bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Neuronal Susceptibility and Apoptosis in Congenital Zika Virus Infection
Authors: Ho Cheng-Ying , Ames Heather , Tipton Ashley , Vezina Gilbert , Liu Judy , Scafidi Joseph , Torii Masaaki , Rodriguez Fausto , duPlessis Adre , DeBiasi Roberta 
Published: October 2017

Abstract

Background
Zika virus (ZIKV) infection during pregnancy may result in severe neurologic injury to the fetus. The mechanisms by which ZIKV injures fetal brain are not fully characterized. Although cell culture and animal models shed valuable insight into pathogenesis, they do not fully recapitulate human disease.

Methods
To characterize the mechanism of ZIKV-induced human brain injury, we performed immunolabeling on brain tissue from a 20-week fetus with intrauterine ZIKV infection. Formalin-fixed sections of brain tissue were co-immunostained with ZIKV envelope antibody, as well as neuronal and non-neuronal lineage cell markers to assess infection within populations. Apoptosis was assessed by quantifying activated caspase 3 -positive staining cells. Minimum 3–5 random microscopic fields per brain region were photographed and quantified in an automated fashion using the ImageJ Cell Counter plug-in. GraphPad Prism and Microsoft Excel software were used for data analysis.

Results
ZIKV demonstrated a wide range of neuronal and non-neuronal tropism. However, infection rate was highest in Tbr2+ - Intermediate Progenitor Cells (IPC; 81.4±12%) and DCX+ Immature Neurons (IN; 51.5±13.9%), followed by SOX2+/ Nestin+ Neural Precursor Cells (NPC; 26.6±13.4%). NeuN+ Mature Neurons had the lowest frequency of infection (MN; 10.0±7.0 %) (Figure). Apoptosis was observed in both infected and uninfected bystander cortical neurons. A high infection frequency was also observed in non-neuronal cells (astrocytes, microglia, macrophages, lymphocytes).

Conclusion
Our study provides valuable insights into ZIKV pathogenesis in the fetus; it is the first to demonstrate differential infectivity/susceptibility of neuronal lineage cells to ZIKV, and evidence of apoptosis in and around these cells. The high frequency of ZIKV+ IPC and IN implies that that infection can be supported until the immature stage of neuronal differentiation. The resistance of mature neurons to ZIKV infection may also explain why ZIKV infection in the third trimester poses less risk of microcephaly in infants. The high infection rate of non-neuronal cells also suggests potential contribution of immune-mediated mechanisms of brain injury in the setting of congenital ZIKV infection.

Disclosures
All authors: No reported disclosures.
Impact of Prior Vaccination History on Risk of Vaccine Failure with Live Attenuated and Inactivated Influenza Vaccines in Children, 2013–14 through 2015–16
Authors: McLean Huong Q , Caspard Herve , Griffin Marie R , Gaglani Manjusha , Peters Timothy R , Poehling Katherine A , Ambrose Christopher S , Belongia Edward 
Published: October 2017

Abstract

Background
Prior season vaccination may influence influenza vaccine effectiveness; however, little is known about the impact of prior vaccination or vaccine type received. We assessed prior vaccination history and risk of influenza in children over 3 seasons.

Methods
Children aged 2–17 years seeking outpatient care for febrile acute respiratory illness were recruited during the 2013–14 through 2015–16 seasons (1 vaccine-mismatched H3N2 season and 2 H1N1pdm09 seasons) at 4 US sites. Influenza was confirmed by RT-PCR. Vaccination data for the season of enrollment (current) and 3 prior seasons were obtained from medical records and immunization registries. Among children who received 1 dose of influenza vaccine during the current season, risk of vaccine failure (ie, PCR-confirmed influenza) was estimated using test-negative design with logistic regression models adjusted for age, season, enrollment site, enrollment week (relative to peak), and outpatient visits. Risk of failure with live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) were modeled separately. Separate models were used for vaccine history based on number of seasons and vaccine type received (ie, none, LAIV, IIV, both).

Results
Influenza was detected in 191 (12%) of 1601 children who received 1 vaccine dose during the current season: 117 H3N2 and 74 H1N1pdm09. Among 508 current season LAIV recipients, 239 (47%) received LAIV and 144 (28%) received IIV in the prior season. Among 1093 current season IIV recipients, 94 (9%) received LAIV and 711 (65%) received IIV in the prior season. For LAIV, receipt of vaccine (any type) in a prior season was associated with a decreased risk of H3N2 failure (odds ratio 0.23; 95% CI, 0.09–0.57). Prior vaccination was not associated with risk of LAIV vaccine failure against H1N1pdm09. For IIV, there was no evidence that prior vaccination was associated with risk of vaccine failure against H3N2 or H1N1pdm09. Similar results were seen in children without any high-risk conditions.

