title: Preventing Respiratory Viruses in the Neonatal ICU

text: BACKGROUND: Infants in the neonatal ICU can acquire respiratory viruses from ill healthcare personnel (HCP), visitors, or other infants. We describe the epidemiology of respiratory viruses and infection prevention and control interventions aimed to reduce acquisition and transmission of respiratory viruses in our NICU. METHODS: From May 2012 to December 2016, we tracked respiratory viruses detected by a multiplex reverse-transcriptase (RT)-PCR assay (FilmArray, Biofire, Inc.) in our 58-bed level IV NICU (~1,000 annual admissions). Testing was ordered by treating clinicians for symptomatic infants. Infants with positive RT-PCR tests generally remained on contact/ droplet precautions throughout their NICU stay. HCP were instructed not to work sick and report to Workforce Health and Safety if they became ill at work. Ill visitors were not permitted in the NICU, as enforced by written educational materials and signage, but formal screening was not performed. Starting in January 2015, asymptomatic infants exposed to RT-PCR-positive index cases were screened by RT-PCR, put on contact/ droplet precautions for the incubation period (IP) of the index case’s virus, and screened again at IP end. Starting in December 2015, visitors <12 years old were banned year-round. We assessed dyad transmission events (2 infants), clusters (3 infants), and outbreaks (>3 infants); all were defined as detecting geographically related cases within the relevant IP. We determined screened infants who had positive RT-PCR tests. RESULTS: During the 56 month observation period, 79 infants had 83 viruses detected (~1.8% of admissions). Rhino/ enterovirus (RV/EV) were most common (n = 59) and caused 1 outbreak of 7 infants, 4 clusters, and 5 dyad transmissions. Adenovirus caused 1 outbreak of 5 infants. Two dyad transmissions occurred for parainfluenza. Sporadic cases of RSV (n = 5), coronavirus (n = 5), and influenza (n = 2) occurred. Ill household contacts were identified for 10 infants. No HCPs were identified with respiratory illnesses. Since January 2015, 8 screened infants had positive RT-PCR tests. Since December 2015, only 1 transmission dyad (RV/EV) occurred. CONCLUSION: Preliminary data suggest that our interventions have reduced the burden of respiratory viruses in the NICU. DISCLOSURES: All authors: No reported disclosures.


title: Impact of Timing of Diagnosis of Respiratory Syncytial Virus (RSV) Disease on Hospital Length of Stay (LOS) in Adults: Final Analysis from a Retrospective Chart Review Study

text: BACKGROUND: Despite growing clinical awareness of RSV disease in at-risk adult subpopulations, significant gaps remain in knowledge, especially around diagnosis. This analysis aimed to understand the impact of timing of diagnosis on hospital LOS. METHODS: A retrospective review of patient charts was conducted. Data for adults ≥18 years with confirmed RSV (Oct 2014–Oct 2016; USA) were collected. Each physician (n = 132) submitted up to 3 randomly selected patient cases via an online survey. RESULTS: This study comprised 379 patients, collected in 4 groups (Table). >80% of patients received an RT-PCR test; rapid antigen tests were uncommon (≤10%) with an RT-PCR test also performed in 45% of these. Early RSV diagnosis and less severe disease were associated with a shorter mean LOS (Figure 1and2). Patients diagnosed >24h post-admission had a longer mean [SD] LOS (9.8 [8.6] days; n = 29) than patients diagnosed <12h post-admission (6.2 [3.9] days; n = 67; P = 0.006), and patients diagnosed 12–24h post-admission (7.4 [4.2] days; n = 56; P = 0.038). LOS was higher (P = 0.005) in patients diagnosed in the intensive care unit (9.4 days) than the emergency room or hospital ward (both 6.8 days). CONCLUSION: RSV disease in adults was typically diagnosed by PCR. Delayed diagnosis and greater RSV disease severity are associated with longer LOS, but results need to be confirmed by prospective trials. Introduction of diagnostic testing protocols may lead to earlier identification of patients in need of supportive care and reduce mean LOS. DISCLOSURES: E. Walsh, Janssen Pharmaceuticals: Scientific Advisor, Consulting fee; I. Sander, Janssen Pharmaceuticals: Independent Contractor, Licensing agreement or royalty; R. Stolper, Janssen Pharmaceuticals: Independent Contractor, Licensing agreement or royalty; J. Zakar, Janssen: Independent Contractor, Licensing agreement or royalty; G. De La Rosa, Janssen Pharmaceuticals: Employee, Salary; V. Wyffels, Janssen Pharmaceuticals: Employee, Salary; D. Myers, Janssen Pharmaceuticals: Employee, Salary; R. Fleischhackl, Janssen Pharmaceuticals: Employee, Salary


title: Impact of Asymptomatic Bacteriuria (ASBU) Overtreatment During a Controlled Trial of Antimicrobial Stewardship (AS)

text: BACKGROUND: What are the clinical profiles, outcomes, and antimicrobial costs attributed to patients admitted with presumed urinary tract infection (UTI) but deemed to have “no infection” (NI) by infectious diseases (ID) MD reviewers? METHODS: We performed a review of a subset of patients entered into a randomized, controlled, AS trial that began 7.1.2015. Patients with UTI and 3 other ID syndromes were evaluated by ID MDs within 12–24 hours of receiving empirical antimicrobials. The ID MD designated patients as having NI when a patient lacked compatible symptoms, signs, and laboratory evidence to support a diagnosis of UTI. Patients with NI were tracked but not included in the study intervention to identify AS opportunities. RESULTS: Over 21 months 6,402 antimicrobial starts were entered into the AS study; 2,196 (34.3%) were UTI. Of these 564 (25.7%) were designated NI. The initial admission of 104 patients designated NI are the subject of this report. Four had possibly clinically significant UTI and were excluded. Of the remaining 100 the average age was 83.6 years, 80% were female and 50% were admitted with acute or chronic altered mental status (dementia, seizure, or stroke); Sixty-five % of urine cultures were positive. The mean Systemic Inflammatory Response Syndrome (SIRS) score was 0.6; the mean quick Sequential Organ Failure Assessment Score (qSOFA) score was 0.9. A mean 3.7 days of antimicrobials were prescribed during the admission; 3.2 additional days at discharge. Of the 100 NI patients followed (up to 21 months following study entry) 34% have died (all-cause), 49% had a subsequent episode of bacteriuria; the mean number of re-admissions per patient was 2.4(range 0–14) and 9% developed C. difficile infection (CDI). CONCLUSION: AS identified a subset of patients treated for UTI but determined by ID MDs as NI, as an elderly, predominantly female cohort, with a high incidence of new or pre-existing neurological conditions, subsequent bacteriuria, re-admission, and short -term mortality. Low SIRS and qSOFA scores in these patients supported a lack of clinically significant infection. AS programs should focus on early efforts to identify ASBU. Preservation of antimicrobial resources, antibiotic cost savings (estimated over 3 years to be $ 450,000), and avoidance of CDI are among the likely benefits. DISCLOSURES: All authors: No reported disclosures.


title: Use of Unannounced “Mystery Patient Drills” to Assess Hospital Emergency Department Preparedness for Communicable Diseases of Public Health Concern in New York City, 2016

text: BACKGROUND: Recent infectious disease epidemics have highlighted the importance of rapid recognition and isolation of patients with severe infectious diseases. In response, the New York City Department of Health and Mental Hygiene carried out a series of unannounced “Mystery Patient Drills” to assess Emergency Departments (ED) ability to identify and safely respond to patients with communicable diseases of public health concern. METHODS: All 911-receiving hospitals participating in the NYC Hospital Preparedness Program were recruited to participate. Scenarios utilized an actor presenting to an ED describing symptoms and history consistent with measles or MERS-CoV. An exercise evaluation guide captured performance measures to analyze 1) compliance with key infection control measures; 2) association between screening interventions (e.g., travel history) and implementation of infection control measures; 3) times from patient entry to triage, donning a mask, and placement into isolation. Post-drill report narratives were reviewed to identify additional strengths and challenges. RESULTS: Among 50 eligible hospitals, 49 participated in 2 drills (N = 98) during December 2015–May 2016. Three pilot drills were excluded from the analysis. The patient was masked and isolated in 78% of drills; 61% of hospitals completed this process in both drills. Masking and isolation was observed in a higher proportion of drills when travel history was obtained, compared with drills when travel history was not obtained (88% vs. 21%; P < 0.0001). The median time from patient entry to masking was 1 minute and 9 minutes to placement into isolation. Overall, 36% of staff practiced hand hygiene and 77% entered the isolation room wearing Personal Protective Equipment. Identified best practices include the use of triage questionnaires to identify high-risk patients and algorithms to guide masking and isolation procedures. CONCLUSION: ED staff’s ability to identify potentially infectious patients and implement recommended control measures varied. Drill findings were used to inform hospital improvement planning and will guide citywide efforts to improve healthcare system readiness for communicable diseases through addressing identified gaps and supporting implementation of best practice recommendations. DISCLOSURES: All authors: No reported disclosures.


title: Pharmacokinetics (PK) of Eravacycline in Subjects with Renal or Hepatic Impairment Compared with Healthy Subjects

text: BACKGROUND: Eravacycline (ERV) is a fluorocycline being developed for the treatment of serious infections, including those caused by multidrug-resistant pathogens. The PK of ERV in subjects with end stage renal disease (ESRD) or hepatic impairment (HI) were investigated. METHODS: Two multi-center studies were completed; one in subjects with ESRD and one in subjects with mild, moderate or severe HI based upon Child-Pugh scoring. Each included a cohort of healthy subjects (HS) matched by gender, age and BMI. A single IV dose of 1.5 mg/kg ERV was administered. PK parameters were calculated using standard non-compartmental methods and within study comparisons of PK for the ESRD and HI subjects were made with HS. RESULTS: The following comparative AUC(inf) and C(max) values for ERV were observed: CONCLUSION: Following a single IV dose of ERV, the systemic exposures in subjects with ESRD and mild or moderate hepatic impairment were similar to those observed in HS. The 2-fold increase in AUC(inf) observed in subjects with severe HI did not result in increased adverse events. Therefore, no dose adjustment should be required when ERV is given to subjects with either renal or hepatic impairment. Funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No HHSO100201200002C. DISCLOSURES: P. Horn, Tetraphase Pharmaceuticals: Employee, Salary; S. Redican, Tetraphase Pharmaceuticals: Employee, Salary; M. Olesky, Tetraphase Pharmaceuticals: Employee, Salary.


