Issue 26, August 2020

CDC Science Clips: Volume 12, Issue 26, August 4, 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, Science Clips is pleased to collaborate with CDC Vital Signs by featuring scientific articles from the latest issue on Clinical Characteristics of Patients with Confirmed Acute Flaccid Myelitis, United States, 2018. The articles marked with an asterisk are general review articles which may be of particular interest to clinicians and public health professionals seeking background information in this area.

  1. CDC Vital Signs
    • Acute Flaccid Myelitis
      1. Acute flaccid myelitis, defined by acute flaccid limb weakness in the setting of grey matter lesions of the spinal cord, became increasingly recognised in 2014 following outbreaks in Colorado and California, temporally associated with an outbreak of enterovirus D68 respiratory disease. Since then, there have been biennial increases in late summer/early fall. A viral infectious aetiology, most likely enteroviral, is strongly suspected, but a definitive connection has yet to be established. Patients typically present with asymmetric weakness, maximal proximally, in the setting of a febrile illness. MRI demonstrates T2/FLAIR abnormalities in the central grey matter of the spinal cord, and cerebrospinal fluid typically shows a lymphocytic pleocytosis with variable elevation in protein. The weakness may be progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder involvement. There is no clear recommended treatment at this time, although intravenous immunoglobulin, steroids and plasma exchange have been used. Intensive therapies and rehab services have shown benefit in maximising function, and surgical interventions may be considered in cases without optimal response to therapies. Close attention should also be paid to psychosocial factors. Prognosis is generally guarded, and additional factors that predict final outcome, including host factors and treatment effects, have yet to be elucidated. Multicentre collaborative efforts will be required to provide answers about this rare but serious disorder.

      2. *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.

      3. 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.

      4. 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.

      5. 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.

      6. 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.

      7. 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.

      8. 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.

      9. 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.

      10. 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. Effectiveness of interventions to increase colorectal cancer screening among American Indians and Alaska Nativesexternal icon
        Haverkamp D, English K, Jacobs-Wingo J, Tjemsland A, Espey D.
        Prev Chronic Dis. 2020 Jul 16;17:E62.
        INTRODUCTION: Screening rates for colorectal cancer are low in many American Indian and Alaska Native (AI/AN) communities. Direct mailing of a fecal immunochemical test (FIT) kit can address patient and structural barriers to screening. Our objective was to determine if such an evidence-based intervention could increase colorectal cancer screening among AI/AN populations. METHODS: We recruited study participants from 3 tribally operated health care facilities and randomly assigned them to 1 of 3 study groups: 1) usual care, 2) mailing of FIT kits, and 3) mailing of FIT kits plus follow-up outreach by telephone and/or home visit from an American Indian Community Health Representative (CHR). RESULTS: Among participants who received usual care, 6.4% returned completed FIT kits. Among participants who were mailed FIT kits without outreach, 16.9% returned the kits - a significant increase over usual care (P < .01). Among participants who received mailed FIT kits plus CHR outreach, 18.8% returned kits, which was also a significant increase over usual care (P < .01) but not a significant increase compared with the mailed FIT kit-only group (P = .44). Of 165 participants who returned FIT kits during the study, 39 (23.6%) had a positive result and were referred for colonoscopy of which 23 (59.0%) completed the colonoscopy. Twelve participants who completed a colonoscopy had polyps, and 1 was diagnosed with colorectal cancer. CONCLUSION: Direct mailing of FIT kits to eligible community members may be a useful, population-based strategy to increase colorectal cancer screening among AI/AN people.

      2. Depressive symptoms and the arthritis-employment interface. A population-level studyexternal icon
        Jetha A, Theis KA, Boring MA, Murphy LB, Guglielmo D.
        Arthritis Care Res (Hoboken). 2020 Jul 23.
        OBJECTIVES: To examine the relationship between depressive symptoms, arthritis, and employment participation. To determine if this relationship differs across young, middle, and older working-age adults with arthritis. METHODS: Data from the US National Health Interview Survey, years 2013-2017, were analyzed. Analyses were restricted to those with doctor-diagnosed arthritis of working age (18-64 years) with complete data on depressive symptoms (n=11,380). Covariates were sociodemographic, health, and health system use variables. Employment prevalence was compared by self-reported depressive symptoms. We estimated percentages, univariable, and multivariable logistic regression models to examine the relationship between depression and employment among young (18-34 years), middle (35-54 years), and older adults (55-64 years). RESULTS: Among all working-age US adults with arthritis, prevalence of depressive symptoms was 13%. Those reporting depressive symptoms had higher prevalence of fair/poor health (60%) and arthritis-attributable activity limitations (70%) compared with those not reporting depression (23% and 39%, respectively). Respondents with depressive symptoms reported significantly lower employment prevalence (30%) when compared with those not reporting depressive symptoms (66%) and lower multivariable-adjusted association with employment (PR=0.88, 95% CI [confidence interval] 0.83-0.93). Middle-age adults reporting depression were significantly less likely to be employed compared with their counterparts without depression (PR=0.83, 95% CI 0.77-0.90); similar but borderline statistically significant relationships were observed for both younger (PR=0.86, 95% CI 0.74-0.99) and older adults (PR=0.94. 95% CI 0.86-1.03). CONCLUSION: For adults with arthritis, depressive symptoms are associated with not participating in employment. Strategies to reduce arthritis-related work disability may be more effective if they simultaneously address mental health.

      3. Hospital length of stay, charges, and costs associated with a diagnosis of obesity in US children and youth, 2006-2016external icon
        Kompaniyets L, Lundeen EA, Belay B, Goodman AB, Tangka F, Blanck HM.
        Med Care. 2020 Aug;58(8):722-726.
        BACKGROUND: Childhood obesity is linked with adverse health outcomes and associated costs. Current information on the relationship between childhood obesity and inpatient costs is limited. OBJECTIVE: The objective of this study was to describe trends and quantify the link between childhood obesity diagnosis and hospitalization length of stay (LOS), costs, and charges. RESEARCH DESIGN: We use the National Inpatient Sample data from 2006 to 2016. SUBJECTS: The sample includes hospitalizations among children aged 2-19 years. The treatment group of interest includes child hospitalizations with an obesity diagnosis. MEASURES: Hospital LOS, charges, and costs associated with a diagnosis of obesity. RESULTS: We find increases in obesity-coded hospitalizations and associated charges and costs during 2006-2016. Obesity as a primary diagnosis is associated with a shorter hospital LOS (by 1.8 d), but higher charges and costs (by $20,879 and $6049, respectively); obesity as a secondary diagnosis is associated with a longer LOS (by 0.8 d), and higher charges and costs of hospitalizations (by $3453 and $1359, respectively). The most common primary conditions occurring with a secondary diagnosis of obesity are pregnancy conditions, mood disorders, asthma, and diabetes; the effect of a secondary diagnosis of obesity on LOS, charges, and costs holds across these conditions. CONCLUSIONS: Childhood obesity diagnosis-related hospitalizations, charges, and costs increased substantially during 2006-2016, and obesity diagnosis is associated with higher hospitalization charges and costs. Our findings provide clinicians and policymakers with additional evidence of the economic burden of childhood obesity and further justify efforts to prevent and manage the disease.

      4. Weekend effect on in-hospital mortality for ischemic and hemorrhagic stroke in US rural and urban hospitalsexternal icon
        Mekonnen B, Wang G, Rajbhandari-Thapa J, Shi L, Thapa K, Zhang Z, Zhang D.
        J Stroke Cerebrovasc Dis. 2020 ;29(10).
        Introduction: Previous studies have reported a “weekend effect” on stroke mortality, whereby stroke patients admitted during weekends have a higher risk of in-hospital death than those admitted during weekdays. Aims: We aimed to investigate whether patients with different types of stroke admitted during weekends have a higher risk of in-hospital mortality in rural and urban hospitals in the US. Methods: We used data from the 2016 National Inpatient Sample and used logistic regression to assess in-hospital mortality for weekday and weekend admissions among stroke patients aged 18 and older by stroke type (ischemic or hemorrhagic) and rural or urban status. Results: Crude stroke mortality was higher in weekend admissions (p <0.001). After adjusting for confounding variables, in-hospital mortality among hemorrhagic stroke patients was significantly greater (22.0%) for weekend admissions compared to weekday admissions (20.2%, p = 0.009). Among rural hospitals, the in-hospital mortality among hemorrhagic stroke patients was also greater among weekend admissions (36.9%) compared to weekday admissions (25.7%, p = 0.040). Among urban hospitals, the mortality of hemorrhagic stroke patients was 21.1% for weekend and 19.6% for weekday admissions (p = 0.026). No weekend effect was found among ischemic stroke patients admitted to rural or urban hospitals. Conclusions: Our results help to understand mortality differences in hemorrhagic stroke for weekend vs. weekday admissions in urban and rural hospitals. Factors such as density of care providers, stroke centers, and patient level risky behaviors associated with the weekend effect on hemorrhagic stroke mortality need further investigation to improve stroke care services and reduce weekend effect on hemorrhagic stroke mortality.

      5. Identifying optimal survey-based algorithms to distinguish diabetes type among adults with diabetesexternal icon
        Nooney JG, Kirkman MS, Bullard KM, White Z, Meadows K, Campione JR, Mardon R, Rivero G, Benoit SR, Pfaff E, Rolka D, Saydah S.
        J Clin Transl Endocrinol. 2020 Sep;21:100231.
        OBJECTIVES: Surveys for U.S. diabetes surveillance do not reliably distinguish between type 1 and type 2 diabetes, potentially obscuring trends in type 1 among adults. To validate survey-based algorithms for distinguishing diabetes type, we linked survey data collected from adult patients with diabetes to a gold standard diabetes type. RESEARCH DESIGN AND METHODS: We collected data through a telephone survey of 771 adults with diabetes receiving care in a large healthcare system in North Carolina. We tested 34 survey classification algorithms utilizing information on respondents' report of physician-diagnosed diabetes type, age at onset, diabetes drug use, and body mass index. Algorithms were evaluated by calculating type 1 and type 2 sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) relative to a gold standard diagnosis of diabetes type determined through analysis of EHR data and endocrinologist review of selected cases. RESULTS: Algorithms based on self-reported type outperformed those based solely on other data elements. The top-performing algorithm classified as type 1 all respondents who reported type 1 and were prescribed insulin, as "other diabetes type" all respondents who reported "other," and as type 2 the remaining respondents (type 1 sensitivity 91.6%, type 1 specificity 98.9%, type 1 PPV 82.5%, type 1 NPV 99.5%). This algorithm performed well in most demographic subpopulations. CONCLUSIONS: The major federal health surveys should consider including self-reported diabetes type if they do not already, as the gains in the accuracy of typing are substantial compared to classifications based on other data elements. This study provides much-needed guidance on the accuracy of survey-based diabetes typing algorithms.