Conclusion
Risk of vaccine failure among vaccinated children varied by vaccine type and virus subtype. Future studies should examine immunologic effects to better understand these differences.

Disclosures
H. Q. McLean, MedImmune: Grant Investigator, Research support; H. Caspard, MedImmune: Employee, Salary; M. R. Griffin, MedImmune: Grant Investigator, Grant recipient; M. Gaglani, MedImmune: Investigator, Research support; T. R. Peters, MedImmune: Investigator, Research support; K. A. Poehling, MedImmune: Investigator, Research support; C. S. Ambrose, AstraZeneca: Employee, Salary; E. Belongia, MedImmune: Grant Investigator, Research support
Impact of a Provider Communication Training Intervention on Adolescent Human Papillomavirus Vaccination: A Cluster Randomized, Clinical Trial
Authors: O’Leary Sean , Pyrzanowski Jennifer , Lockhart Steven , Barnard Juliana , Campagna Elizabeth , Garrett Kathleen , Fisher Alison , Dickinson Miriam , Dempsey Amanda 
Published: October 2017

Abstract

Background
Effective human papillomavirus (HPV) vaccines have been available in the US for several years but are underutilized. Provider communication about the vaccine is a key factor influencing uptake, yet effective communication tools are lacking or untested. Our objective was to evaluate the impact of a Motivational Interviewing-based 5-component provider HPV vaccine communication intervention on adolescent HPV vaccine uptake.

Methods
This was a cluster randomized controlled trial of 16 primary care practices in the Denver area that included 188 medical providers and 43,132 adolescent (11–17 years old) patients. The 5-components of the intervention included an HPV fact library to create practice-specific HPV fact sheets, a tailored parent education website, HPV-related disease images, an HPV vaccine decision aid, and 2 hours of in-person communication training on using a presumptive vaccine recommendation followed by Motivational Interviewing (MI) if parents were vaccine hesitant. Each practice participated in a series of 4 intervention development meetings over a 6 month period (8/2014 – 1/2015) before launching the intervention. Primary outcomes were differences between control and intervention practices over time (i.e., “difference in difference” (DID)) in HPV series initiation (≥1 dose), and completion (≥3 doses) among 11–17 year old patients seen between 09/01/2013-08/31/2014 and 2/1/2015-1/31/2016. Vaccination data were obtained from clinics’ records and augmented with a state immunization registry.

Results
Adolescents in the intervention practices had a significantly higher odds of HPV series initiation over time than those in control practices (DID Adjusted Odds Ratio (AOR) 1.46, 95% Confidence Interval (CI) 1.31–1.62) and completion (AOR 1.56, 95% CI 1.27–1.92). This translated into a 9.5 absolute percentage point (PP) increase in HPV series initiation, and a 4.4 PP increase in HPV series completion in intervention practices over control practices. The intervention had a greater impact in pediatric compared with family medicine practices, and in private practices compared with public.

Conclusion
Implementation of a 5-component HPV vaccine provider communication intervention significantly improved HPV vaccine series initiation and completion among adolescent patients.

Disclosures
A. Dempsey, Merck, Pfizer, Sanofi pasteur: Consultant, no research funding
Decrease in Antibiotic Sales in Brazil After New Control Legislation
Authors: Slain Douglas , Lopes-Júnior Rogerio , De Toledo Maria Inês , Del Fiol Fernando , Barberato-Filho Silvio 
Published: October 2017

Abstract

Background
Brazil, like many Latin American countries, has struggled with the inappropriate use of antibiotics in the community without a prescription form a physician. Since November 2010, The Brazilian Health Surveillance Agency has established stricter control of antibiotic sales, which requires that a copy of antibiotic prescriptions be retained by the pharmacy for audit. Pharmacists now also have more severe civil and criminal liability if they allow the sale of antibiotics without a prescription. The aim of this study was to analyze the impact of the new legislation preventing the sale of antibiotics in pharmacies without a prescription.

Methods
The data for antibiotic usage in units was collected from electronic monitoring of pharmacy members of the Brazilian Federation of Pharmacies (FEBRAFAR), which tracked information about the antibiotics sold in approximately 3,000 pharmacies from 1,500 municipalities across Brazil. We compared the sale of antibiotics during two time periods: 12 months prior to the new legislation and 12 months after.