title: Incidence and Outcomes of Cytomegalovirus (CMV) Infection among Hematopoietic Stem Cell Transplant (HSCT) Recipients

text: BACKGROUND: Outcomes of CMV infection among HSCT recipients likely vary by patient population and treatment modality. However, data on these outcomes have been reported by relatively few centers. METHODS: This was a retrospective cohort study of allogenic HSCT recipients age ≥18 years at Oregon Health and Science University Hospital (OHSU) between 2010–2015. During the study period, OHSU standard practice was to preemptively treat CMV-viremic patients (quantitative PCR assay ≥ 200 copies/mL or consecutive PCR assays <200 copies/mL) with first-line valganciclovir or ganciclovir and second line foscarnet if there were contraindications to first-line agents. Study data were collected from an electronic health record repository and local Center for International Blood and Marrow Transplant Research (CIBMTR) database. Primary outcomes were clinical manifestations of CMV disease, death, and cause of death within 1 year of transplant. RESULTS: Among 409 HSCT recipients, mean age was 53 (standard deviation: 13) years and 41% were female. 192 (47%) patients had CMV viremia and the median (interquartile range) time to CMV reactivation was 42 (31–53) days (Figure 1). Patients with acute myeloid leukemia were significantly less likely to have CMV reactivation (39% vs. 55%, P < 0.01) and those with myelodysplastic syndromes had a non-significantly higher risk (24% vs. 17%, P = 0.06). 4 (1%) patients had a documented clinical manifestation of CMV disease (3 pneumonia and 1 pancreatitis). One-year mortality was 36% (148/409); there was no significant difference in mortality (37.5% vs. 35.0%, P = 0.60) or cause of death (P = 0.30) between patients with and without CMV reactivation (Figure 2). The most frequent causes of death among CMV viremic patients were recurrent/persistent disease (35%), acute graft vs. host disease (GVHD) (22%), infection (19%), and chronic GVHD (11%). CMV was documented as the primary cause of death for 2 patients. CONCLUSION: Nearly half of HSCT recipients had CMV reactivation and more than a third died within one year of transplant. However, incidence of CMV disease was rare and reactivation was not associated with increased mortality. Further study is needed to identify risk factors for CMV reactivation, infection and mortality in this population. DISCLOSURES: J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. L. Strasfeld, Merck: Independent Contractor, Salary. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant


title: Congenital Zika Syndrome (CZS) Phenotype Seen in Older Children

text: BACKGROUND: Zika virus (ZIKV) has been documented in Africa since 1947 and Asia since 1969. However, the association of congenital ZIKV infection with microcephaly and serious brain defects was not recognized until a large ZIKV outbreak began in Brazil in 2015. A similar association was retrospectively identified in a 2013–2014 French Polynesian outbreak. In this report, we describe two children, ages 6 (Case 1) and 7 years (Case 2), who display a phenotype consistent with CZS. In both cases, the mothers were residing in Cambodia during their pregnancies (2011 and 2010, respectively); Cambodia has reported ZIKV infections since 2007. METHODS: We review epidemiologic, clinical and laboratory data, and the neurodevelopmental status of these two children. RESULTS: Both mothers reported low-grade fever and erythematous rash during their early second trimesters. The infants were born with severe microcephaly (>3 SD below the mean) with central hypotonia and peripheral spasticity (Figure 1). Both had normal karyotypes, negative TORCH results, and neuroimaging suggestive of CZS with subcortical calcifications, polymicrogyria, abnormal corpus callosum, ex-vacuo ventriculomegaly, and reduced white matter (Figure 2). Case 1 had overlapping cranial sutures and redundant scalp (Figure 3). In 2016, serology immunofluorescence assay, immunoglobulin G, and plaque reduction neutralization test for the mother of Case 1 was positive for Zika. Serology for the mother of Case 2 is pending. Presently, both children have severe developmental delays; neither can sit or hold up their head, and both are nonverbal. Case 1 has bilateral hip contractures and hearing loss. Both are visually impaired and require gastrostomy-tube feedings. Case 2 is tracheostomy dependent. CONCLUSION: Given the maternal febrile rash illness, residence in a ZIKV region during pregnancy, infant features consistent with CZS, and the lack of other identified etiology, CZS should be considered as a possible diagnosis in these cases. It suggests that CZS may have occurred prior to the Brazil and French Polynesia outbreaks. Investigations into neurodevelopmental status of older children with possible CZS can provide insights into the possible long-term effects of CZS. DISCLOSURES: All authors: No reported disclosures.


title: A Cross-Sectional Surveillance Study of Acute Respiratory Illness (ARI) in Pregnant Women

text: BACKGROUND: Among pregnant women, pneumonia is the third-leading cause of death and the most common non-obstetric infection resulting in death. Pregnant women who become infected with influenza have hospitalization rates comparable to non-pregnant women with high-risk medical conditions. Other than influenza, little is known about the consequences of viral-related ARI on the pregnant woman and the fetus. Our objective was to determine the respiratory viruses causing ARI and their clinical outcomes during pregnancy. METHODS: Pregnant women in their second and third trimester were enrolled prospectively at a Houston clinic between October 1, 2015 and April 30, 2016 during their regular prenatal visits. Pregnant women were enrolled if they reported having symptoms of ARI or were healthy within the preceding two weeks. Nasal-pharyngeal secretions were evaluated for respiratory viruses by real time-PCR. Clinical outcomes and complications of illness were obtained at enrollment and two weeks after the initial visit. RESULTS: A total of 155 pregnant women were enrolled. The average age at enrollment was 30.7 years among women with ARI and 29.7 among healthy controls. Average gestational age at enrollment was 26.0 weeks among women with ARI and 26.3 among healthy controls. Among the 91 healthy controls, 10 (11%) tested positive for a respiratory virus, with rhinovirus (n = 6) being the most common of the viruses detected. On the other hand, of the 81 cases of ARI, 51 (63%) tested positive for a virus. The most frequently detected viruses were rhinovirus (n = 22), coronavirus (n = 14), and respiratory syncytial virus (n = 8). Twelve patients reported fever during the course of their ARI. Seventeen ARI patients reported at least one symptom of lower respiratory tract illness (LRTI). Of those patients with LRTI, two reported decreased fetal heart rate and one was hospitalized for her illness. CONCLUSION: Respiratory viruses were frequently detected in pregnant women with ARI. One-third of pregnant women with viral ARI had evidence of LRTI. Hospitalization and non-reassuring fetal heart tones were among the complications reported by pregnant women with LRTI. Viral ARI during pregnancy appears common and is associated with significant morbidity. DISCLOSURES: All authors: No reported disclosures.


title: Antiviral Activity of Peptide Nucleic Acid against Human Parechovirus Type 3

text: BACKGROUND: Human parechovirus (HPeV) type 3 (HPeV3) is an emerging pathogen causing sepsis and meningoencephalitis in neonates and young infants. However, specific treatment for HPeV3 infection is currently unavailable. The application of antisense technology, such as peptide nucleic acids (PNAs), to viral infection has opened a new era of therapeutics. The aim of this study is to develop PNAs inhibiting HPeV3 gene expression in an in vitro model. METHODS: We designed four PNAs that target domains I, J (base and head of domain J structure), and K of an internal ribosomal entry site (IRES) region within the 5’ untranslated region of HPeV3. The IRES region is needed for the cap-independent translation. The PNAs were conjugated to cell-penetrating peptide (RXR)(4)XB (R = L-arginine, X = 6-aminohexanoic acid, B = β-alanine). LLC-MK2 cells were treated with 0.1–10µM of each PNA or water-containing growth medium for 4h. The cells were then infected with HPeV3 at the multiplicity of infection (MOI) of 10 for 1h. The infected cells were incubated for 7 days at 37ºC in 5% CO(2). Extracellular levels of HPeV3 RNA were measured by real-time PCR on days 0 and 7. RESULTS: Without any treatment, an extracellular level of HPeV3 RNA increased to 8.2 × 10(6) copies/µL on day 7. When the cells were treated with 10µM of PNA targeting the domain I of IRES, an extracellular level of HPeV3 RNA was suppressed to 4.7 × 10(4) copies/µL (−99%) on day 7. Using the same PNA with lower concentrations, 1 µM and 0.1 µM of the PNA suppressed 24% and 0% of extracellular levels of HPeV3 RNA, respectively, which demonstrated the effect is dose-dependent. In contrast, 10µM of PNAs targeting domain J (base), J (head), and K suppressed 94%, 92%, and 20% of extracellular levels of HPeV3 RNA, respectively, compared with control. CONCLUSION: The PNA-(RXR)(4)XB targeting the domain I of IRES suppressed extracellular levels of HPeV3 RNA in an in vitro model in a dose-dependent manner. Thus, PNA treatment may be a therapeutic candidate for HPeV3-infected patients. This novel therapy could target other HPeV genotypes given that the target sequence used in this study is identical to those of other clinically significant HPeVs. DISCLOSURES: All authors: No reported disclosures.


title: Le contrôle des infections au cabinet du pédiatre

text: La transmission des infections au cabinet du pédiatre est de plus en plus préoccupante. Le présent document expose les voies de transmission des infections et les principes sousjacents aux mesures actuelles pour contrôler les infections. Pour prévenir les infections, il faut bien concevoir le cabinet et adopter des politiques administratives et de triage convenables, de même que des pratiques de base pour les soins de tous les patients (p. ex., hygiène des mains, port de gants, de masques, de lunettes de protection et d’une blouse d’hôpital pour des interventions précises; nettoyage, désinfection et stérilisation convenables des surfaces et du matériel, y compris les jouets, et techniques d’asepsie en cas d’interventions effractives) et des précautions additionnelles en cas d’infections précises. Le personnel doit avoir reçu les vaccins pertinents, et les personnes infectées doivent respecter les politiques de restriction au travail.


