bluuebunny/crossref_metadata_2025_split huggingface dataset:
726. Viral Genomic Load, Cytokine Profiles and Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants
Authors: Ferolla Fausto Martin , Caratozzolo Ana , Toledano Analía , Anselmino Cecilia , Lobo Carlos Mauricio Vergara , Chiormi Maria Agustina , Visingardi Gabriela , Ratto Patricia , Theiler Graciela , Neira Pablo , Dastugue Mónica , Mascardi Normando , Contrini Maria Marta , Lopez Eduardo 
Published: November 2018

Abstract

Background
Data are controversial regarding the role of viral load and the host immune response in the severity of respiratory syncytial virus (RSV) infection. The objective of this study was t. o analyze the relationship between viral load (VL) and host cytokine responses with RSV life-threatening disease (LTD).

Methods
Prospective cohort study including previously healthy infants &lt;12 months, hospitalized with a first RSV infection in 2017. Viral titers were assessed by qPCR and cytokine levels measured in nasopharyngeal aspirates obtained on admission. All patients with LTD were admitted to the intensive care unit.

Results
Fifty-one patients, median age 3 months (IQR 2–4), 29(56.9%) male. Eight developed LTD (1,569 LTD cases/10,000 RSV-hospitalizations/year [95% CI 702–2.859]). Antibiotic prescription was significantly higher (42.9 vs. 87.5%, P &lt; 0.001) and length of hospitalization significantly prolonged (5.2 ± 1.9 vs. 16.1 ± 12.7 days, P &lt; 0.001) in infants with LTD. No differences were seen in the number of amplification cycles needed for a positive qPCR test (CT) nor in the viral titers of patients with LTD compared with those with better outcome (P = 0.71), Figure 1. VL was not a predictor of LTD (AUC = 0.53); however, no LTD was seen with ≤159,200 copies/mL. CT/VL did not correlate with other outcomes (Figure 2). IFN-y levels (Th1 response) were significantly lower in infants with LTD (P = 0.034). We detected no differences in TNF-α (pro-inflammatory), IL-9, IL-13 (Th2), IL-10 or IL-17 (regulatory) levels from mildly/severely or extremely severe ill patients; lower IL-5 levels were seen in LTD (Figure 3). VL correlated with TNF-α (P &lt; 0.001) and IL-10 (P &lt; 0.001) levels. After logistic regression analysis, socioeconomic, pregnancy and infant variables showed no association with bad outcomes; only frequent consumption of fruits and vegetables during pregnancy conferred protection (aOR 0.03; P &lt; 0.001).

Conclusion
RSV titers did not correlate with LTD. Lower levels of IFN-γ were associated with increased disease severity.
These findings could provide additional data for future RSV preventive and therapeutic strategies.

Disclosures
All authors: No reported disclosures.
745. Surveillance for Oseltamivir-Resistant Influenza A(H1N1)pdm09 Virus Infections During 2016–2017 and 2017–2018, United States
Authors: Spencer Sarah , Nguyen Ha , Elal Anwar Abd , Laplante Jennifer , George Kirsten St , Fry Alicia M , Gubareva Larisa , Campbell Angela P 
Published: November 2018

Abstract

Background
Three neuraminidase inhibitors (NAIs) are approved and recommended for treatment of influenza in the United States; however, antiviral resistance can emerge during or after treatment, and sporadic resistant viruses unrelated to NAI exposure may occur, especially in influenza A(H1N1)pdm09 viruses. Limited transmission of oseltamivir-resistant A(H1N1)pdm09 viruses between persons has also occurred. Oseltamivir resistance is most commonly caused by an H275Y substitution in the neuraminidase (NA). We describe findings from surveillance for oseltamivir-resistant A(H1N1)pdm09 viruses.

Methods
The CDC requested state public health laboratories to submit up to eight viruses (two of each subtype/lineage) every 2 weeks for virus sequencing and NA inhibition assay testing; up to five additional A(H1N1)pdm09 clinical specimens were requested for H275Y pyrosequencing. NA sequencing and functional phenotypic NA inhibition assays were performed on drug-resistant virus isolates. A standard case form was collected on persons infected with oseltamivir-resistant viruses.