Results
We observed a reduction in pharmacy sales of each class of antibiotics included in this study following the implementation of the new legislation. Pharmacy sales for 27 (84.4%) of the 32 antibiotics included in the study were reduced in response to the new legislation, whereas sales of five antibiotics were increased. Overall, tetracycline (−57.8%), co-trimoxazole (−28.8%), and amoxicillin (−29.1%) showed the largest reduction of all agents. With month to month analysis, the greatest reduction in units sold/month was observed for the following therapeutic classes: tetracyclines (30.5%), sulfonamides (28.5%), macrolides (25.0%), and penicillins (20.5%). Yearly trend analysis showed a significant reduction in antibiotics during the winter months (average monthly difference: −31.5%, P &lt; 0.05)

Conclusion
The reduction in the number of antibiotic units sold by pharmacies after the implementation of legislation designed to regulate antibiotic use in Brazil suggests that the policy is successful and will contribute to rational use of antibiotics in Brazil.

Disclosures
All authors: No reported disclosures.
Outcomes of a Provincial Pilot Program to Reduce Unnecessary Urine Culturing and Antibiotic Overuse in Long-term Care
Authors: Brown Kevin , Chambers Andrea , Leung Valerie , Langford Bradley , Quirk Jacquelyn , Garber Gary 
Published: October 2017

Abstract

Background
Antibiotics are frequently prescribed for long-term care residents with asymptomatic bacteriuria, for which there is no indication. In order to help reduce unnecessary urine culturing and concomitant antibiotic use, C. difficile infection, and antibiotic resistance, Public Health Ontario (PHO) developed a multi-component organizational change program. The program focuses on five practice changes, recommends nine implementation strategies that have been linked to barriers, and includes an implementation planning process.

Methods
A purposive sampling strategy was used to recruit 12 long-term care homes (LTCHs) in the province of Ontario, Canada. LTCHs worked with PHO staff to implement the program over a 4-month period in mid-2016. The outcome evaluation compared rates of urine cultures sent, total antibiotics, and urinary antibiotics (ciprofloxacin, nitrofurantoin, TMP/SMX, and fosfomycin) per 1,000 resident days before and after the implementation phase. A Poisson regression model adjusting for time-trends, seasonality and controlling for autocorrelation, was used.

Results
Of the 12 LTCHs recruited, as of May 2017, 9 LTCHs provided data, totaling 106 facility-months. During the pre-implementation phase, inter-facility variation in urine culturing rates (mean = 2.4, inter-decile range [IDR] = 4.3), total antibiotic use (median = 3.2, IDR = 5.5), and urinary antibiotic use (median = 1.2, IDR = 2.2), were large (Figure 1). Comparing the post-implementation period to the pre-implementation period, we observed a 31% adjusted decline in urine culturing (incidence rate ration [IRR] = 0.69, 95% CI: 0.51 to 0.94, Figure 2), a 65% adjusted decline in total antibiotic use (IRR = 0.35, 95% CI: 0.13 to 0.92), and a 38% adjusted decline in urinary antibiotic use (IRR = 0.62, 95% CI: 0.23 to 1.68) across the participating facilities.

Conclusion
While there was variation in baseline urine culturing rates and antibiotic use across LTCHs, preliminary data indicate that these outcomes declined in a relatively short time period following implementation of an organizational change program. Plans to expand the program to the provinces 600 LTCHs could prioritize facilities with high baseline urine culturing rates.

Disclosures
All authors: No reported disclosures.
A population-based Study of Recurrent Symptomatic Bordetella pertussis Infections in Children in California, 2010–2015
Authors: Platt Lauren , Thun Melissa , Harriman Kathleen , Winter Kathleen 
Published: October 2017

Abstract

Background
Natural infection with Bordetella pertussis is thought to result in 4–20 years of immunity against subsequent symptomatic pertussis infection. However, these estimates are based on studies in unvaccinated or whole-cell vaccinated children. We conducted a population-based study of pertussis infection and reinfection during a 5-year period in California in an exclusively acellular-pertussis vaccinated cohort.

Methods
California surveillance data were reviewed to identify all children with two reported incidents of pertussis with symptom onset from January 1, 2010 through December 31, 2015. Case investigation reports were reviewed and children with at least two episodes of symptomatic pertussis infection that met the case definition were included.