      6. Comparison of three devices for 24-hour ambulatory blood pressure monitoring in a nonclinical environment through a randomized trialexternal icon
        Nwankwo T, Coleman King SM, Ostchega Y, Zhang G, Loustalot F, Gillespie C, Chang TE, Begley EB, George MG, Shimbo D, Schwartz JE, Muntner P, Kronish IM, Hong Y, Merritt R.
        Am J Hypertens. 2020 Jul 23.
        BACKGROUND: The U.S. Preventive Services Task Force recommends the use of 24-hour ambulatory blood pressure monitoring (ABPM) as part of screening and diagnosis of hypertension. The optimal ABPM device for population-based surveys is unknown. OBJECTIVE: Among three ABPM devices, we compared the proportion of valid BP readings, mean awake and asleep BP readings, differences between awake ABPM readings and initial standardized BP readings, and sleep experience. RESULTS: The proportions of valid blood pressure readings were not different among the three devices ( p > 0.45). Mean awake and asleep systolic BP were significantly higher for STO device (WA vs. STO vs. SL: 126.65 mmHg, 138.09 mmHg, 127.44 mmHg; 114.34 mmHg, 120.34 mmHg, 113.13 mmHg; p <0.0001 for both). The difference between the initial average standardized mercury systolic BP readings and the ABPM mean awake systolic BP was larger for STO device (WA vs. STO. vs. SL: -5.26 mmHg, -16.24 mmHg, -5.36 mmHg; p <0.0001); diastolic BP mean differences were ~ -6 mmHg for all three devices ( p =0.6). Approximately 55% of participants reported that the devices interfered with sleep; however, there were no sleep differences across the devices (p >0.4 for all). CONCLUSION: Most of the participants met the threshold of 70% valid readings over 24 hours. Sleep disturbance was common but did not interfere with completion of measurement in most of the participants.

      7. Examination of laws allowing sunscreen use in schools in the context of UV levels by stateexternal icon
        Patterson B, Holman DM, Qin J, Smith K, Zhou Y.
        J Adolesc Health. 2020 Jul 18.
        PURPOSE: Sunscreen use provides ultraviolet radiation (UV) protection but is often limited in school settings because sunscreen is classified as an over-the-counter drug product. Some US states have laws allowing students to carry and self-apply sunscreen. We examined these laws in the context of state UV levels. METHODS: We obtained legislative information through April 2020 from the American Society for Dermatologic Surgery Association website and UV data for years 2005-2015 from Centers for Disease Control and Prevention's National Environmental Public Health Tracking website. RESULTS: Twenty-three states and District of Columbia have sunscreen laws, including 11 states with UV levels above the median UV level across states. There was no significant association between state UV levels and sunscreen laws. CONCLUSIONS: The presence of state sunscreen legislation has increased but is not associated with UV levels. Future research could examine the implementation and public health effects of these laws.

      8. Prevalence and predictors of high blood pressure among women of reproductive age and children aged 10 to 14 years in Guatemalaexternal icon
        Pickens CM, Flores-Ayala R, Addo OY, Whitehead RD, Palmieri M, Ramirez-Zea M, Hong Y, Jefferds ME.
        Prev Chronic Dis. 2020 Jul 23;17:E66.
        INTRODUCTION: Data on the prevalence and predictors of high blood pressure among children and non-pregnant women of reproductive age are sparse in Guatemala. Our objective was to identify the prevalence and predictors of high blood pressure among women of reproductive age and children in Guatemala. METHODS: We analyzed data on blood pressure among 560 children aged 10 to 14 years and 1,182 non-pregnant women aged 15 to 49 from a cross-sectional, nationally representative household survey, SIVESNU (Sistema de Vigilancia Epidemiológica de Salud y Nutrición). We defined high blood pressure among children by using 2004 and 2017 US pediatric guidelines. We defined high blood pressure among women by using 1999 World Health Organization (WHO) and 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. We used multivariable logistic regression to identify significant predictors of high blood pressure. A base model included key covariates (age, ethnicity, socioeconomic index, anthropometric indicators) and accounted for complex sampling. We used backward elimination to identify additional candidate predictor variables. RESULTS: High blood pressure was prevalent among 8.0% (95% confidence interval [CI], 5.4%-10.7%) and 14.0% (95% CI, 10.6%-17.5%) of children using 2004 and 2017 guidelines, respectively; and among 12.7% (95% CI, 10.7%-14.8%) and 41.1% (95% CI, 37.7%-44.4%) of women using 1999 WHO and 2017 ACC/AHA guidelines, respectively. Levels of awareness, treatment, and control of high blood pressure were low in women. Among children, significant predictors of high blood pressure were obesity, overweight, and indigenous ethnicity. Among women, significant predictors of high blood pressure included obesity, overweight, and diabetes. CONCLUSION: The prevalence of high blood pressure was high among Guatemalan women and children. Overweight and obesity were strong risk factors for high blood pressure. Increasing obesity prevention and control programs may help prevent high blood pressure, and expanding high blood pressure screening and treatment could increase awareness and control of high blood pressure in Guatemala.

      9. Hemophilia without prophylaxis: Assessment of joint range of motion and factor activityexternal icon
        Wang M, Recht M, Iyer NN, Cooper DL, Soucie JM.
        Res Pract Thromb Haemost. 2020 .
        Background: Recurrent joint bleeding in hemophilia results in arthropathy and functional impairment. The relationship of arthropathy development and factor activity (FA) has not been reported in patients with FA levels <15%-20%. Method(s): During the Centers for Disease Control and Prevention Universal Data Collection, joint range-of-motion (ROM) measurements were taken at each comprehensive visit. Data were extracted from male patients with hemophilia (PWH) age >=2 years with baseline factor activity levels <=40%, excluding those prescribed prophylaxis, and used to calculate a proportion of normal ROM (PN-ROM) measure. Data were analyzed using regression models. Result(s): There were 6703 eligible PWH with 30 102 visits. PN-ROM declined with increasing age, and was associated with hemophilia severity, race/ethnicity, obesity, and viral illnesses. PWH >=30 years old with fFA <=2% and those >=50 years old with FA <=5% had mean PN-ROM values >10% less than controls; those >=40 years old with FA <1% had values >20% less than controls. In the multivariable analysis, subjects with <1% FA had a 0.43% greater decrease (-0.49 to -0.37, 95% confidence interval) in PN-ROM each year relative to those with 16%-40% factor activity. A less pronounced effect was seen with 1%-5% or 6%-9% FA. Conclusion(s): The effect of FA on ROM loss is far greater than that of any of the other characteristics, especially with FA <10%. This emphasizes the need to maintain a high index of suspicion for arthropathy in individuals with moderate and low-mild hemophilia.

      10. BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of hip fracture, but lower likelihood of having arthroplasties than non-IBD patients in Nationwide Inpatient Sample. Little is known about hip fracture-associated hospitalization outcomes. AIMS: We assessed the trends in hip fracture hospitalization rates from 2000 to 2017 and estimated 30-day readmission, 30-day mortality, and length of stay in 2016 and 2017. METHODS: We estimated trends of age-adjusted hospitalization rates using a piecewise linear regression. Medicare beneficiaries aged ≥ 66 years with Crohn's disease (CD, n = 2014) or ulcerative colitis (UC, n = 2971) hospitalized for hip fracture were identified. We performed propensity score matching to create 1:3 matched samples on age, race/ethnicity, sex, and chronic conditions and compared hospitalization outcomes between matched samples. RESULTS: In 2017, the age-adjusted hospitalization rates (per 100) were 1.15 [95% CI = (1.07-1.24)] for CD, 0.86 [95% CI = (0.82-0.89)] for UC, and 0.59 [95% CI = (0.59-0.59)] for no IBD. The hospitalization rates for CD and UC decreased from 2000 to 2012 and then increased from 2012 to 2017. Compared to matched cohorts, CD patients had longer hospital stays (5.55 days vs. 5.30 days, p = 0.01); UC patients were more likely to have 30-day readmissions (17.27% vs. 13.71%, p < 0.001), longer hospital stays (5.59 days vs. 5.40 days, p = 0.02), and less likely to have 30-day mortality (3.77% vs. 5.15%, p = 0.003). CONCLUSIONS: Prevention of hip fracture is important for older adults with IBD, especially CD. Strategies that improve quality of inpatient care for IBD patients hospitalized for hip fracture should be considered.

    • Communicable Diseases
      1. Typhoid fever transmission occurs through ingestion of food or water contaminated with Salmonella Typhi, and case-control studies are often conducted to identify outbreak sources and transmission vehicles. However, there is no current summary of the associations among water, sanitation, and hygiene (WASH); and food exposures and typhoid from case-control studies. We conducted a systematic review and meta-analysis of case-control studies to evaluate the associations among typhoid fever and predicted WASH or food exposure risk factors (13), and protective factors (7). Overall, 19 manuscripts describing 22 case-control studies were included. Two studies were characterized as having low risk of bias, one as medium risk, and 19 as high risk. In total, nine of 13 predicted risk factors were associated with increased odds of typhoid (odds ratio [OR] = 1.4-2.4, I (2) = 30.5-74.8%.), whereas five of seven predicted protective factors were associated with lower odds of typhoid (OR = 0.52-0.73, I (2) = 38.7-84.3%). In five types of sensitivity analyses, two (8%) of 26 summary associations changed significance from the original analysis. Results highlight the following: the importance of household hygiene transmission pathways, the need for further research around appropriate food interventions and the risk of consuming specific foods and beverages outside the home, and the absence of any observed association between sanitation exposures and typhoid fever. We recommend that typhoid interventions focus on interrupting household transmission routes and that future studies provide more detailed information about WASH and food exposures to inform better targeted interventions.

