bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concomitant Administration of Mycobacterium bovis BCG with the Meningococcal C Conjugate Vaccine to Neonatal Mice Enhances Antibody Response and Protective Efficacy
Authors: Brynjolfsson Siggeir F. , Bjarnarson Stefania P. , Mori Elena , Del Giudice Giuseppe , Jonsdottir Ingileif 
Published: September 2011

ABSTRACTMycobacterium bovisBCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM197, in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM197. BCG was administered concomitantly, a day or a week before MenC-CRM197. An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM197,with increased IgG response (P= 0.002) and SBA (8-fold) after a second immunization with MenC-CRM197without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM197together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM197alone (P= 0.0015). Sixteen days after the second immunization with MenC-CRM197, increased IgG (P< 0.05), IgG1 (P< 0.05), IgG2a (P= 0.06), and IgG2b (P< 0.05) were observed, and only mice primed with MenC-CRM197plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth.
High Incidence of Severe Influenza among Individuals over 50 Years of Age
Authors: Zhang Anna J. X. , To Kelvin K. W. , Tse Herman , Chan Kwok-Hung , Guo Kun-Yuan , Li Can , Hung Ivan F. N. , Chan Jasper F. W. , Chen Honglin , Tam Sidney , Yuen Kwok-Yung 
Published: September 2011

ABSTRACT

Age-specific epidemiological data on asymptomatic, symptomatic, and severe infections are essential for public health policies on combating influenza. In this study, we incorporated data on microbiologically confirmed infections and seroprevalence to comprehensively describe the epidemiology of pandemic H1N1 2009 influenza. Seroprevalence was determined from 1,795 random serum samples collected in our hospital in January 2007 (before the first wave of the pandemic) and March 2010 (after the second wave). Data on microbiologically confirmed infection and severe cases were obtained from the Centre for Health Protection in Hong Kong. Severe cases were most common in the 51- to 60-year-old age group. The microbiologically confirmed incidence rate was highest for children aged ≤10 years and dropped sharply for the adult population (ρ = −1.0;
P
< 0.01), but the incidence rate for severe disease was highest for the 51- to 60-year-old age group. For the 51- to 60-year-old age group, the seroprevalence was similar to that for the younger age groups, but the proportion of severe cases relative to seroprevalence was significantly higher than that for 11- to 50-year-old age groups. As judged from the percentage of specimens positive for other respiratory viruses compared with that for pandemic H1N1 virus, the impact of symptomatic disease due to pandemic H1N1 virus was higher than that for other respiratory viruses in people aged ≤50 years. In conclusion, the 51- to 60-year-old age group, which had the highest overall incidence and the highest rate of severe disease but is currently not considered by the World Health Organization to be an at-risk group, should be prioritized for influenza vaccination in areas where universal influenza vaccination is not practiced.
A Critical Appraisal of the Role of the Clinical Microbiology Laboratory in Diagnosis of Invasive Fungal Infections
Authors: Klutts J. Stacey , Robinson-Dunn Barbara 
Published: September 2011

ABSTRACT
The incidence of invasive fungal infections (IFIs) continues to rise in industrialized countries, primarily due to both increasingly potent iatrogenic immunosuppression and immunocompromising therapies aimed at treating hematologic malignancies. As this situation continues to evolve, the clinical microbiology laboratory has few new, innovative methodologies to diagnose these serious infections and existing methods lack sensitivity. This represents a difficult clinical situation for health care providers, as they are left to rely on clinical instincts for the management of patients with potential IFIs, as mycology test results are not consistently reliable. The goals of this session of Camp Clin Micro (CCM) were to critically assess currently available methods and practices for diagnosing IFIs, to discuss the potential of current investigational methods, to evaluate the role of antifungal susceptibility testing, and finally to identify action items that can help move the field of diagnostic mycology in a direction that will improve our ability to identify IFIs in a timely manner. This is meant to be not a comprehensive overview of the diagnosis of IFIs but rather a detailed account of the discussion at CCM among clinical microbiologists with experience in diagnostic mycology and knowledge of the literature.
Molecular Bacterial Load Assay, a Culture-Free Biomarker for Rapid and Accurate Quantification of Sputum Mycobacterium tuberculosis Bacillary Load during Treatment
Authors: Honeyborne Isobella , McHugh Timothy D. , Phillips Patrick P. J. , Bannoo Selina , Bateson Anna , Carroll Nora , Perrin Felicity M. , Ronacher Katharina , Wright Laura , van Helden Paul D. , Walzl Gerhard , Gillespie Stephen H. 
Published: September 2011

