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Search Results for all work with filters:

  • 2017
  • infecti

Work 1-10 of 95

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Article

HIVR4P 2016, Partnering for Prevention: Conference Summary and Highlights

by Barbara L. Shacklett; Cynthia Derdeyn; Morenike Oluwatoyin Folayan; Raphael J. Landovitz; Colin Anthony; Anna-Janina Behrens; Thomas J. Hope; Elise Landais; Lorna Leal; Jeanne M. Marrazzo; Lynn Morris; Nelly Mugo; Kenneth Ngure; Veronica Noseda; Srinika Ranasinghe; Damien C. Tully; Yegor Voronin; Mitchell Warren; Constantinos Kurt Wibmer; Irene Y. Xie; Gabriella Scarlatti; Bargavi Thyagarajan

2017

Subjects
  • Health Sciences, Immunology
  • Health Sciences, Public Health
  • File Download
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Abstract:Close

HIV Research for Prevention: AIDS Vaccine, Microbicide, and ARV-based Prevention Science (HIVR4P) was built on a growing consensus that effective HIV prevention requires a combination of approaches and that understanding, analyzing, and debating the cross-cutting issues that impact prevention research are all essential to combat the global HIV/AIDS epidemic. To that end, the biennial HIVR4P conference is dedicated to all biomedical HIV prevention research approaches, including HIV vaccines, microbicides, pre-exposure prophylaxis, and treatment as prevention. The HIVR4P 2016 conference was held in Chicago, Illinois (USA), on October 17-21, and included more than 700 scientific presentations and 21 satellite sessions covering the latest and most promising advances across the HIV prevention research field. The theme "Partnering for Prevention" represented the conference's commitment to breaking down silos between research disciplines as well as between researchers, program developers, care providers, advocates, communities, and funders. Delegates spanning 42 countries attended the conference. One-third of those in attendance were early career investigators, which reflects a firm commitment to emerging researchers and ultimately to the goal of developing a sustainable scientific enterprise well into the future. This article presents a concise summary of highlights from the conference. For a more detailed account, one may find full abstracts, daily summaries, and webcasts on the conference website at hivr4p.org.

Article

The role of supplementary environmental surveillance to complement acute flaccid paralysis surveillance for wild poliovirus in Pakistan-2011-2013

by Tori L. Cowger; Cara C. Burns; Salmaan Sharif; Howard E. Gary; Jane Iber; Elizabeth Henderson; Farzana Malik; Syed Sohail Zahoor Zaidi; Shahzad Shaukat; Lubna Rehman; Mark A. Pallansch; Walter Orenstein

2017

Subjects
  • Biology, Virology
  • Health Sciences, Public Health
  • Health Sciences, Immunology
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Abstract:Close

Background: More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection. Methods: Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of ‘orphan viruses’ (1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case. Findings: A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011–2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance. Interpretation: Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy.

Article

Mechanisms of action and in vivo antibacterial efficacy assessment of five novel hybrid peptides derived from Indolicidin and Ranalexin against Streptococcus pneumoniae

by Hassan Mahmood Jindal; Keivan Zandi; Kien Chai Ong; Rukumani Devi Velayuthan; Sara Maisha Rasid; Chandramathi Samudi Raju; Shamala Devi Sekaran

2017

Subjects
  • Biology, Microbiology
  • Health Sciences, Immunology
  • Biology, Virology
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Abstract:Close

Background. Antimicrobial peptides (AMPs) are of great potential as novel antibiotics for the treatment of broad spectrum of pathogenic microorganisms including resistant bacteria. In this study, the mechanisms of action and the therapeutic efficacy of the hybrid peptides were examined. Methods. TEM, SEM and ATP efflux assay were used to evaluate the effect of hybrid peptides on the integrity of the pneumococcal cell wall/membrane. DNA retardation assay was assessed to measure the impact of hybrid peptides on the migration of genomic DNA through the agarose gel. In vitro synergistic effect was checked using the chequerboard assay. ICR male mice were used to evaluate the in vivo toxicity and antibacterial activity of the hybrid peptides in a standalone form and in combination with ceftriaxone. Results. The results obtained from TEM and SEM indicated that the hybrid pep- tides caused significant morphological alterations in Streptococcus pneumoniae and disrupting the integrity of the cell wall/membrane. The rapid release of ATP from pneumococcal cells after one hour of incubation proposing that the antibacterial action for the hybrid peptides is based on membrane permeabilization and damage. The DNA retardation assay revealed that at 62.5 μg/ml all the hybrid peptides were capable of binding and preventing the pneumococcal genomic DNA from migrating through the agarose gel. In vitro synergy was observed when pneumococcal cells treated with combinations of hybrid peptides with each other and with conventional drugs erythromycin and ceftriaxone. The in vivo therapeutic efficacy results revealed that the hybrid peptide RN7-IN8 at 20 mg/kg could improve the survival rate of pneumococcal bacteremia infected mice, as 50% of the infected mice survived up to seven days post- infection. In vivo antibacterial efficacy of the hybrid peptide RN7-IN8 was signficantly improved when combined with the standard antibiotic ceftriaxone at (20 mg/kg + 20 mg/kg) as 100% of the infected mice survived up to seven days post-infection. Discussion. Our results suggest that attacking and breaching the cell wall/membrane is most probably the principal mechanism for the hybrid peptides. In addition, the hybrid peptides could possess another mechanism of action by inhibiting intracellular functions such as DNA synthesis. AMPs could play a great role in combating antibiotic resistance as they can reduce the therapeutic concentrations of standard drugs.