      2. This report provides an introduction and reference tool for tuberculosis (TB) controllers regarding the essential components of a public health program to prevent, control, and eliminate TB. The Advisory Council for the Elimination of Tuberculosis and the National Tuberculosis Controllers Association recommendations in this report update those previously published (Advisory Council for the Elimination of Tuberculosis. Essential components of a tuberculosis prevention and control program. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep 1995;44[No. RR-11]). The report has been written collaboratively on the basis of experience and expert opinion on approaches to organizing programs engaged in diagnosis, treatment, prevention, and surveillance for TB at state and local levels.This report reemphasizes the importance of well-established priority strategies for TB prevention and control: identification of and completion of treatment for persons with active TB disease; finding and screening persons who have had contact with TB patients; and screening, testing, and treatment of other selected persons and populations at high risk for latent TB infection (LTBI) and subsequent active TB disease.Health departments are responsible for public safety and population health. To meet their responsibilities, TB control programs should institute or ensure completion of numerous responsibilities and activities described in this report: preparing and maintaining an overall plan and policy for TB control; maintaining a surveillance system; collecting and analyzing data; participating in program evaluation and research; prioritizing TB control efforts; ensuring access to recommended laboratory and radiology tests; identifying, managing, and treating contacts and other persons at high risk for Mycobacterium tuberculosis infection; managing persons who have TB disease or who are being evaluated for TB disease; providing TB training and education; and collaborating in the coordination of patient care and other TB control activities. Descriptions of CDC-funded resources, tests for evaluation of persons with TB or LTBI, and treatment regimens for LTBI are provided (Supplementary Appendices;

      3. Characteristics of sexual partnerships among men with diagnosed HIV who have sex with men, United States and Puerto Rico-2015-2019external icon
        Dasgupta S, Tie Y, Bradley H, Beer L, Rosenberg ES, Holtgrave D, Fagan J, Green S, Shouse RL.
        J Acquir Immune Defic Syndr. 2020 Aug 15;84(5):443-452.
        BACKGROUND: Understanding sexual partnerships of HIV-positive persons, particularly at the dyad level, can help in quantifying HIV transmission risk. We described sexual partnerships among HIV-positive men who have sex with men (MSM), including partnerships with a high risk for sexual HIV transmission. SETTING: The Medical Monitoring Project is an annual, cross-sectional study that reports representative estimates on U.S. HIV-positive adults. METHODS: During 2015-2019, we assessed sexual behaviors by interview, and viral load results from medical records. Among sexually active HIV-positive MSM (n = 4923), we described prevalence of high-risk sex, defined as: (1) not having sustained viral suppression, and (2) having condomless sex with an HIV-negative partner not known to be taking pre-exposure prophylaxis or an HIV-unknown partner. We described sexual partnerships among HIV-positive MSM (n = 13,024 partnerships among 4923 MSM). For HIV-discordant partnerships (n = 7768), we reported the proportion involved in high-risk sex, and associations with high-risk sex using prevalence ratios with predicted marginal means, controlling for age of the HIV-positive partner (P < 0.05). RESULTS: More than half (66%) of sexually active HIV-positive MSM had condomless sex; 11% had high-risk sex. Blacks were more likely to have detectable viral loads, but less likely to have condomless sex, making prevalence of high-risk sex comparable between racial/ethnic groups. Dyad-level analyses among HIV-discordant partnerships indicated that prevalence of high-risk sex was higher among partnerships with HIV-positive white MSM, which was not observed using person-level data alone. CONCLUSIONS: In the context of ending the HIV epidemic, behavioral and clinical surveillance data can help monitor HIV transmission risk and target prevention efforts to reduce transmission among populations at disproportionate risk.

      4. Awareness and willingness to use biomedical prevention strategies for HIV among sexual and gender minority youth: Results from a national surveyexternal icon
        Dunville R, Harper C, Johns MM, Heim Viox M, Avripas S, Fordyce E, Stern M, Schlissel A, Carpenter R, Michaels S.
        J Adolesc Health. 2020 Jul 18.
        PURPOSE: Sexual and gender minority youth (SGM), an umbrella term encompassing gay, bisexual, and transgender youth, experience disproportionately high rates of new HIV infections, and recent advances in biomedical HIV prevention modalities hold promise in reducing new infections. However, the extent to which SGM youth are aware of and willing to use these modalities is unknown. METHODS: Using data from the Survey of Today's Adolescents Relationships and Transitions, we analyze awareness of and willingness to take HIV pre-exposure prophylaxis (PrEP), nonoccupational HIV post-exposure prophylaxis, and rectal microbicides among adolescent sexual minority males aged 13-18 years and transgender youth aged 13-24 years. RESULTS: Overall, we found a majority of our respondents were not aware of any of these prevention modalities. Across both subsamples, age and outness to a health care provider were associated with increased PrEP awareness, and any anal sex was associated with PrEP willingness. CONCLUSIONS: These findings highlight the importance of provider education on how to discuss SGM issues with patients and educate them about HIV prevention options.

      5. Ventilator-associated pneumonia involving Aspergillus flavus in a patient with coronavirus disease 2019 (COVID-19) from Argentinaexternal icon
        Fernandez NB, Caceres DH, Beer KD, Irrazabal C, Delgado G, Farias L, Chiller TM, Verweij PE, Stecher D.
        Medical Mycology Case Reports. 2020 .
        Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, emerged in Wuhan, China, in December 2019 and rapidly spread around the world. Invasive aspergillosis has been reported as a complication of severe influenza pneumonia among intensive care patients. Similarities between COVID-19 and influenza pneumonia, together with limited published case series, suggest that aspergillosis may be an important complication of COVID-19. This report describes a case of ventilator-associated pneumonia involving Aspergillus flavus in a patient with COVID-19 from Buenos Aires, Argentina.

      6. Systematic testing for influenza and COVID-19 among patients with respiratory illnessexternal icon
        Flannery B, Meece JK, Williams JV, Martin ET, Gaglani M, Jackson ML, Talbot HK.
        Clin Infect Dis. 2020 Jul 20.

      7. Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020external icon
        Havers FP, Reed C, Lim T, Montgomery JM, Klena JD, Hall AJ, Fry AM, Cannon DL, Chiang CF, Gibbons A, Krapiunaya I, Morales-Betoulle M, Roguski K, Rasheed MA, Freeman B, Lester S, Mills L, Carroll DS, Owen SM, Johnson JA, Semenova V, Blackmore C, Blog D, Chai SJ, Dunn A, Hand J, Jain S, Lindquist S, Lynfield R, Pritchard S, Sokol T, Sosa L, Turabelidze G, Watkins SM, Wiesman J, Williams RW, Yendell S, Schiffer J, Thornburg NJ.
        JAMA Intern Med. 2020 Jul 21.
        IMPORTANCE: Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. OBJECTIVE: To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State. EXPOSURES: Infection with SARS-CoV-2. MAIN OUTCOMES AND MEASURES: The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date. RESULTS: Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases. CONCLUSIONS AND RELEVANCE: During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

      8. Parainfluenza virus types 1-3 infections among children and adults hospitalized with community-acquired pneumoniaexternal icon
        Howard LM, Edwards KM, Zhu Y, Williams DJ, Self WH, Jain S, Ampofo K, Pavia AT, Arnold SR, McCullers JA, Anderson EJ, Wunderink RG, Grijalva CG.
        Clin Infect Dis. 2020 Jul 18.
        BACKGROUND: Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia. METHODS: We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in eight United States hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression. RESULTS: PIV was more commonly detected in children (155/2354 [6.6%]) than in adults (66/2297 [2.9%]) (p<0.001). Other pathogens were commonly co-detected among PIV cases (110/221 [50%]). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other non-bacterial pneumonia; whereas children with bacterial pneumonia, exhibited increased severity (OR 8.42 [95% CI 1.88, 37.80]). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens. CONCLUSIONS: Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia.

      9. Infectious disease hospitalizations, New York City, 2001-2014external icon
        Huang CC, Lucero DE, Lim S, Zhao Y, Arciuolo RJ, Burzynski J, Daskalakis D, Fine AD, Kennedy J, Haberling D, Vora NM.
        Public Health Rep. 2020 Jul 20.
        OBJECTIVE: Hospital discharge data are a means of monitoring infectious diseases in a population. We investigated rates of infectious disease hospitalizations in New York City. METHODS: We analyzed data for residents discharged from New York State hospitals with a principal diagnosis of an infectious disease during 2001-2014 by using the Statewide Planning and Research Cooperative System. We calculated annual age-adjusted hospitalization rates and the percentage of hospitalizations in which in-hospital death occurred. We examined diagnoses by site of infection or sepsis and by pathogen type. RESULTS: During 2001-2014, the mean annual age-adjusted rate of infectious disease hospitalizations in New York City was 1661.6 (95% CI, 1659.2-1663.9) per 100 000 population; the mean annual age-adjusted hospitalization rate decreased from 2001-2003 to 2012-2014 (rate ratio = 0.9; 95% CI, 0.9-0.9). The percentage of in-hospital death during 2001-2014 was 5.9%. The diagnoses with the highest mean annual age-adjusted hospitalization rates among all sites of infection and sepsis diagnoses were the lower respiratory tract, followed by sepsis. From 2001-2003 to 2012-2014, the mean annual age-adjusted hospitalization rate per 100 000 population for HIV decreased from 123.1 (95% CI, 121.7-124.5) to 40.0 (95% CI, 39.2-40.7) and for tuberculosis decreased from 10.2 (95% CI, 9.8-10.6) to 4.6 (95% CI, 4.4-4.9). CONCLUSIONS: Although hospital discharge data are subject to limitations, particularly for tracking sepsis, lower respiratory tract infections and sepsis are important causes of infectious disease hospitalizations in New York City. Hospitalizations for HIV infection and tuberculosis appear to be declining.

      10. Bringing women's voices to PMTCT CARE: adapting CARE's Community Score Card to engage women living with HIV to build quality health systems in Malawiexternal icon
        Laterra A, Callahan T, Msiska T, Woelk G, Chowdhary P, Gullo S, Mwale PM, Modi S, Chauwa F, Kayira D, Kalua T, Wako E.
        BMC Health Serv Res. 2020 Jul 22;20(1):679.
        BACKGROUND: Coverage of prevention of mother-to-child transmission of HIV (PMTCT) services has expanded rapidly but approaches to ensure service delivery is patient-centered have not always kept pace. To better understand how the inclusion of women living with HIV in a collective, quality improvement process could address persistent gaps, we adapted a social accountability approach, CARE's Community Score Card© (CSC), to the PMTCT context. The CSC process generates perception-based score cards and facilitates regular quality improvement dialogues between service users and service providers. METHODS: Fifteen indicators were generated by PMTCT service users and providers as part of the CSC process. These indicators were scored by each population during three sequential cycles of the CSC process which culminates in a sharing of scores in a collective meeting followed by action planning. We aggregated these scores across facilities and analyzed the differences in first and last scorings to understand perceived improvements over the course of the project (z-test comparing the significance of two proportions; one-tailed p-value ≤ .05). Data were collected over 12 months from September 2017 to August 2018. RESULTS: Fourteen of the fifteen indicators improved over the course of this project, with eight showing statistically significant improvement. Out of the indicators that showed statistically significant improvement, the majority fell within the control of local communities, local health facilities, or service providers (7 out of 8) and were related to patient or user experience and support from families and community members (6 out of 8). From first to last cycle, scores from service users' and service providers' perspectives converged. At the first scoring cycle, four indicators exhibited statistically significant differences (p-value ≤ .05) between service users and service providers. At the final cycle there were no statistically significant differences between the scores of these two groups. CONCLUSIONS: By creating an opportunity for mothers living with HIV, health service providers, communities, and local government officials to jointly identify issues and implement solutions, the CSC contributed to improvements in the perceived quality of PMTCT services. The success of this model highlights the feasibility and importance of involving people living with HIV in quality improvement and assurance efforts. TRIAL REGISTRATION: Trial registration: NCT04372667 retrospectively registered on May 1st 2020.