title: Ganciclovir-resistant CMV (GCV-R CMV) Infection Leads to Poor Clinical Outcomes and Economic Burden of Ganciclovir-resistant Cytomegalovirus Infection in Lung Transplant Recipients

text: BACKGROUND: GCV-R CMV infection is an emerging cause of morbidity and mortality in lung transplant recipients. The purpose of this study was to evaluate the clinical and economic impact of GCV-R CMV infection in a high-risk population. METHODS: We performed a single-center, retrospective cohort study of lung transplant recipients with genotype confirmed GCV-R CMV and ganciclovir-sensitive (GCV-S) CMV infection, matched (1:3) by year of diagnosis. Clinical outcomes within 1 year following the onset of CMV infection and total hospital costs were assessed. RESULTS: Twenty-eight patients were included in the analysis: 7 with GCV-R CMV infection and 21 with GCV-S CMV infection. Baseline demographics (Table 1) were similar in the two groups. CMV load at diagnosis was numerically higher (282,932 I.U./mL [IQR, 43,181 IU/mL 3,368,931 I.U./mL] vs. 44,604 IU/mL [IQR, 6,314 I.U./mL 88,797 IU/mL], P = 0.10) and days to CMV infection following discontinuation of antiviral prophylaxis was numerically lower (20 [IQR, 0–137] vs. 175 [IQR, 123–190], P = 0.07) in the GCV-R CMV group. All-cause mortality (71.4% vs. 19.0%, P = 0.02) and total hospital days due to CMV infection (63 [IQR, 34–76] vs. 6 [IQR, 2–9], P < 0.01) were significantly higher in the GCV-R CMV cohort. There were no differences in allograft rejection and hospital readmission between the two groups. Total hospital costs were significantly higher amongst patients with GCV-R CMV infection ($208,924 [IQR, $114,555-$253,191] vs. $20,419 [IQR, $12,438-$27,892], P < 0.01). CONCLUSION: GCV-R CMV infection is associated with poor outcomes and considerable healthcare costs. Novel prophylaxis and treatment strategies are needed to combat CMV infection in lung transplant recipients. DISCLOSURES: T. Patel, Merck: Grant Investigator, Research grant. K. Gregg, Merck: Grant Investigator, Research grant


title: Transmission Dynamics of Respiratory Viruses in a Congregated Military Population: Prospective Cohort Study

text: BACKGROUND: Human coronaviruses (HCoVs), rhinoviruses, and non-polio enteroviruses (NPEVs) are leading causes of seasonal acute respiratory infections among children and adults, posing significant health and economic burden annually. Despite this, little is known about their epidemiological dynamics, including the role of asymptomatic shedding in transmission; the durations of virus incubation and shedding; and the effect of immune responses on risk for re-infection during the same season. We studied respiratory virus shedding in military recruits, and used mathematical models to measure pathogen-specific transmission rates and durations of incubation, shedding, and immune protection. METHODS: We tested for shedding of HCoVs, rhinoviruses, and NPEVs in nasal samples collected from 78 military recruits entering basic training and then at staggered, biweekly visits over 65 days during winter 2017. We developed a continuous-time Markov chain model for virus acquisition and clearance, and used Bayesian methods to estimate model parameters for each of HCoV-229E, HCoV-OC43, rhinoviruses, and NPEVs. RESULTS: We observed widespread transmission of HCoV-229E, rhinoviruses, and NPEVs within the first week after entry into basic training, and a subsequent phase of transmission predominantly involving HCoV-OC43 during the second month (Figure). We estimated pre-epidemic reproductive numbers ranging from 1.97 (95% credible interval: 1.49, 2.60) for HCoV-OC43 to 5.69 (3.92, 7.98) for HCoV-229E (Table). Subjects re-acquired HCoV-229E, rhinoviruses, and NPEVs despite previous exposure; for these pathogens, we estimated reversion to pre-infection susceptibility to occur, on average, 28.5 (15.8, 49.7) days, 52.2 (22.3, 151.1), and 144.7 (61.3, 812.5) days, respectively, following clearance of viral shedding. CONCLUSION: Asymptomatic shedding is a source of transmission of common respiratory viruses in the close-contact basic training environment. Protection against re-acquisition is short-lived, and may be inadequate to prevent re-infection by rhinoviruses and NPEVs within a season. Estimated durations of shedding and incubation periods provide a basis for modeling pathogen spread and informing isolation protocols. DISCLOSURES: J. Lewnard, Pfier: Grant Investigator, Research grant. E. Grigorenko, Diatherix Laboratories: Employee, Salary. D. M. Weinberger, Pfizer, Merck, Affinivax: Consultant and Grant Investigator, Consulting fee and Research grant.


title: Predictors of Clinical Respiratory Virus Testing Among Adults Hospitalized with Acute Respiratory Illness (ARI) (2015–2016)

text: BACKGROUND: Vaccine effectiveness (VE) studies require an accurate indicator of influenza infection, often obtained through research testing independent of clinical (physician-ordered) testing. Clinical testing could be used to detect influenza in these studies if factors associated with clinical testing for influenza were better understood. METHODS: Adults hospitalized with ARI at three study sites during the study period were enrolled in CDC’s 2015–16 Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study and tested for influenza by RT-PCR. Clinical testing information, presenting symptoms, and patient characteristics were collected from medical records and patient interview. Logistic regression was used to estimate odds of receiving a clinical test based on age, vaccination status, comorbidities, presentation with influenza-like illness (ILI; defined as fever and cough or sore throat) and other factors. RESULTS: Of 895 enrollees, 571 (64%) patients meeting study inclusion criteria received physician-ordered testing. Of these, 53% had a multipathogen panel, 13% had a rapid antigen test, 7% had singleplex PCR, <1% had viral culture, and 27% had multiple tests; influenza infection was detected in 55 (6%) patients. Of 150 influenza cases identified by study testing, 25 (17%) were not tested clinically. Enrollees who did not receive clinical testing were older, had longer time to admission, and were less likely to present with ILI. Immunosuppressive disorders (aOR=2.05), non-COPD lung conditions (aOR=1.68), presentation with ILI (aOR=4.03), and admission ≤2 days from symptom onset (aOR=1.89) were positively associated with receiving a clinical test (P < 0.01 for all; Figure 1). After adjusting for these factors, enrollees with influenza vaccination were 37% less likely (aOR=0.63) to receive a clinical test (P < 0.01). CONCLUSION: Patients with ARI who were clinically tested for influenza differed from those not tested. A lower likelihood of testing among influenza positive vaccinees could potentially bias VE estimates upward and requires further evaluation. Clinical testing alone may fail to detect a substantial proportion of influenza cases. DISCLOSURES: All authors: No reported disclosures.


title: BK Polyoma Virus Nephropathy in Hematopoietic Cell Transplant Recipients with Renal Dysfunction

text: BACKGROUND: BK polyoma virus (BKV) nephropathy (BKVN) is a well-established cause of allograft loss after kidney transplantation. In contrast BKVN is rarely been reported in hematopoietic cell transplant (HCT) recipients. Renal dysfunction after HCT is common and often attributed to total body irradiation, drug toxicity, hypertension or microangiopathy. As kidney biopsies are rarely performed after HCT, BKVN may be underdiagnosed. We report a Single-center experience of BKVN in HCT recipients. METHODS: Retrospective chart review of HCT recipients from January 1, 2016 through March 31, 2017. Only cases of BKVN confirmed by immunohistochemical stain on renal biopsy are included. Urine and blood BKV PCR was performed at Viracor Eurofins (Lee’s Summit, MO). Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: From 2016 to 2017, 320 patients received HCT and 6 patients underwent kidney biopsy and 4 had BKVN. Patient characteristics are shown in Table 1. Three patients (75%) received ex vivo T-cell depleted (CD34+ selected) peripheral blood (PB) HCT and did not receive pharmacologic GVHD prophylaxis; one patient received cord blood allograft. All patients had BKV viruria with a median BKV viral load of 9.3 log(10) copies/mL (range, 8.6–10.0) and median onset 18 days (range 6–41) post HCT. BKVN was diagnosed at a median of 275.5 days post-HCT (range, 141–637). All patients presented with decreased GFR (median 47.5% reduction, range 16–75%) from GFR at transplant. One patient had proteinuria (3 g over 24 hours); one patient had hydronephrosis. At BKVN diagnosis plasma BKV viral load was a median of 6.2 log(10) copies/mL; range, 6.0–6.3), absolute lymphocyte count median 1027 (range 335–2,536) and CD4+ lymphocyte count median 145 (range 64–172). CONCLUSION: (1) BKVN should be considered in HCT recipients with worsening renal function and high BKV viremia. (2) Early, noninvasive predictors of BKVN could aid in identifying high-risk patients for early intervention prior to irreversible loss of kidney function. (3) Reduction of immunosuppression is often not feasible in HCT. The role of preemptive antiviral therapy and/or adoptive cell therapy for BKV viremia in HCT should be evaluated in clinical trials. DISCLOSURES: G. Papanicolaou, Chimerix: Consultant, Grant Investigator and Investigator, Consulting fee, Grant recipient and Research grant


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title: Intranasal Administration of Integrase Defective Lentiviral Vectors Expressing mAbs Protects from H5 Influenza Virus Challenge In Vivo

text: BACKGROUND: Despite medical advances, we are often unable to rapidly protect non-immune populations from infectious agents. Passive immunotherapy is a fast method of protection, but large-scale administration of monoclonal antibodies (mAbs) in unpractical. The delivery of mAbs using a viral vector can be an attractive alternative to direct mAbs injection. Integrase-defective lentiviral vectors (IDLV) have several advantages including the absence of pre-existing anti-vector immunity and the safety features of non-integration and non-replication. IDLV are maintained in non-dividing cells, and can express steady levels of functional proteins in vivo. We engineered IDLV to express mAbs against the influenza A virus (IAV) hemagglutinin, and tested their ability to protect from IAV in vivo. METHODS: IDLV were produced by co-transfection of transfer, packaging, and envelope plasmids in 293T cells and purification on sucrose gradients. IDLV were normalized using a colorimetric reverse transcriptase assay. Plasmid expressing mAb VN04-2 was provided by B. Hanson. mAb in the supernatant of transduced cells were detected by western blot and quantified by the Easy-Titer Human IgG Assay Kit. For in vivo studies, groups of 6–8 weeks old mice received IDLV either by intranasal (in) or intramuscular (im) route. mAb production was detected by western blot and ELISA. Mice were challenged using the recombinant IAV VNH5N1-PR8/CDC-RG derived from IAV A/Vietnam/1203/2004. RESULTS: We engineered IDLV producing the humanized mAb VN04-2 (IDLV-VN4-2), which is broadly neutralizing against H5 IAV. We found that after transduction of 293T cell with different dosages IDLV-VN4-2, the production of mAb was time and dose dependent. mAb were also functional, and bind specifically H5 HA but not other IAV proteins. We also measured VN04-2 production in the serum of mice 3, 6, 9, 14, 21 and 30 days after in or im administration of IDLV-VN4-2. We found that levels of mAb were sustained. In separate experiments 5/5 mice receiving IDLV-VN4-2 by the in route and 2/5 mice receiving it by the im route were protected from lethal IAV challenge. CONCLUSION: Our data suggest that IDLV may represent an attractive candidate for vector-mediated immunization against infectious disease. DISCLOSURES: All authors: No reported disclosures.


