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Sample records for invasive prevotella infection

  1. Bacteremic skin and soft tissue infection caused by Prevotella loescheii

    PubMed Central

    2014-01-01

    Background Anaerobes are a major component of gut flora. They play an important role in the pathogenesis of infections resulting from breaches in mucus membranes. Because of the difficulties in cultivating and identifying it, their role continues to be undermined. The purpose of this paper is to report a case of Prevotella loescheii bacteremic skin and soft tissue infection and review the literature. Case presentation A 42-year-old Caucasian man was admitted for an elective bariatric surgery. A lengthy intensive care unit stay and buttocks decubitus ulcers complicated his post-operative course. After being transferred to a long-term care facility, the decubitus ulcer became secondarily infected with multiple bacteria including P. loescheii; an anaerobe that grew in blood and wound cultures. The patient was treated successfully with aggressive surgical debridement, antibiotics and subsequent wound care. Conclusion P. loescheii colonizes the gut and plays an important role in periodontal infections. In rare occasions and under suitable circumstances, it can infect skin and soft tissues as well as joints. Given the difficulties in isolating anaerobes in the microbiology lab, considering this bacterium alongside other anaerobes in infections of devitalized tissue is indicated even if cultures were reported negative. PMID:24661318

  2. Invasive fungal infections in transplant recipients

    PubMed Central

    Miceli, Marisa H.; Alangaden, George

    2013-01-01

    Invasive fungal infections are an important cause of morbidity and mortality in hematopoietic stem cell transplant and solid organ transplant recipients. Evolving transplant modalities and techniques, complex and extensive immunosuppressant strategies, and the increased use of broad spectrum antifungal prophylaxis has greatly impacted the epidemiology and temporal pattern of invasive fungal infections in the transplant population. The goal of this article is to provide an up-to-date review of the most commonly encountered invasive fungal infections seen in transplant recipients, including epidemiology, risk factors, clinical features, diagnostic dilemmas, management and their overall influence on outcomes. PMID:25165546

  3. Pathogenicity of Prevotella intermedia and Prevotella nigrescens isolates in a wound chamber model in rabbits.

    PubMed

    Hafström, C; Dahlén, G

    1997-06-01

    The pathogenicity of 14 isolates identified as Prevotella intermedia or Prevotella nigrescens by serogrouping using monoclonal antibodies was compared in a tissue cage model in rabbits. Seven strains from periodontal abscesses, 5 strains from deep periodontal pockets and 2 strains from gingivitis were tested in the animal model comprising 6 Teflon tissue cages implanted on the back each of 34 rabbits. A total of 10(5)-10(8) cells of P. intermedia or P. nigrescens strains were inoculated alone or together with either Actinobacillus actinomycetemcomitans or Streptococcus mitis. Five strains of Porphyromonas gingivalis were used as a reference. The infectivity was recorded as pus formation and log viable count in aspirated material for 3, 7 and 14 days. None of the Prevotella strains inoculated in monoculture survived more than 3 days, and they had no capacity to produce abscess. P. intermedia or P. nigrescens strains in combination with A. actinomycetemcomitans produced abscesses in 33-100% and with S. mitis in 42-100%. No difference in abscess formation or log viable count in samples after 14 days was recorded between serogroup I (P. intermedia) and serogroup II and III (P. nigrescens). The infectivity of P. intermedia or P. nigresceas strains did not differ whether they were isolated from periodontal abscess, periodontal pocket or gingivitis. P. intermedia and P. nigrescens strains produced abscesses in combination with a facultative anaerobic strain and appears to have a similar pathogenicity in the wound chamber model in rabbits. PMID:9467400

  4. [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. PMID:27395023

  5. [Pulmonary non invasive infection by Scedosporium apiospermum].

    PubMed

    Cruz, Rodrigo; Barros, Manuel; Reyes, Mirtha

    2015-08-01

    We reported a case of non-invasive pulmonary infection by Scedosporium apiospermum in 67 years old female with bronchiectasis and caverns secondary to tuberculosis. Diagnosis was made with lung CT and bronchial lavage cultures. The patient was initially treated with itraconazole for six weeks without success and then voriconazole for 16 weeks, with good clinical response. PMID:26436797

  6. Opportunistic invasive fungal infections: diagnosis & clinical management

    PubMed Central

    Badiee, Parisa; Hashemizadeh, Zahra

    2014-01-01

    Invasive fungal infections are a significant health problem in immunocompromised patients. The clinical manifestations vary and can range from colonization in allergic bronchopulmonary disease to active infection in local aetiologic agents. Many factors influence the virulence and pathogenic capacity of the microorganisms, such as enzymes including extracellular phospholipases, lipases and proteinases, dimorphic growth in some Candida species, melanin production, mannitol secretion, superoxide dismutase, rapid growth and affinity to the blood stream, heat tolerance and toxin production. Infection is confirmed when histopathologic examination with special stains demonstrates fungal tissue involvement or when the aetiologic agent is isolated from sterile clinical specimens by culture. Both acquired and congenital immunodeficiency may be associated with increased susceptibility to systemic infections. Fungal infection is difficult to treat because antifungal therapy for Candida infections is still controversial and based on clinical grounds, and for molds, the clinician must assume that the species isolated from the culture medium is the pathogen. Timely initiation of antifungal treatment is a critical component affecting the outcome. Disseminated infection requires the use of systemic agents with or without surgical debridement, and in some cases immunotherapy is also advisable. Preclinical and clinical studies have shown an association between drug dose and treatment outcome. Drug dose monitoring is necessary to ensure that therapeutic levels are achieved for optimal clinical efficacy. The objectives of this review are to discuss opportunistic fungal infections, diagnostic methods and the management of these infections. PMID:24718393

  7. 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. PMID:25902362

  8. [Invasive yeast infections in severely burned patients].

    PubMed

    Renau, Ana Isabel; García-Vidal, Carolina; Salavert, Miguel

    2016-01-01

    Currently, there are few studies on candidaemia in the severely burned patient. These patients share the same risk factors for invasive fungal infections as other critically ill patients, but have certain characteristics that make them particularly susceptible. These include the loss of skin barrier due to extensive burns, fungal colonisation of the latter, and the use of hydrotherapy or other topical therapies (occasionally with antimicrobials). In addition, the increased survival rate achieved in recent decades in critically burned patients due to the advances in treatment has led to the increase of invasive Candida infections. This explains the growing interest in making an earlier and more accurate diagnosis, as well as more effective treatments to reduce morbidity and mortality of candidaemia in severe burned patients. A review is presented on all aspects of the burned patient, including the predisposition and risk factors for invasive candidiasis, pathogenesis of candidaemia, underlying immunodeficiency, local epidemiology and antifungal susceptibility, evolution and prognostic factors, as well as other non-Candida yeast infections. Finally, we include specific data on our local experience in the management of candidaemia in severe burned patients, which may serve to quantify the problem, place it in context, and offer a realistic perspective. PMID:27395025

  9. 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

  10. Invasive Fungal Infections after Renal Transplantation

    PubMed Central

    Ezzatzadegan, S.; Chen, S.; Chapman, J. R.

    2012-01-01

    Background: Invasive fungal infection (IFI) is a leading cause of infection-related mortality among kidney allograft recipients.  Objective: To estimate the incidence and etiology of systemic fungal infection in renal allograft recipients in Sydney transplant facility. Methods: 471 kidney recipients, transplanted between 2000 and 2010 at the Westmead Hospital renal transplantation center, Sydney, Australia, were retrospectively surveyed. Results: IFI developed in 10 (2.1%) of 471 patients. With a mean±SD new kidney transplants per year of 42.9±13, the mean±SD incidence of IFI was 0.9±0.6 for each year of transplantation. 4 patients had received kidneys from living donors and 7 from cadavers with a mean±SD age of 50.5±14 years. The mean time to IFI was 33 months after transplantation with majority within the first 2 years. Cryptococcus neoformans was responsible for 50% of episodes (n=5) followed by Aspergillus fumigatus (n=3), and Pseudallescheria boydii (n=3); there was a single case of mucurmycosis. Lungs (n=5) followed by meninges (n=4) and skin (n=3) were the most commonly involved sites. Conclusion: IFI remains a major concern in renal transplantation. A high index of suspicion is required for early diagnosis and treatment to reduce the mortality. In this regard, appropriate diagnostic tests are necessary, particularly for C. neoformans. PMID:25013619

  11. Inhibition of Prevotella and Capnocytophaga immunoglobulin A1 proteases by human serum.

    PubMed

    Frandsen, E V; Kjeldsen, M; Kilian, M

    1997-07-01

    Oral Prevotella and Capnocytophaga species, regularly isolated from periodontal pockets and associated with extraoral infections, secret specific immunoglobulin A1 (IgA1) proteases cleaving human IgA1 in the hinge region into intact Fab and Fc fragments. To investigate whether these enzymes are subject to inhibition in vivo in humans, we tested 34 sera from periodontally diseased and healthy individuals in an enzyme-linked immunosorbent assay for the presence and titers of inhibition of seven Prevotella and Capnocytophaga proteases. All or nearly all of the sera inhibited the IgA1 protease activity of Prevotella buccae, Prevotella oris, and Prevotella loescheii. A minor proportion of the sera inhibited Prevotella buccalis, Prevotella denticola, and Prevotella melaninogenica IgA1 proteases, while no sera inhibited Capnocytophaga ochracea IgA1 protease. All inhibition titers were low, ranging from 5 to 55, with titer being defined as the reciprocal of the dilution of serum causing 50% inhibition of one defined unit of protease activity. No correlation between periodontal disease status and the presence, absence, or titer of inhibition was observed. The nature of the low titers of inhibition in all sera of the IgA1 proteases of P. buccae, P. oris, and P. loescheii was further examined. In size exclusion chromatography, inhibitory activity corresponded to the peak volume of IgA. Additional inhibition of the P. oris IgA1 protease was found in fractions containing both IgA and IgG. Purification of the IgG fractions of five sera by passage of the sera on a protein G column resulted in recovery of inhibitory IgG antibodies against all three IgA1 proteases, with the highest titer being for the P. oris enzyme. These finding indicate that inhibitory activity is associated with enzyme-neutralizing antibodies. PMID:9220164

  12. First case of invasive human infection caused by Cupriavidus metallidurans.

    PubMed

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

    2011-02-01

    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

  13. Mannan antigenemia in the diagnosis of invasive Candida infections.

    PubMed Central

    Weiner, M H; Yount, W J

    1976-01-01

    Because it is often difficult to diagnose invasive Candida infections, a sensitive hemagglutination inhibition assay to detect the surface antigen, mannan, was developed. Mannan antigenemia was detected early in the course of infection in 4 of 14 patients with systemic candidiasis and 2 of 5 patients with invasive gastrointestinal candidiasis. Mannan was not detected in 48 patients with noninvasive Candida or other systemic mycotic infections or in 99% of 234 patients in other control groups. Mannan antibodies were almost universally present in both candidiasis and control groups. In four patients with systemic candidiasis, an early period of mannan antigenemia was followed by a rapid rise in mannan antibody titer. These findings suggest that antemortem diagnosis would be improved in one-third of cases of invasive Candida infection detected by the hemagglutination inhibition assay. A positive test for serum mannan would be an early and specific signal of invasive disease. Images PMID:993329

  14. 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

  15. Invasive Infections with Nontyphoidal Salmonella in Sub-Saharan Africa.

    PubMed

    Mahon, Barbara E; Fields, Patricia I

    2016-06-01

    Invasive nontyphoidal Salmonella (NTS) infections in Africa cause an enormous burden of illness. These infections are often devastating, with mortality estimated at 20%, even with appropriate antimicrobial therapy. Two major groups-young children and HIV-infected adults-suffer the great majority of these infections. In children, younger age itself, as well as malaria, malnutrition, and HIV infection, are prominent risk factors. In adults, HIV infection is by far the most important risk factor. The most common serotypes in invasive infections are Salmonella enterica serotypes Typhimurium and Enteritidis. In recent years, a specific strain of Salmonella Typhimurium, multilocus sequence type 313, has caused epidemics of invasive disease. Little is known about risk factors for exposure to NTS, making the design of rational interventions to decrease exposure difficult. Antimicrobial therapy is critically important for treatment of invasive NTS infections. Thus, the emergence and spread of resistance to agents commonly used for treatment of invasive NTS infection, now including third-generation cephalosporins, is an ominous development. Already, many invasive NTS infections are essentially untreatable in many health care facilities in sub-Saharan Africa. Several candidate vaccines are in early development and, if safe and effective, could be promising. Interventions to prevent exposure to NTS (e.g., improved sanitation), to prevent the occurrence of disease if exposure does occur (e.g., vaccination, malaria control), and to prevent severe disease and death in those who become ill (e.g., preserving antimicrobial effectiveness) are all important in reducing the toll of invasive NTS disease in sub-Saharan Africa. PMID:27337467

  16. 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. PMID:20163566

  17. Invasive Mold Infections in Solid Organ Transplant Recipients

    PubMed Central

    Crabol, Yoann; Lortholary, Olivier

    2014-01-01

    Invasive mold infections represent an increasing source of morbidity and mortality in solid organ transplant recipients. Whereas there is a large literature regarding invasive molds infections in hematopoietic stem cell transplants, data in solid organ transplants are scarcer. In this comprehensive review, we focused on invasive mold infection in the specific population of solid organ transplant. We highlighted epidemiology and specific risk factors for these infections and we assessed the main clinical and imaging findings by fungi and by type of solid organ transplant. Finally, we attempted to summarize the diagnostic strategy for detection of these fungi and tried to give an overview of the current prophylaxis treatments and outcomes of these infections in solid organ transplant recipients. PMID:25525551

  18. Invasive Illness with Salmonella Virchow Infection

    PubMed Central

    Mani, V.; Brennand, J.; Mandal, B. K.

    1974-01-01

    Salmonella virchow infection in man is usually sporadic and is little known in Britain. We report an outbreak of 21 cases in the Manchester area. The source of infection was believed to be chickens bought at different shops. Symptoms were typhoidal or septicaemic. PMID:4856881

  19. 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. PMID:24565446

  20. 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

  1. Invasive lung infection by Scedosporium apiospermum in an immunocompetent individual.

    PubMed

    Agatha, David; Krishnan, Krishnan Usha; Dillirani, Ved-achalam; Selvi, Rangam

    2014-01-01

    Scedosporium apiospermum previously known as Monospermum apiospermum is a ubiquitous fungus found in soil, polluted water and sewage. It causes broad spectrum of diseases, including soft tissue infections, septic arthritis, osteomyelitis, ophthalmic infections, sinusitis, pneumonia, meningitis, brain abscesses, endocarditis and disseminated infection. In recent years, it has been shown to be pathogenic for both immunocompetent and immunosuppressed patients. It is a significant opportunist with very high levels of antifungal resistance. We report here a case of invasive lung infection due to S. apiospermum in an immunocompetent patient who responded to antifungal therapy and surgical treatment. PMID:25308027

  2. Voriconazole in the management of nosocomial invasive fungal infections.

    PubMed

    Pemán, Javier; Salavert, Miguel; Cantón, Emilia; Jarque, Isidro; Romá, Eva; Zaragoza, Rafael; Viudes, Angel; Gobernado, Miguel

    2006-06-01

    Voriconazole is a new triazole developed for the treatment of life-threatening fungal infections. The drug is available for both oral and intravenous administration; the oral formulation has excellent bioavailability. The side-effect profile of voriconazole presents an acceptable safety and tolerability spectrum: transient visual disturbances, liver enzyme abnormalities, and skin rashes are the most frequently reported side effects but rarely lead to discontinuation. The potential for drug-drug interactions is high, because of its extensive hepatic metabolism. Careful attention to dosage is required, and serum levels and the effects of interacting drugs should be monitored. Review of 25 470 isolates of yeasts and 3216 isolates of filamentous fungi showed voriconazole to have broad-spectrum activity against pathogenic yeasts including intrinsically fluconazole-resistant isolates such as Candida krusei, dimorphic fungi, and opportunistic moulds like Aspergillus spp, amphotericin-B-resistant Aspergillus terreus, Fusarium spp, and Scedosporium apiospermum. It displays excellent clinical efficacy in patients with fluconazole-resistant and -susceptible Candida infections, invasive bone and central nervous system aspergillosis, and various refractory fungal infections. Voriconazole has been approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S. apiospermum, fluconazole-resistant invasive Candida infections, and candidemia in nonneutropenic patients. PMID:18360588

  3. Voriconazole in the management of nosocomial invasive fungal infections

    PubMed Central

    Pemán, Javier; Salavert, Miguel; Cantón, Emilia; Jarque, Isidro; Romá, Eva; Zaragoza, Rafael; Viudes, Ángel; Gobernado, Miguel

    2006-01-01

    Voriconazole is a new triazole developed for the treatment of life-threatening fungal infections. The drug is available for both oral and intravenous administration; the oral formulation has excellent bioavailability. The side-effect profile of voriconazole presents an acceptable safety and tolerability spectrum: transient visual disturbances, liver enzyme abnormalities, and skin rashes are the most frequently reported side effects but rarely lead to discontinuation. The potential for drug–drug interactions is high, because of its extensive hepatic metabolism. Careful attention to dosage is required, and serum levels and the effects of interacting drugs should be monitored. Review of 25 470 isolates of yeasts and 3216 isolates of filamentous fungi showed voriconazole to have broad-spectrum activity against pathogenic yeasts including intrinsically fluconazole-resistant isolates such as Candida krusei, dimorphic fungi, and opportunistic moulds like Aspergillus spp, amphotericin-B-resistant Aspergillus terreus, Fusarium spp, and Scedosporium apiospermum. It displays excellent clinical efficacy in patients with fluconazole-resistant and -susceptible Candida infections, invasive bone and central nervous system aspergillosis, and various refractory fungal infections. Voriconazole has been approved by the US Food and Drug Administration and by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S. apiospermum, fluconazole-resistant invasive Candida infections, and candidemia in nonneutropenic patients. PMID:18360588

  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. PMID:27330318

  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. PMID

  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. PMID:20678175

  9. Epidemiology of invasive Streptococcus pneumoniae infections in adults in Finland.

    PubMed Central

    Sankilampi, U.; Herva, E.; Haikala, R.; Liimatainen, O.; Renkonen, O. V.; Leinonen, M.

    1997-01-01

    Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05). PMID:9042030

  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. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    PubMed Central

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-01-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients. PMID:26937339

  12. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia.

    PubMed

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-03-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients. PMID:26937339

  13. 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

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

    PubMed

    Seale, Anna C; 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

    2016-02-01

    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. Invasive Pulmonary Aspergillosis with Disseminated Infection in Immunocompetent Patient.

    PubMed

    Moreno-González, Gabriel; Ricart de Mesones, Antoni; Tazi-Mezalek, Rachid; Marron-Moya, Maria Teresa; Rosell, Antoni; Mañez, Rafael

    2016-01-01

    Invasive pulmonary aspergillosis (IPA) is a rare pathology with increasing incidence mainly in critical care settings and recently in immunocompetent patients. The mortality of the disease is very high, regardless of an early diagnosis and aggressive treatment. Here, we report a case of a 56 yr old previously healthy woman who was found unconscious at home and admitted to the emergency room with mild respiratory insufficiency. In the first 24 hours she developed an acute respiratory failure with new radiographic infiltrates requiring Intensive Care Unit admission. A severe obstructive pattern with impossibility of ventilation because of bilateral atelectasis was observed, requiring emergent venovenous extracorporeal membrane oxygenator device insertion. Bronchoscopy revealed occlusion of main bronchi, demonstrating by biopsy an invasive infection by Aspergillus fumigatus and A. flavus. Despite an aggressive treatment and vital support the patient had a fatal outcome. The forensic study confirms the diagnosis of IPA but also revealed the presence of disseminated aspergillosis. PMID:27445566

  17. Invasive Streptococcus pneumoniae infections of children in central Taiwan.

    PubMed

    Ma, J S; Chen, P Y; Chi, C S; Lin, J F; Lau, Y J

    2000-09-01

    We carried out a retrospective study on childhood invasive pneumococcal infections (IPI) diagnosed from the January 1990 through the April 2000 at a medical center in central Taiwan. Their clinical features, outcome of the patients and the resistance patterns of the isolates were analyzed. A total of 95 clinical isolates from 72 patients younger than 14 years of age were included in this study. Of these 72 patients, 51 had bacteremia, 28 meningitis, 14 bacteremic pneumonia, 12 pleural empyema, eight otitis media, four arthritis, three sinusitis, two periorbital abscesses, one deep neck infection, one psoas muscle abscess, one peritonitis, one urinary tract infection, and one cutaneous infection. Ancillary diagnostic tests, including Gram stain smears and latex agglutination tests, were applied and the sensitivities were 86.2% and 54.3%, respectively. The prevalence rate of penicillin nonsusceptible Streptococcus pneumoniae has increased dramatically since 1995 in central Taiwan, with rates of 5.6% and 74.1% before and after 1995, and the overall mortality rate was 20.8% and 53.3% respectively. Ten of 19 children (52.6%) with pneumococcal meningitis who survived had long-term sequelae. PMID:11045380

  18. Group B streptococcus neonatal invasive infections, France 2007-2012.

    PubMed

    Joubrel, C; Tazi, A; Six, A; Dmytruk, N; Touak, G; Bidet, P; Raymond, J; Trieu Cuot, P; Fouet, A; Kernéis, S; Poyart, C

    2015-10-01

    Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of invasive infections among newborns in industrialized countries, with two described syndromes: early-onset disease (EOD) and late-onset disease (LOD). Since the introduction in many countries of intrapartum antibioprophylaxis (IAP), the incidence of EOD has dramatically decreased, whereas that of LOD remains unchanged. We describe the clinical and bacteriological characteristics of 438 GBS neonatal invasive infections notified to the French National Reference Centre for Streptococci in France from 2007 to 2012. Clinical data were retrieved from hospitalization reports or questionnaires. Capsular type, assignment to the hypervirulent clonal complex (CC)17 and antibiotic susceptibility profiles were determined. One hundred and seventy-four (39.7%) and 264 (60.3%) isolates were responsible for EOD, including death in utero, and LOD, respectively. EOD was associated with bacteraemia (n = 103, 61%) and LOD with meningitis (n = 145, 55%). EOD was mainly due to capsular polysaccharide (CPS) III isolates (n = 99, 57%) and CPS Ia isolates (n = 40, 23%), and CPS III isolates were responsible for 80% (n = 211) of LOD cases. CC17 accounted for 80% (n = 121) of CPS III isolates responsible for meningitis (n = 151; total cases of meningitis, 188). Bad outcome risk factors were low gestational age and low birthweight. LOD represents almost 60% of cases of neonatal GBS disease in France and other countries in which IAP has been implemented. This observation reinforces the need to develop new prevention strategies targeting CC17, which is predominant in GBS neonatal infections. PMID:26055414

  19. Race and invasive fungal infection in solid organ transplant recipients.

    PubMed

    Boehme, Amelia K; McGwin, Gerald; Andes, David R; Lyon, G Marshall; Chiller, Tom; Pappas, Peter G; Baddley, John W

    2014-01-01

    Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n = 1,214) and controls (n = 16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR = .97, 95% Cl 0.82-1.15, P = .7125), while participants who identified as other ethnicity were less likely to develop IFI (OR = .56, 95% Cl .41-.75, P < .001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95% CI 1.35-3.54, P = .002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients. PMID:25065083

  20. Diagnostics for invasive Salmonella infections: current challenges and future directions

    PubMed Central

    Andrews, Jason R.; Ryan, Edward T.

    2015-01-01

    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. PMID:25937611

  1. 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. PMID:25937611

  2. Antibiotic susceptibility of 33 Prevotella strains isolated from Romanian patients with abscesses in head and neck spaces.

    PubMed

    Bancescu, Gabriela; Didilescu, Andreea; Bancescu, Adrian; Bari, Maria

    2015-10-01

    The purpose of this study was to investigate the susceptibility of a series of 33 Prevotella strains isolated from patients with abscesses in the head and neck spaces, presented to one Romanian hospital. The Etest was applied to determine the value of the minimum inhibitory concentrations for: penicillin G, ampicillin, amoxicillin-clavulanate, metronidazole and clindamycin. In addition, the beta-lactamase activity was detected by the chromogenic cephalosporin disc method. The results indicated that 11 isolates were resistant to both penicillin G and ampicillin due to the beta-lactamase production. All the 33 Prevotella strains were susceptible to the other 3 antimicrobial agents tested, except for only one penicillin G - ampicillin resistant isolate of Prevotella buccae (MIC > 32 and MIC = 12 mg/L, respectively), which showed high resistance to clindamycin (MIC > 256 mg/L) too. Our data underline the necessity for antimicrobial testing including monitoring of beta-lactamase production in cases of oro-maxillo-facial mixed anaerobic infections where antimicrobial treatment is required in addition to the surgical drainage. The results of the study indicated that amoxicillin-clavulanate, like metronidazole, was fully active against the tested Prevotella strains. However, local and multicentre surveys on drug resistance among the clinically significant anaerobic isolates should be carried out periodically. PMID:25463968

  3. Invasive enterococcal infections in Poland: the current epidemiological situation.

    PubMed

    Gawryszewska, I; Żabicka, D; Bojarska, K; Malinowska, K; Hryniewicz, W; Sadowy, E

    2016-05-01

    The aim of this study was to investigate human invasive isolates of enterococci, obtained through prospective surveillance in Poland. The consecutive enterococcal isolates were collected in 30 hospitals between May 2010 and June 2011, and studied by species identification, antimicrobial susceptibility testing and, for Enterococcus faecium by detection of markers specific for the hospital meroclone, multilocus VNTR analysis (MLVA) and multilocus sequence typing (MLST). Additionally, the genomic difference regions (GDRs) characteristic for lineage 78 were searched by PCR. Among 259 isolates, a nearly equal number of Enterococcus faecalis (n = 140; 54.1 %) and E. faecium (n = 112; 43.2 %) was found. The observed 14-day mortality rate of infected patients reached 18.1 %. All isolates were susceptible to linezolid and daptomycin. High-level aminoglycoside resistance occurred in over 50 % of isolates. Vancomycin resistance mediated by vanA or vanB was detected in 7.1 % of E. faecium; 71.4 % of isolates were multidrug resistant. E. faecium isolates ubiquitously carried molecular markers of hospital-associated meroclone (IS16, esp Efm , intA of ICEEfm1) and multilocus sequence typing showed the domination of representatives of lineages 78 and 17/18 (52.7 % and 46.4 %, respectively). Isolates of lineage 78 were significantly enriched in all the GDRs studied. The recent spread of E. faecium from this lineage contributed to the observed increase of E. faecium in enterococcal invasive infections in hospitals in Poland. PMID:26946510

  4. 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. PMID:25977268

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

    PubMed Central

    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. PMID:24516421

  6. Detection of Aspergillus antigens associated with invasive infection.

    PubMed Central

    Haynes, K A; Latge, J P; Rogers, T R

    1990-01-01

    Serial urine samples were collected from 33 neutropenic patients, 10 of whom developed invasive aspergillosis (IA) while undergoing bone marrow transplantation or remission induction therapy for leukemia. Concentrated urine samples from the infected patients were subjected to polyacrylamide gel electrophoresis, blotted, and then incubated with antiserum raised to a cell wall extract of Aspergillus fumigatus (anti-CW) or an immunoglobulin G monoclonal antibody to A. fumigatus galactomannan (EBA1). When IA patient urine blots were probed with anti-CW, major bands at 11 and 18 kilodaltons (kDa); intermediate bands at 13, 14, and 29 kDa; and minor bands at 38 and 44 kDa were seen. In contrast, EBA1 showed diffuse staining at molecular masses larger than 45 kDa and a single weak band at 21 kDa. Urine samples from the 23 patients with no evidence of IA were unreactive with both anti-CW and EBA1. These antigen bands are likely to represent immunodominant antigens which are excreted during IA and should play a valuable role in the development of rapid diagnostic tests for aspergillosis. Images PMID:2229387

  7. [Invasive fungal infections in children: similarities and differences with adults].

    PubMed

    Ramos, J T; Francisco, L; Daoud, Z

    2016-09-01

    Invasive fungal infections (IFI) are a major cause of morbidity and mortality in immunocompromised adults and children. The purpose of this review was to update the epidemiological, clinical and therapeutic options in children, and to compare them with the adult population. Although there are important differences, the epidemiology, clinical features and risk factors for IFI have many similarities. Patient at risk include neutropenic hematology children, in whom Candida spp. y Aspergillus spp. predominate; primary immunodeficiencies, particularly chronic granulomatous disease with high susceptibility for Aspergillus spp.; and extremely premature infants, in whom C. albicans y C. parapsilosis are more prevalent. Premature babies are prone to dissemination, including the central nervous system. There are peculiarities in radiology and diagnostic biomarkers in children. In pulmonary aspergillosis, clasical signs in CT are usually absent. There is scant information on PCR and beta-D-glucan in children, and more limited on the performance of galactomannan enzyme immunoassay, that does not appear to be much different in neutropenic patients. There is a delay in the development of antifungals, limiting their use in children. Most azoles require therapeutic drug monitoring in children to optimize its safety and effectiveness. Pediatric treatment recommendations are mainly extrapolated from results of clinical trials performed in adults. There is no evidence for the benefit of preemptive therapy in children. It is necessary to foster specific pediatric studies with current and new antifungals to evaluate their pharmacokinetics, safety, and effectiveness at different ages in the pediatric population. PMID:27608317

  8. Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

    PubMed Central

    Lehrnbecher, Thomas; Schmidt, Stanislaw; Tramsen, Lars; Klingebiel, Thomas

    2013-01-01

    Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in promising strategies to enhance or restore critical immune functions in allogeneic HSCT recipients. Potential approaches include the administration of granulocytes, since neutropenia is the single most important risk factor for invasive fungal infection, and preliminary clinical results suggest a benefit of adoptively transferred donor-derived antifungal T cells. In vitro data and animal studies demonstrate an antifungal effect of natural killer cells, but clinical data are lacking to date. This review summarizes and critically discusses the available data of immunotherapeutic strategies in allogeneic HSCT recipients suffering from invasive fungal infection. PMID:23404543

  9. Increased phenotypic switching in strains of Candida albicans associated with invasive infections.

    PubMed Central

    Jones, S; White, G; Hunter, P R

    1994-01-01

    This study reports the rates of phenotypic switching in strains of Candida albicans isolated from superficial and invasive infections. Of 19 invasive strains, 68% showed switching activity, often at very high rates, compared with only 28% of 40 strains isolated from superficial sites (P = 0.004). PMID:7852592

  10. Increase in invasive Streptococcus pyogenes and Streptococcus pneumoniae infections in England, December 2010 to January 2011.

    PubMed

    Zakikhany, K; Degail, M A; Lamagni, T; Waight, P; Guy, R; Zhao, H; Efstratiou, A; Pebody, R; George, R; Ramsay, M

    2011-01-01

    Increases in invasive Streptococcus pyogenes and S. pneumoniae above the seasonally expected levels are currently being seen in England. Preliminary analyses suggest that the high level of influenza activity seen this winter may be contributing to an increased risk of concurrent invasive bacterial and influenza infections in children and young adults. PMID:21315057

  11. 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

  12. Rapid emergence of emm84 among invasive Streptococcus pyogenes infections in Finland.

    PubMed

    Siljander, Tuula; Lyytikäinen, Outi; Vähäkuopus, Susanna; Säilä, Petrus; Jalava, Jari; Vuopio-Varkila, Jaana

    2009-02-01

    From 2005 to 2007, in Finland, the incidence of invasive Streptococcus pyogenes disease increased sharply, partly due to the uncommon emm84 gene becoming more prevalent from 2006 onwards. The overall case fatality rate of infections caused by strains carrying emm84 was not significantly different than that of infections caused by other types (7% versus 10%, respectively; P = 0.50). PMID:19073871

  13. Rapid Emergence of emm84 among Invasive Streptococcus pyogenes Infections in Finland▿

    PubMed Central

    Siljander, Tuula; Lyytikäinen, Outi; Vähäkuopus, Susanna; Säilä, Petrus; Jalava, Jari; Vuopio-Varkila, Jaana

    2009-01-01

    From 2005 to 2007, in Finland, the incidence of invasive Streptococcus pyogenes disease increased sharply, partly due to the uncommon emm84 gene becoming more prevalent from 2006 onwards. The overall case fatality rate of infections caused by strains carrying emm84 was not significantly different than that of infections caused by other types (7% versus 10%, respectively; P = 0.50). PMID:19073871

  14. The Forgotten One: Lemierre’s Syndrome Due to Gram-Negative Rods Prevotella Bacteremia

    PubMed Central

    Wani, Priyanka; Antony, Nishaal; Wardi, Miraie; Rodriguez-Castro, Carlos E.; Teleb, Mohamed

    2016-01-01

    Patient: Male, 22 Final Diagnosis: Lemierre’s syndrome Symptoms: Dyspnea • chest pain • swelling Medication: — Clinical Procedure: Thoracentesis Specialty: Infectious Diseases Objective: Rare co-existance of disease or pathology Background: Lemierre’s syndrome (LS) is a rare syndrome caused by an acute oropharyngeal infection with metastatic spreading. It was described in 1939 as jugular vein septic thrombophlebitis associated with retropharyngeal infection. Different organisms can cause LS, such as Fusobacterium species, Peptostreptococcus, group B and C, Streptococcus, Staphylococcus, and Enterococcus species, but the most commonly isolated pathogen is Fusobacterium necrophorum, a common oral flora. Management depends on the initial presentation, type of pathogen isolated, and proper selection of antibiotics. Case Report: We report a case of a 22-year-old man with no past medical history, who presented with left jaw pain and progressive left facial area swelling associated with dyspnea. A final diagnosis of LS was made based on criteria of computed tomography (CT) of the neck and the clinical symptoms. The patient was started on broad-spectrum antibiotics. Subsequent imaging of the chest showed pleural effusion with septic emboli. He underwent thoracentesis and chest tube placement. Final blood cultures were remarkable for gram-negative rods – Prevotella anaerobes – which supported the diagnosis of LS. His condition improved, including the dyspnea, and he was discharged on the proper antibiotics coverage with outpatient follow-up. Conclusions: LS is a rare condition associated with metastatic infection spreading. This syndrome can be associated with further complications, such as pleural effusions and/or empyemas. Early recognition is important to prevent fatal complications and provide adequate antibiotics coverage. We report only the third case in the medical literature of Prevotella-induced LS with a secondary complication of pleural effusion

  15. 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

  16. Invasive candidiasis: from mycobiome to infection, therapy, and prevention.

    PubMed

    Lagunes, L; Rello, J

    2016-08-01

    Candida spp. are commonly found in humans, colonizing most healthy individuals. A high prevalence of invasive candidiasis has been reported in recent years. Here, we assess the relation between Candida spp. as part of the human mycobiome, the host defense mechanisms, and the pathophysiology of invasive disease in critically ill patients. Many hypotheses have been proposed to explain the different immune responses to the process where Candida goes through healthy mycobiome to colonization to invasion; the involvement of other microbiota inhabitants, changes in temperature, low nitrogen levels, and the caspase system activation have been described. Patients admitted to an intensive care unit (ICU) are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. The first approach should be using predictive scores as screening, followed by the determination of biomarkers (when available), and, in the near future, probably immune-genomics and analysis of the clinical background in order to initiate prompt and correct treatment. Regarding treatment, the initiation with an echinocandin is strongly recommended in critically ill patients. In conclusion, prompt treatment and adequate source control in the more severe patients remains the ultimate goal, as well as restoration of a healthy microbiota. PMID:27146877

  17. Invasive gastric mucormycosis and cytomegalovirus infection in an ABO incompatible renal transplant recipient.

    PubMed

    Nandwani, A; Jha, P K; Duggal, R; Kher, V

    2015-01-01

    Opportunistic infections are common in immunocompromised patients, such as solid organ transplant recipients. Both fungal and viral infections in posttransplant period increase morbidity and mortality. Cytomegalovirus (CMV) remains one of the most important pathogens. CMV disease may manifest as a nonspecific febrile syndrome or tissue-invasive infections. Zygomycosis is a rare infection, usually presents in rhino-cerebral, pulmonary and disseminated forms; gastrointestinal (GI) tract being a rare site of involvement. Newer techniques for early diagnosis and efficient therapies are essential for a better outcome of the disease; however, mortality rate remains high despite aggressive therapy. We report a renal transplant recipient, who developed gastric mucormycosis along with tissue invasive CMV disease, within 4 weeks of renal transplant and was diagnosed on the basis of upper GI endoscopy and gastric biopsy. The patient succumbed to the infection in spite of gastrectomy, antifungal and antiviral therapy. PMID:26664215

  18. The Rise of an Oppurtunistic Infection called “Invasive Zygomycosis”

    PubMed Central

    Waness, Abdelkarim; Dawsari, Ghuzayel Al; Jahdali, Hamdan Al

    2009-01-01

    Invasive zygomycosis is a devastating fungal infection seen mostly in immune-compromised patients. We present a case of a 48-year old diabetic man, with aplastic anemia, who developed severe pulmonary mucormycosis that led to his rapid demise despite early diagnosis and treatment with liposomal amphotericin B. We also conducted an extensive review of the pathogenesis of invasive zygomycosis, its history, predisposing factors, clinical aspects, diagnostic modalities, treatment options, morbidity and mortality. PMID:20300403

  19. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2

    PubMed Central

    Desai, Jigar V.; Cheng, Shaoji; Ying, Tammy; Nguyen, M. Hong; Clancy, Cornelius J.; Lanni, Frederick; Mitchell, Aaron P.

    2015-01-01

    The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population. PMID:26213976

  20. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2.

    PubMed

    Desai, Jigar V; Cheng, Shaoji; Ying, Tammy; Nguyen, M Hong; Clancy, Cornelius J; Lanni, Frederick; Mitchell, Aaron P

    2015-01-01

    The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population. PMID:26213976

  1. 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 ...

  2. 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

  3. [Invasive Pasteurella multocida infections: Two clinical cases and literature review].

    PubMed

    Smíšková, Dita; Džupová, Olga

    2015-06-01

    Pasteurella multocida is a common commensal of the gastrointestinal and respiratory tracts of animals, especially cats and dogs. It is transmitted to humans through contact with animals. Bite wound infection is the most common clinical manifestation. Systemic infections are unusual and mainly affect immunocompromised individuals. The article presents two cases of Pasteurella infection. Wound infection in a 75-year-old female following a bite from her pet cat was associated with bacteremia. The disease course was favorable with the initial clindamycin treatment despite in vitro resistance. The other patient was a 62-year-old female diagnosed with acute bacterial meningitis with multiple brain abscesses and transient expressive aphasia. She reported frequent contacts with pets and domestic animals without a recent bite. Hematogenous dissemination of the infection was suspected. Because of poor therapeutic response, cefotaxime was switched to chloramphenicol which was later switched to a combination of cefotaxime with ciprofloxacin due to anemia. Following 6 weeks of intravenous antibiotic therapy and another 10 weeks of oral ciprofloxacin therapy, magnetic resonance imaging showed normal results and the neurological defect resolved. Epidemiological, clinical and therapeutic aspects of Pasteurella infection are discussed and literature is reviewed. PMID:26312375

  4. Amphotericin B lipid complex in the management of invasive fungal infections in immunocompromised patients.

    PubMed

    Bassetti, Matteo; Aversa, Franco; Ballerini, Filippo; Benedetti, Fabio; Busca, Alessandro; Cascavilla, Nicola; Concia, Ercole; Tendas, Andrea; Di Raimondo, Francesco; Mazza, Patrizio; Nosari, Anna Maria; Rossi, Giuseppe

    2011-11-01

    Invasive fungal infections are associated with a poor outcome and their incidence is rising. Amphotericin B has for a long time been the gold standard for treatment of these infections, but the conventional formulation is associated with a high incidence of adverse events. Lipid formulations of amphotericin, developed to overcome these drawbacks, are now routinely used in clinical practice for the treatment of invasive fungal infections in immunocompromised patients. Amphotericin B lipid complex (ABLC) is prepared from amphotericin complexed to two phospholipids, a process that confers a number of important pharmacodynamic and pharmacokinetic properties compared with conventional amphotericin B. The results of retrospective observational studies and the analysis of databases, including the large Collaborative Exchange of Antifungal Research (CLEAR) database, have shown ABLC to be associated with response rates of up to about 80% in patients with confirmed fungal infections and around 60% in those treated empirically. Intranasal administration of ABLC for prophylaxis of invasive fungal infection in immunocompromised patients is safe and appears to be a promising treatment strategy for the future. ABLC is associated with a substantially lower incidence of nephrotoxicity than conventional amphotericin. Infusion-related reactions also occur less frequently than with conventional amphotericin and can be managed using premedication protocols. When direct and indirect costs are measured, ABLC appears to be less expensive than conventional amphotericin. The number of approved antifungal agents that are effective treatments for invasive fungal infections is increasing. However, lipid formulations of amphotericin, such as ABLC, are effective and well tolerated and remain the standard of care in the treatment of invasive fungal infections. Treatment strategies such as intranasal administration for prophylaxis and combination therapy with newer agents are future directions for

  5. 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

  6. Clinical and Molecular Characterization of Invasive Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Infections in Korean Hospitals.

    PubMed

    Kim, Eu Suk; Bae, In-Gyu; Cho, Jeong Eun; Choi, Yun Jung; Kim, Il-Hwan; Kang, Gi-Su; Sin, Hye-yun; Song, Kyoung-Ho; Park, Chulmin; Lee, Dong-Gun; Kim, Moonsuk; Park, Kyoung Un; Kim, Hong Bin

    2016-03-01

    Invasive heteroresistant vancomycin-intermediate Staphylococcus aureus (h-VISA) isolates were identified and characterized in 10 Korean hospitals from July 2009 to June 2011. The prevalence of h-VISA infections was 3.3% (42/1,289). Most (41/42) were health care-associated infections caused by strains belonging to sequence type 5. Cases of persistent bacteremia were frequent (17/42), and 30-day mortality was high (16/40). PMID:26677256

  7. Locally extensive angio-invasive Scedosporium prolificans infection following resection for squamous cell lung carcinoma

    PubMed Central

    Holmes, Natasha E.; Trevillyan, Janine M.; Kidd, Sarah E.; Leong, Trishe Y.-M.

    2013-01-01

    We report a case of Scedosporium prolificans infection in a patient following surgery for squamous cell lung carcinoma. Combination therapy with voriconazole and terbinafine was commenced for intrathoracic infection and mycotic vasculitis. In spite of antifungal treatment, he developed culture-positive sternal and rib osteomyelitis four months later. Scedosporiosis is not commonly reported in patients with solid organ malignancies, and this case highlights its aggressive nature and propensity for direct local invasion. PMID:24432228

  8. Epidemiology of Invasive Fungal Infections in the Mediterranean Area

    PubMed Central

    Binder, Ulrike; Lass-Flörl, Cornelia

    2011-01-01

    Although Candida species remain the relevant cause of IFI, other fungi (especially moulds) have become increasingly prevalent. In particular, Aspergillus species are the leading cause of mould infections but also Glomeromycota (formerly Zygomycetes) and Fusarium species are increasing in frequency, and are associated with high mortality rates. Many of these emerging infections occur as breakthrough infections in patients treated with new antifungal drugs. The causative pathogens, incidence rate and severity are dependent on the underlying condition, as well as on the geographic location of the patient population. France and Italy show the highest incident rates of Fusarium infections in Europe, following the US, where numbers are still increasing. Scedosporium prolificans, which primarily is found in soil in Spain and Australia, is most frequently isolated from blood cultures in a Spanish hospital. Geotrichum capitatum represents another species predominantly found in Europe with especially high rates in Mediterranean countries. The increasing resistance to antifungal drugs especially of these new emerging pathogens is a severe problem for managing these IFIs. PMID:21625305

  9. Invasive group A streptococcal infection concurrent with 2009 H1N1 influenza.

    PubMed

    Jean, Cynthia; Louie, Janice K; Glaser, Carol A; Harriman, Kathleen; Hacker, Jill K; Aranki, Faisal; Bancroft, Elizabeth; Farley, Susan; Ginsberg, Michele; Hernandez, Lisa B; Sallenave, Catherine S; Radner, Allen B

    2010-05-15

    We describe 10 patients with 2009 H1N1 influenza and concurrent invasive group A streptococcal infection with marked associated morbidity and mortality. Seven patients required intensive care, 8 required mechanical ventilation, and 7 died. Five of the patients, including 4 of the fatalities, were previously healthy. PMID:20377405

  10. Approaches to management of invasive fungal infections in patients with hematologic malignancies.

    PubMed

    Forrest, Graeme N; Walsh, Thomas J

    2004-10-01

    Invasive fungal infections have become increasingly common in patients with hematologic malignancies, especially in those at high risk with prolonged neutropenia and graft versus host disease after allogeneic stem cell transplantation, and are associated with significant morbidity, mortality, and cost. New diagnostic techniques and therapeutic agents have emerged recently to assist in the management of these infections. The galactomannan assay in association with routine clinical and radiologic screening may assist in the early diagnosis of invasive aspergillosis such that therapy may be initiated early. Also, several new antifungal agents have become available, allowing the practitioner more options in the prevention and treatment of fungal infections. New antifungal agents such as the lipid amphotericin B products, voriconazole, and the echinocandins appear to be safer to use than conventional amphotericin B. Voriconazole also has shown superiority to conventional amphotericin B in the treatment of invasive aspergillosis, and its well absorbed oral formulation makes it an excellent treatment to complete therapy as an outpatient. All these therapeutic options allow physicians to tailor antifungal therapy to the individual patient based on response and toxicity to prevent or treat invasive fungal infections. There are several new antifungal agents in development, and future studies will evaluate combination therapies to determine safety and efficacy. PMID:18628154

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

    PubMed

    Parahym, Ana Maria Rabelo de Carvalho; Rolim Neto, 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 Neto, Reginaldo Gonçalves; Neves, Rejane Pereira

    2015-06-01

    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

  12. 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

  13. 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

  14. 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

  15. β-d-Glucan Testing Is Important for Diagnosis of Invasive Fungal Infections

    PubMed Central

    Doern, Christopher D.

