Science.gov

Sample records for invasive prevotella infection

  1. Detection of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Prevotella nigrescens in chronic endodontic infection.

    PubMed

    Tomazinho, Luiz Fernando; Avila-Campos, Mario J

    2007-02-01

    Black-pigmented anaerobic rods such as Prevotella spp. and Porphyromonas spp. are involved in the etiology and perpetuation of endodontic infections. The aim of this study was to evaluate the prevalence of these species in chronic endodontic infections by using culture and polymerase chain reaction (PCR) techniques. Samples of 100 patients with root canals displaying chronic endodontic infections were obtained by sterilized paper points. Bacterial identification was performed by using culture and PCR techniques. By culture, in 33% of the samples, P. intermedia-P. nigrescens (75.8%), P. gingivalis (27.3%), and P. endodontalis (9.1%) were identified, and by PCR 60% of the samples harbored P. nigrescens (43.3%), P. gingivalis (43.3%), P. intermedia (31.7%), and P. endodontalis (23.3%). The presence of these black-pigmented anaerobic rods alone or in association in chronic endodontic infections seems to be frequent. PCR is a very sensitive technique for detecting DNA from bacterial cells. Culturing is only able to reveal living bacteria and is less sensitive for the identification of low numbers of bacterial cells.

  2. Culture-based identification of pigmented Porphyromonas and Prevotella species in primary endodontic infections

    PubMed Central

    Rajaram, Anuradha; Kotrashetti, Vijayalakshmi S.; Somannavar, Pradeep D.; Ingalagi, Preeti; Bhat, Kishore

    2016-01-01

    Background. The most common species isolated from primary endodontic infections are black-pigmented bacteria. These species are implicated in apical abscess formation due to their proteolytic activity and are fastidious in nature. Therefore, the present study was carried out to evaluate the presence and identification of various pigmented Porphyromonas and Prevotella species in the infected root canal through culture-based techniques. Methods. Thirty-one patients with primary endodontic infections were selected. Using sterile paper points, samples were collected from the root canals after access opening and prior to obturation, which were cultured using blood and kanamycin blood agar. Subsequently, biochemical test was used to identify the species and the results were analyzed using percentage comparison analysis, McNemar and chi-squared tests, Wilcoxon match pair test and paired t-test. Results. Out of 31 samples 26 were positive for black-pigmented organisms; the predominantly isolated species were Prevotella followed by Porphyromonas. In Porphyromonas only P. gingivalis was isolated. One of the interesting features was isolation of P. gingivalis through culture, which is otherwise very difficult to isolate through culture. Conclusion. The presence of Prevotella and Porphyromonas species suggests that a significant role is played by these organisms in the pathogenesis of endodontic infections. PMID:27651878

  3. Detection and genetic characterization of β-lactamases in Prevotella intermedia and Prevotella nigrescens isolated from oral cavity infections and peritonsillar abscesses.

    PubMed

    Fernández-Canigia, Liliana; Cejas, Daniela; Gutkind, Gabriel; Radice, Marcela

    2015-06-01

    A prospective analysis on β-lactam resistance mechanisms and β-lactamase prevalence was conducted on Prevotella intermedia and Prevotella nigrescens recovered from patients with chronic periodontitis and peritonsillar abscesses. Both phenotypic and genotypic methods were performed to characterize the β-lactamases, their coding genes and their genetic contexts. Overall, β-lactamase production was observed in 64% (16/25) P. intermedia and 23.8% (5/21) P. nigrescens (p < 0.01). Besides higher β-lactamase production rates were observed in P. intermedia (8/16) than in P. nigrescens (2/16) recovered from chronic periodontitis, almost all isolates from peritonsillar abscesses were producers (8/9 and 3/3, respectively). cfxA, but not cepA and cblA, was detected in those isolates, which were previously categorized as β-lactamase producers. CfxA producing isolates displayed higher β-lactam MICs than non-producers in both species. The most frequent allele was cfxA2, followed by cfxA3 and a new allelic variant named cfxA6. The analysis of the downstream flanking region in the three cfxA variants revealed the association with mobA of Tn4555, suggesting their localization in a mobilizable element. β-lactam resistance and cfxA carriage prevalence seems to be not only related to the bacterial species but also to the infection site.

  4. [Emerging invasive fungal infections].

    PubMed

    Alvez, F; Figueras, C; Roselló, E

    2010-07-01

    The frequency and diversity of invasive fungal infections has changed over the last 25 years. The emergence of less common, but medically important fungi has increased, and the children at risk has expanded, with the inclusion of medical conditions such as cancer, mainly haematological malignancy or stem cell transplant, immunosuppressive therapy, prolonged neutropenia, and T-cell immunodeficiency. Among mould infections, fusariosis and phaeohyphomycosis (Dematiaceous fungi) have been increasingly reported in this group of patients. To successfully manage these challenging infections, it is imperative that paediatricians and sub-specialists remain aware of the optimal and timely diagnosis and therapeutic options. Unlike other common mycoses that cause human disease, there no simple antigen or serological tests available to detect these pathogens in tissue or blood. The outcome for these disseminate, and often refractory fungal infections in neutropenic patients and transplant recipients remains extremely poor, requiring early and aggressive therapy. Unfortunately there are no guidelines outlining the choices for optimal therapy in the treatment of paediatric invasive fungal infections do not exist, and on the other hand are limited paediatric data available comparing antifungal agents in children with proven, probable or suspected invasive fungal infection. The options for treatment rest mainly on some adult guidelines that comment on the treatment of these emerging and uncommon important fungi in children. Despite the sparse clinical trials available on treatment and its poor outcome, options for treatment of invasive fungal infections have increased with the advance of new antifungal agents, with improved tolerability and increased range of activity. The epidemiology, clinical manifestations, diagnosis and treatment of fusariosis and phaeohyphomycosis are discussed in this article.

  5. Effects of oxidative stress on the virulence profile of Prevotella intermedia during experimental infection in gnotobiotic mice.

    PubMed

    Santos, Simone G; Diniz, Claúdio G; Silva, Vânia L; Martins, Wanderlany A; Cara, Denise C; Souza, Natalia C; Serufo, José C; Nicoli, Jacques R; Carvalho, Maria Auxiliadora R; Farias, Luiz M

    2007-03-01

    Prevotella intermedia is a component of the indigenous microbiota but is also responsible for anaerobic infections of the gastrointestinal tract and oral cavity. The aim of the present study was to investigate the influence of oxidative stress on the in vivo pathogenicity of P. intermedia. Germ-free mice were challenged intraperitoneally with parental (wt) or oxidative stress adapted (aero) strains. Bacterial virulence was evaluated by histopathology, hyperaemia and blood analysis [C-reactive protein (CRP), serum albumin and white blood cells (WBCs)], 3 and 10 days after challenge. CRP levels and WBC count were higher in animals challenged with the aero strain, and the albumin level was lower in this group, only 10 days after infection (P<0.05). Body weight gain was significantly reduced whereas hyperaemia and ratios of spleen/organ weight were increased in animals challenged with the aero strain (P<0.05). The liver of animals challenged with the aero strain showed hyperaemia, vasodilatation as well as an increase in the number of inflammatory cells and liver/organ weight ratio (P<0.05). Similar, but more discrete, alterations were observed in the small intestine of animals challenged with the aero strain. Studies on stress responses of this putative pathogen may help to better understand the aggressive potential and virulence markers of anaerobic bacteria.

  6. Invasive Bordetella holmesii infections.

    PubMed

    Fishbain, Joel T; Riederer, Kathleen; Sawaf, Hadi; Mody, Rupal

    2015-02-01

    Bordetella holmesii is a rare cause of invasive human disease. The fastidious and unusual nature of this organism makes routine isolation and identification challenging. We report two cases of B. holmesii bacteremia that were rapidly identified by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) when standard techniques failed to provide speciation. There are no current standards for susceptibility testing or treatment recommendations. The rare occurrence and challenges in identifying this pathogen led us to perform a comprehensive review of the epidemiology, clinical presentations, and treatment options for this potentially invasive pathogen.

  7. New insights into Prevotella diversity and medical microbiology.

    PubMed

    Alauzet, Corentine; Marchandin, Hélène; Lozniewski, Alain

    2010-11-01

    In light of recent studies based on cultivation-independent methods, it appears that the diversity of Prevotella in human microbiota is greater than was previously assumed from cultivation-based studies, and that the implication of these bacteria in several human diseases was unrecognized. While some Prevotella taxa were found during opportunistic infections, changes in Prevotella abundance and diversity were discovered during dysbiosis-associated diseases. As member of the microbiota, Prevotella may also be considered as a reservoir for resistance genes. Greater knowledge on Prevotella diversity, as well as new insights into its pathogenic potential and implication in dysbiosis are expected from the use of human microbe identification microarrays, from whole-genome sequence analyse, and from the NIH Human Microbiome Project data. New approaches, including molecular-based methods, could contribute to improve the diagnosis of Prevotella infections.

  8. [Iron and invasive fungal infection].

    PubMed

    Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

    2013-01-01

    Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis.

  9. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  10. Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia

    PubMed Central

    Hieke, Cathleen; Kriebel, Katja; Engelmann, Robby; Müller-Hilke, Brigitte; Lang, Hermann; Kreikemeyer, Bernd

    2016-01-01

    Periodontitis is characterized by inflammation associated with the colonization of different oral pathogens. We here aimed to investigate how bacteria and host cells shape their environment in order to limit inflammation and tissue damage in the presence of the pathogen. Human dental follicle stem cells (hDFSCs) were co-cultured with gram-negative P. intermedia and T. forsythia and were quantified for adherence and internalization as well as migration and interleukin secretion. To delineate hDFSC-specific effects, gingival epithelial cells (Ca9-22) were used as controls. Direct effects of hDFSCs on neutrophils (PMN) after interaction with bacteria were analyzed via chemotactic attraction, phagocytic activity and NET formation. We show that P. intermedia and T. forsythia adhere to and internalize into hDFSCs. This infection decreased the migratory capacity of the hDFSCs by 50%, did not disturb hDFSC differentiation potential and provoked an increase in IL-6 and IL-8 secretion while leaving IL-10 levels unaltered. These environmental modulations correlated with reduced PMN chemotaxis, phagocytic activity and NET formation. Our results suggest that P. intermedia and T. forsythia infected hDFSCs maintain their stem cell functionality, reduce PMN-induced tissue and bone degradation via suppression of PMN-activity, and at the same time allow for the survival of the oral pathogens. PMID:27974831

  11. Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia.

    PubMed

    Hieke, Cathleen; Kriebel, Katja; Engelmann, Robby; Müller-Hilke, Brigitte; Lang, Hermann; Kreikemeyer, Bernd

    2016-12-15

    Periodontitis is characterized by inflammation associated with the colonization of different oral pathogens. We here aimed to investigate how bacteria and host cells shape their environment in order to limit inflammation and tissue damage in the presence of the pathogen. Human dental follicle stem cells (hDFSCs) were co-cultured with gram-negative P. intermedia and T. forsythia and were quantified for adherence and internalization as well as migration and interleukin secretion. To delineate hDFSC-specific effects, gingival epithelial cells (Ca9-22) were used as controls. Direct effects of hDFSCs on neutrophils (PMN) after interaction with bacteria were analyzed via chemotactic attraction, phagocytic activity and NET formation. We show that P. intermedia and T. forsythia adhere to and internalize into hDFSCs. This infection decreased the migratory capacity of the hDFSCs by 50%, did not disturb hDFSC differentiation potential and provoked an increase in IL-6 and IL-8 secretion while leaving IL-10 levels unaltered. These environmental modulations correlated with reduced PMN chemotaxis, phagocytic activity and NET formation. Our results suggest that P. intermedia and T. forsythia infected hDFSCs maintain their stem cell functionality, reduce PMN-induced tissue and bone degradation via suppression of PMN-activity, and at the same time allow for the survival of the oral pathogens.

  12. [Invasive yeast infections in neutropenic patients].

    PubMed

    Ruiz Camps, Isabel; Jarque, Isidro

    2016-01-01

    Invasive fungal diseases caused by yeasts still play an important role in the morbidity and mortality in neutropenic patients with haematological malignancies. Although the overall incidence of invasive candidiasis has decreased due to widespread use of antifungal prophylaxis, the incidence of non-Candida albicans Candida species is increasing compared with that of C.albicans, and mortality of invasive candidiasis continues to be high. In addition, there has been an increase in invasive infections caused by an array of uncommon yeasts, including species of the genus Malassezia, Rhodotorula, Trichosporon and Saprochaete, characterised by their resistance to echinocandins and poor prognosis.

  13. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population.

    PubMed

    Torrungruang, Kitti; Jitpakdeebordin, Supawadee; Charatkulangkun, Orawan; Gleebbua, Yingampa

    2015-01-01

    Periodontitis is a polymicrobial infection of tooth-supporting tissues. This cross-sectional study aimed to examine the associations between five target species and severe periodontitis in a Thai population. Using the CDC/AAP case definition, individuals diagnosed with no/mild and severe periodontitis were included. Quantitative analyses of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi) in subgingival plaque were performed using real-time polymerase chain reaction. The association between target species and severe periodontitis was examined using logistic regression analysis. The study subjects comprised 479 individuals with no/mild periodontitis and 883 with severe periodontitis. Bacterial prevalence and quantity were higher in subjects with severe periodontitis than in those with no/mild disease. In the fully adjusted model, all species except Tf showed a dose-dependent relationship with periodontitis. The mere presence of Pg, even in low amount, was significantly associated with severe periodontitis, while the amount of Aa, Td, and Pi had to reach the critical thresholds to be significantly associated with disease. Compared to individuals with low levels of both Td and Pi, high colonization by either Td or Pi alone significantly increased the odds of having severe periodontitis by 2.5 (95%CI 1.7-3.5) folds. The odds ratio was further increased to 14.8 (95%CI 9.2-23.8) in individuals who were highly colonized by both species. Moreover, the presence of Pg and high colonization by Aa were independently associated with severe periodontitis with odds ratios of 5.6 (95%CI 3.4-9.1) and 2.2 (95%CI 1.5-3.3), respectively. Our findings suggest that the presence of Pg and high colonization by Aa, Td, and Pi play an important role in severe periodontitis in this study population. We also demonstrate for the first time that individuals co-infected with Td and Pi

  14. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola / Prevotella intermedia Co-Infection Are Associated with Severe Periodontitis in a Thai Population

    PubMed Central

    Torrungruang, Kitti; Jitpakdeebordin, Supawadee; Charatkulangkun, Orawan; Gleebbua, Yingampa

    2015-01-01

    Periodontitis is a polymicrobial infection of tooth-supporting tissues. This cross-sectional study aimed to examine the associations between five target species and severe periodontitis in a Thai population. Using the CDC/AAP case definition, individuals diagnosed with no/mild and severe periodontitis were included. Quantitative analyses of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Prevotella intermedia (Pi) in subgingival plaque were performed using real-time polymerase chain reaction. The association between target species and severe periodontitis was examined using logistic regression analysis. The study subjects comprised 479 individuals with no/mild periodontitis and 883 with severe periodontitis. Bacterial prevalence and quantity were higher in subjects with severe periodontitis than in those with no/mild disease. In the fully adjusted model, all species except Tf showed a dose-dependent relationship with periodontitis. The mere presence of Pg, even in low amount, was significantly associated with severe periodontitis, while the amount of Aa, Td, and Pi had to reach the critical thresholds to be significantly associated with disease. Compared to individuals with low levels of both Td and Pi, high colonization by either Td or Pi alone significantly increased the odds of having severe periodontitis by 2.5 (95%CI 1.7–3.5) folds. The odds ratio was further increased to 14.8 (95%CI 9.2–23.8) in individuals who were highly colonized by both species. Moreover, the presence of Pg and high colonization by Aa were independently associated with severe periodontitis with odds ratios of 5.6 (95%CI 3.4–9.1) and 2.2 (95%CI 1.5–3.3), respectively. Our findings suggest that the presence of Pg and high colonization by Aa, Td, and Pi play an important role in severe periodontitis in this study population. We also demonstrate for the first time that individuals co-infected with Td

  15. Pattern of distribution of Prevotella species/phylotypes associated with healthy gingiva and periodontal disease.

    PubMed

    Nadkarni, M A; Browne, G V; Chhour, K-L; Byun, R; Nguyen, K-A; Chapple, C C; Jacques, N A; Hunter, N

    2012-11-01

    The purpose of the present study was to obtain diverse profiles of Prevotella species associated with gingival sites in an isolated Aboriginal and an urban community by phylogenetic analysis and to establish patterns of association of identified Prevotella species in gingival sites. Species/phylotypes identified from the phylogenetic analysis of near full-length Bacteroidetes 16S rRNA gene sequences cloned from subgingival plaque samples obtained from an Aboriginal community were compared with those from an ethnically diverse urban metropolitan population suffering from periodontal disease. Specific primer sets were designed and validated for 22 distinct Prevotella species from the 24 species/phylotypes identified from both populations. Within the isolated Aboriginal community, gingival sites in adults were colonised by a mean of 15 different Prevotella species. Prevotella sp. oral clone P4PB24, Prevotella intermedia, Prevotella oralis, Prevotella denticola and Prevotella sp. strain P4P62 had the highest association with increasing probing depth in diseased sites (p < 0.05). P. intermedia and Prevotella sp. oral clone P4PB24, the Prevotella species significantly associated with increasing probing depth in diseased gingival sites and also strongly associated with P. gingivalis load (p < 0.05) in diseased gingival sites, showed significant correlation for co-colonisation (r = 0.6). Prevotella sp. oral clone B31FD, showing strong association with P. gingivalis load (p < 0.05) in diseased gingival sites, showed no significant correlation for co-colonisation with any other Prevotella species. This study provides a comprehensive analysis of Prevotella species associated with gingival sites for the informative evaluation of the epidemiology of infection by this genus.

  16. Live attenuated vaccines for invasive Salmonella infections

    PubMed Central

    Tennant, Sharon M.; Levine, Myron M.

    2015-01-01

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed S. Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: S. Typhi, S. Paratyphi A, S. Paratyphi B (currently uncommon but may become dominant again), S. Typhimurium, S. Enteritidis and S. Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines. PMID:25902362

  17. Live attenuated vaccines for invasive Salmonella infections.

    PubMed

    Tennant, Sharon M; Levine, Myron M

    2015-06-19

    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

  18. Burden of Invasive Staphylococcus aureus Infections in Hospitalized Infants

    PubMed Central

    Ericson, Jessica E.; Popoola, Victor O.; Smith, P. Brian; Benjamin, Daniel K.; Fowler, Vance G.; Benjamin, Daniel K.; Clark, Reese H.; Milstone, Aaron M.

    2015-01-01

    Importance Staphylococcus aureus is a frequent cause of infection in hospitalized infants. These infections are associated with increased mortality and morbidity, and longer hospital stays, but data on the burden of S. aureus disease in hospitalized infants are limited. Objective To compare demographics and mortality of infants with invasive methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), determine the annual proportion of S. aureus infections that were MRSA, and compare the risk of death following an invasive MRSA infection to the risk following an invasive MSSA infection. Design Multicenter retrospective study of a large, nationally representative cohort. Setting 348 neonatal intensive care units managed by the Pediatrix Medical Group. Participants 3888 infants with an invasive S. aureus infection who were discharged between 1997 and 2012. Exposure Invasive S. aureus infection. Main Outcomes and Measures Incidence of invasive S. aureus infections. Infant characteristics and mortality following MRSA or MSSA infection. Results The 3888 infants had 3978 invasive S. aureus infections (2868 MSSA, 1110 MRSA). The incidence of invasive S. aureus infection was 44.8 infections/10,000 infants. The yearly proportion of invasive infections caused by MRSA increased from 1997 to 2006 and has remained relatively stable since then. Infants with invasive MRSA or MSSA infections had similar gestational ages and birth weights. Invasive MRSA infections occurred more often at a younger postnatal age. For infants with available mortality data, more infants with invasive MSSA infections died at hospital discharge (N=237) than those with invasive MRSA infections (N=110). The proportion of infants who died following invasive MSSA or MRSA infection were similar: 237/2474 (9.6%) and 110/926 (11.9%), P=.05, respectively. Adjusted risk of death at hospital discharge was similar after invasive MSSA and MRSA infections overall (risk ratio, 1.19; 95% CI, 0

  19. Complete Genome Sequence of Prevotella intermedia Strain 17-2.

    PubMed

    Nambu, Takayuki; Yamane, Kazuyoshi; Maruyama, Hugo; Mashimo, Chiho; Yamanaka, Takeshi

    2015-08-20

    Prevotella intermedia, a Gram-negative black-pigmented anaerobic rod, is frequently isolated from not only periodontal pockets but also purulent infections. We report here the complete genome sequence of P. intermedia strain 17-2, which is a non-exopolysaccharide-producing variant obtained from exopolysaccharide (EPS)-producing P. intermedia strain 17 stock culture.

  20. Combinatorial strategies for combating invasive fungal infections.

    PubMed

    Spitzer, Michaela; Robbins, Nicole; Wright, Gerard D

    2017-02-17

    Invasive fungal infections are an important cause of human mortality and morbidity, particularly for immunocompromised populations. However, there remains a paucity of antifungal drug treatments available to combat these fungal pathogens. Further, antifungal compounds are plagued with problems such as host toxicity, fungistatic activity, and the emergence of drug resistance in pathogen populations. A promising therapeutic strategy to increase drug effectiveness and mitigate the emergence of drug resistance is through the use of combination drug therapy. In this review we describe the current arsenal of antifungals in medicine and elaborate on the benefits of combination therapy to expand our current antifungal drug repertoire. We examine those antifungal combinations that have shown potential against fungal pathogens and discuss strategies being employed to discover novel combination therapeutics, in particular combining antifungal agents with non-antifungal bioactive compounds. The findings summarized in this review highlight the promise of combinatorial strategies in combatting invasive mycoses.

  1. [Toxoplasmosis in HIV infection: invasion reactivation criteria].

    PubMed

    Goncharov, D B; Gubareva, E V; Kobets, N V; Domonova, E A; Ievleva, E S

    2012-01-01

    Contemporary representation of toxoplasmosis reactivation criteria in HIV infection is generalized. Significance of the issue is justified: toxoplasmosis is a leading neurological pathology in AIDS with a high lethality percentage due to complexity of clinical confirmation and difficulties of laboratory confirmation of the start of reactivation. Clinical, instrumental, immunologic, molecular genetic invasion reactivation criteria are discussed in the article and analysis of their effectiveness is performed; their most feasible combinations are justified. Further system analysis of the cerebral toxoplasmosis reactivation criteria specified in the article in combination with search of new pathogen dissemination markers will allow to obtain important information that has both fundamental interest and important practical significance.

  2. Combat-Related Invasive Fungal Wound Infections

    PubMed Central

    Rodriguez, Carlos J.

    2014-01-01

    Combat-related invasive fungal (mold) wound infections (IFIs) have emerged as an important and morbid complication following explosive blast injuries among military personnel. Similar to trauma-associated IFI cases among civilian populations, as in agricultural accidents and natural disasters, these infections occur in the setting of penetrating wounds contaminated by environmental debris. Specific risk factors for combat-related IFI include dismounted (patrolling on foot) blast injuries occurring mostly in southern Afghanistan, resulting in above knee amputations requiring resuscitation with large-volume blood transfusions. Diagnosis of IFI is based upon early identification of a recurrently necrotic wound following serial debridement and tissue-based histopathology examination with special stains to detect invasive disease. Fungal culture of affected tissue also provides supportive information. Aggressive surgical debridement of affected tissue is the primary therapy. Empiric antifungal therapy should be considered when there is a strong suspicion for IFI. Both liposomal amphotericin B and voriconazole should be considered initially for treatment since many of the cases involve not only Mucorales species but also Aspergillus or Fusarium spp., with narrowing of regimen based upon clinical mycology findings. PMID:25530825

  3. Invasive Fungal Infections in Acute Leukemia

    PubMed Central

    Bhatt, Vijaya R.; Viola, George M.; Ferrajoli, Alessandra

    2011-01-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed. PMID:23556092

  4. Invasive fungal infections in acute leukemia.

    PubMed

    Bhatt, Vijaya R; Viola, George M; Ferrajoli, Alessandra

    2011-08-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.

  5. Periodontal status and Prevotella intermedia antibody in acute coronary syndrome.

    PubMed

    Soejima, Hirofumi; Oe, Yoko; Nakayama, Hideki; Matsuo, Katsuhiko; Fukunaga, Takashi; Sugamura, Koichi; Kawano, Hiroaki; Sugiyama, Seigo; Shinohara, Masanori; Izumi, Yuichi; Ogawa, Hisao

    2009-11-12

    We performed periodontal examination and measured serum antibody levels against Prevotella intermedia in patients with acute coronary syndrome (ACS). Composite periodontal risk scores were significantly higher in the ACS group than in the coronary artery disease (CAD) group. Serum antibody levels were higher in the ACS group than in the CAD group and those were significantly correlated with the composite periodontal risk scores. These results provided important information about the status of P. intermedia infection in patients with ACS.

  6. Posaconazole salvage treatment for invasive fungal infection.

    PubMed

    Kim, Jong Hun; Williams, Kali

    2014-10-01

    Invasive fungal infection (IFI) is an important cause of morbidity and mortality. Posaconazole is a second generation triazole with a broad spectrum, and it may be suitable for salvage antifungal treatment although posaconazole is not usually considered to be as first-line antifungal therapy for IFI. The purpose of this study was to assess the utility of posaconazole salvage treatment for IFI. We conducted a retrospective review of patients with salvage antifungal treatment with posaconazole for IFI at our institution between December 2007 and July 2012. A total of ten patients received posaconazole salvage IFI. Etiology of IFI was consisting of mucormycosis (four patients), Paecilomyces variotii (one patient), and unspecified IFI etiology (five patients). Causes of posaconazole treatment were following; intolerance of previous antifungal therapy in five patients, refractory IFI on previous antifungal therapy in four patients, and both intolerance of previous antifungal therapy and refractory IFI on previous antifungal therapy in one patient. Duration of posaconazole salvage treatment ranged from 15 to 355 days with median 47 days. The overall successful posaconazole salvage treatment response rate was 80.0 % (8 of 10 patients). There were three patients who died during the study period. However, only one death was attributed to the progression of IFI. Two patients discontinued posaconazole due to adverse events. Posaconazole salvage treatment was effective antifungal therapy for IFI. Further studies are needed to define the optimal therapeutic strategy.

  7. Invasive Trichosporon cutaneum infection in an infant with wilms’ tumor

    PubMed Central

    de Carvalho, Ana Maria Rabelo; de Melo, Luciana Resende Bandeira; Moraes, Vera Lúcia; Neves, Rejane Pereira

    2008-01-01

    Fungal infections are increasingly being reported in immuno-compromised patients. In this study we report a case of systemic Trichosporon cutaneum infection in an infant with Wilms’ tumor. This is the first time that an invasive infection for T. cutaneum has been reported in a Wilms’ tumor patient. PMID:24031179

  8. First Case of Invasive Human Infection Caused by Cupriavidus metallidurans▿

    PubMed Central

    Langevin, Stéphanie; Vincelette, Jean; Bekal, Sadjia; Gaudreau, Christiane

    2011-01-01

    We describe the first case of invasive human infection (a nosocomial septicemia) caused by Cupriavidus metallidurans. This metal-resistant bacterium has not been reported to be pathogenic in humans or animals. PMID:21106795

  9. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    PubMed Central

    Joye, Sebastien; Gao, Anja; Kayemba-Kay’s, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-01

    Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death. PMID:24765491

  10. Invasive pneumococcal infection despite 7-valent conjugated vaccine.

    PubMed

    Joye, Sebastien; Gao, Anja; Kayemba-Kay's, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-25

    Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death.

  11. Invasive filamentous fungal infections associated with renal transplant tourism.

    PubMed

    Shoham, S; Hinestrosa, F; Moore, J; O'Donnell, S; Ruiz, M; Light, J

    2010-08-01

    'Transplant tourism,' the practice of traveling abroad to acquire an organ, has emerged as an issue in kidney transplantation. We treated a patient who developed invasive aspergillosis of the allograft vascular anastomosis after receiving a kidney transplant in Pakistan, prompting us to review the literature of invasive mycoses among commercial organ transplant recipients. We reviewed all published cases of infections in solid organ transplant recipients who bought their organs abroad and analyzed these reports for invasive fungal infections. Including the new case reported here, 19 cases of invasive fungal infections post commercial kidney transplant occurring in 17 patients were analyzed. Infecting organisms were Aspergillus species (12/19; 63%), Zygomycetes (5/19; 26%), and other fungi (2/19; 5%). Invasive mold infections were present at the transplanted graft in 6/17 patients (35%) with graft loss or death in 13/17 (76%) of patients and overall mortality (10/17) 59%. Invasive fungal infections, frequently originating at the graft site, have emerged as a devastating complication of commercial renal transplant and are associated with high rates of graft loss and death.

  12. Invasive Group B Streptococcal Infections in Infants, France

    PubMed Central

    Réglier-Poupet, Hélène; Tazi, Asmaa; Billoët, Annick; Dmytruk, Nicolas; Bidet, Philippe; Bingen, Edouard; Raymond, Josette; Trieu-Cuot, Patrick

    2008-01-01

    Clinical features and molecular characterization of 109 group B streptococci causing neonatal invasive infections were determined over an 18-month period in France. Sixty-four percent of the strains were from late-onset infections, and 75% were capsular type III. The hypervirulent clone ST-17 was recovered in 80% of meningitis cases. PMID:18826837

  13. Invasive group B streptococcal infections in infants, France.

    PubMed

    Poyart, Claire; Réglier-Poupet, Hélène; Tazi, Asmaa; Billoët, Annick; Dmytruk, Nicolas; Bidet, Philippe; Bingen, Edouard; Raymond, Josette; Trieu-Cuot, Patrick

    2008-10-01

    Clinical features and molecular characterization of 109 group B streptococci causing neonatal invasive infections were determined over an 18-month period in France. Sixty-four percent of the strains were from late-onset infections, and 75% were capsular type III. The hypervirulent clone ST-17 was recovered in 80% of meningitis cases.

  14. Invasive Mold Infections: Virulence and Pathogenesis of Mucorales

    PubMed Central

    Morace, Giulia; Borghi, Elisa

    2012-01-01

    Mucorales have been increasingly reported as cause of invasive fungal infections in immunocompromised subjects, particularly in patients with haematological malignancies or uncontrolled diabetes mellitus and in those under deferoxamine treatment or undergoing dialysis. The disease often leads to a fatal outcome, but the pathogenesis of the infection is still poorly understood as well as the role of specific virulence determinants and the interaction with the host immune system. Members of the order Mucorales are responsible of almost all cases of invasive mucormycoses, the majority of the etiological agents belonging to the Mucoraceae family. Mucorales are able to produce various proteins and metabolic products toxic to animals and humans, but the pathogenic role of these potential virulence factors is unknown. The availability of free iron in plasma and tissues is believed to be crucial for the pathogenesis of these mycoses. Vascular invasion and neurotropism are considered common pathogenic features of invasive mucormycoses. PMID:22121366

  15. Invasive Fungal Infections after Natural Disasters

    PubMed Central

    Benedict, Kaitlin

    2014-01-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed. PMID:24565446

  16. Invasive fungal infections after natural disasters.

    PubMed

    Benedict, Kaitlin; Park, Benjamin J

    2014-03-01

    The link between natural disasters and subsequent fungal infections in disaster-affected persons has been increasingly recognized. Fungal respiratory conditions associated with disasters include coccidioidomycosis, and fungi are among several organisms that can cause near-drowning pneumonia. Wound contamination with organic matter can lead to post-disaster skin and soft tissue fungal infections, notably mucormycosis. The role of climate change in the environmental growth, distribution, and dispersal mechanisms of pathogenic fungi is not fully understood; however, ongoing climate change could lead to increased disaster-associated fungal infections. Fungal infections are an often-overlooked clinical and public health issue, and increased awareness by health care providers, public health professionals, and community members regarding disaster-associated fungal infections is needed.

  17. Recent advances in antifungal pharmacotherapy for invasive fungal infections.

    PubMed

    Gallagher, Jason C; MacDougall, Conan; Ashley, Elizabeth S Dodds; Perfect, John R

    2004-04-01

    Invasive fungal infections carry significant morbidity and mortality. Candida species have become one of the most frequent causes of bloodstream infections, and infections caused by molds such as Aspergillus are becoming more frequent in immunocompromised patients. As this population grows, more invasive fungal infections can be anticipated. In the past, treatment options have been limited for many of these infections due to toxicity and efficacy concerns with the available antifungals. Fortunately, the past few years have brought exciting developments in antifungal pharmacotherapy. Lipid-based formulations of amphotericin B were introduced in the 1990s to attenuate adverse effects caused by amphotericin B deoxycholate (Fungizone, Bristol-Myers Squibb). Most recently, the echinocandins have been added to our antifungal regimen with the introduction of caspofungin (Cancidas, Merck and Co.) and voriconazole (Vfend, Pfizer), a new triazole, has come to market. The introduction of the echinocandins has invigorated the discussion about combination antifungal therapy. Evidence-based studies using these new agents are accumulating, and they are assuming important roles in the pharmacotherapy of invasive fungal infections in seriously ill and complex patients.

  18. Prevotella falsenii sp. nov., a Prevotella intermedia-like organism isolated from monkey dental plaque.

    PubMed

    Sakamoto, Mitsuo; Kumada, Hidefumi; Hamada, Nobushiro; Takahashi, Yusuke; Okamoto, Masaaki; Bakir, Mohammad Abdul; Benno, Yoshimi

    2009-02-01

    Eight anaerobic, pigmented, non-spore-forming, Gram-negative, rod-shaped strains isolated from monkey oral cavities were characterized phenotypically and chemotaxonomically and their phylogenetic positions were determined using 16S rRNA gene sequence analysis. The 16S rRNA gene sequence analysis showed that these isolates represent a single species of the genus Prevotella. These strains were most closely related to Prevotella intermedia ATCC 25611(T), with 95.0 % 16S rRNA gene sequence similarity. The next most closely related species were Prevotella pallens and Prevotella nigrescens (92.7 and 92.1 % similarity to the respective type strains). The phenotypic and biochemical characteristics of the isolates were the same as those of P. intermedia JCM 12248(T) and P. nigrescens JCM 12250(T). The isolates could be differentiated from P. pallens JCM 11140(T) on the basis of mannose fermentation and alpha-fucosidase activity. The isolates could not be distinguished from P. intermedia or P. nigrescens using conventional biochemical tests. DNA-DNA hybridization experiments revealed the genomic distinctiveness of these eight strains with respect to P. pallens JCM 11140(T), P. intermedia JCM 12248(T) and P. nigrescens JCM 12250(T). On the basis of these data, strains 04013, 04021, 04043, 04052(T), 0406, 04113, 04111 and 04161 represent a novel Prevotella species, for which the name Prevotella falsenii sp. nov. is proposed. The type strain is 04052(T) (=JCM 15124(T) =CCUG 56137(T)).

  19. Invasive Vibrio cholerae Infection Following Burn Injury

    DTIC Science & Technology

    2008-06-01

    as asymptomatic col- onization, otitis , gastroenteritis, soft-tissue infection, sepsis, or even cerebritis. In contrast, epidemic V. cholerae (O-1 or...cholerae grows well on common blood agar, with decreased bacterial over- growth on selective media , such as TCBS agar. As noted in our case (Figure 1), it...is possible for both epidemic and nonepidemic strains to have a “rugose” phenotype on nonselective media , and usually a smooth phenotype on TCBS.11

  20. Invasive fungal infections in solid organ transplant recipients

    PubMed Central

    Shoham, Shmuel; Marr, Kieren A

    2014-01-01

    Invasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by aspergillosis and cryptococcosis, except in lung transplant recipients, where aspergillosis is most common. Development of invasive disease hinges on the interplay between host factors (e.g., integrity of anatomical barriers, innate and acquired immunity) and fungal factors (e.g., exposure, virulence and resistance to prophylaxis). In this article, we describe the epidemiology and clinical features of the most common fungal infections in organ transplantation. Within this context, we review recent advances in diagnostic modalities and antifungal chemotherapy, and their impact on evolving prophylaxis and treatment paradigms. PMID:22568718

  1. Management of invasive fungal infections: a role for polyenes.

    PubMed

    Chandrasekar, Pranatharthi

    2011-03-01

    The spectrum of invasive fungal infections (IFIs) continues to evolve with the emergence of rare and resistant fungal pathogens. Clinicians are faced with difficult diagnostic and treatment challenges in the management of immunocompromised patients at high risk of developing IFIs. Early and appropriate antifungal therapy is essential for a successful outcome when treating invasive mycoses. The armamentarium of antifungal drugs continues to grow; the three main classes of commonly administered drugs are the polyenes, azoles and echinocandins. The newer triazoles and the echinocandins have changed primary treatment options for some fungal infections, such as aspergillosis and candidiasis. However, despite their toxic potential, the oldest antifungal drugs, polyenes, remain useful in the treatment of IFIs because of their broad-spectrum activity, low rates of resistance and established clinical record, particularly in immunocompromised patients with breakthrough fungal infections. This review highlights important issues in the treatment of IFIs for consideration by clinicians.

  2. Trends in antibiotic resistance in Prevotella species from patients of the University Hospital of Maxillofacial Surgery, Sofia, Bulgaria, in 2003-2009.

    PubMed

    Boyanova, Lyudmila; Kolarov, Rossen; Gergova, Galina; Dimitrova, Liliana; Mitov, Ivan

    2010-10-01

    Head-and-neck infections often involve anaerobes such as Prevotella species. Aim of the present study was to assess the evolution and the factors associated with resistance in Prevotella species to penicillin, clindamycin, metronidazole, tetracycline and β-lactams/β-lactamase inhibitors (BL/BLIs). In total, 192 Prevotella strains, isolated from patients with oral and head-and-neck infections, were evaluated. Common isolates were Prevotella intermedia and Prevotella melaninogenica within the pigmented species as well as Prevotella oris and Prevotella oralis group within the non-pigmented species. Overall resistance was 43.2% for penicillin, 10.9% for clindamycin, 0% for metronidazole. Nonsusceptibility to tetracycline was 29.1% without significant differences in resistance rates between pigmented and other species. Penicillin resistant strains were β-lactamase positive. From 2003-2004 to 2007-2009, penicillin resistance rates increased about four-fold (from 15.4% to 60.6%). Clindamycin resistance did not show evolution, whereas tetracycline nonsusceptibility decreased from 43.3% in 2003-2004 to 20.7% in 2007-2009. Except for one (0.5%) P. oralis strain with intermediate susceptibility to BL/BLIs, the other strains were susceptible to the agents. In conclusion, in Prevotella strains from patients with head-and-neck infections, the resistance rate to penicillin increased, that to clindamycin remained stable and the nonsusceptibility rate to tetracycline decreased during the period. Activity against >99% of Prevotella strains was observed with metronidazole and BL/BLIs. The penicillin resistance and tetracycline nonsusceptibility were associated with the year of study, national antibiotic consumption and possibly with previous treatment (for tetracycline). The evolution of penicillin resistance in Prevotella strains was highly dynamic.

  3. Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia and Prevotella nigrescens in endodontic lesions detected by culture and by PCR.

    PubMed

    Gomes, B P F A; Jacinto, R C; Pinheiro, E T; Sousa, E L R; Zaia, A A; Ferraz, C C R; Souza-Filho, F J

    2005-08-01

    he aim of this study was to investigate the presence of four black-pigmented bacteria, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia and Prevotella nigrescens, in endodontic infections by culture and polymerase chain reaction (PCR) analyses. Microbial samples were obtained from 50 teeth with untreated necrotic pulps (primary infection) and from 50 teeth with failing endodontic treatment (secondary infection). Microbiological strict anaerobic techniques were used for serial dilution, plating, incubation, and identification. For PCR detection, the samples were analyzed using species-specific primers of 16S rDNA and the downstream intergenic spacer region. Culture and PCR detected the test species in 13/100 and 50/100 of the study teeth, respectively. The organisms were cultured from 11/50 (22%) of primarily infected root canal samples and from 2/50 (4%) of secondary root canal samples. PCR detection identified the target species in 32/50 (64%) and 18/50 (36%) of primary and secondary infections, respectively. P. gingivalis was rarely isolated by culture methods (1%), but was the most frequently identified test species by PCR (38%). Similarly, P. endodontalis was not recovered by culture from any tooth studied, but was detected by PCR in 25% of the sampled teeth. PCR-based identification also showed higher detection rates of P. intermedia (33%) and P. nigrescens (22%) than culture (13%). In conclusion, P. gingivalis, P. endodontalis, P. intermedia, and P. nigrescens were identified more frequently in teeth with necrotic pulp than in teeth with failing endodontic treatment. Also, a higher frequency of black-pigmented species was detected by PCR than by culture.

  4. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections.

    PubMed

    Donnelley, Monica A; Zhu, Elizabeth S; Thompson, George R

    2016-01-01

    We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole's broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy.

  5. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections

    PubMed Central

    Donnelley, Monica A; Zhu, Elizabeth S; Thompson, George R

    2016-01-01

    We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate is commercially available in both an oral and intravenous formulation and is generally well tolerated. Isavuconazole’s broad spectrum of activity, limited side effect profile, and favorable pharmacokinetics will likely solidify its place in therapy. PMID:27330318

  6. Role of isavuconazole in the treatment of invasive fungal infections

    PubMed Central

    Wilson, Dustin T; Dimondi, V Paul; Johnson, Steven W; Jones, Travis M; Drew, Richard H

    2016-01-01

    Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug–drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug–drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring

  7. Role of isavuconazole in the treatment of invasive fungal infections.

    PubMed

    Wilson, Dustin T; Dimondi, V Paul; Johnson, Steven W; Jones, Travis M; Drew, Richard H

    2016-01-01

    Despite recent advances in both diagnosis and prevention, the incidence of invasive fungal infections continues to rise. Available antifungal agents to treat invasive fungal infections include polyenes, triazoles, and echinocandins. Unfortunately, individual agents within each class may be limited by spectrum of activity, resistance, lack of oral formulations, significant adverse event profiles, substantial drug-drug interactions, and/or variable pharmacokinetic profiles. Isavuconazole, a second-generation triazole, was approved by the US Food and Drug Administration in March 2015 and the European Medicines Agency in July 2015 for the treatment of adults with invasive aspergillosis (IA) or mucormycosis. Similar to amphotericin B and posaconazole, isavuconazole exhibits a broad spectrum of in vitro activity against yeasts, dimorphic fungi, and molds. Isavuconazole is available in both oral and intravenous formulations, exhibits a favorable safety profile (notably the absence of QTc prolongation), and reduced drug-drug interactions (relative to voriconazole). Phase 3 studies have evaluated the efficacy of isavuconazole in the management of IA, mucormycosis, and invasive candidiasis. Based on the results of these studies, isavuconazole appears to be a viable treatment option for patients with IA as well as those patients with mucormycosis who are not able to tolerate or fail amphotericin B or posaconazole therapy. In contrast, evidence of isavuconazole for invasive candidiasis (relative to comparator agents such as echinocandins) is not as robust. Therefore, isavuconazole use for invasive candidiasis may initially be reserved as a step-down oral option in those patients who cannot receive other azoles due to tolerability or spectrum of activity limitations. Post-marketing surveillance of isavuconazole will be important to better understand the safety and efficacy of this agent, as well as to better define the need for isavuconazole serum concentration monitoring.

  8. Diagnosis of invasive fungal infections in immunocompromised children.

    PubMed

    Dornbusch, H J; Groll, A; Walsh, T J

    2010-09-01

    Early recognition and rapid initiation of effective treatment is a prerequisite for successful management of children with invasive fungal infections. The increasing diversity of fungal pathogens in high-risk patients, the differences in the antifungal spectra of available agents and the increasing rates of resistance call for identification of the infecting isolate at the species level and for information on drug resistance, in order to provide state-of-the-art patient care. Microscopy and culture of appropriate specimens remain the reference standard for mycological diagnosis, despite difficulties in obtaining appropriate and/or sufficient specimens, long durations of culture and false-negative results. Modern imaging studies and detection of circulating fungal cell wall components and DNA in blood and other body fluids or in affected tissues may improve the laboratory diagnosis of invasive mycoses.

  9. Minireview: Invasive fungal infection complicating acute Plasmodium falciparum malaria.

    PubMed

    Däbritz, Jan; Schneider, Markward; Just-Nuebling, Gudrun; Groll, Andreas H

    2011-07-01

    Malaria is the most important parasitic infection in people, affecting 5-10% of the world's population with more than two million deaths a year. Whereas invasive bacterial infections are not uncommon during severe Plasmodium falciparum malaria, only a few cases of opportunistic fungal infections have been reported. Here, we present a fatal case of disseminated hyalohyphomycosis associated with acute P. falciparum malaria in a non-immune traveller, review the cases reported in the literature and discuss the theoretical foundations for the increased susceptibility of non-immune individuals with severe P. falciparum malaria to opportunistic fungal infections. Apart from the availability of free iron as sequelae of massive haemolysis, tissue damage, acidosis and measures of advanced life support, patients with complicated P. falciparum malaria also are profoundly immunosuppressed by the organism's interaction with innate and adaptive host immune mechanisms.

  10. Salmonella typhimurium Invasion Induces Apoptosis in Infected Macrophages

    NASA Astrophysics Data System (ADS)

    Monack, Denise M.; Raupach, Barbel; Hromockyj, Alexander E.; Falkow, Stanley

    1996-09-01

    Invasive Salmonella typhimurium induces dramatic cytoskeletal changes on the membrane surface of mammalian epithelial cells and RAW264.7 macrophages as part of its entry mechanism. Noninvasive S. typhimurium strains are unable to induce this membrane ruffling. Invasive S. typhimurium strains invade RAW264.7 macrophages in 2 h with 7- to 10-fold higher levels than noninvasive strains. Invasive S. typhimurium and Salmonella typhi, independent of their ability to replicate intracellularly, are cytotoxic to RAW264.7 macrophages and, to a greater degree, to murine bone marrow-derived macrophages. Here, we show that the macrophage cytotoxicity mediated by invasive Salmonella is apoptosis, as shown by nuclear morphology, cytoplasmic vacuolization, and host cell DNA fragmentation. S. typhimurium that enter cells causing ruffles but are mutant for subsequent intracellular replication also initiate host cell apoptosis. Mutant S. typhimurium that are incapable of inducing host cell membrane ruffling fail to induce apoptosis. The activation state of the macrophage plays a significant role in the response of macrophages to Salmonella invasion, perhaps indicating that the signal or receptor for initiating programmed cell death is upregulated in activated macrophages. The ability of Salmonella to promote apoptosis may be important for the initiation of infection, bacterial survival, and escape of the host immune response.

  11. Invasive Haemophilus influenzae Infection in Patients With Cancer.

    PubMed

    Singh, Vivek; Nanjappa, Sowmya; Pabbathi, Smitha; Greene, John N

    2017-01-01

    A major cause of morbidity and mortality in patients with cancer is infection. Since the introduction of the Haemophilus influenzae type b (Hib) vaccine in the United States in the 1990s, invasive H influenzae infection has become less common. We report on 5 patients with cancer and invasive H influenzae infection. A literature review was also performed of the dominant Haemophilus subtype and the clinical features associated with the infection and concomitant cancer. Of the 17 cases found in the literature, had hematological malignancies and 1 case each had thymoma, schwannoma, teratoma, and pancreatic, Merkel cell, pharyngeal, laryngeal, and rectal carcinomas. Two cases occurred with AIDS and Kaposi sarcoma. Pneumonia with bacteremia was seen in 8 cases, whereas pleuritis, neck cellulitis, septic arthritis, meningitis, and mediastinitis were diagnosed in the others. No focus of infection was identified in 2 cases. Nontypable H influenzae (NTHi) occurred in 4 cases, and Hib was isolated in 2 cases; serotyping was not reported in the others. Leukocytosis occurred in 7 cases and lymphopenia in 3; no cases presented with neutropenia. Four isolates were positive for beta-lactamase. Susceptibility data were unavailable in 5 case patients. Among serotyped cases, 67% were of the NTHi strain - a finding consistent with the change in the epidemiology of H influenzae since the introduction of the Hib vaccine.

  12. Comparative genome analysis of Prevotella ruminicola and Prevotella bryantii: insights into their environmental niche.

    PubMed

    Purushe, Janaki; Fouts, Derrick E; Morrison, Mark; White, Bryan A; Mackie, Roderick I; Coutinho, Pedro M; Henrissat, Bernard; Nelson, Karen E

    2010-11-01

    The Prevotellas comprise a diverse group of bacteria that has received surprisingly limited attention at the whole genome-sequencing level. In this communication, we present the comparative analysis of the genomes of Prevotella ruminicola 23 (GenBank: CP002006) and Prevotella bryantii B(1)4 (GenBank: ADWO00000000), two gastrointestinal isolates. Both P. ruminicola and P. bryantii have acquired an extensive repertoire of glycoside hydrolases that are targeted towards non-cellulosic polysaccharides, especially GH43 bifunctional enzymes. Our analysis demonstrates the diversity of this genus. The results from these analyses highlight their role in the gastrointestinal tract, and provide a template for additional work on genetic characterization of these species.

  13. [Management of severe invasive group A streptococcal infections].

    PubMed

    Faye, A; Lorrot, M; Bidet, Ph; Bonacorsi, S; Cohen, R

    2014-11-01

    The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a β-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention.

  14. Invasive Group A Streptococcus Infection among Children, Rural Kenya

    PubMed Central

    Davies, Mark R.; Anampiu, Kirimi; Morpeth, Susan C.; Nyongesa, Sammy; Mwarumba, Salim; Smeesters, Pierre R.; Efstratiou, Androulla; Karugutu, Rosylene; Mturi, Neema; Williams, Thomas N.; Scott, J. Anthony G.; Kariuki, Samuel; Dougan, Gordon; Berkley, James A.

    2016-01-01

    To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the serotypes that cause disease, we analyzed surveillance data for 64,741 hospital admissions in Kilifi, Kenya, during 1998–2011. We evaluated incidence, clinical presentations, and emm types that cause invasive GAS infection. We detected 370 cases; of the 369 for which we had data, most were skin and soft tissue infections (70%), severe pneumonia (23%), and primary bacteremia (14%). Overall case-fatality risk was 12%. Incidence of invasive GAS infection was 0.6 cases/1,000 live births among neonates, 101/100,000 person-years among children <1 year of age, and 35/100,000 among children <5 years of age. Genome sequencing identified 88 emm types. GAS causes serious disease in children in rural Kenya, especially neonates, and the causative organisms have considerable genotypic diversity. Benefit from the most advanced GAS type–specific vaccines may be limited, and efforts must be directed to protect against disease in regions of high incidence. PMID:26811918

  15. Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

    PubMed Central

    Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

    2014-01-01

    SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

  16. Does Minimally Invasive Spine Surgery Minimize Surgical Site Infections?

    PubMed Central

    Patel, Ravish Shammi; Dutta, Shumayou

    2016-01-01

    Study Design Retrospective review of prospectively collected data. Purpose To evaluate the incidence of surgical site infections (SSIs) in minimally invasive spine surgery (MISS) in a cohort of patients and compare with available historical data on SSI in open spinal surgery cohorts, and to evaluate additional direct costs incurred due to SSI. Overview of Literature SSI can lead to prolonged antibiotic therapy, extended hospitalization, repeated operations, and implant removal. Small incisions and minimal dissection intrinsic to MISS may minimize the risk of postoperative infections. However, there is a dearth of literature on infections after MISS and their additional direct financial implications. Methods All patients from January 2007 to January 2015 undergoing posterior spinal surgery with tubular retractor system and microscope in our institution were included. The procedures performed included tubular discectomies, tubular decompressions for spinal stenosis and minimal invasive transforaminal lumbar interbody fusion (TLIF). The incidence of postoperative SSI was calculated and compared to the range of cited SSI rates from published studies. Direct costs were calculated from medical billing for index cases and for patients with SSI. Results A total of 1,043 patients underwent 763 noninstrumented surgeries (discectomies, decompressions) and 280 instrumented (TLIF) procedures. The mean age was 52.2 years with male:female ratio of 1.08:1. Three infections were encountered with fusion surgeries (mean detection time, 7 days). All three required wound wash and debridement with one patient requiring unilateral implant removal. Additional direct cost due to infection was $2,678 per 100 MISS-TLIF. SSI increased hospital expenditure per patient 1.5-fold after instrumented MISS. Conclusions Overall infection rate after MISS was 0.29%, with SSI rate of 0% in non-instrumented MISS and 1.07% with instrumented MISS. MISS can markedly reduce the SSI rate and can be an

  17. [Saccharomyces cerevisiae invasive infection: The first reported case in Morocco].

    PubMed

    Maleb, A; Sebbar, E; Frikh, M; Boubker, S; Moussaoui, A; El Mekkaoui, A; Khannoussi, W; Kharrasse, G; Belefquih, B; Lemnouer, A; Ismaili, Z; Elouennass, M

    2017-02-07

    Saccharomyces cerevisiae is a cosmopolitan yeast, widely used in agro-alimentary and pharmaceutical industry. Its impact in human pathology is rare, but maybe still underestimated compared to the real situation. This yeast is currently considered as an emerging and opportunistic pathogen. Risk factors are immunosuppression and intravascular device carrying. Fungemias are the most frequent clinical forms. We report the first case of S. cerevisiae invasive infection described in Morocco, and to propose a review of the literature cases of S. cerevisiae infections described worldwide. A 77-year-old patient, with no notable medical history, who was hospitalized for a upper gastrointestinal stenosis secondary to impassable metastatic gastric tumor. Its history was marked by the onset of septic shock, with S. cerevisiae in his urine and in his blood, with arguments for confirmation of invasion: the presence of several risk factors in the patient, positive direct microbiological examination, abundant and exclusive culture of S. cerevisiae from clinical samples. Species identification was confirmed by the study of biochemical characteristics of the isolated yeast. Confirmation of S. cerevisiae infection requires a clinical suspicion in patients with risk factors, but also a correct microbiological diagnosis.

  18. Direct quantitative differentiation between Prevotella intermedia and Prevotella nigrescens in clinical specimens.

    PubMed

    Gmür, Rudolf; Thurnheer, Thomas

    2002-05-01

    This paper describes a quantitative fluorescent in situ hybridization (FISH) assay for the differential identification of Prevotella intermedia and Prevotella nigrescens in clinical samples, and compares its performance with less discriminatory culture and quantitative immunofluorescence (IF) assays. Fluorescence-labelled oligonucleotide probes directed to specific 16S rRNA sequences of P. intermedia, P. nigrescens, Prevotella pallens and Prevotella denticola were hybridized under stringent conditions with cultured reference strains or plaque samples from deep periodontal pockets. Probe specificity was defined with strains from multiple oral Prevotella species. The lower detection level of the assays was approximately 3x10(3) target cells per ml of plaque-sample suspension. P. intermedia, P. nigrescens, P. pallens and P. denticola were detected in plaques with prevalences of 69, 67, 0 and 28%, respectively. On average, 3.9 x 10(6) P. intermedia, 3.1 x 10(6) P. nigrescens and 5.6 x 10(5) P. denticola cells were counted per positive sample. All three species were found almost exclusively in dense mixed aggregates. Quantitative FISH data agreed satisfactorily with corresponding IF data (r=0.711). Both FISH and IF enumerations of the sum of P. intermedia and P. nigrescens markedly exceeded the c.f.u. counts of black-pigmented colonies in Porphyromonas gingivalis-free cultured subgingival plaques. The results demonstrate the validity of this new assay. Unlike established IF, culture, PCR or checkerboard DNA hybridization assays, this FISH assay differentiates quantitatively between P. intermedia and P. nigrescens, provides visual accuracy control, and offers insights into the spatial distribution of the target cells within a clinical sample.

  19. Molecular epidemiology of the sil streptococcal invasive locus in group A streptococci causing invasive infections in French children.

    PubMed

    Bidet, Philippe; Courroux, Céline; Salgueiro, Christophe; Carol, Agnès; Mariani-Kurkdjian, Patricia; Bonacorsi, Stéphane; Bingen, Edouard

    2007-06-01

    We found 31 different emm-toxin genotypes among 74 group A streptococcal isolates causing invasive infections in French children. The predominant emm types were emm1 (25%), emm3 (8%), emm4 (8%), emm6 (7%), and emm89 (9%). Sixteen percent of isolates harbored the streptococcal invasive locus, half of them belonging to emm4.

  20. Azole antifungals: 35 years of invasive fungal infection management.

    PubMed

    Allen, David; Wilson, Dustin; Drew, Richard; Perfect, John

    2015-06-01

    Prior to 1981, treatment options for invasive fungal infections were limited and associated with significant toxicities. The introduction of ketoconazole marked the beginning of an era of dramatic improvements over previous therapies for non-life-threatening mycosis. After nearly a decade of use, ketoconazole was quickly replaced by the triazoles fluconazole and itraconazole due to significant improvements in pharmacokinetic profile, spectrum of activity and safety. The triazoles posaconazole and voriconazole followed, and were better known for their further extended spectrum, specifically against emerging mold infections. With the exception of fluconazole, the triazoles have been plagued with significant inter- and intrapatient pharmacokinetic variability and all possess significant drug interactions. Azoles currently in development appear to combine an in vitro spectrum of activity comparable to voriconazole and posaconazole with more predictable pharmacokinetics and fewer adverse effects.

  1. Invasive mould infections in the ICU setting: complexities and solutions.

    PubMed

    Bassetti, Matteo; Bouza, Emilio

    2017-03-01

    Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing conditions, e.g. corticosteroid treatment, chronic obstructive pulmonary disease, liver cirrhosis, solid organ cancer, HIV infection and transplantation. Diagnosis is challenging because the signs and symptoms are non-specific, and initiation of additional diagnostic examinations is often delayed because clinical suspicion is low. Isolation of an Aspergillus species from the respiratory tract in critically ill patients, and tests such as serum galactomannan, bronchoalveolar lavage 1-3-β-d-glucan and specific PCR should be interpreted with caution. ICU patients should start adequate antifungal therapy upon suspicion of invasive aspergillosis, without awaiting definitive proof. Voriconazole, and now isavuconazole, are the drugs of choice. Mucormycosis is a rare, but increasingly prevalent disease that occurs mainly in patients with uncontrolled diabetes mellitus, immunocompromised individuals or previously healthy patients with open wounds contaminated with Mucorales. A high proportion of cases are diagnosed in the ICU. Rapidly progressing necrotizing lesions in the rhino-sinusal area, the lungs or skin and soft tissues are the characteristic presentation. Confirmation of diagnosis is based on demonstration of tissue invasion by non-septate hyphae, and by new promising molecular techniques. Control of underlying predisposing conditions, rapid surgical resection and administration of liposomal amphotericin B are the main therapeutic actions, but new agents such as isavuconazole are a promising alternative. Patients with mucormycosis receive a substantial part of their care in ICUs and, despite advances in diagnosis and treatment, mortality remains very high.

  2. Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment

    PubMed Central

    Domínguez-Hüttinger, Elisa; Boon, Neville J.; Clarke, Thomas B.; Tanaka, Reiko J.

    2017-01-01

    Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We

  3. Mathematical Modeling of Streptococcus pneumoniae Colonization, Invasive Infection and Treatment.

    PubMed

    Domínguez-Hüttinger, Elisa; Boon, Neville J; Clarke, Thomas B; Tanaka, Reiko J

    2017-01-01

    Streptococcus pneumoniae (Sp) is a commensal bacterium that normally resides on the upper airway epithelium without causing infection. However, factors such as co-infection with influenza virus can impair the complex Sp-host interactions and the subsequent development of many life-threatening infectious and inflammatory diseases, including pneumonia, meningitis or even sepsis. With the increased threat of Sp infection due to the emergence of new antibiotic resistant Sp strains, there is an urgent need for better treatment strategies that effectively prevent progression of disease triggered by Sp infection, minimizing the use of antibiotics. The complexity of the host-pathogen interactions has left the full understanding of underlying mechanisms of Sp-triggered pathogenesis as a challenge, despite its critical importance in the identification of effective treatments. To achieve a systems-level and quantitative understanding of the complex and dynamically-changing host-Sp interactions, here we developed a mechanistic mathematical model describing dynamic interplays between Sp, immune cells, and epithelial tissues, where the host-pathogen interactions initiate. The model serves as a mathematical framework that coherently explains various in vitro and in vitro studies, to which the model parameters were fitted. Our model simulations reproduced the robust homeostatic Sp-host interaction, as well as three qualitatively different pathogenic behaviors: immunological scarring, invasive infection and their combination. Parameter sensitivity and bifurcation analyses of the model identified the processes that are responsible for qualitative transitions from healthy to such pathological behaviors. Our model also predicted that the onset of invasive infection occurs within less than 2 days from transient Sp challenges. This prediction provides arguments in favor of the use of vaccinations, since adaptive immune responses cannot be developed de novo in such a short time. We

  4. Dipeptide utilization by the periodontal pathogens Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum.

    PubMed

    Takahashi, Nobuhiro; Sato, T

    2002-02-01

    Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Fusobacterium nucleatum, which can frequently be isolated from periodontal pockets, preferentially utilize proteins and peptides as growth substrates. In this study, we determined the size of peptide that is preferentially utilized as a source of energy and material for cell growth by P. gingivalis, P. intermedia, P. nigrescens and F. nucleatum using various sizes of poly amino acids consisting of two to approximately 100 molecules of aspartate or glutamate. Resting cells of P. gingivalis, P. intermedia and P. nigrescens utilized aspartylaspartate, while cells of P. gingivalis and F. nucleatum utilized glutamylglutamate. The addition of aspartylaspartate to the culture medium increased the growth of P. gingivalis, P. intermedia and P. nigrescens, while the addition of glutamylglutamate promoted the growth of P. gingivalis and F. nucleatum. These results clearly indicate that dipeptides such as aspartylaspartate and glutamylglutamate can be utilized as growth substrates for P. gingivalis, P. intermedia, P. nigrescens and F. nucleatum.

  5. Multiple extracellular phospholipase activities from Prevotella intermedia.

    PubMed

    Bulkacz, Jaime; Faull, Kym F

    2009-06-01

    Enzyme preparations obtained from Prevotella intermedia culture supernatants were partially purified by ammonium sulfate precipitation and ion-exchange column chromatography. Hydrolytic activities were revealed by an assay that uses silicic acid thin layer chromatography to separate the products derived from (14)C-labeled phosphatidyl-choline (PC) hydrolysis. These products were then measured by liquid scintillation spectrometry after iodine visualization. The assays revealed linearity of substrate depletion and product formation with respect to time and protein concentration up to 30 min of incubation. The products had retention times consistent with lyso-phospholipids and phosphoryl-choline. These data strongly suggests the presence of both phospholipase A (PL-A) and phospholipase C (PL-C) activities.

  6. Degradation of human hemoglobin by Prevotella intermedia.

    PubMed

    Guan, Su-Min; Nagata, Hideki; Shizukuishi, Satoshi; Wu, Jun-Zheng

    2006-01-01

    In this study, the ability of Prevotella intermedia, an obligate anaerobic rod, to degrade human hemoglobin was determined by SDS-PAGE and the degradation was quantified by scanning densitometry. Both bacterial cells and culture supernatants degraded hemoglobin. The hemoglobin degradation by P. intermedia was time-dependent, heat sensitive, pH related and was not influenced by iron restriction. Inhibition studies demonstrated that a cysteine protease might be involved in hemoglobin degradation and this protease might require metal ions for its activity and it might be thiol-requiring and trypsin-inducible. The results indicate that P. intermedia is capable to release heme from hemoglobin, hence provide a source of iron for its proliferation.

  7. The identification of genes specific to Prevotella intermedia and Prevotella nigrescens using genomic subtractive hybridization.

    PubMed

    Masakiyo, Yoshiaki; Yoshida, Akihiro; Shintani, Yasuyuki; Takahashi, Yusuke; Ansai, Toshihiro; Takehara, Tadamichi

    2010-06-01

    Prevotella intermedia and Prevotella nigrescens, which are often isolated from periodontal sites, were once considered two different genotypes of P. intermedia. Although the genomic sequence of P. intermedia was determined recently, little is known about the genetic differences between P. intermedia and P. nigrescens. The subtractive hybridization technique is a powerful method for generating a set of DNA fragments differing between two closely related bacterial strains or species. We used subtractive hybridization to identify the DNA regions specific to P. intermedia ATCC 25611 and P. nigrescens ATCC 25261. Using this method, four P. intermedia ATCC 25611-specific and three P. nigrescens ATCC 25261-specific regions were determined. From the species-specific regions, insertion sequence (IS) elements were isolated for P. intermedia. IS elements play an important role in the pathogenicity of bacteria. For the P. intermedia-specific regions, the genes adenine-specific DNA-methyltransferase and 8-amino-7-oxononanoate synthase were isolated. The P. nigrescens-specific region contained a Flavobacterium psychrophilum SprA homologue, a cell-surface protein involved in gliding motility, Prevotella melaninogenica ATCC 25845 glutathione peroxide, and Porphyromonas gingivalis ATCC 33277 leucyl-tRNA synthetase. The results demonstrate that the subtractive hybridization technique was useful for distinguishing between the two closely related species. Furthermore, this technique will contribute to our understanding of the virulence of these species.

  8. Diagnostics for invasive Salmonella infections: Current challenges and future directions.

    PubMed

    Andrews, Jason R; Ryan, Edward T

    2015-06-19

    Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics.

