NEJM â Collection Updates for Infectious DiseasesBOOK REVIEW: Laboratory medicine has no more urgent role than in the diagnosis and management of infections in immunocompromised patients. For this vulnerable population, clinical algorithms are logically rooted in the need...
ORIGINAL ARTICLE: Evaluation of Universal Antenatal Screening for Group B StreptococcusMelissa K. Van Dyke, Ph.D., Christina R. Phares, Ph.D., Ruth Lynfield, M.D., Ann R. Thomas, M.D., Kathryn E. Arnold, M.D., Allen S. Craig, M.D., Janet Mohle-Boetani, M.D., Ken Gershman, M.D., William Schaffner, M.D., Susan Petit, M.P.H., Shelley M. Zansky, Ph.D., Craig A. Morin, M.P.H., Nancy L. Spina, M.P.H., Kathryn Wymore, M.P.H., Lee H. Harrison, M.D., Kathleen A. Shutt, M.S., Joseph Bareta, M.P.H., Sandra N. Bulens, M.P.H., Elizabeth R. Zell, M.Stat., Anne Schuchat, M.D., and Stephanie J. Schrag, D.Phil.Background: Group B streptococcal disease is one of the most common infections in the first week after birth. In 2002, national guidelines recommended universal late antenatal screening of pregnant women...
IMAGES IN CLINICAL MEDICINE: Biliary StonesPing-Hsien Chen, M.D. and Chiao-Hsiung Chuang, M.D.A 63-year-old woman presented with a 2-day history of fever, abdominal pain, and vomiting. There was no history of previous episodes. Physical examination revealed fever and moderate abdominal tenderness in...
Centers for Disease Control and PreventionCDC Recommends Shingles VaccinePeople age 60 and older should be vaccinated against shingles, or herpes zoster, a condition often marked by debilitating chronic pain...
New CDC Study Finds Arthritis Can be a Barrier for Adults Seeking to Manage Diabetes through Physical ActivityMore than half of adults with diagnosed diabetes also have arthritis, a painful condition that can be a barrier to physical activity—an important health strategy for managing diabetes...
Falls a Leading Cause of Injury-Related Emergency Department Visits for Infants Each Year, CDC Study ShowsHalf of the estimated 328,500 infants 12 months of age or younger who were treated for injuries in hospital emergency departments each year from 2001 to 2004 were injured as a result of a fall, according to a study by the Centers for Disease Control and Prevention.
BMC Infectious Diseases - Latest ArticlesUse of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area Niclas WinqvistPer BjorkmanAnn NorenHakan Miorner Fri, 03 Jul 2009 00:00:00 -0000
Background:
In settings with low background prevalence of tuberculosis (TB) infection, interferon-gamma release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON(R)-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed.
Methods:
From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed.
Results:
Among 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9E9/L vs. 8.8E9/L; P<0.001) and a higher median body mass index (22.7 vs. 20.7; P=0.043) as compared to QFT-G-negative TB patients.
Conclusions:
The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is questionable. However, a high PPV was observed for extrapulmonary TB and QFT-G might be considered in the diagnostic process in this situation. The PPV and NPV for identifying active TB among persons originating from regions with high-and intermediate TB incidence was similar to that observed in subjects originating in the low-incidence region.
Role of pathogenic oral flora in postoperative pneumonia following brain surgeryKinga BagyiAngela HaczkuIldiko MartonJudit SzaboAttila GasparMelinda AndrasiImre VargaJudit TothAlmos Klekner Mon, 29 Jun 2009 00:00:00 -0000
Background:
Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.
Methods:
A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.
Results:
The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p=0.031 and p=0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p<0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.
Conclusions:
Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.
Truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates does not predict increased biological activity of Toxin B or Toxin A.Ruth MurrayDave BoydMichael MulveyPaul LevettMichelle Alfa Sun, 28 Jun 2009 00:00:00 -0000
Background:
The increased severity of disease associated with the NAP1 strain of Clostridium difficile has been attributed to mutations to the tcdC gene which codes for a negative regulator of toxin production. To assess the role of hyper-production of Toxins A and B in clinical isolates of Clostridium difficile, two NAP1-related and five NAP1 non-related strains were compared.
Methods:
Sequencing was performed on tcdC, tcdR, and tcdE to determine if there were differences that might account for hyper-production of Toxin A and Toxin B in NAP1-related strains. Biological activity of Toxin B was evaluated using the HFF cell CPE assay and Toxin A biological activity was assessed using the Caco-2 Trans-membrane resistance assay.
Results:
Our results confirm that Toxin A and Toxin B production in NAP1-related strains and ATCC 43255 occurs earlier in the exponential growth phase compared to most NAP1-nonrelated clinical isolates. Despite the hyper-production observed in ATCC 43255 it had no mutations in tcdC, tcdR or tcdE. Analysis of the other clinical isolates indicated that the kinetics and ultimate final concentration of Toxin A and B did not correlate with the presence or lack of alterations in tcdC, tcdR or tcdE.