    2013-01-01

    Invasive fungal infections are a significant cause of morbidity and mortality in patients who receive immunosuppressive therapy, such as solid organ and hematopoietic stem cell transplant (HSCT) recipients. Many of the fungi associated with these infections are angioinvasive and are best diagnosed by visualizing the organism in or culturing the organism from deep tissue. However, obtaining such tissue often requires an invasive procedure. Many HSCT recipients are thrombocytopenic, making such procedure too risky because of potential bleeding complications. Additionally, positive blood cultures are rare for patients with angioinvasive fungal infections, making this diagnostic strategy of little value. Undiagnosed fungal infections in these patient populations are a significant cause of mortality. Prophylactic use of antifungal agents, such as the echinocandins, during periods of neutropenia or graft-versus-host disease may prevent some fungal infections but increase the risk for others. Detection of fungal antigens in body fluids, including cryptococcus capsular polysaccharide, histoplasma antigen, galactomannan, and β-d-glucan, is viewed as being clinically useful for at least the presumptive diagnosis of invasive fungal infections. β-d-Glucan is an attractive antigen in that it is found in a broad range of fungal agents, including the commonly encountered agents Candida spp., Aspergillus spp., and Pneumocystis jirovecii. Cross-reactions with certain hemodialysis filters, beta-lactam antimicrobials, and immunoglobulins, which raise concerns about false-positive tests, have also been described. As a result, the use of this testing must be closely monitored. In this point-counterpoint, we have asked Elitza Theel, who directs the Infectious Disease Serology Laboratory at the Mayo Clinic, to address why she believes that this test has value in the diagnosis of invasive fungal infections. We have asked Christopher Doern, Director of Clinical Microbiology at Children

  16. Characterization of nontypeable Haemophilus influenzae collected from respiratory infections and invasive disease cases in Manitoba, Canada.

    PubMed

    Shuel, Michelle; Law, Dennis; Skinner, Stuart; Wylie, John; Karlowsky, James; Tsang, Raymond S W

    2010-03-01

    With the introduction of the Haemophilus influenzae serotype b (Hib) vaccine, invasive Hib disease has decreased substantially, but nontypeable H. influenzae (NT Hi) disease appears to be increasing. In order to understand the origin of NT Hi strains and their relationship with serotypeable strains, we analysed 125 NT Hi isolates collected from individual patients with either invasive disease (70 isolates) or respiratory tract infections (55 isolates). Serotype-specific and capsular transport genes were absent by PCR analysis, confirming their nonencapsulated status, which also suggested the NT Hi isolates were not encapsulated strains that shed their capsules. Multilocus sequence typing confirmed the NT Hi isolates did not have the same genetic background as serotypeable strains, including Hib. Despite the genetic heterogeneity found, two major genetic clusters were identified, both containing invasive and respiratory isolates. Fourteen invasive isolates and nine respiratory isolates produced beta-lactamase and were ampicillin resistant. More invasive (26.8%) than respiratory isolates (10.9%) showed decreased susceptibility towards ampicillin by a mechanism unrelated to beta-lactamase production. Besides a change in the capsule status of invasive Hi strains, the burden of invasive Hi disease, which used to be mainly a childhood disease, has now shifted to involve both adults and infants. PMID:20041949

  17. Invasive candidiasis in critical care setting, updated recommendations from “Invasive Fungal Infections-Clinical Forum”, Iran

    PubMed Central

    Elhoufi, Ashraf; Ahmadi, Arezoo; Asnaashari, Amir Mohammad Hashem; Davarpanah, Mohammad Ali; Bidgoli, Behrooz Farzanegan; Moghaddam, Omid Moradi; Torabi-Nami, Mohammad; Abbasi, Saeed; El-Sobky, Malak; Ghaziani, Ali; Jarrahzadeh, Mohammad Hossein; Shahrami, Reza; Shirazian, Farzad; Soltani, Farhad; Yazdinejad, Homeira; Zand, Farid

    2014-01-01

    Invasive candidiasis (IC) bears a high risk of morbidity and mortality in the intensive care units (ICU). With the current advances in critical care and the use of wide-spectrum antibiotics, invasive fungal infections (IFIs) and IC in particular, have turned into a growing concern in the ICU. Further to blood cultures, some auxiliary laboratory tests and biomarkers are developed to enable an earlier detection of infection, however these test are neither consistently available nor validated in our setting. On the other hand, patients’ clinical status and local epidemiology data may justify the empiric antifungal approach using the proper antifungal option. The clinical approach to the management of IC in febrile, non-neutropenic critically ill patients has been defined in available international guidelines; nevertheless such recommendations need to be customized when applied to our local practice. Over the past three years, Iranian experts from intensive care and infectious diseases disciplines have tried to draw a consensus on the management of IFI with a particular focus on IC in the ICU. The established IFI-clinical forum (IFI-CF), comprising the scientific leaders in the field, has recently come up with and updated recommendation on the same (June 2014). The purpose of this review is to put together literature insights and Iranian experts’ opinion at the IFI-CF, to propose an updated practical overview on recommended approaches for the management of IC in the ICU. PMID:25374806

  18. The Association between Invasive Group A Streptococcal Diseases and Viral Respiratory Tract Infections

    PubMed Central

    Herrera, Andrea L.; Huber, Victor C.; Chaussee, Michael S.

    2016-01-01

    Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses. PMID:27047460

  19. Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency.

    PubMed

    Alves de Medeiros, Ana Karina; Lodewick, Evelyn; Bogaert, Delfien J A; Haerynck, Filomeen; Van Daele, Sabine; Lambrecht, Bart; Bosma, Sara; Vanderdonckt, Laure; Lortholary, Olivier; Migaud, Mélanie; Casanova, Jean-Laurent; Puel, Anne; Lanternier, Fanny; Lambert, Jo; Brochez, Lieve; Dullaers, Melissa

    2016-04-01

    Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans. Patients with recurrent fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal infection predisposition. PMID:26961233

  20. Neuro-invasion by a ‘Trojan Horse’ strategy and vasculopathy during intrauterine flavivirus infection

    PubMed Central

    Bielefeldt-Ohmann, Helle; Smirnova, Natalia P; Tolnay, Airn-Elizabeth; Webb, Brett T; Antoniazzi, Alfredo Q; van Campen, Hana; Hansen, Thomas R

    2012-01-01

    The central nervous system (CNS) is a major target of several important human and animal viral pathogens causing congenital infections. However, despite the importance of neuropathological outcomes, for humans in particular, the pathogenesis, including mode of neuro-invasion, remains unresolved for most congenital virus infections. Using a natural model of congenital infection with an RNA virus, bovine viral diarrhoea virus in pregnant cattle, we sought to delineate the timing and mode of virus neuro-invasion of and spread within the brain of foetuses following experimental respiratory tract infection of the dams at day 75 of pregnancy, a time of maximal risk of tissue pathology without foetal death. Virus antigen was first detected in the foetal brains 14 days postinfection of dams and was initially restricted to amoeboid microglial cells in the periventricular germinal layer. The appearance of these cells was preceded by or concurrent with vasculopathy in the same region. While the affected microvessels were negative for virus antigen, they expressed high levels of the type I interferon-stimulated protein ISG15 and eventually disappeared in parallel with the appearance of microcavitary lesions. Subsequently, the virus spread to neurons and other glial cells. Our findings suggest that the virus enters the CNS via infected microglial precursors, the amoeboid microglial cells, in a ‘Trojan horse’ mode of invasion and that the microcavitary lesions are associated with loss of periventricular microvasculature, perhaps as a consequence of high, unrestricted induction of interferon-regulated proteins. PMID:22264283

  1. 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. PMID:25500441

  2. Inherited CARD9 Deficiency in 2 Unrelated Patients With Invasive Exophiala Infection

    PubMed Central

    Lanternier, Fanny; Barbati, Elisa; Meinzer, Ulrich; Liu, Luyan; Pedergnana, Vincent; Migaud, Mélanie; Héritier, Sébastien; Chomton, Maryline; Frémond, Marie-Louise; Gonzales, Emmanuel; Galeotti, Caroline; Romana, Serge; Jacquemin, Emmanuel; Angoulvant, Adela; Bidault, Valeska; Canioni, Danielle; Lachenaud, Julie; Mansouri, Davood; Mahdaviani, Seyed Alireza; Adimi, Parvaneh; Mansouri, Nahal; Jamshidi, Mahin; Bougnoux, Marie-Elisabeth; Abel, Laurent; Lortholary, Olivier; Blanche, Stéphane; Casanova, Jean-Laurent; Picard, Capucine; Puel, Anne

    2015-01-01

    Background. Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa. Methods. We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy. Results. We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele. Conclusions. These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections. PMID:25057046

  3. Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections.

    PubMed

    Golińska, E; van der Linden, M; Więcek, G; Mikołajczyk, D; Machul, A; Samet, A; Piórkowska, A; Dorycka, M; Heczko, P B; Strus, M

    2016-05-01

    Invasive group A streptococcal (GAS) infections constitute an important epidemiological problem. Many cases occur in women during the postnatal period. The objective of this study was to evaluate the presence of the genes responsible for production of iron-chelating protein (perR) and superantigens (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, and ssa) in S. pyogenes strains isolated from invasive infections in women after delivery. Furthermore, this study sought to verify whether S. pyogenes strains show special phenotypic and genotypic (sla, spy1325) characteristics that may play a decisive role in adherence to the genital tract epithelium. Moreover, the emm-types and antibiotic susceptibility were determined. We tested 30 invasive S. pyogenes strains isolated from postpartum invasive infection and 37 GAS control strains isolated from the genital tracts of asymptomatic multiparous women. The majority of the tested strains were shown to express two types of emm genes (1 and 28), though emm -12, -28, -75 and -89 were uniquely expressed in the group of strains isolated from invasive infections. A significantly higher prevalence of perR in the strains from puerperal fever was shown. Significant differences were also found between the two groups with respect to the incidence of the genes related to adherence; GAS strains originating from women with sepsis/puerperal fever showed presence of these genes less frequently than those of the control group. Although differences in frequencies of the gene coding for various superantigens were noted between the compared groups of GAS strains, they were not significant. PMID:26873375

  4. 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

  5. Fusobacterium invasive infections in children: a retrospective study in two French tertiary care centres.

    PubMed

    Bailhache, M; Mariani-Kurkdjian, P; Lehours, P; Sarlangue, J; Pillet, P; Bingen, E; Faye, A

    2013-08-01

    The purpose of this investigation was to describe the clinical and biological characteristics and evolution of invasive Fusobacterium infections in children admitted to two French paediatric tertiary care centres. Children who were admitted from 1998 to 2009 to two tertiary care centres for invasive Fusobacterium infection were included in a retrospective study. Thirty-one children with a median age of 5.7 years (interquartile range, IQR [2.3; 9.3]) were included. Nine children had an underlying condition, most commonly sickle cell disease (n = 3) or immunodeficiency (n = 3). Two children had skin effraction prior to the infection. The major sites of infection were the head and neck (n = 14) and abdomen (n = 10). Three children suffered from atypical Lemierre's syndrome. More than half of the children had a bacterial co-infection (58 %). Six children were hospitalised in an intensive care unit, and 67 % of them had a chronic underlying disease. None of the children died. Six children with negative cultures had Fusobacterium identified through 16S RNA-PCR. Fusobacterium is responsible for severe infection in children. Microbiological diagnosis might be improved by the wider use of molecular detection. PMID:23471481

  6. 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. PMID:27074753

  7. 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

  8. 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

  9. 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. PMID:25832301

  10. 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. PMID:24268829

  11. Invasive Microascus trigonosporus Species Complex Pulmonary Infection in a Lung Transplant Recipient

    PubMed Central

    Schoeppler, Kelly E.; Zamora, Martin R.; Northcutt, Noelle M.; Barber, Gerard R.; O'Malley-Schroeder, Gayle; Lyu, Dennis M.

    2015-01-01

    Because of the high incidence of morbidity and mortality associated with invasive fungal infections, antifungal prophylaxis is often used in solid organ transplant recipients. However, this prophylaxis is not universally effective and may contribute to the selection of emerging, resistant pathogens. Here we present a rare case of invasive infection caused by Microascus trigonosporus species complex in a human, which developed during voriconazole prophylaxis in a lung transplant recipient. Nebulized liposomal amphotericin B was used in addition to systemic therapy in order to optimize antifungal drug exposure; this regimen appeared to reduce the patient's fungal burden. Despite this apparent improvement, the patient's pulmonary status progressively declined in the setting of multiple comorbidities, ultimately leading to respiratory failure and death. PMID:26075134

  12. Invasive Microascus trigonosporus Species Complex Pulmonary Infection in a Lung Transplant Recipient.

    PubMed

    Schoeppler, Kelly E; Zamora, Martin R; Northcutt, Noelle M; Barber, Gerard R; O'Malley-Schroeder, Gayle; Lyu, Dennis M

    2015-01-01

    Because of the high incidence of morbidity and mortality associated with invasive fungal infections, antifungal prophylaxis is often used in solid organ transplant recipients. However, this prophylaxis is not universally effective and may contribute to the selection of emerging, resistant pathogens. Here we present a rare case of invasive infection caused by Microascus trigonosporus species complex in a human, which developed during voriconazole prophylaxis in a lung transplant recipient. Nebulized liposomal amphotericin B was used in addition to systemic therapy in order to optimize antifungal drug exposure; this regimen appeared to reduce the patient's fungal burden. Despite this apparent improvement, the patient's pulmonary status progressively declined in the setting of multiple comorbidities, ultimately leading to respiratory failure and death. PMID:26075134

  13. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient.

    PubMed

    Çetinkaya, Erdoğan; Çörtük, Mustafa; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  14. Simultaneous Chronic Invasive Fungal Infection and Tracheal Fungus Ball Mimicking Cancer in an Immunocompetent Patient

    PubMed Central

    Çetinkaya, Erdoğan; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H. Erhan

    2016-01-01

    Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930

  15. Successful treatment of an invasive fungal infection caused by Talaromyces sp. with voriconazole

    PubMed Central

    Sili, Uluhan; Bilgin, Huseyin; Masania, Rikesh; Eryuksel, Emel; Cimsit, Nuri Cagatay; Ayranci, Gulcicek; Richardson, Malcolm; Korten, Volkan

    2015-01-01

    Invasive fungal infections (IFI) are on the rise due to increasing numbers of immunosuppressed and critically ill patients. A malignant-looking pulmonary nodule in an immunosuppressed patient may indeed be caused by a fungal organism. We report a patient, who was eventually diagnosed with an IFI caused by an agent of hyalohyphomycosis, Talaromyces sp. determined via molecular methods and succesfully treated with voriconazole. PMID:25830087

  16. Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

    PubMed

    Lamoth, Frédéric; Damonti, Lauro; Alexander, Barbara D

    2016-06-01

    No clinical breakpoints are available to delineate antifungal drug efficacy in non-Aspergillus invasive mold infections (NAIMIs). In this analysis of 39 NAIMI episodes, the MIC of the first-line antifungal drug was the most important predictor of therapeutic response. For amphotericin B, an MIC of ≤0.5 μg/ml was significantly associated with better 6-week outcomes. PMID:27008871

  17. IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae.

    PubMed

    Grazioli, Serge; Hamilton, Sara J; McKinnon, Margaret L; Del Bel, Kate L; Hoang, Linda; Cook, Victoria E; Hildebrand, Kyla J; Junker, Anne K; Turvey, Stuart E

    2016-02-01

    In this Letter to the Editor we report the case of two siblings with fatal pneumococcal meningitis as the initial manifestation of IRAK-4 deficiency caused by previously undescribed mutations in IRAK4. The letter also highlights the importance of invasive pneumococcal infection as a critical 'red flag' warning of the potential for an underlying primary immunodeficiency and identifies some of the challenges in making the clinical diagnosis of IRAK-4 deficiency. PMID:26698383

  18. Invasive Pasteurella multocida Infections - Report of Five Cases at a Minnesota Hospital, 2014.

    PubMed

    Talley, P; Snippes-Vagnone, P; Smith, K

    2016-09-01

    During October 2014, the Minnesota Department of Health was notified of five Hospital A patients with Pasteurella multocida bacteraemia; three had died. Human soft tissue infection with P. multocida typically results from cat or dog bites or scratches. Invasive infection, defined as a P. multocida isolate from a usually sterile site, is rare. We evaluated P. multocida isolations at Hospital A, compared with other Minnesota hospitals to understand invasive infection trends. A case was defined as clinically confirmed P. multocida in a Minnesota resident during 2012-2014. All hospital laboratories were queried; Fisher's exact test was used for comparison. Medical charts were reviewed for 2014 Hospital A patients with P. multocida infections. The Minnesota clinical laboratories survey response rate was 79% (63/80). At Hospital A, proportion of P. multocida isolates from usually sterile sites increased from 0% (0/2) during 2012 to 11% (1/9) during 2013, and to 86% (5/6) during 2014. The proportion of patients with P. multocida isolated from sterile sites was 35% (6/17) at Hospital A compared with 10% (58/583) statewide during 2012-2014 combined (P < 0.05). Among 2014 Hospital A patients with invasive P. multocida infection, all five were men; median age was 70 (range: 44-78) years. Four were temporally clustered within a 33-day period; three of those had bacteraemia on admission, making hospital acquisition possible in only one. Among five bacteraemia patients, four had cirrhosis and/or skin ulcerations, and three died. The proportion of invasive P. multocida cases was substantially higher at Hospital A during 2014. No epidemiologic links between patients were found. Three had known pet exposure. Collaborative educational efforts of chronically ill pet owners by physicians and veterinarians can acknowledge the health benefits of pet ownership, while minimizing risk for serious invasive zoonotic infections, including those caused by P. multocida. PMID

  19. (1-3)-β-D-Glucan vs Galactomannan Antigen in Diagnosing Invasive Fungal Infections (IFIs)

    PubMed Central

    Fontana, C; Gaziano, R; Favaro, M; Casalinuovo, IA; Pistoia, ES; Di Francesco, P

    2012-01-01

    Invasive fungal infections (IFIs) are serious and often life-threatening complications in patients with haematological malignancies. Early diagnosis and the initiation of efficacious antifungal treatments could affect the prognosis of these patients. The detection of (1-3)-β-D-Glucan (BDG) could be a promising non-culture-based, noninvasive tool for IFI analyses in haemato-oncological patients, allowing the diagnosis of the two major IFIs, invasive aspergillosis (IA) and invasive candidiasis (IC), with a single test. The aim of this work was to evaluate and compare the use of the BDG in combination with the galactomannan antigen (GAL) assay in order to exclude or confirm suspected IFIs. Sera from 46 haemato-oncological patients (24 with proven/probable IFI and 22 without IFI symptoms) were evaluated retrospectively for the detection of GAL and BDG. In 24 patients, the serum BDG levels facilitated IFI diagnosis: 18 probable IA, 3 proven IA and 3 IC. In the remaining 22 patients, the BDG level helped exclude IFIs. The BDG was positive earlier than GAL in 5/24 cases [three of probable invasive aspergillosis (IA), one of proven IA and one case of proven invasive candidiasis (IC)] and was positive at the same time as GAL in 19/24 cases; in no case was GAL positive before BDG was. The BDG detection is useful, however, the test has a great limitation because it is a completely manual procedure. PMID:22942923

  20. Molecular Characterization of Nonhemolytic and Nonpigmented Group B Streptococci Responsible for Human Invasive Infections

    PubMed Central

    Six, Anne; Firon, Arnaud; Plainvert, Céline; Caplain, Camille; Touak, Gérald; Dmytruk, Nicolas; Longo, Magalie; Letourneur, Franck; Fouet, Agnès; Trieu-Cuot, Patrick

    2015-01-01

    Group B Streptococcus (GBS) is a common commensal bacterium in adults, but is also the leading cause of invasive bacterial infections in neonates in developed countries. The β-hemolysin/cytolysin (β-h/c), which is always associated with the production of an orange-to-red pigment, is a major virulence factor that is also used for GBS diagnosis. A collection of 1,776 independent clinical GBS strains isolated in France between 2006 and 2013 was evaluated on specific medium for β-h/c activity and pigment production. The genomic sequences of nonhemolytic and nonpigmented (NH/NP) strains were analyzed to identify the molecular basis of this phenotype. Gene deletions or complementations were carried out to confirm the genotype-phenotype association. Sixty-three GBS strains (3.5%) were NH/NP, and 47 of these (74.6%) originated from invasive infections, including bacteremia and meningitis, in neonates or adults. The mutations are localized predominantly in the cyl operon, encoding the β-h/c pigment biosynthetic pathway and, in the abx1 gene, encoding a CovSR regulator partner. In conclusion, although usually associated with GBS virulence, β-h/c pigment production is not absolutely required to cause human invasive infections. Caution should therefore be taken in the use of hemolysis and pigmentation as criteria for GBS diagnosis in routine clinical laboratory settings. PMID:26491182

  1. Empyema Caused by Prevotella bivia Complicating an Unusual Case of Spontaneous Chylothorax

    PubMed Central

    Di Marco Berardino, Alessandro; Smargiassi, Andrea; Re, Antonina; Torelli, Riccardo; Fiori, Barbara; d'Inzeo, Tiziana; Corbo, Giuseppe Maria; Valente, Salvatore; Sanguinetti, Maurizio; Spanu, Teresa

    2014-01-01

    Spontaneous chylothorax is rare in adults. We present an unusual case that was complicated by Prevotella bivia empyema. Full recovery was achieved with chest tube drainage and prompt treatment with intravenous clindamycin. PMID:24452170

  2. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of rare invasive yeast infections.

    PubMed

    Arendrup, M C; Boekhout, T; Akova, M; Meis, J F; Cornely, O A; Lortholary, O

    2014-04-01

    The mortality associated with invasive fungal infections remains high with that involving rare yeast pathogens other than Candida being no exception. This is in part due to the severe underlying conditions typically predisposing patients to these healthcare-related infections (most often severe neutropenia in patients with haematological malignancies), and in part due to the often challenging intrinsic susceptibility pattern of the pathogens that potentially leads to delayed appropriate antifungal treatment. A panel of experts of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and the European Confederation of Medical Mycology (ECMM) undertook a data review and compiled guidelines for the diagnostic tests and procedures for detection and management of rare invasive yeast infections. The rare yeast pathogens were defined and limited to the following genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus uniguttulatus (often published under the name Filobasidium uniguttulatum), Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii, Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the microbiological investigation and detection of invasive infection were made and current knowledge on the most appropriate antifungal and supportive

  3. Invasive Fusobacterium necrophorum infections and Lemièrre's syndrome: the role of thrombophilia and EBV.

    PubMed

    Holm, K; Svensson, P J; Rasmussen, M

    2015-11-01

    The purpose of this investigation was to describe the clinical spectrum of invasive Fusobacterium necrophorum infections and Lemièrre's syndrome, to examine the role of underlying thrombophilia and concomitant mononucleosis in Lemièrre's syndrome, and to describe thromboembolic complications. Patients with invasive F. necrophorum infections were identified either prospectively or retrospectively through the regional database of clinical microbiology from 2000 to 2015. Patient records were reviewed and blood samples from patients with Lemièrre's syndrome were collected for Epstein-Barr virus (EBV) serology and screening for thrombophilia. Of the 65 patients included, 33 had Lemièrre's syndrome. Of the remaining 32 patients, other infections of the respiratory tract and abdominal or urogenital infections were most common. Patients with Lemièrre's syndrome or other tonsillar infections were younger than patients from the other groups. For Lemièrre's syndrome, the 26 patients with severe sepsis on admittance had longer duration of symptoms. Three of five patients who developed distant manifestations had more than 14 days of symptoms. Jugular vein thrombosis was verified in 14 patients, two of whom developed serious complications. Three of 26 patients tested had factor V Leiden mutation, corresponding to the background prevalence. One of 22 patients tested had a concomitant EBV infection. This study confirms earlier studies of the clinical spectrum caused by F. necrophorum. For Lemièrre's syndrome, the study adds to the knowledge on thromboembolic outcome, demonstrating that jugular vein thrombosis may cause severe complications. The time to treatment seems to be important for the risk of severe disease. In this study, concomitant EBV infection or underlying thrombophilia was uncommon. PMID:26272176

  4. Invasion of Herpes Simplex Virus Type 1 into Murine Epidermis: An Ex Vivo Infection Study.

    PubMed

    Rahn, Elena; Petermann, Philipp; Thier, Katharina; Bloch, Wilhelm; Morgner, Jessica; Wickström, Sara A; Knebel-Mörsdorf, Dagmar

    2015-12-01

    Herpes simplex virus type 1 (HSV-1) invades its human host via the skin or mucosa. We aim to understand how HSV-1 overcomes the barrier function of the host epithelia, and for this reason, we established an ex vivo infection assay initially with murine skin samples. Here, we report how tissue has to be prepared to be susceptible to HSV-1 infection. Most efficient infection of the epidermis was achieved by removing the dermis. HSV-1 initially invaded the basal epidermal layer, and from there, spreading to the suprabasal layers was observed. Strikingly, in resting stage hair follicles, only the hair germ was infected, whereas the quiescent bulge stem cells (SCs) were resistant to infection. However, during the growth phase, infected cells were also detected in the activated bulge SCs. We demonstrated that cell proliferation was not a precondition for HSV-1 invasion, but SC activation was required as shown by infection of aberrantly activated bulge SCs in integrin-linked kinase (ILK)-deficient hair follicles. These results suggest that the status of the bulge SCs determines whether HSV-1 can reach its receptors, whereas the receptors on basal keratinocytes are accessible irrespective of their proliferation status. PMID:26203638

  5. 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

  6. Ceftaroline Fosamil Use in 2 Pediatric Patients With Invasive Methicillin-Resistant Staphylococcus aureus Infections.

    PubMed

    Williams, Amanda W; Newman, Patrick M; Ocheltree, Sara; Beaty, Rachel; Hassoun, Ali

    2015-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common pathogens causing pediatric infections including skin and soft tissue infections, pyogenic arthritis, osteomyelitis, and septic shock. For decades, patients were treated with antibiotics such as vancomycin and clindamycin, but there is an increasing incidence of resistance to these traditional therapies. We describe 2 cases of patients with CA-MRSA invasive infections with bacteremia who experienced vancomycin therapy failure but who were successfully treated with ceftaroline fosamil. Case 1 involves an 8-year-old Hispanic male who was diagnosed with CA-MRSA bacteremia, thigh abscess, and osteomyelitis. The patient was admitted to the pediatric intensive care unit in septic shock. Case 2 involves an 8-year-old Caucasian male who was diagnosed with CA-MRSA sepsis, right arm abscess, and osteomyelitis. We were able to successfully treat both patients with CA-MRSA sepsis and invasive infection-who failed vancomycin therapy-with ceftaroline fosamil with no adverse efiects. Despite the positive outcome in both pediatric patients, clinical trials with ceftaroline fosamil are needed to further support its use in pediatric patients. PMID:26766937

  7. Cleavage of CD14 and LBP by a protease from Prevotella intermedia

    PubMed Central

    Deschner, James; Singhal, Anuradha; Long, Ping; Liu, Chau-Ching; Piesco, Nicholas

    2016-01-01

    Periodontitis is an inflammatory disease caused by subgingival microorganisms and their components, such as lipopolysaccharide (LPS). Responses of the host to LPS are mediated by CD14 and LPS-binding protein (LBP). In this study, it was determined that proteases from a periodontal pathogen, Prevotella intermedia, cleave CD14 and LBP, and thereby modulate the virulence of LPS. Culture supernatants from two strains of P. intermedia (ATCC 25611 and 25261) cleaved CD14 and LBP in a concentration-dependent manner. Zymographic and molecular mass analysis revealed the presence of a membrane-associated, 170-kDa, monomeric protease. Class-specific inhibitors and stimulators demonstrated that this enzyme is a metal-requiring, thiol-activated, cysteine protease. The protease was stable over a wide range of temperatures (4–56 °C) and pH values (4.5–8.5). This enzyme also decreased the expression of interleukin-1β (IL-1β)-specific mRNA in the LPS-activated macrophage-like cell lines U937 and THP-1 in a concentration-dependent manner, indicating that it also cleaves membrane-associated CD14. Furthermore, addition of soluble CD14 abrogated protease-mediated inhibition of IL-1 mRNA expression induced by LPS. The observations suggest that proteolysis of CD14 and LBP by P. intermedia protease might modulate the virulence of LPS at sites of periodontal infections. PMID:12728301

  8. Streptococcus tigurinus, a Novel Member of the Streptococcus mitis Group, Causes Invasive Infections

    PubMed Central

    Mueller, Nicolas J.; Tarr, Philip E.; Eich, Gerhard; Schulthess, Bettina; Bahlmann, Anna S.; Keller, Peter M.; Bloemberg, Guido V.

    2012-01-01

    We recently described the novel species Streptococcus tigurinus sp. nov. belonging to the Streptococcus mitis group. The type strain AZ_3aT of S. tigurinus was originally isolated from a patient with infective endocarditis. According to its phenotypic and molecular characteristics, S. tigurinus is most closely related to Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pseudopneumoniae, Streptococcus oralis, and Streptococcus infantis. Accurate identification of S. tigurinus is facilitated by 16S rRNA gene analysis. We retrospectively analyzed our 16S rRNA gene molecular database, which contains sequences of all clinical samples obtained in our institute since 2003. We detected 17 16S rRNA gene sequences which were assigned to S. tigurinus, including sequences from the 3 S. tigurinus strains described previously. S. tigurinus originated from normally sterile body sites, such as blood, cerebrospinal fluid, or heart valves, of 14 patients and was initially detected by culture or broad-range 16S rRNA gene PCR, followed by sequencing. The 14 patients had serious invasive infections, i.e., infective endocarditis (n = 6), spondylodiscitis (n = 3), bacteremia (n = 2), meningitis (n = 1), prosthetic joint infection (n = 1), and thoracic empyema (n = 1). To evaluate the presence of Streptococcus tigurinus in the endogenous oral microbial flora, we screened saliva specimens of 31 volunteers. After selective growth, alpha-hemolytic growing colonies were analyzed by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and subsequent molecular methods. S. tigurinus was not identified among 608 strains analyzed. These data indicate that S. tigurinus is not widely distributed in the oral cavity. In conclusion, S. tigurinus is a novel agent of invasive infections, particularly infective endocarditis. PMID:22760039

  9. Clinical practice guidelines for the treatment of invasive Aspergillus infections in adults in the Middle East region: Expert panel recommendations.

    PubMed

    Al-Abdely, Hail M; Alothman, Adel F; Salman, Jameela Al; Al-Musawi, Tariq; Almaslamani, Muna; Butt, Adeel A; Al Thaqafi, Abdulhakeem O; Raghubir, Nirvana; Morsi, Waleed El; Yared, Nadine A

    2014-02-01

    The incidence of invasive Aspergillus infections in the Middle East continues to rise with the increase in the number of immunocompromised patients, and carries significant morbidity and mortality. A panel of experts analysed the evidence from the most recent international guidelines and relevant published literature to reach consensus and develop clear clinical practice guidelines to aid diagnosis and treatment of invasive Aspergillus infections in the Middle East. Disease-specific recommendations were provided for the management of invasive aspergillosis. The expert panel acknowledged that these guidelines should be followed as closely as possible but used alongside clinical judgement. PMID:24029495

  10. Detection of retroviral super-infection from non-invasive samples.

    PubMed

    Goffe, Adeelia S; Blasse, Anja; Mundry, Roger; Leendertz, Fabian H; Calvignac-Spencer, Sébastien

    2012-01-01

    While much attention has been focused on the molecular epidemiology of retroviruses in wild primate populations, the correlated question of the frequency and nature of super-infection events, i.e., the simultaneous infection of the same individual host with several strains of the same virus, has remained largely neglected. In particular, methods possibly allowing the investigation of super-infection from samples collected non-invasively (such as faeces) have never been properly compared. Here, we fill in this gap by assessing the costs and benefits of end-point dilution PCR (EPD-PCR) and multiple bulk-PCR cloning, as applied to a case study focusing on simian foamy virus super-infection in wild chimpanzees (Pan troglodytes). We show that, although considered to be the gold standard, EPD-PCR can lead to massive consumption of biological material when only low copy numbers of the target are expected. This constitutes a serious drawback in a field in which rarity of biological material is a fundamental constraint. In addition, we demonstrate that EPD-PCR results (single/multiple infection; founder strains) can be well predicted from multiple bulk-PCR clone experiments, by applying simple statistical and network analyses to sequence alignments. We therefore recommend the implementation of the latter method when the focus is put on retroviral super-infection and only low retroviral loads are encountered. PMID:22590569

  11. Escherichia coli uropathogenesis in vitro: invasion, cellular escape, and secondary infection analyzed in a human bladder cell infection model.

    PubMed

    Andersen, Thomas E; Khandige, Surabhi; Madelung, Michelle; Brewer, Jonathan; Kolmos, Hans J; Møller-Jensen, Jakob

    2012-05-01

    Uropathogenic Escherichia coli (UPEC) strains are capable of invading bladder epithelial cells (BECs) on the bladder luminal surface. Based primarily on studies in mouse models, invasion is proposed to trigger an intracellular uropathogenic cascade involving intracellular bacterial proliferation followed by escape of elongated, filamentous bacteria from colonized BECs. UPEC filaments on the mouse bladder epithelium are able to revert to rod-shaped bacteria, which are believed to invade neighboring cells to initiate new rounds of intracellular colonization. So far, however, these late-stage infection events have not been replicated in vitro. We have established an in vitro model of human bladder cell infection by the use of a flow chamber (FC)-based culture system, which allows investigation of steps subsequent to initial invasion. Short-term bacterial colonization on the FC-BEC layer led to intracellular colonization. Exposing invaded BECs to a flow of urine, i.e., establishing conditions similar to those faced by UPEC reemerging on the bladder luminal surface, led to outgrowth of filamentous bacteria similar to what has been reported to occur in mice. These filaments were capable of reverting to rods that could invade other BECs. Hence, under growth conditions established to resemble those present in vivo, the elements of the proposed uropathogenic cascade were inducible in a human BEC model system. Here, we describe the model and show how these characteristics are reproduced in vitro. PMID:22354025

  12. Ceftaroline Fosamil Use in 2 Pediatric Patients With Invasive Methicillin-Resistant Staphylococcus aureus Infections

    PubMed Central

    Newman, Patrick M.; Ocheltree, Sara; Beaty, Rachel; Hassoun, Ali

    2015-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common pathogens causing pediatric infections including skin and soft tissue infections, pyogenic arthritis, osteomyelitis, and septic shock. For decades, patients were treated with antibiotics such as vancomycin and clindamycin, but there is an increasing incidence of resistance to these traditional therapies. We describe 2 cases of patients with CA-MRSA invasive infections with bacteremia who experienced vancomycin therapy failure but who were successfully treated with ceftaroline fosamil. Case 1 involves an 8-year-old Hispanic male who was diagnosed with CA-MRSA bacteremia, thigh abscess, and osteomyelitis. The patient was admitted to the pediatric intensive care unit in septic shock. Case 2 involves an 8-year-old Caucasian male who was diagnosed with CA-MRSA sepsis, right arm abscess, and osteomyelitis. We were able to successfully treat both patients with CA-MRSA sepsis and invasive infection—who failed vancomycin therapy—with ceftaroline fosamil with no adverse efiects. Despite the positive outcome in both pediatric patients, clinical trials with ceftaroline fosamil are needed to further support its use in pediatric patients. PMID:26766937

  13. A Peptide of Heparin Cofactor II Inhibits Endotoxin-Mediated Shock and Invasive Pseudomonas aeruginosa Infection

    PubMed Central

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; van der Plas, Mariena J. A.; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2014-01-01

    Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections. PMID:25047075

  14. Population-Based Analysis of Invasive Fungal Infections, France, 2001–2010

    PubMed Central

    Bitar, Dounia; Lortholary, Olivier; Le Strat, Yann; Nicolau, Javier; Coignard, Bruno; Tattevin, Pierre; Dromer, Françoise

    2014-01-01

    To determine the epidemiology and trends of invasive fungal infections (IFIs) in France, we analyzed incidence, risk factors, and in-hospital death rates related to the most frequent IFIs registered in the national hospital discharge database during 2001–2010. The identified 35,876 IFI cases included candidemia (43.4%), Pneumocystis jirovecii pneumonia (26.1%), invasive aspergillosis (IA, 23.9%), cryptococcosis (5.2%), and mucormycosis (1.5%). The overall incidence was 5.9/100,000 cases/year and the mortality rate was 27.6%; both increased over the period (+1.5%, +2.9%/year, respectively). Incidences substantially increased for candidemia, IA, and mucormycosis. Pneumocystis jirovecii pneumonia incidence decreased among AIDS patients (−14.3%/year) but increased in non-HIV–infected patients (+13.3%/year). Candidemia and IA incidence was increased among patients with hematologic malignancies (>+4%/year) and those with chronic renal failure (>+10%/year). In-hospital deaths substantially increased in some groups, e.g., in those with hematologic malignancies. IFIs occur among a broad spectrum of non–HIV-infected patients and should be a major public health priority. PMID:24960557

  15. Development of a non-invasive murine infection model for acute otitis media.

    PubMed

    Stol, K; van Selm, S; van den Berg, S; Bootsma, H J; Blokx, W A M; Graamans, K; Tonnaer, E L G M; Hermans, P W M

    2009-12-01

    Otitis media (OM) is one of the most frequent diseases in childhood, and Streptococcus pneumoniae is among the main causative bacterial agents. Since current experimental models used to study the bacterial pathogenesis of OM have several limitations, such as the invasiveness of the experimental procedures, we developed a non-invasive murine OM model. In our model, adapted from a previously developed rat OM model, a pressure cabin is used in which a 40 kPa pressure increase is applied to translocate pneumococci from the nasopharyngeal cavity into both mouse middle ears. Wild-type pneumococci were found to persist in the middle ear cavity for 144 h after infection, with a maximum bacterial load at 96 h. Inflammation was confirmed at 96 and 144 h post-infection by IL-1beta and TNF-alpha cytokine analysis and histopathology. Subsequently, we investigated the contribution of two surface-associated pneumococcal proteins, the streptococcal lipoprotein rotamase A (SlrA) and the putative proteinase maturation protein A (PpmA), to experimental OM in our model. Pneumococci lacking the slrA gene, but not those lacking the ppmA gene, were significantly reduced in virulence in the OM model. Importantly, pneumococci lacking both genes were significantly more attenuated than the DeltaslrA single mutant. This additive effect suggests that SlrA and PpmA exert complementary functions during experimental OM. In conclusion, we have developed a highly reproducible and non-invasive murine infection model for pneumococcal OM using a pressure cabin, which is very suitable to study pneumococcal pathogenesis and virulence in vivo. PMID:19762437

  16. 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. PMID:12679266

  17. Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome.

    PubMed

    Zhao, Yanlin; Marple, Andrew H; Ferguson, David J P; Bzik, David J; Yap, George S

    2014-04-29

    Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially used by avirulent strains of T. gondii and confers an infectious advantage over virulent strains for macrophage tropism. PMID:24733931

  18. Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome

    PubMed Central

    Zhao, Yanlin; Marple, Andrew H.; Ferguson, David J. P.; Bzik, David J.; Yap, George S.

    2014-01-01

    Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially used by avirulent strains of T. gondii and confers an infectious advantage over virulent strains for macrophage tropism. PMID:24733931

  19. 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

  20. 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.

  1. 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.). PMID:26083206

  2. 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

  3. Incidence of invasive meticillin-resistant Staphylococcus aureus infections in Germany, 2010 to 2014.

    PubMed

    Walter, Jan; Haller, Sebastian; Blank, Hans-Peter; Eckmanns, Tim; Abu Sin, Muna; Hermes, Julia

    2015-01-01

    Voluntary surveillance systems in Germany suggest a recent decline in the incidence of infections (subsequent to at least 2010) with meticillin-resistant Staphylococcus aureus (MRSA) from various types of specimens and settings. We asked whether this decline is reflected by data from the mandatory national surveillance system for invasive MRSA infections. Our analysis is based on the population in Germany in 2010 to 2014. Cases were identified from passive reporting by microbiological laboratories of the diagnosis of MRSA from blood culture or cerebrospinal fluid. Respective clinical data were subsequently added to the notification. We calculated risk ratios (RR) between consecutive years, stratifying cases by sex, age and federal state of residence. The national incidence increased from 4.6 episodes per 100,000 persons in 2010 to 5.6 in 2012 (2011 vs 2010: RR: 1.13, 95% confidence interval (CI): 1.08-1.18; 2012 vs 2011: RR: 1.08, 95% CI: 1.04-1.13). It stagnated at 5.4 per 100,000 in 2013 (RR: 0.97, 95% CI: 0.93-1.01) before declining to 4.8 in 2014 (RR: 0.88, 95% CI: 0.84-0.91). This trend was observed in most, but not all federal states and strata of sex and age groups. Only 204 of 20,679 (1%) episodes of infection were notified as belonging to an outbreak. Our analysis corroborates previous findings that the incidence of invasive MRSA infections in Germany may be declining. PMID:26607355

  4. Cucumispora ornata n. sp. (Fungi: Microsporidia) infecting invasive 'demon shrimp' (Dikerogammarus haemobaphes) in the United Kingdom.

    PubMed

    Bojko, Jamie; Dunn, Alison M; Stebbing, Paul D; Ross, Stuart H; Kerr, Rose C; Stentiford, Grant D

    2015-06-01

    Dikerogammarus haemobaphes, the 'demon shrimp', is an amphipod native to the Ponto-Caspian region. This species invaded the UK in 2012 and has become widely established. Dikerogammarus haemobaphes has the potential to introduce non-native pathogens into the UK, creating a potential threat to native fauna. This study describes a novel species of microsporidian parasite infecting 72.8% of invasive D. haemobaphes located in the River Trent, UK. The microsporidium infection was systemic throughout the host; mainly targeting the sarcolemma of muscle tissues. Electron microscopy revealed this parasite to be diplokaryotic and have 7-9 turns of the polar filament. The microsporidium is placed into the 'Cucumispora' genus based on host histopathology, fine detail parasite ultrastructure, a highly similar life-cycle and SSU rDNA sequence phylogeny. Using this data this novel microsporidian species is named Cucumispora ornata, where 'ornata' refers to the external beading present on the mature spore stage of this organism. Alongside a taxonomic discussion, the presence of a novel Cucumispora sp. in the United Kingdom is discussed and related to the potential control of invasive Dikerogammarus spp. in the UK and the health of native species which may come into contact with this parasite. PMID:25929755

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

    PubMed Central

    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. PMID:26392781

  6. Neurological disease associated with Mycoplasma pneumoniae infection. PCR evidence against a direct invasive mechanism

    PubMed Central

    Fink, C G; Sillis, M; Read, S J; Butler, L; Pike, M

    1995-01-01

    Aims—To investigate the pathology in patients presenting with sudden onset neurological illnesses associated with Mycoplasma pneumoniae infection. Methods—M pneumoniae infection was diagnosed by a highly rigorous interpretation of serological markers initially using complement fixation, agglutination and IgM antibodies. Confirmation of the serological diagnosis was achieved using indirect immunofluorescence for IgM, IgA, and IgG. Serum and cerebrospinal fluid (CSF) samples from these patients were examined using the polymerase chain reaction to look for evidence of M pneumoniae DNA. Results—No M pneumoniae DNA was found in any serum or CSF samples. Diagnosis of M pneumoniae infection by agglutination and complement fixation antibodies was not always confirmed by indirect immunofluorescence. Conclusion—The neurological lesions in these patients do not appear to be caused by the direct invasion of M pneumoniae into the nervous system. The lesions may be an immune response to infection. Serological diagnosis of M pneumoniae continues to be a laboratory problem. PMID:16695976

  7. [The impact of nematode invasions on the pattern of Cryptosporidium parvum infection in wild rodents].

    PubMed

    Kuliś-Małkowska, Karolina

    2007-01-01

    Fragmentation of the environment by natural barriers (lakes, mountain ranges) and human activities (towns, major roads, agriculture) can lead to isolated subpopulations of hosts. The study was carried out in Mazury Lake District in North-East of Poland, the region rich in forests, lakes, rivers and canals, which are able to create passable such barriers. Population of bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis)--dominant woodland rodents--showed local differences in helminth communities in fragmented forest habitat. The sites were chosen on the basis of the similarity of their habitat structure and type, and isolation from one another. The impact of nematode (Heligmosomoididae) infections on co-occurrence and dynamic of Cryptosporidium parvum infection was studied in both rodent species Myodes glareolus (n=781) and Apodemusflavicollis (n=302) from three different habitats. Presented results clearly revealed that natural nematode invasion could facilitate the presence of chronic infections of Cryptosporidium parvum in wild rodent populations. Also, the intrinsic (host sex and year) as well as extrinsic (season and year of study) factors have obvious effect on dynamics of infections with both groups of parasites. However, there are also some evidences that steroids hormones associated with stress and reproduction may mediate trade-offs between physiology and immune function and can affect co-occurrence of both groups of parasites. PMID:18075159

  8. 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. PMID:26730212

  9. 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

  10. [Nosocomial infections associated to invasive devices in the intensive care units of a national hospital of Lima, Peru].