ABSTRACT

A molecular assay to quantify
Mycobacterium tuberculosis
is described.
In vitro
, 98% (
n
= 96) of sputum samples with a known number of bacilli (10
7
to 10
2
bacilli) could be enumerated within 0.5 log
10
. In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log
10
(95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml
−1
sputum at day 0 (linear regression,
P
= 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log
10
increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).
Optimizing Antimicrobial Susceptibility Test Reporting
Authors: Schreckenberger Paul C. , Binnicker Matthew J. 
Published: September 2011

ABSTRACT
A meeting of clinical microbiologists, representing a diverse group of practice settings, together with representatives from industry partners, discussed the pitfalls of current practices for testing and reporting antimicrobial susceptibility test results. The participants in this session identified several needs. Regarding what antibiotics to test, the discussants noted that the CLSI M100 documents must be readily accessible to all those who need them and presented in a way that is easily understood. Engineering controls (e.g., software programs) are needed that incorporate intrinsic resistance and susceptibility information and contain pathways that would allow the reporting of antibiotics for only those body locations where the antibiotic reaches therapeutic concentrations. These programs should be linked with the patient electronic medical record (EMR) and flag the physician or clinical pharmacist using an active alert messenger when testing reveals that the antibiotic(s) that the patient is receiving may not be optimal or de-escalation of the antibiotic treatment regimen is indicated. Guidelines for the practice of cascade reporting are needed and should be developed to assist laboratories in the identification and reporting of therapeutic and cost-effective antimicrobials. Personalized antibiotic reporting (PAR) software programs are needed that would deduce the optimal antibiotic for each individual patient based on a number of clinical and laboratory features. These would include the following: (i) organism identification; (ii) MIC; (iii) patient-specific factors such as weight, immune status, allergies, creatinine clearance, and albumin level; (iv) site of infection; (v) desired method of dosing (bolus versus continuous infusion); (vi) patient convenience (oral versus intravenous); (vii) drug interactions; and (viii) cost.
A Critical Appraisal of the Role of the Clinical Microbiology Laboratory in the Diagnosis of Bloodstream Infections
Authors: Weinstein Melvin P. , Doern Gary V. 
Published: September 2011

ABSTRACT
The detection of bloodstream infections is one of the most important functions of clinical microbiology laboratories. Despite advances in blood culture technology and clinical studies that have focused on the detection of bacteremia and fungemia, perfection has not been achieved and uncertainties persist. This review provides perspectives on a number of areas, including the recommended number of blood cultures, duration of incubation of blood cultures, use of anaerobic, in addition to aerobic, blood culture media, value of the lysis-centrifugation method, processing and reporting of probable blood culture contaminants, and limitations of current blood culture methods and systems. We also address the handling of blood cultures in point-of-care locations that lack full microbiology capabilities.
Three-Locus Identification, Genotyping, and Antifungal Susceptibilities of Medically Important Trichosporon Species from China
Authors: Guo Li-Na , Xiao Meng , Kong Fanrong , Chen Sharon C.-A. , Wang He , Sorrell Tania C. , Jiang Wei , Dou Hong-Tao , Li Ruo-Yu , Xu Ying-Chun 
Published: September 2011