      11. Advanced HIV disease in the Botswana Combination Prevention Project: prevalence, risk factors, and outcomesexternal icon
        Lebelonyane R, Mills LA, Mogorosi C, Ussery F, Marukutira T, Theu J, Kapanda M, Matambo S, Block L, Raizes E, Makhema J, Lockman S, Bachanas P, Moore J, Jarvis JN.
        Aids. 2020 Jul 17.
        OBJECTIVE(S): To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4 ≤200 cells/μL) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes. DESIGN: A sub-analysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16-64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral-therapy (ART) were referred to local Ministry of Health and Wellness clinics for treatment. METHODS: Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4 strata (CD4 ≤200 cells/μL vs. > 200 cells/μL). RESULTS: Overall, 17.2% (430/2,499; 95% confidence interval [CI] 15.7-18.8%) of study participants had advanced HIV disease (CD4 ≤200 cells/μL) at time of clinic linkage. Men were significantly more likely to present with CD4 ≤200 cells/μL than women (23.7% versus 13.4%, adjusted odds ratio [aOR] 1.9, 95% CI 1.5-2.3). The risk of advanced HIV disease increased with increasing age (aOR 2.2, 95% CI 1.4-3.2 > 35 years versus < 25 years). Patients with CD4 ≤200 cells/μL had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1-2.1). CONCLUSIONS: Advanced HIV disease due to late presentation to or disengagement from ART care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care.

      12. They are likely to be there: using a family-centered index testing approach to identify children living with HIV in Kenyaexternal icon
        Okoko N, Kulzer JL, Ohe K, Mburu M, Muttai H, Abuogi LL, Bukusi EA, Cohen CR, Penner J.
        Int J STD AIDS. 2020 Jul 21.
        In Kenya, only half of children with a parent living with HIV have been tested for HIV. The effectiveness of family-centered index testing to identify children (0-14 years) living with HIV was examined. A retrospective record review was conducted among adult index patients newly enrolled in HIV care between May and July 2015; family testing, results, and linkage to treatment outcomes were followed through May 2016 at 60 high-volume clinics in Kenya. Chi square test compared yield (percentage of HIV tests positive) among children tested through family-centered index testing, outpatient and inpatient testing. Review of 1937 index client charts led to 3005 eligible children identified for testing. Of 2848 (94.8%) children tested through family-centered index testing, 127 (4.5%) had HIV diagnosed, 100 (78.7%) were linked to care, and 85 of those eligible (91.4%) initiated antiretroviral therapy (ART).Family testing resulted in higher yield compared to inpatient (1.8%, p < 0.001) or outpatient testing (1.6%, p < 0.001). The absolute number of children living with HIV identified was highest with outpatient testing. The relative contribution of testing approach to total children identified with HIV was outpatient testing (69%), family testing (26%), and inpatient testing (5%). The family testing approach demonstrated promise in achieving the first two "90s" (identification and ART initiation) of the 90-90-90 targets for children, with additional effort required to improve linkage from testing to treatment.

      13. Notes from the field: Public health efforts to mitigate COVID-19 transmission during the April 7, 2020, election - city of Milwaukee, Wisconsin, March 13-May 5, 2020external icon
        Paradis H, Katrichis J, Stevenson M, Tomaro N, Mukai R, Torres G, Bhattacharyya S, Kowalik J, Schlanger K, Leidman E.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):1002-1003.

      14. Progress toward hepatitis B control - South-East Asia Region, 2016-2019external icon
        Sandhu HS, Roesel S, Sharifuzzaman M, Chunsuttiwat S, Tohme RA.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):988-992.
        In 2015, the World Health Organization (WHO) South-East Asia Region (SEAR)* reported an estimated 40 million persons living with chronic hepatitis B virus (HBV) infection and 285,000 deaths from complications of chronic infection, cirrhosis, and hepatocellular carcinoma (1). Most chronic HBV infections, indicated by the presence of hepatitis B surface antigen (HBsAg) on serologic testing, are acquired in infancy through perinatal or early childhood transmission (2). To prevent perinatal and childhood infections, WHO recommends that all infants receive at least 3 doses of hepatitis B vaccine (HepB), including a timely birth dose (HepB-BD)(†) (1). In 2016, the SEAR Immunization Technical Advisory Group endorsed a regional hepatitis B control goal with a target of achieving hepatitis B surface antigen (HBsAg) seroprevalence of ≤1% among children aged ≥5 years by 2020, which is in line with the WHO Global Health Sector Strategy on Viral Hepatitis 2016-2021 (2,3). The South-East Asia Regional Vaccine Action Plan 2016-2020 (SEARVAP) (4) identified the acceleration of hepatitis B control as one of the eight regional goals for immunization. The plan outlined four main strategies for achieving hepatitis B control: 1) achieving ≥90% coverage with 3 doses of HepB (HepB3), 2) providing timely vaccination with a HepB birth dose (HepB-BD), 3) providing catch-up vaccination of older children, and 4) vaccinating adult populations at high risk and health care workers (1,4). In 2019, SEAR established a regional expert panel on hepatitis B to assess countries' HBV control status. This report describes the progress made toward hepatitis B control in SEAR during 2016-2019. By 2016, all 11 countries in the region had introduced HepB in their national immunization programs, and eight countries had introduced HepB-BD. During 2016-2019, regional HepB3 coverage increased from 89% to 91%, and HepB-BD coverage increased from 34% to 54%. In 2019, nine countries in the region achieved ≥90% HepB3 coverage, and three of the eight countries that provide HepB-BD achieved ≥90% HepB-BD coverage. By December 2019, four countries had been verified to have achieved the hepatitis B control goal. Countries in the region can make further progress toward hepatitis B control by using proven strategies to improve HepB-BD and HepB3 coverage rates. Conducting nationally representative hepatitis B serosurveys among children will be key to tracking and verifying the regional control targets.

      15. Use of drug-level testing and single-genome sequencing to unravel a case of HIV seroconversion on PrEPexternal icon
        Spinelli MA, Lowery B, Shuford JA, Spindler J, Kearney MF, McFarlane JR, McDonald C, Okochi H, Phung N, Kuncze K, Jee K, Johannessen D, Anderson PL, Smith DK, Defechereux P, Grant RM, Gandhi M.
        Clin Infect Dis. 2020 Jul 20.
        Cases of seroconversion on PrEP should be carefully investigated given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.

      16. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network - United States, March-June 2020external icon
        Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, Gibbs KW, Erickson HL, Steingrub JS, Smithline HA, Gong MN, Aboodi MS, Exline MC, Henning DJ, Wilson JG, Khan A, Qadir N, Brown SM, Peltan ID, Rice TW, Hager DN, Ginde AA, Stubblefield WB, Patel MM, Self WH, Feldstein LR, IVY Network Investigators , CDC COVID-19 Response Team .
        MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):993-998.
        Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.

    • Environmental Health
      1. Prenatal and early childhood exposure to phthalates and childhood behavior at age 7 yearsexternal icon
        Daniel S, Balalian AA, Insel BJ, Liu X, Whyatt RM, Calafat AM, Rauh VA, Perera FP, Hoepner LA, Herbstman J, Factor-Litvak P.
        Environ Int. 2020 Jul 14;143:105894.
        BACKGROUND: Emerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific. METHODS: In a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately. RESULTS: Among boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations. CONCLUSION: Concentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific.

      2. Heat-associated mortality in a hot climate: Maricopa County, Arizona, 2006-2016external icon
        Iverson SA, Gettel A, Bezold CP, Goodin K, McKinney B, Sunenshine R, Berisha V.
        Public Health Rep. 2020 Jul 20.
        OBJECTIVES: Maricopa County, Arizona (2017 population about 4.3 million), is located in the Sonoran Desert. In 2005, the Maricopa County Department of Public Health (MCDPH) established a heat-associated mortality surveillance system that captures data on circumstances of death for Maricopa County residents and visitors. We analyzed 2006-2016 surveillance system data to understand the characteristics and circumstances of heat-associated deaths. METHODS: We classified heat-associated deaths based on International Classification of Diseases, Tenth Revision codes (X30, T67.X, and P81.0) and phrases (heat exposure, environ, exhaustion, sun, heat stress, heat stroke, or hyperthermia) in part I or part II of the death certificate. We summarized data on decedents' demographic characteristics, years lived in Arizona, location of death (indoors vs outdoors), presence and functionality of air conditioning, and whether the decedent had been homeless. We examined significant associations between variables by using the Pearson χ(2) tests and logistic regression. RESULTS: During 2006-2016, MCDPH recorded data on 920 heat-associated deaths, 912 of which included location of injury. Of 565 (62%) heat-associated deaths that occurred outdoors, 458 (81%) were among male decedents and 243 (43%) were among decedents aged 20-49. Of 347 (38%) heat-associated deaths that occurred indoors, 201 (58%) were among decedents aged ≥65. Non-Arizona residents were 5 times as likely as Arizona residents to have a heat-associated death outdoors (P < .001). Of 727 decedents with data on duration of Arizona residency, 438 (60%) had resided in Arizona ≥20 years. CONCLUSIONS: Ongoing evaluation of interventions that target populations at risk for both outdoor and indoor heat-associated deaths can further inform refinement of the surveillance system and identify best practices to prevent heat-associated deaths.

