus TM, Read JS, Rissman T, Taylor J, Tate JE, Midgley CM.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):904-908.
        Coronavirus disease 2019 (COVID-19) was first detected in the United States in January 2020 (1), and by mid-July, approximately 3.4 million cases had been reported in the United States (2). Information about symptoms among U.S. COVID-19 patients is limited, especially among nonhospitalized patients. To better understand symptom profiles of patients with laboratory-confirmed COVID-19 in the United States, CDC used an optional questionnaire to collect detailed information on a convenience sample of COVID-19 patients from participating states. Symptom data were analyzed by age group, sex, hospitalization status, and symptom onset date relative to expansion of testing guidelines on March 8, 2020 (3). Among 164 symptomatic patients with known onset during January 14-April 4, 2020, a total of 158 (96%) reported fever, cough, or shortness of breath. Among 57 hospitalized adult patients (aged >/=18 years), 39 (68%) reported all three of these symptoms, compared with 25 (31%) of the 81 nonhospitalized adult patients. Gastrointestinal (GI) symptoms and other symptoms, such as chills, myalgia, headache, and fatigue, also were commonly reported, especially after expansion of testing guidelines. To aid prompt recognition of COVID-19, clinicians and public health professionals should be aware that COVID-19 can cause a wide variety of symptoms.

      3. Risk factors for healthcare personnel infection with endemic coronaviruses (HKU1, OC43, NL63, 229E): Results from the Respiratory Protection Effectiveness Clinical Trial (ResPECT)external icon
        Cummings DA, Radonovich LJ, Gorse GJ, Gaydos CA, Bessesen MT, Brown AC, Gibert CL, Hitchings MD, Lessler J, Nyquist AC, Rattigan SM, Rodriguez-Barradas MC, Price CS, Reich NG, Simberkoff MS, Perl TM.
        Clin Infect Dis. 2020 Jul 9.
        BACKGROUND: SARS-CoV-2 presents a large risk to healthcare personnel. Quantifying the risk of coronavirus infection associated with workplace activities is an urgent need. METHODS: We assessed the association of worker characteristics, occupational roles and behaviors, and participation in procedures with the risk of endemic coronavirus infection among healthcare personnel who participated in the Respiratory Protection Effectiveness Trial (ResPECT), a cluster randomized trial to assess personal protective equipment to prevent respiratory infections and illness conducted from 2011 to 2016. RESULTS: Among 4,689 HCP-seasons, we detected coronavirus infection in 387 (8%). HCP who participated in an aerosol generation procedure (AGP) at least once during the viral respiratory season were 105% (95% CI 21%, 240%) more likely to be diagnosed with a laboratory-confirmed coronavirus infection. Younger individuals, those who saw pediatric patients and those with household members under the age of five were at increased risk of coronavirus infection. CONCLUSIONS: Our analysis suggests the risk of HCP becoming infected with an endemic coronavirus increases approximately two-fold with exposures to AGP. Our findings may be relevant to the Coronavirus Disease 2019 (COVID-19) pandemic; however, SARS-COV-2, the virus that causes COVID-19, may differ from endemic coronaviruses in important ways.

      4. HIV antiretroviral therapy and prevention use in US blood donors: A new blood safety concernexternal icon
        Custer B, Quiner CA, Haaland R, Martin A, Stone M, Reik RF, Steele WR, Kessler D, Williamson PC, Anderson SA, Williams AE, Raymond HF, McFarland W, Robinson WT, Glick SN, Sey K, Melton CD, Glynn SA, Stramer SL, Busch MP.
        Blood. 2020 Jul 9.
        CONTEXT: Antiretroviral therapy (ART) to treat and pre-exposure prophylaxis (PrEP) to prevent HIV infection are effective tools to help end the HIV epidemic. However, their use could affect HIV transfusion-transmission risk. OBJECTIVES: Three different ART/PrEP prevalence analyses in blood donors were conducted. METHODS: First, blood samples from HIV-positive and a comparison group of infection-nonreactive donors were tested under blind using liquid chromatography-tandem mass spectrometry for ART. Second, blood donor samples from infection-nonreactive, 18-45 year-old, male, first-time blood donors in six US locations were tested for emtricitabine and tenofovir. Third, in men who have sex with men (MSM) participating in the 2017 CDC National HIV Behavioral Surveillance (NHBS) from five US cities self-reported PrEP use proximate to donation was assessed. FINDINGS: In blind testing, no ART was detected in 300 infection-nonreactive donor samples, but in 299 HIV-confirmed infected donor samples, 46 (15.4%, 95% CI 11.5 - 20.0%) had evidence of ART. Of the 1,494 samples tested from first-time, male donors, 9 (0.6%, 95% CI 0.03 - 1.1%) had tenofovir and emtricitabine. In the NHBS MSM survey, 27 of 591 respondents (4.8%, 95% CI 3.2 - 6.9%) reported donating blood in 2016 or 2017 and PrEP use within the same time frame as blood donation. CONCLUSIONS: Persons who are HIV-positive and taking ART and persons taking PrEP to prevent HIV infection are donating blood. Both situations could lead to increased risk of HIV transfusion transmission if blood screening assays are unable to detect HIV in donations from infected donors.

      5. Neurological associations of COVID-19external icon
        Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, Kneen R, Defres S, Sejvar J, Solomon T.
        Lancet Neurol. 2020 Jul 2.
        BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. RECENT DEVELOPMENTS: A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barre syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2-6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. WHERE NEXT?: Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barre syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.

      6. Factors associated with cloth face covering use among adults during the COVID-19 pandemic - United States, April and May 2020external icon
        Fisher KA, Barile JP, Guerin RJ, Vanden Esschert KL, Jeffers A, Tian LH, Garcia-Williams A, Gurbaxani B, Thompson WW, Prue CE.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):933-937.
        On April 3, 2020, the White House Coronavirus Task Force and CDC announced a new behavioral recommendation to help slow the spread of coronavirus disease 2019 (COVID-19) by encouraging the use of a cloth face covering when out in public (1). Widespread use of cloth face coverings has not been studied among the U.S. population, and therefore, little is known about encouraging the public to adopt this behavior. Immediately following the recommendation, an Internet survey sampled 503 adults during April 7-9 to assess their use of cloth face coverings and the behavioral and sociodemographic factors that might influence adherence to this recommendation. The same survey was administered 1 month later, during May 11-13, to another sample of 502 adults to assess changes in the prevalence estimates of use of cloth face coverings from April to May. Within days of the release of the first national recommendation for use of cloth face coverings, a majority of persons who reported leaving their home in the previous week reported using a cloth face covering (61.9%). Prevalence of use increased to 76.4% 1 month later, primarily associated with increases in use among non-Hispanic white persons (54.3% to 75.1%), persons aged >/=65 years (36.6% to 79.2%), and persons residing in the Midwest (43.7% to 73.8%). High rates were observed in April and by May, increased further among non-Hispanic black persons (74.4% to 82.3%), Hispanic or Latino persons (77.3% to 76.2%), non-Hispanic persons of other race (70.8% to 77.3%), persons aged 18-29 years (70.1% to 74.9%) and 30-39 years (73.9% to 84.4%), and persons residing in the Northeast (76.9% to 87.0%). The use of a cloth face covering was associated with theory-derived constructs that indicate a favorable attitude toward them, intention to use them, ability to use them, social support for using them, and beliefs that they offered protection for self, others, and the community. Research is needed to understand possible barriers to using cloth face coverings and ways to promote their consistent and correct use among those who have yet to adopt this behavior.

      7. Mental health (MH) disorders are associated with HIV-related risk and health outcomes. Primary care providers (PCPs) conducting MH screenings can link persons living with HIV (PWH) to appropriate services, particularly in HIV burden areas of Southeastern States (the South). Little data exist on PCPs' MH screening practices. Depression, MH history, and substance use screenings among PCPs were examined in the South. Rao-Scott chi-square (chi(2)[df]) statistics (p </= 0.05) analyzed MH screening between PCPs with and without PWH patients. Compared with PCPs without PWH patients, PCPs with PWH patients routinely screened for substance use more frequently (50.6% vs. 43.2%; chi(2)[1] = 20.3; p < 0.0001). Compared with PCPs without PWH patients, PCPs with PWH patients routinely screened for depression less frequently (36.2% vs. 50.9%; chi(2)[1] = 32.0; p < 0.0001). Providers increasing MH screenings will improve HIV-related outcomes in the South.

      8. Another step forward in using surveillance for preventionexternal icon
        Hogben M, Renfro KJ.
        Lancet HIV. 2020 Jul;7(7):e453-e454.

      9. Factors associated with testing for hepatitis C infections among a commercially insured population of persons with HIV, United States 2008-2016external icon
        King H, Bull-Otterson L, Hoover KW, Huang HY, Zhu W, Thompson W.
        Open Forum Infect Dis. 2020 Jun;7(6):ofaa222.
        Background: Hepatitis C virus (HCV) infection is an important public health problem among people with HIV. People with HIV who are coinfected with HCV infection are at increased risk for cirrhosis, liver failure, and hepatitis C-related mortality; as such, national guidelines recommend that persons with HIV be tested for HCV infection. Methods: Data from the 2003-2017 IBM Watson Health MarketScan database were used for this study. We used diagnostic, procedural, and drug codes to identify patients with >/=1 inpatient or outpatient medical claim of HIV diagnosis. Patients with prior HIV or hepatitis C diagnoses were excluded. We calculated hepatitis C testing rates among newly diagnosed HIV-infected persons within 12 months of the initial HIV diagnosis date (January 1, 2008-December 31, 2016). We used Poisson regression to identify the factors associated with hepatitis C testing. Lastly, we assessed hepatitis C testing trends using the Cochran-Armitage test. Results: The prevalence of testing for hepatitis C in newly identified persons with HIV (n = 46 277) was 50% within 12 months of the index HIV diagnosis. From 2008 to 2017, the testing rate increased by 13%. Significant predictors of hepatitis C testing were age, sex, and urbanicity. Women with HIV were less likely to have been tested compared with men (relative risk, 0.79; 95% CI, 0.77-0.81). Only 40% of patients between 50 and 59 years of age were tested for hepatitis C within 12 months of the index HIV diagnosis, while 56% of persons with HIV aged 20-29 years were tested for hepatitis C. Conclusions: Overall, 50% of newly diagnosed HIV patients were tested for hepatitis C within 12 months of HIV diagnosis. Although there were increases in hepatitis C testing rates over the study period, there were missed opportunities to detect HCV infection among people newly diagnosed with HIV.