title: Burden of Community-Acquired Pneumonia due to PCV-13 Streptococcus pneumoniae Serotypes Among Hospitalized Adults in the United States

text: BACKGROUND: The burden of disease for US adult patients hospitalized with community-acquired pneumonia (CAP) due to S. pneumoniae (Sp) PCV13 vaccine types (VT) is not known. The objective of this study was to determine the incidence, patients’ characteristics, length of stay and mortality for US adults hospitalized with CAP due to Sp-PCV13VT. METHODS: This was a prospective observational study of adults hospitalized between October 7, 2013 and September 30, 2016 with radiographically confirmed CAP in 19 centers in the US. Patients were included if the following 5 criteria were met: 1) Age 18 years and older; 2) Presence of two or more of the following: fever, hypothermia, chills or rigors, pleuritic chest pain, cough, sputum production, dyspnea, tachypnea, malaise, and abnormal auscultatory findings suggestive of pneumonia; 3) Radiographic finding consistent with pneumonia; 4) Able to provide urine sample; 5) Signed informed consent. The presence of Sp-PCV13VT was investigated using a Luminex-based urinary antigen detection (UAD) assay or serotyping from a positive Sp isolate. Data on patients’ characteristics, length of stay (LOS) and in-hospital mortality (IHM) were collected. RESULTS: From a total of 12,055 hospitalized patients with CAP, VT Sp-PCV13 was detected in 552 patients via UAD or culture (4.6%). Among patients hospitalized with CAP due to Sp-PCV13VT, median age was 64 years, and the most common comorbidities were chronic obstructive pulmonary disease (46.2%) and diabetes (27.3%). Median LOS was 6 days, and IHM was 5.4%. There were no clinically significant differences when this population was compared with the population of patients with non-PCV13 VT Sp-CAP. CONCLUSION: In approximately 5% of US adults hospitalized with CAP, the etiologic agent is VT Sp-PCV13. Clinical characteristics and outcomes in this population were similar when compared with the general population of hospitalized patients with CAP. In conclusion, this study indicates a persistent burden of disease for adult patients hospitalized with CAP due to vaccine preventable Sp serotypes. DISCLOSURES: All authors: No reported disclosures.


title: A Varicella Outbreak Among Preschool Children Despite One-dose Vaccination

text: BACKGROUND: In Turkey, a single-dose varicella vaccine was introduced into the National Immunization Program in 2013. Before this implementation, varicella vaccine had been available in the private sector since 2000. However, varicella outbreaks continued to occur in preschools and elementary schools. We investigated a varicella outbreak to estimate the effectiveness of 1-dose varicella vaccine and to evaluate potential risk factors for breakthrough disease. METHODS: This study was carried out during a varicella outbreak in 3 preschools in İzmir, Turkey, in April 2016. Using questionnaires, data including children’s medical and vaccination history were collected from their parents. Vaccination status of children was also verified with immunization records. Attack rates in vaccinated and unvaccinated children were calculated and the analysis of vaccine effectiveness and of risk factors for breakthrough disease were conducted. Vaccine effectiveness was calculated using the equation: (attack rates in unvaccinated children-attack rates in vaccinated children/ attack rates in unvaccinated children) × 100%. RESULTS: A total of 124 children were enrolled in the study. Of the 124 children, 77 (62%) had received 1-dose varicella vaccine before the outbreak. Varicella developed in 34 of 124 children during the outbreak, and 18 of them (53%) had breakthrough varicella. The attack rate was 23.4% among vaccinated children and 34% among unvaccinated children. The effectiveness of single-dose varicella vaccine was 33.6% against varicella disease of any severity and 82.5% against moderate or severe varicella. Children vaccinated 5 or more years before the outbreak had 3.5 times the risk of disease than those who had been vaccinated more recently (OR 3.5 [95% CI, 1.08–11.5]); P = 0.046). Age at vaccination (<15 months vs.≥15 months) and the brands of varicella vaccine were not associated with the increased risk of breakthrough varicella. CONCLUSION: One-dose of varicella vaccine is not sufficient to prevent school outbreaks. For this reason, varicella outbreaks continued to occur in schools and kindergartens among healthy vaccinated children in Turkey. A 2-dose varicella vaccination program may help to prevent varicella outbreaks and achieve effective control of the disease. DISCLOSURES: All authors: No reported disclosures.


title: Assessment of a Healthcare-Associated Pneumonia (HCAP) Risk Stratification and Empiric Treatment Guideline: A New Antimicrobial Stewardship Initiative

text: BACKGROUND: Risk stratification of HCAP patients is a possible Antimicrobial Stewardship (AST) intervention for the treatment of multidrug resistant (MDR) Gram-negative (GN) vs. community-acquired pneumonia (CAP) pathogens. This study assessed the impact of a risk stratification guideline for empiric antimicrobial selection relative to acceptance rates and clinical outcomes. METHODS: In 2017, a guideline for inpatients with HCAP was launched. High risk (HR) of MDR GN was defined as patients admitted to the intensive care unit (ICU), or with >1 risk factor including: receipt of any antimicrobial within 30 days or broad spectrum antimicrobials within 90 days, hemodialysis dependence, or immunocompromised. HR patients were recommended to receive antimicrobials covering MDR GN and low-risk patients to narrower CAP regimens. Patients treated for HCAP post guideline implementation were compared with a historic 2014 cohort for guideline concordance, antimicrobial selection, and clinical outcomes. AST interventions were also assessed. RESULTS: Overall, 105 patients in the post-implementation period were compared with 309 historic patients. Guideline-concordant risk-stratified therapy increased 13% [95% CI (3%, 24%)] overall. Clinical failure rates were similar with 11% vs 10% (P = 0.608) in the pre- and post-implementation periods, with an 84% AST acceptance rate (Figure 1). Treatment length decreased [8.1 to 6.6 days (P < 0.001)] and de-escalation increased [31% to 72% (P < 0.001)] as seen in Table 1. CONCLUSION: Introduction of a risk stratified guideline through AST intervention changed practice by matching MDR risk with empiric HCAP therapy. Failure rates were comparable. Secondary benefits included: decreased treatment duration and hospital stay, increased de-escalation rates and decreased MDR GN antimicrobial use in low-risk patients. DISCLOSURES: All authors: No reported disclosures.


title: Epidemiology of Polymyxin Use in a Tertiary Care Setting of South India

text: BACKGROUND: Polymyxin B(PB) and Colistin (PE) use have increased in India due to emergence of resistant Gram-negative organisms. The Indian Council of Medical Research has identified carbapenems, polymyxins (PE and PB) as key antimicrobials which require restriction in hospitals. We describe epidemiology of PB and PE use following implementation of an Antibiotic Stewardship Program (ASP) in a 1300-bed, private, tertiary-care center in Southern India. METHODS: An ASP was established at Amrita Hospital in Feb 2016 consisting of an administrative champion, hospitalist, microbiologist, intensivist and 5 pharmacists. Institutional guidelines for polymyxins were established and disseminated. The ASP team performed daily post-prescriptive reviews, evaluated and tracked appropriateness of PB and PE use, including administration of a loading dose (LD), maintenance dose (MD), frequency, route and duration of therapy. ASP recommendations and compliance were recorded. RESULTS: During the 12-month study period (Feb ‘16-Jan ‘17), 348 patients received 295 PE and 94 PB courses. Mean age was 50 yrs and 73% were male. Patients on Medicine and Hematology/Oncology teams accounted for 42% of all prescriptions. The most common infections were bacteremia (34%), pneumonia (29%) and UTI (23%). Pathogens were recovered in 69% (269/389) of cases, Klebsiella pneumoniae 23% (90/389) and Acinetobacter baumanii11 % (45/389) were most common. 290 (75%) of polymyxin course were judged to be inappropriate (78% of PE and 22% of PB). The most frequent reasons for inappropriate therapy included incorrect frequency of administration (64% for PB and 58% for PE), inappropriate MD (60% for PB and 48% for PE) and wrong duration of therapy (54% for PE and 48% for PB). 95% of incorrect MD for both PE and PB were too low. The reasons for inappropriateness were similar for both polymyxins.While all inappropriate LD episodes for PB (n = 22 %) were due to lack of a LD, errors for PE (n = 34%) involved either omission of LD or administration of LD that was too low.ASP recommendations were made in 190 instances with 58% provider compliance. CONCLUSION: Review of PB and PE use in our hospital indicates a high percentage of inappropriate use and highlights stewardship opportunities for improving care of patients with resistant infections. DISCLOSURES: K. S. Kaye, Xellia: Consultant, Consulting fee; Merck: Consultant and Grant Investigator, Consulting fee and Research support; The Medicines Company: Consultant and Grant Investigator, Consulting fee and Research support


docid: cjdofske

title: Impact of CMV Blips in Transplant Recipients

text: BACKGROUND: Management of CMV infection in solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) recipients mainly relies on screening of emerging CMV DNA in plasma or whole blood by PCR. However, a first positive CMV PCR may not be reproducible, but constitute a CMV blip (single positive CMV PCR measurements). Such blips are known from monitoring of other viral infections using PCR technology, and may either constitute a false positive read due to assay variability or reflect transient low-level viral replication. We investigated the impact of CMV blips in a cohort of SOT and HSCT recipients. METHODS: SOT and HSCT recipients transplanted between 2010 and 2015, who had a known donor (D)/recipient (R) CMV IgG serostatus (D+/R+, D+/R- or D-/R+), and with ≥3 CMV PCRs fulfilling the CMV PCR triplicate criteria (Figure 1) were included (N = 851). Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model. RESULTS: 851 transplant recipients generated 3883 CMV PCR triplicates (104 blips, 307 infections, 3472 negatives, Figure 1). In the 411 positive triplicates, the OR of a triplicate being a blip decreased with increasing CMV viral load of the second measurement ([vs. = 273 IU/mL]; >273–910 IU/mL: OR 0.2 [95% CI 0.1–0.4], >910 IU/mL: OR 0.07 [95% CI 0.03–0.2], P < 0.0001) and was elevated in recipients with intermediary/low-risk CMV IgG serostatus ([vs. those with high] OR 2.2 [95% CI 1.3–3.6] P = 0.003). If the cumulative exposure to viremia in the CMV blips was >910 IU/mL, there was a higher risk of subsequent CMV infection (HR 4.6 [95% CI 1.2–17.2] P = 0.02) (Figure 2). CONCLUSION: CMV blips are frequent while screening transplant recipients with CMV PCR. CMV blips >910 IU/mL is a risk factor for subsequent infection, indicating that CMV blips at least partly reflect transient low-level CMV infection in transplant recipients. These observations suggest that first positive CMV PCR results should be confirmed before initiation of anti-CMV treatment, especially if the viral load of the first positive PCR is <910 IU/mL, or if the patient has intermediary/low-risk serostatus. DISCLOSURES: All authors: No reported disclosures.