Results
Of 26,259 pertussis cases reported in children &lt;18 years, 27 children met the inclusion criteria. Recurrent cases occurred among children of all ages, and the median age for the first and second pertussis episodes were 3.5 years (range, 1.3 months-14 years) and 6.5 years (range, 5.2 months–16.3 years) respectively. The median duration of time between initial infection and reinfection was 1.3 years (range, 2.9 months–4.4 years). Twenty-one children (78%) had received ≥3 doses of DTaP vaccine at the time of their first pertussis infection, 1 (4%) had received 1 dose, and 5 (19%) were unvaccinated.

Conclusion
Recurrent cases of pertussis infection are very rare. Contrary to previous reports that natural infection with B. pertussis results in 4–20 years of sterilizing immunity, we demonstrate that symptomatic reinfection with pertussis can occur as soon as 89 days following the first infection. More research is needed to understand the immune response to B. pertussis infection in children vaccinated with acellular-pertussis vaccines.

Disclosures
All authors: No reported disclosures.
Cervical Adenocarcinoma in Situ in the United States: Results from Population-based Laboratory Surveillance, 2008–2014
Authors: Cleveland Angela Ahlquist , Johnson Michelle L , Gargano Julia W , Park Ina U , Griffin Marie R , Niccolai Linda M , Schafer Sean , Bennett Nancy M , Markowitz Lauri E , Unger Elizabeth R 
Published: October 2017

Abstract

Background
Cervical cancer screening methods are more effective for detection of squamous cell carcinoma precursor lesions (cervical intraepithelial neoplasia; CIN2 and 3) than for less-common adenocarcinoma precursors (adenocarcinoma in situ; AIS). Primary prevention through human papillomavirus (HPV) vaccination is expected to impact both CIN and AIS, although less data exist about the HPV types associated with AIS. We analyzed HPV types detected in AIS and CIN identified through population-based surveillance.

Methods
The Centers for Disease Control and Prevention and partners conduct surveillance for CIN2, CIN3, and AIS (CIN2+) among women aged ≥18 years in five locations in the United States. Specimen blocks for women aged 18–39 are sent to CDC for HPV typing using L1 consensus PCR. We analyzed cases with AIS only, AIS with CIN2 or 3 (AIS+CIN), and CIN3 only, the highest grade squamous cell precursor. We used chi-square tests to compare HPV types by histology. Types evaluated were HPV16 and 18 (high-risk (HR) types targeted by all HPV vaccines), 5 additional HR types targeted by the 9-valent vaccine (31/33/45/52/58; “additional 9vHPV”), and 7 other HR non-vaccine types (35/39/51/56/59/66/68).

Results
Between 2008 and 2014, 18,394 women were diagnosed with CIN2+. Of those, 517 (2.8%) had AIS (283 AIS only, 234 AIS+CIN) and 5,766 (31%) had CIN3 only. Median ages at diagnosis for AIS, AIS+CIN, and CIN3 were 37, 32, and 31 years, respectively. HPV typing results were available for 89 AIS, 99 AIS+CIN, and 2,923 CIN3 cases; HPV was detected in nearly all specimens (99% AIS, 100% AIS+CIN, 98% CIN3), and 21% of positive specimens had &gt;1 HPV type identified. HPV16 (AIS: 51%, AIS+CIN: 64%, CIN3: 59%; p ≤ 0.001) and HPV18 (AIS: 39%, AIS+CIN: 31%, CIN3: 5%; P ≤ 0.001) were most common. Additional 9vHPV types (AIS: 3%, AIS+CIN: 12%, CIN3: 26%; P ≤ 0.001), and HR non-vaccine types (AIS: 6%, AIS+CIN2+: 2%, CIN3+: 9%; P ≤ 0.001) were detected less frequently.

Conclusion
HPV types differed by histology, with AIS having a greater proportion of HPV 18 and a lower proportion of additional 9vHPV and HR non-vaccine types. This report on the largest sample of genotyped AIS cases to date provides data for vaccine impact monitoring, and suggests a high opportunity for vaccine prevention of AIS.

Disclosures
M. R. Griffin, MedImmune: Grant Investigator, Grant recipient
Asymptomatic Lymphogranuloma Venereum among Nigerian Men who have Sex with Men
Authors: Crowell Trevor , Hardick Justin , Lombardi Kara , Amusu Senate , Odeyemi Sunday , Ivo Andrew , Baral Stefan , Nowak Rebecca , Adebajo Sylvia , Charurat Manhattan , Ake Julie , Gaydos Charlotte 
Published: October 2017

Abstract

Background
Among men who have sex with men (MSM), lymphogranuloma venereum (LGV) has been associated with proctocolitis that can lead to chronic complications and requires a longer course of antibiotic therapy than is recommended for infections due to other serovars of Chlamydia trachomatis (CT). We describe the prevalence and clinical features of LGV among Nigerian MSM diagnosed with anorectal CT.