      10. Mumps cases disproportionately affecting persons living with HIV infection and men who have sex with men - Chicago, Illinois, 2018external icon
        McPherson TD, Ramirez E, Ringness M, Ruestow P, Marlow M, Fricchione MJ.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):909-912.
        During January 1-March 2, 2018, the number of mumps cases among adults reported to the Chicago Department of Public Health (CDPH) doubled compared with the same period in 2017. In response, CDPH created a supplementary questionnaire to collect additional information on populations affected and potential transmission routes. An epidemiologic analysis of routine and supplementary data, including spatiotemporal analysis, was performed to describe mumps cases reported to CDPH during 2018. A fourfold increase in mumps cases was reported during 2018 compared with 2017, with men who have sex with men (MSM) and persons living with human immunodeficiency virus (HIV) infection disproportionately represented among cases. A spatiotemporal, residential cluster was identified in a 9-square-mile area within six adjacent communities. The majority of persons affected were MSM, and this area was visited by many other persons with mumps diagnoses. Spatiotemporal analyses could be used in real time to identify case clusters to target public health response efforts, including to guide recommendations for additional measles, mumps, and rubella (MMR) vaccine and to identify specific transmission venues.

      11. Impact of effective global tuberculosis control on health and economic outcomes in the United Statesexternal icon
        Menzies NA, Bellerose M, Testa C, Swartwood N, Malyuta Y, Cohen T, Marks SM, Hill AN, Date AA, Maloney SA, Bowden SE, Grills AW, Salomon JA.
        Am J Respir Crit Care Med. 2020 Jul 9.
        RATIONALE: Most United States residents who develop tuberculosis were born abroad, and US TB incidence is increasingly driven by infection risks in other countries. OBJECTIVES: To estimate the potential impact of effective global TB control on health and economic outcomes in the United States. METHODS: We estimated outcomes using linked mathematical models of TB epidemiology in the United States and migrants' birth countries. A base-case scenario extrapolated country-specific TB incidence trends. We compared this to scenarios in which countries achieve 90% TB incidence reductions between 2015 and 2035, as targeted by the Global End TB Strategy ("effective global TB control"). We also considered pessimistic scenarios of flat TB incidence trends in individual countries. MEASUREMENTS AND MAIN RESULTS: We estimated TB cases, TB deaths, costs, and the total economic burden of TB in the US. Compared to the base-case, effective global TB control would avert 40,000 (95% uncertainty interval: 29,000-55,000) TB cases in the United States over 2020-2035. TB incidence rates in 2035 would be 43% (34-54) lower than the base-case, and 49% (44-55) lower than in 2020. Summed over 2020-2035, this represents $0.8 (0.6-1.0) billion dollars in averted healthcare costs and $2.5 (1.7-3.6) billion in productivity gains. The total US economic burden of TB (including the value of averted TB deaths) would be 21% (16-28) lower ($18 (8-32) billion). CONCLUSIONS: In addition to producing major health benefits for high-burden countries, strengthened efforts to achieve effective global TB control could produce substantial health and economic benefits for the United States.

      12. Seroprevalence of measles, rubella, tetanus, and diphtheria antibodies among children in Haiti, 2017external icon
        Minta AA, Andre-Alboth J, Childs L, Nace D, Rey-Benito G, Boncy J, Adrien P, Francois J, Phaimyr Jn Charles N, Blot V, Vanden Eng J, Priest JW, Rogier E, Tohme RA.
        Am J Trop Med Hyg. 2020 Jul 6.
        In Haiti, measles, rubella, and maternal and neonatal tetanus have been eliminated, but a diphtheria outbreak is ongoing as of 2019. We conducted a national representative, household-based, two-stage cluster survey among children aged 5-7 years in 2017 to assess progress toward maintenance of control and elimination of selected vaccine-preventable diseases (VPDs). We stratified Haiti into west region (west department, including the capital city) and non-west region (all other departments). We obtained vaccination history and dried blood spots, and measured antibody concentrations to VPDs on a multiplex bead assay. Among 1,146 children, national seropositivity was 83% (95% CI: 80-86%) for tetanus, 83% (95% CI: 81-85%) for diphtheria, 87% (95% CI: 85-89%) for measles, and 84% (95% CI: 81-87%) for rubella. None of the children had long-term immunity to tetanus or diphtheria (IgG concentration >/= 1 international unit/mL). Seropositivity in the west region was lower than that in the non-west region. Vaccination coverage was 68% (95% CI: 61-74%) for >/= 3 doses of tetanus- and diphtheria-containing vaccine (DTP3), 84% (95% CI: 80-87%) for one dose of measles-rubella (MR1) vaccine, and 20% (95% CI: 16-24%) for MR2. The seroprevalence of measles, rubella, and diphtheria antibodies is lower than population immunity levels needed to prevent disease transmission, particularly in the west region; reintroduction of these diseases could lead to an outbreak. To maintain VPD control and elimination, Haiti should achieve DTP3 and MR2 coverage >/= 95%, and include tetanus and diphtheria booster doses in the routine immunization schedule.

      13. Tackling cryptococcal meningitis in Nigeria, one-step at a time; the impact of trainingexternal icon
        Oladele RO, Jordan A, Akande P, Akanmu SA, Akase IE, Aliyu S, Denning DW, Chiller T.
        PLoS One. 2020 ;15(7):e0235577.
        BACKGROUND: Nigeria is estimated to have 25,000 cases of cryptococcal antigenemia (CrAg) annually. CrAg screening with pre-emptive fluconazole treatment is recommended but not yet implemented in Nigeria. Trainings were conducted to improve health-care provider (HCP) awareness and clinical skills in the management and prevention of cryptococcal meningitis (CM). METHODS: HCPs providing care for people living with HIV were targeted for training at 13 sites from April to November 2018 Course content was adapted from CDC Cryptococcal Screening Program Training Manual and LIFE-website. "Hands-on" training on CrAg testing and lumbar puncture was included. A 14-point pre and post-test assessment instrument was designed to capture the impact of the training and focus group discussions (FGDs) were conducted. RESULTS: A total of 761 HCPs were trained. 519 HCPs completed the pre-test evaluation while 470 (90.6%) took part in the post-test evaluation. Post-training, HCPs were significantly more likely to respond correctly to all 14 assessment items, with the mean percentage score rising to 91.0% from a pre-training value of 60.0%. FGDs revealed that many of the HCPs were not aware of the CrAg screening and pre-emptive treatment recommendations in Nigerian guidelines, and reported not having seen or managed a case of CM. Also, they highlighted challenges with routine CrAg screening due to a lack of access to CD4 testing, CrAg test kits, antifungal drugs, as well as the need for similar trainings across all tiers of care in Nigeria. CONCLUSION: Training significantly improved HCPs' understanding of Nigerian policy on CrAg screening, CM diagnosis and best management practices. This training could be included in routine capacity building efforts for HCPs involved in HIV care in Nigeria.


      15. Sociodemographic, ecological, and spatiotemporal factors associated with HIV drug resistance in Florida: a retrospective analysisexternal icon
        Rich SN, Poschman K, Hu H, Mavian C, Cook RL, Salemi M, Spencer EC, Prosperi M.
        J Infect Dis. 2020 Jul 9.
        BACKGROUND: Persons living with HIV (PWH) with resistance to antiretroviral therapy (ART) are vulnerable to adverse HIV-related health outcomes and can contribute to transmission of HIV drug resistance (HIVDR) when non-virally suppressed. The degree to which HIVDR contributes to disease burden in Florida -the US state with the highest HIV incidence- is unknown. METHODS: We explored sociodemographic, ecological, and spatial-temporal associations of HIVDR. HIV-1 sequences (n=34,447) collected during 2012-2017 were obtained from the Florida Department of Health. HIVDR was categorized by ART class: nucleoside reverse transcriptase inhibitors (NRTI), non-NRTI (NNRTI), protease inhibitors (PI), and integrase inhibitors (INSTI). Multi-drug resistance (MDR) and transmitted-drug resistance (TDR) were also evaluated. Multivariable fixed-effects logistic regression models were fitted to associate individual and county-level sociodemographic and ecological health indicators with HIVDR. RESULTS: HIVDR prevalence was 19.2% (NRTI), 29.7% (NNRTI), 6.6% (PI), 23.5% (TDR), 13.2% (MDR), and 8.2% (INSTI) with significant variation by Florida county. Individuals who were older, Black, or acquired HIV through mother-to-child transmission had significantly higher odds of HIVDR. HIVDR was linked to counties with lower socioeconomic status, higher unemployment, and poor mental health. CONCLUSIONS: Our findings indicate HIVDR prevalence is higher in Florida than aggregate North American estimates with significant geographic and socioecological heterogeneity.

      16. Integration of fungal diseases into health systems in Latin Americaexternal icon
        Rodriguez Tudela JL, Cole DC, Ravasi G, Bruisma N, Chiller TC, Ford N, Denning DW.
        Lancet Infect Dis. 2020 Jun 30.


      18. Seroprevalence of SARS-CoV-2 among frontline healthcare personnel during the first month of caring for COVID-19 patients - Nashville, Tennesseeexternal icon
        Stubblefield WB, Talbot HK, Feldstein L, Tenforde MW, Rasheed MA, Mills L, Lester SN, Freeman B, Thornburg NJ, Jones ID, Ward MJ, Lindsell CJ, Baughman A, Halasa N, Grijalva CG, Rice TW, Patel MM, Self WH.
        Clin Infect Dis. 2020 Jul 6.
        Among 249 healthcare personnel who worked in hospital units with COVID-19 patients for one month, 19 (7.6%) tested positive for SARS-CoV-2 antibodies. Only 11 (57.9%) of the 19 personnel with positive serology reported symptoms of a prior illness, suggesting asymptomatic healthcare personnel could be an important source of SARS-CoV-2 transmission.