    • Epidemiology and Surveillance

    • Health Behavior and Risk
      1. Exchange sex among high school students - Washington, DC, 2017external icon
        Head SK, Eaton D, Lloyd PC, McLaughlin A, Davies-Cole J.
        J Adolesc Health. 2020 Jul 14.
        PURPOSE: Exchange sex, the exchange of money or nonmonetary items for sex, is associated with sexually transmitted diseases and HIV. We sought to identify prevalence and characteristics associated with exchange sex among District of Columbia (DC) high school students. METHODS: We used the 2017 DC Youth Risk Behavior Survey, a cross-sectional survey of students in grades 9-12 (n = 8,578). We performed multivariable logistic regression to examine associations between exchange sex and demographic, home environment, and substance use measures. RESULTS: In 2017, a total of 7.4% (95% confidence interval [CI]: 6.6-8.2) of students reported ever having engaged in exchange sex. Odds of exchange sex were higher among males (adjusted odds ratio [AOR]: 2.5; 95% CI: 1.6-4.0) and students who had sexual contact with partners of both sexes (AOR: 2.4; 95% CI: 1.2-4.9), compared with students having sexual contact with partners of opposite sex only. Exchange sex was also associated with having been kicked out, run away, or abandoned during the past 30 days (AOR: 10.7; 95% CI: 7.0-16.3]); going hungry during the past 30 days (AOR: 2.2; 95% CI: 1.1-4.5); and ever using synthetic marijuana (AOR: 2.6; 95% CI: 1.3-5.0) or cocaine, heroin, methamphetamines, or ecstasy (AOR: 2.9; 95% CI: 1.6-5.3]), compared with those who had not. CONCLUSIONS: Approximately one in 14 DC high school students engaged in exchange sex. Programs providing services to youth with unstable housing, food insecurity, or who use drugs should incorporate sexual health services to address exchange sex practices.

    • Healthcare Associated Infections
      1. BACKGROUND: Escherichia coli is one of the most common causes of healthcare-associated infections (HAI); multidrug resistance reduces available options for antibiotic treatment. We examined factors associated with the spread of multidrug-resistant E. coli phenotypes responsible for device- and procedure-related HAI from acute care hospitals, long term acute care hospitals and inpatient rehabilitation facilities, using isolate and antimicrobial susceptibility data reported to the National Healthcare Safety Network (NHSN) from 2013-2017. METHODS: We used multivariable logistic regression to examine associations between co-resistant phenotypes, patient and healthcare facility characteristics, and time. We also examined the geographic distributione of co-resistant phenotypes each year by state and by hospital referral region to identify hot spots. RESULTS: A total of 96,672 E. coli isolates were included. Patient median age was 62 years; 60% were females; over half (54%) were reported from catheter-associated urinary tract infections. From 2013-2017, 35% of the isolates were non-susceptible to FQs; 17% to ESCs; and 13% to both ESCs and FQs. The proportion of isolates co-resistant to ESCs and FQs was higher in 2017 (14%) than in 2013 (11%) (P<0.0001); overall prevalence and increases were heterogeneously distributed across healthcare referral regions. Co-resistance to FQs and ESCs was independently associated with male sex, central line-associated bloodstream infections, long-term acute care hospitals, and the 2016-17 (v. 2013-14) reporting period. CONCLUSIONS: Multidrug-resistance among E.coli causing device- and procedure-related HAIs has increased in the United States. FQ and ESC co-resistant strains appear to be spreading heterogeneously across hospital referral regions.

    • Immunity and Immunization
      1. The origins and genomic diversity of American Civil War Era smallpox vaccine strainsexternal icon
        Duggan AT, Klunk J, Porter AF, Dhody AN, Hicks R, Smith GL, Humphreys M, McCollum AM, Davidson WB, Wilkins K, Li Y, Burke A, Polasky H, Flanders L, Poinar D, Raphenya AR, Lau TT, Alcock B, McArthur AG, Golding GB, Holmes EC, Poinar HN.
        Genome Biol. 2020 Jul 20;21(1):175.
        Vaccination has transformed public health, most notably including the eradication of smallpox. Despite its profound historical importance, little is known of the origins and diversity of the viruses used in smallpox vaccination. Prior to the twentieth century, the method, source and origin of smallpox vaccinations remained unstandardised and opaque. We reconstruct and analyse viral vaccine genomes associated with smallpox vaccination from historical artefacts. Significantly, we recover viral molecules through non-destructive sampling of historical materials lacking signs of biological residues. We use the authenticated ancient genomes to reveal the evolutionary relationships of smallpox vaccination viruses within the poxviruses as a whole.

      2. Notes from the field: Rebound in routine childhood vaccine administration following decline during the COVID-19 pandemic - New York City, March 1-June 27, 2020external icon
        Langdon-Embry M, Papadouka V, Cheng I, Almashhadani M, Ternier A, Zucker JR.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):999-1001.

      3. Incidence of meningococcal disease before and after implementation of quadrivalent meningococcal conjugate vaccine in the United Statesexternal icon
        Mbaeyi S, Pondo T, Blain A, Yankey D, Potts C, Cohn A, Hariri S, Shang N, MacNeil JR.
        JAMA Pediatr. 2020 Jul 20.
        IMPORTANCE: In 2005, the US Advisory Committee on Immunization Practices recommended routine quadrivalent meningococcal conjugate (MenACWY) vaccine for all adolescents aged 11 to 12 years, and in 2010, a booster dose for adolescents aged 16 years. Measuring the association between MenACWY vaccination and the incidence of meningococcal disease in adolescents is critical for evaluating the adolescent vaccination program and informing future vaccine policy. OBJECTIVE: To describe the association between MenACWY vaccination and the incidence of meningococcal disease in US adolescents. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, analysis of surveillance data included all confirmed and probable cases of Neisseria meningitidis reported to the National Notifiable Diseases Surveillance System from January 1, 2000, to December 31, 2017. Statistical analysis was conducted from October 1, 2018, to August 31, 2019. EXPOSURES: Routine MenACWY vaccination among US adolescents. MAIN OUTCOMES AND MEASURES: Poisson segmented regression analysis was used to model the annual incidence of meningococcal disease among adolescents aged 11 to 15 years and 16 to 22 years before the introduction of the MenACWY vaccine (2000-2005), after the primary dose recommendation (2006-2010), and after the booster dose recommendation (2011-2017); 95% CIs were used to determine significant differences between time periods. RESULTS: The national incidence of meningococcal disease declined from 0.61 cases per 100 000 population during the prevaccine period (2000-2005) to 0.15 cases per 100 000 population during the post-booster dose period (2011-2017). The greatest percentage decline was observed for serogroup C, W, and Y combined (CWY) among adolescents aged 11 to 15 years and 16 to 22 years in the periods after vaccine introduction. Incidence of serogroup CWY meningococcal disease among adolescents aged 11 to 15 years decreased by 16.3% (95% CI, 12.1%-20.3%) annually during the prevaccine period and 27.8% (95% CI, 20.6%-34.4%) during the post-primary dose period (P = .02); among adolescents aged 16 to 22 years, the incidence decreased by 10.6% (95% CI, 6.8%-14.3%) annually in the post-primary dose period and 35.6% (95% CI, 29.3%-41.0%) annually in the post-booster dose period (P < .001). An estimated 222 cases of meningococcal disease due to serogroup CWY among adolescents were averted through vaccination during the evaluation period. CONCLUSIONS AND RELEVANCE: After introduction of a primary and booster MenACWY dose, the rates of decline in incidence of meningococcal disease due to serogroup C, W, or Y accelerated nearly 2-fold to 3-fold in vaccinated adolescent age groups. Although the MenACWY vaccine alone cannot explain the decline of meningococcal disease in the United States, these data suggest that MenACWY vaccination is associated with reduced disease rates in adolescents.

      4. Implementing the routine immunisation data module and dashboard of DHIS2 in Nigeria, 2014-2019external icon
        Shuaib F, Garba AB, Meribole E, Obasi S, Sule A, Nnadi C, Waziri NE, Bolu O, Nguku PM, Ghiselli M, Adegoke OJ, Jacenko S, Mungure E, Gidado S, Wilson I, Wiesen E, Elmousaad H, Bloland P, Rosencrans L, Mahoney F, MacNeil A, Franka R, Vertefeuille J.
        BMJ Glob Health. 2020 Jul;5(7).
        In 2010, Nigeria adopted the use of web-based software District Health Information System, V.2 (DHIS2) as the platform for the National Health Management Information System. The platform supports real-time data reporting and promotes government ownership and accountability. To strengthen its routine immunisation (RI) component, the US Centers for Disease Control and Prevention (CDC) through its implementing partner, the African Field Epidemiology Network-National Stop Transmission of Polio, in collaboration with the Government of Nigeria, developed the RI module and dashboard and piloted it in Kano state in 2014. The module was scaled up nationally over the next 4 years with funding from the Bill & Melinda Gates Foundation and CDC. One implementation officer was deployed per state for 2 years to support operations. Over 60 000 RI healthcare workers were trained on data collection, entry and interpretation and each local immunisation officer in the 774 local government areas (LGAs) received a laptop and stock of RI paper data tools. Templates for national-level and state-level RI bulletins and LGA quarterly performance tools were developed to promote real-time data use for feedback and decision making, and enhance the performance of RI services. By December 2017, the DHIS2 RI module had been rolled out in all 36 states and the Federal Capital Territory, and all states now report their RI data through the RI Module. All states identified at least one government DHIS2 focal person for oversight of the system's reporting and management operations. Government officials routinely collect RI data and use them to improve RI vaccination coverage. This article describes the implementation process-including planning and implementation activities, achievements, lessons learnt, challenges and innovative solutions-and reports the achievements in improving timeliness and completeness rates.

    • Informatics
      1. Public health reporting and outbreak response: synergies with evolving clinical standards for interoperabilityexternal icon
        Mishra NK, Duke J, Lenert L, Karki S.
        J Am Med Inform Assoc. 2020 Jul 1;27(7):1136-1138.
        Public health needs up-to-date information for surveillance and response. As healthcare application programming interfaces become widely available, a novel data gathering mechanism could provide public health with critical information in a timely fashion to respond to a fast-moving epidemic. In this article, we extrapolate from our experiences using a Fast Healthcare Interoperability Resource-based architecture for infectious disease surveillance for sexually transmitted diseases to its application to gather case information for an outbreak. One of the challenges with a fast-moving outbreak is to accurately assess its demand on healthcare resources, since information specific to comorbidities is often not available. These comorbidities are often associated with poor prognosis and higher resource utilization. If the comorbidity data and other clinical information were readily available to public health workers, they could better address community disruption and manage healthcare resources. The use of FHIR resources available through application programming and filtered through tools such as described herein will give public health the flexibility needed to investigate rapidly emerging disease while protecting patient privacy.