  9. Early diagnosis of invasive mould infections and disease.

    PubMed

    Lamoth, Frédéric; Calandra, Thierry

    2017-03-01

    Invasive mould infections (IMIs), such as invasive aspergillosis or mucormycosis, are a major cause of death in patients with haematological cancer and in patients receiving long-term immunosuppressive therapy. Early diagnosis and prompt initiation of antifungal therapy are crucial steps in the management of patients with IMI. The diagnosis of IMI remains a major challenge, with an increased spectrum of fungal pathogens and a diversity of clinical and radiological presentations within the expanding spectrum of immunocompromised hosts. Diagnosis is difficult to establish and is expressed on a scale of probability (proven, probable and possible). Imaging (CT scan), microbiological tools (direct examination, culture, PCR, fungal biomarkers) and histopathology are the pillars of the diagnostic work-up of IMI. None of the currently available diagnostic tests provides sufficient sensitivity and specificity alone, so the optimal approach relies on a combination of multiple diagnostic strategies, including imaging, fungal biomarkers (galactomannan and 1,3-β-d-glucan) and molecular tools. In recent years, the development of PCR for filamentous fungi (primarily Aspergillus or Mucorales) and the progress made in the standardization of fungal PCR technology, may lead to future advances in the field. The appropriate diagnostic approach for IMI should be individualized to each centre, taking into account the local epidemiology of IMI and the availability of diagnostic tests.

  10. Invasive pneumococcal infection in South and West England.

    PubMed Central

    Smith, M. D.; Stuart, J.; Andrews, N. J.; Telfer Brunton, W. A.; Cartwright, K. A.

    1998-01-01

    Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines. PMID:9593479

  11. PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.

    PubMed

    Wójtowicz, Agnieszka; Lecompte, T Doco; Bibert, Stephanie; Manuel, Oriol; Rüeger, Sina; Berger, Christoph; Boggian, Katia; Cusini, Alexia; Garzoni, Christian; Hirsch, Hans; Khanna, Nina; Mueller, Nicolas J; Meylan, Pascal R; Pascual, Manuel; van Delden, Christian; Bochud, Pierre-Yves

    2015-08-15

    Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.

  12. Diagnosis of Helicobacter pylori infection by invasive and noninvasive tests.

    PubMed

    Pourakbari, Babak; Ghazi, Mona; Mahmoudi, Shima; Mamishi, Setareh; Azhdarkosh, Hossein; Najafi, Mehri; Kazemi, Bahram; Salavati, Ali; Mirsalehian, Akbar

    2013-01-01

    Although several invasive and noninvasive tests have been developed for the diagnosis of Helicobacter pylori infection, all of the tests have their limitations. We conducted a study to investigate and compare the suitability of rapid urease test (RUT), serology, histopathology and stool antigen tests with polymerase chain reaction (PCR) for detection of H. pylori, and correlate the diagnostic methods with PCR. Eighty nine patients (61 adults, 28 children) referred to the Firoozgar Hospital and Children Medical Center Hospital for diagnostic upper gastrointestinal endoscopy entered to the study and noninvasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in feces were measured. The biopsies were utilized for histological examination, RUT and PCR. The H. pylori statuses were evaluated by the positivity of ureC PCR in biopsy specimens and 53 subjects had H. pylori positive result. Histopathology showed high overall performance in adults and children with sensitivity and specificity 100% and 90%, respectively. Sensitivity, specificity, and accuracy for stool antigen test were 87.8%, 75% and 82%, respectively. Correlation of RUT, serology (IgG), histopathology and stool antigen tests with PCR were 0.82, 0.32, 0.91 and 0.63, respectively. In conclusion, the RUT and histopathology are as accurate as the PCR of biopsy and stool antigen test can consider as appropriate noninvasive test for detection of H. pylori infection.

  13. Production of extended-spectrum β-lactamases and the potential indirect pathogenic role of Prevotella isolates from the cystic fibrosis respiratory microbiota

    PubMed Central

    Sherrard, Laura J.; McGrath, Stef J.; McIlreavey, Leanne; Hatch, Joseph; Wolfgang, Matthew C.; Muhlebach, Marianne S.; Gilpin, Deirdre F.; Elborn, J. Stuart; Tunney, Michael M.

    2016-01-01

    Extended-spectrum β-lactamase (ESBL) production and the prevalence of the β-lactamase-encoding gene blaTEM were determined in Prevotella isolates (n = 50) cultured from the respiratory tract of adults and young people with cystic fibrosis (CF). Time–kill studies were used to investigate the concept of passive antibiotic resistance and to ascertain whether a β-lactamase-positive Prevotella isolate can protect a recognised CF pathogen from the action of ceftazidime in vitro. The results indicated that approximately three-quarters (38/50; 76%) of Prevotella isolates produced ESBLs. Isolates positive for ESBL production had higher minimum inhibitory concentrations (MICs) of β-lactam antibiotics compared with isolates negative for production of ESBLs (P < 0.001). The blaTEM gene was detected more frequently in CF Prevotella isolates from paediatric patients compared with isolates from adults (P = 0.002), with sequence analysis demonstrating that 21/22 (95%) partial blaTEM genes detected were identical to blaTEM-116. Furthermore, a β-lactamase-positive Prevotella isolate protected Pseudomonas aeruginosa from the antimicrobial effects of ceftazidime (P = 0.03). Prevotella isolated from the CF respiratory microbiota produce ESBLs and may influence the pathogenesis of chronic lung infection via indirect methods, including shielding recognised pathogens from the action of ceftazidime. PMID:26774156

  14. Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts.

    PubMed

    Metcalf, S C; Dockrell, D H

    2007-10-01

    Invasive fungal infections cause substantial morbidity and mortality in immunocompromised hosts. The response rate to therapy, in particular for invasive aspergillosis and invasive mould infections, has been poor. Recently a number of techniques to facilitate early diagnosis of these infections, in parallel with the development of a number of antifungals with increased potency and lower toxicity, have raised optimism that outcomes for invasive fungal infection can be improved upon. The availability of lipid formulations of amphotericin B, azoles with extended spectrum against filamentous fungi and the development of a new class of antifungal agents, the echinocandins, presents the clinician with a range of therapeutic choices. Recent clinical trials have provided important insights into how these agents should be used. In particular, voriconazole has demonstrated superior efficacy to amphotericin B in the management of invasive aspergillosis, posaconazole has been shown to have significant efficacy in the prophylaxis of invasive fungal infection in high-risk individuals and a role in salvage therapy of invasive aspergillosis, caspofungin has demonstrated efficacy in salvage therapy of invasive aspergillosis, and each of the echinocandins show activity without significant toxicity in invasive candidiasis. Nevertheless, many therapeutic areas of uncertainty remain, including the role of combination therapy, and will provide the focus for future studies.

  15. Nucleases from Prevotella intermedia can degrade neutrophil extracellular traps.

    PubMed

    Doke, M; Fukamachi, H; Morisaki, H; Arimoto, T; Kataoka, H; Kuwata, H

    2016-08-01

    Periodontitis is an inflammatory disease caused by periodontal bacteria in subgingival plaque. These bacteria are able to colonize the periodontal region by evading the host immune response. Neutrophils, the host's first line of defense against infection, use various strategies to kill invading pathogens, including neutrophil extracellular traps (NETs). These are extracellular net-like fibers comprising DNA and antimicrobial components such as histones, LL-37, defensins, myeloperoxidase, and neutrophil elastase from neutrophils that disarm and kill bacteria extracellularly. Bacterial nuclease degrades the NETs to escape NET killing. It has now been shown that extracellular nucleases enable bacteria to evade this host antimicrobial mechanism, leading to increased pathogenicity. Here, we compared the DNA degradation activity of major Gram-negative periodontopathogenic bacteria, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We found that Pr. intermedia showed the highest DNA degradation activity. A genome search of Pr. intermedia revealed the presence of two genes, nucA and nucD, putatively encoding secreted nucleases, although their enzymatic and biological activities are unknown. We cloned nucA- and nucD-encoding nucleases from Pr. intermedia ATCC 25611 and characterized their gene products. Recombinant NucA and NucD digested DNA and RNA, which required both Mg(2+) and Ca(2+) for optimal activity. In addition, NucA and NucD were able to degrade the DNA matrix comprising NETs.

  16. In vitro activation of the hemolysin in Prevotella nigrescens ATCC 33563 and Prevotella intermedia ATCC 25611.

    PubMed

    Silva, Tarcília Aparecida; Noronha, Fátima Soares M; de Macêdo Farias, Luiz; Carvalho, Maria Auxiliadora R

    2004-01-01

    Hemolytic activity was evaluated in the putative periodontopathogens Prevotella intermedia and Prevotella nigrescens. Whole cells of both species present weak hemolytic activity evidenced only by solid media assays after 48 h of bacterial growth or after 5 h of interaction with erythrocytes at 37 degrees C in liquid assays. In this work we show that the use of crude extract allowed the detection of a higher hemolytic activity for P. intermedia, but surprisingly not for P. nigrescens. Incubation at 37 degrees C for 9 h, or treatment with trypsin or proteinase K, increased or exposed the hemolytic activity of P. intermedia and P. nigrescens crude extract, respectively. The activation process was inhibited by TLCK and PMSF but not by EDTA, E-64 or pepstatin A, indicating the serino-protease nature of the factor involved in activation of P. intermedia and P. nigrescens hemolysins. Both the buffer and the pH employed for cell fractionation influenced the activation of hemolysin, and the best results were obtained with Universal buffer at pH 8.0. The activated hemolysins acted optimally at pH 6.5 at 37 degrees C and the maximum hemolytic activity was detected at the early log phase of growth. The results of this study show for the first time a strong hemolytic activity for P. nigrescens and evidence of proteolytic activation of hemolysins produced by periodontopathogens.

  17. Prevotella aurantiaca sp. nov., isolated from the human oral cavity.

    PubMed

    Sakamoto, Mitsuo; Suzuki, Natsuko; Okamoto, Masaaki

    2010-03-01

    Two anaerobic, pigmented, non-spore-forming, Gram-stain-negative, rod-shaped strains isolated from the human oral cavity, OMA31(T) and OMA130, were characterized by determining their phenotypic and biochemical features, cellular fatty acid profiles and phylogenetic positions based on 16S rRNA gene sequence analysis. 16S rRNA gene sequence analysis showed that the new isolates belonged to a single species of the genus Prevotella. The two isolates showed 100 % 16S rRNA gene sequence similarity with each other and were most closely related to Prevotella intermedia ATCC 25611(T) with 96.4 % 16S rRNA gene sequence similarity; the next most closely related strains to the isolates were Prevotella pallens AHN 10371(T) (96.1 %) and Prevotella falsenii JCM 15124(T) (95.3 %). Phenotypic and biochemical characteristics of the isolates were the same as those of P. intermedia JCM 12248(T), P. falsenii JCM 15124(T) and Prevotella nigrescens JCM 12250(T). The isolates could be differentiated from P. pallens JCM 11140( T) by mannose fermentation and alpha-fucosidase activity. Conventional biochemical tests were unable to differentiate the new isolates from P. intermedia, P. falsenii and P. nigrescens. However, hsp60 gene sequence analysis suggested that strain OMA31(T) was not a representative of P. intermedia, P. pallens, P. falsenii or P. nigrescens. Based on these data, a novel species of the genus Prevotella, Prevotella aurantiaca sp. nov., is proposed, with OMA31(T) (=JCM 15754(T)=CCUG 57723(T)) as the type strain.

  18. Challenges in microbiological diagnosis of invasive Aspergillus infections.

    PubMed

    Alanio, Alexandre; Bretagne, Stéphane

    2017-01-01

    Invasive aspergillosis (IA) has been increasingly reported in populations other than the historical hematology patients and there are new questions about the performance of microbiological tools. Microscopy and culture have been completed by biomarkers, either antigens or DNA, and in blood or respiratory specimens or both. First studied in hematology, the antigen galactomannan performance in serum is low in other patient populations where the pathophysiology of the infection can be different and the prevalence of IA is much lower. DNA detection with polymerase chain reaction (PCR) in blood or serum (or both) has reached a certain level of acceptance thanks to consensus methods based on real-time quantitative PCR (qPCR). When used on respiratory specimens, galactomannan and qPCR depend on standardization of the sampling and the diverse mycological procedures. Thus, culture remains the main diagnostic criterion in critically ill patients. The current trend toward more effective anti-mold prophylaxis in hematology hampers the yield of a screening strategy, as is usually performed in hematology. Therefore, circulating biomarkers as confirmatory tests should be considered and their performance should be reappraised in each new setting. The use of azole prophylaxis also raises the issue of selecting azole-resistance Aspergillus fumigatus isolates. Ideally, the biomarkers will be more efficient when individual genetic risks of IA are defined. Culture, though not standardized, remains a key element for the diagnosis of IA and has the advantage to easily detect molds other than A. fumigatus. It is still unclear whether next-generation sequencing will replace culture in the future.

  19. Challenges in microbiological diagnosis of invasive Aspergillus infections

    PubMed Central

    Alanio, Alexandre; Bretagne, Stéphane

    2017-01-01

    Invasive aspergillosis (IA) has been increasingly reported in populations other than the historical hematology patients and there are new questions about the performance of microbiological tools. Microscopy and culture have been completed by biomarkers, either antigens or DNA, and in blood or respiratory specimens or both. First studied in hematology, the antigen galactomannan performance in serum is low in other patient populations where the pathophysiology of the infection can be different and the prevalence of IA is much lower. DNA detection with polymerase chain reaction (PCR) in blood or serum (or both) has reached a certain level of acceptance thanks to consensus methods based on real-time quantitative PCR (qPCR). When used on respiratory specimens, galactomannan and qPCR depend on standardization of the sampling and the diverse mycological procedures. Thus, culture remains the main diagnostic criterion in critically ill patients. The current trend toward more effective anti-mold prophylaxis in hematology hampers the yield of a screening strategy, as is usually performed in hematology. Therefore, circulating biomarkers as confirmatory tests should be considered and their performance should be reappraised in each new setting. The use of azole prophylaxis also raises the issue of selecting azole-resistance Aspergillus fumigatus isolates. Ideally, the biomarkers will be more efficient when individual genetic risks of IA are defined. Culture, though not standardized, remains a key element for the diagnosis of IA and has the advantage to easily detect molds other than A. fumigatus. It is still unclear whether next-generation sequencing will replace culture in the future. PMID:28299183

  20. Invasive Aspergillus Sinusitis in Human Immunodeficiency Virus Infection: Case Report and Review of the Literature

    PubMed Central

    Humphrey, John M.; Walsh, Thomas J.; Gulick, Roy M.

    2016-01-01

    Invasive Aspergillus (IA) sinusitis is a life-threatening opportunistic infection in immunocompromised individuals, but it is uncommon in human immunodeficiency virus (HIV) infection. To gain a better understanding of the characteristics of IA sinusitis in this population, we present a unique case of chronic IA sinusitis in an HIV-infected patient taking antiretroviral therapy and review the literature summarizing published cases of invasive aspergillosis of the paranasal (n = 41) and mastoid (n = 17) sinuses in HIV-infected individuals. Among these cases, only 4 were reported after 1999, and 98% of patients had acquired immune deficiency syndrome. Orbital invasion occurred in 54% of paranasal sinus cases, whereas intracranial invasion was reported in 53% of mastoid sinus cases. The overall mortality was 79%. We also discuss various clinical and immunologic factors that may play a role in the development of IA and consider the changing epidemiology of aspergillosis in the era of effective antiretroviral therapy. PMID:27800523

  1. [Epidemiological analysis of the incidence of invasive and non-invasive pneumococcal infections in different population groups].

    PubMed

    Martynova, A V; Turkutiukov, V B

    2007-01-01

    Despite modern achievements in diagnostics and treatment, invasive and non-invasive pneumococcal infections remain a topical public health problem. To a large extent, it is connected with the absence or inconsistence of evidence-based information on this kind of infection. In this paper, retrospective analysis of the incidence of pneumococcal infections was performed on the basis of medical records available today in every health institution; the peculiarities of their nosologic structure were revealed. Among invasive forms, pneumococcal pneumonias prevailed (50.06%); apparent hypodiagnostics of pneumococcal meningitis was noted (only 4.02%). Among non-invasive forms, acute otitis with various complications prevailed (47.5%), acute sinusitis was registered in 37.5% of cases, and other ENT diseases (sphenoiditis, frontitis, ethmoiditis, etc.) were registered in 15% of cases. The study found that the main risk factors in these patients had been different ENT diseases which the patients had suffered from during the previous three months before the actual illness. Thus, the necessity for the development and perfection of techniques of microbiological diagnostics and the development of epidemiological control methods on their basis are obvious.

  2. Phylogenetic analysis of Prevotella nigrescens, Prevotella intermedia and Porphyromonas gingivalis clinical strains reveals a clear species clustering.

    PubMed

    Kuhnert, Peter; Frey, Joachim; Lang, Niklaus P; Mayfield, Lisa

    2002-07-01

    Prevotella nigrescens, Prevotella intermedia and Porphyromonas gingivalis are oral pathogens from the family Bacteroidaceae, regularly isolated from cases of gingivitis and periodontitis. In this study, the phylogenetic variability of these three bacterial species was investigated by means of 16S rRNA (rrs) gene sequence comparisons of a set of epidemiologically and geographically diverse isolates. For each of the three species, the rrs gene sequences of 11 clinical isolates as well as the corresponding type strains was determined. Comparison of all rrs sequences obtained with those of closely related species revealed a clear clustering of species, with only a little intraspecies variability but a clear difference in the rrs gene with respect to the next related taxon. The results indicate that the three species form stable, homogeneous genetic groups, which favours an rrs-based species identification of these oral pathogens. This is especially useful given the 7% sequence divergence between Prevotella intermedia and Prevotella nigrescens, since phenotypic distinction between the two Prevotella species is inconsistent or involves techniques not applicable in routine identification.

  3. Risk Factors Associated with Invasive Fungal Infections in Combat Trauma

    PubMed Central

    Rodriguez, Carlos J.; Weintrob, Amy C.; Shah, Jinesh; Malone, Debra; Dunne, James R.; Weisbrod, Allison B.; Lloyd, Bradley A.; Warkentien, Tyler E.; Murray, Clinton K.; Wilkins, Kenneth; Shaikh, Faraz; Carson, M. Leigh; Aggarwal, Deepak

    2014-01-01

    Abstract Background: In recent years, invasive fungal infections (IFI) have complicated the clinical course of patients with combat-related injuries. Commonalities in injury patterns and characteristics among patients with IFI led to the development of a Joint Trauma System (JTS) clinical practice guideline (CPG) for IFI management. We performed a case-control study to confirm and further delineate risk factors associated with IFI development in combat casualties with the objective of generating data to refine the CPG and promote timelier initiation of treatment. Methods: Data were collected retrospectively for United States (U.S.) military personnel injured during deployment in Afghanistan from June 2009 through August 2011. Cases were identified as IFI based upon wound cultures with fungal growth and/or fungal elements seen on histology, in addition to the presence of recurrent wound necrosis. Controls were matched using date of injury (±3 mo) and injury severity score (±10). Risk factor parameters analyzed included injury circumstances, blood transfusion requirements, amputations after first operative intervention, and associated injuries. Data are expressed as multivariate odds ratios (OR; 95% confidence interval [CI]). Results: Seventy-six IFI cases were identified from 1,133 U.S. military personnel wounded in Afghanistan and matched to 150 controls. Parameters associated significantly with the development of IFI multivariate analysis were blast injuries (OR: 5.7; CI: 1.1–29.6), dismounted at time of injury (OR: 8.5; CI: 1.2–59.8); above the knee amputations (OR: 4.1; CI: 1.3-12.7), and large-volume packed red blood cell (PRBC; >20 U) transfusions within first 24 h (OR: 7.0; CI: 2.5-19.7). Conclusions: Our analysis indicates that dismounted blast injuries, resulting in above the knee amputations, and requirement of large volume PRBC transfusions are independent predictors of IFI development. These data confirm all the preliminary risk factors, except for

  4. Subtyping of emm1 Group A Streptococci Causing Invasive Infections in France ▿

    PubMed Central

    Bidet, P.; Lesteven, E.; Doit, C.; Liguori, S.; Mariani-Kurkdjian, P.; Bonacorsi, S.; Bingen, E.

    2009-01-01

    By combining PCR amplification of toxin-encoding genes and sic gene sequencing, we distinguished 24 genotypes among 47 M/emm1 group A streptococci isolated from children and adults in France in 9 cases of infection comprising four clusters and 38 unrelated invasive infection cases used as controls. PMID:19846638

  5. Invasive infection in an acute myeloblastic leukemia patient due to triazole-resistant Candida tropicalis.

    PubMed

    de Carvalho Parahym, Ana Maria Rabelo; da Silva, Carolina Maria; Leão, Mariele Porto Carneiro; Macario, Michele Chianca; Filho, Gustavo Antônio da Trindade Meira Henriques; de Oliveira, Neiva Tinti; Neves, Rejane Pereira

    2011-11-01

    Non-albicans Candida species are being increasingly reported as causes of nosocomial fungal infections. For example, invasive candidiasis caused by C. tropicalis has been associated with hematologic malignancies. In this study, we report a fatal case of fungemia and a possible urinary and pulmonary infection in a leukemia patient that was due to a strain of C. tropicalis resistant to 2 triazole antifungals.

  6. Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

    PubMed Central

    Dando, Samantha J.; Mackay-Sim, Alan; Norton, Robert; Currie, Bart J.; St. John, James A.; Ekberg, Jenny A. K.; Batzloff, Michael

    2014-01-01

    SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis. PMID:25278572

  7. Synergy in biofilm formation between Fusobacterium nucleatum and Prevotella species.

    PubMed

    Okuda, Tamaki; Kokubu, Eitoyo; Kawana, Tomoko; Saito, Atsushi; Okuda, Katsuji; Ishihara, Kazuyuki

    2012-02-01

    The formation of biofilm by anaerobic, Gram-negative bacteria in the subgingival crevice plays an important role in the development of chronic periodontitis. The aim of this study was to characterize the role of coaggregation between Fusobacterium nucleatum and Prevotella species in biofilm formation. Coaggregation between F. nucleatum and Prevotella species was determined by visual assay. Effect of co-culture of the species on biofilm formation was assessed by crystal violet staining. Effect of soluble factor on biofilm formation was also examined using culture supernatant and two-compartment co-culture separated by a porous membrane. Production of autoinducer-2 (AI-2) by the organisms was evaluated using Vibrio harveyi BB170. Cells of all F. nucleatum strains coaggregated with Prevotella intermedia or Prevotella nigrescens with a score of 1-4. Addition of ethylenediamine tetraacetic acid or l-lysine inhibited coaggregation. Coaggregation disappeared after heating of P. intermedia or P. nigrescens cells, or Proteinase K treatment of P. nigrescens cells. Co-culture of F. nucleatum ATCC 25586 with P. intermedia or P. nigrescens strains increased biofilm formation compared with single culture (p < 0.01); co-culture with culture supernatant of these strains, however, did not enhance biofilm formation by F. nucleatum. Production of AI-2 in Prevotella species was not related to enhancement of biofilm formation by F. nucleatum. These findings indicate that physical contact by coaggregation of F. nucleatum strains with P. intermedia or P. nigrescens plays a key role in the formation of biofilm by these strains.

  8. Epidemiology of invasive fungal infections after liver transplantation and the risk factors of late-onset invasive aspergillosis.

    PubMed

    Nagao, Miki; Fujimoto, Yasuhiro; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Takakura, Shunji; Uemoto, Shinji; Ichiyama, Satoshi

    2016-02-01

    Invasive fungal infection (IFI) in liver transplant recipients is associated with poor outcomes. Targeted antifungal prophylaxis is recommended for high-risk populations; however, the epidemiology of IFI has changed, and the risk criteria remain unclear. In addition, the risk factors for late-onset invasive aspergillosis (IA) have not been fully characterized. We examined 279 recipients over 16 years of age to uncover their IFI epidemiology, clinical characteristics and outcomes. In addition, a case-control study was performed to identify the risk factors of late-onset IA. Of the 279 recipients, 96.1% underwent living donor liver transplantation. Antifungal prophylaxis was administered to 80.6% of the recipients. IFI occurred in 15 patients, among which 8 cases were early-onset (≤90 days after liver transplantation) and 7 cases were late-onset (>90 days after liver transplantation). Five of the late-onset cases were invasive pulmonary aspergillosis, and 2 were fungemia cases. The mortality rate of late-onset IA was 80.0%. According to a multivariate analysis, steroid use before liver transplantation, bloodstream infection within 90 days after liver transplantation and reoperation within 90 days after liver transplantation were significant risk factors for late-onset IA after liver transplantation. The prevalence of IFI was low in our population given that over 80% of liver recipients received antifungal prophylaxis. The prognosis of late-onset IA remains poor, and predictors associated with late-onset IA, such as steroid use before liver transplantation, bloodstream infection and reoperation after liver transplantation, may help clinicians to optimize prevention measures for these devastating infections.

  9. Invasive Aspergillus niger complex infections in a Belgian tertiary care hospital.

    PubMed

    Vermeulen, E; Maertens, J; Meersseman, P; Saegeman, V; Dupont, L; Lagrou, K

    2014-05-01

    The incidence of invasive infections caused by the Aspergillus niger species complex was 0.043 cases/10 000 patient-days in a Belgian university hospital (2005-2011). Molecular typing was performed on six available A. niger complex isolates involved in invasive disease from 2010 to 2011, revealing A. tubingensis, which has higher triazole minimal inhibitory concentrations, in five out of six cases.

  10. Invasive Candidiasis

    MedlinePlus

    ... Invasive candidiasis is an infection caused by a yeast (a type of fungus) called Candida . Unlike Candida ... mouth and throat (also called “thrush”) or vaginal “yeast infections,” invasive candidiasis is a serious infection that ...

  11. [Epidemiology of invasive group A streptococcal infections in developed countries : the Canadian experience with necrotizing fasciitis].

    PubMed

    Ovetchkine, Ph; Bidet, Ph; Minodier, Ph; Frère, J; Bingen, E

    2014-11-01

    In industrialized countries, group A streptococcal infections were a source of concern, mainly due to the occurrence of rheumatic fever and its cardiac complications. At present, the incidence of rheumatic fever is decreasing in these countries, giving way to an increasing occurrence of invasive streptococcal group A infections with high level of morbidity and mortality. Streptococcal necrotizing fasciitis, a specific entity, emerged these last decades, often in association with chickenpox. The introduction of the varicella vaccine in the province of Quebec routine immunization program, was followed by a significant decrease in the number of necrotizing fasciitis or other skin and soft-tissues infections in our pediatric population. However, in our experience at the CHU Sainte-Justine, this immunization program has not been helpful to reduce the overall incidence of invasive group A streptococcal infections. Conversely, an increase in the number of pleuro-pulmonary and osteo-articular infections was observed.

  12. Amebic infections in asymptomatic homosexual men, lack of evidence of invasive disease.

    PubMed Central

    Sorvillo, F J; Strassburg, M A; Seidel, J; Visvesvara, G S; Mori, K; Todd, A; Portigal, L; Finn, M; Agee, B A

    1986-01-01

    A survey for enteric infections in 140 asymptomatic homosexual men who attended a community clinic revealed a high prevalence of infection with Entamoeba histolytica (27.1 per cent) and Giardia lamblia (15.7 per cent). In contrast, the prevalence of elevated indirect hemagglutination (IHA) titers (greater than or equal to 1:128), which indicate invasive amebiasis, was low (5.7 per cent). Our findings suggest that only a limited amount of invasive amebic disease is occurring in this group of homosexual men. PMID:2874747

  13. Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia

    PubMed Central

    Mandal, Ranajit; Kundu, Pratip; Biswas, Jaydip

    2016-01-01

    Human papillomavirus (HPV) is a well-established causative agent of malignancy of the female genital tract and a common Sexually Transmitted Infection. The probable co-factors that prevent spontaneous clearance of HPV and progression to neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory conditions can lead to pre-neoplastic manifestations in the cervical epithelium; however their specific role in cervical carcinogenesis is not yet established. Therefore it is imperative to study the likely association between HPV and co-infection with various common pathogens in the genital tract of women having cervical precancer or cancer. A “Pubmed” search was made for articles in Literature on this topic using the words: Cervical neoplasia, HPV, co-infections, Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida, Chlamydia and the relevant information obtained was used to draft the review. PMID:27042571

  14. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series

    PubMed Central

    2014-01-01

    Background Invasive fungal infections are very severe infections associated with high mortality rates, despite the availability of new classes of antifungal agents. Based on pathophysiological mechanisms and limited pre-clinical and clinical data, adjunctive immune-stimulatory therapy with interferon-gamma (IFN-γ) may represent a promising candidate to improve outcome of invasive fungal infections by enhancing host defence mechanisms. Methods In this open-label, prospective case series, we describe eight patients with invasive Candida and/or Aspergillus infections who were treated with recombinant IFN-γ (rIFN-γ, 100 μg s.c., thrice a week) for 2 weeks in addition to standard antifungal therapy. Results Recombinant IFN-γ treatment in patients with invasive Candida and/or Aspergillus infections partially restored immune function, as characterized by an increased HLA-DR expression in those patients with a baseline expression below 50%, and an enhanced capacity of leukocytes from treated patients to produce proinflammatory cytokines involved in antifungal defence. Conclusions The present study provides evidence that adjunctive immunotherapy with IFN-γ can restore immune function in fungal sepsis patients, warranting future clinical studies to assess its potential clinical benefit. Trial registration ClinicalTrials.gov - NCT01270490 PMID:24669841

  15. Minimally invasive spine surgery in spinal infections. An up-date.

    PubMed

    Verdú López, Francisco; Vanaclocha Vanaclocha, Vicente; Mayorga-Villa, Juan D

    2016-10-27

    Although spinal infections have always been present recently their incidence has increased, in partly fostered by the advances in medicine (i.e. compromised 10 immunity, chronic diseases, increasingly complex spinal procedures...) and increased life expectancy. Using PubMed for this systematic review, the main spine infections types will be addressed focusing in the minimally invasive surgical techniques that can be used in their treatment. Spontaneous and iatrogenic pyogenic and non-pyogenic spine infections can be treated in many different ways depending on their extension and 15 location as well as on their causative microorganisms. The indications of percutaneous image-guided, endoscopic and microsurgical treatment techniques will be updated. In spine infections minimally invasive surgical techniques show a great potential as to be safe, effective, with low surgical morbidity and fast patients' recovery.

  16. Purulent Proctitis Caused by Prevotella bivia in a Homosexual Male

    PubMed Central

    Hossain, Sarah; Dunkelberg, Jeffrey; Gerke, Henning

    2016-01-01

    A 32-year-old homosexual male presented with suprapubic pain. Computed tomography showed rectal wall thickening. Flexible sigmoidoscopy showed small pockets of pus that were opened with mucosal biopsies, and additional pus was diffusely expressed from the rectal wall by applying blunt pressure with the biopsy forceps. Cultures from the pus grew Prevotella bivia. Symptoms resolved after treatment with doxycycline and metronidazole. Proctitis due to P. bivia was not previously reported. PMID:28008411

  17. Study of Invasive Pneumococcal Infection in Adults with Reference to Penicillin Resistance

    PubMed Central

    Muley, Vrishali Avinash; Ghadage, Dnyaneshwari Purushottam; Yadav, Gauri Eknath; Bhore, Arvind Vamanrao

    2017-01-01

    Background: Invasive pneumococcal infections often prove rapidly fatal, even where good medical treatment is readily available. In developed countries, up to 20% of people who contract pneumococcal meningitis die; however, in developing world, mortality is closer to 50%, even among hospitalized patients. The World Health Organization estimated 600,000–800,000 adult deaths each year from pneumococcal pneumonia, meningitis, and sepsis. Aims: This study aims to estimate isolation rate of invasive pneumococcal infection in adults, to determine the antimicrobial susceptibility profile of Streptococcus pneumoniae isolates and to study the associated risk factors. Materials and Methods: A total of 120 patients with suspected invasive infection such as meningitis, septicemia, and pleural effusion, were included in the study. Various clinical specimens such as pus, cerebrospinal fluid, and other sterile body fluids were processed for isolation and identification of S. pneumoniae. Kirby–Bauer disc diffusion method was performed to determine the antimicrobial susceptibility profile. Minimum inhibitory concentration test was performed to determine the penicillin resistance. Results: Of 120 patients, 40 (33.33%) cases were proven by culture to have an invasive pneumococcal infection. The most common clinical condition observed was meningitis followed by pneumonia with pleural effusion and sepsis. Pneumococcal isolates exhibited 40% resistance to cotrimoxazole and 12.73% to chloramphenicol. Two meningeal isolates exhibited penicillin resistance. Comorbidities observed in 21 (52.5%) cases were mainly Diabetes mellitus, smoking, and alcoholism. Conclusions: Invasive pneumococcal infection has poor prognosis and penicillin-resistant strains have become increasingly common. This study emphasizes the importance of judicious use of antibiotics, especially to refrain their use in mild self-limiting upper respiratory infections. PMID:28042214

  18. Invasive Infections with Multidrug-Resistant Yeast Candida auris, Colombia

    PubMed Central

    Morales-López, Soraya E.; Parra-Giraldo, Claudia M.; Ceballos-Garzón, Andrés; Martínez, Heidys P.; Rodríguez, Gerson J.; Álvarez-Moreno, Carlos A.

    2017-01-01

    Candida auris is an emerging multidrug-resistant fungus that causes a wide range of symptoms. We report finding 17 cases of C. auris infection that were originally misclassified but correctly identified 27.5 days later on average. Patients with a delayed diagnosis of C. auris had a 30-day mortality rate of 35.2%. PMID:27983941

  19. Coaggregation of Prevotella intermedia with oral Actinomyces species.

    PubMed Central

    Nesbitt, W E; Fukushima, H; Leung, K P; Clark, W B

    1993-01-01

    Five strains of Prevotella intermedia were examined for their ability to coaggregate with various gram-positive and gram-negative species of oral bacteria. Two of the P. intermedia strains coaggregated with selected Actinomyces species, P. intermedia 27 with Actinomyces viscosus T14V and Actinomyces naeslundii ATCC 12104, PK606, PK984, and PK947, and P. intermedia 113 with Actinomyces odontolyticus WVU 1546 and Actinomyces israelii WVU 838. Exposure of both Prevotella strains but not the Actinomyces strains to heat, trypsin, or proteinase K abolished most coaggregations. All pairs were disaggregated by the addition of sodium dodecyl sulfate, but only those coaggregations involving P. intermedia 113 were reversed by the addition of 2.0 M urea. P. intermedia 27 was sensitive to periodate oxidation, whereas the partner strains were stable to this treatment. Most coaggregations occurred in the presence of saliva; however, reactions involving P. intermedia 27 were not as strong as those of buffer-suspended cells. Treatment of both P. intermedia 113 coaggregations pairs with proteinase K and the results obtained from suspensions of these pairs in saliva suggest that different surface molecules of this P. intermedia strain may mediate each of these coaggregations. These data suggest that all of these coaggregations involve either a protein or glycoprotein on the Prevotella strain, which may interact with carbohydrates or carbohydrate-containing molecules on the surface of the Actinomyces strain. PMID:8478088

  20. Voriconazole: a broad-spectrum triazole for the treatment of invasive fungal infections.

    PubMed

    Cecil, Jane A; Wenzel, Richard P

    2009-06-01

    Over the last 20 years, the frequency of life-threatening, invasive fungal infections has risen dramatically, corresponding to an increase in the number of immunocompromised patients. Thus, the development of newer, better tolerated, more effective antifungal drugs has become critically important. Voriconazole was the first second-generation triazole to be approved by the US FDA and the EMEA, both in 2002. Voriconazole is currently approved for the treatment of invasive aspergillosis, candidemia, candidal esophagitis and disseminated candidiasis in adults, and serious fungal infections due to Scedosporium apiospermum and Fusarium species. In addition to providing an alternative treatment option for Candida infections and many emerging and refractory invasive fungal infections, voriconazole is currently the treatment of choice for invasive aspergillosis. Voriconazole has excellent in vitro activity against a wide spectrum of yeasts and molds, with only a few notable exceptions. Although it has the potential for some unique and interesting side effects, as well as important drug-drug interactions, the use of therapeutic drug monitoring can be used to optimize its efficacy and safety.

  1. Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections

    PubMed Central

    Siemens, Nikolai; Kittang, Bård R.; Chakrakodi, Bhavya; Oppegaard, Oddvar; Johansson, Linda; Bruun, Trond; Mylvaganam, Haima; Arnell, Per; Hyldegaard, Ole; Nekludov, Michael; Karlsson, Ylva; Svensson, Mattias; Skrede, Steiner; Norrby-Teglund, Anna

    2015-01-01

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 69) were analyzed with respect to virulence factor expression and cytotoxic or inflammatory effects on human cells and 3D skin tissue models. SDSE strains efficiently infected the 3D-skin model and severe tissue pathology, inflammatory responses and altered production of host structural framework proteins associated with epithelial barrier integrity were evident already at 8 hours post-infection. Invasive strains were significantly more cytotoxic towards keratinocytes and expressed higher Streptokinase and Streptolysin O (SLO) activities, as compared to non-invasive strains. The opposite was true for Streptolysin S (SLS). Fractionation and proteomic analysis of the cytotoxic fractions implicated SLO as a factor likely contributing to the keratinocyte cytotoxicity and tissue pathology. Analyses of patient tissue biopsies revealed massive bacterial load, high expression of slo, as well as immune cell infiltration and pro-inflammatory markers. Our findings suggest the contribution of SLO to epithelial cytotoxicity and tissue pathology in SDSE tissue infections. PMID:26601609

  2. Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections.

    PubMed

    Siemens, Nikolai; Kittang, Bård R; Chakrakodi, Bhavya; Oppegaard, Oddvar; Johansson, Linda; Bruun, Trond; Mylvaganam, Haima; Svensson, Mattias; Skrede, Steiner; Norrby-Teglund, Anna

    2015-11-25

    Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 69) were analyzed with respect to virulence factor expression and cytotoxic or inflammatory effects on human cells and 3D skin tissue models. SDSE strains efficiently infected the 3D-skin model and severe tissue pathology, inflammatory responses and altered production of host structural framework proteins associated with epithelial barrier integrity were evident already at 8 hours post-infection. Invasive strains were significantly more cytotoxic towards keratinocytes and expressed higher Streptokinase and Streptolysin O (SLO) activities, as compared to non-invasive strains. The opposite was true for Streptolysin S (SLS). Fractionation and proteomic analysis of the cytotoxic fractions implicated SLO as a factor likely contributing to the keratinocyte cytotoxicity and tissue pathology. Analyses of patient tissue biopsies revealed massive bacterial load, high expression of slo, as well as immune cell infiltration and pro-inflammatory markers. Our findings suggest the contribution of SLO to epithelial cytotoxicity and tissue pathology in SDSE tissue infections.

  3. Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies

    PubMed Central

    Parahym, Ana Maria Rabelo de Carvalho; Rolim, Pedro José; da Silva, Carolina Maria; Domingos, Igor de Farias; Gonçalves, Sarah Santos; Leite, Edinalva Pereira; de Morais, Vera Lúcia Lins; Macêdo, Danielle Patrícia Cerqueira; de Lima, Reginaldo Gonçalves; Neves, Rejane Pereira

    2015-01-01

    We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole. PMID:26273269

  4. Epidemiology and emm types of invasive group A streptococcal infections in Finland, 2008-2013.

    PubMed

    Smit, P W; Lindholm, L; Lyytikäinen, O; Jalava, J; Pätäri-Sampo, A; Vuopio, J

    2015-10-01

    Invasive Streptococcus pyogenes (group A streptococcus, GAS) infections are a major global cause of morbidity and mortality. We analysed the surveillance data on invasive GAS and the microbiological characteristics of corresponding isolates to assess the incidence and emm type distribution of invasive GAS infections in Finland. Cases defined as patients with isolations of blood and cerebrospinal fluid S. pyogenes are mandatorily notified to the National Infectious Disease Registry and sent to the national reference laboratory for emm typing. Antimicrobial data were collected through the network including all clinical microbiology laboratories. Pulsed-field gel electrophoresis (PFGE) analysis was performed to assess clonality. In total, 1165 cases of invasive GAS were reported in Finland during 2008-2013; the median age was 52 years (range, 0-100) and 54% were male. The overall day 7 case fatality rate was 5.1% (59 cases). The average annual incidence was 3.6 cases per 100,000 population. A total of 1122 invasive GAS isolates (96%) were analysed by emm typing; 72 different emm types were identified, of which emm28 (297 isolates, 26%), emm89 (193 isolates, 12%) and emm1 (132 isolates, 12%) were the most common types. During 2008-2013, an increase of erythromycin resistance (1.9% to 8.7%) and clindamycin (0.9% to 9.2%) was observed. This resistance increase was in parallel with the introduction of a novel clone emm33 into Finland. The overall incidence of invasive GAS infections remained stable over the study period in Finland. We identified clonal spread of macrolide-resistant invasive emm33 GAS type, highlighting the importance of molecular surveillance.

  5. Dominance of Serotype Ia among Group B Streptococci Causing Invasive Infections in Nonpregnant Adults in Portugal

    PubMed Central

    Martins, E. R.; Melo-Cristino, J.

    2012-01-01

    The population of group B streptococci (GBS) associated with invasive infections in nonpregnant adults from 2001 to 2008 was analyzed in isolates submitted from 24 hospital laboratories in Portugal (n = 225). The isolates were characterized by antimicrobial susceptibility, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and surface protein gene profiling. GBS invasive cases were found more frequently among men in all age groups. In addition, serotype Ia was the most frequent in our collection, whereas serotype V is dominant elsewhere. Serotype Ia was represented mainly by a single PFGE cluster defined by sequence type 23 (ST23) and surface protein gene eps and by ST24 and bca, similarly to neonatal invasive infections in Portugal, indicating that the same genetic lineages can be responsible for both vaginal colonization and invasive disease in all age groups. In contrast, the hypervirulent serotype III/ST17 neonatal lineage was responsible for a minority of infections. Serotype V isolates were distributed into two genetic lineages, one defined by ST1 and surface protein gene alp3 and macrolide resistant, and another presenting with ST2 and eps and fully susceptible to all antimicrobials tested. The erm(TR) gene was the most frequently found among erythromycin-resistant isolates, while the bovine-associated tet(O) gene was found in a minority of tetracycline-resistant isolates. Our data emphasize the importance of local identification of the genetic lineages responsible for GBS invasive infections in nonpregnant adults. The dominance of serotype Ia in invasive disease in Portugal highlights the importance of this serotype in GBS pathogenesis. PMID:22219307

  6. Dominance of serotype Ia among group B Streptococci causing invasive infections in nonpregnant adults in Portugal.

    PubMed

    Martins, E R; Melo-Cristino, J; Ramirez, M

    2012-04-01

    The population of group B streptococci (GBS) associated with invasive infections in nonpregnant adults from 2001 to 2008 was analyzed in isolates submitted from 24 hospital laboratories in Portugal (n = 225). The isolates were characterized by antimicrobial susceptibility, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and surface protein gene profiling. GBS invasive cases were found more frequently among men in all age groups. In addition, serotype Ia was the most frequent in our collection, whereas serotype V is dominant elsewhere. Serotype Ia was represented mainly by a single PFGE cluster defined by sequence type 23 (ST23) and surface protein gene eps and by ST24 and bca, similarly to neonatal invasive infections in Portugal, indicating that the same genetic lineages can be responsible for both vaginal colonization and invasive disease in all age groups. In contrast, the hypervirulent serotype III/ST17 neonatal lineage was responsible for a minority of infections. Serotype V isolates were distributed into two genetic lineages, one defined by ST1 and surface protein gene alp3 and macrolide resistant, and another presenting with ST2 and eps and fully susceptible to all antimicrobials tested. The erm(TR) gene was the most frequently found among erythromycin-resistant isolates, while the bovine-associated tet(O) gene was found in a minority of tetracycline-resistant isolates. Our data emphasize the importance of local identification of the genetic lineages responsible for GBS invasive infections in nonpregnant adults. The dominance of serotype Ia in invasive disease in Portugal highlights the importance of this serotype in GBS pathogenesis.

  7. AdpC is a Prevotella intermedia 17 leucine-rich repeat internalin-like protein.

    PubMed

    Iyer, Divya; Anaya-Bergman, Cecilia; Jones, Kevin; Yanamandra, Sai; Sengupta, Dipanwita; Miyazaki, Hiroshi; Lewis, Janina P

    2010-06-01

    The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRR(TP)) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17.

  8. TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN IMMUNOCOMPETENT PATIENT

    PubMed Central

    CHEN, Xiao-Hua; GAO, Yun-Chao; ZHANG, Yi; TANG, Zheng-Hao; YU, Yong-Sheng; ZANG, Guo-Qing

    2015-01-01

    Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicansand spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient. PMID:26200971

  9. Kingella kingae: an emerging cause of invasive infections in young children.

    PubMed

    Yagupsky, P; Dagan, R

    1997-05-01

    Kingella kingae, a fastidious hemolytic gram-negative bacillus once considered to be an exceptional cause of disease, has emerged in recent years as an important invasive pathogen in children. When synovial fluid and other exudates were inoculated into blood culture bottles, enhanced recovery of the organism was observed, and an annual incidence of invasive K. kingae infections of 27.4 per 100,000 children younger than age 24 months was demonstrated in southern Israel. Skeletal infections are the most common clinical presentation of K. kingae, and studies conducted in that region have shown that this organism is the most common etiology of septic arthritis in children below the age of 24 months. Other invasive diseases caused by K. kingae include bacteremia, endocarditis, and infections involving the lower respiratory tract, the eyes, or the central nervous system. Recent studies have demonstrated that K. kingae is part of the normal oropharyngeal flora of young children. Clinical data suggest that the organism may gain access to the bloodstream in the course of an upper respiratory infection or stomatitis. The organism is susceptible to a wide range of antimicrobial drugs, and with the exception of some cases of endocarditis, K. kingae infections in children usually run a benign clinical course.

  10. Temperature rise and parasitic infection interact to increase the impact of an invasive species.

    PubMed

    Laverty, Ciaran; Brenner, David; McIlwaine, Christopher; Lennon, Jack J; Dick, Jaimie T A; Lucy, Frances E; Christian, Keith A

    2017-04-01

    Invasive species often detrimentally impact native biota, e.g. through predation, but predicting such impacts is difficult due to multiple and perhaps interacting abiotic and biotic context dependencies. Higher mean and peak temperatures, together with parasites, might influence the impact of predatory invasive host species additively, synergistically or antagonistically. Here, we apply the comparative functional response methodology (relationship between resource consumption rate and resource supply) in one experiment and conduct a second scaled-up mesocosm experiment to assess any differential predatory impacts of the freshwater invasive amphipod Gammarus pulex, when uninfected and infected with the acanthocephalan Echinorhynchus truttae, at three temperatures representative of current and future climate. Individual G. pulex showed Type II predatory functional responses. In both experiments, infection was associated with higher maximum feeding rates, which also increased with increasing temperatures. Additionally, infection interacted with higher temperatures to synergistically elevate functional responses and feeding rates. Parasitic infection also generally increased Q10 values. We thus suggest that the differential metabolic responses of the host and parasite to increasing temperatures drives the synergy between infection and temperature, elevating feeding rates and thus enhancing the ecological impact of the invader.

  11. Invasive mucinous adenocarcinoma mimicking organizing pneumonia associated with Mycobacterium fortuitum infection.

    PubMed

    Morichika, Daisuke; Miyahara, Nobuaki; Hotta, Katsuyuki; Okamoto, Yoshiko; Minami, Daisuke; Irie, Masahiro; Tanimoto, Yasushi; Kanehiro, Arihiko; Tanimoto, Mitsune; Kiura, Katsuyuki

    2014-01-01

    We herein report the case of a 68-year-old man diagnosed with invasive mucinous adenocarcinoma of the lungs. Chest computed tomography showed subpleural ground-glass opacity and small nodules with cavitation. A culture of the bronchoalveolar lavage fluid resulted in the detection of Mycobacterium fortuitum. The patient's lung consolidation rapidly progressed; however, repeated bronchoscopy showed no atypical cells, thus suggesting a diagnosis of organizing pneumonia associated with M. fortuitum infection. However, the surgical biopsy specimen was diagnostic for adenocarcinoma, with no mycobacterial infection. Invasive mucinous adenocarcinoma should not be excluded in the differential diagnosis of patients with clinical features of organizing pneumonia and nontuberculous mycobacterium infection, even if a transbronchial biopsy confirms the absence of malignancy.

  12. Analysis of Haemophilus influenzae serotype f isolated from three Japanese children with invasive H. influenzae infection.

    PubMed

    Hoshino, Tadashi; Hachisu, Yushi; Kikuchi, Takashi; Tokutake, Shoko; Okui, Hideyuki; Kutsuna, Satoru; Fukasawa, Chie; Murayama, Kei; Oohara, Asami; Shimizu, Hiroyuki; Ito, Midori; Takahashi, Yoshiko; Ishiwada, Naruhiko

    2015-04-01

    In Japan, publicly subsidized Haemophilus influenzae serotype b vaccines became available in 2011; consequently, the incidence of invasive H. influenzae infection in paediatric patients of less than 5 years of age decreased dramatically. In 2013, the first case of H. influenzae serotype f (Hif) meningitis in a Japanese infant was reported, and another case of Hif meningitis in a Japanese infant was observed in 2013. We experienced a fatal paediatric case of Hif bacteraemia in 2004; therefore, we conducted an analysis of the three Hif strains isolated from these three Japanese children with invasive Hif infections. All three strains were β-lactamase-non-producing, ampicillin-sensitive strains, with MICs of 1 µg ml(-1) or less. However, one of the three strains showed slightly elevated MICs for ampicillin (1 µg ml(-1)), cefotaxime (0.25 µg ml(-1)) and meropenem (0.13 µg ml(-1)). A molecular analysis by multilocus sequence typing identified all three strains as sequence type (ST) 124, which is a predominant invasive Hif strain in many countries. SmaI-digested PFGE showed variable DNA fragmentation patterns among the strains, suggesting that some highly virulent strains have originated from a single ST124 clone and caused invasive Hif infections in Japan. Additional studies are needed to determine the factors that have led to the clonal expansion of virulent ST124 strains.

  13. New developments in the diagnosis and management of invasive fungal infections.

    PubMed

    De Marie, S

    2000-01-01

    Invasive fungal infections in cancer patients are on the increase. Candidemia is now the fourth leading cause of bloodstream infections in many intensive care units (ICUs). Although a number of risk factors have been identified, antifungal therapy should not be started in non-neutropenic patients until a diagnosis of invasive candidiasis or candidemia is made or presumed in order to avoid the development of resistance. Even a single positive blood culture should be treated, and requires removal of intravascular lines. Fluconazole is the first line agent for treatment candidemia other than that caused by Candida glabrata or C. krusei. High-resolution CT scan pictures showing a halo sign or crescent air sign are helpful for establishing the diagnosis of invasive aspergillosis. Sandwich ELISA can be used to detect circulating galactomannan in serial serum samples. Polymerase chain reaction (PCR) of blood samples may also be used. There are only a few randomized studies of newly developed antifungal drugs compared to conventional amphotericin B (AmB). So far, both AmB colloidal dispersion and AmB lipid complex have failed to show more favorable efficacy or lesser toxicity rates, except for nephrotoxicity. Liposomal AmB, used during febrile neutropenia, did have a significantly lower toxicity rate. In neutropenic patients with invasive fungal infections liposomal AmB proved to be better than conventional AmB in terms of clinical efficacy, mortality and nephrotoxicity rates. The use of tests to achieve an earlier diagnosis combined with more potent treatment formulations such as liposomal AmB may be significant steps towards successful management of invasive fungal infections.

  14. Studies on the pathogenicity of anaerobes, especially Prevotella bivia, in a rat pyometra model.

    PubMed Central

    Mikamo, H; Kawazoe, K; Izumi, K; Watanabe, K; Ueno, K; Tamaya, T

    1998-01-01

    OBJECTIVE: Prevotella bivia is one of the anaerobic bacteria that resides in the flora of the female genital tract. We studied the pathogenicity of P. bivia in a rat pyometra model. METHODS: The experimental animal (rat) model of pyometra was developed to investigate the pathogenicity of P. bivia in a rat pyometra model. RESULTS: In the groups inoculated with aerobes alone, the infection rate was 10% (1/10) in the Staphylococcus aureus- or Staphylococcus agalactiae-inoculated group and 20% (2/10) in the Escherichia coli-inoculated group. Infection was not established in the groups inoculated with anaerobes alone. High infection rates were observed in all the mixed-infection groups. In the S. agalactiae- and Bacteroides fragilis-, S. agalactiae- and P. bivia-, F. coli- and B. fragilis-, and E. coli- and P. bivia-inoculated groups, an infection rate of 100% (10/10) was demonstrated. The efficacy of antibiotics such as flomoxef (FMOX) could be determined using a rat pyometra model. In relation to the alteration of vaginal microbial flora during the menstrual cycle, estrogen increased the growth of P. bivia. CONCLUSION: Mixture of aerobic bacteria and P. bivia increased the pathogenicity of P. bivia. Estrogen would be useful for raising up the inflammatory change of the uterus in experimental models of genital tract infection due to P. bivia. PMID:9702587

  15. Emerging causes of superficial and invasive infections following marine injuries and exposures.

    PubMed

    Diaz, James H

    2014-01-01

    Soft tissue bacterial infections following aquatic animal bites, stings, and minor injuries occur commonly and usually on the extremities in fishermen and beachgoers worldwide after freshwater and saltwater exposures. Louisiana has more tidal, saltwater, and brackish water shorelines (more than 7,000 miles) than any other state, including Alaska and Hawaii. As a result, Louisiana residents are often exposed to marine pathogens when fishing or working offshore or when enjoying Louisiana's miles of shorelines. Although many species of bacteria have been isolated from marine wounds, superficial soft tissue and invasive infections following marine injuries and exposures are most commonly caused by a small number of bacterial species, including Aeromonas hydrophila, Edwardsiella tarda, Erysipelothrix rhusiopathiae, Mycobacterium marinum, and Vibrio vulnificus. In addition to these species, several other aquatic bacteria have recently been identified as emerging causes of superficial and invasive infections following marine injuries and exposures, including marine mammal (dolphins and seals) Brucella species, Chromobacterium violaceum, Comamonas species, Shewanella algae, and Streptococcus iniae. The objectives of this review are to describe the epidemiology, presenting clinical manifestations, diagnostic and treatment strategies, and outcomes of both the superficial and the deeper invasive infections caused by the newly emerging marine bacterial pathogens.

  16. Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

    PubMed Central

    Schlecht, Lisa Marie; Peters, Brian M.; Krom, Bastiaan P.; Freiberg, Jeffrey A.; Hänsch, Gertrud M.; Filler, Scott G.

    2015-01-01

    Candida albicans and Staphylococcus aureus are often co-isolated in cases of biofilm-associated infections. C. albicans can cause systemic disease through morphological switch from the rounded yeast to the invasive hyphal form. Alternatively, systemic S. aureus infections arise from seeding through breaks in host epithelial layers although many patients have no documented portal of entry. We describe a novel strategy by which S. aureus is able to invade host tissue and disseminate via adherence to the invasive hyphal elements of Candida albicans. In vitro and ex vivo findings demonstrate a specific binding of the staphylococci to the candida hyphal elements. The C. albicans cell wall adhesin Als3p binds to multiple staphylococcal adhesins. Furthermore, Als3p is required for C. albicans to transport S. aureus into the tissue and cause a disseminated infection in an oral co-colonization model. These findings suggest that C. albicans can facilitate the invasion of S. aureus across mucosal barriers, leading to systemic infection in co-colonized patients. PMID:25332378

  17. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases.

    PubMed

    Walsh, T J; Hiemenz, J W; Seibel, N L; Perfect, J R; Horwith, G; Lee, L; Silber, J L; DiNubile, M J; Reboli, A; Bow, E; Lister, J; Anaissie, E J

    1998-06-01

    The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P < .02). Among 162 patients with serum creatinine values > or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.

  18. Comparison between invasive and noninvasive tests in diagnosis of Helicobacter pylori infection.

    PubMed

    Mahmood, Saffari; Hamid, Abtahi

    2010-05-15

    In this study, the invasive and noninvasive diagnotic tests were compared to choose the appropriate test for diagnostice of H. pylori infection. Helicobacter pylori (H. pylori) is a human pathogen that causes chronic gastritis, has a role in gastric and duodenal ulcer, is involved in gastric carcinogenesis and is regarded as a possible important factor in at least a subset of patients with functional dyspepsia. The diagnosis of H. pylori is an essential element in the management of many common gastrointestinal pathologies. The assessment of each routine invasive and noninvasive test is important. We studied a total of 127 outpatients for the detection of H. pylori infection. The presence of H. pylori infection by invasive tests containing the Rapid Urease Test (RUT), histology (Giemsa staining) and culture in 127 patients. Patients who were positive in culture, or two tests from four tests, invasive and noninvasive, were considered to have H. pylori infection. In noninvasive tests, we evaluated anti-H. pylori IgG and anti-CagA antibodies using commercial Enzyme-Linked Immunoassay (ELISA) and Western blot in dyspeptic patients. Eighty five out of the 127 patients were positive for H. pylori. Helicobacter pylori IgG seropositivity and 35 out of the 127 patients were positive for immunoblot. RUT had sensitivity, specifity and accuracy of 96, 80 and 90.5%, respectively; for Elisa these were 85.2, 33 and 70.5%, respectively and for ELISA with immunoblotting they were 65, 45 and 58.8%, respectively. The results of this study suggest that noninvasive tests (ELISA, immunoblotting) have the lowest and RUT with histology have the highest accuracy. These earlier tests can not be used for accurate infection diagnosis.

  19. Invasive Fungal Infections Acquired from Contaminated Food or Nutritional Supplements: A Review of the Literature.

    PubMed

    Benedict, Kaitlin; Chiller, Tom M; Mody, Rajal K

    2016-07-01

    Fungi are an integral part of the natural environment and, therefore, play many roles in relation to food: some fungi are used in food production, some are food sources themselves, and some are agents of food spoilage. Some fungi that contaminate food can also be harmful to human health. The harmful but noninfectious health consequences of mycotoxins have been well-characterized, but the extent to which fungi in food pose a risk for invasive infections is unknown. We conducted a literature review to identify cases of invasive fungal infections (IFIs) believed to have resulted from ingestion or inhalation of food, beverages, or dietary supplements (excluding Saccharomyces infections). We identified 11 publications describing cases or small outbreaks of IFIs related to foods or beverages and three describing IFIs related to dietary supplements. These food-associated IFIs were predominantly mold infections, and the few yeast infections were associated with dairy products. Suspected foodborne IFIs appear to be rare, but are increasingly described in the electronically searchable literature. They are associated with a variety of foods, are due to a variety of fungal pathogens, and primarily occur in persons with immunosuppressive conditions or other predisposing factors. Various guidelines for high-risk patients recommend avoidance of certain food products that may contain high levels of fungi, but further work is needed to evaluate the effectiveness of these restrictive diets in preventing fungal infections. The relationships between food spoilage, food insecurity, and IFI risk are another area that may warrant further exploration.

  20. Chlorine gas exposure increases susceptibility to invasive lung fungal infection

    PubMed Central

    Gessner, Melissa A.; Doran, Stephen F.; Yu, Zhihong; Dunaway, Chad W.; Matalon, Sadis

    2013-01-01

    Chlorine (Cl2) is a highly irritating and reactive gas with potential occupational and environmental hazards. Acute exposure to Cl2 induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. Herein, we investigated whether Cl2 exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infections. Mice exposed to Cl2 and challenged intratracheally 24 h thereafter with the opportunistic mold Aspergillus fumigatus demonstrated an >500-fold increase in A. fumigatus lung burden 72 h postchallenge compared with A. fumigatus mice exposed to room air. Cl2-exposed A. fumigatus challenged mice also demonstrated significantly higher lung resistance following methacholine challenge and increased levels of plasma proteins (albumin and IgG) in the bronchoalveolar lavage fluid. Despite enhanced recruitment of inflammatory cells to the lungs of Cl2-exposed A. fumigatus challenged mice, these cells (>60% of which were neutrophils) demonstrated a profound impairment in generating superoxide. Significantly higher A. fumigatus burden in the lungs of Cl2 exposed mice correlated with enhanced production of IL-6, TNF-α, CXCL1, CCL2, and CCL3. Surprisingly, however, Cl2-exposed A. fumigatus challenged mice had a specific impairment in the production of IL-17A and IL-22 in the lungs compared with mice exposed to room air and challenged with A. fumigatus. In summary, our results indicate that Cl2 exposure markedly impairs the antimicrobial activity and inflammatory reactivity of myeloid cells in the lung leading to increased susceptibility to opportunistic pathogens. PMID:23564508

  1. Alarmin(g) the innate immune system to invasive fungal infections.

    PubMed

    Caffrey, Alayna K; Obar, Joshua J

    2016-08-01

    Fungi encounter numerous stresses in a mammalian host, including the immune system, which they must adapt to in order to grow and cause disease. The host immune system tunes its response to the threat level posed by the invading pathogen. We discuss recent findings on how interleukin (IL)-1 signaling is central to tuning the immune response to the virulence potential of invasive fungi, as well as other pathogens. Moreover, we discuss fungal factors that may drive tissue invasion and destruction that regulate IL-1 cytokine release. Moving forward understanding the mechanisms of fungal adaption to the host, together with understanding how the host innate immune system recognizes invading fungal pathogens will increase our therapeutic options for treatment of invasive fungal infections.

  2. [Epidemiology, clinical and microbiological characteristics of invasive streptococcal infections in Turkey, 2010-2011].

    PubMed

    Topkaya, Aynur Eren; Balıkcı, Ahmet; Aydın, Faruk; Hasçelik, Gülşen; Kayman, Tuba; Kesli, Recep; Aydemir, Söhret; Akyar, Işın; Gökalp, Aslı; Dündar, Günnur; Gürler, Nezahat; Perçin, Duygu; Fındık, Duygu; Avunduk, Haluk; Bayraktar, Banu

    2014-01-01

    A one-year active surveillance study was conducted to investigate the epidemiological and microbiological characteristics of invasive group A streptococci (GAS) infections in Turkey and to provide data for the establishment of national preventive strategies related to invasive GAS infections. A total of 46 clinical microbiology laboratories from 12 different regions of Turkey (Istanbul; Eastern and Western Marmara; Eastern and Western Blacksea; Aegean; Mediterranean; Western, Central, Northeastern, Middle-eastern and Southeastern Anatolia) participated in the study. Accordingly, GAS strains isolated from sterile body sites (blood, cerebrospinal, synovial, pleural, peritoneal, pericardial fluids) in the study centers between June 2010-June 2011, were sent to Maltepe University Hospital Clinical Microbiology Laboratory for microbiological confirmation and further analysis. The isolates were identified by conventional methods, and for serotyping, opacity factor (OF) and T protein types were investigated. For genotyping GAS lysate preparation, emm gene amplification and sequencing were performed by using the protocols recommended by Centers for Disease Control and Prevention. A total of 65 invasive GAS strains were isolated in 15 of the participant centers, during the study period. The rate of invasive GAS isolation exhibited regional variation, with the highest rates in the Eastern Blacksea (Trabzon, n= 19), followed by Istanbul (n= 17) and Western Anatolia (Ankara, Konya, n= 14). Of the patients with invasive GAS infection 33 were female, 32 were male, with the age range of 0-89 years. GAS strains were most commonly isolated from soft tissue specimens (n= 18), followed by abscess material (n= 10), sterile body fluids (n= 8) and blood (n= 7) samples. Serotyping revealed that 55% (36/65) of the strains were OF positive, and the majority of T protein was polygroup T (n= 20), followed by U (n= 14), B (n= 5), X (n= 3) and Y (n= 2). T protein was not detected in 22

  3. Characterizing the burden of invasive Pseudomonas infection on neonatal units in the UK between 2005 and 2011.

    PubMed

    Kadambari, S; Botgros, A; Clarke, P; Vergnano, S; Anthony, M; Chang, J; Collinson, A; Embleton, N; Kennea, N; Settle, P; Heath, P T; Menson, E N

    2014-10-01

    Concern about Pseudomonas infection in neonatal units has focused on outbreaks. This study analysed cases of invasive Pseudomonas infection in 18 UK neonatal units participating in the NeonIN Neonatal Infection Surveillance Network from January 2005 to December 2011. Forty-two cases were reported. The majority (35/42, 93%) of cases were late-onset (median 14 days, range 2-262 days), the highest incidence was seen in extremely-low-birthweight infants and all cases were sporadic. One-third of cases were known to be colonized prior to invasive disease. Attributable mortality was 18%. Opportunities for preventing invasive disease due to this important pathogen should be prioritized.

  4. Haemophilus influenzae serotype a as a cause of serious invasive infections.

    PubMed

    Ulanova, Marina; Tsang, Raymond S W

    2014-01-01

    Haemophilus influenzae, particularly H influenzae serotype b (Hib), is an important pathogen that causes serious diseases like meningitis and septicaemia. Since the introduction of Hib conjugate vaccines in the 1990s, the epidemiology of invasive H influenzae disease has changed substantially, with most infections now caused by non-Hib strains. We discuss the importance of H influenzae serotype a (Hia) as a cause of serious morbidity and mortality and its global epidemiology, clinical presentation, microbiology, immunology, prevention, and control. Much like Hib, the capsule of Hia is an important virulence factor contributing to the development of invasive disease. Molecular typing of Hia has identified distinct clonal groups, with some linked to severe disease and high case-fatality rates. Similarities between Hia and Hib capsules, their clinical presentation, and immunology of infection suggest that a bivalent Hia-Hib capsular polysaccharide-protein conjugate vaccine could offer protection against these two important serotypes of H influenzae.