      19. A mobile health-facilitated behavioural intervention for community health workers improves exclusive breastfeeding and early infant HIV diagnosis in India: a cluster randomized trialexternal icon
        Suryavanshi N, Kadam A, Gupte N, Hegde A, Kanade S, Sivalenka S, Kumar VS, Gupta A, Bollinger RC, Shankar A, McKenzie-White J, Mave V.
        J Int AIDS Soc. 2020 Jul;23(7):e25555.
        INTRODUCTION: India's national AIDS Control Organization implemented World Health Organization's option B+ HIV prevention of mother-to-child transmission (PMTCT) guidelines in 2013. However, scalable strategies to improve uptake of new PMTCT guidelines to reduce new infection rates are needed. This study assessed impact of Mobile Health-Facilitated Behavioral Intervention on the uptake of PMTCT services. METHODS: A cluster-randomized trial of a mobile health (mHealth)-supported behavioural training intervention targeting outreach workers (ORWs) was conducted in four districts of Maharashtra, India. Clusters (one Integrated Counselling and Testing Center (ICTC, n = 119), all affiliated ORWs (n = 116) and their assigned HIV-positive pregnant/postpartum clients (n = 1191)) were randomized to standard-of-care (SOC) ORW training vs. the COMmunity home Based INDia (COMBIND) intervention - specialized behavioural training plus a tablet-based mHealth application to support ORW-patient communication and patient engagement in HIV care. Impact on uptake of maternal antiretroviral therapy at delivery, exclusive breastfeeding at six months, infant nevirapine prophylaxis, and early infant diagnosis at six months was assessed using multi-level random-effects logistic regression models. RESULTS: Of 1191 HIV-positive pregnant/postpartum women, 884 were eligible for primary outcome assessment; 487 were randomized to COMBIND. Multivariable analyses identified no statistically significant differences in any primary outcome by study arm. COMBIND was associated with higher uptake of exclusive breastfeeding at two months (adjusted Odds Ratio (aOR), 2.10; 95% CI 1.06 to 4.15) and early infant diagnosis at six weeks (aOR, 2.19; 95% CI 1.05 to 3.98) than SOC. CONCLUSIONS: The COMBIND intervention was easily integrated into India's existing PMTCT programme and improved early uptake of two PMTCT components that require self-motivated health-seeking behaviour, thus providing preliminary evidence to support COMBIND as a potentially scalable PMTCT strategy. Further study would identify modifications needed to optimize other PMTCT outcomes.

      20. Prevalence of HBV and HCV infections, Bhutan, 2017: Progress and next stepsexternal icon
        Tshering N, Dhakal GP, Wangchuk U, Wangdi S, Khandu L, Pelden S, Nogareda F, Patel MK, Hutin YJ, Wannemuehler K, Rewari BB, Wangchuk S.
        BMC Infect Dis. 2020 Jul 8;20(1):485.
        BACKGROUND: Bhutan is committed to eliminating hepatitis B and hepatitis C, though recent baseline estimates of disease burden in the general population are unknown. In 2017, we carried out a biomarker survey in the general population to estimate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) biomarkers to evaluate the impact of immunization and guide further efforts. METHODS: In 2017, a cross-sectional, population-based, three-stage cluster survey was undertaken of the general population (1-17 and 20+ years of age). We visited households, collected blood specimens and administered a standard questionnaire. Specimens were collected for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We calculated prevalence of infection and selected characteristics, along with confidence intervals (CIs). RESULTS: Of 1372 individuals approached, 1358 (99%) participated. Of those, 1321 (97%) had a specimen tested for HBsAg, and among 1173 enrolled individuals 5 years of age or older, 1150 (98%) individuals were tested for anti-HCV. The prevalence of HBsAg was 2.0% in 775 persons 20 years of age or older (95% CI: 1.0-4.0) and 0.5% in 546 persons 1-17 years of age (95% CI: 0.1-1.8). The prevalence of anti-HCV was 0.3% (95% CI: 0.1-0.8) among persons >/=5 years. CONCLUSIONS: Universal hepatitis B immunization of infants has resulted in a low prevalence of chronic HBV infection in persons 1-17 years of age and the prevalence of anti-HCV is low among persons aged >/=5 years. Efforts should continue to reach high coverage of the timely birth dose along with completion of the hepatitis B vaccine series. To reduce the chronic liver disease burden among adults, HBV and HCV testing and treatment as indicated might be restricted to pregnant women, blood donors, individuals with chronic liver diseases, and other groups with history of high-risk exposures.


      22. Characteristics of persons who died with COVID-19 - United States, February 12-May 18, 2020external icon
        Wortham JM, Lee JT, Althomsons S, Latash J, Davidson A, Guerra K, Murray K, McGibbon E, Pichardo C, Toro B, Li L, Paladini M, Eddy ML, Reilly KH, McHugh L, Thomas D, Tsai S, Ojo M, Rolland S, Bhat M, Hutchinson K, Sabel J, Eckel S, Collins J, Donovan C, Cope A, Kawasaki B, McLafferty S, Alden N, Herlihy R, Barbeau B, Dunn AC, Clark C, Pontones P, McLafferty ML, Sidelinger DE, Krueger A, Kollmann L, Larson L, Holzbauer S, Lynfield R, Westergaard R, Crawford R, Zhao L, Bressler JM, Read JS, Dunn J, Lewis A, Richardson G, Hand J, Sokol T, Adkins SH, Leitgeb B, Pindyck T, Eure T, Wong K, Datta D, Appiah GD, Brown J, Traxler R, Koumans EH, Reagan-Steiner S.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):923-929.
        During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

    • Community Health Services
      1. OBJECTIVES: Adult day service centers (ADSCs) may serve as an entree to advance care planning. This study examined state requirements for ADSCs to provide advance directives (AD) information to ADSC participants, ADSCs' awareness of requirements, ADSCs' practice of providing AD information, and their associations with the percentage of participants with ADs. METHODS: Using the 2016 National Study of Long-Term Care Providers, analyses included 3,305 ADSCs that documented ADs in participants' files. Bivariate and linear regression analyses were conducted. RESULTS: Nine states had a requirement to provide AD information. 80.8% of ADSCs provided AD information. 41.3% of participants had documented ADs. There were significant associations between state requirement, awareness, and providing information with AD prevalence. State requirement was mediated by awareness. DISCUSSION: This study found many ADSCs provided AD information, and ADSCs that thought their state had a requirement and provided information was associated with AD prevalence, regardless of state requirements.

    • Disease Reservoirs and Vectors
      1. Continuation of mosquito surveillance and control during public health emergencies and natural disastersexternal icon
        Connelly CR, Gerding JA, Jennings SM, Ruiz A, Barrera R, Partridge S, Ben Beard C.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):938-940.
        Mosquitoborne disease outbreaks occur every year in the United States from one or more of the arboviral diseases dengue, West Nile, LaCrosse, Eastern equine encephalitis, and Zika (1). Public opinion communicated through traditional and social media and the Internet, competing public health and resource priorities, and local conditions can impede the ability of vector control organizations to prevent and respond to outbreaks of mosquitoborne disease. The Environmental Protection Agency (EPA) and CDC performed a coordinated review of the concerns and challenges associated with continuation of mosquito surveillance and control during public health emergencies and disasters. This report highlights the first joint recommendation from EPA and CDC. Mosquito surveillance and control should be maintained by state and local mosquito control organizations to the extent that local conditions and resources will allow during public health emergencies and natural disasters. Integrated pest management (IPM) is the best approach for mosquito control (2). IPM uses a combination of methods, including both physical and chemical means of control (3). For chemical means of control, CDC and EPA recommend the use of larvicides and adulticides following the EPA label. It is imperative that public health recommendations be followed to ensure the safety of the pesticide applicator and the public.

    • Environmental Health
      1. Pregnancy per- and polyfluoroalkyl substance concentrations and postpartum health in Project Viva, a prospective cohortexternal icon
        Mitro SD, Sagiv SK, Fleisch AF, Jaacks LM, Williams PL, Rifas-Shiman SL, Calafat AM, Hivert MF, Oken E, James-Todd TM.
        J Clin Endocrinol Metab. 2020 Jul 4.
        CONTEXT: Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. OBJECTIVE: We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. DESIGN, PATIENTS, MEASURES: We studied women recruited between 1999-2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786-801 women, blood pressure from 761 women, and blood biomarkers from 450-454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c [HbA1c], interleukin-6 [IL-6], C-reactive protein [CRP]), adjusting for age, pre-pregnancy BMI, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. RESULTS: Pregnancy concentrations of certain PFAS were associated with greater adiposity (e.g., 0.4 cm [95%CI: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (e.g., 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at three years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. CONCLUSIONS: Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

      2. Dioxin-like compound exposures and DNA methylation in the Anniston Community Health Survey Phase IIexternal icon
        Pittman GS, Wang X, Campbell MR, Coulter SJ, Olson JR, Pavuk M, Birnbaum LS, Bell DA.
        Sci Total Environ. 2020 Jun 22;742:140424.
        The Anniston Community Health Survey (ACHS-I) was initially conducted from 2005 to 2007 to assess polychlorinated biphenyl (PCB) exposures in Anniston, Alabama residents. In 2014, a follow-up study (ACHS-II) was conducted to measure the same PCBs as in ACHS-I and additional compounds e.g., polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like non-ortho (cPCBs) substituted PCBs. In this epigenome-wide association study (EWAS), we examined the associations between PCDD, PCDF, and PCB exposures and DNA methylation. Whole blood DNA methylation was measured using Illumina EPIC arrays (n=292). We modeled lipid-adjusted toxic equivalencies (TEQs) for: SigmaDioxins (sum of 28 PCDDs, PCDFs, cPCBs, and mPCBs), PCDDs, PCDFs, cPCBs, and mPCBs using robust multivariable linear regression adjusting for age, race, sex, smoking, bisulfite conversion batch, and estimated percentages of six blood cell types. Among all exposures we identified 10 genome-wide (Bonferroni p</=6.74E-08) and 116 FDR (p</=5.00E-02) significant associations representing 10 and 113 unique CpGs, respectively. Of the 10 genome-wide associations, seven (70%) occurred in the PCDDs and four (40%) of these associations had an absolute differential methylation >/=1.00%, based on the methylation difference between the highest and lowest exposure quartiles. Most of the associations (six, 60%) represented hypomethylation changes. Of the 10 unique CpGs, eight (80%) were in genes shown to be associated with dioxins and/or PCBs based on data from the 2019 Comparative Toxicogenomics Database. In this study, we have identified a set of CpGs in blood DNA that may be particularly susceptible to dioxin, furan, and dioxin-like PCB exposures.

    • Genetics and Genomics
      1. We recently developed a test based on the Agilent SureSelect target enrichment system capturing genomic fragments from 191 human papillomaviruses (HPV) types for Illumina sequencing. This enriched whole genome sequencing (eWGS) assay provides an approach to identify all HPV types in a sample. Here we present a machine learning algorithm that calls HPV types based on the eWGS output. The algorithm based on the support vector machine (SVM) technique was trained on eWGS data from 122 control samples with known HPV types. The new algorithm demonstrated good performance in HPV type detection for designed samples with 25 or greater HPV plasmid copies per sample. We compared the results of HPV typing made by the new algorithm for 261 residual epidemiologic samples with the results of the typing delivered by the standard HPV Linear Array (LA). The agreement between methods (97.4%) was substantial (kappa= 0.783). However, the new algorithm identified additionally 428 instances of HPV types not detectable by the LA assay by design. Overall, we have demonstrated that the bioinformatics pipeline is an accurate tool for calling HPV types by analyzing data generated by eWGS processing of DNA fragments extracted from control and epidemiological samples.