ABSTRACT

Three reference and 45 clinical isolates of
Trichosporon
were analyzed by conventional phenotypic and molecular methods to determine the species and genotypes of
Trichosporon
isolates from China. Target loci for molecular methods included the internal transcribed spacer (ITS) region, the D1/D2 domain of the 26S rRNA gene, and the intergenic spacer 1 (IGS1) region. Identification of eight
Trichosporon
species was achieved, of which
Trichosporon asahii
was the most common. Of the sequence-based molecular methods, the one targeting the D1/D2 domain assigned 97.9% (47/48) of isolates (seven species) correctly, while tests targeting both the ITS and IGS1 regions correctly identified all 48 isolates. The commercial API 20C AUX and Vitek 2 Compact YST systems correctly identified 91.9% and 73% of isolates when their biochemical profiles were queried against those of species contained in the databases, respectively, and misidentified 63.6% and 36.4% of isolates of species that were unclaimed by the databases, respectively. The predominant genotype among
T. asahii
clinical isolates, genotype 4 (51.4%), is rarely found in other countries. Voriconazole and itraconazole were the most active drugs
in vitro
against all the
Trichosporon
species tested, while caspofungin and amphotericin B demonstrated poor activity.
Recovery of a Catalase-Negative Staphylococcus epidermidis Strain in Blood and Urine Cultures from a Patient with Pyelonephritis
Authors: Kallstrom George , Chang Tom , Albertson Marc , Morilla Daniel , Fisher Mark A. , Eberly Bardwell 
Published: September 2011

ABSTRACT

This report describes a 60-year-old patient with bilateral nephrolithiasis. A catalase-negative
Staphylococcus epidermidis
strain was recovered from both urine and blood cultures. Although rare, isolates of catalase-negative
Staphylococcus
spp., including
Staphylococcus aureus
, have been reported. Here, we describe the first report of a catalase-negative
S. epidermidis
strain.
Haemophilus influenzae Infections in the H. influenzae Type b Conjugate Vaccine Era
Authors: Agrawal Aarti , Murphy Timothy F. 
Published: September 2011

ABSTRACTThe widespread use ofHaemophilus influenzaetype b (Hib) conjugate vaccines has nearly eradicated invasive Hib disease where the vaccines are used. This success was accompanied by a shift in capsular serotypes of invasiveH. influenzaedisease, with nontypeable strains replacing type b strains as the most common bloodstream isolate, but there is no convincing evidence of a true increase in the incidence of non-serotype b invasive infections.H. influenzaecauses predominantly mucosal infections. The introduction of vaccines for otitis media and global shifts in antimicrobial susceptibility emphasize the importance of continued surveillance ofH. influenzaecolonization and disease patterns.
Annexin II Binds to Capsid Protein VP1 of Enterovirus 71 and Enhances Viral Infectivity
Authors: Yang Su-Lin , Chou Ying-Ting , Wu Cheng-Nan , Ho Mei-Shang 
Published: September 2011

ABSTRACT

Enterovirus type 71 (EV71) causes hand, foot, and mouth disease (HFMD), which is mostly self-limited but may be complicated with a severe to fatal neurological syndrome in some children. Understanding the molecular basis of virus-host interactions might help clarify the largely unknown neuropathogenic mechanisms of EV71. In this study, we showed that human annexin II (Anx2) protein could bind to the EV71 virion via the capsid protein VP1. Either pretreatment of EV71 with soluble recombinant Anx2 or pretreatment of host cells with an anti-Anx2 antibody could result in reduced viral attachment to the cell surface and a reduction of the subsequent virus yield
in vitro
. HepG2 cells, which do not express Anx2, remained permissive to EV71 infection, though the virus yield was lower than that for a cognate lineage expressing Anx2. Stable transfection of plasmids expressing Anx2 protein into HepG2 cells (HepG2-Anx2 cells) could enhance EV71 infectivity, with an increased virus yield, especially at a low infective dose, and the enhanced infectivity could be reversed by pretreating HepG2-Anx2 cells with an anti-Anx2 antibody. The Anx2-interacting domain was mapped by yeast two-hybrid analysis to VP1 amino acids 40 to 100, a region different from the known receptor binding domain on the surface of the picornavirus virion. Our data suggest that binding of EV71 to Anx2 on the cell surface can enhance viral entry and infectivity, especially at a low infective dose.
Vaccine Protection against Simian Immunodeficiency Virus in Monkeys Using Recombinant Gamma-2 Herpesvirus
Authors: Bilello John P. , Manrique Julieta M. , Shin Young C. , Lauer William , Li Wenjun , Lifson Jeffrey D. , Mansfield Keith G. , Johnson R. Paul , Desrosiers Ronald C. 
Published: September 2011