title: Frailty Hinders Recovery From Acute Respiratory Illness in Older Adults

text: BACKGROUND: Influenza vaccination programs aim to prevent serious outcomes. Given that frailty may impact recovery from influenza, we examined frailty as a predictor of recovery in older adults hospitalized with acute respiratory illness. METHODS: Data came from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network during the 2011/12, 2012/13, and 2013/14 influenza seasons; all patients were aged 65+. Frailty was measured using a previously validated Frailty Index (FI) of health and functional deficits; baseline frailty was categorized using published cutoffs (0-.1 non-frail, >.1-.21 pre-frail, >.21-.45 frail, >.45 most frail). Recovery was operationalized as being alive 30 days post-discharge with less than two additional health/functional deficits (<=0.06 FI increase). Logistic regression was used to examine the change in odds of recovery for every 0.1 increase in baseline FI, controlling for age, sex, season, lab-confirmed influenza status, and seasonal influenza vaccination status. RESULTS: Of 5125 hospitalized older adults, 15% were non-frail, 39% pre-frail, 40% frail, and 6% most frail. 11% died, and poor recovery was experienced by 520/4544=11% of survivors. Poor recovery was inversely associated with baseline frailty (11% non-frail, 17% pre-frail, 28% frail, 38% most frail; P < .001). Frailty was associated with lower odds of recovery in all three seasons [2011/12 (OR=0.71; 95% CI 0.60–0.85), 2012/13 (OR=0.72; 0.66–0.78), 2013/14 (OR=0.76; 0.70–0.82)] though results varied by season, influenza status, and vaccination status. In 2011/12, frailty was associated with poor recovery in unvaccinated (OR=0.46. 95% CI=0.32–0.67) but not vaccinated older patients (OR=0.83, 95% CI=0.68–1.02). CONCLUSION: Increasing frailty was consistently associated with lower odds of recovery in older adults admitted with influenza and other acute respiratory illnesses; depending on seasonal factors, vaccination may offer some buffering of this impact. Understanding frailty and functional status is important, both because frailty is predictive of poor recovery and because persistence of new health/functional deficits is an adverse outcome with important implications for patients, families and health systems. DISCLOSURES: M. K. Andrew, GSK: Grant Investigator, Research grant; Pfizer: Grant Investigator, Research grant; Sanofi-Pasteur: Grant Investigator, Research grant; J. McElhaney, GSK Vaccines: Scientific Advisor, Speaker honorarium; M. Elsherif, Canadian Institutes of Health Research: Investigator, Research grant; Public Health Agency of Canada: Investigator, Research grant; GSK: Investigator, Research grant; S. A. Halperin, GSK: Scientific Advisor, Consulting fee; GSK: Grant Investigator, Research grant; T. Hatchette, GSK: Grant Investigator, Grant recipient; Pfizer: Grant Investigator, Grant recipient; Abbvie: Speaker for a talk on biologics and risk of TB reactivation, Speaker honorarium; J. M. Langley, GSK: Investigator, Research grant; Canadian Institutes of Health Research: Investigator, Research grant; A. Mcgeer, Hoffman La Roche: Investigator, Research grant; GSK: Investigator, Research grant; sanofi pasteur: Investigator, Research grant; J. Powis, Merck: Grant Investigator, Research grant; GSK: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Synthetic Biologicals: Investigator, Research grant; M. Semret, GSK: Investigator, Research grant; Pfizer: Investigator, Research grant; S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant; L. Valiquette, GSK: Investigator, Research grant; S. McNeil, GSK: Contract Clinical Trials and Grant Investigator, Research grant; Merck: Contract Clinical Trials and Speaker’s Bureau, Speaker honorarium; Novartis: Contract Clinical Trials, No personal renumeration; sanofi pasteur: Contract Clinical Trials, No personal renumeration


title: Improving Patient and Employee Safety through Implementation of an Infection Risk Screening Process for International Patients at Boston Children’s Hospital—The “AIRSHIP” Protocol

text: BACKGROUND: Vaccine-preventable diseases and multi-drug-resistant organisms (MDROs) are common outside of the US, and multiple infectious outbreaks have been linked to travelers. Boston Children’s Hospital cared for 2796 international patients in 2016 but lacked an infection risk screening process for these patients, placing patients and staff at risk. We developed the Assessing Infection Risks for Safe Healthcare of International Patients (AIRSHIP) protocol to identify risks to guide infection prevention and control (IPC) measures. METHODS: A multidisciplinary team of IPC, infectious diseases, and International Health Services (IHS) experts assessed current IHS intake procedures and stakeholder engagement. We then developed AIRSHIP, devising standardized processes and forms to (1) assess underimmunization, MDRO and tuberculosis history, recent exposures, and current symptoms and (2) triage cases for catch-up immunization, urgent healthcare evaluation, and/or IPC intervention (Figure 1). We piloted incorporation of AIRSHIP into existing intake procedures. We tracked process, outcome, and balancing measures to evaluate feasibility, effectiveness, and acceptability to families (Figure 2) and made iterative improvements through Plan-Do-Study-Act (PDSA) cycles. RESULTS: For our first 13 cases, we completed pre-arrival family and referring provider interviews in 5 cases and on-arrival family interviews in 8 cases (in no cases were both pre-arrival and on-arrival interviews feasible). We were able to assign a risk category in all cases, identifying 5 patients with infection risks (38%) and 4 who were undervaccinated (30%). In 7 of 8 cases (88%) in which on-arrival interviews were performed, the interview and referring provider records yielded complete and reliable data. The average duration of family interviews was 18 minutes. All 13 families reported being “very satisfied” with AIRSHIP. CONCLUSION: International patients often present with active infections and are commonly undervaccinated. A feasible and effective strategy for infection risk screening of international patients is review of records pre-arrival, together with on-arrival family interview to gather additional data and identify acute symptoms and exposures. DISCLOSURES: All authors: No reported disclosures.


title: Evaluating Symptom Severity of Influenza Viral Infection Using the Influenza Patient-reported Outcomes Instrument (FLU-PRO) in a Healthy Human Challenge Model

text: BACKGROUND: To apply the validated FLU-PRO scoring method to assess influenza symptom severity in a healthy human challenge model. METHODS: Healthy adults admitted to the NIH Clinical Center (Day -1) underwent a 9 day inpatient quarantine after intranasal challenge with H1N1pdm (Day 0). Participants completed the 32 item FLU-PRO diary twice daily for 14 days to assess presence and severity of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare severity scores on Day 3 post-challenge by viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers. RESULTS: 61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of which 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (<40) HAI and NAI titers, respectively. Mean daily FLU-PRO symptom severity domain and total scores are shown in Figure 1. Symptoms were present across all FLU-PRO domains from Day 1 post-challenge. Nose, throat, body, and GI symptoms reached peak severity at Day 3, followed by chest and eye symptoms at Day 4. Subjects with viral shedding had significantly higher mean FLU-PRO scores compared with those without, except for Eye and GI domains (P < .05); mean FLU-PRO scores were significantly higher for subjects with low NAI titer (P < .05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (P < .05) ((high HAI-low NAI (n = 22), low HAI-high NAI (n = 29)). CONCLUSION: The FLU-PRO can be used to track symptom onset, severity, and recovery from influenza infection in clinical research. In this challenge study, scores were responsive to change even in mild disease and distinguished known clinical subgroups. The use of NAI as an independent predictor of influenza disease severity was also supported. Funded by NCI Contract No. HHSN261200800001E and in part by the Intramural Research Program of the NIH, NIAID DISCLOSURES: J. L. Poon, Evidera: Employee, Salary; R. Yu, Evidera: Employee, Salary; N. K. Leidy, Evidera: Employee, Salary


title: A Cloud Based Epidemiology Network to Investigate Geographical Dynamics of Respiratory Disease

text: BACKGROUND: Real-time data collection of respiratory disease is important for understanding the spatiotemporal dynamics of disease transmission in the US. Healthcare professionals use tools such as FluView to help identify local pathogen circulation; however, these tools are limited to syndromic surveillance, and track a limited set of pathogens. Understanding respiratory disease dynamics requires 1) a large, pathogen rich data set 2) geographically dispersed data sources, and 3) fine temporal resolution. Here we utilize FilmArray® Trend, a research epidemiology system containing exported data from FilmArray® Respiratory Panel (RP) tests, to investigate geographic patterns of 20 common pathogens. METHODS: Over 6,000,000 individual pathogen assays from 19 clinical sites were exported to the Trend database from 2013 to present. Trend data were smoothed and normalized to produce the time series of pathogen incidence. A cross-correlation analysis was performed to compare sites to one another and determine offset of pathogen incidence. The results were plotted on a map of the US with visual indicators of correlation strength and directional movement as defined by cross-correlation lag values. RESULTS: The respiratory pathogens detected by the FilmArray RP test show a diverse set of spatial and temporal behaviors Most striking was the spread of the virus Coronavirus OC43, and Respiratory Syncytial Virus (RSV), with RSV traveling from east coast sites to west coast sites across the US over 20 days. In contrast Parainfluenza virus 3 (PIV3) shows a small cross-correlation lag across all of the Trend sites during the regular summer season, indicating near simultaneous onset of detection nationwide. A localized cluster of PIV3 in the winter of 2016 was observed in the midwest and west, identifying the significance of localized regional trends. CONCLUSION: FilmArray Trend shows great promise in deciphering spatiotemporal dynamics of these common respiratory pathogens. This system can identify localized outbreaks and directional movement of pathogens over time. Future work with finer geographic distribution of contributing sites will aide in making conclusions regarding spatial dynamics of all 20 RP pathogens. Other pathogen transmission models may also be explored using this data set. DISCLOSURES: C. Cook, BioFire Diagnostics: Employee, Salary. A. Wallin, BioFire Defense: Employee, Salary. A. Faucett, BioFire Diagnostics: Employee, Salary. L. Meyers, BioFire Diagnostics: Employee, Salary


docid: cigsnckg

title: Infectious Complications of Intravenous Drug Use: A Single-Center Review of Hospitalized Patients in Massachusetts, 2012-2015

text: BACKGROUND: The national opioid epidemic has been accompanied by precipitous increases in overdose deaths and hospitalizations for infectious complications of injection drug use (IDU). Despite this, there is scant literature addressing the topic. We aimed to describe demographic characteristics, type of infection, healthcare utilization, disposition and outcomes among patients hospitalized for IDU-related infection over a multi-year period at a large tertiary care referral center in Boston, MA. METHODS: We conducted a retrospective chart review of patients hospitalized for IDU-related infection from 1/1/2012-9/30/2015. 901 charts were initially identified using administrative codes; 234 met the following inclusion criteria: 1) hospitalization within the study period for treatment of ≥1 of 6 selected infections and 2) IDU within 6-months preceding qualifying hospitalization. During the study period, 234 patients had 488 cumulative admissions. Admissions for IDU-related infection and ≤30-day readmission, all-cause, underwent detailed abstraction (N = 338; 69%). RESULTS: Of 234 patients, over half were male (57%; N = 134), 78% white (N = 183), 17% homeless (N = 37), 88% had public insurance (N = 210); 53% had a history of Hepatitis C infection (N = 124), most with untreated or unknown infection status (86%; N = 107). Average age was 38 (range 18-75). Fifty-eight percent (N = 136) of patients had one admission during the study period, the remainder had between 2-13 (mean = 3.6). Sentinel admission infection types were 1) skin and soft tissue (SSTI) N = 111 (42%), 2) endocarditis N = 70 (30%), 3) bone and joint N = 26 (10%), 4) pyogenic spinal N = 39 (15%), 5) isolated bacteremia N = 9 (3%) 6) and acute viral hepatitis N = 8 (3%). Of 338 admissions, 57% (N = 192) included infectious disease consultation; 50% resulted in discharge to another facility and 82% (excluding isolated SSTI) required multi-week intravenous antibiotics on discharge. By 15-months following the study period, 12% were deceased (N = 28); 5 died during hospitalization. CONCLUSION: Our study describes the characteristics of patients hospitalized with IDU-related infection over a multi-year period in a region highly impacted by the opioid epidemic. High rates of hospital readmission, prolonged antibiotic therapy and out-of- hospital death were common in this young cohort. DISCLOSURES: All authors: No reported disclosures.