      2. Complete genome sequence of a baboon simian foamy virus isolated from an infected humanexternal icon
        Shankar A, Shanmugam V, Switzer WM.
        Microbiol Resour Announc. 2020 Jul 2;9(27).
        We obtained the full-length genome of a simian foamy virus (SFV) from an infected human. This virus originated from a baboon (Papio species, strain SFVpxx_hu9406). The genome is 13,113 nucleotides long with the canonical SFV genome structure. Phylogenetically, SFVpxx_hu9406 clustered closely with SFVpan_V909/03F from a captive baboon and other Cercopithecidae SFVs.

    • Healthcare Associated Infections
      1. Donor-derived human herpesvirus 8 and development of Kaposi sarcoma among six recipients of organs from donors with high risk sexual and substance use behaviorexternal icon
        Dollard SC, Annambhotla P, Wong P, Meneses K, Amin MM, La Hoz RM, Lease ED, Budev M, Arrossi AV, Basavaraju SV, Thomas CP.
        Am J Transplant. 2020 Jul 6.
        Kaposi sarcoma (KS) can develop following organ transplantation through reactivation of recipient human herpesvirus 8 (HHV-8) infection or through donor-derived HHV-8 transmission. We describe six cases of donor-derived HHV-8 infection and KS investigated July 2018 - January 2020. Organs from six donors, retrospectively identified as HHV-8-positive, with a history of drug use disorder, were transplanted into 22 recipients. Four of six donors had risk factors for HHV-8 infection reported in donor history questionnaires. Fourteen of twenty-two organ recipients (64%) had evidence of post-transplant HHV-8 infection. Lung recipients were particularly susceptible to KS. Four of the six recipients who developed KS died from KS or associated complications. The U.S. opioid crisis has resulted in an increasing number and proportion of organ donors with substance use disorder, and particularly injection drug use history, which may increase risk of HHV-8 transmission to recipients. Better awareness of the risk of post-transplant KS for recipients of organs from donors with HHV-8 infection risk could be useful for recipient management. Testing donors and recipients for HHV-8 is currently challenging with no validated commercial serology kits available. Limited HHV-8 antibody testing is available through some U.S. reference laboratories and the Centers for Disease Control and Prevention.

      2. Assessment of health care exposures and outcomes in adult patients with sepsis and septic shockexternal icon
        Fay K, Sapiano MR, Gokhale R, Dantes R, Thompson N, Katz DE, Ray SM, Wilson LE, Perlmutter R, Nadle J, Godine D, Frank L, Brousseau G, Johnston H, Bamberg W, Dumyati G, Nelson D, Lynfield R, DeSilva M, Kainer M, Zhang A, Ocampo V, Samper M, Pierce R, Irizarry L, Sievers M, Maloney M, Fiore A, Magill SS, Epstein L.
        JAMA Netw Open. 2020 Jul 1;3(7):e206004.
        Importance: Current information on the characteristics of patients who develop sepsis may help in identifying opportunities to improve outcomes. Most recent studies of sepsis epidemiology have focused on changes in incidence or have used administrative data sets that provided limited patient-level data. Objective: To describe sepsis epidemiology in adults. Design, Setting, and Participants: This retrospective cohort study reviewed the medical records, death certificates, and hospital discharge data of adult patients with sepsis or septic shock who were discharged from the hospital between October 1, 2014, and September 30, 2015. The convenience sample was obtained from hospitals in the Centers for Disease Control and Prevention Emerging Infections Program in 10 states (California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee). Patients 18 years and older with discharge diagnosis codes for severe sepsis or septic shock were randomly selected. Data were analyzed between May 1, 2018, and January 31, 2019. Main Outcomes and Measures: The population's demographic characteristics, health care exposures, and sepsis-associated infections and pathogens were described, and risk factors for death within 30 days after sepsis diagnosis were assessed. Results: Among 1078 adult patients with sepsis (569 men [52.8%]; median age, 64 years [interquartile range, 53-75 years]), 973 patients (90.3%) were classified as having community-onset sepsis (ie, sepsis diagnosed within 3 days of hospital admission). In total, 654 patients (60.7%) had health care exposures before their hospital admission for sepsis; 260 patients (24.1%) had outpatient encounters in the 7 days before admission, and 447 patients (41.5%) received medical treatment, including antimicrobial drugs, chemotherapy, wound care, dialysis, or surgery, in the 30 days before admission. A pathogen associated with sepsis was found in 613 patients (56.9%); the most common pathogens identified were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Clostridioides difficile. After controlling for other factors, an association was found between underlying comorbidities, such as cirrhosis (odds ratio, 3.59; 95% CI, 2.03-6.32), immunosuppression (odds ratio, 2.52; 95% CI, 1.81-3.52), vascular disease (odds ratio, 1.54; 95% CI, 1.10-2.15), and 30-day mortality. Conclusions and Relevance: Most adults experienced sepsis onset outside of the hospital and had recent encounters with the health care system. A sepsis-associated pathogen was identified in more than half of patients. Future efforts to improve sepsis outcomes may benefit from examination of health maintenance practices and recent health care exposures as potential opportunities among high-risk patients.

      3. Development of an electronic definition for de-escalation of antibiotics in hospitalized patientsexternal icon
        Moehring RW, Ashley ED, Davis AE, Dyer AP, Parish A, Ren X, Lokhnygina Y, Hicks LA, Srinivasan A, Anderson DJ.
        Clin Infect Dis. 2020 Jul 8.
        BACKGROUND: Antimicrobial stewardship programs (ASPs) promote the principle of de-escalation: moving from broad to narrow spectrum agents and stopping antibiotics when no longer indicated. A standard, objective definition of de-escalation applied to electronic data could be useful for ASP assessments. METHODS: We derived an electronic definition of antibiotic de-escalation and performed a retrospective study among five hospitals. Antibiotics were ranked into 4 categories: narrow spectrum, broad spectrum, extended spectrum, and agents targeted for protection. Eligible adult patients were cared for on inpatient units, had antibiotic therapy for at least 2 days, and were hospitalized for at least 3 days after starting antibiotics. Number of antibiotics and rank were assessed at two time points: day of antibiotic initiation and either day of discharge or day 5. De-escalation was defined as reduction in either the number of antibiotics or rank. Escalation was an increase in either number or rank. Unchanged was either no change or discordant directions of change. We summarized outcomes among hospitals, units, and diagnoses. RESULTS: Among 39,226 eligible admissions, de-escalation occurred in 14,138 (36%), escalation in 5,129 (13%), and antibiotics were unchanged in 19,959 (51%). De-escalation varied among hospitals (median 37%, range 31-39%, p<.001). Diagnoses with lower de-escalation rates included intra-abdominal (23%) and skin and soft tissue (28%) infections. Critical care had higher rates of both de-escalation and escalation compared with wards. CONCLUSIONS: Our electronic de-escalation metric demonstrated variation among hospitals, units, and diagnoses. This metric may be useful for assessing stewardship opportunities and impact.

    • Immunity and Immunization
      1. A randomized phase 4 study of immunogenicity and safety following monovalent oral type 2 Sabin polio vaccine challenge in IPV-vaccinated children in Lithuaniaexternal icon
        Bandyopadhyay AS, Gast C, Brickley EB, Ruttimann R, Clemens R, Oberste MS, Weldon WC, Ackerman ME, Connor RI, Wieland-Alter WF, Wright P, Usonis V.
        J Infect Dis. 2020 Jul 4.
        BACKGROUND: Understanding immunogenicity and safety of monovalent type-2 oral polio vaccine (mOPV2) in inactivated polio vaccine (IPV)-immunized children is of major importance to inform global policy to control circulating vaccine-derived poliovirus (cVDPV) outbreaks. METHODS: In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1-5-year-olds we measured humoral and intestinal type-2 polio neutralizing antibodies before and 28 days after one or two mOPV2 doses given 28 days apart, and stool viral shedding after each dose. Parents recorded solicited adverse events (AE) for 7 days after each dose and unsolicited AEs for 6 weeks postvaccination. RESULTS: After one mOPV2 challenge the type-2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 (50%, 95% CI: 38-62) children were shedding virus; 9 of 37 (24%, 12-41) were shedding 28 days after a second challenge. Before challenge type-2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers >/= 32 after one mOPV2 dose. No vaccine-related serious or severe AEs were reported. CONCLUSIONS: High viral excretion following mOPV2 among exclusively IPV-vaccinated children was substantially lower following a subsequent dose, indicating induction of intestinal immunity against type-2 poliovirus.


      3. After the globally coordinated cessation of any serotype of oral poliovirus vaccine (OPV), some risks remain from undetected, existing homotypic OPV-related transmission and/or restarting transmission due to several possible reintroduction risks. The Global Polio Eradication Initiative (GPEI) coordinated global cessation of serotype 2-containing OPV (OPV2) in 2016. Following OPV2 cessation, the GPEI and countries implemented activities to withdraw all the remaining trivalent OPV, which contains all three poliovirus serotypes (i.e., 1, 2, and 3), from the supply chain and replace it with bivalent OPV (containing only serotypes 1 and 3). However, as of early 2020, monovalent OPV2 use for outbreak response continues in many countries. In addition, outbreaks observed in 2019 demonstrated evidence of different types of risks than previously modeled. We briefly review the 2019 epidemiological experience with serotype 2 live poliovirus outbreaks and propose a new risk for unexpected OPV introduction for inclusion in global modeling of OPV cessation. Using an updated model of global poliovirus transmission and OPV evolution with and without consideration of this new risk, we explore the implications of the current global situation with respect to the likely need to restart preventive use of OPV2 in OPV-using countries. Simulation results without this new risk suggest OPV2 restart will likely need to occur (81% of 100 iterations) to manage the polio endgame based on the GPEI performance to date with existing vaccine tools, and with the new risk of unexpected OPV introduction the expected OPV2 restart probability increases to 89%. Contingency planning requires new OPV2 bulk production, including genetically stabilized OPV2 strains.