Article

Blockage of regulatory T cells augments induction of protective immune responses by influenza virus-like particles in aged mice

by Zhiyuan Wen; Xi Wang; Ke Dong; Huizhong Zhang; Zhigao Bu; Ling Ye; Chinglai Yang

2017

Subjects
  • Health Sciences, Immunology
  • Biology, Microbiology
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Abstract:Close

Elderly humans over 65 years old are at great risk to pathogenesis by influenza virus infection. However, although influenza vaccines provide effective protection in healthy young adults, protection of elderly adults is substantially lower even with a good match between the vaccine and the circulating influenza virus. To gain insight of the underlying mechanism for the reduced immunogenicity of influenza vaccines in the aged population, we investigated immunogenicity of influenza virus-like particle vaccines in aged mice, which represent a useful model for studying aging associated impairment in immune responses. Specifically, we investigated the effect of inhibiting regulatory T cells in aged mice on induction of protective immune responses by influenza vaccines. Our results showed that injecting anti-CD25 antibodies could down-regulate CD25 on the surface of regulatory T cells and significantly increase the levels of antibody responses induced by VLP immunization in aged mice. Further, the profiles of antibody responses were also changed towards Th1 type by regulatory T cell blockage in aged mice. Moreover, aged mice that were treated by anti-CD25 antibodies prior to vaccination were more effectively protected against lethal influenza virus challenge.

Article

A Nutrient-Regulated Cyclic Diguanylate Phosphodiesterase Controls Clostridium difficile Biofilm and Toxin Production during Stationary Phase

by Erin B. Purcell; Robert W. McKee; David S. Courson; Elizabeth M. Garrett; Shonna McBride; Richard E. Cheney; Rita Tamayo

2017

Subjects
  • Biology, Microbiology
  • Health Sciences, Immunology
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The signa ling molecule cyclic diguanylate (c-di-GMP) mediates physiological adaptation to extracellular stimuli in a wide range of bacteria. The complex metabolic pathways governing c-di-GMP synthesis and degradation are highly regulated, but the specific cues that impact c-di-GMP signaling are largely unknown. In the intestinal pathogen Clostridium difficile, c-di-GMP inhibits flagellar motility and toxin production and promotes pilus-dependent biofilm formation, but no specific biological functions have been ascribed to any of the individual c-di-GMP synthases or phosphodiesterases (PDEs). Here, we report the functional and biochemical characterization of a c-di-GMP PDE, PdcA, 1 of 37 confirmed or putative c-di-GMP metabolism proteins in C. difficile 630. Our studies reveal that pdcA transcription is controlled by the nutrient-regulated transcriptional regulator CodY and accordingly increases during stationary phase. In addition, PdcA PDE activity is allosterically regulated by GTP, further linking c-di-GMP levels to nutrient availability. Mutation of pdcA increased biofilm formation and reduced toxin biosynthesis without affecting swimming motility or global intracellular c-di-GMP. Analysis of the transcriptional response to pdcA mutation indicates that PdcA-dependent phenotypes manifest during stationary phase, consistent with regulation by CodY. These results demonstrate that inactivation of this single PDE gene is sufficient to impact multiple c-di-GMPdependent phenotypes, including the production of major virulence factors, and suggest a link between c-di-GMP signaling and nutrient availability.

Article

Identification of HIV infection-related DNA methylation sites and advanced epigenetic aging in HIV-positive, treatment-naive US veterans

by Kristin N. Nelson; Qin Hui; David Rimland; Ke Xu; Matthew S. Freiberg; Amy C. Justice; Vincent Marconi; Yan Sun

2017

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
  • File Download
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Abstract:Close