ABSTRACTRecombinant strains of replication-competent rhesus monkey rhadinovirus (RRV) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant strain were shown to express the expected protein. Three RRV-negative and two RRV-positive rhesus monkeys were inoculated intravenously with a mixture of these three recombinant RRVs. Expression of SIV Gag was readily detected in lymph node biopsy specimens taken at 3 weeks postimmunization. Impressive anti-SIV cellular immune responses were elicited on the basis of major histocompatibility complex (MHC) tetramer staining and gamma interferon enzyme-linked immunospot (ELISPOT) assays. Responses were much greater in magnitude in the monkeys that were initially RRV negative but were still readily detected in the two monkeys that were naturally infected with RRV at the time of immunization. By 3 weeks postimmunization, responses measured by MHC tetramer staining in the twoMamu-A*01+RRV-negative monkeys reached 9.3% and 13.1% of all CD8+T cells in peripheral blood to the Gag CM9 epitope and 2.3% and 7.3% of all CD8+T cells in peripheral blood to the Tat SL8 epitope. Virus-specific CD8+T cell responses persisted at high levels up to the time of challenge at 18 weeks postimmunization, and responding cells maintained an effector memory phenotype. Despite the ability of the RRVenv recombinant to express high levels of Env in cultured cells, and despite the appearance of strong anti-RRV antibody responses in immunized monkeys, anti-Env antibody responses were below our ability to detect them. Immunized monkeys, together with three unimmunized controls, were challenged intravenously with 10 monkey infectious doses of SIVmac239. All five immunized monkeys and all three controls became infected with SIV, but peak viral loads were 1.2 to 3.0 log10units lower and chronic-phase viral loads were 1.0 to 3.0 log10units lower in immunized animals than the geometric mean of unimmunized controls. These differences were statistically significant. Anti-Env antibody responses following challenge indicated an anamnestic response in the vaccinated monkeys. These findings further demonstrate the potential of recombinant herpesviruses as preventive vaccines for AIDS. We hypothesize that this live, replication-competent, persistent herpesvirus vector could match, or come close to matching, live attenuated strains of SIV in the degree of protection if the difficulty with elicitation of anti-Env antibody responses can be overcome.
The Fecal Virome of Pigs on a High-Density Farm
Authors: Shan Tongling , Li Linlin , Simmonds Peter , Wang Chunlin , Moeser Adam , Delwart Eric 
Published: September 2011

ABSTRACTSwine are an important source of proteins worldwide but are subject to frequent viral outbreaks and numerous infections capable of infecting humans. Modern farming conditions may also increase viral transmission and potential zoonotic spread. We describe here the metagenomics-derived virome in the feces of 24 healthy and 12 diarrheic piglets on a high-density farm. An average of 4.2 different mammalian viruses were shed by healthy piglets, reflecting a high level of asymptomatic infections. Diarrheic pigs shed an average of 5.4 different mammalian viruses. Ninety-nine percent of the viral sequences were related to the RNA virus familiesPicornaviridae,Astroviridae,Coronaviridae, andCaliciviridae, while 1% were related to the small DNA virus familiesCircoviridae,and Parvoviridae.Porcine RNA viruses identified, in order of decreasing number of sequence reads, consisted of kobuviruses, astroviruses, enteroviruses, sapoviruses, sapeloviruses, coronaviruses, bocaviruses, and teschoviruses. The near-full genomes of multiple novel species of porcine astroviruses and bocaviruses were generated and phylogenetically analyzed. Multiple small circular DNA genomes encoding replicase proteins plus two highly divergent members of thePicornaviralesorder were also characterized. The possible origin of these viral genomes from pig-infecting protozoans and nematodes, based on closest sequence similarities, is discussed. In summary, an unbiased survey of viruses in the feces of intensely farmed animals revealed frequent coinfections with a highly diverse set of viruses providing favorable conditions for viral recombination. Viral surveys of animals can readily document the circulation of known and new viruses, facilitating the detection of emerging viruses and prospective evaluation of their pathogenic and zoonotic potentials.
Roles of the Envelope Proteins in the Amplification of Covalently Closed Circular DNA and Completion of Synthesis of the Plus-Strand DNA in Hepatitis B Virus
Authors: Lentz Thomas B. , Loeb Daniel D. 
Published: September 2011