      4. Duration of cellular and humoral responses after quadrivalent human papillomavirus vaccination in healthy female adults with or without prior type 16 and/or 18 exposureexternal icon
        Lai L, Ault K, Rouphael N, Beck A, Domjahn B, Xu Y, Anderson EJ, Cheng A, Nakamura A, Hoagland RJ, Kelley C, Edupuganti S, Mask K, Nesin M, Unger ER, Panicker G, David H, Mulligan MJ.
        Vaccines (Basel). 2020 Jun 30;8(3).
        Human papillomavirus virus (HPV) vaccines aim to provide durable protection and are ideal to study the association of cellular with humoral responses. We assessed the duration and characteristics of immune responses provided by the quadrivalent HPV (4vHPV) vaccine in healthy female adults with or without prior exposure with type 16 and 18 HPV. In a prospective cohort, vaccine naive females received three doses of 4vHPV vaccine and were followed for two years to assess cellular (intracellular cytokine staining, proliferation and B cell ELISpot assays) and humoral (multiplex L1/L2 viral-like particles (VLP) and M4 ELISAs) responses. Frequencies of vaccine-specific CD4+ T cells correlated with antibody responses. Higher HPV antibody titers were found at all time points in participants previously exposed to HPV, except for anti-HPV-18 at Day 187 (one week post the third vaccination). Retrospective cohorts enrolled females who had previously received two or three 4vHPV doses and tested antibody titers by M4 ELISA and pseudovirion neutralization assay along with memory B cells (MBCs). Almost all women enrolled in a retrospective cohort with two prior doses and all women enrolled in a retrospective cohort with three prior doses had sustained antibody and memory responses. Our findings indicate that HPV vaccination induces a long-lasting, robust cellular and humoral immune responses.

      5. Update on immunodeficiency-associated vaccine-derived polioviruses - worldwide, July 2018-December 2019external icon
        Macklin G, Diop OM, Humayun A, Shahmahmoodi S, El-Sayed ZA, Triki H, Rey G, Avagyan T, Grabovac V, Jorba J, Farag N, Mach O.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):913-917.
        Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses.

      6. A microneedle patch for measles and rubella vaccination: a game changer for achieving eliminationexternal icon
        Prausnitz MR, Goodson JL, Rota PA, Orenstein WA.
        Curr Opin Virol. 2020 Jul 1;41:68-76.
        While morbidity and mortality associated with measles and rubella (MR) have dramatically decreased, there are still >100000 estimated deaths due to measles and an estimated 100000 infants born with congenital rubella syndrome annually. Given highly effective MR vaccines, the primary barrier to global elimination of these diseases is low vaccination coverage, especially among the most underserved populations in resource-limited settings. In contrast to conventional MR vaccination by hypodermic injection, microneedle patches are being developed to enable MR vaccination by minimally trained personnel. Simplified supply chain, reduced need for cold chain storage, elimination of vaccine reconstitution, no sharps waste, reduced vaccine wastage, and reduced total system cost of vaccination are advantages of this approach. Preclinical work to develop a MR vaccine patch has proceeded through successful immunization studies in rodents and non-human primates. On-going programs seek to make MR vaccine patches available to support MR elimination efforts around the world.

      7. Improvement in the analysis of Vaccine Adverse Event Reporting System databaseexternal icon
        Zhao L, Lee S, Li R, Ong E, He Y, Freed G.
        Stat Biopharm Res. 2020 .
        As a national public health surveillance resource, Vaccine Adverse Event Reporting System (VAERS) is a key component in ensuring the safety of vaccines. Numerous methods have been used to conduct safety studies with the VAERS database. These efforts focus on the downstream statistical analysis of the vaccine and adverse event associations. In this article, we primarily focus on processing the raw data in VAERS before the analysis step, which is also an important part of the signal detection process. Due to the semiannual update in the Medical Dictionary for Regulatory Activities (MedDRA) coding system, adverse event terms that describe the same symptom might change in VAERS; therefore, we identify these terms and combine them to increase the signal detection power. We also consider the uncertainty of the vaccine and adverse event pairs that arise from reports with multiple vaccines. Finally, we discuss four commonly used statistics in assessing the vaccine and adverse event associations, and propose to use the statistics that are robust to the reporting bias in VAERS and adjust for potential confounders of the vaccine and adverse event association to increase signal detection accuracy.

    • Injury and Violence
      1. CDC's 2018 Guideline for current practices in pediatric mild traumatic brain injury (mTBI; also referred to as concussion herein) systematically identified the best up-to-date practices based on current evidence and, specifically, identified recommended practices regarding CT, MRI, and skull radiograph imaging. In this commentary, we discuss types of neuroimaging not discussed in the guideline in terms of their safety for pediatric populations, their potential application, and the research investigating the future use of certain modalities to aid in the diagnosis and treatment of mTBI in children. The role of neuroimaging in pediatric mTBI cases should be considered for the potential contribution to children's neural and social development, in addition to the immediate clinical value (as in the case of acute structural findings).Selective use of specific neuroimaging modalities in research has already been shown to detect aspects of diffuse brain injury, disrupted cerebral blood flow, and correlate physiological factors with persistent symptoms following mTBI. However, these advanced neuroimaging modalities are currently limited to the research arena, and any future clinical application of advanced imaging modalities in pediatric mTBI will require robust evidence for each modality's ability to provide measurement of the subtle conditions of brain development, disease, damage, or degeneration while accounting for variables at both non-injury and time-post-injury epochs. Continued collaboration and communication between researchers and health care providers is essential to investigate, develop, and validate the potential of advanced imaging modalities in pediatric mTBI diagnostics and management.

      2. Sexual violence prevalence and related pregnancy among girls and young women: A multicountry analysisexternal icon
        Stamatakis CE, Sumner SA, Massetti G, Kress H, Basile KC, Marcelin LH, Cela T, Wadonda-Kabondo N, Onotu D, Ogbanufe O, Chipimo PJ, Conkling M, Apondi R, Aluzimbi G.
        J Interpers Violence. 2020 Jul 3:886260520936366.
        This study aims to quantify the prevalence of forced sex, pressured sex, and related pregnancy among adolescent girls and young women in five low- and middle-income countries. Nationally representative, cross-sectional household surveys were conducted in Haiti, Malawi, Nigeria, Zambia, and Uganda among girls and young women aged 13 to 24 years. A stratified three-stage cluster sample design was used. Respondents were interviewed to assess prevalence of sexual violence, pregnancy related to the first or most recent experience of forced or pressured sex, relationship to perpetrator, mean age at sexual debut, mean age at pregnancy related to forced or pressured sex, and prevalence of forced/coerced sexual debut. Frequencies, weighted percentages, and weighted means are presented. The lifetime prevalence of forced or pressured sex ranged from 10.4% to 18.0%. Among these adolescent girls and young women, the percentage who experienced pregnancy related to their first or most recent experience of forced or pressured sex ranged from 13.2% to 36.6%. In three countries, the most common perpetrator associated with the first pregnancy related to forced or pressured sex was a current or previous intimate partner. Mean age at pregnancy related to forced or pressured sex was similar to mean age at sexual debut in all countries. Preventing sexual violence against girls and young women will prevent a significant proportion of adverse effects on health, including unintended pregnancy. Implementation of strategies to prevent and respond to sexual violence against adolescent girls and young women is urgently needed.

      3. Rates of suicide in the United States are at a more than 20-y high. Suicide contagion, or spread of suicide-related thoughts and behaviors through exposure to sensationalized and harmful content is a well-recognized phenomenon. Health authorities have published guidelines for news media reporting on suicide to help prevent contagion; however, uptake of recommendations remains limited. A key barrier to widespread voluntary uptake of suicide-reporting guidelines is that more sensational content is perceived to be more engaging to readers and thus enhances publisher visibility and engagement; however, no empirical information exists on the actual influence of adherence to safe-reporting practices on reader engagement. Hence, we conducted a study to analyze adherence to suicide-reporting guidelines on news shared on social media and to assess how adherence affects reader engagement. Our analysis of Facebook data revealed that harmful elements were prevalent in news articles about suicide shared on social media while the presence of protective elements was generally rare. Contrary to popular perception, closer adherence to safe-reporting practices was associated with a greater likelihood of an article being reshared (adjusted odds ratio [AOR] = 1.19, 95% confidence interval [CI] = 1.10 to 1.27) and receiving positive engagement ("love" reactions) (AOR = 1.20, 95% CI = 1.13 to 1.26). Mean safe-reporting scores were lower in the US than other English-speaking nations and variation existed by publisher characteristics. Our results provide empirical evidence that improved adherence to suicide-reporting guidelines may benefit not only the health of individuals, but also support publisher goals of reach and engagement.

    • Laboratory Sciences
      1. Strengthening biosafety and biosecurity status in Bangladesh: A sustainable approachexternal icon
        Asadulghani M, Angra P, Giasuddin M, Bari ML, Islam MS, Roy CK, Islam MR, Islam Z, Hasan KN, Islam MA, Nabi AH, Farzana T, Chowdhury JP, Sultana M, Mannan T, Rahman MH, Sikder AJ, Salimullah M.
        Applied Biosafety. 2020 .
        Introduction: Many emerging and reemerging pathogens have been identified as major public health threats in Bangladesh. Collection, transportation, and storage of infectious materials and management of generated waste from diagnosing those diseases require strict adherence to biosafety and biosecurity practices. Such activities in Bangladesh need substantial development. Methods: A novel multipronged approach was followed to create awareness and provide resources to strengthen nationwide biosafety and biosecurity status. The approach included, but was not limited to, developing resource persons (RPs), developing laboratories’ baseline assessment tools, training assessors, conducting assessments, organizing awareness and training programs, identifying laboratories dealing with biohazards, developing a biosafety cabinet certification program, developing a Web site, and developing customized biosafety and biosecurity guidelines. Results: Currently, 133 RPs and 29 assessors are available in Bangladesh. The RPs organized 8 divisional awareness programs and trained about 3,000 professionals. Assessors conducted baseline assessments of 18 key laboratories, and RPs identified 127 laboratories in Bangladesh dealing with biohazards. NSF-accredited certifiers are now certifying biosafety cabinets in Bangladesh. Guidelines were developed and disseminated to the members. Those RPs who were organizing activities under the program are now organizing biosafety and biosecurity training sessions as academic activities. Conclusions: There is a shift from no biosafety and biosecurity practice toward a growing culture of biosafety and biosecurity practices in research and diagnostics in Bangladesh. To sustain the momentum of this development and to further strengthen the program, allocation of necessary resources and strong leadership support from the government of Bangladesh and donor groups are indispensable.