    PubMed

    Chincha, Omayra; Cornelio, Elia; Valverde, Violeta; Acevedo, Mónica

    2013-01-01

    In order to describe the incidence of nosocomial infections associated to invasive devices in intensive care units (UCI) of the National Hospital Cayetano Heredia, a retrospective observational study was conducted using the data from the Office of Epidemiology and Environmental Health from 2010 to 2012. A total number of 222 nosocomial infections were reported; the general medicine UCI reported the highest incidence of pneumonia cases associated to a mechanical ventilator in 1000 days of use of the device (28.6); infection of the blood stream associated to central venous catheter (11.9), and infection of the urinary tract associated to a catheter (8,1). The main infectious agents isolated were Pseudomona sp. (32.3%) in the emergency UCI, negative Staphylococcus coagulasa (36%) in the general medicine UCI and Candida sp (69.2%) in the Surgery UCI. The rates of infections associated to invasive devices were high as in other national hospitals with limited resources and infrastructure. PMID:24448938

  11. Geographic Distribution of Staphylococcus aureus Causing Invasive Infections in Europe: A Molecular-Epidemiological Analysis

    PubMed Central

    Grundmann, Hajo; Aanensen, David M.; van den Wijngaard, Cees C.; Spratt, Brian G.; Harmsen, Dag; Friedrich, Alexander W.

    2010-01-01

    Background Staphylococcus aureus is one of the most important human pathogens and methicillin-resistant variants (MRSAs) are a major cause of hospital and community-acquired infection. We aimed to map the geographic distribution of the dominant clones that cause invasive infections in Europe. Methods and Findings In each country, staphylococcal reference laboratories secured the participation of a sufficient number of hospital laboratories to achieve national geo-demographic representation. Participating laboratories collected successive methicillin-susceptible (MSSA) and MRSA isolates from patients with invasive S. aureus infection using an agreed protocol. All isolates were sent to the respective national reference laboratories and characterised by quality-controlled sequence typing of the variable region of the staphylococcal spa gene (spa typing), and data were uploaded to a central database. Relevant genetic and phenotypic information was assembled for interactive interrogation by a purpose-built Web-based mapping application. Between September 2006 and February 2007, 357 laboratories serving 450 hospitals in 26 countries collected 2,890 MSSA and MRSA isolates from patients with invasive S. aureus infection. A wide geographical distribution of spa types was found with some prevalent in all European countries. MSSA were more diverse than MRSA. Genetic diversity of MRSA differed considerably between countries with dominant MRSA spa types forming distinctive geographical clusters. We provide evidence that a network approach consisting of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of MRSA populations such as early signalling of emerging strains, cross border spread, and importation by travel. Conclusions In contrast to MSSA, MRSA spa types have a predominantly regional distribution in Europe. This finding is indicative of the selection and spread of a limited number

  12. 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

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

    PubMed

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

    2016-06-01

    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

  14. Impact of Mucorales and Other Invasive Molds on Clinical Outcomes of Polymicrobial Traumatic Wound Infections.

    PubMed

    Warkentien, Tyler E; Shaikh, Faraz; Weintrob, Amy C; Rodriguez, Carlos J; Murray, Clinton K; Lloyd, Bradley A; Ganesan, Anuradha; Aggarwal, Deepak; Carson, M Leigh; Tribble, David R

    2015-07-01

    Combat trauma wounds with invasive fungal infections (IFIs) are often polymicrobial with fungal and bacterial growth, but the impact of the wound microbiology on clinical outcomes is uncertain. Our objectives were to compare the microbiological features between IFI and non-IFI wounds and evaluate whether clinical outcomes differed among IFI wounds based upon mold type. Data from U.S. military personnel injured in Afghanistan with IFI wounds were examined. Controls were matched by the pattern/severity of injury, including blood transfusion requirements. Wound closure timing was compared between IFI and non-IFI control wounds (with/without bacterial infections). IFI wound closure was also assessed according to mold species isolation. Eighty-two IFI wounds and 136 non-IFI wounds (63 with skin and soft tissue infections [SSTIs] and 73 without) were examined. The time to wound closure was longer for the IFI wounds (median, 16 days) than for the non-IFI controls with/without SSTIs (medians, 12 and 9 days, respectively; P < 0.001). The growth of multidrug-resistant Gram-negative rods was reported among 35% and 41% of the IFI and non-IFI wounds with SSTIs, respectively. Among the IFI wounds, times to wound closure were significantly longer for wounds with Mucorales growth than for wounds with non-Mucorales growth (median, 17 days versus 13 days; P < 0.01). When wounds with Mucorales and Aspergillus spp. growth were compared, there was no significant difference in wound closure timing. Trauma wounds with SSTIs were often polymicrobial, yet the presence of invasive molds (predominant types: order Mucorales, Aspergillus spp., and Fusarium spp.) significantly prolonged the time to wound closure. Overall, the times to wound closure were longest for the IFI wounds with Mucorales growth. PMID:25972413

  15. 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

  16. Assessing the effects of trematode infection on invasive green crabs in eastern north america.

    PubMed

    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

  17. 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

  18. 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

  19. 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. PMID:26180063

  20. Successful long-term management of invasive cerebral fungal infection following liver transplantation.

    PubMed

    Patel, Madhukar S; Wright, Alissa J; Kohn, Rachel; Markmann, James F; Kotton, Camille N; Vagefi, Parsia A

    2015-03-01

    Central nervous system (CNS) infections after liver transplantation may be fungal in aetiology, with involvement from either common organisms such as Cryptococcus neoformans and Aspergillus spp. as well as less common organisms, such as the Mucorales and Scedosporium spp. Although the mortality of CNS fungal infections was nearly 100% in early series, more recent data has suggested that good outcomes can be achieved. This may be due to both improved diagnostic capabilities, such as the ability to obtain fungal susceptibilities and therapeutic drug levels, and improved therapeutic options, such as the newer triazoles- voriconazole and posaconazole. Due to improved outcomes, issues have now arisen around the long-term tolerability of these agents. The following two cases of invasive cerebral fungal infections following liver transplantation, one with Aspergillus flavus, and the other with Scedosporium boydii/apiospermum highlight the success that can be seen with the modern management of a previously fatal diagnosis. In particular, we highlight the issues around therapeutic monitoring and discontinuation of therapy. PMID:25590987

  1. Non-invasive Imaging of Staphylococcus aureus Infections with a Nuclease-Activated Probe

    PubMed Central

    Hernandez, Frank J.; Huang, Lingyan; Olson, Michael E.; Powers, Kristy M.; Hernandez, Luiza I.; Meyerholz, David K.; Thedens, Daniel R.; Behlke, Mark A.; Horswill, Alexander R.; McNamara, James O.

    2013-01-01

    Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, non-invasive detection of S. aureus based on the activity of its secreted nuclease, micrococcal nuclease (MN). Several short, synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications, flanked with a fluorophore and quencher, were activated upon degradation by recombinant MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing bioluminescent S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This novel bacterial imaging approach has potential clinical applicability for S. aureus and several other medically significant pathogens. PMID:24487433

  2. Non-invasive Imaging of the Innate Immune Response in a Zebrafish Larval Model of Streptococcus iniae Infection

    PubMed Central

    Harvie, Elizabeth A.; Huttenlocher, Anna

    2015-01-01

    The aquatic pathogen, Streptococcus iniae, is responsible for over 100 million dollars in annual losses for the aquaculture industry and is capable of causing systemic disease in both fish and humans. A better understanding of S. iniae disease pathogenesis requires an appropriate model system. The genetic tractability and the optical transparency of the early developmental stages of zebrafish allow for the generation and non-invasive imaging of transgenic lines with fluorescently tagged immune cells. The adaptive immune system is not fully functional until several weeks post fertilization, but zebrafish larvae have a conserved vertebrate innate immune system with both neutrophils and macrophages. Thus, the generation of a larval infection model allows the study of the specific contribution of innate immunity in controlling S. iniae infection. The site of microinjection will determine whether an infection is systemic or initially localized. Here, we present our protocols for otic vesicle injection of zebrafish aged 2-3 days post fertilization as well as our techniques for fluorescent confocal imaging of infection. A localized infection site allows observation of initial microbe invasion, recruitment of host cells and dissemination of infection. Our findings using the zebrafish larval model of S. iniae infection indicate that zebrafish can be used to examine the differing contributions of host neutrophils and macrophages in localized bacterial infections. In addition, we describe how photolabeling of immune cells can be used to track individual host cell fate during the course of infection. PMID:25938624

  3. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.

    PubMed

    Drewniak, Agata; Gazendam, Roel P; Tool, Anton T J; van Houdt, Michel; Jansen, Machiel H; van Hamme, John L; van Leeuwen, Ester M M; Roos, Dirk; Scalais, Emmanuel; de Beaufort, Carine; Janssen, Hans; van den Berg, Timo K; Kuijpers, Taco W

    2013-03-28

    Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing interleukin-17 (Th17 cells) and important in antifungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis, mutations in the CARD9 gene were found to result in the loss of protein expression. Apart from the reduced numbers of CD4(+) Th17 lymphocytes, we identified a lack of monocyte-derived cytokines in response to Candida strains. Importantly, CARD9-deficient neutrophils showed a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae. The neutrophil killing defect was independent of the generation of reactive oxygen species by the reduced NAD phosphate oxidase system. Taken together, this demonstrates that human CARD9 deficiency results in selective defect in the host defense against invasive fungal infection, caused by an impaired phagocyte killing. PMID:23335372

  4. [Microbiological procedures for the diagnosis, management, and study of invasive fungal infections].

    PubMed

    Canton, Emilia; García-Rodríguez, Julio; Martín-Mazuelos, Estrella; Pemán, Javier; Guinea, Jesús

    2014-01-01

    Invasive fungal infections (IFIs) are difficult to diagnose and cause a high mortality to an expanding spectrum of patients. Culture of clinical samples has limitations for the diagnosis of IFI and alternative procedures have been developed. Among them, serum determination of galactomannan or beta-1,3-d-glucan, and antimicelium and antimannan antibodies are relevant. The use of molecular procedures and mass spectrometry (MALDI-TOF) are encouraging tools for the optimization of the diagnosis and management of patients with IFI. The proposal of species-specific breakpoint to classify the isolates as resistant or susceptible to antifungal agents and the necessity of monitor the azole serum levels deserve greater attention. PMID:23499525

  5. Blautia and Prevotella sequences distinguish human and animal fecal pollution in Brazil surface waters.

    PubMed

    Koskey, Amber M; Fisher, Jenny C; Eren, A Murat; Ponce-Terashima, Rafael; Reis, Mitermayer G; Blanton, Ronald E; McLellan, Sandra L

    2014-12-01

    Untreated sewage discharges and limited agricultural manure management practices contribute to fecal pollution in rural Brazilian waterways. Most microbial source tracking studies have focused on Bacteroidales, and few have tested host-specific indicators in underdeveloped regions. Sequencing of sewage and human and animal feces with Illumina HiSeq revealed Prevotellaceae as the most abundant family in humans, with Lachnospiraceae and Ruminococcaceae also comprising a large proportion of the microbiome. These same families were also dominant in animals. Bacteroides, the genus containing the most commonly utilized human-specific marker in the United States was present in very low abundance. We used oligotyping to identify Prevotella and Blautia sequences that can distinguish human fecal contamination. Thirty-five of 61 Blautia oligotypes and 13 of 108 Prevotella oligotypes in humans were host-specific or highly abundant (i.e. host-preferred) compared to pig, dog, horse and cow sources. Certain human Prevotella and Blautia oligotypes increased more than an order of magnitude along a polluted river transect in rural Brazil, but traditional fecal indicator levels followed a steady or even decreasing trend. While both Prevotella and Blautia oligotypes distinguished human and animal fecal pollution in Brazil surface waters, Blautia appears to contain more discriminatory and globally applicable markers for tracking sources of fecal pollution. PMID:25360571

  6. Clinical Laboratory Response to a Mock Outbreak of Invasive Bacterial Infections: a Preparedness Study

    PubMed Central

    Fittipaldi, Nahuel; Kachroo, Priyanka; Sanson, Misu A.; Long, S. Wesley; Como-Sabetti, Kathryn J.; Valson, Chandni; Cantu, Concepcion; Lynfield, Ruth; Van Beneden, Chris; Beres, Stephen B.; Musser, James M.

    2014-01-01

    Large hospital-based clinical laboratories must be prepared to rapidly investigate potential infectious disease outbreaks. To challenge the ability of our molecular diagnostics laboratory to use whole-genome sequencing in a potential outbreak scenario and identify impediments to these efforts, we studied 84 invasive serotype emm59 group A streptococcus (GAS) strains collected in the United States. We performed a rapid-response exercise to the mock outbreak scenario using whole-genome sequencing, genome-wide transcript analysis, and mouse virulence studies. The protocol changes installed in response to the lessons learned were tested in a second iteration. The initial investigation was completed in 9 days. Whole-genome sequencing showed that the invasive infections were caused by multiple subclones of epidemic emm59 GAS strains likely spread to the United States from Canada. The phylogenetic tree showed a strong temporal-spatial structure with diversity in mobile genetic element content, features that are useful for identifying closely related strains and possible transmission events. The genome data informed the epidemiology, identifying multiple patients who likely acquired the organisms through direct person-to-person transmission. Transcriptome analysis unexpectedly revealed significantly altered expression of genes encoding a two-component regulator and the hyaluronic acid capsule virulence factor. Mouse infection studies confirmed a high-virulence capacity of these emm59 organisms. Whole-genome sequencing, coupled with transcriptome analysis and animal virulence studies, can be rapidly performed in a clinical environment to effectively contribute to patient care decisions and public health maneuvers. PMID:25253790

  7. 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. PMID:22711526

  8. 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

  9. Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections.

    PubMed

    Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

    2012-01-01

    We determined the serotype and antimicrobial susceptibility of 1100 isolates responsible for adult invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes 3 (13%), 1 (12%), 7F (11%), 19A (10%) and 14 (7%) were the most frequent causes of IPD and the two later serotypes accounted for the majority of erythromycin and penicillin nonsusceptible isolates. Serotype 1 was associated with younger adults whereas serotype 3 was associated with older adults. Despite the availability of the 23-valent polysaccharide vaccine (PPV23) in Portugal since 1996, the proportion of PPV23 preventable IPD remained stable and above 80%. Comparing with previous data from Portugal, we showed a continued decline of the serotypes included in the 7-valent conjugate vaccine (PCV7) in adult IPD and a rise of serotypes included in the 13-valent conjugate vaccine, increasing its potential coverage of adult IPD to 70% in 2008. Penicillin non-susceptibility remained stable (17%) whereas erythromycin resistance (18%) has continued to rise in the post-PCV7 years. PMID:22100892

  10. 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. PMID:26386229

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

    PubMed Central

    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. PMID

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

    PubMed

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

    2015-10-01

    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

  13. 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.

  14. Differences in the epidemiology between paediatric and adult invasive Streptococcus pyogenes infections.

    PubMed

    Zachariadou, L; Stathi, A; Tassios, P T; Pangalis, A; Legakis, N J; Papaparaskevas, J

    2014-03-01

    In order to investigate for possible differences between paediatric and adult invasive Streptococcus pyogenes (iGAS) infections, a total of 142 cases were identified in 17 Greek hospitals during 2003-2007, of which 96 were children and 46 adults. Bacteraemia, soft tissue infections, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis were the main clinical presentations (67·6%, 45·1%, 13·4%, and 12·0% of cases, respectively). Bacteraemia and lymphadenitis were significantly more frequent in children (P=0·019 and 0·021, respectively), whereas STSS was more frequent in adults (P=0·017). The main predisposing factors in children were varicella and streptococcal pharyngotonsillitis (25% and 19·8%, respectively), as opposed to malignancy, intravenous drug abuse and diabetes mellitus in adults (19·6%, 15·2% and 10·9%, respectively). Of the two dominant emm-types, 1 and 12 (28·2% and 8·5%, respectively), the proportion of emm-type 12 remained stable during the study period, whereas emm-type 1 rates fluctuated considerably. Strains of emm-type 1 from children were associated with erythromycin susceptibility, STSS and intensive-care-unit admission, whereas emm-type 12 isolates from adults were associated with erythromycin and clindamycin resistance. Finally, specific emm-types were detected exclusively in adults or in children. In conclusion, several clinical and epidemiological differences were detected, that could prove useful in designing age-focused strategies for prevention and treatment of iGAS infections. PMID:23746128

  15. [Molecular features of beta-hemolytic streptococci isolated from blood in adult invasive infection and the clinical background factors].

    PubMed

    Asami, Ryoko; Okada, Keisuke; Chiba, Naoko; Ubukata, Kimiko; Takahashi, Takashi

    2010-05-01

    We studied the relationship between features of beta-hemolytic streptococci (n = 45) isolated from blood in adult invasive infection and the clinical background factors observed from January 2001 through August at a hospital for the elderly. The meanage of subjects having invasive streptococcal infection with 22 invasive Streptococcus dysgalactiae subspecies equisimilis (SDSE) strains, 2 S. pyogenes isolates, and 21 S. agalactiae (GBS) was 80 years, and 85.7% and 86.4% had underly diseases in the GBS and SDSE infections. SDSE-infected were mainly emergency woman outpatients and GBS infected were mainly man inpatients. The clinical syndrome involved pneumonia, urosepsis, and cellulitis. GBS mortality was 14.3% and SDSE mortality 27.3%. Compared to survivors, nonsurvivors had more thrombocytopenia and marked serum C-reactive protein elevation when blood culture were performed. No difference was seen in white blood cell count between bath groups. Our observations suggest that blood culture should be obtained before antimicrobials administration in elderly individuals with underlying illness who are seen at the emergency department and have laboratory blood data suggestive of infectious disease. PMID:20560419

  16. Clinical practice guidelines for the management of invasive Candida infections in adults in the Middle East region: Expert panel recommendations.

    PubMed

    Alothman, Adel F; Al-Musawi, Tariq; Al-Abdely, Hail M; Salman, Jameela Al; Almaslamani, Muna; Yared, Nadine; Butt, Adeel A; Raghubir, Nirvana; Morsi, Waleed El; Al Thaqafi, Abdulhakeem O

    2014-02-01

    Invasive Candida infections contribute to significant morbidity and mortality in patients with healthcare-associated infections. They represent a major burden on the public health system, and are challenging to diagnose and treat. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for the management of invasive Candida infections in the Middle East. Based on diagnosis, recommendations were provided for the management of Candida infections in non-neutropenic and neutropenic patients. Polyenes (amphotericin B-deoxycholate [AmB-d] and lipid formulations amphotericin B [LFAmB]), triazoles (fluconazole, itraconazole and voriconazole), echinocandins (caspofungin, anidulafungin, and micafungin) and flucytosine are the recommended categories of antifungal agents for treatment of Candida infections. Echinocandins are preferred for treatment of proven and suspected Candida infections, especially in critically ill patients or those with previous exposure to azoles. Recommendations were also provided for infections caused by specific Candida species as well as management of different disease conditions. The experts highlighted that the guidelines should be used along with clinical judgment. Given the paucity of published data from the region, research in the form of randomized clinical trials should be given priority. PMID:24035607

  17. 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. PMID:26980093

  18. Clinical features and molecular characteristics of invasive community-acquired methicillin-resistant Staphylococcus aureus infections in Taiwanese children.

    PubMed

    Chen, Chih-Jung; Su, Lin-Hui; Chiu, Cheng-Hsun; Lin, Tzou-Yien; Wong, Kin-Sun; Chen, Yi-Ywan M; Huang, Yhu-Chering

    2007-11-01

    Highly virulent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has been associated with morbidity and mortality in various countries of the world. We characterized the clinical and molecular features of pediatric invasive CA-MRSA infections in Taiwan. Between July 2000 and June 2005, 31 previously healthy children with invasive CA-MRSA infections were identified from 423 children with community-onset methicillin-resistant S. aureus infections. The medical records were reviewed. The clinical isolates, if available, were collected for molecular characterization. Sixteen (51.6%) patients were male, and the mean age was 5.7 years. Adolescents accounted for 9 (29%) cases. Eighteen children had bone and/or joint infections, 14 had deep-seated soft tissue infections, 11 had pneumonia, and 2 had central nervous system infections. Multiorgan involvement was identified in 8 of 20 bacteremic cases. Twenty-two patients (71%) required surgical interventions. The mean hospital stay was 27.4 days. All of the 15 available isolates were classified as sequence type (ST) 59 or its single locus variant and belonged to 2 previously reported community-associated clones containing staphylococcal cassette chromosome mec (SCCmec) type IV or type V(T) in Taiwan. Most of the isolates were multiresistant to clindamycin (94%) and erythromycin (97%). Eleven (73.3%) isolates carried pvl genes, and the strains harboring pvl genes were significantly associated with lung involvement. In conclusion, invasive CA-MRSA infections in pediatric population were not limited to young children. Surgical interventions were often required, and a prolonged course of antibiotic therapy was needed. A multiresistant CA-MRSA clone characterized as ST59 was identified from these children in Taiwan. PMID:17662565

  19. 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.

  20. 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. PMID:24875331

  1. [Large-scale questionnaire surveillance concerning invasive infections with group C and G streptococci].

    PubMed

    Ubukata, Kimiko; Sunaoshi, Katsuhiko; Kobayashi, Reiko; Okuzumi, Katsuko

    2006-09-01

    A large-scale questionnaire surveillance was conducted regarding the onset of invasive infections with beta-hemolytic group C (GCS) and group G (GGS) streptococci from clinical specimens that are normally aseptic and the backgrounds of these cases. The surveillance period of the questionnaire was 8 months from January to August 2005. Completed questionnaires were received from the clinical laboratories of 193 medical institutions. One hundred two clinical laboratories (52.8%) had isolated these beta-hemolytic streptococci. Of all the isolates, GCS and GGS accounted for 25 and 216 cases, respectively, or a ratio of almost 1:10. Isolates from blood cultures accounted for half the number of all isolates, followed by isolates from atretic pus or joint fluid. The isolates gradually became more prevalent from patients in their 40s, and peaked in patients in their 70s. The most prevalent disorder, described in 184 cases, was suppurative disease followed by (in descending order), bacteremia, sepsis, arthritis purulenta and cellulitis. A small number of patients had developed with streptococcal toxic shock syndrome, empyema or meningitis. Most of the patients had an underlying disease, such as diabetes mellitus, malignancy or cerebrovascular disease (in descending order). We conclude from the above findings that background factors in patients as well as identification of the pathogen should be made public when GCS or GGS is isolated from normally aseptic clinical specimens. PMID:17073260

  2. Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients.

    PubMed

    Hol, J A; Wolfs, T F W; Bierings, M B; Lindemans, C A; Versluys, A B J; Wildt de, A; Gerhardt, C E; Boelens, J J

    2014-01-01

    This study was aimed at finding predictors of invasive fungal infection (IFI) after pediatric allogeneic hematopoietic SCT (HSCT). All children who received allogeneic HSCT in the Wilhelmina Children's Hospital Utrecht between 2004 and 2012 were included. HSCT data were prospectively collected. Patients were retrospectively classified into high- or low-risk groups for developing IFI using criteria based on available literature. Predictors for the occurrence of IFI were analyzed using Cox regression models. We used logistic regression models to analyze the association between other HSCT-related complications and IFI. Secondary outcomes were overall survival and treatment-related mortality (TRM). Two-hundred nine patients were included in the analysis; median age was 6.6 years. The cumulative incidence of IFI was 12%. In patients classified as 'low risk' (n=75), only 5.3% developed IFI (odds ratio (OR): 0.325; P=0.047). In multivariate analysis, a predictor for the occurrence of IFI was an a priori determined HSCT TRM risk >20% (based on EBMT-risk score). Post-HSCT, the administration of high-dose steroids was associated with IFI (OR: 4.458; P=0.010). Patients who developed IFI showed an increased risk of TRM (OR: 3.773; P=0.004). These results confirm that risk group stratification should guide intensity of monitoring for IFI and use of antifungal prophylaxis. PMID:24121212

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

    PubMed Central

    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. PMID:26949702

  4. Invasive fungal infection in neonatal intensive care units: a multicenter survey.

    PubMed

    Baptista, Monica Isabel; Nona, José; Ferreira, Marta; Sampaio, Isabel; Abrantes, Margarida; Tomé, Maria Teresa; Neto, Maria Teresa; Barroso, Rosalina; Serelha, Micaella; Virella, Daniel

    2016-02-01

    This study assesses the epidemiology of invasive fungal infection (IFI) in Portuguese Neonatal Intensive Care Units (NICUs) and compares the effectiveness and safety of antifungal therapies. A survey concerning the period 2005-2010 was carried out in NICUs of Greater Lisbon. Among 10 473 admitted neonates, 44 cases were identified, 29 among extreme low birth weight neonates (65.9%). Cumulative incidence rate was 0.42% (95%CI 0.309-0.559). A central vascular catheter was present before IFI in all cases. Candida albicans and Candida parapsilosis were the most frequent isolates. The initial antifungic was fluconazole in 22 cases and liposomal amphotericin B (L-AmB) in 18. Therapy was switched in 10 patients on fluconazole and 3 on L-AmB. Case fatality rate was 11.4% (95%CI 4.39-23.91). No serious adverse drugs reactions (SADRs) or clinical side effects were observed. The knowledge of the local epidemiology helps to identify adequate prophylactic and treatment strategies. PMID:25365503

  5. Heterogeneity in the Infection Biology of Campylobacter jejuni Isolates in Three Infection Models Reveals an Invasive and Virulent Phenotype in a ST21 Isolate from Poultry

    PubMed Central

    Humphrey, Suzanne; Lacharme-Lora, Lizeth; Chaloner, Gemma; Gibbs, Kirsty; Humphrey, Tom; Williams, Nicola; Wigley, Paul

    2015-01-01

    Although Campylobacter is the leading cause of bacterial foodborne gastroenteritis in the world and the importance of poultry as a source of infection is well understood we know relatively little about its infection biology in the broiler chicken. Much of what we know about the biology of Campylobacter jejuni is based on infection of inbred or SPF laboratory lines of chickens with a small number of isolates used in most laboratory studies. Recently we have shown that both the host response and microbial ecology of C. jejuni in the broiler chicken varies with both the host-type and significantly between C. jejuni isolates. Here we describe heterogeneity in infection within a panel of C. jejuni isolates in two broiler chicken breeds, human intestinal epithelial cells and the Galleria insect model of virulence. All C. jejuni isolates colonised the chicken caeca, though colonisation of other parts of the gastrointestinal tract varied between isolates. Extra-intestinal spread to the liver varied between isolates and bird breed but a poultry isolate 13126 (sequence type 21) showed the greatest levels of extra-intestinal spread to the liver in both broiler breeds with over 70% of birds of the fast growing breed and 50% of the slower growing breed having C. jejuni in their livers. Crucially 13126 is significantly more invasive than other isolates in human intestinal epithelial cells and gave the highest mortality in the Galleria infection model. Taken together our findings suggest that not only is there considerable heterogeneity in the infection biology of C. jejuni in avian, mammalian and alternative models, but that some isolates have an invasive and virulent phenotype. Isolates with an invasive phenotype would pose a significant risk and increased difficulty in control in chicken production and coupled with the virulent phenotype seen in 13126 could be an increased risk to public health. PMID:26496441

  6. Heterogeneity in the Infection Biology of Campylobacter jejuni Isolates in Three Infection Models Reveals an Invasive and Virulent Phenotype in a ST21 Isolate from Poultry.

    PubMed

    Humphrey, Suzanne; Lacharme-Lora, Lizeth; Chaloner, Gemma; Gibbs, Kirsty; Humphrey, Tom; Williams, Nicola; Wigley, Paul

    2015-01-01

    Although Campylobacter is the leading cause of bacterial foodborne gastroenteritis in the world and the importance of poultry as a source of infection is well understood we know relatively little about its infection biology in the broiler chicken. Much of what we know about the biology of Campylobacter jejuni is based on infection of inbred or SPF laboratory lines of chickens with a small number of isolates used in most laboratory studies. Recently we have shown that both the host response and microbial ecology of C. jejuni in the broiler chicken varies with both the host-type and significantly between C. jejuni isolates. Here we describe heterogeneity in infection within a panel of C. jejuni isolates in two broiler chicken breeds, human intestinal epithelial cells and the Galleria insect model of virulence. All C. jejuni isolates colonised the chicken caeca, though colonisation of other parts of the gastrointestinal tract varied between isolates. Extra-intestinal spread to the liver varied between isolates and bird breed but a poultry isolate 13126 (sequence type 21) showed the greatest levels of extra-intestinal spread to the liver in both broiler breeds with over 70% of birds of the fast growing breed and 50% of the slower growing breed having C. jejuni in their livers. Crucially 13126 is significantly more invasive than other isolates in human intestinal epithelial cells and gave the highest mortality in the Galleria infection model. Taken together our findings suggest that not only is there considerable heterogeneity in the infection biology of C. jejuni in avian, mammalian and alternative models, but that some isolates have an invasive and virulent phenotype. Isolates with an invasive phenotype would pose a significant risk and increased difficulty in control in chicken production and coupled with the virulent phenotype seen in 13126 could be an increased risk to public health. PMID:26496441

  7. Association between polymorphisms in the csrRS two-component regulatory system and invasive group A streptococcal infection.

    PubMed

    Lin, J-N; Chang, L-L; Lai, C-H; Lin, H-H; Chen, Y-H

    2014-05-01

    The csrRS two-component regulatory system is an important element in the pathogenesis of group A Streptococcus (GAS). The main goal of this study is to understand the association between csrRS polymorphisms and GAS infection. We sequenced the csrRS genes from 172 clinical isolates, including 81 invasive and 91 noninvasive isolates, and then employed phylogenetic analyses to determine the consequences of the csrRS polymorphisms. In total, 13 and 26 polymorphic loci were detected in the csrR and csrS genes, respectively. These polymorphisms constituted 14 csrR and 25 csrS alleles, producing two CsrR and seven CsrS variants, respectively. Three invasive isolates contained an indel in csrS, but no indel was identified in csrR. The frequency and distribution of polymorphisms in csrR and csrS was significantly different between the invasive and noninvasive infection isolates (p < 0.001). For CsrR, only one noninvasive isolate was identified to have a V29I mutation. The amino acid substitutions in CsrS included S32P (0.6 %), E265G (0.6 %), E265K (0.6 %), I332V (1.7 %), and N498K (82.6 %). Isolates with an N498K single mutation were more likely to be associated with invasive infections (p < 0.001). The dN/dS ratio indicated that both csrR and csrS were under purifying selection. The fixation index suggested a moderate evolutionary differentiation of the csrR and csrS alleles between invasive and noninvasive isolates. The identification of these genetic differences within the csrRS loci will provide a better understanding of the pathogenesis of GAS. PMID:24158687

  8. [Warning about risk of invasive infections in splenectomized patients. Experiences from University Hospital Brno, Czech Republic, in 2011].

    PubMed

    Polák, P; Freibergerová, M; Husa, P; Slesinger, P; Svoboda, R; Sťásek, J; Frola, L; Macháček, C

    2012-09-01

    Syndrome of fulminant sepsis in splenectomized (overwhelming postsplenectomy infection - OPSI) is feared and often fatal infectious complication in patients after splenectomy. The risk of syndrome of fulminant sepsis in splenectomized in these persons persists lifelong and doesn't diminish during the time. Etiologically, encapsulated bacterias like Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis are involved. As the mortality of syndrome of fulminant sepsis in splenectomized is very high, it is indispensable to educate and vaccinate persons in risk. The authors present case reports of three splenectomized patients who were hospitalized for invasive pneumococcal infection in the University Hospital Brno, Czech Republic, in 2011. PMID:23094812

  9. Invasive Saccharomyces cerevisiae in a liver transplant patient: case report and review of infection in transplant recipients.

    PubMed

    Popiel, K Y; Wong, P; Lee, M J; Langelier, M; Sheppard, D C; Vinh, D C

    2015-06-01

    Saccharomyces cerevisiae, an ascosporogenous yeast commonly used in the production of food, is an emerging infection in immunocompromised patients. We report the case of a 60-year-old man whose orthotopic liver transplant was complicated by S. cerevisiae fungemia and peritoneal abscess, successfully treated with caspofungin and drainage. We also review the literature of invasive saccharomycoses in recipients of hematologic and solid organ transplants. PMID:25827213

  10. In Vivo Fluorescence Imaging of Biomaterial-Associated Inflammation and Infection in a Minimally-Invasive Manner

    PubMed Central

    Suri, Shalu; Lehman, Susan M.; Selvam, Shivaram; Reddie, Khalilah; Maity, Santanu; Murthy, Niren; García, Andrés J.

    2014-01-01

    Implant-associated inflammation and bacterial infection severely limit the functional performance of medical devices and are a major cause of implant failure. Therefore, it is crucial to develop methodologies to monitor/image implant-associated aseptic inflammation and bacterial infection in a minimally invasive manner. Here, we exploited near-infrared fluorescence (NIRF) molecular probes injected locally at the implant site to perform minimally invasive, simultaneous imaging of inflammation and infection associated with implanted polymer disks. The hydro-sulpho-Cy5 (H-s-Cy5) probe detected reactive oxygen species associated with inflammatory responses to both aseptic and biofilm-containing implants, whereas diaminocyanine sulphonate (DAC-S) selectively detected nitric oxide (NO) associated with a biofilm on the biomaterial at acute time points (<4 days). This imaging modality also allows longitudinal monitoring because of high specificity and fast clearance rate of the fluorescent probes. Taken together, these NIRF molecular probes represent a useful tool to directly image inflammatory responses and infections associated with implanted devices for the diagnosis of device-associated inflammation and infection as well as the development of effective therapies. PMID:24616254

  11. Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue.

    PubMed

    Castiglia, Virginia; Piersigilli, Alessandra; Ebner, Florian; Janos, Marton; Goldmann, Oliver; Damböck, Ursula; Kröger, Andrea; Weiss, Sigfried; Knapp, Sylvia; Jamieson, Amanda M; Kirschning, Carsten; Kalinke, Ulrich; Strobl, Birgit; Müller, Mathias; Stoiber, Dagmar; Lienenklaus, Stefan; Kovarik, Pavel

    2016-03-01

    Type I interferons (IFN-Is) are fundamental for antiviral immunity, but their role in bacterial infections is contradictory and incompletely described. Streptococcus pyogenes activates IFN-I production in innate immune cells, and IFN-I receptor 1 (Ifnar1)-deficient mice are highly susceptible to S. pyogenes infection. Here we report that IFN-I signaling protects the host against invasive S. pyogenes infection by restricting inflammation-driven damage in distant tissues. Lethality following infection in Ifnar1-deficient mice is caused by systemically exacerbated levels of the proinflammatory cytokine IL-1β. Critical cellular effectors of IFN-I in vivo are LysM+ and CD11c+ myeloid cells, which exhibit suppression of Il1b transcription upon Ifnar1 engagement. These cells are also the major source of IFN-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection. PMID:26962946

  12. Three Epidemics of Invasive Multidrug-Resistant Salmonella Bloodstream Infection in Blantyre, Malawi, 1998–2014

    PubMed Central

    Feasey, Nicholas A.; Masesa, Clemens; Jassi, Chikondi; Faragher, E. Brian; Mallewa, Jane; Mallewa, Macpherson; MacLennan, Calman A.; Msefula, Chisomo; Heyderman, Robert S.; Gordon, Melita A.

    2015-01-01

    Background. The Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) has routinely collected specimens for blood culture from febrile patients, and cerebrospinal fluid from patients with suspected meningitis, presenting to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, since 1998. Methods. We present bloodstream infection (BSI) and meningitis surveillance data from 1998 to 2014. Automated blood culture, manual speciation, serotyping, and antimicrobial susceptibility testing were performed at MLW. Population data for minimum-incidence estimates in urban Blantyre were drawn from published estimates. Results. Between 1998 and 2014, 167 028 blood cultures were taken from adult and pediatric medical patients presenting to QECH; Salmonella Typhi was isolated on 2054 occasions (1.2%) and nontyphoidal Salmonella (NTS) serovars were isolated 10 139 times (6.1%), of which 8017 (79.1%) were Salmonella Typhimurium and 1608 (15.8%) were Salmonella Enteritidis. There were 392 cases of NTS meningitis and 9 cases of Salmonella Typhi meningitis. There have been 3 epidemics of Salmonella BSI in Blantyre; Salmonella Enteritidis from 1999 to 2002, Salmonella Typhimurium from 2002 to 2008, and Salmonella Typhi, which began in 2011 and was ongoing in 2014. Multidrug resistance has emerged in all 3 serovars and is seen in the overwhelming majority of isolates, while resistance to third-generation cephalosporins and fluoroquinolones is currently uncommon but has been identified. Conclusions. Invasive Salmonella disease in Malawi is dynamic and not clearly attributable to a single risk factor, although all 3 epidemics were associated with multidrug resistance. To inform nonvaccine and vaccine interventions, reservoirs of disease and modes of transmission require further investigation. PMID:26449953

  13. Epidemiology, outcome and emm types of invasive group A streptococcal infections in Finland.

    PubMed

    Siljander, T; Lyytikäinen, O; Vähäkuopus, S; Snellman, M; Jalava, J; Vuopio, J

    2010-10-01

    In 2006, Finnish nationwide surveillance showed an increase of invasive group A streptococcal (iGAS) disease and clinicians were alarmed by severe disease manifestations, prompting the investigation of recent trends and outcome for iGAS. A case of iGAS was defined as Streptococcus pyogenes isolated from blood or cerebrospinal fluid. Cases during 1998-2007 and isolates during 2004-2007 were included. Case-patients' 7-day outcome was available for 2004-2007. Isolates were emm typed. A total of 1,318 cases of iGAS were identified. The average annual incidence was 2.5/100,000 population. The rate was higher in males than females in persons aged 45-64 years, but lower in persons aged 25-34 years. The annual incidence was highest in 2007 (3.9/100,000). Occasional peaks occurred during midwinter and midsummer. The most common emm types were 28 (21%), 1 (16%), 84 (10%), 75 (7%) and 89 (6%). During 2004-2007, emm1 replaced emm28 as the most predominant type. The overall case fatality was 8%. Cases with emm1 were associated with high case fatality (14% vs. 8% in other types; p < 0.02); that of emm28 infections was 2% (p < 0.01). Changes in emm type prevalence influenced incidence and case fatality. Differences in age- and sex-specific incidence and seasonal patterns suggest variations in predisposing factors and underlying conditions. PMID:20563620

  14. Virus infection and grazing exert counteracting influences on survivorship of native bunchgrass seedlings competing with invasive exotics

    PubMed Central

    MALMSTROM, CM; STONER, CJ; BRANDENBURG, S; NEWTON, LA

    2006-01-01

    Summary  Invasive annual grasses introduced by European settlers have largely displaced native grassland vegetation in California and now form dense stands that constrain the establishment of native perennial bunchgrass seedlings. Bunchgrass seedlings face additional pressures from both livestock grazing and barley and cereal yellow dwarf viruses (B/CYDVs), which infect both young and established grasses throughout the state.  Previous work suggested that B/CYDVs could mediate apparent competition between invasive exotic grasses and native bunchgrasses in California.  To investigate the potential significance of virus-mediated mortality for early survivorship of bunchgrass seedlings, we compared the separate and combined effects of virus infection, competition and simulated grazing in a field experiment. We infected two species of young bunchgrasses that show different sensitivity to B/CYDV infection, subjected them to competition with three different densities of exotic annuals crossed with two clipping treatments, and monitored their growth and first-year survivorship.  Although virus infection alone did not reduce first-year survivorship, it halved the survivorship of bunchgrasses competing with exotics. Within an environment in which competition strongly reduces seedling survivorship (as in natural grasslands), virus infection therefore has the power to cause additional seedling mortality and alter patterns of establishment.  Surprisingly, clipping did not reduce bunchgrass survivorship further, but rather doubled it and disproportionately increased survivorship of infected bunchgrasses.  Together with previous work, these findings show that B/CYDVs can be potentially powerful elements influencing species interactions in natural grasslands.  More generally, our findings demonstrate the potential significance of multitrophic interactions in virus ecology. Although sometimes treated collectively as plant ‘predators’, viruses and herbivores may

  15. Community-Associated Methicillin-Resistant Staphylococcus aureus Lacking PVL, as a Cause of Severe Invasive Infection Treated with Linezolid

    PubMed Central

    Gavino, Alexandra; Miragaia, Maria; Varandas, Luis; de Lencastre, Herminia; Brito, Maria Joao

    2013-01-01

    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging public health problem worldwide. Severe invasive infections have been described, mostly associated with the presence of Panton-Valentine leukocidin (PVL). In Portugal limited information exists regarding CA-MRSA infections. In this study we describe the case of a previously healthy 12-year-old female, sport athlete, who presented to the hospital with acetabulofemoral septic arthritis, myositis, fasciitis, acetabulum osteomyelitis, and pneumonia. The MRSA isolated from blood and synovial fluid was PVL negative and staphylococcal enterotoxin type P (SEP) and type L (SEL) positive, with a vancomycin MIC of 1.0 mg/L and resistant to clindamycin and ciprofloxacin. The patient was submitted to multiple surgical drainages and started on vancomycin, rifampicin, and gentamycin. Due to persistence of fever and no microbiological clearance, linezolid was started with improvement. This is one of the few reported cases of severe invasive infection caused by CA-MRSA in Portugal, which was successfully treated with linezolid. In spite of the severity of infection, the MRSA isolate did not produce PVL. PMID:23509655

  16. 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. PMID:26091096

  17. 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

  18. The hitchhiker's guide to Europe: the infection dynamics of an ongoing Wolbachia invasion and mitochondrial selective sweep in Rhagoletis cerasi.

    PubMed

    Schuler, Hannes; Köppler, Kirsten; Daxböck-Horvath, Sabine; Rasool, Bilal; Krumböck, Susanne; Schwarz, Dietmar; Hoffmeister, Thomas S; Schlick-Steiner, Birgit C; Steiner, Florian M; Telschow, Arndt; Stauffer, Christian; Arthofer, Wolfgang; Riegler, Markus

    2016-04-01

    Wolbachia is a maternally inherited and ubiquitous endosymbiont of insects. It can hijack host reproduction by manipulations such as cytoplasmic incompatibility (CI) to enhance vertical transmission. Horizontal transmission of Wolbachia can also result in the colonization of new mitochondrial lineages. In this study, we present a 15-year-long survey of Wolbachia in the cherry fruit fly Rhagoletis cerasi across Europe and the spatiotemporal distribution of two prevalent strains, wCer1 and wCer2, and associated mitochondrial haplotypes in Germany. Across most of Europe, populations consisted of either 100% singly (wCer1) infected individuals with haplotype HT1, or 100% doubly (wCer1&2) infected individuals with haplotype HT2, differentiated only by a single nucleotide polymorphism. In central Germany, singly infected populations were surrounded by transitional populations, consisting of both singly and doubly infected individuals, sandwiched between populations fixed for wCer1&2. Populations with fixed infection status showed perfect association of infection and mitochondria, suggesting a recent CI-driven selective sweep of wCer2 linked with HT2. Spatial analysis revealed a range expansion for wCer2 and a large transition zone in which wCer2 splashes appeared to coalesce into doubly infected populations. Unexpectedly, the transition zone contained a large proportion (22%) of wCer1&2 individuals with HT1, suggesting frequent intraspecific horizontal transmission. However, this horizontal transmission did not break the strict association between infection types and haplotypes in populations outside the transition zone, suggesting that this horizontally acquired Wolbachia infection may be transient. Our study provides new insights into the rarely studied Wolbachia invasion dynamics in field populations. PMID:26846713

  19. 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. PMID

  20. Widespread and invasive Trichophyton rubrum infection mimicking Kaposi's sarcoma in a patient with AIDS.

    PubMed

    Kwon, Kyung-Sool; Jang, Ho-Sun; Son, Hyo-Sung; Oh, Chang-Keun; Kwon, Yoo-Wook; Kim, Ki-Hong; Suh, Soon-Bong

    2004-10-01

    Opportunistic fungal infections are commonly encountered in AIDS patients. Candidiasis, tinea pedis, onychomycosis, and deep mycotic infections have been the fungal infections most frequently reported in these patients. Dermatophyte infections can appear to be atypical and aggressive in these patients and may lead to a misdiagnosis. We report a Trichophyton rubrum infection in a 44-year-old man with AIDS that presented as a widespread and multiple tumor-like appearance. After the patient was treated with terbinafine for 21 weeks, the lesions cleared completely. We think that this type of dermatophyte infection is very unusual in patients with AIDS and could lead to inappropriate diagnostic processes and treatments. PMID:15672716

  1. Invasive Bacillus cereus infection in a renal transplant patient: A case report and review.

    PubMed

    John, Susan; Neary, John; Lee, Christine H

    2012-01-01

    Bacillus cereus is a common cause of gastrointestinal diseases. The majority of individuals with B cereus-related food poisoning recover without any specific treatment. It can, however, rarely cause invasive disease in immunocompromised patients. PMID:24294281

  2. Three cases of severe invasive infections caused by Campylobacter rectus and first report of fatal C. rectus infection.