  5. Bone marrow aspiration, biopsy, and culture in the evaluation of HIV-infected patients for invasive mycobacteria and histoplasma infections.

    PubMed

    Akpek, G; Lee, S M; Gagnon, D R; Cooley, T P; Wright, D G

    2001-06-01

    Bone marrow (BM) aspiration and biopsy are used commonly in clinical practice to diagnose invasive tissue infections caused by Mycobacterium avium intracellulare (MAC), Mycobacterium tuberculosis (TB), and Histoplasma capsulatum (HC) in patients with human immunodeficiency virus-1 (HIV) infection. However, the value of these invasive procedures relative to other diagnostic approaches has not been clearly defined. To determine the value of BM culture and BM histology in the diagnosis of opportunistic MAC/TB and HC infections in immunosuppressed patients with HIV, we retrospectively reviewed the records of 56 adult patients with HIV who underwent a single BM aspiration, biopsy, and culture because of unexplained fever and/or other clinical features suggestive of MAC/TB or HC infection. Thirty-two patients (57%) were ultimately diagnosed with MAC/TB or HC infection by positive cultures of BM, blood, sputum, or bronchoalveolar lavage fluid or by the histologic detection of organisms in biopsies of BM or other tissues. The diagnostic sensitivity of BM cultures was equal to that of blood cultures (20/32, or 63%). Granuloma and/or histologically apparent organisms were seen in BM biopsy specimens in 11 of 32 individuals (34%) ultimately diagnosed with MAC/TB or HC infections. Among these 11 cases, both granuloma and acid-fast staining organisms were found in the BM biopsy specimens of 2 individuals for whom both BM and blood cultures were negative. Certain clinical symptoms and signs at the time of BM examination were found by logistic regression analysis to be significantly associated with a subsequent diagnosis of MAC/TB or HC infections; these included high fever, long duration of febrile days prior to BM examination, and elevated direct bilirubin. In conclusion, while the diagnostic sensitivity of BM cultures was found to be no greater than that of blood cultures in detecting MAC/TB or HC infections in immunosuppressed HIV+ patients, histopathologic examination of BM

  6. Combat-Related Pythium aphanidermatum Invasive Wound Infection: Case Report and Discussion of Utility of Molecular Diagnostics.

    PubMed

    Farmer, Aaron R; Murray, Clinton K; Driscoll, Ian R; Wickes, Brian L; Wiederhold, Nathan; Sutton, Deanna A; Sanders, Carmita; Mende, Katrin; Enniss, Brent; Feig, James; Ganesan, Anuradha; Rini, Elizabeth A; Vento, Todd J

    2015-06-01

    We describe a 22-year-old soldier with 19% total body surface area burns, polytrauma, and sequence- and culture-confirmed Pythium aphanidermatum wound infection. Antemortem histopathology suggested disseminated Pythium infection, including brain involvement; however, postmortem PCR revealed Cunninghamella elegans, Lichtheimia corymbifera, and Saksenaea vasiformis coinfection. The utility of molecular diagnostics in invasive fungal infections is discussed.

  7. Combat-Related Pythium aphanidermatum Invasive Wound Infection: Case Report and Discussion of Utility of Molecular Diagnostics

    PubMed Central

    Murray, Clinton K.; Driscoll, Ian R.; Wickes, Brian L.; Wiederhold, Nathan; Sutton, Deanna A.; Sanders, Carmita; Mende, Katrin; Enniss, Brent; Feig, James; Ganesan, Anuradha; Rini, Elizabeth A.; Vento, Todd J.

    2015-01-01

    We describe a 22-year-old soldier with 19% total body surface area burns, polytrauma, and sequence- and culture-confirmed Pythium aphanidermatum wound infection. Antemortem histopathology suggested disseminated Pythium infection, including brain involvement; however, postmortem PCR revealed Cunninghamella elegans, Lichtheimia corymbifera, and Saksenaea vasiformis coinfection. The utility of molecular diagnostics in invasive fungal infections is discussed. PMID:25832301

  8. Non-Invasive Methods to Diagnose Fungal Infections in Pediatric Patients with Hematologic Disorders

    PubMed Central

    Badiee, Parisa; Hashemizadeh, Zahra; Ramzi, Mani; Karimi, Mohammad; Mohammadi, Rasoul

    2016-01-01

    Background Invasive fungal infection (IFIs) is a major infectious complication in immunocompromised patients. Early diagnosis and initiation of antifungal therapy is important to achieve the best outcome. Objectives The current study aimed to investigate the incidence of IFIs and evaluate the diagnostic performance of non-invasive laboratory tests: serologic (β-D-glucan, galactomannan) and molecular (nested polymerase chain reaction) tests to diagnose fungal infections in hematologic pediatric patients. Patients and Methods In a cross-sectional study from October 2014 to January 2015, 321 blood samples of 62 pediatric patients with hematologic disorders and at high risk for fungal infections were analyzed. Non-invasive tests including the Platelia Aspergillus enzyme immunoassay (EIA) to detect galactomannan antigen, Glucatell for β–D–glucan and nested PCR to detect Candida and Aspergillus species-specific DNA were used in a weekly screening strategy. Results Twenty six patients (42%) were considered as proven and probable IFIs, including 3 (5%) proven and 23 (37%) probable cases. Eighteen patients (29%) were considered as possible cases. The sensitivity, specificity, positive and negative predictive values for galactomannan test in 26 patients with proven and probable fungal infections were 94.4%, 100%, 100% and 94.7%; for β-D-glucan test 92.3%, 77.7%, 85%, 87.5% and for nested-PCR were 84.6%, 88.8%, 91.7% and 80%, respectively. Conclusions The rate of IFIs in pediatric patients with hematologic disorders is high, and sample collection from the sterile sites cannot be performed in immunocompromised patients. Detection of circulating fungal cell wall components and DNA in the blood using non-invasive methods can offer diagnostic help in patients with suspected IFIs. Their results should be interpreted in combination with clinical, radiological and microbiological findings. PMID:28138379

  9. [Regional laboratory network for surveillance of invasive fungal infections and antifungal susceptibility in Latin America].

    PubMed

    Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan L; Córdoba, Susana; Melhem, Marcia C; Szeszs, María W; Castañeda, Elizabeth; Martínez, Gerardo; Gabastou, Jean-Marc

    2008-02-01

    This article describes the general objectives of the Regional Laboratory Network for Surveillance of Invasive Fungal Infections and Antifungal Susceptibility in Latin America. Formation of the Network was coordinated by the Essential Medicines, Vaccines, and Health Technologies Unit of the Pan American Health Organization, with the technical and financial support of the National Center for Microbiology of the Carlos III Health Institute (Spain), and the technical support of the Microbiology Department of the Dr. C. Malbrán National Institute on Infectious Diseases (Argentina) and the Microbiology Unit of the Parasitology Service of the Adolfo Lutz Institute (Brazil). The Network's principle objectives are epidemiological surveillance of invasive fungal infections through detection of antifungal resistance and identification of emergent, invasive fungal infections; establishment of norms and common protocols for early diagnosis of mycoses; and strengthening coordination, communications, and transference mechanisms among countries. The Network must be gradually implemented and must include staff training, a systematic process for sharing technology, evaluation of diagnostic techniques, identification of fungal species, and standardized tests for antifungal susceptibility.

  10. Stability of the wMel Wolbachia Infection following Invasion into Aedes aegypti Populations

    PubMed Central

    Hoffmann, Ary A.; Iturbe-Ormaetxe, Inaki; Callahan, Ashley G.; Phillips, Ben L.; Billington, Katrina; Axford, Jason K.; Montgomery, Brian; Turley, Andrew P.; O'Neill, Scott L.

    2014-01-01

    The wMel infection of Drosophila melanogaster was successfully transferred into Aedes aegypti mosquitoes where it has the potential to suppress dengue and other arboviruses. The infection was subsequently spread into two natural populations at Yorkeys Knob and Gordonvale near Cairns, Queensland in 2011. Here we report on the stability of the infection following introduction and we characterize factors influencing the ongoing dynamics of the infection in these two populations. While the Wolbachia infection always remained high and near fixation in both locations, there was a persistent low frequency of uninfected mosquitoes. These uninfected mosquitoes showed weak spatial structure at both release sites although there was some clustering around two areas in Gordonvale. Infected females from both locations showed perfect maternal transmission consistent with patterns previously established pre-release in laboratory tests. After >2 years under field conditions, the infection continued to show complete cytoplasmic incompatibility across multiple gonotrophic cycles but persistent deleterious fitness effects, suggesting that host effects were stable over time. These results point to the stability of Wolbachia infections and their impact on hosts following local invasion, and also highlight the continued persistence of uninfected individuals at a low frequency most likely due to immigration. PMID:25211492

  11. Anatomical route of invasion and protective mucosal immunity in Trypanosoma cruzi conjunctival infection.

    PubMed

    Giddings, O K; Eickhoff, C S; Smith, T J; Bryant, L A; Hoft, D F

    2006-10-01

    Trypanosoma cruzi is a protozoan parasite that can initiate mucosal infection after conjunctival exposure. The anatomical route of T. cruzi invasion and spread after conjunctival parasite contamination remains poorly characterized. In the present work we have identified the sites of initial invasion and replication after contaminative conjunctival challenges with T. cruzi metacyclic trypomastigotes using a combination of immunohistochemical and real-time PCR confirmatory techniques in 56 mice between 3 and 14 days after challenge. Our results demonstrate that the predominant route of infection involves drainage of parasites through the nasolacrimal duct into the nasal cavity. Initial parasite invasion occurs within the ductal and respiratory epithelia. After successive waves of intracellular replication and cell-to-cell spread, parasites drain via local lymphatic channels to lymph nodes and then disseminate through the blood to distant tissues. This model of conjunctival challenge was used to identify immune responses associated with protection against mucosal infection. Preceding mucosal infection induces mucosal immunity, resulting in at least 50-fold reductions in recoverable tissue parasite DNA in immune mice compared to controls 10 days after conjunctival challenge (P < 0.05). Antigen-specific gamma interferon production by T cells was increased at least 100-fold in cells harvested from immune mice (P < 0.05). Mucosal secretions containing T. cruzi-specific secretory immunoglobulin A harvested from immune mice were shown to protect against mucosal parasite infection (P < 0.05), demonstrating that mucosal antibodies can play a role in T. cruzi immunity. This model provides an important tool for detailed studies of mucosal immunity necessary for the development of mucosal vaccines.

  12. Two Atypical Cases of Kingella kingae Invasive Infection with Concomitant Human Rhinovirus Infection

    PubMed Central

    Basmaci, Romain; Ilharreborde, Brice; Doit, Catherine; Presedo, Ana; Lorrot, Mathie; Alison, Marianne; Mazda, Keyvan; Bidet, Philippe

    2013-01-01

    We describe two atypical cases of Kingella kingae infection in children diagnosed by PCR, one case involving a soft tissue abscess and one case a femoral Brodie abscess. Both patients had concomitant human rhinovirus infection. K. kingae strains, isolated from an oropharyngeal swab, were characterized by multilocus sequence typing and rtxA sequencing. PMID:23784119

  13. The optimum timing to wean invasive ventilation for patients with AECOPD or COPD with pulmonary infection

    PubMed Central

    Song, Yuanlin; Chen, Rongchang; Zhan, Qingyuan; Chen, Shujing; Luo, Zujin; Ou, Jiaxian; Wang, Chen

    2016-01-01

    COPD is characterized by a progressive decline in lung function and mental and physical comorbidities. It is a significant burden worldwide due to its growing prevalence, comorbidities, and mortality. Complication by bronchial-pulmonary infection causes 50%–90% of acute exacerbations of COPD (AECOPD), which may lead to the aggregation of COPD symptoms and the development of acute respiratory failure. Non-invasive or invasive ventilation (IV) is usually implemented to treat acute respiratory failure. However, ventilatory support (mainly IV) should be discarded as soon as possible to prevent the onset of time-dependent complications. To withdraw IV, an optimum timing has to be selected based on weaning assessment and spontaneous breathing trial or replacement of IV by non-IV at pulmonary infection control window. The former method is more suitable for patients with AECOPD without significant bronchial-pulmonary infection while the latter method is more suitable for patients with AECOPD with acute significant bronchial-pulmonary infection. PMID:27042042

  14. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations.

    PubMed

    Pagano, Livio; Busca, Alessandro; Candoni, Anna; Cattaneo, Chiara; Cesaro, Simone; Fanci, Rosa; Nadali, Gianpaolo; Potenza, Leonardo; Russo, Domenico; Tumbarello, Mario; Nosari, Annamaria; Aversa, Franco

    2017-03-01

    Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. The extensive use of antifungal prophylaxis has reduced the infections from yeasts (e.g., candidemia) even though they are still associated with high mortality rates. This paper analyzes concurrent multiple predisposing factors that could favor the onset of fungal infections. Although neutropenia is common to almost all hematologic patients, other factors play a key role in specific patients, in particular in patients with AML or allogeneic HSCT recipients. Defining those patients at higher risk of IFIs may help to design the most appropriate diagnostic work-up and antifungal strategy.

  15. Mycoplasma gallisepticum: Influence of cell invasiveness on the outcome of experimental infection in chickens.

    PubMed

    Much, Peter; Winner, Florian; Stipkovits, László; Rosengarten, Renate; Citti, Christine

    2002-11-15

    Recently we have shown that a low (R(low)) and a high laboratory passage (R(high)) of the poultry pathogen Mycoplasma gallisepticum prototype strain R differ markedly in their capability to invade non-phagocytic eukaryotic cells. In the present study the infection traits of these two mycoplasma passages were compared in an in vivo setting. After aerosol inoculation of chickens, M. gallisepticum was re-isolated from the inner organs of birds infected with R(low), whereas no mycoplasma was recovered from the inner organs of birds infected with R(high). These results indicate that the two mycoplasma populations derived from strain R differ in their capacity to cross the mucosal barrier and suggest that cell invasion may play a major role in the observed systemic spreading of M. gallisepticum in its chicken host.

  16. The Membrane Mucin Msb2 Regulates Invasive Growth and Plant Infection in Fusarium oxysporum[W

    PubMed Central

    Pérez-Nadales, Elena; Di Pietro, Antonio

    2011-01-01

    Fungal pathogenicity in plants requires a conserved mitogen-activated protein kinase (MAPK) cascade homologous to the yeast filamentous growth pathway. How this signaling cascade is activated during infection remains poorly understood. In the soil-borne vascular wilt fungus Fusarium oxysporum, the orthologous MAPK Fmk1 (Fusarium MAPK1) is essential for root penetration and pathogenicity in tomato (Solanum lycopersicum) plants. Here, we show that Msb2, a highly glycosylated transmembrane protein, is required for surface-induced phosphorylation of Fmk1 and contributes to a subset of Fmk1-regulated functions related to invasive growth and virulence. Mutants lacking Msb2 share characteristic phenotypes with the Δfmk1 mutant, including defects in cellophane invasion, penetration of the root surface, and induction of vascular wilt symptoms in tomato plants. In contrast with Δfmk1, Δmsb2 mutants were hypersensitive to cell wall targeting compounds, a phenotype that was exacerbated in a Δmsb2 Δfmk1 double mutant. These results suggest that the membrane mucin Msb2 promotes invasive growth and plant infection upstream of Fmk1 while contributing to cell integrity through a distinct pathway. PMID:21441438

  17. Interaction with host factors exacerbates Trypanosoma cruzi cell invasion capacity upon oral infection.

    PubMed

    Covarrubias, Charles; Cortez, Mauro; Ferreira, Daniele; Yoshida, Nobuko

    2007-12-01

    Outbreaks of severe acute Chagas' disease acquired by oral infection, leading to death in some cases, have occurred in recent years. Using the mouse model, we investigated the basis of such virulence by analyzing a Trypanosoma cruzi isolate, SC, from a patient with severe acute clinical symptoms, who was infected by oral route. It has previously been shown that, upon oral inoculation into mice, T. cruzi metacyclic trypomastigotes invade the gastric mucosal epithelium by engaging the stage-specific surface glycoprotein gp82, whereas the surface molecule gp90 functions as a down-modulator of cell invasion. We found that, when orally inoculated into mice, metacyclic forms of the SC isolate, which express high levels of gp90, produced high parasitemias and high mortality, in sharp contrast with the reduced infectivity in vitro. Upon recovery from the mouse stomach 1h after oral inoculation, the gp90 molecule of the parasites was completely degraded, and their entry into HeLa cells, as well as into Caco-2 cells, was increased. The gp82 molecule was more resistant to digestive action of the gastric juice. Host cell invasion of SC isolate metacyclic trypomastigotes was augmented in the presence of gastric mucin. No alteration in infectivity was observed in T. cruzi strains CL and G which were used as references and which express gp90 molecules resistant to degradation by gastric juice. Taken together, our findings suggest that the exacerbation of T. cruzi infectivity, such as observed upon interaction of the SC isolate with the mouse stomach components, may be responsible for the severity of acute Chagas' disease that has been reported in outbreaks of oral T. cruzi infection.

  18. Starvation response and growth in serum of Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia, and Pseudoramibacter alactolyticus.

    PubMed

    Brundin, Malin; Figdor, David; Sundqvist, Göran; Sjögren, Ulf

    2009-07-01

    The microbiota inhabiting the untreated root canal differ markedly from those found in post-treatment disease, yet there is limited information on the microbial characteristics distinguishing the different infections. We hypothesized that starvation survival is a key microbial property in species selection. This study analyzed starvation-survival behavior over 60 days of species representative of the untreated root canal infection: Fusobacterium nucleatum, Peptostreptococcus anaerobius, Prevotella intermedia and Pseudoramibacter alactolyticus. All species did not survive 1 day in water. In 1% serum, the 4 species could not survive beyond 2-3 weeks. They required a high initial cell density and >or=10% serum to survive the observation period. The results highlight a poor starvation-survival capacity of these 4 species compared with species prevalent in post-treatment infection, which are well equipped to endure starvation and survive in low numbers on minimal serum. These findings point to starvation-survival capacity as a selection factor for microbial participation in post-treatment disease.

  19. Differentially regulated proteins in Prevotella intermedia after oxidative stress analyzed by 2D electrophoresis and mass spectrometry.

    PubMed

    Santos, Simone G; Diniz, Cláudio G; Silva, Vânia L; Lima, Francisca L; Andrade, Hélida M; Chapeaurouge, Donat A; Perales, Jonas; Serufo, José Carlos; Carvalho, Maria Auxiliadora R; Farias, Luiz M

    2012-02-01

    Prevotella intermedia is a rod-shaped, Gram-negative anaerobic bacterium found in human indigenous microbiota that plays an important role in opportunistic infections. The successful colonization depends on the ability of anaerobes to respond to oxidative stress (OS) in oxygenated tissues as well as to resist oxidative events from the host immune system until anaerobic conditions are present at the infection site. As knowledge of the mechanisms of protection against OS in Prevotella is limited, studies are needed to clarify aspects of molecular biology, physiology and ecology of this bacterium. The aim of this study was to access the proteins differentially regulated in P. intermedia after exposure to molecular oxygen by using two-dimensional gel electrophoresis (2DE) associated with the approach of MALDI-TOF/TOF Tandem Mass Spectrometry. The identity of the protein was evaluated by database search for homologous genomic sequences of P. intermedia strain 17 (TIGR). Twenty five out of 72 proteins found were identified as up-regulated (17) or down-regulated (9). These proteins were related to a variety of metabolic process, some of which could be associated to antioxidant and redox regulatory roles. Our data indicate that OS may stimulate an adaptive response in P. intermedia whose effect on its biology may be evidenced by the increase in aerotolerance and changes in protein abundance in the oxygen adapted cells.

  20. Clinical and Molecular Characteristics of Invasive and Noninvasive Skin and Soft Tissue Infections Caused by Group A Streptococcus▿

    PubMed Central

    Lin, Jiun-Nong; Chang, Lin-Li; Lai, Chung-Hsu; Lin, Hsi-Hsun; Chen, Yen-Hsu

    2011-01-01

    The severity of skin and soft tissue infections caused by group A Streptococcus (GAS) is variable, and there are only a limited number of studies evaluating the characteristics of these infections in the literature. From May 2005 to November 2007, 73 patients with skin and soft tissue infections caused by group A Streptococcus were included in this study. Among these patients, 34 (46.6%) had invasive diseases. Diabetes mellitus, alcoholism, and hypertension were the most common underlying disorders. The overall mortality rate was 6.8%, and the elderly were predisposed to invasive infections (P < 0.001). Neutrophil percentages of ≥80, serum creatinine levels of ≥2 mg/dl, and high serum C-reactive protein levels were noted more frequently in patients with invasive infections than in patients with noninvasive infections, as were bacteremia and a high mortality rate. Of the 73 isolates, 93.2%, 97.3%, and 37% exhibited susceptibility to erythromycin, clindamycin, and tetracycline, respectively. The five most prevalent emm types were emm106 (24.7%), emm11 (12.3%), emm102 (9.6%), emm4 (8.2%), and emm12 (8.2%). Compared to other types, the emm106 type was significantly more likely to be associated with invasive diseases (P = 0.012). Dendrogram analysis showed a unique SmaI-digested pulsed-field gel electrophoresis pattern of the emm106 type that was particularly prone to cause invasive skin and soft tissue infections (P < 0.001). The results of this study suggest that isolates with the emm106 gene may be an emerging group A Streptococcus strain that causes invasive skin and soft tissue infections. Further surveillance study to understand the significance of this invasive strain is critical. PMID:21865425

  1. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients.

    PubMed

    Walsh, T J; Hiemenz, J W; Anaissie, E

    1996-06-01

    Invasive fungal infections, including disseminated candidiasis and invasive pulmonary aspergillosis, are important causes of morbidity and mortality in neutropenic patients. The recent development of fluconazole, itraconazole, lipid formulations of amphotericin B, and recombinant cytokines have expanded our therapeutic armamentarium. Clinical trials have elucidated new strategies for utilizing these compounds in the prevention and treatment of opportunistic mycoses. The population of more severely immunocompromised patients, however, continues to expand and the spectrum of drug-resistant fungi, including but not limited to Candida spp, Fusarium spp, Zygomycetes, and dematiaceous moulds, continues to evolve, thus presenting new challenges to recent therapeutic advances. Development of new antifungal chemotherapeutic agents and novel approaches for augmentation of host response will be required to meet these new mycologic challenges.

  2. An elderly woman with Prevotella bacteraemia secondary to pyometra

    PubMed Central

    Guerrero, Patricia Perez; Zamorano, Marina Martin; Trujillo, Ignacio Garcia; Gonzalez, Jose Antonio Giron

    2009-01-01

    An 87-year-old woman was admitted to our hospital with sepsis and foetid vaginal discharge. She presented an abdominal mass that had been present for the last 20 years, refused diagnostic or therapeutic procedures. A computed tomography scan detected a uterine body with multiple calcifications and an internal collection of 10 cm. No other infectious sources were apparent. A tentative diagnostic of pyometra was made and empiric antibiotic treatment was initiated. A hysteroscopy was performed with incomplete drainage of purulent material, due to important vaginal atrophy. In both blood and vaginal fluid cultures Prevotella spp. was isolated. Clinical evolution was favourable with metronidazole. The patient refused a hysterectomy or other surgical drainages, and she was discharged from hospital with oral antibiotics. The patient underwent antibiotic therapy during 1 month; 1 week after finishing this treatment, the patient died. The characteristics of clinical evolution in these last days were not known. PMID:21686575

  3. Epidemiology of invasive fungal infections in lung transplant recipients on long-term azole antifungal prophylaxis.

    PubMed

    Chong, Pearlie P; Kennedy, Cassie C; Hathcock, Matthew A; Kremers, Walter K; Razonable, Raymund R

    2015-04-01

    Lung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single-center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15-15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58-4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.

  4. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases.

    PubMed

    Ruhnke, Markus; Schwartz, Stefan

    2016-12-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay (Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the 'traditional' empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  5. Recent developments in the management of invasive fungal infections in patients with oncohematological diseases

    PubMed Central

    Ruhnke, Markus; Schwartz, Stefan

    2016-01-01

    Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation. For definite diagnosis of IFD, various diagnostic tools have to be applied, including conventional mycological culture and nonconventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. In the last few years, various laboratory methods, like the Aspergillus GM immunoassay (Aspergillus GM EIA), 1,3-ß-D-glucan (BG) assay or polymerase chain reaction (PCR) techniques have been developed for better diagnosis. Since no single indirect test, including radiological methods, provides the definite diagnosis of an invasive fungal infection, the combination of different diagnostic procedures, which include microbiological cultures, histological, serological and molecular methods like PCR together with the pattern of clinical presentation, may currently be the best strategy for the prompt diagnosis, initiation and monitoring of IFDs. Early start of antifungal therapy is mandatory, but clinical diagnostics often do not provide clear evidence of IFD. Integrated care pathways have been proposed for management and therapy of IFDs with either the diagnostic driven strategy using the preemptive antifungal therapy as opposed to the clinical or empirical driven strategy using the ‘traditional’ empirical antifungal therapy. Antifungal agents preferentially used for systemic therapy of invasive fungal infections are amphotericin B

  6. Micafungin: a review of its use in the prophylaxis and treatment of invasive Candida infections.

    PubMed

    Scott, Lesley J

    2012-11-12

    Intravenous micafungin (Mycamine®; Fungard®), an echinocandin, is approved in the EU for the treatment of adult (aged ≥ 16 years) and paediatric patients with invasive candidiasis and for the treatment of adult patients with oesophageal candidiasis. It is also approved in the EU as prophylactic treatment to prevent Candida infections in adult and paediatric patients undergoing haematopoietic stem cell transplant (HSCT) or patients who are expected to have neutropenia for ≥ 10 days. This article reviews the therapeutic use of micafungin for the treatment and prophylaxis of Candida infections in adult and paediatric patients, focusing on approved indications in Europe, and briefly discusses the pharmacology of the drug. Micafungin shows very good in vitro activity against clinically relevant isolates of Candida spp., with a low propensity to be associated with the emergence of resistant isolates. The drug has a convenient once-daily dosage regimen and is associated with relatively few drug-drug interactions. In large, multinational trials in adult and/or paediatric patients with invasive candidiasis, micafungin was noninferior to intravenous caspofungin or liposomal amphotericin B. In similarly designed trials in adult patients with oesophageal candidiasis, treatment with micafungin was noninferior to that with intravenous fluconazole or caspofungin. As prophylactic treatment in adult and paediatric patients who had undergone HSCT, micafungin was superior to fluconazole therapy and noninferior to oral itraconazole in large, multicentre trials. Micafungin was generally well tolerated by participants in these clinical trials, given the severe morbidity of the underlying conditions of patients, with a similar tolerability profile to caspofungin and, in general, to fluconazole. It was better tolerated than liposomal amphotericin B or oral itraconazole. Thus, micafungin is a valuable first-line or alternative option to other antifungal agents for the management of

  7. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    PubMed Central

    de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

    2016-01-01

    Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV. Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection. PMID:27331659

  8. Comparative pan genome analysis of oral Prevotella species implicated in periodontitis.

    PubMed

    Ibrahim, Maziya; Subramanian, Ahalyaa; Anishetty, Sharmila

    2017-02-24

    Prevotella is part of the oral bacterial community implicated in periodontitis. Pan genome analyses of eight oral Prevotella species, P. dentalis, P. enoeca, P. fusca, P. melaninogenica, P. denticola, P. intermedia 17, P. intermedia 17-2 and P. sp. oral taxon 299 are presented in this study. Analysis of the Prevotella pan genome revealed features such as secretion systems, resistance to oxidative stress and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems that enable the bacteria to adapt to the oral environment. We identified the presence of type VI secretion system (T6SS) in P. fusca and P. intermedia strains. For some VgrG and Hcp proteins which were not part of the core T6SS loci, we used gene neighborhood analysis and identified putative effector proteins and putative polyimmunity loci in P. fusca and polymorphic toxin systems in P. intermedia strains. Earlier studies have identified the presence of Por secretion system (PorSS) in P. gingivalis, P. melaninogenica and P. intermedia. We noted the presence of their homologs in six other oral Prevotella studied here. We suggest that in Prevotella, PorSS is used to secrete cysteine proteases such as interpain and C-terminal domain containing proteins with a "Por_secre_tail" domain. We identified subtype I-B CRISPR-Cas system in P. enoeca. Putative CRISPR-Cas system subtypes for 37 oral Prevotella and 30 non-oral Prevotella species were also predicted. Further, we performed a BLASTp search of the Prevotella proteins which are also conserved in the red-complex pathogens, against the human proteome to identify potential broad-spectrum drug targets. In summary, the use of a pan genome approach enabled identification of secretion systems and defense mechanisms in Prevotella that confer adaptation to the oral cavity.

  9. Four Clones of Borrelia burgdorferi Sensu Stricto Cause Invasive Infection in Humans

    PubMed Central

    Seinost, Gerald; Dykhuizen, Daniel E.; Dattwyler, Raymond J.; Golde, William T.; Dunn, John J.; Wang, Ing-Nang; Wormser, Gary P.; Schriefer, Martin E.; Luft, Benjamin J.

    1999-01-01

    Lyme disease begins at the site of a tick bite, producing a primary infection with spread of the organism to secondary sites occurring early in the course of infection. A major outer surface protein expressed by the spirochete early in infection is outer surface protein C (OspC). In Borrelia burgdorferi sensu stricto, OspC is highly variable. Based on sequence divergence, alleles of ospC can be divided into 21 major groups. To assess whether strain differences defined by ospC group are linked to invasiveness and pathogenicity, we compared the frequency distributions of major ospC groups from ticks, from the primary erythema migrans skin lesion, and from secondary sites, principally from blood and spinal fluid. The frequency distribution of ospC groups from ticks is significantly different from that from primary sites, which in turn is significantly different from that from secondary sites. The major groups A, B, I, and K had higher frequencies in the primary sites than in ticks and were the only groups found in secondary sites. We define three categories of major ospC groups: one that is common in ticks but very rarely if ever causes human disease, a second that causes only local infection at the tick bite site, and a third that causes systemic disease. The finding that all systemic B. burgdorferi sensu stricto infections are associated with four ospC groups has importance in the diagnosis, treatment, and prevention of Lyme disease. PMID:10377134

  10. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts.

    PubMed

    Georgiadou, Sarah P; Sipsas, Nikolaos V; Marom, Edith M; Kontoyiannis, Dimitrios P

    2011-05-01

    The halo sign is a CT finding of ground-glass opacity surrounding a pulmonary nodule or mass. The reversed halo sign is a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation. In severely immunocompromised patients, these signs are highly suggestive of early infection by an angioinvasive fungus. The halo sign and reversed halo sign are most commonly associated with invasive pulmonary aspergillosis and pulmonary mucormycosis, respectively. Many other infections and noninfectious conditions, such as neoplastic and inflammatory processes, may also manifest with pulmonary nodules associated with either sign. Although nonspecific, both signs can be useful for preemptive initiation of antifungal therapy in the appropriate clinical setting. This review aims to evaluate the diagnostic value of the halo sign and reversed halo sign in immunocompromised hosts and describes the wide spectrum of diseases associated with them.

  11. The Diagnostic Value of Halo and Reversed Halo Signs for Invasive Mold Infections in Compromised Hosts

    PubMed Central

    Georgiadou, Sarah P.; Sipsas, Nikolaos V.; Marom, Edith M.

    2011-01-01

    The halo sign is a CT finding of ground-glass opacity surrounding a pulmonary nodule or mass. The reversed halo sign is a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation. In severely immunocompromised patients, these signs are highly suggestive of early infection by an angioinvasive fungus. The halo sign and reversed halo sign are most commonly associated with invasive pulmonary aspergillosis and pulmonary mucormycosis, respectively. Many other infections and noninfectious conditions, such as neoplastic and inflammatory processes, may also manifest with pulmonary nodules associated with either sign. Although nonspecific, both signs can be useful for preemptive initiation of antifungal therapy in the appropriate clinical setting. This review aims to evaluate the diagnostic value of the halo sign and reversed halo sign in immunocompromised hosts and describes the wide spectrum of diseases associated with them. PMID:21467021

  12. Outbreak of invasive Aspergillus infection in surgical patients, associated with a contaminated air-handling system.

    PubMed

    Lutz, Brock D; Jin, Jiankang; Rinaldi, Michael G; Wickes, Brian L; Huycke, Mark M

    2003-09-15

    An outbreak of Aspergillus infection at a tertiary care hospital was identified among inpatients who had amputation wounds, peritonitis, allograft nephritis, or mediastinitis. During a 2-year period, 6 patients were identified, all of whom had Aspergillus species recovered from samples from normally sterile sites. All cases clustered in the operating theater during a single 12-day period. To assess operating theater air quality, particle counts were measured as surrogate markers for Aspergillus conidia. A substantial increase in the proportion of airborne particles > or =3 microm in size (range, 3-fold to 1000-fold) was observed in many operating rooms. A confined space video camera identified moisture and contamination of insulating material in ductwork and variable airflow volume units downstream of final filters. No additional invasive Aspergillus wound infections were identified after the operating theater air-handling systems were remediated, suggesting that this unusual outbreak was due to the deterioration of insulating material in variable airflow volume units.

  13. Quantitative non-invasive intracellular imaging of Plasmodium falciparum infected human erythrocytes

    NASA Astrophysics Data System (ADS)

    Edward, Kert; Farahi, Faramarz

    2014-05-01

    Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition.

  14. British Society for Medical Mycology proposed standards of care for patients with invasive fungal infections.

    PubMed

    Denning, David W; Kibbler, Christopher C; Barnes, Rosemary A

    2003-04-01

    Outcomes for invasive fungal infections have greatly improved in the past decade, and several new antifungal drugs have been or will be licensed in the next few years. Early accurate diagnosis and appropriate treatment have major impact on survival. In a 1995 survey of laboratory practice in the UK for mycology, major disparities were seen, with many laboratories not undertaking even simple diagnostic procedures. Delays in processing and inadequate procedures for handling samples, incomplete or delayed reporting of results, or a combination of these, compromise the care of patients. In randomised trials of antifungal chemotherapy, optimum treatments and good alternatives for others have been defined for some infections. High-quality care requires a multidisciplinary approach to diagnosis and management. In this review, we propose microbiology, histopathology, radiology, and clinical auditing standards, with the evidence base for each reviewed. The standards are absolutes, and, therefore, provide a straightforward basis for improving services to patients if they are all implemented.

  15. [In vitro activity of ampicillin-ceftriaxone against Enterococcus faecalis isolates recovered from invasive infections].

    PubMed

    Burguer Moreira, Noelia; Nastro, Marcela; Vay, Carlos; Famiglietti, Ángela; Rodríguez, Carlos Hernán

    2016-01-01

    In vitro activity of the combination of ampicillin- ceftriaxone against 30 Enterococcus faecalis isolates recovered from invasive infections in patients admitted to Hospital de Clínicas José de San Martin in the city of Buenos Aires was assessed. Ampicillin- ceftriaxone synergies were determined by microdilution in Müeller-Hinton (MH) broth with and without subinhibitory concentrations of ceftriaxone. Synergy was detected in 22/30 isolates. A decrease in both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was observed in 14/30 isolates, whereas in 6/30 isolates the decrease was observed in the MIC value and only in the MBC value in the 2 remaining isolates. The bactericidal activity of the combination showed to be higher at low concentrations of ampicillin (< 1 μg/ml). We detected in vitro synergy using the ampicillin-ceftriaxone combination and thus, its efficacy was confirmed in the treatment of severe infections by E. faecalis.

  16. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients.

    PubMed

    Neofytos, D; Fishman, J A; Horn, D; Anaissie, E; Chang, C-H; Olyaei, A; Pfaller, M; Steinbach, W J; Webster, K M; Marr, K A

    2010-06-01

    Contemporary epidemiology and outcomes of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients are not well described. From March 2004 through September 2007, proven and probable IFIs were prospectively identified in 17 transplant centers in the United States. A total 429 adult SOT recipients with 515 IFIs were identified; 362 patients received a single and 67 patients received >or=2 organs. Most IFIs were caused by Candida species (59.0%), followed by Aspergillus species (24.8%), Cryptococcus species (7.0%), and other molds (5.8%). Invasive candidiasis (IC) was the most frequently observed IFI in all groups, except for lung recipients where invasive aspergillosis (IA) was the most common IFI (P<0.0001). Almost half of IC cases in liver, heart, and lung transplant recipients occurred during the first 100 days post transplant. Over half of IA cases in lung recipients occurred >1 year post transplant. Overall 12-week mortality was 29.6%; liver recipients had the highest mortality (P=0.05). Organ damage, neutropenia, and administration of corticosteroids were predictors of death. These results extend our knowledge on the epidemiology of IFI in SOT recipients, emphasizing the occurrence of IC early after non-lung transplant, and late complications with molds after lung transplant. Overall survival appears to have improved compared with historical reports.

  17. Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

    PubMed

    Miyakoshi, Shigesaburo; Kusumi, Eiji; Matsumura, Tomoko; Hori, Akiko; Murashige, Naoko; Hamaki, Tamae; Yuji, Koichiro; Uchida, Naoyuki; Masuoka, Kazuhiro; Wake, Atsushi; Kanda, Yoshinobu; Kami, Masahiro; Tanaka, Yuji; Taniguchi, Shuichi

    2007-07-01

    Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.

  18. Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.

    PubMed

    Dobbs, Kerry; Domínguez Conde, Cecilia; Zhang, Shen-Ying; Parolini, Silvia; Audry, Magali; Chou, Janet; Haapaniemi, Emma; Keles, Sevgi; Bilic, Ivan; Okada, Satoshi; Massaad, Michel J; Rounioja, Samuli; Alwahadneh, Adel M; Serwas, Nina K; Capuder, Kelly; Çiftçi, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K; Pedergnana, Vincent; Boisson, Bertrand; Haskoloğlu, Şule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slavé; Goldstein, David B; Parrott, Roberta E; Savas, Berna; Schambach, Axel; Tabellini, Giovanna; Bock, Christoph; Chatila, Talal A; Comeau, Anne Marie; Geha, Raif S; Abel, Laurent; Buckley, Rebecca H; İkincioğulları, Aydan; Al-Herz, Waleed; Helminen, Merja; Doğu, Figen; Casanova, Jean-Laurent; Boztuğ, Kaan; Notarangelo, Luigi D

    2015-06-18

    Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that are present are quantitatively or functionally deficient. Impaired humoral immunity is also common. Patients have severe infections, autoimmunity, or both. The specific molecular, cellular, and clinical features of many types of combined immunodeficiencies remain unknown. Methods We performed genetic and cellular immunologic studies involving five unrelated children with early-onset invasive bacterial and viral infections, lymphopenia, and defective T-cell, B-cell, and natural killer (NK)-cell responses. Two patients died early in childhood; after allogeneic hematopoietic stem-cell transplantation, the other three had normalization of T-cell function and clinical improvement. Results We identified biallelic mutations in the dedicator of cytokinesis 2 gene (DOCK2) in these five patients. RAC1 activation was impaired in the T cells. Chemokine-induced migration and actin polymerization were defective in the T cells, B cells, and NK cells. NK-cell degranulation was also affected. Interferon-α and interferon-λ production by peripheral-blood mononuclear cells was diminished after viral infection. Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a new mendelian disorder with pleiotropic defects of hematopoietic and nonhematopoietic immunity. Children with clinical features of combined immunodeficiencies, especially with early-onset, invasive infections, may have this condition. (Supported by the National Institutes of Health and others.).

  19. DOCK2 and a Recessive Immunodeficiency with Early-Onset Invasive Infections

    PubMed Central

    Dobbs, Kerry; Domínguez Conde, Cecilia; Zhang, Shen-Ying; Parolini, Silvia; Audry, Magali; Chou, Janet; Haapaniemi, Emma; Keles, Sevgi; Bilic, Ivan; Okada, Satoshi; Massaad, Michel J.; Rounioja, Samuli; Alwahadneh, Adel M.; Serwas, Nina K.; Capuder, Kelly; Ciftci, Ergin; Felgentreff, Kerstin; Ohsumi, Toshiro K.; Pedergnana, Vincent; Boisson, Bertrand; Haskoloğlu, Sule; Ensari, Arzu; Schuster, Michael; Moretta, Alessandro; Itan, Yuval; Patrizi, Ornella; Rozenberg, Flore; Lebon, Pierre; Saarela, Janna; Knip, Mikael; Petrovski, Slavé; Goldstein, David B.; Parrott, Roberta E.; Savas, Berna; Schambach, Axel; Tabellini, Giovanna; Bock, Christoph; Chatila, Talal; Comeau, Anne Marie; Geha, Raif S.; Abel, Laurent; Buckley, Rebecca H.; Ikincioğullari, Aydan; Al-Herz, Waleed; Helminen, Merja; Doğu, Figen; Casanova, Jean-Laurent; Boztuğ, Kaan; Notarangelo, Luigi D.

    2015-01-01

    Background Combined immunodeficiencies (CIDs) denote inborn errors of T-cell immunity with T cells present but quantitatively or functionally deficient. Impaired humoral immunity, either due to a primary B cell defect or secondary to the T-cell defect, is also frequent. Consequently, patients with CID display severe infections and/or autoimmunity. The specific molecular, cellular, and clinical features of many types of CID remain unknown. Methods We performed genetic and cellular immunological studies in five unrelated children who shared a history of early-onset invasive bacterial and viral infections, with lymphopenia and defective T-, B-, and NK-cell responses. Two patients died early in childhood, whereas the other three underwent allogeneic hematopoietic stem cell transplantation with normalization of T cell function and clinical improvement. Results We identified bi-allelic mutations in the Dedicator Of Cytokinesis 2 (DOCK2) gene in these five patients. RAC1 activation was impaired in T cells. Chemokine-induced migration and actin polymerization were defective in T, B, and NK cells. NK-cell degranulation was also affected. The production of interferon (IFN)-α and -λ by peripheral blood mononuclear cells (PBMCs) was diminished following virus infection. Moreover, in DOCK2-deficient fibroblasts, virus replication was increased and there was enhanced virus-induced cell death, which could be normalized by treatment with IFN-α2β or upon expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 deficiency is a Mendelian disorder with pleiotropic defects of hematopoietic and non-hematopoietic immunity. Children with clinical features of CID, especially in the presence of early-onset, invasive infections may have this condition. PMID:26083206

  20. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole.

    PubMed

    Soysal, Ahmet

    2015-01-01

    Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.

  1. Posaconazole: a review of the gastro-resistant tablet and intravenous solution in invasive fungal infections.

    PubMed

    McKeage, Kate

    2015-03-01

    Posaconazole (Noxafil(®)) is a triazole antifungal agent with an extended spectrum of antifungal activity. It is approved for the prophylaxis of invasive fungal infections in patients with neutropenia or in haematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft-versus-host disease, and for the treatment of fungal infections. The efficacy and good tolerability of posaconazole oral suspension administered three or four times daily is well established. However, in order to overcome pharmacokinetic limitations associated with the suspension, a new gastro-resistant tablet and intravenous (IV) solution were developed. This article reviews the pharmacokinetic properties of the new posaconazole formulations and briefly summarizes efficacy data relating to the suspension. The pharmacokinetic advantages of the posaconazole gastro-resistant tablet compared with the suspension formulation include less interpatient variability, better systemic availability enabling once-daily administration, and absorption that is unaffected by changes in gastric pH or motility; in addition the tablets may be taken with or without food. The posaconazole tablet achieves higher and more consistent mean plasma concentrations than the suspension and, therefore, it is the preferred option to optimize efficacy in the prophylaxis or treatment of invasive fungal disease. The posaconazole IV solution provides an option for these same indications in patients who are unable to receive oral formulations.

  2. Invasive Group A Streptococcal Infection and Vaccine Implications, Auckland, New Zealand

    PubMed Central

    Safar, Atheer; Stewart, Joanna; Trenholme, Adrian; Drinkovic, Dragana; Peat, Briar; Taylor, Susan; Read, Kerry; Roberts, Sally; Voss, Lesley

    2011-01-01

    We aimed to assess the effect of invasive group A streptococcal (GAS) infection and the potential effects of a multivalent GAS vaccine in New Zealand. During January 2005–December 2006, we conducted prospective population-based laboratory surveillance of Auckland residents admitted to all public hospitals with isolation of GAS from normally sterile sites. Using emm typing, we identified 225 persons with confirmed invasive GAS infection (median 53 years of age; range 0–97 years). Overall incidence was 8.1 cases per 100,00 persons per year (20.4/100,000/year for Maori and Pacific Islanders; 24.4/100,000/year for persons >65 years of age; 33/100,000/year for infants <1 year of age). Nearly half (49%) of all cases occurred in Auckland’s lowest socioeconomic quintile. Twenty-two persons died, for an overall case-fatality rate of 10% (63% for toxic shock syndrome). Seventy-four percent of patients who died had an underlying condition. To the population in our study, the proposed 26-valent vaccine would provide limited benefit. PMID:21749758

  3. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    PubMed Central

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. PMID:26730212

  4. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    PubMed

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed.

  5. Clinical considerations in the early treatment of invasive mould infections and disease.

    PubMed

    Mercier, Toine; Maertens, Johan

    2017-03-01

    Different therapeutic strategies for invasive fungal diseases have been explored, each with particular strengths and weaknesses. Broad-spectrum antifungal prophylaxis seems logical, but selective use is important due to its substantial disadvantages, including interference with diagnostic assays, selection for resistance, drug toxicity and drug-drug interactions. Antimould prophylaxis should be restricted to high-risk groups, such as patients undergoing intensive chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, allogeneic HSCT patients with prior invasive fungal infection, graft-versus-host-disease or extended neutropenia, recipients of a solid organ transplant, or patients with a high-risk inherited immunodeficiency. An empirical approach, whereby mould-active therapy is started in neutropenic patients with fever unresponsive to broad-spectrum antibiotics, is widely applied but incurs the clinical and cost penalties associated with overtreatment. A benefit for all-cause mortality using empirical therapy has not been shown, but it is recommended for high-risk patients who remain febrile after 4-7 days of broad-spectrum antibiotics and in whom extended neutropenia is anticipated. There is growing interest in delaying antifungal treatment until an invasive fungal infection is confirmed ('pre-emptive' or 'diagnostics-driven' management), prompted by the development of more sensitive diagnostic techniques. Comparisons of empirical versus pre-emptive regimens are sparse, particularly with modern triazole agents, but treatment costs are lower with pre-emptive therapy and the available evidence has not indicated reduced efficacy. Pre-emptive treatment may be appropriate in neutropenic patients who remain febrile after administration of broad-spectrum antibiotics but who are clinically stable. Further work is required to define accurately the specific patient subgroups in which each management approach is optimal.

  6. Enzyme immunoassays for invasive Candida infections: reactivity of somatic antigens of Candida albicans.

    PubMed Central

    Zöller, L; Krämer, I; Kappe, R; Sonntag, H G

    1991-01-01

    The main problem encountered with serodiagnostic tests for Candida infections is their failure to differentiate between invasive and superficial candidosis. Recent immunoblotting studies suggested that the use of selective somatic proteins of Candida albicans as antigens might be a promising approach toward developing a new generation of serodiagnostic assays. In this study major cytoplasmic protein antigens with molecular weights of 47,000 (47K), 46,000 (46K), 45,000 (45K), and 29,000 (29K) were identified as potential marker antigens for antibody detection in invasive candidosis. Continuous-flow isoelectric focusing was employed to enrich the proteins in two fractions, one of them containing the 47K and 29K proteins and the other one containing predominantly the 47K and 45K major proteins. These antigens and a whole somatic antigen extract were used to establish enzyme immunoassays (EIAs) for antibody detection. Whereas all tests were able to discriminate between patients with invasive candidosis (n = 27) and normal healthy volunteers (n = 167), as proved by graphic marker analysis, the selective antigen EIAs were highly superior to the whole somatic antigen EIA and two serological standard assays (indirect immunofluorescence assay and indirect hemagglutination assay) when a panel of sera from patients with superficial candidosis (n = 34) was used as a negative control group. The use of the 47K-29K antigen fraction allowed the best differentiation between invasive and noninvasive candidosis. The corresponding immunoglobulin G class-specific EIA had a sensitivity of 81.5% and a specificity of 97% for both negative control groups as well. Images PMID:1774309

  7. Invasive Trichosporon Infection: a Systematic Review on a Re-emerging Fungal Pathogen

    PubMed Central

    de Almeida Júnior, João N.; Hennequin, Christophe

    2016-01-01

    Objectives: This review aimed to better depict the clinical features and address the issue of therapeutic management of Trichosporon deep-seated infections. Methods: We comprehensively reviewed the cases of invasive Trichosporon infection reported in the literature from 1994 (date of taxonomic modification) to 2015. Data from antifungal susceptibility testing (AST) studies were also analyzed. Results: Two hundred and three cases were retained and split into four groups: homeopathy (n = 79), other immunodeficiency conditions (n = 41), miscellaneous (n = 58) and newborns (n = 25). Trichosporon asahii was the main causative species (46.7%) and may exhibit cross-resistance to different antifungal classes. The unfavorable outcome rate was at 44.3%. By multivariate analysis, breakthrough infection (OR 2.45) was associated with unfavorable outcome, whilst the use of an azole-based therapy improved the prognosis (OR 0.16). Voriconazole-based treatment was associated with favorable outcome in hematological patients (73.6 vs. 41.8%; p = 0.016). Compiled data from AST demonstrated that (i) T. asahii exhibits the highest MICs to amphotericin B and (ii) voriconazole has the best in vitro efficacy against clinical isolates of Trichosporon spp. Conclusions: Trichosporon infection is not only restricted to hematological patients. Analysis of compiled data from AST and clinical outcome support the use of voriconazole as first line therapy. PMID:27799926

  8. Six-Month Multicenter Study on Invasive Infections Due to Group B Streptococci in Argentina

    PubMed Central

    Lopardo, Horacio A.; Vidal, Patricia; Jeric, Paola; Centron, Daniela; Paganini, Hugo; Facklam, Richard R.; Elliott, John

    2003-01-01

    There is little information about invasive infections by group B streptococci (GBS) and their antimicrobial susceptibilities in Latin America. We performed a prospective multicenter study to determine the serotype distribution and the antimicrobial susceptibility of GBS in Argentina. We identified 58 cases, but only 44 had sufficient data to be evaluated. Eight early-, four late-, and one fatal late, late-onset neonatal infections due to GBS were found. A total of 31 patients were adults with bacteremia, skin and soft tissue infections, osteomyelitis, arthritis, meningitis, abdominal infections, and renal abscess. Serotype III was prevalent in late-onset neonatal disease, and several serotypes (Ia/c, III, Ia, and II) were involved in early-onset neonatal infections. Serotypes II, Ia/c, III, and IV were commonly found in adults, with serotype II prevalent in younger adults (18 to 69 years old) and serotype Ia/c prevalent in elderly adults (>70 years old). The mortality rate attributable to GBS infections was 10.8%. All GBS were susceptible to penicillin and ceftriaxone. Resistance to clindamycin (1.7%), erythromycin (5.2%), azithromycin (5.2%), minocycline (69%), and tetracycline (72.4%), to high levels of kanamycin and amikacin (1.7%), and to intermediately high levels of gentamicin (1.7%) was observed. The bifunctional enzyme AAC6′-APH2" was detected in the isolate resistant to aminoglycosides, and other genetic determinants were identified in other resistant isolates: tetM and tetO in tetracycline-resistant streptococci and mefA and ermTR for efflux-mediated and inducible macrolide-lincosamide-streptogramin B-resistant streptococci, respectively. For clinical purposes and rapid and easy detection of high-level aminoglycoside-resistant GBS, a screening method that used 1,000-μg kanamycin disks is proposed. PMID:14532204

  9. ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2

    PubMed Central

    Das, Lopamudra; Kokate, Shrikant Babanrao; Rath, Suvasmita; Rout, Niranjan; Singh, Shivaram Prasad; Crowe, Sheila Eileen; Mukhopadhyay, Asish K.; Bhattacharyya, Asima

    2016-01-01

    Helicobacter pylori infection is one of the most potent factors leading to gastric carcinogenesis. The seven in absentia homologue (Siah2) is an E3 ubiquitin ligase which has been implicated in various cancers but its role in H. pylori-mediated gastric carcinogenesis has not been established. We investigated the involvement of Siah2 in gastric cancer metastasis which was assessed by invasiveness and migration of H. pylori-infected gastric epithelial cancer cells. Cultured gastric cancer cells (GCCs) MKN45, AGS and Kato III showed significantly induced expression of Siah2, increased invasiveness and migration after being challenged with the pathogen. Siah2-expressing stable cells showed increased invasiveness and migration after H. pylori infection. Siah2 was transcriptionally activated by E26 transformation-specific sequence 2 (ETS2)- and Twist-related protein 1 (Twist1) induced in H. pylori-infected gastric epithelial cells. These transcription factors dose-dependently enhanced the aggressiveness of infected GCCs. Our data suggested that H. pylori-infected GCCs gained cell motility and invasiveness through Siah2 induction. As gastric cancer biopsy samples also showed highly induced expression of ETS2, Twist1 and Siah2 compared with noncancerous gastric tissue, we surmise that ETS2- and Twist1-mediated Siah2 up-regulation has potential diagnostic and prognostic significance and could be targeted for therapeutic purpose. PMID:27048589

  10. Seasonality in the infection and invasion of Marteilioides chungmuensis in the Pacific oyster Crassostrea gigas.

    PubMed

    Tun, Kay Lwin; Shimizu, Yasuko; Yamanoi, Hideo; Yoshinaga, Tomoyoshi; Ogawa, Kazuo

    2008-07-07

    The protozoan parasite Marteilioides chungmuensis causes irregular enlargement of the ovary in the Pacific oyster Crassostrea gigas. The parasite invades the oyster through the epithelial tissue of the labial palp, replicates in the connective tissue, and then moves to the gonad, producing spores inside the oocytes. In this study the seasonality and invasion period of the parasite into the host was investigated over a 1 yr cycle. Uninfected 1 and 0 yr old (spat) oysters were placed in an epizootic area every month from July 2004 to July 2005 and September 2005 to March 2006, respectively, and left for 1 mo. Labial palps and gonad were sampled monthly and examined for infection by nested PCR and histological observations. Prevalence of infection detected by PCR was 70% or higher from August to October, but declined sharply in November and reached 7% or lower from February to April. To explain the low detection rate in winter, 1 yr old uninfected oysters were placed in an epizootic area in winter (water temperature: 8 to 10 degrees C) for 2 wk and then transferred to M. chungmuensis-free seawater at 24 degrees C. Although prevalence of infection was ca. 7% before transfer to heated seawater, levels of 87% were detected after 1 wk. After a 3 wk exposure to heated seawater, parasites were found in host oocytes by histological observation. It was concluded that the low prevalence in winter was due to insufficient replication of M. chungmuensis at low seawater temperatures, resulting in levels not detectable by nested PCR, and not to the absence of invasion.

  11. Antibacterial and antibiofilm effects of iron chelators against Prevotella intermedia.

    PubMed

    Moon, Ji-Hoi; Kim, Cheul; Lee, Hee-Su; Kim, Sung-Woon; Lee, Jin-Yong

    2013-09-01

    Prevotella intermedia, a major periodontopathogen, has been shown to be resistant to many antibiotics. In the present study, we examined the effect of the FDA-approved iron chelators deferoxamine (DFO) and deferasirox (DFRA) against planktonic and biofilm cells of P. intermedia in order to evaluate the possibility of using these iron chelators as alternative control agents against P. intermedia. DFRA showed strong antimicrobial activity (MIC and MBC values of 0.16 mg ml(-1)) against planktonic P. intermedia. At subMICs, DFRA partially inhibited the bacterial growth and considerably prolonged the bacterial doubling time. DFO was unable to completely inhibit the bacterial growth in the concentration range tested and was not bactericidal. Crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that DFRA significantly decreased the biofilm-forming activity as well as the biofilm formation, while DFO was less effective. DFRA was chosen for further study. In the ATP-bioluminescent assay, which reflects viable cell counts, subMICs of DFRA significantly decreased the bioactivity of biofilms in a concentration-dependent manner. Under the scanning electron microscope, P. intermedia cells in DFRA-treated biofilm were significantly elongated compared to those in untreated biofilm. Further experiments are necessary to show that iron chelators may be used as a therapeutic agent for periodontal disease.

  12. Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

    PubMed

    Guan, S-M; Fu, S-M; He, J-J; Zhang, M

    2011-01-01

    Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

  13. Assessing the Effects of Trematode Infection on Invasive Green Crabs in Eastern North America

    PubMed Central

    Blakeslee, April M. H.; Keogh, Carolyn L.; Fowler, Amy E.; Griffen, Blaine D.

    2015-01-01

    A common signature of marine invasions worldwide is a significant loss of parasites (= parasite escape) in non-native host populations, which may confer a release from some of the harmful effects of parasitism (e.g., castration, energy extraction, immune activation, behavioral manipulation) and possibly enhance the success of non-indigenous species. In eastern North America, the notorious invader Carcinus maenas (European green crab) has escaped more than two-thirds its native parasite load. However, one of its parasites, a trematode (Microphallus similis), can be highly prevalent in the non-native region; yet little is known about its potential impacts. We employed a series of laboratory experiments to determine whether and how M. similis infection intensity influences C. maenas, focusing on physiological assays of body mass index, energy storage, and immune activation, as well as behavioral analyses of foraging, shelter utilization, and conspicuousness. We found little evidence for enduring physiological or behavioral impacts four weeks after experimental infection, with the exception of mussel handling time which positively correlated with cyst intensity. However, we did find evidence for a short-term effect of M. similis infection during early stages of infection (soon after cercarial penetration) via a significant drop in circulating immune cells, and a significant increase in the crabs’ righting response time. Considering M. similis is the only common parasite infecting C. maenas in eastern North America, our results for minimal lasting effects of the trematode on the crab’s physiology and behavior may help explain the crab’s continued prominence as a strong predator and competitor in the region. PMID:26030816

  14. Frequent House Invasion of Trypanosoma cruzi-Infected Triatomines in a Suburban Area of Brazil

    PubMed Central

    Ribeiro Jr., Gilmar; Gurgel-Gonçalves, Rodrigo; Reis, Renato Barbosa; dos Santos, Carlos Gustavo Silva; Amorim, Alekhine; Andrade, Sônia Gumes; Reis, Mitermayer G.

    2015-01-01

    Background The demographic transition of populations from rural areas to large urban centers often results in a disordered occupation of forest remnants and increased economic pressure to develop high-income buildings in these areas. Ecological and socioeconomic factors associated with these urban transitions create conditions for the potential transmission of infectious diseases, which was demonstrated for Chagas disease. Methodology/Principal Findings We analyzed 930 triatomines, mainly Triatoma tibiamaculata, collected in artificial and sylvatic environments (forests near houses) of a suburban area of the city of Salvador, Bahia State, Brazil between 2007 and 2011. Most triatomines were captured at peridomiciles. Adult bugs predominated in all studied environments, and nymphs were scarce inside houses. Molecular analyses of a randomly selected sub-sample (n=212) of triatomines showed Trypanosoma cruzi infection rates of 65%, 50% and 56% in intradomestic, peridomestic and sylvatic environments, respectively. We detected the T. cruzi lineages I and II and mixed infections. We also showed that T. tibiamaculata fed on blood from birds (50%), marsupials (38%), ruminants (7%) and rodents (5%). The probability of T. cruzi infection was higher in triatomines that fed on marsupial blood (odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.22-3.11). Moreover, we observed a protective effect against infection in bugs that fed on bird blood (OR = 0.43, 95% CI = 0.30-0.73). Conclusions/Significance The frequent invasion of houses by infected triatomines indicates a potential risk of T. cruzi transmission to inhabitants in this area. Our results reinforce that continuous epidemiological surveillance should be performed in areas where domestic transmission is controlled but enzootic transmission persists. PMID:25909509

  15. Immunosuppressive effects of Prevotella intermedia on in vitro human lymphocyte activation.

    PubMed Central

    Shenker, B J; Vitale, L; Slots, J

    1991-01-01

    In this study, we have assessed four strains of Prevotella intermedia, isolated from periodontally involved lesions, for their ability to inhibit lymphocyte functions. All four strains were found to cause a dose-dependent inhibition of B- and T-cell proliferation in response to mitogens and antigens. This was reflected in altered DNA, RNA, and protein syntheses. Furthermore, P. intermedia appeared to affect the early stages of cell activation. This was ascertained by kinetic analysis in which it was determined that the extract had to be present during the first 24 h of incubation to cause suppression. Moreover, direct assessment of the early stages of cell activation indicated that release of cytokines and expression of the interleukin 2 receptor and CD69 on T cells were inhibited by P. intermedia sonic extracts. Finally, preliminary characterization of the immunosuppressive agent indicates that it has a molecular mass of approximately 50 kDa and is heat labile. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbially mediated immunosuppression may contribute to the pathogenesis of periodontal disease by altering the nature and consequences of host-parasite interactions. PMID:1937818

  16. Predators, environment and host characteristics influence the probability of infection by an invasive castrating parasite.

    PubMed

    Gehman, Alyssa-Lois M; Grabowski, Jonathan H; Hughes, A Randall; Kimbro, David L; Piehler, Michael F; Byers, James E

    2017-01-01

    Not all hosts, communities or environments are equally hospitable for parasites. Direct and indirect interactions between parasites and their predators, competitors and the environment can influence variability in host exposure, susceptibility and subsequent infection, and these influences may vary across spatial scales. To determine the relative influences of abiotic, biotic and host characteristics on probability of infection across both local and estuary scales, we surveyed the oyster reef-dwelling mud crab Eurypanopeus depressus and its parasite Loxothylacus panopaei, an invasive castrating rhizocephalan, in a hierarchical design across >900 km of the southeastern USA. We quantified the density of hosts, predators of the parasite and host, the host's oyster reef habitat, and environmental variables that might affect the parasite either directly or indirectly on oyster reefs within 10 estuaries throughout this biogeographic range. Our analyses revealed that both between and within estuary-scale variation and host characteristics influenced L. panopaei prevalence. Several additional biotic and abiotic factors were positive predictors of infection, including predator abundance and the depth of water inundation over reefs at high tide. We demonstrate that in addition to host characteristics, biotic and abiotic community-level variables both serve as large-scale indicators of parasite dynamics.

  17. [Experimental infection of 2 species of laboratory rodents with invasive larvae of Elaphostrongylus cervi (Nematoda, Metastrongyloidea)].

    PubMed

    Demiaszkiewicz, A W

    1989-01-01

    Single doses (from 300 to 1000 larvi per an animal) of invasive larvae E. cervi Cameron, 1931, obtained from experimentally infected snails Helix pomatia L. were given to 17 guinea pigs and 17 golden hamsters. Clinical nervous symptoms in the form of paresis and paralysis of limbs occurred only in the guinea pigs which were given a dose of 1000 larvi. These animals died in the period from the 75th to 117th day of infection. From their central nervous system single adult males and females of E. cervi were isolated. In the lungs and mesenteries of 2 dead pigs live larvae of E. cervi were found. This fact proves that the guinea pig can fulfil the role of a final and a paratenic host of E. cervi. No clinical symptoms were noticed in any hamster. In hamsters dissected on the 7th day of infection live larvae of E. cervi were found in the mesentery and in the fleshy part of the diaphgram. After 14 days the larvae found both in the mesentery and in the diaphragm were dead and surrounded by cellular infiltration. A strong tissue reaction of the hamster after the administration of E. cervi larvae is responsible for the larvae destruction and resorption.

  18. Invasive fungal infections among inpatients with acquired immune deficiency syndrome at a Chinese university hospital.

    PubMed

    Shen, Yin Zhong; Qi, Tang Kai; Ma, Jian Xin; Jiang, Xue Yan; Wang, Jiang Rong; Xu, Qing Nian; Huang, Qin; Liu, Xi Nian; Sun, Hong Qing; Lu, Hong Zhou

    2007-11-01

    Invasive fungal infections (IFIs) have become a major cause of morbidity and mortality among people with acquired immune deficiency syndrome (AIDS), however, little is known about the clinical features and prognosis of IFI in AIDS in China. This study aimed to characterise the clinical features and prognosis of IFI in AIDS patients in China. We retrospectively reviewed the records of all HIV-infected patients at a Chinese university hospital between December 2004 and May 2006. We identified 35 patients with IFI. IFIs included thrush, oesophageal candidiasis, fungal pneumonia, cryptococcosis, penicilliosis and fungaemia, 44.4% of IFIs occurred in the digestive tract, 71.8% of IFIs occurred in patients with CD4(+)T-lymphocyte counts <100 cells mm(-3). Candida albicans accounted for 57.4% of fungal pathogens isolated. All the patients received both antiretroviral and antifungal therapy; 27 patients were cured and eight died. IFI is one of the most common opportunistic infections in AIDS patients in China. IFIs mainly occur in patients with low CD4(+)T-lymphocyte counts. The majority of IFIs occur in the digestive tract. The most common pathogen causing IFI is C. albicans. The mortality rate remains high although antiretroviral therapy and many newer antifungals are available in China.