      2. Fluorescent markers rhodamine B and uranine for Anopheles gambiae adults and matingsexternal icon
        Aviles EI, Rotenberry RD, Collins CM, Dotson EM, Benedict MQ.
        Malar J. 2020 Jul 6;19(1):236.
        BACKGROUND: Marking mosquitoes is vital for mark-release-recapture and many laboratory studies, but their small size precludes the use of methods that are available for larger animals such as unique identifier tags and radio devices. Fluorescent dust is the most commonly used method to distinguish released individuals from the wild population. Numerous colours and combinations can be used, however, dust sometimes affects longevity and behaviour so alternatives that do not have these effects would contribute substantially. Rhodamine B has previously been demonstrated to be useful for marking adult Aedes aegypti males when added to the sugar meal. Unlike dust, this also marked the seminal fluid making it possible to detect matings by marked males in the spermatheca of females. Here, marking of Anopheles gambiae sensu stricto with rhodamine B and uranine was performed to estimate their potential contribution. METHODS: Two fluorescent markers, rhodamine B and uranine, were dissolved in sugar water and fed to adult An. gambiae. Concentrations that are useful for marking individuals and seminal fluid were determined. The effects on adult longevity, the durability of the marking and detection of the marker in mated females was determined. Male mating competitiveness was also evaluated. RESULTS: Rhodamine B marking in adults is detectable for at least 3 weeks, however uranine marking declines with time and at low doses can be confused with auto-fluorescence. Both can be used for marking seminal fluid which can be detected in females mated by marked males, but, again, at low concentrations uranine-marking is more easily confused with the natural fluorescence of seminal fluid. Neither dye affected mating competitiveness. CONCLUSIONS: Both markers tested could be useful for field and laboratory studies. Their use has substantial potential to contribute to a greater understanding of the bio-ecology of this important malaria vector. Rhodamine B has the advantage that it appears to be permanent and is less easily confused with auto-fluorescence. The primary limitation of both methods is that sugar feeding is necessary for marking and adults must be held for at least 2 nights to ensure all individuals are marked whereas dusts provide immediate and thorough marking.

      3. RATIONALE: Over 2,800 e-cigarette, or vaping, product use-associated lung injury (EVALI) cases were reported to the Centers for Disease Control and Prevention (CDC) during August 2019-February 2020. Bronchoalveolar lavage (BAL) fluid samples from 51 EVALI and 99 non-EVALI cases were analyzed for toxicants including terpenes. We describe a novel method to measure selected terpenes in BAL fluid by gas chromatography-tandem mass spectrometry (GC/MS/MS). METHODS: alpha-Pinene, ss-pinene, ss-myrcene, 3-carene, and limonene were measured in BAL fluid specimens by headspace solid-phase microextraction/gas chromatography/tandem mass spectrometry. We created and characterized BAL fluid pools from non-EVALI individuals to determine assay accuracy, precision, linearity, limits of detection, and analytical specificity. All measurements were conducted in accordance with the CDC's Division of Laboratory Sciences rigorous method validation procedures. RESULTS: Matrix validation experiments showed that calibration curves in BAL fluid and saline had similar slopes, with differences of less than 7%. The assay precision ranged from 2.52% to 5.30%. In addition, the limits of detection for the five analytes ranged from 1.80 to 16.8 ng/L, and the linearity was confirmed with R(2) values >0.99. CONCLUSIONS: We developed and validated a method to quantify selected terpenes in BAL fluid specimens using GC/MS/MS. The assay provided accurate and precise analyses of EVALI and non-EVALI BAL fluid specimens in support of CDC's EVALI response. This method is applicable to the determination of a broad range of terpenes in BAL fluid specimens.

      4. Polarization of immune cells is commonly observed in host responses associated with microbial immunity, inflammation, tumorigenesis, and tissue repair and fibrosis. In this process, immune cells adopt distinct programs and perform specialized functions in response to specific signals. Accumulating evidence indicates that inhalation of micro- and nano-sized particulates activates barrier immune programs in the lung in a time- and context-dependent manner, including type 1 and type 2 inflammation, and T helper (Th) 17 cell, regulatory T cell (Treg), innate lymphoid cell (ILC), and myeloid-derived suppressor cell (MDSC) responses, which highlight the polarization of several major immune cell types. These responses facilitate the pulmonary clearance and repair under physiological conditions. When exposure persists and overwhelms the clearance capacity, they foster the chronic progression of inflammation and development of progressive disease conditions, such as fibrosis and cancer. The pulmonary response to insoluble particulates thus represents a distinctive disease process wherein non-infectious, persistent exposures stimulate the polarization of immune cells to orchestrate dynamic inflammatory and immune reactions, leading to pulmonary and pleural chronic inflammation, fibrosis, and malignancy. Despite large variations in particles and their associated disease outcomes, the early response to inhaled particles often follows a common path. The initial reactions entail a barrier immune response dominated by type 1 inflammation that features active phagocytosis by M1 macrophages and recruitment of neutrophils, both of which are fueled by Th1 and proinflammatory cytokines. Acute inflammation is immediately followed by resolution and tissue repair mediated through specialized pro-resolving mediators (SPMs) and type 2 cytokines and cells including M2 macrophages and Th2 lymphocytes. As many particles and fibers cannot be digested by phagocytes, resolution is often extended and incomplete, and type 2 inflammation becomes heightened, which promotes interstitial fibrosis, granuloma formation, and tumorigenesis. Recent studies also reveal the involvement of Th17-, Treg-, ILC-, and MDSC-mediated responses in the pathogenesis caused by inhaled particulates. This review synopsizes the progress in understanding the interplay between inhaled particles and the pulmonary immune functions in disease pathogenesis, with focus on particle-induced polarization of immune cells and its role in the development of chronic inflammation, fibrosis, and cancer in the lung.

      5. Uncertainty in model predictions of exposure response at low exposures is a problem for risk assessment. A particular interest is the internal concentration of an agent in biological systems as a function of external exposure concentrations. Physiologically based pharmacokinetic (PBPK) models permit estimation of internal exposure concentrations in target tissues but most assume that model parameters are either fixed or instantaneously dose-dependent. Taking into account response times for biological regulatory mechanisms introduces new dynamic behaviors that have implications for low-dose exposure response in chronic exposure. A simple one-compartment simulation model is described in which internal concentrations summed over time exhibit significant nonlinearity and nonmonotonicity in relation to external concentrations due to delayed up- or downregulation of a metabolic pathway. These behaviors could be the mechanistic basis for homeostasis and for some apparent hormetic effects.

      6. Dried blood spots for Streptococcus pneumoniae and Haemophilus influenzae detection and serotyping among children < 5 years old in rural Mozambiqueexternal icon
        Pimenta FC, Moiane B, Lessa FC, Venero AL, Moura I, Larson S, Massora S, Chauque A, Tembe N, Mucavele H, Verani JR, Whitney CG, Sigauque B, Carvalho MG.
        BMC Pediatr. 2020 Jul 2;20(1):326.
        BACKGROUND: Dried blood spots (DBS) have been proposed as potentially tool for detecting invasive bacterial diseases. METHODS: We evaluated the use of DBS for S. pneumoniae and H. influenzae detection among children in Mozambique. Blood for DBS and nasopharyngeal (NP) swabs were collected from children with pneumonia and healthy aged < 5 years. Bacterial detection and serotyping were performed by quantitative PCR (qPCR) (NP and DBS; lytA gene for pneumococcus and hpd for H. influenzae) and culture (NP). Combined detection rates were compared between children with pneumonia and healthy. RESULTS: Of 325 children enrolled, 205 had pneumonia and 120 were healthy. Pneumococci were detected in DBS from 20.5 and 64.2% of children with pneumonia and healthy, respectively; NP specimens were positive for pneumococcus in 80.0 and 80.8%, respectively. H. influenzae was detected in DBS from 22.9% of children with pneumonia and 59.2% of healthy; 81.4 and 81.5% of NP specimens were positive for H. influenzae, respectively. CONCLUSION: DBS detected pneumococcal and H. influenzae DNA in children with pneumonia and healthy. Healthy children were often DBS positive for both bacteria, suggesting that qPCR of DBS specimens does not differentiate disease from colonization and is therefore not a useful diagnostic tool for children.

      7. Conserved oligomeric golgi (COG) complex proteins facilitate orthopoxvirus entry, fusion and spreadexternal icon
        Realegeno S, Priyamvada L, Kumar A, Blackburn JB, Hartloge C, Puschnik AS, Sambhara S, Olson VA, Carette JE, Lupashin V, Satheshkumar PS.
        Viruses. 2020 Jun 30;12(7).
        Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes required for monkeypox virus (MPXV) infection, including the individual genes that form the conserved oligomeric Golgi (COG) complex. The COG complex is an eight-protein (COG1-COG8) vesicle tethering complex important for regulating membrane trafficking, glycosylation enzymes, and maintaining Golgi structure. In this study, we investigated the role of the COG complex in OPXV infection using cell lines with individual COG gene knockout (KO) mutations. COG KO cells infected with MPXV and vaccinia virus (VACV) produced small plaques and a lower virus yield compared to wild type (WT) cells. In cells where the KO phenotype was reversed using a rescue plasmid, the size of virus plaques increased demonstrating a direct link between the decrease in viral spread and the KO of COG genes. KO cells infected with VACV displayed lower levels of viral fusion and entry compared to WT suggesting that the COG complex is important for early events in OPXV infection. Additionally, fewer actin tails were observed in VACV-infected KO cells compared to WT. Since COG complex proteins are required for cellular trafficking of glycosylated membrane proteins, the disruption of this process due to lack of individual COG complex proteins may potentially impair the virus-cell interactions required for viral entry and egress. These data validate that the COG complex previously identified in our genetic screens plays a role in OPXV infection.

    • Maternal and Child Health
      1. Characteristics of adults with congenital heart defects in the United Statesexternal icon
        Gurvitz M, Dunn JE, Bhatt A, Book WM, Glidewell J, Hogue C, Lin AE, Lui G, McGarry C, Raskind-Hood C, Van Zutphen A, Zaidi A, Jenkins K, Riehle-Colarusso T.
        J Am Coll Cardiol. 2020 Jul 14;76(2):175-182.
        BACKGROUND: In the United States, >1 million adults are living with congenital heart defects (CHDs), but gaps exist in understanding the health care needs of this growing population. OBJECTIVES: This study assessed the demographics, comorbidities, and health care use of adults ages 20 to 64 years with CHDs. METHODS: Adults with International Classification of Disease-9th Revision-Clinical Modification CHD-coded health care encounters between January 1, 2008 (January 1, 2009 for Massachusetts) and December 31, 2010 were identified from multiple data sources at 3 U.S. sites: Emory University (EU) in Atlanta, Georgia (5 counties), Massachusetts Department of Public Health (statewide), and New York State Department of Health (11 counties). Demographics, insurance type, comorbidities, and encounter data were collected. CHDs were categorized as severe or not severe, excluding cases with isolated atrial septal defect and/or patent foramen ovale. RESULTS: CHD severity and comorbidities varied across sites, with up to 20% of adults having severe CHD and >50% having ≥1 additional cardiovascular comorbidity. Most adults had ≥1 outpatient encounters (80% EU, 90% Massachusetts, and 53% New York). Insurance type differed across sites, with Massachusetts having a large proportion of Medicaid (75%) and EU and New York having large proportions of private insurance (44% EU, 67% New York). Estimated proportions of adults with CHD-coded health care encounters varied greatly by location, with 1.2 (EU), 10 (Massachusetts), and 0.6 (New York) per 1,000 adults based on 2010 census data. CONCLUSIONS: This was the first surveillance effort of adults with CHD-coded inpatient and outpatient health care encounters in 3 U.S. geographic locations using both administrative and clinical data sources. This information will provide a clearer understanding of health care use in this growing population.