Results
From October 1, 16 to April 18, 18, 1,368 A(H1N1)pdm09 viruses were tested (median 89 specimens, range 20–328, tested/month during the influenza season). Overall, 12 (~0.9%) oseltamivir-resistant A(H1N1)pdm09 viruses were detected from nine states; all contained H275Y in the NA. All viruses were also resistant to peramivir, but none to zanamivir. The 12 patients had a median age of 34 years (range, 2 months–69 years). Eight (67%) had an immunosuppressive condition. Six (50%) reported no exposure to NAIs before specimen collection, two were taking oseltamivir (for 1 and 20 days) at the time of specimen collection, and antiviral receipt was unknown for 4. Three (23%) patients were hospitalized; there were no deaths.

Conclusion
During the 2016–2017 and 2017–2018 influenza seasons, influenza A(H1N1)pdm09 viruses resistant to both oseltamivir and peramivir were infrequently detected; all retained susceptibility to zanamivir. Among those with available information, half had no exposure to oseltamivir. Viruses harboring H275Y continue to circulate at low levels in the community. Ongoing surveillance for trends in oseltamivir- and peramivir-resistant A(H1N1)pdm09 is critical to inform clinical care and public health policies.

Disclosures
All authors: No reported disclosures.
749. Healthcare Utilization After Hospitalization for Respiratory Syncytial Virus or Unspecified Bronchiolitis in the First Year of Life
Authors: Ledbetter Joel , Brannman Lance , Wade Sally , Diakun David , Gonzales Tara , Kong Amanda 
Published: November 2018

Abstract

Background
Respiratory syncytial virus (RSV) is the leading cause of infant hospitalizations and risk varies by gestational age (GA). Healthcare utilization following early hospitalizations caused by RSV (RSVH) or unspecified bronchiolitis (UBH) is not well understood. This study examined healthcare resource utilization (HRU) across GA categories within 12 months after an initial RSVH or UBH occurring in the first year of life.

Methods
Infants born July 1, 2009 to June 30, 2015 were identified in the MarketScan Commercial (COM) and Multistate Medicaid (MED) databases and assigned to GA categories using DRG and ICD codes and to an initial hospitalization cohort using inpatient claim diagnosis codes (RSVH, UBH without RSVH, or COMP [a comparator without RSVH or UBH]). Index dates (first admission dates for hospitalized infants) were assigned to COMP infants using times from birth to index dates among RSVH infants. HRU (hospitalizations, outpatient pharmacy fills, and visits for emergency department [ED], urgent care, wellness, other office or outpatient) excluded index hospitalizations and was assessed from 14 days post-index (or discharge if later) through 12 months post-index. Results were propensity score weighted to balance pre-index characteristics (age, sex, region, GA, birth hospitalization characteristics) across cohorts. Proportions were compared with chi-squared tests.

Results
Among all infants (all GA categories combined), the proportions of RSVH and UBH cohorts with follow-up hospitalizations or ED visits were greater (P &lt; 0.05) than COMP (hospitalizations: COM +5.8%, +9.3%; MED +9.1%, +12.0%; ED visits: COM +15.8%, +16.2%; MED +14.4%, +17.1%). Follow-up hospitalizations in COM and MED and ED visits in COM declined with greater GA (Figures 1 and 2). HRU in other categories (fills, visits) was significantly (P &lt; 0.05) greater among RSVH or UBH infants relative to COMP for nearly all GA categories in both COM and MED.

Conclusion
Infants hospitalized for RSV or UB in their first year of life had greater use of inpatient and outpatient resources in the 12 months following their initial hospitalizations compared with nonhospitalized infants. Inpatient care during follow-up was greatest among infants born at earlier GA.
Funded by AstraZeneca

Disclosures
J. Ledbetter, AstraZeneca: Speaker’s Bureau, Speaker honorarium. L. Brannman, AstraZeneca: Employee, Salary and Stocks. S. Wade, Wade Outcomes Research and Consulting: Employee, Salary. D. Diakun, Truven Health Analytics, an IBM Company: Employee, Salary. T. Gonzales, AstraZeneca: Employee, Salary and Stocks. A. Kong, Truven Health Analytics, an IBM Company: Employee, Salary.
756. Targeting the Birth-Cohort of the Pre-antibiotic Era: A Proposal to Screen for Tuberculosis in Seniors in Arkansas
Authors: Gu Mofan , Fischbach Lori , Patil Naveen , Bates Joseph , Mukasa Leonard 
Published: November 2018

Abstract

Background
Approximately 13 million (4.7%) people in the United States have latent TB infection (LTBI). Persons born prior to 1951 have disproportionately higher LTBI prevalence, and frequently experience delays in TB diagnosis and TB deaths. Nevertheless, this birth-cohort was overlooked in the 2016 US Preventive Service Task Force (USPSTF) recommendation for LTBI screening. The aims of this project are to (1) determine the LTBI prevalence in this birth-cohort, (2) assess TB complications prevented by LTBI screening in this birth-cohort, and (3) raise TB awareness among providers and the community.