New evidence-based clinical practice guideline timely supports hospital infection control of coronavirus disease 2019


title: Hand hygiene: Knowledge and Practices of Clinical Teachers in Selected Teaching Hospitals in Kenya

text: BACKGROUND: Healthcare-associated infections lead to substantial morbidity and mortality worldwide, and adequate hand hygiene (HH) in the clinical setting is essential for prevention. Clinical teachers are central to the training of healthcare workers (HCW) as they teach and model safe practices in the clinical environment. However, there is limited research on the knowledge and practices of clinical teachers related to HH in teaching hospitals, particularly in African settings. We describe the knowledge and practices of HH amongst clinical teachers in selected teaching hospitals in Kenya. METHODS: Data were collected through self-administered standardized questionnaires with basic demographic, knowledge and practices about HH from clinical teachers employed at two teaching hospitals. Participating clinical teachers were anonymously audited for HH practices using an adapted World Health Organization tool. The audits consisted of 20–30 minutes observations in each ward RESULTS: Among 57 participants overall, 42 (73.7%) were nurses, 8 (14.0%) clinicians, and 5 (8.8%) therapists. Twenty-one (36.8%) of the participants had knowledge regarding the minimum time needed to practice HH using alcohol based hand rub, 14 (24.6%) knew that hand washing and hand rubbing should be performed in sequence. The combined knowledge score for each individual ranged from 0% to 94.1% with a mean of 50.1% (SD=20.1, Cl 95% 44.7- 55.4%). Hand hygiene compliance significantly varied by clinical instructor’s type; nurses (42.7%) and therapists (38.0%) had the highest adherence and clinicians had the lowest 33.7% (P = 0.0001). CONCLUSION: Clinical teachers in this study demonstrated knowledge gaps and poor practices related to HH. Since they serve as role models for future generations of healthcare workers, clinical teachers must recognize the importance of HH in preventing hospital-acquired infections, including when and how HH should be performed while following recommended practices. DISCLOSURES: All authors: No reported disclosures.


title: Mumps Outbreak—Colorado, 2017

text: BACKGROUND: During 2016, an unusually high number (>5,000) of mumps cases were reported in the United States. On January 20, 2017, we identified a mumps outbreak in the Denver metropolitan area among a Marshallese community. We performed active surveillance to assess outbreak magnitude and guide implementation of control measures. METHODS: On January 22, local and state health departments initiated active case surveillance by using a church-based community roster. Each household was contacted by telephone ≥3 times to identify mumps cases, according to the 2012 CDC/Council of State and Territorial Epidemiologists case definition, and risk factors (e.g., household size). Measles, mumps, and rubella (MMR) vaccination status was reviewed in the Colorado Immunization Information System (CIIS). Four church-based vaccination clinics were held to bring participants up-to-date for MMR vaccination. Targeted messaging about mumps, MMR vaccine, and vaccination clinics was distributed through social media, churches, and Marshallese-language radio. RESULTS: Of the 21 households on the church roster, 17 were successfully contacted, 13 of which (76%) provided data for 85 persons (median household size: 6 persons; range: 5–12). Through household interviews and laboratory reporting, we identified 47 mumps cases (17 confirmed; 30 probable). Median patient age was 20 years (range: 3 months–44 years), 24 (51%) were male, and 34 (72%) reported no or unknown prior mumps vaccination and had no MMR vaccination documented in CIIS. During vaccination clinics, 118 (80%) of 148 presenting Marshallese persons were eligible for and received MMR vaccine; of those vaccinated, median age was 21 years (range: 1–55 years) and 104 (88%) had no prior MMR vaccine documentation. CONCLUSION: Active surveillance, facilitated through culturally appropriate communication with church leaders, helped identify cases, disseminate materials, and promote MMR vaccination. Household interviews provided timely data to define outbreak magnitude and need for urgent MMR vaccination. DISCLOSURES: All authors: No reported disclosures. sdsdsdsd


title: Clinical Features and Outcomes of Immunocompromised Adults Hospitalized with Laboratory-confirmed Influenza in the USA, 2011–2015

text: BACKGROUND: Data on immunocompromised (IC) adults with influenza are limited but suggest they may present differently and have worse outcomes than non-IC adults. Using a national surveillance system, we describe the epidemiology of IC adults hospitalized with influenza. METHODS: We analyzed data on adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza during the 2011–2012 through 2014–2015 seasons and reported to CDC’s Influenza Hospitalization Surveillance Network (FluSurv-NET). We defined IC patients as having ≥1 of the following: HIV, AIDS, cancer, stem cell or organ transplantation, non-steroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and other rare conditions. We compared IC and non-IC patients using χ(2) or Fisher’s exact tests and t-tests or Mann–Whitney U tests. RESULTS: Among 35,348 adults hospitalized over four seasons, 3,633 (10%) were IC. The most common IC conditions were cancer (44%), non-steroid immunosuppressive therapy (44%), and HIV (17%). IC patients were younger than non-IC patients (mean 61 ± 17 vs. 67 ± 20 years; P < 0.01). IC patients were more likely to have underlying renal disease (27% vs. 18%) and liver disease (7% vs. 3%) and less likely to have most other chronic underlying conditions including obesity (18% vs. 23%), cardiovascular disease (40% vs. 47%), and chronic lung disease (35% vs. 41%; P < 0.01 for all). IC patients were more likely to have received influenza vaccination (53% vs. 46%; P < 0.01). Among cases with symptom data (2014–2015), IC patients were more likely to present with fever (68% vs. 61%; P < 0.01) but respiratory distress was similar (53% vs. 54%; P = 0.3). Overall, the majority of IC and non-IC patients received antivirals (87% vs. 85%; P < 0.01). IC patients had a longer duration of hospitalization (median (IQR) 4 (2–6) vs. 3 (2–6) days; P < 0.01) and were more likely to be diagnosed with pneumonia (34 vs. 31%; P < 0.01) and to require intensive care (18% vs. 16%; P = 0.01). Death during hospitalization occurred in 135 (3.7%) IC and 945 (3.0%) non-IC patients (P = 0.01). CONCLUSION: Among adults hospitalized with influenza, IC patients had worse outcomes including a longer duration of hospitalization and higher probability of pneumonia and intensive care unit admission, and increased all-cause mortality, although these results are not adjusted for potential confounders. DISCLOSURES: W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. E. J. Anderson, AbbVie: Consultant, Consulting fee. NovaVax: Research Contractor, Research support. Regeneron: Research Contractor, Research grant. MedImmune: Research Contractor, Research grant and Research support


title: The Impact of Respiratory Viral Testing in Hospitalized Adult Patients at a Tertiary Care Facility

text: BACKGROUND: The use of multiplex nucleic acid amplification assays to detect respiratory viruses is increasing. However, these tests are expensive, and the clinical significance of a positive result is often unclear. Positive viral results have the potential to decrease antibiotic use and length of stay, but their actual impact is unknown. METHODS: We completed a retrospective review of all adult patients with positive respiratory viral panel (RVP; GenMark) and/or rapid RSV/influenza PCR tests (Cepheid Xpert) collected within 48 hours of admission to the general inpatient or stepdown units of an academic tertiary care hospital between September 1, 2015 and March 15, 2016. Data collected included demographics, comorbidities, clinical presentation, time of test collection and result, additional diagnostic evaluation, and antibiotic use. RESULTS: A total of 221 positive respiratory viral tests were collected on 215 patients during the study period. The median age at time of testing was 56.8 years; 48% were female. Respiratory symptoms were documented in 92.8% of cases. COPD was the most common respiratory co-morbidity (20.2%), while 30% of patients had cancer, and 3.2% were HIV-infected. Respiratory support on admission was common (51.6%). A rapid PCR and RVP were performed in 58.8% of cases, while 28.5% had only an RVP and 12.7% had only a rapid PCR. Of the patients who had a positive rapid PCR, 17.6% also had an RVP done. Antibiotics were started within 24 hours of presentation in 87.4% of all cases and 70.6% of patients who had a positive rapid PCR. Rhinovirus was the most frequently isolated pathogen (44.6% of positive tests) followed by metapneumovirus (14%), respiratory syncytial virus (13.5%), and coronavirus (13.5%). Median time from specimen collection to result was 38.8 hours for RVP, and 15.3% were resulted after patient discharge. For those who had a rapid PCR alone, median time from collection to result was 1.5 hours. CONCLUSION: In this non-critically ill cohort, most patients with positive viral assays received antibiotics, and a substantial number of RVPs were resulted after discharge. This suggests that there are many lost opportunities to impact clinical management with respiratory viral testing. DISCLOSURES: M. Miller, GenMark Diagnostics: Grant Investigator, Research support and Salary; R. Jhaveri, GenMark: Investigator, Grant recipient


title: Long-term Respiratory Complication in Patients with Middle East Respiratory Syndrome: 1-year Follow-up After the 2015 Outbreak in South Korea

text: BACKGROUND: There are few data about long-term respiratory complications following Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection. This study aimed to evaluate respiratory functions and radiologic sequelae according to the severity of infection one year after the patients experienced MERS-CoV infection. METHODS: A total of 73 patients undergoing MERS-CoV infection during the 2015 MERS outbreak in South Korea were enrolled in this prospective multicenter study. Pulmonary function tests and 6-minute walking tests were performed 1 year after infection. Radiologic sequelae was defined as fibrosis or atelectasis on chest computer tomography and severe pneumonia was defined as that requiring oxygen therapy. Multivariate linear regression tests were used to evaluate the effect of infection severity on respiratory function. RESULTS: At the time of MERS-CoV infection, 18 patients had no pneumonia, 35 experienced mild pneumonia, and 20 did severe pneumonia. The median age was not different between groups (P = 0.942). Forced vital capacity (FVC) was 102.6%, 94.9%, and 88.7% in the no, mild, and severe pneumonia group, respectively (P = 0.010) and forced expiratory volume in 1 second was 105.3%, 95.7%, and 91.7% (P = 0.057). Diffusing capacity (DLCO) was significantly lower in the severe pneumonia group than in the no or mild pneumonia group (78.3% vs. 89.4% or 88.6%, P = 0.035). In multivariate analyses, FVC and DLCO were significantly correlated with infection severity after adjustment with age, sex, underlying lung disease, and smoking. There was no difference in the walking distance of 6 minute tests between groups. Radiologic sequelae were shown in 18.8%, 65.6%, and 100% in the no, mild, and severe pneumonia group, respectively (P < 0.001). CONCLUSION: The patients with more severe pneumonia by MERS-CoV had more impaired respiratory function in one year follow-up, which was compatible with radiologic sequelae. DISCLOSURES: All authors: No reported disclosures.