    PubMed

    Lam, Jimmy Y W; Wu, Alan K L; Ngai, Dickson C; Teng, Jade L L; Wong, Elsa S Y; Lau, Susanna K P; Lee, Rodney A; Woo, Patrick C Y

    2011-04-01

    We report the first fatal case of Campylobacter rectus infection due to a subdural empyema and ruptured mycotic intracranial aneurysm and two cases of limb-threatening C. rectus necrotizing soft tissue and bone infection and empyema thoracis that responded to amoxicillin-clavulanate and surgical debridement and drainage. All three strains were identified by 16S rRNA sequencing. PMID:21270212

  3. Epidemiology of invasive Haemophilus influenzae infections in England and Wales in the pre-vaccination era (1990-2).

    PubMed Central

    Anderson, E. C.; Begg, N. T.; Crawshaw, S. C.; Hargreaves, R. M.; Howard, A. J.; Slack, M. P.

    1995-01-01

    This survey defined the pattern of invasive Haemophilus influenzae infections during 1990-2 in six regions in England and Wales during the pre-vaccination era providing a baseline against which any changes in patterns of disease due to the introduction of the Haemophilus influenzae type b vaccination programme can be monitored. A total of 946 cases of invasive Haemophilus influenzae were recorded during the survey period of which almost 90% were due to type b and most of the remainder were non-typeable. Type b infections occurred predominantly in children less than 5 years of age (88%) with the highest attack rate in male infants in the 6-11 month age group. Diagnostic category varied with both age and serotype; meningitis was the commonest presentation overall but pneumonia and bacteraemia were more common in adults and non-typeable isolates. Mortality was highest in neonates and the elderly (over 65 years of age) who were more likely to have an underlying predisposing condition than older children and adults. Children under 5 years of age had a higher case fatality rate for non-typeable than for type b infections. Ampicillin resistance was 15% and there were no cefotaxime resistant type b isolates. PMID:7641841

  4. Application of the 1,3-β-D-Glucan (Fungitell) Assay in the Diagnosis of Invasive Fungal Infections.

    PubMed

    Tran, Tuan; Beal, Stacy G

    2016-02-01

    With the high mortality rate associated with invasive fungal infections, methods for timely detection and diagnosis are necessary for appropriate and effective treatment. Testing for 1,3-β-D-glucan, a cell wall component of many medically important fungi, can be a useful adjunct in diagnosing such infections. The Fungitell assay (Associates of Cape Cod, East Falmouth, Massachusetts) is a US Food and Drug Administration-approved laboratory test that quantitatively measures 1,3-β-D-glucan levels and is widely available for clinical use as a relatively noninvasive method to aid in detecting the presence of invasive fungal infections. Numerous studies have evaluated its performance in clinical settings, and results have, overall, been favorable. It is not without its drawbacks, however, and the test must be interpreted and applied with care. Ordering practices are also widely variable among clinicians, and official guidelines have not been readily available. We present the details of this test and aim to propose evidence-based guidance for its use. PMID:26910223

  5. Candida speciation, antifungal treatment and adverse events in pediatric invasive candidiasis: results from 441 infections in a prospective, multi-national study.

    PubMed

    Palazzi, Debra L; Arrieta, Antonio; Castagnola, Elio; Halasa, Natasha; Hubbard, Sydney; Brozovich, Ava A; Fisher, Brian T; Steinbach, William J

    2014-12-01

    A multi-national prospective study of pediatric patients with invasive candidiasis between August 2007 and September 2012 was performed and included 441 infections. Variation in infecting Candida species and antifungals used was noted between US and non-US sites. Antifungal-associated adverse events were most common with polyene use. PMID:24892850

  6. 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

  7. 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. PMID:25965545

  8. 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

  9. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections.

    PubMed

    Pickering, Jerry W; Sant, Howard W; Bowles, Catherine A P; Roberts, William L; Woods, Gail L

    2005-12-01

    The Fungitell assay (Associates of Cape Cod, Inc.) is a commercial test that detects (1-3)-beta-D-glucan (BG) and is intended for diagnosis of invasive fungal infections. To evaluate the Fungitell assay, we tested serum and plasma samples from healthy blood donors and from patients with blood cultures positive for yeast or bacteria. All 36 blood donors were BG negative, and 13 of 15 candidemic patients were BG positive. Of 25 bacteremic patients, 14 (10 with gram-positive bacteremia) were BG positive. One of the latter patients with Staphylococcus aureus bacteremia also had invasive candidiasis, based on histological findings in a tissue biopsy; therefore, the BG result was a true positive. The sensitivity, specificity, and positive and negative predictive values of the Fungitell assay, by patient, for these three groups were 93.3%, 77.2%, 51.9%, and 97.8%, respectively. We also performed the Fungitell assay on sera that had been tested for Aspergillus galactomannan or Histoplasma antigen. All six Histoplasma antigen-positive patients and 31 of 32 Aspergillus galactomannan-positive patients were also BG positive. BG results for the 10 Histoplasma antigen-negative and the 32 Aspergillus galactomannan-negative patients varied, but we were unable to confirm many of the results. Between-run coefficients of variance (CVs) for the assay ranged from 3.2% to 16.8%; within-run CVs were < or =4.8%. The correlation coefficient for an interlaboratory reproducibility study was 0.9892. Concentrations of hemoglobulin, bilirubin, and triglycerides that caused 20% interference were 588, 72, and 466 mg/dl, respectively. Our results suggest that the Fungitel assay may be most useful for excluding invasive fungal infection. PMID:16333082

  10. Changes in Streptococcus pneumoniae Serotype 19A Invasive Infections in Children from 1993 to 2011

    PubMed Central

    Kaplan, Sheldon L.; Lamberth, Linda B.; Barson, William J.; Romero, José R.; Lin, Philana Ling; Bradley, John S.; Givner, Laurence B.; Tan, Tina Q.; Hoffman, Jill A.; Mason, Edward O.

    2013-01-01

    Among 594 Streptococcus pneumoniae serotype 19A invasive pneumococcal disease (IPD) isolates collected from 1993 to 2011, we identified 85 sequence types by multilocus sequence typing. CC320 was associated with multidrug resistance and reduced susceptibility to penicillin and ceftriaxone and still predominated among declining serotype 19A IPD isolates following PCV13 introduction. PMID:23390277

  11. Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

    PubMed Central

    Mutschlechner, Wolfgang; Aigner, Maria; Grif, Katharina; Marth, Claudia; Girschikofsky, Michael; Grander, Wilhelm; Greil, Richard; Russ, Gudrun; Cerkl, Peter; Eller, Mirjam; Kropshofer, Gabriele; Eschertzhuber, Stephan; Kathrein, Hermann; Schmid, Stefan; Beer, Ronny; Lorenz, Ingo; Theurl, Igor; Nachbaur, David

    2013-01-01

    Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the “gold standard.” In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of 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. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests. PMID:23269732

  12. Absence of a cysteine protease effect on bacterial virulence in two murine models of human invasive group A streptococcal infection.

    PubMed

    Ashbaugh, C D; Wessels, M R

    2001-11-01

    The cysteine protease of group A streptococci has been suggested to contribute to the pathogenesis of invasive infection through degradation of host tissue, activation of the host inflammatory response, release of protective molecules from the bacterial cell surface, or other mechanisms. However, studies of the effects on virulence of inactivating the cysteine protease gene speB have yielded conflicting results. In some reports, a speB mutant was relatively avirulent in mouse models of invasive infection whereas little or no attenuation of virulence was observed in other studies of similar mutant strains. Possible reasons for these discordant results include differences in the streptococcal strains from which the speB mutants were derived, differences in the infection models employed, or unintended effects on another virulence determinant(s) that arose during the derivation of a speB mutant. We attempted to clarify these issues by characterizing the phenotypic properties and relative virulence in mice of two speB mutant strains, both derived from wild-type strain AM3: speB mutant AM3speB, which has been shown to be markedly attenuated in virulence in mice after intraperitoneal or subcutaneous challenge, and AM3speBOmega, a new mutant strain derived for this investigation. Both mutant strains were negative for protease activity, as expected, and both produced wild-type amounts of type 3 M protein and streptolysin O. However, AM3speB produced significantly less cell-associated hyaluronic acid capsule than did parent strain AM3 or strain AM3speBOmega. Compared to wild-type strain AM3, AM3speB was more sensitive to opsonophagocytic killing in vitro and was significantly less virulent in mice after intraperitoneal challenge. By contrast, AM3speBOmega was fully resistant to phagocytosis and did not differ significantly from the wild-type strain in mouse virulence after an intraperitoneal or subcutaneous challenge. We concluded that previous reports attributing loss of

  13. Absence of a Cysteine Protease Effect on Bacterial Virulence in Two Murine Models of Human Invasive Group A Streptococcal Infection

    PubMed Central

    Ashbaugh, Cameron D.; Wessels, Michael R.

    2001-01-01

    The cysteine protease of group A streptococci has been suggested to contribute to the pathogenesis of invasive infection through degradation of host tissue, activation of the host inflammatory response, release of protective molecules from the bacterial cell surface, or other mechanisms. However, studies of the effects on virulence of inactivating the cysteine protease gene speB have yielded conflicting results. In some reports, a speB mutant was relatively avirulent in mouse models of invasive infection whereas little or no attenuation of virulence was observed in other studies of similar mutant strains. Possible reasons for these discordant results include differences in the streptococcal strains from which the speB mutants were derived, differences in the infection models employed, or unintended effects on another virulence determinant(s) that arose during the derivation of a speB mutant. We attempted to clarify these issues by characterizing the phenotypic properties and relative virulence in mice of two speB mutant strains, both derived from wild-type strain AM3: speB mutant AM3speB, which has been shown to be markedly attenuated in virulence in mice after intraperitoneal or subcutaneous challenge, and AM3speBΩ, a new mutant strain derived for this investigation. Both mutant strains were negative for protease activity, as expected, and both produced wild-type amounts of type 3 M protein and streptolysin O. However, AM3speB produced significantly less cell-associated hyaluronic acid capsule than did parent strain AM3 or strain AM3speBΩ. Compared to wild-type strain AM3, AM3speB was more sensitive to opsonophagocytic killing in vitro and was significantly less virulent in mice after intraperitoneal challenge. By contrast, AM3speBΩ was fully resistant to phagocytosis and did not differ significantly from the wild-type strain in mouse virulence after an intraperitoneal or subcutaneous challenge. We concluded that previous reports attributing loss of virulence

  14. Invasive Salmonella enterica serotype typhimurium infections, Democratic Republic of the Congo, 2007-2011.

    PubMed

    Ley, Benedikt; Le Hello, Simon; Lunguya, Octavie; Lejon, Veerle; Muyembe, Jean-Jacques; Weill, François-Xavier; Jacobs, Jan

    2014-04-01

    Infection with Salmonella enterica serotype Typhimurium sequence type (ST) 313 is associated with high rates of drug resistance, bloodstream infections, and death. To determine whether ST313 is dominant in the Democratic Republic of the Congo, we studied 180 isolates collected during 2007-2011; 96% belonged to CRISPOL type CT28, which is associated with ST313. PMID:24655438

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

    PubMed

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

    2016-04-01

    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 ImmunoCardSTAT! 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 distinctemmtypes, including a predominance ofemm1 (33.3%),emm89 (10.6%), andemm12 (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

  16. Contribution of the (1-->3)-beta-D-glucan assay for diagnosis of invasive fungal infections.

    PubMed

    Persat, Florence; Ranque, Stéphane; Derouin, Francis; Michel-Nguyen, Annie; Picot, Stéphane; Sulahian, Annie

    2008-03-01

    Diagnosis of invasive fungal infection (IFI) remains a challenge. A retrospective study was performed on 279 patients at three French university hospitals to evaluate the performance of the (1-->3)-beta-D-glucan assay (BG assay; Fungitell; Associates of Cape Cod, Inc.) for the diagnosis of IFI. The results of one serum per subject were analyzed for 117 patients who had probable or proven IFI according to the European Organization for Research and Treatment of Cancer criteria (70 invasive pulmonary aspergilloses [IPA], 27 fungal bloodstream infections, and 20 Pneumocystis jiroveci pneumonias), 40 blood donors, and 122 patients who were hospitalized in hematology wards or intensive care units and were at risk for IFI but in whom IFI had not been diagnosed. For the overall IFI diagnosis, the BG assay had 77.8% sensitivity and specificities of 92.5 and 70.5% for blood donors and patients at risk, respectively. The assay was positive in 48 patients with IPA (68%), in 23 with bloodstream infections (85.2%), and in all who had P. jiroveci pneumonias (100%), and the false-positive rate varied depending on the controls used. It allowed a higher rate of detection among IPA patients compared to the galactomannan enzyme-linked immunosorbent assay (ELISA) (48 versus 39 patients, respectively) and among candidemia patients compared to the mannan ELISA (20 versus 11 patients, respectively). This assay therefore appears to be useful in the diagnosis of IFI, particularly for serum analysis of pneumocystosis pneumonia patients, but further studies are needed to evaluate false-positive rates and its future role in IFI diagnosis. PMID:18160456

  17. (1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies

    PubMed Central

    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

    2016-01-01

    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. PMID:26910891

  18. [THE CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS OF MALARIA CONCURRENT WITH OTHER INFECTIONS AND INVASIONS].

    PubMed

    Kondrashin, A V; Tokmalaev, A K; Morozov, E N; Morozova, L F

    2016-01-01

    The present review considers malaria infection concurrent with different species of helminths, bacterial and viral infections, as well as mixed malaria pathogens in the subtropical and tropical countries of the world, causing the clinical picture and epidemiological situation to be different. Malaria co-infections with different pathogenic micro-organisms, such as HIV, tuberculosis, viral hepatitides, and others, affect almost one third of the planet's population. It is known that people who are at risk for malaria may be also at risk for other parasitic and infectious diseases, most commonly helminthisms. PMID:27405219

  19. Managing invasive fungal infections: relying on clinical instincts or on a rational navigation system?

    PubMed

    de Pauw, Ben E; Viscoli, Claudio

    2011-01-01

    The management of invasive fungal disease in the immunocompromised host is complex and requires the specialized knowledge of physicians whose primary interest is actually the underlying disease rather than infectious complications. This Supplement aims to provide these physicians with some tools that may help to guide them through the maze of suspicion that an invasive fungal disease is present by offering an integrated care pathway of rational patient management. Such pathways will inevitably vary in detail in different centres and depend for their success on the presence of multidisciplinary teams and an explicit agreement on at least the minimum requirements for effective management. The integrated care pathways presented constitute an objective instrument to allow regular audits for recognizing opportunities to change practice if and when weaknesses are identified. PMID:21177405

  20. 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.

  1. Comparison of bacteroides-prevotella 16S rRNA genetic markers for fecal samples from different animal species.

    PubMed

    Fogarty, Lisa R; Voytek, Mary A

    2005-10-01

    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. PMID:16204514

  2. Vitamin B12-dependent propionate production by the ruminal bacterium Prevotella ruminicola 23.

    PubMed

    Strobel, H J

    1992-07-01

    When Prevotella ruminicola 23 was grown in a defined medium containing a vitamin mixture, significant amounts of propionate were formed. Succinate and acetate were the major fermentation acids produced when vitamins were omitted, and further experiments demonstrated that propionate formation was dependent on vitamin B12. When the organism was grown in continuous culture at dilution rates of less than 0.20 h-1, propionate and acetate were the predominant fermentation products and little succinate was formed when vitamin B12 was present. However, at higher dilution rates, propionate formation declined and succinate accumulated. Since cell protein yields were reduced 15 to 25% in the absence of vitamin B12, the pathway for propionate formation may contain an energy-conserving step. PMID:1637169

  3. Purification and partial characterization of an elastolytic serine protease of Prevotella intermedia.

    PubMed Central

    Shibata, Y; Fujimura, S; Nakamura, T

    1993-01-01

    Elastolytic strains of Prevotella intermedia were isolated from pus samples of adult periodontal lesions. Elastase was found to associate with envelope, and it could be solubilized with guanidine-HCl. The enzyme was purified to homogeneity by sequential procedures including ion-exchange chromatography, gel filtration, and hydrophobic interaction chromatography. This elastase was a serine protease, and its mass was 31 kDa. It hydrolyzed elastin powder, but collagen and azodye-conjugated proteins were not degraded by this enzyme. Both synthetic substrates for human pancreatic (glutaryl-L-alanyl-L-alanyl-L-prolyl-L-leucine p-nitroanilide) and leukocyte elastase (methoxy succinyl-L-alanyl-alanyl-L-prolyl-L-valine p-nitroanilide) were hydrolyzed. Images PMID:8357246

  4. Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children

    PubMed Central

    Ilhan, Zehra Esra; Wallstrom, Garrick; LaBaer, Joshua; Adams, James B.; Krajmalnik-Brown, Rosa

    2013-01-01

    High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae. PMID:23844187

  5. 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

  6. 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

  7. Invasive fungal infections in patients with hematologic malignancies (aurora project): lights and shadows during 18-months surveillance.

    PubMed

    Montagna, Maria Teresa; De Giglio, Osvalda; Napoli, Christian; Lovero, Grazia; Caggiano, Giuseppina; Delia, Mario; Pastore, Domenico; Santoro, Nicola; Specchia, Giorgina

    2012-01-01

    The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-β-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients. PMID:22312285

  8. A Case of Waterhouse-Friderichsen Syndrome Resulting from an Invasive Pneumococcal Infection in a Patient with a Hypoplastic Spleen

    PubMed Central

    Emori, Kazumasa; Takeuchi, Nobuhiro; Soneda, Junichi

    2016-01-01

    A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen. PMID:26942021

  9. A Case of Waterhouse-Friderichsen Syndrome Resulting from an Invasive Pneumococcal Infection in a Patient with a Hypoplastic Spleen.

    PubMed

    Emori, Kazumasa; Takeuchi, Nobuhiro; Soneda, Junichi

    2016-01-01

    A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen. PMID:26942021

  10. Invasive Fungal Infections in Patients with Hematologic Malignancies (Aurora Project): Lights and Shadows During 18-Months Surveillance

    PubMed Central

    Montagna, Maria Teresa; De Giglio, Osvalda; Napoli, Christian; Lovero, Grazia; Caggiano, Giuseppina; Delia, Mario; Pastore, Domenico; Santoro, Nicola; Specchia, Giorgina

    2012-01-01

    The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-β-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients. PMID:22312285

  11. Methicillin-resistant Staphylococcus aureus ST30-SCCmec IVc clone as the major cause of community-acquired invasive infections in Argentina.

    PubMed

    Fernandez, S; de Vedia, L; Lopez Furst, M J; Gardella, N; Di Gregorio, S; Ganaha, M C; Prieto, S; Carbone, E; Lista, N; Rotrying, F; Stryjewski, M E; Mollerach, M

    2013-03-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have become a major concern worldwide. We conducted a prospective multicenter study of invasive CA-MRSA to evaluate clinical features and genotype of strains causing invasive infections in Argentina. A total of 55 patients with invasive CA-MRSA infections were included. Most patients (60%) had bloodstream infections, 42% required admission to intensive care unit and 16% died. No CA-MRSA isolates were multiresistant (resistant ⩾3 classes of antibiotics). All isolates carried Panton-Valentine leukocidin (PVL) genes and staphylococcal cassette chromosome (SCCmec) type IV. The majority CA-MRSA strains belonged to ST30 and had identical pulsed-field gel electrophoresis (PFGE) patterns, qualifying as a clonal dissemination of a highly transmissible strain. The main clone recovered from patients with CA-MRSA invasive infections was genotyped as pulsed-field gel electrophoresis type C-ST30, SCCmec type IVc-spa type 019, PVL positive. It has become predominant and replaced the previously described CA-MRSA clone (PFGE type A, ST5, SCCmec type IV, spa type 311). PMID:23340226

  12. Invasive non-typhoidal salmonella infection with multifocal seeding in an immunocompetent host: an emerging disease in the developed world

    PubMed Central

    Hall, Rebecca Louise; Partridge, Rebecca; Venkatraman, Navin; Wiselka, Martin

    2013-01-01

    We report an immunocompetent 24-year-old man who presented with a severe, invasive non-typhoidal salmonella (iNTS) infection. He presented with lumbar back pain associated with fever and rigours, which had been preceded by diarrhoea. Blood cultures grew Salmonella enteritidis. An MRI scan of his pelvis and spine showed that he had a small gluteal abscess and sacroiliitis. His condition subsequently deteriorated due to the development of a secondary pneumonia and respiratory failure. He was managed conservatively with 2 weeks of intravenous ceftriaxone, followed by 6 weeks of oral ciprofloxacin. Detailed investigations did not reveal any predisposing factors or evidence of an underlying immunodeficiency. Follow-up showed complete resolution of symptoms with no long-term sequelae. PMID:23370956

  13. Mechanism of Trypanosoma cruzi Placenta Invasion and Infection: The Use of Human Chorionic Villi Explants

    PubMed Central

    Fretes, Ricardo E.; Kemmerling, Ulrike

    2012-01-01

    Congenital Chagas disease, a neglected tropical disease, endemic in Latin America, is associated with premature labor and miscarriage. During vertical transmission the parasite Trypanosoma cruzi (T. cruzi) crosses the placental barrier. However, the exact mechanism of the placental infection remains unclear. We review the congenital transmission of T. cruzi, particularly the role of possible local placental factors that contribute to the vertical transmission of the parasite. Additionally, we analyze the different methods available for studying the congenital transmission of the parasite. In that context, the ex vivo infection with T. cruzi trypomastigotes of human placental chorionic villi constitutes an excellent tool for studying parasite infection strategies as well as possible local antiparasitic mechanisms. PMID:22701129

  14. 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

  15. Current strategies against invasive fungal infections in patients with aplastic anemia, strong power and weak weapon, a case report and review of literature.

    PubMed

    Zekavat, Omid Reza; Amanati, Ali; Saleh, Fazl; Abdolkarimi, Babak; Fathpour, Gholamreza; Badiee, Parisa; Geramizadeh, Bita

    2016-03-01

    We report an 18 year old boy with Aplastic anemia complicated by serious fungal rhinosinusitis. Despite prompt treatment and early repeated surgical debridements, he died after about more than 6 weeks of hard challenges with fungal infections. Current strategies against invasive fungal infections (IFIs) in patients with Aplastic anemia may be inadequate for the management of serious complications. Antifungal prophylaxis is highly recommended in pre-transplant period for severe form of Aplastic anemia. PMID:27047751

  16. The urea breath test: a non-invasive clinical tool for detecting Helicobacter pylori infection.

    PubMed

    Perri, F; Ghoos, Y; Hiele, M; Andriulli, A; Rutgeerts, P

    1995-03-01

    The urea breath test exploits the urease enzyme of Helicobacter pylori. The hydrolysis of labelled urea releases labelled carbon dioxide that is excreted in the breath. Distribution of urea throughout the stomach prevents sampling errors and allows for semiquantitative assessment of the extent of Helicobacter pylori infection. The urea breath test is very specific and sensitive and can be proposed as the method of choice for detecting Helicobacter pylori infection in ulcer patients before and after eradicating treatment as well as in epidemiological studies. PMID:7579592

  17. Microbiology and management of endodontic infections in children.

    PubMed

    Brook, Itzhak

    2003-01-01

    The first step in the origination of caries is the formation of a dental plaque. Dental caries can lead to destruction of enamel and dentin resulting in bacterial invasion of the pulp. Invasion of the pulp and the periapical areas can promote the development of dento-alveolar abscess and spread of the infection to other anatomical areas. Several oral acid producing aerobic and anaerobic bacteria, including Streptococcus mutans, Lactobacillus acidophilus, and Actinomyces viscosus, are capable of initiating the carious lesion. The organisms that predominate in pulpitis and dento-alveolar abscess are Prevotella, Porphyromonas, Fusobacterium, and Peptostreptococcus spp. Treatment of caries involves removal of all affected tooth structure and proper replacement with a restorative material. Once pulpitis has developed the infected tissue should be removed and root canal therapy instituted, or the tooth should be extracted. Extraction, root canal therapy and/or drainage of pus usually are indicated for an abscess. Antimicrobial therapy supplementing the dental care should be considered, especially when local or systemic spread of the infection is suspected. Penicillin or amoxicillin are generally effective against most of the aerobic and anaerobic bacteria recovered. The patient whose oral cavity may harbor penicillin-resistant organisms should be considered for treatment with drugs effective against these organisms. These agents include amoxicillin-clavulanate, clindamycin or the combination of metronidazole plus amoxicillin or a macrolide. PMID:14604136

  18. Systems Biology Analysis of Brucella Infected Peyer's Patch Reveals Rapid Invasion with Modest Transient Perturbations of the Host Transcriptome

    PubMed Central

    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

  19. 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

  20. Invasive Nattrassia mangiferae infections: case report, literature review, and therapeutic and taxonomic appraisal.

    PubMed Central

    Sigler, L; Summerbell, R C; Poole, L; Wieden, M; Sutton, D A; Rinaldi, M G; Aguirre, M; Estes, G W; Galgiani, J N

    1997-01-01

    We report on a case of subcutaneous infection of the arm caused by the coelomycetous fungus Nattrassia mangiferae (formerly Hendersonula toruloidea) in a steroid-dependent diabetic man with chronic obstructive lung disease. The man was a resident of Arizona, where the fungus is known to be endemic on Eucalyptus camaldulensis and on citrus trees. Diagnosis of fungal infection was made by observation of narrow hyphal filaments by histopathology of biopsy specimens and isolation of a fast-growing black mold which demonstrated hyphae and arthroconidia of varying widths typical of the Scytalidium synanamorph (S. dimidiatum). The formation of pycnidia, which at maturity expressed conidia with a central median dark band, allowed for the confirmation of the isolate as N. mangiferae. Remission of the lesions occurred following intravenous therapy with amphotericin B, followed by topical clotrimazole treatment. We use this patient's case report as an opportunity to review the literature on cases of deep infection caused by Scytalidium species, to evaluate the antifungal susceptibilities of a spectrum of Scytalidium isolates, and to review the taxonomy of Scytalidium species isolated from human infections. PMID:9003611

  1. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

    PubMed

    Brown, Aisling F; Murphy, Alison G; Lalor, Stephen J; Leech, John M; O'Keeffe, Kate M; Mac Aogáin, Micheál; O'Halloran, Dara P; Lacey, Keenan A; Tavakol, Mehri; Hearnden, Claire H; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P; van Wamel, Willem J; Foster, Timothy J; Geoghegan, Joan A; Lavelle, Ed C; Rogers, Thomas R; McLoughlin, Rachel M

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  2. Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

    PubMed Central

    Lalor, Stephen J.; Leech, John M.; O’Keeffe, Kate M.; Mac Aogáin, Micheál; O’Halloran, Dara P.; Lacey, Keenan A.; Tavakol, Mehri; Hearnden, Claire H.; Fitzgerald-Hughes, Deirdre; Humphreys, Hilary; Fennell, Jérôme P.; van Wamel, Willem J.; Foster, Timothy J.; Geoghegan, Joan A.; Lavelle, Ed C.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2015-01-01

    Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans. PMID:26539822

  3. [Non-invasive diagnostic methods of fibrosis in chronic hepatitis C virus infection: their role in treatment indication, follow-up and assessment of prognosis].

    PubMed

    Pár, Alajos; Vincze, Áron; Pár, Gabriella

    2015-05-24

    Chronic hepatitis C virus infection associated with necroinflammation predisposes to liver fibrosis and cirrhosis, which lead to severe end-stage complications. Staging of fibrosis is of basic importance for the indication of antiviral treatment, for monitoring the response and predicting the prognosis of patients with hepatitis C virus related liver disease. Since liver biopsy, the "gold standard" diagnosis of fibrosis is invasive and it has some other limitations, non-invasive methods have been developed and widely used in the clinical practice. Serum biomarkers and physical approaches measuring liver stiffness by elastography as well as combination algorithms have been gradually been integrated into guidelines resulting in a reduction of the need for liver biopsy. The authors review these non-invasive fibrosis markers and discuss their role in the indication of treatment, follow-up, and assessment of prognosis of patients with chronic hepatitis C virus infection. PMID:26038993

  4. Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic-driven approach and itraconazole oral solution.

    PubMed

    Tzadok, Roie; Shapira, Michael Y; Moses, Allon E; Or, Reuven; Block, Colin; Strahilevitz, Jacob

    2015-12-01

    Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic-driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non-significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic-driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non-statistically significant, number of IFI in our medical centre. PMID:26429354

  5. The Probiotic Escherichia coli Nissle 1917 Reduces Pathogen Invasion and Modulates Cytokine Expression in Caco-2 Cells Infected with Crohn's Disease-Associated E. coli LF82 ▿

    PubMed Central

    Huebner, Claudia; Ding, Yaoyao; Petermann, Ivonne; Knapp, Christoph; Ferguson, Lynnette R.

    2011-01-01

    Increased numbers of adherent invasive Escherichia coli (AIEC) have been found in Crohn's disease (CD) patients. In this report, we investigate the potential of the probiotic Escherichia coli Nissle 1917 (EcN) to reduce features associated with AIEC pathogenicity in an already established infection with AIEC reference strain LF82. PMID:21317252

  6. Application of the C3-Binding Motif of Streptococcal Pyrogenic Exotoxin B to Protect Mice from Invasive Group A Streptococcal Infection

    PubMed Central

    Kuo, Chih-Feng; Tsao, Nina; Cheng, Miao-Hui; Yang, Hsiu-Chen; Wang, Yu-Chieh; Chen, Ying-Pin; Lin, Kai-Jen

    2015-01-01

    Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345–398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection. PMID:25629609

  7. Genetic polymorphisms and the development of invasive bacterial infections in children.

    PubMed

    Esposito, Susanna; Bosis, Samantha; Orenti, Annalisa; Spena, Silvia; Montinaro, Valentina; Bianchini, Sonia; Zampiero, Alberto; Principi, Nicola

    2016-03-01

    To evaluate the associations between single nucleotide polymorphisms (SNPs) of factors involved in the development of invasive bacterial disease (IBD) in children, 47 SNPs of 18 candidate genes were analysed in 49 children with IBD and 100 controls. The G/T genotype of TLR2 rs2149356 and the C genotype of LTA rs2229094 were associated with significantly reduced risk of developing IBD (P=0.04 and P=0.05, respectively), whereas the C/T genotype of RFP175 rs1585110 was associated with a significantly higher risk of developing IBD (P=0.02). These results support the evidence that some genetic variants of factors involved in innate immunity may influence IBD risk in children. PMID:26684632

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

    PubMed

    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

  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. PMID:26787129

  11. A Critical Appraisal of the Role of the Clinical Microbiology Laboratory in Diagnosis of Invasive Fungal Infections

    PubMed Central

    Klutts, J. Stacey; Robinson-Dunn, Barbara

    2011-01-01

    The incidence of invasive fungal infections (IFIs) continues to rise in industrialized countries, primarily due to both increasingly potent iatrogenic immunosuppression and immunocompromising therapies aimed at treating hematologic malignancies. As this situation continues to evolve, the clinical microbiology laboratory has few new, innovative methodologies to diagnose these serious infections and existing methods lack sensitivity. This represents a difficult clinical situation for health care providers, as they are left to rely on clinical instincts for the management of patients with potential IFIs, as mycology test results are not consistently reliable. The goals of this session of Camp Clin Micro (CCM) were to critically assess currently available methods and practices for diagnosing IFIs, to discuss the potential of current investigational methods, to evaluate the role of antifungal susceptibility testing, and finally to identify action items that can help move the field of diagnostic mycology in a direction that will improve our ability to identify IFIs in a timely manner. This is meant to be not a comprehensive overview of the diagnosis of IFIs but rather a detailed account of the discussion at CCM among clinical microbiologists with experience in diagnostic mycology and knowledge of the literature.

  12. 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

  13. 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

  14. Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions.

    PubMed

    Meng, Fandan; Wu, Nai-Huei; Seitz, Maren; Herrler, Georg; Valentin-Weigand, Peter

    2016-01-01

    Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens. PMID:27229328

  15. Efficient suilysin-mediated invasion and apoptosis in porcine respiratory epithelial cells after streptococcal infection under air-liquid interface conditions

    PubMed Central

    Meng, Fandan; Wu, Nai-Huei; Seitz, Maren; Herrler, Georg; Valentin-Weigand, Peter

    2016-01-01

    Streptococci may colonize the epithelium in the airways and other entry sites. While local infection often remains asymptomatic, severe or even fatal diseases occur when streptococci become invasive and spread to different sites in the infected host. We have established porcine respiratory air-liquid interface cultures (ALI) from the porcine lung to analyze the interaction of streptococci with their primary target cells. As representative of the streptococcal family we chose Streptococcus suis (S. suis) that is not only a major swine respiratory pathogen but can also infect humans. Suilysin, a cholesterol-dependent cytolysin (CDC), is an important virulence factor. By comparing a S. suis wt strain with a suilysin-deficient mutant, we demonstrate that suilysin contributes to (i) adherence to airway cells (ii) loss of ciliated cells (iii) apoptosis, and (iv) invasion. Furthermore, we show that cytolytic activity of suilysin is crucial for these effects. A striking result of our analysis was the high efficiency of S. suis-induced apoptosis and invasion upon infection under ALI conditions. These properties have been reported to be less efficient when analyzed with immortalized cells. We hypothesize that soluble effectors such as suilysin are present at higher concentrations in cells kept at ALI conditions and thus more effective. These results should be relevant also for infection of the respiratory tract by other respiratory pathogens. PMID:27229328

  16. Viral infection of tobacco plants improves performance of Bemisia tabaci but more so for an invasive than for an indigenous biotype of the whitefly.

    PubMed

    Liu, Jian; Li, Meng; Li, Jun-min; Huang, Chang-jun; Zhou, Xue-ping; Xu, Fang-cheng; Liu, Shu-sheng

    2010-01-01

    The ecological effects of plant-virus-vector interactions on invasion of alien plant viral vectors have been rarely investigated. We examined the transmission of Tomato yellow leaf curl China virus (TYLCCNV) by the invasive Q biotype and the indigenous ZHJ2 biotype of the whitefly Bemisia tabaci, a plant viral vector, as well as the influence of TYLCCNV-infection of plants on the performance of the two whitefly biotypes. Both whitefly biotypes were able to acquire viruses from infected plants and retained them in their bodies, but were unable to transmit them to either tobacco or tomato plants. However, when the Q biotype fed on tobacco plants infected with TYLCCNV, its fecundity and longevity were increased by 7- and 1-fold, respectively, compared to those of the Q biotype fed on uninfected tobacco plants. When the ZHJ2 biotype fed on virus-infected plants, its fecundity and longevity were increased by only 2- and 0.5-fold, respectively. These data show that the Q biotype acquired higher beneficial effects from TYLCCNV-infection of tobacco plants than the ZHJ2 biotype. Thus, the Q biotype whitefly may have advantages in its invasion and displacement of the indigenous ZHJ2 biotype. PMID:20043350

  17. 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

  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. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

    PubMed Central

    Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon; Marovich, Mary; Lerdlum, Sukalaya; Suttichom, Duanghathai; Suwanwela, Nijasri C.; Jagodzinski, Linda; Michael, Nelson; Spudich, Serena; van Griensven, Frits; de Souza, Mark; Kim, Jerome; Ananworanich, Jintanat

    2012-01-01

    Background. Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. Methods. Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. Results. HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ–induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. Conclusions. CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection. PMID:22551810

  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. PMID:25352630

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

    PubMed

    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. [Refractory acute myeloid leukemia developed malignancy-associated hemophagocytic lymphohistiocytosis during treatment of invasive fungal infection].

    PubMed

    Yamada, Ai; Moritake, Hiroshi; Sawa, Daisuke; Shimonodan, Hidemi; Kojima, Hitomi; Kamimura, Sachiyo; Nunoi, Hiroyuki

    2013-04-01

    We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients. PMID:23666221

  3. 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. PMID:26709146

  4. Isolation and characterisation of dipeptidyl peptidase IV from Prevotella loescheii ATCC 15930.

    PubMed

    Koreeda, Y; Hayakawa, M; Ikemi, T; Abiko, Y

    2001-08-01

    A proline-specific dipeptidyl aminopeptidase, dipeptidyl peptidase IV (EC 3.4.14.5), was purified from a cell sonicate soluble fraction of Prevotella loescheii ATCC 15930 by sequential column chromatography. The molecular mass of the native enzyme was estimated as 160 kDa by high-pressure liquid gel filtration column chromatography and unheated sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The subunit molecular mass was 80 kDa when the enzyme was heated to 100 degrees C in the presence of 2-mercaptoethanol before SDS-PAGE, suggesting that the native enzyme consists of two identical subunits and is folded in 2% SDS. The optimum pH, with glycyl-prolyl-4-methyl-coumaryl-7-amide as the substrate, was 8.0; the isoelectric point was 5.2. Purified enzyme showed a strong preference for dipeptide substrates containing proline and, less efficiently, alanine in the P1 position. The enzyme was markedly inhibited by Cd(2+), Zn(2+), Hg(2+), Co(2+), and serine proteinase inhibitor di-isopropylfluorophosphate. PMID:11389867

  5. 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

  6. Rapid detection of Actinobacillus actinomycetemcomitans, Prevotella intermedia and Porphyromona gingivalis by multiplex PCR.

    PubMed

    García, L; Tercero, J C; Legido, B; Ramos, J A; Alemany, J; Sanz, M

    1998-01-01

    The identification of specific periodontal pathogens by conventional methods, mainly anaerobic cultivation, is difficult, time consuming and even sometimes unreliable. Therefore, a multiplex PCR method for simultaneous detection of Actinobacillus actinomycetemcomitans (A.a.), Porphyromona gingivalis (P.g.) and Prevotella intermedia (P.i.) was developed for rapid and easy identification of these specific bacterial pathogens in subgingival plaque samples. In this paper, there is a detailed description of the oligonucleotide primer selection, DNA extraction and PCR conditions and the sequencing of the amplified products. The locus chosen to be amplified is a highly variable region in the 16S ribosomal DNA. For the development of this technique ATCC cultures and pure cultures from subgingival plaque samples taken from periodontitis patients were used. As an internal positive control a recombinant plasmid was developed. This simple DNA extraction procedure and the DNA amplification and visualization of the amplified product permits the detection of the bacteria in a working day. Thus, this multiplex PCR method is a rapid and effective detection method for specific periodontal pathogens. PMID:9524322

  7. 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

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

    PubMed

    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

  9. 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

  10. Fetal infection from rubeovirus or cytomegalovirus: correlation among maternal serological profiles, invasive diagnostic procedures, and long-term follow-up.

    PubMed

    Noia, G; Masini, L; De Santis, M; Scavo, M; Pomini, F; Grillo, R; Cattani, P; Ranno, O; Caruso, A; Mancuso, S

    1998-01-01

    Different variables influence the possibility that maternal viral infection may be transmitted to the fetus, although not all fetal infections result in fetal "illness" with consequent fetopathy. As concerns the fetus, prenatal diagnosis includes invasive techniques necessary for fetal tissue sampling. These techniques carry some risks. The fetal infectious risk, as determined by maternal clinico-serological profile and according to sonographic investigation, always should be weighed against the risks and benefits of invasive diagnostic procedures. The present study re-elaborates the criteria necessary for defining fetal risk as related to the maternal serological profile. In the 26 mothers with rubeola infection, the incidence of fetal mortality was 7.7%. Fetal prognosis worsens with the precocity of eruption. In these cases the esantema is the most reliable prognostic element as an indication to perform the invasive procedure. In the 15 patients with cytomegalovirus infection, no fetal or postnatal losses occurred. Morbidity occurred in 13.3% of cases, and the two ill fetuses were classified in the same risk group. In this group of patients, the maternal serological profile is a significant predictor of fetal morbidity. PMID:9502669

  11. Ribonucleotide Reductase NrdR as a Novel Regulator for Motility and Chemotaxis during Adherent-Invasive Escherichia coli Infection

    PubMed Central

    Dreux, Nicolas; Cendra, Maria del Mar; Massier, Sébastien; Darfeuille-Michaud, Arlette

    2015-01-01

    A critical step in the life cycle of all organisms is the duplication of the genetic material during cell division. Ribonucleotide reductases (RNRs) are essential enzymes for this step because they control the de novo production of the deoxyribonucleotides required for DNA synthesis and repair. Enterobacteriaceae have three functional classes of RNRs (Ia, Ib, and III), which are transcribed from separate operons and encoded by the genes nrdAB, nrdHIEF, and nrdDG, respectively. Here, we investigated the role of RNRs in the virulence of adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease (CD) patients. Interestingly, the LF82 strain of AIEC harbors four different RNRs (two class Ia, one class Ib, and one class III). Although the E. coli RNR enzymes have been extensively characterized both biochemically and enzymatically, little is known about their roles during bacterial infection. We found that RNR expression was modified in AIEC LF82 bacteria during cell infection, suggesting that RNRs play an important role in AIEC virulence. Knockout of the nrdR and nrdD genes, which encode a transcriptional regulator of RNRs and class III anaerobic RNR, respectively, decreased AIEC LF82's ability to colonize the gut mucosa of transgenic mice that express human CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6). Microarray experiments demonstrated that NrdR plays an indirect role in AIEC virulence by interfering with bacterial motility and chemotaxis. Thus, the development of drugs targeting RNR classes, in particular NrdR and NrdD, could be a promising new strategy to control gut colonization by AIEC bacteria in CD patients. PMID:25605769

  12. Economic evaluation of a preemptive treatment strategy for invasive fungal infection in neutropenic patients with hematological diseases.

    PubMed

    Kimura, S-I; Murata, T; Akahoshi, Y; Nakano, H; Ugai, T; Wada, H; Yamasaki, R; Ishihara, Y; Kawamura, K; Sakamoto, K; Ashizawa, M; Sato, M; Terasako-Saito, K; Nakasone, H; Kikuchi, M; Yamazaki, R; Kako, S; Kanda, J; Tanihara, A; Nishida, J; Kanda, Y

    2015-05-01

    We compared the expected medical costs of empirical and preemptive treatment strategies for invasive fungal infection in neutropenic patients with hematological diseases. Based on the results of two clinical trials with different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350-355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051; PREVERT study], we developed a decision tree model that represented the outcomes of empirical and preemptive treatment strategies, and estimated the expected medical costs of medications and examinations in the two strategies. We assumed that micafungin was started in the empirical group at 5 days after fever had developed, while voriconazole was started in the preemptive group only when certain criteria, such as positive test results of imaging studies and/or serum markers, were fulfilled. When we used an incidence of positive test results of 6.7 % based on the Oshima study, the expected medical costs of the empirical and preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of the PREVERT study, in which the incidence of positive test results was 32.9 %, the expected medical costs in the empirical and preemptive groups were 291,871 and 284,944 yen, respectively. A sensitivity analysis indicated that the expected medical costs in the preemptive group would exceed those in the empirical group when the incidence of positive test results in the former was over 34.4 %. These results suggest that a preemptive treatment strategy can be expected to reduce medical costs compared with empirical therapy in most clinical settings. PMID:25577175

  13. Lactobacillus strains isolated from the vaginal microbiota of healthy women inhibit Prevotella bivia and Gardnerella vaginalis in coculture and cell culture.

    PubMed

    Atassi, Fabrice; Brassart, Dominique; Grob, Philipp; Graf, Federico; Servin, Alain L

    2006-12-01

    The purpose of this study was to investigate how human vaginal isolates of Lactobacillus acidophilus, Lactobacillus jensenii, Lactobacillus gasseri and Lactobacillus crispatus inhibit the vaginosis-associated pathogens Gardnerella vaginalis and Prevotella bivia. Results show that all the strains in coculture condition reduced the viability of G. vaginalis and P. bivia, but with differing degrees of efficacy. The treatment of G. vaginalis- and P. bivia-infected cultured human cervix epithelial HeLa cells with L. gasseri strain KS120.1 culture or cell-free culture supernatant (CFCS) results in the killing of the pathogens that are adhering to the cells. The mechanism of the killing activity is not attributable to low pH and the presence of lactic acid alone, but rather to the presence of hydrogen peroxide and proteolytic enzyme-resistant compound(s) present in the CFCSs. In addition, coculture of G. vaginalis or P. bivia with L. gasseri KS120.1 culture or KS120.1 bacteria results in inhibition of the adhesion of the pathogens onto HeLa cells. PMID:17059467

  14. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis?

    PubMed

    Pomares, Helena; Arnan, Montserrat; Sánchez-Ortega, Isabel; Sureda, Anna; Duarte, Rafael F

    2016-08-01

    The aim of this study is to analyse the risk of invasive fungal infection (IFI) and the need for antifungal prophylaxis in patients with acute myeloid leukaemia and myelodysplastic syndromes (AML/MDS) treated with azacitidine. We retrospectively analysed the incidence of IFI according to EORTC-MSG criteria in 121 consecutive AML/MDS patients receiving 948 azacitidine courses (median 5, range 1-43) between June 2007 and June 2015. Four cases of IFI (two possible, one probable aspergillosis and one proven candidemia) occurred in this series. The incidence rate of proven/probable IFI was 0.21% per treatment cycle and 1.6% per patient treated for the whole series, and 0.73% per treatment cycle and 4.1% per patient treated in those with severe neutropenia. Two patients died from IFI, leading to an IFI-attributable mortality rate of 1.65% per patient and 0.21% per treatment cycle. The numbers needed to treat with prophylaxis to prevent one case of IFI are 238 azacitidine cycles or 30 patients throughout their whole treatment course, and 137 azacitidine cycles or 24 patients among those with severe neutropenia. AML/MDS patients treated with azacitidine, including those with severe prolonged neutropenia, have a very low risk of IFI which does not justify the use of antifungal prophylaxis. PMID:27027972

  15. Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers.

    PubMed

    Ilczyszyn, Weronika M; Sabat, Artur J; Akkerboom, Viktoria; Szkarlat, Anna; Klepacka, Joanna; Sowa-Sierant, Iwona; Wasik, Barbara; Kosecka-Strojek, Maja; Buda, Aneta; Miedzobrodzki, Jacek; Friedrich, Alexander W

    2016-01-01

    The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children's Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5

  16. Clonal Structure and Characterization of Staphylococcus aureus Strains from Invasive Infections in Paediatric Patients from South Poland: Association between Age, spa Types, Clonal Complexes, and Genetic Markers

    PubMed Central

    Ilczyszyn, Weronika M.; Sabat, Artur J.; Akkerboom, Viktoria; Szkarlat, Anna; Klepacka, Joanna; Sowa-Sierant, Iwona; Wasik, Barbara; Kosecka-Strojek, Maja; Buda, Aneta; Miedzobrodzki, Jacek; Friedrich, Alexander W.

    2016-01-01

    The aim of current study was to examine clonal structure and genetic profile of invasive Staphylococcus aureus isolates recovered from infants and children treated at the Jagiellonian University Children’s Hospital of Krakow, Poland. The 107 invasive S. aureus isolates, collected between February 2012 and August 2014, were analysed retrospectively. Antimicrobial susceptibility testing, spa typing and DNA microarray analysis were performed to determine clonal distribution, diversity and gene content in regard to patients characteristics. In total, 107 isolates were recovered from 88 patients with clinical symptoms of invasive bacterial infection. The final set of 92 non-duplicate samples included 38 MRSA isolates. Additionally, a set of 54 S. aureus isolates collected during epidemiological screening was genotyped and analysed. There were 72 healthcare-associated (HCA) and 20 community-onset (CO) infection events caused by 33 and 5 MRSA isolates, respectively. The majority of isolates were affiliated with the major European clonal complexes CC5 (t003, spa-CC 002), CC45 (spa-CC 015), CC7 or CC15 (t084, t091, spa-CC 084). Two epidemic clones (CC5-MRSA-II or CC45-MRSA-IV) dominated among MRSA isolates, while MSSA population contained 15 different CCs. The epidemiological screening isolates belonged to similar genetic lineages as those collected from invasive infection cases. The HCA infection events, spa types t003, t2642 or CC5 were significantly associated with infections occurring in neonates and children under 5 years of age. Moreover, carriage of several genetic markers, including erm(A), sea (N315), egc-cluster, chp was significantly higher in isolates obtained from children in this age group. The spa types t091 and t008 were underrepresented among patients aged 5 years or younger, whereas spa type t008, CC8 and presence of splE was associated with infection in children aged 10 years or older. The HCA-MRSA strains were most frequently found in children under 5

  17. Challenges in measuring complications and death due to invasive Salmonella infections.

    PubMed

    Qamar, Farah Naz; Azmatullah, Asma; Bhutta, Zulfiqar A

    2015-06-19

    Despite the highest burden of Typhoid fever in children globally, exact estimates of morbidity and mortality are lacking due to scarcity of published data. Despite a high prevalence and a socioeconomic burden in developing countries, published data with morbidity and mortality figures are limited especially Africa and South American regions. Data from the community is insufficient and most case fatality estimates are extrapolations from hospital based studies that do not cover all geographical regions, and include cases which may or not be culture confirmed, MDR resistant or sensitive cases, or from mixed populations of age (adults and children). Complications of typhoid such as intestinal perforation, bone marrow suppression, and encephalopathy are dependent on MDR/Fluoroquinolone resistant Salmonella infection, comorbidities such as malnutrition, and health-care access. Data is again insufficient to estimate the true burden of Typhoid Fever in different regions and groups of populations. Although there has been a rapid decline in cases in developed countries with the advent of improved sanitization, timely and easy access to health care and laboratories, this is still not the case in the developing countries where Typhoid deaths are still occurring. The way forward is to develop rapid and cost effective point of care diagnostic tests, put in place validated clinical algorithms for suspected clinical cases, and design prospective, and community based studies in different groups, implement maintenance of electronic health records in large public sector hospitals and regions to identify populations that will benefit most from the implementation of vaccine. Policies on public health education and typhoid vaccine may help to reduce morbidity and mortality due to the disease. PMID:25921727

  18. 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. PMID:26596937

  19. 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

  20. Purification, Characterization, and Expression of Multiple Glutamine Synthetases from Prevotella ruminicola 23

    PubMed Central

    Kim, Jong Nam; Cann, Isaac K. O.

    2012-01-01

    The Prevotella ruminicola 23 genome encodes three different glutamine synthetase (GS) enzymes: glutamine synthetase I (GSI) (ORF02151), GSIII-1 (ORF01459), and GSIII-2 (ORF02034). GSI, GSIII-1, and GSIII-2 have each been heterologously expressed in and purified from Escherichia coli. The subunit molecular mass of GSI was 56 kDa, while GSIII-1 and GSIII-2 were both 83 kDa. Optimal conditions for γ-glutamyl transferase activity were found to be 35°C at pH 5.6 with 0.25 mM Mn2+ ions (GSI) or 37°C at pH 6.0 (GSIII-1 and GSIII-2) with 0.50 to 1.00 mM Mn2+ ions. GSIII biosynthetic activity was found to be optimal at 50 to 60°C and pH 6.8 to 7.0 with 10 mM Mn2+ ions, while GSI displayed no GS biosynthetic activity. Kinetic analysis revealed Km values for glutamate and ammonium as well as for hydrolysis of ATP to be 8.58, 0.48, and 1.91 mM, respectively, for GSIII-1 and 1.72, 0.43, and 2.65 mM, respectively, for GSIII-2. A quantitative reverse transcriptase PCR assay (qRT-PCR) revealed GSIII-2 to be significantly induced by high concentrations of ammonia, and this corresponded with increases in measured GS activity. Collectively, these results show that both GSIII enzymes in P. ruminicola 23 are functional and indicate that GSIII-2, flanked by GOGAT (gltB and gltD genes), plays an important role in the acquisition and metabolism of ammonia, particularly under nonlimiting ammonia growth conditions. PMID:22020637

  1. 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.

  2. A new therapeutic challenge for old pathogens: community-acquired invasive infections caused by ceftriaxone- and ciprofloxacin-resistant Salmonella enterica serotype choleraesuis.

    PubMed

    Ko, Wen-Chien; Yan, Jing-Joung; Yu, Wen-Liang; Lee, Hsin-Chun; Lee, Nan-Yao; Wang, Li-Rong; Chuang, Yin-Ching

    2005-01-15

    Recently, antimicrobial resistance among nontyphoid Salmonella serotypes has been increasingly recognized. In southern Taiwan, we encountered 3 cases of invasive infections caused by Salmonella enterica serotype Choleraesuis with resistance to ciprofloxacin and ceftriaxone. Resistance to ciprofloxacin was related to nucleotide mutations in gyrA and parC, and resistance to ceftriaxone was related to the presence of CMY-2 beta -lactamase. PMID:15655754

  3. The First Case of Invasive Mixed-Mold Infections Due to Emericella nidulans var. echinulata and Rasamsonia piperina in a Patient with Chronic Granulomatous Disease.

    PubMed

    Ishiwada, Naruhiko; Takeshita, Kenichi; Yaguchi, Takashi; Nagasawa, Koo; Takeuchi, Noriko; Hishiki, Haruka; Watanabe, Akira; Kamei, Katsuhiko; Shimojo, Naoki

    2016-04-01

    A 16-year-old boy with chronic granulomatous disease presented with pneumonia and rib osteomyelitis. Emericella nidulans var. echinulata was isolated from his sputum. After starting voriconazole, Rasamsonia piperina was isolated from the rib swelling. A combination therapy of voriconazole and micafungin effectively eradicated this invasive mixed-mold infection. In immunocompromised patients, a precise pathogenic diagnosis is clinically useful for administration of an appropriate treatment regimen. PMID:26563166

  4. Human Mesenchymal Stem Cells of Diverse Origins Support Persistent Infection with Kaposi’s Sarcoma-Associated Herpesvirus and Manifest Distinct Angiogenic, Invasive, and Transforming Phenotypes

    PubMed Central

    Lee, Myung-Shin; Yuan, Hongfeng; Jeon, Hyungtaek; Zhu, Ying; Yoo, Seungmin; Shi, Songtao; Krueger, Brian; Renne, Rolf; Lu, Chun; Jung, Jae U.

    2016-01-01

    ABSTRACT Kaposi’s sarcoma (KS), a highly angiogenic and invasive tumor often involving different organ sites, including the oral cavity, is caused by infection with Kaposi’s sarcoma-associated herpesvirus (KSHV). Diverse cell markers have been identified on KS tumor cells, but their origin remains an enigma. We previously showed that KSHV could efficiently infect, transform, and reprogram rat primary mesenchymal stem cells (MSCs) into KS-like tumor cells. In this study, we showed that human primary MSCs derived from diverse organs, including bone marrow (MSCbm), adipose tissue (MSCa), dental pulp, gingiva tissue (GMSC), and exfoliated deciduous teeth, were permissive to KSHV infection. We successfully established long-term cultures of KSHV-infected MSCa, MSCbm, and GMSC (LTC-KMSCs). While LTC-KMSCs had lower proliferation rates than the uninfected cells, they expressed mixtures of KS markers and displayed differential angiogenic, invasive, and transforming phenotypes. Genetic analysis identified KSHV-derived microRNAs that mediated KSHV-induced angiogenic activity by activating the AKT pathway. These results indicated that human MSCs could be the KSHV target cells in vivo and established valid models for delineating the mechanism of KSHV infection, replication, and malignant transformation in biologically relevant cell types. PMID:26814175

  5. Fitness of wAlbB Wolbachia Infection in Aedes aegypti: Parameter Estimates in an Outcrossed Background and Potential for Population Invasion.

    PubMed

    Axford, Jason K; Ross, Perran A; Yeap, Heng Lin; Callahan, Ashley G; Hoffmann, Ary A

    2016-03-01

    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

  6. Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam

    PubMed Central

    Phu Huong Lan, Nguyen; Le Thi Phuong, Tu; Nguyen Huu, Hien; Thuy, Le; Mather, Alison E.; Park, Se Eun; Marks, Florian; Thwaites, Guy E.; Van Vinh Chau, Nguyen; Thompson, Corinne N.; Baker, Stephen

    2016-01-01

    Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men. PMID:27513951

  7. Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam.

    PubMed

    Phu Huong Lan, Nguyen; Le Thi Phuong, Tu; Nguyen Huu, Hien; Thuy, Le; Mather, Alison E; Park, Se Eun; Marks, Florian; Thwaites, Guy E; Van Vinh Chau, Nguyen; Thompson, Corinne N; Baker, Stephen

    2016-08-01

    Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men. PMID:27513951

  8. 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

  9. Impact of pretransplant serum ferritin level on risk of invasive mold infection after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Dadwal, Sanjeet S; Tegtmeier, Bernard; Liu, Xueli; Frankel, Paul; Ito, James; Forman, Stephen J; Pullarkat, Vinod

    2015-03-01

    Invasive mold infections (IMI) are life-threatening complications of allogeneic hematopoietic stem cell transplantation (HSCT) and are mostly caused by Aspergillus species and Mucorales. We examined whether elevated serum ferritin prior to HSCT was associated with increased risk of IMI after allogeneic HSCT. Elevated serum ferritin was defined as values ≥ 1000 ng/mL. Pretransplant ferritin levels were available for 477 transplants. Nine developed IMI at day 30 and 21 had IMI at day 100 for a cumulative incidence of 1.9% and 4.4%, respectively. Among the high ferritin group, eight of 220 transplant cases (3.6%) developed an IMI within 30 d after HSCT compared with one of 257 (0.4%) in the low ferritin group (P = 0.01). Fourteen of 220 (6.4%) and seven of 257 transplant cases (2.7%) in the high and low ferritin groups, respectively, had developed an IMI by day 100 after HSCT (P = 0.07). Nine of 53 (17%) patients with grades III and IV acute GVHD and iron overload experienced IMI, when compared to three of 37 (8.1%) with high-grade aGVHD, but no iron overload. Among patients without aGVHD, those with elevated ferritin had a 2.7% incidence of IMI compared with 0.9% for patients without elevated ferritin. There was a marginally significant difference in cumulative incidence function between high and low ferritin groups for IMI (P = 0.06). However, elevated serum ferritin (≥ 1000 ng/mL) was not a significant risk factor for IMI in a multivariate competing risk regression model after adjusting for aGVHD. PMID:25082161

  10. Randomized Trial of Micafungin for the Prevention of Invasive Fungal Infection in High-Risk Liver Transplant Recipients

    PubMed Central

    Saliba, Faouzi; Pascher, Andreas; Cointault, Olivier; Laterre, Pierre-François; Cervera, Carlos; De Waele, Jan J.; Cillo, Umberto; Langer, Róbert M.; Lugano, Manuela; Göran-Ericzon, Bo; Phillips, Stephen; Tweddle, Lorraine; Karas, Andreas; Brown, Malcolm; Fischer, Lutz; Pratschke, Johann; Decruyenaere, Johan; De Waele, Jan J.; Laterre, Pierre-François; Moreno, Christophe; Michielsen, Peter; Cointault, Olivier; Fischer, Lutz; Neuhaus, Peter; Pascher, Andreas; Schemmer, Peter; Cervera, Carlos; Varo, Evaristo; Montejo, Miguel; Bouza, Emilio; Blanes, Marino; De La Torre, Julián; Fortun, Jesus; Saliba, Faouzi; Rostaing, Lionel; Paugam-Burtz, Catherine; Eyraud, Daniel; Shah, Tahir; Heaton, Nigel; Langer, Róbert M.; McCormick, Aiden; Cillo, Umberto; Salizzoni, Mauro; Lugano, Manuela; De Gasperi, Andrea; Tomé, Luís; Daniel, Jorge; Popescu, Irinel; Moysyuk, Yan G.; Chzhao, Alexey V.; Zagaynov, Vladimir E.; Ericzon, Bo-Göran

    2015-01-01

    Background. Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk. Methods. In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests. Results. The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for micafungin and 99.3% for standard care (Δ standard care – micafungin [95% confidence interval], 0.7% [−2.7% to 4.4%]) in the per protocol set and 96.5% and 93.6%, respectively (−2.9% [−8.0% to 1.9%]), in the full analysis set. Incidences of drug-related adverse events for micafungin and standard care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. At EOP, liver function tests were similar but creatinine clearance was higher in micafungin- vs standard care–treated patients. Conclusions. Micafungin was noninferior to standard care as antifungal prophylaxis in liver transplant patients at high risk for IFI. Adverse event profiles and liver function at EOP were similar, although kidney function was better with micafungin. Clinical Trials Registration. NCT01058174. PMID:25520332

  11. Risk Factors for Invasive Mold Infections and Implications for Choice of Prophylaxis after Allogeneic Stem Cell Transplantation.

    PubMed

    Blennow, Ola; Remberger, Mats; Törlén, Johan; Szakos, Attila; Ljungman, Per; Mattsson, Jonas

    2016-09-01

    Invasive mold infections (IMIs) are major complications after allogeneic hematopoietic stem cell transplantation (HSCT) with high mortality. We retrospectively investigated incidence and risk factors for IMI after 797 HSCTs in a center with high autopsy frequency, trying to identify patient groups that would potentially benefit from mold-active prophylaxis. The cumulative 1-year incidence of IMI was 2.1% in patients aged 21 to 40, 7.1% in patients aged 41 to 60, and 16.4% in patients > 60 years of age (P < .01 for patients aged 21 to 40 versus 41 to 60, P < .001 for patients aged 21 to 40 versus patients > 60). Risk factors for a new IMI in multivariate analysis were older age, grades II to IV acute graft-versus-host disease (GVHD) (risk hazard, 4.1; 95% CI, 1.9 to 8.8; P < .001), treatment with mesenchymal stromal cells (risk hazard, 4.0; 95% CI, 2.1 to 7.8; P < .001), transplantation with female donor to male recipient (risk hazard, 2.2; 95% CI, 1.1 to 4.3; P = .02), and hematopoietic stem cell transplantation-specific comorbidity index over 5 (risk hazard, 2.8; 95% CI, 1.1 to 6.8; P = .03). In patients with grade II acute GVHD, no IMI was seen after onset of acute GVHD in 109 HSCTs performed in patients < 40 years of age, as compared with 14 IMIs in 97 HSCTs (14%) performed in patients > 40 years of age (P < .001). To conclude, older age is an important risk factor for developing IMIs, and patients < 40 years of age with grade II acute GVHD do not appear to need mold-active prophylaxis unless receiving prolonged treatment with corticosteroids. PMID:27311967

  12. 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

    2016-01-01

    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

  13. Ruminal Prevotella spp. may play an important role in the conversion of plant lignans into human health beneficial antioxidants.

    PubMed

    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

  14. Implementation of a Pan-Genomic Approach to Investigate Holobiont-Infecting Microbe Interaction: A Case Report of a Leukemic Patient with Invasive Mucormycosis.

    PubMed

    Shelburne, Samuel A; Ajami, Nadim J; Chibucos, Marcus C; 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

  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. 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...

  17. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China.

    PubMed

    Sun, Yuqian; Huang, He; Chen, Jing; Li, Jianyong; Ma, Jun; Li, Juan; Liang, Yingmin; Wang, Jianmin; Li, Yan; Yu, Kang; Hu, Jianda; Jin, Jie; Wang, Chun; Wu, Depei; Xiao, Yang; Huang, Xiaojun

    2015-02-01

    This stud y examined the epidemiology, risk factors, management, and outcome of invasive fungal infection (IFI) in patients receiving chemotherapy for hematological malignancy in China. IFI risk factors were analyzed using univariate analysis and multivariate logistic regression. In total, 4,192 patients receiving 4,889 chemotherapy courses were enrolled [mean age 40.7 years, 58.4% male, 16.9% children (<18 years)]. The most common hematological diseases were acute myeloid leukemia (AML, 28.5%), non-Hodgkin lymphoma (NHL, 26.3%), and acute lymphoblastic leukemia (ALL, 20.2%). Severe neutropenia (absolute neutrophil count [ANC] <500/mm(3)) occurred after one third (1,633/4,889, 33.4%) of chemotherapy courses. Incidence of proven/probable IFI was 2.1% per chemotherapy course and higher in patients with myelodysplastic syndrome (MDS, 4.94%), acute hyperleukocytic leukemia (AHL, 4.76%), AML (3.83%), or induction chemotherapy. Risk factors included ANC <500/mm(3) [odds ratio (OR) 3.60], AML or MDS (OR 1.97), induction chemotherapy (OR 2.58), previous IFI (OR 3.08), and being male (OR 1.74). Antifungal agents, prescribed in one quarter (1,211/4,889, 24.8%) of chemotherapy courses, included primary/secondary prophylaxis (n = 827, 16.9%) and/or treatment (n = 655, 13.4%; 86.9 % triazoles), which was empirical (84.3%), pre-emptive (8.6%), or targeted (7.1%). Overall mortality following each chemotherapy course (1.5%) increased in proven/probable (11.7%) and possible IFI (8.2%). In summary, IFI was more common in MDS, AHL, AML, or induction chemotherapy, and substantially increased mortality. Neutropenic patients receiving induction chemotherapy for AML or MDS and those with previous IFI were at particular risk. Antifungal prophylaxis showed an independent protective effect but was not commonly used, even in high-risk patients. By contrast, empiric antifungals were widely used. PMID:25293517

  18. Effect of Early Screening for Invasive Fungal Infections in U.S. Service Members with Explosive Blast Injuries

    PubMed Central

    Weintrob, Amy C.; Rodriguez, Carlos; Dunne, James R.; Weisbrod, Allison B.; Hinkle, Mary; Warkentien, Tyler; Murray, Clinton K.; Oh, John; Millar, Eugene V.; Shah, Jinesh; Shaikh, Faraz; Gregg, Stacie; Lloyd, Gina; Stevens, Julie; Carson, M. Leigh; Aggarwal, Deepak; Tribble, David R.

    2014-01-01

    Abstract Background: An outbreak of invasive fungal infections (IFI) began in 2009 among United States servicemen who sustained blast injuries in Afghanistan. In response, the military trauma community sought a uniform approach to early diagnosis and treatment. Toward this goal, a local clinical practice guideline (CPG) was implemented at Landstuhl Regional Medical Center (LRMC) in early 2011 to screen for IFI in high-risk patients using tissue histopathology and fungal cultures. Methods: We compared IFI cases identified after initiation of the CPG (February through August 2011) to cases from a pre-CPG period (June 2009 through January 2011). Results: Sixty-one patients were screened in the CPG period, among whom 30 IFI cases were identified and compared with 44 pre-CPG IFI cases. Demographics between the two study periods were similar, although significantly higher transfusion requirements (p<0.05) and non-significant trends in injury severity scores and early lower extremity amputation rates suggested more severe injuries in CPG-period cases. Pre-CPG IFI cases were more likely to be associated with angioinvasion on histopathology than CPG IFI cases (48% versus 17%; p<0.001). Time to IFI diagnosis (three versus nine days) and to initiation of antifungal therapy (seven versus 14 days) were significantly decreased in the CPG period (p<0.001). Additionally, more IFI patients received antifungal agent at LRMC during the CPG period (30%) versus pre-CPG period (5%; p=0.005). The CPG IFI cases were also prescribed more commonly dual antifungal therapy (73% versus 36%; p=0.002). There was no statistical difference in length of stay or mortality between pre-CPG and CPG IFI cases; although a non-significant reduction in crude mortality from 11.4% to 6.7% was observed. Conclusions: Angioinvasive IFI as a percentage of total IFI cases decreased during the CPG period. Earlier diagnosis and commencement of more timely treatment was achieved. Despite these improvements, no

  19. 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

  20. 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. PMID:26351276

  1. Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study.

    PubMed

    Berndsen, M R; Erlendsdóttir, H; Gottfredsson, M

    2012-09-01

    Historically, Haemophilus influenzae (Hi) serotype b (Hib) caused most invasive Haemophilus infections worldwide, mainly in children. In 1989 routine childhood vaccination against Hib was initiated in Iceland. We conducted a population-based study of all patients in the country with Haemophilus spp. isolated from sterile sites (n = 202), from 1983 to 2008. Epidemiology, clinical characteristics of the infections and serotypes of the isolates were compared during the pre-vaccination (1983-1989) and post-vaccination era (1990-2008). Following the vaccination, the overall incidence of Hib decreased from 6.4 to 0.3/100,000 per year (p <0.05) whereas the incidence did not change significantly for infections caused by Haemophilus sensu lato not serotype b, hereafter referred to as non-type b Hi (0.9 vs 1.2, respectively). The most frequent diagnosis prior to 1990 was meningitis caused by Hib, which was subsequently replaced by pneumonia and bacteraemia caused by non-type b Hi. Most commonly, non-type b Hi were non-typeable (NTHi; 40/59), followed by Hi serotype f (14/59) and Hi serotype a (3/59). Pregnancy was associated with a markedly increased susceptibility to invasive Haemophilus infections (RR 25.7; 95% CI 8.0-95.9, p <0.0001) compared with non-pregnant women. The case fatality rate for Hib was 2.4% but 14% for non-type b Hi, highest at the extremes of age. Hib vaccination gives young children excellent protection and decreases incidence in the elderly due to herd effect in the community. Replacement with other species or serotypes has not been noted. Pregnant women are an overlooked risk group. PMID:22070637

  2. The transmembrane protein Sho1 cooperates with the mucin Msb2 to regulate invasive growth and plant infection in Fusarium oxysporum.

    PubMed

    Perez-Nadales, Elena; Di Pietro, Antonio

    2015-08-01

    In the vascular wilt pathogen Fusarium oxysporum, the mitogen-activated protein kinase (MAPK) Fmk1 is essential for plant infection. The mucin-like membrane protein Msb2 regulates a subset of Fmk1-dependent functions. Here, we examined the role of the tetraspan transmembrane protein Sho1 as an additional regulator of the Fmk1 pathway and determined its genetic interaction with Msb2. Targeted Δsho1 mutants were generated in wild-type and Δmsb2 backgrounds to test possible interactions between the two genes. The mutants were examined for hyphal growth under different stress conditions, phosphorylation of the MAPK Fmk1 and an array of Fmk1-dependent virulence functions. Similar to Msb2, Sho1 was required for the activation of Fmk1 phosphorylation, as well as Fmk1-dependent gene expression and invasive growth functions, including extracellular pectinolytic activity, cellophane penetration, plant tissue colonization and virulence on tomato plants. Δsho1 mutants were hypersensitive to the cell wall-perturbing compound Calcofluor White, and this phenotype was exacerbated in the Δmsb2 Δsho1 double mutant. These results highlight that Sho1 and Msb2 have partially overlapping functions upstream of the Fmk1 MAPK cascade, to promote invasive growth and plant infection, as well as cell wall integrity, in F. oxysporum. PMID:25382187

  3. HIV Infection and the Epidemiology of Invasive Pneumococcal Disease (IPD) in South African Adults and Older Children Prior to the Introduction of a Pneumococcal Conjugate Vaccine (PCV)

    PubMed Central

    Meiring, Susan; Cohen, Cheryl; Quan, Vanessa; de Gouveia, Linda; Feldman, Charles; Karstaedt, Alan; Klugman, Keith P.; Madhi, Shabir A.; Rabie, Helene; Sriruttan, Charlotte; von Gottberg, Anne

    2016-01-01

    Introduction Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV) programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD) in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use. Methods National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES) hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI) in 2009. Results In South Africa, from 2003–2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734) of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000), with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190). HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV) than HIV-infected persons (39% (210/544) vs. 19% (790/4190), p<0.001). During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7–1.1). Conclusion Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk

  4. Characterization of B-cell epitopes on IpaB, an invasion-associated antigen of Shigella flexneri: identification of an immunodominant domain recognized during natural infection.

    PubMed

    Barzu, S; Nato, F; Rouyre, S; Mazie, J C; Sansonetti, P; Phalipon, A

    1993-09-01

    The invasion plasmid antigen B (IpaB), a 62-kDa plasmid-encoded protein associated with the ability of shigellae to invade epithelial cells, is the bacterial antigen most strongly and consistently recognized by the host during infection. The strong systemic and mucosal immune responses observed against this invasin prompted us to map its B-cell epitopes. For this purpose, IpaB was first overexpressed in Shigella flexneri and used to raise rabbit polyclonal antiserum and murine monoclonal antibodies, which were subsequently used to screen a lambda gt11 ipaB library. Inserts of recombinant DNA clones that were specifically recognized by the antisera and antibodies were sequenced, and three distinct determinants were identified. Further characterization of these determinants showed that they were recognized by sera from patients convalescent from shigellosis, suggesting that they are relevant to the humoral response during natural infection. Moreover, the IpaB region comprising the three determinants was systematically recognized by all sera from infected patients that we tested, whereas other regions of the protein were not. These data suggest that this region, located between amino acid residues 147 and 258, is the major immunogenic domain of the invasin in the course of natural infection. PMID:7689541

  5. 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

    2016-02-01

    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. PMID:26723514

  6. Nitric oxide-releasing indomethacin enhances susceptibility to Trypanosoma cruzi infection acting in the cell invasion and oxidative stress associated with anemia.

    PubMed

    Tatakihara, Vera Lucia Hideko; Malvezi, Aparecida Donizette; Panis, Carolina; Cecchini, Rubens; Zanluqui, Nagela Ghabdan; Yamauchi, Lucy Megumi; Martins, Maria Isabel Lovo; da Silva, Rosiane Valeriano; Yamada-Ogatta, Sueli Fumie; Rizzo, Luiz Vicente; Martins-Pinge, Marli Cardoso; Pinge-Filho, Phileno

    2015-02-01

    Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected with this disease worldwide. T. cruzi infection causes an intense inflammatory response, which is critical for the control of parasite proliferation and disease development. Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as chemopreventive agents. In this study, we investigated the effect of NO-indomethacin on parasite burden, cell invasion, and oxidative stress in erythrocytes during the acute phase of infection. NO-indomethacin was dissolved in dimethyl formamide followed by i.p. administration of 50 ppm into mice 30 min after infection with 5×10(3) blood trypomastigote forms (Y strain). The drug was administered every day until the animals died. Control animals received 100 μL of drug vehicle via the same route. Within the NO-indomethacin-treatment group, parasitemia and mortality (100%) were higher and oxidative stress in erythrocytes, anemia, and entry of parasites into macrophages were significantly greater than that seen in controls. Increase in the entry and survival of intracellular T. cruzi was associated with inhibition of nitric oxide production by macrophages treated with NO-indomethacin (2.5 μM). The results of this study provide strong evidence that NO-NSAIDs potently inhibit nitric oxide production, suggesting that NO-NSAID-based therapies against infections would be difficult to design and would require caution. PMID:25559858

  7. Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection.

    PubMed Central

    Troncone, G; Martinez, J C; Palombini, L; De Rosa, G; Mugica, C; Rodriguez, J A; Zeppa, P; Di Vizio, D; Lucariello, A; Piris, M A

    1998-01-01

    AIM: To investigate the immunocytochemical staining pattern of mdm2 and p21WAF1 proteins in invasive cervical cancer and to determine its relation with the expression of p53 and with the high risk HPV infection. METHODS: Immunocytochemistry for p53, mdm2, and p21WAF1 was performed in 31 paraffin embedded sections of invasive cervical cancer. The results were assessed by image analysis, evaluating for each protein the optical density of the immunostained area, scored as percentage of the total nuclear area. The presence of high risk human papillomavirus (HPV) infection was detected by using the polymerase chain reaction. RESULTS: Immunostaining for both mdm2 and p21WAF1 was correlated with p53 expression; however, the correlation between p53 and mdm2 (R = 0.49; p < 0.01) was more significant than between p53 and p21WAF1 (R = 0.31; p < 0.05); the less stringent correlation between p53 and p21WAF1 might reflect the p53 independent mechanisms of p21WAF1 induction. Similar average levels of p53, mdm2, and p21WAF1 immunostaining were found in the presence or absence of high risk HPV-DNA, without significant differences between the two groups. CONCLUSIONS: These data suggest that mdm2 and p21WAF1 proteins are expressed in invasive cervical cancer and that their immunocytochemical staining pattern is not abrogated by the presence of high risk HPV genomic sequences. Images PMID:10023338

  8. 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

  9. Increase in Invasive Streptococcus pneumoniae Infections in Children with Sickle Cell Disease since Pneumococcal Conjugate Vaccine Licensure

    PubMed Central

    McCavit, Timothy L.; Quinn, Charles T.; Techasaensiri, Chonnamet; Rogers, Zora R.

    2010-01-01

    Invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine (PCV7) usage. We report 10 IPD cases since PCV7 licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in SCD. PMID:21193205

  10. 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. PMID:27324802

  11. Three Cases of Severe Invasive Infections Caused by Campylobacter rectus and First Report of Fatal C. rectus Infection▿

    PubMed Central

    Lam, Jimmy Y. W.; Wu, Alan K. L.; Ngai, Dickson C.; Teng, Jade L. L.; Wong, Elsa S. Y.; Lau, Susanna K. P.; Lee, Rodney A.; Woo, Patrick C. Y.

    2011-01-01

    We report the first fatal case of Campylobacter rectus infection due to a subdural empyema and ruptured mycotic intracranial aneurysm and two cases of limb-threatening C. rectus necrotizing soft tissue and bone infection and empyema thoracis that responded to amoxicillin-clavulanate and surgical debridement and drainage. All three strains were identified by 16S rRNA sequencing. PMID:21270212

  12. [Invasive Campylobacter jejuni/coli Infections: 9 Case Reports at a Single Center between 2000 and 2015, and a Review of Literature Describing Japanese Patients].

    PubMed

    Tasaka, Keiji; Matsubara, Kousaku; Nigami, Hiroyuki; Iwata, Aya; Isome, Kenichi; Yamamoto, Go

    2016-05-01

    There have been few coherent reports on extraintestinal infection or bacteremia caused by Campylobacter jejuni (C. jejuni) or C. coli in Japan. To clarify the clinical and microbiological characteristics of invasive infections caused by these two species, we retrospectively analyzed the records of patients from whom these pathogens had been isolated from sterile sites between 2000 and 2015. During this study period, we identified 9 patients. The clinical syndrome of all of these patients was bacteremia. Three patients had underlying diseases with both liver cirrhosis and malignant neoplasm, and all of these patients were aged 60 years or older. The remaining 6 patients were immunocompetent and younger than 40 years of age. All 9 patients had a fever of 38.5 degrees C or higher. The proportion of patients with gastrointestinal symptoms was lower for the 3 patients with underlying diseases, compared with the 6 patients without underlying diseases (1/3 cases vs, 4/6 cases). Of the 8 strains evaluated for antimicrobial susceptibility, all were susceptible to imipenem/cilastatin, kanamycin and erythromycin, and 2 were resistant to levofloxacin. Antimicrobial treatment was administered to 8 patients, but one spontaneously recovered without any treatment. We were able to follow the outcomes of 8 patients, and all of these patients completely recovered without relapses. We also reviewed 14 Japanese patients reported in the Japanese and English literature and found similar clinical features consisting of a high-grade fever and an association with underlying diseases and gastrointestinal symptoms. Of note, 3 agammaglobulinemic patients presented with bacteremia and extraintestinal infections and had multiple relapses. Based on the findings of our 9 cases and previous reports, the affected patients were divided into two groups according to clinical syndrome and therapeutic intervention. One group consisted of previously healthy children or young adults showing bacteremia

  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. PMID:24421045

  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. Residual gas analyzer mass spectrometry for human breath analysis: a new tool for the non-invasive diagnosis of Helicobacter pylori infection.

    PubMed

    Maity, Abhijit; Banik, Gourab D; Ghosh, Chiranjit; Som, Suman; Chaudhuri, Sujit; Daschakraborty, Sunil B; Ghosh, Shibendu; Ghosh, Barnali; Raychaudhuri, Arup K; Pradhan, Manik

    2014-03-01

    A residual gas analyzer (RGA) coupled with a high vacuum chamber is described for the non-invasive diagnosis of the Helicobacter pylori (H. pylori) infection through ¹³C-urea breath analysis. The present RGA-based mass spectrometry (MS) method is capable of measuring high-precision ¹³CO₂ isotope enrichments in exhaled breath samples from individuals harboring the H. pylori infection. The system exhibited 100% diagnostic sensitivity, and 93% specificity alongside positive and negative predictive values of 95% and 100%, respectively, compared with invasive endoscopy-based biopsy tests. A statistically sound diagnostic cut-off value for the presence of H. pylori was determined to be 3.0‰ using a receiver operating characteristic curve analysis. The diagnostic accuracy and validity of the results are also supported by optical off-axis integrated cavity output spectroscopy measurements. The δ¹³(DOB)C‰ values of both methods correlated well (R² = 0.9973 at 30 min). The RGA-based instrumental setup described here is simple, robust, easy-to-use and more portable and cost-effective compared to all other currently available detection methods, thus making it a new point-of-care medical diagnostic tool for the purpose of large-scale screening of the H. pylori infection in real time. The RGA-MS technique should have broad applicability for ¹³C-breath tests in a wide range of biomedical research and clinical diagnostics for many other diseases and metabolic disorders. PMID:24566134

  16. Prospective trial finds nystatin mouthwash effective prophylaxis for pulmonary invasive fungal infections that originate in the throat of patients with hematologic malignancies.

    PubMed

    Hu, R; Jiang, X; Wu, Y

    2013-01-01

    We investigated the source of fungi in the lungs of patients with hematological malignancies who had invasive pulmonary fungal infections (IPFI). We also conducted a prospective study to evaluate the efficacy of different mouthwash solutions in preventing IPFI in patients with hematologic malignancies. In order to determine the source of fungi in the lungs of 30 patients with hematologic malignancies who had IPFI, we collected samples from sites with suspected fungal infection and used PCR and sequencing for pathogen identification. For the prospective study, we enrolled 158 patients with hematological malignancies who had IPFI and randomly assigned them to one of three mouthwash groups: 1% nystatin, 2.5% sodium bicarbonate, or normal saline. Fungal staining and incidence of IPFI, oral fungal infection, and intestinal fungal infection were evaluated. We showed that 96.7% of the fungi isolated from the throats and the lungs were identical; 76.9% of the fungi from the lungs and digestive tracts were identical and, 84.6 % of the fungi from the throats and digestive tract were identical. Patients using 1% nystatin had lower incidence of IPFI (1.6%) and fungal enteritis (1.6%) than those using sodium bicarbonate (16.3% and 14.3%) or normal saline (27.7% and 12.8%). All treatments had low incidences of oral fungal infections (0 to 4.3%). Our data showed that fungi originating from mouth and throat cause IPFI. We also showed that use of a prophylactic mouthwash containing 1% nystatin was effective in preventing IPFI in patients with hematological malignancies. PMID:23374002

  17. Invasive swimbladder parasite Anguillicoloides crassus: infection status 15 years after discovery in wild populations of American eel Anguilla rostrata.

    PubMed

    Hein, Jennifer L; Arnott, Stephen A; Roumillat, William A; Allen, Dennis M; de Buron, Isaure

    2014-01-16

    A year-round survey of American eels Anguilla rostrata was performed at 5 localities in South Carolina (SC), USA, 15 yr after the first infection by the nematode Anguillicoloides crassus was reported from Winyah Bay, SC. Infections by adult stages of A. crassus in the swimbladder lumen occurred with a prevalence of 45% (n = 479), a mean intensity (± SE) of 2.3 ± 0.2 worms per infected eel (range = 1-22), and a mean abundance of 2.0 ± 0.1 among all eels. Infections by larval stages of A. crassus in the swimbladder wall occurred with a prevalence, intensity, and abundance of 29%, 2.4 ± 0.3 (range = 1-15), and 0.7 ± 0.1, respectively (n = 471). Overall prevalence of the parasite (any stage) was 58%, with a mean intensity ± SE of 3.0 ± 0.2 and a mean abundance of 1.8 ± 0.2. Biomass of the adult parasite stage varied significantly with eel body length, but the direction of the effect depended on salinity. Prevalence and intensity of infection by adult nematodes varied by locality but not by eel total length, salinity, or season. Larval prevalence was significantly greater in the winter and spring and also differed among localities. The lack of seasonal effects on infection by the adult worm stage contrasts with studies from higher latitudes in North America and Europe and may be due to the warmer winter temperatures at southern latitudes. Significant variation in infection among localities reflects possible differences in abundance of intermediate and/or paratenic hosts. Overall, infection levels were higher than previous reports for eels in SC but comparable to more recent reports from other areas in North America. PMID:24429471

  18. Increased S-Nitrosylation and Proteasomal Degradation of Caspase-3 during Infection Contribute to the Persistence of Adherent Invasive Escherichia coli (AIEC) in Immune Cells

    PubMed Central

    Dunne, Karl A.; Allam, Amr; McIntosh, Anne; Houston, Stephanie A.; Cerovic, Vuk; Goodyear, Carl S.; Roe, Andrew J.; Beatson, Scott A.; Milling, Simon W.; Walker, Daniel; Wall, Daniel M.

    2013-01-01

    Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn’s disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients. PMID:23861899

  19. Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

    PubMed

    Xu, J-H; Dai, W-J; Chen, B; Fan, X-Y

    2015-03-01

    As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections. PMID:25565478

  20. Randomized, double-blind trial of anidulafungin versus fluconazole for prophylaxis of invasive fungal infections in high-risk liver transplant recipients.

    PubMed

    Winston, D J; Limaye, A P; Pelletier, S; Safdar, N; Morris, M I; Meneses, K; Busuttil, R W; Singh, N

    2014-12-01

    Invasive fungal infections (IFIs) are a common complication in liver transplant recipients. There are no previous randomized trials of an echinocandin for the prevention of IFIs in solid organ transplant recipients. In a randomized, double-blind trial conducted at University-affiliated transplant centers, 200 high-risk liver transplant recipients (100 patients per group) received either anidulafungin or fluconazole for antifungal prophylaxis. Randomization was stratified by Model for End-Stage Liver Disease score ≥30 and receipt of a pretransplant antifungal agent. The primary end point was IFI in a modified intent-to-treat analysis. The overall incidence of IFI was similar for the anidulafungin (5.1%) and the fluconazole groups (8.0%) (OR 0.61, 95% CI 0.19-1.94, p = 0.40). However, anidulafungin prophylaxis was associated with less Aspergillus colonization or infection (3% vs. 9%, p = 0.08), lower breakthrough IFIs among patients who had received pretransplant fluconazole (0% vs. 27%, p = 0.07), and fewer cases of antifungal resistance (no cases vs. 5 cases). Both drugs were well-tolerated. Graft rejection, fungal-free survival, and mortality were similar for both groups. Thus, anidulafungin and fluconazole have similar efficacy for antifungal prophylaxis in most liver transplant recipients. Anidulafungin may be beneficial if the patient has an increased risk for Aspergillus infection or received fluconazole before transplantation. PMID:25376267

  1. Development of monoclonal antibody-based galactomannoprotein antigen-capture ELISAs to detect Aspergillus fumigatus infection in the invasive aspergillosis rabbit models.

    PubMed

    Wang, Z-Y; Cai, J-P; Qiu, L-W; Hao, W; Pan, Y-X; Tung, E T K; Lau, C C Y; Woo, P C Y; Lau, S K P; Yuen, K-Y; Che, X-Y

    2012-11-01

    Aspergillus fumigatus is one of the most prominent opportunistic fungal pathogens in immunocompromised hosts. Early recognition of this infection along with prompt antifungal therapy may increase the survival rate. We expressed two potential bio-markers of A. fumigatus infection-galactomannoprotein Afmp1p and Afmp4p in Pichia pastoris. We generated 33 monoclonal antibodies (MAbs), 20 against recombinant Afmp1p (rAfmp1p) and the other 13 against recombinant Afmp4p (rAfmp4p). Subsequently, we developed two antigen-capture enzyme-linked immunosorbent assays (ELISAs) which employed MAbs as both the capture and the detection antibodies for rAfmp1p and rAfmp4p. The two antigen-capture ELISAs specifically detected Afmp1p/Afmp4p in cultures of A. fumigatus and had no cross-reaction with other tested pathogenic fungi, including Penicillium marneffei and other pathogenic Aspergillus species. The Afmp1p-captured ELISA would be positive even when the culture supernatant of A. fumigatus had been diluted to 128-fold of its original concentration. The two antigen ELISAs could capture circulating or excreted antigens during the acute phase of invasive aspergillosis (IA) in the animal model, and had no cross-reactivity to other Aspergillus-challenged animal models. We developed two antigen-capture ELISAs for the laboratory diagnosis of A. fumigatus infection. These two antigen-capture ELISAs may be useful in the clinical diagnosis of aspergillosis. PMID:22669560

  2. 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

  3. Beta-d-Glucan Detection as a Diagnostic Test for Invasive Aspergillosis in Immunocompromised Critically Ill Patients with Symptoms of Respiratory Infection: an Autopsy-Based Study ▿

    PubMed Central

    De Vlieger, Greet; Lagrou, Katrien; Maertens, Johan; Verbeken, Eric; Meersseman, Wouter; Van Wijngaerden, Eric

    2011-01-01

    Beta-(1,3)-d-glucan (BG) detection is an emerging tool to diagnose invasive fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in immunocompromised ICU patients with proven IA and in immunocompromised ICU patients in whom autopsy failed to show IFI. The study was performed in a 17-bed medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were eligible for inclusion when at least two additional clinical signs were present. Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients who had no IFI were eligible for inclusion. Serum BG levels were significantly higher in patients with IA than patients without an IFI (P < 0.01). Using a cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%, respectively; the positive and negative predictive values were 54.5 and 92.0%, respectively. The positive and negative likelihood ratios were 2.83 and 0.21, respectively. Although serum BG concentrations were higher in immunocompromised ICU patients with IA than in patients with the same risk factors who did not have IFI on autopsy, the moderate performance characteristics of this test limit its use as a diagnostic test for IA in this population. PMID:21880959

  4. Beta-D-glucan detection as a diagnostic test for invasive aspergillosis in immunocompromised critically ill patients with symptoms of respiratory infection: an autopsy-based study.

    PubMed

    De Vlieger, Greet; Lagrou, Katrien; Maertens, Johan; Verbeken, Eric; Meersseman, Wouter; Van Wijngaerden, Eric

    2011-11-01

    Beta-(1,3)-D-glucan (BG) detection is an emerging tool to diagnose invasive fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in immunocompromised ICU patients with proven IA and in immunocompromised ICU patients in whom autopsy failed to show IFI. The study was performed in a 17-bed medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were eligible for inclusion when at least two additional clinical signs were present. Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients who had no IFI were eligible for inclusion. Serum BG levels were significantly higher in patients with IA than patients without an IFI (P < 0.01). Using a cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%, respectively; the positive and negative predictive values were 54.5 and 92.0%, respectively. The positive and negative likelihood ratios were 2.83 and 0.21, respectively. Although serum BG concentrations were higher in immunocompromised ICU patients with IA than in patients with the same risk factors who did not have IFI on autopsy, the moderate performance characteristics of this test limit its use as a diagnostic test for IA in this population. PMID:21880959

  5. 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. PMID:18576875

  6. Increase of integration events and infection loads of human papillomavirus type 52 with lesion severity from low-grade cervical lesion to invasive cancer.