      2. Student-perceived school climate is associated with ADHD medication treatment among adolescents in Medicaidexternal icon
        Visser SN, Kramer D, Snyder AB, Sebian J, McGiboney G, Handler A.
        J Atten Disord. 2019 Feb;23(3):234-245.
        OBJECTIVE: The objective of this study was to evaluate the relationship between school climate and ADHD medication treatment among adolescents in Medicaid in Georgia. METHOD: School climate and Medicaid claims data were aggregated for 159 GA counties. County-level school climate percentile and medicated ADHD prevalence were calculated. The t tests and regression models evaluated the relationship between school climate, medicated ADHD, and demographics, weighted by county population. Poorer 2008 school climate (<25th percentile) was regressed on 2011 medicated ADHD prevalence, controlling for potential confounders. RESULTS: The prevalence of medicated ADHD was 7.8% among Medicaid-enrolled GA adolescents. The average county-level prevalence of medicated ADHD was 10.0% ( SD = 2.9%). Poorer school climate was associated with lower rates of medicated ADHD ( p < .0001); along with demographics, these factors accounted for 50% of the county variation in medicated ADHD. CONCLUSION: School climate is associated with medicated ADHD among adolescents in Medicaid. Additional research may reveal whether high medicated ADHD may reflect a lack of access to non-pharmacological therapies in some communities.

    • Occupational Safety and Health
      1. Despite the high burden of sleep disturbances among the general population, there is limited information on prevalence and impact of poor sleep among injured workers. This study: (a) estimated the prevalence of sleep disturbance following work-related injury; and (b) examined the longitudinal association between sleep disturbances and disability/functioning, accounting for reciprocal relationships and mental illness. Longitudinal survey data were collected from workers' compensation claimants with a time-loss claim in Victoria, Australia (N = 700). Surveys were conducted at baseline, 6 months and 12 months. Sleep disturbance was measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. Disability/functioning was based on self-reported activity limitations, participation restrictions and emotional functioning. Path models examined the association between disability/functioning and sleep. Mean sleep disturbance T-scores were 55.2 (SD 11.4) at 6 months, with 36.4% of the sample having a T-score of 60+. Longitudinal relationships were observed between disability (specifically, emotional functioning) and sleep disturbances across successive follow-up waves. For example, each unit increase in T2 emotional functioning (five-point scale) was associated with a 1.1 unit increase in T3 sleep disturbance (approximately 29-76 scale). Cross-lagged path models found evidence of a reciprocal relationship between disability and sleep, although adjustment for mental illness attenuated the estimates to the null. In conclusion, sleep disturbances are common among workers' compensation claimants with work injuries/illnesses. Given the links between some dimensions of disability, mental health and sleep disturbances, the findings have implications for the development of interventions that target the high prevalence of sleep problems among working populations.

      2. Causes and phenotypes of work-related asthmaexternal icon
        Maestrelli P, Henneberger PK, Tarlo S, Mason P, Boschetto P.
        Int J Environ Res Public Health. 2020 Jun 30;17(13).
        Work-related asthma (WRA) includes heterogeneous conditions, which have in common (i) symptoms and signs compatible with asthma and (ii) a relationship with exposures in the workplace. The types of WRA described in this review are distinguished by their etiology, comprising of work-exacerbated asthma (WEA), irritant-induced asthma (IIA), and immunologic occupational asthma (OA). There have been significant advances in the definition and characterization of the different forms of WRA by international panels of experts. The present review provides a comprehensive and updated view of the current knowledge on causes and phenotypes of WRA. Health care practitioners should consider WRA in any case of adult asthma, given that one fifth of workers with asthma report symptoms of WEA and it has been estimated that OA represents 10% to 25% of asthma in adulthood. The information provided in this review will facilitate the physician in the recognition of the different forms of WRA, since it has been established that five categories of agents are responsible for at least 60% of WEA cases and seven groups of agents are the cause of 70% of immunologic OA. In addition, there is agreement that IIA can be elicited not only by a single massive irritant exposure, but also by low/moderate repeated irritant exposures.


      4. Background: Excessive alcohol use, including binge drinking (i.e., >/=5 drinks (males); >/=4 drinks (females), per occasion during the past 30 days), is associated with work-related injuries, absenteeism, and lost productivity. Binge drinking varies by sociodemographic characteristics (e.g., age, sex, income). However, information on binge drinking by occupation is limited. Purpose: This study examined binge drinking prevalence, frequency, intensity, and total binge drinks per binge drinker by sociodemographic characteristics and occupation. Methods: Data were analyzed from 358,355 currently employed U.S. adults who resided in the 32 states that administered the Behavioral Risk Factor Surveillance System industry and occupation questions during 2013-2016. Binge drinking was evaluated using weighted and adjusted prevalence models. Results: Among currently employed adults in the 32 states, 20.8% reported binge drinking, with an average of nearly 49 times per year and an average intensity of 7.4 drinks per binge episode, resulting in 478 total binge drinks per binge drinker. The adjusted binge drinking prevalence ranged from 15.9% among community and social services workers to 26.3% among construction and extraction workers. The total annual binge drinks per binge drinker ranged from 207 drinks among community and social services workers to 749 drinks among construction and extraction workers. Conclusions: One in five employed adults binge drink, and binge drinking varied across occupation groups. Widespread use of effective community-based strategies for preventing excessive alcohol use (e.g., regulating alcohol outlet density), as well as interventions tailored to specific occupation groups, and could reduce binge drinking and improve occupational safety and health.

      5. Characterizing vibration responses of a handheld workpiece and the hand–arm systemexternal icon
        Xu XS, Welcome DE, McDowell TW, Warren C, Lin H, Xiao B, Chen Q, Dong RG.
        J Low Freq Noise Vib Act Control. 2020 .
        The objective of this study is to characterize the vibration responses of a handheld workpiece and the hand–arm system, which is an important step toward identifying and developing effective methods and technologies for controlling the vibration exposures to workers performing the grinding of handheld workpieces. This study established a method for measuring the vibration responses of the entire workpiece–hand–arm system; the vibration exposure of a worker holding and pressing a typical workpiece against a sanding belt or grinding wheel in order to shape the workpiece was simulated. This method was applied to measure the apparent mass and vibration transmissibility of the system under two different feed forces (15 N and 30 N) and six simulated grinding interfaces with different stiffness values. A major resonance was observed in each transmissibility spectrum of the workpiece, which was correlated with the major resonance of the impedance of the entire system. This resonant frequency depended primarily on the workpiece mass and the grinding interface stiffness, but the hand–arm system could substantially affect the resonance magnitude. The feed force also significantly affected the resonance frequency and magnitude. While increasing the feed force increased the overall vibration transmissibility on the hand–arm system, the transmissibility with respect to the workpiece was not significantly affected by the interface conditions. The implications of the results are discussed.

    • Parasitic Diseases
      1. An atypical case of autochthonous cutaneous leishmaniasis associated with naturally infected phlebotomine sand flies in Texas, United Statesexternal icon
        Kipp EJ, de Almeida M, Marcet PL, Bradbury RS, Benedict T, Lin W, Dotson EM, Hergert M.
        Am J Trop Med Hyg. 2020 Jul 6.
        In the United States, phlebotomine sand flies carrying Leishmania (Leishmania) mexicana are endemic along the southern border. However, relatively little is known about the enzootic and zoonotic transmission of L. (L.) mexicana within the United States, and autochthonous cases of the consequent disease are rarely reported. We investigated an atypical case of cutaneous leishmaniasis (CL) caused by L. (L.) mexicana in a patient from central Texas which did not respond to a typical antileishmanial chemotherapy. We also investigated sand fly vectors around the patient's residence. PCR followed by DNA sequencing was used for determination of Leishmania spp., sand fly species, and host blood meal source. The L. (L.) mexicana genotype from the patient was identical to one found in a positive sand fly. Moreover, this genotype presented the same single-nucleotide polymorphisms as other historical CL cases acquired in Texas over the last 10 years, but distinct from those originating in Mexico and Central America. Three sand fly species were identified among the samples analyzed (n = 194), the majority of which were Lutzomyia (Dampfomyia) anthophora (n = 190), of which four specimens tested positive for Leishmania and two blood-fed specimens showed the presence of a human blood meal. This study highlights the complexity of clinical management of CL in a setting where the disease is infrequently encountered. The detection of human blood in Lu. (D.) anthophora is the first documentation of anthropophagy in this species. This is the first report of wild-caught, naturally infected sand flies found in association with an autochthonous case of human leishmaniasis and the specific strain of Leishmania (Leishmania) mexicana in the United States.

    • Physical Activity
      1. The importance of engaging in any type of physical activity regularly, for both physical and mental health, is well established, and may be particularly beneficial in protecting the body and limiting the damage caused by the coronavirus disease 2019 (COVID-19). Exposure to nature or green space also has positive physical and mental health benefits. Closures of parks and green spaces during the COVID-19 pandemic has limited the options for physical activity and may affect vulnerable populations more than others. We provide both short-term and long-term recommendations to encourage access to green space for people while allowing for physical distancing.

      2. Physical activity before and during pregnancy, Colorado Pregnancy Risk Assessment Monitoring System, 2012-2015external icon
        Ussery EN, Hyde ET, Bombard JM, Juhl AL, Kim SY, Carlson SA.
        Prev Chronic Dis. 2020 Jul 9;17:E55.
        We used 2012-2015 data from the Colorado Pregnancy Risk Assessment Monitoring System to describe changes in self-reported physical activity (PA) before and during pregnancy and used logistic regression to examine factors associated with regular PA. The prevalence of regular PA (ie, 30 or more minutes per day on 5 or more days per week) was 19.1% before pregnancy and decreased to 10.2% during pregnancy. At both times, adjusted odds of regular PA were lower among women who were overweight or had obesity before pregnancy than among those with normal weight. Findings suggest that most women with a recent live birth in Colorado, particularly those who are overweight or have obesity, are not obtaining many health benefits of PA either before or during pregnancy.