title: Use of Oral Ribavirin for the Treatment of RSV Infections in Hematopoietic Cell Transplant (HCT) Recipients

text: BACKGROUND: The benefit of aerosolized ribavirin (AR) in reducing the risk of progression of RSV infections and RSV-associated mortality in HCT recipients has been recognized, yet there is a paucity of data assessing the use of oral ribavirin (OR) in this patient population. We evaluated outcomes associated with the use of OR compared with AR in HCT recipients. METHODS: Retrospective review of all HCT recipients with RSV infection treated with OR or AR during three RSV seasons (September 2014 – February 2017). An established immunodeficiency Scoring Index (ISI) was applied to identify patients at high risk for progression and death based on host risk factors. Mortality, progression to lower respiratory infection (LRI), and need for ICU admission was compared among recipients of AR and OR. RESULTS: A total of 107 patients were treated with OR (n = 42, 39%) or AR (n = 65, 61%). Recipients of AR and OR were equally likely to be high-risk by ISI scoring (11% vs. 10%, P = 1.00). Fifty-three patients (50%) presented with upper respiratory infection (URI) of whom 13 (25%) progressed to LRI. There was no difference in the rate of progression to LRI between patients who received AR and OR (28% vs. 19%, P = 0.53). No difference was found in 30-day mortality rates based on treatment strategy (8% AR vs. 5% OR, P = 0.70). Interestingly, 90-day mortality was found to be significantly lower among patients who received OR vs. AR (20% vs. 5%, P = 0.04). No differences in rates of ICU admission and requirement for mechanical ventilation were found between the two groups. For the 99 inpatients at time of diagnosis, median (interquartile range) length of stay was 7 (5 – 19) days, and was similar for patients on either treatment modality. Eight patients were treated for RSV on an outpatient basis and all received OR. CONCLUSION: HCT patients with RSV had similar outcomes when treated with AR and OR. OR may be a safe and effective alternative to AR for prevention and treatment of RSV in HCT patients with significantly reduced cost. DISCLOSURES: R. Chemaly, Gilead: Consultant and Investigator, Consulting fee and Research grant. Ansun: Investigator, Research grant. GSK: Investigator, Research grant.


The Association of Physicians of Great Britain and Ireland 1994: Eighty-Eighth Annual General Meeting


title: Impact of formaldehyde addition to spray-dried plasma on functional parameters and animal performance()

text: Experimental objectives of this study were to determine effects of formaldehyde treatment on the chemical composition of spray-dried plasma (SDP) and to test the hypothesis that growth performance of pigs fed formaldehyde-treated diets containing SDP or diets containing formaldehyde-treated SDP is not reduced compared with pigs fed untreated control diets. Sal CURB ASF liquid antimicrobial and CURB RM Extra liquid mold inhibitor (Kemin Industries, Des Moines, IA) were applied on SDP at 0.1% or 0.3% to determine effects of the products on chemical and functional properties of SDP. Regardless of product, there were no changes in SDP for analyzed protein, ash, pH, or moisture concentration, but IgG concentration in SDP was decreased 8% and 24%, respectively, for 0.1% and 0.3% inclusion of Sal CURB or CURB RM. Two feeding studies using weaned pigs were conducted to determine effects of formaldehyde applied at 0.3% to SDP (experiment 1) or 0.3% to a complete diet containing 5% SDP (experiment 2). Experiment 1 pigs (n = 265) were weaned at 20 ± 2 d of age and allotted to five treatment groups. Experiment 2 pigs (n = 135) were weaned in two groups at 20 ± 2 d of age and allotted to three treatments groups. In experiment 1, the untreated control diet contained soy protein concentrate (SPC) and test diets contained 2.5% or 5.0% SDP without or with formaldehyde treatment. In experiment 2, formaldehyde was applied to a diet containing 5% SDP and an untreated SPC control diet and an untreated diet containing 5% SDP were also included in the experiment. In experiment 1, linear increases (P < 0.05) in average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were observed as SDP was included in the diets and the relative bioavailability of formaldehyde-treated SDP was 62% (P = 0.018) if calculations were based on ADG and 15% (P = 0.031) if calculations were based on ADFI. In experiment 2, pigs fed the SDP diet untreated or treated with formaldehyde had increased (P < 0.05) final body weight, ADG, ADFI, and G:F compared with pigs fed the control diet. However, formaldehyde treatment of the plasma-containing diet did not affect pig growth performance compared with pigs fed the untreated SDP diet. In conclusion, formaldehyde treatment applied directly on SDP affects analyzed concentrations of IgG and reduces growth rate of pigs. Treating a complete diet containing 5% SDP with formaldehyde did not affect pig growth performance, and pigs fed diets containing SDP had improved growth performance than those fed the control diet without SDP.


Twenty-First Century Plague. The Story of SARS


Viral Infections and the Development of Disinfection: 100 Years of Progress at I&ECR


title: Viruses in Ixodes Uriae (Acari: Ixodidae) from Seabird Colonies at RøSt Islands, Lofoten, Norway1

text: A total of 1929 Ixodes uriae collected from Røst Islands, Lofoten, Norway, in July 1974, was divided into 204 pools and inoculated into suckling mice and chick embryo cell cultures for virus isolation. Virus was detected in 6.6% of the laboratory-molted female ticks, 5.4% of the males and 1.8% of the nymphs. No isolates were obtained from 149 unengorged adult ticks. Of 50 viral strains recovered, 30 belonged to the Uukuniemi group, 13 to the Kemerovo group, and I was a strain of Tyuleniy of Group B. Of 6 untyped strains, I was orbiviruslike and I resembled a coronavirus in a negative-staining electron microscopy. The infection rates of I. uria in Lofoten were similar to those reported in the Murmansk area in the northern USSR.


Managing SARS Amidst Uncertainty Wenzel RP, Edmond MB The New England Journal Of Medicine. 2003;348:1947–1948


Selected Bibliography


Veterinary Medicine (902)


Emerging Infectious Disease in Transfusion Medicine


A Large Variation in the Rates of Synonymous Substitution for RNA Viruses and Its Relationship to a Diversity of Viral Infection and Transmission Modes


title: Probability Sampling by Connecting Space with Households Using GIS/GPS Technologies

text: Sampling methods for survey studies are challenged by the replacement of landline telephones with mobile phones, the lack of timely census data, and the growing need for studies to address new health challenges. GIS/GPS-assisted methods provide a promising alternative, but these methods need further improvement. We established a stratified 3-stage GIS/GPS-assisted sampling method in which residential areas of a target population are divided into mutually exclusive cells – geographic units (geounits) as the primary sampling frame (PSF). Geounits with residential households were randomly selected from the PSF with a semi-automatic algorithm implemented in R. Novel methods were used to sample households and participants. Simulations and application studies indicated adequate feasibility, efficiency and validity of the method in sampling rural-to-urban migrants from a large city with complex residential arrangements. With this method, researchers can determine sample size and number of geounits, households and participants to be sampled; optimally allocate geounits; determine area size of sampled geounits and estimate sample weights; and complete sampling for field data collection in a short period. Our method adds an integrative approach for GIS/GPS-assisted random sampling with a de facto population assumption. Additional evaluation studies are needed to assess the utility of this method in different settings.


docid: zyiqigck

title: Veterinary Immunology and Serology: Clinical Laboratory Diagnostics

text: Methods used in clinical laboratory diagnosis in the veterinary laboratory closely parallel the common techniques used in the human laboratory. Immunology procedures include immunohematology, autoimmune testing, and assays for detection of immune deficiencies and infectious diseases. Veterinary immunohematology procedures deal with immune-mediated hemolysis, as well as blood typing, cross matching, and transfusion. Diseases of the immune system in animals include rheumatoid arthritis, systemic lupus erythematosus (SLE), and immunodeficiency disorders. The number of infectious diseases that can be diagnosed in a veterinary laboratory is almost limitless, but perhaps two of the most prevalent and significant are heartworm disease and feline infectious peritonitis (FIP).


Emerging Pathogens: What Are the Sources and How Can They Be Spotted Quickly?


title: Matrix Issues Associated With Analysis of Veterinary Specimens

text: Accurate analysis and interpretation of veterinary samples may be hampered by differences in sample matrix, compared with human samples. In addition to differences in sample collection methods, abnormal findings include lipemia, hemolysis, icterus, higher protein concentrations, and different therapeutic drug concentrations. Although many of these findings are similar to those in human sample testing, significant differences are present that affect several areas of the laboratory.


docid: iugrhyaq

title: Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases

text: Often, patients with neurodegenerative or neurobehavioral diseases have chronic, neuropathic infections that could be important in disease inception, disease progression, or increasing the types or severities of signs and symptoms. Although controversial, the majority of patients with various neurodegenerative or neurobehavioral conditions, such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and autistic spectrum disorders, show evidence of central nervous system or systemic bacterial and viral infections. For example, using serology or polymerase chain reaction evidence of Chlamydia pneumoniae, Borrelia burgdorferi, Mycoplasma species, human herpesvirus-1 and -6, and other bacterial and viral infections revealed high infection rates that were not found in control subjects. Although chronic infections were not found in some studies, and the specific role of chronic infections in neurological disease pathogenesis has not been determined or is inconclusive, the data suggest that chronic bacterial or viral infections could be common features of progressive neurodegenerative and neurobehavioral diseases.