    • Injury and Violence
      1. Fall-related emergency department visits involving alcohol among older adultsexternal icon
        Shakya I, Bergen G, Haddad YK, Kakara R, Moreland BL.
        J Safety Res. 2020 .
        Problem: Falls are the leading cause of injury deaths among adults aged 65 years and older. Characteristics of these falls may vary with alcohol use. Objective: Describe and compare characteristics of older adult fall-related emergency department (ED) visits with indication of alcohol to visits with no indication. Methods: Using nationally-representative 2015 National Electronic Injury Surveillance System-All Injury Program data, we compared demographic characteristics for fall-related ED visits by indication of alcohol consumption. Alcohol-indicated ED visits were matched on age group, sex, treatment month, and treatment day to ED visits with no alcohol indication using a 1:4 ratio and injury characteristics (i.e., diagnosis, body part injured, disposition) were compared. Results and discussion: Of 38,640 ED records, 906 (1.9%) indicated use of alcohol. Fall-related ED visits among women were less likely to indicate alcohol (1.0%) compared to ED visits among men (3.8%). ED visits indicating alcohol decreased with age from 4.1% for those 65–74 years to 1.5% for those 75–84 and <1% for those 85+. After controlling for age-group, sex, and month and day of treatment, 17.0% of ED visits with no alcohol indication had a traumatic brain injury compared to 34.8% of alcohol-indicated ED visits. Practical applications: Alcohol-indicated fall ED visits resulted in more severe head injury than those that did not indicate alcohol. To determine whether alcohol use should be part of clinical risk assessment for older adult falls, more routinely collected data and detailed information on the amount of alcohol consumed at the time of the fall are needed.

      2. OBJECTIVE: The objective of this study is to describe concussion reporting and return to learn and play among high school students. METHODS: Self-reported survey data of 1,999 New England private preparatory high school students who played sports or engaged in recreational activities were collected in 2018. Descriptive and bivariate statistics are presented. RESULTS: Three in ten respondents (31.4%) reported ever sustaining a concussion and 22.0% did not report at least one concussion to an adult. The most common reasons for not reporting included wanting to keep playing their sport (58.0%) and not thinking the injury was that serious (53.6%). Girls and students in higher grades took longer to return to school and sports. A quarter of students reported pretending to have a faster recovery in order to return to school or sports. CONCLUSION: Private school students who play sports or engage in recreational activity may be at risk of sustaining concussions and may not report their symptoms due to a lack of understanding the seriousness of concussion, not wanting to fall behind in school, or out of desire to continue playing their sport. Teachers, coaches, and parents can stress reporting as the first step in recovery.

    • Laboratory Sciences
      1. Potential antitumor activity of digitoxin and user-designed analog administered to human lung cancer cellsexternal icon
        Eldawud R, Wagner A, Dong C, Gupta N, Rojanasakul Y, O'Doherty G, Stueckle TA, Dinu CZ.
        Biochim Biophys Acta Gen Subj. 2020 Jul 14:129683.
        BACKGROUND: Cardiac glycosides (CGs), such as digitoxin, are traditionally used for treatment of congestive heart failure; recently they also gained attention for their anticancer properties. Previous studies showed that digitoxin and a synthetic L-sugar monosaccharide analog treatment decreases cancer cell proliferation, increases apoptosis, and pro-adhesion abilities; however, no reports are available on their potential to alter lung cancer cell cytoskeleton structure and reduce migratory ability. Herein, we investigated the anticancer effects of digitoxin and its analog, digitoxigenin-α-L-rhamnoside (D6MA), to establish whether cytoskeleton reorganization and reduced motility are drug-induced cellular outcomes. METHODS: We treated non-small cell lung carcinoma cells (NSCLCs) with sub-therapeutic, therapeutic, and toxic concentrations of digitoxin and D6MA respectively, followed by both single point and real-time assays to evaluate changes in cellular gene and protein expression, adhesion, elasticity, and migration. RESULTS: Digitoxin and D6MA induced a decrease in matrix metalloproteinases expression via altered focal adhesion signaling and a suppression of the phosphoinositide 3-kinases / protein kinase B pathway which lead to enhanced adhesion, altered elasticity, and reduced motility of NSCLCs. Global gene expression analysis identified dose-dependent changes to nuclear factor kappa-light-chain-enhancer, epithelial tumor, and microtubule dynamics signaling. CONCLUSIONS: Our study demonstrates that digitoxin and D6MA can target antitumor signaling pathways to alter NSCLC cytoskeleton and migratory ability to thus potentially reduce their tumorigenicity. SIGNIFICANCE: Discovering signaling pathways that control cancer's cell phenotype and how such pathways are affected by CG treatment will potentially allow for active usage of synthetic CG analogs as therapeutic agents in advanced lung conditions.

      2. Lyssavirus vaccine with a chimeric glycoprotein protects across phylogroupsexternal icon
        Fisher CR, Lowe DE, Smith TG, Yang Y, Hutson CL, Wirblich C, Cingolani G, Schnell MJ.
        Cell Rep. 2020 Jul 21;32(3):107920.
        Rabies is nearly 100% lethal in the absence of treatment, killing an estimated 59,000 people annually. Vaccines and biologics are highly efficacious when administered properly. Sixteen rabies-related viruses (lyssaviruses) are similarly lethal, but some are divergent enough to evade protection from current vaccines and biologics, which are based only on the classical rabies virus (RABV). Here we present the development and characterization of LyssaVax, a vaccine featuring a structurally designed, functional chimeric glycoprotein (G) containing immunologically important domains from both RABV G and the highly divergent Mokola virus (MOKV) G. LyssaVax elicits high titers of antibodies specific to both RABV and MOKV Gs in mice. Immune sera also neutralize a range of wild-type lyssaviruses across the major phylogroups. LyssaVax-immunized mice are protected against challenge with recombinant RABV and MOKV. Altogether, LyssaVax demonstrates the utility of structural modeling in vaccine design and constitutes a broadened lyssavirus vaccine candidate.

      3. IMVAMUNE and ACAM2000 provide different protection against disease when administered postexposure in an intranasal monkeypox challenge prairie dog modelexternal icon
        Keckler MS, Salzer JS, Patel N, Townsend MB, Nakazawa YJ, Doty JB, Gallardo-Romero NF, Satheshkumar PS, Carroll DS, Karem KL, Damon IK.
        Vaccines (Basel). 2020 Jul 20;8(3).
        The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today's populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 10(4) pfu (2× LD(50)) or 10(6) pfu (170× LD(50)) and vaccinated the animals with IMVAMUNE(®) or ACAM2000(®) either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD(50), but not the 170× LD(5) challenge. In the 2× LD(50) challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE(®), but ACAM2000(®) was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.

      4. BACKGROUND: In Gram-negative species, β-lactam antibiotics target penicillin binding proteins (PBPs) resulting in morphological alterations of bacterial cells. Observations of antibiotic-induced cell morphology changes can rapidly and accurately differentiate drug susceptible from resistant bacterial strains; however, resistant cells do not always remain unchanged. Burkholderia pseudomallei is a Gram-negative, biothreat pathogen and the causative agent of melioidosis, an often fatal infectious disease for humans. RESULTS: Here, we identified β-lactam targets in B. pseudomallei by in silico analysis. Ten genes encoding putative PBPs, including PBP-1, PBP-2, PBP-3 and PBP-6, were detected in the genomes of susceptible and resistant strains. Real-time, live-cell imaging of B. pseudomallei strains demonstrated dynamic morphological changes in broth containing clinically relevant β-lactam antibiotics. At sub-inhibitory concentrations of ceftazidime (CAZ), amoxicillin-clavulanic acid (AMC), and imipenem (IPM), filamentation, varying in length and proportion, was an initial response of the multidrug-resistant strain Bp1651 in exponential phase. However, a dominant morphotype reemerged during stationary phase that resembled cells unexposed to antibiotics. Similar morphology dynamics were observed for AMC-resistant strains, MSHR1655 and 724644, when exposed to sub-inhibitory concentrations of AMC. For all B. pseudomallei strains evaluated, increased exposure time and exposure to increased concentrations of AMC at and above minimal inhibitory concentrations (MICs) in broth resulted in cell morphology shifts from filaments to spheroplasts and/or cell lysis. B. pseudomallei morphology changes were more consistent in IPM. Spheroplast formation followed by cell lysis was observed for all strains in broth containing IPM at concentrations greater than or equal to MICs, however, the time to cell lysis was variable. B. pseudomallei cell lengths were strain-, drug- and drug concentration-dependent. CONCLUSIONS: Both resistant and susceptible B. pseudomallei strains exhibited filamentation during early exposure to AMC and CAZ at concentrations used to interpret susceptibility (based on CLSI guidelines). While developing a rapid β-lactam antimicrobial susceptibility test based on cell-shape alone requires more extensive analyses, optical microscopy detected B. pseudomallei growth attributes that lend insight into antibiotic response and antibacterial mechanisms of action.

      5. Estimation of the critical external heat leading to the failure of lithium-ion batteriesexternal icon
        Tang W, Tam WC, Yuan L, Dubaniewicz T, Thomas R, Soles J.
        Appl Therm Eng. 2020 ;179.
        A detailed experimental investigation on the critical external heat leading to the failure of lithium-ion (Li-ion) batteries was conducted using an Accelerating Rate Calorimeter (ARC) at the National Institute for Occupational Safety and Health (NIOSH). Several types of commercial Li-ion batteries were selected for the study, including an iron phosphate Li-ion battery (LFP), a lithium-titanate battery (LTO), and a lithium-nickel-manganese-cobalt-oxide battery (NMC). Each battery was placed in a specially designed sealed steel canister and heated in the ARC. Battery voltage throughout the test was monitored and used to indicate the time to a battery failure. Three thermocouples, one attached to the battery surface, one measuring air temperature inside the canister, and one attached to the canister's internal surface, were used to record temperature changes during the heating tests. Different thermal behaviors were observed for the various battery types. An analytical model was developed to estimate the total external heat received by the battery using the measured temperatures. Experimental data ranked the batteries tested in terms of the heat to failure as: LFP 26,650 (11 kJ) > LFP 18650 (4.3 kJ) > NMC 18650 MH1 (3.6 kJ) ≈ LTO 18650 (3.6 kJ) > NMC 18650 HG2 (3 kJ). Total heat normalized to the battery nominal energy capacity was also calculated and ranked as: LTO 18650 ≈ LFP 26650 ≈ LFP 18650 > NMC 18650 MH1 ≈ NMC 18650 HG2. The test and analysis method developed can be extended to other types of batteries with a cylindrical shape. Results from this work provide insights to the thermal safety of Li-ion batteries and can help enhance battery thermal design and management.