  19. Invasion Dynamics of Teratogenic Infections in Light of Rubella Control: Implications for Zika Virus

    PubMed Central

    Metcalf, C. Jessica E.; Barrett, Alan

    2016-01-01

    Introduction: The greatest burden for a subset of pathogens is associated with infection during pregnancy. Evidence for teratogenic effects of Zika Virus have highlighted the importance of understanding the epidemiology of such pathogens. Rubella is perhaps the most classic example, and there is much to be learned from the long history of modelling associated with this virus. Methods: We extended an existing framework for modeling age-specific dynamics of rubella to illustrate how the body of knowledge of rubella dynamics informs the dynamics of teratogenic infections more broadly, and particularly the impact of control on such infections in different transmission settings. Results: During invasion, the burden in women of childbearing age is expected to peak, but then fall to low levels before eventually levelling out. Importantly, as illustrated by rubella dynamics, there is potential for a paradoxical effect, where inadequate control efforts can increase the burden. Conclusions: Drawing on the existing body of work on rubella dynamics highlights key knowledge gaps for understanding the risks associated with Zika Virus. The magnitude and impacts of sterilizing immunity, plus antigenic maps measuring cross-protection with other flaviviruses, and the magnitude of transmission, as well as likely impact of control efforts on transmission are likely to be key variables for robust inference into the outcome of management efforts for Zika Virus. PMID:27617170

  20. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections

    PubMed Central

    Sjölund-Karlsson, Maria; Gordon, Melita A.; Parry, Christopher M.

    2015-01-01

    SUMMARY Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015. PMID:26180063

  1. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections.

    PubMed

    Crump, John A; Sjölund-Karlsson, Maria; Gordon, Melita A; Parry, Christopher M

    2015-10-01

    Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral drug in areas where fluoroquinolone resistance is common. In 2013, CLSI lowered the ciprofloxacin susceptibility breakpoints to account for accumulating clinical, microbiologic, and pharmacokinetic-pharmacodynamic data suggesting that revision was needed for contemporary invasive Salmonella infections. Newly established CLSI guidelines for azithromycin and Salmonella enterica serovar Typhi were published in CLSI document M100 in 2015.

  2. Invasive group A streptococcal infections in the San Francisco Bay area, 1989-99.

    PubMed Central

    Passaro, D. J.; Smitht, D. S.; Hett, E. C.; Reingold, A. L.; Daily, P.; van Beneden, C. A.; Vugia, D. J.

    2002-01-01

    To describe the epidemiology of invasive group A streptococcal (iGAS) infections in the San Francisco Bay Area, population-based active surveillance for laboratory-confirmed iGAS was conducted by the California Emerging Infections Program in three California counties. From January 1989 to December 1999, 1415 cases of iGAS were identified. Mean iGAS incidence was 4.06/100,000 person-years and case fatality ratio was 13%, with no linear trends over time. Incidence was lowest in adolescents, was higher in men than women (4.4 vs. 3.2/100,000 person-years), and was higher in African-Americans (6.7) than in non-Hispanic (4.1) or Hispanic (3.4) Whites, Asians (2.2) or Native Americans (17/100,000 person-years). Injecting drug use was the riskiest underlying condition and was associated with the highest attributable risk. Cases were associated with several underlying conditions, but 23% occurred in previously healthy persons. From 1989-1999, iGAS infections in the San Francisco Bay Area became neither more common nor more deadly. PMID:12558329

  3. Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.

    PubMed

    van der Geest, Patrick J; Rijnders, Bart J A; Vonk, Alieke G; Groeneveld, A B Johan

    2016-03-01

    Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.

  4. Treatment of Invasive Fungal Infections in Renally Impaired Patients with Amphotericin B Colloidal Dispersion

    PubMed Central

    Anaissie, Elias J.; Mattiuzzi, Gloria N.; Miller, Carole B.; Noskin, Gary A.; Gurwith, Marc J.; Mamelok, Richard D.; Pietrelli, Larry A.

    1998-01-01

    Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional amphotericin B designed to minimize drug distribution in the kidney and reduce nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally compromised patients with invasive fungal infections. Patients had either nephrotoxicity from amphotericin B or preexisting renal disease. Intravenous treatment with ABCD (4 mg/kg of body weight daily) was administered for up to 6 weeks. Evaluations included clinical response to treatment and adverse events, with emphasis on changes in serum creatinine levels. ABCD did not appear to have an adverse effect on renal function: mean serum creatinine level tended to decrease slightly with days on therapy, and increases were not dose related. Complete or partial response to treatment was reported for 50% of the 133 intent-to-treat patients and 67% of the 58 evaluable patients. PMID:9517940

  5. Isavuconazole: a new and promising antifungal triazole for the treatment of invasive fungal infections.

    PubMed

    Guinea, Jesús; Bouza, Emilio

    2008-12-01

    Invasive fungal infections (IFIs) are an important cause of morbidity and mortality. Isavuconazole (BAL4815) is a promising novel broad-spectrum triazole in late-stage clinical development that has proven to be active in vitro against Aspergillus, Candida and Cryptococcus neoformans, the most common agents of IFIs. Furthermore, isavuconazole has a pharmacokinetic profile that allows oral and intravenous administration with no severe toxicity. In vivo data from animal models are also encouraging. However, very little information on clinical efficacy is available. Four clinical trials are currently in progress to demonstrate the safety and efficacy of isavuconazole for the treatment and prevention of IFIs. In the absence of clinical and cost data, the real possibilities of this agent as a competitor for the treatment and prevention of IFIs in the clinical setting are still unknown.

  6. New and investigational triazole agents for the treatment of invasive fungal infections.

    PubMed

    De Sarro, A; La Camera, E; Fera, M T

    2008-12-01

    The incidence of invasive fungal infections (IFIs) caused by both common and uncommon opportunistic fungi is increasing along with emerging fungal resistance. Since traditional agents (amphotericin B, fluconazole, itraconazole) are limited by an inadequate spectrum of activity, drug resistance or toxicity, there is a great interest in the development of new antifungal agents for treatment of IFIs in high-risk populations. In recent years a number of systemic antifungal drugs have become available and options for treatment of IFIs have expanded. A new generation of triazole agents (voriconazole, posaconazole, isavuconazole, ravuconazole and albaconazole), with a broad spectrum of activity and sufficient improvements in potency to overcome resistance have emerged and represent an alternative to conventional antifungals for the prevention and treatment of IFIs. This article focuses on the microbiology, pharmacology, clinical efficacy and safety of the new antifungal triazole generation.

  7. Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections.

    PubMed

    Sanz-Rodriguez, C; Lopez-Duarte, M; Jurado, M; Lopez, J; Arranz, R; Cisneros, J-M; Martino, M L; Garcia-Sanchez, P J; Morales, P; Olivé, T; Rovira, M; Solano, C

    2004-07-01

    Caspofungin, an echinocandin antifungal agent, is active against invasive Aspergillus and Candida infections. In a phase I study in healthy volunteers, mild transient increases in serum aminotransferases were observed with the concomitant administration of caspofungin and cyclosporin A (CsA). As a result, it is recommended that the concomitant use of the two drugs be limited to those settings with appropriate risk-benefit balance. We retrospectively assessed safety data in 14 patients with refractory invasive mycoses who were treated concomitantly with CsA and caspofungin before the drug was licensed in Spain. In all, 13 patients were adults (median age, 31.5 years; range, 14-67 years). The average duration of concomitant therapy was 15 days (range, 2-43 days). No clinically significant elevations of serum aminotransferases were observed, and no patient had concomitant therapy discontinued or interrupted due to a drug-related adverse event. In this study of a limited number of patients, the coadministration of caspofungin and CsA was generally well tolerated.

  8. Invasive group B streptococcal disease in infants: a 19-year nationwide study. Serotype distribution, incidence and recurrent infection.

    PubMed Central

    Ekelund, K.; Konradsen, H. B.

    2004-01-01

    During the period 1984-2002, 472 cases of invasive group B streptococcal (GBS) disease in infants aged 0-90 days in Denmark were registered. The overall incidence was 0.4/1000 live births. Most infants (73%) had early-onset GBS infection with 53% registered within the first day. Serotype III predominated (59%) with other serotypes as follows: Ia (16%), Ib (8%), NT (7%), II (6%), other serotypes (5%). Recurrence of GBS infection was registered in six infants, and the interval with no antibiotic therapy varied from 2 to 39 days. The serotypes of the isolates obtained from first and second episodes were identical (serotype III in five, and serotype Ia in one infant). Paired isolates were indistinguishable by PFGE and antibiotic susceptibility testing. Invasive GBS infections in infants are still a problem in Denmark, and recurrent infections are registered in 1% of these infants. PMID:15635965

  9. Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer.

    PubMed

    Geraets, Daan; Alemany, Laia; Guimera, Nuria; de Sanjose, Silvia; de Koning, Maurits; Molijn, Anco; Jenkins, David; Bosch, Xavier; Quint, Wim

    2012-12-01

    The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV-positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR-DEIA-LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α-species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role.

  10. Microbiological and Clinical Characteristics of Hypermucoviscous Klebsiella pneumoniae Isolates Associated with Invasive Infections in China

    PubMed Central

    Guo, Yinjuan; Wang, Shanshan; Zhan, Lingling; Jin, Ye; Duan, Jingjing; Hao, Zhihao; Lv, Jingnan; Qi, Xiuqin; Chen, Liang; Kreiswirth, Barry N.; Wang, Liangxing; Yu, Fangyou

    2017-01-01

    A distinctive syndrome caused by hypermucoviscous Klebsiella pneumoniae (HMKP) including pyogenic liver abscess (PLA) is now becoming a globally emerging disease. In the present study, 22.8% (84/369) of K. pneumoniae clinical isolates associated with various types of invasive infections were identified as HMKP, with 45.2% associated with PLA. Multivariate regression analysis showed that male patients with 41–50 years, PLA, diabetes mellitus, and hypertension were independent risk factors for HMKP infections. K2 (42.9%, 36/84) was the most common capsular serotype among HMKP isolates, followed by K1 (23.8%, 20/84). Seventy-five percentage of K1 HMKP isolates were associated with PLA, while K2 HMKP isolates accounted for more types of invasive infections. The positive rates of iutA, mrkD, aerobactin, iroN, and rmpA among HMKP isolates were significantly higher than those among non-HMKP isolates (p < 0.05). There was a correlation between magA, ybtS, alls, and wcaG and K1 isolates. Interestingly, mrkD was exclusively detected among HMKP (32.1%, 27/84) and K2 isolates (65.9%, 27/41). All K1 and K2 HMKP and non-HMKP isolates were positive for rmpA. Aerobactin was found among 95.0 and 97.5% of K1 and K2 isolates. ST23 was found to be the most prevalent ST among 69 HMKP isolates with K1, K2, K5, K20, and K57 (27.5%, 19/69) and was only found among K1 isolates. ST65 was the second most prevalent ST (26.1%, 18/69) and was also only found among K2 isolates. ST23-K1 HMKP isolates (84.2%, 16/19) were associated with PLA, while ST65-K2 isolates were correlated with more types of infections relative to ST23-K1 isolates. PFGE results showed that the homology of 84 HMKP isolates was diverse. Only five PFGE clusters with more than 75% similarity accounted for more than three isolates. These five PFGE clusters only accounted for 35 (41.7%, 35/84) isolates. In conclusion, our study first found that hypertension and male patients with 41–50 years old were independent risk factors

  11. The haem pigment of the oral anaerobes Prevotella nigrescens and Prevotella intermedia is composed of iron(III) protoporphyrin IX in the monomeric form.

    PubMed

    Smalley, John W; Silver, Jack; Birss, Andrew J; Withnall, Robert; Titler, Philip J

    2003-07-01

    The haem pigment of Porphyromonas gingivalis is composed of micro -oxo bishaem, [Fe(III)PPIX](2)O, but the nature of that generated by Prevotella species has not been established. Mössbauer, Raman and UV-visible spectrophotometry were used to characterize the haem pigment of Prevotella intermedia and Prevotella nigrescens. Mössbauer and Raman spectroscopy revealed the major haem species to be monomeric iron protoporphyrin IX, Fe(III)PPIX.OH (haematin). The terminal growth pH of both species on blood agar was between 5.8 and 6.0, which favours the formation and maintenance of monomeric Fe(III)PPIX.OH. Incubation of Pr. nigrescens and Pr. intermedia with oxyhaemoglobin at pH 6.5 resulted in formation of aquomethaemoglobin which was degraded to generate Fe(III)PPIX.OH which in turn became cell-associated, whilst incubation at pH 7.5 resulted in formation of [Fe(III)PPIX](2)O. It is concluded that both Prevotella species degrade oxyhaemoglobin to form [Fe(III)PPIX](2)O as an intermediate, which is converted to Fe(III)PPIX.OH through a depression in pH. The low pH encourages cell-surface deposition of insoluble Fe(III)PPIX.OH which would act as a barrier against oxygen and reactive oxygen species, and also protect against H(2)O(2) through its inherent catalase activity.

  12. Non-invasive detection and successful treatment of a Helicobacter pylori infection in a captive rhesus macaque.

    PubMed

    Semrau, Antje; Gerold, Susanne; Frick, Julia-Stefanie; Iglauer, Franz

    2017-04-01

    Gastritis is a commonly diagnosed condition in non-human primates used in biomedical research. As in humans, Helicobacter pylori infection may cause gastritis. The following report presents a method of non-invasive detection and a successful treatment protocol for this common pathogen.

  13. Clinical and Microbiological Characteristics of Invasive Group A Streptococcal Infections Before and After Implementation of a Universal Varicella Vaccine Program.

    PubMed

    Frère, Julie; Bidet, Philippe; Tapiéro, Bruce; Rallu, Fabien; Minodier, Philippe; Bonacorsi, Stephane; Bingen, Edouard; Ovetchkine, Philippe

    2016-01-01

    Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly.

  14. Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

    PubMed Central

    Ge, H.F.; Liu, X.Q.; Zhu, Y.Q.; Chen, H.Q.; Chen, G.Z.

    2016-01-01

    Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI. PMID:27683823

  15. Wolbachia in European Populations of the Invasive Pest Drosophila suzukii: Regional Variation in Infection Frequencies

    PubMed Central

    Gibert, Patricia; Martinez, Julien; Fraimout, Antoine; Jiggins, Francis; Andrieux, Thibault; Siozios, Stefanos; Anfora, Gianfranco; Miller, Wolfgang; Rota-Stabelli, Omar; Mouton, Laurence

    2016-01-01

    The invasive pest Drosophila suzukii is characterized by a specific fresh-fruit targeting behavior and has quickly become a menace for the fruit economy of newly infested North American and European regions. D. suzukii carries a strain of the endosymbiotic bacterium Wolbachia, named wSuz, which has a low infection frequency and no reproductive manipulation capabilities in American populations of D. suzukii. To further understand the nature of wSuz biology and assess its utility as a tool for controlling this pest’s populations, we investigated the prevalence of Wolbachia in 23 European D. suzukii populations, and compared our results with those available in American populations. Our data showed a highly variable infection frequency with a mean prevalence of 46%, which is significantly higher than the 17% found in American populations. Based on Multilocus Sequence Typing analysis, a single wSuz strain was diagnosed in all European populations of D. suzukii. In agreement with American data, we found no evidence of cytoplasmic incompatibility induced by wSuz. These findings raise two questions: a) why Wolbachia is maintained in field populations of D. suzukii and b) what are the selective forces responsible for the variation in prevalence within populations, particularly between European and American continents? Our results provide new insights into the D. suzukii-Wolbachia association and highlight regional variations that await further investigation and that should be taken into account for using Wolbachia-based pest management programs. PMID:26809119

  16. Wolbachia in European Populations of the Invasive Pest Drosophila suzukii: Regional Variation in Infection Frequencies.

    PubMed

    Cattel, Julien; Kaur, Rupinder; Gibert, Patricia; Martinez, Julien; Fraimout, Antoine; Jiggins, Francis; Andrieux, Thibault; Siozios, Stefanos; Anfora, Gianfranco; Miller, Wolfgang; Rota-Stabelli, Omar; Mouton, Laurence

    2016-01-01

    The invasive pest Drosophila suzukii is characterized by a specific fresh-fruit targeting behavior and has quickly become a menace for the fruit economy of newly infested North American and European regions. D. suzukii carries a strain of the endosymbiotic bacterium Wolbachia, named wSuz, which has a low infection frequency and no reproductive manipulation capabilities in American populations of D. suzukii. To further understand the nature of wSuz biology and assess its utility as a tool for controlling this pest's populations, we investigated the prevalence of Wolbachia in 23 European D. suzukii populations, and compared our results with those available in American populations. Our data showed a highly variable infection frequency with a mean prevalence of 46%, which is significantly higher than the 17% found in American populations. Based on Multilocus Sequence Typing analysis, a single wSuz strain was diagnosed in all European populations of D. suzukii. In agreement with American data, we found no evidence of cytoplasmic incompatibility induced by wSuz. These findings raise two questions: a) why Wolbachia is maintained in field populations of D. suzukii and b) what are the selective forces responsible for the variation in prevalence within populations, particularly between European and American continents? Our results provide new insights into the D. suzukii-Wolbachia association and highlight regional variations that await further investigation and that should be taken into account for using Wolbachia-based pest management programs.

  17. Iron metabolism and resistance to infection by invasive bacteria in the social amoeba Dictyostelium discoideum.

    PubMed

    Bozzaro, Salvatore; Buracco, Simona; Peracino, Barbara

    2013-01-01

    Dictyostelium cells are forest soil amoebae, which feed on bacteria and proliferate as solitary cells until bacteria are consumed. Starvation triggers a change in life style, forcing cells to gather into aggregates to form multicellular organisms capable of cell differentiation and morphogenesis. As a soil amoeba and a phagocyte that grazes on bacteria as the obligate source of food, Dictyostelium could be a natural host of pathogenic bacteria. Indeed, many pathogens that occasionally infect humans are hosted for most of their time in protozoa or free-living amoebae, where evolution of their virulence traits occurs. Due to these features and its amenability to genetic manipulation, Dictyostelium has become a valuable model organism for studying strategies of both the host to resist infection and the pathogen to escape the defense mechanisms. Similarly to higher eukaryotes, iron homeostasis is crucial for Dictyostelium resistance to invasive bacteria. Iron is essential for Dictyostelium, as both iron deficiency or overload inhibit cell growth. The Dictyostelium genome shares with mammals many genes regulating iron homeostasis. Iron transporters of the Nramp (Slc11A) family are represented with two genes, encoding Nramp1 and Nramp2. Like the mammalian ortholog, Nramp1 is recruited to phagosomes and macropinosomes, whereas Nramp2 is a membrane protein of the contractile vacuole network, which regulates osmolarity. Nramp1 and Nramp2 localization in distinct compartments suggests that both proteins synergistically regulate iron homeostasis. Rather than by absorption via membrane transporters, iron is likely gained by degradation of ingested bacteria and efflux via Nramp1 from phagosomes to the cytosol. Nramp gene disruption increases Dictyostelium sensitivity to infection, enhancing intracellular growth of Legionella or Mycobacteria. Generation of mutants in other "iron genes" will help identify genes essential for iron homeostasis and resistance to pathogens.

  18. Comparative phosphoproteomics reveals components of host cell invasion and post-transcriptional regulation during Francisella infection

    SciTech Connect

    Nakayasu, Ernesto S.; Tempel, Rebecca; Cambronne, Xiaolu A.; Petyuk, Vladislav A.; Jones, Marcus B.; Gritsenko, Marina A.; Monroe, Matthew E.; Yang, Feng; Smith, Richard D.; Adkins, Joshua N.; Heffron, Fred

    2013-09-22

    Francisella tularensis is a facultative intracellular bacterium that causes the deadly disease tularemia. Most evidence suggests that Francisella is not well recognized by the innate immune system that normally leads to cytokine expression and cell death. In previous work, we identified new bacterial factors that were hyper-cytotoxic to macrophages. Four of the identified hyper-cytotoxic strains (lpcC, manB, manC and kdtA) had an impaired lipopolysaccharide (LPS) synthesis and produced an exposed lipid A lacking the O-antigen. These mutants were not only hyper-cytotoxic but also were phagocytosed at much higher rates compared to the wild type parent strain. To elucidate the cellular signaling underlying this enhanced phagocytosis and cell death, we performed a large-scale comparative phosphoproteomic analysis of cells infected with wild-type and delta-lpcC F. novicida. Our data suggest that not only actin but also intermediate filaments and microtubules are important for F. novicida entry into the host cells. In addition, we observed differential phosphorylation of tristetraprolin (TTP), a key component of the mRNA-degrading machinery that controls the expression of a variety of genes including many cytokines. Infection with the delta-lpcC mutant induced the hyper-phosphorylation and inhibition of TTP, leading to the production of cytokines such as IL-1beta and TNF-alpha which may kill the host cells by triggering apoptosis. Together, our data provide new insights for Francisella invasion and a post-transcriptional mechanism that prevents the expression of host immune response factors that controls infection by this pathogen.

  19. Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

    PubMed Central

    Song, Jiasheng; Cai, Zhengxin; White, Alexander G.; Jin, Tao; Wang, Xiaolei; Kadayakkara, Deepak; Anderson, Carolyn J.; Ambrose, Zandrea

    2015-01-01

    In vivo imaging can provide real-time information and three-dimensional (3D) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. Current in vivo imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint the spatial location of target cells, which is urgently needed for revealing human immunodeficiency virus (HIV) dissemination in real-time and HIV-1 reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that in vivo imaging can be used to visualize and quantify simian immunodeficiency virus (SIV)-transduced cells, we genetically engineered SIV to carry different imaging reporters. Based on the expression of the reporter genes, we could visualize and quantify the SIV-transduced cells via vesicular stomatitis virus glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also engineered a chimeric EcoSIV for in vivo infection study. Our results demonstrated that BLI is sensitive enough to detect as few as five single cells transduced with virus, whilst PET-CT can provide 3D images of the spatial location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI can provide images with high spatial resolution in a 3D anatomical context to distinguish a small population of SIV-transduced cells. The in vivo imaging platform described here can potentially serve as a powerful tool to visualize lentiviral infection, including when and where viraemia rebounds, and how reservoirs are formed and maintained during latency or suppressive ART. PMID:26297664

  20. Non-Type b Haemophilus influenzae Invasive Infections in North Dakota and South Dakota, 2013-2015.

    PubMed

    Antony, Stephanie; Kaushik, Ashlesha; Mauriello, Clifford; Chatterjee, Archana

    2016-09-20

    Reports of children with non-type b Haemophilus influenzae infection in the United States in recent years have been limited. Here, we report the spectrum and severity of disease associated with invasive non-type b H influenzae infection in 17 patients at 2 tertiary-care children's hospitals over a 2-year period. Meningitis was the most common diagnosis. The majority of the patients had neurologic sequelae, and 1 patient died. The high proportions of hospitalization, intensive care utilization, and neurologic complications reveal that non-type b H influenzae infection was associated with significant morbidity in this pediatric population.

  1. Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review

    PubMed Central

    2014-01-01

    Background Severe malaria remains a major cause of pediatric hospital admission across Africa. Invasive bacterial infection (IBI) is a recognized complication of Plasmodium falciparum malaria, resulting in a substantially worse outcome. Whether a biological relationship exists between malaria infection and IBI susceptibility remains unclear. We, therefore, examined the extent, nature and evidence of this association. Methods We conducted a systematic search in August 2012 of three major scientific databases, PubMed, Embase and Africa Wide Information, for articles describing bacterial infection among children with P. falciparum malaria using the search string ‘(malaria OR plasmodium) AND (bacteria OR bacterial OR bacteremia OR bacteraemia OR sepsis OR septicaemia OR septicemia).’ Eligiblity criteria also included studies of children hospitalized with malaria or outpatient attendances in sub-Saharan Africa. Results A total of 25 studies across 11 African countries fulfilled our criteria. They comprised twenty cohort analyses, two randomized controlled trials and three prospective epidemiological studies. In the meta-analysis of 7,208 children with severe malaria the mean prevalence of IBI was 6.4% (95% confidence interval (CI) 5.81 to 6.98%). In a further meta-analysis of 20,889 children hospitalised with all-severity malaria and 27,641 children with non-malarial febrile illness the mean prevalence of IBI was 5.58 (95% CI 5.5 to 5.66%) in children with malaria and 7.77% (95% CI 7.72 to 7.83%) in non-malaria illness. Ten studies reported mortality stratified by IBI. Case fatality was higher at 81 of 336, 24.1% (95% CI 18.9 to 29.4) in children with malaria/IBI co-infection compared to 585 of 5,760, 10.2% (95% CI 9.3 to 10.98) with malaria alone. Enteric gram-negative organisms were over-represented in malaria cases, non-typhoidal Salmonellae being the most commonest isolate. There was weak evidence indicating IBI was more common in the severe anemia manifestation

  2. Successful management of gastropulmonary fistula due to invasive fungal infection after chemotherapy and autologous stem cell transplantation: a case report

    PubMed Central

    Ričardas, Janilionis; Lina, Lukoševičiūtė; Virgilijus, Beiša; Valdemaras, Jotautas; Roberta, Petrauskaitė; Valdas, Pečeliūnas; Renata, Jucaitienė

    2016-01-01

    Background. Invasive fungal infections (IFI) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for hematologic malignancies. Acquired gastropulmonary fistula is a rare complication of IFI. Material and methods. We present a case history of a patient with malignant myeloma. She was treated with autologous stem cell transplantation and chemotherapy for three years. She had been treated with antifungal agents as well. Following a specific treatment, she developed an invasive fungal infection (IFI) of the left lung which had been complicated with left gastropulmonary fistula. The patient’s general condition was deteriorating, so it was decided to perform a surgical intervention. At the first procedure, open-window thoracostomy was created in order to facilitate treatment by daily packing of the cavity. Four weeks after the thoracostomy, a thoracomyoplasty was performed to repair a gastropleural fistula. During the laparotomy, the gastric fundus was freed from adjacent tissues and repaired. Intrathoracic transposition of the latissimus dorsi and anterior serratus muscle flaps was performed simultaneously to create a new diaphragm. The open-window thoracostomy was left open due to some small bronchial fistulas. The thoracostomy opening healed spontaneously during the following six months. Conclusion. We report what is, to the best of our knowledge, the first case of an invasive fungal infection (Geotrichum capitatum) successfully treated with intravenous amphotericin B, voriconazole, and surgery on infected soft tissues (organs) for a patient with multiple myeloma in prolonged neutropenia. The efficacy and safety of the surgery for infected soft tissues requires further evaluation. PMID:28356805

  3. Streptococcus suis in invasive human infections in Poland: clonality and determinants of virulence and antimicrobial resistance.

    PubMed

    Bojarska, A; Molska, E; Janas, K; Skoczyńska, A; Stefaniuk, E; Hryniewicz, W; Sadowy, E

    2016-06-01

    The purpose of this study was to perform an analysis of Streptococcus suis human invasive isolates, collected in Poland by the National Reference Centre for Bacterial Meningitis. Isolates obtained from 21 patients during 2000-2013 were investigated by phenotypic tests, multilocus sequence typing (MLST), analysis of the TR9 locus from the multilocus variable number tandem repeat (VNTR) analysis (MLVA) scheme and pulsed-field gel electrophoresis (PFGE) of SmaI-digested DNA. Determinants of virulence and antimicrobial resistance were detected by polymerase chain reaction (PCR) and analysed by sequencing. All isolates represented sequence type 1 (ST1) and were suggested to be serotype 2. PFGE and analysis of the TR9 locus allowed the discrimination of four and 17 types, respectively. Most of the isolates were haemolysis- and DNase-positive, and around half of them formed biofilm. Genes encoding suilysin, extracellular protein factor, fibronectin-binding protein, muramidase-released protein, surface antigen one, enolase, serum opacity factor and pili were ubiquitous in the studied group, while none of the isolates carried sequences characteristic for the 89K pathogenicity island. All isolates were susceptible to penicillin, cefotaxime, imipenem, moxifloxacin, chloramphenicol, rifampicin, gentamicin, linezolid, vancomycin and daptomycin. Five isolates (24 %) were concomitantly non-susceptible to erythromycin, clindamycin and tetracycline, and harboured the tet(O) and erm(B) genes; for one isolate, lsa(E) and lnu(B) were additionally detected. Streptococcus suis isolated in Poland from human invasive infections belongs to a globally distributed clonal complex of this pathogen, enriched in virulence markers. This is the first report of the lsa(E) and lnu(B) resistance genes in S. suis.

  4. Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections

    PubMed Central

    Mery, Alexandre; Sendid, Boualem; François, Nadine; Cornu, Marjorie; Poissy, Julien; Guerardel, Yann

    2016-01-01

    We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Here, we compare the performance of MS-DS for the diagnosis of IC, invasive aspergillosis (IA), and mucormycosis (MM) with those of commercially available antigen detection tests. This retrospective study included 48 patients (23 IC patients [74 serum samples], 15 IA patients [40 serum samples], and 10 MM patients [15 serum samples]) and 49 appropriate controls (102 serum samples). MS-DS, mannan (Mnn), galactomannan (GM), and (1,3)-β-d-glucan (BDG) were detected by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS, Platelia, and Fungitell assays, respectively. For IC, the sensitivity and specificity of the MS-DS index, BDG detection, and Mnn detection were 62% and 84%, 82% and 60%, and 33% and 94% per serum sample and 83% and 69%, 96% and 31%, and 39% and 86% per patient, respectively. For IA, the corresponding values in comparison to BDG and GM detection were 83% and 81%, 62% and 95%, and 62% and 100% per serum sample and 93% and 76%, 87% and 90%, and 93% and 100% per patient, respectively. Nine of the 10 MM patients had a positive MS-DS result. MS-DS gave an early diagnosis in IC (73% positivity before blood culture), IA (positive before GM detection in six patients), and MM (positivity mainly preceded the date of diagnosis) patients. For IC, persisting MS-DS was associated with a poor prognosis. The different biomarkers were rarely detected simultaneously, suggesting different kinetics of release and clearance. For IA, MS-DS provided better complementation to GM monitoring than BDG monitoring. MS-DS detects panfungal molecules circulating during invasive fungal infections. The performance of MS-DS compared favorably with those of biological tests currently recommended for monitoring at-risk patients. Further validation of this test in multicenter studies is required. PMID:27605710

  5. A new non-invasive approach based on polyhexamethylene biguanide increases the regression rate of HPV infection

    PubMed Central

    2012-01-01

    Background HPV infection is a worldwide problem strictly linked to the development of cervical cancer. Persistence of the infection is one of the main factors responsible for the invasive progression and women diagnosed with intraepithelial squamous lesions are referred for further assessment and surgical treatments which are prone to complications. Despite this, there are several reports on the spontaneous regression of the infection. This study was carried out to evaluate the effectiveness of a long term polyhexamethylene biguanide (PHMB)-based local treatment in improving the viral clearance, reducing the time exposure to the infection and avoiding the complications associated with the invasive treatments currently available. Method 100 women diagnosed with HPV infection were randomly assigned to receive six months of treatment with a PHMB-based gynecological solution (Monogin®, Lo.Li. Pharma, Rome - Italy) or to remain untreated for the same period of time. Results A greater number of patients, who received the treatment were cleared of the infection at the two time points of the study (three and six months) compared to that of the control group. A significant difference in the regression rate (90% Monogin group vs 70% control group) was observed at the end of the study highlighting the time-dependent ability of PHMB to interact with the infection progression. Conclusions The topic treatment with PHMB is a preliminary safe and promising approach for patients with detected HPV infection increasing the chance of clearance and avoiding the use of invasive treatments when not strictly necessary. Trial registration ClinicalTrials.gov Identifier NCT01571141 PMID:23009652

  6. Lipooligosaccharide locus class of Campylobacter jejuni: sialylation is not needed for invasive infection.

    PubMed

    Ellström, P; Feodoroff, B; Hänninen, M-L; Rautelin, H

    2014-06-01

    Campylobacter jejuni is a highly diverse enteropathogen that is commonly detected worldwide. It can sometimes cause bacteraemia, but the bacterial characteristics facilitating bloodstream infection are not known. A total of 73 C. jejuni isolates, consecutively collected from blood-borne infections during a 10-year period all over Finland and for which detailed clinical information of the patients were available, were included. We screened the isolates by PCR for the lipooligosaccharide (LOS) locus class and for the presence of the putative virulence genes ceuE, ciaB, fucP, and virB11. The isolates were also tested for γ-glutamyl transpeptidase production. The results were analysed with respect to the clinical characteristics of the patients, and the multilocus sequence types (MLSTs) and serum resistance of the isolates. LOS locus classes A, B, and C, which carry genes for sialylation of LOS, were detected in only 23% of the isolates. These isolates were not more resistant to human serum than those with the genes of non-sialylated LOS locus classes, but were significantly more prevalent among patients with underlying diseases (p 0.02). The fucose permease gene fucP was quite uncommon, but was associated with the isolates with the potential to sialylate LOS (p <0.0001). LOS locus classes and some of the putative virulence factors were associated with MLST clonal complexes. Although some of the bacterial characteristics studied here have been suggested to be important for the invasiveness of C. jejuni, they did not explain why the clinical isolates in the present study were able to cause bacteraemia.

  7. New Panfungal Real-Time PCR Assay for Diagnosis of Invasive Fungal Infections.

    PubMed

    Valero, Clara; de la Cruz-Villar, Laura; Zaragoza, Óscar; Buitrago, María José

    2016-12-01

    The diagnosis of invasive fungal infections (IFIs) is usually based on the isolation of the fungus in culture and histopathological techniques. However, these methods have many limitations often delaying the definitive diagnosis. In recent years, molecular diagnostics methods have emerged as a suitable alternative for IFI diagnosis. When there is not a clear suspicion of the fungus involved in the IFI, panfungal real-time PCR assays have been used, allowing amplification of any fungal DNA. However, this approach requires subsequent amplicon sequencing to identify the fungal species involved, increasing response time. In this work, a new panfungal real-time PCR assay using the combination of an intercalating dye and sequence-specific probes was developed. After DNA amplification, a melting curve analysis was also performed. The technique was standardized by using 11 different fungal species and validated in 60 clinical samples from patients with proven and probable IFI. A melting curve database was constructed by collecting those melting curves obtained from fungal species included in the standardization assay. Results showed high reproducibility (coefficient of variation [CV] < 5%; r > 0.95) and specificity (100%). The overall sensitivity of the technique was 83.3%, with the group of fungi involved in the infection detected in 77.8% of the positive samples with IFIs covered by molecular beacon probes. Moreover, sequencing was avoided in 67.8% of these "probe-positive" results, enabling report of a positive result in 24 h. This technique is fast, sensitive, and specific and promises to be useful for improving early diagnosis of IFIs.

  8. Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3.

    PubMed

    Potempa, Michal; Potempa, Jan; Kantyka, Tomasz; Nguyen, Ky-Anh; Wawrzonek, Katarzyna; Manandhar, Surya P; Popadiak, Katarzyna; Riesbeck, Kristian; Eick, Sigrun; Blom, Anna M

    2009-02-01

    Periodontitis is an inflammatory disease of the supporting structures of the teeth caused by, among other pathogens, Prevotella intermedia. Many strains of P. intermedia are resistant to killing by the human complement system, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with recombinant cysteine protease of P. intermedia (interpain A) resulted in a drastic decrease in bactericidal activity of the serum. Furthermore, a clinical strain 59 expressing interpain A was more serum-resistant than another clinical strain 57, which did not express interpain A, as determined by Western blotting. Moreover, in the presence of the cysteine protease inhibitor E64, the killing of strain 59 by human serum was enhanced. Importantly, we found that the majority of P. intermedia strains isolated from chronic and aggressive periodontitis carry and express the interpain A gene. The protective effect of interpain A against serum bactericidal activity was found to be attributable to its ability to inhibit all three complement pathways through the efficient degradation of the alpha-chain of C3 -- the major complement factor common to all three pathways. P. intermedia has been known to co-aggregate with P. gingivalis, which produce gingipains to efficiently degrade complement factors. Here, interpain A was found to have a synergistic effect with gingipains on complement degradation. In addition, interpain A was able to activate the C1 complex in serum, causing deposition of C1q on inert and bacterial surfaces, which may be important at initial stages of infection when local inflammatory reaction may be beneficial for a pathogen. Taken together, the newly characterized interpain A proteinase appears to be an important virulence factor of P. intermedia.

  9. Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

    PubMed

    Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

    2014-02-01

    Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

  10. Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection.

    PubMed

    Kim, Jong Hun; Benefield, Russell J; Ditolla, Kali

    2016-11-01

    Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed-released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL(-1) ) compared to posaconazole SUS (median 1.0 μg mL(-1) ). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.

  11. Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years*

    PubMed Central

    Shi, Ji-min; Pei, Xu-ying; Luo, Yi; Tan, Ya-min; Tie, Ru-xiu; He, Jing-song; Zheng, Wei-yan; Zhang, Jie; Cai, Zhen; Lin, Mao-fang; Huang, He

    2015-01-01

    Invasive fungal infection (IFI) is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively reviewed the records of 408 patients undergoing allo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 (22.5%) episodes suffered proven or probable IFI (4 patients were proven, 88 patients were probable). Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen (HLA) mismatch, long-time neutropenia, and acute graft-versus-host-disease (GVHD) were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus (CMV) disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival (OS) rate for IFI was significantly lower than that of patients without IFI (41.9% vs. 63.6%, P<0.01). PMID:26365122

  12. Natural infection of the feline lungworm Aelurostrongylus abstrusus in the invasive snail Achatina fulica from Argentina.

    PubMed

    Valente, Romina; Diaz, Julia Ines; Salomón, Oscar Daniel; Navone, Graciela Teresa

    2017-02-15

    The giant African snail Achatina fulica is an invasive mollusk native to Africa, the first record in Argentina was in Puerto Iguazú, in northeastern Argentina in 2010. Recently it was reported in Corrientes Province. This snail can act as an intermediate host of Metastrongyloidea nematodes of importance in public health as: Angiostrongylus cantonensis, Angiostrongylus costaricensis and Angiostrongylus vasorum. Taking into account the presence of A. fulica in Argentina, the objectives of this study is to assess the presence of Metastrongyloidea nematodes in this mollusk species in Puerto Iguazú, Misiones, close to the international border with Brazil and Paraguay. A total of 451 samples were collected from February 2014 to November 2015. The snails were processed using a digestion technique to recover the parasites. A total of 206 nematodes larvae were founded in the digestion solution of 10 hosts (P=2%; MA=0.5; MI=21). Third larval stage (L3) nematodes identified as Aelurostrongylus abstrusus were founded parasitizing the snails. No other larval stage was observed. This species has veterinary importance because it causes 'aelurostrongilosis', also known as feline strongyloidosis. This study constitutes the first record of a Metastrongyloidea nematode in A. fulica in Argentina and also highlights the susceptibility of this mollusk as intermediate host of other helminthes of health importance. The present study suggests that there is a need to establish an epidemiological monitoring system in order to prevent the possible installation of an infected mollusks focus.

  13. Evaluation of Hepatotoxicity with Treatment Doses of Flucytosine and Amphotericin B for Invasive Fungal Infections.

    PubMed

    Folk, Alexandra; Cotoraci, Coralia; Balta, Cornel; Suciu, Maria; Herman, Hildegard; Boldura, Oana Maria; Dinescu, Sorina; Paiusan, Lucian; Ardelean, Aurel; Hermenean, Anca

    2016-01-01

    Invasive fungal infection is a well-known cause of morbidity and mortality in immunocompromised patients. In this study we aimed to evaluate the hepatotoxicity induced by combined therapy of flucytosine and amphotericin B, at three different doses administered to mice for 14 days: 50 mg/kg flucytosine and 300 μg/kg amphotericin B; 100 mg/kg flucytosine and 600 μg/kg amphotericin B; 150 mg/kg flucytosine and 900 μg/kg amphotericin B. Liver injuries were evaluated by analysis of optic and electron microscopy samples, changes in TNF-α, IL-6, and NF-κB inflammation markers levels of expression, and evaluation of mRNA profiles. Histological and ultrastructural analysis revealed an increase in parenchymal and portal inflammation in mice and Kupffer cells activation. Combined antifungal treatment stimulated activation of an inflammatory pathway, demonstrated by a significant dose-dependent increase of TNF-α and IL-6 immunoreactivity, together with mRNA upregulation. Also, NF-κB was activated, as suggested by the high levels found in hepatic tissue and upregulation of target genes. Our results suggest that antifungal combined therapy exerts a synergistic inflammatory activation in a dose-dependent manner, through NF-κB pathway, which promotes an inflammatory cascade during inflammation. The use of combined antifungal therapy needs to be dose limiting due to the associated risk of liver injury, especially for those patients with hepatic dysfunction.

  14. Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection

    PubMed Central

    Sainz, Juan; Lupiáñez, Carmen Belén; Segura-Catena, Juana; Vazquez, Lourdes; Ríos, Rafael; Oyonarte, Salvador; Hemminki, Kari; Försti, Asta; Jurado, Manuel

    2012-01-01

    The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1rs3901533 T/T and Dectin-1rs7309123 G/G genotypes and DC-SIGNrs4804800 G, DC-SIGNrs11465384 T, DC-SIGN7248637 A and DC-SIGN7252229 C alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37–22.77; OR = 4.91 95%CI 1.52–15.89; OR = 2.75 95%CI 1.27–5.95; OR = 2.70 95%CI 1.24–5.90; OR = 2.39 95%CI 1.09–5.22 and OR = 2.05 95%CI 1.00–4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1rs3901533_T allele and Dectin-1rs7309123_G/G genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1rs7309123 polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in

  15. Six-Month Multicenter Study on Invasive Infections Due to Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis in Argentina

    PubMed Central

    Lopardo, Horacio A.; Vidal, Patricia; Sparo, Monica; Jeric, Paola; Centron, Daniela; Facklam, Richard R.; Paganini, Hugo; Pagniez, N. Gaston; Lovgren, Marguerite; Beall, Bernard

    2005-01-01

    During a 6-month period, 95 invasive infections due to Streptococcus pyogenes and group C or group G Streptococcus dysgalactiae subsp. equisimilis were recorded from 40 centers of 16 cities in Argentina. We describe here epidemiologic data available for 55 and 19 patients, respectively, associated with invasive infections due to S. pyogenes and S. dysgalactiae subsp. equisimilis. The associated isolates and 58 additional pharyngeal isolates were genotyped and subjected to serologic and/or antibiotic susceptibility testing. Group A streptococcal emm type distribution and strain association with toxic shock appeared to differ somewhat from results found within the United States; however, serologic characterization and sof sequence typing suggested that emm types found in both countries are reflective of shared clonal types. PMID:15695683

  16. Diagnostic strategies for invasive fungal infections in patients with hematologic malignancies and hematopoietic stem cell transplant recipients.

    PubMed

    Norkin, Maxim; Wingard, John R

    2013-08-01

    Invasive fungal infections (IFIs) frequently occur and are associated with high morbidity and mortality in patients with hematologic malignancies (HMs) and hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis of IFI in these patients facilitates prompt institution of therapy and leads to improved clinical outcomes. This article reviews widely used methodologies for diagnosing IFIs in patients with HM and HSCT recipients. Advantages and limitations of radiologic studies; microbiologic and histopathologic techniques; fungal biomarker assays, including those for galactomannan antigen and β-(1-3)-D-glucan; and molecular assays that are available to establish an early diagnosis of clinically relevant invasive fungal infections are discussed. Recommendations are provided regarding effective use of these methodologies in clinical practice.

  17. Effect of oral infection of La Crosse virus on survival and fecundity of native Ochlerotatus triseriatus and invasive Stegomyia albopicta.

    PubMed

    Costanzo, K S; Muturi, E J; Montgomery, A V; Alto, B W

    2014-03-01

    Arboviruses can have benign, deleterious, or beneficial effects on the vector. We tested the hypothesis that oral infection with La Crosse virus (LACV) will have little to no effect on mosquito longevity and fecundity, a prediction of low virulence selected in a system with frequent vertical transmission. We tested the effects of infection in native Ochlerotatus triseriatus Say and invasive Stegomyia albopicta Skuse (Diptera: Culicidae). We artificially fed adult female mosquitoes of each species with either LACV-infected or uninfected bovine blood and determined adult longevity and fecundity. For females fed LACV-infected blood, bodies and legs, respectively, were separately homogenized and assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to determine the LACV infection and dissemination rates. Ochlerotatus triseriatus had a higher infection and dissemination rate than St. albopicta. For both species, female size had no effect on infection status. Infection status also had no effect on longevity or fecundity for both species. We suggest that the high frequency of vertical transmission may have selected for strains of the virus with low virulence in two vectors, in spite of their different evolutionary histories with the virus.

  18. Molecular basis of indole production catalyzed by tryptophanase in the genus Prevotella.

    PubMed

    Sasaki-Imamura, Takako; Yoshida, Yasuo; Suwabe, Kyosuke; Yoshimura, Fuminobu; Kato, Hirohisa

    2011-09-01

    Indole is most commonly known as a diagnostic marker and a malodorous chemorepellent. More recently, it has been recognized that indole also functions as an extracellular signaling molecule that controls bacterial physiology and virulence. The gene (tnaA) for tryptophanase, which produces indole, ammonia, and pyruvate via β-elimination of L-tryptophan, was cloned from Prevotella intermedia ATCC 25611 and recombinant TnaA was purified and enzymatically characterized. Analysis by reverse transcriptase-mediated PCR showed that the gene was not cotranscribed with flanking genes in P. intermedia. The results of gel-filtration chromatography suggested that P. intermedia TnaA forms homodimers, unlike other reported TnaA proteins. Recombinant TnaA exhibited a K(m) of 0.23 ± 0.01 mM and k(cat) of 0.45 ± 0.01 s(-1). Of 22 Prevotella species tested, detectable levels of indole were present in the culture supernatants of six, including P. intermedia. Southern hybridization showed that tnaA-positive signals were present in the genomic DNA from the six indole-producing strains, but not the other 16 strains tested. The indole-producing strains, with the exception of Prevotella micans, formed a phylogenetic cluster based on trees constructed using 16S rRNA gene sequences, which suggested that tnaA in P. micans might have been transferred from other Prevotella species relatively recently.

  19. Development and evaluation of new primers for PCR-based identification of Prevotella intermedia.

    PubMed

    Zhou, Yanbin; Liu, Dali; Wang, Yiwei; Zhu, Cailian; Liang, Jingping; Shu, Rong

    2014-08-01

    The aim of this study was to develop new Prevotella intermedia-specific PCR primers based on the 16S rRNA. The new primer set, Pi-192 and Pi-468, increased the accuracy of PCR-based P. intermedia identification and could be useful in the detection of P. intermedia as well as epidemiological studies on periodontal disease.

  20. Serum posaconazole levels during acute myeloid leukaemia induction therapy: correlations with breakthrough invasive fungal infections.

    PubMed

    Cattaneo, Chiara; Panzali, Annafranca; Passi, Angela; Borlenghi, Erika; Lamorgese, Cinzia; Petullà, Marta; Re, Alessandro; Caimi, Luigi; Rossi, Giuseppe

    2015-06-01

    The usefulness of posaconazole therapeutic drug monitoring (TDM) is still a matter of debate. A correlation between posaconazole serum levels and breakthrough invasive fungal infections (IFI) has not been clearly demonstrated so far. We analysed posaconazole serum levels in patients with acute myeloid leukaemia (AML) during induction therapy and correlated them with the incidence of breakthrough IFI and the need of systemic antifungal therapy. Overall, 77 AML patients receiving posaconazole were evaluated for serum levels; breakthrough IFI were observed in five with at least one posaconazole TDM (6.5%). Median serum level was 534 ng ml(-1) (IQ range: 298.5-750.5 ng ml(-1) ) and did not change significantly over time. Four of the 40 patients with median posaconazole levels <500 ng ml(-1) developed IFI, as compared with only 1 of the 37 patients with median levels ≥500 (10% vs. 2.7%, P = 0.19). Median posaconazole levels on day 7 were 384.5 ng ml(-1) (IQ range: 207-659 ng ml(-1) ) and 560.5 ng ml(-1) (IQ range: 395-756 ng ml(-1) ) in patients requiring or not systemic antifungal treatment respectively (P = 0.067). These results seem to confirm that higher median serum levels of posaconazole correlate with higher prophylactic efficacy against proven/probable IFI and with lesser need of systemic antifungal therapy.

  1. Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

    PubMed Central

    Tüfekçi, Özlem; Yılmaz Bengoa, Şebnem; Demir Yenigürbüz, Fatma; Şimşek, Erdem; Karapınar, Tuba Hilkay; İrken, Gülersu; Ören, Hale

    2015-01-01

    Objective: Rapid and effective treatment of invasive fungal infection (IFI) in patients with leukemia is important for survival. In this study, we aimed to describe variations regarding clinical features, treatment modalities, time of restarting chemotherapy, and outcome in children with IFI and acute leukemia (AL). Materials and Methods: The charts of all pediatric AL patients in our clinic between the years of 2001 and 2013 were retrospectively reviewed. All patients received prophylactic fluconazole during the chemotherapy period. Results: IFI was identified in 25 (14%) of 174 AL patients. Most of them were in the consolidation phase of chemotherapy and the patients had severe neutropenia. The median time between leukemia diagnosis and definition of IFI was 122 days. Twenty-four patients had pulmonary IFI. The most frequent finding on computed tomography was typical parenchymal nodules. The episodes were defined as proven in 4 (16%) patients, probable in 7 (28%) patients, and possible in 14 (56%) patients. The median time for discontinuation of chemotherapy was 27 days. IFI was treated successfully in all patients with voriconazole, amphotericin B, caspofungin, or posaconazole alone or in combination. Chemotherapy was restarted in 50% of the patients safely within 4 weeks and none of those patients experienced reactivation of IFI. All of them were given secondary prophylaxis. The median time for antifungal treatment and for secondary prophylaxis was 26 and 90 days, respectively. None of the patients died due to IFI. Conclusion: Our data show that rapid and effective antifungal therapy with rational treatment modalities may decrease the incidence of death and that restarting chemotherapy within several weeks may be safe in children with AL and IFI. PMID:25913290

  2. Survival following lung resection in immunocompromised patients with pulmonary invasive fungal infection

    PubMed Central

    Wu, Geena X.; Khojabekyan, Marine; Wang, Jami; Tegtmeier, Bernard R.; O'Donnell, Margaret R.; Kim, Jae Y.; Grannis, Frederic W.; Raz, Dan J.

    2016-01-01

    OBJECTIVES Pulmonary invasive fungal infections (IFIs) are associated with high mortality in patients being treated for haematological malignancy. There is limited understanding of the role for surgical lung resection and outcomes in this patient population. METHODS This is a retrospective cohort of 50 immunocompromised patients who underwent lung resection for IFI. Patient charts were reviewed for details on primary malignancy and treatment course, presentation and work-up of IFI, reasons for surgery, type of resection and outcomes including postoperative complications, mortality, disease relapse and survival. Analysis was also performed on two subgroups based on year of surgery from 1990–2000 and 2001–2014. RESULTS The median age was 39 years (range: 5–64 years). Forty-seven patients (94%) had haematological malignancies and 38 (76%) underwent haematopoietic stem cell transplantation (HSCT). Surgical indications included haemoptysis, antifungal therapy failure and need for eradication before HSCT. The most common pathogen was Aspergillus in 34 patients (74%). Wedge resections were performed in 32 patients (64%), lobectomy in 9 (18%), segmentectomy in 2 (4%) and some combination of the 3 in 7 (14%) for locally extensive, multifocal disease. There were 9 (18%) minor and 14 (28%) major postoperative complications. Postoperative mortality at 30 days was 12% (n = 6). Acute respiratory distress syndrome was the most common cause of postoperative death. Overall 5-year survival was 19%. Patients who had surgery in the early period had a median survival of 24 months compared with 5 months for those who had surgery before 2001 (P = 0.046). At the time of death, 15 patients (30%) had probable or proven recurrent IFI. Causes of death were predominantly related to refractory malignancy, fungal lung disease or complications of graft versus host disease (GVHD). Patients who had positive preoperative bronchoscopy cultures had a trend towards worse survival compared with

  3. Enterohemorrhagic Escherichia coli promotes the invasion and tissue damage of enterocytes infected with Candida albicans in vitro

    PubMed Central

    Yang, Weiming; Zhou, Yanjun; Wu, Chunrong; Tang, Jianguo

    2016-01-01

    The principal aim of this study was to investigate the in vitro co-infection of Caco-2 cells with Candida albicans and enterohemorrhage Escherichia coli (EHEC). The ability of both species to colonize or invade the Caco-2 cells was evaluated by indirect immunofluorescence and inverted microscopy. The damage to Caco-2 cells was evaluated by measuring lactate dehydrogenase (LDH) activity. C. albicans virulence gene expression (HWP1, ALS3, PLB1, SAP4, and EFG1) was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Compared to single infections with enterohemorrhage Escherichia coli or C. albicans, a co-infection colonized or invaded Caco-2 cells more quickly, and C. albicans tended to accumulate more easily, accompanied by the upregulation of related genes. In addition, the LDH activity in the co-infected group was higher than in cells infected with C. albicans or with enterohemorrhage Escherichia coli, accompanied by the upregulation of toxicity-related genes. Using Caco-2 cells as an infection model, this study demonstrated that co-infecting in vitro enterocytes with C. albicans and enterohemorrhage Escherichia coli enhanced the invasiveness and tissue damaging effects of C. albicans. PMID:27874093

  4. Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

    PubMed

    Fteita, Dareen; Könönen, Eija; Gürsoy, Mervi; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2015-12-01

    Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis.

  5. Invasive Pneumococcal Disease Among HIV-Infected and HIV-Uninfected Adults in a Large Integrated Healthcare System.

    PubMed

    Marcus, Julia L; Baxter, Roger; Leyden, Wendy A; Muthulingam, Dharushana; Yee, Arnold; Horberg, Michael A; Klein, Daniel B; Towner, William J; Chao, Chun R; Quesenberry, Charles P; Silverberg, Michael J

    2016-10-01

    It is unclear whether HIV-infected individuals remain at higher risk of invasive pneumococcal disease (IPD) compared with HIV-uninfected individuals. We conducted a cohort study of HIV-infected and demographically matched HIV-uninfected adults within Kaiser Permanente Northern California during the period 1996-2011. We used Poisson models to obtain rate ratios (RRs) for incident IPD associated with HIV infection and other risk factors. Among 13,079 HIV-infected and 137,643 HIV-uninfected adults, the IPD rate per 100,000 person-years was 160 (n = 109 events) for HIV-infected and 8 (n = 75 events) for HIV-uninfected subjects, with an adjusted RR of 13.0 [95% confidence interval (CI): 9.1-18.7]. For HIV-infected individuals, IPD incidence per 100,000 person-years decreased by 71% during study follow-up, from 305 in 1996-1999 to 88 in 2010-2011 (p < 0.001), with an adjusted RR of 6.6 (95% CI: 2.7-16.1) compared with HIV-uninfected subjects in 2010-2011. Risk factors for IPD among HIV-infected individuals included black compared with white race/ethnicity, smoking, cancer, and higher HIV RNA levels. The 23-valent pneumococcal polysaccharide vaccination was not associated with a reduced risk of IPD in HIV-infected or HIV-uninfected individuals. Among HIV-infected IPD cases, the most common serotype was 19A (33%), and 59% of serotypes were covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Despite a dramatic decline in IPD incidence for HIV-infected adults since 1996, IPD rates were nearly sevenfold higher compared with HIV-uninfected adults in recent years, even after adjustment for risk factors. Timely antiretroviral therapy initiation, risk reduction strategies, and recent guidelines recommending PCV13 use may further reduce IPD incidence among HIV patients.

  6. Interleukin-12 and interleukin-2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model.

    PubMed

    Zhang, Chang-Ran; Lin, Jian-Cong; Xu, Wen-Ming; Li, Ming; Ye, Hui-Shao; Cui, Wei-Ling; Lin, Qing

    2013-03-01

    Aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. Th1 cytokines could enhance fungicidal activity. The effects from the combination of interleukin-12 (IL-12) and IL-2 are rarely known in invasive pulmonary aspergillosis infection. To assess the cleaning of A. fumigatus infection in the pulmonary tissues by IL-12 and IL-2, interferon-γ (IFN-γ) was detected in the sera using ELISA, quantification of IFN-γ mRNA using real-time RT-PCR and lung Colony-forming unit was assayed by cultivation. Morphology was analysed by histopathological examination. Our results showed that IL-12 and/or IL-2 could enhance the IFN-γ expression in the pulmonary tissue, reduce the colony load in the pulmonary tissue and increase the survival rate of mouse. The combination of IL-12 and IL-2 could assist in increasing the IFN-γ expression in the pulmonary tissue, but neither reduce colony load in the pulmonary tissue nor increase the survival rate of mouse significantly. It was demonstrated that IL-12 and IL-2 were strong immunomodulatory cytokines as a prerequisite for protecting the host from infectious agents.

  7. Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection

    PubMed Central

    Roland, Kenneth L.; Kilbourne, Jacquelyn; Ott, C. Mark; Forsyth, Rebecca J.; Nickerson, Cheryl A.

    2015-01-01

    A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 105 CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580. PMID:26091096

  8. Characterization of the Invasive, Multidrug Resistant Non-typhoidal Salmonella Strain D23580 in a Murine Model of Infection.

    PubMed

    Yang, Jiseon; Barrila, Jennifer; Roland, Kenneth L; Kilbourne, Jacquelyn; Ott, C Mark; Forsyth, Rebecca J; Nickerson, Cheryl A

    2015-06-01

    A distinct pathovar of Salmonella enterica serovar Typhimurium, ST313, has emerged in sub-Saharan Africa as a major cause of fatal bacteremia in young children and HIV-infected adults. D23580, a multidrug resistant clinical isolate of ST313, was previously shown to have undergone genome reduction in a manner that resembles that of the more human-restricted pathogen, Salmonella enterica serovar Typhi. It has since been shown through tissue distribution studies that D23580 is able to establish an invasive infection in chickens. However, it remains unclear whether ST313 can cause lethal disease in a non-human host following a natural course of infection. Herein we report that D23580 causes lethal and invasive disease in a murine model of infection following peroral challenge. The LD50 of D23580 in female BALB/c mice was 4.7 x 10(5) CFU. Tissue distribution studies performed 3 and 5 days post-infection confirmed that D23580 was able to more rapidly colonize the spleen, mesenteric lymph nodes and gall bladder in mice when compared to the well-characterized S. Typhimurium strain SL1344. D23580 exhibited enhanced resistance to acid stress relative to SL1344, which may lend towards increased capability to survive passage through the gastrointestinal tract as well as during its intracellular lifecycle. Interestingly, D23580 also displayed higher swimming motility relative to SL1344, S. Typhi strain Ty2, and the ST313 strain A130. Biochemical tests revealed that D23580 shares many similar metabolic features with SL1344, with several notable differences in the Voges-Proskauer and catalase tests, as well alterations in melibiose, and inositol utilization. These results represent the first full duration infection study using an ST313 strain following the entire natural course of disease progression, and serve as a benchmark for ongoing and future studies into the pathogenesis of D23580.

  9. The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance.

    PubMed

    Rees, J R; Pinner, R W; Hajjeh, R A; Brandt, M E; Reingold, A L

    1998-11-01

    Population-based active laboratory surveillance for invasive mycotic infections was conducted during 1992 and 1993 in three California counties: Alameda, Contra Costa, and San Francisco (population, 2.94 million). The cumulative incidence of invasive mycotic infections was 178.3 per million per year. Invasive mycoses were most commonly caused by Candida (72.8 per million per year), Cryptococcus (65.5), Coccidioides (15.3), Aspergillus (12.4), and Histoplasma (7.1). The clinical significance of other, less common fungi was determined by detailed chart review. The cumulative incidence was determined for zygomycosis (1.7 per million per year), hyalohyphomycosis (1.2), and phaeohyphomycosis (1.0). The most common underlying conditions were human immunodeficiency virus infection (47.4%), nonhematologic malignancy (14.7%), diabetes mellitus (9.9%), and chronic lung disease (9.3%). This represents the first population-based epidemiological assessment of invasive mycoses in the United States.

  10. Epidemiology and identification of potential fungal pathogens causing invasive fungal infections in a tertiary care hospital in northeast Thailand.

    PubMed

    Faksri, Kiatichai; Kaewkes, Wanlop; Chaicumpar, Kunyaluk; Chaimanee, Prajuab; Wongwajana, Suwin

    2014-11-01

    Invasive fungal infections (IFIs) are life threatening and associated with a high mortality rate. Here, we describe the distribution of pathogens, host risk factors, and significance of fungi isolated from patients with IFIs. The study included 861 fungal isolates recovered between 2006 and 2011 from 802 patients at Srinagarind Hospital, Thailand. Based on the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group 2008 criteria, 28.5% (245/861 isolates) of the fungal isolates were considered to be causative agents of IFIs. The most common fungus was Candida albicans (46%, 396/861 isolates). However, the most common yeast causing IFIs was Cryptococcus neoformans (34.7%, 85/245 isolates), while the most common mould was Penicillium marneffei (10.6%, 26/245 isolates). Cryptococcosis was significantly associated with human immunodeficiency virus infections (P < 0.001). Trend analysis revealed that there was no significant increase in IFI cases (P = 0.34) from 2006 to 2011 or from 2007 to 2011 (P = 0.05), but there was a trend toward significant increases in candidiasis (P = 0.04). The fungal isolates were categorized according to the positive predictive value of their recovery in cultures as being true (>95%), moderate (5%-95%), and rare (<5%) pathogens. This classification system could facilitate the prediction of the likelihood of diseases caused by the isolated fungi.

  11. High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain.

    PubMed

    Rodriguez-Dominguez, Mario; Gonzalez-Alba, Jose Maria; Puerta, Teresa; Menendez, Blanca; Sanchez-Diaz, Ana Maria; Canton, Rafael; del Romero, Jorge; Galan, Juan Carlos

    2015-01-01

    The evolution of Chlamydia trachomatis is mainly driven by recombination events. This fact can be fuelled by the coincidence in several European regions of the high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum (LGV) outbreaks. This scenario could modify the local epidemiology and favor the selection of new C. trachomatis variants. Quantifying the prevalence of co-infection could help to predict the potential risk in the selection of new variants with unpredictable results in pathogenesis or transmissibility. In the 2009-2013 period, 287 clinical samples with demonstrated presence of C. trachomatis were selected. They were divided in two groups. The first group was constituted by 137 samples with C. trachomatis of the LGV genotypes, and the second by the remaining 150 samples in which the presence of LGV genotypes was previously excluded. They were analyzed to detect the simultaneous presence of non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections were detected in 10.9% of the cases whereas in the second group the prevalence was 14.6%, which is the highest percentage ever described among European countries. Moreover, bioinformatic analyses suggested the presence among men who have sex with men of a pmpH-recombinant variant, similar to strains described in Seattle in 2002. This variant was the result of genetic exchange between genotypes belonging to LGV and members of G-genotype. Sequencing of other genes, phylogenetically related to pathotype, confirmed that the putative recombinant found in Madrid could have a common origin with the strains described in Seattle. Countries with a high prevalence of co-infections and high migration flows should enhance surveillance programs in at least their vulnerable population.