    PubMed

    Cheung, Jo L K; Cheung, T H; Tang, Julian W T; Chan, Paul K S

    2008-04-01

    Infection load and the integration of human papillomaviruses (HPV) have been implicated as determinants for oncogenesis, but whether variation among different HPV types exists remains unclear. We investigated 91 women infected with HPV type 52 (HPV-52), a type that is rare worldwide but common in East Asia. The median viral load increased with the severity of the lesion (248 copies/cell equivalent for normal/cervical intraepithelial neoplasia [CIN] grade 1, 402 copies/cell equivalent for CIN 2, 523 copies/cell equivalent for CIN 3, and 1,435 copies/cell equivalent for invasive cancer). The proportion of specimens with integration increased significantly with the severity of the lesion (P < 0.001). The viral load was associated with the physical status of the viral genome, with higher levels for the pure episomal form (P = 0.001). Infection status should be considered when interpreting viral load data for HPV-52, as single infections with this HPV type were found to have marginally higher viral loads than coinfections (P = 0.051). All except one sample had E2 disruption restricted to only a part of the gene. Integration is a critical step in HPV-52-induced carcinogenesis. The profile of E2 disruption was different from that described for HPV-16, with the amino-terminal region being most frequently involved. Selecting the appropriate E2 region for amplification is critical in studying the integration of HPV-52. In summary, the HPV-52 viral load and the integrated proportion increased with the severity of the cervical lesions but had a different pattern than that of HPV-16. PMID:18272718

  7. Bacterial Hypoxic Responses Revealed as Critical Determinants of the Host-Pathogen Outcome by TnSeq Analysis of Staphylococcus aureus Invasive Infection.

    PubMed

    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

    2015-12-01

    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. 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

  9. 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

  10. 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...

  11. Saprochaete clavata invasive infection in a patient with severe aplastic anemia: Efficacy of voriconazole and liposomal amphotericin B with adjuvant granulocyte transfusions before neutrophil recovery following allogeneic bone marrow transplantation

    PubMed Central

    Favre, Simon; Rougeron, Amandine; Levoir, Laure; Pérard, Baptiste; Milpied, Noël; Accoceberry, Isabelle; Gabriel, Frédéric; Vigouroux, Stéphane

    2016-01-01

    We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery. PMID:27069848

  12. Saprochaete clavata invasive infection in a patient with severe aplastic anemia: Efficacy of voriconazole and liposomal amphotericin B with adjuvant granulocyte transfusions before neutrophil recovery following allogeneic bone marrow transplantation.

    PubMed

    Favre, Simon; Rougeron, Amandine; Levoir, Laure; Pérard, Baptiste; Milpied, Noël; Accoceberry, Isabelle; Gabriel, Frédéric; Vigouroux, Stéphane

    2016-03-01

    We report a case of a 27-year old man with severe aplastic anemia who developed a Saprochaete clavata (Geotrichum clavatum) disseminated invasive infection shortly prior a scheduled allogeneic bone marrow transplantation. Treatment with a combination of voriconazole, liposomal amphotericin B and adjuvant granulocyte transfusions was successful before neutrophil recovery. PMID:27069848

  13. 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

  14. 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

  15. 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. PMID:16339957

  16. New potential role of serum apolipoprotein E mediated by its binding to clumping factor A during Staphylococcus aureus invasive infections to humans

    PubMed Central

    Hair, Pamela S.; Nyalwidhe, Julius O.; Cunnion, Kenji M.

    2015-01-01

    Staphylococcus aureus is a crucial human pathogen expressing various immune-evasion proteins that interact with the host-cell molecules. Clumping factor A (ClfA) is a microbial surface protein that promotes S. aureus binding to fibrinogen, and is associated with septic arthritis and infective endocarditis. In order to identify the major human serum proteins that bind the ClfA, we utilized recombinant ClfA region A in a plate-based assay. SDS-PAGE analysis of the bound proteins yielded five prominent bands, which were analysed by MS yielding apolipoprotein E (ApoE) as the predominant protein. ClfA-sufficient S. aureus bound purified ApoE by more than one log greater than an isogenic ClfA-deficient mutant. An immunodot-blot assay yielded a linearity model for ClfA binding to human ApoE with a stoichiometric-binding ratio of 1.702 at maximal Pearson's correlation coefficient (0.927). These data suggest that ApoE could be a major and novel binding target for the S. aureus virulence factor ClfA. Thus, ClfA recruitment of serum ApoE to the S. aureus surface may sequester ApoE and blunt its host defence function against S. aureus-invasive infections to humans. In this context, compounds that can block or suppress ClfA binding to ApoE might be utilized as prophylactic or therapeutic agents. PMID:25878259

  17. New potential role of serum apolipoprotein E mediated by its binding to clumping factor A during Staphylococcus aureus invasive infections to humans.

    PubMed

    Elkhatib, Walid F; Hair, Pamela S; Nyalwidhe, Julius O; Cunnion, Kenji M

    2015-04-01

    Staphylococcus aureus is a crucial human pathogen expressing various immune-evasion proteins that interact with the host-cell molecules. Clumping factor A (ClfA) is a microbial surface protein that promotes S. aureus binding to fibrinogen, and is associated with septic arthritis and infective endocarditis. In order to identify the major human serum proteins that bind the ClfA, we utilized recombinant ClfA region A in a plate-based assay. SDS-PAGE analysis of the bound proteins yielded five prominent bands, which were analysed by MS yielding apolipoprotein E (ApoE) as the predominant protein. ClfA-sufficient S. aureus bound purified ApoE by more than one log greater than an isogenic ClfA-deficient mutant. An immunodot-blot assay yielded a linearity model for ClfA binding to human ApoE with a stoichiometric-binding ratio of 1.702 at maximal Pearson's correlation coefficient (0.927). These data suggest that ApoE could be a major and novel binding target for the S. aureus virulence factor ClfA. Thus, ClfA recruitment of serum ApoE to the S. aureus surface may sequester ApoE and blunt its host defence function against S. aureus-invasive infections to humans. In this context, compounds that can block or suppress ClfA binding to ApoE might be utilized as prophylactic or therapeutic agents. PMID:25878259

  18. Diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology.

    PubMed

    Rodríguez-Baño, Jesús; Cisneros, José Miguel; Cobos-Trigueros, Nazaret; Fresco, Gema; Navarro-San Francisco, Carolina; Gudiol, Carlota; Horcajada, Juan Pablo; López-Cerero, Lorena; Martínez, José Antonio; Molina, José; Montero, Milagro; Paño-Pardo, José R; Pascual, Alvaro; Peña, Carmen; Pintado, Vicente; Retamar, Pilar; Tomás, María; Borges-Sa, Marcio; Garnacho-Montero, José; Bou, Germán

    2015-05-01

    The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum β-lactamases and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. Clinically relevant questions were selected and the literature was reviewed for each of them. The information from the selected articles was extracted and recommendations were provided and graded according to the strength of the recommendations and quality of the evidence. The document was opened to comments from the members from the Spanish Society of Infectious Diseases and Clinical Microbiology, which were considered for inclusion in the final version. Evidence-based recommendations are provided for the use of microbiological techniques for the detection of extended-spectrum β-lactamases and carbapenemases in Enterobacteriaceae, and for antibiotic therapy for invasive/severe infections caused by these organisms. The absence of randomised controlled trials is noteworthy; thus, recommendations are mainly based on observational studies (that have important methodological limitations), pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified. PMID:25600218

  19. Encephalitozoon cuniculi, Toxoplasma gondii and Neospora caninum infection in invasive Eastern Cottontail Rabbits Sylvilagus floridanus in Northwestern Italy.

    PubMed

    Zanet, S; Palese, V; Trisciuoglio, A; Cantón Alonso, C; Ferroglio, E

    2013-11-01

    Sylvilagus floridanus is a lagomorph introduced for hunting purposes from North America to Europe where, in certain areas like Northern Italy, its population reached high densities. Brain, kidney and skeletal muscle of 144 Eastern Cottontail Rabbits S. floridanus were examined by PCR for Encephalitozoon cuniculi, Toxoplasma gondii and Neospora caninum. DNA of E. cuniculi was found with a prevalence of 9.72% (CI 95% 0.058-0.156). T. gondii and N. caninum DNA was detected in 2.08% (CI 95% 0.0071-0.0595) and 2.78% (CI 95% 0.0109-0.0692) of the samples examined, respectively. This is the first report of E. cuniculi infection in a lagomorph species other than in its natural host Oryctolagus cuniculus, and this is also the first time N. caninum is found to naturally infect S. floridanus. E. cuniculi, T. gondii and N. caninum infect S. floridanus at low but relevant prevalences, considered the important role that these pathogens could play in both animal and human health. PMID:23747104

  20. Five-year cumulative incidence of invasive anal cancer among HIV-infected patients according to baseline anal cytology results: an inception cohort analysis

    PubMed Central

    Cachay, E.; Agmas, W.; Mathews, C.

    2015-01-01

    Objectives The aim of the study was to estimate the cumulative incidence of, and rates of progression to, invasive anal cancer (IAC) according to baseline anal cytology screening category in an unselected HIV clinical care cohort in the antiretroviral era. Methods A retrospective cohort analysis of HIV-infected patients under care at the University of California at San Diego Owen Clinic was carried out. Patients were eligible for this analysis if they had at least two anal cytohistological results available for longitudinal analysis. Kaplan-Meier analysis was used to estimate the cumulative incidence of IAC over time according to baseline cytology category [less than high-grade intraepithelial lesion (HSIL) versus HSIL]. Cox regression analysis was used to adjust for the following covariates: antiretroviral use, level of HIV viraemia, smoking status and infrared photocoagulation (IRC) ablation therapy. Results Between 2000 and 2012, we followed 2804 HIV-infected patients for a median of 4 years under a clinic protocol requiring baseline anal cytology screening. Incident IAC was diagnosed in 23 patients. Patients with a baseline HSIL anal cytology had an estimated 5-year probability of progression to IAC of 1.7% and an estimated annual progression risk of 1 in 263. None of the examined covariates was significantly associated with IAC incidence when examined in separate unadjusted Cox models. Conclusions HIV-infected patients with a baseline HSIL anal cytology had a 5-year cumulative incidence of IAC of 1.65%, with an upper 95% confidence bound of 4.5%. This population-based study provides quantitative risk estimates that may be used for counselling patients regarding management options for abnormal cytology results. PMID:25197003

  1. Does ampicillin-sulbactam cause false positivity of (1,3)-beta-D-glucan assay? A prospective evaluation of 15 patients without invasive fungal infections.

    PubMed

    Metan, Gokhan; Agkus, Cigdem; Nedret Koc, A; Elmali, Ferhan; Finkelman, Malcolm A

    2012-07-01

    The purpose of this study was to investigate the interaction between intravenous ampicillin-sulbactam treatment and (1,3)-beta-D-glucan (BDG) assay. Fifteen patients with a median age of 60 (16-81) without known risk factors for invasive fungal infections who received a daily dose of 3×2g ampicillin-sulbactam monotherapy from different batches were included in the study. Thirteen patients had soft tissue infections. The 5 of 13 patients who went under surgery had surgical dressings. Serum samples were obtained both before and after antibiotic infusion on the first, third, seventh and tenth days of an ampicillin-sulbactam treatment course. BDG was assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA, USA) according to manufacturers' specifications. All serum samples were also tested for galactomannan (GM) antigenemia by Platelia Aspergillus ELISA (Bio-Rad Laboratories, Marnes-la-Coquette, France). A total of 37 of 117 serum samples were positive for BDG at a threshold of 80pg ml(-1) . Seven of 37 BDG positive serum samples had a GM index ≥0.5. When a cutoff value of ≥0.5 was used for GM positivity, 16 (13.3%) serum samples were positive. For a cutoff value of ≥0.7, eight (6.6%) serum samples were positive. There were no statistically significant differences in the median BDG levels (P=0.47) or median GM indices (P =0.28) of the various sampling times. None of the SAM vials tested positive for BDG or GM. After ruling out fungal infections and all known potential causes of false BDG positivity, environmental contamination remained possible cause of BDG reactivity. We did not observe any significant association of ampicillin-sulbactam administration and positive assays for BDG or GM. PMID:22040530

  2. Efficacy and cost-effectiveness of the 13C-urea breath test as the primary diagnostic investigation for the detection of Helicobacter pylori infection compared to invasive and non-invasive diagnostic tests

    PubMed Central

    Nocon, Marc; Kuhlmann, Alexander; Leodolter, Andreas; Roll, Stephanie; Vauth, Christoph; Willich, Stefan N.; Greiner, Wolfgang

    2009-01-01

    Background Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans. There is a risk factor for gastric or duodenal ulcers, gastric cancer and MALT (Mucosa Associated Lymphoid Tissue)-Lymphomas. There are several invasive and non-invasive methods available for the diagnosis of H. pylori. The 13C-urea breath test is a non-invasive method recommended for monitoring H. pylori eradication therapy. However, this test is not yet used for primary assessment of H. pylori in Germany. Objectives What are the clinical and health economic benefits of the 13C-urea breath test in the primary assessment of H. pylori compared to other invasive and non-invasive methods? Methods A systematic literature search including a hand search was performed for studies investigating test criteria and cost-effectiveness of the 13C-urea breath test in comparison to other methods used in the primary assessment of H. pylori. Only studies that directly compared the 13C-urea breath test to other H. pylori-tests were included. For the medical part, biopsy-based tests were used as the gold standard. Results 30 medical studies are included. Compared to the immunoglobulin G (IgG) test, the sensitivity of the 13C-urea breath test is higher in twelve studies, lower in six studies and one study reports no differences. The specificity is higher in 13 studies, lower in three studies and two studies report no differences. Compared to the stool antigen test, the sensitivity of the 13C-urea breath test is higher in nine studies, lower in three studies and one study reports no difference. The specificity is higher in nine studies, lower in two studies and two studies report no differences. Compared to the urease test, the sensitivity of the 13C-urea breath test is higher in four studies, lower in three studies and four studies report no differences. The specificity is higher in five studies, lower in five studies and one study reports no difference. Compared to histology, the

  3. First report of a mermithid nematode infecting the invasive Megacopta cribraria (Hemiptera: Plataspidae) in the United States.

    PubMed

    Stubbins, F L; Agudelo, P; Reay-Jones, F P F; Greene, J K

    2015-05-01

    Megacopta cribraria (Hemiptera: Plataspidae) has become a pest of soybean, Glycine max (L.), in the United States. While several natural enemies of M. cribraria have been reported, our study is the first to report nematodes beneath the pleural membranes in the abdominal cavities of adults. Morphological and molecular analyses suggest this nematode belongs to the family Mermithidae. This first report of a nematode infection in M. cribraria adds to the current inventory of enemies attacking this insect. Our observations provide a basis for future research to examine the impact of nematodes on M. cribraria mortality and to investigate their capacity to reduce populations. PMID:25731127

  4. Public Health Risk Communication by Text Message in Response to a Cluster of Invasive Meningococcal Infection in a Primary School

    PubMed Central

    Bradley, Declan T; Johnston, Jillian; Smyth, Brian

    2014-01-01

    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. PMID:24894450

  5. Listeria monocytogenes Isolates from Invasive Infections: Variation of Sero- and Genotypes during an 11-Year Period in Finland

    PubMed Central

    Lukinmaa, Susanna; Miettinen, Maria; Nakari, Ulla-Maija; Korkeala, Hannu; Siitonen, Anja

    2003-01-01

    Listeria monocytogenes strains that were isolated from 314 human listeriosis cases in Finland during an 11-year period were analyzed by O:H serotyping and pulsed-field gel electrophoresis (PFGE). Serotyping divided the isolates into five serotypes, the most common being 1/2a (53%) and 4b (27%). During the study period, the number of cases caused by serotype 1/2a increased from 22% in 1990 to 67% in 2001, and those caused by serotype 4b decreased from 61 to 27%, respectively. PFGE with restriction enzyme AscI divided the strains into 81 PFGE genotypes; among strains of serotypes 1/2a and 4b, 49 and 18 PFGE types were seen, respectively. PFGE type 1 (serotype 1/2a) was the most prevalent single type (37 strains). Together with six other, closely related PFGE types, PFGE type 1 formed a group of 71 strains, representing 23% of all 314 strains. Strains of PFGE type 1 have also been isolated from cold smoked fish, suggesting a source of human infections caused by this type. Moreover, PFGE type 24 (serotype 1/2c) was significantly associated with gender: 5% of 180 male subjects but none of 132 female subjects (P = 0.012). An electronic database library was created from the PFGE profiles to make possible the prompt detection of new emerging profiles and the tracing of potential infection clusters in the future. PMID:12682162

  6. 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…

  7. 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. PMID:24296499

  8. Intersubspecific Recombination in Xylella fastidiosa Strains Native to the United States: Infection of Novel Hosts Associated with an Unsuccessful Invasion

    PubMed Central

    Hopkins, Donald L.; Morano, Lisa D.; Russell, Stephanie E.; Stouthamer, Richard

    2014-01-01

    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. PMID:24296499

  9. Role of the cysteine protease interpain A of Prevotella intermedia in breakdown and release of haem from haemoglobin

    PubMed Central

    Byrne, Dominic P; Wawrzonek, Katarzyna; Jaworska, Anna; Birss, Andrew J; Potempa, Jan; Smalley, John W

    2010-01-01

    SUMMARY The Gram-negative oral anaerobe Prevotella intermedia forms an iron(III) protoporphyrin IX pigment from haemoglobin. The microorganism expresses a 90 kDa cysteine protease, Interpain A (InpA), 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 oxidised 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-TOF 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) stable 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 H2O as sixth co-ordinate ligand), and resulted in its complete breakdown and haem loss. Aquo-methaemoglobin proteolysis and haem release was prevented by blocking haem dissociation by ligation with azide, whilst 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 E64. 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. PMID:19814715

  10. 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

  11. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice

    PubMed Central

    Dziarski, Roman; Dowd, Scot E.; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species. PMID

  12. Pglyrp-Regulated Gut Microflora Prevotella falsenii, Parabacteroides distasonis and Bacteroides eggerthii Enhance and Alistipes finegoldii Attenuates Colitis in Mice.

    PubMed

    Dziarski, Roman; Park, Shin Yong; Kashyap, Des Raj; Dowd, Scot E; Gupta, Dipika

    2016-01-01

    Dysbiosis is a hallmark of inflammatory bowel disease (IBD), but it is unclear which specific intestinal bacteria predispose to and which protect from IBD and how they are regulated. Peptidoglycan recognition proteins (Pglyrps) are antibacterial, participate in maintaining intestinal microflora, and modulate inflammatory responses. Mice deficient in any one of the four Pglyrp genes are more sensitive to dextran sulfate sodium (DSS)-induced colitis, and stools from Pglyrp-deficient mice transferred to wild type (WT) germ-free mice predispose them to much more severe colitis than stools from WT mice. However, the identities of these Pglyrp-regulated bacteria that predispose Pglyrp-deficient mice to colitis or protect WT mice from colitis are not known. Here we identified significant changes in β-diversity of stool bacteria in Pglyrp-deficient mice compared with WT mice. The most consistent changes in microbiome in all Pglyrp-deficient mice were in Bacteroidales, from which we selected four species, two with increased abundance (Prevotella falsenii and Parabacteroides distasonis) and two with decreased abundance (Bacteroides eggerthii and Alistipes finegoldii). We then gavaged WT mice with stock type strains of these species to test the hypothesis that they predispose to or protect from DSS-induced colitis. P. falsenii, P. distasonis, and B. eggerthii all enhanced DSS-induced colitis in both WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora. By contrast, A. finegoldii (which is the most abundant species in WT mice) attenuated DSS-induced colitis both in WT mice with otherwise undisturbed intestinal microflora and in WT mice with antibiotic-depleted intestinal microflora, similar to the colitis protective effect of the entire normal microflora. These results identify P. falsenii, P. distasonis, and B. eggerthii as colitis-promoting species and A. finegoldii as colitis-protective species. PMID

  13. Scanning electron microscopy study of the adhesion of Prevotella nigrescens to the dentin of prepared root canals.

    PubMed

    Yang, Sung-Eun; Bae, Kwang-Shik

    2002-06-01

    The purpose of this study was to evaluate the effect of the presence or absence of amorphous, irregular smear layers on the adhesion of Prevotella nigrescens, to the dentin of the root canal by using scanning electron microscopy (SEM). Human incisors extracted within 7 days, with no cavities, no fractures, and no evidence of calcification of the canal, were selected. After cutting the crown portion at the CEJ, root canal preparation was undertaken by using a modified crown-down technique with Profile and Gates Glidden drills. Ten milliliters of physiologic saline solution (groups 1 and 4), 10 ml of 3.5% NaOCl (groups 2 and 5), or 10 ml of NaOCl and 10 ml of 0.5 M EDTA (groups 3 and 6) were used as irrigation solution while preparing the canal. After vertical sectioning and ethylene oxide gas sterilization, samples (groups 1, 2, and 3) were immersed in brain-heart infusion broth with yeast extract, hemin, and menadione, inoculated with P. nigrescens (ATCC 33563), and incubated for 3 h at 37 degrees C. All samples were prepared for and observed with SEM. The data were analyzed by using t test and one-way ANOVA. Smear layer was observed to cover the entire root canal surface after root canal preparation. Smear layer was removed and the entrances of dentinal tubules opened widely after applying 3.5% NaOCl and 0.5 M EDTA. A significantly greater number of bacteria were found to adhere to those teeth in which a smear layer was present (p < 0.05). Given that the smear layer produced during root canal preparation promoted adhesion and colonization of P. nigrescens to the dentin matrix, it might also increase the likelihood of canal reinfection. PMID:12067123

  14. A cluster of mucormycosis infections in hematology patients: challenges in investigation and control of invasive mold infections in high-risk patient populations.

    PubMed

    Llata, Eloisa; Blossom, David B; Khoury, H Jean; Rao, Carol Y; Wannemuehler, Kathleen A; Noble-Wang, Judith; Langston, Amelia A; Ribner, Bruce S; Lyon, G Marshall; Arnold, Kathryn E; Jackson, Deonne R; Brandt, Mary E; Chiller, Tom M; Balajee, S Arunmozhi; Srinivasan, Arjun; Magill, Shelley S

    2011-09-01

    Mucormycosis has been reported to be occurring more frequently in hematopoietic stem cell transplant (HSCT) recipients in recent years. We investigated a hospital cluster of mucormycosis cases among patients with hematologic disorders. Case-patients were identified through hospital microbiology and pathology database searches and compared to randomly selected controls matched on underlying disease and hospital discharge date using conditional logistic regression. Environmental assessments, including collection of samples for fungal cultures, were performed. Of 11 case-patients, 6 (55%) had acute myelogenous leukemia and 3 (27%) were allogeneic HSCT recipients. Five case-patients (45%) died. In univariate analysis, case-patients were more likely than controls to have refractory hematologic disease (odds ratio [OR], 13.75; 95% confidence interval [CI], 1.31-689); neutropenia >14 days (OR, 11.50; 95% CI, 1.27-558) or to have received voriconazole prophylaxis (OR, 11.26; 95% CI, 1.11-infinity). A point source was not identified. Factors such as underlying disease state and antifungal prophylaxis type may identify hematology patients at highest risk for mucormycosis. Our investigation highlighted critical knowledge gaps, including strain typing methods, the role of the hospital environment in mucormycosis outbreaks, and hospital environmental infection control measures most likely to reduce exposure of immunosuppressed persons to mucormycetes. PMID:21851872

  15. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

  16. 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. PMID:24438353

  17. The (1,3){beta}-D-glucan test as an aid to early diagnosis of invasive fungal infections following lung transplantation.

    PubMed

    Alexander, Barbara D; Smith, P Brian; Davis, R Duane; Perfect, John R; Reller, L Barth

    2010-11-01

    The Fungitell assay for (1,3)β-D-glucan (BG) detection in serum has been evaluated in patients with invasive fungal infections (IFIs) and healthy controls and for the early diagnosis of IFI in cancer patients. We evaluated the BG assay for the detection of IFI in lung transplant recipients. Serial serum samples were prospectively collected from patients undergoing lung transplants at Duke Hospital. Fungal infections were classified according to revised European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. A receiver operator characteristic (ROC) curve was generated; possible causes for false-positive and false-negative tests were investigated by linear regression analysis. Seven hundred fifty-six serum specimens from 59 subjects without IFI and 41 specimens from 14 patients with proven or probable IFI were tested. The area under the ROC curve was 0.69. Based on a 60-pg/ml positive cutoff, per-patient sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 64%, 9%, 14%, and 50%, respectively; per-test estimates were 71%, 59%, 9%, and 97%, respectively. The majority (92%) of patients not diagnosed with an IFI had at least one BG level of ≥60 pg/ml, and 90% had at least one BG level of ≥80 pg/ml. Respiratory colonization with mold and hemodialysis significantly affected mean BG levels. In conclusion, the accuracy of the BG test is marginal and its utility as a tool for the early diagnosis of IFI is questionable in the lung transplant population. Although the NPV of the BG test is high, the low PPV limits its utility as a screening tool for early diagnosis of IFI. PMID:20720025

  18. Usefulness of non-invasive serum markers for predicting liver fibrosis in Egyptian patients with chronic HCV infection.

    PubMed

    El Guesiry, Dalal; Moez, Pacinte; Hossam, Nermine; Kassem, Mohamed

    2011-01-01

    Accurate monitoring of liver fibrosis changes in patients with hepatitis C virus (HCV) infection would be helpful in defining the need to intervene, implement the appropriate response in treatment and to minimize the use of liver biopsy. We aimed to evaluate the diagnostic utility of the different serum markers and indices in detecting liver fibrosis in study patients. Initial liver biopsy, routine liver function tests, estimation of hyaluronic acid, MMP-1, and PIIINP levels was performed for 30 Egyptian patients with HCV and 15 controls. Marker algorithms based on common laboratory such APRI score, Fibrotest and Actitest. PIIINP and MMP-1 serum markers were combined and entered into a stepwise logistic regression analysis with formulation of a score equation for fibrosis staging. Combined PIIINP and MMP-1 yielded different cut off scores to estimate two clinically relevant fibrosis stages: "significant fibrosis" versus "extensive fibrosis. Apri score also showed AUC of 1.0 with 100 % sensitivity and specificity to exclude the presence of cirrhosis and was significantly correlated to Metavair fibrosis stage in early fibrosis. On the other hand, PIIINP, Fibrotest and acti test were significantly correlated to Metavair fibrosis stage in both early and late fibrosis. In conclusion, integrating PIIINP/MMP-1 score was able to provide reliable information about the degree of liver fibrosis in chronic hepatitis C patients using different cut-offs values. A combination of liver markers as well as its related indices is an emerging tool to differentiate early from advanced liver fibrosis in HCV patients. PMID:23082465

  19. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    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

  20. 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

  1. Routine pre-and post-hematopoietic stem cell transplant computed tomography of the abdomen for detecting invasive fungal infection has limited value

    PubMed Central

    Kaste, Sue C.; Kaufman, Robert A.; Sunkara, Anusha; Kang, Guolian; Morris, Cynthia; Leung, Wing; Srinivasan, Ashok

    2015-01-01

    The diagnostic utility of obtaining chest and abdomen CT evaluating for invasive fungal infection (IFI) pre-and post-HSCT remains unclear. The study was conducted as a Quality Improvement project. Chest and abdomen CT of patients who underwent an allogeneic HSCT over a 13 month period were reviewed. Scans included those done pre-transplant in all patients, and day 0–100 post-transplant in selected patients. There were 66 patients with chest and abdomen CT scans pre-transplant. Chest CT was suggestive of IFI in 9 (13.6%) patients including 3 patients with prior history of IFI. After transplant, 37 patients had initial chest CT, and 14 patients had initial abdominal CT. The first chest CT post-transplant was suggestive of IFI in 3 patients; all had an abnormal CT pre-transplant. Following the initial post-transplant evaluation 15 patients had 28 additional CT scans of the chest, and 12 patients had 19 additional CT scans of the abdomen. An abnormal chest CT with proven evidence of IFI was seen in only one patient. None of the 99 abdominal CT scans performed pre-or post-transplant had evidence of IFI. There is little benefit in obtaining abdominal CT scans in HSCT patients for detecting IFI either pre-or post-transplant. PMID:25748273

  2. Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections.

    PubMed

    Wang, Taotao; Zhu, Huifang; Sun, Jinyao; Cheng, Xiaoliang; Xie, Jiao; Dong, Haiyan; Chen, Limei; Wang, Xue; Xing, Jianfeng; Dong, Yalin

    2014-11-01

    The aim of this study was to determine an optimum voriconazole target concentration, to study the influence of CYP2C19 gene status on metabolism of voriconazole and to identify a dose-adjustment strategy for voriconazole according to CYP2C19 polymorphism in patients with invasive fungal infections. A total of 328 voriconazole trough plasma concentrations (C(min)) were collected and monitored from 144 patients. Information on efficacy and safety was obtained. Voriconazole therapy was effective in 81.9% of patients (118/144), and 12.5% (18/144) exhibited signs of hepatotoxicity. The relationships between voriconazole C(min) and clinical response and hepatotoxicity were explored using logistic regression, and a target clinical C(min) range of 1.5-4 mg/L was identified. Values of voriconazole C(min) and the ratio of C(min) to concentration of voriconazole-N-oxide (C(min)/C(N)) of poor metabolisers (PMs) were significantly higher than extensive metabolisers and intermediate metabolisers. Model-based simulations showed that PM patients could be safely and effectively treated with 200 mg twice daily orally or intravenously, and non-PM patients with 300 mg twice daily orally or 200mg twice daily intravenously. This study highlighted that voriconazole C(min) and C(min)/C(N) are strongly influenced by CYP2C19 polymorphism, and gene-adjusted dosing is important to achieve therapeutic levels that maximise therapeutic response and minimise hepatotoxicity. PMID:25239277

  3. Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

    PubMed Central

    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

    2014-01-01

    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.) PMID:25049247

  4. 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

  5. Routine pre- and post-hematopoietic stem cell transplant computed tomography of the abdomen for detecting invasive fungal infection has limited value.

    PubMed

    Kaste, Sue C; Kaufman, Robert A; Sunkara, Anusha; Kang, Guolian; Morris, Cynthia; Leung, Wing; Srinivasan, Ashok

    2015-06-01

    The diagnostic utility of obtaining chest and abdomen computed tomography (CT) to evaluate for invasive fungal infection (IFI) before and after hematopoietic stem cell transplant (HSCT) remains unclear. The study was conducted as a quality improvement project. Chest and abdomen CT of patients who underwent an allogeneic HSCT over a 13-month period were reviewed. Scans included those performed pretransplant in all patients and days 0 to 100 post-transplant in selected patients. Sixty-six patients had chest and abdomen CT scans pretransplant. Chest CT was suggestive of IFI in 9 patients (13.6%), including 3 patients with prior history of IFI. After transplant, 37 patients had an initial chest CT and 14 patients an initial abdominal CT. The first chest CT post-transplant was suggestive of IFI in 3 patients; all had an abnormal CT pretransplant. After the initial post-transplant evaluation, 15 patients had 28 additional CT scans of the chest and 12 patients 19 additional CT scans of the abdomen. An abnormal chest CT with proven evidence of IFI was seen in only 1 patient. None of the 99 abdominal CT scans performed pre- or post-transplant had evidence of IFI. There is little benefit in obtaining abdominal CT scans in HSCT patients for detecting IFI either pre- or post-transplant. PMID:25748273

  6. 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

    2010-01-01

    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. PMID:19814715

  7. 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

  8. 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

  9. The majority of adult pneumococcal invasive infections in Portugal are still potentially vaccine preventable in spite of significant declines of serotypes 1 and 5.

    PubMed

    Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

    2013-01-01

    In Portugal, pneumococcal conjugate vaccines have been administered to children outside of the national immunization plan since 2001. We determined the serotype and antimicrobial susceptibility of 1265 isolates responsible for adult invasive pneumococcal infections (IPD) between 2009 and 2011 and compared the results with previously published data from 1999 to 2008. Serotypes 3 (12.6%), 7F (10.0%), 19A (9.1%), 14 (8.4%), 1 (6.9%) and 8 (6.2%) were the most frequent and together accounted for 53.2% of adult IPD. Serotypes 1 and 5 declined significantly while serotype 34, not included in any vaccine, increased. Taken together, the serotypes included in the 13-valent conjugate vaccine (PCV13) peaked among adult IPD isolates in 2008 (70.2%) and declined since then reaching 53.5% in 2011. The decline in the serotypes included in the 23-valent polysaccharide vaccine since 2007 was also significant but much more modest with 79.2% of the isolates causing IPD in 2011 expressing these serotypes. Since the changes in serotypes causing IPD in adults coincided with the 10-valent and PCV13 introduction in children, it is unlikely that vaccination triggered these changes although it may have accelerated them. The proportion of IPD caused by serotypes included in the 7-valent conjugate vaccine remained stable (19.0%). Both penicillin non-susceptibility and erythromycin resistance increased in the study period, with serotypes 14 and 19A accounting for the majority of resistant isolates. PMID:24066064

  10. Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections.

    PubMed

    Jakobsen, H; Schulz, D; Pizza, M; Rappuoli, R; Jónsdóttir, I

    1999-11-01

    Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans. PMID:10531245

  11. 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

    Chung, Tae-Ho; Kim, Hee-Dong; Lee, Young-Sun; Hwang, Cheol-Yong

    2014-01-01

    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

  12. Immunoglobulin G and A Antibody Responses to Bacteroides forsythus and Prevotella intermedia in Sera and Synovial Fluids of Arthritis Patients

    PubMed Central

    Moen, Ketil; Brun, Johan G.; Madland, Tor Magne; Tynning, Turid; Jonsson, Roland

    2003-01-01

    The objective of the present study was to investigate immunoglobulin G (IgG) and IgA antibody immune responses to Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Candida albicans in the sera of patients with rheumatoid arthritis (RA), the synovial fluid (SF) of patients with RA (RA-SF samples), and the SF of patients without RA (non-RA-SF samples). An enzyme-linked immunosorbent assay was used to determine IgG and IgA antibody levels in 116 serum samples from patients with RA, 52 RA-SF samples, and 43 non-RA-SF samples; and these were compared with those in SF samples from 9 patients with osteoarthritis (OA-SF samples) and the blood from 100 donors (the control [CTR] group). Higher levels of IgG antibodies against B. forsythus (P < 0.0001) and P. intermedia (P < 0.0001) were found in non-RA-SF samples than in OA-SF samples, and higher levels of IgG antibodies against B. forsythus (P = 0.003) and P. intermedia (P = 0.024) were found in RA-SF samples than in OA-SF samples. Significantly higher levels of IgA antibodies against B. forsythus were demonstrated in both RA-SF and non-RA-SF samples than in OA-SF samples. When corrected for total Ig levels, levels of IgG antibody against B. forsythus were elevated in RA-SF and non-RA-SF samples compared to those in OA-SF samples. Lower levels of Ig antibodies against B. forsythus were found in the sera of patients with RA than in the plasma of the CTR group for both IgG (P = 0.003) and IgA (P < 0.0001). When corrected for total Ig levels, the levels of IgG and IgA antibodies against B. forsythus were still found to be lower in the sera from patients with RA than in the plasma of the CTR group (P < 0.0001). The levels of antibodies against P. gingivalis and C. albicans in the sera and SF of RA and non-RA patients were comparable to those found in the respective controls. The levels of IgG and IgA antibodies against B. forsythus were elevated in SF from patients with RA and non-RA-SF samples

  13. 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

  14. 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 SiglecFlow Alveolar Macrophages

    PubMed Central

    Sanfilippo, Alan M.; Furuya, Yoichi; Roberts, Sean; Salmon, Sharon L.

    2015-01-01

    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 SiglecFlow 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. PMID:25964474

  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. PMID:25964474

  16. Isolation of invasive Plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors.

    PubMed

    Mutungi, Joe Kimanthi; Yahata, Kazuhide; Sakaguchi, Miako; Kaneko, Osamu

    2015-11-01

    Malaria symptoms and pathogenesis are caused by blood stage parasite burdens of Plasmodium spp., for which invasion of red blood cells (RBCs) by merozoites is essential. Successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding RBC invasion. To understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activity in vitro. Accordingly, methods have been developed to isolate invasive Plasmodium knowlesi and Plasmodium falciparum merozoites. Rodent malaria parasite models offer ease in laboratory maintenance and experimental genetic modifications; however, no methods have been reported regarding isolation of high numbers of invasive rodent malaria merozoites. In this study, Plasmodium yoelii-infected RBCs were obtained from infected mice, and mature schizont-infected RBCs enriched via Histodenz™ density gradients. Merozoites retaining invasion activity were then isolated by passing the preparations through a filter membrane. RBC-invaded parasites developed to mature stages in vitro in a synchronous manner. Isolated merozoites were evaluated for retention of invasion activity following storage at different temperatures prior to incubation with uninfected mouse RBCs. Isolated merozoites retained their invasion activity 4h after isolation at 10 or 15 °C, whereas their invasion activity reduced to 0-10% within 30 min when incubated on ice or at 37 °C prior to RBC invasion assay. Images of merozoites at successive steps during RBC invasion were captured by light and transmission electron microscopy. Synthetic peptides derived from the amino acid sequence of the P. yoelii invasion protein RON2 efficiently inhibited RBC invasion. The developed method to isolate and keep invasive P. yoelii merozoites for up to 4h is a powerful tool to study the RBC invasion biology of this parasite

  17. Invasive pneumococcal disease leads to activation and hyperreactivity of platelets.

    PubMed

    Tunjungputri, Rahajeng N; de Jonge, Marien I; de Greeff, Astrid; van Selm, Saskia; Buys, Herma; Harders-Westerveen, Jose F; Stockhofe-Zurwieden, Norbert; Urbanus, Rolf T; de Groot, Phillip G; Smith, Hilde E; van der Ven, Andre J; de Mast, Quirijn

    2016-08-01

    Using a novel porcine model of intravenous Streptococcus pneumoniae infection, we showed that invasive pneumococcal infections induce marked platelet activation and hyperreactivity. This may contribute to the vascular complications seen in pneumococcal infection. PMID:27322088

  18. Incidence Density of Invasive Fungal Infections during Primary Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Patients in a Tertiary Cancer Center, 2009 to 2011

    PubMed Central

    Mulanovich, Victor E.; Jiang, Y.; Lewis, Russell E.

    2014-01-01

    Although primary antifungal prophylaxis (PAP) is routinely administered in patients with acute myeloid leukemia (AML) during remission-induction and consolidation chemotherapy, the impact of PAP on the incidence of invasive fungal infections (IFIs) is not well described. We retrospectively analyzed the incidence of IFIs in 152 patients with AML who had been admitted to a tertiary cancer center between August 2009 and March 2011 and received PAP within 120 days after first remission-induction chemotherapy. We excluded patients who had undergone stem cell transplantation. Patients received a PAP drug with anti-Aspergillus activity during 72% (7,660/10,572) of prophylaxis-days. The incidence of documented IFIs (definite or probable according to revised European Organization for Research and Treatment of Cancer [EORTC] criteria) was 2.0/1,000 prophylaxis-days (95% confidence interval [CI], 1.23 to 3.04). IFIs due to molds were more common than IFIs due to yeasts (1.5/1,000 prophylaxis-days versus 0.4/1,000 prophylaxis-days; P = 0.01). Echinocandin-based PAP (8.6 and 7.1/1,000 prophylaxis-days, respectively) was associated with higher rates of documented IFIs than anti-Aspergillus azoles (voriconazole or posaconazole) (2.4 and 1.1/1,000 prophylaxis-days, respectively) at both 42 days (P = 0.03) and 120 days (P < 0.0001) after first remission-induction chemotherapy. The incidence of overall (documented and presumed) IFIs (P < 0.001), documented IFIs (P < 0.01), and empirical antifungal therapies (P < 0.0001) was higher during the first 42 days than after day 42. Despite the broad use of PAP with anti-Aspergillus activity, IFIs, especially molds, remain a significant cause of morbidity and mortality in AML patients, predominantly during the remission-induction phase. Patients receiving echinocandin-based PAP experienced higher rates of IFIs than did those receiving anti-Aspergillus azoles. PMID:24277033

  19. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-β-D-glucan for invasive fungal infection: Focus on cutoff levels.

    PubMed

    He, Song; Hang, Ju-Ping; Zhang, Ling; Wang, Fang; Zhang, De-Chun; Gong, Fang-Hong

    2015-08-01

    To assess the diagnostic accuracy of 1,3-β-D-glucan (BDG) assay for diagnosing invasive fungal infections (IFI), we searched the Medline and Embase databases, and studies reporting the performance of BDG assays for the diagnosis of IFI were identified. Our analysis was mainly focused on the cutoff level. Meta-analysis was performed using conventional meta-analytical pooling and bivariate analysis. Our meta-analysis covered 28 individual studies, in which 896 out of 4214 patients were identified as IFI positive. The pooled sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating characteristic (AUC-SROC) curve were 0.78 [95% confidence interval (CI), 0.75-0.81], 0.81 (95% CI, 0.80-0.83), 21.88 (95% CI, 12.62-37.93), and 0.8855, respectively. Subgroup analyses indicated that in cohort studies, the cutoff value of BDG at 80 pg/mL had the best diagnostic accuracy, whereas in case-control studies the cutoff value of 20 pg/mL had the best diagnostic accuracy; moreover, the AUC-SROC in cohort studies was lower than that in case-control studies. The cutoff value of 60 pg/mL has the best diagnostic accuracy with the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria as a reference standard. The 60 pg/mL cutoff value has the best diagnostic accuracy with the Fungitell assay compared to the BDG detection assay. The cutoff value of 20 pg/mL has the best diagnostic accuracy with the Fungitec G-test assay, and the cutoff value of 11 pg/mL has the best diagnostic accuracy with the Wako assay. Serum BDG detection is highly accurate for diagnosing IFIs. As such, 60 pg/mL of BDG level can be used as the best cutoff value to distinguish patients with IFIs from patients without IFI (mainly due to Candida and Aspergillus). PMID:25081986

  20. 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

  1. 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. PMID:27015202

  2. 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

  3. 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

  4. 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

  5. Executive summary of the diagnosis and antimicrobial treatment of invasive infections due to multidrug-resistant Enterobacteriaceae. Guidelines of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

    PubMed

    Rodríguez-Baño, Jesús; Cisneros, José Miguel; Cobos-Trigueros, Nazaret; Fresco, Gema; Navarro-San Francisco, Carolina; Gudiol, Carlota; Horcajada, Juan Pablo; López-Cerero, Lorena; Martínez, José Antonio; Molina, José; Montero, Milagro; Paño-Pardo, José R; Pascual, Alvaro; Peña, Carmen; Pintado, Vicente; Retamar, Pilar; Tomás, María; Borges-Sa, Marcio; Garnacho-Montero, José; Bou, Germán

    2015-05-01

    The spread of multidrug-resistant Enterobacteriaceae related to the production of extended-spectrum β-lactamases (ESBL) and carbapenemases is a serious public health problem worldwide. Microbiological diagnosis and therapy of these infections are challenging and controversial. After the selection of clinically relevant questions, this document provides evidence-based recommendations for the use of microbiological techniques for the detection of ESBL- and carbapenemase-producing Enterobacteriaceae, and for antibiotic therapy for invasive infections caused by these organisms. The absence of randomized-controlled trials is noteworthy, thus recommendations are mainly based on observational studies, that have important methodological limitations, pharmacokinetic and pharmacodynamics models, and data from animal studies. Additionally, areas for future research were identified. PMID:25563393

  6. 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

    Evans, Holly; Killoran, Kristin E; Mitre, Blima K; Morris, C Paul; Kim, So-Young; Mitre, Edward

    2015-10-01

    In this study, we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to OVA. Ten 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 most likely due to increased Ab catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed Ab production. Ear histology 24 h 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 Ab-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases. PMID:26324775

  7. Imaging infection.

    PubMed

    Ketai, Loren; Jordan, Kirk; Busby, Katrina H

    2015-06-01

    Thoracic imaging is widely used to detect lower respiratory tract infections, identify their complications, and aid in differentiating infectious from noninfectious thoracic disease. Less commonly, the combination of imaging findings and a clinical setting can favor infection with a specific organism. This confluence can occur in cases of bronchiectatic nontuberculous mycobacterial infections in immune-competent hosts, invasive fungal disease among neutropenic patients, Pneumocystis jiroveci pneumonia in patients with AIDS, and in cytomegalovirus infections in patients with recent hematopoietic cell transplantation. These specific diagnoses often depend on computed tomography scanning rather than chest radiography alone. PMID:26024600

  8. Inverse relation between disease severity and expression of the streptococcal cysteine protease, SpeB, among clonal M1T1 isolates recovered from invasive group A streptococcal infection cases.

    PubMed

    Kansal, R G; McGeer, A; Low, D E; Norrby-Teglund, A; Kotb, M

    2000-11-01

    The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases. The expression and amount of the 28-kDa SpeB protein produced were determined by quantitative Western blotting, and protease activity was measured by a fluorescent enzymatic assay. A high degree of variation in SpeB expression was seen among the isolates, and this variation seemed to correlate with the severity and/or clinical manifestation of the invasive infection. The mean amount of 28-kDa SpeB protein and cysteine protease activity produced by isolates from nonsevere cases was significantly higher than that from STSS cases (P = 0.001). This difference was partly due to the fact that 41% of STSS isolates produced little or no SpeB compared to only 14% of isolates recovered in nonsevere cases. Moreover, the cysteine protease activity among those isolates that expressed SpeB was significantly lower for STSS isolates than for isolates from nonsevere cases (P = 0.001). Increased SpeB production was also inversely correlated with intact M protein expression, and inhibition of cysteine protease activity blocked the cleavage of the surface M protein. Together, the data support the existence of both an "on-off" and a posttranslational regulatory mechanism(s) controlling SpeB production, and they suggest that isolates with the speB gene in the "off" state are more likely to spare the surface M protein and to be isolated from cases of severe rather than nonsevere invasive infection. These findings may have important implications for the role of SpeB in host-pathogen interactions via regulation of the expression of GAS

  9. Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases

    PubMed Central

    Kansal, Rita G.; McGeer, Allison; Low, Donald E.; Norrby-Teglund, Anna; Kotb, Malak

    2000-01-01

    The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases. The expression and amount of the 28-kDa SpeB protein produced were determined by quantitative Western blotting, and protease activity was measured by a fluorescent enzymatic assay. A high degree of variation in SpeB expression was seen among the isolates, and this variation seemed to correlate with the severity and/or clinical manifestation of the invasive infection. The mean amount of 28-kDa SpeB protein and cysteine protease activity produced by isolates from nonsevere cases was significantly higher than that from STSS cases (P = 0.001). This difference was partly due to the fact that 41% of STSS isolates produced little or no SpeB compared to only 14% of isolates recovered in nonsevere cases. Moreover, the cysteine protease activity among those isolates that expressed SpeB was significantly lower for STSS isolates than for isolates from nonsevere cases (P = 0.001). Increased SpeB production was also inversely correlated with intact M protein expression, and inhibition of cysteine protease activity blocked the cleavage of the surface M protein. Together, the data support the existence of both an “on-off” and a posttranslational regulatory mechanism(s) controlling SpeB production, and they suggest that isolates with the speB gene in the “off” state are more likely to spare the surface M protein and to be isolated from cases of severe rather than nonsevere invasive infection. These findings may have important implications for the role of SpeB in host-pathogen interactions via regulation of the expression of

  10. Comparison of in vitro susceptibility characteristics of Candida species from cases of invasive candidiasis in solid organ and stem cell transplant recipients: Transplant-Associated Infections Surveillance Network (TRANSNET), 2001 to 2006.

    PubMed

    Lockhart, Shawn R; Wagner, Debra; Iqbal, Naureen; Pappas, Peter G; Andes, David R; Kauffman, Carol A; Brumble, Lisa M; Hadley, Susan; Walker, Randall; Ito, James I; Baddley, John W; Chiller, Tom; Park, Benjamin J

    2011-07-01

    Invasive fungal infections (IFI) are a major cause of morbidity and mortality among both solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. Candida is the most common cause of IFI in SOT recipients and the second most common cause of IFI in HSCT recipients. We determined susceptibilities to fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, and caspofungin for 383 invasive Candida sp. isolates from SOT and HSCT recipients enrolled in the Transplant-Associated Infection Surveillance Network and correlated these results to clinical data. Fluconazole resistance in C. albicans, C. tropicalis, and C. parapsilosis isolates was low (1%), but the high percentage of C. glabrata and C. krusei isolates within this group of patients increased the overall percentage of fluconazole resistance to 16%. Voriconazole resistance was 3% overall but was 8% among C. glabrata isolates. On multivariable analysis, among HSCT recipients fluconazole nonsusceptibility was independently associated with C. glabrata, non-Hodgkin's lymphoma, cytomegalovirus (CMV) antigenemia, diabetes active at the time of the IFI, and any prior amphotericin B use; among SOT recipients, fluconazole nonsusceptibility was independently associated with any fluconazole use in the 3 months prior to the IFI, C. glabrata, ganciclovir use in the 3 months prior to the IFI, diabetes acquired since the transplant, and gender. PMID:21562099

  11. Comparison of host cell invasion and proliferation among Neospora caninum isolates obtained from oocysts and from clinical cases of naturally infected dogs.

    PubMed

    Dellarupe, A; Regidor-Cerrillo, J; Jiménez-Ruiz, E; Schares, G; Unzaga, J M; Venturini, M C; Ortega-Mora, L M

    2014-10-01

    In a previous study we have shown that the in vitro invasion rate (IR) and tachyzoite yield (TY) are associated with the virulence phenotypes of Neospora caninum isolates of bovine origin. In addition, we recently observed marked differences in virulence when canine isolates were compared in a pregnant BALB/c mouse model. In this study, we investigated whether invasion and proliferation capacities could be used as virulence-related N. caninum phenotypic traits. Of the isolates compared in mice, four canine isolates obtained from oocysts (Nc-Ger2, Nc-Ger3, Nc-Ger-6, Nc-6 Arg) had shown a low-moderate virulence, and two further isolates obtained from dogs with neurological signs (Nc-Bahia, Nc-Liv) were highly virulent. The IR for each isolate was determined by a plaque assay and the counting of immunofluorescence-labeled parasitophorous vacuoles at 3 days post-inoculation (p.i.). The TY was determined by the quantification of tachyzoites at 56 h p.i. by real-time PCR. Most of the canine isolates showed similar IR values under controlled invasion conditions for 4h and 72 h p.i., indicating a limited time period for invasion similar to that observed for bovine isolates. The Nc-Ger3, Nc-Bahia, and Nc-Liv isolates showed a significantly higher IR and TY than the Nc-Ger2 and Nc-Ger6 isolates (P<0.0001). A correlation was found between the IRs and TY (ρ>0.885, P<0.033), as well as between the TY and both dam morbidity (ρ=0.8452, P<0.033) and pup mortality (ρ>0.8117, P<0.058) in mice. These results demonstrate the importance both the invasive and proliferative capacities have on the virulence of canine N. caninum isolates. PMID:25045851

  12. 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

  13. 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

  14. 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

    Colombier, Marie-Alice; Alanio, Alexandre; Denis, Blandine; Melica, Giovanna; Garcia-Hermoso, Dea; Levy, Bénédicte; Peraldi, Marie-Noëlle; Glotz, Denis; Bretagne, Stéphane; Gallien, Sébastien

    2015-07-01

    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

  15. Invasive aspergillosis in primary immunodeficiencies.

    PubMed

    Almyroudis, N G; Holland, S M; Segal, B H

    2005-05-01

    Primary immunodeficiencies are rare and usually first manifest during childhood. Invasive aspergillosis is the leading cause of mortality in chronic granulomatous disease (CGD), reflecting the key role of the phagocyte NADPH oxidase in host defense against opportunistic fungi. Despite interferon-gamma prophylaxis, invasive filamentous fungal infections are a persistent problem in CGD. Key principles of management of fungal infections involve early recognition and aggressive treatment and appropriate surgical debridement of localized disease. Because CGD is a disorder of phagocyte stem cells in which the gene defects are well defined, it is a model disease to evaluate immune reconstitution through stem cell transplantation and gene therapy. Patients with the hyper-IgE syndrome with recurrent infections (Job syndrome) are prone to colonization of lung cavities (pneumatoceles) by Aspergillus species leading to local invasion and rarely disseminated infection. Other primary phagocytic disorders, T-cell disorders, and mitochondrial disorders are uncommonly associated with invasive aspergillosis. Taken together, these rare primary immunodeficiencies highlight the complex coordination of both innate and acquired pathways mediating host defense against Aspergillus infection. PMID:16110817

  16. [Invasive disease due to Streptococcus pyogenes in a patient with A H1N1 influenza infection. Report of one case].

    PubMed

    Guerrero S, Gonzalo; Marín S, Felipe

    2015-08-01

    Bacterial superinfection is a known complication among patients affected by viral respiratory tract infections. Streptococcus pyogenes, a major bacterial agent involved in acute tonsillopharyngitis, skin and soft tissue infections, was reported as a co-infecting microorganism during the 2009 A H1N1 influenza pandemic. We report a 65-year-old male patient who evolved with multifocal pneumonia and multiple organ failure with a fatal outcome. Influenza A H1N1 was detected by a polymerase chain reaction-based technique from a tracheal aspirate sample. S. pyogenes was identified by a rapid test from a nasopharyngeal sample and isolated afterwards from a positive blood culture. PMID:26436938

  17. Invasive mammals.

    PubMed

    Moutou, F; Pastoret, P P

    2010-08-01

    Every region of the world is concerned by potential mammal invasions, as humans are already present on all the world's land masses. All these invasions are a result of species introductions by humans for one reason or another. The authors briefly review the known movements and observed consequences of mammal-related invasions. They take examples from all five continents, as well as from a few island systems. The ancient introduction of game species, and later of domestic species, has been followed more recently by movements of commercial species. We are now seeing the emergence of what are known as entertainment species. In a number of cases, such introductions have led to the establishment of new epidemiological cycles that previously might never have been thought possible. According to current indicators, this phenomenon is not on the wane. PMID:20919577

  18. 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

  19. Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/Prevotella in Diet-Induced Obese Mice

    PubMed Central

    Neyrinck, Audrey M.; Possemiers, Sam; Druart, Céline; Van de Wiele, Tom; De Backer, Fabienne; Cani, Patrice D.; Larondelle, Yvan; Delzenne, Nathalie M.

    2011-01-01

    Background Alterations in the composition of gut microbiota - known as dysbiosis - has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice. Methodology/Principal Findings Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters. Conclusions/Significance Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti

  20. Invasive streptococcal infections in the era before the acquired immune deficiency syndrome: a 10 years' compilation of patients with streptococcal bacteraemia in North Yorkshire.

    PubMed

    Barnham, M

    1989-05-01

    Significant streptococcal (non-pneumococcal, non-enterococcal) bacteraemia was detected in 100 patients in two Health Districts of North Yorkshire in the decade 1978-1988. Patients with these infections accounted for 11% of the total 902 patients in the districts in whom bacteraemia was diagnosed during the period. Infection was most often seen with beta-haemolytic streptococci (52 patients) comprising Lancefield group A (Streptococcus pyogenes) (20 patients), group B (13), group C (5), group G (9), haemolytic Streptococcus milleri and non-groupable streptococci (5). The wide variety of serious infections included cellulitis, abscess, septicaemia, pneumonia, septic arthritis, necrotising fasciitis, acute endocarditis and mycotic aneurysm. Of these 52 patients, 21 (40%) died. alpha-Haemolytic streptococcal bacteraemia was diagnosed in 38 patients of whom 24 (63%) suffered from endocarditis and three (8%) died. Three of ten patients with non-haemolytic or anaerobic streptococcal bacteraemia died also. Six of the 100 patients with streptococcal bacteraemia had concomitant acute virus infections. Of the total 56 patients with infective endocarditis diagnosed in the districts during the period, streptococci were responsible in 30 (54%) of them. The predisposing factors, clinical features and outcome of the infections are described and discussed. PMID:2663996

  1. 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. PMID:27168588

  2. 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...

  3. Current and future therapies for invasive aspergillosis.

    PubMed

    Bassetti, Matteo; Pecori, Davide; Della Siega, Paola; Corcione, Silvia; De Rosa, Francesco Giuseppe

    2015-06-01

    Invasive fungal infections have increase worldwide and represent a threat for immunocompromised patients including HIV-infected, recipients of solid organ and stem cell transplants, and patients receiving immunosuppressive therapies. High mortality rates and difficulties in early diagnosis characterize pulmonary fungal infections. Invasive pulmonary aspergillosis has been reviewed focussing on therapeutic management. Although new compounds have become available in the past years (i.e., amphotericin B lipid formulations, last-generation azoles, and echinocandines), new diagnostic tools and careful therapeutic management are mandatory to assure an early appropriate targeted treatment that represents the key factor for a successful conservative approach in respiratory fungal infections. PMID:24994691

  4. Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice.

    PubMed

    Wu, Xilin; Liu, Li; Cheung, Ka-Wai; Wang, Hui; Lu, Xiaofan; Cheung, Allen Ka Loon; Liu, Wan; Huang, Xiuyan; Li, Yanlei; Chen, Zhiwei W; Chen, Samantha M Y; Zhang, Tong; Wu, Hao; Chen, Zhiwei

    2016-09-01

    Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV-1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24(+) cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4(+) T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24(+)/CD3(+) T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1(+) microglial cells and GFAP(+) astrocytes, respectively. The increased Iba1(+) microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN(+) neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG-HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis. PMID:26838362

  5. Invasive aspergillosis complicating Cushing's syndrome.

    PubMed

    Walsh, T J; Mendelsohn, G

    1981-08-01

    Patients with Cushing's syndrome are susceptible to opportunistic infections. Invasive fungal infections in patients with Cushing's syndrome caused by endogenous glucocorticoid excess rarely are reported, and aspergillosis occurring in this setting, to our knowledge, has not been described. Two patients with Cushing's syndrome and notably elevated levels of circulating cortisol had invasive aspergillosis develop. A patient with endogenous hypercortisolism caused by adrenal cortical carcinoma suffered a subarachnoid hemorrhage from rupture of an Aspergillus mycotic aneurysm. The other patient, who had an adrenocorticotrophic hormone-producing prostatic carcinoma, had pulmonary and disseminated aspergillosis develop. Exogenous corticosteroids are known clinically and experimentally to facilitate disseminated aspergillosis. Endogenous hypercortisolism also may bae an important factor predisposing to invasive aspergillosis. PMID:7259386

  6. Evaluation of anti-microbial activity of spore powder of Ganoderma lucidum on clinical isolates of Prevotella intermedia: A pilot study

    PubMed Central

    Nayak, Ranganath N.; Dixitraj, P. T.; Nayak, Aarati; Bhat, Kishore

    2015-01-01

    Aim: This study aimed at evaluating the anti-microbial activity of spore powder of Ganoderma lucidum on Prevotella intermedia isolated from subgingival plaque from chronic periodontitis patients. Settings and Design: Written informed consent was obtained from each subject enrolled in the study. The Institutional Ethics Committee granted the ethical clearance for the study. Materials and Methods: This study included 20 patients diagnosed with chronic periodontitis. Pooled subgingival plaque samples were collected using sterile curettes from the deepest sites of periodontal pockets. The collected samples were then transported in 1 mL of reduced transport fluid. The organisms were cultured and confirmed. These organisms were then used for minimum inhibitory concentration (MIC) procedure. Statistical Analysis: Mean of the MIC value obtained was calculated. Results: Thirteen out of the 20 clinical samples were tested that showed sensitivity at various concentrations. Five samples showed sensitivity at all concentrations. Twelve samples showed sensitivity at 8 mcg/ml. Eleven samples showed sensitivity at 4 mcg/ml, 8 samples showed sensitivity at 2 mcg/ml, and 5 samples showed sensitivity even at 1 mcg/ml. Mean MIC value of G. lucidum spore powder for P. intermedia obtained was 3.62 mcg/ml. Conclusion: G. lucidum with its multipotential bioactivity could be used as an anti-microbial, in conjunction with conventional therapy in periodontal disease. PMID:26604581

  7. 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

  8. Clinical viability of Fungitell, a new (1→3)-β-D: -glucan measurement kit, for diagnosis of invasive fungal infection, and comparison with other kits available in Japan.

    PubMed

    Yoshida, Koichiro; Shoji, Hisashi; Takuma, Takahiro; Niki, Yoshihito

    2011-08-01

    Fungitell, a (1→3)-β-D: -glucan (β-D: -glucan) measurement kit, was approved in the United States in 2004. Three other kits for measurement of β-D: -glucan, Fungitec G test MK (G-MK), β-Glucan test Wako (Wako), and β-Glucan test Maruha (Maruha), are commonly used for diagnosis of invasive fungal diseases in Japan. We evaluated the clinical viability of the Fungitell kit and compared it with the 3 kits generally used in Japan. The plasma β-D: -glucan values measured with each kit showed some differences, possibly because different β-D: -glucan standards, blood pretreatment methods, and kinds of horseshoe crab (a raw material for the main reagent) are used in each kit. Measures of diagnostic efficiency, for example the sensitivity, specificity, and positive and negative predictive values, varied among the kits. Although the areas under the receiver operating characteristic curves of the kits were not significantly different, the sensitivity of the Fungitell kit was the highest, followed by that of the G-MK kit. The sensitivity of the Wako and Maruha kits was low, but the specificity of these tests was higher than that of the G-MK or Fungitell kits. These inconsistent β-D: -glucan measurements could interfere with diagnosis of invasive fungal infection. Early establishment of an international standard method for measurement of β-D: -glucan is required. PMID:21210174

  9. The successful use of amphotericin B followed by oral posaconazole in a rare case of invasive fungal sinusitis caused by co-infection with mucormycosis and aspergillus

    PubMed Central

    Mahomed, Sharana; Basanth, Sujith; Mlisana, Koleka

    2015-01-01

    We report on an unusual case of oro-rhinocerebral disease caused by mucormycosis and aspergillus co-infection in a 54-year-old insulin dependent diabetic patient. Although she was successfully treated with parenteral amphotericin B followed by oral posaconazole, she was left with irreversible blindness of the right eye and multiple cranial nerve palsies. PMID:26793475

  10. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    PubMed

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  11. Progression of anal high-grade squamous intraepithelial lesions to invasive anal cancer among HIV-infected men who have sex with men.

    PubMed

    Berry, J Michael; Jay, Naomi; Cranston, Ross D; Darragh, Teresa M; Holly, Elizabeth A; Welton, Mark L; Palefsky, Joel M

    2014-03-01

    The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed. PMID:23934991

  12. Activation of the EIF2AK4-EIF2A/eIF2α-ATF4 pathway triggers autophagy response to Crohn disease-associated adherent-invasive Escherichia coli infection

    PubMed Central

    Bretin, Alexis; Carrière, Jessica; Dalmasso, Guillaume; Bergougnoux, Agnès; B'chir, Wafa; Maurin, Anne-Catherine; Müller, Stefan; Seibold, Frank; Barnich, Nicolas; Bruhat, Alain; Darfeuille-Michaud, Arlette; Nguyen, Hang Thi Thu

    2016-01-01

    ABSTRACT The intestinal mucosa of Crohn disease (CD) patients is abnormally colonized by adherent-invasive E. coli (AIEC). Upon AIEC infection, autophagy is induced in host cells to restrain bacterial intracellular replication. The underlying mechanism, however, remains unknown. Here, we investigated the role of the EIF2AK4-EIF2A/eIF2α-ATF4 pathway in the autophagic response to AIEC infection. We showed that infection of human intestinal epithelial T84 cells with the AIEC reference strain LF82 activated the EIF2AK4-EIF2A-ATF4 pathway, as evidenced by increased phospho-EIF2AK4, phospho-EIF2A and ATF4 levels. EIF2AK4 depletion inhibited autophagy activation in response to LF82 infection, leading to increased LF82 intracellular replication and elevated pro-inflammatory cytokine production. Mechanistically, EIF2AK4 depletion suppressed the LF82-induced ATF4 binding to promoters of several autophagy genes including MAP1LC3B, BECN1, SQSTM1, ATG3 and ATG7, and this subsequently inhibited transcription of these genes. LF82 infection of wild-type (WT), but not eif2ak4−/−, mice activated the EIF2AK4-EIF2A-ATF4 pathway, inducing autophagy gene transcription and autophagy response in enterocytes. Consequently, eif2ak4−/− mice exhibited increased intestinal colonization by LF82 bacteria and aggravated inflammation compared to WT mice. Activation of the EIF2AK4-EIF2A-ATF4 pathway was observed in ileal biopsies from patients with noninflamed CD, and this was suppressed in inflamed CD, suggesting that a defect in the activation of this pathway could be one of the mechanisms contributing to active disease. In conclusion, we show that activation of the EIF2AK4-EIF2A-ATF4 pathway upon AIEC infection serves as a host defense mechanism to induce functional autophagy to control AIEC intracellular replication. PMID:26986695

  13. Rapidly advancing invasive endomyocardial aspergillosis.

    PubMed

    Davutoglu, Vedat; Soydinc, Serdar; Aydin, Abdullah; Karakok, Metin

    2005-02-01

    The exposure to Aspergillus organisms/spores is likely common, but disease caused by tissue invasion with these fungi is uncommon and occurs primarily in the setting of immunosuppression. We report a case of rapidly advancing invasive endomyocardial aspergillosis secondary to prolonged usage of multiple broad-spectrum antibiotics in a nonimmunocompromised host. A 36-year-old cotton textile worker presented to our institution with a 3-month history of weight loss and fatigue. He reported receiving prolonged use of multiple broad-spectrum antibiotic treatment. The echocardiogram demonstrated multiple endomyocardial vegetations and a mass in the left atrium. Myocardial biopsy specimen revealed an invasive endomyocardial aspergillosis. The patient was investigated for immune deficiency including HIV, and this workup was negative. Treatment was started with amphotericin B and heparin for presumed left atrial thrombus. The patient died because of a rupture of mycotic aneurysm that resulted in cerebral hemorrhage. This case illustrates the risk of an invasive fungal infection in a nonimmunocompromised host who is a prolonged user of antibiotics in the setting of environmental exposure of opportunistic invasive fungal infections. PMID:15682058

  14. Spatial and taxonomical overlap of fungi on phylloplanes and invasive alien ladybirds with fungal infections in tree crowns of urban green spaces.

    PubMed

    Howe, Andy G; Ravn, Hans Peter; Jensen, Annette B; Meyling, Nicolai V

    2016-09-01

    Occurrence of entomopathogenic fungi on phylloplanes in Tilia × europaea crowns between 1 and 13 m was assessed in urban parks. Prevalence of fungal infections in ladybirds (Coleoptera: Coccinellidae) collected from Tilia × europaea was assessed to determine whether fungi found on phylloplanes also occurred as infections in ladybirds. Isaria spp. was most abundant on phylloplanes (mean colony forming units (CFU) per leaf ± SE, 0.33 ± 0.03) followed by Beauveria spp. (0.22 ± 0.02 CFU per leaf) and Lecanicillium spp. (0.19 ± 0.02 CFU per leaf). Densities of inoculum were higher in inner crowns and decreased with height, although Lecanicillium spp. peaked at 5-7 m. Upper phylloplane surfaces harboured higher densities of Isaria spp. and Beauveria spp. than lower surfaces, whereas Lecanicillium spp. was equally distributed. Most prevalent on ladybirds were Isaria spp. (20.6% Harmonia axyridis; 4.8% natives), Lecanicillium spp. (13.6% H. axyridis; 4.8% natives), with fewer Beauveria spp. infections (2.6% H. axyridis). Molecular identification revealed Beauveria bassiana, B. pseudobassiana, Isaria farinosa and Lecanicillium muscarium among isolates of both tree and ladybird origin. Tilia × europaea phylloplanes support a diverse assemblage of entomopathogenic fungal species with a different prevalence in coccinellids compared to their relative abundance in this habitat. PMID:27353660

  15. Cloning, sequencing, and characterization of a membrane-associated Prevotella ruminicola B(1)4 beta-glucosidase with cellodextrinase and cyanoglycosidase activities.

    PubMed Central

    Wulff-Strobel, C R; Wilson, D B

    1995-01-01

    Prevotella ruminicola B(1)4 is a gram-negative, anaerobic gastrointestinal bacterium. A 2.4-kbp chromosomal fragment from P. ruminicola encoding an 87-kDa aryl-glucosidase (CdxA) with cellodextrinase activity was cloned into Escherichia coli DH5 alpha and sequenced. CdxA activity was found predominantly in the membrane fraction of both P. ruminicola and E. coli, but P. ruminicola localized the protein extracellularly while E. coli did not. The hydrolase had the highest activity on cellodextrins (3.43 to 4.13 mumol of glucose released min-1 mg of protein-1) and p-nitrophenyl-beta-D-glucoside (3.54 mumol min-1 mg of protein-1). Significant activity (70% of p-nitrophenyl-beta-D-glucoside activity) was also detected on arbutin and prunasin. Less activity was obtained with cellobiose, amygdalin, or gentiobiose. CdxA attacks cellodextrins from the nonreducing end, releasing glucose units, and appears to be an exo-1,4-beta-glucosidase (EC 3.2.1.74) which also is able to attack beta-1,6 linkages. Comparison of the deduced amino acid sequence with other glycosyl-hydrolases suggests that this enzyme belongs to family 3 (B. Henrissat, Biochem. J. 280:309-316, 1991). On the basis of this sequence alignment, the catalytic residues are believed to be Asp-275 and Glu-265. This is the first report of a cloned ruminal bacterial enzyme which can cleave cyanogenic plant compounds and which may therefore contribute to cyanide toxicity in ruminants. PMID:7592339

  16. Structure-Function Analysis of a Mixed-linkage β-Glucanase/Xyloglucanase from the Key Ruminal Bacteroidetes Prevotella bryantii B(1)4.

    PubMed

    McGregor, Nicholas; Morar, Mariya; Fenger, Thomas Hauch; Stogios, Peter; Lenfant, Nicolas; Yin, Victor; Xu, Xiaohui; Evdokimova, Elena; Cui, Hong; Henrissat, Bernard; Savchenko, Alexei; Brumer, Harry

    2016-01-15

    The recent classification of glycoside hydrolase family 5 (GH5) members into subfamilies enhances the prediction of substrate specificity by phylogenetic analysis. However, the small number of well characterized members is a current limitation to understanding the molecular basis of the diverse specificity observed across individual GH5 subfamilies. GH5 subfamily 4 (GH5_4) is one of the largest, with known activities comprising (carboxymethyl)cellulases, mixed-linkage endo-glucanases, and endo-xyloglucanases. Through detailed structure-function analysis, we have revisited the characterization of a classic GH5_4 carboxymethylcellulase, PbGH5A (also known as Orf4, carboxymethylcellulase, and Cel5A), from the symbiotic rumen Bacteroidetes Prevotella bryantii B14. We demonstrate that carboxymethylcellulose and phosphoric acid-swollen cellulose are in fact relatively poor substrates for PbGH5A, which instead exhibits clear primary specificity for the plant storage and cell wall polysaccharide, mixed-linkage β-glucan. Significant activity toward the plant cell wall polysaccharide xyloglucan was also observed. Determination of PbGH5A crystal structures in the apo-form and in complex with (xylo)glucan oligosaccharides and an active-site affinity label, together with detailed kinetic analysis using a variety of well defined oligosaccharide substrates, revealed the structural determinants of polysaccharide substrate specificity. In particular, this analysis highlighted the PbGH5A active-site motifs that engender predominant mixed-linkage endo-glucanase activity vis à vis predominant endo-xyloglucanases in GH5_4. However the detailed phylogenetic analysis of GH5_4 members did not delineate particular clades of enzymes sharing these sequence motifs; the phylogeny was instead dominated by bacterial taxonomy. Nonetheless, our results provide key enzyme functional and structural reference data for future bioinformatics analyses of (meta)genomes to elucidate the biology of

  17. Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection.

    PubMed

    Dillon, S M; Lee, E J; Kotter, C V; Austin, G L; Gianella, S; Siewe, B; Smith, D M; Landay, A L; McManus, M C; Robertson, C E; Frank, D N; McCarter, M D; Wilson, C C

    2016-01-01

    HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c(+) and CD1c(neg)) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c(+) mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percentage of CD83(+)CD1c(+) mDCs negatively correlated with frequencies of interferon-γ-producing colon CD4(+) and CD8(+) T cells. CD40 expression on CD1c(+) mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and Prevotella stercorea but negatively associated with a number of low prevalence mucosal species, including Rumminococcus bromii. CD1c(+) mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that, during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation. PMID:25921339

  18. Relative telomere length: a novel non-invasive biomarker for the risk of non-cirrhotic hepatocellular carcinoma in patients with chronic hepatitis B infection

    PubMed Central

    Fu, Xiaoying; Wan, Shaogui; Hann, Hie-Won; Myers, Ronald E.; Hann, Richard S.; Au, Jennifer; Chen, Bicui; Xing, Jinliang; Yang, Hushan

    2012-01-01

    Background and Aims Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker. Methods We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 HBV-related HCC cases and 280 frequency-matched cancer-free HBV controls. Results Cases had a significantly longer RTL (median, 0.31; range, 0.02–2.31) than controls (median, 0.20; range, 0.01–1.60) (P=0.003). Consistently, longer RTLs conferred a significantly increased HCC risk compared to short RTLs in a univariate logistic regression analysis (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.02–2.33, P=0.038). This association attenuated after multivariate adjustment (OR=1.40, 95% CI=0.90–2.19, P=0.132). In a quartile analysis, a significant dose-response relationship was noted in univariate analysis (Ptrend=0.017) which was again attenuated in multivariate analysis (Ptrend=0.079). Further analyses revealed that the significant association between serum RTL and HCC risk was evident in non-cirrhotic (OR=3.54, 95% CI 1.58–7.93 P=0.002), but not cirrhotic (OR=0.95, 95% CI 0.55–1.64, P=0.860) HBV patients. Moreover, the significantly increased HCC risk conferred by cirrhosis was modulated by RTL with a significant interaction effect (Pinteraction=0.013). Conclusions RTL in circulating cell-free serum DNA could potentially be used as a novel non-invasive biomarker for non-cirrhotic HCC. Prospective cohort studies are warranted to validate this finding and assess its clinical significance in HCC prevention. PMID:22444598

  19. Community-Based Outbreaks in Vulnerable Populations of Invasive Infections Caused by Streptococcus pneumoniae Serotypes 5 and 8 in Calgary, Canada

    PubMed Central

    Vanderkooi, Otto G.; Church, Deirdre L.; MacDonald, Judy; Zucol, Franziska; Kellner, James D.

    2011-01-01

    Background Outbreaks of invasive pneumococcal disease (IPD) typically occur within institutions. Beginning in 2005, we detected an increase in serotype (ST) 5 and ST8 IPD cases, predominantly in homeless persons living in an open community. Methodology/Principal Findings CASPER (Calgary Area S. pneumoniae Epidemiology Research) surveillance study of all IPD (sterile site isolates) in our region (pop ∼1,100,000). Interviews and chart reviews of all cases and all isolates phenotypically analyzed and selected isolated tested by multi-locus sequence typing (MLST). Conclusions/Significance During 2005–2007, 162 cases of ST5 IPD and 45 cases of ST8 IPD were identified. The isolates demonstrated phenotypic and genotypic clonality. The ST5 isolates were sequence type (ST) 289 and demonstrated intermediate susceptibility to TMP-SMX. The ST8 isolates were predominantly ST1268, with a susceptible antimicrobial susceptibility profile. Individuals with ST5 IPD were more likely to be middle aged (OR 2.6), homeless (OR 4.4), using illicit drugs(OR 4.8), and asthmatic(OR 2.6). Those with ST8 were more likely to be male (OR 4.4), homeless (OR 2.6), aboriginal (OR7.3), and a current smoker (OR 2.5). Overlapping outbreaks of ST5 and ST8 IPD occurred in an open community in Calgary, Canada and homelessness was a predominant risk factor. Homelessness represents a unique community in which pneumococcal outbreaks can occur. PMID:22216100

  20. New surgical techniques and surgical site infections.

    PubMed Central

    Gordon, S. M.

    2001-01-01

    Technologic advances in surgery include a trend toward less invasive procedures, driven by potential benefits to patients and by health-care economics. These less invasive procedures provide infection control personnel opportunities for direct involvement in outcomes measurement. PMID:11294710

  1. Distribution of streptococcal inhibitor of complement variants in pharyngitis and invasive isolates in an epidemic of serotype M1 group A Streptococcus infection.

    PubMed

    Hoe, N P; Vuopio-Varkila, J; Vaara, M; Grigsby, D; De Lorenzo, D; Fu, Y X; Dou, S J; Pan, X; Nakashima, K; Musser, J M

    2001-02-15

    Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made predominantly by serotype M1 group A Streptococcus (GAS). New variants of the Sic protein frequently appear in M1 epidemics as a result of positive natural selection. To gain further understanding of the molecular basis of M1 epidemics, the sic gene was sequenced from 471 pharyngitis and 127 pyogenic and blood isolates recovered from 598 patients living in metropolitan Helsinki, Finland, during a 37-month population-based surveillance study. Most M1 GAS subclones recovered from pyogenic infections and blood were abundantly represented in the pool of subclones causing pharyngitis. Alleles shared among the pharyngitis, pyogenic, and blood samples were identified in throat isolates a mean of 9.8 months before their recovery from pyogenic infections and blood, which indicates that selection of most sic variants occurs on mucosal surfaces. In contrast, no variation was identified in the emm and covR/covS genes. PMID:11170990

  2. Gut Microbiota Linked to Sexual Preference and HIV Infection.

    PubMed

    Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

    2016-03-01

    The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

  3. Gut Microbiota Linked to Sexual Preference and HIV Infection

    PubMed Central

    Noguera-Julian, Marc; Rocafort, Muntsa; Guillén, Yolanda; Rivera, Javier; Casadellà, Maria; Nowak, Piotr; Hildebrand, Falk; Zeller, Georg; Parera, Mariona; Bellido, Rocío; Rodríguez, Cristina; Carrillo, Jorge; Mothe, Beatriz; Coll, Josep; Bravo, Isabel; Estany, Carla; Herrero, Cristina; Saz, Jorge; Sirera, Guillem; Torrela, Ariadna; Navarro, Jordi; Crespo, Manel; Brander, Christian; Negredo, Eugènia; Blanco, Julià; Guarner, Francisco; Calle, Maria Luz; Bork, Peer; Sönnerborg, Anders; Clotet, Bonaventura; Paredes, Roger

    2016-01-01

    The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. PMID:27077120

  4. Changes in the Swine Gut Microbiota in Response to Porcine Epidemic Diarrhea Infection

    PubMed Central

    Koh, Hyeon-Woo; Kim, Myun Soo; Lee, Jong-Soo; Kim, Hongik; Park, Soo-Je

    2015-01-01

    The gastrointestinal tract of mammals is a complex ecosystem with distinct environments and comprises hundreds of different types of bacterial cells. The gut microbiota may play a critical role in the gut health of the host. We herein attempted to identify a microbiota shift that may be affected by porcine epidemic diarrhea (PED). We observed significant differences in microbiota between the control and PED virus (PEDV)-infected groups at both the phylum and genus level. Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in the healthy gastrointestinal tract were decreased due to dysbiosis induced by PEDV infection. PMID:26212519

  5. Molecular Identification of Cultivable Bacteria From Infected Root Canals Associated With Acute Apical Abscess.

    PubMed

    Nóbrega, Letícia M M; Montagner, Francisco; Ribeiro, Adriana C; Mayer, Márcia A P; Gomes, Brenda P F A

    2016-01-01

    The objective of this study was to investigate the bacterial composition present in root canals of teeth associated with acute apical abscess by molecular identification (16S rRNA) of cultivable bacteria. Two hundred and twenty strains isolated by culture from 20 root canals were subjected to DNA extraction and amplification of the 16S rRNA gene (PCR), followed by sequencing. The resulting nucleotide sequences were compared to the GenBank database from the National Center of Biotechnology Information through BLAST. Strains not identified by sequencing were submitted to clonal analysis. The association of microbiological findings with clinical features and the association between microbial species were also investigated. Fifty-nine different cultivable bacteria were identified by 16S rRNA gene sequencing, belonging to 6 phyla, with an average number of 6 species per root canal. Molecular approaches allowed identification of 99% of isolates. The most frequently identified bacteria were Prevotella spp., Pseudoramibacter alactolyticus, Parvimonas micra, Dialister invisus, Filifactor alocis, and Peptostreptococcus stomatis. Positive association was found between Prevotella buccae and Pseudoramibacter alactolyticus and between Parvimonas micra and Prevotella nigrescens (both p<0.05). It was concluded that the microbiota of infected root canals associated with acute apical abscess is diverse and heterogeneous, composed mainly of anaerobic Gram-negative bacteria, with the great majority belonging to the phyla Firmicutes and Bacteroidetes. PMID:27224567

  6. Invasive aspergillosis in near drowning nonneutropenic patient

    PubMed Central

    Munta, Kartik; Gopal, Palepu B. N.; Vigg, Ajit

    2015-01-01

    Invasive aspergillosis in immunosuppressed people has been well documented, but to diagnose and treat in an immunocompetent individual after near drowning, it requires early suspicion and proper empirical treatment. We report a case diagnosed to have invasive aspergillosis with systemic dissemination of the infection to the brain, gluteal muscles, and kidneys after a fall in a chemical tank of a paper manufacturing company. He was ventilated for acute respiratory distress syndrome and managed with antibiotics and vasopressors. Due to nonresolving pneumonia and positive serum galactomannan, trans-tracheal biopsy was performed which confirmed invasive aspergillosis and was treated with antifungals. With the availability of galactomannan assay and better radiological investigative modalities, occurrence of such invasive fungal infections in cases of drowning patients should be considered early in such patients and treated with appropriate antifungals. PMID:26816451

  7. Esophagectomy - minimally invasive

    MedlinePlus

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  8. Invasive Disease Caused by Nontypeable Haemophilus influenzae

    PubMed Central

    de Jonge, Marien I.

    2015-01-01

    The incidence of severe Haemophilus influenza infections, such as sepsis and meningitis, has declined substantially since the introduction of the H. influenzae serotype b vaccine. However, the H. influenzae type b vaccine fails to protect against nontypeable H. influenzae strains, which have become increasingly frequent causes of invasive disease, especially among children and the elderly. We summarize recent literature supporting the emergence of invasive nontypeable H. influenzae and describe mechanisms that may explain its increasing prevalence over the past 2 decades. PMID:26407156

  9. Fusarium Infection

    PubMed Central

    Muhammed, Maged; Anagnostou, Theodora; Desalermos, Athanasios; Kourkoumpetis, Themistoklis K.; Carneiro, Herman A.; Glavis-Bloom, Justin; Coleman, Jeffrey J.

    2013-01-01

    Abstract Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested. PMID:24145697

  10. Invasion Assays and Genomotyping to Investigate Differences in Virulence of Campylobacter spp. Isolates from Iceland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter spp. are the leading cause of human gastroenteritis worldwide. Epithelial cell invasion is thought to be essential for Campylobacter spp. infection. Previous invasion studies with intestinal epithelial cells revealed that the ability of different Campylobacter jejuni isolates to inva...

  11. Early Detection of Autism (ASD) by a Non-invasive Quick Measurement of Markedly Reduced Acetylcholine & DHEA and Increased β-Amyloid (1-42), Asbestos (Chrysotile), Titanium Dioxide, Al, Hg & often Coexisting Virus Infections (CMV, HPV 16 and 18), Bacterial Infections etc. in the Brain and Corresponding Safe Individualized Effective Treatment.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Ahdallah; Duvvi, Harsha; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    A brief historical background on Autism & some of the important symptoms associated with Autism are summarized. Using strong Electro Magnetic Field Resonance Phenomenon between 2 identical molecules with identical weight (which received U.S. Patent) non-invasively & rapidly we can detect various molecules including neurotransmitters, bacteria, virus, fungus, metals & abnormal molecules. Simple non- invasive measurement of various molecules through pupils & head of diagnosed or suspected Autism patients indicated that in Autism patients following changes were often found: 1) Acetylcholine is markedly reduced; 2) Alzheimer's disease markers (i.e. β-Amyloid (1-42), Tau Protein, Apolipoprotein (Apo E4)) are markedly increased; 3) Chrysotile Asbestos is increased; 4) Titanium Dioxide (TiO2) is moderately increased; 5) Al is moderately increased; 6) Hg is moderately increased; 7) Dopamine, Serotonin & GABA are significantly reduced (up to about 1/10 of normal); 8) Often viral infections (such as CMV, HHV-6, HPV-16, HPV-18, etc.), and Bacterial infections (such as Chlamydia trachomatis, Mycobacterium TB, Borrelia Burgdorferi, etc.) coexist. Research by others on Autism spectrum disorder (ASD) shows that it is a group of complex neurodevelopmental disorders, with about 70% of ASD patients also suffering from gastro-intestinal problems. While Alzheimer disease (AD) is characterized by formation of 1) Amyloid plaques, 2) Neurofibrillary tangles inside of neurons, and 3) Loss of connections between neurons. More than 90% of AD develops in people over the age of 65. These 3 characteristics often progressively worsen over time. Although Autism Spectrum Disorder and Alzheimer's disease are completely different diseases they have some similar biochemical changes. Eight examples of such measurement & analysis are shown for comparison. Most of Autism patients improved significantly by removing the source or preventing intake of Asbestos, TiO2, Al & Hg or enhancing urinary output

  12. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia.

    PubMed

    Dillon, S M; Lee, E J; Kotter, C V; Austin, G L; Dong, Z; Hecht, D K; Gianella, S; Siewe, B; Smith, D M; Landay, A L; Robertson, C E; Frank, D N; Wilson, C C

    2014-07-01

    Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection. PMID:24399150

  13. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia

    PubMed Central

    Dillon, SM; Lee, EJ; Kotter, CV; Austin, GL; Dong, Z; Hecht, DK; Gianella, S; Siewe, B; Smith, DM; Landay, AL; Robertson, CE; Frank, DN; Wilson, CC

    2014-01-01

    HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T cell activation, inflammation and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1 infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared to uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1 infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation and blood T cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection. PMID:24399150

  14. Typhoid fever and invasive nontyphoid salmonellosis, Malawi and South Africa.

    PubMed

    Feasey, Nicholas A; Archer, Brett N; Heyderman, Robert S; Sooka, Arvinda; Dennis, Brigitte; Gordon, Melita A; Keddy, Karen H

    2010-09-01

    To determine the prevalence of invasive nontyphoid salmonellosis and typhoid fever in Malawi and South Africa, we compared case frequency and patient age distribution. Invasive nontyphoid salmonellosis showed a clear bimodal age distribution; the infection developed in women at a younger age than in men. Case frequency for typhoid fever was lower than for salmonellosis. PMID:20735930

  15. Typhoid Fever and Invasive Nontyphoid Salmonellosis, Malawi and South Africa

    PubMed Central

    Feasey, Nicholas A.; Archer, Brett N.; Heyderman, Robert S.; Sooka, Arvinda; Dennis, Brigitte; Keddy, Karen H.

    2010-01-01

    To determine the prevalence of invasive nontyphoid salmonellosis and typhoid fever in Malawi and South Africa, we compared case frequency and patient age distribution. Invasive nontyphoid salmonellosis showed a clear bimodal age distribution; the infection developed in women at a younger age than in men. Case frequency for typhoid fever was lower than for salmonellosis. PMID:20735930

  16. [Combination therapy for invasive aspergillosis].

    PubMed

    Ruiz-Camps, Isabel

    2011-03-01

    The frequency of invasive fungal infections, and specifically invasive aspergillosis, has increased in the last few decades. Despite the development of new antifungal agents, these infections are associated with high mortality, ranging from 40% to 80%, depending on the patient and the localization of the infection. To reduce these figures, several therapeutic strategies have been proposed, including combination therapy. Most of the available data on the efficacy of these combinations are from experimental models, in vitro data and retrospective observational studies or studies with a small number of patients that have included both patients in first-line treatment and those receiving rescue therapy; in addition there are many patients with possible forms of aspergillosis and few with demonstrated or probable forms. To date, there is no evidence that combination therapy has significantly higher efficacy than monotherapy; however, combination therapy could be indicated in severe forms of aspergillosis, or forms with central nervous involvement or extensive pulmonary involvement with respiratory insufficiency, etc. Among the combinations, the association of an echinocandin--the group that includes micafungin--with voriconazole or liposomal amphotericin B seems to show synergy. These combinations are those most extensively studied in clinical trials and therefore, although the grade of evidence is low, are recommended by the various scientific societies. PMID:21420576

  17. Invasive mucormycosis in chronic granulomatous disease.

    PubMed

    Al-Otaibi, Abdulnasir M; Al-Shahrani, Dayel A; Al-Idrissi, Eman M; Al-Abdely, Hail M

    2016-05-01

    Mucormycosis is a rare opportunistic fungal infection that occurs in certain immunocompromised patients. We present 2 cases of invasive mucormycosis due to Rhizopus spp. in patients with chronic granulomatous disease (CGD) and discuss their clinical presentation, management challenges, and outcomes. PMID:27146621

  18. Invasive mucormycosis in chronic granulomatous disease

    PubMed Central

    Al-Otaibi, Abdulnasir M.; Al-Shahrani, Dayel A.; Al-Idrissi, Eman M.; Al-Abdely, Hail M.

    2016-01-01

    Mucormycosis is a rare opportunistic fungal infection that occurs in certain immunocompromised patients. We present 2 cases of invasive mucormycosis due to Rhizopus spp. in patients with chronic granulomatous disease (CGD) and discuss their clinical presentation, management challenges, and outcomes. PMID:27146621

  19. Invasive epiglottic aspergillosis: A case report and literature review.

    PubMed

    Ohashi, Toshimitsu; Mizuta, Keisuke; Kuze, Bunya; Aoki, Mitsuhiro; Ito, Yatsuji

    2015-12-01

    Invasive aspergillosis is a life-threatening infection in immunocompromised hosts and occurs most frequently in the lungs. Invasive laryngeal aspergillosis is extremely rare. Due to the potential progression of invasive aspergillosis, antifungal therapy must be started immediately in cases involving clinical suspicion of the disease. A 65-year-old male with agranulocytosis complained of sore throat and dysphagia. His epiglottis was covered with caseating granulomatous lesions and the tissue was easily disrupted. A histopathological examination showed an aggressive invasion of Aspergillus species and cartilage destruction. Therefore, we made a diagnosis of primary invasive epiglottic aspergillosis. The invasive aspergillosis resolved with antifungal therapy and an increase in neutrophils. It is therefore necessary to include invasive laryngeal aspergillosis in the differential diagnosis when encountering immunocompromised patients presenting with laryngeal granulomatous lesions and laryngitis-like symptoms. PMID:26025177

  20. Infective endocarditis.

    PubMed

    Cahill, Thomas J; Prendergast, Bernard D

    2016-02-27

    Infective endocarditis occurs worldwide, and is defined by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device. The causes and epidemiology of the disease have evolved in recent decades with a doubling of the average patient age and an increased prevalence in patients with indwelling cardiac devices. The microbiology of the disease has also changed, and staphylococci, most often associated with health-care contact and invasive procedures, have overtaken streptococci as the most common cause of the disease. Although novel diagnostic and therapeutic strategies have emerged, 1 year mortality has not improved and remains at 30%, which is worse than for many cancers. Logistical barriers and an absence of randomised trials hinder clinical management, and longstanding controversies such as use of antibiotic prophylaxis remain unresolved. In this Seminar, we discuss clinical practice, controversies, and strategies needed to target this potentially devastating disease. PMID:26341945

  1. Attacking invasive grasses

    USGS Publications Warehouse

    Keeley, Jon E.

    2015-01-01

    In grasslands fire may play a role in the plant invasion process, both by creating disturbances that potentially favour non-native invasions and as a possible tool for controlling alien invasions. Havill et al. (Applied Vegetation Science, 18, 2015, this issue) determine how native and non-native species respond to different fire regimes as a first step in understanding the potential control of invasive grasses.

  2. [Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age].

    PubMed

    Albrecht, Piotr; Antczak, Adam; Hryniewicz, Waleria; Skoczyńska, Anna; Radzikowski, Andrzej; Kedziora-Kornatowska, Kornelia; Bernatowska, Ewa; Stompór, Tomasz; Grodzicki, Tomasz; Gyrczuk, Ewa; Imiela, Jacek; Jedrzejczak, Wiesław; Windak, Adam

    2014-02-01

    Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD

  3. Highly Invasive Listeria monocytogenes Strains Have Growth and Invasion Advantages in Strain Competition

    PubMed Central

    Manthou, Evanthia; Ciolacu, Luminita; Wagner, Martin; Skandamis, Panagiotis N.

    2015-01-01

    Multiple Listeria monocytogenes strains can be present in the same food sample; moreover, infection with more than one L. monocytogenes strain can also occur. In this study we investigated the impact of strain competition on the growth and in vitro virulence potential of L. monocytogenes. We identified two strong competitor strains, whose growth was not (or only slightly) influenced by the presence of other strains and two weak competitor strains, which were outcompeted by other strains. Cell contact was essential for growth inhibition. In vitro virulence assays using human intestinal epithelial Caco2 cells showed a correlation between the invasion efficiency and growth inhibition: the strong growth competitor strains showed high invasiveness. Moreover, invasion efficiency of the highly invasive strain was further increased in certain combinations by the presence of a low invasive strain. In all tested combinations, the less invasive strain was outcompeted by the higher invasive strain. Studying the effect of cell contact on in vitro virulence competition revealed a complex pattern in which the observed effects depended only partially on cell-contact suggesting that competition occurs at two different levels: i) during co-cultivation prior to infection, which might influence the expression of virulence factors, and ii) during infection, when bacterial cells compete for the host cell. In conclusion, we show that growth of L. monocytogenes can be inhibited by strains of the same species leading potentially to biased recovery during enrichment procedures. Furthermore, the presence of more than one L. monocytogenes strain in food can lead to increased infection rates due to synergistic effects on the virulence potential. PMID:26529510

  4. Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times

  5. Evaluation of Eukaryotic Cell Invasion on a Library of Genetically Diverse Campylobacter spp. Isolates.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Campylobacter spp. are the largest cause of sporadic bacterial gastrointestinal infection in the industrialized world. Epithelial cell invasion is thought to be necessary to bring about infection in humans. Invasion studies have shown that different Campylobacter jejuni isolates may differ in thei...

  6. Diagnosis and management of invasive candidiasis in the ICU: an updated approach to an old enemy.

    PubMed

    Calandra, Thierry; Roberts, Jason A; Antonelli, Massimo; Bassetti, Matteo; Vincent, Jean-Louis

    2016-01-01

    Invasive fungal infections, particularly those caused by Candida species, are not uncommon in critically ill patients and are associated with considerable morbidity and mortality. Diagnosis and management of these infections can be challenging. In this review, we will briefly discuss recent epidemiological data on invasive candidiasis and current diagnostic approaches before concentrating on antifungal treatments. PMID:27230564

  7. Invasive Salmonellosis in Kilifi, Kenya

    PubMed Central

    Muthumbi, Esther; Morpeth, Susan C.; Ooko, Michael; Mwanzu, Alfred; Mwarumba, Salim; Mturi, Neema; Etyang, Anthony O.; Berkley, James A.; Williams, Thomas N.; Kariuki, Samuel; Scott, J. Anthony G.

    2015-01-01

    Background. Invasive salmonelloses are a major cause of morbidity and mortality in Africa, but the incidence and case fatality of each disease vary markedly by region. We aimed to describe the incidence, clinical characteristics, and antimicrobial susceptibility patterns of invasive salmonelloses among children and adults in Kilifi, Kenya. Methods. We analyzed integrated clinical and laboratory records for patients presenting to the Kilifi County Hospital between 1998 and 2014. We calculated incidence, and summarized clinical features and multidrug resistance. Results. Nontyphoidal Salmonella (NTS) accounted for 10.8% and 5.8% of bacteremia cases in children and adults, respectively, while Salmonella Typhi accounted for 0.5% and 2.1%, respectively. Among 351 NTS isolates serotyped, 160 (45.6%) were Salmonella Enteritidis and 152 (43.3%) were Salmonella Typhimurium. The incidence of NTS in children aged <5 years was 36.6 per 100 000 person-years, being highest in infants aged <7 days (174/100 000 person-years). The overall incidence of NTS in children varied markedly by location and declined significantly during the study period; the pattern of dominance of the NTS serotypes also shifted from Salmonella Enteritidis to Salmonella Typhimurium. Risk factors for invasive NTS disease were human immunodeficiency virus infection, malaria, and malnutrition; the case fatality ratio was 22.1% (71/321) in children aged <5 years and 36.7% (11/30) in adults. Multidrug resistance was present in 23.9% (84/351) of NTS isolates and 46.2% (12/26) of Salmonella Typhi isolates. Conclusions. In Kilifi, the incidence of invasive NTS was high, especially among newborn infants, but typhoid fever was uncommon. NTS remains an important cause of bacteremia in children <5 years of age. PMID:26449944

  8. Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling.

    PubMed

    Faulstich, Michaela; Böttcher, Jan-Peter; Meyer, Thomas F; Fraunholz, Martin; Rudel, Thomas

    2013-01-01

    Many pathogenic bacteria cause local infections but occasionally invade into the blood stream, often with fatal outcome. Very little is known about the mechanism underlying the switch from local to invasive infection. In the case of Neisseria gonorrhoeae, phase variable type 4 pili (T4P) stabilize local infection by mediating microcolony formation and inducing anti-invasive signals. Outer membrane porin PorB(IA), in contrast, is associated with disseminated infection and facilitates the efficient invasion of gonococci into host cells. Here we demonstrate that loss of pili by natural pilus phase variation is a prerequisite for the transition from local to invasive infection. Unexpectedly, both T4P-mediated inhibition of invasion and PorB(IA)-triggered invasion utilize membrane rafts and signaling pathways that depend on caveolin-1-Y14 phosphorylation (Cav1-pY14). We identified p85 regulatory subunit of PI3 kinase (PI3K) and phospholipase Cγ1 as new, exclusive and essential interaction partners for Cav1-pY14 in the course of PorBIA-induced invasion. Active PI3K induces the uptake of gonococci via a new invasion pathway involving protein kinase D1. Our data describe a novel route of bacterial entry into epithelial cells and offer the first mechanistic insight into the switch from local to invasive gonococcal infection. PMID:23717204

  9. Treatment of invasive candidiasis in the elderly: a review

    PubMed Central

    Flevari, Aikaterini; Theodorakopoulou, Maria; Velegraki, Aristea; Armaganidis, Apostolos; Dimopoulos, George

    2013-01-01

    Fungi are major causes of infections among immunocompromised or hospitalized patients with serious underlying diseases and comorbidities. Candida species remain the most important cause of opportunistic infections worldwide, affecting predominantly patients over 65 years old, while they are considered to be the fourth most common cause of nosocomial bloodstream infections. The rapidly growing elderly population has specific physiological characteristics, which makes it susceptible to colonization and subsequent infection due to Candida species. Comorbidities and multidrug use should be taken into account any time the therapeutic regimen is under consideration. Different classes of antifungal drugs are available for the treatment of invasive fungal infections but echinocandins, apart from their activity against resistant strains (Candida glabrata and Candida krusei), seem to be safe, with limited adverse events and minimal drug–drug interactions in comparison to the other regimens. Therefore, these agents are strongly recommended when dealing with elderly patients suffering from an invasive form of Candida infection. PMID:24043935

  10. Performance of Panfungal- and Specific-PCR-Based Procedures for Etiological Diagnosis of Invasive Fungal Diseases on Tissue Biopsy Specimens with Proven Infection: a 7-Year Retrospective Analysis from a Reference Laboratory

    PubMed Central

    Bernal-Martinez, L.; Castelli, M. V.; Rodriguez-Tudela, J. L.; Cuenca-Estrella, M.

    2014-01-01

    A retrospective analysis of real-time PCR (RT-PCR) results for 151 biopsy samples obtained from 132 patients with proven invasive fungal diseases was performed. PCR-based techniques proved to be fast and sensitive and enabled definitive diagnosis in all cases studied, with detection of a total of 28 fungal species. PMID:24574295

  11. Organ Transplant Patients and Fungal Infections

    MedlinePlus

    ... of hospital-associated infections for more information. Fungal infections can happen any time after your surgery. Fungal infections can happen ... Neofytos D, Fishman JA, Horn D, et al. Epidemiology and outcome of invasive ... in solid organ transplant recipients. Transplant Infectious Disease ...

  12. LOUISIANA INVASIVE SPECIES PLAN

    EPA Science Inventory

    Identify the species, locations, and effects of invasive species within the state and the effects of these invasive species in Louisiana. Also identify how these species are spread, and the authorities that exist to manage and control them. With this information, create a m...

  13. Invasion of the Whiteflies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As invasive alien species spread, they often displace indigenous species, thus altering ecological communities and adversely affecting agricultural pest management, human health and well-being, and biodiversity. Despite the importance of invasive species, the processes enabling them to become estab...

  14. Invasion of dentinal tubules by oral bacteria.

    PubMed

    Love, R M; Jenkinson, H F

    2002-01-01

    Bacterial invasion of dentinal tubules commonly occurs when dentin is exposed following a breach in the integrity of the overlying enamel or cementum. Bacterial products diffuse through the dentinal tubule toward the pulp and evoke inflammatory changes in the pulpo-dentin complex. These may eliminate the bacterial insult and block the route of infection. Unchecked, invasion results in pulpitis and pulp necrosis, infection of the root canal system, and periapical disease. While several hundred bacterial species are known to inhabit the oral cavity, a relatively small and select group of bacteria is involved in the invasion of dentinal tubules and subsequent infection of the root canal space. Gram-positive organisms dominate the tubule microflora in both carious and non-carious dentin. The relatively high numbers of obligate anaerobes present-such as Eubacterium spp., Propionibacterium spp., Bifidobacterium spp., Peptostreptococcus micros, and Veillonella spp.-suggest that the environment favors growth of these bacteria. Gram-negative obligate anaerobic rods, e.g., Porphyromonas spp., are less frequently recovered. Streptococci are among the most commonly identified bacteria that invade dentin. Recent evidence suggests that streptococci may recognize components present within dentinal tubules, such as collagen type I, which stimulate bacterial adhesion and intra-tubular growth. Specific interactions of other oral bacteria with invading streptococci may then facilitate the invasion of dentin by select bacterial groupings. An understanding the mechanisms involved in dentinal tubule invasion by bacteria should allow for the development of new control strategies, such as inhibitory compounds incorporated into oral health care products or dental materials, which would assist in the practice of endodontics. PMID:12097359

  15. Healthcare associated infections (HAI) perspectives.

    PubMed

    Al-Tawfiq, Jaffar A; Tambyah, Paul A

    2014-01-01

    Healthcare associated infections (HAI) are among the major complications of modern medical therapy. The most important HAIs are those related to invasive devices: central line-associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), ventilator-associated pneumonia (VAP) as well as surgical site infections (SSI). HAIs are associated with significant mortality, morbidities and increasing healthcare cost. The cited case-fatality rate ranges from 2.3% to 14.4% depending on the type of infection. In this mini-review, we shed light on these aspects as well as drivers to decrease HAIs. PMID:24861643

  16. Shigella infections.

    PubMed

    Shears, P

    1996-04-01

    Shigella dysentery is a major public-health problem in many tropical areas. Despite improvements in water supplies and sanitation, it continues to be a disease of poor rural and urban communities and in populations affected by migration and crowding following disasters. Pathogenesis is due to colonic invasion, endotoxin, and, in Shigella dysenteriae 1, shiga toxin. As well as the local manifestations of dysentery, systemic complications include convulsions, haemolytic-uraemic syndrome, hyponatraemia and hypoglycaemia. The spread of shigella infection is most commonly person-person, although water and food-borne outbreaks have been reported. Since 1970, multiple antimicrobial resistance, particularly in Sh. dysenteriae 1, has complicated strategies for management. Multiply resistant strains have occurred in Latin America, Central Africa and southern and south-eastern Asia. No vaccines are currently available, and prevention and control will depend on public-health improvements and improved case management. PMID:8762400

  17. Actinomyces Species Isolated from Breast Infections

    PubMed Central

    Loh, S. F.; Morris, T.; Hughes, H.; Dixon, J. M.

    2015-01-01

    Actinomycosis is a chronic infection caused by Actinomyces species characterized by abscess formation, tissue fibrosis, and draining sinuses. The spectrum of infections caused by Actinomyces species ranges from classical invasive actinomycosis to a less invasive form of superficial skin and soft tissue infection. We present a review detailing all Actinomyces species isolated from breast infections in NHS Lothian between 2005 and 2013, Actinomyces species isolated from breast infections referred to the United Kingdom Anaerobe Reference Unit between 1988 and 2014, and cases describing Actinomyces breast infections published in the medical literature since 1994. Actinomyces species are fastidious organisms which can be difficult to identify and are likely to be underascertained as a cause of breast infections. Due to improved diagnostic methods, they are increasingly associated with chronic, recurrent breast infections and may play a more significant role in these infections than has previously been appreciated. PMID:26224846

  18. Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

    PubMed Central

    Hsu, Joe L.; Khan, Mohammad A.; Sobel, Raymond A.; Jiang, Xinguo; Clemons, Karl V.; Nguyen, Tom T.; Stevens, David A.; Martinez, Marife; Nicolls, Mark R.

    2013-01-01

    Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections. PMID:24155924

  19. Scaling and root planning, and locally delivered minocycline reduces the load of Prevotella intermedia in an interdependent pattern, correlating with symptomatic improvements of chronic periodontitis: a short-term randomized clinical trial

    PubMed Central

    Deng, Shuli; Wang, Ying; Sun, Wei; Chen, Hui; Wu, Gang

    2015-01-01

    Background To evaluate the respective or combinatory efficacy of locally delivered 2% minocycline (MO), and scaling and root planning (SRP) by assessing both clinical parameters and the loads of four main periodontal pathogens in treating chronic periodontitis (CP). Methods Seventy adults with CP were randomly assigned to the three treatment groups: 1) SRP alone; 2) MO alone; and 3) combinatory use of SRP and MO (SRP + MO). Before and 7 days after the treatments, we evaluated both clinical parameters (pocket depth [PD] and sulcus bleeding index [SBI]) and the gene load of four main periodontal pathogens (Aggregatibacter actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Porphyromonas gingivalis [Pg], and Prevotella intermedia [Pi]). Results The bacterial prevalence per patient was: Aa, 31.25%; Fn, 100%; Pg, 95.31%; and Pi, 98.44%. Seven days after treatment, the three treatments significantly reduced both PD and SBI, but not detection frequencies of the four pathogens. For PD, the reduction efficacy of SRP + MO was significantly higher than that of either MO or SRP. Only Pg responded significantly to SRP. Pg and Fn were significantly reduced in the presence of MO. Only SRP + MO showed a significant reduction effect on the gene load of Pi. The reduction of PD significantly correlated with the gene load of Pi (r=0.26; P=0.042) but not of the other bacteria. Conclusion SRP and MO reduced the load of Pi in an interdependent pattern, which correlated with symptomatic improvements of CP. PMID:26676022

  20. Invasive Cervical Resorption: A Review

    PubMed Central

    Kandalgaonkar, Shilpa D; Gharat, Leena A; Tupsakhare, Suyog D; Gabhane, Mahesh H

    2013-01-01

    Invasive cervical resorption is a relatively uncommon form of external root resorption exhibiting no external signs. The resorptive condition is often detected by routine radiographic examination. The clinical features vary from a small defect at the gingival margin to a pink coronal discoloration of the tooth crown resulting in ultimate cavitation of the overlying enamel which is painless unless pulpal or periodontal infection supervenes. Radiographic features of lesions vary from well-delineated to irregularly bordered mottled radiolucencies, and these can be confused with dental caries. A characteristic radiopaque line generally separates the image of the lesion from that of the root canal, because the pulp remains protected by a thin layer of predentin until late in the process. Histopathologically, the lesions contain fibrovascular tissue with resorbing clastic cells adjacent to the dentin surface. More advanced lesions display fibro-osseous characteristics with deposition of ectopic bonelike calcifications both within the resorbing tissue and directly on the dentin surface. How to cite this article: Kandalgaonkar SD, Gharat LA, Tupsakhare SD, Gabhane MH. Invasive Cervical Resorption: A Review. J Int Oral Health 2013;5(6):124-30 . PMID:24453457

  1. Gut Dendritic Cell Activation Links an Altered Colonic Microbiome to Mucosal and Systemic T Cell Activation in Untreated HIV-1 infection

    PubMed Central

    Dillon, SM; Lee, EJ; Kotter, CV; Austin, GL; Gianella, S; Siewe, B; Smith, DM; Landay, AL; McManus, MC; Robertson, CE; Frank, DN; McCarter, MD; Wilson, CC

    2015-01-01

    HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c+ and CD1cneg) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c+ mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percent of CD83+CD1c+ mDCs negatively correlated with frequencies of IFN-γ-producing colon CD4+ and CD8+ T cells. CD40 expression on CD1c+ mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and P. stercorea, but negatively associated with a number of low prevalence mucosal species including Rumminococcus bromii. CD1c+ mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation. PMID:25921339

  2. Minimally Invasive Valve Surgery

    PubMed Central

    Pope, Nicolas H.; Ailawadi, Gorav

    2014-01-01

    Cardiac valve surgery is life saving for many patients. The advent of minimally invasive surgical techniques has historically allowed for improvement in both post-operative convalescence and important clinical outcomes. The development of minimally invasive cardiac valve repair and replacement surgery over the past decade is poised to revolutionize the care of cardiac valve patients. Here, we present a review of the history and current trends in minimally invasive aortic and mitral valve repair and replacement, including the development of sutureless bioprosthetic valves. PMID:24797148

  3. Invasion of Ureaplasma diversum in Hep-2 cells

    PubMed Central

    2010-01-01

    Background Understanding mollicutes is challenging due to their variety and relationship with host cells. Invasion has explained issues related to their opportunistic role. Few studies have been done on the Ureaplasma diversum mollicute, which is detected in healthy or diseased bovine. The invasion in Hep-2 cells of four clinical isolates and two reference strains of their ureaplasma was studied by Confocal Laser Scanning Microscopy and gentamicin invasion assay. Results The isolates and strains used were detected inside the cells after infection of one minute without difference in the arrangement for adhesion and invasion. The adhesion was scattered throughout the cells, and after three hours, the invasion of the ureaplasmas surrounded the nuclear region but were not observed inside the nuclei. The gentamicin invasion assay detected that 1% of the ATCC strains were inside the infected Hep-2 cells in contrast to 10% to the clinical isolates. A high level of phospholipase C activity was also detected in all studied ureaplasma. Conclusions The results presented herein will help better understand U. diversum infections, aswell as cellular attachment and virulence. PMID:20236540

  4. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  5. Invasive aspergillosis: new insights into disease, diagnostic and treatment.

    PubMed

    Karthaus, Meinolf; Buchheidt, Dieter

    2013-01-01

    Aspergillus infections are a threat to in patients with hematological malignancies. Known risk factors are profound and long lasting neutropenia, uncontrolled graft versus host disease, continuous administration of steroids and environmental factors such as hospital construction. Numerous efforts have been undertaken for prophylaxis of invasive aspergillosis in high-risk populations. Most of them failed to demonstrate survival advantages. Prophylaxis makes sense, since diagnosis and treatment of invasive aspergillosis remain difficult. The introduction of non-culture based tools for the diagnosis of invasive aspergillosis is an important step forward for early and sensitive diagnosis of invasive aspergillosis. Early treatment is the cornerstone of a successful management of invasive aspergillosis. Substantial improvement came with the introduction of lipid formulations of amphotericin B in the early 1990s. Voriconazole was the first azole that improved the overall survival for patients with invasive aspergillosis. Newer azoles and the echinocandins were introduced for the treatment of invasive aspergillosis in the late 1990s. Voriconazole and liposomal amphotericin B allow a safer and more effective treatment of invasive aspergillosis when compared with amphotericin B-desoxycholate. Combination of antifungal agents has been introduced in clinical trials. Up to now no significant benefit has been obtained with antifungal combination compared to voriconazole alone. Because mortality of invasive aspergillosis remains up to more than 50%, prophylaxis, early diagnosis and early initiation of antifungal therapy are of utmost importance for the reduction of invasive aspergillosis related mortality. Despite all advances in the management of invasive aspergillosis important questions remain unresolved. This article reviews the current state and new insights in the management of invasive aspergillosis and points out clinicians unmet needs. PMID:23278538

  6. Intracranial bacterial infections of oral origin.

    PubMed

    Moazzam, Alan A; Rajagopal, Sowmya M; Sedghizadeh, Parish P; Zada, Gabriel; Habibian, Mina

    2015-05-01

    Brain abscesses are rare but potentially deadly complications of odontogenic infections. This phenomenon has been described mainly in the form of case reports, as large-scale studies are difficult to perform. We compiled a total of 60 previously published cases of such a complication to investigate the predisposing factors, microbiology, and clinical outcomes of intracranial abscesses of odontogenic origin. A systematic review of the literature using the PubMed database was performed. Men accounted for 82.1% of cases, and the mean age was 42.1 years. Caries with periapical involvement and periodontitis were the two most common intra-oral sources, and wisdom tooth extraction was the most common preceding dental procedure. In 56.4% of cases, there were obvious signs of dental disease prior to development of intracranial infection. Commonly implicated microorganisms included Streptococcus viridans (especially the anginosus group), Actinomyces, Peptostreptococcus, Prevotella, Fusobacterium, Aggregatibacter actinomycetemcomitans and Eikenella corrodens. There was an 8.3% mortality rate. Intracranial abscesses can form anywhere within the brain, and appear unrelated to the side of dental involvement. This suggests that hematogenous spread is the most likely route of dissemination. PMID:25800939

  7. Minimally invasive hip replacement

    MedlinePlus

    ... Smits SA, Swinford RR, Bahamonde RE. A randomized, prospective study of 3 minimally invasive surgical approaches in total hip arthroplasty: comprehensive gait analysis. J Arthroplasty . 2008;23:68-73. PMID: 18722305 ...

  8. Minimally invasive surgery for the treatment of ureteral stump syndrome

    PubMed Central

    Alenezi, Husain; Eltiraifi, Abdelmoniem E.; Alomar, Mohammad

    2015-01-01

    Objective: The aim was to highlight the advantages and the feasibility of treating ureteral stump syndrome (USS) by different minimally invasive procedures. Materials and Methods: Four patients with USS who were treated by different minimally invasive surgery approaches depending on their presentation and findings on radiologic investigations. Results: Three patients had complete resolution of their symptoms, whereas the fourth patient had persistence of urinary tract infection. Conclusion: Minimally invasive surgery is a valid treatment option for patients with USS with possible less morbidity than conventional open surgical excision. PMID:26692664

  9. Invasion of the Fungal Pathogen Batrachochytrium dendrobatidis on California Islands.

    PubMed

    Yap, Tiffany A; Gillespie, Lauren; Ellison, Silas; Flechas, Sandra V; Koo, Michelle S; Martinez, Ari E; Vredenburg, Vance T

    2016-03-01

    Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen, has infected >500 species and caused extinctions or declines in >200 species worldwide. Despite over a decade of research, little is known about its invasion biology. To better understand this, we conducted a museum specimen survey (1910-1997) of Bd in amphibians on 11 California islands and found a pattern consistent with the emergence of Bd epizootics on the mainland, suggesting that geographic isolation did not prevent Bd invasion. We propose that suitable habitat, host diversity, and human visitation overcome isolation from the mainland and play a role in Bd invasion. PMID:26493624

  10. Death by edible mushroom: first report of Volvariella volvacea as an etiologic agent of invasive disease in a patient following double umbilical cord blood transplantation.

    PubMed

    Salit, R B; Shea, Y R; Gea-Banacloche, J; Fahle, G A; Abu-Asab, M; Sugui, J A; Carpenter, A E; Quezado, M M; Bishop, M R; Kwon-Chung, K J

    2010-11-01

    We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales. PMID:20826647

  11. MARveling at parasite invasion.

    PubMed

    Hager, Kristin M; Carruthers, Vern B

    2008-02-01

    Micronemal proteins (MICs) are key mediators of cytoadherence and invasion for Toxoplasma gondii. Emerging evidence indicates that carbohydrate binding facilitates Toxoplasma entry into host cells. The recently solved Toxoplasma MIC1s (TgMIC1s) structure reveals the presence of novel specialized domains that can discriminate between glycan residues. Comparison with Plasmodium erythrocyte-binding antigen 175 reveals that terminal sialic acid residues might represent a shared but tailored invasion pathway among apicomplexan parasites. PMID:18203663

  12. Primary immunodeficiencies underlying fungal infections

    PubMed Central

    Lanternier, Fanny; Cypowyj, Sophie; Picard, Capucine; Bustamante, Jacinta; Lortholary, Olivier; Casanova, Jean-Laurent; Puel, Anne

    2014-01-01

    Purpose of review We review the primary immunodeficiencies underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors. Recent findings An increasing number of primary immunodeficiencies are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of IFN-γ immunity underlie endemic mycoses. Inborn errors of IL-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis, whereas inborn errors of CARD9 immunity underlie deep dermatophytosis and invasive candidiasis. Summary Chronic mucocutaneous candidiasis, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by primary immunodeficiencies. Each type of infection is highly suggestive of a specific type of primary immunodeficiency. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases. PMID:24240293

  13. Anidulafungin in Treatment of Experimental Invasive Infection by Candida parapsilosis: In Vitro Activity, (1→3)-β-d-Glucan and Mannan Serum Levels, Histopathological Findings, and In Vivo Efficacy▿

    PubMed Central

    Salas, Valentina; Pastor, F. Javier; Calvo, Enrique; Mayayo, Emilio; Quindós, Guillermo; Carrillo, Alfonso J.; Guarro, Josep

    2011-01-01

    We have evaluated the in vitro activity of anidulafungin (AFG) against 31 strains of Candida parapsilosis sensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive of in vivo outcomes, six strains representing different AFG MICs (0.12 to 2 μg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 μg/ml). PMID:21844324

  14. [Invasive pulmonary aspergillosis. Necropsy series].

    PubMed

    Alba, D; Gómez-Cerezo, J; Cobo, J; Fachal, C; Molina, F; Vázquez, J J

    1995-01-01

    Invasive pulmonary aspergillosis (IPA) is a severe infection which is usually diagnosed at postmortem examination. This infection occurs mainly in immunosuppressed patients, although it has also been reported in immunocompetent patients. Clinical records from patients diagnosed with IPA in our institution from 1983 to 1992 were retrospectively studied to analyse clinical and therapeutical characteristics of IPA. Sixteen episodes of IPA were recorded, all of them but one from necrotic specimens. A total of 18.7% of patients were immunocompetent, one patient had the acquired immunodeficiency syndrome (AIDS), and the remaining patients had a classical immunosuppression. Fever and dyspnea were noted in all patients; hemoptysis was recorded in 12.5% of patients. The predominant radiological pattern was a bilateral alveolar infiltrate (75%). Diagnosis was made at postmortem examination in 15 cases (93.7%), and a clinical premortem suspicion was obtained only in 25% of patients. IPA can occur in immunocompetent patients more frequently than considered until now. The suspicion index for IPA is low, even in immunosuppressed patients. PMID:7878262

  15. Fungal invasion of the rhizosphere microbiome.

    PubMed

    Chapelle, Emilie; Mendes, Rodrigo; Bakker, Peter A H M; Raaijmakers, Jos M

    2016-01-01

    The rhizosphere is the infection court where soil-borne pathogens establish a parasitic relationship with the plant. To infect root tissue, pathogens have to compete with members of the rhizosphere microbiome for available nutrients and microsites. In disease-suppressive soils, pathogens are strongly restricted in growth by the activities of specific rhizosphere microorganisms. Here, we sequenced metagenomic DNA and RNA of the rhizosphere microbiome of sugar beet seedlings grown in a soil suppressive to the fungal pathogen Rhizoctonia solani. rRNA-based analyses showed that Oxalobacteraceae, Burkholderiaceae, Sphingobacteriaceae and Sphingomonadaceae were significantly more abundant in the rhizosphere upon fungal invasion. Metatranscriptomics revealed that stress-related genes (ppGpp metabolism and oxidative stress) were upregulated in these bacterial families. We postulate that the invading pathogenic fungus induces, directly or via the plant, stress responses in the rhizobacterial community that lead to shifts in microbiome composition and to activation of antagonistic traits that restrict pathogen infection. PMID:26023875

  16. A unified approach for quantifying invasibility and degree of invasion.

    PubMed

    Guo, Qinfeng; Fei, Songlin; Dukes, Jeffrey S; Oswalt, Christopher M; Iannone, Basil V; Potter, Kevin M

    2015-10-01

    Habitat invasibility is a central focus of invasion biology, with implications for basic ecological patterns and processes and for effective invasion management. "Invasibility" is, however, one of the most elusive metrics and misused terms in ecology. Empirical studies and meta-analyses of invasibility have produced inconsistent and even conflicting results. This lack of consistency, and subsequent difficulty in making broad cross-habitat comparisons, stem in part from (1) the indiscriminant use of a closely related, but fundamentally different concept, that of degree of invasion (DI) or level of invasion; and (2) the lack of common invasibility metrics, as illustrated by our review of all invasibility-related papers published in 2013. To facilitate both cross-habitat comparison and more robust ecological generalizations, we clarify the definitions of invasibility and DI, and for the first time propose a common metric for quantifying invasibility based on a habitat's resource availability as inferred from relative resident species richness and biomass. We demonstrate the feasibility of our metric using empirical data collected from 2475 plots from three forest ecosystems in the eastern United States. We also propose a similar metric for DI. Our unified, resource-based metrics are scaled from 0 to 1, facilitating cross-habitat comparisons. Our proposed metrics clearly distinguish invasibility and DI from each other, which will help to (1) advance invasion ecology by allowing more robust testing of generalizations and (2) facilitate more effective invasive species control and management. PMID:26649383

  17. Minimally invasive procedures

    PubMed Central

    Baltayiannis, Nikolaos; Michail, Chandrinos; Lazaridis, George; Anagnostopoulos, Dimitrios; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Kioumis, Ioannis; Pitsiou, Georgia; Katsikogiannis, Nikolaos; Tsakiridis, Kosmas; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos

    2015-01-01

    Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small “ports” from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry—meaning only one small incision, like the “uniport” video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional “open” surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery. PMID:25861610

  18. Minimally invasive pancreatic surgery.

    PubMed

    Yiannakopoulou, E

    2015-12-01

    Minimally invasive pancreatic surgery is feasible and safe. Laparoscopic distal pancreatectomy should be widely adopted for benign lesions of the pancreas. Laparoscopic pancreaticoduodenectomy, although technically demanding, in the setting of pancreatic ductal adenocarcinoma has a number of advantages including shorter hospital stay, faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. Furthermore, it seems that progression-free survival is longer in patients undergoing laparoscopic pancreaticoduodenectomy in comparison with those undergoing open pancreaticoduodenectomy. Minimally invasive middle pancreatectomy seems appropriate for benign or borderline tumors of the neck of the pancreas. Technological advances including intraoperative ultrasound and intraoperative fluorescence imaging systems are expected to facilitate the wide adoption of minimally invasive pancreatic surgery. Although, the oncological outcome seems similar with that of open surgery, there are still concerns, as the majority of relevant evidence comes from retrospective studies. Large multicenter randomized studies comparing laparoscopic with open pancreatectomy as well as robotic assisted with both open and laparoscopic approaches are needed. Robotic approach could be possibly shown to be less invasive than conventional laparoscopic approach through the less traumatic intra-abdominal handling of tissues. In addition, robotic approach could enable the wide adoption of the technique by surgeon who is not that trained in advanced laparoscopic surgery. A putative clinical benefit of minimally invasive pancreatic surgery could be the attenuated surgical stress response leading to reduced morbidity and mortality as well as lack of the detrimental immunosuppressive effect especially for the oncological patients. PMID:26530291

  19. Alien invasive birds.

    PubMed

    Brochier, B; Vangeluwe, D; van den Berg, T

    2010-08-01

    A bird species is regarded as alien invasive if it has been introduced, intentionally or accidentally, to a location where it did not previously occur naturally, becomes capable of establishing a breeding population without further intervention by humans, spreads and becomes a pest affecting the environment, the local biodiversity, the economy and/or society, including human health. European Starling (Sturnus vulgaris), Common Myna (Acridotheres tristis) and Red-vented Bulbul (Pycnonotus cafer) have been included on the list of '100 of the World's Worst Invasive Alien Species', a subset of the Global Invasive Species Database. The 'Delivering Alien Invasive Species Inventories for Europe' project has selected Canada Goose (Branta canadensis), Ruddy Duck (Oxyura jamaicensis), Rose-ringed Parakeet (Psittacula krameri) and Sacred Ibis (Threskiornis aethiopicus) as among 100 of the worst invasive species in Europe. For each of these alien bird species, the geographic range (native and introduced range), the introduction pathway, the general impacts and the management methods are presented. PMID:20919578

  20. Distribution of emm types in invasive and non-invasive group A and G streptococci.

    PubMed

    Vähäkuopus, S; Vuento, R; Siljander, T; Syrjänen, J; Vuopio, J

    2012-06-01

    Our study describes the emm type distributions of invasive and non-invasive group A streptococci (GAS) and group G streptococci (GGS) strains in one of the biggest Health Districts in Finland. A total of 571 GAS or GGS were recovered from patients with invasive or non-invasive infections during a 1-year period in 2008-2009 in Pirkanmaa Health District in Finland. We describe here the emm type distributions of GAS and GGS collected from throat (n = 246), pus (n = 217), deep tissue (n = 56) and blood (n = 52). The most common emm types among GAS were emm77, emm1, emm28, emm89 and emm12. Among GGS, the most common emm types were stG480, stG643, stG6, stC6979 and stG485. Some emm types were found to associate with certain infection focus. In GAS, emm77 associated with pus isolates, whereas emm1 and emm12 were more frequent among throat isolates. In GGS, stG480 was more commonly found from throat isolates. PMID:22002182

  1. [Invasive fungal disease due to Scedosporium, Fusarium and mucorales].

    PubMed

    Pemán, Javier; Salavert, Miguel

    2014-01-01

    The number of emerging organisms causing invasive fungal infections has increased in the last decades. These etiological agents include Scedosporium, Fusarium and mucorales. All of them can cause disseminated, virulent, and difficult-to treat infections in immunosuppressed patients, the most affected, due to their resistance to most available antifungal agents. Current trends in transplantation including the use of new immunosuppressive treatments, the common prescription of antifungal agents for prophylaxis, and new ecological niches could explain the emergence of these fungal pathogens. These pathogens can also affect immunocompetent individuals, especially after natural disasters (earthquakes, floods, tsunamis), combat wounds or near drowning. All the invasive infections caused by Scedosporium, Fusarium, and mucorales are potentially lethal and a favourable outcome is associated with rapid diagnosis by direct microscopic examination of the involved tissue, wide debridement of infected material, early use of antifungal agents including combination therapy, and an improvement in host defenses, especially neutropenia. PMID:25442383

  2. Invasion triangle: an organizational framework for species invasion

    PubMed Central

    Perkins, Lora B; Leger, Elizabeth A; Nowak, Robert S

    2011-01-01

    Species invasion is a complex, multifactor process. To encapsulate this complexity into an intuitively appealing, simple, and straightforward manner, we present an organizational framework in the form of an invasion triangle. The invasion triangle is an adaptation of the disease triangle used by plant pathologists to help envision and evaluate interactions among a host, a pathogen, and an environment. Our modification of this framework for invasive species incorporates the major processes that result in invasion as the three sides of the triangle: (1) attributes of the potential invader; (2) biotic characteristics of a potentially invaded site; and (3) environmental conditions of the site. The invasion triangle also includes the impact of external influences on each side of the triangle, such as climate and land use change. This paper introduces the invasion triangle, discusses how accepted invasion hypotheses are integrated in this framework, describes how the invasion triangle can be used to focus research and management, and provides examples of application. The framework provided by the invasion triangle is easy to use by both researchers and managers and also applicable at any level of data intensity, from expert opinion to highly controlled experiments. The organizational framework provided by the invasion triangle is beneficial for understanding and predicting why species are invasive in specific environments, for identifying knowledge gaps, for facilitating communication, and for directing management in regard to invasive species. PMID:22393528

  3. Deletion of Invasion Protein B in Salmonella enterica Serovar Typhimurium Influences Bacterial Invasion and Virulence.

    PubMed

    Chen, Songbiao; Zhang, Chunjie; Liao, Chengshui; Li, Jing; Yu, Chuan; Cheng, Xiangchao; Yu, Zuhua; Zhang, Mingliang; Wang, Yang

    2015-12-01

    Salmonella enterica serovar Typhimurium (S. Typhimurium) has a wide host range and causes infections ranging from severe gastroenteritis to systemic infections in human, as well as causing typhoid-like disease in murine models of infection. S. Typhimurium translocates its effector proteins through the Salmonella pathogenicity island-I (SPI-I)-encoded T3SS-I needle complex. This study focuses on invasion protein B (SipB) of S. Typhimurium, which plays an active role in SPI-I invasion efficiency. To test our hypothesis, a sipB deletion mutant was constructed through double-crossover allelic using the suicide vector pRE112ΔsipB, and its biological characteristics were analyzed. The results showed that the SipB does not affect the growth of Salmonella, but the adherence, invasion, and virulence of the mutant were significantly decreased compared with wild-type S. Typhimurium (SL1344). This research indicates that SipB is an important virulence factor in the pathogenicity of S. Typhimurium. PMID:26341924

  4. Infections and antibiotic resistance in nursing homes.

    PubMed Central

    Nicolle, L E; Strausbaugh, L J; Garibaldi, R A

    1996-01-01

    Infections occur frequently in nursing home residents. The most common infections are pneumonia, urinary tract infection, and skin and soft tissue infection. Aging-associated physiologic and pathologic changes, functional disability, institutionalization, and invasive devices all contribute to the high occurrence of infection. Antimicrobial agent use in nursing homes is intense and usually empiric. All of these factors contribute to the increasing frequency of antimicrobial agent-resistant organisms in nursing homes. Programs that will limit the emergence and impact of antimicrobial resistance and infections in nursing homes need to be developed. PMID:8665472

  5. Intracellular Parasite Invasion Strategies

    NASA Astrophysics Data System (ADS)

    Sibley, L. D.

    2004-04-01

    Intracellular parasites use various strategies to invade cells and to subvert cellular signaling pathways and, thus, to gain a foothold against host defenses. Efficient cell entry, ability to exploit intracellular niches, and persistence make these parasites treacherous pathogens. Most intracellular parasites gain entry via host-mediated processes, but apicomplexans use a system of adhesion-based motility called ``gliding'' to actively penetrate host cells. Actin polymerization-dependent motility facilitates parasite migration across cellular barriers, enables dissemination within tissues, and powers invasion of host cells. Efficient invasion has brought widespread success to this group, which includes Toxoplasma, Plasmodium, and Cryptosporidium.

  6. Mechanisms of Perineural Invasion.

    PubMed

    Bakst, Richard L; Wong, Richard J

    2016-04-01

    Perineural invasion (PNI) is the neoplastic invasion of nerves. PNI is widely recognized as an important adverse pathological feature of many malignancies, including pancreatic, prostate, and head and neck cancers and is associated with a poor prognosis. Despite widespread acknowledgment of the clinical significance of PNI, the mechanisms underlying its pathogenesis remain largely unknown. Recent theories of PNI pathogenesis have placed a significant emphasis on the active role of the nerve microenvironment, with PNI resulting from well-orchestrated reciprocal interactions between cancer and host. Elucidating the mechanisms involved in PNI may translate into targeted therapies for this ominous process. PMID:27123385

  7. Minimally Invasive Radiofrequency Devices.

    PubMed

    Sadick, Neil; Rothaus, Kenneth O

    2016-07-01

    This article reviews minimally invasive radiofrequency options for skin tightening, focusing on describing their mechanism of action and clinical profile in terms of safety and efficacy and presenting peer-reviewed articles associated with the specific technologies. Treatments offered by minimally invasive radiofrequency devices (fractional, microneedling, temperature-controlled) are increasing in popularity due to the dramatic effects they can have without requiring skin excision, downtime, or even extreme financial burden from the patient's perspective. Clinical applications thus far have yielded impressive results in treating signs of the aging face and neck, either as stand-alone or as postoperative maintenance treatments. PMID:27363771

  8. Airway centered invasive pulmonary aspergillosis in an immunocompetent patient: case report and literature review

    PubMed Central

    Kim, Jun Ho; Lee, Hong Lyeol; Kim, Lucia; Kim, Jung Soo; Kim, Yeo Ju; Lee, Ha Young

    2016-01-01

    Invasive pulmonary aspergillosis is a major problem that occurs in severely immunocompromised patients. Airway centered invasive pulmonary aspergillosis is rare in patients with normal immunity or those without critical illness. Computed tomography (CT) is a very useful diagnostic modality, yielding characteristic imaging findings for early diagnosis of this infection in immunocompromised and immunocompetent patients. We describe the case of an immunocompetent patient with airway centered invasive aspergillosis, who was successfully treated with voriconazole. PMID:27076982

  9. No holes barred: Invasion of the intestinal mucosa by Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The infection biology of Mycobacterium avium subspecies paratuberculosis (MAP) has recently crystalized with added details surrounding intestinal invasion. The involvement of pathogen-derived effector proteins such as the major membrane protein, oxidoreductase and fibronectin attachment proteins hav...

  10. Enhancement of invasiveness of Yersinia enterocolitica and Escherichia coli in HEp-2 cells by centrifugation.

    PubMed Central

    Vesikari, T; Bromirska, J; Mäki, M

    1982-01-01

    Centrifugation enhanced the infectivity of invasive Escherichia coli and Yersinia enterocolitica for HEp-2 cells. Noninvasive bacteria were not endocytosed after centrifugation. The centrifugation procedure may increase the sensitivity of testing for bacterial invasiveness in cell culture without causing false-positive results. PMID:7044978

  11. Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice.

    PubMed

    Feng, Wenchao; Liu, Mengyao; Chen, Daniel G; Yiu, Rossana; Fang, Ferric C; Lei, Benfang

    2016-01-01

    Group A Streptococcus (GAS) causes diverse infections ranging from common pharyngitis to rare severe invasive infections. Invasive GAS isolates can have natural mutations in the virulence regulator CovRS, which result in enhanced expression of multiple virulence genes, suppressed the expression of the protease SpeB, and increased virulence. It is believed that CovRS mutations arise during human infections with GAS carrying wild-type CovRS and are not transmissible. CovRS mutants of invasive GAS of the emm1 genotype arise readily during experimental infection in mice. It is possible that invasive GAS arises from pharyngeal GAS through rare genetic mutations that confer the capacity of mutated GAS to acquire covRS mutations during infection. The objective of this study was to determine whether contemporary pharyngeal emm1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28 SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined during subcutaneo