ABSTRACT
Covalently closed circular DNA (cccDNA), the nuclear form of hepatitis B virus (HBV), is synthesized by repair of the relaxed circular (RC) DNA genome. Initially, cccDNA is derived from RC DNA from the infecting virion, but additional copies of cccDNA are derived from newly synthesized RC DNA molecules in a process termed intracellular amplification. It has been shown that the large viral envelope protein limits the intracellular amplification of cccDNA for duck hepatitis B virus. The role of the envelope proteins in regulating the amplification of cccDNA in HBV is not well characterized. The present report demonstrates regulation of synthesis of cccDNA by the envelope proteins of HBV. Ablation of expression of the envelope proteins led to an increase (>6-fold) in the level of cccDNA. Subsequent restoration of envelope protein expression led to a decrease (>50%) in the level of cccDNA, which inversely correlated with the level of the envelope proteins. We found that the expression of L protein alone or in combination with M and/or S proteins led to a decrease in cccDNA levels, indicating that L contributes to the regulation of cccDNA. Coexpression of L and M led to greater regulation than either L alone or L and S. Coexpression of all three envelope proteins was also found to limit completion of plus-strand DNA synthesis, and the degree of this effect correlated with the level of the proteins and virion secretion.
Human Cytomegalovirus US7 Is Regulated Synergistically by Two Virally Encoded MicroRNAs and by Two Distinct Mechanisms
Authors: Tirabassi Rebecca , Hook Lauren , Landais Igor , Grey Finn , Meyers Heather , Hewitt Helen , Nelson Jay 
Published: September 2011

ABSTRACT
Human cytomegalovirus (HCMV) encodes at least 14 microRNAs (miRNAs) that act posttranscriptionally to repress gene expression. Although several HCMV miRNA targets of both cellular and viral origin have been identified, our knowledge of their function remains limited. HCMV miRNA targets, as well as phenotypes associated with HCMV miRNA mutants, have been difficult to identify since the downregulation of targets by a single miRNA is often less than 2-fold. Several factors can contribute to the strength of repression, including the mechanism of translational inhibition, the degree of complementarity between the miRNA and target mRNA, the number of binding sites for one miRNA, and cooperativity or antagonism between miRNAs. To determine the effect of multiple miRNAs on one gene, we examined the repression of a viral gene, US7. Here we demonstrate that the HCMV-encoded miRNAs miR-US5-1 and miR-US5-2 function in a highly synergistic manner to regulate US7, even at very low miRNA concentrations. Regulation of US7 involves three functional miRNA binding sites: two that are completely complementary to the 3′ untranslated region (3′UTR) and one that is imperfectly matched. Surprisingly, we observed equal contributions to inhibition from both complete and partially complementary sites, and repression was not completely abrogated until all three sites were mutated simultaneously. We also observed that the miRNA binding sites did not follow the spacing constraints for corepressive miRNAs observed in earlier reports. These results underscore the importance of evaluating the contribution of multiple miRNAs on gene regulation and shed new insight into miRNA:mRNA interactions.