Methods
We propose to: (1) Develop educational pamphlets for the physicians and community. (2) Screen 10,000 members of the target birth-cohort during their routine clinical visits for 1 year, using T-SPOT.TB. County health officers, the partners of Arkansas Department of Health, will enroll physicians in their jurisdictions to participate in TB screening. LTBI prevalence in the birth cohort will be determined, and TB complications will be compared among cohort TB cases that were screened to those not previously screened. (3) Incorporate LTBI and birth-cohort status in patient medical forms.

Results
In our preliminary study, for the period 2009–2014, 142 of 326 TB cases (43.6% of all US-born TB cases) were reported from the target birth-cohort; 72.6% of the cases had unique genotype strains.

Conclusion
If the LTBI prevalence in this birth cohort exceeds 8–10%, we recommend a nation-wide screening program for this birth-cohort. Even without treatment, we believe that screening and noting diagnosis of LTBI in the patient record will impact delayed diagnosis and mortality.

Disclosures
All authors: No reported disclosures.
761. Age-Related Incidence of TB Infection Supporting Efficacy of BCG Vaccination
Authors: Sweeney Eileen , Dahly Darren , Seddiq Nahed , Horgan Mary , Corcoran Dan , Sadlier Corinna 
Published: November 2018

Abstract

Background
Mycobacterium tuberculosis (MTB) is a major, and potentially preventable, cause of morbidity and mortality worldwide. Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine for TB, and while efficacy has been demonstrated in some populations, many uncertainties remain. Three BCG vaccination policies were implemented across bordering geographical regions in the South West of Ireland from 1972; neonatal vaccination (vaccinated region-a), vaccination of children aged 10–12 years (vaccinated region-b) and no vaccination (unvaccinated region-c). The aim of this study was to investigate the impact of BCG vaccination on incidence of MTB during the study period.

Methods
Surveillance data were used to identify all M. tuberculosis complex (MTC) isolates from 2003 to 2016. Residential addresses for each case were geocoded using the Google Maps API. Case locations were spatially linked to 2011 census population data and to Local Health Offices (LHO) BCG coverage data for study regions a–c. The 13-year incidence of TB was calculated assuming a steady-state population. Using SatScan (v9.4.4), spatial clusters were identified at the small area level with the spatial scan statistic based on the discrete Poisson probability distribution.

Results
Of 638 MTC infections identified (621 MTB, 16 M. bovis, 1 M. africanum), 510 occurred in study regions a–c (median age 42 years (4 months–94 years), 65% male and 66% Irish born). The incidence of MTB was higher in the unvaccinated population, region-c 132/100,000 (95% CI 116–150) vs. vaccinated region-a 56/100,000 (95% CI 45–69) and region-b 44/100,000 (95% CI 29–63). A single high-risk cluster of 138 cases within a population of 46,000 was identified in unvaccinated region-c (relative risk 4.94 (95% CI 4–6). The year-on-year incidence rates in the 20- to 35-year-old age range suggested a decreasing risk consistent with a beneficial impact of vaccination policies.

Conclusion
Prevention and treatment of TB remains a significant challenge worldwide. Our study demonstrates significant differences in incidence of MTC infection in demographically similar populations based on BCG immunization policy and thus further supports efficacy of BCG for prevention of tuberculosis infection.

Disclosures
All authors: No reported disclosures.
763. Risk Factors for Homeless Status and Mortality Among Homeless TB Cases in Texas, 2010–2017
Authors: Agarwal Saroochi , Nguyen Duc T , Graviss Edward A 
Published: November 2018

Abstract

Background
A disproportionate amount of tuberculosis (TB) cases and mortality occur among people experiencing homelessness in the United States. Our objective was to identify risk factors for mortality among reported homeless TB cases in Texas, a state with an increased TB prevalence in the United States.

Methods
Using data from the Centers for Disease Control and Prevention TB Genotyping Information Management System (TB GIMS), we evaluated the demographic, laboratory and clinical characteristics of people identified as being homeless in the year preceding TB diagnosis in Texas from January 1, 2010 to December 31, 2017. TB cases with missing or unknown homeless status were removed from the analysis. Multivariate logistic regression was used to analyze and evaluate risk factors associated with homeless status and mortality among homeless TB cases.