    • Reproductive Health
      1. Postpartum depressive symptoms and screening opportunities at health care encountersexternal icon
        Haight SC, Ko JY, Yogman MW, Farr SL.
        J Womens Health (Larchmt). 2020 Jul 6.
        Background: The American College of Obstetricians and Gynecologists recommends that providers screen women for depression at the postpartum checkup. If this checkup is the only screening opportunity, women who do not attend or whose depressive episode occurs at a different time may not be identified. We evaluated women's encounters with postpartum health care to identify screening opportunities for postpartum depressive symptoms (PDS). Materials and Methods: Pregnancy Risk Assessment Monitoring System (PRAMS) data for 2012-2015 from eight jurisdictions (n = 23,990, representing 1,939,865 women) were used to calculate percentage of women reporting attendance at postpartum checkups, well-child visits, or postpartum home visitation, by presence of PDS. PDS were assessed using a modified two-item Patient Health Questionnaire. Using Modified Poisson regression, adjusted prevalence ratios (aPR) and confidence intervals (95% CI) were calculated to compare health services by PDS, adjusted for sociodemographic characteristics. Results: Almost all women with or without PDS attended a postpartum checkup (85.1% and 91.4%; aPR: 0.96; 95% CI: 0.93-0.99) and their infants attended a well-child visit (97.3% and 98.9%; aPR: 0.99; 95% CI: 0.98-1.00); 13.7% and 10.9% received home visitation (aPR: 1.18; 95% CI: 1.02-1.35). Of women with PDS who missed their postpartum checkup, 13.5% reported infant attendance at well-child visits, and 2.0% received home visitation. Of women with PDS, 98.8%, 86.1%, and 11.2% attended 1, 2, or 3 health services. Conclusion: A large percentage of women with PDS may attend well-child visits or receive home visitation, representing opportunities for depression screening and referral for care.

    • Statistics as Topic
      1. Protection and safety authorities recommend the use of model averaging to determine the benchmark dose approach as a scientifically more advanced method compared with the no-observed-adverse-effect-level approach for obtaining a reference point and deriving health-based guidance values. Model averaging however highly depends on the set of candidate dose–response models and such a set should be rich enough to ensure that a well-fitting model is included. The currently applied set of candidate models for continuous endpoints is typically limited to two models, the exponential and Hill model, and differs completely from the richer set of candidate models currently used for binary endpoints. The objective of this article is to propose a general and wide framework of dose response models, which can be applied both to continuous and binary endpoints and covers the current models for both type of endpoints. In combination with the bootstrap, this framework offers a unified approach to benchmark dose estimation. The methodology is illustrated using two data sets, one with a continuous and another with a binary endpoint.

    • Substance Use and Abuse
      1. Trends in indicators of injection drug use, Indian Health Service, 2010-2014: A study of health care encounter dataexternal icon
        Evans ME, Person M, Reilley B, Leston J, Haverkate R, McCollum JT, Apostolou A, Bohm MK, Van Handel M, Bixler D, Mitsch AJ, Haberling DL, Hatcher SM, Weiser T, Elmore K, Teshale EH, Weidle PJ, Peters PJ, Buchacz K.
        Public Health Rep. 2020 Jul 7.
        OBJECTIVES: Hepatitis C virus (HCV) and HIV transmission in the United States may increase as a result of increasing rates of opioid use disorder (OUD) and associated injection drug use (IDU). Epidemiologic trends among American Indian/Alaska Native (AI/AN) persons are not well known. METHODS: We analyzed 2010-2014 Indian Health Service data on health care encounters to assess regional and temporal trends in IDU indicators among adults aged >/=18 years. IDU indicators included acute or chronic HCV infection (only among adults aged 18-35 years), arm cellulitis and abscess, OUD, and opioid-related overdose. We calculated rates per 10 000 AI/AN adults for each IDU indicator overall and stratified by sex, age group, and region and evaluated rate ratios and trends by using Poisson regression analysis. RESULTS: Rates of HCV infection among adults aged 18-35 increased 9.4% per year, and rates of OUD among all adults increased 13.3% per year from 2010 to 2014. The rate of HCV infection among young women was approximately 1.3 times that among young men. Rates of opioid-related overdose among adults aged <50 years were approximately 1.4 times the rates among adults aged >/=50 years. Among young adults with HCV infection, 25.6% had concurrent OUD. Among all adults with arm cellulitis and abscess, 5.6% had concurrent OUD. CONCLUSIONS: Rates of HCV infection and OUD increased significantly in the AI/AN population. Strengthened public health efforts could ensure that AI/AN communities can address increasing needs for culturally appropriate interventions, including comprehensive syringe services programs, medication-assisted treatment, and opioid-related overdose prevention and can meet the growing need for treatment of HCV infection.

      2. Vital Signs: Prescription opioid pain reliever use during pregnancy - 34 U.S. jurisdictions, 2019external icon
        Ko JY, D'Angelo DV, Haight SC, Morrow B, Cox S, Salvesen von Essen B, Strahan AE, Harrison L, Tevendale HD, Warner L, Kroelinger CD, Barfield WD.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 17;69(28):897-903.
        BACKGROUND: Prescription opioid use during pregnancy has been associated with poor outcomes for mothers and infants. Studies using administrative data have estimated that 14%-22% of women filled a prescription for opioids during pregnancy; however, data on self-reported prescription opioid use during pregnancy are limited. METHODS: CDC analyzed 2019 data from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey in 32 jurisdictions and maternal and infant health surveys in two additional jurisdictions not participating in PRAMS to estimate self-reported prescription opioid pain reliever (prescription opioid) use during pregnancy overall and by maternal characteristics among women with a recent live birth. This study describes source of prescription opioids, reasons for use, want or need to cut down or stop use, and receipt of health care provider counseling on how use during pregnancy can affect an infant. RESULTS: An estimated 6.6% of respondents reported prescription opioid use during pregnancy. Among these women, 21.2% reported misuse (a source other than a health care provider or a reason for use other than pain), 27.1% indicated wanting or needing to cut down or stop using, and 68.1% received counseling from a provider on how prescription opioid use during pregnancy could affect an infant. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Among respondents reporting opioid use during pregnancy, most indicated receiving prescription opioids from a health care provider and using for pain reasons; however, answers from one in five women indicated misuse. Improved screening for opioid misuse and treatment of opioid use disorder in pregnant patients might prevent adverse outcomes. Implementation of public health strategies (e.g., improving state prescription drug monitoring program use and enhancing provider training) can support delivery of evidence-based care for pregnant women.

    • Zoonotic and Vectorborne Diseases
      1. Rat-bite fever in the United States: An analysis using multiple national data sources, 2001-2015external icon
        Kache PA, Person MK, Seeman SM, McQuiston JR, McCollum J, Traxler RM.
        Open Forum Infect Dis. 2020 Jun;7(6):ofaa197.
        Background: Rat-bite fever is a rare disease associated with rat bites or direct/indirect rodent contact. Methods: We examined rat-bite fever and rat-bite injury diagnoses in the United States during 2001-2015. We analyzed national, state, and Indian Health Service healthcare encounter datasets for rat-bite fever and rat-bite injury diagnoses. We calculated average-annual encounter rates per 1 000 000 persons. Results: Nationally, the rat-bite fever Emergency Department visit rate was 0.33 (95% confidence interval [CI], 0.19-0.47) and the hospitalization rate was 0.20 (95% CI, 0.17-0.24). The rat-bite injury Emergency Department visit rate was 10.51 (95% CI, 10.13-10.88) and the hospitalization rate was 0.27 (95% CI, 0.23-0.30). The Indian Health Service Emergency Department/outpatient visit rate was 3.00 for rat-bite fever and 18.89 for rat-bite injury. The majority of rat-bite fever encounters were among individuals 0-19 years of age. Conclusions: Our results support the literature that rat-bite fever is rare and affects children and young adults. Targeted education could benefit specific risk groups.

      2. Dengue viral (DENV) infection results in a wide spectrum of clinical manifestations from asymptomatic, mild fever to severe hemorrhage diseases upon infection. Severe dengue is the leading cause of pediatric deaths and/or hospitalizations, which are a major public health burden in dengue-endemic or hyperendemic countries. Like other RNA viruses, DENV continues to evolve. Adaptive mutations are obscured by the major consensus sequence (so-called wild-type sequences) and can only be identified once they become the dominant viruses in the virus population, a process that can take months or years. Traditional surveillance systems still rely on Sanger consensus sequencing. However, with the recent advancement of high-throughput next-generation sequencing (NGS) technologies, the genome-wide investigation of virus population within-host and between-hosts becomes achievable. Thus, viral population sequencing by NGS can increase our understanding of the changing epidemiology and evolution of viral genomics at the molecular level. This review focuses on the studies within the recent decade utilizing NGS in different experimental and epidemiological settings to understand how the adaptive evolution of dengue variants shapes the dengue epidemic and disease severity through its transmission. We propose three types of studies that can be pursued in the future to enhance our surveillance for epidemic prediction and better medical management.

      3. Dog-rabies elimination programs have typically relied upon parenteral vaccination at central-point locations; however, dog-ownership practices, accessibility to hard-to-reach sub-populations, resource limitations, and logistics may impact a country's ability to reach the 70% coverage goal recommended by the World Organization for Animal Health (OIE) and World Health Organization (WHO). Here we report the cost-effectiveness of different dog-vaccination strategies during a dog-rabies outbreak in urban and peri-urban sections of Croix-des-Bouquets commune of the West Department, Haiti, in 2016. Three strategies, mobile static point (MSP), mobile static point with capture-vaccinate-release (MSP+CVR), and door-to-door vaccination with oral vaccination (DDV+ORV), were applied at five randomly assigned sites and assessed for free-roaming dog vaccination coverage and total population coverage. A total of 7065 dogs were vaccinated against rabies during the vaccination campaign. Overall, free-roaming dog vaccination coverage was estimated at 52% (47%-56%) for MSP, 53% (47%-60%) for DDV+ORV, and 65% (61%-69%) for MSP+CVR (differences with MSP and DDV+ORV significant at p<0.01). Total dog vaccination coverage was 33% (95% CI: 26%-43%) for MSP, 49% (95% CI: 40%-61%) for MSP+CVR and 78% (77%-80%) for DDV+ORV (differences significant at p<0.001). Overall, the least expensive campaign was MSP, with an estimated cost of about $2039 per day ($4078 total), and the most expensive was DDV+ORV with a cost of $3246 per day ($6492 total). Despite the relative high cost of an ORV bait, combining DDV and ORV was the most cost-effective strategy in our study ($1.97 per vaccinated dog), largely due to increased efficiency of the vaccinators to target less accessible dogs. Costs per vaccinated dog were $2.20 for MSP and $2.28 for MSP+CVR. We hope the results from this study will support the design and implementation of effective dog vaccination campaigns to achieve the goal of eliminating dog-mediated human rabies deaths by 2030.


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