Conclusions:
Our data do not support a direct role for alterations in the tcdC gene as a predictor of hyperproduction of Toxin A and B in NAP1-related strains.
pubmed: 0019-9567Toxoplasma gondii cyclophilin 18-mediated production of nitric oxide induces bradyzoite conversion in a CCR5-dependent manner. Ibrahim HM, Bannai H, Xuan X, Nishikawa Y
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Toxoplasma gondii cyclophilin 18-mediated production of nitric oxide induces bradyzoite conversion in a CCR5-dependent manner.
Infect Immun. 2009 Jun 29;
Authors: Ibrahim HM, Bannai H, Xuan X, Nishikawa Y
Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites to slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. The recombinant TgCyp18 induced the production of nitric oxide (NO), IL-12 and TNF-alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of IFN-gamma and IL-6 in a CCR5-independent manner. Interestingly, treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host-cell responses in a TgCyp18-mediated process.
PMID: 19564392 [PubMed - as supplied by publisher]
Roles of RseB, {sigma}E, and DegP in virulence and phase variation of colony morphotype of Vibrio vulnificus. Brown RN, Gulig PA
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Roles of RseB, {sigma}E, and DegP in virulence and phase variation of colony morphotype of Vibrio vulnificus.
Infect Immun. 2009 Jun 29;
Authors: Brown RN, Gulig PA
Vibrio vulnificus is an estuarine bacterium capable of causing serious and often fatal wound infection and primary septicemia. We used alkaline phosphatase insertion mutagenesis to identify genes necessary for virulence of this pathogen. One mutant had an in-frame fusion of 'phoA to the gene encoding RseB, a periplasmic negative regulator of the alternative sigma factor sigma(E). sigma(E) controls an extensive regulon involved in responding to cell envelope stresses. Colonies of the rseB mutant were less opaque than wild-type and underwent phase variation between translucent and opaque morphologies. rseB mutants were attenuated for virulence in subcutaneously inoculated iron dextran-treated mice. To gain insight into the role of rseB and the extracytoplasmic stress response in V. vulnificus, defined mutations in rseB and two important members of the extracytoplasmic stress regulon, rpoE and degP, were constructed for analysis of virulence, colony morphology, and stress-associated phenotypes. Deletion of rseB caused a reversible phase variation in colony morphotype that was associated with extracellular polysaccharides. Translucent and transparent morphotype strains were attenuated for virulence. Deletion mutants for rpoE and degP were sensitive to membrane-perturbing agents and heat but were not significantly attenuated for virulence of V. vulnificus in mice. These results reveal complex relationships between regulation of the extracytoplasmic stress response, exopolysaccharides, and virulence of V. vulnificus.
PMID: 19564391 [PubMed - as supplied by publisher]
A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence. Bergmann A, Hartmann T, Cairns T, Bignell EM, Krappmann S
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A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence.
Infect Immun. 2009 Jun 29;
Authors: Bergmann A, Hartmann T, Cairns T, Bignell EM, Krappmann S
Virulence of the fungal pathogen Aspergillus fumigatus is in part based on the saprophytic lifestyle this mould has evolved. A crucial function for saprophytism resides in secreted proteases that allow assimilation of proteinaceous substrates. The impact of extracellular proteolytic activities on the pathogenesis of aspergillosis, however, remains controversial. In order to address this issue, characterisation of a conserved regulatory factor, PrtT, that acts on expression of secreted proteases was pursued. Expression of PrtT appears to be regulated post-transcriptionally, and the existence of an mRNA leader sequence implies translational control via eIF2alpha kinase signalling. Phenotypic classification of a prtT Delta deletion mutant revealed that expression of several major extracellular proteases is PrtT-dependent, resulting in the inability to utilise protein as nutritional source. Certain genes encoding secreted proteases are not regulated by PrtT. Most strikingly, the deletant strain is not attenuated in virulence when tested in a leukopenic mouse model, which makes a strong case for reconsidering any impact of secreted proteases in pulmonary aspergillosis.
PMID: 19564390 [PubMed - as supplied by publisher]
Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence. Kulasekara BR, Jacobs M, Zhou Y, Wu Z, Sims E, Saenphimmachak C, Rohmer L, Ritchie JM, Radey M, McKevitt M, Freeman TL, Hayden H, Haugen E, Gillett W, Fong C, Chang J, Beskhlebnaya V, Waldor MK, Samadpour M, Whittam TS, Kaul R, Brittnacher M, Miller SI
Related Articles
Analysis of the genome of the Escherichia coli O157:H7 2006 spinach-associated outbreak isolate indicates candidate genes that may enhance virulence.