Results
Of the 10,103 newly diagnosed TB cases over the 8-year period, 543 (5.4%) were reported as being homeless in the year preceding TB diagnosis. In 412 homeless TB patients with a reported outcome as “died” or “completed,” 57 (13.8%) died during treatment and 355 (86.2%) completed therapy. Age &gt;45, male, black ethnicity, foreign-born, urban living, excessive alcohol consumption, IDU, long-term care facility resident, diabetes, previous TB, and pulmonary TB were associated with homeless TB cases. Being homeless and having TB increased the risk of mortality compared with having TB alone (OR 2.26, P &lt; 0.01). Age &gt;45 years, positive HIV status, cavitary and miliary radiographic findings, no or unknown culture conversion and TB case confirmation by a positive culture/NAA/smear compared with clinical case definition/provider diagnosis were independent risk factors for mortality among homeless TB cases in Texas.

Conclusion
Being homeless increased the risk of TB mortality by nearly 130% compared with being housed prior to TB diagnosis. Our findings indicate that homelessness may be being diagnosed and treated in more advanced TB diseased homeless individuals who probably have poorer health due to the stresses of poverty, comorbidities, and lack of access to healthcare, leading to higher mortality. Additionally, testing and treatment for HIV among those reporting homelessness may reduce mortality among this high-risk group.

Disclosures
All authors: No reported disclosures.
765. Tuberculosis and Diabetes Mellitus Among Prison Inmates in Peru: Results of a National Survey, 2016
Authors: Rojas-Bolivar Daniel , Zhu Zheng , Hurtado Yamilee , Zavaleta Milagros , Sanchez Jorge , Jandarov Roman , Alarcon Jorge , Huaman Moises 
Published: November 2018

Abstract

Background
Diabetes mellitus (DM) increases the risk of tuberculosis disease (TB) and is associated with poor TB treatment outcomes in the general population. We examined the relationship between TB and DM in prison inmates in Peru.

Methods
We analyzed data from a cross-sectional, national survey of adult prison inmates in Peru conducted in 2016. The survey collected sociodemographic and medical information via standardized interview. Medical conditions were defined by self-report. We used multivariate logistic models for adjusted analyses of the relationship between TB and DM.

Results
Of 75,971 inmates, 3,104 (4.3%) reported a history of TB diagnosis. Table 1 shows the characteristics of the TB and non-TB groups. The prevalence of DM was higher in the TB group compared with the non-TB group (4.2% vs. 2.4%; P &lt; 0.001). In multivariate analysis, DM was associated with twice the odds of having had a diagnosis of TB (adjusted OR = 2.2; 95% CI: 1.8–2.7). Male sex, Spanish language, no college/university education, reimprisonment, hypertension, and HIV infection were also associated with increased odds of prevalent TB (Figure 1).

Conclusion
There was a high prevalence of TB among prison inmates in Peru. DM was associated with an increased likelihood of prevalent TB. Our results are consistent with findings in noninstitutionalized populations and underscore the need to implement aggressive screening and treatment interventions for both TB and DM in prison settings.

Disclosures
All authors: No reported disclosures.
780. Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in US Medicare, 2008–2015
Authors: Winthrop Kevin L , Adjemian Jennifer , Mirsaeidi Mehdi , Marras Theodore , Eagle Gina , Zhang Raymond , Wang Ping , Chou Engels , Zhang Quanwu 
Published: November 2018

Abstract

Background
Previous research has reported nontuberculous mycobacterial lung disease (NTMLD) prevalence of 47 per 100,000 among Medicare beneficiaries ≥65 years in 2007, with an average increase of 8.2% annually between 1997 and 2007. In this study, we have evaluated NTMLD incidence and prevalence in Medicare between 2008 and 2015.

Methods
Patients diagnosed for NTMLD with an ICD9 031.0 were identified from the Medicare database (N≈30 million yearly), not including the Part C portion. Individuals who incurred at least 2 medical claims ≥30 days apart between 2007 and 2015 were considered as a positive NTMLD case, yielding 58,294 patients. All individuals fulfilling the case definition each calendar year were considered as prevalent cases. Incident cases included those meeting case criteria and who did not have a Medicare claim for NTMLD in the prior year. Poisson regression was used to estimate yearly confidence intervals. ARIMA models were used to forecast incidence and prevalence over 2016–2025.