  12. High Prevalence of Co-Infections by Invasive and Non-Invasive Chlamydia trachomatis Genotypes during the Lymphogranuloma Venereum Outbreak in Spain

    PubMed Central

    Rodriguez-Dominguez, Mario; Gonzalez-Alba, Jose Maria; Puerta, Teresa; Menendez, Blanca; Sanchez-Diaz, Ana Maria; Canton, Rafael; del Romero, Jorge; Galan, Juan Carlos

    2015-01-01

    The evolution of Chlamydia trachomatis is mainly driven by recombination events. This fact can be fuelled by the coincidence in several European regions of the high prevalence of non-invasive urogenital genotypes and lymphogranuloma venereum (LGV) outbreaks. This scenario could modify the local epidemiology and favor the selection of new C. trachomatis variants. Quantifying the prevalence of co-infection could help to predict the potential risk in the selection of new variants with unpredictable results in pathogenesis or transmissibility. In the 2009-2013 period, 287 clinical samples with demonstrated presence of C. trachomatis were selected. They were divided in two groups. The first group was constituted by 137 samples with C. trachomatis of the LGV genotypes, and the second by the remaining 150 samples in which the presence of LGV genotypes was previously excluded. They were analyzed to detect the simultaneous presence of non-LGV genotypes based on pmpH and ompA genes. In the first group, co-infections were detected in 10.9% of the cases whereas in the second group the prevalence was 14.6%, which is the highest percentage ever described among European countries. Moreover, bioinformatic analyses suggested the presence among men who have sex with men of a pmpH-recombinant variant, similar to strains described in Seattle in 2002. This variant was the result of genetic exchange between genotypes belonging to LGV and members of G-genotype. Sequencing of other genes, phylogenetically related to pathotype, confirmed that the putative recombinant found in Madrid could have a common origin with the strains described in Seattle. Countries with a high prevalence of co-infections and high migration flows should enhance surveillance programs in at least their vulnerable population. PMID:25965545

  13. Multiple preinvasive and invasive HPV-related lesions of the anogenital tract in a female patient with HIV infection

    PubMed Central

    Clemente, Nicolò; Alessandrini, Lara; Vaccher, Emanuela; De Paoli, Antonino; Buttignol, Monica; Canzonieri, Vincenzo; Sopracordevole, Francesco

    2017-01-01

    Abstract Rationale: Patients with human immunodeficiency virus (HIV) infection have been shown to be at increased risk for high-risk human papillomavirus (HR-HPV) infection of the anogenital tract. Furthermore, in the last decades, the introduction of highly active antiretroviral therapy (HAART) has increased the longevity of these patients who now live long enough to develop HPV-related cancers; hence, the impact of HPV infection on HIV-positive patients is of increasing concern. Patient concerns: We reported the case of an HIV-positive female patient on HAART with a good virological and immunological response and with a long history of HPV-related intraepithelial and invasive lesions of the anogenital tract. Diagnoses: From 1996 to 2016, this patient was diagnosed with a high grade cervical intraepithelial neoplasia; a HR-HPV positive inguinal lymph node metastasis from clinically undetectable primary squamous cell carcinoma; a HPV-related vulvar high-grade squamous intraepithelial lesion and an invasive squamous cell carcinoma of the anus. Interventions: All the intraepithelial and invasive lesions detected were properly treated, and subsequent follow up visits with gynecologic examination, anoscopy, pap smear and anal cytology were performed. Outcomes: After a recurrence of the anal cancer and a subsequent salvage surgery with abdominoperineal resection, at the last available follow up visit no sign of disease recurrence was found. Lessons: This case stresses the importance of an accurate multidisciplinary follow-up in HIV-positive patients, including not only the routine medical, immunological, and virological evaluation, but also a periodical complete examination of the anogenital tract with cervicovaginal and anal cytology, colposcopy, high resolution anoscopy, and vulvar examination. PMID:28121939

  14. Non-contiguous finished genome sequence of the opportunistic oral pathogen Prevotella multisaccharivorax type strain (PPPA20T)

    SciTech Connect

    Pati, Amrita; Gronow, Sabine; Lu, Megan; Lapidus, Alla L.; Nolan, Matt; Lucas, Susan; Hammon, Nancy; Deshpande, Shweta; Cheng, Jan-Fang; Tapia, Roxanne; Han, Cliff; Goodwin, Lynne A.; Pitluck, Sam; Liolios, Konstantinos; Pagani, Ioanna; Mavromatis, K; Mikhailova, Natalia; Huntemann, Marcel; Chen, Amy; Palaniappan, Krishna; Land, Miriam L; Hauser, Loren John; Detter, J. Chris; Brambilla, Evelyne-Marie; Rohde, Manfred; Goker, Markus; Woyke, Tanja; Bristow, James; Eisen, Jonathan; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter; Ivanova, N

    2011-01-01

    Prevotella multisaccharivorax Sakamoto et al. 2005 is a species of the large genus Prevotella, which belongs to the family Prevotellaceae. The species is of medical interest because its members are able to cause diseases in the human oral cavity such as periodontitis, root caries and others. Although 77 Prevotella genomes have already been sequenced or are targeted for sequencing, this is only the second completed genome sequence of a type strain of a species within the genus Prevotella to be published. The 3,388,644 bp long genome is assembled in three non-contiguous contigs, harbors 2,876 protein-coding and 75 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

  15. The use of infrared thermography as a non-invasive method for fever detection in sheep infected with bluetongue virus.

    PubMed

    Pérez de Diego, Ana C; Sánchez-Cordón, Pedro J; Pedrera, Miriam; Martínez-López, Beatriz; Gómez-Villamandos, José C; Sánchez-Vizcaíno, José M

    2013-10-01

    Fever, which is closely linked to viraemia, is considered to be both the main and the earliest clinical sign in sheep infected with bluetongue virus (BTV). The aim of this study was to evaluate the potential use of infrared thermography (IRT) for early detection of fever in sheep experimentally infected with bluetongue virus serotype 1 (BTV-1) and serotype 8 (BTV-8). This would reduce animal stress during experimental assays and assist in the development of a screening method for the identification of fever in animals suspected of being infected with BTV. Rectal and infrared eye temperatures were collected before and after BTV inoculation. The two temperature measures were positively correlated (r=0.504, P<0.05). The highest correlation between rectal and infrared temperatures was observed when temperatures were above physiological levels. IRT discriminated between febrile and non-febrile sheep with a sensitivity of 85% and specificity of 97%. The results showed that eye temperature measured using IRT was a useful non-invasive method for the assessment of fever in sheep infected with BTV under experimental conditions. Further research is required to evaluate the use of IRT under field conditions to identify potentially infected animals in bluetongue surveillance programmes.

  16. Epidemiology of invasive fungal infections in patients with acquired immunodeficiency syndrome at a reference hospital for infectious diseases in Brazil.

    PubMed

    de Oliveira, Renata Buccheri; Atobe, Jane Harumi; Souza, Simone Aparecida; de Castro Lima Santos, Daniel Wagner

    2014-08-01

    Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as Candida spp. and Aspergillus spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20-25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by Candida spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.

  17. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

    PubMed Central

    Scher, Jose U; Sczesnak, Andrew; Longman, Randy S; Segata, Nicola; Ubeda, Carles; Bielski, Craig; Rostron, Tim; Cerundolo, Vincenzo; Pamer, Eric G; Abramson, Steven B; Huttenhower, Curtis; Littman, Dan R

    2013-01-01

    Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.001 PMID:24192039

  18. [Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) guidelines for the diagnosis of invasive fungal infections. 2010 update].

    PubMed

    Ayats, Josefina; Martín-Mazuelos, Estrella; Pemán, Javier; Quindós, Guillermo; Sánchez, Fernando; García-Rodríguez, Julio; Guarro, Josep; Guinea, Jesús; Linares, María J; Pontón, José; Rodríguez-Tudela, Juan L; Cuenca-Estrella, Manuel

    2011-01-01

    These guidelines are an update of recommendations for the diagnosis of invasive fungal infections by the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) published in 2004 (Enferm Infecc Microbiol Clin. 2004, 22:32-9). In this updated version of the guidelines, a comprehensive review of the most recent diagnostic innovations and levels of evidence to recommend those diagnostic procedures are included. We first analyse conventional diagnostic methods, microscopic examination and culture, underlining their limitations which have led to the development of alternative methods, such as fungal antigen and DNA quantification. Those alternative methods of diagnosis are analysed by fungal infection. We also briefly review the methods for molecular identification of fungal species and recommendations for carrying out susceptibility tests for antifungal drugs, including reference procedures, commercial techniques and their indications.

  19. [Serotype distribution of Streptococcus pneumoniae isolated from invasive infections at the Hospital de Niños of Santa Fe].

    PubMed

    Mayoral, C; Baroni, M R; Giani, R; Virgolini, S; Zurbriggen, L; Regueira, M

    2008-01-01

    The serotype distribution of Streptococcus pneumoniae varies through time. The introduction of pneumococcal conjugate vaccines showed a decreased prevalence of pneumococcal invasive isolates belonging to serotype 14 and an increase of serotypes not therein included. In 1993, the Hospital de Niños of Santa Fe began surveillance of the serotype distribution of invasive S. pneumoniae disease. In the period 2003-2005, 76 isolates were analysed by studying the correlation between serotype and pathology, age and MIC of penicillin. Serotype 14 was the most frequent followed by serotypes 1, 6B, 18C, 7F, 19 F and 5. Serotype 14 showed a statistically significant correlation with MICs of penicillin ranging from 0,5 to 2 mg/l. Although this serotype was more frequently observed in pneumonia than in meningitis, there was not a significant association with any particular pathology. Serotypes 14 and 1, were prevalent among children under and over 2 years old, respectively. Most of these isolates with MICs of penicillin = 2 mg/l, were from patients with pneumonia and not with meningitis. The serotype distribution was similar to that during the period 1993-99, with the exception of serotypes 18C, 4, 12F and 22F which had never been found before. The emergence of these serotypes makes it essential to continue surveillance to determine which conjugated vaccine formulation would be suitable to prevent the most frequent pneumococcal invasive infections.

  20. Evaluation of the (1,3)-β-D-glucan assay for the diagnosis of neonatal invasive yeast infections.

    PubMed

    Cornu, Marjorie; Goudjil, Sabrina; Kongolo, Guy; Leke, André; Poulain, Daniel; Chouaki, Taieb; Sendid, Boualem

    2017-03-24

    Most newborns in the neonatal intensive care unit (NICU) are premature and at risk of invasive fungal infections (IFIs). Invasive yeast infections (IYIs) are the most common fungal infections in this population. These infections are difficult to diagnose because symptoms are nonspecific, and the sensitivity of blood cultures is low. The serum (1,3)-β-D-glucan (BDG) assay provides a reliable marker for the diagnosis of IFIs in adults with haematological malignancies. We assessed the diagnostic performance of this test in neonatal IYIs and its contribution to the monitoring of antifungal treatment. A retrospective study was performed in the NICU of the French University Hospital of Amiens from February 2012 to February 2014. Forty-seven neonates (33 males, 14 females) with a median gestational age of 30 weeks (IQR: 27-31) and median birth weight of 1200 g (IQR: 968-1700) were included and divided into three groups: 21 control neonates (CTRL), 20 neonates with probable IYI (PB), and six with proven IYI (PV). Median BDG levels were significantly higher in the global IYI group (PB + PV): 149 pg/ml (IQR: 85-364) vs. CTRL group: 39 pg/ml (IQR: 20-94) (P < .001). The optimal cut-off was 106 pg/ml (sensitivity 61.5%; specificity 81%). BDG levels decreased with antifungal treatment. BDG was detectable in cerebrospinal fluid, but the interest of this for diagnostic purposes remains unclear. Our results suggest that the BDG assay may be useful for the early identification of IYIs in neonates and for monitoring antifungal therapy efficacy.

  1. Association between tea ingestion and invasive Bacillus cereus infection among children with cancer.

    PubMed

    El Saleeby, C M; Howard, S C; Hayden, R T; McCullers, J A

    2004-11-15

    Bacillus cereus is an emerging pathogen that causes invasive disease in immunocompromised hosts. A case-control study, prompted by a clinical case, demonstrated an association between dietary tea ingestion and B. cereus bacteremia. Policies designed to interrupt transmission of this pathogen to susceptible patients should be considered.

  2. Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: a 20-year autopsy study.

    PubMed

    Lewis, Russell E; Cahyame-Zuniga, Lizebeth; Leventakos, Konstantinos; Chamilos, Georgios; Ben-Ami, Ronen; Tamboli, Pheroze; Tarrand, Jeffrey; Bodey, Gerald P; Luna, Mario; Kontoyiannis, Dimitrios P

    2013-11-01

    Autopsy studies remain an essential tool for understanding the patterns of fungal disease not detected ante mortem with current diagnostic approaches. We collected data concerning the microbiological trends, patient clinical characteristics and sites of involvement for invasive fungal infections (IFIs) identified at autopsy in a single large cancer treatment centre over a 20-year period (1989-2008). The autopsy rate and IFI prevalence both declined significantly during the study period. The prevalence of Aspergillus spp. decreased significantly from the first 15 years of the study (from 0.12 to 0.14 cases per 100 autopsies to 0.07 in 2004-2008; P = 0.04), with only Mucorales accounting for a greater proportion of IFIs over the duration of the study period (0.06 to 0.2 cases per 100 autopsies, P = 0.04). After 2003, moulds accounted for the majority of infections identified at autopsy in the spleen, kidney, heart and gastrointestinal tract. Despite a trend of decreasing prevalence from 1989 to 2004, invasive candidiasis increased in prevalence during later periods 2004-2008 (0.02-0.05 per 100 autopsies) with decreasing kidney, heart and spleen involvement. Despite a declining autopsy rate, these data suggest a decreasing prevalence overall of IFIs with changing patterns of dissemination in patients with haematological malignancies.

  3. Prevotella jejuni sp. nov., isolated from the small intestine of a child with coeliac disease.

    PubMed

    Hedberg, Maria E; Israelsson, Anne; Moore, Edward R B; Svensson-Stadler, Liselott; Wai, Sun Nyunt; Pietz, Grzegorz; Sandström, Olof; Hernell, Olle; Hammarström, Marie-Louise; Hammarström, Sten

    2013-11-01

    Five obligately anaerobic, Gram-stain-negative, saccharolytic and proteolytic, non-spore-forming bacilli (strains CD3 : 27, CD3 : 28(T), CD3 : 33, CD3 : 32 and CD3 : 34) are described. All five strains were isolated from the small intestine of a female child with coeliac disease. Cells of the five strains were short rods or coccoid cells with longer filamentous forms seen sporadically. The organisms produced acetic acid and succinic acid as major metabolic end products. Phylogenetic analysis based on comparative 16S rRNA gene sequence analysis revealed close relationships between CD3 : 27, CD3 : 28(T) and CD3 : 33, between CD3 : 32 and Prevotella histicola CCUG 55407(T), and between CD3 : 34 and Prevotella melaninogenica CCUG 4944B(T). Strains CD3 : 27, CD3 : 28(T) and CD3 : 33 were clearly different from all recognized species within the genus Prevotella and related most closely to but distinct from P. melaninogenica. Based on 16S rRNA, RNA polymerase β-subunit (rpoB) and 60 kDa chaperonin protein subunit (cpn60) gene sequencing, and phenotypic, chemical and biochemical properties, strains CD3 : 27, CD3 : 28(T) and CD3 : 33 are considered to represent a novel species within the genus Prevotella, for which the name Prevotella jejuni sp. nov. is proposed. Strain CD3 : 28(T) ( = CCUG 60371(T) = DSM 26989(T)) is the type strain of the proposed novel species. All five strains were able to form homologous aggregates, in which tube-like structures were connecting individual bacteria cells. The five strains were able to bind to human intestinal carcinoma cell lines at 37 °C.

  4. Liposomal amphotericin B (AmBisome) efficacy in confirmed invasive aspergillosis and other filamentous fungal infections in immunocompromised hosts: a pooled analysis.

    PubMed

    Cordonnier, C; Bresnik, M; Ebrahimi, R

    2007-05-01

    A pooled efficacy analysis applying current diagnostic standards for case selection was performed on previously published trials of liposomal amphotericin B for invasive filamentous fungal infections (IFFI). Favourable responses were observed in 51% of microbiologically confirmed cases of proven or probable IFFI. Despite the limitations inherent in a retrospective analysis of pooled studies, the response rates observed in this analysis were consistent with previous reports for antifungal therapy with amphotericin B deoxycholate or voriconazole in the treatment of invasive aspergillosis.

  5. Infection patterns in invasive and native snail hosts exposed to a parasite associated with waterfowl mortality in the upper Mississippi River, USA.

    PubMed

    Sandland, Gregory J; Gillis, Rick; Haro, Roger J; Peirce, James P

    2014-01-01

    Bithynia tentaculata is an aquatic invasive snail first detected in the upper Mississippi River (UMR) in 2002. The snail harbors a number of parasitic trematode species, including Sphaeridiotrema pseudoglobulus, that have been implicated in waterfowl mortality in the region. We assessed the capacity of S. pseudoglobulus cercariae to infect B. tentaculata and native snails found in the UMR. Four snail species (one invasive and three native) were individually exposed to S. pseudoglobulus larvae and all were successfully infected. A subsequent experiment examining infection patterns in invasive and native hosts exposed singly or in mixed treatments revealed no difference in parasite establishment among snail species. Our results add to our understanding of S. pseudoglobulus transmission and provide insight into processes underlying waterfowl disease in the UMR.

  6. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

    PubMed

    Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

    2016-04-19

    Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.

  7. Reassessment of the Role of Rapid Antigen Detection Tests in Diagnosis of Invasive Group A Streptococcal Infections

    PubMed Central

    Gazzano, Vincent; Berger, Anne; Benito, Yvonne; Freydiere, Anne-Marie; Tristan, Anne; Boisset, Sandrine; Carricajo, Anne; Poyart, Claire; Vandenesch, François

    2016-01-01

    Rapid antigen detection tests (RADTs) for group A streptococci (GAS) are widely used for diagnosing acute pharyngitis, which has led to a considerable reduction in antibiotic prescriptions over the past decade. Beyond this intended use, their reassessment on invasive samples may be relevant in the management of life-threatening GAS infections. To this end, we evaluated the performances of three RADTs, culture, GAS PCR, and 16S rRNA gene PCR assays, and compared them with a composite gold standard (GAS-PCR assay and/or culture) for the diagnosis of severe GAS infection. A total of 192 specimens from deep-tissue (mostly normally sterile) sites enriched for 75 GAS-positive samples were enrolled in the study. The three evaluated RADTs showed sensitivities ranging from 88.0% to 94.7% versus 98.7% for GAS PCR, 84% for 16S rRNA gene PCR, and 77.3% for culture. The sensitivities of the ImmunoCard STAT! Strep A test (Meridian Bioscience) and the NADAL Strep A strip (Nal Von Minden) were similar to that of GAS PCR (P = 0.25 and 0.03, respectively) and higher than that of culture (P = 0.001 and 0.006, respectively), whereas the SD Bioline Strep A test strip (Standard Diagnostics) showed a performance similar to that of culture (P = 0.02). The three RADTs detected 10 distinct emm types, including a predominance of emm 1 (33.3%), emm 89 (10.6%), and emm 12 (7.6%). No false-positive results were observed, leading to a specificity of 100% for all the evaluated RADTs. The GAS RADTs turned out to be sensitive, specific, and easy-to-use tools that may aid in the management of invasive GAS infections in 24/7 point-of-care laboratories by enabling early diagnosis and focused therapy. PMID:26818671

  8. Cluster of invasive Neisseria meningitidis infections on a cruise ship, Italy, October 2012.

    PubMed

    Stefanelli, P; Fazio, C; Neri, A; Isola, P; Sani, S; Marelli, P; Martinelli, C; Mastrantonio, P; Pompa, M G

    2012-12-13

    We describe a cluster of four cases of invasive meningococcal disease that occurred on a cruise ship sailing along the Italian coast in October 2012. All four cases were hospitalised with severe illness and one of them died. This report illustrates the importance of rapid implementation of emergency control measures such as administration of prophylaxis to all crew members and passengers to prevent the spread of the disease in such a close environment.

  9. Distribution of emm genotypes among group A streptococcus isolates from patients with severe invasive streptococcal infections in Japan, 2001-2005.

    PubMed

    Ikebe, T; Hirasawa, K; Suzuki, R; Ohya, H; Isobe, J; Tanaka, D; Katsukawa, C; Kawahara, R; Tomita, M; Ogata, K; Endoh, M; Okuno, R; Tada, Y; Okabe, N; Watanabe, H

    2007-10-01

    We surveyed emm genotypes of group A streptococcus (GAS) isolates from patients with severe invasive streptococcal infections during 2001-2005 and compared their prevalence with that of the preceding 5 years. Genotype emm1 remained dominant throughout 2001 to 2005, but the frequency rate of this type decreased compared with the earlier period. Various other emm types have appeared in recent years indicating alterations in the prevalent strains causing severe invasive streptococcal infections. The cover of the new 26-valent GAS vaccine fell from 93.5% for genotypes of isolates from 1996-2000 to 81.8% in 2001-2005.

  10. In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model.

    PubMed

    Hegde, Shivanand; Hegde, Shrilakshmi; Spergser, Joachim; Brunthaler, René; Rosengarten, Renate; Chopra-Dewasthaly, Rohini

    2014-11-01

    Generally regarded as extracellular pathogens, molecular mechanisms of mycoplasma persistence, chronicity and disease spread are largely unknown. Mycoplasma agalactiae, an economically important pathogen of small ruminants, causes chronic infections that are difficult to eradicate. Animals continue to shed the agent for several months and even years after the initial infection, in spite of long antibiotic treatment. However, little is known about the strategies that M. agalactiae employs to survive and spread within an immunocompetent host to cause chronic disease. Here, we demonstrate for the first time its ability to invade cultured human (HeLa) and ruminant (BEND and BLF) host cells. Presence of intracellular mycoplasmas is clearly substantiated using differential immunofluorescence technique and quantitative gentamicin invasion assays. Internalized M. agalactiae could survive and exit the cells in a viable state to repopulate the extracellular environment after complete removal of extracellular bacteria with gentamicin. Furthermore, an experimental sheep intramammary infection was carried out to evaluate its systemic spread to organs and host niches distant from the site of initial infection. Positive results obtained via PCR, culture and immunohistochemistry, especially the latter depicting the presence of M. agalactiae in the cytoplasm of mammary duct epithelium and macrophages, clearly provide the first formal proof of M. agalactiae's capability to translocate across the mammary epithelium and systemically disseminate to distant inner organs. Altogether, the findings of these in vitro and in vivo studies indicate that M. agalactiae is capable of entering host cells and this might be the strategy that it employs at a population level to ward off the host immune response and antibiotic action, and to disseminate to new and safer niches to later egress and once again proliferate upon the return of favorable conditions to cause persistent chronic infections.

  11. A novel ENU-induced ankyrin-1 mutation impairs parasite invasion and increases erythrocyte clearance during malaria infection in mice

    PubMed Central

    Huang, Hong Ming; Bauer, Denis C.; Lelliott, Patrick M.; Greth, Andreas; McMorran, Brendan J.; Foote, Simon J.; Burgio, Gaetan

    2016-01-01

    Genetic defects in various red blood cell (RBC) cytoskeletal proteins have been long associated with changes in susceptibility towards malaria infection. In particular, while ankyrin (Ank-1) mutations account for approximately 50% of hereditary spherocytosis (HS) cases, an association with malaria is not well-established, and conflicting evidence has been reported. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced ankyrin mutation MRI61689 that gives rise to two different ankyrin transcripts: one with an introduced splice acceptor site resulting a frameshift, the other with a skipped exon. Ank-1(MRI61689/+) mice exhibit an HS-like phenotype including reduction in mean corpuscular volume (MCV), increased osmotic fragility and reduced RBC deformability. They were also found to be resistant to rodent malaria Plasmodium chabaudi infection. Parasites in Ank-1(MRI61689/+) erythrocytes grew normally, but red cells showed resistance to merozoite invasion. Uninfected Ank-1(MRI61689/+) erythrocytes were also more likely to be cleared from circulation during infection; the “bystander effect”. This increased clearance is a novel resistance mechanism which was not observed in previous ankyrin mouse models. We propose that this bystander effect is due to reduced deformability of Ank-1(MRI61689/+) erythrocytes. This paper highlights the complex roles ankyrin plays in mediating malaria resistance. PMID:27848995

  12. Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

    PubMed

    Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2014-06-01

    Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis.

  13. Potential role of aerosolized amphotericin B formulations in the prevention and adjunctive treatment of invasive fungal infections.

    PubMed

    Drew, Richard

    2006-06-01

    The incidence of invasive fungal infections (IFIs) continues to increase, largely due to the steady rise in the number of at-risk patients and the increased use of aggressive immunosuppressant agents. Many available treatments are often limited by concerns about efficacy, safety, drug interactions, and/or cost. Owing to the poor treatment outcomes of immunosuppressed patients with IFIs, new preventative and treatment strategies are being investigated. Among these are the aerosolized formulations of amphotericin B. Published experience with the use of aerosolized amphotericin B deoxycholate (AmBd) in the prevention of IFIs has raised concerns regarding challenges in drug administration and tolerability. However, evolving data regarding administration of lipid-based formulations of amphotericin B indicate potential advantages over AmBd in the prevention and adjunctive treatment of IFIs.

  14. Salmonella infection in green anoles (Anolis carolinensis), an invasive alien species on Chichi Island of the Ogasawara archipelago in Japan.

    PubMed

    Sumiyama, Daisuke; Izumiya, Hidemasa; Kanazawa, Tomoko; Murata, Koichi

    2014-03-01

    We investigated the presence of Salmonella in the green anole (Anolis carolinensis), an invasive alien species on Chichi Island, Japan. Samples were also collected from feral goats and public toilets on the island to examine infectious routes. Salmonellae were isolated from 27.1% of 199 samples; 32.6% of 141 cloacal samples from anoles, 62.5% of 8 intestinal samples from anole carcasses, 16.7% of 12 fecal samples from goats and 2.6% of 38 toilet bowl swabs. The serotype of most isolates was Salmonella Oranienburg (94.4% of 54). Although we did not confirm the infection pathways, our results indicated that green anoles are a risk factor as a source of Salmonella for public health. It is important to consider endemic pathogens that may be amplified by alien species within their introduced areas.

  15. THE UTILITY OF BRONCHOALVEOLAR LAVAGE BETA-D-GLUCAN TESTING FOR THE DIAGNOSIS OF INVASIVE FUNGAL INFECTIONS

    PubMed Central

    Rose, Stacey R.; Vallabhajosyula, Saraschandra; Velez, Miguel G.; Fedorko, Daniel P.; VanRaden, Mark J.; Gea-Banacloche, Juan C.; Lionakis, Michail S.

    2014-01-01

    SUMMARY Objectives To investigate the utility of beta-D-glucan (BDG) testing in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive fungal infection (IFI), as compared to BAL galactomannan (GM). Methods We retrospectively reviewed medical records of 132 consecutive patients at the National Institutes of Health (NIH) in whom BAL BDG testing was performed for diagnosis of pneumonia. Using the European Organization for Research and Treatment of Cancer/Mycoses Study Group guidelines, we determined which patients had proven or probable IFI, and assessed the diagnostic performance of BAL BDG testing, relative to BAL GM. We also determined the reproducibility of the BDG assay in BAL via repeat testing of patient samples. Results Ten patients had Pneumocystis pneumonia, and 34 patients had proven/probable IFI, including 14 with invasive aspergillosis (IA). BAL BDG was 100% sensitive for Pneumocystis. Although BAL BDG had similar sensitivity to BAL GM for the diagnosis of IA and IFI, it exhibited inferior specificity. Repeat testing demonstrated poor reproducibility of the BDG assay in BAL but not in serum. Conclusions BDG testing exhibits poor specificity and reproducibility in BAL. Identification of the BAL-specific factors that may interfere with the performance of the assay could improve the clinical usefulness of BAL BDG testing. PMID:24797077

  16. Non-invasive Presymptomatic Detection of Cercospora beticola Infection and Identification of Early Metabolic Responses in Sugar Beet

    PubMed Central

    Arens, Nadja; Backhaus, Andreas; Döll, Stefanie; Fischer, Sandra; Seiffert, Udo; Mock, Hans-Peter

    2016-01-01

    Cercospora beticola is an economically significant fungal pathogen of sugar beet, and is the causative pathogen of Cercospora leaf spot. Selected host genotypes with contrasting degree of susceptibility to the disease have been exploited to characterize the patterns of metabolite responses to fungal infection, and to devise a pre-symptomatic, non-invasive method of detecting the presence of the pathogen. Sugar beet genotypes were analyzed for metabolite profiles and hyperspectral signatures. Correlation of data matrices from both approaches facilitated identification of candidates for metabolic markers. Hyperspectral imaging was highly predictive with a classification accuracy of 98.5–99.9% in detecting C. beticola. Metabolite analysis revealed metabolites altered by the host as part of a successful defense response: these were L-DOPA, 12-hydroxyjasmonic acid 12-O-β-D-glucoside, pantothenic acid, and 5-O-feruloylquinic acid. The accumulation of glucosylvitexin in the resistant cultivar suggests it acts as a constitutively produced protectant. The study establishes a proof-of-concept for an unbiased, presymptomatic and non-invasive detection system for the presence of C. beticola. The test needs to be validated with a larger set of genotypes, to be scalable to the level of a crop improvement program, aiming to speed up the selection for resistant cultivars of sugar beet. Untargeted metabolic profiling is a valuable tool to identify metabolites which correlate with hyperspectral data. PMID:27713750

  17. Invasive group B streptococcal infections in Finland: a population-based study.

    PubMed

    Lyytikäinen, Outi; Nuorti, J Pekka; Halmesmäki, Erja; Carlson, Petteri; Uotila, Jukka; Vuento, Risto; Ranta, Tapio; Sarkkinen, Hannu; Ammälä, Martti; Kostiala, Anja; Järvenpää, Anna-Liisa

    2003-04-01

    We analyzed surveillance data on group B streptococcus (GBS) infection in Finland from 1995 to 2000 and reviewed neonatal cases of early-onset GBS infection in selected hospitals in 1999 to 2000. From 1995 to 2000, 853 cases were reported (annual incidence 2.2-3.0/100,000 population). We found 32-38 neonatal cases of early-onset GBS disease per year (annual incidence 0.6-0.7/1,000 live births). In five hospitals, 35% of 26 neonatal cases of early-onset GBS infection had at least one risk factor: prolonged rupture of membranes, preterm delivery, or intrapartum fever. Five of eight mothers screened for GBS were colonized. In one case, disease developed despite intrapartum chemoprophylaxis. Although the incidence of early-onset GBS disease in Finland is relatively low, some geographic variation exists, and current prevention practices are suboptimal. Establishing national guidelines to prevent perinatal GBS is likely to reduce the incidence of the disease.

  18. Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain.

    PubMed

    Strobel, M; Pförtner, H; Tuchscherr, L; Völker, U; Schmidt, F; Kramko, N; Schnittler, H-J; Fraunholz, M J; Löffler, B; Peters, G; Niemann, S

    2016-09-01

    Host cell invasion is a major feature of Staphylococcus aureus and contributes to infection development. The intracellular metabolically active bacteria can induce host cell activation and death but they can also persist for long time periods. In this study a comparative analysis was performed of different well-characterized S. aureus strains in their interaction with a variety of host cell types. Staphylococcus aureus (strains 6850, USA300, LS1, SH1000, Cowan1) invasion was compared in different human cell types (epithelial and endothelial cells, keratinocytes, fibroblasts, osteoblasts). The number of intracellular bacteria was determined, cell inflammation was investigated, as well as cell death and phagosomal escape of bacteria. To explain strain-dependent differences in the secretome, a proteomic approach was used. Barrier cells took up high amounts of bacteria and were killed by aggressive strains. These strains expressed high levels of toxins, and possessed the ability to escape from phagolysosomes. Osteoblasts and keratinocytes ingested less bacteria, and were not killed, even though the primary osteoblasts were strongly activated by S. aureus. In all cell types S. aureus was able to persist. Strong differences in uptake, cytotoxicity, and inflammatory response were observed between primary cells and their corresponding cell lines, demonstrating that cell lines reflect only partially the functions and physiology of primary cells. This study provides a contribution for a better understanding of the pathomechanisms of S. aureus infections. The proteomic data provide important basic knowledge on strains commonly used in the analysis of S. aureus-host cell interaction.

  19. Colonization and organ invasion in chicks experimentally infected with Dermanyssus gallinae contaminated by Salmonella Enteritidis.

    PubMed

    Moro, Claire Valiente; Fravalo, Philippe; Amelot, Michel; Chauve, Claude; Zenner, Lionel; Salvat, Gilles

    2007-08-01

    The poultry red mite (Dermanyssus gallinae) is the most important and common ectoparasite of laying hens in Europe. This haematophagous mite has been experimentally demonstrated to be a vector of Salmonella Enteritidis by acquiring bacteria through the blood meal or cuticular contact. We have evaluated another route of infection by orally inoculating chicks with mites previously infected by S. Enteritidis. Two methods of infecting the mites were tested: mites contaminated by cuticular contact or during the blood meal. After the washing of mites with paraformaldehyde, groups of 10 Salmonella-contaminated mites were inoculated individually into 1-day-old chicks. The titre of the inoculum suspension was evaluated by crushing mites and followed by bacteriological counting. It was 3x10(4) colony-forming units/chick and 2.7x10(6) colony-forming units/chick, respectively, for cuticular contact and orally mediated contamination of mites. Each bird was found to be positive 12 days post-inoculation. Salmonella colonized the intestinal tracts and invaded the livers and spleens. The caecal content concentration reached a mean level of S. Enteritidis of 8.5x10(4) most probable number (MPN) Salmonella/g. This experiment demonstrated the ability of mites to orally infect 1-day-old chicks with subsequent colonization and multiplication of Salmonella. Consequently, mites infected by S. Enteritidis constitute potential reservoir hosts of this bacterium, allowing it to persist in the poultry house as a source of infection for newly introduced animals. If contaminated mites are found in poultry facilities, effective red mite control should be performed before new batches are introduced into the facility.

  20. Clinical and microbiological features of invasive nontyphoidal Salmonella associated with HIV-infected patients, Gauteng Province, South Africa

    PubMed Central

    Keddy, Karen H.; Musekiwa, Alfred; Sooka, Arvinda; Karstaedt, Alan; Nana, Trusha; Seetharam, Sharona; Nchabaleng, Maphoshane; Lekalakala, Ruth; Angulo, Frederick J.; Klugman, Keith P.

    2017-01-01

    Abstract The aim of this study was to define factors associated with HIV-infected versus uninfected patients with invasive nontyphoidal Salmonella (iNTS) and factors associated with mortality, which are inadequately described in Africa. Laboratory-based surveillance for iNTS was undertaken. At selected sentinel sites, clinical data (age, sex, HIV status, severity of illness, and outcome) were collected. Surveillance was conducted in Gauteng, South Africa, from 2003 to 2013. Clinical and microbiological differences between HIV-infected and uninfected patients were defined and risk factors for mortality established. Of 4886 iNTS infections in Gauteng from 2003 to 2013, 3106 (63.5%) were diagnosed at sentinel sites. Among persons with iNTS infections, more HIV-infected persons were aged ≥5 years (χ2 = 417.6; P < 0.001) and more HIV-infected children were malnourished (χ2 = 5.8; P = 0.02). Although 760 (30.6%) patients died, mortality decreased between 2003 [97/263 (36.9%)] and 2013 [926/120 (21.7%)]. On univariate analysis, mortality was associated with patients aged 25 to 49 years [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.7–2.7; P < 0.001 and ≥50 years (OR = 3.0; 95% CI = 2.2–4.1; P < 0.001) compared with children < 5 years, HIV-infected patients (OR = 2.4; 95% CI = 1.7–3.4; P < 0.001), and severe illness (OR = 5.4; 95% CI = 3.6–8.1; P < 0.001). On multivariate analysis, mortality was associated with patients aged ≥50 years [adjusted OR (AOR) = 3.6, 95% CI = 2.1–6.1, P < 0.001] and severe illness (AOR = 6.3; 95% CI = 3.8–10.5; P < 0.001). Mortality due to iNTS in Gauteng remains high primarily due to disease severity. Interventions must be aimed at predisposing conditions, including HIV, other immune-suppressive conditions, and malignancy. PMID:28353576

  1. Invasive Squamous Carcinoma and Adenocarcinoma of an Unreconstructed Exstrophic Bladder with HPV Infection

    PubMed Central

    Altan, Mesut; Çıtamak, Burak; Haberal, Hakan Bahadır; Söğütdelen, Emrullah; Bozaci, Ali Cansu; Baydar, Dilek Ertoy; Doğan, Hasan Serkan; Tekgül, Serdar

    2016-01-01

    Bladder exstrophy is a complex abnormality and is traditionally treated within the early years of life. It is associated with an increased risk of bladder cancer, with 95% of the arising tumors being adenocarcinomas and 3 to 5% being squamous cell carcinomas. HPV infections are also associated with an increased risk of bladder cancer. This case represents a patient with bladder exstrophy that gave rise to coinciding squamous cell carcinoma and adenocarcinoma. Final pathology results showed an infection with HPV. We presented the management of the case and discussed the diagnosis and treatment methods for this patient. PMID:27390585

  2. Systems biology analysis of Brucella infected Peyer's patch reveals rapid invasion with modest transient perturbations of the host transcriptome.

    PubMed

    Rossetti, Carlos A; Drake, Kenneth L; Siddavatam, Prasad; Lawhon, Sara D; Nunes, Jairo E S; Gull, Tamara; Khare, Sangeeta; Everts, Robin E; Lewin, Harris A; Adams, Leslie Garry

    2013-01-01

    Brucella melitensis causes the most severe and acute symptoms of all Brucella species in human beings and infects hosts primarily through the oral route. The epithelium covering domed villi of jejunal-ileal Peyer's patches is an important site of entry for several pathogens, including Brucella. Here, we use the calf ligated ileal loop model to study temporal in vivo Brucella-infected host molecular and morphological responses. Our results document Brucella bacteremia occurring within 30 min after intraluminal inoculation of the ileum without histopathologic traces of lesions. Based on a system biology Dynamic Bayesian Network modeling approach (DBN) of microarray data, a very early transient perturbation of the host enteric transcriptome was associated with the initial host response to Brucella contact that is rapidly averted allowing invasion and dissemination. A detailed analysis revealed active expression of Syndecan 2, Integrin alpha L and Integrin beta 2 genes, which may favor initial Brucella adhesion. Also, two intestinal barrier-related pathways (Tight Junction and Trefoil Factors Initiated Mucosal Healing) were significantly repressed in the early stage of infection, suggesting subversion of mucosal epithelial barrier function to facilitate Brucella transepithelial migration. Simultaneously, the strong activation of the innate immune response pathways would suggest that the host mounts an appropriate protective immune response; however, the expression of the two key genes that encode innate immunity anti-Brucella cytokines such as TNF-α and IL12p40 were not significantly changed throughout the study. Furthermore, the defective expression of Toll-Like Receptor Signaling pathways may partially explain the lack of proinflammatory cytokine production and consequently the absence of morphologically detectable inflammation at the site of infection. Cumulatively, our results indicate that the in vivo pathogenesis of the early infectious process of Brucella is

  3. Group A streptococci clones associated with invasive infections and pharyngitis in Portugal present differences in emm types, superantigen gene content and antimicrobial resistance

    PubMed Central

    2012-01-01

    Background A few lineages of Group A streptococci (GAS) have been associated with a reemergence of severe invasive streptococcal disease in developed countries. However, the majority of the comparisons between invasive and non-invasive GAS isolates have been performed for collections of reduced genetic diversity or relied on limited typing information to distinguish clones. We characterized by several typing methods and compared a collection of 160 isolates recovered from normally sterile sites with 320 isolates associated with pharyngitis and recovered in the same time period in Portugal. Results Although most of the isolates belonged to clones that were equally prevalent in invasive infections and pharyngitis, we identified markers of invasiveness, namely the emm types 1 and 64, and the presence of the speA and speJ genes. In contrast, emm4, emm75, and the ssa and speL/M genes were significantly associated with pharyngitis. There was a strong agreement between the emm type, the superantigen (SAg) genes and the clusters defined by pulsed-field gel electrophoresis (PFGE) profiling. Therefore, combinations of particular emm types and SAg genes frequently co-occurred in the same PFGE cluster, but there was no synergistic or antagonistic interaction between them in determining invasiveness. Only macrolide-susceptible PFGE clones were significantly associated with invasive infections or pharyngitis, while the clones of resistant isolates sharing all other molecular properties analyzed were equally prevalent in the two groups of isolates. Conclusions This study confirmed the importance of the widely disseminated emm1-T1-ST28 clone in invasive infections but also identified other clones linked to either invasive infections (emm64-ST164) or pharyngitis (emm4-T4-ST39), which may be more limited in their temporal and geographical spread. Clonal properties like some emm types or SAg genes were associated with disease presentation, highlighting the importance of bacterial

  4. Detection of circulating Leishmania chagasi DNA for the non-invasive diagnosis of human infection.

    PubMed

    Disch, J; Maciel, F C; de Oliveira, M C; Orsini, M; Rabello, A

    2003-01-01

    A polymerase chain reaction (PCR) assay for the detection of Leishmania spp. DNA in peripheral blood was optimized and evaluated for the diagnosis of human visceral leishmaniasis (VL) in Brazil during May 2001 to December 2002. Optimization of the technique resulted in a detection limit of 1.65 fg of purified L. (L.) chagasi DNA, equivalent to 1.65 x 10(-2) parasites. Leishmania DNA was detected in the blood of 48 of 53 patients with parasitologically-confirmed VL, which corresponds to a sensitivity of 91%. No DNA was detected in the peripheral blood of 15 healthy, non-exposed volunteers, giving a specificity of 100%. We conclude that detection of parasite DNA in peripheral blood offers a non-invasive, sensitive and rapid method for the detection of VL caused by L. (L.) chagasi.

  5. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections.

    PubMed

    Falci, Diego R; Pasqualotto, Alessandro C

    2013-10-22

    The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium.

  6. Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections

    PubMed Central

    Falci, Diego R; Pasqualotto, Alessandro C

    2013-01-01

    The triazole class of antifungal drugs comprises first-line agents for the treatment of several invasive fungal diseases. Isavuconazole is a novel broad-spectrum triazole agent. Here we summarize its characteristics and compare it with the currently available antifungal agents. Isavuconazole is administered as a prodrug, and it is water soluble. Oral and intravenous formulations are available. Its intravenous formulation does not contain cyclodextrin, which is an advantage over voriconazole, considering the potential for nephrotoxicity of cyclodextrin. As with other azoles, isavuconazole requires a loading dose. Due to its prolonged half-life, a once-a-day regimen is possible. Considering that isavuconazole shares the same mechanism of action with the other triazoles, cross-resistance is an important concern in the class. Tolerability and safety profiles are favorable, and no serious adverse events have been consistently reported. Significant interactions with drugs metabolized by cytochrome P450 are expected to occur, especially with substrates and inducers of the CYP3A4 enzyme. Isavuconazole has in vitro activity against most medically important fungi, including species of Candida, Aspergillus, and Cryptococcus. It has some activity against the agents of mucormycosis. Clinical data regarding isavuconazole remain limited because ongoing trials have not yet been completed or published. Isavuconazole has the potential to become first-line therapy for invasive aspergillosis. It also has the potential for use in the context of antifungal prophylaxis, salvage therapy, or in combination regimens. Results of clinical trials are ultimately expected in order to adequately position isavuconazole in the current antifungal armamentarium. PMID:24187505

  7. High loading dose AmBisome is efficacious and well tolerated in the management of invasive fungal infection in hematology patients.

    PubMed

    McLintock, Lorna A; Cook, Gordon; Holyoake, Tessa L; Jones, Brian L; Kinsey, Sally E; Jackson, Graham H

    2007-04-01

    Despite improved supportive care, and the introduction of less toxic lipid-formulations of amphotericin B deoxycholate and other new antifungal agents the mortality from invasive fungal infection (IFI) in hematology patients remains high. New management strategies are therefore required to improve outcome.

  8. Influence of prior pandemic A(H1N1)2009 virus infection on invasion of MDCK cells by community-associated methicillin-resistant Staphylococcus aureus.

    PubMed

    Takayama, Yoko; Yano, Hisakazu; Nojima, Yasuhiro; Nakano, Ryuichi; Okamoto, Ryoichi; Hirakata, Yoichi; Sunakawa, Keisuke; Akahoshi, Tohru; Kaku, Mitsuo

    2014-01-01

    Secondary bacterial pneumonia due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a highly publicized cause of death associated with influenza. In this study, we performed the gentamicin-killing assay using Madin-Darby canine kidney (MDCK) cells and MRSA strains to investigate whether prior infection from pandemic A(H1N1)2009 virus (A[H1N1]pdm09) lead to increased invasion of MDCK cells by MRSA. We found that the invasion rate of two MRSA strains (ATCC BAA-1680 [USA 300] and ATCC BAA-1699 [USA 100]) into intact MDCK cell monolayers was 0.29 ± 0.15% and 0.007 ± 0.002%, respectively (p < 0.01, n ≥ 3). In addition, the relative invasion rate of both ATCC BAA-1680 and ATCC BAA-1699 was significantly increased by prior A(H1N1)pdm09 infection of MDCK monolayers from 1 ± 0.28 to 1.38 ± 0.02 and from 1 ± 0.24 to 1.73 ± 0.29, respectively (p < 0.01). These results indicate that ATCC BAA-1680 displays much stronger invasiveness of MDCK cells than ATCC BAA-1699, although invasion of both strains was increased by prior A(H1N1)pdm09 infection. In conclusion, this study provided the first evidence that prior A(H1N1)pdm09 infection facilitates the invasion of MDCK cells by MRSA, presumably due to cellular injury caused by the virus.

  9. EGFR and HER2 receptor kinase signaling mediate epithelial cell invasion by Candida albicans during oropharyngeal infection

    PubMed Central

    Zhu, Weidong; Phan, Quynh T.; Boontheung, Pinmanee; Solis, Norma V.; Loo, Joseph A.; Filler, Scott G.

    2012-01-01

    The fungus Candida albicans is the major cause of oropharyngeal candidiasis (OPC). A key feature of this disease is fungal invasion of oral epithelial cells, a process that can occur by active penetration and fungal-induced endocytosis. Two invasins, Als3 and Ssa1, induce epithelial cell endocytosis of C. albicans, in part by binding to E-cadherin. However, inhibition of E-cadherin function only partially reduces C. albicans endocytosis, suggesting that there are additional epithelial cell receptors for this organism. Here, we show that the EGF receptor (EGFR) and HER2 function cooperatively to induce the endocytosis of C. albicans hyphae. EGFR and HER2 interact with C. albicans in an Als3- and Ssa1-dependent manner, and this interaction induces receptor autophosphorylation. Signaling through both EGFR and HER2 is required for maximal epithelial cell endocytosis of C. albicans in vitro. Importantly, oral infection with C. albicans stimulates the phosphorylation of EGFR and HER2 in the oral mucosa of mice, and treatment with a dual EGFR and HER2 kinase inhibitor significantly decreases this phosphorylation and reduces the severity of OPC. These results show the importance of EGFR and HER2 signaling in the pathogenesis of OPC and indicate the feasibility of treating candidal infections by targeting the host cell receptors with which the fungus interacts. PMID:22891338

  10. Effects of phosphate supplementation on Pseudomonas aeruginosa invasive behavior in burn wound infections: A simple approach to a big problem.

    PubMed

    Mohammadi-Samani, Soliman; Kouroshfard, Shahriyar; Azarpira, Negar

    2016-03-01

    This study was designed to investigate the effect of inorganic phosphate supplementation on invasive behavior of Pseudomonas aeruginosa in burn wound infections. An emulsion-based lotion containing sodium dihydrogen phosphate was formulated and then 50 female Sprague-Dawley rats with burn wounds were used to assess the effect of phosphate supplementation on swarming motility of P. aeruginosa. On the second day after burn, four groups of rats were inoculated with P. aeruginosa and one group was left as negative control. The treatment was started on day 3 and the animals were followed up for 4 weeks. Significant improvement in wound healing was observed in the phosphate-receiving group after the 4-week follow-up, compared to the negative control, positive control, and silver sulfadiazine-receiving groups. Histopathological assessment of the tissue samples also indicated the healing process in phosphate-enriched lotion receiving group. The results showed that inorganic phosphate supplementation results in alteration of the virulence behavior of P. aeruginosa and improvement in the wound healing process. In conclusion, phosphate supplementation would be a rational strategy in the eradication of P. aeruginosa wound infection.

  11. Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients.

    PubMed

    Noskin, G; Pietrelli, L; Gurwith, M; Bowden, R

    1999-04-01

    Amphotericin B colloidal dispersion (ABCD, AMPHOTEC, AMPHOCIL), a lipid complex of amphotericin B, was developed to reduce the nephrotoxicity of amphotericin B while retaining its antifungal efficacy. In this retrospective review, the efficacy and safety of ABCD were evaluated in 220 BMT recipients (167 allogeneic; 53 autologous) with suspected or documented life-threatening fungal infections (primarily Candida or Aspergillus species). Patients were treated in five open-label clinical trials of ABCD therapy. ABCD was administered intravenously once daily, median dose of 4 mg/kg, for up to 409 days (mean 23 days, median 16 days). Successful therapeutic response to treatment (complete or partial) was reported in 52% of the 99 evaluable patients with proven infection, and in 40% of all 220 patients. In the evaluable population, the response and mortality rates were 51% and 73%, respectively, in the allogeneic BMT patients, compared to 52% and 48% in the autologous BMT patients. The response rate for evaluable patients with Candida spp was 65%, 38% for patients with Aspergillus spp, and 42 % for patients with other or multiple fungal infections. In this patient population at high risk of nephrotoxicity due to concomitant cyclosporine and/or other nephrotoxic agents, ABCD did not cause renal dysfunction. Although the majority of patients had pre-existing renal impairment (median baseline serum creatinine 1.8 mg/dl), there was no trend towards increasing serum creatinine. No unexpected toxicities were observed. In conclusion, ABCD appears to be safe and effective for the treatment of severe fungal infections in BMT patients.

  12. Molecular analysis of the role of streptococcal pyrogenic Exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes.

    PubMed

    Sriskandan, S; Unnikrishnan, M; Krausz, T; Cohen, J

    1999-08-01

    Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (SPEA), in the pathogenesis of necrotizing soft-tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. SPEA can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild-type spea gene in an M1 streptococcal isolate. Supernatants from toxin-negative mutant bacteria demonstrated a 50% reduction in pro-mitogenic activity in HLA DQ-positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild-type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain-induced mortality was seen after intravenous infection. Intramuscular infection with the SPEA-negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified SPEA led to a dose-dependent increase in peritoneal neutrophils 6 h after administration. SPEA is not a critical virulence factor in invasive soft-tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.

  13. Invasive Group B Streptococcal Infections in Finland: A Population-based Study

    PubMed Central

    Nuorti, J. Pekka; Halmesmäki, Erja; Carlson, Petteri; Uotila, Jukka; Vuento, Risto; Ranta, Tapio; Sarkkinen, Hannu; Ämmälä, Martti; Kostiala, Anja; Järvenpää, Anna-Liisa

    2003-01-01

    We analyzed surveillance data on group B streptococcus (GBS) infection in Finland from 1995 to 2000 and reviewed neonatal cases of early-onset GBS infection in selected hospitals in 1999 to 2000. From 1995 to 2000, 853 cases were reported (annual incidence 2.2–3.0/100,000 population). We found 32–38 neonatal cases of early-onset GBS disease per year (annual incidence 0.6–0.7/1,000 live births). In five hospitals, 35% of 26 neonatal cases of early-onset GBS infection had at least one risk factor: prolonged rupture of membranes, preterm delivery, or intrapartum fever. Five of eight mothers screened for GBS were colonized. In one case, disease developed despite intrapartum chemoprophylaxis. Although the incidence of early-onset GBS disease in Finland is relatively low, some geographic variation exists, and current prevention practices are suboptimal. Establishing national guidelines to prevent perinatal GBS is likely to reduce the incidence of the disease. PMID:12702228

  14. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

    PubMed Central

    De Pauw, Ben; Walsh, Thomas J.; Donnelly, J. Peter; Stevens, David A.; Edwards, John E.; Calandra, Thierry; Pappas, Peter G.; Maertens, Johan; Lortholary, Olivier; Kauffman, Carol A.; Denning, David W.; Patterson, Thomas F.; Maschmeyer, Georg; Bille, Jacques; Dismukes, William E.; Herbrecht, Raoul; Hope, William W.; Kibbler, Christopher C.; Kullberg, Bart Jan; Marr, Kieren A.; Muñoz, Patricia; Odds, Frank C.; Perfect, John R.; Restrepo, Angela; Ruhnke, Markus; Segal, Brahm H.; Sobel, Jack D.; Sorrell, Tania C.; Viscoli, Claudio; Wingard, John R.; Zaoutis, Theoklis; Bennett, John E.

    2009-01-01

    Background Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results The revised definitions retain the original classifications of “proven,” “probable,” and “possible” invasive fungal disease, but the definition of “probable” has been expanded, whereas the scope of the category “possible” has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients. PMID:18462102

  15. Prevotella intermedia induces matrix metalloproteinase-9 expression in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; Shu, Lei; Fu, Shan-Min; Liu, Bin; Xu, Xiu-Li; Wu, Jun-Zheng

    2008-06-01

    Matrix metalloproteinases (MMPs) play pivotal roles in inflammatory diseases including chronic periodontitis. The effects of Prevotella intermedia, a major periodontal pathogen, on MMP-9 production in primary human periodontal ligament (hPDL) cells were examined in the present study. MMP-9 mRNA expression was measured by semiquantitative reverse transcriptase PCR and its protein secretion was assayed by gelatin zymography. Prevotella intermedia ATCC 25611 supernatant time and dose-dependently induced MMP-9 expression. In contrast, Porphyromanas gingivalis ATCC 33277 supernatants, Escherichia coli lipopolysacchride and IL-1beta exhibited no stimulatory effects on MMP-9 production in hPDL cells. Mitogen-activated protein kinases [MAPK, including extracellular signal-related kinases (ERK), c-jun N-terminal kinases (JNK) and p38] inhibitors exerted no effect on the P. intermedia-induced MMP-9 production, indicating that P. intermedia induced MMP-9 production through an MAPK-independent pathway. Our results demonstrated that P. intermedia may contribute to periodontal tissue destruction during chronic periodontitis by inducing MMP-9 production in hPDL cells.

  16. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors.

    PubMed

    Barbosa, Graziela Murta; Colombo, Andrea Vieira; Rodrigues, Paulo Henrique; Simionato, Maria Regina Lorenzetti

    2015-01-01

    It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P. gingivalis and P

  17. Intraspecies Variability Affects Heterotypic Biofilms of Porphyromonas gingivalis and Prevotella intermedia: Evidences of Strain-Dependence Biofilm Modulation by Physical Contact and by Released Soluble Factors

    PubMed Central

    Barbosa, Graziela Murta; Colombo, Andrea Vieira; Rodrigues, Paulo Henrique; Simionato, Maria Regina Lorenzetti

    2015-01-01

    It is well known that strain and virulence diversity exist within the population structure of Porphyromonas gingivalis. In the present study we investigate intra- and inter-species variability in biofilm formation of Porphyromonas gingivalis and partners Prevotella intermedia and Prevotella nigrescens. All strains tested showed similar hydrophobicity, except for P. gingivalis W83 which has roughly half of the hydrophobicity of P. gingivalis ATCC33277. An intraspecies variability in coaggregation of P. gingivalis with P. intermedia was also found. The association P. gingivalis W83/P. intermedia 17 produced the thickest biofilm and strain 17 was prevalent. In a two-compartment system P. gingivalis W83 stimulates an increase in biomass of strain 17 and the latter did not stimulate the growth of P. gingivalis W83. In addition, P. gingivalis W83 also stimulates the growth of P. intermedia ATCC25611 although strain W83 was prevalent in the association with P. intermedia ATCC25611. P. gingivalis ATCC33277 was prevalent in both associations with P. intermedia and both strains of P. intermedia stimulate the growth of P. gingivalis ATCC33277. FISH images also showed variability in biofilm structure. Thus, the outcome of the association P. gingivalis/P. intermedia seems to be strain-dependent, and both soluble factors and physical contact are relevant. The association P. gingivalis-P. nigrescens ATCC33563 produced larger biomass than each monotypic biofilm, and P. gingivalis was favored in consortia, while no differences were found in the two-compartment system. Therefore, in consortia P. gingivalis-P. nigrescens physical contact seems to favor P. gingivalis growth. The intraspecies variability found in our study suggests strain-dependence in ability of microorganisms to recognize molecules in other bacteria which may further elucidate the dysbiosis event during periodontitis development giving additional explanation for periodontal bacteria, such as P. gingivalis and P

  18. Biochar as a biosecurity tool for the management of invasive and/or infected plants.

    NASA Astrophysics Data System (ADS)

    Harries, Philip J. E.; Fielding, J. James; Alayne Street-Perrott, F.; Doerr, Stefan H.; Brackenbury, Sion

    2014-05-01

    Control of invasive alien/native plants and diseased trees is often achieved using labour-intensive mechanical methods, incurring high costs and significant carbon debt. Disposal of cleared biomass may be heavily regulated. The commonly used method, burning, wastes a potentially valuable resource. Biochar may offer a safe, cost-effective solution to the problem of disposal. Large areas of Wales are covered by bracken (Pteridium aquilinum) (37x103 ha) or invasive Rhododendron ponticum (area not yet quantified). Clearance of these plants is often necessary for agriculture or maintenance of biodiversity (bracken), or to curb the rapid dispersal of the fungus-like pathogen Phytophthora ramorum from rhododendron (the principal host) into commercial timber stands, notably Japanese larch (Larix kaempferi). In addition, ash dieback (the fungal disease Hymenoscyphus pseudoalbidus aka Chalara fraxinea) is now spreading aggressively in common ash trees (Fraxinus excelsior) in the UK. Pilot-scale experiments are being conducted using a BiGchar 1000 mobile, fast pyrolysis -gasification unit, focussing on chipped rhododendron, Japanese larch and common ash feedstocks. Preliminary results of these experiments will be presented. The biochars produced are being subjected to a range of physical and chemical analyses. Levels of micro- and macro-nutrients retained from the original feedstocks are being evaluated. Organic and inorganic contaminants are also being compared with those in the respective feedstocks. Biochar produced from R. ponticum comprised C 63.7-85.9%, H 0.4-0.8%, N 0.4-0.8%, S 0.27-1.79% and O 4.1-27.4%, with most of the mineral nutrients being retained from the original feedstock, especially Mn. Larch biochar comprised C 84.1-91.7%, H 1.8-3.1%, N 0.3-0.8%, S 0.42-0.69% and O 4.1-10.7%. Heavy-metal concentrations were below recommended limits (International Biochar Initiative, 2012), although R. ponticum growing on highly acidified soils showed some tendency to bio

  19. Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection

    PubMed Central

    Marks, Laura R.; Kong, Yong; Gent, Janneane F.; Roche-Hakansson, Hazeline

    2014-01-01

    Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis. PMID:25135685

  20. Update on epidemiology of and preventive strategies for invasive fungal infections in cancer patients.

    PubMed

    Perfect, John R; Hachem, Ray; Wingard, John R

    2014-11-15

    Changes in antineoplastic treatments and transplant practices are driving shifts in the epidemiology of invasive fungal diseases (IFDs). Patients with acute myelogenous leukemia (AML) and those undergoing bone marrow transplant (BMT) are at greatest risk for contracting IFDs. Unfortunately, there are few large population studies that can be used to track trends and help us to better understand why certain individuals within recognized high-risk groups are at greater risks than others for contracting IFDs. The growing use of antifungals in prophylaxis and treatment influences which species will cause an IFD as well as the resistance patterns of these fungi. On the one hand, antifungal prophylaxis has mitigated, but not eliminated, the threat of candidiasis. Furthermore, prophylaxis trials have shown trends of reduced aspergillosis in BMT patients; however, no survival benefits were seen, and 1 trial indicated a lower rate of aspergillosis and survival benefits in patients with AML. Future prophylaxis trials should reduce the heterogeneity of risk in study participants in order to better assess benefit; these trials should also incorporate fungal biomarkers into their design. The threat of emerging fungal resistance in prophylaxis strategies is real and must be monitored.

  1. Effects of genotypic and phenotypic variation on establishment are important for conservation, invasion, and infection biology

    PubMed Central

    Forsman, Anders

    2014-01-01

    There is abundant evidence that the probability of successful establishment in novel environments increases with number of individuals in founder groups and with number of repeated introductions. Theory posits that the genotypic and phenotypic variation among individuals should also be important, but few studies have examined whether founder diversity influences establishment independent of propagule pressure, nor whether the effect is model or context dependent. I summarize the results of 18 experimental studies and report on a metaanalysis that provides strong evidence that higher levels of genotypic and phenotypic diversity in founder groups increase establishment success in plants and animals. The effect of diversity is stronger in experiments carried out under natural conditions in the wild than under seminatural or standardized laboratory conditions. The realization that genetic and phenotypic variation is key to successful establishment may improve the outcome of reintroduction and translocation programs used to vitalize or restore declining and extinct populations. Founder diversity may also improve the ability of invasive species to establish and subsequently spread in environments outside of their native community, and enhance the ability of pathogens and parasites to colonize and invade the environment constituted by their hosts. It is argued that exchange of ideas, methodological approaches, and insights of the role of diversity for establishment in different contexts may further our knowledge, vitalize future research, and improve management plans in different disciplines. PMID:24367109

  2. Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion

    PubMed Central

    Tenor, Jennifer L.; Oehlers, Stefan H.; Yang, Jialu L.

    2015-01-01

    ABSTRACT The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of Cryptococcus mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that C. neoformans is able to penetrate the zebrafish brain following intravenous infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformans platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. PMID:26419880

  3. Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases

    PubMed Central

    Yonezawa, Ryuta; Kuwana, Tsukasa; Kawamura, Kengo; Inamo, Yasuji

    2015-01-01

    Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan. PMID:26819794

  4. Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria. Bacterial entry induces epithelial prostaglandin h synthase-2 expression and prostaglandin E2 and F2alpha production.

    PubMed Central

    Eckmann, L; Stenson, W F; Savidge, T C; Lowe, D C; Barrett, K E; Fierer, J; Smith, J R; Kagnoff, M F

    1997-01-01

    Increased intestinal fluid secretion is a protective host response after enteric infection with invasive bacteria that is initiated within hours after infection, and is mediated by prostaglandin H synthase (PGHS) products in animal models of infection. Intestinal epithelial cells are the first host cells to become infected with invasive bacteria, which enter and pass through these cells to initiate mucosal, and ultimately systemic, infection. The present studies characterized the role of intestinal epithelial cells in the host secretory response after infection with invasive bacteria. Infection of cultured human intestinal epithelial cell lines with invasive bacteria, but not noninvasive bacteria, is shown to induce the expression of one of the rate-limiting enzymes for prostaglandin formation, PGHS-2, and the production of PGE2 and PGF2alpha. Furthermore, increased PGHS-2 expression was observed in intestinal epithelial cells in vivo after infection with invasive bacteria, using a human intestinal xenograft model in SCID mice. In support of the physiologic importance of epithelial PGHS-2 expression, supernatants from bacteria-infected intestinal epithelial cells were shown to increase chloride secretion in an in vitro model using polarized epithelial cells, and this activity was accounted for by PGE2. These studies define a novel autocrine/paracrine function of mediators produced by intestinal epithelial cells in the rapid induction of increased fluid secretion in response to intestinal infection with invasive bacteria. PMID:9218506

  5. Mutual dilution of infection by an introduced parasite in native and invasive stream fishes across Hawaii.

    PubMed

    Gagne, Roderick B; Heins, David C; McIntyre, Peter B; Gilliam, James F; Blum, Michael J

    2016-10-01

    The presence of introduced hosts can increase or decrease infections of co-introduced parasites in native species of conservation concern. In this study, we compared parasite abundance, intensity, and prevalence between native Awaous stamineus and introduced poeciliid fishes by a co-introduced nematode parasite (Camallanus cotti) in 42 watersheds across the Hawaiian Islands. We found that parasite abundance, intensity and prevalence were greater in native than introduced hosts. Parasite abundance, intensity and prevalence within A. stamineus varied between years, which largely reflected a transient spike in infection in three remote watersheds on Molokai. At each site we measured host factors (length, density of native host, density of introduced host) and environmental factors (per cent agricultural and urban land use, water chemistry, watershed area and precipitation) hypothesized to influence C. cotti abundance, intensity and prevalence. Factors associated with parasitism differed between native and introduced hosts. Notably, parasitism of native hosts was higher in streams with lower water quality, whereas parasitism of introduced hosts was lower in streams with lower water quality. We also found that parasite burdens were lower in both native and introduced hosts when coincident. Evidence of a mutual dilution effect indicates that introduced hosts can ameliorate parasitism of native fishes by co-introduced parasites, which raises questions about the value of remediation actions, such as the removal of introduced hosts, in stemming the rise of infectious disease in species of conservation concern.

  6. Identification by PCR of Non-typhoidal Salmonella enterica Serovars Associated with Invasive Infections among Febrile Patients in Mali

    PubMed Central

    Tennant, Sharon M.; Diallo, Souleymane; Levy, Haim; Livio, Sofie; Sow, Samba O.; Tapia, Milagritos; Fields, Patricia I.; Mikoleit, Matthew; Tamboura, Boubou; Kotloff, Karen L.; Nataro, James P.; Galen, James E.; Levine, Myron M.

    2010-01-01

    Background In sub-Saharan Africa, non-typhoidal Salmonella (NTS) are emerging as a prominent cause of invasive disease (bacteremia and focal infections such as meningitis) in infants and young children. Importantly, including data from Mali, three serovars, Salmonella enterica serovar Typhimurium, Salmonella Enteritidis and Salmonella Dublin, account for the majority of non-typhoidal Salmonella isolated from these patients. Methods We have extended a previously developed series of polymerase chain reactions (PCRs) based on O serogrouping and H typing to identify Salmonella Typhimurium and variants (mostly I 4,[5],12:i:-), Salmonella Enteritidis and Salmonella Dublin. We also designed primers to detect Salmonella Stanleyville, a serovar found in West Africa. Another PCR was used to differentiate diphasic Salmonella Typhimurium and monophasic Salmonella Typhimurium from other O serogroup B, H:i serovars. We used these PCRs to blind-test 327 Salmonella serogroup B and D isolates that were obtained from the blood cultures of febrile patients in Bamako, Mali. Principal Findings We have shown that when used in conjunction with our previously described O-serogrouping PCR, our PCRs are 100% sensitive and specific in identifying Salmonella Typhimurium and variants, Salmonella Enteritidis, Salmonella Dublin and Salmonella Stanleyville. When we attempted to differentiate 171 Salmonella Typhimurium (I 4,[ 5],12:i:1,2) strains from 52 monophasic Salmonella Typhimurium (I 4,[5],12:i:-) strains, we were able to correctly identify 170 of the Salmonella Typhimurium and 51 of the Salmonella I 4,[5],12:i:- strains. Conclusion We have described a simple yet effective PCR method to support surveillance of the incidence of invasive disease caused by NTS in developing countries. PMID:20231882

  7. Caspofungin versus fluconazole as prophylaxis of invasive fungal infection in high-risk liver transplantation recipients: A propensity score analysis.