Methods
MSM were recruited into the ongoing RV368 cohort in Lagos, Nigeria, using respondent-driven sampling. Participants were screened for HIV and bacterial sexually transmitted infections (STIs) every three months for up to 18 months. HIV was diagnosed using a parallel algorithm of rapid tests on fingerstick blood samples. PCR testing for Neisseria gonorrheae and CTwas performed on voided urine, oropharyngeal swab, and rectal swab specimens. For this analysis, prevalent and incident cases of rectal CT infection underwent additional testing to identify LGV serovars utilizing novel real-time PCR assays specific for the L serovars of CT Chlamydia trachomatis.

Results
From 28 April 2014–19 July 2016, 420 men underwent screening for rectal STIs, including 66 (15.7%) who had prevalent rectal infection with CT. An additional 68 participants developed incident infections during 208 person-years of follow-up. Of 134 eligible rectal swab specimens, 128 underwent further testing for LGV serovars. Seven (5.5%) of the tested samples were identified as LGV serovars of CT. None of the seven participants with LGV reported any symptoms such as fever or rectal pain. Two of the participants with LGV were simultaneously co-infected with rectal gonorrhea. HIV co-infection was common among participants with both LGV and non-LGV serovars of CT (71% and 77%, respectively, P = 0.74).

Conclusion
LGV was uncommon but present among Nigerian MSM in this study. LGV needs to be considered even in asymptomatic cases, particularly if anorectal CT infection fails to respond to the usual course of therapy. Consistent screening for L serovars of CT, or empiric treatment for LGV in cases with a high suspicion for this diagnosis, could potentially improve patient outcomes and decrease transmission.

Disclosures
All authors: No reported disclosures.
Electronic Reminder Notifications Improve Uptake of Targeted Ciprofloxacin Therapy for Neisseria gonorrheae Infections at the University of California, Los Angeles Health System
Authors: Allan-Blitz Lao-Tzu , Humphries Romney , Hemarajata Peera , Kimble Mabel , Elias Samuel , Klausner Jeffrey 
Published: October 2017

Abstract

Background
A wild-type gyrase A (gyrA) genotype of N. gonorrheae reliably predicts susceptibility to ciprofloxacin, which can reduce selection pressure for ceftriaxone-resistant infections, an urgent public health threat. In November 2015, UCLA Health began gyrA genotyping all N. gonorrheae positive specimens. In May 2016, we began sending reminder notifications of treatment recommendations to providers of patients with wild-type infections.

Methods
We reviewed records for all laboratory confirmed N. gonorrheae cases from November 1, 2015–April 30, 2017. Infections in different anatomic sites were considered unique infections, while unique infections in a single patient on the same date were considered a case. Empiric therapy was defined as treatment within 1 day of specimen collection. We also collected test-of-cure data among patients with wild-type infections treated with ciprofloxacin.

Results
Among 423 patients (23% HIV infected) there were 460 cases and 514 anatomic site-specific N. gonorrheae infections. Of infections, 218 (43%) had a wild-type gyrA genotype, 138 (27%) mutant, 153 (30%) indeterminate, 4 were not attempted, and 1 had missing data. There were 255 (55%) cases and 283 (55%) infections treated non-empirically. The median time-to-treatment among those cases was 4 days (interquartile range 3–6 days). Ciprofloxacin was used in 2 (3%) of 66 nonempirically treated infections prior to the start of reminder notifications, compared with 40 (18%) of 217 nonempirically treated infections after notifications began (P = 0.002). Of the 55 providers who received an email on or before the day of treatment for non-empirically treated patients, 32 (58%) used ciprofloxacin. There was no ciprofloxacin use prior to assay implementation. The trend in treatment by quarter among non-empirically treated infections is shown the Figure.
Among 30 patients treated with ciprofloxacin, 6 had a test of cure at one week, and all (100%; 95% CI 61%–100%) of those tests were negative for N. gonorrheae; 5 were from urethral specimens, and 1 was from the pharynx.

Conclusion
Electronic provider notifications augmented targeted ciprofloxacin therapy for N. gonorrheae infections. Preliminary test-of-cure data are promising.

Disclosures
All authors: No reported disclosures.