Results
Patients with NTMLD in the Medicare database had a mean age of 74 (standard deviation: ±10) years. Sixty-nine percent were women and 89% white. Yearly NTMLD incidence increased from 20.7 (95% CI: 20.2–21.3) in 2008 to 28.1 (27.5–28.7) in 2013 per 100,000 Medicare beneficiaries and leveled to 27.6 (26.9–28.2) in 2014 and 25.9 (25.3–26.5) in 2015 per 100,000. Yearly NTMLD prevalence increased throughout the observation period from 41.6 (40.9–42.3) in 2008 to 63.1 (62.2–64.0) in 2015 per 100,000 Medicare beneficiaries. Incidence was 28.1 vs. 14.7 per 100,000 in 2015 in Medicare beneficiaries ≥65 years vs. those &lt;65 years, respectively. Prevalence was 70.2 vs. 27.9 per 100,000 in 2015 in Medicare beneficiaries ≥65 years vs. those &lt;65 years, respectively. In 2015, incidence and prevalence were higher in women than men (33.9 vs. 16.0/100,000 and 86.2 vs. 34.6/100,000, respectively) and among individuals of Asian origin compared with White (41.1 vs. 27.6/100,000 and 89.4 vs. 68.7/100,000, respectively). The 10-year incidence and prevalence forecasts were presented in figures.

Conclusion
In US Medicare beneficiaries, NTMLD incidence increased from 2008 through 2013 and leveled off in more recent years, while NTMLD prevalence continued to rise through 2015.

Disclosures
K. L. Winthrop, Insmed Incorporated: Scientific Advisor, Consulting fee and Research grant. T. Marras, Insmed Incorporated: Investigator, Consulting fee and Research grant, Horizon Pharmaceuticals: Consultant, Consulting fee, Red Hill: Consultant, Consulting fee, AstraZeneca: CME, Speaker honorarium. G. Eagle, Insmed Incorporated: Employee, Salary. R. Zhang, Insmed Incorporated: Consultant, Consulting fee. P. Wang, Insmed Incorporated: Employee, Salary. E. Chou, Insmed Incorporated: Employee, Salary. Q. Zhang, Insmed Incorporated: Employee, Salary.
792. Number and Volume of Cavitary Lesions on Chest Computed Tomography Associated With Prolonged Time to Culture Conversion in Drug-Susceptible Pulmonary Tuberculosis
Authors: Hernandez Alfonso 
Published: November 2018

Abstract

Background
Cavitary lesions (CLs) may be a marker of poor treatment response in pulmonary tuberculosis (PTB). Identification of CLs by chest roentgenogram (CXR) has important limitations. Chest computed tomography (CT) is more sensitive than CXR to detect CLs but the clinical relevance of CLs identified by CT remains understudied. We compared detection of CLs between CT and CXR and assessed their association with time to sputum culture conversion (tSCC). We hypothesized that increasing number and volume of CLs on CT would be associated with prolonged tSCC.

Methods
Retrospective cohort study of 141 culture confirmed PTB patients who underwent chest CT. We used multivariate Cox proportional hazards models to evaluate the association between chest radiological features and tSCC.

Results
Seventy-five (53%) patients had one or more CLs on CT. CT identified cavities in 31% of patients without a CL on CXR. Detection of cavity on CT was associated with an increased median [IQR] time to culture conversion (15 [7–35] days among noncavitary CT vs. 39 [25–55] days among cavitary CT; P &lt; 0.0001). Among patients without CL on CXR, detection of CL on CT was associated with prolonged tSCC (median difference (CI): 16 (7–25) days, P = 0.0008). Similar results were observed among patients with 3–4+ sputum smear (median difference: 19.5 (8–31) days, P = 0.001). Adjusted Kaplan–Meier curves of number and volume of CLs and tSCC are shown in Figure 1. After confounder adjustment patients with single and multiple CL had a prolonged tSCC relative to patients without CLs on CT (adjusted Hazard Ratio [aHR] 0.56 (0.32–0.97) and 0.31 (0.16–0.60), respectively). Similarly, patients with CL volume 25 mL or more had a prolonged tSCC (aHR 0.39 (0.21–0.72)). CXR CL was not associated with prolonged tSCC.

Conclusion
We observed a dose–response relationship between increasing number and volume of CLs on CT and delayed tSCC independent of sputum bacillary load. Our findings highlight a role for CT in a clinical research setting to predict shorter time to culture conversion.

Disclosures
All authors: No reported disclosures.