    PubMed

    Fortún, Jesús; Muriel, Alfonso; Martín-Dávila, Pilar; Montejo, Miguel; Len, Oscar; Torre-Cisneros, Julian; Carratalá, Jordi; Muñoz, Patricia; Fariñas, Carmen; Moreno, Asunción; Fresco, Gema; Goikoetxea, Josune; Gavaldá, Joan; Pozo, Juan Carlos; Bodro, Marta; Vena, Antonio; Casafont, Fernando; Cervera, Carlos; Silva, José Tiago; Aguado, José M

    2016-04-01

    Targeted prophylaxis has proven to be an efficient strategy in liver transplantation recipients (LTRs). The aim of this study was to compare the effectiveness and safety of caspofungin with that of fluconazole in high-risk (HR) LTRs. Caspofungin and fluconazole were compared in a multicenter, retrospective, cohort study in HR-LTRs in Spain. Outcomes were assessed at 180 days after transplantation. A propensity score approach was applied. During the study period (2005-2012), we analyzed 195 HR-LTRs from 9 hospitals. By type of prophylaxis, 97 patients received caspofungin and 98 received fluconazole. Of a total of 17 (8.7%) global invasive fungal infections (IFIs), breakthrough IFIs accounted for 11 (5.6%) and invasive aspergillosis (IA) accounted for 6 (3.1%). By univariate analysis, no differences were observed in the prevention of global IFIs. However, caspofungin was associated with a significant reduction in the rate of breakthrough IFIs (2.1% versus 9.2%, P = 0.04). In patients requiring dialysis (n = 62), caspofungin significantly reduced the frequency of breakthrough IFIs (P = 0.03). The propensity score analysis confirmed a significant reduction in the frequency of IA in patients receiving caspofungin (absolute risk reduction, 0.06; 95% confidence interval [CI], 0.001-0.11; P = 0.044). Linear regression analysis revealed a significant decrease in blood alanine aminotransferase levels and a significant increase in bilirubin levels after administration of caspofungin. Caspofungin and fluconazole have similar efficacy for the prevention of global IFIs in HR-LTRs in this observational, multicenter cohort study. However, caspofungin was associated with a significant reduction of breakthrough IFIs and, after adjusting for confounders, caspofungin was associated with a lower rate of IA. This benefit is probably more favorable in patients on dialysis. Caspofungin is safe in HR-LTRs, although bilirubin levels may be increased.

  8. Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains isolated from invasive and non-invasive infections from Mexico and the USA during 1999–2010

    PubMed Central

    Villaseñor-Sierra, Alberto; Katahira, Eva; Jaramillo-Valdivia, Abril N.; de los Angeles Barajas-García, María; Bryant, Amy; Morfín-Otero, Rayo; Márquez-Díaz, Francisco; Tinoco, Juan Carlos; Sánchez-Corona, José; Stevens, Dennis L.

    2012-01-01

    Summary Objective To compare the prevalence, phenotypes, and genes responsible for erythromycin resistance among Streptococcus pyogenes isolates from Mexico and the USA. Methods Eighty-nine invasive and 378 non-invasive isolates from Mexico, plus 148 invasive, 21 non-invasive, and five unclassified isolates from the USA were studied. Susceptibilities to penicillin, erythromycin, clindamycin, ceftriaxone, and vancomycin were evaluated according to Clinical and Laboratory Standards Institute (CLSI) standards. Phenotypes of erythromycin resistance were identified by triple disk test, and screening for mefA, ermTR, and ermB genes was carried out by PCR. Results All isolates were susceptible to penicillin, ceftriaxone, and vancomycin. Erythromycin resistance was found in 4.9% of Mexican strains and 5.2% of USA strains. Phenotypes in Mexican strains were 95% M and 5% cMLS; in strains from the USA, phenotypes were 33.3% iMLS, 33.3% iMLS-D, and 33.3% M. Erythromycin resistance genes in strains from Mexico were mefA (95%) and ermB (5%); USA strains harbored ermTR (56%), mefA (33%), and none (11%). In Mexico, all erythromycin-resistant strains were non-invasive, whereas 89% of strains from the USA were invasive. Conclusions Erythromycin resistance continues to exist at low levels in both Mexico and the USA, although the genetic mechanisms responsible differ between the two nations. These genetic differences may be related to the invasive character of the S. pyogenes isolated. PMID:22217469

  9. Key Points Concerning Amyloid Infectivity and Prion-Like Neuronal Invasion

    PubMed Central

    Espargaró, Alba; Busquets, Maria Antònia; Estelrich, Joan; Sabate, Raimon

    2016-01-01

    Amyloid aggregation has been related to an increasing number of human illnesses, from Alzheimer’s and Parkinson’s diseases (AD/PD) to Creutzfeldt-Jakob disease. Commonly, only prions have been considered as infectious agents with a high capacity of propagation. However, recent publications have shown that many amyloid proteins, including amyloid β-peptide, α-synuclein (α-syn) and tau protein, also propagate in a “prion-like” manner. Meanwhile, no link between propagation of pathological proteins and neurotoxicity has been demonstrated. The extremely low infectivity under natural conditions of most non-prion amyloids is far below the capacity to spread exhibited by prions. Nonetheless, it is important to elucidate the key factors that cause non-prion amyloids to become infectious agents. In recent years, important advances in our understanding of the amyloid processes of amyloid-like proteins and unrelated prions (i.e., yeast and fungal prions) have yielded essential information that can shed light on the prion phenomenon in mammals and humans. As shown in this review, recent evidence suggests that there are key factors that could dramatically modulate the prion capacity of proteins in the amyloid conformation. The concentration of nuclei, the presence of oligomers, and the toxicity, resistance and localization of these aggregates could all be key factors affecting their spread. In short, those factors that favor the high concentration of extracellular nuclei or oligomers, characterized by small size, with a low toxicity could dramatically increase prion propensity; whereas low concentrations of highly toxic intracellular amyloids, with a large size, would effectively prevent infectivity. PMID:27147962

  10. Invaded Invaders: Infection of Invasive Brown Treesnakes on Guam by an Exotic Larval Cestode with a Life Cycle Comprised of Non-Native Hosts

    PubMed Central

    Klug, Page E.; Reed, Robert N.

    2015-01-01

    Background Multiple host introductions to the same non-native environment have the potential to complete life cycles of parasites incidentally transported with them. Our goal was to identify a recently detected parasitic flatworm in the invasive Brown Treesnake (Boiga irregularis) on the remote Pacific island of Guam. We considered possible factors influencing parasite transmission, and tested for correlations between infection status and potential indicators of host fitness. We used genetic data from the parasite and information about the native ranges of other possible non-native hosts to hypothesize how it arrived on Guam and how its life cycle may be currently supported. Methods We identified the parasite by comparing larval morphology and mtDNA sequences with other Pseudophyllid tapeworms. We assessed probability of infection in individual snakes using logistic regression and examined different factors influencing presence of parasites in hosts. Results We identified the parasite as the pseudophyllid cestode Spirometra erinaceieuropaei, with all sampled worms from multiple snakes sharing a single mtDNA haplotype. Infection appears to be limited to the only freshwater watershed on the island, where infection prevalence was high (77.5%). Larger snakes had a higher probability of being infected, consistent with the chronic nature of such infections. While infection status was positively correlated with body condition, infected snakes tended to have lower intra-peritoneal fat body mass, potentially indicating a negative effect on energy stores. Conclusions We discovered that B. irregularis inhabiting a small area of forested habitat in a freshwater watershed on Guam are often infected by a novel parasite of Asian origin. While further work is needed, this species of Spirometra, itself a non-native species, likely depends on a suite of recently introduced hosts from different parts of the world to complete the life cycle. This baseline study provides little

  11. Comparison of Bacteroides-Prevotella 16S rRNA genetic markers for fecal samples from different animal species

    USGS Publications Warehouse

    Fogarty, L.R.; Voytek, M.A.

    2005-01-01

    To effectively manage surface and ground waters it is necessary to improve our ability to detect and identify sources of fecal contamination. We evaluated the use of the anaerobic bacterial group Bacteroides-Prevotella as a potential fecal indicator. Terminal restriction length polymorphism (T-RFLP) of the 16S rRNA genes from this group was used to determine differences in populations and to identify any unique populations in chickens, cows, deer, dogs, geese, horses, humans, pigs, and seagulls. The group appears to be a good potential fecal indicator in all groups tested except for avians. Cluster analysis of Bacteroides-Prevotella community T-RFLP profiles indicates that Bacteroides-Prevotella populations from samples of the same host species are much more similar to each other than to samples from different source species. We were unable to identify unique peaks that were exclusive to any source species; however, for most host species, at least one T-RFLP peak was identified to be more commonly found in that species, and a combination of peaks could be used to identify the source. T-RFLP profiles obtained from water spiked with known-source feces contained the expected diagnostic peaks from the source. These results indicate that the approach of identifying Bacteroides-Prevotella molecular markers associated with host species might be useful in identifying sources of fecal contamination in the environment.

  12. Fermentation of model hemicelluloses by Prevotella strains and Butyrivibrio fibrisolvens in pure culture and in ruminal enrichment cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hemicelluloses are major components of plant biomass, but their fermentation in the rumens of cattle and other ruminants is poorly understood. We compared four species of the ruminally dominant genus Prevotella and the well-known hemicellulose utilizer, Butyrivibrio fibrisolvens, with respect to deg...

  13. Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations.

    PubMed

    Pitman, Stuart K; Drew, Richard H; Perfect, John R

    2011-09-01

    Introduction: Morbidity and mortality associated with invasive fungal infections (IFIs) remains unacceptably high. Such diseases represent a substantial burden to the healthcare system. New options are needed to address antifungal resistance in existing and emerging pathogens and improve treatment outcomes while minimizing drug-related toxicities and interactions. Awareness of new and potential future options is of great value for those healthcare professionals who care for patients with IFIs. Areas covered: A search of PubMed, infectious diseases conference abstracts and reference lists from relevant publications was conducted and relevant information abstracted. This review describes the limitations of existing systemic antifungal therapies (e.g., resistance, drug-drug interactions, drug-related toxicities) and summarizes data regarding several emerging antifungal compounds including (but not limited to) new triazoles (e.g. isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin Z. Agents in clinical trials such as (but not limited to) new triazoles (e.g., isavuconazole, ravuconazole), echinocandins (e.g., aminocandin) and nikkomycin are included. New formulations of existing drugs including reformulations of miconazole, posaconazole and amphotericin B are also reviewed. Finally, new or novel administration strategies for existing drugs such as combination antifungal therapy, antifungal dose escalation, adjunctive use of iron chelators and preemptive therapy are discussed. Expert opinion: All present antifungal agents have some deficiencies in antifungal spectra, toxicity, pharmacokinetics and/or drug-drug interactions, making them less than ideal for some fungal infections. Therefore, there remains an urgent need to find safe, effective, rapidly fungicidal, broad-spectrum antifungal agents with excellent pharmacodynamics to effectively eliminate the fungus from the body with short antifungal courses.

  14. Early Complications and Outcomes in Combat Injury Related Invasive Fungal Wound Infections: A Case-Control Analysis

    PubMed Central

    Lewandowski, Louis R.; Weintrob, Amy C.; Tribble, David R.; Rodriguez, Carlos J.; Petfield, Joseph; Lloyd, Bradley A.; Murray, Clinton K.; Stinner, Daniel; Aggarwal, Deepak; Shaikh, Faraz; Potter, Benjamin K.

    2015-01-01

    Objective Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures prior to initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure. Design Retrospective review and case-control analysis. Setting Military hospitals. Patients/Participants United States military personnel injured during combat operations (2009–2011). The IFI cases were identified based upon the presence of recurrent, necrotic extremity wounds with mold growth in culture and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury. Intervention None. Main Outcome Measurements Amputation revision rate and loss of functional levels. Results Seventy-one IFI cases (112 fungal-infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (p<0.001). Additionally, significantly (p<0.001) higher number of operative procedures and longer duration to initial wound closure was associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% CI: 1.17, 2.01). The supplemental matching analysis found similar results. Conclusions Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates. PMID:26360542

  15. Clonal relatedness of Salmonella isolates associated with invasive infections in captive and wild-caught rattlesnakes.

    PubMed

    Bemis, David A; Grupka, Lisa M; Liamthong, Sumalee; Folland, Douglas W; Sykes, John M; Ramsay, Edward C

    2007-03-10

    This study examines the serotype distribution and clonal relatedness among Salmonella isolates obtained from healthy and diseased snakes. Isolates from extraintestinal body sites were obtained through routine diagnostic lab submissions from snakes in two facilities that had experienced a high prevalence of osteomyelitis in Crotalus species. Gastrointestinal isolates were predominantly from fecal samples collected from healthy snakes of both crotalid and non-crotalid species in one facility. PFGE macrorestriction analysis of Salmonella isolates confirmed the clonal and species-restricted nature of Salmonella serotype IIIa 56: z4, z23: - in one facility. Fourteen of 15 isolates from suspected osteomyelitis lesions in wild-caught snakes at the second facility were also from Salmonella subgroup IIIa (serotype IIIa 18: z4, z23: -) and appeared to be closely related by PFGE. Evaluation of a PCR assay for the spvC gene in 209 isolates demonstrated that this method consistently distinguished isolates of subgroup IIIa from those of subgroup IIIb. The data presented establish that Salmonella of subgroup IIIb are abundant and regularly associated with gastrointestinal shedding in snakes but that Salmonella in subgroup IIIa disproportionately cause infections in bone or other extraintestinal sites.

  16. Pharmacoeconomic evaluation of caspofungin versus liposomal amphotericin B in empirical treatment of invasive fungal infections in Turkey.

    PubMed

    Turner, S J; Senol, E; Kara, A; Al-Badriyeh, D; Kong, D C M; Dinleyici, E C

    2013-09-01

    Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB.

  17. Probiotic supplementation for preventing invasive fungal infections in preterm neonates--a systematic review and meta-analysis.

    PubMed

    Agrawal, Sachin; Rao, Shripada; Patole, Sanjay

    2015-11-01

    Invasive fungal infections (IFI) are associated with significant health burden in preterm neonates. The objective of this study was to systematically review effect of probiotic supplementation (PS) for preventing IFI in preterm neonates. We searched Cochrane Central Register of Controlled Trials, Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, and proceedings of the Pediatric Academic Society meetings in August 2014. Study selection was performed on randomised controlled trials (RCT) of PS in neonates born <37 weeks. Primary outcome of this study was IFI (Isolation of fungus in blood/body fluids) and secondary outcome was fungal gut colonisation. Information on IFI/colonisation was available in 8 of 27 RCT. Meta-analysis (fixed effects model) showed that PS reduced the risk of IFI (RR: 0.50, 95% CI: 0.34, 0.73, I(2) = 39%). Results were not significant with random effects model (RR: 0.64, 95%, CI: 0.30, 1.38, P = 0.25, I(2) = 39%). Analysis after excluding the study with a high baseline incidence (75%) of IFI showed that PS had no significant benefits (RR: 0.89; 95% CI: 0.44, 1.78). Of the five studies reporting on fungal gut colonisation, three reported benefits of probiotics; two did not. Current evidence is limited to derive firm conclusions on the effect of PS for preventing IFI/gut colonisation in preterm neonates.

  18. Utility of bronchoalveolar lavage in diagnosing respiratory tract infections in patients with hematological malignancies: are invasive diagnostics still needed?

    PubMed Central

    Svensson, Tobias; Lundström, Kristina Lamberg; Höglund, Martin; Cherif, Honar

    2017-01-01

    Background Patients treated for hematological malignancies have an increased risk of serious infections. Diagnosis and prompt initiation of therapy are essential. Bronchoalveolar lavage (BAL) is a well-established investigation for identifying the cause of pulmonary infiltrates in immunocompromised patients. The aim of the study was to determine the diagnostic yield of BAL in patients treated for hematological malignancies and how often it contributed to a modification of the anti-infectious therapy. Methods We reviewed records from 151 consecutive BAL procedures in 133 adult patients with hematological malignancies, treated at a tertiary hematology unit from 2004 to 2013. Extensive microbiological work-ups on BAL samples had been performed according to a standardized protocol. Results A microbiological finding causing the infectious episode could be identified in 59 (39%) cases. In 44 (29%) of the cases, results from BAL had an impact on clinical management either by contributing to a specific diagnosis (25%) or by leading to cessation of ongoing microbiological therapy. The most common diagnoses were invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). Diagnoses of IPA and PJP were based on results from BAL in 65% and 93% of cases, respectively. Several microbiological tests on BAL samples rendered no positive results. Complications were few and mainly mild. Conclusion BAL is still important for either verifying or excluding some of the most important respiratory tract pathogens in patients with hematological malignancies, particularly IPA and PJP. Standardized procedures for BAL sampling should be continually revised to exclude unnecessary microbiological tests. PMID:27739337

  19. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation.

    PubMed

    van Burik, Jo-Anne H; Ratanatharathorn, Voravit; Stepan, Daniel E; Miller, Carole B; Lipton, Jeffrey H; Vesole, David H; Bunin, Nancy; Wall, Donna A; Hiemenz, John W; Satoi, Yoichi; Lee, Jeanette M; Walsh, Thomas J

    2004-11-15

    We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing <50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing <50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm [difference, 6.5%]; 95% confidence interval, 0.9%-12%; P=.03). This randomized trial demonstrates the efficacy of an echinocandin for antifungal prophylaxis in neutropenic patients.

  20. Epidemiology and outcomes of patients with invasive mould infections: a retrospective observational study from a single centre (2005-2009).

    PubMed

    Klingspor, Lena; Saaedi, Baharak; Ljungman, Per; Szakos, Attila

    2015-08-01

    Invasive mould infection (IMI) is an important cause of morbidity and mortality in immunocompromised patients. However, Swedish epidemiology data are lacking. The aim of this study was to investigate the epidemiology and outcome of IMI. Cases of proven/probable IMI at Karolinska University Hospital, Stockholm, from 2005 to 2009, were included. A total of 100 patients with 104 episodes of IMI were enrolled. Identified isolates included 101 mould isolates. The majority of the isolates were Aspergillus spp. (74.3%), followed by Mucorales spp. (13.9%), Fusarium spp. (4.9%) and other mould spp. (6.9%). In 13% of the episodes, more than one mould caused the IMI. The lung was most often affected (88.5%). The most frequent underlying disease was haematological malignancies (70%). Following diagnosis, 83.7% initially received antifungal monotherapy, 9.6% received combination therapy and 6.7% no treatment. The overall 90-day and 1-year overall survival was 49% and 46% respectively. Survival at 90 days post diagnosis was 71.4% in the solid tumour cohort, 62.5% in patients with solid organ transplants, 43.5% in haematological malignancy (HMs) and 37% in those undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Overall survival was poor in the studied cohort, but is variable among different host categories, with particular opportunities for improvement in patients with underlying HMs and allogeneic HSCT.

  1. pH gradient and distribution of streptococci, lactobacilli, prevotellae, and fusobacteria in carious dentine

    PubMed Central

    Nguyen, Ky-Anh T.; Browne, Gina V.; Simonian, Mary; Hunter, Neil

    2013-01-01

    Objectives Caries process comprises acidogenic and aciduric bacteria that are responsible for lowering the pH and subsequent destruction of hydroxyapatite matrix in enamel and dentine. The aim of this study was to identify the correlation between the pH gradient of a carious lesion and proportion and distribution of four bacterial genera; lactobacilli, streptococci, prevotellae, and fusobacteria with regard to total load of bacteria. Materials and methods A total of 25 teeth with extensive dentinal caries were sampled in sequential layers. Using quantitative real-time PCR of 16S rRNA gene, we quantified the total load of bacteria as well as the proportion of the abovementioned genera following pH measurement of each sample with a fine microelectrode. Results We demonstrated the presence of a pH gradient across the lesion with a strong association between the quantity of lactobacilli and the lowest pH range (pH 4.5–5.0; p = 0.003). Streptococci had a tendency to occupy the most superficial aspect of the carious lesion but showed no correlation to any pH value. Prevotellae showed clear preference for the pH range 5.5–6.0 (p = 0.042). The total representation of these four genera did not reach more than one quarter of the total bacterial load in most carious samples. Conclusion We revealed differential colonization behavior of bacteria with respect to pH gradient and a lower than expected abundance of lactobacilli and streptococci in established carious lesions. The data indicate the numerical importance of relatively unexplored taxa within the lesion of dentinal caries. Clinical relevance The gradient nature of pH in the lesion as well as colonization difference of examined bacterial taxa with reference to pH provides a new insight in regard to conservative caries management. PMID:23771212

  2. Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease

    PubMed Central

    Tran, H. Luu; Mahmoudjafari, Zahra; Rockey, Michelle; Henry, Dave; Grauer, Dennis; Aljitawi, Omar; Abhyankar, Sunil; Ganguly, Siddhartha; Lin, Tara; McGuirk, Joseph

    2015-01-01

    Background Invasive fungal infections remain problematic in immunosuppressed allogeneic stem cell transplant recipients and the use of corticosteroids for the treatment of graft-versus-host-disease can increase the risk three-fold. Although antifungal prophylaxis has been shown to decrease the incidence of infection, the optimal antifungal prophylactic regimen in this patient population has yet to be identified. Since early diagnosis of fungal infections might not be possible and the treatment of established fungal infections might be difficult and associated with high infection related mortality, prevention has become an important strategy in reducing overall morbidity and mortality. While triazoles are the preferred agents, some patients are unable to tolerate them and an alternative drug is warranted. Objectives To assess the tolerability of once weekly liposomal amphotericin B as a prophylactic strategy in patients undergoing stem cell transplantation by evaluating any adverse events leading to its discontinuation. In terms of efficacy, to also compare the outcome and incidence of invasive fungal infections in patients who received amphotericin B, triazoles, and echinocandins. Results A total of 101 allogeneic transplant recipients receiving corticosteroids for the treatment of graft-versus-host-disease and antifungal prophylaxis were evaluated from August 2009 to September 2012. Liposomal amphotericin B 3 mg/kg intravenous once weekly was found to be well-tolerated. The incidence of invasive fungal infections was 19%, 17%, and 7% in the liposomal amphotericin B, echinocandin, and triazole groups, respectively. Two deaths occurred in the liposomal amphotericin B group and one death occurred in the echinocandin group. None of the deaths were fungal infection-related. Conclusion Antifungal prophylaxis with liposomal amphotericin B was well-tolerated but the incidence of invasive fungal infections in patients receiving liposomal amphotericin B was higher than

  3. Clinical and epidemiological factors associated with methicillin resistance in community-onset invasive Staphylococcus aureus infections: prospective multicenter cross-sectional study in Korea.

    PubMed

    Kim, Eu Suk; Kim, Hong Bin; Kim, Gayeon; Kim, Kye-Hyung; Park, Kyung-Hwa; Lee, Shinwon; Choi, Young Hwa; Yi, Jongyoun; Kim, Chung Jong; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Kim, Nam-Joong; Lee, Yeong-Seon; Oh, Myoung-Don

    2014-01-01

    Successful empirical therapy of Staphylococcus aureus infections requires the ability to predict methicillin resistance. Our aim was to identify predictors of methicillin resistance in community-onset (CO) invasive S. aureus infections. Sixteen hospitals across Korea participated in this study from May to December 2012. We prospectively included cases of S. aureus infection in which S. aureus was isolated from sterile clinical specimens ≤ 72 hours after hospitalization. Clinical and epidemiological data were gathered and compared in methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) cases. Community-associated (CA) infections were defined as in previous studies. In total, there were 786 cases of community-onset S. aureus infection, 102 (13.0%) of which were CA-MRSA. In addition to known risk factors, exposure to 3rd generation cephalosporins in the past 6 months [odds ratio (OR), 1.922; 95% confidence interval (CI), 1.176-3.142] and close contact with chronically ill patients in the past month (OR, 2.647; 95% CI, 1.189-5.891) were independent risk factors for MRSA infection. However, no clinical predictors of CA-MRSA were identified. Methicillin resistance, CO infection, and appropriateness of empirical antibiotics were not significantly related to 30-day mortality. MRSA infection should be suspected in patients recently exposed to 3rd generation cephalosporins or chronically-ill patients. There were no reliable predictors of CA-MRSA infection, and mortality was not affected by methicillin resistance.

  4. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology

    PubMed Central

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-01-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system. PMID:25179236

  5. Chronic obstructive pulmonary disease and asthma-associated Proteobacteria, but not commensal Prevotella spp., promote Toll-like receptor 2-independent lung inflammation and pathology.

    PubMed

    Larsen, Jeppe M; Musavian, Hanieh S; Butt, Tariq M; Ingvorsen, Camilla; Thysen, Anna H; Brix, Susanne

    2015-02-01

    Recent studies of healthy human airways have revealed colonization by a distinct commensal bacterial microbiota containing Gram-negative Prevotella spp. However, the immunological properties of these bacteria in the respiratory system remain unknown. Here we compare the innate respiratory immune response to three Gram-negative commensal Prevotella strains (Prevotella melaninogenica, Prevotella nanceiensis and Prevotella salivae) and three Gram-negative pathogenic Proteobacteria known to colonize lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma (Haemophilus influenzae B, non-typeable Haemophilus influenzae and Moraxella catarrhalis). The commensal Prevotella spp. and pathogenic Proteobacteria were found to exhibit intrinsic differences in innate inflammatory capacities on murine lung cells in vitro. In vivo in mice, non-typeable H. influenzae induced severe Toll-like receptor 2 (TLR2)-independent COPD-like inflammation characterized by predominant airway neutrophilia, expression of a neutrophilic cytokine/chemokine profile in lung tissue, and lung immunopathology. In comparison, P. nanceiensis induced a diminished neutrophilic airway inflammation and no detectable lung pathology. Interestingly, the inflammatory airway response to the Gram-negative bacteria P. nanceiensis was completely TLR2-dependent. These findings demonstrate weak inflammatory properties of Gram-negative airway commensal Prevotella spp. that may make colonization by these bacteria tolerable by the respiratory immune system.

  6. Invaded invaders: Infection of invasive Brown Treesnakes on Guam by an exotic larval cestode with a life cycle comprised of non-native hosts

    USGS Publications Warehouse

    Holldorf, Elden T; Siers, Shane R; Richmond, Jonathan Q.; Klug, Page E.; Reed, Robert

    2015-01-01

    We discovered that B. irregularis inhabiting a small area of forested habitat in a freshwater watershed on Guam are often infected by a novel parasite of Asian origin. While further work is needed, this species of Spirometra, itself a non-native species, likely depends on a suite of recently introduced hosts from different parts of the world to complete the life cycle. This baseline study provides little evidence of any effects on host fitness, but additional data are needed to more thoroughly explore the consequences of infection in this invasive snake population.

  7. [Recommendations of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the prevention of invasive fungal infection due to filamentous fungi].

    PubMed

    Ruiz-Camps, Isabel; Aguado, Jose María; Almirante, Benito; Bouza, Emilio; Ferrer Barbera, Carmen; Len, Oscar; López-Cerero, Lorena; Rodríguez-Tudela, Juan Luis; Ruiz, Miguel; Solé, Amparo; Vallejo, Carlos; Vázquez, Lourdes; Zaragoza, Rafael; Cuenca-Estrella, Manuel

    2010-03-01

    Invasive fungal infections (IFI) due to filamentous fungi still have high rates of mortality associated with the difficulties of early detection of the infection and their therapeutic limitations. Consequently, a useful approach is to prevent patients at risk of fungal infection from getting in contact with conidia of Aspergillus and other mould species. This document describes the recommendations to prevent IFI due to filamentous fungi, prepared by Spanish experts from different medical and professional fields. The paper reviews the incidence of the IFI in different risk populations and the questions related to environmental measures of prevention, control of hospital infections, additional procedures for prevention, prevention of IFI outside hospitals, as well as antifungal prophylaxis.

  8. Fitness of wAlbB Wolbachia Infection in Aedes aegypti: Parameter Estimates in an Outcrossed Background and Potential for Population Invasion

    PubMed Central

    Axford, Jason K.; Ross, Perran A.; Yeap, Heng Lin; Callahan, Ashley G.; Hoffmann, Ary A.

    2016-01-01

    Wolbachia endosymbionts are potentially useful tools for suppressing disease transmission by Aedes aegypti mosquitoes because Wolbachia can interfere with the transmission of dengue and other viruses as well as causing deleterious effects on their mosquito hosts. Most recent research has focused on the wMel infection, but other infections also influence viral transmission and may spread in natural populations. Here, we focus on the wAlbB infection in an Australian outbred background and show that this infection has many features that facilitate its invasion into natural populations including strong cytoplasmic incompatibility, a lack of effect on larval development, an equivalent mating success to uninfected males and perfect maternal transmission fidelity. On the other hand, the infection has deleterious effects when eggs are held in a dried state, falling between wMel and the more virulent wMelPop Wolbachia strains. The impact of this infection on lifespan also appears to be intermediate, consistent with the observation that this infection has a titer in adults between wMel and wMelPop. Population cage experiments indicate that the wAlbB infection establishes in cages when introduced at a frequency of 22%, suggesting that this strain could be successfully introduced into populations and subsequently persist and spread. PMID:26711515

  9. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    PubMed

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  10. Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

    PubMed

    Zhao, Ying Jiao; Khoo, Ai Leng; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

    2015-11-02

    Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care

  11. Impact of CYP2C19 genetic polymorphisms on voriconazole dosing and exposure in adult patients with invasive fungal infections.

    PubMed

    Lamoureux, Fabien; Duflot, Thomas; Woillard, Jean-Baptiste; Metsu, David; Pereira, Tony; Compagnon, Patricia; Morisse-Pradier, Hélène; El Kholy, Mona; Thiberville, Luc; Stojanova, Jana; Thuillez, Christian

    2016-02-01

    Voriconazole (VCZ) use is limited by its narrow therapeutic range and significant interpatient variability in exposure. This study aimed to assess (i) the impact of CYP2C19 genotype on VCZ exposure and (ii) the doses required to achieve the therapeutic range in adult patients with invasive fungal infections (IFIs). Therapeutic drug monitoring (TDM) of VCZ, based on trough concentration measurement, and CYP2C19 genotyping were used to guide VCZ dosing in Caucasian patients with IFIs. The two common polymorphisms in Caucasians (CYP2C19*2 and *17), associated with decreased or increased CYP2C19 activity, respectively, were correlated with the daily VCZ dose, pharmacokinetic parameters and concentration-to-dose ratio. In total, 111 trough concentration measurements from 35 genotyped patients were analysed using linear mixed-effect models. The mean VCZ doses required to achieve target concentrations were significantly higher in CYP2C19*17 carriers compared with CYP2C19*1/*1 individuals (P<0.001): 2.57±0.25mg/kg twice daily in CYP2C19*1/*1 patients versus 3.94±0.39mg/kg and 6.75±0.54mg/kg in *1/*17 and *17/*17 patients, respectively. In addition, exposure to VCZ correlated with the CYP2C19*17 variant. Indices of exposure for CYP2C19*2 carriers were in line with the functional effect of this polymorphism compared with CYP2C19*1/*1 individuals, however comparisons of doses required to achieve target concentrations were not statistically different. The CYP2C19*17 allele predicted both VCZ exposure and dose required to achieve effective and non-toxic concentrations. CYP2C19 genotyping appears useful to guide VCZ initial dosing when coupled with TDM and to explain subtherapeutic concentrations frequently observed in clinical practice.

  12. Susceptibility trends including emergence of linezolid resistance among coagulase-negative staphylococci and meticillin-resistant Staphylococcus aureus from invasive infections.

    PubMed

    Decousser, Jean-Winoc; Desroches, Marine; Bourgeois-Nicolaos, Nadège; Potier, Julien; Jehl, François; Lina, Gérard; Cattoir, Vincent; Vandenesh, François; Doucet-Populaire, Florence

    2015-12-01

    Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern.

  13. Loss of microbial (pathogen) infections associated with recent invasions of the red imported fire ant Solenopsis invicta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Loss of natural enemies during colonization is a prominent hypothesis explaining enhanced performance of invasive species in introduced areas. Numerous studies have tested this enemy release hypothesis in a wide range of taxa but few studies have focused on invasive ants. We conducted extensive surv...

  14. Increased Risk of Group B Streptococcus Invasive Infection in HIV-Exposed but Uninfected Infants: A Review of the Evidence and Possible Mechanisms

    PubMed Central

    Dauby, Nicolas; Chamekh, Mustapha; Melin, Pierrette; Slogrove, Amy L.; Goetghebuer, Tessa

    2016-01-01

    Group B Streptococcus (GBS) is a major cause of neonatal sepsis and mortality worldwide. Studies from both developed and developing countries have shown that HIV-exposed but uninfected (HEU) infants are at increased risk of infectious morbidity, as compared to HIV-unexposed uninfected infants (HUU). A higher susceptibility to GBS infections has been reported in HEU infants, particularly late-onset diseases and more severe manifestations of GBS diseases. We review here the possible explanations for increased susceptibility to GBS infection. Maternal GBS colonization during pregnancy is a major risk factor for early-onset GBS invasive disease, but colonization rates are not higher in HIV-infected compared to HIV-uninfected pregnant women, while selective colonization with more virulent strains in HIV-infected women is suggested in some studies. Lower serotype-specific GBS maternal antibody transfer and quantitative and qualitative defects of innate immune responses in HEU infants may play a role in the increased risk of GBS invasive disease. The impact of maternal antiretroviral treatment and its consequences on immune activation in HEU newborns are important to study. Maternal immunization presents a promising intervention to reduce GBS burden in the growing HEU population. PMID:27899925

  15. Implementation of a Pan-Genomic Approach to Investigate Holobiont-Infecting Microbe Interaction: A Case Report of a Leukemic Patient with Invasive Mucormycosis

    PubMed Central

    Shelburne, Samuel A.; Beird, Hannah C.; Tarrand, Jeffrey; Galloway-Peña, Jessica; Albert, Nathan; Chemaly, Roy F.; Ghantoji, Shashank S.; Marsh, Lisa; Pemmaraju, Naveen; Andreeff, Michael; Shpall, Elizabeth J.; Wargo, Jennifer A.; Rezvani, Katayoun; Alousi, Amin; Bruno, Vincent M.; Futreal, Phillip A.; Petrosino, Joseph F.; Kontoyiannis, Dimitrios P.

    2015-01-01

    Disease can be conceptualized as the result of interactions between infecting microbe and holobiont, the combination of a host and its microbial communities. It is likely that genomic variation in the host, infecting microbe, and commensal microbiota are key determinants of infectious disease clinical outcomes. However, until recently, simultaneous, multiomic investigation of infecting microbe and holobiont components has rarely been explored. Herein, we characterized the infecting microbe, host, micro- and mycobiomes leading up to infection onset in a leukemia patient that developed invasive mucormycosis. We discovered that the patient was infected with a strain of the recently described Mucor velutinosus species which we determined was hypervirulent in a Drosophila challenge model and has a predisposition for skin dissemination. After completing the infecting M. velutinosus genome and genomes from four other Mucor species, comparative pathogenomics was performed and assisted in identifying 66 M. velutinosus-specific putatively secreted proteins, including multiple novel secreted aspartyl proteinases which may contribute to the unique clinical presentation of skin dissemination. Whole exome sequencing of the patient revealed multiple non-synonymous polymorphisms in genes critical to control of fungal proliferation, such as TLR6 and PTX3. Moreover, the patient had a non-synonymous polymorphism in the NOD2 gene and a missense mutation in FUT2, which have been linked to microbial dysbiosis and microbiome diversity maintenance during physiologic stress, respectively. In concert with host genetic polymorphism data, the micro- and mycobiome analyses revealed that the infection developed amid a dysbiotic microbiome with low α-diversity, dominated by staphylococci. Additionally, longitudinal mycobiome data showed that M. velutinosus DNA was detectable in oral samples preceding disease onset. Our genome-level study of the host-infecting microbe-commensal triad extends the

  16. Detection of invasive infection caused by Fusarium solani and non-Fusarium solani species using a duplex quantitative PCR-based assay in a murine model of fusariosis.

    PubMed

    Bernal-Martínez, Leticia; Buitrago, Maria J; Castelli, Maria V; Rodríguez-Tudela, Juan L; Cuenca-Estrella, Manuel

    2012-04-01

    A duplex Real Time PCR (RT-PCR) assay for detecting DNA of members of the genus Fusarium has been developed and validated by using two mouse models of invasive infection. The duplex RT-PCR technique employed two specific molecular beacon probes targeting a highly conserved region of the fungal rDNA gene. This technique showed a detection limit of 10 fg DNA per μl of sample and a specificity of 100%. The sensitivity in a total of 48 samples from a murine model of Fusarium solani infection was 93.9% for lung tissues and 86.7% for serum samples. In comparison, the sensitivity in a total of 45 samples of a F. oxysporum murine model infection was 87% for lung tissues and 42.8% for serum samples. This molecular technique could be a reliable method for the quantification and the evaluation of the disease in animal models and for the clinical diagnosis of fusariosis.

  17. Effect of the corn silage to grass silage ratio and feed particle size of diets for ruminants on the ruminal Bacteroides-Prevotella community in vitro.

    PubMed

    Witzig, M; Boguhn, J; Kleinsteuber, S; Fetzer, I; Rodehutscord, M

    2010-08-01

    This study examined whether different corn silage to grass silage ratios in ruminant rations and different grinding levels of the feed affect the composition of the ruminal Bacteroides-Prevotella community in vitro. Three diets, composed of 10% soybean meal as well as of different corn silage and grass silage proportions, were ground through 1mm or 4mm screened sieves and incubated in a semi-continuous rumen simulation system. On day 14 of the incubation microbes were harvested by centrifugation from the liquid effluent of fermenter vessels. Microbial DNA was extracted for single strand conformation polymorphism (SSCP) analysis of 16S rRNA genes followed by sequencing of single SSCP bands. Fluorescence in situ hybridization (FISH) and real-time quantitative (q) PCR were used to quantify differences in the relative abundance of Bacteroides-Prevotella and Prevotella bryantii. SSCP profiles revealed a significant influence of the forage source as well as of the feed particle size on the community structure of the Bacteroides-Prevotella group. Different, phylogenetically distinct, so far uncultured Prevotella species were detected by sequence analysis of several treatment-dependent occurring SSCP bands indicating different nutritional requirements of these organisms for growth. No quantitative differences in the occurrence of Bacteroides-Prevotella-related species were detected between diets by FISH with probe BAC303. However, real-time qPCR data revealed a higher abundance of P. bryantii with increasing grass silage to corn silage ratio, thus again indicating changes within the community composition of the Bacteroides-Prevotella group. As P. bryantii possesses high proteolytic activity its higher abundance may have been caused by the higher contents of crude protein in the grass silage containing diets. To conclude, results of this study show an influence of the forage source on the ruminal community of Bacteroides-Prevotella. Furthermore, they suggest an effect of

  18. Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy☆,☆☆,★,★★

    PubMed Central

    Neofytos, Dionissios; Lu, Kit; Hatfield-Seung, Amy; Blackford, Amanda; Marr, Kieren A.; Treadway, Suzanne; Ostrander, Darin; Nussenblatt, Veronique; Karp, Judith

    2014-01-01

    This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (≥50 years; hazard ratio [HR]: 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series. PMID:23142166

  19. Characterization of sil in Invasive Group A and G Streptococci: Antibodies against Bacterial Pheromone Peptide SilCR Result in Severe Infection

    PubMed Central

    Michael-Gayego, Ayelet; Dan-Goor, Mary; Jaffe, Joseph; Hidalgo-Grass, Carlos

    2013-01-01

    Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus, sil, was identified in GAS. sil encodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found that sil is present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that contained sil expressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that the sil locus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria. PMID:23980111

  20. Mammary Gland Pathology Subsequent to Acute Infection with Strong versus Weak Biofilm Forming Staphylococcus aureus Bovine Mastitis Isolates: A Pilot Study Using Non-Invasive Mouse Mastitis Model

    PubMed Central

    Gogoi-Tiwari, Jully; Williams, Vincent; Waryah, Charlene Babra; Costantino, Paul; Al-Salami, Hani; Mathavan, Sangeetha; Wells, Kelsi; Tiwari, Harish Kumar; Hegde, Nagendra; Isloor, Shrikrishna; Al-Sallami, Hesham; Mukkur, Trilochan

    2017-01-01

    Background Biofilm formation by Staphylococcus aureus is an important virulence attribute because of its potential to induce persistent antibiotic resistance, retard phagocytosis and either attenuate or promote inflammation, depending upon the disease syndrome, in vivo. This study was undertaken to evaluate the potential significance of strength of biofilm formation by clinical bovine mastitis-associated S. aureus in mammary tissue damage by using a mouse mastitis model. Methods Two S. aureus strains of the same capsular phenotype with different biofilm forming strengths were used to non-invasively infect mammary glands of lactating mice. Biofilm forming potential of these strains were determined by tissue culture plate method, ica typing and virulence gene profile per detection by PCR. Delivery of the infectious dose of S. aureus was directly through the teat lactiferous duct without invasive scraping of the teat surface. Both bacteriological and histological methods were used for analysis of mammary gland pathology of mice post-infection. Results Histopathological analysis of the infected mammary glands revealed that mice inoculated with the strong biofilm forming S. aureus strain produced marked acute mastitic lesions, showing profuse infiltration predominantly with neutrophils, with evidence of necrosis in the affected mammary glands. In contrast, the damage was significantly less severe in mammary glands of mice infected with the weak biofilm-forming S. aureus strain. Although both IL-1β and TNF-α inflammatory biomarkers were produced in infected mice, level of TNF-α produced was significantly higher (p<0.05) in mice inoculated with strong biofilm forming S. aureus than the weak biofilm forming strain. Conclusion This finding suggests an important role of TNF-α in mammary gland pathology post-infection with strong biofilm-forming S. aureus in the acute mouse mastitis model, and offers an opportunity for the development of novel strategies for reduction of

  1. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A

    PubMed Central

    Mallorquí-Fernández, Noemí; Manandhar, Surya P.; Mallorquí-Fernández, Goretti; Usón, Isabel; Wawrzonek, Katarzyna; Kantyka, Tomasz; Solà, Maria; Thøgersen, Ida B.; Enghild, Jan J.; Potempa, Jan; Gomis-Rüth, F.Xavier

    2009-01-01

    Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defences and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and its self-processed mature form. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin and a latency flap in the zymogen. Dramatic rearrangement of up to 20Å of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain. PMID:17993455

  2. Utility of enzymes from Fibrobacter succinogenes and Prevotella ruminicola as detergent additives.

    PubMed

    Chen, Bo-Yuan; Wang, Han-Tsung

    2008-08-01

    In this study, we investigated the application of cellulase and protease purified from rumen bacteria as detergent additives. Cellulase and protease were purified from the rumen cellulytic bacteria Fibrobacter succinogenes S85, and Prevotella ruminicola 23, respectively. An inhibitor test indicated that the purified protease belongs to the category of serine proteases and metalloproteases. Both the enzymes were effective at a high temperature (50 degrees C) and neutral pH (pH 7-8), but the protease activity increased with the increase in temperature and pH. The purified protease was treated with ten types of surfactants/detergents; it was found to retain over 60% of its activity in the presence of anionic and nonionic detergents. The cellulose plus protease combination was still effective after treatment with Triton X-100 and Tween 80, but the residual activity was low after treatment with Tween 20 than that after treatment with other nonionic detergents. Washing tests indicated that enzyme addition produced no significant improvement in the removal of grass stains, but individual enzyme addition in surfactants/detergents, especially in nonionic detergents, could improve the washing performance of the detergents by improving its ability to remove blood stains. This suggested that the surfactant/detergent class, enzyme properties, and the mixing ratio of ingredients should be considered simultaneously to enhance the washing performance.

  3. A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A.

    PubMed

    Mallorquí-Fernández, Noemí; Manandhar, Surya P; Mallorquí-Fernández, Goretti; Usón, Isabel; Wawrzonek, Katarzyna; Kantyka, Tomasz; Solà, Maria; Thøgersen, Ida B; Enghild, Jan J; Potempa, Jan; Gomis-Rüth, F Xavier

    2008-02-01

    Prevotella intermedia is a major periodontopathogen contributing to human gingivitis and periodontitis. Such pathogens release proteases as virulence factors that cause deterrence of host defenses and tissue destruction. A new cysteine protease from the cysteine-histidine-dyad class, interpain A, was studied in its zymogenic and self-processed mature forms. The latter consists of a bivalved moiety made up by two subdomains. In the structure of a catalytic cysteine-to-alanine zymogen variant, the right subdomain interacts with an unusual prodomain, thus contributing to latency. Unlike the catalytic cysteine residue, already in its competent conformation in the zymogen, the catalytic histidine is swung out from its active conformation and trapped in a cage shaped by a backing helix, a zymogenic hairpin, and a latency flap in the zymogen. Dramatic rearrangement of up to 20A of these elements triggered by a tryptophan switch occurs during activation and accounts for a new activation mechanism for proteolytic enzymes. These findings can be extrapolated to related potentially pathogenic cysteine proteases such as Streprococcus pyogenes SpeB and Porphyromonas gingivalis periodontain.

  4. Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-15

    Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-κB, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease.

  5. Identification and functional analysis of the gene cluster for fructan utilization in Prevotella intermedia.

    PubMed

    Fuse, Haruka; Fukamachi, Haruka; Inoue, Mitsuko; Igarashi, Takeshi

    2013-02-25

    Fructanase enzymes hydrolyze the β-2,6 and β-2,1 linkages of levan and inulin fructans, respectively. We analyzed the influence of fructan on the growth of Prevotella intermedia. The growth of P. intermedia was enhanced by addition of inulin, implying that P. intermedia could also use inulin. Based on this finding, we identified and analyzed the genes encoding a putative fructanase (FruA), sugar transporter (FruB), and fructokinase (FruK) in the genome of strain ATCC25611. Transcript analysis by RT-PCR showed that the fruABK genes were co-transcribed as a single mRNA and semi-quantitative analysis confirmed that the fruA gene was induced in response to fructose and inulin. Recombinant FruA and FruK were purified and characterized biochemically. FruA strongly hydrolyzed inulin, with slight degradation of levan via an exo-type mechanism, revealing that FruA is an exo-β-d-fructanase. FruK converted fructose to fructose-6-phosphate in the presence of ATP, confirming that FruK is an ATP-dependent fructokinase. These results suggest that P. intermedia can utilize fructan as a carbon source for growth, and that the fructanase, sugar transporter, and fructokinase proteins we identified are involved in this fructan utilization.

  6. Prevotella intermedia upregulates MMP-1 and MMP-8 expression in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; Shu, Lei; Fu, Shan-Min; Liu, Bin; Xu, Xiu-Li; Wu, Jun-Zheng

    2009-10-01

    Prevotella intermedia, a major periodontal pathogen, plays important roles in the initiation and development of periodontitis by stimulating the release of proinflammatory cytokines, proteinases and matrix metalloproteinases (MMPs). Our previous study demonstrated that P. intermedia induced MMP-9 expression in human periodontal ligament (hPDL) cells. In this study, we examined the effects of P. intermedia on other MMPs' expression. Semi-quantitative reverse transcriptase (RT)-PCR analysis revealed that P. intermedia ATCC 25611 supernatant increased MMP-1 and MMP-8 mRNA expression in a concentration- and time-dependent manner. Enzyme-linked immunosorbent assay and Western blot results confirmed the RT-PCR results at the protein level. Cyclooxygenase inhibitor indomethacin significantly attenuated the upregulatory effects of P. intermedia on MMP-1 and MMP-8 expression. Extracellular signal-related kinase inhibitor PD98059 and c-Jun N-terminal kinase inhibitor SP600125 considerably decreased the upregulated level of MMP-1, whereas p38 inhibitor SB203580 markedly inhibited MMP-8 expression, suggesting that prostaglandin E(2) and mitogen-activated protein kinase signaling pathways are involved in P. intermedia-induced MMP-1 and MMP-8 upregulation. Our results indicate that P. intermedia might contribute to periodontal connective tissue and bone matrix destruction through upregulating MMP production.

  7. The effects of tetracycline, minocycline, doxycycline and ofloxacin on Prevotella intermedia biofilm.

    PubMed

    Takahashi, N; Ishihara, K; Kimizuka, R; Okuda, K; Kato, T

    2006-12-01

    Prevotella intermedia, a black-pigmented, anaerobic, gram-negative bacterium, is associated with various type of periodontitis. Antibiotic treatments via a systemic or local route have been reported as being useful for treating periodontal disease. The purpose of this study was to examine the effects of four antibiotics, tetracycline (TET), minocycline (MINO), doxycycline (DOXY) and ofloxacin (OFLX) on P. intermedia biofilms at minimum inhibitory concentrations (MIC) from one-fold to 100-fold. MICs were determined for planktonic cells. Biofilm formation was determined with the crystal violet stain method and the bioactivities in the biofilms were determined with the adenosine triphosphate (ATP) -bioluminescent assay using a 96-well culture plate. At one-fold MIC, DOXY inhibited biofilm formation by P. intermedia ATCC 25611. Other antibiotics at one-fold MIC had no effects on the biofilm formation of tested bacterial strains. In P. intermedia ATCC 25611 biofilms, all the antibiotics tested showed inhibitory activities at five- to 100-fold MICs. In the biofilms of P. intermedia strains, except ATCC 25611, treated with three tetracycline antibiotics, the bioactivities were significantly increased, indicating the difficulties involved in designing antibiotic therapy for periodontal disease.

  8. Effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection

    PubMed Central

    Zhang, Yu; Gu, Fang; Wang, Fengxian; Zhang, Yuanda

    2016-01-01

    Objective: To evaluate the effects of early enteral nutrition on the gastrointestinal motility and intestinal mucosal barrier of patients with burn-induced invasive fungal infection. Methods: A total of 120 patients with burn-induced invasive fungal infection were randomly divided into an early enteral nutrition (EN) group and a parenteral nutrition (PN) group (n=60). The patients were given nutritional support intervention for 14 days, and the expression levels of serum transferrin, albumin, total protein, endotoxin, D-lactic acid and inflammatory cytokines were detected on the 1st, 7th and 14th days respectively. Results: As the treatment progressed, the levels of serum transferrin, albumin and total protein of the EN group were significantly higher than those of the PN group (P<0.05), while the levels of serum endotoxin and D-lactic acid of the form group were significantly lower (P<0.05). After treatment, the expression levels of IL-6 and TNF-α were decreased in the EN group, which were significantly different from those of the PN group (P<0.05). During treatment, the incidence rates of complications such as abdominal distension, diarrhea, sepsis, nausea, vomiting and gastric retention were similar. The mean healing time of wound surface was 9.34±0.78 days in the EN group and 12.46±2.19 days in the PN group, i.e. such time of the former was significantly shorter than that of the latter (P<0.05). Conclusion: Treating patients having burn-induced invasive fungal infection by early enteral nutrition support with arginine can safely alleviate malnutrition and stress reaction, strengthen cellular immune function and promote wound healing, thereby facilitating the recovery of gastrointestinal motility and the function of intestinal mucosal barrier. PMID:27375697

  9. The invA gene of Brucella melitensis is involved in intracellular invasion and is required to establish infection in a mouse model.

    PubMed

    Alva-Pérez, Jorge; Arellano-Reynoso, Beatriz; Hernández-Castro, Rigoberto; Suárez-Güemes, Francisco

    2014-05-15

    Some of the mechanisms underlying the invasion and intracellular survival of B. melitensis are still unknown, including the role of a subfamily of NUDIX enzymes, which have been described in other bacterial species as invasins and are present in Brucella spp. We have generated a mutation in the coding gene of one of these proteins, the invA gene (BMEI0215) of B. melitensis strain 133, to understand its role in virulence. HeLa cell invasion results showed that mutant strain survival was decreased 5-fold compared with that of the parental strain at 2 h pi (P<0.001). In a goat macrophage infection assay, mutant strain replication was 8-fold less than in the parental strain at 24 h pi (P<0.001); yet, at 48 h pi, no significant differences in intracellular replication were observed. Additionally, colocalization of the invA mutant with calregulin was significantly lower at 24 h pi compared with that of the parental strain. Furthermore, the mutant strain exhibited a low level of colocalization with cathepsin D, which was similar to the parental strain colocalization at 24 h pi. In vivo infection results demonstrated that spleen colonization was significantly lower with the mutant than with the parental strain. The immune response, measured in terms of antibody switching and IFN-γ transcription, was similar for Rev1 and infection with the mutant, although it was lower than the immune response elicited by the parental strain. Consequently, these results indicate that the invA gene is important during invasion but not for intracellular replication. Additionally, mutation of the invA gene results in in vivo attenuation.

  10. Cluster of fatal group A streptococcal emm87 infection within a single family: molecular basis for invasion and transmission.

    PubMed

    Flores, Anthony R; Luna, Ruth Ann; Runge, Jessica K; Shelburne, Samuel A; Baker, Carol J

    2017-04-05

    Hypervirulent disease due to group A Streptococcus (GAS) can result from strains with mutations that enhance virulence gene expression but reduce subsequent transmission. We used whole genome sequencing to investigate intra-familial spread between 4 siblings of a hypervirulent GAS strain resulting in a fatality. All invasive and pharyngeal GAS isolates had an identical mutation in a gene encoding a key regulatory protein that yielded a hyperinvasive phenotype. These data challenge the prevailing theory of reduced transmission induced by mutations that lead to hypervirulent GAS by showing that spread of hypervirulent GAS may lead to clusters of invasive disease.

  11. Nonsurgical endodontic therapy along with minimal invasive treatment utilizing Bhasker's hypothesis for the management of infected radicular cystic lesion: A rare case report

    PubMed Central

    Salaria, Sanjeev Kumar; Kamra, Shilpa; Ghuman, Simrat Kaur; Sharma, Garima

    2016-01-01

    Radicular cyst (RC) is the most common odontogenic cyst of inflammatory origin affecting the jaws; involves the roots of the carious or traumatic non-vital tooth. Different therapeutic modalities, such as nonsurgical endodontic therapy or surgical enucleation with primary closure, decompression etc., were proposed for the management of such lesions. Presenting a case of a 28-year-old otherwise healthy male patient who reported with pain and swelling with respect to tooth #41, 31. Diagnosis of infected RC at a rare location was established on the basis of clinical, radiographical and fine needle aspiration cytological examination. Looking after the clinical characteristics, origin, extension, size of cystic lesion and patient cooperation; nonsurgical endodontic therapy utilizing Bhasker's hypothesis was opted. One year post-operative result suggested that nonsurgical endodontic therapy along with minimally invasive treatment utilizing Bhasker's hypothesis is an effective tool to transform infected radicular cystic lesion to healthy periapical periodontal tissue. PMID:27994430

  12. DHA suppresses Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

    PubMed

    Choi, Eun-Young; Jin, Ji-Young; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

    2014-04-14

    Several reports have indicated that dietary intake of DHA is associated with lower prevalence of periodontitis. In the present study, we investigated the effect of DHA on the production of proinflammatory mediators in murine macrophage-like RAW264.7 cells stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. LPS was isolated from lyophilised P. intermedia ATCC 25,611 cells using the standard hot-phenol-water protocol. Culture supernatants were collected and assayed for NO, IL-1β and IL-6. Real-time PCR analysis was carried out to detect the expression of inducible NO synthase (iNOS), IL-1β, IL-6 and haeme oxygenase-1 (HO-1) mRNA. Immunoblot analysis was carried out to quantify the expression of iNOS and HO-1 protein and concentrations of signalling proteins. DNA-binding activities of NF-κB subunits were determined using an ELISA-based assay kit. DHA significantly attenuated the production of NO, IL-1β and IL-6 at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. DHA induced the expression of HO-1 in cells treated with P. intermedia LPS. Selective inhibition of HO-1 activity by tin protoporphyrin IX significantly mitigated the inhibitory effects of DHA on LPS-induced NO production. DHA significantly attenuated the phosphorylation of c-Jun N-terminal kinase induced by LPS. In addition, DHA suppressed the transcriptional activity of NF-κB by regulating the nuclear translocation and DNA-binding activity of NF-κB p50 subunit and inhibited the phosphorylation of signal transducer and activator of transcription 1. Further in vivo studies are needed to better evaluate the potential of DHA in humans as a therapeutic agent to treat periodontal disease.

  13. Contribution of hly homologs to the hemolytic activity of Prevotella intermedia.

    PubMed

    Suzuki, Naoko; Fukamachi, Haruka; Arimoto, Takafumi; Yamamoto, Matsuo; Igarashi, Takeshi

    2012-06-01

    Prevotella intermedia is a periodontal pathogen that requires iron for its growth. Although this organism has hemolytic activity, the precise nature of its hemolytic substances and their associated hemolytic actions are yet to be fully determined. In the present study, we identified and characterized several putative hly genes in P. intermedia ATCC25611 which appear to encode hemolysins. Six hly genes (hlyA, B, C, D, E, and hlyI) of P. intermedia were identified by comparing their nucleotide sequences to those of known hly genes of Bacteroides fragilis NCTC9343. The hlyA-E, and hlyI genes were overexpressed individually in the non-hemolytic Escherichia coli strain JW5181 and examined its contribution to the hemolytic activity on sheep blood agar plates. E. coli cells expressing the hlyA and hlyI genes exhibited hemolytic activity under anaerobic conditions. On the other hand, only E. coli cells stably expressing the hlyA gene were able to lyse the red blood cells when cultured under aerobic conditions. In addition, expression of the hlyA and hlyI genes was significantly upregulated in the presence of red blood cells. Furthermore, we found that the growth of P. intermedia was similar in an iron-limited medium supplemented with either red blood cells or heme. Taken together, our results indicate that the hlyA and hlyI genes of P. intermedia encode putative hemolysins that appear to be involved in the lysis of red blood cells, and suggest that these hemolysins might play important roles in the iron-dependent growth of this organism.

  14. In Vitro Effects of Polyphosphate against Prevotella intermedia in Planktonic Phase and Biofilm.

    PubMed

    Jang, Eun-Young; Kim, Minjung; Noh, Mi Hee; Moon, Ji-Hoi; Lee, Jin-Yong

    2016-02-01

    Polyphosphate (polyP) has gained a wide interest in the food industry due to its potential as a decontaminating agent. In this study, we examined the effect of sodium tripolyphosphate (polyP3; Na5P3O10) against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. The MIC of polyP3 against P. intermedia ATCC 49046 determined by agar dilution method was 0.075%, while 0.05% polyP3 was bactericidal against P. intermedia in time-kill analysis performed using liquid medium. A crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that sub-MICs of polyP3 significantly decreased biofilm formation. Under the scanning electron microscope, decreased numbers of P. intermedia cells forming the biofilms were observed when the bacterial cells were incubated with 0.025% or higher concentrations of polyP3. Assessment of biofilm viability with LIVE/DEAD staining and viable cell count methods showed that 0.05% or higher concentrations of polyP3 significantly decreased the viability of the preformed biofilms in a concentration-dependent manner. The zone sizes of alpha-hemolysis formed on horse blood agar produced by P. intermedia were decreased in the presence of polyP3. The expression of the genes encoding hemolysins and the genes of the hemin uptake (hmu) locus was downregulated by polyP3. Collectively, our results show that polyP is an effective antimicrobial agent against P. intermedia in biofilms as well as planktonic phase, interfering with the process of hemin acquisition by the bacterium.

  15. Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia.

    PubMed

    Wakabayashi, Hiroyuki; Yamauchi, Koji; Kobayashi, Tetsuo; Yaeshima, Tomoko; Iwatsuki, Keiji; Yoshie, Hiromasa

    2009-08-01

    Lactoferrin (LF) is an iron-binding antimicrobial protein present in saliva and gingival crevicular fluids, and it is possibly associated with host defense against oral pathogens, including periodontopathic bacteria. In the present study, we evaluated the in vitro effects of LF-related agents on the growth and biofilm formation of two periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, which reside as biofilms in the subgingival plaque. The planktonic growth of P. gingivalis and P. intermedia was suppressed for up to 5 h by incubation with >or=130 microg/ml of human LF (hLF), iron-free and iron-saturated bovine LF (apo-bLF and holo-bLF, respectively), and >or=6 microg/ml of bLF-derived antimicrobial peptide lactoferricin B (LFcin B); but those effects were weak after 8 h. The biofilm formation of P. gingivalis and P. intermedia over 24 h was effectively inhibited by lower concentrations (>or=8 microg/ml) of various iron-bound forms (the apo, native, and holo forms) of bLF and hLF but not LFcin B. A preformed biofilm of P. gingivalis and P. intermedia was also reduced by incubation with various iron-bound bLFs, hLF, and LFcin B for 5 h. In an examination of the effectiveness of native bLF when it was used in combination with four antibiotics, it was found that treatment with ciprofloxacin, clarithromycin, and minocycline in combination with native bLF for 24 h reduced the amount of a preformed biofilm of P. gingivalis compared with the level of reduction achieved with each agent alone. These results demonstrate the antibiofilm activity of LF with lower iron dependency against P. gingivalis and P. intermedia and the potential usefulness of LF for the prevention and treatment of periodontal diseases and as adjunct therapy for periodontal diseases.

  16. In Vitro Effects of Polyphosphate against Prevotella intermedia in Planktonic Phase and Biofilm

    PubMed Central

    Jang, Eun-Young; Kim, Minjung; Noh, Mi Hee

    2015-01-01

    Polyphosphate (polyP) has gained a wide interest in the food industry due to its potential as a decontaminating agent. In this study, we examined the effect of sodium tripolyphosphate (polyP3; Na5P3O10) against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. The MIC of polyP3 against P. intermedia ATCC 49046 determined by agar dilution method was 0.075%, while 0.05% polyP3 was bactericidal against P. intermedia in time-kill analysis performed using liquid medium. A crystal violet binding assay for the assessment of biofilm formation by P. intermedia showed that sub-MICs of polyP3 significantly decreased biofilm formation. Under the scanning electron microscope, decreased numbers of P. intermedia cells forming the biofilms were observed when the bacterial cells were incubated with 0.025% or higher concentrations of polyP3. Assessment of biofilm viability with LIVE/DEAD staining and viable cell count methods showed that 0.05% or higher concentrations of polyP3 significantly decreased the viability of the preformed biofilms in a concentration-dependent manner. The zone sizes of alpha-hemolysis formed on horse blood agar produced by P. intermedia were decreased in the presence of polyP3. The expression of the genes encoding hemolysins and the genes of the hemin uptake (hmu) locus was downregulated by polyP3. Collectively, our results show that polyP is an effective antimicrobial agent against P. intermedia in biofilms as well as planktonic phase, interfering with the process of hemin acquisition by the bacterium. PMID:26596937

  17. Transcriptomic Analyses of Xylan Degradation by Prevotella bryantii and Insights into Energy Acquisition by Xylanolytic Bacteroidetes*

    PubMed Central

    Dodd, Dylan; Moon, Young-Hwan; Swaminathan, Kankshita; Mackie, Roderick I.; Cann, Isaac K. O.

    2010-01-01

    Enzymatic depolymerization of lignocellulose by microbes in the bovine rumen and the human colon is critical to gut health and function within the host. Prevotella bryantii B14 is a rumen bacterium that efficiently degrades soluble xylan. To identify the genes harnessed by this bacterium to degrade xylan, the transcriptomes of P. bryantii cultured on either wheat arabinoxylan or a mixture of its monosaccharide components were compared by DNA microarray and RNA sequencing approaches. The most highly induced genes formed a cluster that contained putative outer membrane proteins analogous to the starch utilization system identified in the prominent human gut symbiont Bacteroides thetaiotaomicron. The arrangement of genes in the cluster was highly conserved in other xylanolytic Bacteroidetes, suggesting that the mechanism employed by xylan utilizers in this phylum is conserved. A number of genes encoding proteins with unassigned function were also induced on wheat arabinoxylan. Among these proteins, a hypothetical protein with low similarity to glycoside hydrolases was shown to possess endoxylanase activity and subsequently assigned to glycoside hydrolase family 5. The enzyme was designated PbXyn5A. Two of the most similar proteins to PbXyn5A were hypothetical proteins from human colonic Bacteroides spp., and when expressed each protein exhibited endoxylanase activity. By using site-directed mutagenesis, we identified two amino acid residues that likely serve as the catalytic acid/base and nucleophile as in other GH5 proteins. This study therefore provides insights into capture of energy by xylanolytic Bacteroidetes and the application of their enzymes as a resource in the biofuel industry. PMID:20622018

  18. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.

    PubMed

    Girmenia, Corrado; Pagano, Livio; Martino, Bruno; D'Antonio, Domenico; Fanci, Rosa; Specchia, Giorgina; Melillo, Lorella; Buelli, Massimo; Pizzarelli, Giampaolo; Venditti, Mario; Martino, Pietro

    2005-04-01

    Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.

  19. Bioluminescent imaging reveals novel patterns of colonization and invasion in systemic Escherichia coli K1 experimental infection in the neonatal rat.

    PubMed

    Witcomb, Luci A; Collins, James W; McCarthy, Alex J; Frankel, Gadi; Taylor, Peter W

    2015-12-01

    Key features of Escherichia coli K1-mediated neonatal sepsis and meningitis, such as a strong age dependency and development along the gut-mesentery-blood-brain course of infection, can be replicated in the newborn rat. We examined temporal and spatial aspects of E. coli K1 infection following initiation of gastrointestinal colonization in 2-day-old (P2) rats after oral administration of E. coli K1 strain A192PP and a virulent bioluminescent derivative, E. coli A192PP-lux2. A combination of bacterial enumeration in the major organs, two-dimensional bioluminescence imaging, and three-dimensional diffuse light imaging tomography with integrated micro-computed tomography indicated multiple sites of colonization within the alimentary canal; these included the tongue, esophagus, and stomach in addition to the small intestine and colon. After invasion of the blood compartment, the bacteria entered the central nervous system, with restricted colonization of the brain, and also invaded the major organs, in line with increases in the severity of symptoms of infection. Both keratinized and nonkeratinized surfaces of esophagi were colonized to a considerably greater extent in susceptible P2 neonates than in corresponding tissues from infection-resistant 9-day-old rat pups; the bacteria appeared to damage and penetrate the nonkeratinized esophageal epithelium of infection-susceptible P2 animals, suggesting the esophagus represents a portal of entry for E. coli K1 into the systemic circulation. Thus, multimodality imaging of experimental systemic infections in real time indicates complex dynamic patterns of colonization and dissemination that provide new insights into the E. coli K1 infection of the neonatal rat.