      6. Clindamycin protects nonhuman primates against inhalational anthrax but does not enhance reduction of circulating toxin levels when combined with ciprofloxacinexternal icon
        Vietri NJ, Tobery SA, Chabot DJ, Ingavale S, Somerville BC, Miller JA, Schellhase CW, Twenhafel NA, Fetterer DP, Cote CK, Klimko CP, Boyer AE, Woolfitt AR, Barr JR, Wright ME, Friedlander AM.
        J Infect Dis. 2020 Jul 22.
        BACKGROUND: Inhalational anthrax is rare and clinical experience limited. Expert guidelines recommend treatment with combination antibiotics including protein synthesis-inhibitors to decrease toxin production and increase survival, although evidence is lacking. METHODS: Rhesus macaques exposed to an aerosol of Bacillus anthracis spores were treated with ciprofloxacin, clindamycin, or ciprofloxacin + clindamycin after becoming bacteremic. Circulating anthrax lethal factor and protective antigen were quantitated pretreatment and 1.5 and 12 hours after beginning antibiotics. RESULTS: In the clindamycin group, 8 of 11 (73%) survived demonstrating its efficacy for the first time in inhalational anthrax, compared to 9 of 9 (100%) with ciprofloxacin, and 8 of 11 (73%) with ciprofloxacin + clindamycin. These differences were not statistically significant. There were no significant differences between groups in lethal factor or protective antigen levels from pretreatment to 12 hours after starting antibiotics. Animals that died after clindamycin had a greater incidence of meningitis compared to those given ciprofloxacin or ciprofloxacin + clindamycin, but numbers of animals were very low and no definitive conclusion could be reached. CONCLUSION: Treatment of inhalational anthrax with clindamycin was as effective as ciprofloxacin in the nonhuman primate. Addition of clindamycin to ciprofloxacin did not enhance reduction of circulating toxin levels.

      7. Toxicity evaluation following pulmonary exposure to an as-manufactured dispersed boron nitride nanotube (BNNT) material in vivoexternal icon
        Xin X, Barger M, Roach KA, Bowers L, Stefaniak AB, Kodali V, Glassford E, Dunn KL, Dunn KH, Wolfarth M, Friend S, Leonard SS, Kashon M, Porter DW, Erdely A, Roberts JR.
        NanoImpact. 2020 ;19.
        Boron nitride nanotubes (BNNT) are multi-walled nanotubes composed of hexagonal B[sbnd]N bonds and possess many unique physical and chemical properties, creating a rapidly expanding market for this newly emerging nanomaterial which is still primarily in the research and development stage. The shape and high aspect ratio give rise to concern for the potential toxicity that may be associated with pulmonary exposure, especially in an occupational setting. The goal of this study was to assess lung toxicity using an in vivo time course model. The sample was manufactured to be 5 nm wide and up to 200 μm long, with ~50% purity covalently bound with hexagonal boron nitride (hBN) in the sample. Following preparation for in vivo studies, sonication of the material disrupted the longer tubes in the complex and the size distribution in dispersion medium (DM) of the structures was 13–23 nm in diameter and 0.6–1.6 μm in length. Male C57BL/6 J mice were exposed to 4 or 40 μg of BNNT or DM (vehicle control) by a single oropharyngeal aspiration. Pulmonary and systemic toxicity were investigated at 4 h, 1 d, 7 d, 1 mo and 2 mo post-exposure. Bronchoalveolar lavage (BAL) studies determined pulmonary inflammation (neutrophil influx) and cytotoxicity (lactate dehydrogenase activity) occurred at early time points and peaked at 7 d post-exposure in the high dose group. Histopathological analysis showed a minimal level of inflammatory cell infiltration in the high dose group with resolution over time and no fibrosis, and lung clearance analysis showed ~50% of the material cleared over the time course. The expression of inflammatory- and acute phase response-associated genes in the lung and liver were significantly increased by the high dose at 4 h and 1 d post-exposure. The increases in lung gene expression of Cxcl2, Ccl2, Il6, Ccl22, Ccl11, and Spp1 were significant up to 2 mo but decreased with time. The low dose exposure did not result in significant changes in any toxicological parameters measured. In summary, the BNNT-hBN sample used in this study caused acute pulmonary inflammation and injury at the higher dose, which peaked by 7 d post-exposure and showed resolution over time. Further studies are needed to determine if physicochemical properties and purity will impact the toxicity profile of BNNT and to investigate the underlying mechanisms of BNNT toxicity.

      8. Development of dried blood spot quality control materials for adenosine deaminase severe combined immunodeficiency and an LC-MS/MS method for their characterizationexternal icon
        Young B, Hendricks J, Foreman D, Pickens CA, Hovell C, De Jesus VR, Haynes C, Petritis K.
        Clinical Mass Spectrometry. 2020 ;17:4-11.
        Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is an autosomal recessive disorder in which a lack of ADA enzyme prevents the maturation of T- and B-cells; early intervention is crucial for restoring immune function in affected neonates. ADA is responsible for purine metabolism and—in its absence—adenosine, deoxyadenosine, and S-adenosylhomocysteine build up and can be detected in the blood. Preparing dried blood spot (DBS) quality control (QC) materials for these analytes is challenging because enrichments are quickly metabolized by the endogenous ADA in normal donor blood. Adding an inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), has been previously reported to minimize enzyme activity, although this adds additional cost and complexity. We describe an alternative method using unnatural L-enantiomer nucleosides (L-adenosine and L-2′-deoxyadenosine) which eliminates the need for enzyme inhibition. We also present a novel method for characterization of the materials using liquid chromatography mass spectrometry to quantify the analytes of interest.

    • Maternal and Child Health
      1. OBJECTIVE: To evaluate the association between neonatal intensive care unit (NICU) admission and breastfeeding practices, infant supine sleep positioning, and postnatal smoking among mothers of late preterm infants. STUDY DESIGN: Data from 36 states using the 2000-2013 Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed. Chi-square tests and 95% confidence intervals (CI) assessed infant and maternal characteristics and recommended care practices for late preterm infants based on NICU admission after birth. Adjusted prevalence ratios (APR) for BF initiation and continuation at 10 weeks, supine sleep position, and postnatal smoking were estimated using multivariable logistic regression models, controlling for infant and maternal characteristics. Analyses were weighted and standard errors accounted for the complex survey design. RESULTS: Our sample included 62,494 late preterm infants, representing a weighted population of 1,441,451 late preterm infants. In the adjusted analysis, mothers of late preterm infants admitted to a NICU were more likely to initiate BF (APR 1.07; 95% CI 1.05-1.09) and place their infants in supine sleep position (1.04; 95% CI 1.01-1.06) than mothers of late preterm infants not admitted to a NICU. There was no significant difference between groups for BF continuation or postnatal smoking. CONCLUSIONS: Mothers of late preterm infants admitted to a NICU were more likely to initiate BF and practice supine sleep position than mothers of late preterm infants not admitted to a NICU. Future work should seek to identify the drivers of these differences to develop effective strategies to engage mothers in these health promoting infant care practices.

      2. A qualitative evaluation of parenting to support early development among Spanish-speaking Legacy for Children participantsexternal icon
        Kotzky K, Robinson LR, Stanhope KK, Rojo AL, Beasley LO, Morris AS, Silovsky JF, Esparza I.
        Journal of Child and Family Studies. 2020 .
        Legacy for Children™ is a group-based parenting intervention that has been culturally adapted for Spanish-speaking mothers (Legacy Spanish). In the current study, we used qualitative methods to examine how Legacy Spanish informed parenting knowledge and practices related to early development. Fourteen low-income Spanish-speaking Latina mothers of children aged 21–31 months participated in focus groups that explored their experience in Legacy Spanish. A template analysis procedure was used to analyze focus group transcripts and identify themes. We identified five primary themes and two secondary themes. Mothers described gaining new knowledge about parenting and child development from Legacy Spanish and attributed positive changes in their parenting and self-efficacy to the program. Reported changes included use of more sensitive behavioral management strategies, increased maternal investment of time and energy, and improved mother-child communication. Mothers also attributed changes in their child’s cognitive and socioemotional development to Legacy Spanish, perceived long-term benefits of program participation, and shared lessons learned from Legacy Spanish with their social network. Additionally, mothers noted that Legacy Spanish provided a unique opportunity for one-to-one time with their child. To provide additional context for the focus group data, we present scores on an observational measure of parent-child interactions. Mean scores in the Affection, Responsiveness, and Teaching domains, which measure behaviors discussed in the focus groups, fell in the average score range. Together, these findings demonstrate that a culturally adapted parenting intervention has the potential to support nurturing parent-child relationships among low-income Spanish-speaking Latino families.

    • Occupational Safety and Health
      1. The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in flux core arc welding fume at three facilities. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Sixty-seven worker-days were monitored for either total or respirable Mn. The samples were analyzed using an experimental method to separate four Mn fractions based on chemical solubility: soluble Mn in a mild ammonium acetate solution; Mn0,2+ in 25% acetic acid; Mn3+,4+ in hydroxylamine hydrochloride in 25% acetic acid; and insoluble Mn fractions in hydrochloric/nitric acid. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.51 to 43; 2.9 to 850; 1.7 to 620; and 0.56 to 331 µg·m-3, for the different Mn fractions, respectively. The summation of all the total particulate Mn fractions yielded results that ranged from 16 to 1,530 µg m-3. The ranges of respirable size Mn TWA concentrations were 0.27 to 75 for soluble Mn; 1.6 to 690 for Mn0,2+; 1.3 to 740 for Mn3+,4+; 0.52 to 570 for insoluble Mn; and 3.8 to 1,800 µg·m-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn(sum) were 56 (GSD = 4.0), 380 (GSD = 2.7), and 176 (GSD = 3.3) µg·m-3 for the shipyard, structural steel and custom parts facilities. Although most of the workers’ exposures measured were below the NIOSH Recommended Exposure Limit for Mn (1,000 µg·m-3), 44 welders’ exposures exceeded the ACGIH Threshold Limit Values® for total Mn (100 µg·m-3) and 46 exceeded the new respirable Mn TLV (20 µg·m-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding in enclosed or confined spaces.