Severe Acute Respiratory Syndrome Epidemiology and Control


MP647 OUTCOMES OF HEMODIALYSIS PATIENTS WITH MERS-COV EXPOSURE IN KOREA


MP722 POSTTRAUMATIC STRESS DISORDER OF HEMODIALYSIS PATIENTS WITH MERS-COV EXPOSURE


In the Literature


1122 Increase in Influenza-Like Illness in the Spring of 2014 Associated with Human Metapneumovirus


15 October News


docid: psuqndqt

title: 129 Acute Respiratory Viral Infection among Outpatient Healthcare Personnel


Bennett & Brachman's Hospital Infections Edited by William R. Jarvis Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2007. 832 pp., Illustrated. $210.00 (hardcover)


DIALYSIS. EPIDEMIOLOGY, OUTCOME RESEARCH, HEALTH SERVICES 1


1 January News


Editors' selection of papers from China's academic journals


1 December News


1 February News


1 November News


Cyclosporin


Infectious Diseases: Hot Topics Edited by Vincent Lo Re, III Philadelphia: Hanley and Belfus, 2004. 395 pp. $29.95 (cloth)


SP675 CIRCULATING CELL FREE DNA AND MITOCHONDRIAL DNA IN THE PATIENTS ON HEMODIALYSIS AND MEDICAL STAFFS DURING ISOLATION BY MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS IN KOREA


Reemergence of Established Pathogens in the 21st Century Edited by I. W. Fong and Karla Drlica New York: Kluwer Academic/Plenum Publishers, 2003. 367pp., illustrated. $139.50 (cloth)


Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 6th Edition Edited by Gerald L. Mandell, John E. Bennett, and Raphael Dolin Philadelphia: Elsevier Churchill Livingstone, 2005. 3661 pp., illustrated. $329 (cloth)


MP747 EFFECTS OF ISOLATION ON HEMODIALYSIS PATIENTS WITH MERS-COV EXPOSURE IN KOREA: A COHORT STUDY


1 October News


1 May News


Beasts of the Earth: Animals, Humans, and Disease E. Fuller Torrey and Robert H. Yolken New Brunswick, NJ: Rutgers University Press, 2005. 191 pp. $23.95 (cloth)


1403 Evaluation of Diatherix Laboratories TEM-PCR: a novel multiplex diagnostic panel for detection of bacterial and viral respiratory pathogens


Clinical Virology, 3rd Edition Edited by D. D. Richman, R. J. Whitley, and F. G. Hayden Washington, DC: ASM Press, 2009. 1408 pp, Illustrated. $259.59 (hardcover)


1 September News


1 June News


title: A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes

text: Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.


15 November News


Imported Infectious Diseases: The Impact in Developed Countries


Viruses and the Lung: Infections and Non-Infectious Viral-Linked Lung Disorders


15 August News


Emerging Infectious Diseases: Clinical Case Studies


1 April News


1 August News


docid: xfjxbefc

title: 15 December News


Genetics and Evolution of Infectious Diseases


ACCENT® Continuing Education Credit for Readers of Clinical Chemistry


How viruses use cells


title: Molecular diagnostic techniques

text: Clinical microbiology laboratories increasingly rely on molecular diagnostic techniques. The various formats of nucleic acid amplification are the most frequently used molecular tests in the diagnosis of infectious diseases. In many clinical settings, polymerase chain reaction (PCR) is clearly the method of choice due to its exquisite sensitivity and specificity. Today, many conventional PCR methods are being replaced by real-time PCR, which allows more rapid detection and quantification of the PCR product, as well as detection of different strains of the pathogen by melting curve analysis. The ability to measure the quantity of microbe by quantitative PCR has become increasingly important, providing information on the progression and prognosis of disease, and effectiveness of treatment. Other widely used molecular diagnostic techniques are isothermal amplification methods and nucleic acid hybridization techniques. Microarray is a technique which holds promise and has an exceptional sensitivity and the capacity to detect several pathogens simultaneously. However, microarrays are currently too expensive to be adapted for routine diagnostics, and their diagnostic use requires broad-based nucleic acid amplification prior to analysis which is not well established. Several molecular methods can be used for genotyping, which allows the identification of different subtypes of the pathogen; genotyping plays a role in the risk assessment and management of infections. Clinicians need to recognize the enhanced accuracy and speed of the molecular diagnostic techniques for the diagnosis of infections, but also to understand their limitations. Laboratory results should always be interpreted in the context of the clinical presentation of the patient, and appropriate site, quality, and timing of specimen collection are required for reliable test results.


title: Invasive and non-invasive mechanical ventilation

text: Early recognition of patients who might potentially require ventilatory support is a key goal of critical care outreach programmes and an important skill for all hospital medical staff. Decisions about the initiation and timing of invasive ventilation can be difficult, and early discussion with critical care colleagues is essential. Appropriateness of invasive ventilatory support can also require advanced discussion with patients and families. In the past 10–15 years, the role of non-invasive ventilation (NIV) has expanded, not least in an attempt to minimize the complications inherent in invasive ventilation. Indeed, NIV is now considered first-line therapy in some conditions (chronic obstructive pulmonary disease, pulmonary oedema, mild to moderate hypoxaemic respiratory failure in immunocompromised patients), and a ‘trial of NIV’ is often considered in respiratory failure resulting from an increasingly wide range of causes. With NIV, the importance of the environment (setting, monitoring, experience of staff) and forward planning cannot be overemphasized. When used for other than the standard indications, NIV should be employed in a high-dependency or intensive care setting in patients for whom invasive ventilation would be considered.


title: Acute exacerbations of chronic obstructive pulmonary disease: treatment and prevention

text: An acute exacerbation of chronic obstructive pulmonary disease (COPD) is sustained worsening of dyspnoea and sputum production in patients with COPD. They may be managed in the community with oral steroids and antibiotics but hospital referral is required where there is doubt about the diagnosis or if there are features of severity such as confusion, respiratory distress or haemodynamic instability. Regular review is required as failure to improve should prompt consideration of another diagnosis. In the emergency department, nebulized β(2)–agonists and anticholinergic bronchodilators should be given and arterial blood gases assessed. Patients with an arterial pH of 7.35 or less should be assessed for non-invasive ventilation. Patients who are stable and are not in type 2 respiratory failure should be considered for discharge if there is adequate home support. Warded patients should be discharged if they are stable for 24 hours and if both patient and doctor are confident that they can manage at home with outpatient follow-up at 4 to 6 weeks. About 25% of COPD patients may not have recovered to baseline lung function at this time.


text: Early recognition of patients who might potentially require ventilatory support is a key goal of critical care outreach programs and an important skill for all hospital medical staff. Decisions about the initiation and timing of invasive ventilation can be difficult and early discussion with critical care colleagues is essential. Appropriateness of invasive ventilatory support may also be an issue requiring advanced discussion with patients and their families. In the past 10–15 years, the role of non-invasive ventilation (NIV) has expanded, not least in an attempt to minimize the complications inherent with invasive ventilation. As such, NIV is now considered first-line therapy in some conditions (chronic obstructive pulmonary disease, pulmonary oedema, mild-to-moderate hypoxaemic respiratory failure in immunocompromised patients), and a ‘trial of NIV’ is often considered in respiratory failure resulting from an increasingly wide range of causes. When using NIV, the importance of the environment (setting, monitoring and experience of staff) and forward planning cannot be overemphasized. When used for other than the standard indications, NIV should be employed in a high-dependency/intensive care setting only in patients for whom invasive ventilation would be considered.


Methods in Molecular Medicine: Microarrays in Clinical Diagnostics. Thomas O. Joos and Paolo Fortina, editors. Totowa, NJ: Humana Press, 2005, 288 pp., $121.50, hardcover. ISBN 1-58829-394-7.


The next pandemic: on the front lines against humankind's gravest dangers


Program and Abstracts for the 2007 Meeting of the Society for Glycobiology


title: China vs the WHO: a behavioural norm conflict in the SARS crisis

text: This article studies a conflict over two competing norms in which the actors demonstrated incompatible positions not through arguments, but through actions. During the SARS crisis, China and the World Health Organization (WHO) entered a norm conflict over the precedence of sovereignty or global health security. Both resorted to behavioural, not discursive contestation: while the WHO practically but not rhetorically challenged the sovereignty norm by acting according to the norm of global health security, China—without openly acknowledging it—contravened the basic principles of global health security by acting according to the overlapping sovereignty norm. Why and with what consequences do actors choose to contest norms through actions rather than words? The article accounts for the resort to behavioural contestation by pointing to the strategic advantages it offers for furthering a contentious norm understanding without facing the social costs of making it explicit. It furthermore highlights that behavioural contestation may feed back into and change the odds of discursive contestation as its practical effects provide rhetorical resources to (de-)legitimate one or the other position. The propositions are illustrated in the interactions of China and the WHO during the SARS crisis and the subsequent norm development. This article forms part of the special section of the May 2019 issue of International Affairs on ‘The dynamics of dissent’, guest-edited by Anette Stimmer and Lea Wisken.


The New Global Threat. Severe Acute Respiratory Syndrome and Its Impacts. Tommy Koh, Aileen Plant, Eng Hin Lee. Singapore: World Scientific Publishing Company, 2004, pp. 356, $17.00 (PB) ISBN: 9812386688


IN THIS ISSUE


Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreak and National and Hospital Response in Korea


title: 171 Molecular breeding value prediction of pregnancy rate in Holstein dairy cows managed in a heat-stressed environment using candidate gene SNP

text: Reproductive performance in Holstein dairy cattle managed during summer in southern Sonora is a challenge because of high ambient temperature and relative humidity. Both of these factors contribute to heat stress, which influences cow behavior. The physiological response of cows to heat stress is one component of a system-wide gene network. Within this environment, a superior cow's ability to get pregnant early during postpartum is favorable as to reduce the trait days open and to increase productive life. Recently, many reproductive specialists have recommended using pregnancy rate as a measure of reproductive success, after converting this trait into a quantitative value using a linear formula. In comparison to the traditional measure of days open, pregnancy rate calculation includes more easily cows that do not become pregnant; furthermore, the output variable indicates that larger values are more desirable, and therefore, more understandable by dairy producers. The objective herein was to predict pregnancy rate in lactating Holstein cows using molecular markers associated with fertility in Holstein cows under a heat-stressed environment. This study included 500 cows from three dairy herds located in the Yaqui Valley of Sonora. A blood sample was collected from every cow and spotted onto FTA cards. The DNA was extracted from each card and used to genotype 179 tag SNP within 43 genes in the prolactin and GH-IGF1 pathways. Five SNP within the genes IGFBP7, IGFBP2, PAPPA1, SSTR2, and STAT6 were associated with pregnancy rate using a mixed effects model. The genotype term was later included in this model to calculate allele substitution effects. Molecular breeding values of the individual cows were calculated by summing the additive genotype effect for each SNP that showed a significant independent association with pregnancy rate, and the average MBV was 0.46 ± 0.01%. Two statistical regression models were used to predict the variable pregnancy rate: a full model that included effects of days and number of lactations, contemporary group (e.g., farm management group), health status, and MBV and a reduced model that only included MBV. Coefficients of determination were 37.61% and 3.07% for full and reduced models, respectively (P < 0.01). These results indicate that five SNP explained only a small proportion of the additive genetic variance for pregnancy rate. Additional research is needed to understand if these results are due to low heritability/repeatability of a fertility and (or) if these results are also influenced by heat stress.