  20. Interaction of Prevotella intermedia strain 17 leucine-rich repeat domain protein AdpF with eukaryotic cells promotes bacterial internalization.

    PubMed

    Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K; Miyazaki, Hiroshi; Lewis, Janina P

    2014-06-01

    Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells.

  1. Interaction of Prevotella intermedia Strain 17 Leucine-Rich Repeat Domain Protein AdpF with Eukaryotic Cells Promotes Bacterial Internalization

    PubMed Central

    Sengupta, Dipanwita; Kang, Dae-Joong; Anaya-Bergman, Cecilia; Wyant, Tiana; Ghosh, Arnab K.; Miyazaki, Hiroshi

    2014-01-01

    Prevotella intermedia is an oral bacterium implicated in a variety of oral diseases. Although internalization of this bacterium by nonphagocytic host cells is well established, the molecular players mediating the process are not well known. Here, the properties of a leucine-rich repeat (LRR) domain protein, designated AdpF, are described. This protein contains a leucine-rich region composed of 663 amino acid residues, and molecular modeling shows that it folds into a classical curved solenoid structure. The cell surface localization of recombinant AdpF (rAdpF) was confirmed by electron and confocal microscopy analyses. The recombinant form of this protein bound fibronectin in a dose-dependent manner. Furthermore, the protein was internalized by host cells, with the majority of the process accomplished within 30 min. The internalization of rAdpF was inhibited by nystatin, cytochalasin, latrunculin, nocodazole, and wortmannin, indicating that microtubules, microfilaments, and signal transduction are required for the invasion. It is noteworthy that preincubation of eukaryotic cells with AdpF increased P. intermedia 17 internalization by 5- and 10-fold for HeLa and NIH 3T3 fibroblast cell lines, respectively. The addition of the rAdpF protein was also very effective in inducing bacterial internalization into the oral epithelial cell line HN4, as well as into primary cells, including human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs). Finally, cells exposed to P. intermedia 17 internalized the bacteria more readily upon reinfection. Taken together, our data demonstrate that rAdpF plays a role in the internalization of P. intermedia 17 by a variety of host cells. PMID:24711565

  2. Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections.

    PubMed

    Moen, Marit D; Lyseng-Williamson, Katherine A; Scott, Lesley J

    2009-01-01

    Liposomal amphotericin B (AmBisome) is a lipid-associated formulation of the broad-spectrum polyene antifungal agent amphotericin B. It is active against clinically relevant yeasts and moulds, including Candida spp., Aspergillus spp. and filamentous moulds such as Zygomycetes, and is approved for the treatment of invasive fungal infections in many countries worldwide. It was developed to improve the tolerability profile of amphotericin B deoxycholate, which was for many decades considered the gold standard of antifungal treatment, despite being associated with infusion-related events and nephrotoxicity. In well controlled trials, liposomal amphotericin B had similar efficacy to amphotericin B deoxycholate and amphotericin B lipid complex as empirical therapy in adult and paediatric patients with febrile neutropenia. In addition, caspofungin was noninferior to liposomal amphotericin B as empirical therapy in adult patients with febrile neutropenia. For the treatment of confirmed invasive fungal infections, liposomal amphotericin B was more effective than amphotericin B deoxycholate treatment in patients with disseminated histoplasmosis and AIDS, and was noninferior to amphotericin B deoxycholate in patients with acute cryptococcal meningitis and AIDS. In adults, micafungin was shown to be noninferior to liposomal amphotericin B for the treatment of candidaemia and invasive candidiasis. Data from animal studies suggested that higher dosages of liposomal amphotericin B might improve efficacy; however, in the AmBiLoad trial in patients with invasive mould infection, there was no statistical difference in efficacy between the standard dosage of liposomal amphotericin B 3 mg/kg/day and a higher 10 mg/kg/day dosage, although the standard dosage was better tolerated. Despite being associated with fewer infusion-related adverse events and less nephrotoxicity than amphotericin B deoxycholate and amphotericin B lipid complex, liposomal amphotericin B use is still limited to

  3. Successful use of posaconazole to treat invasive cutaneous fungal infection in a liver transplant patient on sirolimus.

    PubMed

    Dahlan, Randah; Patel, Ameen; Haider, Shariq

    2012-01-01

    Fungi are an important and common cause of cutaneous infections affecting solid organ transplant recipients. These infections can represent a primary site of infection with the potential for dissemination, or a manifestation of metastatic infection. The high morbidity and mortality associated with these infections necessitates urgent therapy with antifungal drugs; however, the interaction between these drugs and immunosuppressive therapies can be a major limitation because of drug toxicity. A case of soft tissue infection of the toe caused by Fusarium chlamydosporum and Candida guilliermondii in a liver transplant patient on sirolimus, who was successfully treated with the new antifungal agent posaconazole, is described. The pharmacokinetic interactions of sirolimus and the new triazoles, and their impact on treatment choices are briefly discussed.

  4. Clinical evidence for caspofungin monotherapy in the first-line and salvage therapy of invasive Aspergillus infections.

    PubMed

    Heinz, Werner J; Buchheidt, Dieter; Ullmann, Andrew J

    2016-08-01

    In 2001, caspofungin received market authorisation by the FDA and EMA and is globally licensed for several indications, including candidiasis, empirical antifungal therapy in patients with neutropenic fever of unknown origin and treatment of invasive aspergillosis in patients refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B or itraconazole. Despite the lack of phase III data in first-line treatment of invasive aspergillosis, increasing evidence supports the use of first-line therapy. Here, we analyse the evidence of therapeutic activity, represented by favourable response rates, of caspofungin for invasive aspergillosis. A systematic literature search was conducted to identify international presentations and papers reporting monotherapy with caspofungin. Efficacy data are summarised separately for first-line and salvage therapy. Thirty-one papers and published abstracts reported caspofungin therapy for aspergillosis. Fifteen full papers and two abstracts fulfilled the criteria of reporting significant outcome data for caspofungin monotherapy for invasive aspergillosis. Consistent with other analyses and the known safety profile, few adverse events and associated terminations of caspofungin medication have been reported. Although a randomised, comparative, prospective study using caspofungin in this indication is still lacking, growing evidence supports the efficacy of this echinocandin not only for salvage but also for first-line therapy.

  5. High-level aminoglycoside resistance in Enterococcus faecalis and Enterococcus faecium causing invasive infection: Twelve-year surveillance in the Minami Ibaraki Area.

    PubMed

    Osuka, Hanako; Nakajima, Jun; Oishi, Tsuyoshi; Funayama, Yasunori; Ebihara, Tsugio; Ishikawa, Hiroichi; Saito, Kazuto; Koganemaru, Hiroshi; Hitomi, Shigemi

    2016-01-01

    We examined prevalence of high-level aminoglycoside resistance (HLAR) in Enterococcus faecalis and Enterococcus faecium causing invasive infection in the Minami Ibaraki Area. Ten strains of both species each, recovered from the blood or the cerebrospinal fluid between 2003 and 2014, were randomly selected every year. High-level resistance to gentamicin (HLR-GM) and streptomycin (HLR-SM) was detected in 34% (41 of 120 strains) and 18% (21) of E. faecalis and 9% (11) and 39% (48) of E. faecium, respectively. In comparisons of the proportions among three four-year periods, HLR-SM among E. faecium was significantly lower in the 2011-2014 period. All strains with HLR-GM were positive for the aac(6')-Ie-aph(2″)-Ia gene. The ant(6')-Ia gene was detected in all with HLR-SM except for one E. faecalis strain. The present study showed that prevalence of HLR-GM among E. faecalis and E. faecium causing invasive infection in this area was nearly equivalent to that described in previous studies in Japan and that proportions of strains with HLAR did not vary during the study period except for that of HLR-SM among E. faecium.

  6. Susceptibility to Plasmodium yoelii Preerythrocytic Infection in BALB/c Substrains Is Determined at the Point of Hepatocyte Invasion

    PubMed Central

    Kaushansky, Alexis; Austin, Laura S.; Mikolajczak, Sebastian A.; Lo, Fang Y.; Miller, Jessica L.; Douglass, Alyse N.; Arang, Nadia; Vaughan, Ashley M.; Gardner, Malcolm J.

    2014-01-01

    After transmission by Anopheles mosquitoes, Plasmodium sporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. This has been mainly attributed to differences in innate immune responses and parasite infectivity. Here, we report that BALB/cByJ mice are more susceptible to Plasmodium yoelii preerythrocytic infection than BALB/cJ mice. This difference occurs at the level of early hepatocyte infection, but expression levels of reported host factors that are involved in infection do not correlate with susceptibility. Interestingly, BALB/cByJ hepatocytes are more frequently polyploid; thus, their susceptibility converges on the previously observed preference of sporozoites to infect polyploid hepatocytes. Gene expression analysis demonstrates hepatocyte-specific differences in mRNA abundance for numerous genes between BALB/cByJ and BALB/cJ mice, some of which encode hepatocyte surface molecules. These data suggest that a yet-unknown receptor for sporozoite infection, present at elevated levels on BALB/cByJ hepatocytes and also polyploid hepatocytes, might facilitate Plasmodium liver infection. PMID:25312960

  7. Micafungin: a review of its use in adults for the treatment of invasive and oesophageal candidiasis, and as prophylaxis against Candida infections.

    PubMed

    Cross, Sarah A; Scott, Lesley J

    2008-01-01

    Intravenous micafungin (Mycamine; Fungard), an echinocandin, inhibits the synthesis of 1,3-beta-D-glucan, an essential cell wall component in many fungi. It is approved in adults (focus of this review) and in neonates and paediatric patients (Pediatric Drugs [in press]) in the EU and elsewhere for the treatment of invasive candidiasis and oesophageal candidiasis, and as prophylactic treatment to prevent Candida infections in haematopoietic stem cell transplant (HSCT) recipients.Intravenous micafungin shows very good activity against clinically relevant isolates of Candida spp. Furthermore, the pharmacokinetic profile of micafungin permits once-daily treatment and means that it is associated with relatively few drug-drug interactions. However, like all of the echinocandins and all formulations of amphotericin B, micafungin must be given intravenously. In large, well designed clinical trials in adult patients (>or=16 years of age) with invasive candidiasis, intravenous micafungin was shown to be noninferior to intravenous caspofungin or liposomal amphotericin B. In similarly designed trials in adult patients with oesophageal candidiasis, intravenous micafungin was shown to be noninferior to fluconazole or caspofungin treatment. As prophylactic treatment in adult and paediatric patients who had undergone HSCT, micafungin was superior to fluconazole therapy in a large, well designed trial. Micafungin was generally well tolerated by participants in these clinical trials. Furthermore, it was as well tolerated as caspofungin and fluconazole, and better tolerated than liposomal amphotericin B. The position of micafungin relative to newer antifungal therapies, such as anidulafungin, voriconazole and posaconazole, remains to be fully determined. Thus, micafungin is an emerging option for the treatment of adult patients with invasive or oesophageal candidiasis, and as prophylaxis against Candida infections in HSCT recipients.

  8. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology.

    PubMed

    Cornely, Oliver A; Böhme, Angelika; Buchheidt, Dieter; Einsele, Hermann; Heinz, Werner J; Karthaus, Meinolf; Krause, Stefan W; Krüger, William; Maschmeyer, Georg; Penack, Olaf; Ritter, Jörg; Ruhnke, Markus; Sandherr, Michael; Sieniawski, Michal; Vehreschild, Jörg-Janne; Wolf, Hans-Heinrich; Ullmann, Andrew J

    2009-01-01

    There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

  9. Comparison of Three Distinct Prophylactic Agents Against Invasive Fungal Infections in Patients Undergoing Haplo-identical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

    PubMed Central

    El-Cheikh, Jean; Crocchiolo, Roberto; Vai, Andrea; Furst, Sabine; Bramanti, Stefania; Sarina, Barbara; Granata, Angela; Faucher, Catherine; Mohty, Bilal; Harbi, Samia; Bouabdallah, Reda; Vey, Norbert; Santoro, Armando; Chabannon, Christian; Castagna, Luca; Blaise, Didier

    2015-01-01

    Over the past decade, invasive fungal infections (IFIs) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to bedetermined. We conducted a retrospective analysis, comparing the safety and efficacy of micafungin 50mg/day vs. fluconazole 400mg/day vs. itraconazole 200mg/day as prophylaxis for adult patients with various haematological diseases receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) followed by high-dose cyclophosphamide (PT-Cy). Overall, 99 patients were identified: 30 patients received micafungin, 50 and 19 patients received itraconazole and fluconazole, respectively. After a median follow-up of 12 months (range: 1–51), proven or probable IFIs were reported in 3 patients (10%) in the micafungin, 5 patients in the itraconazole (10%) and 2 patients (11%) in the fluconazole group (p=0.998). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 3 [6%] in the itraconazole vs. 2 [11%] in the fluconazole group, p=0.589). Four patients (13%) in the micafungin group vs 13 (26%) patients in the itraconazole group and 10 (53%) patients in the fluconazole received empirical antifungal therapy (P = 0.19). No serious adverse events related to treatment were reported by patients, and there was no treatment discontinuation because of drug-related adverse events in both groups. The present analysis shows that micafungin did better than fluconazole in preventing invasive aspergillosis after transplant in these high-risk hematological diseases, as expected. In addition, micafungin was more effective than itraconazole in preventing all IFI episodes when also considering possible fungal infections. Future prospective studies would shed light on this issue, concerning this increasingly used transplant platform. PMID:26401237

  10. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

    PubMed

    Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

    2016-02-05

    Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients.

  11. Ruminal Prevotella spp. May Play an Important Role in the Conversion of Plant Lignans into Human Health Beneficial Antioxidants

    PubMed Central

    Schogor, Ana L. B.; Huws, Sharon A.; Santos, Geraldo T. D.; Scollan, Nigel D.; Hauck, Barbara D.; Winters, Ana L.; Kim, Eun J.; Petit, Hélène V.

    2014-01-01

    Secoisolariciresinol diglucoside (SDG), the most abundant lignan in flaxseed, is metabolized by the ruminal microbiota into enterolignans, which are strong antioxidants. Enterolactone (EL), the main mammalian enterolignan produced in the rumen, is transferred into physiological fluids, with potentially human health benefits with respect to menopausal symptoms, hormone-dependent cancers, cardiovascular diseases, osteoporosis and diabetes. However, no information exists to our knowledge on bacterial taxa that play a role in converting plant lignans into EL in ruminants. In order to investigate this, eight rumen cannulated cows were used in a double 4×4 Latin square design and fed with four treatments: control with no flax meal (FM), or 5%, 10% and 15% FM (on a dry matter basis). Concentration of EL in the rumen increased linearly with increasing FM inclusion. Total rumen bacterial 16S rRNA concentration obtained using Q-PCR did not differ among treatments. PCR-T-RFLP based dendrograms revealed no global clustering based on diet indicating between animal variation. PCR-DGGE showed a clustering by diet effect within four cows that had similar basal ruminal microbiota. DNA extracted from bands present following feeding 15% FM and absent with no FM supplementation were sequenced and it showed that many genera, in particular Prevotella spp., contributed to the metabolism of lignans. A subsequent in vitro study using selected pure cultures of ruminal bacteria incubated with SDG indicated that 11 ruminal bacteria were able to convert SDG into secoisolariciresinol (SECO), with Prevotella spp. being the main converters. These data suggest that Prevotella spp. is one genus playing an important role in the conversion of plant lignans to human health beneficial antioxidants in the rumen. PMID:24709940

  12. A comparative study on invasion, survival, modulation of oxidative burst, and nitric oxide responses of macrophages (HD11), and systemic infection in chickens by prevalent poultry Salmonella serovars.

    PubMed

    He, Haiqi; Genovese, Kenneth J; Swaggerty, Christina L; Nisbet, David J; Kogut, Michael H

    2012-12-01

    Poultry is a major reservoir for foodborne Salmonella serovars. Salmonella Typhimurium, Salmonella Enteritidis, Salmonella Heidelberg, Salmonella Kentucky, and Salmonella Senftenberg are the most prevalent serovars in U.S. poultry. Information concerning the interactions between different Salmonella species and host cells in poultry is lacking. In the present study, the above mentioned Salmonella serovars were examined for invasion, intracellular survival, and their ability to modulate oxidative burst and nitric oxide (NO) responses in chicken macrophage HD11 cells. All Salmonella serovars demonstrated similar capacity to invade HD11 cells. At 24 h post-infection, a 36-43% reduction of intracellular bacteria, in log(10)(CFU), was observed for Salmonella Typhimurium, Salmonella Heidelberg, Salmonella Kentucky, and Salmonella Senftenberg, whereas a significantly lower reduction (16%) was observed for Salmonella Enteritidis, indicating its higher resistance to the killing by HD11 cells. Production of NO was completely diminished in HD11 cells infected with Salmonella Typhimurium and Salmonella Enteritidis, but remained intact when infected with Salmonella Heidelberg, Salmonella Kentucky, and Salmonella Senftenberg. Phorbol myristate acetate-stimulated oxidative burst in HD11 cells was greatly impaired after infection by each of the five serovars. When newly hatched chickens were challenged orally, a high rate (86-98%) of systemic infection (Salmonella positive in liver/spleen) was observed in birds challenged with Salmonella Typhimurium, Salmonella Enteritidis, Salmonella Heidelberg, and Salmonella Kentucky, while only 14% of the birds were Salmonella Senftenberg positive. However, there was no direct correlation between systemic infection and in vitro differential intracellular survival and modulation of NO response among the tested serovars.

  13. Repression of flagella is a common trait in field isolates of Salmonella enterica serovar Dublin and is associated with invasive human infections.

    PubMed

    Yim, Lucía; Sasías, Sebastián; Martínez, Arací; Betancor, Laura; Estevez, Verónica; Scavone, Paola; Bielli, Alejandro; Sirok, Alfredo; Chabalgoity, José Alejandro

    2014-04-01

    The nontyphoidal Salmonella enterica serovar Dublin is adapted to cattle but infrequently infects humans, very often resulting in invasive infections with high levels of morbidity and mortality. A Salmonella-induced intestinal acute inflammatory response is postulated as a mechanism to prevent bacterial dissemination to systemic sites. In S. enterica serovar Typhimurium, flagella contribute to this response by providing motility and FliC-mediated activation of pattern recognition receptors. In this study, we found 4 Salmonella enterica isolates, with the antigenic formula 9,12:-:-, that, based on fliC sequence and multilocus sequence type (MLST) analyses, are aflagellate S. Dublin isolates. Interestingly, all were obtained from human bloodstream infections. Thus, we investigated the potential role of flagella in the unusual invasiveness exhibited by S. Dublin in humans by analyzing flagellation and proinflammatory properties of a collection of 10 S. Dublin human clinical isolates. We found that 4 of 7 blood isolates were aflagellate due to significantly reduced levels of fliC expression, whereas all 3 isolates from other sources were flagellated. Lack of flagella correlated with a reduced ability of triggering interleukin-8 (IL-8) and CCL20 chemokine expression in human intestinal Caco-2 cells and with reduced early inflammation in the ceca of streptomycin-pretreated C57/BL6 mice. These results indicate that flagella contribute to the host intestinal inflammatory response to Salmonella serovar Dublin and suggest that their absence may contribute to its systemic dissemination through dampening of the gut immune response. Analysis of FliC production in a collection of cattle isolates indicated that the aflagellate phenotype is widely distributed in field isolates of S. Dublin.

  14. Repression of Flagella Is a Common Trait in Field Isolates of Salmonella enterica Serovar Dublin and Is Associated with Invasive Human Infections

    PubMed Central

    Sasías, Sebastián; Martínez, Arací; Betancor, Laura; Estevez, Verónica; Scavone, Paola; Bielli, Alejandro; Sirok, Alfredo; Chabalgoity, José Alejandro

    2014-01-01

    The nontyphoidal Salmonella enterica serovar Dublin is adapted to cattle but infrequently infects humans, very often resulting in invasive infections with high levels of morbidity and mortality. A Salmonella-induced intestinal acute inflammatory response is postulated as a mechanism to prevent bacterial dissemination to systemic sites. In S. enterica serovar Typhimurium, flagella contribute to this response by providing motility and FliC-mediated activation of pattern recognition receptors. In this study, we found 4 Salmonella enterica isolates, with the antigenic formula 9,12:−:−, that, based on fliC sequence and multilocus sequence type (MLST) analyses, are aflagellate S. Dublin isolates. Interestingly, all were obtained from human bloodstream infections. Thus, we investigated the potential role of flagella in the unusual invasiveness exhibited by S. Dublin in humans by analyzing flagellation and proinflammatory properties of a collection of 10 S. Dublin human clinical isolates. We found that 4 of 7 blood isolates were aflagellate due to significantly reduced levels of fliC expression, whereas all 3 isolates from other sources were flagellated. Lack of flagella correlated with a reduced ability of triggering interleukin-8 (IL-8) and CCL20 chemokine expression in human intestinal Caco-2 cells and with reduced early inflammation in the ceca of streptomycin-pretreated C57/BL6 mice. These results indicate that flagella contribute to the host intestinal inflammatory response to Salmonella serovar Dublin and suggest that their absence may contribute to its systemic dissemination through dampening of the gut immune response. Analysis of FliC production in a collection of cattle isolates indicated that the aflagellate phenotype is widely distributed in field isolates of S. Dublin. PMID:24421045

  15. PilY1 Promotes Legionella pneumophila Infection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility

    PubMed Central

    Hoppe, Julia; Ünal, Can M.; Thiem, Stefanie; Grimpe, Louisa; Goldmann, Torsten; Gaßler, Nikolaus; Richter, Matthias; Shevchuk, Olga; Steinert, Michael

    2017-01-01

    Legionnaires' disease is an acute fibrinopurulent pneumonia. During infection Legionella pneumophila adheres to the alveolar lining and replicates intracellularly within recruited macrophages. Here we provide a sequence and domain composition analysis of the L. pneumophila PilY1 protein, which has a high homology to PilY1 of Pseudomonas aeruginosa. PilY1 proteins of both pathogens contain a von Willebrand factor A (vWFa) and a C-terminal PilY domain. Using cellular fractionation, we assigned the L. pneumophila PilY1 as an outer membrane protein that is only expressed during the transmissive stationary growth phase. PilY1 contributes to infection of human lung tissue explants (HLTEs). A detailed analysis using THP-1 macrophages and A549 lung epithelial cells revealed that this contribution is due to multiple effects depending on host cell type. Deletion of PilY1 resulted in a lower replication rate in THP-1 macrophages but not in A549 cells. Further on, adhesion to THP-1 macrophages and A549 epithelial cells was decreased. Additionally, the invasion into non-phagocytic A549 epithelial cells was drastically reduced when PilY1 was absent. Complementation variants of a PilY1-negative mutant revealed that the C-terminal PilY domain is essential for restoring the wild type phenotype in adhesion, while the putatively mechanosensitive vWFa domain facilitates invasion into non-phagocytic cells. Since PilY1 also promotes twitching motility of L. pneumophila, we discuss the putative contribution of this newly described virulence factor for bacterial dissemination within infected lung tissue. PMID:28326293

  16. Activity of telithromycin against penicillin-resistant Streptococcus pneumoniae isolates recovered from French children with invasive and noninvasive infections.

    PubMed

    Bingen, Edouard; Doit, Catherine; Loukil, Chawki; Brahimi, Naima; Bidet, Philippe; Deforche, Dominique; Geslin, Pierre

    2003-07-01

    We compared the activities of telithromycin, erythromycin, azithromycin, josamycin, penicillin G, amoxicillin, cefpodoxime, and ceftriaxone against invasive and noninvasive non-penicillin-susceptible Streptococcus pneumoniae isolates recovered from children. Of the 186 isolates tested, 89% were positive for erm(B) by PCR. Telithromycin had the lowest MICs, with MICs at which 90% of the isolates tested are inhibited of 0.032 and 0.25 micro g/ml for erythromycin-sensitive and -resistant isolates, respectively.

  17. Selection of a Highly Monensin-Resistant Prevotella bryantii Subpopulation with Altered Outer Membrane Characteristics

    PubMed Central

    Callaway, Todd R.; Russell, James B.

    1999-01-01

    Prevotella bryantii cultures treated with monensin grew more slowly than untreated cultures, but only if the monensin concentration was greater than 1 μM. Cultures that were repeatedly transferred (eight transfers or 25 doublings) with monensin always grew rapidly, even at a 10 μM concentration. The amount of monensin needed to facilitate half-maximal potassium depletion (Kd) from monensin-selected cells was 16-fold greater than “unadapted” wild-type cultures (3,200 versus 200 nM). Cells taken from continuous culture had a Kd of 100 nM, and these inocula could not grow in batch culture when the monensin concentration was greater than 300 nM. Continuous cultures treated with monensin nearly washed out, but the surviving cells had a Kd of 1,300 nM. When wild-type cells were transferred in batch culture with 10 μM monensin, the Kd did not reach its maximum value (3,200 nM) until after eight transfers (25 doublings). Kd declined when monensin was removed, and it took eight transfers to reach the control value (200 nM). The most probable number of wild-type cells was 1,000-fold lower than of the monensin-selected cells, but calculations based on relative growth advantage and Kd indicated that the wild-type culture had 1 to 10% highly monensin-resistant cells. Cell pellets of wild-type cultures were more difficult to disperse than were monensin-selected cells, and water-soluble phenol extracts of monensin-selected cells had 1.8-fold more anthrone-reactive material than did the wild type. Wild-type cultures that were washed in Tris buffer (pH 8.0) released little alkaline phosphatase and were agglutinated by lysozyme. Monensin-selected cultures leaked ninefold more alkaline phosphatase and were not agglutinated by lysozyme. Wild-type colonies taken from high-dilution agar roll tubes retained the lysozyme agglutination phenotype even if transferred with monensin, and monensin-selected colonies were never agglutinated. These observations indicated that wild-type P

  18. Infection prevention in the intensive care unit: review of the recent literature on the management of invasive devices.

    PubMed

    Di Filippo, Alessandro; Casini, Andrea; de Gaudio, Angelo Raffaele

    2011-04-01

    Over the last 5 y, clinical trials investigating products, procedures, and treatments aimed at preventing infections in the intensive care unit have been described. The findings of these studies appear to confirm the effectiveness of certain preventive procedures. With regard to ventilator-associated pneumonia, the efficacies of decontamination of the oral cavity, continuous suction of subglottic secretions, positioning of the patient, selective decontamination of the digestive tract, and (for higher-risk patients) endotracheal tubes coated with silver, have been demonstrated. Medicated catheters and chlorhexidine-based dressings have been found useful for catheter-related bloodstream infections, and medical catheters have also been shown to be efficacious against urinary tract infections. All these procedures can be incorporated into departmental protocols for the prevention of nosocomial infections in the intensive care unit.

  19. Evaluating the effect of local pH on fluorescence emissions from oral bacteria of the genus Prevotella

    NASA Astrophysics Data System (ADS)

    Hope, Christopher K.; Higham, Susan M.

    2016-08-01

    A number of anaerobic oral bacteria, notably Prevotellaceae, exhibit red fluorescence when excited by short-wavelength visible light due to their accumulation of porphyrins, particularly protoporphyrin IX. pH affects the fluorescence of abiotic preparations of porphyrins due to transformations in speciation between monomers, higher aggregates, and dimers. To elucidate whether the porphyrin speciation phenomenon could be manifested within a microbiological system, suspensions of Prevotella intermedia and Prevotella nigrescens were examined by fluorescence spectrophotometry while being titrated against NaOH. The initial pH of the samples was <6, which was then raised toward the maximum found within a diseased periodontal pocket, being ˜pH 8.7. The intensity of the fluorescence emissions increased between 600 and 650 nm with increasing pH. Peak fluorescence emissions occurred at 635±1 nm with a second emission peak developing with increasing pH at 622 nm. A linear relationship was demonstrated between pH and the log10 ratio of 635:622 nm excitation fluorescence intensities. These findings suggest that the pH range found within the oral cavity could affect the fluorescence of oral bacteria in vivo, which may in turn have connotations for any clinical diagnoses that may be inferred from dental plaque fluorescence.

  20. Bioinformatic evidence and characterization of novel putative large conjugative transposons residing in genomes of genera Bacteroides and Prevotella.

    PubMed

    Gorenc, Katja; Accetto, Tomaž; Avguštin, Gorazd

    2012-07-01

    Bioinformatic evidence of the presence of a large conjugative transposon in ruminal bacterium Prevotella bryantii B(1)4(T) is presented. The described transposon appears to be related to another large conjugative transposon CTnBST, described in Bacteroides uniformis WH207 and to the conjugative transposon CTn3-Bf, which was observed in the genome of Bacteroides fragilis strain YCH46. All three transposons share tra gene regions with high amino acid identity and clearly conserved gene order. Additionally, a second conserved region consisting of hypothetical genes was discovered in all three transposons and named the GG region. This region served as a specific sequence signature and made possible the discovery of several other apparently related hypothetical conjugative transposons in bacteria from the genus Bacteroides. A cluster of genes involved in sugar utilization and metabolism was discovered within the hypothetical CTnB(1)4, to a certain extent resembling the polysaccharide utilization loci which were described recently in some Bacteroides strains. This is the first firm report on the presence of a large mobile genetic element in any strain from the genus Prevotella.

  1. Pi30 DNA probe may be useful for the identification of Prevotella intermedia at the species or strain level.

    PubMed

    Shin, Yong Kook; Jeong, Seung-U; Yoo, So Young; Kim, Mi-Kwang; Kim, Hwa-Sook; Kim, Byung-Ock; Kim, Do Kyung; Hwang, Ho-Keel; Kook, Joong-Ki

    2004-01-01

    Recently, we introduced a new method for the rapid screening of bacterial species-or subspecies-specific DNA probes, named the "inverted dot blot hybridization screening method." This method has subsequently been then applied to develop species-or strain-specific DNA probes for Prevotella intermedia and Prevotella nigrescens. In a previous study, the inverted dot blot hybridization data showed that a probe, Pi30, was specific for P. intermedia. In this study, the DNA probe Pi30 was evaluated by Southern blot analysis to determine if it could distinguish P. intermedia from P. nigrescens. The data showed that the probe Pi30 reacted with the genomic DNAs from the reference strains and clinical isolates of both P. intermedia and P. nigrescens, but the size of the signal bands was different. In addition, the probe Pi30 reacted with a 1.4 kbp fragment from the genomic DNAs digested with Pst I of the P. intermedia strains but not with any fragments of P. nigrescens strains. The result indicates that the probe Pi30 could be useful for the identification of P. intermedia by restriction fragment length polymorphism (RFLP) at the species or strain level.

  2. Restriction Endonucleases from Invasive Neisseria gonorrhoeae Cause Double-Strand Breaks and Distort Mitosis in Epithelial Cells during Infection

    PubMed Central

    Weyler, Linda; Engelbrecht, Mattias; Mata Forsberg, Manuel; Brehwens, Karl; Vare, Daniel; Vielfort, Katarina; Wojcik, Andrzej; Aro, Helena

    2014-01-01

    The host epithelium is both a barrier against, and the target for microbial infections. Maintaining regulated cell growth ensures an intact protective layer towards microbial-induced cellular damage. Neisseria gonorrhoeae infections disrupt host cell cycle regulation machinery and the infection causes DNA double strand breaks that delay progression through the G2/M phase. We show that intracellular gonococci upregulate and release restriction endonucleases that enter the nucleus and damage human chromosomal DNA. Bacterial lysates containing restriction endonucleases were able to fragment genomic DNA as detected by PFGE. Lysates were also microinjected into the cytoplasm of cells in interphase and after 20 h, DNA double strand breaks were identified by 53BP1 staining. In addition, by using live-cell microscopy and NHS-ester stained live gonococci we visualized the subcellular location of the bacteria upon mitosis. Infected cells show dysregulation of the spindle assembly checkpoint proteins MAD1 and MAD2, impaired and prolonged M-phase, nuclear swelling, micronuclei formation and chromosomal instability. These data highlight basic molecular functions of how gonococcal infections affect host cell cycle regulation, cause DNA double strand breaks and predispose cellular malignancies. PMID:25460012

  3. Comparative evaluation of pan-fungal real-time PCR, galactomannan and (1-3)-β-D-glucan assay for invasive fungal infection in paediatric cancer patients.

    PubMed

    Gupta, Prashant; Ahmad, Abrar; Khare, Vineeta; Kumar, Archana; Banerjee, Gopa; Verma, Nitya; Singh, Mastan

    2017-04-01

    Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non-invasive tests; Platelia Aspergillus EIA for galactomannan (GM), β-D-glucan (BDG) assay and pan-fungal real-time PCR for fungal DNA in blood were evaluated. One hundred twenty-five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan-fungal real-time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.

  4. Digenean trematode infections of native freshwater snails and invasive Potamopyrgus antipodarum in the Grand Teton National Park/John D. Rockefeller Memorial Parkway Area.

    PubMed

    Adema, C M; Lun, C-M; Hanelt, B; Seville, R S

    2009-02-01

    Outside its native range, the invasive New Zealand mud snail (NZMS), Potamopyrgus antipodarum, is rarely reported to harbor parasites. To test this observation, 7 sites along the Snake River and Polecat Creek in the Grand Teton National Park/John D Rockefeller Memorial Parkway area (Wyoming) were surveyed for native aquatic snails, NZMS, and associated digenean trematodes, in July 2005. At 6 sites, native snails harbored patent digenean infections; within 2 hr, < or =10% of lymnaeid snails shed furcocercariae or xiphidiocercariae, and < or =42% of physid snails released furcocercariae or echinostome cercariae. Partial 18S rDNA sequences were recovered from several furcocercariae. Potamopyrgus antipodarum was present at, and collected from, 5 sites. Polymerase chain reaction assays targeting digenean rDNA sequences in DNA extracted from pools of 150 NZMS snails did not detect parasites. The examination of 960 NZMS by overnight shedding yielded 1 occurrence of (surface-encysted) metacercariae of an unclassified notocotylid (based on 18S and 28S rDNA sequences). The dissection of 150 ethanol-fixed NZMS (30/site) revealed 2 types of digenean metacercariae encysted in tissues of 5 snails from Polecat Creek. Thus, invasive NZMS may serve as first and second intermediate host for digenean parasites.

  5. Invasive fungal infection caused by geotrichum capitatum in patients with acute lymphoblastic leukemia: a case study and literature review

    PubMed Central

    Gao, Guang-Xun; Tang, Hai-Long; Zhang, Xuan; Xin, Xiao-Li; Feng, Juan; Chen, Xie-Qun

    2015-01-01

    Geotrichum capitatum infection has a very low incidence rate with atypical clinical symptoms, making diagnosis difficult, and it has a poor prognosis. The incidence is even more rare in China. This paper reports the first case of infection caused by G. capitatum during bone marrow suppression after chemotherapy in a Chinese patient with acute lymphoblastic leukemia. In addition, it reports a systematic literature review of diagnosis and treatment. The patient with acute lymphoblastic leukemia was confirmed to be infected with G. capitatum, involving lung, liver and skin, through a blood culture test. Caspofungin, amphotericin B loposome, and a combination therapy of amphotericin B liposome and voriconazole were used in succession for treatment. Despite normal body temperature and a slight improvement of clinical symptoms with the combination therapy treatment, the patient died 40 days after chemotherapy due to heart and lung failure. PMID:26550401

  6. Treatment of invasive fungal infections in high risk hematological patients. The outcome with liposomal amphotericin B is not negatively affected by prior administration of mold-active azoles.

    PubMed

    De la Serna, Javier; Jarque, Isidro; López-Jiménez, Javier; Fernández-Navarro, Jose María; Gómez, Valle; Jurado, Manuel; Pascual, Adriana; Serrano, Josefina; Romero, Mónica; Vallejo, Carlos

    2013-03-01

    There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.

  7. Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection

    PubMed Central

    Wilde, Aimee D.; Snyder, Daniel J.; Putnam, Nicole E.; Valentino, Michael D.; Hammer, Neal D.; Lonergan, Zachery R.; Hinger, Scott A.; Aysanoa, Esar E.; Blanchard, Catlyn; Dunman, Paul M.; Wasserman, Gregory A.; Chen, John; Shopsin, Bo; Gilmore, Michael S.; Skaar, Eric P.; Cassat, James E.

    2015-01-01

    Staphylococcus aureus is capable of infecting nearly every organ in the human body. In order to infiltrate and thrive in such diverse host tissues, staphylococci must possess remarkable flexibility in both metabolic and virulence programs. To investigate the genetic requirements for bacterial survival during invasive infection, we performed a transposon sequencing (TnSeq) analysis of S. aureus during experimental osteomyelitis. TnSeq identified 65 genes essential for staphylococcal survival in infected bone and an additional 148 mutants with compromised fitness in vivo. Among the loci essential for in vivo survival was SrrAB, a staphylococcal two-component system previously reported to coordinate hypoxic and nitrosative stress responses in vitro. Healthy bone is intrinsically hypoxic, and intravital oxygen monitoring revealed further decreases in skeletal oxygen concentrations upon S. aureus infection. The fitness of an srrAB mutant during osteomyelitis was significantly increased by depletion of neutrophils, suggesting that neutrophils impose hypoxic and/or nitrosative stresses on invading bacteria. To more globally evaluate staphylococcal responses to changing oxygenation, we examined quorum sensing and virulence factor production in staphylococci grown under aerobic or hypoxic conditions. Hypoxic growth resulted in a profound increase in quorum sensing-dependent toxin production, and a concomitant increase in cytotoxicity toward mammalian cells. Moreover, aerobic growth limited quorum sensing and cytotoxicity in an SrrAB-dependent manner, suggesting a mechanism by which S. aureus modulates quorum sensing and toxin production in response to environmental oxygenation. Collectively, our results demonstrate that bacterial hypoxic responses are key determinants of the staphylococcal-host interaction. PMID:26684646

  8. Head space analysis to non-invasively distinguish between vaccinated and bovine tuberculosis-infected white-tailed deer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White-tailed deer (WTD; Odocoileus virginianus) can act as a reservoir for bovine tuberculosis (bTB), caused by Mycobacterium bovis, and can be a source of infection in cattle. Presently, no method exists to noninvasively monitor the presence of bTB in wildlife. In addition, due to similarities betw...

  9. Investigating Invasives

    ERIC Educational Resources Information Center

    Lightbody, Mary

    2008-01-01

    Invasive species, commonly known as "invasives," are nonnative plants, animals, and microbes that completely take over and change an established ecosystem. The consequences of invasives' spread are significant. In fact, many of the species that appear on the Endangered Species list are threatened by invasives. Therefore, the topic of invasive…

  10. Infection

    DTIC Science & Technology

    2010-09-01

    standing, diagnosis, and treatment of musculoskeletal infections. Key Words: musculoskeletal infection, biofilm , bacteria, biomaterial (J Orthop Trauma...form a biofilm , or slime layer.1 The recurrence of infections is often the result of microbial biofilm formation on the implant, enabling the persistence...Klebsiella pneumoniae). Staphylococcus species is by far the most studied pathogen in musculoskeletal infections and can produce a multilayered biofilm

  11. Multidisciplinary approach to the treatment of invasive fungal infections in adult patients. Prophylaxis, empirical, preemptive or targeted therapy, which is the best in the different hosts?

    PubMed Central

    Zaragoza, Rafael; Pemán, Javier; Salavert, Miguel; Viudes, Ángel; Solé, Amparo; Jarque, Isidro; Monte, Emilio; Romá, Eva; Cantón, Emilia

    2008-01-01

    The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients. PMID:19337433

  12. Public health risk communication by text message in response to a cluster of invasive meningococcal infection in a primary school.

    PubMed

    Bradley, Declan T; Johnston, Jillian; Smyth, Brian

    2014-05-01

    Public health risk communication during emergencies should be rapid and accurate in order to allow the audience to take steps to prevent adverse outcomes. Delays to official communications may cause unnecessary anxiety due to uncertainty or inaccurate information circulating within the at-risk group. Modern electronic communications present opportunities for rapid, targeted public health risk communication. We present a case report of a cluster of invasive meningococcal disease in a primary school in which we used the school's mass short message service (SMS) text message system to inform parents and guardians of pupils about the incident, to tell them that chemoprophylaxis would be offered to all pupils and staff, and to advise them when to attend the school to obtain further information and antibiotics. Following notification to public health on a Saturday, an incident team met on Sunday, sent the SMS messages that afternoon, and administered chemoprophyaxis to 93% of 404 pupils on Monday. The use of mass SMS messages enabled rapid communication from an official source and greatly aided the public health response to the cluster.

  13. Infection Cycle of Artichoke Italian Latent Virus in Tobacco Plants: Meristem Invasion and Recovery from Disease Symptoms

    PubMed Central

    Santovito, Elisa; Mascia, Tiziana; Siddiqui, Shahid A.; Minutillo, Serena Anna; Valkonen, Jari P. T.; Gallitelli, Donato

    2014-01-01

    Nepoviral infections induce recovery in fully expanded leaves but persist in shoot apical meristem (SAM) by a largely unknown mechanism. The dynamics of infection of a grapevine isolate of Artichoke Italian latent virus (AILV-V, genus Nepovirus) in tobacco plants, including colonization of SAM, symptom induction and subsequent recovery of mature leaves from symptoms, were characterized. AILV-V moved from the inoculated leaves systemically and invaded SAM in 7 days post-inoculation (dpi), remaining detectable in SAM at least up to 40 dpi. The new top leaves recovered from viral symptoms earliest at 21 dpi. Accumulation of viral RNA to a threshold level was required to trigger the overexpression of RDR6 and DCL4. Consequently, accumulation of viral RNA decreased in the systemically infected leaves, reaching the lowest concentration in the 3rd and 4th leaves at 23 dpi, which was concomitant with recovery of the younger, upper leaves from disease symptoms. No evidence of virus replication was found in the recovered leaves, but they contained infectious virus particles and were protected against re-inoculation with AILV-V. In this study we also showed that AILV-V did not suppress initiation or maintenance of RNA silencing in transgenic plants, but was able to interfere with the cell-to-cell movement of the RNA silencing signal. Our results suggest that AILV-V entrance in SAM and activation of RNA silencing may be distinct processes since the latter is triggered in fully expanded leaves by the accumulation of viral RNA above a threshold level rather than by virus entrance in SAM. PMID:24911029

  14. Clindamycin resistant emm33 Streptococcus pyogenes emerged among invasive infections in Helsinki metropolitan area, Finland, 2012 to 2013.

    PubMed

    Pesola, A K; Sihvonen, R; Lindholm, L; Pätäri-Sampo, A

    2015-05-07

    In 2012, blood, skin and soft tissue infections caused by clindamycin resistant Streptococcus pyogenes (group A streptococcus; GAS) appeared to be increasing in the Helsinki metropolitan area. We compared monthly percentages of clindamycin resistant isolates in the area between 2012 and 2013, with those in 2010 and 2011. Resistance frequency in terms of patient age was also studied. We reviewed the medical records of bacteraemic cases in 2012 and 2013 and linked the data to emm types. To inform on the emm distribution among GAS isolated from skin and soft tissue infections during the epidemic, GAS isolates of one month (March 2013) were emm typed. For GAS blood, skin, and soft tissue isolates taken together, the proportions of clindamycin resistant isolates were significantly higher in 2012 and 2013 (23% and 17%, respectively) compared with the two previous years (3%, p<0,001). The erythromycin resistance percentages were almost equal to clindamycin (22% and 17%) in 2012 and 2013, respectively. Clindamycin resistance was most frequent in GAS isolates of 40 to 60 year-old patients (148/417; 36%). Among clindamycin resistant isolates, 12 of 14 blood isolates from 2012 to 2013, and 11 of 13 skin and soft tissue isolates from March 2013, were emm33. Emm33 GAS bacteraemia was associated with clindamycin and erythromycin resistance (odds ratio (OR): 7.0; 95% confidence interval (CI): 1.9-25.3). Infection focus was mainly the skin; either cellulitis (7/12) or necrotising fasciitis (3/12). All emm33 GAS isolates harboured the ermTR resistance gene with constitutive macrolides, lincosamides and streptogramines B (MLS(B)) phenotype. Emm33 GAS was responsible for the higher proportion of clindamycin resistance in skin, soft tissue, and blood isolates locally in 2012 and 2013.

  15. Invasive disease caused by nontuberculous mycobacteria, Tanzania.

    PubMed

    Crump, John A; van Ingen, Jakko; Morrissey, Anne B; Boeree, Martin J; Mavura, Daudi R; Swai, Britta; Thielman, Nathan M; Bartlett, John A; Grossman, Henning; Maro, Venance P; van Soolingen, Dick

    2009-01-01

    Data on nontuberculous mycobacterial (NTM) disease in sub-Saharan Africa are limited. During 2006-2008, we identified 3 HIV-infected patients in northern Tanzania who had invasive NTM; 2 were infected with "Mycobacterium sherrisii" and 1 with M. avium complex sequevar MAC-D. Invasive NTM disease is present in HIV-infected patients in sub-Saharan Africa.

  16. Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection

    PubMed Central

    Kuo, Chih-Feng; Tsao, Nina; Hsieh, I-Chen; Lin, Yee-Shin; Wu, Jiunn-Jong; Hung, Yu-Ting

    2017-01-01

    Streptococcus pyogenes (group A Streptococcus; GAS) causes clinical diseases, including pharyngitis, scarlet fever, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. A number of group A streptococcus vaccine candidates have been developed, but only one 26-valent recombinant M protein vaccine has entered clinical trials. Differing from the design of a 26-valent recombinant M protein vaccine, we provide here a vaccination using the polyvalence epitope recombinant FSBM protein (rFSBM), which contains four different epitopes, including the fibronectin-binding repeats domain of streptococcal fibronectin binding protein Sfb1, the C-terminal immunogenic segment of streptolysin S, the C3-binding motif of streptococcal pyrogenic exotoxin B, and the C-terminal conserved segment of M protein. Vaccination with the rFSBM protein successfully prevented mortality and skin lesions caused by several emm strains of GAS infection. Anti-FSBM antibodies collected from the rFSBM-immunized mice were able to opsonize at least six emm strains and can neutralize the hemolytic activity of streptolysin S. Furthermore, the internalization of GAS into nonphagocytic cells is also reduced by anti-FSBM serum. These findings suggest that rFSBM can be applied as a vaccine candidate to prevent different emm strains of GAS infection. PMID:28355251

  17. Association Between Type-specific HPV Infections and hTERT DNA Methylation in Patients with Invasive Cervical Cancer

    PubMed Central

    MOLANO, MÓNICA; MORENO-ACOSTA, PABLO; MORALES, NICOLÁS; BURGOS, MARCELA; BUITRAGO, LINA; GAMBOA, OSCAR; ALVAREZ, RAYNER; M. GARLAND, SUZANNE; N. TABRIZI, SEPEHR; D.M. STEENBERGEN, RENSKE; CARLOS MEJÍA, JUAN

    2016-01-01

    Background: There exists limited information on the role of hTERT methylation, and its association with type-specific HPV infections in cervical cancer. Materials and Methods: Eighty-seven frozen samples were analyzed for type-specific HPV infection using a GP5+/GP6+ PCR-RLB assay (RLB). hTERT DNA methylation analysis was performed using a newly developed PCR-RLB-hTERT. Results: Ninety-three percent of samples were HPV-positive and fifteen different types were detected. hTERT methylation analysis of region 1 revealed no methylation in 78.8% of the samples and partial methylation in 21.2%. In region two, 68.2% showed no methylation and 31.8% showed a pattern of partial methylation. An association between the alpha 9 and alpha 7 species with a pattern of no methylation of hTERT in the region 1 was established (p=0.02 and p=0.03, respectively). Conclusion: Differences in patterns of methylation of the hTERT core promoter [region 1 (nt -208 to -1) and region 2 (nt +1 to +104) relative to first ATG] are related to the HPV species present. PMID:27807071

  18. Variant of X-Linked Chronic Granulomatous Disease Revealed by a Severe Burkholderia cepacia Invasive Infection in an Infant

    PubMed Central

    Prando, Carolina; Blancas Galicia, Lizbeth; Hubeau, Marjorie; Blanche, Stéphane; Picard, Capucine; Casanova, Jean-Laurent; Bustamante, Jacinta

    2013-01-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by increased susceptibility to bacteria and fungi since early in life, caused by mutations in any of the five genes coding for protein subunits in NADPH oxidase. X-linked variant CGD can be missed during routine evaluation or present later in life due to hypomorphic mutations and a residual superoxide production. The case of a 10-month-old boy who died of pneumonia is reported. The isolation of Burkholderia cepacia from his lung, together with a marginally low nitroblue tetrazolium reduction assay (NBT), made us suspect and pursue the molecular diagnosis of CGD. A postmortem genetic analysis finally demonstrated CGD caused by a hypomorphic missense mutation with normal gp91phox expression. In a patient being investigated for unusually severe or recurrent infection, a high index of suspicion of immunodeficiency must be maintained. PMID:25374740

  19. Development, clinical utility, and place in therapy of posaconazole for prevention and treatment of invasive fungal infections

    PubMed Central

    Zoller, Emily; Valente, Connie; Baker, Kyle; Klepser, Michael E

    2010-01-01

    Posaconazole is an extended-spectrum azole antifungal that exhibits activity against a broad range of fungal pathogens, including yeasts and moulds. Clinical data have demonstrated the clinical utility of posaconazole against many therapy-refractory pathogens, including Aspergillus spp, Fusarium spp, and Zygomycetes. These data have provided clinicians with hope in these difficult situations. Some of the limitations that have emerged with the use of posaconazole are the lack of an intravenous formulation and erratic drug absorption. This fact is further complicated by the existence of saturable posaconazole absorption. Despite these drawbacks, posaconazole appears poised to become a prominent therapeutic modality for the prophylaxis and management of various fungal infections among high-risk patients. PMID:21116336

  20. Intersubspecific recombination in Xylella fastidiosa Strains native to the United States: infection of novel hosts associated with an unsuccessful invasion.

    PubMed

    Nunney, Leonard; Hopkins, Donald L; Morano, Lisa D; Russell, Stephanie E; Stouthamer, Richard

    2014-02-01

    The bacterial pathogen Xylella fastidiosa infects xylem and causes disease in many plant species in the Americas. Different subspecies of this bacterium and different genotypes within subspecies infect different plant hosts, but the genetics of host adaptation are unknown. Here we examined the hypothesis that the introduction of novel genetic variation via intersubspecific homologous recombination (IHR) facilitates host shifts. We investigated IHR in 33 X. fastidiosa subsp. multiplex isolates previously identified as recombinant based on 8 loci (7 multilocus sequence typing [MLST] loci plus 1 locus). We found significant evidence of introgression from X. fastidiosa subsp. fastidiosa in 4 of the loci and, using published data, evidence of IHR in 6 of 9 additional loci. Our data showed that IHR regions in 2 of the 4 loci were inconsistent (12 mismatches) with X. fastidiosa subsp. fastidiosa alleles found in the United States but consistent with alleles from Central America. The other two loci were consistent with alleles from both regions. We propose that the recombinant forms all originated via genomewide recombination of one X. fastidiosa subsp. multiplex ancestor with one X. fastidiosa subsp. fastidiosa donor from Central America that was introduced into the United States but subsequently disappeared. Using all of the available data, 5 plant hosts of the recombinant types were identified, 3 of which also supported non-IHR X. fastidiosa subsp. multiplex, but 2 were unique to recombinant types from blueberry (7 isolates from Georgia, 3 from Florida); and blackberry (1 each from Florida and North Carolina), strongly supporting the hypothesis that IHR facilitated a host shift to blueberry and possibly blackberry.

  1. Prenatal invasive procedures in women with hepatitis B, hepatitis C, and/or human immunodeficiency virus infections.

    PubMed

    Gagnon, Alain; Davies, Gregory; Wilson, R Douglas; Wilson, R Douglas; Audibert, Francois; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chitaya, David T; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Murphy-Kaulbeck, Lynn; Okun, Nanette; Pastuck, Melanie

    2014-07-01

    Objectif : Analyser le risque d’infection in utero attribuable aux interventions effractives prénatales chez les femmes qui présentent des infections par le virus de l’hépatite B, le virus de l’hépatite C et/ou le virus de l’immunodéficience humaine (VIH). Issues : Morbidité et mortalité foetales et néonatales. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline, CINAHL et The Cochrane Library au moyen d’un vocabulaire contrôlé (p. ex. « amniocentesis », « chorionic villus sampling », « cordocentesis », « fetal and neonatal infection ») et de mots clés (p. ex. « hepatitis B », « hepatitis C », « HIV ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles publiés en anglais ou en français entre 2002 et 2012 (les études publiées entre 1966 et 2002 ont déjà fait l’objet d’une analyse dans le cadre de la directive clinique n° 123). Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu’en février 2014. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d’étude canadien sur les soins de santé préventifs (Tableau). Recommandations 1. Pour l’évaluation du risque prénatal chez les femmes infectées par le virus de l’hépatite B, le virus de l’hépatite C et/ou le virus de l

  2. Invasive Species

    EPA Pesticide Factsheets

    Invasive species have significantly changed the Great Lakes ecosystem. An invasive species is a plant or animal that is not native to an ecosystem, and whose introduction is likely to cause economic, human health, or environmental damage.

  3. The role of surgery in the treatment of invasive fungal infection in paediatric haematology patients: a retrospective single-centre survey.

    PubMed

    Cesaro, Simone; Pegoraro, Anna; Tridello, Gloria; Pillon, Marta; Cannata, Elisa; Faggin, Stefano; Cecchetto, Giovanni

    2014-07-01

    Surgery may improve the control of fungal disease and patient survival. The aim of this study was to report a single-centre experience in using surgery for the treatment of paediatric invasive fungal infection (IFI). From 2001 to 2009, 18 paediatric onco-haematology patients underwent 24 surgical procedures as treatment of IFI. At surgery, severe thrombocytopenia and neutropenia were present in four and one episodes respectively. Complications were one pleural effusion, one pleural effusion and surgical wound infection, one pneumothorax with wound dehiscence and one wound dehiscence. None of them required repeat surgery. The median duration of hospitalisation for four complicated procedures was 11 days, range 3-16, and 7 days, range 2-13, for the 20 uncomplicated procedures. No surgery-related deaths occurred. Fourteen patients resumed chemotherapy after a median of 26 days, range 9-77, whereas nine patients underwent hematopoietic stem cell transplantation after a median of 42 days, range 27-110. At 3 months from IFI, 17 patients were alive (94%) and one patient (6%) died from mycosis; the 3-month overall survival (OS) being 94.4%, CI 66.6-99.2. After a median follow-up of 7.1 years (CI 2.8-7.5), the OS was 54.5%, CI 29.2-74.2. Surgery is a feasible and valuable option in paediatric patients because it is associated with a low incidence of complications and an acceptable delay in resuming the chemotherapeutic plan.

  4. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  5. Resistant ticks inhibit Metarhizium infection prior to haemocoel invasion by reducing fungal viability on the cuticle surface.

    PubMed

    Ment, Dana; Churchill, Alice C L; Gindin, Galina; Belausov, Eduard; Glazer, Itamar; Rehner, Stephen A; Rot, Asael; Donzelli, Bruno G G; Samish, Michael

    2012-06-01

    We studied disease progression of, and host responses to, four species in the Metarhizium anisopliae complex expressing green fluorescent protein (GFP). We compared development and determined their relative levels of virulence against two susceptible arthropods, the cattle tick Rhipicephalus annulatus and the lepidopteran Galleria mellonella, and two resistant ticks, Hyalomma excavatum and Rhipicephalus sanguineus. Metarhizium brunneum Ma7 caused the greatest mortality of R. annulatus, Metarhizium robertsii ARSEF 2575 and Metarhizium pingshaense PPRC51 exhibited intermediate levels of virulence, and Metarhizium majus PPRC27 caused low mortality of cattle ticks. Conidia of all four species germinated on all hosts examined, but on resistant hosts, sustained hyphal growth was inhibited and GFP emission steadily and significantly decreased over time, suggesting a loss of fungal viability. Cuticle penetration was observed only for the three most virulent species infecting susceptible hosts. Cuticles of resistant and susceptible engorged female ticks showed significant increases in red autofluorescence at sites immediately under fungal hyphae. This is the first report (i) of tick mortality occurring after cuticle penetration but prior to haemocoel colonization and (ii) that resistant ticks do not support development of Metarhizium germlings on the outer surface of the cuticle. Whether reduced Metarhizium viability on resistant tick cuticles is due to antibiosis or limited nutrient availability is unknown.

  6. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation.

    PubMed Central

    Agus, Allison; Denizot, Jérémy; Thévenot, Jonathan; Martinez-Medina, Margarita; Massier, Sébastien; Sauvanet, Pierre; Bernalier-Donadille, Annick; Denis, Sylvain; Hofman, Paul; Bonnet, Richard; Billard, Elisabeth; Barnich, Nicolas

    2016-01-01

    Recent advances have shown that the abnormal inflammatory response observed in CD involves an interplay among intestinal microbiota, host genetics and environmental factors. The escalating consumption of fat and sugar in Western countries parallels an increased incidence of CD during the latter 20th century. The impact of a HF/HS diet in mice was evaluated for the gut micro-inflammation, intestinal microbiota composition, function and selection of an E. coli population. The HF/HS diet created a specific inflammatory environment in the gut, correlated with intestinal mucosa dysbiosis characterized by an overgrowth of pro-inflammatory Proteobacteria such as E. coli, a decrease in protective bacteria, and a significantly decreased of SCFA concentrations. The expression of GPR43, a SCFA receptor was reduced in mice treated with a HF/HS diet and reduced in CD patients compared with controls. Interestingly, mice treated with an agonist of GPR43 were protected against DSS-induced colitis. Finally, the transplantation of feces from HF/HS treated mice to GF mice increased susceptibility to AIEC infection. Together, our results demonstrate that a Western diet could aggravate the inflammatory process and that the activation of the GPR43 receptor pathway could be used as a new strategy to treat CD patients. PMID:26742586

  7. Immune dynamics following infection of avian macrophages and epithelial cells with typhoidal and non-typhoidal Salmonella enterica serovars; bacterial invasion and persistence, nitric oxide and oxygen production, differential host gene expression, NF-κB signalling and cell cytotoxicity.

    PubMed

    Setta, Ahmed; Barrow, Paul A; Kaiser, Pete; Jones, Michael A

    2012-05-15

    Poultry-derived food is a common source of infection of human with the non-host-adapted salmonellae while fowl typhoid and pullorum disease are serious diseases in poultry. Development of novel immune-based control strategies against Salmonella infection necessitates a better understanding of the host-pathogen interactions at the cellular level. Intestinal epithelial cells are the first line of defence against enteric infections and the role of macrophages is crucial in Salmonella infection and pathogenesis. While gene expression following Salmonella infection has been investigated, a comparison between different serovars has not been, as yet, extensively studied in poultry. In this study, chicken macrophage-like cells (HD11) and chick kidney epithelial cells (CKC) were used to study and compare the immune responses and mechanisms that develop after infection with different Salmonella serotypes. Salmonella serovars Typhimurium, Enteritidis, Hadar and Infantis showed a greater level of invasion and/or uptake characters when compared with S. Pullorum or S. Gallinarum. Nitrate and reactive oxygen species were greater in Salmonella-infected HD11 cells with the expression of iNOS and nuclear factor-κB by chicken macrophages infected with both systemic and broad host range serovars. HD11 cells revealed higher mRNA gene expression for CXCLi2, IL-6 and iNOS genes in response to S. Enteritidis infection when compared to S. Pullorum-infected cells. S. Typhimurium- and S. Hadar-infected HD11 showed higher gene expression for CXCLi2 versus S. Pullorum-infected cells. Higher mRNA gene expression levels of pro-inflammatory cytokine IL-6, chemokines CXCLi1 and CXCLi2 and iNOS genes were detected in S. Typhimurium- and S. Enteritidis-infected CKC followed by S. Hadar and S. Infantis while no significant changes were observed in S. Pullorum or S. Gallinarum-infected CKC.

  8. Phase 1b study of new posaconazole tablet for prevention of invasive fungal infections in high-risk patients with neutropenia.

    PubMed

    Duarte, Rafael F; López-Jiménez, Javier; Cornely, Oliver A; Laverdiere, Michel; Helfgott, David; Haider, Shariq; Chandrasekar, Pranatharthi; Langston, Amelia; Perfect, John; Ma, Lei; van Iersel, Marlou L P S; Connelly, Nancy; Kartsonis, Nicholas; Waskin, Hetty

    2014-10-01

    Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).

  9. Infection néonatale invasive à entérovirus associant une myocardite sévère et une méningite

    PubMed Central

    Mohamed, Boulyana

    2014-01-01

    L'infection néonatale invasive à entérovirus (EV) reste rare mais souvent fatale et devrait être prise dans le diagnostic différentiel chez les enfants septiques. Nous rapportons le cas d'un nouveau-né hospitalisé pour un sepsis grave à EV avec une méningite et une myocardite sévère d'évolution favorable après une corticothérapie. Nous présentons une discussion basée sur une revue de la littérature pour aider le clinicien à reconnaitre les facteurs de gravité et à apprécier les nouvelles stratégies diagnostiques telle la PCR (Polymerase Chain Reaction) et l'imagerie par résonance magnétique (IRM) cardiaque. Nous passons également en revue les nouvelles approches thérapeutiques telles les biothérapies, les antiviraux spécifiques et l'Oxygénation par Membrane Extra-Corporelle (ECMO). PMID:25883734

  10. Serotype distribution of pneumococci isolated from pediatric patients with acute otitis media and invasive infections, and potential coverage of pneumococcal conjugated vaccines.

    PubMed

    Reijtman, Vanesa; Fossati, Sofía; Hernández, Claudia; Sommerfleck, Patricia; Bernáldez, Patricia; Litterio, Mirta; Berberian, Griselda; Regueira, Mabel; Lopardo, Horacio

    2013-01-01

    A 16-month prospective, descriptive study was conducted on pneumococcal serotype distribution isolated from children with acute otitis media (AOM) and invasive infections (INV). Eighty-nine children with pneumococcal INV and 324 with a first episode of AOM were included. Bacterial pathogens (N = 326) were isolated from the middle-ear fluid of 250 patients. A total of 30 pneumococcal serotypes were identified. Prevalent serotypes were 14, 19A, 9V, 3, 19F, 6A, 23F, and 18C in AOM and 14, 1, 19A, 5, 12F, 6B, and 18C in INV. Potential coverage with PCV10 vaccine would be 46.5 % and 60.7 % for pneumococci involved in AOM and INV, respectively; it would be 71.7 % and 73 % with PCV13. PCV10, conjugated with a Haemophilus protein, would have an immunologic coverage of 39.9 % for AOM vs. 18.5 % with PCV13. However, differences in the prevention of INV were crucial for the decision to include the 13-valent vaccine in the national calendar for children less than two years old in Argentina.

  11. Comparative RNA-seq analysis of early-infected peach leaves by the invasive phytopathogen Xanthomonas arboricola pv. pruni.

    PubMed

    Socquet-Juglard, Didier; Kamber, Tim; Pothier, Joël F; Christen, Danilo; Gessler, Cesare; Duffy, Brion; Patocchi, Andrea

    2013-01-01

    Xanthomonas arboricola pv. pruni is a quarantine bacterial pathogen that threatens peach production by causing necrotic spots on leaves and fruits, thus with the potential of severely reducing yields. The current understanding of the host plant defense responses to the pathogen is very limited. Using whole transcriptome sequencing, differential gene expression was analyzed at two time points, 2 h and 12 h post inoculation (hpi), by comparing the inoculated samples to their respective controls. On the total of 19,781 known peach genes that were expressed in all time points and conditions, 34 and 263 were differentially expressed at 2 and 12 hpi, respectively. Of those, 82% and 40% were up-regulated, respectively; and 18% and 60% were down-regulated, respectively. The functional annotation based on gene ontology (GO) analysis highlighted that genes involved in metabolic process and response to stress were particularly represented at 2 hpi whereas at 12 hpi cellular and metabolic processes were the categories with the highest number of genes differentially expressed. Of particular interest among the differentially expressed genes identified were several pathogen-associated molecular pattern (PAMP) receptors, disease resistance genes including several RPM1-like and pathogenesis related thaumatin encoding genes. Other genes involved in photosynthesis, in cell wall reorganization, in hormone signaling pathways or encoding cytochrome were also differentially expressed. In addition, novel transcripts were identified, providing another basis for further characterization of plant defense-related genes. Overall, this study gives a first insight of the peach defense mechanisms during the very early stages of infection with a bacterial disease in the case of a compatible interaction.

  12. Infection

    MedlinePlus

    ... 23(4):251-69. Association for Professionals in Infection Control and Epidemiology (APIC) guideline. Back to Top Administration ... : Hospital Scope | Glossary | References | Site Map | Credits Freedom of ...

  13. Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy

    PubMed Central

    Schmid, Patrick; Bregenzer, Andrea; Huber, Milo; Rauch, Andri; Jochum, Wolfram; Müllhaupt, Beat; Vernazza, Pietro; Opravil, Milos; Weber, Rainer

    2015-01-01

    Objectives To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Methods Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Results Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. Conclusion TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy. PMID:26418061

  14. Fermentable non-starch polysaccharides increases the abundance of Bacteroides-Prevotella-Porphyromonas in ileal microbial community of growing pigs.