Infect Immun. 2009 Jun 29;
Authors: Kulasekara BR, Jacobs M, Zhou Y, Wu Z, Sims E, Saenphimmachak C, Rohmer L, Ritchie JM, Radey M, McKevitt M, Freeman TL, Hayden H, Haugen E, Gillett W, Fong C, Chang J, Beskhlebnaya V, Waldor MK, Samadpour M, Whittam TS, Kaul R, Brittnacher M, Miller SI
In addition to causing diarrhea, Escherichia coli O157:H7 infection can lead to hemolytic uremic syndrome (HUS), a severe disease characterized by hemolysis and renal failure. Differences in HUS frequency among E. coli O157:H7 outbreaks have been noted, but there is incomplete understanding of bacterial factors that promote HUS. In 2006, an outbreak of E. coli O157:H7, caused by consumption of contaminated spinach, occurred with a notably high frequency of HUS. We sequenced the genome of this strain (TW14359) with the goal of identifying candidate genetic factors that contribute to an enhanced ability to cause HUS. The TW14359 genome contains 70-kb of DNA segments not present in either of the two reference O157:H7 genomes. We identified seven putative virulence determinants, including two putative Type III secretion system effector proteins, candidate genes that could result in increased pathogenicity or, alternatively, adaptation to plants, and an intact anaerobic nitric oxide reductase gene, norV. We surveyed one hundred O157:H7 isolates for the presence of these putative virulence determinants. A norV deletion was found in over half of strains surveyed and correlates strikingly with the absence of stx1. The other putative virulence factors were found in eight to thirty-five percent of O157:H7 isolates surveyed and their presence also correlates with the presence of norV and absence of stx1 indicating the presence of norV may serve as a marker of greater propensity for HUS similar to the correlation between the absence of stx1 and HUS propensity.
PMID: 19564389 [PubMed - as supplied by publisher]
The role of dendritic cells and alveolar macrophages in regulating early host defense against pulmonary infection with Cryptococcus neoformans. Osterholzer JJ, Milam JE, Chen GH, Toews GB, Huffnagle GB, Olszewski MA
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The role of dendritic cells and alveolar macrophages in regulating early host defense against pulmonary infection with Cryptococcus neoformans.
Infect Immun. 2009 Jun 29;
Authors: Osterholzer JJ, Milam JE, Chen GH, Toews GB, Huffnagle GB, Olszewski MA
Successful pulmonary clearance of the encapsulated yeast Cryptococcus neoformans requires a T1 adaptive immune response. This response takes up to three weeks to fully develop. The role of the initial, innate immune response against the organism is uncertain. In this study, an established model of diphtheria toxin-mediated depletion of resident pulmonary dendritic cells (DC) and alveolar macrophages (AM) was used to assess the contribution of these cells to the initial host response against cryptococcal infection. Results demonstrate that depletion of DC and AM one day prior to infection results in rapid clinical deterioration and death of mice within 6 days post-infection; this effect was not observed in infected groups of control mice not depleted of DC and AM. Depletion did not alter the microbial burden or total leukocyte recruitment in the lung. Mortality (in mice depleted of DC and AM) was associated with increased neutrophil and B cell accumulation accompanied by histopathologic evidence of suppurative neutrophilic bronchopneumonia, cyst formation, and alveolar damage. Collectively, these data define an important role for DC and AM in regulating the initial innate immune response following pulmonary infection with C. neoformans. These findings provide important insight into the cellular mechanisms which coordinate early host defense against an invasive fungal pathogen in the lung.
PMID: 19564388 [PubMed - as supplied by publisher]
Aggregatibacter actinomycetemcomitans Builds Mutualistic Biofilm Communities in Saliva With Fusobacterium nucleatum and Veillonella sp. Periasamy S, Kolenbrander PE
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Aggregatibacter actinomycetemcomitans Builds Mutualistic Biofilm Communities in Saliva With Fusobacterium nucleatum and Veillonella sp.
Infect Immun. 2009 Jun 29;
Authors: Periasamy S, Kolenbrander PE
Human oral bacterial pathogens grow in attached multi-species biofilm communities. Unattached cells are quickly removed by swallowing. Therefore, surface attachment is essential for growth, and we investigated multi-species community interactions resulting in mutualistic growth on saliva as sole nutritional source. We used two model systems, saliva-coated transferable solid phase-polystyrene (Peg) and flowcells with saliva-coated glass surfaces. Fluorescent antibody staining and image analysis quantified biomass in flowcells: quantitative real time PCR with species-specific primers quantified biomass in Peg biofilms. Veillonella sp. PK1910, Aggregatibacter actinomycetemcomitans JP2 and Fusobacterium nucleatum ATCC 10953 were unable to grow as mono-species in flowcells. Only A. actinomycetemcomitans grew after 36 h when Pegs remained submerged in saliva from time of inoculation. Mixed-species coaggregates were used for dual- and triple-species inoculations. Biomass in dual-species biofilms increased in both systems when Veillonella sp. PK1910 was present as one of the partners. Enhanced growth of all strains was observed in triple-species biofilms in flowcells. Interestingly, in flowcells F. nucleatum and A. actinomycetemcomitans exhibited mutualism and, although F. nucleatum was unable to grow with either species in the Peg system, F. nucleatum stimulated growth of Veillonella sp. and together they enhanced the total biomass of A. actinomycetemcomitans in triple-species Peg biofilms. We propose that mutualistic dual-species and multi-species oral biofilm communities form in vivo and that mutualism between commensal veillonellae and late colonizing pathogens such as aggregatibacteria contribute to the development of periodontal disease.
PMID: 19564387 [PubMed - as supplied by publisher]
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