Objective: HIV-positive individuals are at higher risk than healthy persons for agingrelated diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNA methylation (DNAm) age, an aging marker involving multiple age-related cytosine-guanine dinucleotide (CpG) sites, among antiretroviral treatment (ART)-naive HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study. Design: Peripheral blood samples were collected from 19 ART-naive, HIV-positive, and 19 HIV-negative male participants, matched by age and race. Blood samples were collected from HIV-positive participants 7-11 years after ART initiation. Methods: We compared DNAm age between HIV-positive and HIV-negative groups at baseline and between HIV-positive patients at baseline and follow-up. We also performed an epigenome-wide analysis to identify CpG methylation sites associated with HIV infection. Results: DNAm age in HIV-positive individuals is, on average, 11.2 years higher than HIV study participants at baseline, and two of 10 HIV-positive individuals showed an increase in DNAm age after ART initiation. Epigenome-wide association studies showed an association of HIV infection with one site, in gene VPS37B, which approached statistical significance in our cohort (P=3.30×10 -6 , Bonferroni-corrected threshold=1.22×10 -7 ) and was replicated in a second, larger cohort. Conclusion: ART treatment-naive HIV-positive individuals have significantly older DNAm age compared to HIV-negative individuals in the Veterans Aging Cohort Study cohort. Longitudinal changes in DNAm age are highly variable across individuals after initiation of antiretroviral therapy.

Article

Drivers of airborne human-to-human pathogen transmission

by Sander Herfst; Michael Böhringer; Basel Karo; Philip Lawrence; Nicola S. Lewis; Michael J. Mina; Charles J. Russell; John Steel; Rik L. de Swart; Christian Menge

2017

Subjects
  • Biology, Virology
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Abstract:Close

Airborne pathogens — either transmitted via aerosol or droplets — include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergency preparedness plans. In particular, we propose a framework of drivers facilitating human-to-human transmission with the airspace between individuals as an intermediate stage. The model is expected to enhance identification and risk assessment of novel pathogens.

Article

Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation

by Jung Joo Hong; Eduardo L V Silveira; Praveen K Amancha; Siddappa N. Byrareddy; Sanjeev Gumber; Kyu-Tae Chang; Aftab A Ansari; Francois Villinger

2017

Subjects
  • Health Sciences, Pharmacology
  • Health Sciences, Pathology
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Objective: Germinal center resident follicular helper T (TFH) cells in lymphoid follicles are a potential sanctuary for HIV/simian immunodeficiency virus (SIV) replication. But the dynamics of germinal centers upon early initiation of antiretroviral therapy (ART) and their potential role in the formation of viral sanctuaries post-SIV infection are not fully understood. Design: Sequential lymph node biopsies (n = 10) were collected from SIVmac239-infected rhesus macaques before infection, at 5 weeks postinfection/pre-ART, 6 and 12 weeks following ART initiation. These tissues and cells were analyzed for frequencies of TFH cells and assignment of germinal center scores. Results: Modest but significant increases in TFH cells and hyperplastic follicles with large germinal centers were noted during the acute phase of SIV infection (week 5/pre-ART). However, 6 weeks after ART initiation, substantial increases in germinal center TFH cells, germinal center B cells, hyperplastic follicles with large germinal centers, and abundant local IL-21 production were observed, whereas levels of SIV RNA and DNA of lymph nodes had decreased to barely detectable values along with barely detectable levels of SIV antibody-producing cells. An additional 6 weeks of ART did not appreciably decrease germinal center TFH or germinal center scores. Conclusion: Thus, although early ART rapidly controls SIV replication, it does not regulate early lymphoid activation, which may contribute to the seeding and magnitude of viral reservoirs.

Article

Clinical Management of Patients with Ebola Virus Disease in High-Resource Settings

by G Marshall Lyon III; Aneesh Mehta; Bruce Ribner

2017

Subjects
  • Biology, Microbiology
  • Biology, Virology
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Like most viral illnesses in humans, supportive care of the patient is the mainstay of clinical care for patients with Ebola virus disease (EVD). The goal is to maintain and sustain the patient until a specific immune response develops and clears the viral infection. Clearly, antiviral therapy may eventually help speed recovery, but supportive care will likely always be the centerpiece of care of the patient with EVD. While terrible in terms of human suffering and loss, the EVD outbreak of 2014–2016 provided an unheralded opportunity to advance our understanding in the care of patients (WHO 2016). Regardless of the care setting, resource-rich or resource-constrained, it is beneficial to have an established team of care providers. This team should consist of nurses and physicians who are familiar with clinical care of patients with EVD and have demonstrated competency using necessary personal protective equipment (PPE). Consideration should be given to having several physician specialties on the team, including critical care, infectious diseases, and anesthesiology. Additional individuals in other medical specialties should be identified in case needed during the course of caring for a patient. The National Ebola Training and Education Center (NETEC) has detailed guidance on preparations for developing a high-containment unit and care team (NETEC 2016).

Article

Capturing HIV Incidence Among MSM Through At-Home and Self-reported Facility-based Testing

by Eric W. Hall; Alexandra V. Ricca; Christine M. Khosropour; Patrick S Sullivan

2017

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
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