    • Parasitic Diseases
      1. One-step PCR: A novel protocol for determination of pfhrp2 deletion status in Plasmodium falciparumexternal icon
        Jones S, Subramaniam G, Plucinski MM, Patel D, Padilla J, Aidoo M, Talundzic E.
        PLoS One. 2020 ;15(7):e0236369.
        Histidine-rich protein 2 (HRP2) detecting rapid diagnostic tests (RDTs) have played an important role in enabling prompt malaria diagnosis in remote locations. However, emergence of pfhrp2 deleted parasites is threatening the efficacy of RDTs, and the World Health Organization (WHO) has highlighted surveillance of these deletions as a priority. Nested PCR is used to confirm pfhrp2 deletion but is costly and laborious. Due to spurious amplification of paralogue pfhrp3, the identity of nested exon 1 PCR product must be confirmed by sequencing. Here we describe a new one-step PCR method for detection of pfhrp2. To determine sensitivity and specificity, all PCRs were performed in triplicate. Using photo-induced electron transfer (PET) PCR detecting 18srRNA as true positive, one-step had comparable sensitivity of 95.0% (88.7-98.4%) to nested exon 1, 99.0% (94.6-99.9%) and nested exon 2, 98.0% (93.0-99.8%), and comparable specificity 93.8% (69.8-99.8%) to nested exon 1 100.0% (79.4-100.0%) and nested exon 2, 100.0% (74.4-100.0%). Sequencing revealed that one step PCR does not amplify pfhrp3. Logistic regression models applied to measure the 95% level of detection of the one-step PCR in clinical isolates provided estimates of 133p/μL (95% confidence interval (CI): 3-793p/μL) for whole blood (WB) samples and 385p/μL (95% CI: 31-2133 p/μL) for dried blood spots (DBSs). When considering protocol attributes, the one-step PCR is less expensive, faster and more suitable for high throughput. In summary, we have developed a more accurate PCR method that may be ideal for the application of the WHO protocol for investigating pfhrp2 deletions in symptomatic individuals presenting to health care facilities.

    • Reproductive Health
      1. Ovarian hyperstimulation syndrome after assisted reproductive technologies: trends, predictors, and pregnancy outcomesexternal icon
        Schirmer DA, Kulkarni AD, Zhang Y, Kawwass JF, Boulet SL, Kissin DM.
        Fertil Steril. 2020 Jul 14.
        OBJECTIVES: To assess trends, predictors, and perinatal outcomes of ovarian hyperstimulation syndrome (OHSS) associated with in vitro fertilization (IVF) cycles in the United States. DESIGN: Retrospective cohort study using National Assisted Reproductive Technology Surveillance System (NASS) data. SETTING: Not applicable. PATIENT(S): Fresh autologous and embryo-banking cycles performed from 2000 to 2015. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): OHSS, first-trimester loss, second-trimester loss, stillbirth, low birth weight, and preterm delivery. RESULT(S): The proportion of IVF cycles complicated by OHSS increased from 10.0 to 14.3 cases per 1,000 from 2000 to 2006, and decreased to 5.3 per 1,000 from 2006 to 2015. The risk of OHSS was highest for cycles with more than 30 oocytes retrieved (adjusted risk ratio [aRR] 3.85). OHSS was associated with a diagnosis of ovulatory disorder (aRR 2.61), tubal factor (aRR 1.14), uterine factor (aRR 1.17) and cycles resulting in pregnancy (aRR 3.12). In singleton pregnancies, OHSS was associated with increased risk of low birth weight (aRR 1.29) and preterm delivery (aRR 1.32). In twin pregnancies, OHSS was associated with an increased risk of second-trimester loss (aRR 1.81), low birth weight (aRR 1.06), and preterm delivery (aRR 1.16). CONCLUSION(S): Modifiable predictive factors for OHSS include number of oocytes retrieved, pregnancy following fresh embryo transfer, and the type of medication used for pituitary suppression during controlled ovarian hyperstimulation. Patients affected by OHSS had a higher risk of preterm delivery and low birth weight. Clinicians should take measures to reduce the risk of OHSS whenever possible.

    • Substance Use and Abuse
      1. Deaths and years of potential life lost from excessive alcohol use - United States, 2011-2015external icon
        Esser MB, Sherk A, Liu Y, Naimi TS, Stockwell T, Stahre M, Kanny D, Landen M, Saitz R, Brewer RD.
        MMWR Morb Mortal Wkly Rep. 2020 Jul 31;69(30):981-987.
        Excessive alcohol use is a leading cause of preventable death in the United States (1) and costs associated with it, such as those from losses in workplace productivity, health care expenditures, and criminal justice, were $249 billion in 2010 (2). CDC used the Alcohol-Related Disease Impact (ARDI) application* to estimate national and state average annual alcohol-attributable deaths and years of potential life lost (YPLL) during 2011-2015, including deaths from one's own excessive drinking (e.g., liver disease) and from others' drinking (e.g., passengers killed in alcohol-related motor vehicle crashes). This study found an average of 93,296 alcohol-attributable deaths (255 deaths per day) and 2.7 million YPLL (29 years of life lost per death, on average) in the United States each year. Of all alcohol-attributable deaths, 51,078 (54.7%) were caused by chronic conditions, and 52,361 (56.0%) involved adults aged 35-64 years. Age-adjusted alcohol-attributable deaths per 100,000 population ranged from 20.3 in New Jersey and New York to 52.3 in New Mexico. YPLL per 100,000 population ranged from 613.8 in New York to 1,651.7 in New Mexico. Implementation of effective strategies for preventing excessive drinking, including those recommended by the Community Preventive Services Task Force (e.g., increasing alcohol taxes and regulating the number and concentration of alcohol outlets), could reduce alcohol-attributable deaths and YPLL.(†).

      2. Current marijuana use among women of reproductive ageexternal icon
        Ewing AC, Schauer GL, Grant-Lenzy AM, Njai R, Coy KC, Ko JY.
        Drug Alcohol Depend. 2020 Jul 2;214:108161.
        BACKGROUND: The objective of this study was to estimate the prevalence of current (past 30 days) marijuana use and its associations with demographic, other substance use, chronic disease, physical health and mental health measures among women of reproductive age (18-44 years) in 12 US states. METHODS: This analysis used 2016 Behavioral Risk Factor Surveillance System (BRFSS) data from 16,556 women of reproductive age in 12 US states. Women self-reported current marijuana use and covariates. Weighted χ(2) statistics and adjusted prevalence ratios (aPR) were calculated accounting for the complex survey design. RESULTS: Among women of reproductive age, 9.9 % reported current marijuana use. Current cigarette use (aPR: 2.0, 95 % CI: 1.6, 2.6), current e-cigarette use (aPR: 1.9, 95 % CI: 1.4, 2.6), binge drinking (aPR: 2.6, 95 % CI: 1.9, 3.6), ever having received a depression diagnosis (aPR: 1.6, 95 % CI: 1.2, 2.1), and ≥14 days of poor mental health in the past 30 days (aPR: 1.8, 95 % CI: 1.3, 2.4) were all associated with higher adjusted prevalence of current marijuana use. Reporting ≥14 days of poor physical health within the last 30 was associated with a 40 % lower adjusted prevalence of current marijuana use (aPR: 0.6, 95 % CI: 0.4, 0.8). CONCLUSION: Current marijuana use among women of reproductive age was associated with other substance use, poor mental health, and depression. As state laws concerning marijuana use continue to change, it is important to monitor usage patterns and to assess associated health risks in this population.

      3. BACKGROUND: Expanding access to treatment and recovery services is key to reducing substance use-related harms. Fundamental to expanding such services is better understanding the populations identifying themselves as in recovery. This study uses nationally representative data to estimate prevalence and correlates of recovery in the U.S. METHODS: Data are from the 43,026 adults (aged 18 or older) participating in the 2018 National Survey on Drug Use and Health. Based on self-reported data, we estimate prevalence of ever having a substance use problem, the percentage in recovery among those with a substance use problem, and a multivariable logistic regression model to explore associations of recovery status with demographic characteristics and lifetime mental health problems. Among adults reporting a substance use problem, we compare prevalence of substance use by recovery status, followed by a multivariable model examining associations between each substance used and being in recovery. RESULTS: More than 1 in 10 adults (27.5 million) in the U.S. reported ever having a substance use problem, and, among those with a problem, nearly 75 % (20.5 million) reported being in recovery. Reporting lower prevalence of using substances in the past year and having received treatment for their substance use problem were associated with being in recovery. Ever having a mental health problem was highly prevalent among those reporting a substance use problem. CONCLUSIONS: The provision and expansion of substance use treatment services continues to be important to reduce harms related to substance use, especially for those with both substance use and mental health disorders.

    • Zoonotic and Vectorborne Diseases
      1. Homecare for sick family members while waiting for medical help during the 2014-2015 Ebola outbreak in Sierra Leone: a mixed methods studyexternal icon
        Schmidt-Hellerau K, Winters M, Lyons P, Leigh B, Jalloh MB, Sengeh P, Sawaneh AB, Zeebari Z, Salazar M, Jalloh MF, Nordenstedt H.
        BMJ Glob Health. 2020 Jul;5(7).
        INTRODUCTION: Caring for an Ebola patient is a known risk factor for disease transmission. In Sierra Leone during the outbreak in 2014/2015, isolation of patients in specialised facilities was not always immediately available and caring for a relative at home was sometimes the only alternative. This study sought to assess population-level protective caregiving intentions, to understand how families cared for their sick and to explore perceived barriers and facilitators influencing caregiving behaviours. METHODS: Data from a nationwide household survey conducted in December 2014 were used to assess intended protective behaviours if caring for a family member with suspected Ebola. Their association with socio-demographic variables, Ebola-specific knowledge and risk perception was analysed using multilevel logistic regression. To put the results into context, semi-structured interviews with caregivers were conducted in Freetown. RESULTS: Ebola-specific knowledge was positively associated with the intention to avoid touching a sick person and their bodily fluids (adjusted OR (AOR) 1.29; 95% CI 1.01 to 1.54) and the intention to take multiple protective measures (AOR 1.38; 95% CI 1.16 to 1.63). Compared with residing in the mostly urban Western Area, respondents from the initial epicentre of the outbreak (Eastern Province) had increased odds to avoid touching a sick person or their body fluids (AOR 4.74; 95% CI 2.55 to 8.81) and to take more than one protective measure (AOR 2.94; 95% CI 1.37 to 6.34). However, interviews revealed that caregivers, who were mostly aware of the risk of transmission and general protective measures, felt constrained by different contextual factors. Withholding care was not seen as an option and there was a perceived lack of practical advice. CONCLUSIONS: Ebola outbreak responses need to take the sociocultural reality of caregiving and the availability of resources into account, offering adapted and acceptable practical advice. The necessity to care for a loved one when no alternatives exist should not be underestimated.

Back to Top

CDC Science Clips Production Staff

  • Takudzwa Sayi, Editor
  • Gail Bang, MLIS, Librarian
  • Kathy Tucker, Librarian
  • William (Bill) Thomas, MLIS, Librarian
  • Jarvis Sims, MIT, MLIS, Librarian


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

Page last reviewed: August 11, 2020