    PubMed

    Ivarsson, E; Roos, S; Liu, H Y; Lindberg, J E

    2014-11-01

    Most plant-origin fiber sources used in pig production contains a mixture of soluble and insoluble non-starch polysaccharides (NSP). The knowledge about effects of these sources of NSP on the gut microbiota and its fermentation products is still scarce. The aim of this study was to investigate effects of feeding diets with native sources of NSP on the ileal and fecal microbial composition and the dietary impact on the concentration of short-chain fatty acids (SCFA) and lactic acid. The experiment comprised four diets and four periods in a change-over design with seven post valve t-cecum cannulated growing pigs. The four diets were balanced to be similar in NSP content and included one of four fiber sources, two diets were rich in pectins, through inclusion of chicory forage (CFO) and sugar beet pulp, and two were rich in arabinoxylan, through inclusion of wheat bran (WB) and grass meal. The gut microbial composition was assessed with terminal restriction fragment (TRF) length polymorphism and the abundance of Lactobacillus spp., Enterobacteriaceae, Bacteroides-Prevotella-Porphyromonas and the β-xylosidase gene, xynB, were assessed with quantitative PCR. The gut microbiota did not cluster based on NSP structure (arabinoxylan or pectin) rather, the effect was to a high degree ingredient specific. In pigs fed diet CFO, three TRFs related to Prevotellaceae together consisted of more than 25% of the fecal microbiota, which is about 3 to 23 times higher (P<0.05) than in pigs fed the other diets. Whereas pigs fed diet WB had about 2 to 22 times higher abundance (P<0.05) of Megasphaera elsdenii in feces and about six times higher abundance (P<0.05) of Lactobacillus reuteri in ileal digesta than pigs fed the other diets. The total amount of digested NSP (r=0.57; P=0.002), xylose (r=0.53; P=0.004) and dietary fiber (r=0.60; P=0.001) in ileal digesta were positively correlated with an increased abundance of Bacteroides-Prevotella-Porphyromonas. The effect on SCFA was

  15. The complete genome sequencing of Prevotella intermedia strain OMA14 and a subsequent fine-scale, intra-species genomic comparison reveal an unusual amplification of conjugative and mobile transposons and identify a novel Prevotella-lineage-specific repeat.

    PubMed

    Naito, Mariko; Ogura, Yoshitoshi; Itoh, Takehiko; Shoji, Mikio; Okamoto, Masaaki; Hayashi, Tetsuya; Nakayama, Koji

    2016-02-01

    Prevotella intermedia is a pathogenic bacterium involved in periodontal diseases. Here, we present the complete genome sequence of a clinical strain, OMA14, of this bacterium along with the results of comparative genome analysis with strain 17 of the same species whose genome has also been sequenced, but not fully analysed yet. The genomes of both strains consist of two circular chromosomes: the larger chromosomes are similar in size and exhibit a high overall linearity of gene organizations, whereas the smaller chromosomes show a significant size variation and have undergone remarkable genome rearrangements. Unique features of the Pre. intermedia genomes are the presence of a remarkable number of essential genes on the second chromosomes and the abundance of conjugative and mobilizable transposons (CTns and MTns). The CTns/MTns are particularly abundant in the second chromosomes, involved in its extensive genome rearrangement, and have introduced a number of strain-specific genes into each strain. We also found a novel 188-bp repeat sequence that has been highly amplified in Pre. intermedia and are specifically distributed among the Pre. intermedia-related species. These findings expand our understanding of the genetic features of Pre. intermedia and the roles of CTns and MTns in the evolution of bacteria.

  16. Tapeworm Infection

    MedlinePlus

    ... a laboratory for testing. A laboratory uses microscopic identification techniques to check for eggs or tapeworm segments ... to the anus to collect eggs for microscopic identification. Blood test. For tissue-invasive infections, your doctor ...

  17. Medium- to large-sized xylo-oligosaccharides are responsible for xylanase induction in Prevotella bryantii B14.

    PubMed

    Miyazaki, Kohji; Hirase, Tatsuaki; Kojima, Yoichi; Flint, Harry James

    2005-12-01

    Experiments were done to define the nature of the xylan-derived induction signal for xylanase activity, and evaluate which xylanase genes among the three known ones (xynA, xynB and xynC) are induced by the presence of xylan in Prevotella bryantii B(1)4. During the later stages of exponential growth on glucose, addition of 0.05 % water-soluble xylan (WS-X) stimulated xylanase formation within 30 min. Xylose, xylobiose, xylotriose, xylotetraose, xylopentaose, arabinose and glucuronic acid all failed to induce the xylanase activity. An acid-ethanol-soluble fraction of WS-X (approximate degree of polymerization 30) enhanced the activity significantly, whereas the acid-ethanol-insoluble fraction had no effect, unless first digested by the cloned P. bryantii XynC xylanase. These results indicate that medium- to large-sized xylo-oligosaccharides are responsible for induction. The transcription of all three known xylanase genes from P. bryantii was upregulated coordinately by addition of WS-X. There have been relatively few investigations into the regulation of xylanase activity in bacteria, and it appears to be unique that medium- to large-sized xylo-oligosaccharides are responsible for induction.

  18. Molecular Characterization and Meta-Analysis of Gut Microbial Communities Illustrate Enrichment of Prevotella and Megasphaera in Indian Subjects

    PubMed Central

    Bhute, Shrikant; Pande, Pranav; Shetty, Sudarshan A.; Shelar, Rahul; Mane, Sachin; Kumbhare, Shreyas V.; Gawali, Ashwini; Makhani, Hemal; Navandar, Mohit; Dhotre, Dhiraj; Lubree, Himangi; Agarwal, Dhiraj; Patil, Rutuja; Ozarkar, Shantanu; Ghaskadbi, Saroj; Yajnik, Chittaranjan; Juvekar, Sanjay; Makharia, Govind K.; Shouche, Yogesh S.

    2016-01-01

    The gut microbiome has varied impact on the wellbeing of humans. It is influenced by different factors such as age, dietary habits, socio-economic status, geographic location, and genetic makeup of individuals. For devising microbiome-based therapies, it is crucial to identify population specific features of the gut microbiome. Indian population is one of the most ethnically, culturally, and geographically diverse, but the gut microbiome features remain largely unknown. The present study describes gut microbial communities of healthy Indian subjects and compares it with the microbiota from other populations. Based on large differences in alpha diversity indices, abundance of 11 bacterial phyla and individual specific OTUs, we report inter-individual variations in gut microbial communities of these subjects. While the gut microbiome of Indians is different from that of Americans, it shared high similarity to individuals from the Indian subcontinent i.e., Bangladeshi. Distinctive feature of Indian gut microbiota is the predominance of genus Prevotella and Megasphaera. Further, when compared with other non-human primates, it appears that Indians share more OTUs with omnivorous mammals. Our metagenomic imputation indicates higher potential for glycan biosynthesis and xenobiotic metabolism in these subjects. Our study indicates urgent need of identification of population specific microbiome biomarkers of Indian subpopulations to have more holistic view of the Indian gut microbiome and its health implications. PMID:27242691

  19. Development of Prevotella intermedia-specific PCR primers based on the nucleotide sequences of a DNA probe Pig27.

    PubMed

    Kim, Min Jung; Hwang, Kyung Hwan; Lee, Young-Seok; Park, Jae-Yoon; Kook, Joong-Ki

    2011-03-01

    The aim of this study was to develop Prevotella intermedia-specific PCR primers based on the P. intermedia-specific DNA probe. The P. intermedia-specific DNA probe was screened by inverted dot blot hybridization and confirmed by Southern blot hybridization. The nucleotide sequences of the species-specific DNA probes were determined using a chain termination method. Southern blot analysis showed that the DNA probe, Pig27, detected only the genomic DNA of P. intermedia strains. PCR showed that the PCR primers, Pin-F1/Pin-R1, had species-specificity for P. intermedia. The detection limits of the PCR primer sets were 0.4pg of the purified genomic DNA of P. intermedia ATCC 49046. These results suggest that the PCR primers, Pin-F1/Pin-R1, could be useful in the detection of P. intermedia as well as in the development of a PCR kit in epidemiological studies related to periodontal diseases.

  20. Outer membrane proteome of Prevotella intermedia 17: identification of thioredoxin and iron-repressible hemin uptake loci.

    PubMed

    Yu, Fan; Anaya, Cecilia; Lewis, Janina P

    2007-02-01

    Although hemin is an indispensable nutrient for the oral pathogen Prevotella intermedia, not much is known regarding the molecular mechanisms of hemin acquisition. The availability of the genomic sequence of the bacterium allowed us to apply proteomic approaches to identify proteins that may be mediating the hemin acquisition process. As hemin acquisition mechanisms have been shown to be induced in iron-depleted conditions, we applied proteomic approaches to detect those proteins whose expressions were affected by iron. We analyzed 40 protein spots and identified 19 such proteins. Interestingly, two proteins drastically upregulated in iron-depleted conditions, PIN0009 and PINA0611, are homologs of hemin uptake receptors in other bacteria. PIN0009 is predicted to be an outer membrane lipoprotein. It is encoded by a gene that is the first of a seven-gene genomic locus encoding proteins of a novel hemin acquisition system. The second protein, PINA0611, is a homolog of numerous TonB-dependent outer membrane receptors including outer membrane iron uptake receptors of various Gram-negative bacteria. There was also another protein, regulated by iron, that was previously demonstrated to bind hemoglobin in P. intermedia. Finally, we identified a thioredoxin-like protein that has a novel outer membrane location.

  1. A Preliminary Study of the Effects of pH upon Fluorescence in Suspensions of Prevotella intermedia.

    PubMed

    Hope, Christopher K; Billingsley, Karen; de Josselin de Jong, Elbert; Higham, Susan M

    2016-01-01

    The quantification of fluorescence in dental plaque is currently being developed as a diagnostic tool to help inform and improve oral health. The oral anaerobe Prevotella intermedia exhibits red fluorescence due to the accumulation of porphyrins. pH affects the fluorescence of abiotic preparations of porphyrins caused by changes in speciation between monomers, higher aggregates and dimers, but this phenomenon has not been demonstrated in bacteria. Fluorescence spectra were obtained from suspensions of P. intermedia that were adjusted to pHs commensurate with the range found within dental plaque. Two fluorescent motifs were identified; 410 nm excitation / 634 nm emission (peak A) and 398 nm excitation / 622 nm emission (peak B). A transition in the fluorescence spectra was observed from peak A to peak B with increasing pH which was also evident as culture age increased from 24 hours to 96 hours. In addition to these 'blue-shifts', the intensity of peak A increased with pH whilst decreasing with culture age from 24 to 96 hours. A bacterium's relationship with the local physiochemical environment at the time of image capture may therefore affect the quantification of dental plaque fluorescence.

  2. In vitro effects of N-acetyl cysteine alone and in combination with antibiotics on Prevotella intermedia.

    PubMed

    Moon, Ji-Hoi; Jang, Eun-Young; Shim, Kyu Sang; Lee, Jin-Yong

    2015-05-01

    N-acetyl cysteine (NAC) is an antioxidant that possesses anti-inflammatory activities in tissues. In the field of dentistry, NAC was demonstrated to prevent the expression of LPS-induced inflammatory mediators in phagocytic cells and gingival fibroblasts during the inflammatory process, but the effect of NAC on oral pathogens has been rarely studied. Here, we examined the effect of NAC against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. NAC showed antibacterial activity against the planktonic P. intermedia with MIC value of 3 mg/ml and significantly decreased biofilm formation by the bacterium even at sub MIC. NAC did not affect the antibiotic susceptibility of planktonic P. intermedia, showing indifference (fractional inhibitory concentration index of 0.5-4) results against the bacterium in combination with ampicillin, ciprofloxacin, tetracycline or metronidazole. On the other hand, viability of the pre-established bacterial biofilm exposed to the antibiotics except metronidazole was increased in the presence of NAC. Collectively, NAC may be used for prevention of the biofilm formation by P. intermedia rather than eradication of the pre-established bacterial biofilm. Further studies are required to explore antibacterial and anti-biofilm activity of NAC against mixed population of oral bacteria and its modulatory effect on antibiotics used for oral infectious diseases.

  3. Effects of mushroom and chicory extracts on the physiology and shape of Prevotella intermedia, a periodontopathogenic bacterium.

    PubMed

    Signoretto, Caterina; Marchi, Anna; Bertoncelli, Anna; Burlacchini, Gloria; Tessarolo, Francesco; Caola, Iole; Pezzati, Elisabetta; Zaura, Egija; Papetti, Adele; Lingström, Peter; Pratten, Jonathan; Spratt, David A; Wilson, Michael; Canepari, Pietro

    2011-01-01

    Contrary to the common assumption that food has a negative impact on oral health, research has shown that several foods contain a number of components with antibacterial and antiplaque activity. These natural compounds may be useful for improving daily oral hygiene. In this study we evaluate the mode of antimicrobial action of fractions of mushroom and red chicory extracts on Prevotella intermedia, a periodontopathogenic bacterium. The minimal inhibitory concentration corresponded to 0.5x compared to the natural food concentration for both extracts. This concentration resulted in a bacteriostatic effect in mushroom extract and in a slightly bactericidal effect in chicory extract. Cell mass continued to increase even after division stopped. As regards macromolecular synthesis, DNA was almost totally inhibited upon addition of either mushroom or chicory extract, and RNA to a lesser extent, while protein synthesis continued. Cell elongation occurred after septum inhibition as documented by scanning electron microscopy and cell measurement. The morphogenetic effects are reminiscent of the mode of action of antibiotics such as quinolones or β-lactams. The discovery of an antibiotic-like mode of action suggests that these extracts can be advantageously employed for daily oral hygiene in formulations of cosmetic products such as mouthwashes and toothpastes.

  4. A Preliminary Study of the Effects of pH upon Fluorescence in Suspensions of Prevotella intermedia

    PubMed Central

    Hope, Christopher K.; Billingsley, Karen; de Josselin de Jong, Elbert; Higham, Susan M.

    2016-01-01

    The quantification of fluorescence in dental plaque is currently being developed as a diagnostic tool to help inform and improve oral health. The oral anaerobe Prevotella intermedia exhibits red fluorescence due to the accumulation of porphyrins. pH affects the fluorescence of abiotic preparations of porphyrins caused by changes in speciation between monomers, higher aggregates and dimers, but this phenomenon has not been demonstrated in bacteria. Fluorescence spectra were obtained from suspensions of P. intermedia that were adjusted to pHs commensurate with the range found within dental plaque. Two fluorescent motifs were identified; 410 nm excitation / 634 nm emission (peak A) and 398 nm excitation / 622 nm emission (peak B). A transition in the fluorescence spectra was observed from peak A to peak B with increasing pH which was also evident as culture age increased from 24 hours to 96 hours. In addition to these ‘blue-shifts’, the intensity of peak A increased with pH whilst decreasing with culture age from 24 to 96 hours. A bacterium’s relationship with the local physiochemical environment at the time of image capture may therefore affect the quantification of dental plaque fluorescence. PMID:27441707

  5. Diagnostic Values and Limitations of (1,3)-β-D-Glucans and Galactomannan Assays for Invasive Fungal Infection in Patients Admitted to Pediatric Intensive Care Unit.

    PubMed

    Zheng, Fang; Zha, Hui; Yang, Dandan; Deng, Jun; Zhang, Zhiquan

    2017-04-01

    The relationship among (1,3)-β-D-glucans (BG), galactomannan (GM), and the risk of developing invasive fungal infections (IFI) has been observed in adult ICU and in children with hematological malignancies. Only scant data evaluated the value of BG/GM assays for diagnosis of IFI in patients with nonhematological diseases in pediatric intensive care unit (PICU). In this study, we assessed the diagnostic value of these markers for IFI in PICU. The records of 230 patients were retrospectively evaluated. Out of 117 patients (7 proven, 23 probable, and 87 cases without evidence of IFI) performed GM and BG assays. The results showed many factors were associated with false-positive test results. Patients who aged over 3 years had higher levels of GM and BG than younger infants. The levels of BG were higher in subjects with dairy, human blood products, antibiotics, and corticosteroids therapy than in cases without these treatments. Unlike BG assay, GM assay was less susceptible to above-mentioned factors expect blood products. The levels of BG and GM in IFI cases were dramatically higher than in controls. The diagnostic performance of these assays showed that GM assay had better results when compared with BG assay. On the whole, negative predictive value in both GM and BG assays was dramatically higher than other diagnostic parameters. In conclusion, BG assay was highly susceptible to many factors, and GM assay could be useful for diagnosis of IFI for its high sensitivity, but the over benefit of this assay limited in its inadequate specificity. The comparative advantage of BG and BG assays lied in excluding IFI in non-hematological PICU patients.

  6. Prophylaxis and therapy using liposomal amphotericin B (AmBisome) for invasive fungal infections in children undergoing organ or allogeneic bone-marrow transplantation.

    PubMed

    Ringdén, O; Andström, E E; Remberger, M; Dahllöf, G; Svahn, B M; Tollemar, J

    1997-11-01

    Sixty-one children with a median age of 6 years (range 1-16) were given prophylaxis/therapy for 78 courses of treatment with liposomal amphotericin (AmBisome) and were reviewed retrospectively. Thirty-six received allogeneic bone marrow, 22 a liver transplant, 2 kidneys and 1 a liver and kidney. AmBisome was given as prophylaxis in 30 episodes, as treatment for suspected invasive fungal infections (IFI) in 33 and for a verified IFI in 15. AmBisome prophylaxis was given for a median of 14 days in a dose of 1 mg/kg/day. The median dose of AmBisome was 2.1 mg/kg/day (range 0.9-5.0). The median duration of therapy was 10 days in children with suspected IFI and 20 days in children with verified IFI. The total dose ranged from 0.025 g up to a maximum of 3.95 g. Proven and probable side effects of AmBisome were a decrease in the level of serum potassium (30/78 cases), renal toxicity (22), an increase in the alkaline phosphatases (24), back pain (2), fever and abdominal pain (2), anaphylactic reaction (1), an increase in the bilirubin level (1), nausea (1), chest pain (1) and fever (1). Of 31 children with suspected IFI, fever disappeared in 21 (68%). In 14 verified or suspected IFI cases treated for 5 days or more, the clinical cure rate was 12 (86%). Eradication of fungi from a deep site was verified in 8/10 and the survival rate from 1 1/2 years to more than 7 years was 7/12 (58%). We conclude that AmBisome was well tolerated as prophylaxis and therapy in transplanted children, few acute toxic side effects were seen and the cure rate in verified IFI was high.

  7. Salmonella enterica Serovar Enteritidis Core O Polysaccharide Conjugated to H:g,m Flagellin as a Candidate Vaccine for Protection against Invasive Infection with S. Enteritidis▿†

    PubMed Central

    Simon, Raphael; Tennant, Sharon M.; Wang, Jin Y.; Schmidlein, Patrick J.; Lees, Andrew; Ernst, Robert K.; Pasetti, Marcela F.; Galen, James E.; Levine, Myron M.

    2011-01-01

    Nontyphoidal Salmonella enterica serovars Enteritidis and Typhimurium are a common cause of gastroenteritis but also cause invasive infections and enteric fever in certain hosts (young children in sub-Saharan Africa, the elderly, and immunocompromised individuals). Salmonella O polysaccharides (OPS) and flagellar proteins are virulence factors and protective antigens. The surface polysaccharides of Salmonella are poorly immunogenic and do not confer immunologic memory, limitations overcome by covalently attaching them to carrier proteins. We conjugated core polysaccharide-OPS (COPS) of Salmonella Enteritidis lipopolysaccharide (LPS) to flagellin protein from the homologous strain. COPS and flagellin were purified from a genetically attenuated (ΔguaBA) “reagent strain” (derived from an isolate from a patient with clinical bacteremia) engineered for increased flagellin production (ΔclpPX). Conjugates were constructed by linking flagellin monomers or polymers at random COPS hydroxyls with various polysaccharide/protein ratios by 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) or at the 3-deoxy-d-manno-octulosonic acid (KDO) terminus by thioether chemistry. Mice immunized on days 0, 28, and 56 with COPS-flagellin conjugates mounted higher anti-LPS IgG levels than mice receiving unconjugated COPS and exhibited high antiflagellin IgG; anti-LPS and antiflagellin IgG levels increased following booster doses. Antibodies generated by COPS-flagellin conjugates mediated opsonophagocytosis of S. Enteritidis cells into mouse macrophages. Mice immunized with flagellin alone, COPS-CRM197, or COPS-flagellin conjugates were significantly protected from lethal challenge with wild-type S. Enteritidis (80 to 100% vaccine efficacy). PMID:21807909

  8. High Incidences of Invasive Fungal Infections in Acute Myeloid Leukemia Patients Receiving Induction Chemotherapy without Systemic Antifungal Prophylaxis: A Prospective Observational Study in Taiwan

    PubMed Central

    Kung, Hsiang-Chi; Yao, Ming; Wu, Un-In; Hsu, Szu-Chun; Lin, Chien-Ting; Li, Chi-Cheng; Wu, Shang-Ju; Hou, Hsin-An; Chou, Wen-Chien; Huang, Shang-Yi; Tsay, Woei; Chen, Yao-Chang; Chen, Yee-Chun; Chang, Shan-Chwen; Ko, Bor-Sheng; Tien, Hwei-Fang

    2015-01-01

    Invasive fungal infections (IFIs) is an important complication for acute myeloid leukemia (AML) patients receiving induction chemotherapy. However, the epidemiological information is not clear in Southeastern Asia, an area of potential high incidences of IFIs. To clarify it, we enrolled 298 non-M3 adult AML patients receiving induction chemotherapy without systemic anti-fungal prophylaxis from Jan 2004 to Dec 2009, when we applied a prospective diagnostic and treatment algorithm for IFIs. Their demographic parameters, IFI characters, and treatment outcome were collected for analysis. The median age of these patients was 51 years. Standard induction chemotherapy was used for 246 (82.6%) patients, and 66.8% of patients achieved complete remission (CR) or partial remission. The incidence of all-category IFIs was 34.6% (5.7% proven IFIs, 5.0% probable IFIs and 23.8% possible IFIs). Candida tropicalis was the leading pathogen among yeast, and lower respiratory tract was the most common site for IFIs (75.4%, 80/106). Standard induction chemotherapy and failure to CR were identified as risk factors for IFIs. The presence of IFI in induction independently predicted worse survival (hazard ratio 1.536 (1.100–2.141), p value = 0.012). Even in those who survived from the initial IFI insults after 3 months, the presence of IFIs in induction still predicted a poor long-term survival. This study confirms high incidences of IFIs in Southeastern Asia, and illustrates potential risk factors; poor short-term and long-term outcomes are also demonstrated. This epidemiological information will provide useful perspectives for anti-fungal prophylaxis and treatment for AML patients during induction, so that best chances of cure and survival can be provided. PMID:26061179

  9. Burden and treatment patterns of invasive fungal infections in hospitalized patients in the Middle East: real-world data from Saudi Arabia and Lebanon

    PubMed Central

    Alothman, Adel F; Althaqafi, Abdulhakeem O; Matar, Madonna J; Moghnieh, Rima; Alenazi, Thamer H; Farahat, Fayssal M; Corman, Shelby; Solem, Caitlyn T; Raghubir, Nirvana; Macahilig, Cynthia; Charbonneau, Claudie; Stephens, Jennifer M

    2017-01-01

    Objectives The objective of this study was to document the burden and treatment patterns associated with invasive fungal infections (IFIs) due to Candida and Aspergillus species in Saudi Arabia and Lebanon. Methods A retrospective chart review study was conducted using data recorded from 2011 to 2012 from hospitals in Saudi Arabia and Lebanon. Patients were included if they had been discharged with a diagnosis of IFI due to Candida or Aspergillus, which was culture proven or suspected based on clinical criteria. Hospital data were abstracted for a random sample of patients to capture demographics, treatment patterns, hospital resource utilization, and clinical outcomes. Descriptive results were reported. Results Five hospitals participated and provided data on 102 patients with IFI (51 from Lebanon and 51 from Saudi Arabia). The mean age of the patients was 55 years, and 55% were males. Comorbidities included diabetes (41%), coronary artery disease (24%), leukemia (19%), moderate-to-severe renal disease (16%), congestive heart failure (15%), and chronic obstructive pulmonary disease (15%). Twenty percent of patients received corticosteroids prior to admission and 26% had received chemotherapy in the past 90 days. Inpatient mortality was 42%, and the mean hospital length of stay was 32.4±28.6 days. Fifty-five percent of patients required intensive care unit admission (17.2±14.1 days), 37% required mechanical ventilation (13.7±13.2 days), and 11% required dialysis (14.6±14.2 days). The most commonly used first-line antifungal was fluconazole. Conclusion Patients with IFI in Saudi Arabia and Lebanon frequently have multiple medical comorbidities and may not have traditionally observed IFI risk factors. Efforts to increase use of rapid diagnostic tests and appropriate antifungal treatments may impact the substantial mortality and high length of stay observed in these patients. PMID:28203095

  10. Infection,

    DTIC Science & Technology

    1980-10-16

    inapparent infection. A refeeding program may thus become complicated by the sudden appearance of a life-threatening infectious illness (3). (3) The...Beisel, W. R. 23 Unusually low serum concentrations of inorganic phosphate have been reported in patients with gram-negative sepsis and in Reye’s syndrome ...infection should be corrected by a well-managed program of convalescent-period refeeding . This aspect of nutritional support is too often ignored. On the

  11. Parasites and marine invasions

    USGS Publications Warehouse

    Torchin, M.E.; Lafferty, K.D.; Kuris, A.M.

    2002-01-01

    Introduced marine species are a major environmental and economic problem. The rate of these biological invasions has substantially increased in recent years due to the globalization of the world's economies. The damage caused by invasive species is often a result of the higher densities and larger sizes they attain compared to where they are native. A prominent hypothesis explaining the success of introduced species is that they are relatively free of the effects of natural enemies. Most notably, they may encounter fewer parasites in their introduced range compared to their native range. Parasites are ubiquitous and pervasive in marine systems, yet their role in marine invasions is relatively unexplored. Although data on parasites of marine organisms exist, the extent to which parasites can mediate marine invasions, or the extent to which invasive parasites and pathogens are responsible for infecting or potentially decimating native marine species have not been examined. In this review, we present a theoretical framework to model invasion success and examine the evidence for a relationship between parasite presence and the success of introduced marine species. For this, we compare the prevalence and species richness of parasites in several introduced populations of marine species with populations where they are native. We also discuss the potential impacts of introduced marine parasites on native ecosystems.

  12. Molecular analysis of the role of the group A streptococcal cysteine protease, hyaluronic acid capsule, and M protein in a murine model of human invasive soft-tissue infection.

    PubMed Central

    Ashbaugh, C D; Warren, H B; Carey, V J; Wessels, M R

    1998-01-01

    Human invasive soft-tissue infections caused by group A Streptococcus are associated with significant morbidity and mortality. To investigate the pathogenesis of these serious infections, we characterized the host response to bacterial challenge with an M-type 3 isolate recovered from a patient with necrotizing fasciitis, or with isogenic gene replacement mutants deficient in cysteine protease, hyaluronic acid capsule, or M protein in a murine model of human invasive soft-tissue infection. Animals challenged with the wild-type or cysteine protease-deficient strain developed spreading tissue necrosis at the site of inoculation, became bacteremic, and subsequently died. Histopathologic examination of the necrotic lesion revealed bacteria throughout inflamed subcutaneous tissue. Arterioles and venules in the subcutaneous layer were thrombosed and the overlying tissue was infarcted. In contrast, animals challenged with either an acapsular or M protein-deficient mutant developed a focal area of tissue swelling at the site of inoculation without necrosis or subsequent systemic disease. Histopathologic examination of the soft-tissue lesion demonstrated bacteria confined within a well-formed subcutaneous abscess. We conclude that the group A streptococcal hyaluronic acid capsule and M protein, but not the cysteine protease, are critical for the development of tissue necrosis, secondary bacteremia, and lethal infection in a murine model of human necrotizing fasciitis. PMID:9691092

  13. Determination of the Prevalence of Helicobacter heilmannii-Like Organisms Type 2 (HHLO-2) Infection in Humans and Dogs Using Non-Invasive Genus/Species-Specific PCR in Korea

    PubMed Central

    CHUNG, Tae-Ho; KIM, Hee-Dong; LEE, Young-Sun; HWANG, Cheol-Yong

    2013-01-01

    ABSTRACT Helicobacter spp. may have multiple routes of transmission. It is unclear, however, whether the agent is zoonotic and therefore transmitted from an animal reservoir, including dogs. The aim of this population-based study was to assess the relationship between pet ownership or frequent exposure to dogs and Helicobacter spp. infection, especially focusing on HHLO-2 (Helicobacter heilmannii-like organisms type 2) in saliva and feces samples in Korea, using non-invasive genus/species-specific PCR. One hundred twenty-four eligible human subjects and 39 dogs participated in this study. Relativity of contact with dogs and Helicobacter spp. infection diagnosed by genus-specific PCR showed a statistically significant result (P<0.01), but in the relativity analyses between contact with dogs and H. pylori, H. felis and H. bizzozeronii infections diagnosed using species-specific PCR, only Helicobacter felis showed a statistically significant result. Although H. pylori infection showed a statistically significant relativity, no statistically significant association was found between veterinarian subjects and Helicobacter. spp., H. felis and H. bizzozeronii infections. On performing risk factor analyses of HHLO-2 infection by transmission, using matching species, between HHLO-2-positive dog owners and HHLO-2-positive dogs, Helicobacter felis infection showed an extremely significant relativity (P<0.0001), and Helicobacter bizzozeronii may also be a possible significant risk factor (P<0.01). These results suggest that HHLO-2 infection might be a zoonotic infection, because continuous contact with dogs was proved to be correlated with human H. felis and H. bizzozeronii infections in this study. PMID:24065079

  14. A Novel Molecular Microbiologic Technique for the Rapid Diagnosis of Microbial Invasion of the Amniotic Cavity and Intra-Amniotic Infection in Preterm Labor with Intact Membranes

    PubMed Central

    Romero, Roberto; Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Yoon, Bo Hyun; Hassan, Sonia; Kim, Chong J.; Korzeniewski, Steven J.; Yeo, Lami

    2014-01-01

    Objective The major challenges in using amniotic fluid (AF) cultivation techniques to diagnose microbial invasion of the amniotic cavity (MIAC) are: 1) several days are typically required to obtain results, and 2) many organisms implicated in the pathogenesis of human disease are difficult to culture. Here, we compare the performance of AF culture with a novel technique for the diagnosis of MIAC that can provide results within eight hours by combining broad-range real-time polymerase chain reaction with electrospray ionization mass spectrometry (PCR/ESI-MS) to identify and quantify genomic material from bacteria and viruses in AF. Methods AF samples obtained by transabdominal amniocentesis from 142 women with preterm labor (PTL) and intact membranes were analyzed using cultivation techniques (aerobic, anaerobic and genital mycoplasmas) as well as PCR/ESI-MS. The prevalence and relative magnitude of intra-amniotic inflammation [AF Interleukin 6 (IL-6) concentration ≥ 2.6 ng/mL], acute histologic chorioamnionitis, spontaneous preterm delivery, and perinatal mortality were examined according to the results of these two tests. Results 1) The prevalence of MIAC in patients with preterm labor and intact membranes was 7% using standard cultivation techniques and 12% using PCR/ESI-MS; 2) seven of ten patients with positive AF culture also had positive PCR/ESI-MS [≥17 genome equivalents per PCR reaction well (GE/well)] 3) patients with positive PCR/ESI-MS (≥17 GE/well) and negative AF cultures had significantly higher rates of intra-amniotic inflammation and histologic acute chorioamnionitis, shorter intervals to delivery [median (interquartile range-IQR)], and offspring at higher risk of perinatal mortality, than women with both tests negative [90% (9/10) vs. 32% (39/122); (p<0.001); 70% (7/10) vs. 35% (39/112); (p=0.04); 1 (IQR: <1 – 2) days vs. 25 (IQR: 5 – 51) days; (p=0.002); OR: 5.6; 95% CI: 1.4 – 22, respectively]; 5) there were no significant differences

  15. Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF(low) Alveolar Macrophages.

    PubMed

    Sanfilippo, Alan M; Furuya, Yoichi; Roberts, Sean; Salmon, Sharon L; Metzger, Dennis W

    2015-07-01

    Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF(low) alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes.

  16. Functional Diversity of Four Glycoside Hydrolase Family 3 Enzymes from the Rumen Bacterium Prevotella bryantii B14 ▿ †

    PubMed Central

    Dodd, Dylan; Kiyonari, Shinichi; Mackie, Roderick I.; Cann, Isaac K. O.

    2010-01-01

    Prevotella bryantii B14 is a member of the phylum Bacteroidetes and contributes to the degradation of hemicellulose in the rumen. The genome of P. bryantii harbors four genes predicted to encode glycoside hydrolase (GH) family 3 (GH3) enzymes. To evaluate whether these genes encode enzymes with redundant biological functions, each gene was cloned and expressed in Escherichia coli. Biochemical analysis of the recombinant proteins revealed that the enzymes exhibit different substrate specificities. One gene encoded a cellodextrinase (CdxA), and three genes encoded β-xylosidase enzymes (Xyl3A, Xyl3B, and Xyl3C) with different specificities for either para-nitrophenyl (pNP)-linked substrates or substituted xylooligosaccharides. To identify the amino acid residues that contribute to catalysis and substrate specificity within this family of enzymes, the roles of conserved residues (R177, K214, H215, M251, and D286) in Xyl3B were probed by site-directed mutagenesis. Each mutation led to a severely decreased catalytic efficiency without a change in the overall structure of the mutant enzymes. Through amino acid sequence alignments, an amino acid residue (E115) that, when mutated to aspartic acid, resulted in a 14-fold decrease in the kcat/Km for pNP-β-d-xylopyranoside (pNPX) with a concurrent 1.1-fold increase in the kcat/Km for pNP-β-d-glucopyranoside (pNPG) was identified. Amino acid residue E115 may therefore contribute to the discrimination between β-xylosides and β-glucosides. Our results demonstrate that each of the four GH3 enzymes has evolved to perform a specific role in lignopolysaccharide hydrolysis and provide insight into the role of active-site residues in catalysis and substrate specificity for GH3 enzymes. PMID:20190048

  17. Functional diversity of four glycoside hydrolase family 3 enzymes from the rumen bacterium Prevotella bryantii B14.

    PubMed

    Dodd, Dylan; Kiyonari, Shinichi; Mackie, Roderick I; Cann, Isaac K O

    2010-05-01

    Prevotella bryantii B(1)4 is a member of the phylum Bacteroidetes and contributes to the degradation of hemicellulose in the rumen. The genome of P. bryantii harbors four genes predicted to encode glycoside hydrolase (GH) family 3 (GH3) enzymes. To evaluate whether these genes encode enzymes with redundant biological functions, each gene was cloned and expressed in Escherichia coli. Biochemical analysis of the recombinant proteins revealed that the enzymes exhibit different substrate specificities. One gene encoded a cellodextrinase (CdxA), and three genes encoded beta-xylosidase enzymes (Xyl3A, Xyl3B, and Xyl3C) with different specificities for either para-nitrophenyl (pNP)-linked substrates or substituted xylooligosaccharides. To identify the amino acid residues that contribute to catalysis and substrate specificity within this family of enzymes, the roles of conserved residues (R177, K214, H215, M251, and D286) in Xyl3B were probed by site-directed mutagenesis. Each mutation led to a severely decreased catalytic efficiency without a change in the overall structure of the mutant enzymes. Through amino acid sequence alignments, an amino acid residue (E115) that, when mutated to aspartic acid, resulted in a 14-fold decrease in the k(cat)/K(m) for pNP-beta-d-xylopyranoside (pNPX) with a concurrent 1.1-fold increase in the k(cat)/K(m) for pNP-beta-d-glucopyranoside (pNPG) was identified. Amino acid residue E115 may therefore contribute to the discrimination between beta-xylosides and beta-glucosides. Our results demonstrate that each of the four GH3 enzymes has evolved to perform a specific role in lignopolysaccharide hydrolysis and provide insight into the role of active-site residues in catalysis and substrate specificity for GH3 enzymes.

  18. Community-Onset Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Invasive Infections in Children in a University Hospital in France

    PubMed Central

    Toubiana, Julie; Timsit, Sandra; Ferroni, Agnès; Grasseau, Marie; Nassif, Xavier; Lortholary, Olivier; Zahar, Jean-Ralph; Chalumeau, Martin

    2016-01-01

    Abstract Limited data is available on pediatric community-onset infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), but such infections may affect both the efficacy of empiric antibiotic therapy and the rational use of antibiotics. We retrospectively analyzed data from 2007 to 2012 for all children ≤16 years old with a positive ESBL-PE strain from usually sterile sites within 48 hours of admission in a tertiary hospital in France. We analyzed healthcare- and community-associated infections among community-onset infections. In total, 3612 Enterobacteriaceae isolates were collected; the prevalence of ESBL-PE infection increased over the study period, from 2.4% to 5.1% (P < 0.001). Among the 90 children with a first community-onset ESBL-PE infection, 58% (n = 52) had a healthcare-associated infection, and 87% of isolates were susceptible to amikacin. As compared with patients with community-associated infections, those with healthcare-associated infections had fewer urinary tract infections (UTIs) (86% vs 97%) and Escherichia coli infections (35% vs 84%) and more Klebsiella pneumoniae infections (46% vs 8%). Inappropriate empiric treatment was prescribed for 54 patients (64%), but a favorable outcome was observed in 46 of 49 (94%) and 1 of 5 (20%) patients with UTIs and non-UTIs, respectively (P < 0.001). Among patients with community-associated infections, 85% had at least 1 risk factor for ESBL-PE infections. In conclusion, the prevalence of community-onset ESBL-PE infections doubled during the study period. These infections mainly occurred among children with healthcare-associated criteria or identified risk factors. Amikacin is an alternative to carbapenems for empiric treatment because most of these infections involved urinary tract and susceptible isolates. PMID:27015202

  19. Community-Onset Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Invasive Infections in Children in a University Hospital in France.

    PubMed

    Toubiana, Julie; Timsit, Sandra; Ferroni, Agnès; Grasseau, Marie; Nassif, Xavier; Lortholary, Olivier; Zahar, Jean-Ralph; Chalumeau, Martin

    2016-03-01

    Limited data is available on pediatric community-onset infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), but such infections may affect both the efficacy of empiric antibiotic therapy and the rational use of antibiotics.We retrospectively analyzed data from 2007 to 2012 for all children ≤16 years old with a positive ESBL-PE strain from usually sterile sites within 48 hours of admission in a tertiary hospital in France. We analyzed healthcare- and community-associated infections among community-onset infections. In total, 3612 Enterobacteriaceae isolates were collected; the prevalence of ESBL-PE infection increased over the study period, from 2.4% to 5.1% (P < 0.001). Among the 90 children with a first community-onset ESBL-PE infection, 58% (n = 52) had a healthcare-associated infection, and 87% of isolates were susceptible to amikacin. As compared with patients with community-associated infections, those with healthcare-associated infections had fewer urinary tract infections (UTIs) (86% vs 97%) and Escherichia coli infections (35% vs 84%) and more Klebsiella pneumoniae infections (46% vs 8%). Inappropriate empiric treatment was prescribed for 54 patients (64%), but a favorable outcome was observed in 46 of 49 (94%) and 1 of 5 (20%) patients with UTIs and non-UTIs, respectively (P < 0.001). Among patients with community-associated infections, 85% had at least 1 risk factor for ESBL-PE infections. In conclusion, the prevalence of community-onset ESBL-PE infections doubled during the study period. These infections mainly occurred among children with healthcare-associated criteria or identified risk factors. Amikacin is an alternative to carbapenems for empiric treatment because most of these infections involved urinary tract and susceptible isolates.

  20. Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi.

    PubMed

    Desai, Amit; Kovanda, Laura; Kowalski, Donna; Lu, Qiaoyang; Townsend, Robert; Bonate, Peter L

    2016-09-01

    Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent used for the treatment of invasive fungal infections. The objective of this analysis was to develop a population pharmacokinetic (PPK) model to identify covariates that affect isavuconazole pharmacokinetics and to determine the probability of target attainment (PTA) for invasive aspergillosis patients. Data from nine phase 1 studies and one phase 3 clinical trial (SECURE) were pooled to develop the PPK model (NONMEM, version 7.2). Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 3.7.6. The area under the curve (AUC) at steady state was calculated for 5,000 patients by using Monte Carlo simulations. The PTA using the estimated pharmacodynamic (PD) target value (total AUC/MIC ratio) estimated from in vivo PD studies of invasive aspergillosis over a range of MIC values was calculated using simulated patient AUC values. A two-compartment model with a Weibull absorption function and a first-order elimination process adequately described plasma isavuconazole concentrations. The mean estimate for isavuconazole clearance was 2.360 liters/h (percent coefficient of variation [%CV], 34%), and the mean AUC from 0 to 24 h (AUC0-24) was ∼100 mg·h/liter. Clearance was approximately 36% lower in Asians than in Caucasians. The PTA calculated over a range of MIC values by use of the nonneutropenic murine efficacy index corresponding to 90% survival indicated that adequate isavuconazole exposures were achieved in >90% of simulated patients to treat infections with MICs up to and including 1 mg/liter according to European Committee on Antimicrobial Susceptibility Testing methodology and in >90% of simulated patients for infections with MICs up to and including 0.5 mg/liter according to Clinical and Laboratory Standards Institute methodology. The highest MIC result for PTA was the same for Caucasian and Asian patients.

  1. Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi

    PubMed Central

    Kovanda, Laura; Kowalski, Donna; Lu, Qiaoyang; Townsend, Robert; Bonate, Peter L.

    2016-01-01

    Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent used for the treatment of invasive fungal infections. The objective of this analysis was to develop a population pharmacokinetic (PPK) model to identify covariates that affect isavuconazole pharmacokinetics and to determine the probability of target attainment (PTA) for invasive aspergillosis patients. Data from nine phase 1 studies and one phase 3 clinical trial (SECURE) were pooled to develop the PPK model (NONMEM, version 7.2). Stepwise covariate modeling was performed in Perl-speaks-NONMEM, version 3.7.6. The area under the curve (AUC) at steady state was calculated for 5,000 patients by using Monte Carlo simulations. The PTA using the estimated pharmacodynamic (PD) target value (total AUC/MIC ratio) estimated from in vivo PD studies of invasive aspergillosis over a range of MIC values was calculated using simulated patient AUC values. A two-compartment model with a Weibull absorption function and a first-order elimination process adequately described plasma isavuconazole concentrations. The mean estimate for isavuconazole clearance was 2.360 liters/h (percent coefficient of variation [%CV], 34%), and the mean AUC from 0 to 24 h (AUC0–24) was ∼100 mg·h/liter. Clearance was approximately 36% lower in Asians than in Caucasians. The PTA calculated over a range of MIC values by use of the nonneutropenic murine efficacy index corresponding to 90% survival indicated that adequate isavuconazole exposures were achieved in >90% of simulated patients to treat infections with MICs up to and including 1 mg/liter according to European Committee on Antimicrobial Susceptibility Testing methodology and in >90% of simulated patients for infections with MICs up to and including 0.5 mg/liter according to Clinical and Laboratory Standards Institute methodology. The highest MIC result for PTA was the same for Caucasian and Asian patients. PMID:27381396

  2. Transluminal endoscopic step-up approach versus minimally invasive surgical step-up approach in patients with infected necrotising pancreatitis (TENSION trial): design and rationale of a randomised controlled multicenter trial [ISRCTN09186711

    PubMed Central

    2013-01-01

    Background Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes. Methods/Design The TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs. Discussion The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis. PMID:24274589

  3. Genome sequence of Prevotella intermedia SUNY aB G8-9K-3, a biofilm forming strain with drug-resistance.

    PubMed

    Moon, Ji-Hoi; Kim, Minjung; Lee, Jae-Hyung

    Prevotella intermedia has long been known to be as the principal etiologic agent of periodontal diseases and associated with various systemic diseases. Previous studies showed that the intra-species difference exists in capacity of biofilm formation, antibiotic resistance, and serological reaction among P. intermedia strains. Here we report the genome sequence of P. intermedia SUNY aB G8-9K-3 (designated ATCC49046) that displays a relatively high antimicrobial resistant and biofilm-forming capacity. Genome sequencing information provides important clues in understanding the genetic bases of phenotypic differences among P. intermedia strains.

  4. Role of the cysteine protease interpain A of Prevotella intermedia in breakdown and release of haem from haemoglobin.

    PubMed

    Byrne, Dominic P; Wawrzonek, Katarzyna; Jaworska, Anna; Birss, Andrew J; Potempa, Jan; Smalley, John W

    2009-12-14

    The gram-negative oral anaerobe Prevotella intermedia forms an iron(III) protoporphyrin IX pigment from haemoglobin. The bacterium expresses a 90 kDa cysteine protease, InpA (interpain A), a homologue of Streptococcus pyogenes streptopain (SpeB). The role of InpA in haemoglobin breakdown and haem release was investigated. At pH 7.5, InpA mediated oxidation of oxyhaemoglobin to hydroxymethaemoglobin [in which the haem iron is oxidized to the Fe(III) state and which carries OH- as the sixth co-ordinate ligand] by limited proteolysis of globin chains as indicated by SDS/PAGE and MALDI (matrix-assisted laser-desorption ionization)-TOF (time-of-flight) analysis. Prolonged incubation at pH 7.5 did not result in further haemoglobin protein breakdown, but in the formation of a haemoglobin haemichrome (where the haem Fe atom is co-ordinated by another amino acid ligand in addition to the proximal histidine residue) resistant to degradation by InpA. InpA-mediated haem release from hydroxymethaemoglobin-agarose was minimal compared with trypsin at pH 7.5. At pH 6.0, InpA increased oxidation at a rate greater than auto-oxidation, producing aquomethaemoglobin (with water as sixth co-ordinate ligand), and resulted in its complete breakdown and haem loss. Aquomethaemoglobin proteolysis and haem release was prevented by blocking haem dissociation by ligation with azide, whereas InpA proteolysis of haem-free globin was rapid, even at pH 7.5. Both oxidation of oxyhaemoglobin and breakdown of methaemoglobin by InpA were inhibited by the cysteine protease inhibitor E-64 [trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane]. In summary, we conclude that InpA may play a central role in haem acquisition by mediating oxyhaemoglobin oxidation, and by degrading aquomethaemoglobin in which haem-globin affinity is weakened under acidic conditions.

  5. Ten weeks of infection with a tissue-invasive helminth protects against local immune complex-mediated inflammation, but not cutaneous type I hypersensitivity, in previously sensitized mice

    PubMed Central

    Evans, Holly; Killoran, Kristin E.; Mitre, Blima K.; Morris, C. Paul; Kim, So-Young; Mitre, Edward

    2015-01-01

    In this study we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to ovalbumin (OVA). 10 weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity following intradermal OVA challenge. However, late phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were reduced in the setting of infection. These reductions were likely due to increased antibody catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed antibody production. Ear histology 24 hours after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this, infected animals had less neutrophil-specific chemokines CXCL-1 and CXCL-2 in the ear following challenge. Additionally, in vitro stimulation with immune-complexes resulted in significantly less CXCL-1 and CXCL-2 production by eosinophils from chronically infected mice. Expression of FcγRI was also significantly reduced on eosinophils from infected animals. These data indicate that chronic filarial infection suppresses eosinophilic responses to antibody-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases. PMID:26324775

  6. Microparasites and Placental Invasiveness in Eutherian Mammals

    PubMed Central

    Capellini, Isabella; Nunn, Charles L.; Barton, Robert A.

    2015-01-01

    Placental invasiveness—the number of maternal tissue layers separating fetal tissues from maternal blood—is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative pre- versus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness. PMID:26168031

  7. Invasive Candidiasis.

    PubMed

    McCarty, Todd P; Pappas, Peter G

    2016-03-01

    Invasive candidiasis is a collective term that refers to a group of infectious syndromes caused by a variety of species of Candida, 5 of which cause most cases. Candidemia is the most commonly recognized syndrome associated with invasive candidiasis. Certain conditions may influence the likelihood for one species versus another in a specific clinical scenario, and this can have important implications for selection of antifungal therapy and the duration of treatment. Molecular diagnostic technology plays an ever-increasing role as an adjunct to traditional culture-based diagnostics, offering significant potential toward improvement in patient care.

  8. Proof of principle: non-invasive sampling for early detection of foot-and-mouth disease virus infection in wild boar using a rope-in-a-bait sampling technique.

    PubMed

    Mouchantat, Susan; Haas, Bernd; Böhle, Wolfgang; Globig, Anja; Lange, Elke; Mettenleiter, Thomas C; Depner, Klaus

    2014-08-06

    In this study we describe the use of a rope-in-a-bait sampling method ("pSWAB": pathogen sampling wild animals with baits) for non-invasive saliva sampling aimed at the detection of foot-and-mouth disease (FMD) viral genome in wild boar. The pSWABs are produced in the form of a standardized product by embedding a 10 cm long cotton rope in a cereal-based bait matrix. To assess the general suitability of this novel sampling technique an animal experiment was conducted to detect FMD viral genome in saliva of infected wild boar. Two juvenile animals were inoculated in the bulb of the heel with a recent wild boar FMD virus isolate and kept together with three noninoculated wild boar of the same age. Over a period of 29 days, the animals were sampled by using five pSWABs per day in addition to the collection of blood and conventional saliva swabs taken every three to four days. Viral RNA in pSWABs was identified already 24 h after infection during the incubation period and until 23 dpi. Comparison of the results of pSWAB sampling with those of conventional saliva swabs or serum samples showed satisfactory sensitivity. These experimental data demonstrate the suitability of non-invasive sampling of wild boar by using pSWABs as a sensitive, cheap and feasible sample collection technique independent of hunting activities. In addition, the use of non-invasive sampling in an appropriate surveillance strategy is discussed.

  9. Microbial transformation from normal oral microbiota to acute endodontic infections

    PubMed Central

    2012-01-01

    Background Endodontic infections are a leading cause of oro-facial pain and tooth loss in western countries, and may lead to severe life-threatening infections. These infections are polymicrobial with high bacterial diversity. Understanding the spatial transition of microbiota from normal oral cavities through the infected root canal to the acute periapical abscess can improve our knowledge of the pathogenesis of endodontic infections and lead to more effective treatment. We obtained samples from the oral cavity, infected root canal and periapical abscess of 8 patients (5 with localized and 3 with systemic infections). Microbial populations in these samples were analyzed using next-generation sequencing of 16S rRNA amplicons. Bioinformatics tools and statistical tests with rigorous criteria were used to elucidate the spatial transition of the microbiota from normal to diseased sites. Results On average, 10,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. The microbial diversity in root canal and abscess samples was significantly lower than in the oral samples. Streptococcus was the most abundant genus in oral cavities while Prevotella and Fusobacterium were most abundant in diseased samples. The microbiota community structures of root canal and abscess samples were, however, more similar to each other than to the oral cavity microbiota. Using rigorous criteria and novel bioinformatics tools, we found that Granulicatella adiacens, Eubacterium yurii, Prevotella melaninogenica, Prevotella salivae, Streptococcus mitis, and Atopobium rimae were over-represented in diseased samples. Conclusions We used a novel approach and high-throughput methodologies to characterize the microbiota associated normal and diseased oral sites in the same individuals. PMID:22839737

  10. Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

    PubMed Central

    Colombier, Marie-Alice; Alanio, Alexandre; Denis, Blandine; Melica, Giovanna; Garcia-Hermoso, Dea; Levy, Bénédicte; Peraldi, Marie-Noëlle; Glotz, Denis; Bretagne, Stéphane

    2015-01-01

    Despite increasing reports of human infection, data about the optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides, initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation (n = 17), diabetes or glucose intolerance (n = 10), rheumatoid arthritis or Still's disease (n = 4), chronic hematological diseases (n = 3), or chronic granulomatous disease (n = 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections (n = 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections (n = 6). The main antifungal drugs used were azoles (n = 41) and amphotericin B (n = 16). Surgical excision or drainage was performed in 64% of cases (n = 27). The cure rate was 67% (n = 28). There were 10% cases of treatment failure or partial response (n = 4), 19% relapses (n = 8), and 7% losses to follow-up (n = 3). The death rate was 19% (n = 8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy. PMID:25903573

  11. Increased Biofilm Formation by Nontypeable Haemophilus influenzae Isolates from Patients with Invasive Disease or Otitis Media versus Strains Recovered from Cases of Respiratory Infections

    PubMed Central

    Puig, Carmen; Domenech, Arnau; Garmendia, Junkal; Langereis, Jeroen D.; Mayer, Pascal; Calatayud, Laura; Liñares, Josefina

    2014-01-01

    Biofilm formation by nontypeable (NT) Haemophilus influenzae remains a controversial topic. Nevertheless, biofilm-like structures have been observed in the middle-ear mucosa of experimental chinchilla models of otitis media (OM). To date, there have been no studies of biofilm formation in large collections of clinical isolates. This study aimed to investigate the initial adhesion to a solid surface and biofilm formation by NT H. influenzae by comparing isolates from healthy carriers, those with noninvasive respiratory disease, and those with invasive respiratory disease. We used 352 isolates from patients with nonbacteremic community-acquired pneumonia (NB-CAP), chronic obstructive pulmonary disease (COPD), OM, and invasive disease and a group of healthy colonized children. We then determined the speed of initial adhesion to a solid surface by the BioFilm ring test and quantified biofilm formation by crystal violet staining. Isolates from different clinical sources displayed high levels of biofilm formation on a static solid support after growth for 24 h. We observed clear differences in initial attachment and biofilm formation depending on the pathology associated with NT H. influenzae isolation, with significantly increased biofilm formation for NT H. influenzae isolates collected from patients with invasive disease and OM compared with NT H. influenzae isolates from patients with NB-CAP or COPD and healthy colonized subjects. In all cases, biofilm structures were detached by proteinase K treatment, suggesting an important role for proteins in the initial adhesion and static biofilm formation measured by crystal violet staining. PMID:25192997

  12. Indirect effects of parasites in invasions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduced species disrupt native communities and biodiversity worldwide. Parasitic infections (and at times, their absence) are thought to be a key component in the success and impact of biological invasions by plants and animals. They can facilitate or limit invasions, and positively or negatively...

  13. Nosocomial Fungal Infections: Epidemiology, Infection Control, and Prevention.

    PubMed

    Suleyman, Geehan; Alangaden, George J

    2016-12-01

    Invasive fungal infections are an important cause of morbidity and mortality in hospitalized patients and in the immunocompromised population. This article reviews the current epidemiology of nosocomial fungal infections in adult patients, with an emphasis on invasive candidiasis and aspergillosis. Recently published recommendations and guidelines for the control and prevention of these nosocomial fungal infections are summarized in this article.

  14. Neonatal invasive candidiasis.

    PubMed

    Stronati, M; Decembrino, L

    2006-12-01

    Over the last two decades, systemic fungal infections have emerged to play a primary role in hospital-acquired infections. C. albicans is involved in 75% of neonatal candidiasis; however, the incidence of infection from C. parapsilosis is also increasing significantly. The higher incidence observed in the high-risk group of very low birth weight (VLBW) infants is linked to their special physical characteristics and the diagnostic and therapeutic invasive procedures they undergo. Colonization is a relevant risk factor depending on the colonized site , the fungal species and the type of colonization. Serological tests have a low specificity and sensitivity; in many cases, they do not distinguish between colonization and infection. Blood culture, although the best diagnostic test for determining systemic infection, can result negative, even in cases of deep organ involvement. In addition, fungi grow more slowly than bacteria in cultures. So, the difficulty in diagnosing systemic candidiasis and its aspecific clinical features may make empirical therapy appropriate. Amphotericin B (AmB) alone or combined with 5-fluorocytosine remains the drug of choice. Fluconazole represents a valid alternative. Recently developed new formulations of amphotericin incapsulated in liposomes can avoid possible adverse effects. Prognosis depends on the specific micro-organism involved; mortality is higher in the presence of C. albicans. As prognosis is associated with high mortality, prevention measures to reduce risk factors are of critical importance.

  15. Helicobacter pylori infection related long noncoding RNA (lncRNA) AF147447 inhibits gastric cancer proliferation and invasion by targeting MUC2 and up-regulating miR-34c.

    PubMed

    Zhou, Xiaoying; Chen, Han; Zhu, Li; Hao, Bo; Zhang, Weifeng; Hua, Jie; Gu, Huiyuan; Jin, Wujuan; Zhang, Guoxin

    2016-12-13

    Long non-coding RNAs (lncRNAs) were shown to play critical roles in cancer biology. We investigated whether H. pylori infection could promote gastric cancer by regulating lncRNAs expression. Differentially expressed lncRNAs between H. pylori positive and negative tissues were identified by microarray and validated by qRT-PCR. Our results indicated that H. pylori positive tissues have a specific profile of lncRNAs. Cell biological assays with siRNA-mediated knockdown or lentivirus vector-mediated over-expression were performed to probe the functional relevance of the lncRNAs. We identified an lncRNA-AF147447 decreased expressed by H. pylori infection, which can inhibit GC proliferation and invasion in vitro and in vivo, act as a tumor suppressor in the development of H. pylori induced GC. LncRNA AF147447 could repress MUC2 expression by direct binding or increasing miR-34c expression. We also found that transcription factor E2F1 could be recruited to lncRNA AF147447 promoter by RNA immunoprecipatation and RNA pull down assays. These findings support a role of lncRNA AF147447 in tumor suppression. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by H. pylori infection and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of H. pylori-related gastric cancer.

  16. Contamination during production of heater-cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016.

    PubMed

    Haller, Sebastian; Höller, Christiane; Jacobshagen, Anja; Hamouda, Osamah; Abu Sin, Muna; Monnet, Dominique L; Plachouras, Diamantis; Eckmanns, Tim

    2016-04-28

    Invasive infections with Mycobacterium chimaera were reported in patients with previous open chest surgery and exposure to contaminated heater-cooler units (HCUs). We present results of the surveillance of clinical cases and of contaminated HCUs as well as environmental investigations in Germany up until February 2016. Clinical infections occurred in five male German cases over 50 years of age (range 53-80). Cases had been exposed to HCUs from one single manufacturer during open chest surgery up to five years prior to onset of symptoms. During environmental investigations, M. chimaera was detected in samples from used HCUs from three different countries and samples from new HCUs as well as in the environment at the manufacturing site of one manufacturer in Germany. Our investigation suggests that at least some of the M. chimaera infections may have been caused by contamination of HCUs at manufacturing site. We recommend that until sustainable measures for safe use of HCUs in operation theatres are implemented, users continue to adhere to instructions for use of HCUs and Field Safety Notices issued by the manufacturer, implement local monitoring for bacterial contamination and continuously check the websites of national and European authorities for current recommendations for the safe operation of HCUs.

  17. micro RNA 172 (miR172) signals epidermal infection and is expressed in cells primed for bacterial invasion in Lotus japonicus roots and nodules.

    PubMed

    Holt, Dennis B; Gupta, Vikas; Meyer, Dörte; Abel, Nikolaj B; Andersen, Stig U; Stougaard, Jens; Markmann, Katharina

    2015-10-01

    Legumes interact with rhizobial bacteria to form nitrogen-fixing root nodules. Host signalling following mutual recognition ensures a specific response, but is only partially understood. Focusing on the stage of epidermal infection with Mesorhizobium loti, we analysed endogenous small RNAs (sRNAs) of the model legume Lotus japonicus to investigate their involvement in host response regulation. We used Illumina sequencing to annotate the L. japonicus sRNA-ome and isolate infection-responsive sRNAs, followed by candidate-based functional characterization. Sequences from four libraries revealed 219 novel L. japonicus micro RNAs (miRNAs) from 114 newly assigned families, and 76 infection-responsive sRNAs. Unlike infection-associated coding genes such as NODULE INCEPTION (NIN), a micro RNA 172 (miR172) isoform showed strong accumulation in dependency of both Nodulation (Nod) factor and compatible rhizobia. The genetics of miR172 induction support the existence of distinct epidermal and cortical signalling events. MIR172a promoter activity followed a previously unseen pattern preceding infection thread progression in epidermal and cortical cells. Nodule-associated miR172a expression was infection-independent, representing the second of two genetically separable activity waves. The combined data provide a valuable resource for further study, and identify miR172 as an sRNA marking successful epidermal infection. We show that miR172 acts upstream of several APETALA2-type (AP2) transcription factors, and suggest that it has a role in fine-tuning AP2 levels during bacterial symbiosis.

  18. Determination of antibacterial activity of green coffee bean extract on periodontogenic bacteria like Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans: An in vitro study

    PubMed Central

    Bharath, Nagaraj; Sowmya, Nagur Karibasappa; Mehta, Dhoom Singh

    2015-01-01

    Background: The aim of this study was to evaluate the antibacterial activity of pure green coffee bean extract on periodonto pathogenic bacteria Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa). Materials and Methods: Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were used to assess the antibacterial effect of pure green coffee bean extract against periodonto pathogenic bacteria by micro dilution method and culture method, respectively. Results: MIC values of Pg, Pi and Aa were 0.2 μg/ml whereas Fn showed sensitive at concentration of 3.125 μg/ml. MBC values mirrors the values same as that of MIC. Conclusion: Antimicrobial activity of pure green coffee bean extract against Pg, Pi, Fn and Aa suggests that it could be recommended as an adjunct to mechanical therapy in the management of periodontal disease. PMID:26097349

  19. Diagnosis of invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO).

    PubMed

    Ruhnke, M; Böhme, A; Buchheidt, D; Cornely, O; Donhuijsen, K; Einsele, H; Enzensberger, R; Hebart, H; Heussel, C P; Horger, M; Hof, H; Karthaus, M; Krüger, W; Maschmeyer, G; Penack, O; Ritter, J; Schwartz, S

    2012-04-01

    Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

  20. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.

    PubMed

    Groll, Andreas H; Castagnola, Elio; Cesaro, Simone; Dalle, Jean-Hugues; Engelhard, Dan; Hope, William; Roilides, Emmanuel; Styczynski, Jan; Warris, Adilia; Lehrnbecher, Thomas

    2014-07-01

    Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.

  1. Genome-Wide siRNA Screen Identifies Complementary Signaling Pathways Involved in Listeria Infection and Reveals Different Actin Nucleation Mechanisms during Listeria Cell Invasion and Actin Comet Tail Formation

    PubMed Central

    Kühbacher, Andreas; Emmenlauer, Mario; Rämo, Pauli; Kafai, Natasha; Dehio, Christoph

    2015-01-01

    ABSTRACT Listeria monocytogenes enters nonphagocytic cells by a receptor-mediated mechanism that is dependent on a clathrin-based molecular machinery and actin rearrangements. Bacterial intra- and intercellular movements are also actin dependent and rely on the actin nucleating Arp2/3 complex, which is activated by host-derived nucleation-promoting factors downstream of the cell receptor Met during entry and by the bacterial nucleation-promoting factor ActA during comet tail formation. By genome-wide small interfering RNA (siRNA) screening for host factors involved in bacterial infection, we identified diverse cellular signaling networks and protein complexes that support or limit these processes. In addition, we could precise previously described molecular pathways involved in Listeria invasion. In particular our results show that the requirements for actin nucleators during Listeria entry and actin comet tail formation are different. Knockdown of several actin nucleators, including SPIRE2, reduced bacterial invasion while not affecting the generation of comet tails. Most interestingly, we observed that in contrast to our expectations, not all of the seven subunits of the Arp2/3 complex are required for Listeria entry into cells or actin tail formation and that the subunit requirements for each of these processes differ, highlighting a previously unsuspected versatility in Arp2/3 complex composition and function. PMID:25991686

  2. Description of Alloprevotella rava gen. nov., sp. nov., isolated from the human oral cavity, and reclassification of Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov.

    PubMed

    Downes, Julia; Dewhirst, Floyd E; Tanner, Anne C R; Wade, William G

    2013-04-01

    Five strains of anaerobic, gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group. Phylogenetic analysis of full-length 16S rRNA gene sequences showed that these strains represented a novel group within the family Prevotellaceae, and the most closely related species was Prevotella tannerae. P. tannerae and the novel taxon are deeply branched from the genus Prevotella, with sequence identities to the type strain of the type species of Prevotella, Prevotella melaninogenica, of 82.2 and 85.6 %, respectively. The novel genus Alloprevotella gen. nov. is proposed to accommodate the novel species Alloprevotella rava gen. nov., sp. nov. and the previously named Prevotella tannerae Moore et al. 1994 as Alloprevotella tannerae gen. nov., comb. nov. The type species is Alloprevotella tannerae. The type strain of Alloprevotella rava is 81/4-12(T) ( = DSM 22548(T)  = CCUG 58091(T)) and the type strain of Alloprevotella tannerae is ATCC 51259(T)  = CCUG 34292(T)  = CIP 104476(T)  = NCTC 13073(T). Alloprevotella rava is weakly to moderately saccharolytic and produces moderate amounts of acetic acid and major amounts of succinic acid as end products of fermentation. Strains are sensitive to 20 % bile and hydrolyse gelatin. The principal cellular long-chain fatty acids are anteiso-C15 : 0, iso-C15 : 0, C16 : 0, iso-C17 : 0 and iso-C17 : 0 3-OH. The G+C content of the DNA of the type strain is 47 mol%.

  3. Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

    2011-06-01

    Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways.