Sample records for host disease prophylaxis

  1. Multipotent Mesenchymal Stromal Cells for the Prophylaxis of Acute Graft-versus-Host Disease-A Phase II Study.

    PubMed

    Kuzmina, Larisa A; Petinati, Natalia A; Parovichnikova, Elena N; Lubimova, Lidia S; Gribanova, Elena O; Gaponova, Tatjana V; Shipounova, Irina N; Zhironkina, Oxana A; Bigildeev, Alexey E; Svinareva, Daria A; Drize, Nina J; Savchenko, Valery G

    2012-01-01

    The efficacy and the safety of the administration of multipotent mesenchymal stromal cells (MMSCs) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic hematopoietic cell transplantation (HSCT) were studied. This prospective clinical trial was based on the random patient allocation to the following two groups receiving (1) standard GVHD prophylaxis and (2) standard GVHD prophylaxis combined with MMSCs infusion. Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9-1.3 × 10(6)/kg when the blood counts indicated recovery. aGVHD of stage II-IV developed in 38.9% and 5.3% of patients in group 1 and group 2, respectively, (P = 0.002). There were no differences in the graft rejection rates, chronic GVHD development, or infectious complications. Overall mortality was 16.7% for patients in group 1 and 5.3% for patients in group 2. The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study.

  2. Analysis of multipotent mesenchymal stromal cells used for acute graft-versus-host disease prophylaxis.

    PubMed

    Kuzmina, Larisa A; Petinati, Nataliya A; Shipounova, Irina N; Sats, Natalia V; Bigildeev, Alexey E; Zezina, Ekaterina A; Popova, Maria D; Drize, Nina J; Parovichnikova, Elena N; Savchenko, Valery G

    2016-04-01

    Multipotent mesenchymal stromal cells (MSCs) are used for prophylaxis of acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Not all samples of MSC are efficient for aGvHD prevention. The suitability of MSCs for aGvHD prophylaxis was studied. MSCs were derived from the bone marrow (BM) of HCT donor and cultivated for no more than three passages. The characteristics of donor BM samples including colony-forming unit fibroblast (CFU-F) concentration, growth parameters of MSCs, and the relative expression levels (REL) of different genes were analyzed. MSCs were injected intravenously precisely at the moment of blood cell reconstitution. MSCs infusion induced a significant threefold decrease in aGvHD development and improved overall survival compared with the standard prophylaxis group. In ineffective MSC samples (9.4%), a significant decrease in total cell production and the REL of CSF1, FGFR1, and PDGFRB was observed. In all studied BM samples, the cumulative MSC production and CFU-F concentrations decreased with age. The expression levels of FGFR2, PPARG, and VEGF differed by age. A universal single indicator for the prediction of MSC eligibility for aGvHD prophylaxis was not identified. A multiparameter mathematical model for selecting MSC samples effective for the prevention of aGvHD was proposed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

    PubMed

    Tekgündüz, Emre; Kaya, Ali Hakan; Bozdağ, Sinem Civriz; Koçubaba, Şerife; Kayıkçı, Ömür; Namdaroğlu, Sinem; Uğur, Bilge; Akpınar, Seval; Batgi, Hikmetullah; Bekdemir, Filiz; Altuntaş, Fevzi

    2016-02-01

    There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D+180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius.

    PubMed

    Socié, Gérard; Schmoor, Claudia; Bethge, Wolfgang A; Ottinger, Hellmut D; Stelljes, Matthias; Zander, Axel R; Volin, Liisa; Ruutu, Tapani; Heim, Dominik A; Schwerdtfeger, Rainer; Kolbe, Karin; Mayer, Jiri; Maertens, Johan A; Linkesch, Werner; Holler, Ernst; Koza, Vladimir; Bornhäuser, Martin; Einsele, Hermann; Kolb, Hans-Jochem; Bertz, Hartmut; Egger, Matthias; Grishina, Olga; Finke, Jürgen

    2011-06-09

    Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD). Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the control group (hazard ratio [HR] = 1.21, P = .47, and HR = 0.68, P = .18), respectively. This nonsignificant reduction in nonrelapse mortality without increased relapse risk led to an overall survival rate after 3 years of 55.2% in the ATG-F group and 43.3% in the control group (HR = 0.84, P = .39, nonsignificant). The HR for receiving immunosuppressive therapy (IST) was 0.31 after ATG-F (P < .0001), and the 3-year probability of survival free of IST was 52.9% and 16.9% in the ATG-F versus control, respectively. The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate. ATG-F prophylaxis reduces cGVHD morbidity.

  5. Outcomes of matched sibling donor bone marrow transplantation in children using single-agent calcineurin inhibitors as prophylaxis for graft versus host disease.

    PubMed

    Elgarten, Caitlin W; Arnold, Danielle E; Bunin, Nancy J; Seif, Alix E

    2018-01-01

    Optimal graft versus host disease (GVHD) prophylaxis prevents severe manifestations without excess immunosuppression. Standard prophylaxis includes a calcineurin inhibitor (CNI) with low-dose methotrexate. However, single-agent CNI may be sufficient prophylaxis for a defined group of patients. Single-agent CNI has been used for GVHD prophylaxis for human leukocyte antigen (HLA)-matched sibling donor (MSD) bone marrow transplants (BMTs) in young patients at the Children's Hospital of Philadelphia for over 20 years. Here, we describe outcomes using this prophylactic strategy in a recent cohort. We performed a single-institution chart review and retrospective analysis of consecutive children undergoing MSD BMT who received single-agent CNI for GVHD prophylaxis between January 2002 and December 2014. Fifty-two children with a median age of 6.1 years (interquartile range [IQR] 2.5-8.3) and donor age of 6 years (IQR 3-10), with malignant and nonmalignant diseases (n = 35 and 17, respectively) were evaluated. Forty-three (82.6%) received oral prophylaxis with single-agent tacrolimus after initial intravenous therapy. Rates of GVHD were consistent with reported rates on dual prophylaxis: the overall incidence of grades 2-4 acute GVHD was 25.5%, grades 3-4 GVHD 9.8%, and chronic GVHD 10.4%. The cumulative incidence of relapse among children with malignancy was 20% at a median of 237 days (IQR 194-318) post-transplant. Two-year overall survival was 82.7% (95% confidence interval [CI]: 69.4-90.6%) and event-free survival was 78.9% (95% CI: 65.1-87.7%). No patient experienced graft failure. Single-agent CNI is a safe, effective approach to GVHD prophylaxis in young patients undergoing HLA-identical sibling BMT. Additionally, single-agent oral tacrolimus is a reasonable alternative to cyclosporine in this population. © 2017 Wiley Periodicals, Inc.

  6. Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation.

    PubMed

    Kanate, Abraham S; Hari, Parameswaran N; Pasquini, Marcelo C; Visotcky, Alexis; Ahn, Kwang W; Boyd, Jennifer; Guru Murthy, Guru Subramanian; Rizzo, J Douglas; Saber, Wael; Drobyski, William; Michaelis, Laura; Atallah, Ehab; Carlson, Karen S; D'Souza, Anita; Fenske, Timothy S; Cumpston, Aaron; Bunner, Pamela; Craig, Michael; Horowitz, Mary M; Hamadani, Mehdi

    2017-08-01

    Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in

  7. Sibling Donor and Recipient Immune Modulation With Atorvastatin for the Prophylaxis of Acute Graft-Versus-Host Disease

    PubMed Central

    Hamadani, Mehdi; Gibson, Laura F.; Remick, Scot C.; Wen, Sijin; Petros, William; Tse, William; Brundage, Kathleen M.; Vos, Jeffrey A.; Cumpston, Aaron; Bunner, Pamela; Craig, Michael D.

    2013-01-01

    Purpose Graft-versus-host disease (GVHD) is major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Atorvastatin is a potent immunomodulatory agent that holds promise as a novel and safe agent for acute GVHD prophylaxis. Patients and Methods We conducted a phase II trial to evaluate the safety and efficacy of atorvastatin administration for GVHD prophylaxis in both adult donors and recipients of matched sibling allogeneic HCT. Atorvastatin (40 mg per day orally) was administered to sibling donors, starting 14 to 28 days before the anticipated first day of stem-cell collection. In HCT recipients (n = 30), GVHD prophylaxis consisted of tacrolimus, short-course methotrexate, and atorvastatin (40 mg per day orally). Results Atorvastatin administration in healthy donors and recipients was not associated with any grade 3 to 4 adverse events. Cumulative incidence rates of grade 2 to 4 acute GVHD at days +100 and +180 were 3.3% (95% CI, 0.2% to 14.8%) and 11.1% (95% CI, 2.7% to 26.4%), respectively. One-year cumulative incidence of chronic GVHD was 52.3% (95% CI, 27.6% to 72.1%). Viral and fungal infections were infrequent. One-year cumulative incidences of nonrelapse mortality and relapse were 9.8% (95% CI, 1.4% to 28%) and 25.4% (95% CI, 10.9% to 42.9%), respectively. One-year overall survival and progression-free survival were 74% (95% CI, 58% to 96%) and 65% (95% CI, 48% to 87%), respectively. Compared with baseline, atorvastatin administration in sibling donors was associated with a trend toward increased mean plasma interleukin-10 concentrations (5.6 v 7.1 pg/mL; P = .06). Conclusion A novel two-pronged strategy of atorvastatin administration in both donors and recipients of matched sibling allogeneic HCT seems to be a feasible, safe, and potentially effective strategy to prevent acute GVHD. PMID:24166529

  8. Multipotent Mesenchymal Stromal Cells for the Prophylaxis of Acute Graft-versus-Host Disease—A Phase II Study

    PubMed Central

    Kuzmina, Larisa A.; Petinati, Natalia A.; Parovichnikova, Elena N.; Lubimova, Lidia S.; Gribanova, Elena O.; Gaponova, Tatjana V.; Shipounova, Irina N.; Zhironkina, Oxana A.; Bigildeev, Alexey E.; Svinareva, Daria A.; Drize, Nina J.; Savchenko, Valery G.

    2012-01-01

    The efficacy and the safety of the administration of multipotent mesenchymal stromal cells (MMSCs) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic hematopoietic cell transplantation (HSCT) were studied. This prospective clinical trial was based on the random patient allocation to the following two groups receiving (1) standard GVHD prophylaxis and (2) standard GVHD prophylaxis combined with MMSCs infusion. Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9–1.3 × 106/kg when the blood counts indicated recovery. aGVHD of stage II–IV developed in 38.9% and 5.3% of patients in group 1 and group 2, respectively, (P = 0.002). There were no differences in the graft rejection rates, chronic GVHD development, or infectious complications. Overall mortality was 16.7% for patients in group 1 and 5.3% for patients in group 2. The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study. PMID:22242033

  9. Role of vaccinations and prophylaxis in rheumatic diseases.

    PubMed

    Papadopoulou, Despoina; Tsoulas, Christos; Tragiannidis, Athanassios; Sipsas, Nikolaos V

    2015-04-01

    Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Treatment of Tularemia in Patient with Chronic Graft-versus-Host Disease

    PubMed Central

    Seibold, Erik; Knabbe, Cornelius; Kaufmann, Martin; Splettstoesser, Wolf

    2013-01-01

    We describe a case of human tularemia caused by Francisella tularensis subsp. holarctica in a stem cell transplant recipient with chronic graft-versus-host disease who was receiving levofloxacin prophylaxis. The infection was characterized by pneumonia with septic complications. The patient was successfully treated with doxycycline. PMID:23647853

  11. Mammalian target of rapamycin inhibitor-associated stomatitis in hematopoietic stem cell transplantation patients receiving sirolimus prophylaxis for graft-versus-host disease.

    PubMed

    Villa, Alessandro; Aboalela, Ali; Luskin, Katharine A; Cutler, Corey S; Sonis, Stephen T; Woo, Sook Bin; Peterson, Douglas E; Treister, Nathaniel S

    2015-03-01

    The mammalian target of rapamycin (mTOR) inhibitor sirolimus is effective in reducing incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Agents that inhibit the mTOR pathway are known to be associated with significant and potentially dose-limiting toxicities, including stomatitis. The objective of this study was to report the clinical features and management outcomes of sirolimus-associated oral ulcers in the context of post-HSCT prophylaxis of GVHD. Seventeen patients, from a study cohort of 967, who were treated with sirolimus as prophylaxis for GVHD after allogeneic HSCT at the Dana-Farber/Brigham and Women's Cancer Center developed oral ulcers and were referred to the oral medicine clinic for evaluation and treatment over a period of 6 years. Clinical characteristics (appearance, anatomic site, size) and therapeutic outcomes (time to complete resolution) were documented. Median time to onset of oral ulceration was 55 days after allogeneic HSCT (range, 6 to 387 days); 92.9% of ulcers were located on nonkeratinized mucosa, with the ventrolateral tongue the most common site of involvement. Thirteen patients were treated with topical corticosteroid therapy; 12 of these patients also required intralesional corticosteroid injections. Clinical improvement (resolution of the lesions and improvement of symptoms) was noted in all cases, with no reported adverse events. Median time to complete resolution after onset of therapy was 14 days (range, 2 to 70 days). Patients receiving sirolimus for GVHD prophylaxis may develop painful oral ulcerations, which can be effectively managed with topical steroid treatment. Further prospective studies are needed to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of interventions. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Prophylaxis against Pneumocystis pneumonia in patients with inflammatory bowel disease: toward a standard of care.

    PubMed

    Poppers, David M; Scherl, Ellen J

    2008-01-01

    Patients with Crohn's Disease and ulcerative colitis are increasingly treated with a host of immunomodulatory and immunosuppressive medications, including thiopurines and antibody-based biologic agents. Despite the known infectious complications associated with these therapies from the HIV and solid organ transplant literature, there are currently no well-defined concise guidelines to assist gastroenterologists and other physicians in the utility and indication for prophylaxis against Pneumocystis pneumonia and other infections in inflammatory bowel disease (IBD) patients. In this article, we discuss the evidence of various infections associated with immunocompromise in HIV/AIDS, organ transplantation, and in other immunocompromised states, and discuss the evidence for the efficacy and safety of various infectious prophylaxis protocols. In addition, we discuss the evidence for Pneumocystis and other infections in IBD patients treated with corticosteroids, azathioprine/6-MP, biologic agents and other therapies, and we present the case for various antibiotic (and antiviral) regimens to prevent such infections. Based on the review of the literature, this discussion represents a true call for guidelines for infection prophylaxis, to help guide gastroenterologists and all practitioners who care for the challenging population of IBD patients.

  13. Cytomegalovirus disease in lung transplantation: impact of recipient seropositivity and duration of antiviral prophylaxis.

    PubMed

    Hammond, S P; Martin, S T; Roberts, K; Gabardi, S; Fuhlbrigge, A L; Camp, P C; Goldberg, H J; Marty, F M; Baden, L R

    2013-04-01

    A recent randomized trial demonstrated that 1 year of antiviral prophylaxis for cytomegalovirus (CMV) after lung transplantation is superior to 3 months of treatment for prevention of CMV disease. However, it is uncertain if a shorter duration of prophylaxis might result in a similar rate of CMV disease among select lung transplant (LT) recipients who are at lower risk for CMV disease, based on baseline donor (D) and recipient (R) CMV serologies. We retrospectively assessed incidence, cumulative probability, and predictors of CMV disease and viremia in LT recipients transplanted between July 2004 and December 2009 at our center, where antiviral CMV prophylaxis for 6-12 months is standard. Of 129 LT recipients, 94 were at risk for CMV infection based on donor CMV seropositivity (D+) or recipient seropositivity (R+); 14 developed CMV disease (14.9%): 11 with CMV syndrome, 2 with pneumonitis, and 1 with gastrointestinal disease by the end of follow-up (October 2010); 17 developed asymptomatic CMV viremia (18.1%). The cumulative probability of CMV disease was 17.4% 18 months after transplantation. CMV D+/R- recipients who routinely received 1 year of prophylaxis were more likely to develop CMV disease compared with D+/R+ or D-/R+ recipients, who routinely received 6 months of prophylaxis (12/45 vs. 2/25 vs. 0/24, P = 0.005). Recipients who stopped CMV prophylaxis before 12 months (in D+/R- recipients) and 6 months (in R+ recipients) tended to develop CMV disease more than those who did not (9/39 vs. 3/41, P = 0.06). On a 6-month CMV prophylaxis protocol, few R+ recipients developed CMV disease in this cohort. In contrast, despite a 12-month prophylaxis protocol, D+/R- LT recipients remained at highest risk for CMV disease. © 2012 John Wiley & Sons A/S.

  14. Analysis of results of acute graft-versus-host disease prophylaxis with donor multipotent mesenchymal stromal cells in patients with hemoblastoses after allogeneic bone marrow transplantation.

    PubMed

    Shipounova, I N; Petinati, N A; Bigildeev, A E; Zezina, E A; Drize, N I; Kuzmina, L A; Parovichnikova, E N; Savchenko, V G

    2014-12-01

    Allogeneic bone marrow transplantation (allo-BMT) is currently the only way to cure many hematoproliferative disorders. However, allo-BMT use is limited by severe complications, the foremost being graft-versus-host disease (GVHD). Due to the lack of efficiency of the existing methods of GVHD prophylaxis, new methods are being actively explored, including the use of donors' multipotent mesenchymal stromal cells (MMSC). In this work, we analyzed the results of acute GVHD (aGVHD) prophylaxis by means of MMSC injections after allo-BMT in patients with hematological malignancies. The study included 77 patients. They were randomized into two groups - those receiving standard prophylaxis of aGVHD and those who were additionally infused with MMSC derived from the bone marrow of hematopoietic stem cell donors. We found that the infusion of MMSC halves the incidence of aGVHD and increases the overall survival of patients. Four of 39 MMSC samples were ineffective for preventing aGVHD. Analysis of individual donor characteristics (gender, age, body mass index) and the MMSC properties of these donors (growth parameters, level of expression of 30 genes involved in proliferation, differentiation, and immunomodulation) revealed no significant difference between the MMSC that were effective or ineffective for preventing aGVHD. We used multiple logistic regression to establish a combination of features that characterize the most suitable MMSC samples for the prevention of aGVHD. A model predicting MMSC sample success for aGVHD prophylaxis was constructed. Significant model parameters were increased relative expression of the FGFR1 gene in combination with reduced expression levels of the PPARG and IGF1 genes. Depending on the chosen margin for probability of successful application of MMSC, this model correctly predicts the outcome of the use of MMSC in 82-94% of cases. The proposed model of prospective evaluation of the effectiveness of MMSC samples will enable prevention of the

  15. Using a point-of-dispensing clinic for prophylaxis of meningococcal disease.

    PubMed

    Ngo, Van P; Civen, Rachel H; Dassey, David E; Davenport, Deborah; Mascola, Laurene

    2010-03-01

    A point-of-dispensing clinic was held to distribute ciprofloxacin prophylaxis when 2 high school students were reported to the health department with invasive meningococcal disease. Of more than 3,100 school staff and students in attendance, 2,861 received prophylaxis. A survey was administered to students 2 weeks postclinic to better understand the motivations for clinic attendance and to quantify side effects of oral 500-mg ciprofloxacin prophylaxis. Data collected included reasons for attendance and perception of risk for acquiring meningococcal disease, rated on a 1-to-5 scale; type of contact with cases; and side effects. Of 2,888 students, 1,624 completed surveys; 1,390 took ciprofloxacin. The students rated parental influence and directives from the high school as reasons for attendance a mean of 3.97 and 3.34, respectively. The mean rating for risk of acquiring meningococcal disease was 1.49. Only 3% reported direct contact with case(s). Side effects, most commonly headache (17%) and stomachache (10%), were reported in 40% of students. Serious side effects such as rash and facial swelling were reported in <1%. In this adolescent population, few serious side effects and no joint disorders were reported after they ingested single-dose ciprofloxacin; however, many received the prophylaxis unnecessarily. Students were motivated by parents and school officials. Health departments should collaborate with schools to prepare and disseminate messages that balance the risks of unnecessary antibiotic use with those of exposure to disease.

  16. Ocular toxoplasmosis: background and evidence for an antibiotic prophylaxis.

    PubMed

    Reich, Michael; Mackensen, Friederike

    2015-11-01

    The purpose of this review was to provide an overview of current data on antibiotic prophylaxis in ocular toxoplasmosis. Studies showing the prophylactic effect of long-term antibiotics are discussed. Prophylaxis seems to be justified in patients with a high risk of recurrence because of antibiotic's potential side-effects. Therefore, predisposing factors leading to a higher risk of recurrence and the time period during which an antibiotic prophylaxis is most appropriate are reviewed. Finally, a patient-individualized treatment recommendation is summarized. In the current literature, two prospective, randomized case-control studies exist, which show the protective effect of an antibiotic prophylaxis. Hematologic, gastrointestinal and dermatologic complications are potential side-effects. Especially during the first year after suffering a recurrence, an antibiotic prophylaxis seems to be justified. The risk of a recurrence is inter alia influenced by the duration of the disease, the immune status of the host and the patient's age. Therefore, an antibiotic prophylaxis should be considered for patients who have recently been infected with ocular toxoplasmosis, for middle-aged and elderly patients and patients with a compromised immune system. This should be discussed with each patient individually, especially if the lesion is close to the macula.

  17. Acute graft-versus-host disease: a bench-to-bedside update.

    PubMed

    Holtan, Shernan G; Pasquini, Marcelo; Weisdorf, Daniel J

    2014-07-17

    Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need. © 2014 by The American Society of Hematology.

  18. Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease--friends or foes?

    PubMed

    Balan, A; Lucchini, G; Schmidt, S; Schneider, A; Tramsen, L; Kuçi, S; Meisel, R; Bader, P; Lehrnbecher, T

    2014-10-01

    Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.

  19. Effect of HLA mismatch on acute graft-versus-host disease.

    PubMed

    Kanda, Junya

    2013-09-01

    HLA matching between donors and recipients is the most important factor associated with acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

  20. Randomized study of surgical prophylaxis in immunocompromised hosts.

    PubMed

    Lopes, D R; Peres, M P S M; Levin, A S

    2011-02-01

    Although prophylaxis is current practice, there are no randomized controlled studies evaluating preoperative antimicrobial prophylaxis in dental procedures in patients immunocompromised by chemotherapy or organ transplants. To evaluate prophylaxis in dental-invasive procedures in patients with cancer or solid organ transplants, 414 patients were randomized to receive one oral 500-mg dose 2 hours before the procedure (1-dose group) or a 500-mg dose 2 hours before the procedure and an additional dose 8 hours later (2-dose group). Procedures were exodontia or periodontal scaling/root planing. Follow-up was 4 weeks. No deaths or surgical site infections occurred. Six patients (1.4%) presented with use of pain medication > 3 days or hospitalization during follow-up: 4 of 207 (2%) in the 1-dose group and 2 of 207 (1%) in the 2-dose group (relative risk, 2.02; 95% confidence interval, 0.37-11.15). In conclusion, no statistically significant difference occurred in outcome using 1 or 2 doses of prophylactic amoxicillin for invasive dental procedures in immunocompromised patients.

  1. Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment.

    PubMed

    Vereerstraeten, P; Stolear, J C; Schoutens-Serruys, E; Maes, N; Thys, J P; Liesnard, C; Rost, F; Kinnaert, P; Toussaint, C

    1986-01-01

    Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease. Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions. In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized. From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded. During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group. We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.

  2. RSV prophylaxis guideline changes and outcomes in children with congenital heart disease.

    PubMed

    Walpert, Adam S; Thomas, Ian D; Lowe, Merlin C; Seckeler, Michael D

    2018-05-01

    The aim of this study was to compare inpatient outcomes and costs for children with respiratory syncytial virus and congenital heart disease before and after the change in management guidelines for respiratory syncytial virus prophylaxis. Hospital discharge data from the Vizient (formerly University HealthSystem Consortium) were queried from October 2012 to June 2014 (Era 1) and July 2014 to April 2016 (Era 2) for patients aged <24 months with an any International Classification of Disease (ICD)-9 or ICD-10 code for congenital heart disease (745-747.49, Q20.0-Q26.4) and a primary or secondary admitting diagnosis of respiratory syncytial virus infection (079.6, J20.5), acute bronchiolitis due to respiratory syncytial virus (466.11, J21.0) or respiratory syncytial virus pneumonia (480.1, J12.1). This study is a review of a national administrative discharge database. Respiratory syncytial virus admissions were identified in 1269 patients aged <24 months with congenital heart disease, with 644 patients in Era 1 and 625 in Era 2. Patients 0-12 months old represented 83% of admissions. Prior to 2014, children aged 0-24 months with congenital heart disease were eligible to receive respiratory syncytial virus prophylaxis. Updated guidelines, published in 2014, restricted the recommendation to administer palivizumab respiratory syncytial virus prophylaxis to children with congenital heart disease only if they are ≤12 months old. The outcome measures are hospital length of stay, ICU admission rate, mortality, and direct costs. There was no change in length of stay, ICU admission rate, in-hospital mortality, or direct costs for children 13-24 months old with congenital heart disease after the change in guidelines. There were no deaths in 13-24 month olds, regardless of era. Our findings provide additional support for the new guideline recommendations to provide respiratory syncytial virus prophylaxis only for children ≤12 months old with congenital heart disease.

  3. Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: outcome and risk factors for late CMV disease.

    PubMed

    Reusing, Jose O; Feitosa, Emanoela B; Agena, Fabiana; Pierroti, Lígia C; Azevedo, Luiz S F; Kotton, Camille N; David-Neto, Elias

    2018-05-29

    Anti-thymocyte globulin (ATG) therapy is a risk factor for CMV disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. 54 (13%) patients developed cytomegalovirus (CMV) disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤ 40 ml/min/1.73 m 2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤ 45 and lymphocyte count ≤ 800 cells/mm 3 at the end of prophylaxis remained predictive of late CMV disease occurrence. These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Antimicrobial Prophylaxis in Adults

    PubMed Central

    Enzler, Mark J.; Berbari, Elie; Osmon, Douglas R.

    2011-01-01

    Antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infections. Optimal antimicrobial agents for prophylaxis should be bactericidal, nontoxic, inexpensive, and active against the typical pathogens that can cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be administered within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis should be of short duration to decrease toxicity and antimicrobial resistance and to reduce cost. PMID:21719623

  5. Effect of secondary penicillin prophylaxis on valvular changes in patients with rheumatic heart disease in Far North Queensland.

    PubMed

    Haran, Shankar; Crane, Natalie; Kazi, Saniya; Axford-Haines, Louise; White, Andrew

    2018-04-01

    To determine the effect of secondary penicillin prophylaxis on echocardiographic diagnosed valvular changes in patients with rheumatic heart disease or history of acute rheumatic fever in the Townsville Health district. Patients with known were identified from the North Queensland register, serial echocardiogram results and number of secondary penicillin prophylaxis doses received in 2014 were collated. Descriptive statistics were utilised. Townsville Hospital and outreach clinics within the Townsville Health catchment zone. All patients diagnosed with acute rheumatic fever or rheumatic heart disease between 2010 and October 2013 who had serial echocardiograms prior to and post commencement of secondary penicillin prophylaxis were included. All patients were of Aboriginal or Torres Strait Islander descent. Progression of echocardiographic valvular changes and association with secondary penicillin prophylaxis compliance. Compliance with secondary penicillin prophylaxis among the study population was a secondary outcome measure. Twenty-three patients were recruited. Only those patients who were compliant with secondary penicillin prophylaxis had any improvement in valvular changes on echocardiogram. Four of six patients without any baseline valvular involvement developed new valvular changes. Seventy percent of patients received >75% of secondary penicillin prophylaxis doses. This small study of patients in Townsville suggests that with good secondary penicillin prophylaxis compliance there is regression of some cardiac lesions over time in people with rheumatic heart disease. Furthermore the natural history of acute rheumatic fever in the Indigenous population is progressive requiring strict adherence to secondary penicillin prophylaxis. Prospective studies or use of data from the nationwide RHD register and standardised reporting of cardiac echocardiograms will provide more robust evidence. © 2017 National Rural Health Alliance Inc.

  6. Graft-versus-host disease

    MedlinePlus

    GVHD; Bone marrow transplant - graft-versus-host disease; Stem cell transplant - graft-versus-host disease; Allogeneic transplant - ... GVHD may occur after a bone marrow, or stem cell, transplant in which someone receives bone marrow ...

  7. Bandage soft contact lenses for ocular graft-versus-host disease

    PubMed Central

    Inamoto, Yoshihiro; Sun, Yi-Chen; Flowers, Mary E. D.; Carpenter, Paul A.; Martin, Paul J.; Li, Peng; Wang, Ruikang; Chai, Xiaoyu; Storer, Barry E.; Shen, Tueng T.; Lee, Stephanie J.

    2015-01-01

    To examine safety and efficacy of bandage soft contact lenses (BSCLs) for ocular chronic graft-versus host disease (GVHD), we conducted a phase II clinical trial. Extended-wear BSCLs were applied under daily topical antibiotics prophylaxis. Patients completed standardized symptom questionnaires at enrollment and at 2 weeks, 4 weeks and 3 months afterwards. Ophthalmologic assessment was performed at enrollment, at 2 weeks and afterwards as medically needed. Assessments at follow-up were compared with baseline by paired t-test. Nineteen patients with ocular GVHD who remained symptomatic despite conventional treatments were studied. The mean Lee eye subscale score was 75.4 at enrollment, and improved significantly to 63.2 at 2 weeks (p=0.01), to 61.8 at 4 weeks (p=0.005) and to 56.3 at 3 months (p=0.02). The ocular surface disease index score and 11-point eye symptom ratings also improved significantly. According to the Lee eye subscale, clinically meaningful improvement was observed in 9 patients (47%) at 2 weeks, in 11 (58%) at 4 weeks and in 9 (47%) at 3 months. Visual acuity improved significantly at 2 weeks compared with enrollment values. Based on slit lamp exam at 2 weeks, punctate epithelial erosions improved in 58% of the patients, showed stability in 16% and worsened in 5%. No corneal ulceration or ocular infection occurred. BSCLs are a widely available, safe and effective treatment option that improves manifestations of ocular graft-versus host disease in approximately 50% of patients. This study was registered at www.clinicaltrials.gov as NCT01616056. PMID:26189353

  8. Defibrotide for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Prophylaxis in High-Risk Adult Patients: A Single-Center Experience Study.

    PubMed

    Picod, Adrien; Bonnin, Agnès; Battipaglia, Giorgia; Giannotti, Federica; Ruggeri, Annalisa; Brissot, Eolia; Malard, Florent; Médiavilla, Clémence; Belhocine, Ramdane; Vekhoff, Anne; Gueye, Mor Sény; Lapusan, Simona; Adaeva, Rosa; Isnard, Françoise; Legrand, Ollivier; Baylatry, Minh-Tam; Joly, Anne-Christine; Labopin, Myriam; Duléry, Rémy; Mohty, Mohamad

    2018-03-01

    Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Rheumatic Heart Disease Prophylaxis in Older Patients: A Register-Based Audit of Adherence to Guidelines

    PubMed Central

    Holland, James V; Hardie, Kate; de Dassel, Jessica; Ralph, Anna P

    2018-01-01

    Abstract Background Prevention of rheumatic heart disease (RHD) remains challenging in high-burden settings globally. After acute rheumatic fever (ARF), secondary antibiotic prophylaxis is required to prevent RHD. International guidelines on recommended durations of secondary prophylaxis differ, with scope for clinician discretion. Because ARF risk decreases with age, ongoing prophylaxis is generally considered unnecessary beyond approximately the third decade. Concordance with guidelines on timely cessation of prophylaxis is unknown. Methods We undertook a register-based audit to determine the appropriateness of antibiotic prophylaxis among clients aged ≥35 years in Australia’s Northern Territory. Data on demographics, ARF episode(s), RHD severity, prophylaxis type, and relevant clinical notes were extracted. The determination of guideline concordance was based on whether (1) national guidelines were followed; (2) a reason for departure from guidelines was documented; (3) lifelong continuation was considered appropriate in all cases of severe RHD. Results We identified 343 clients aged ≥35 years prescribed secondary prophylaxis. Guideline concordance was 39% according to national guidelines, 68% when documented reasons for departures from guidelines were included and 82% if patients with severe RHD were deemed to need lifelong prophylaxis. Shorter times since last echocardiogram or cardiologist review were associated with greater likelihood of guideline concordance (P < .001). The median time since last ARF was 5.9 years in the guideline-concordant group and 24.0 years in the nonconcordant group (P < .001). Thirty-two people had an ARF episode after age 40 years. Conclusions In this setting, appropriate discontinuation of RHD prophylaxis could be improved through timely specialist review to reduce unnecessary burden on clients and health systems.

  10. Ulcer disease prophylaxis in koi carp by bath immersion with chicken egg yolk containing anti-Aeromonas salmonicida IgY.

    PubMed

    Gan, Hongjian; He, Haiwen; Sato, Atsushi; Hatta, Hajime; Nakao, Miki; Somamoto, Tomonori

    2015-04-01

    Ulcer disease, caused by atypical Aeromonas salmonicida, is a serious concern in ornamental koi carp, because it induces skin ulceration, disfiguring ornamental fish and causing economic loses. The present study aimed to establish a novel prophylaxis with chicken egg yolk immunoglobulin, IgY, against ulcer disease and to assess its feasibility in the ornamental fish industry. Addition of egg yolk powder containing anti-A. salmonicida IgY to rearing water provided significant protection against an A. salmonicida bath infection, whereas administration of non-specific IgY did not. Consecutive immersion of fish into rearing water containing specific IgY completely prevented ulcer disease resulting from cohabitation infection, indicating that this prophylaxis could prevent infection from such type of contact. Thus, passive immunization induced by immersing fish into aquarium water containing specific IgY is a prospective prophylaxis against diseases caused by pathogens that invade the skin and gills. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Cranberry juice for prophylaxis of urinary tract infections--conclusions from clinical experience and research.

    PubMed

    Nowack, Rainer; Schmitt, Wilhelm

    2008-09-01

    Cranberry juice (Vaccinium macrocarpon) is a widely used and recommended North-American folk remedy for prophylaxis of urinary tract infections (UTI). Clinical trials have documented its efficacy in women with recurrent UTI, but so far not in other groups of patients. The composition of effective cranberry products and its dosage in UTI prophylaxis have not been defined. Intriguing experimental research has identified an anti-adhesive mechanism of cranberry juice that prevents docking of bacteria on host tissues. This efficacy mechanism can be traced in patients' urine following oral intake of cranberry products and appears to be due to proanthocyanidins with an A-type linkage of flavanols. The application of this anti-adhesion mechanism of cranberry-proanthocyandins is currently also investigated in other common diseases of bacterial pathogenesis, for example Helicobacter pylori-associated gastritis and dental caries/periodontal disease. The use of cranberry products appears to be safe and provide additional benefits by anti-oxidant and cholesterol-lowering activity.

  12. Pneumocystis jiroveci pneumonia in patients with inflammatory bowel disease: a survey of prophylaxis patterns among gastroenterology providers.

    PubMed

    Okafor, Philip N; Wasan, Sharmeel K; Farraye, Francis A

    2013-01-01

    The use of combination immunosuppressive agents is associated with reports of pneumocystis jiroveci pneumonia (PJP). The aim of this study was to determine practice patterns among gastroenterology providers for PJP prophylaxis in patients with inflammatory bowel disease (IBD) on immunosuppressive therapy. An internet-based survey of 14 questions was sent through e-mail to a random sampling of 4000 gastroenterologists, nurse practitioners, and physician assistants between November 2011 and February 2012. Three reminder e-mails were sent to providers who had not completed the survey. The invitation e-mail that contained the link to the survey was clicked by 504 providers and the completed surveys were returned by 123 of them (78% physicians, 11% nurse practitioners, 11% physician assistants). The response rate was 24.4%. Seventy-nine percent of the respondents had managed >25 patients with IBD in the past year, with as much as one-third of all respondents managing >100 patients. Eight percent of the respondents reported patients who had developed PJP on immunosuppressive therapy, 11% reported initiating PJP prophylaxis, mostly for patients on triple immunosuppressive therapy. Prescription of PJP prophylaxis was not significantly associated with the number of years in practice or the number of IBD patients treated. However, providers with patients that had developed PJP were 7.4 times more likely to prescribe prophylaxis (P = 0.01). In addition, providers in academic centers were 4 times more likely to initiate PJP prophylaxis than those in nonacademic centers (P = 0.03). The most common reasons for not prescribing PJP prophylaxis included the absence of guidelines on the benefits of prophylaxis, lack of personal experience with PJP, and the lack of knowledge on the need for prophylaxis in patients with IBD on combination immunosuppressive therapy. The lack of guidelines seems to influence the decision on not to prescribe PJP prophylaxis in patients with IBD

  13. Rabies: changing prophylaxis and new insights in pathophysiology.

    PubMed

    Ugolini, Gabriella; Hemachudha, Thiravat

    2018-02-01

    Despite great progress in decoding disease mechanisms, rabies remains one of the leading causes of human death worldwide. Towards the elimination of human rabies deaths by 2030, feasible and affordable post (PEP) and pre-exposure prophylaxis (PrEP) must be available with expansion to rural areas in rabies endemic countries. Vaccination and population control of dogs, principal reservoirs and transmitters, must be done in concert. Advances in the understanding of rabies neuropathogenesis and pathophysiology are reviewed, including recent experimental findings on host- and virus-specific mechanisms mediating neuronal survival and explaining clinical differences in furious and paralytic rabies. The forthcoming World Health Organization guide on rabies based on pathogenesis and immunization mechanisms data with support by clinical evidence provide new accelerated 1 week intradermal PrEP and PEP schedules. Rabies immunoglobulin injected into the wound only is endorsed at amounts not exceeding the dose interfering with active immunization. Potential therapeutics as designed in accord with rabies neuro-pathophysiology are plausible. Clinical practice and rabies awareness can be leveraged by transboundary collaboration among different areas. Advancement in prophylaxis and perspectives on animal control offer a new path to conquer rabies by 2030.

  14. [Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment].

    PubMed

    Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

    2015-10-01

    In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  15. Graft-versus-host disease targets ovary and causes female infertility in mice.

    PubMed

    Shimoji, Sonoko; Hashimoto, Daigo; Tsujigiwa, Hidetsugu; Miyawaki, Kohta; Kato, Koji; Takahashi, Shuichiro; Ogasawara, Reiki; Jiromaru, Takashi; Iwasaki, Hiromi; Miyamoto, Toshihiro; Akashi, Koichi; Teshima, Takanori

    2017-03-02

    Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). Although pretransplant conditioning regimen has been appreciated as a cause of ovarian failure, increased application of reduced-intensity conditioning allowed us to revisit other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell-mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice. Histological evaluation of the ovaries after SCT demonstrated donor T-cell infiltration in close proximity to apoptotic granulosa cells in the ovarian follicles, resulting in impaired follicular hormone production and maturation of ovarian follicles. Mating experiments showed that female recipients of allogeneic SCT deliver significantly fewer newborns than recipients of syngeneic SCT. GVHD-mediated ovary insufficiency and infertility were independent of conditioning. Pharmacologic GVHD prophylaxis protected the ovary from GVHD and preserved fertility. These results demonstrate for the first time that GVHD targets the ovary and impairs ovarian function and fertility and has important clinical implications in young female transplant recipients with nonmalignant diseases, in whom minimally toxic regimens are used. © 2017 by The American Society of Hematology.

  16. Appropriate VTE prophylaxis is associated with lower direct medical costs.

    PubMed

    Amin, Alpesh; Hussein, Mohamed; Battleman, David; Lin, Jay; Stemkowski, Stephen; Merli, Geno J

    2010-11-01

    To calculate and compare the direct medical costs of guideline-recommended prophylaxis with prophylaxis that does not fully adhere with guideline recommendations in a large, real-world population. Discharge records were retrieved from the US Premier Perspective™ database (January 2003-December 2003) for patients aged≥40 years with a primary diagnosis of cancer, chronic heart failure, lung disease, or severe infectious disease who received some form of thromboprophylaxis. Univariate analysis and multivariate regression modeling were performed to compare direct medical costs between discharges who received appropriate prophylaxis (correct type, dose, and duration based on sixth edition American College of Chest Physicians [ACCP] recommendations) and partial prophylaxis (not in full accordance with ACCP recommendations). Market segmentation analysis was used to compare costs stratified by hospital and patient characteristics. Of the 683 005 discharges included, 148,171 (21.7%) received appropriate prophylaxis and 534,834 (78.3%) received partial prophylaxis. The total direct unadjusted costs were $15,439 in the appropriate prophylaxis group and $17,763 in the partial prophylaxis group. After adjustment, mean adjusted total costs per discharge were lower for those receiving appropriate prophylaxis ($11,713; 95% confidence interval [CI], $11,675-$11,753) compared with partial prophylaxis ($13,369; 95% CI, $13,332-$13 406; P<0.01). Appropriate prophylaxis appeared to be associated with numerically lower unadjusted costs than partial prophylaxis, regardless of hospital size, rural/urban location, teaching status, and patient age and gender. This large, real-world analysis suggests that appropriate prophylaxis, in adherence with ACCP guidelines, is potentially cost-saving compared with partial prophylaxis in at-risk medical patients.

  17. Host-seeking strategies of mosquito disease vectors.

    PubMed

    Day, Jonathan F

    2005-12-01

    Disease transmission by arthropods normally requires at least 2 host contacts. During the first, a pathogen (nematode, protozoan, or virus) is acquired along with the blood from an infected vertebrate host. The pathogen penetrates the vector's midgut and infects a variety of tissues, where replication may occur during an extrinsic incubation period lasting 3-30, days depending on vector and parasite physiology and ambient temperature. Following salivary-gland infection, the pathogen is usually transmitted to additional susceptible vertebrate hosts during future probing or blood feeding. The host-seeking strategies used by arthropod vectors can, in part, affect the efficiency of disease transmission. Vector abundance, seasonal distribution, habitat and host preference, and susceptibility to infection are all important components of disease-transmission cycles. Examples of 3 mosquito vectors of human disease are presented here to highlight the diversity of host seeking and to show how specific behaviors may influence disease-transmission cycles. In the African tropics, Anopheles gambiae s.s. is an efficient vector of human malaria due to its remarkably focused preference for human blood. Aedes aegypti is the main vector of dengue viruses in the New and Old World tropics and subtropics. This mosquito has evolved a domestic lifestyle and shares human habitations throughout much of its range. It prospers in settings where humans are its main source of blood. In south Florida, Culex nigripalpus is the major vector of St. Louis encephalitis (SLE) and West Nile (WN) viruses. This mosquito is opportunistic and blood feeds on virtually any available vertebrate host. It serves as an arboviral vector, in part, due to its ability to produce large populations in a short period of time. These 3 host-seeking and blood-feeding strategies make the specialist, as well as the opportunist, equally dangerous disease vectors.

  18. Antifungal prophylaxis during neutropenia and immunodeficiency.

    PubMed Central

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylactic strategies have been extensively developed. However, only a few well-designed studies involving strict criteria have been performed, mostly in patients with hematological malignancies or AIDS. In these situations, the best dose and duration of administration of the antifungal drug often remain to be determined. In high-risk neutropenic or bone marrow transplant patients, fluconazole is effective for the prevention of superficial and/or systemic candidal infections but is not always able to prolong overall survival and potentially selects less susceptible or resistant Candida spp. Primary prophylaxis against aspergillosis remains investigative. At present, no standard general recommendation for primary antifungal prophylaxis can be proposed for AIDS patients or transplant recipients. However, for persistently immunocompromised patients who previously experienced a noncandidal systemic fungal infection, prolonged suppressive antifungal therapy is often indicated to prevent a relapse. Better strategies for controlling immune deficiencies should also help to avoid some potentially life-threatening deep mycoses. When prescribing antifungal prophylaxis, physicians should be aware of the potential emergence of resistant strains, drug-drug interactions, and the cost. Well-designed, randomized, multicenter clinical trials in high-risk immunocompromised hosts are urgently needed to better define how to prevent severe invasive mycoses. PMID:9227863

  19. Health education policy 1916-1926: venereal disease and the prophylaxis dilemma

    PubMed Central

    Towers, Bridget A.

    1980-01-01

    This paper seeks to account for the development of a public health education policy with respect to venereal disease during the period 1916-1926. Two competing pressure groups, the National Council for Combatting Venereal Disease and the Society for the Prevention of Venereal Disease, defended opposing programmes; the one based on moral education (NCCVD) and the other (SPVD) on medical prophylaxis. Many of the interests represented by the groups and the political dimensions that they took, were influenced by factors only very tangentially connected to health education. Any account of the development of policy in this field needs placing in the context of the early history of nineteenth-century anti-vice crusades; the role of the Army Medical Corps during the 1914-18 war; and the bureaucratic protectionism of the Ministry of Health personnel. PMID:6990122

  20. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Cell surface receptors and associated signaling pathways).

    PubMed

    Aguilar-Company, J; Fernández-Ruiz, M; García-Campelo, R; Garrido-Castro, A C; Ruiz-Camps, I

    2018-06-01

    The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies. To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations. Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. Vascular endothelial growth factor (VEGF)-targeted agents (bevacizumab and aflibercept) are associated with a meaningful increase in the risk of infection, likely due to drug-induced neutropaenia, although no clear benefit is expected from the universal use of anti-infective prophylaxis. VEGF tyrosine kinase inhibitors (i.e. sorafenib or sunitinib) do not seem to significantly affect host's susceptibility to infection, and universal anti-infective prophylaxis is not recommended either. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) induce neutropaenia and secondary skin and soft tissue infection in cases of severe papulopustular rash. Systemic antibiotics (doxycycline or minocycline) should be administered to prevent the latter complication, whereas no recommendation can be established on the benefit from antiviral, antifungal or anti-Pneumocystis prophylaxis. A lower risk of infection is reported for anti-ErbB2/HER2 monoclonal antibodies (trastuzumab and pertuzumab) and ErbB receptor tyrosine kinase inhibitors (including dual-EGFR/ErbB2 inhibitors such as lapatinib or neratinib) compared to conventional chemotherapy, presumably as a result of the decreased occurrence of drug-induced neutropaenia. With the exception of VEGF-targeted agents, the overall risk of infection associated with the reviewed therapies seems to be low. Copyright © 2018 European Society of Clinical

  1. Graft-versus-host disease in the ovary potentially causes female infertility after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Shimoji, Sonoko; Hashimoto, Daigo; Teshima, Takanori

    2017-01-01

    Ovarian failure-associated infertility is a serious late complication for female patients who have undergone allogeneic hematopoietic stem cell transplantation (SCT). Although the role of a pretransplant conditioning regimen has been well appreciated, the increasing application of reduced-intensity conditioning has led us to reconsider other factors possibly affecting ovarian function after allogeneic SCT. We recently reported that graft-versus-host disease (GVHD) targets granulosa cells of the ovarian follicles, thereby significantly reducing ovarian reserves and fertility after SCT. We also found that ovarian GVHD impairs fertility independently of the toxicities of the conditioning regimens, and pharmacological GVHD prophylaxis preserves fertility after SCT. For the first time, these results demonstrated that GVHD targets the ovary and impairs ovarian functions and fertility, thereby having important clinical implications in young female transplant recipients with nonmalignant diseases, for whom minimally toxic regimens are used. Here we review recently published articles regarding clinical and basic researches on female infertility after SCT.

  2. Prophylaxis for infective endocarditis. Who needs it? How effective is it?

    PubMed Central

    Press, N.; Montessori, V.

    2000-01-01

    OBJECTIVE: To review guidelines for using antibiotic prophylaxis to prevent infective endocarditis, and to present recent changes and controversies regarding these guidelines. QUALITY OF EVIDENCE: Data are from physiologic and in vitro studies, as well as studies of animal models, and from retrospective analyses of human endocarditis cases. Systematic reviews and guidelines are also examined. As no randomized clinical trials have examined prophylaxis for bacterial endocarditis, many recommendations presented are based on consensus guidelines. MAIN MESSAGE: Antibiotic prophylaxis to prevent bacterial endocarditis should be used in high- and moderate-risk patients with cardiac disease. It should be given before procedures in which bacteremias are likely with organisms that cause endocarditis, such as viridans streptococci. For most procedures, a single dose of amoxicillin (2 g by mouth 1 hour before the procedure) is sufficient to ensure adequate serum levels before and after the procedure. CONCLUSION: Infective endocarditis continues to have high rates of morbidity and mortality. Antibiotic prophylaxis, therefore, is important to combat this preventable disease. For high- and moderate-risk patients with cardiac disease, the cost-benefit ratio favours prophylaxis. PMID:11143584

  3. Prophylaxis for infective endocarditis. Who needs it? How effective is it?

    PubMed

    Press, N; Montessori, V

    2000-11-01

    To review guidelines for using antibiotic prophylaxis to prevent infective endocarditis, and to present recent changes and controversies regarding these guidelines. Data are from physiologic and in vitro studies, as well as studies of animal models, and from retrospective analyses of human endocarditis cases. Systematic reviews and guidelines are also examined. As no randomized clinical trials have examined prophylaxis for bacterial endocarditis, many recommendations presented are based on consensus guidelines. Antibiotic prophylaxis to prevent bacterial endocarditis should be used in high- and moderate-risk patients with cardiac disease. It should be given before procedures in which bacteremias are likely with organisms that cause endocarditis, such as viridans streptococci. For most procedures, a single dose of amoxicillin (2 g by mouth 1 hour before the procedure) is sufficient to ensure adequate serum levels before and after the procedure. Infective endocarditis continues to have high rates of morbidity and mortality. Antibiotic prophylaxis, therefore, is important to combat this preventable disease. For high- and moderate-risk patients with cardiac disease, the cost-benefit ratio favours prophylaxis.

  4. Antibiotic prophylaxis for children with sickle cell disease: a survey of pediatric dentistry residency program directors and pediatric hematologists.

    PubMed

    Tate, Anupama Rao; Norris, Chelita Kaye; Minniti, Caterina P

    2006-01-01

    The purposes of this study were to: (1) investigate the current clinical practice regarding the use of antibiotic prophylaxis by pediatric dentistry residency program directors and pediatric hematologists for children with sickle cell disease (SCD) requiring dental treatment; and (2) evaluate the perceived relative risk of bacteremia following specific dental procedures, as defined by pediatric dentistry residency program directors and pediatric hematologists. A written survey depicting various clinical scenarios of SCD children requiring common dental procedures was mailed to directors of pediatric dental advanced education programs and distributed to pediatric hematologists attending the 2003 Annual Sickle Cell Disease Association of America conference in Washington, DC. Surveys were returned by 60% (N=34/57) of the pediatric dentistry residency program directors. The surveys were obtained from 51% of pediatric hematologists at the meeting (N=72/140). At least 50% of all respondents recommended prophylaxis for the following clinical situations: dental extractions, treatment under general anesthesia, and status post splenectomy. The perceived risk of infectious complication was highest for extractions, followed by restorative treatment and tooth polishing. Dental residency program directors were more likely (71%, N=24/34) to recommend additional antibiotic therapy for patients taking penicillin prophylaxis if they required an invasive oral surgical procedure. Conversely, only 38% (N=25/66) of pediatric hematologists recommended additional antibiotic therapy (P=.001). Eighty-six percent of dental residency program directors (N=25/29) chose amoxicillin for prophylaxis whereas only 62% of pediatric hematologists (N=36/58) recommended amoxicillin. (P<.05). There is a lack of consensus on the appropriate use of antibiotic prophylaxis in SCD children undergoing dental treatments. Further research and risk/benefit assessment is needed to create a unified approach.

  5. Multiscale model within-host and between-host for viral infectious diseases.

    PubMed

    Almocera, Alexis Erich S; Nguyen, Van Kinh; Hernandez-Vargas, Esteban A

    2018-05-08

    Multiscale models possess the potential to uncover new insights into infectious diseases. Here, a rigorous stability analysis of a multiscale model within-host and between-host is presented. The within-host model describes viral replication and the respective immune response while disease transmission is represented by a susceptible-infected model. The bridging of scales from within- to between-host considered transmission as a function of the viral load. Consequently, stability and bifurcation analyses were developed coupling the two basic reproduction numbers [Formula: see text] and [Formula: see text] for the within- and the between-host subsystems, respectively. Local stability results for each subsystem, including a unique stable equilibrium point, recapitulate classical approaches to infection and epidemic control. Using a Lyapunov function, global stability of the between-host system was obtained. Our main result was the derivation of the [Formula: see text] as an increasing function of [Formula: see text]. Numerical analyses reveal that a Michaelis-Menten form based on the virus is more likely to recapitulate the behavior between the scales than a form directly proportional to the virus. Our work contributes basic understandings of the two models and casts light on the potential effects of the coupling function on linking the two scales.

  6. Guidelines for prophylaxis of Pneumocystis pneumonia cannot rely solely on CD4-cell count in autoimmune and inflammatory diseases.

    PubMed

    Baulier, Gildas; Issa, Nahema; Gabriel, Frederic; Accoceberry, Isabelle; Camou, Fabrice; Duffau, Pierre

    2018-02-26

    Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD. CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016. 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3. Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.

  7. Clinical research, prophylaxis, therapy, and care for HIV disease in Africa.

    PubMed Central

    De Cock, K M; Lucas, S B; Lucas, S; Agness, J; Kadio, A; Gayle, H D

    1993-01-01

    By the end of the century, citizens of resource-poor countries will constitute 90% of the world's human immunodeficiency virus (HIV)-infected people. Clinical management of such persons in developing countries has been neglected; most AIDS research has concentrated on epidemiology, and donor agencies have generally invested in the prevention of HIV infection. The heavy burden of HIV disease in Africa requires that care for AIDS be addressed, and prevention and care should be seen as interrelated. Prevention and treatment of tuberculosis, the commonest severe infection in persons with AIDS in Africa, illustrate this interrelationship. We outline priorities for applied research on the management of HIV disease in a resource-poor environment, and discuss prophylaxis, therapy for opportunistic diseases, terminal care, and use of antiretroviral therapy. Research should define the standard of care that can realistically be demanded for HIV disease in a resource-poor environment. Research and public health programs for AIDS in developing countries must address AIDS care and attempt to reduce the widening gap between interventions available for HIV-infected persons in different parts of the world. PMID:8214225

  8. Duelling timescales of host mixing and disease spread determine invasion of disease in structured populations

    USGS Publications Warehouse

    Cross, P.C.; Lloyd-Smith, James O.; Johnson, P.L.F.; Getz, W.M.

    2005-01-01

    The epidemic potential of a disease is traditionally assessed using the basic reproductive number, R0. However, in populations with social or spatial structure a chronic disease is more likely to invade than an acute disease with the same R0, because it persists longer within each group and allows for more host movement between groups. Acute diseases ‘perceive’ a more structured host population, and it is more important to consider host population structure in analyses of these diseases. The probability of a pandemic does not arise independently from characteristics of either the host or disease, but rather from the interaction of host movement and disease recovery timescales. The R* statistic, a group-level equivalent of R0, is a better indicator of disease invasion in structured populations than the individual-level R0.

  9. Mycobacterium leprae–host-cell interactions and genetic determinants in leprosy: an overview

    PubMed Central

    Pinheiro, Roberta Olmo; de Souza Salles, Jorgenilce; Sarno, Euzenir Nunes; Sampaio, Elizabeth Pereira

    2011-01-01

    Leprosy, also known as Hansen’s disease, is a chronic infectious disease caused by Mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. Even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. Owing to its singular features, M. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced disease. Leprosy is one of the most common causes of nontraumatic peripheral neuropathy worldwide. The proportion of patients with disabilities is affected by the type of leprosy and delay in diagnosis. This article briefly reviews the clinical features as well as the immunopathological mechanisms related to the establishment of the different polar forms of leprosy, the mechanisms related to M. leprae–host cell interactions and prophylaxis and diagnosis of this complex disease. Host genetic factors are summarized and the impact of the development of interventions that prevent, reverse or limit leprosy-related nerve impairments are discussed. PMID:21366421

  10. Oral prophylaxis and its effects on halitosis-associated and inflammatory parameters in patients with chronic periodontitis.

    PubMed

    Guentsch, A; Pfister, W; Cachovan, G; Raschke, G; Kuepper, H; Schaefer, O; Eick, S

    2014-08-01

    A controlled clinical trial was conducted to evaluate the effects of oral prophylaxis on halitosis-associated, immunological and microbiological parameters. Thirty subjects were included in this controlled clinical trial (patients with generalized chronic periodontitis and controls without clinical attachment loss; each n = 15). Before oral prophylaxis and 14 days after (including tongue cleaning) volatile sulphur compounds (VSC), organoleptic scores and a tongue coating index were evaluated. The levels of IL-1β, IL-8, IL-10 and MMP-8 were measured in GCF, and also major periodontal pathogens were detected. Data were statistically analysed using anova and paired t-test. Supragingival plaque and calculus removal with combined tongue cleaning was able to reduce significantly (P < 0.05) the VSC values in both groups (no significant differences between both groups). Two weeks after periodontal debridement, the VSC values were observed in the periodontitis group, but not in the control group, similar to the baseline values. The difference between the groups was statistically significant (P < 0.05). Only a repeated prophylaxis session in the periodontitis group was able to reduce VSC values significantly in comparison with baseline (P < 0.05). Organoleptic scores (10 and 30 cm) were significantly different (P < 0.05) between both groups before and after the treatment. Periodontal pathogens and host-derived markers were not significantly affected by a single prophylaxis session. Oral prophylaxis may result in a significant decrease in VSC values. However, in periodontal diseases, a more complex treatment seems to be necessary. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Viral infections in acute graft-versus-host disease: a review of diagnostic and therapeutic approaches.

    PubMed

    Tong, Lana X; Worswick, Scott D

    2015-04-01

    While immunosuppressive therapy for acute graft-versus-host disease (aGVHD) advances, viral reactivation has been found to be an increasingly common complication in these patients. Dermatologists may often be consulted on inpatient services for evaluation. We investigated the literature for the role of viral infections in aGVHD and review the current evidence regarding management. Articles in the public domain regarding aGVHD, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis viruses, parvovirus B19, and respiratory viruses were included. Dermatologic findings vary between different viral antigens, and some infections may be a marker for the development of aGVHD or worsen prognosis. The heterogeneous cohorts of the studies reviewed often preclude direct comparison between results. The relationship between viral reactivation and aGVHD may be bidirectional and is worthy of further exploration. Additional studies are needed to determine appropriate prophylaxis and treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  12. Biodiversity decreases disease through predictable changes in host community competence.

    PubMed

    Johnson, Pieter T J; Preston, Daniel L; Hoverman, Jason T; Richgels, Katherine L D

    2013-02-14

    Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in biodiversity affect disease outcomes. Over the past decade, a growing number of studies have reported negative correlations between host biodiversity and disease risk, prompting suggestions that biodiversity conservation could promote human and wildlife health. Yet the generality of the diversity-disease linkage remains conjectural, in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity-disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.

  13. Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

    PubMed Central

    Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

    2013-01-01

    Abstract Objective: This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. Materials and methods: We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. Results: During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit – 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Conclusion: Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. PMID:24868262

  14. Is antibiotic prophylaxis mandatory after the insertion of levonorgestrel-releasing intrauterine systemin order to decrease the risk of pelvic inflammatory disease?

    PubMed

    Munteanu, O; Radulescu, L; Bodean, O; Cirstoiu, C; Secara, D; Cirstoiu, M

    2013-01-01

    This study was undertaken in order to determine if antibiotic prophylaxis is mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease. We prospectively evaluated 44 patients, admitted in the Bucharest Emergency Hospital between the 1ⁱ of February 2012 and the 1ⁱ of October 2012, in whom the levonorgestrel-releasing intrauterine system was inserted. The patients enrolled were divided into two groups. In group A, a number of 22 patients, received, after the insertion of levonorgestrel-releasing intrauterine system, 875mg Amoxicillin Trihydrate + 125 mg Potassium Clavulanate, a dose every 12 hours for 5 days. Group B was represented by the other 22 patients who did not receive antibiotic prophylaxis. All patients were reevaluated at 4 and 12 weeks after the insertion of levonorgestrel-releasing intrauterine system. During the first 4 weeks after the insertion of levonorgestrel-releasing intrauterine system only two patients, one from group A and one from group B were diagnosed with pelvic inflammatory disease. At a second follow up visit - 12 weeks after the insertion of levonorgestrel-releasing intrauterine system, no other patient was diagnosed with pelvic inflammatory disease. Antibiotic prophylaxis is not mandatory, after the insertion of levonorgestrel-releasing intrauterine system in order to decrease the risk of pelvic inflammatory disease.

  15. [Host-microbiota crosstalk and cardiovascular diseases].

    PubMed

    Amar, Jacques

    2018-06-13

    When analyzing the microbiota-host crosstalk, we have to consider three participants in this dialogue: the gut microbiota, the intestinal barrier and bacterial translocation. Experimental data demonstrate that host microbiota crosstalk plays a causal on the regulation of blood pressure, glucose metabolism and the development of atherosclerosis. Host microbiota crosstalk is associated in humans with main cardiovascular risk factors notably hypertension and type 2 diabetes. Host microbiota crosstalk is associated in humans with the onset of cardiovascular diseases. The Mediterranean diet has proven as proven to be an effective strategy in improving cardiovascular prognosis and in changing gut microbiota. Copyright © 2018. Published by Elsevier Masson SAS.

  16. Current practices for the prophylaxis against bone mineral density loss in patients with autoimmune blistering disease treated with corticosteroids: an expert survey.

    PubMed

    Amber, K T; Grando, S A

    2018-04-28

    Managing corticosteroid related comorbidities, including bone mineral density loss (BMDL), is an essential part of caring for the autoimmune blistering disease (AIBD) patient. The American College of Rheumatology (ACR) issued an evidence-based BMDL prophylaxis guideline for patients receiving systemic corticosteroids. 2010 guidelines divided patients as low, medium, and high-risk. Accordingly, for patients greater than 50 and on corticosteroids for ≥3 months, low-risk patients should receive bisphosphonate prophylaxis if receiving ≥7.5mg of prednisone daily, while medium and high-risk patients should receive bisphosphonate prophylaxis regardless of dose. Supplementation with calcium and Vitamin D are recommended for all patients receiving corticosteroids, regardless of duration [1]. Patients with a history of fragility fractures if receiving ≥1 month of corticosteroids also should receive prophylaxis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Viral Perturbations of Host Networks Reflect Disease Etiology

    PubMed Central

    Dricot, Amélie; Padi, Megha; Byrdsong, Danielle; Franchi, Rachel; Lee, Deok-Sun; Rozenblatt-Rosen, Orit; Mar, Jessica C.; Calderwood, Michael A.; Baldwin, Amy; Zhao, Bo; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Huh, Kyung-Won; Hellner, Karin; Grace, Miranda; Chen, Alyce; Rubio, Renee; Marto, Jarrod A.; Christakis, Nicholas A.; Kieff, Elliott; Roth, Frederick P.; Roecklein-Canfield, Jennifer; DeCaprio, James A.; Cusick, Michael E.; Quackenbush, John; Hill, David E.; Münger, Karl; Vidal, Marc; Barabási, Albert-László

    2012-01-01

    Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia. PMID:22761553

  18. [The evaluation of cost-effectiveness and cost-utility of valganciclovir for the prophylaxis of cytomegalovirus disease to 200 days after kidney transplantation].

    PubMed

    Kawalec, Paweł; Holko, Przemysław; Szkultecka-Debek, Monika; Paszulewicz, Anna; Boratyńska, Maria; Głyda, Maciej; Ignacak, Ewa; Maks, Justyna; Russel-Szymczyk, Monika; Kaweczyńska-Lasoń, Aneta

    2013-06-01

    Standard procedure for cytomegalovirus disease (CMV) prophylaxis in kidney transplant patients was the administration of valganciclovir for up to 110 days after organ transplant. This prophylaxis has been extended up to 200 days in Poland since 2011. The decision was based on the results of clinical trials which showed significant clinical benefit in case of prolonged administration of the drug. The aim of the analysis was to provide the economic evaluation of extending the CMV prophylaxis with co-financed from public funds Valcyte (valganciclovirum; 60 tab. a 450 mg; Roche Polska Sp. z o.o.) from 110 to 200 days, in the high risk patients group after kidney transplant (seronegative recipient and infected donor, D+/R-). The analysis was performed from the Polish healthcare payer's perspective. All methods used in the following study were consistent with the Requirements of the Polish HTA Agency (AHTAPOL). The cost-effectiveness and the cost-utility analysis were performed on the basis of a randomised study which was identified as a result of the systematic search of the medical databases, comparing 200 days valgancyclovir administration with 100 days drug use as a prophylaxis of CMV disease in the patients group mentioned above. The Markov model was developed, simulating the disease evolution over time considering a high risk patient after kidney transplant treated with valgancicloviras the CMV disease prophylaxis. The disease period was divided into health states that are the most probable for this condition and the transitions probabilities between them were identified and assigned. Based on the clinical trial results, registry database of health conditions usability and experts' opinion, all health states (i.e. death, kidney transplant, CMV disease) were attributed with utilities and costs. The direct costs, important from the Polish healthcare payer's perspective, were included in the analysis. Extension of the proposed model in the series of one month time

  19. Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice.

    PubMed

    Curtis, Lauren M; Datiles, Manuel B; Steinberg, Seth M; Mitchell, Sandra A; Bishop, Rachel J; Cowen, Edward W; Mays, Jacqueline; McCarty, John M; Kuzmina, Zoya; Pirsl, Filip; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2015-09-01

    Ocular chronic graft-versus-host disease is one of the most bothersome common complications following allogeneic hematopoietic stem cell transplantation. The National Institutes of Health Chronic Graft-versus-Host Disease Consensus Project provided expert recommendations for diagnosis and organ severity scoring. However, ocular chronic graft-versus-host disease can be diagnosed only after examination by an ophthalmologist. There are no currently accepted definitions of ocular chronic graft-versus-host disease activity. The goal of this study was to identify predictive models of diagnosis and activity for use in clinical transplant practice. A total of 210 patients with moderate or severe chronic graft-versus-host disease were enrolled in a prospective, cross-sectional, observational study (clinicaltrials.gov identifier: 00092235). Experienced ophthalmologists determined presence of ocular chronic graft-versus-host disease, diagnosis and activity. Measures gathered by the transplant clinician included Schirmer's tear test and National Institutes of Health 0-3 Eye Score. Patient-reported outcome measures were the ocular subscale of the Lee Chronic Graft-versus-Host Disease Symptom Scale and Chief Eye Symptom Intensity Score. Altogether, 157 (75%) patients were diagnosed with ocular chronic graft-versus-host disease; 133 of 157 patients (85%) had active disease. In a multivariable model, the National Institutes of Health Eye Score (P<0.0001) and Schirmer's tear test (P<0.0001) were independent predictors of ocular chronic graft-versus-host disease (sensitivity 93.0%, specificity 92.2%). The Lee ocular subscale was the strongest predictor of active ocular chronic graft-versus-host disease (P<0.0001) (sensitivity 68.5%, specificity 82.6%). Ophthalmology specialist measures that were most strongly predictive of diagnosis in a multivariate model were Oxford grand total staining (P<0.0001) and meibomian score (P=0.027). These results support the use of selected transplant

  20. Predictive models for ocular chronic graft-versus-host disease diagnosis and disease activity in transplant clinical practice

    PubMed Central

    Curtis, Lauren M.; Datiles, Manuel B.; Steinberg, Seth M.; Mitchell, Sandra A.; Bishop, Rachel J.; Cowen, Edward W.; Mays, Jacqueline; McCarty, John M.; Kuzmina, Zoya; Pirsl, Filip; Fowler, Daniel H.; Gress, Ronald E.; Pavletic, Steven Z.

    2015-01-01

    Ocular chronic graft-versus-host disease is one of the most bothersome common complications following allogeneic hematopoietic stem cell transplantation. The National Institutes of Health Chronic Graft-versus-Host Disease Consensus Project provided expert recommendations for diagnosis and organ severity scoring. However, ocular chronic graft-versus-host disease can be diagnosed only after examination by an ophthalmologist. There are no currently accepted definitions of ocular chronic graft-versus-host disease activity. The goal of this study was to identify predictive models of diagnosis and activity for use in clinical transplant practice. A total of 210 patients with moderate or severe chronic graft-versus-host disease were enrolled in a prospective, cross-sectional, observational study (clinicaltrials.gov identifier: 00092235). Experienced ophthalmologists determined presence of ocular chronic graft-versus-host disease, diagnosis and activity. Measures gathered by the transplant clinician included Schirmer’s tear test and National Institutes of Health 0–3 Eye Score. Patient-reported outcome measures were the ocular subscale of the Lee Chronic Graft-versus-Host Disease Symptom Scale and Chief Eye Symptom Intensity Score. Altogether, 157 (75%) patients were diagnosed with ocular chronic graft-versus-host disease; 133 of 157 patients (85%) had active disease. In a multivariable model, the National Institutes of Health Eye Score (P<0.0001) and Schirmer’s tear test (P<0.0001) were independent predictors of ocular chronic graft-versus-host disease (sensitivity 93.0%, specificity 92.2%). The Lee ocular subscale was the strongest predictor of active ocular chronic graft-versus-host disease (P<0.0001) (sensitivity 68.5%, specificity 82.6%). Ophthalmology specialist measures that were most strongly predictive of diagnosis in a multivariate model were Oxford grand total staining (P<0.0001) and meibomian score (P=0.027). These results support the use of selected

  1. Primary prophylaxis of venous thromboembolism in children.

    PubMed

    Cole, Catherine H

    2010-06-01

    Venous thromboembolism (VTE) is rare in children and young adolescents, and occurs predominantly in those with congenital heart disease in whom guidelines exist for VTE prophylaxis. For other paediatric patients, the rarity of the event makes writing an evidence-based clinical practice guideline difficult because each of the known risk factors contributes only a small increase in risk. Thrombophilia screening is controversial because few results assist with prediction of likely thrombosis and may not alter recommendations for prophylaxis. Recent publications highlight the importance of non-pharmacological prevention of VTE in children and adolescents undergoing surgery and the importance of liaison among surgeon, anaesthetist and haematologist. This annotation was written with the aim of collating current evidence for VTE prophylaxis and emphasising the need for further research in vulnerable subgroups.

  2. Patient-reported outcomes and health status associated with chronic graft-versus-host disease.

    PubMed

    Lee, Stephanie J; Onstad, Lynn; Chow, Eric J; Shaw, Bronwen E; Jim, Heather S L; Syrjala, Karen L; Baker, K Scott; Buckley, Sarah; Flowers, Mary E

    2018-06-01

    Chronic graft-versus-host disease occurs in 20-50% of allogeneic hematopoietic cell transplantation survivors. We surveyed patients about their quality of life, symptoms, health status, comorbid conditions and medication. Instruments included the Short-Form-36 (SF-36), the Patient-Reported Outcomes Measurement Information System (PROMIS) Global and PROMIS-29 scales and the Lee Chronic Graft-versus-Host Disease Symptom Scale. Functional status was measured by self-reported Karnofsky and work status. Of 3027 surveys sent to recipients surviving one or more years after transplantation, 1377 (45%) were returned. Among these, patients reported their chronic graft-versus-host disease was mild (n=257, 18.7%), moderate (n=110, 8.0%) or severe (n=25, 1.8%). Another 377 (27.4%) never had chronic graft-versus-host disease and 280 (20.3%) had chronic graft-versus-host disease but it resolved. We excluded 328 (23.8%) who did not answer the questions about chronic graft-versus-host disease. Patients who reported moderate or severe chronic graft-versus-host disease reported worse quality of life, lower performance status, a higher symptom burden and were more likely to be taking prescription medications for pain, anxiety and depression compared to those with resolved chronic graft-versus-host disease. Self-reported measures were similar between patients with resolved chronic graft-versus-host disease and those who never had it. Our data suggest that the PROMIS measures may be able to replace the SF-36 in chronic graft-versus-host disease assessment. Between 26.7-39.4% of people with active chronic graft-versus-host disease were unable to work due to health reasons, compared with 12.1% whose chronic graft-versus-host disease had resolved and 15.4% who never had chronic graft-versus-host disease. Mouth, eye and nutrition symptoms persisted after resolution of chronic graft-versus-host disease. These results show that better prevention of and treatment for chronic graft-versus-host

  3. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

    PubMed

    Corbacioglu, Selim; Cesaro, Simone; Faraci, Maura; Valteau-Couanet, Dominique; Gruhn, Bernd; Rovelli, Attilio; Boelens, Jaap J; Hewitt, Annette; Schrum, Johanna; Schulz, Ansgar S; Müller, Ingo; Stein, Jerry; Wynn, Robert; Greil, Johann; Sykora, Karl-Walter; Matthes-Martin, Susanne; Führer, Monika; O'Meara, Anne; Toporski, Jacek; Sedlacek, Petr; Schlegel, Paul G; Ehlert, Karoline; Fasth, Anders; Winiarski, Jacek; Arvidson, Johan; Mauz-Körholz, Christine; Ozsahin, Hulya; Schrauder, Andre; Bader, Peter; Massaro, Joseph; D'Agostino, Ralph; Hoyle, Margaret; Iacobelli, Massimo; Debatin, Klaus-Michael; Peters, Christina; Dini, Giorgio

    2012-04-07

    Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well

  4. Molecular biology of viroid-host interactions and disease control strategies.

    PubMed

    Kovalskaya, Natalia; Hammond, Rosemarie W

    2014-11-01

    Viroids are single-stranded, covalently closed, circular, highly structured noncoding RNAs that cause disease in several economically important crop plants. They replicate autonomously and move systemically in host plants with the aid of the host machinery. In addition to symptomatic infections, viroids also cause latent infections where there is no visual evidence of infection in the host; however, transfer to a susceptible host can result in devastating disease. While there are non-hosts for viroids, no naturally occurring durable resistance has been observed in most host species. Current effective control methods for viroid diseases include detection and eradication, and cultural controls. In addition, heat or cold therapy combined with meristem tip culture has been shown to be effective for elimination of viroids for some viroid-host combinations. An understanding of viroid-host interactions, host susceptibility, and non-host resistance could provide guidance for the design of viroid-resistant plants. Efforts to engineer viroid resistance into host species have been underway for several years, and include the use of antisense RNA, antisense RNA plus ribozymes, a dsRNase, and siRNAs, among others. The results of those efforts and the challenges associated with creating viroid resistant plants are summarized in this review. Published by Elsevier Ireland Ltd.

  5. Cryptic disease-induced mortality may cause host extinction in an apparently stable host-parasite system.

    PubMed

    Valenzuela-Sánchez, Andrés; Schmidt, Benedikt R; Uribe-Rivera, David E; Costas, Francisco; Cunningham, Andrew A; Soto-Azat, Claudio

    2017-09-27

    The decline of wildlife populations due to emerging infectious disease often shows a common pattern: the parasite invades a naive host population, producing epidemic disease and a population decline, sometimes with extirpation. Some susceptible host populations can survive the epidemic phase and persist with endemic parasitic infection. Understanding host-parasite dynamics leading to persistence of the system is imperative to adequately inform conservation practice. Here we combine field data, statistical and mathematical modelling to explore the dynamics of the apparently stable Rhinoderma darwinii - Batrachochytrium dendrobatidis (Bd) system. Our results indicate that Bd-induced population extirpation may occur even in the absence of epidemics and where parasite prevalence is relatively low. These empirical findings are consistent with previous theoretical predictions showing that highly pathogenic parasites are able to regulate host populations even at extremely low prevalence, highlighting that disease threats should be investigated as a cause of population declines even in the absence of an overt increase in mortality. © 2017 The Author(s).

  6. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

    PubMed

    Yeshurun, Moshe; Shpilberg, Ofer; Herscovici, Corina; Shargian, Liat; Dreyer, Juliet; Peck, Anat; Israeli, Moshe; Levy-Assaraf, Maly; Gruenewald, Tsipora; Mechoulam, Raphael; Raanani, Pia; Ram, Ron

    2015-10-01

    Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted

  7. Fluconazole prophylaxis in preterm infants: a systematic review.

    PubMed

    Rios, Juliana Ferreira da Silva; Camargos, Paulo Augusto Moreira; Corrêa, Luísa Petri; Romanelli, Roberta Maia de Castro

    This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  8. The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review.

    PubMed

    AlDabbagh, M A; Gitman, M R; Kumar, D; Humar, A; Rotstein, C; Husain, S

    2017-03-01

    The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Effects of secondary prophylaxis started in adolescent and adult haemophiliacs.

    PubMed

    Tagliaferri, A; Franchini, M; Coppola, A; Rivolta, G F; Santoro, C; Rossetti, G; Feola, G; Zanon, E; Dragani, A; Iannaccaro, P; Radossi, P; Mannucci, P M

    2008-09-01

    While primary prophylaxis is a well-established and recommended method of care delivery for children with severe haemophilia, fewer studies have documented the benefits of secondary prophylaxis started in adolescence or adulthood. To evaluate the role of secondary prophylaxis started in adolescent and adult severe haemophiliacs, a retrospective observational cohort study was conducted in 10 Italian Centres that investigated 84 haemophiliacs who had bled frequently and had thus switched from on-demand to prophylactic treatment during adolescence (n = 30) or adulthood (n = 54). The consumption of clotting factor concentrates, the orthopaedic and radiological scores, quality of life and disease-related morbidity were compared before and after starting secondary prophylaxis. Prophylaxis reduced the mean annual number of total and joint bleeds (35.8 vs. 4.2 and 32.4 vs. 3.3; P < 0.01) and of days lost from work/school (34.6 vs. 3.0, P < 0.01). A statistically significant reduction in the orthopaedic score was observed during prophylaxis in adolescents, but not in the whole cohort. Patients used more factor concentrates with corresponding higher costs on prophylaxis, but experienced a better quality of life. With respect to on-demand treatment, higher factor consumption and cost of secondary prophylaxis were balanced by marked clinical benefits and greater well-being in this cohort of adolescent/adult haemophiliacs.

  10. Role of Host-Defence Peptides in Eye Diseases

    PubMed Central

    Kolar, Satya S.; McDermott, Alison M.

    2013-01-01

    The eye and its associated tissues including the lacrimal system and lids have evolved several defence mechanisms to prevent microbial invasion. Included among this armory are several host-defence peptides. These multifunctional molecules are being studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects. Here the current knowledge of host-defence peptide expression in the eye will be summarized. The role of these peptides in eye disease will be discussed with the primary focus being on infectious keratitis, inflammatory conditions including dry eye and wound healing. Finally the potential of using host-defence peptides and their mimetics/derivatives for the treatment and prevention of eye diseases is addressed. PMID:21584809

  11. Methotrexate vs Cyclosporin A as a single agent for graft-versus-host disease prophylaxis in pediatric patients with hematological malignancies undergoing allogeneic bone marrow transplantation from HLA-identical siblings: a single-center analysis in Japan.

    PubMed

    Koga, Y; Nagatoshi, Y; Kawano, Y; Okamura, J

    2003-07-01

    The efficacy of methotrexate (MTX) as a single graft-versus-host disease (GVHD) prophylaxis agent was compared to that of cyclosporin A (CSA) in 62 pediatric patients (median age: 8 years) with hematological malignancies who had undergone bone marrow transplantation (BMT) from HLA-identical sibling donors at National Kyushu Cancer Center since 1977. In all, 30 patients received MTX by intravenous bolus injection, with a dose of 15 mg/m(2) on day +1, followed by 10 mg/m(2) on days +3, +6, and +11, and then once a week until day +100. A total of 32 patients were treated with CSA, which was given intravenously in the early stages and orally thereafter until day +100, and then gradually tapered and stopped 6 months after BMT. There were no differences between the groups in terms of rates of hematopoietic recovery after BMT. The probabilities of acute GVHD (grades II-IV) and chronic GVHD were 29.6 vs 40.6% (P=0.294) and 19 vs 20% (MTX vs CSA), respectively. Relapse rates and event-free survival were identical. These results suggest that MTX and CSA were equally effective when given after BMT in Japanese pediatric patients with hematological malignancies. Since MTX was given over a shorter time than CSA, it might be more practical in the management of such patients.

  12. Post-Exposure Prophylaxis (PEP)

    MedlinePlus

    ... Child Transmission of HIV Post-Exposure Prophylaxis (PEP) Pre-Exposure Prophylaxis (PrEP) HIV Treatment HIV Treatment: The Basics Just ... to HIV frequently. Another HIV prevention method, called pre-exposure prophylaxis or PrEP, is when people at high risk ...

  13. Conspicuous impacts of inconspicuous hosts on the Lyme disease epidemic.

    PubMed

    Brisson, Dustin; Dykhuizen, Daniel E; Ostfeld, Richard S

    2008-01-22

    Emerging zoonotic pathogens are a constant threat to human health throughout the world. Control strategies to protect public health regularly fail, due in part to the tendency to focus on a single host species assumed to be the primary reservoir for a pathogen. Here, we present evidence that a diverse set of species can play an important role in determining disease risk to humans using Lyme disease as a model. Host-targeted public health strategies to control the Lyme disease epidemic in North America have focused on interrupting Borrelia burgdorferi sensu stricto (ss) transmission between blacklegged ticks and the putative dominant reservoir species, white-footed mice. However, B. burgdorferi ss infects more than a dozen vertebrate species, any of which could transmit the pathogen to feeding ticks and increase the density of infected ticks and Lyme disease risk. Using genetic and ecological data, we demonstrate that mice are neither the primary host for ticks nor the primary reservoir for B. burgdorferi ss, feeding 10% of all ticks and 25% of B. burgdorferi-infected ticks. Inconspicuous shrews feed 35% of all ticks and 55% of infected ticks. Because several important host species influence Lyme disease risk, interventions directed at a multiple host species will be required to control this epidemic.

  14. Evaluation of the impact of dental prophylaxis on the oral microbiota of dogs.

    PubMed

    Flancman, Rebecca; Singh, Ameet; Weese, J Scott

    2018-01-01

    Periodontal disease is one of the most commonly diagnosed oral diseases in dogs and can result from undisturbed dental plaque. Dental prophylaxis is a routinely practiced veterinary procedure, but its effects on both the plaque and oral microbiota is not fully understood. The objectives of this study were to evaluate the impact of dental prophylaxis on the composition of the supragingival plaque and composite oral microbiota in clinically healthy dogs and to determine if composite sampling could be used in lieu of sampling the plaque microbiota directly. Thirty dogs received a dental prophylaxis. Supragingival plaque and composite oral samples were collected just prior to, and one week after dental prophylaxis. A subsample of 10 dogs was followed, and additional samples were collected two and five weeks post-prophylaxis. The V4 region of the 16S rRNA gene was used for Illumina MiSeq next-generation sequencing. Results demonstrate that decreases in Treponema as well as increases in Moraxella and Neisseria distinguished the plaque pre- and one week post-prophylaxis timepoints (all P<0.05). Within the oral microbiota, the initially dominant Psychrobacter (20% relative abundance) disappeared one week later (P<0.0001), and Pseudomonas became the dominant taxon one week after treatment (80% relative abundance, P<0.0001). A rapid transition back towards the pre-dental prophylaxis microbiota by five weeks post-treatment was seen for both niches, suggesting the canine oral microbiota is resilient. Direct comparison of the two environments yielded striking differences, with complete separation of groups. Firmicutes (40%) and Spirochaetes (22%) predominated in the plaque while Proteobacteria (58%) was predominant in the oral microbiota. Greater richness was also seen in the plaque microbiota. This study reveals that prophylaxis had a profound impact on both the plaque and oral microbiota, and the longitudinal results help elucidate the pathophysiology of periodontal disease

  15. Cytomegalovirus Hyper Immunoglobulin for CMV Prophylaxis in Thoracic Transplantation

    PubMed Central

    Rea, Federico; Potena, Luciano; Yonan, Nizar; Wagner, Florian; Calabrese, Fiorella

    2016-01-01

    Cytomegalovirus (CMV) infection negatively influences both short- and long-term outcomes after cardiothoracic transplantation. In heart transplantation, registry analyses have shown that CMV immunoglobulin (CMVIG) with or without virostatic prophylaxis is associated with a significant reduction in mortality and graft loss versus no prophylaxis, particularly in high-risk donor (D)+/recipient (R)− transplants. Randomized comparative trials are lacking but retrospective data suggest that addition of CMVIG to antiviral prophylaxis may reduce rates of CMV-related events after heart transplantation, including the incidence of acute rejection or chronic allograft vasculopathy. However, available data consistently indicate that when CMVIG is used, it should be administered with concomitant antiviral therapy, and that evidence concerning preemptive management with CMVIG is limited, but promising. In lung transplantation, CMVIG should again only be used with concomitant antiviral therapy. Retrospective studies have shown convincing evidence that addition of CMVIG to antiviral prophylaxis lowers CMV endpoints and mortality. The current balance of evidence suggests that CMVIG prophylaxis reduces the risk of bronchiolitis obliterans syndrome, but a controlled trial is awaited. Overall, the relatively limited current data set suggests that prophylaxis with CMVIG in combination with antiviral therapy appears effective in D+/R− heart transplant patients, whereas in lung transplantation, addition of CMVIG in recipients of a CMV-positive graft may offer an advantage in terms of CMV infection and disease. PMID:26900991

  16. Host susceptibility hypothesis for shell disease in American lobsters.

    PubMed

    Tlusty, Michael F; Smolowitz, Roxanna M; Halvorson, Harlyn O; DeVito, Simone E

    2007-12-01

    Epizootic shell disease (ESD) in American lobsters Homarus americanus is the bacterial degradation of the carapace resulting in extensive irregular, deep erosions. The disease is having a major impact on the health and mortality of some American lobster populations, and its effects are being transferred to the economics of the fishery. While the onset and progression of ESD in American lobsters is undoubtedly multifactorial, there is little understanding of the direct causality of this disease. The host susceptibility hypothesis developed here states that although numerous environmental and pathological factors may vary around a lobster, it is eventually the lobster's internal state that is permissive to or shields it from the final onset of the diseased state. To support the host susceptibility hypothesis, we conceptualized a model of shell disease onset and severity to allow further research on shell disease to progress from a structured model. The model states that shell disease onset will occur when the net cuticle degradation (bacterial degradation, decrease of host immune response to bacteria, natural wear, and resorption) is greater than the net deposition (growth, maintenance, and inflammatory response) of the shell. Furthermore, lesion severity depends on the extent to which cuticle degradation exceeds deposition. This model is consistent with natural observations of shell disease in American lobster.

  17. Decision making in venous thromboembolism prophylaxis: Is LWMH being inappropriately withheld from patients admitted with chronic liver disease?

    PubMed

    Lau, Clement; Burd, Christian; Abeles, Daniel; Sherman, David

    2015-02-01

    Although chronic liver disease (CLD) constitutes a significant proportion of acute medical admissions, it is not known how CLD influences venous thromboembolism (VTE) prophylaxis decision making and low molecular weight heparin (LMWH) prescription. Furthermore, recent evidence suggests that VTE risk has been underestimated in CLD and that prophylactic LMWH is safe and may improve outcome in this patient group. We therefore evaluated VTE prophylaxis in patients with CLD and aimed to determine the factors contributing to decisions to prescribe LMWH. Prescription of LMWH was significantly less likely in CLD patients than in general medical patients (29% vs 55%; p < 0.01). Patients with CLD who were prescribed LMWH were more likely to have been admitted for a 'non-liver' reason than those that did not receive LMWH (19% vs 52%; p < 0.01). These preliminary results show that many patients admitted with CLD, who may benefit from LMWH prophylaxis, do not receive this therapy, because of perceived contraindications for which there may be little evidence. Decision making appears to be affected by whether an admission is 'liver' or 'non-liver' related. Prophylactic LMWH was safe in this small cohort. Further studies are warranted to further inform LMWH prescription in CLD. © 2015 Royal College of Physicians.

  18. Marek’s disease herpesvirus vaccines integrate into chicken host chromosomes yet lack a virus-host phenotype associated with oncogenic transformation

    USDA-ARS?s Scientific Manuscript database

    Marek's disease (MD) is a lymphotrophic and oncogenic disease of chickens that can lead to death in susceptible and unimmunized host birds. The causative pathogen, Marek's disease virus (MDV), a highly oncogenic alphaherpesvirus, integrates into host genome near the telomeres during viral latency an...

  19. [Prophylaxis of alcoholic disease of the liver].

    PubMed

    Beliakin, S A

    2009-08-01

    Military doctors should have a uniform position to the use of alcohol. Now alcohol is the basic pathogenic factor in development of a lethal cirrhosis of a liver. The most known sayings justifying the use of alcohol, are insolvent. Useful doses of alcohol does not exist. The quantity of used alcohol has the great value. Only at achievement of age 21 year it is possible to use safe doses of alcohol. A safe dose of pure alcohol (ethanol) less than 30,0 in day. In a basis of prophylaxis of a cirrhosis of a liver there is a medical educational activity.

  20. How familiar are our doctors towards Rabies prophylaxis- A study from coastal south India.

    PubMed

    Holla, Ramesh; Darshan, Bhagawan; Guliani, Astha; Unnikrishnan, Bhaskaran; Thapar, Rekha; Mithra, Prasanna; Kumar, Nithin; Kulkarni, Vaman; Kumar, Avinash; Anwar, Salman

    2017-10-01

    Rabies, a 100% fatal disease claims more than 59,000 human lives every year globally. One human life is lost every 15 minutes due to this deadly preventable disease. Timely initiation of post exposure prophylaxis following an animal exposure can result in 100% preventability of this fatal disease. This facility based study was conducted among clinical fraternities of teaching hospitals. A semi structured questionnaire was used for collection of data. Institutional Ethics Committee approval was sought. The study investigators visited the workplace of the participants and distributed the questionnaire. SPSS Ver 16 (Chicago, IL, USA) was used to analyse the data. Most of the participants knew that veterinary groups and zoo-keepers should be given pre-exposure prophylaxis. Many participants knew about the Intra Muscular schedule of anti-rabies vaccine and its site of administration for pre exposure prophylaxis. It was observed that most participants had knowledge regarding correct intramuscular regimen of anti-rabies vaccine for post-exposure prophylaxis but less than half were able to differentiate between the intramuscular and intradermal regimens. Less than half of participants were aware of the fact that local administration of anti-rabies serum is useful. The knowledge regarding WHO categorisation of animal exposure and recommended post exposure prophylaxis according to type of exposure observed to be minimal among clinical fraternity.

  1. Less graft-versus-host disease after rabbit antithymocyte globulin conditioning in unrelated bone marrow transplantation for leukemia and myelodysplasia: comparison with matched related bone marrow transplantation.

    PubMed

    Atta, Elias Hallack; de Oliveira, Danielli Cristina Muniz; Bouzas, Luis Fernando; Nucci, Márcio; Abdelhay, Eliana

    2014-01-01

    One of the major drawbacks for unrelated donor (UD) bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Despite results from randomized trials, antithymocyte globulin (ATG) is not routinely included for GVHD prophylaxis in UD BMT by many centers. One of ways to demonstrate the usefulness of rabbit ATG in UD BMT is to evaluate how its results approximate to those observed in matched related (MRD) BMT. Therefore, we compared the outcomes between UD BMT with rabbit ATG (Thymoglobulin) for GVHD prophylaxis (n = 25) and MRD BMT (n = 91) for leukemia and myelodysplasia. All but one patient received a myeloablative conditioning regimen. Grades II-IV acute GVHD were similar (39.5% vs. 36%, p = 0.83); however, MRD BMT recipients developed more moderate-severe chronic GVHD (36.5% vs. 8.6%, p = 0.01) and GVHD-related deaths (32.5% vs. 5.6%, p = 0.04). UD BMT independently protected against chronic GVHD (hazard ratio 0.23, p = 0.04). The 6-month transplant-related mortality, 1-year relapse incidence, and 5-year survival rates were similar between patients with non-advanced disease in the MRD and UD BMT groups, 13.8% vs. 16.6% (p = 0.50), 20.8% vs. 16.6% (p = 0.37), and 57% vs. 50% (p = 0.67), respectively. Stable full donor chimerism was equally achieved (71.3% vs. 71.4%, p = 1). Incorporation of rabbit ATG in UD BMT promotes less GVHD, without jeopardizing chimerism evolution, and may attain similar survival outcomes as MRD BMT for leukemia and myelodysplasia especially in patients without advanced disease.

  2. Ibrutinib Effective against Graft-Versus-Host Disease

    Cancer.gov

    A Cancer Currents blog post on results from a small clinical trial showing that ibrutinib can effectively treat graft-versus-host-disease, a common and serious complication of allogeneic stem cell transplants.

  3. Land-Use Change Alters Host and Vector Communities and May Elevate Disease Risk.

    PubMed

    Guo, Fengyi; Bonebrake, Timothy C; Gibson, Luke

    2018-04-24

    Land-use change has transformed most of the planet. Concurrently, recent outbreaks of various emerging infectious diseases have raised great attention to the health consequences of anthropogenic environmental degradation. Here, we assessed the global impacts of habitat conversion and other land-use changes on community structures of infectious disease hosts and vectors, using a meta-analysis of 37 studies. From 331 pairwise comparisons of disease hosts/vectors in pristine (undisturbed) and disturbed areas, we found a decrease in species diversity but an increase in body size associated with land-use changes, potentially suggesting higher risk of infectious disease transmission in disturbed habitats. Neither host nor vector abundance, however, changed significantly following disturbance. When grouped by subcategories like disturbance type, taxonomic group, pathogen type and region, changes in host/vector community composition varied considerably. Fragmentation and agriculture in particular benefit host and vector communities and therefore might elevate disease risk. Our results indicate that while habitat disturbance could alter disease host/vector communities in ways that exacerbate pathogen prevalence, the relationship is highly context-dependent and influenced by multiple factors.

  4. [Deep vein thrombosis prophylaxis.

    PubMed

    Sandoval-Chagoya, Gloria Alejandra; Laniado-Laborín, Rafael

    2013-01-01

    Background: despite the proven effectiveness of preventive therapy for deep vein thrombosis, a significant proportion of patients at risk for thromboembolism do not receive prophylaxis during hospitalization. Our objective was to determine the adherence to thrombosis prophylaxis guidelines in a general hospital as a quality control strategy. Methods: a random audit of clinical charts was conducted at the Tijuana General Hospital, Baja California, Mexico, to determine the degree of adherence to deep vein thrombosis prophylaxis guidelines. The instrument used was the Caprini's checklist for thrombosis risk assessment in adult patients. Results: the sample included 300 patient charts; 182 (60.7 %) were surgical patients and 118 were medical patients. Forty six patients (15.3 %) received deep vein thrombosis pharmacologic prophylaxis; 27.1 % of medical patients received deep vein thrombosis prophylaxis versus 8.3 % of surgical patients (p < 0.0001). Conclusions: our results show that adherence to DVT prophylaxis at our hospital is extremely low. Only 15.3 % of our patients at risk received treatment, and even patients with very high risk received treatment in less than 25 % of the cases. We have implemented strategies to increase compliance with clinical guidelines.

  5. Defining dysbiosis and its influence on host immunity and disease

    PubMed Central

    Petersen, Charisse; Round, June L

    2014-01-01

    Mammalian immune system development depends on instruction from resident commensal microorganisms. Diseases associated with abnormal immune responses towards environmental and self antigens have been rapidly increasing over the last 50 years. These diseases include inflammatory bowel disease (IBD), multiple sclerosis (MS), type I diabetes (T1D), allergies and asthma. The observation that people with immune mediated diseases house a different microbial community when compared to healthy individuals suggests that pathogenesis arises from improper training of the immune system by the microbiota. However, with hundreds of different microorganisms on our bodies it is hard to know which of these contribute to health and more importantly how? Microbiologists studying pathogenic organisms have long adhered to Koch's postulates to directly relate a certain disease to a specific microbe, raising the question of whether this might be true of commensal–host relationships as well. Emerging evidence supports that rather than one or two dominant organisms inducing host health, the composition of the entire community of microbial residents influences a balanced immune response. Thus, perturbations to the structure of complex commensal communities (referred to as dysbiosis) can lead to deficient education of the host immune system and subsequent development of immune mediated diseases. Here we will overview the literature that describes the causes of dysbiosis and the mechanisms evolved by the host to prevent these changes to community structure. Building off these studies, we will categorize the different types of dysbiosis and define how collections of microorganisms can influence the host response. This research has broad implications for future therapies that go beyond the introduction of a single organism to induce health. We propose that identifying mechanisms to re-establish a healthy complex microbiota after dysbiosis has occurred, a process we will refer to as rebiosis

  6. Infective endocarditis prophylaxis: current practice trend among paediatric cardiologists: are we following the 2007 guidelines?

    PubMed

    Naik, Ronak J; Patel, Neil R; Wang, Ming; Shah, Nishant C

    2016-08-01

    In 2007, the American Heart Association modified the infective endocarditis prophylaxis guidelines by limiting the use of antibiotics in patients with cardiac conditions associated with the highest risk of adverse outcomes after infective endocarditis. Our objective was to evaluate current practice for infective endocarditis prophylaxis among paediatric cardiologists. A web-based survey focussing on current practice, describing the use of antibiotics for infective endocarditis prophylaxis in various congenital and acquired heart diseases, was distributed via e-mail to paediatric cardiologists. The survey was kept anonymous and was distributed twice. Data from 253 participants were analysed. Most paediatric cardiologists discontinued infective endocarditis prophylaxis in patients with simple lesions such as small ventricular septal defect, patent ductus arteriosus, and bicuspid aortic valve without stenosis or regurgitation; however, significant disagreement persists in prescribing infective endocarditis prophylaxis in certain conditions such as rheumatic heart disease, Fontan palliation without fenestration, and the Ross procedure. Use of antibiotic prophylaxis in certain selected conditions for which infective endocarditis prophylaxis has been indicated as per the current guidelines varies from 44 to 83%. Only 44% follow the current guidelines exclusively, and 34% regularly discuss the importance of oral hygiene with their patients at risk for infective endocarditis. Significant heterogeneity still persists in recommending infective endocarditis prophylaxis for several cardiac lesions among paediatric cardiologists. More than half of the participants (56%) do not follow the current guidelines exclusively in their practice. Counselling for optimal oral health in patients at risk for infective endocarditis needs to be optimised in the current practice.

  7. The benefit of low dose prophylaxis in the treatment of hemophilia: a focus on China.

    PubMed

    Wu, Runhui; Luke, Koon Hung

    2017-11-01

    Currently full dose prophylaxis is the standard of care in the treatment of hemophilia (World Federation of Hemophilia). However, the high costs prevent the use of standard or intermediate dose prophylaxis in China and other developing countries. Low dose prophylaxis would be a viable alternative treatment. At present global research data on the use of low dose prophylaxis is limited. Areas covered: Since 2007, China has been developing low dose prophylaxis as a high priority (90 % of moderate and severe hemophilia boys suffer joint disease by age 6 - 9). 11 studies were successfully conducted and published results showing evidence of the benefits of low dose prophylaxis to reduce joint bleeding. This new knowledge has been implemented into clinical practice in China. However the long-term outcome of arthropathy remains unclear and obstacles in execution exist. Expert commentary: In 2016, the first phenotype-based individualized prophylaxis study using four escalating low dose regimens on severe Chinese hemophilia A boys (China Individualized Prophylaxis Study (CHIP China)) launched. Using the previously published and imminent CHIP data, the goal for China is to establish an effective escalating low dose prophylaxis protocol for use in China as a standard of care.

  8. [SOME ASPECTS OF NON-SPECIFIC PROPHYLAXIS AND THERAPY OF ESPECIALLY DANGEROUS INFECTIONS].

    PubMed

    Filippenko, A V; Omelchenko, N D; Ivanova, I A; Bespalova, I A; Doroshenko, E P; Galicheva, A L

    2015-01-01

    Recently, due to spread of dangerous and especially dangerous infections much attention is given to development of complex approaches to their prophylaxis and therapy. Data on use of immune modulators, cytokines, probiotics, preparations of plant origin for non-specific prophylaxis of especially dangerous infections are analyzed in the review, and expediency of their combined use with specific and emergency prophlaxis of these diseases is evaluated.

  9. Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

    PubMed

    Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

    2011-09-01

    The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

  10. Risk factors for nosocomial pneumonia. Focus on prophylaxis.

    PubMed

    Fleming, C A; Balaguera, H U; Craven, D E

    2001-11-01

    Despite an increased understanding of the pathogenesis of NP and advances in diagnosis and treatment, the risk, cost, morbidity, and mortality of NP remain unacceptably high. This article has identified strategic areas for primary and secondary prophylaxis that are simple and cost-effective. Realizing that the pathogenesis of NP requires bacterial colonization and the subsequent entry of these bacteria into the lower respiratory tree helps highlight the role of cross-infection and the importance of standard infection control procedures. Similarly the role of sedation and devices as risk factors can be reduced by minimizing the duration and intensity of sedation and length of exposure to invasive devices. Additional low-cost interventions that have been shown to be effective in preventing NP are the positioning of patients in a semirecumbent position and the appropriate use of enteral feeding, antibiotics, and selected medical devices. Prophylaxis of NP and VAP is carried out best by a multidisciplinary management team comprised of physicians (critical care, pulmonary medicine, infectious diseases, and primary care), critical care and infection control nurses, and respiratory therapists, even though this approach may result in decreased professional autonomy and freedom. This group should review the current guidelines, pathways, and standards for short-term and long-term prophylaxis of NP and VAP, then integrate them into and monitor their use for routine patient care. The risk factors and prophylaxis strategies for NP discussed in this article apply primarily to patients in acute care facilities, but also are relevant to alternative health care settings as well as the care of ill patients in ambulatory settings. The routine use of effective team policies for prophylaxis needs to be monitored by the Joint Commission for the Accreditation of Health Care or other agencies. Research to delineate the most effective and feasible strategies for prophylaxis NP has been

  11. Cost-effectiveness analysis of pharmacokinetic-driven prophylaxis vs. standard prophylaxis in patients with severe haemophilia A.

    PubMed

    Iannazzo, Sergio; Cortesi, Paolo A; Crea, Roberto; Steinitz, Katharina; Mantovani, Lorenzo G; Gringeri, Alessandro

    2017-09-01

    : The objective of this study was to assess the cost-effectiveness of pharmacokinetic-driven prophylaxis in severe haemophilia A patients. A microsimulation model was developed to evaluate the cost-effectiveness of pharmacokinetic-driven prophylaxis vs. standard prophylaxis and estimate cost, annual joint bleed rate (AJBR), and incremental cost-effectiveness ratio over a 1-year time horizon for a hypothetical population of 10 000 severe haemophilia A patients. A dose of 30 IU/kg per 48 h was assumed for standard prophylaxis. Pharmacokinetic prophylaxis was individually adjusted to maintain trough levels at least 1 and 5 IU/dl or less. AJBR was estimated on the relationship between factor VIII (FVIII) levels and bleeding rate reported in the literature. Sensitivity analyses were performed to assess the stability of the model and the reliability of results. The FVIII dose was reduced in the 27.8% of patients with a trough level more than 5 IU/dl on standard prophylaxis, with a negligible impact on AJBR (+0.1 bleed/year). The FVIII dose was increased in the 10.6% of patients with trough levels less than 1 IU/dl on standard prophylaxis, with a significant reduction of AJBR (-1.9 bleeds/year). On average, overall, pharmacokinetic-driven prophylaxis was shown to decrease the AJBR from 1.012 to 0.845 with a slight reduction of the infusion dose of 0.36 IU/kg, with total saving of 5 197&OV0556; per patient-year. Pharmacokinetic-driven prophylaxis was preferable (i.e. more effective and less costly) compared with standard prophylaxis, with savings of 31 205&OV0556; per bleed avoided. Pharmacokinetic-driven prophylaxis, accounting for patients' individual pharmacokinetic variability, appears to be a promising strategy to improve outcomes with efficient use of available resources in severe haemophilia A patients.

  12. Graft versus host disease after stem cell allotransplantation with low-dose total body irradiation, fludarabine, and antithymocyte globulin.

    PubMed

    Grosskreutz, Celia; Scigliano, Eileen; Osman, Keren; Isola, Luis

    2007-09-15

    We previously showed that antithymocyte globulin (ATG) given with total body irradiation (TBI) 200 cGy and fludarabine results in high rate of donor engraftment. Its influence on acute and chronic graft versus host disease (GVHD) and on graft versus tumor effect is less known. Sixty-five patients underwent nonmyeloablative stem cell transplant with ATG, TBI 200 cGy, and fludarabine. GVHD prophylaxis was mycophenolate mofetil and cyclosporine. Forty-two patients (pts) (65%) had match related donors, 18 (27%) match unrelated, 1 (1.5%) mismatch related, and 4 (6%) mismatch unrelated donors. At a median follow-up of 862 days, 24 patients (37%) developed GVHD. The median age of the patients with and without GVHD was 56 years respectively. Acute GVHD grade II-IV developed in 19 pts (29%). Fatal GVHD of liver and/or gut occurred in nine pts (14%). Forty-one pts survived more than 100 days. Five pts (12%) had chronic GVHD, two had extensive, and three had limited involvement. Relapsed disease was observed in 22 pts (34%). Infections occurred in 15 pts (23%) and were fatal in 13 (20%). The addition of ATG to TBI 200cGy and fludarabine resulted in a modest incidence of GVHD. The best transplant outcomes were observed in pts with lymphoid malignancies.

  13. Crusted scabies in a patient with chronic graft-versus-host disease.

    PubMed

    Magee, K L; Hebert, A A; Rapini, R P

    1991-11-01

    We describe a 20-year-old man with chronic graft-versus-host disease and progressive cutaneous changes. His skin became more lichenified despite therapy with azathioprine, prednisone, and cyclosporine. Although it was initially thought that lichenoid graft-versus-host disease had developed, it was subsequently discovered that the patient had crusted (Norwegian) scabies.

  14. [Diagnosis, prophylaxis and treatment of central nervous system involvement by non-Hodgkin lymphoma in HIV-infected patients].

    PubMed

    Miralles, Pilar; Berenguer, Juan; Ribera, Josep-Maria

    2010-09-18

    With the widespread use of highly active antiretroviral therapy (HAART) the incidence of systemic non-Hodgkin lymphoma (NHL) in patients infected with the Human Immunodeficiency Virus (HIV) has declined. HAART has also modified the clinical manifestations of these tumors, with a lower frequency of involvement of the central nervous system (CNS). Currently, the frequency of meningeal involvement at the time of diagnosis of NHL in HIV-infected patients varies between 3% and 5%. These figures are similar to those observed among immunocompetent hosts. The diagnosis of meningeal lymphoma relies in clinical findings, imaging techniques, and cerebrospinal fluid (CSF) examination. Flow cytometry is a diagnostic technique with a higher sensitivity and specificity than conventional cytology for the diagnosis of meningeal lymphoma. However, flow cytometry is not yet considered to be the gold standard for this purpose. Until recently, most experts recommended neuromeningeal prophylaxis for all HIV-infected patients with aggressive NHL. However, at present this prophylaxis is recommended only in patients with higher risk of CNS relapse according to different sites of involvement, stage and histological subtype. There are different regimens of prophylaxis and treatment for meningeal lymphoma. The drugs most commonly used for this purpose are methotrexate and cytosine arabinoside. However, there are other alternatives such as liposomal cytosine arabinoside that requires fewer spinal taps for drug administration and whose results are very promising. In summary, in the context of an effective HAART, HIV infected patients with NHL have a frequency of CNS involvement by lymphoma similar to that found among immunocompetent hosts. Consequently, indications and regimens for CNS prophylaxis in HIV-infected patients with NHL should not be different than those employed in the general population. Universal CNS prophylaxis should be reserved for the few patients unable to receive an

  15. Guidelines for antimicrobial prophylaxis.

    PubMed

    Nahata, M C

    1996-08-01

    Antimicrobials are frequently used to prevent infections. Principles of prophylaxis, and antimicrobial prophylaxis in surgery, tuberculosis, acquired immunodeficiency syndrome, influenza A, traveller's diarrhoea, malaria, recurrent otitis media, Haemophilus influenzae type b infection, pertussis, rheumatic fever, and urinary tract infection are described. Various strategies to improve the prophylactic use of antibiotics are discussed. Collaborative efforts among health care disciplines are needed to assure optimal antimicrobial prophylaxis. This should maximize efficacy and minimize adverse effects, the development of bacterial resistance and associated costs.

  16. Update on host-pathogen interactions in cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Frey, Nina; Hartl, Dominik

    2016-12-01

    Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease.

  17. Adherence to secondary prophylaxis for rheumatic heart disease is underestimated by register data

    PubMed Central

    de Dassel, Jessica Langloh; Fittock, Marea Therese; Wilks, Sagen Cheyenne; Poole, Jane Elizabeth; Carapetis, Jonathan Rhys; Ralph, Anna P.

    2017-01-01

    Objective In high-burden Australian states and territories, registers of patients with acute rheumatic fever and rheumatic heart disease are maintained for patient management, monitoring of system performance and research. Data validation was undertaken for the Australian Northern Territory Rheumatic Heart Disease Register to determine quality and impact of data cleaning on reporting against key performance indicators: overall adherence, and proportion of patients receiving ≥80% of scheduled penicillin doses for secondary prophylaxis. Methods Register data were compared with data from health centres. Inconsistencies were identified and corrected; adherence was calculated before and after cleaning. Results 2780 penicillin doses were validated; 426 inconsistencies were identified, including 102 incorrect dose dates. After cleaning, mean adherence increased (63.5% to 67.3%, p<0.001) and proportion of patients receiving ≥80% of doses increased (34.2% to 42.1%, p = 0.06). Conclusions The Northern Territory Rheumatic Heart Disease Register underestimates adherence, although the key performance indicator of ≥80% adherence was not significantly affected. Program performance is better than hitherto appreciated. However some errors could affect patient management, as well as accuracy of longitudinal or inter-jurisdictional comparisons. Adequate resources are needed for maintenance of data quality in acute rheumatic fever/rheumatic heart disease registers to ensure provision of evidence-based care and accurate assessment of program impact. PMID:28562621

  18. Cost effectiveness of mesh prophylaxis to prevent parastomal hernia in patients undergoing permanent colostomy for rectal cancer.

    PubMed

    Lee, Lawrence; Saleem, Abdulaziz; Landry, Tara; Latimer, Eric; Chaudhury, Prosanto; Feldman, Liane S

    2014-01-01

    Parastomal hernia (PSH) is common after stoma formation. Studies have reported that mesh prophylaxis reduces PSH, but there are no cost-effectiveness data. Our objective was to determine the cost effectiveness of mesh prophylaxis vs no prophylaxis to prevent PSH in patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer. Using a cohort Markov model, we modeled the costs and effectiveness of mesh prophylaxis vs no prophylaxis at the index operation in a cohort of 60-year-old patients undergoing abdominoperineal resection for rectal cancer during a time horizon of 5 years. Costs were expressed in 2012 Canadian dollars (CAD$) and effectiveness in quality-adjusted life years. Deterministic and probabilistic sensitivity analyses were performed. In patients with stage I to III rectal cancer, prophylactic mesh was dominant (less costly and more effective) compared with no mesh. In patients with stage IV disease, mesh prophylaxis was associated with higher cost (CAD$495 more) and minimally increased effectiveness (0.05 additional quality-adjusted life years), resulting in an incremental cost-effectiveness ratio of CAD$10,818 per quality-adjusted life year. On sensitivity analyses, the decision was sensitive to the probability of mesh infection and the cost of the mesh, and method of diagnosing PSH. In patients undergoing abdominoperineal resection with permanent colostomy for rectal cancer, mesh prophylaxis might be the less costly and more effective strategy compared with no mesh to prevent PSH in patients with stage I to III disease, and might be cost effective in patients with stage IV disease. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Borrelia burgdorferi has minimal impact on the Lyme disease reservoir host Peromyscus leucopus.

    PubMed

    Schwanz, Lisa E; Voordouw, Maarten J; Brisson, Dustin; Ostfeld, Richard S

    2011-02-01

    The epidemiology of vector-borne zoonotic diseases is determined by encounter rates between vectors and hosts. Alterations to the behavior of reservoir hosts caused by the infectious agent have the potential to dramatically alter disease transmission and human risk. We examined the effect of Borrelia burgdorferi, the etiological agent of Lyme disease, on one of its most important reservoir hosts, the white-footed mouse, Peromyscus leucopus. We mimic natural infections in mice using the vector (Black-legged ticks, Ixodes scapularis) and examine the immunological and behavioral responses of mouse hosts. Despite producing antibodies against B. burgdorferi, infected mice did not have elevated white blood cells compared with uninfected mice. In addition, infected and uninfected mice did not differ in their wheel-running activity. Our results suggest that infection with the spirochete B. burgdorferi has little impact on the field activity of white-footed mice. Lyme disease transmission appears to be uncomplicated by pathogen-altered behavior of this reservoir host.

  20. Reservoir-host amplification of disease impact in an endangered amphibian.

    PubMed

    Scheele, Ben C; Hunter, David A; Brannelly, Laura A; Skerratt, Lee F; Driscoll, Don A

    2017-06-01

    Emerging wildlife pathogens are an increasing threat to biodiversity. One of the most serious wildlife diseases is chytridiomycosis, caused by the fungal pathogen, Batrachochytrium dendrobatidis (Bd), which has been documented in over 500 amphibian species. Amphibians vary greatly in their susceptibility to Bd; some species tolerate infection, whereas others experience rapid mortality. Reservoir hosts-species that carry infection while maintaining high abundance but are rarely killed by disease-can increase extinction risk in highly susceptible, sympatric species. However, whether reservoir hosts amplify Bd in declining amphibian species has not been examined. We investigated the role of reservoir hosts in the decline of the threatened northern corroboree frog (Pseudophryne pengilleyi) in an amphibian community in southeastern Australia. In the laboratory, we characterized the response of a potential reservoir host, the (nondeclining) common eastern froglet (Crinia signifera), to Bd infection. In the field, we conducted frog abundance surveys and Bd sampling for both P. pengilleyi and C. signifera. We built multinomial logistic regression models to test whether Crinia signifera and environmental factors were associated with P. pengilleyi decline. C. signifera was a reservoir host for Bd. In the laboratory, many individuals maintained intense infections (>1000 zoospore equivalents) over 12 weeks without mortality, and 79% of individuals sampled in the wild also carried infections. The presence of C. signifera at a site was strongly associated with increased Bd prevalence in sympatric P. pengilleyi. Consistent with disease amplification by a reservoir host, P. pengilleyi declined at sites with high C. signifera abundance. Our results suggest that when reservoir hosts are present, population declines of susceptible species may continue long after the initial emergence of Bd, highlighting an urgent need to assess extinction risk in remnant populations of other declined

  1. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects.

    PubMed

    Zumla, Alimuddin; Rao, Martin; Wallis, Robert S; Kaufmann, Stefan H E; Rustomjee, Roxana; Mwaba, Peter; Vilaplana, Cris; Yeboah-Manu, Dorothy; Chakaya, Jeremiah; Ippolito, Giuseppe; Azhar, Esam; Hoelscher, Michael; Maeurer, Markus

    2016-04-01

    Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Novel venous thromboembolic disease (VTED) prophylaxis for total knee arthroplasty—aspirin and fish oil

    PubMed Central

    Sodhi, Nipun; Patel, Yatindra H.; Sultan, Assem A.; Khlopas, Anton; Chughtai, Morad; Kolisek, Frank R.; Williams, Nick; Mont, Michael A.

    2017-01-01

    Background Despite the demonstrated success of multiple anticoagulation therapies for post-operative prophylaxis of thromboembolic disease in lower extremity arthroplasties, each modality comes with a unique set of limitations. Thus, the ideal anticoagulation medication which provides adequate therapy with minimal cost, complications, or added patient work is yet to be defined. One promising novel thrombophylactic supplement is fish oil, as many preliminary clinical trials have demonstrated a protective effect of fish oil against thrombosis in multiple clinical settings. In addition, others have demonstrated synergistic effect when combined with aspirin. However, there are paucity of studies that compared combined aspirin and fish oil therapy for venous thromboembolism prophylaxis with other pharmacological agents, especially in the field of orthopaedics. Therefore, this study evaluated: (I) risk of post-operative deep vein thrombosis (DVT) and pulmonary embolism (PE), and (II) bleeding complications; among patients who had primary total knee arthroplasty (TKA) and received one of the following regimens: (i) 325 mg aspirin and mechanical pulsatile stocking; (ii) rivaroxaban; or (iii) 325 mg aspirin and 1,000 mg fish oil. Methods This was a 6-year prospective study analyzing the postoperative thromboembolic prophylaxis received by patients who underwent primary TKA. Patients who had a previous history of thromboembolic disease were excluded from the study due to an increased risk of recurrent clot formation. A total of 850 patients were enrolled. A total of 300 patients enrolled between October 2011 and June 2013 received 325 mg aspirin and mechanical pulsatile stocking, while 250 patients enrolled between June 2013 and December 2014 received rivaroxaban. A total of 300 patients enrolled between January 2015 and July 2017 received 325 mg aspirin and 1,000 mg fish oil. Major venous thromboembolic events (VTEs) and bleeding complications within the first 90 days post

  3. Novel venous thromboembolic disease (VTED) prophylaxis for total knee arthroplasty-aspirin and fish oil.

    PubMed

    Bonutti, Peter M; Sodhi, Nipun; Patel, Yatindra H; Sultan, Assem A; Khlopas, Anton; Chughtai, Morad; Kolisek, Frank R; Williams, Nick; Mont, Michael A

    2017-12-01

    Despite the demonstrated success of multiple anticoagulation therapies for post-operative prophylaxis of thromboembolic disease in lower extremity arthroplasties, each modality comes with a unique set of limitations. Thus, the ideal anticoagulation medication which provides adequate therapy with minimal cost, complications, or added patient work is yet to be defined. One promising novel thrombophylactic supplement is fish oil, as many preliminary clinical trials have demonstrated a protective effect of fish oil against thrombosis in multiple clinical settings. In addition, others have demonstrated synergistic effect when combined with aspirin. However, there are paucity of studies that compared combined aspirin and fish oil therapy for venous thromboembolism prophylaxis with other pharmacological agents, especially in the field of orthopaedics. Therefore, this study evaluated: (I) risk of post-operative deep vein thrombosis (DVT) and pulmonary embolism (PE), and (II) bleeding complications; among patients who had primary total knee arthroplasty (TKA) and received one of the following regimens: (i) 325 mg aspirin and mechanical pulsatile stocking; (ii) rivaroxaban; or (iii) 325 mg aspirin and 1,000 mg fish oil. This was a 6-year prospective study analyzing the postoperative thromboembolic prophylaxis received by patients who underwent primary TKA. Patients who had a previous history of thromboembolic disease were excluded from the study due to an increased risk of recurrent clot formation. A total of 850 patients were enrolled. A total of 300 patients enrolled between October 2011 and June 2013 received 325 mg aspirin and mechanical pulsatile stocking, while 250 patients enrolled between June 2013 and December 2014 received rivaroxaban. A total of 300 patients enrolled between January 2015 and July 2017 received 325 mg aspirin and 1,000 mg fish oil. Major venous thromboembolic events (VTEs) and bleeding complications within the first 90 days post-operatively were

  4. Antibiotic prophylaxis in cirrhosis: Good and bad.

    PubMed

    Fernández, Javier; Tandon, Puneeta; Mensa, Jose; Garcia-Tsao, Guadalupe

    2016-06-01

    Patients with cirrhosis, particularly those with decompensated cirrhosis, are at increased risk of bacterial infections that may further precipitate other liver decompensations including acute-on-chronic liver failure. Infections constitute the main cause of death in patients with advanced cirrhosis, and strategies to prevent them are essential. The main current strategy is the use of prophylactic antibiotics targeted at specific subpopulations at high risk of infection: prior episode of spontaneous bacterial peritonitis, upper gastrointestinal bleeding, and low-protein ascites with associated poor liver function. Antibiotic prophylaxis effectively prevents not only the development of bacterial infections in all these indications but also further decompensation (variceal bleeding, hepatorenal syndrome) and improves survival. However, antibiotic prophylaxis is also associated with a clinically relevant and increasing drawback, the development of infections due to multidrug-resistant organisms. Several strategies have been suggested to balance the risks and benefits of antibiotic prophylaxis. Antibiotic stewardship principles such as the restriction of antibiotic prophylaxis to subpopulations at a very high risk for infection, the avoidance of antibiotic overuse, and early deescalation policies are key to achieve this balance; nonantibiotic prophylactic measures such as probiotics, prokinetics, bile acids, statins, and hematopoietic growth factors could also contribute to ameliorate the development and spread of multidrug-resistant bacteria in cirrhosis. (Hepatology 2016;63:2019-2031). © 2015 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. government employees, and their contribution is in the public domain in the U.S.A.

  5. Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose prophylaxis: a prospective FUNGINOS study.

    PubMed

    Orasch, Christina; Mertz, Dominik; Garbino, Jorge; van Delden, Christian; Emonet, Stephane; Schrenzel, Jacques; Zimmerli, Stefan; Damonti, Lauro; Mühlethaler, Konrad; Imhof, Alexander; Ruef, Christian; Fehr, Jan; Zbinden, Reinhard; Boggian, Katia; Bruderer, Thomas; Flückiger, Ursula; Conen, Anna; Khanna, Nina; Frei, Reno; Bregenzer, Thomas; Lamoth, Frédéric; Erard, Véronique; Bochud, Pierre-Yves; Calandra, Thierry; Bille, Jacques; Marchetti, Oscar

    2018-05-01

    Breakthrough candidemia (BTC) on fluconazole was associated with non-susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study analyzed clinical and mycological BTC characteristics. A 3-year prospective study was conducted in 567 consecutive candidemias. Species identification and antifungal susceptibility testing (CLSI) were performed in the FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria. 43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis, median 200 mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock. Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal mucositis (multivariate OR 5.25, 95%CI 2.23-12.40, p < 0.001) and graft-versus-host-disease (6.25, 1.00-38.87, p = 0.05), immunosuppression (2.42, 1.03-5.68, p = 0.043), and parenteral nutrition (2.87, 1.44-5.71, p = 0.003). Non-albicans Candida were isolated in 58% BTC vs. 35% non-BTC (p = 0.005). 63% of 16 BTC occurring after 10-day fluconazole were non-susceptible (Candida glabrata, Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following shorter exposure (7.10, 1.60-31.30, p = 0.007). Median fluconazole MIC was 4 mg/l vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible BTC with 73% accuracy. Outcomes of BTC and non-BTC were similar. Fluconazole non-susceptible BTC occurred in three out of four cases after prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration and rapid de-escalation of empirical therapy in BTC after short fluconazole exposure. Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  6. Recommendations for reporting economic evaluations of haemophilia prophylaxis: a nominal groups consensus statement on behalf of the Economics Expert Working Group of The International Prophylaxis Study Group.

    PubMed

    Nicholson, A; Berger, K; Bohn, R; Carcao, M; Fischer, K; Gringeri, A; Hoots, K; Mantovani, L; Schramm, W; van Hout, B A; Willan, A R; Feldman, B M

    2008-01-01

    The need for clearly reported studies evaluating the cost of prophylaxis and its overall outcomes has been recommended from previous literature. To establish minimal ''core standards'' that can be followed when conducting and reporting economic evaluations of hemophilia prophylaxis. Ten members of the IPSG Economic Analysis Working Group participated in a consensus process using the Nominal Groups Technique (NGT). The following topics relating to the economic analysis of prophylaxis studies were addressed; Whose perspective should be taken? Which is the best methodological approach? Is micro- or macro-costing the best costing strategy? What information must be presented about costs and outcomes in order to facilitate local and international interpretation? The group suggests studies on the economic impact of prophylaxis should be viewed from a societal perspective and be reported using a Cost Utility Analysis (CUA) (with consideration of also reporting Cost Benefit Analysis [CBA]). All costs that exceed $500 should be used to measure the costs of prophylaxis (macro strategy) including items such as clotting factor costs, hospitalizations, surgical procedures, productivity loss and number of days lost from school or work. Generic and disease specific quality of lífe and utility measures should be used to report the outcomes of the study. The IPSG has suggested minimal core standards to be applied to the reporting of economic evaluations of hemophilia prophylaxis. Standardized reporting will facilitate the comparison of studies and will allow for more rational policy decisions and treatment choices.

  7. Host genetics of Epstein-Barr virus infection, latency and disease.

    PubMed

    Houldcroft, Charlotte J; Kellam, Paul

    2015-03-01

    Epstein-Barr virus (EBV) infects 95% of the adult population and is the cause of infectious mononucleosis. It is also associated with 1% of cancers worldwide, such as nasopharyngeal carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma. Human and cancer genetic studies are now major forces determining gene variants associated with many cancers, including nasopharyngeal carcinoma and Hodgkin's lymphoma. Host genetics is also important in infectious disease; however, there have been no large-scale efforts towards understanding the contribution that human genetic variation plays in primary EBV infection and latency. This review covers 25 years of studies into host genetic susceptibility to EBV infection and disease, from candidate gene studies, to the first genome-wide association study of EBV antibody response, and an EBV-status stratified genome-wide association study of Hodgkin's lymphoma. Although many genes are implicated in EBV-related disease, studies are often small, not replicated or followed up in a different disease. Larger, appropriately powered genomic studies to understand the host response to EBV will be needed to move our understanding of the biology of EBV infection beyond the handful of genes currently identified. Fifty years since the discovery of EBV and its identification as a human oncogenic virus, a glimpse of the future is shown by the first whole-genome and whole-exome studies, revealing new human genes at the heart of the host-EBV interaction. © 2014 The Authors Reviews in Medical Virology published by John Wiley & Sons Ltd.

  8. Strategic targeting of essential host-pathogen interactions in chlamydial disease.

    PubMed

    Coombes, B K; Johnson, D L; Mahony, J B

    2002-09-01

    The chlamydiae are obligate intracellular gram-negative bacteria that are exquisitely adapted for exploitation of their hosts and contribute to a wide range of acute and chronic human diseases. Acute infections treated with non-cidal antibiotics can lead to the development of persistent, non-replicating bacteria with the corollary that these persistent (yet viable) chlamydiae can resist eradication by further antimicrobial treatment and cause chronic disease. These findings highlight an urgent need for therapeutics that are effective against persistent infections and call for creative approaches to identify potential drug targets. The C. pneumoniae and C. trachomatis genome projects have greatly expanded our knowledge of chlamydial pathogenesis and have provided an enormous potential for the identification and characterization of unknown genes and potential virulence factors in these bacteria. As intracellular pathogens, chlamydiae rely on host cells for all aspects of their survival, from the initial attachment with host cell membranes, to cellular invasion, acquisition of host cell metabolites and intracellular replication. As such, the molecules participating in interactions with the host could be attractive targets for therapeutic intervention. This review describes recent advances in chlamydial genomics, proteomics and cell biology that have cast light on host-pathogen relations that are essential for chlamydial survival. Using this knowledge, we discuss how strategically interfering with essential interactions between chlamydiae and the host cell could be exploited to develop an innovative, and potentially more relevant arsenal of therapeutic compounds.

  9. 21 CFR 872.6290 - Prophylaxis cup.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6290 Prophylaxis cup. (a) Identification. A prophylaxis cup is a device made of rubber intended to be held by a dental handpiece and used to apply polishing agents during prophylaxis (cleaning). The dental handpiece spins the rubber cup holding the polishing...

  10. 21 CFR 872.6290 - Prophylaxis cup.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6290 Prophylaxis cup. (a) Identification. A prophylaxis cup is a device made of rubber intended to be held by a dental handpiece and used to apply polishing agents during prophylaxis (cleaning). The dental handpiece spins the rubber cup holding the polishing...

  11. 21 CFR 872.6290 - Prophylaxis cup.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6290 Prophylaxis cup. (a) Identification. A prophylaxis cup is a device made of rubber intended to be held by a dental handpiece and used to apply polishing agents during prophylaxis (cleaning). The dental handpiece spins the rubber cup holding the polishing...

  12. Clinicians-related Determinants of Anticoagulation Therapy and Prophylaxis in Nigeria

    PubMed Central

    Anakwue, Raphael; Nwagha, Theresa; Ukpabi, Ogba J.; Obeka, Ndudim; Onwubuya, Emmanuel; Onwuchekwa, Uwa; Azubuike, Benjamin; Okoye, Innocent

    2017-01-01

    Background: Thromboembolic and hypercoagulable diseases are common life-threatening but treatable problems in hospital practice. Fortunately, anticoagulation is an efficacious management practice indicated for arterial, venous, and intracardiac thromboembolism. Clinicians in developing countries may have gaps in their knowledge of anticoagulation therapy/prophylaxis which could affect their clinical decision. Objectives: The study examined the knowledge and attitude of clinicians to anticoagulation therapy/prophylaxis in some tertiary hospitals in Nigeria. Methodology: The study was a multicenter survey. A pretested questionnaire was administered to clinicians in six tertiary hospitals in Southeast Nigeria. Results: A total of 528 questionnaires were returned by 419 (79.4%) residents and 109 (20.6%) consultants. We observed significant abysmal knowledge and lack of awareness of direct oral anticoagulants (DOACs) among most respondents irrespective of their job grades (P = 0.02, odds ratio [OR] 0.59, 95% confidence interval [CI] 0.38–0.90). Their knowledge of anti-Xa assay as laboratory monitoring tool was also significantly inadequate (P = 0.001, OR 0.23, 95% CI 0.10–0.51). On statement analysis on their attitude to anticoagulation therapy/prophylaxis, “Do you think anticoagulation therapy/prophylaxis is clinically relevant” had the highest mean of 4.60, P = 0.01, and a high degree of agreement; while “Should hospital inpatient with > 3 days admission routinely receive anticoagulation/prophylaxis?” had the lowest mean of 2.27, P = 0.02, and a low degree of agreement. Conclusion: There is the need to upscale knowledge of anticoagulation agents and an attitude change to anticoagulation therapy/prophylaxis, especially on the DOACs through continuing medical education activities in emerging countries such as Nigeria. PMID:29063899

  13. Infections on the move: how transient phases of host movement influence disease spread

    PubMed Central

    Fenton, A.; Dell, A. I.

    2017-01-01

    Animal movement impacts the spread of human and wildlife diseases, and there is significant interest in understanding the role of migrations, biological invasions and other wildlife movements in spatial infection dynamics. However, the influence of processes acting on infections during transient phases of host movement is poorly understood. We propose a conceptual framework that explicitly considers infection dynamics during transient phases of host movement to better predict infection spread through spatial host networks. Accounting for host transient movement captures key processes that occur while hosts move between locations, which together determine the rate at which hosts spread infections through networks. We review theoretical and empirical studies of host movement and infection spread, highlighting the multiple factors that impact the infection status of hosts. We then outline characteristics of hosts, parasites and the environment that influence these dynamics. Recent technological advances provide disease ecologists unprecedented ability to track the fine-scale movement of organisms. These, in conjunction with experimental testing of the factors driving infection dynamics during host movement, can inform models of infection spread based on constituent biological processes. PMID:29263283

  14. Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project

    PubMed Central

    Soucie, J. Michael; Gill, Joan Cox

    2017-01-01

    This analysis of the US Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life-span among participants with severe hemophilia A. Data on demographics, clinical characteristics, and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26 614 visits for 6196 males; mean age at first registry visit was 17.7 years; and median was 14 (range, 2 to 69). During this time, prophylaxis use increased from 31% to 59% overall, and by 2010, 75% of children and youths <20 years were on prophylaxis. On cross-sectional analysis, bleeding rates decreased dramatically for the entire population (P < .001) in parallel with increased prophylaxis usage, possibly because frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and nonprophylaxis (23%), and target joints decreased more with prophylaxis (80% vs 61%). Joint, total, and target joint bleeding on prophylaxis were 33%, 41%, and 27%, respectively, compared with nonprophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (P < .001), but only prophylaxis initiation prior to age 4 years and nonobesity predicted preservation of joint motion (P < .001 for each). Using a national registry, care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time. PMID:28183693

  15. Infectious diseases of marine molluscs and host responses as revealed by genomic tools

    PubMed Central

    Ford, Susan E.

    2016-01-01

    More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large-scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance. PMID:26880838

  16. 21 CFR 872.6290 - Prophylaxis cup.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Prophylaxis cup. 872.6290 Section 872.6290 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6290 Prophylaxis cup. (a) Identification. A prophylaxis cup is a device made of rubber intended to be held by a dental handpiece and used to apply polishing...

  17. 21 CFR 872.6290 - Prophylaxis cup.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prophylaxis cup. 872.6290 Section 872.6290 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6290 Prophylaxis cup. (a) Identification. A prophylaxis cup is a device made of rubber intended to be held by a dental handpiece and used to apply polishing...

  18. Molecular Neuro-Pathomechanism of Neurocysticercosis: How Host Genetic Factors Influence Disease Susceptibility.

    PubMed

    Arora, Naina; Tripathi, Shweta; Sao, Reshma; Mondal, Prosenjit; Mishra, Amit; Prasad, Amit

    2018-02-01

    Neurocysticercosis (NCC) is one of the most neglected tropical diseases among widely endemic neurological diseases. It is caused by cysticerci of Taenia solium. The clinical symptom for the outcome of infection and progression of disease is pleomorphic and its neuro-pathomechanism is still illusive. Identification of host genetic factors and their association with disease susceptibility is one of the most important areas of research towards personalized medicine in the era of omics. Several genes and their allelic variations had been identified to be associated with various neurological disorders; however, the information for parasitic diseases affecting the central nervous system is very limited. Both Th1 and Th2 arms of the immune system are reported to be active at different stages of T. solium infection in the brain. Recently, several papers had been published, where the role of host genetic makeup with NCC had been explored. Increased frequency of HLA-A28, HLA-B63, HLA-B58, TLR 4 Asp299Gly, sICAM-1 gene K469E, GSTM1, and GSTT1 were found to be associated with increased risk of NCC occurrence, while HLA-DQW2 and HLA-A11 were shown to be providing protection from disease. In this review, we have summarized these findings and analyzed the influence of host genetic polymorphism on the susceptibility/resistance of host to NCC.

  19. Pre-exposure rabies prophylaxis: a systematic review.

    PubMed

    Kessels, Jocelyn A; Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

    2017-03-01

    To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings. We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

  20. Pre-exposure rabies prophylaxis: a systematic review

    PubMed Central

    Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

    2017-01-01

    Abstract Objective To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings. Methods We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Findings Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Conclusion Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities. PMID:28250534

  1. Chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim in elderly versus non-elderly cancer patients: Patterns, outcomes, and determinants (MONITOR-GCSF study).

    PubMed

    Aapro, Matti; Bokemeyer, Carsten; Ludwig, Heinz; Gascón, Pere; Boccadoro, Mario; Denhaerynck, Kris; Gorray, Michael; Krendyukov, Andriy; MacDonald, Karen; Abraham, Ivo

    2017-03-01

    Myelotoxic chemotherapy is associated with chemotherapy-induced (febrile) neutropenia (CIN/FN). The MONITOR-GCSF study evaluated biosimilar filgrastim (Zarzio®) prophylaxis patterns, associated outcomes, and determinants. We performed stratified analyses comparing elderly and non-elderly patients. Comparative (elderly/non-elderly) analysis of demographics and clinical status, prophylaxis, associated CIN/FN outcomes (CIN grade 4 [CIN4], FN, CIN/FN-related hospitalizations and chemodisturbances, composite), and, per hierarchical modeling, determinants thereof evaluated at the patient- and cycle-level. There were no significant differences between both cohorts in prophylaxis initiation/duration and associated outcomes, but proportionately more elderly patients were correctly-prophylacted and fewer over-prophylacted. Common determinants of poor CIN/FN outcomes included concomitant antibiotic prophylaxis, impaired performance status, and any grade CIN in a previous cycle, whereas common determinants of good outcomes included over-prophylaxis and prophylaxis initiation within 24-72h. In the elderly, female gender, liver/renal/cardiovascular disease, secondary prophylaxis, and under-prophylaxis were associated with poorer outcomes. In the non-elderly, CIN4 at baseline or in a prior cycle was associated with poorer CIN/FN outcomes, and higher biosimilar filgrastim dose and, perhaps counter-intuitively, under-prophylaxis with better outcomes. Adequate GCSF support is essential for all patients, but especially for elderly patients with serious chronic disease, certainly, if concomitant antibiotic prophylaxis is indicated and if a CIN4 episode occurred in a prior cycle. The potential impact of impaired performance status, especially ECOG≥2 at chemotherapy start or a worsening to such during chemotherapy; under-prophylaxis, including inadequate secondary prophylaxis, should be considered in elderly patients. Timely GCSF initiation and over-prophylaxis is associated with

  2. [Graft-versus-host disease as the cause of symptoms mimicking Sjögren's syndrome].

    PubMed

    Tuchocka-Piotrowska, Aleksandra; Puszczewicz, Mariusz; Kołczewska, Aleksandra; Majewski, Dominik

    2006-01-01

    A case of chronic graft-versus-host disease (chronic GvHD) mimicking symptoms associated with idiopathic Sjögren's syndrome is presented. Hypotheses on the pathophysiological origin of clinical syndromes associated with graft-versus-host disease are discussed.

  3. Host gene-microbiome interactions: molecular mechanisms in inflammatory bowel disease.

    PubMed

    Chu, Hiutung

    2017-07-24

    Recent studies have identified links between host genetic variants and microbial recognition of the microbiome. Defects in host-microbiome interactions in individuals harboring inflammatory bowel disease risk alleles may result in imbalances of the microbial community, impaired pathogen clearance, and failure to sense beneficial commensal microbes. These findings highlight the importance of maintaining bi-directional communication at the mucosal interface during intestinal homeostasis.

  4. Emicizumab Prophylaxis in Hemophilia A with Inhibitors.

    PubMed

    Oldenburg, Johannes; Mahlangu, Johnny N; Kim, Benjamin; Schmitt, Christophe; Callaghan, Michael U; Young, Guy; Santagostino, Elena; Kruse-Jarres, Rebecca; Negrier, Claude; Kessler, Craig; Valente, Nancy; Asikanius, Elina; Levy, Gallia G; Windyga, Jerzy; Shima, Midori

    2017-08-31

    Emicizumab (ACE910) bridges activated factor IX and factor X to restore the function of activated factor VIII, which is deficient in persons with hemophilia A. This phase 3, multicenter trial assessed once-weekly subcutaneous emicizumab prophylaxis in persons with hemophilia A with factor VIII inhibitors. We enrolled participants who were 12 years of age or older. Those who had previously received episodic treatment with bypassing agents were randomly assigned in a 2:1 ratio to emicizumab prophylaxis (group A) or no prophylaxis (group B). The primary end point was the difference in bleeding rates between group A and group B. Participants who had previously received prophylactic treatment with bypassing agents received emicizumab prophylaxis in group C. A total of 109 male participants with hemophilia A with inhibitors were enrolled. The annualized bleeding rate was 2.9 events (95% confidence interval [CI], 1.7 to 5.0) among participants who were randomly assigned to emicizumab prophylaxis (group A, 35 participants) versus 23.3 events (95% CI, 12.3 to 43.9) among those assigned to no prophylaxis (group B, 18 participants), representing a significant difference of 87% in favor of emicizumab prophylaxis (P<0.001). A total of 22 participants in group A (63%) had zero bleeding events, as compared with 1 participant (6%) in group B. Among 24 participants in group C who had participated in a noninterventional study, emicizumab prophylaxis resulted in a bleeding rate that was significantly lower by 79% than the rate with previous bypassing-agent prophylaxis (P<0.001). Overall, 198 adverse events were reported in 103 participants receiving emicizumab prophylaxis; the most frequent events were injection-site reactions (in 15% of participants). Thrombotic microangiopathy and thrombosis were reported in 2 participants each (in the primary analysis) who had received multiple infusions of activated prothrombin complex concentrate for breakthrough bleeding. No antidrug antibodies

  5. Unravelling adherence to prophylaxis in haemophilia: a patients' perspective.

    PubMed

    Schrijvers, L H; Kars, M C; Beijlevelt-van der Zande, M; Peters, M; Schuurmans, M J; Fischer, K

    2015-09-01

    Given the lifelong therapy in haemophilia patients, insight in non-adherence behaviour from a patient perspective is important to understand patients' difficulties with the following treatment recommendations. The aim of this study was to clarify the process underlying adherence (behaviour) to prophylactic treatment, from a patients' perspective. To develop a grounded theory, a qualitative study using individual in-depth interviews was performed to understand experiences, perceptions and beliefs concerning adherence to prophylaxis. From two Dutch treatment centres, 21 adults with haemophilia using prophylaxis were interviewed. Patients were asked how they experience their task to administer prophylaxis and how they adhere to this. The interviews were transcribed, coded and analysed in an iterative process, leading to the development of the grounded theory. Adherence was determined by the position of prophylaxis in life. The position of prophylaxis was determined by the perception of prophylaxis and the ability to exert prophylaxis. Patients' perception was influenced by two main factors: acceptance of haemophilia and feeling/fearing symptoms. The ability to exert prophylaxis was influenced by understanding haemophilia and prophylaxis and planning/infusion skills. The combination of different perceptions and skills led to four main positions of prophylaxis in life: (i) prophylaxis integrated in life, (ii) prophylaxis according to doctors' advice, struggling with irregular situations, (iii) prophylaxis is too much to handle, (iv) prophylaxis is a confrontation with illness. The adherence level gradually decreased from position 1 to 4. This information can be used to design tailored interventions to promote adherence. © 2015 John Wiley & Sons Ltd.

  6. Climbing therapy under PK-tailored prophylaxis.

    PubMed

    Stemberger, M; Schmit, E; Czepa, D; Kurnik, K; Spannagl, M

    2014-01-01

    Climbing has a low risk of injury and strengthens the entire musculature. Due to its benefits in physical and mental health as well as its high fun factor climbing is an established way of therapy. So far, the usefulness of climbing therapy has not been shown for people with haemophilia (PWH). A crucial requirement for physical activity in PWH is regular prophylaxis. As the patient's individual pharmacokinetic (PK) response varies significantly, PK-tailored prophylaxis may decrease bleeding frequency. We describe a man (age 25 years) with severe haemophilia A who took part in an 8.5-month weekly climbing program under PK-tailored prophylaxis. Bleeding frequency, factor consumption, joint health (Haemophilia Joint Health Score, HJHS), quality of life (Haemo-QoL-A) and climbing performance (UIAA scale) were assessed before and after the training. Prior to the study, the patient was on demand treatment. The patient was started on standard prophylaxis for a 2 months period and then observed for 6.5 months under PK-tailored prophylaxis. PK-tailored prophylaxis was targeted to a trough level of 1-3%. For high-impact activities a factor activity >15%, for low-impact activities a factor activity >5% was suggested. Climbing therapy was safe. The bleeding rate decreased from 14 (2012) to 1 (during the study period of 8.5 months). The one bleeding event was due to a missed infusion and was not triggered by physical activity. The elimination half-life using Bayesian statistics was determined to be 16h. Using this half-life for PK-tailored prophylaxis reduced the factor VIII consumption in comparison to standard prophylaxis. Joint health was particularly improved in the categories range of motion and swelling. Quality of life scores stayed at a high level. Climbing performance improved by 1 grade. The combination of PK-tailored prophylaxis with therapeutic climbing improved clinical outcome in this young adult with severe haemophilia. The tailored concept for high- and low

  7. Significance of Ethnicity in the Risk of Acute Graft-versus-Host Disease and Leukemia Relapse after Unrelated Donor Hematopoietic Stem Cell Transplantation

    PubMed Central

    Morishima, Yasuo; Kawase, Takakazu; Malkki, Mari; Morishima, Satoko; Spellman, Stephen; Kashiwase, Koichi; Kato, Shunichi; Cesbron, Anne; Tiercy, Jean-Marie; Senitzer, David; Velardi, Andrea; Petersdorf, Effie W.

    2014-01-01

    The significance of patient and donor ethnicity on risk of acute graft-versus-host disease (GVHD) and disease relapse after unrelated donor hematopoietic cell transplantation (HCT) is not known. A total of 4335 patient/donor pairs from the International Histocompatibility Working Group in HCT met the following three criteria: (1) HLA-A, B, C, DRB1 and DQB1 allele matched donor; (2) diagnosis of leukemia, and (3) non-T cell depleted GVHD prophylaxis. Post-transplant risks of acute GVHD and leukemia relapse were defined in Asian/Pacific Islander, Caucasian, African American, Hispanic, and Native American patients transplanted from donors with the same self-described background. Asian patients had a significantly lower incidence of acute GVHD (Japanese patients: 40.0% grades II-IV and 15.3% grades III-IV; non-Japanese Asian patients: 42.1% grades II-IV and 15.7% grades III-IV) compared to Caucasian patients (56.5% grades II-IV and 22.6% grades III-IV) (p< 0.001). The hazard ratio (HR) of acute GVHD for Caucasian patients was significantly higher than for Japanese patients. Unexpectedly, the HR of leukemia relapse in Caucasian patients with early disease status was also significantly higher than that in Japanese patients. These results provide a platform for future investigation into the genetic factors for unrelated donor HCT and clinical implications of diverse ethnic background. PMID:23747601

  8. [Vaccinations and malaria prophylaxis for international travelers].

    PubMed

    Alberer, Martin; Löscher, Thomas

    2015-05-01

    The prevention of infectious diseases by vaccination and by counselling about malaria prophylaxis is a central aspect of travel medicine. Besides mandatory vaccinations required for entry to certain countries various vaccinations may be indicated depending on destination and type of travel as well as on individual risks of the traveler. In addition, pre-travel counselling should always include a check-up of standard vaccinations. Protection against mosquito bites is the basis of malaria prophylaxis. The addition of chemoprophylaxis is warranted in high risk areas. When regular chemoprophylaxis is not applied it is recommended to carry an appropriate antimalarial drug which can be used for emergency stand-by treatment in case of unexplained fever and when medical attention is not available within 24 hours. Travelers should realize that self-treatment is a first-aid measure and that they should still seek medical advice as soon as possible. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact

    PubMed Central

    Oh, Ding Yuan; Lowther, Sue; McCaw, James M.; Sullivan, Sheena G.; Leang, Sook-Kwan; Haining, Jessica; Arkinstall, Rachel; Kelso, Anne; Mcvernon, Jodie; Barr, Ian G.; Middleton, Deborah; Hurt, Aeron C.

    2014-01-01

    Objectives The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting. Methods A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets. Results Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis. Conclusions Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans. PMID:24840623

  10. Host-Derived CD70 Suppresses Murine Graft-versus-Host Disease by Limiting Donor T Cell Expansion and Effector Function.

    PubMed

    Leigh, Nicholas D; O'Neill, Rachel E; Du, Wei; Chen, Chuan; Qiu, Jingxin; Ashwell, Jonathan D; McCarthy, Philip L; Chen, George L; Cao, Xuefang

    2017-07-01

    Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models. However, the role of this pathway in allo-HCT is previously unknown. In this study, we have examined its contribution in GVHD pathogenesis. Surprisingly, Ab blockade of CD70 after allo-HCT significantly increases GVHD. Interestingly, whereas donor T cell- or bone marrow-derived CD70 plays no role in GVHD, host-derived CD70 inhibits GVHD as CD70 -/- hosts show significantly increased GVHD. This is evidenced by reduced survival, more severe weight loss, and increased histopathologic damage compared with wild-type hosts. In addition, CD70 -/- hosts have higher levels of proinflammatory cytokines TNF-α, IFN-γ, IL-2, and IL-17. Moreover, accumulation of donor CD4 + and CD8 + effector T cells is increased in CD70 -/- versus wild-type hosts. Mechanistic analyses suggest that CD70 expressed by host hematopoietic cells is involved in the control of alloreactive T cell apoptosis and expansion. Together, our findings demonstrate that host CD70 serves as a unique negative regulator of allogeneic T cell response by contributing to donor T cell apoptosis and inhibiting expansion of donor effector T cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  11. The thermal mismatch hypothesis explains host susceptibility to an emerging infectious disease.

    PubMed

    Cohen, Jeremy M; Venesky, Matthew D; Sauer, Erin L; Civitello, David J; McMahon, Taegan A; Roznik, Elizabeth A; Rohr, Jason R

    2017-02-01

    Parasites typically have broader thermal limits than hosts, so large performance gaps between pathogens and their cold- and warm-adapted hosts should occur at relatively warm and cold temperatures, respectively. We tested this thermal mismatch hypothesis by quantifying the temperature-dependent susceptibility of cold- and warm-adapted amphibian species to the fungal pathogen Batrachochytrium dendrobatidis (Bd) using laboratory experiments and field prevalence estimates from 15 410 individuals in 598 populations. In both the laboratory and field, we found that the greatest susceptibility of cold- and warm-adapted hosts occurred at relatively warm and cool temperatures, respectively, providing support for the thermal mismatch hypothesis. Our results suggest that as climate change shifts hosts away from their optimal temperatures, the probability of increased host susceptibility to infectious disease might increase, but the effect will depend on the host species and the direction of the climate shift. Our findings help explain the tremendous variation in species responses to Bd across climates and spatial, temporal and species-level variation in disease outbreaks associated with extreme weather events that are becoming more common with climate change. © 2017 John Wiley & Sons Ltd/CNRS.

  12. The effects of host diversity on vector-borne disease: the conditions under which diversity will amplify or dilute the disease risk.

    PubMed

    Miller, Ezer; Huppert, Amit

    2013-01-01

    Multihost vector-borne infectious diseases form a significant fraction of the global infectious disease burden. In this study we explore the relationship between host diversity, vector behavior, and disease risk. To this end, we have developed a new dynamic model which includes two distinct host species and one vector species with variable preferences. With the aid of the model we were able to compute the basic reproductive rate, R 0, a well-established measure of disease risk that serves as a threshold parameter for disease outbreak. The model analysis reveals that the system has two different qualitative behaviors: (i) the well-known dilution effect, where the maximal R0 is obtained in a community which consists a single host (ii) a new amplification effect, denoted by us as diversity amplification, where the maximal R0 is attained in a community which consists both hosts. The model analysis extends on previous results by underlining the mechanism of both, diversity amplification and the dilution, and specifies the exact conditions for their occurrence. We have found that diversity amplification occurs where the vector prefers the host with the highest transmission ability, and dilution is obtained when the vector does not show any preference, or it prefers to bite the host with the lower transmission ability. The mechanisms of dilution and diversity amplification are able to account for the different and contradictory patterns often observed in nature (i.e., in some cases disease risk is increased while in other is decreased when the diversity is increased). Implication of the diversity amplification mechanism also challenges current premises about the interaction between biodiversity, climate change, and disease risk and calls for retrospective thinking in planning intervention policies aimed at protecting the preferred host species.

  13. [The role of the vaccine prophylaxis of cervical cancer among female military personnel].

    PubMed

    Shmidt, A A; Alieva, M T; Ivanova, L V; Molchanov, O V

    2015-06-01

    The authors presented results of the study concerning human papillomavirus infecting of military students of higher military educational institutions of the Ministry of Defence of the Russian Federation. In the Center for Obstetrics and Gynaecology of the Kirov Military-Medical Academy was performed a dynamic examination of 478 female cadets aged 17-25. The high level of high-risk HPV viruses was revealed during the examination what proves the necessity of prophylaxis enhancing with the aim to prevent gynecological diseases and reproductive health promotion. The main ways of cervical cancer prophylaxis are health education, in-depth medical examination of women with the aim to reveal and treat gynecological diseases (this medical examination should be carried out twice a year), primary prevention of cervical cancer by vaccination.

  14. CMV Infection in Bone Marrow and Solid Organ Transplant Patients in the Era of Antiviral Prophylaxis.

    PubMed

    Hebart, Holger; Jahn, Gerhard; Sinzger, Christian; Kanz, Lothar; Einsele, Hermann

    2000-02-01

    Recent developments in the diagnosis and therapy of cytomegalovirus (CMV) infection have helped to reduce CMV-associated morbidity and mortality following allogeneic bone marrow and solid organ transplantation. The clinical symptoms of active CMV infection and the prevalence of life-threatening CMV disease vary widely between different patient populations according to the type of transplant and the intensity of immunosuppression employed. Antiviral prophylaxis with aciclovir, valaciclovir and ganciclovir has been shown to reduce CMV infection and disease following organ transplantation. Antiviral drugs, in particular ganciclovir and foscarnet, have varying sideeffects, however, and antiviral resistance due to prolonged administration of ganciclovir and foscarnet has been reported recently. Short courses of pre-emptive antiviral therapy for documented CMV infection help to reduce the duration and sideeffects of therapy, offering an alternative strategy to antiviral prophylaxis. Studies are required to compare the efficacy and costs of antiviral prophylaxis with pre-emptive therapy.

  15. [Scar prophylaxis and treatment].

    PubMed

    Hammer-Hansen, Niels; Damsgaard, Tine Engberg; Rødgaard, Jes Christian

    2015-10-12

    Scarring is an expected result of trauma to the skin. Scars are a heterogenic group varying from small white non elevated scars to hypertrophic scars and keloids. Many different algorithms for scar prophylaxis and treatment have been presented in the literature. We discuss different types of scar formation and recently published evidence-based guidelines in regards to prophylaxis and treatment of scars written by 24 experts on scar management.

  16. Enterotoxigenic Escherichia coli strains are highly prevalent in Ugandan piggeries but disease outbreaks are masked by antibiotic prophylaxis.

    PubMed

    Okello, Emmanuel; Moonens, Kristof; Erume, Joseph; De Greve, Henri

    2015-01-01

    Post-weaning diarrhea (PWD) caused by enterotoxigenic Escherichia coli (ETEC) is an important disease of newly weaned piglets. ETEC strains commonly express F4 and/or F18 fimbriae that attach to carbohydrate receptors present on the intestinal epithelium during colonization. The disease status in the Ugandan piggeries had previously not been studied. In this cross-sectional sero-survey and clinical outbreak monitoring, we found very high sero-prevalence levels of both anti-F4 (70.5%) and anti-F18 (73.7%) antibodies, despite limited cases of clinical outbreaks. Strains isolated from these cases were typically F18(+) ETEC. High antibiotic resistance and multi-drug resistance were characteristics of the isolates, with highest resistance level of over 95% to commonly used antibiotics such as penicillin and tetracycline. We conclude that ETEC infections are widely spread on farms in Central Uganda but clinical disease outbreaks were masked by the management practices on these farms, like the use of extensive antibiotic prophylaxis.

  17. Current Practice Trends for Use of Early Venous Thromboembolism Prophylaxis After Intracerebral Hemorrhage.

    PubMed

    Cherian, Laurel J; Smith, Eric E; Schwamm, Lee H; Fonarow, Gregg C; Schulte, Phillip J; Xian, Ying; Wu, Jingjing; Prabhakaran, Shyam K

    2018-01-01

    Venous thromboembolism (VTE) is common after intracerebral hemorrhage (ICH). Guidelines recommend early VTE prophylaxis. To determine characteristics associated with early chemoprophylaxis (CP) after ICH in the Get With The Guidelines-Stroke registry. In this observational cohort study, we identified patients with ICH between January 1, 2009 and September 30, 2013, who (1) were non-ambulatory and/or not comfort care measures by hospital day 2; (2) were not transferred to another acute care facility; and (3) had known VTE prophylaxis status at end of hospital day 2. Categories for VTE prophylaxis were as follows: (1) mechanical non-CP or (2) CP with or without mechanical prophylaxis. Early prophylaxis was defined as occurring by hospital day 2. Using multivariable logistic regression, we assessed patient, hospital, and geographic factors independently associated with early CP use. Among 74 283 patients with ICH from 1358 hospitals, 5929 (7.9%) received early CP, 66 444 (89.4%) received early mechanical/non-CP, and 1910 (2.6%) had no prophylaxis, mechanical or CP, within the first 2 days. There was no increase in early CP use over the study period; 60% of hospitals provided early CP to <9% of patients. In multivariable analysis, female sex, atrial fibrillation, diabetes, coronary, carotid, and peripheral artery disease, prior ischemic stroke or transient ischemic attack, hospital size >500 beds, and geographic region were independently associated with early vs no early CP use. Nationwide, the large majority of ICH patients receive early mechanical VTE prophylaxis only, without CP. Patient comorbidities and hospital characteristics such as geographic location are determinants of higher use of early CP. Copyright © 2017 by the Congress of Neurological Surgeons

  18. Linking spring phenology with mechanistic models of host movement to predict disease transmission risk

    USGS Publications Warehouse

    Merkle, Jerod A.; Cross, Paul C.; Scurlock, Brandon M.; Cole, Eric K.; Courtemanch, Alyson B.; Dewey, Sarah R.; Kauffman, Matthew J.

    2018-01-01

    Disease models typically focus on temporal dynamics of infection, while often neglecting environmental processes that determine host movement. In many systems, however, temporal disease dynamics may be slow compared to the scale at which environmental conditions alter host space-use and accelerate disease transmission.Using a mechanistic movement modelling approach, we made space-use predictions of a mobile host (elk [Cervus Canadensis] carrying the bacterial disease brucellosis) under environmental conditions that change daily and annually (e.g., plant phenology, snow depth), and we used these predictions to infer how spring phenology influences the risk of brucellosis transmission from elk (through aborted foetuses) to livestock in the Greater Yellowstone Ecosystem.Using data from 288 female elk monitored with GPS collars, we fit step selection functions (SSFs) during the spring abortion season and then implemented a master equation approach to translate SSFs into predictions of daily elk distribution for five plausible winter weather scenarios (from a heavy snow, to an extreme winter drought year). We predicted abortion events by combining elk distributions with empirical estimates of daily abortion rates, spatially varying elk seroprevelance and elk population counts.Our results reveal strong spatial variation in disease transmission risk at daily and annual scales that is strongly governed by variation in host movement in response to spring phenology. For example, in comparison with an average snow year, years with early snowmelt are predicted to have 64% of the abortions occurring on feedgrounds shift to occurring on mainly public lands, and to a lesser extent on private lands.Synthesis and applications. Linking mechanistic models of host movement with disease dynamics leads to a novel bridge between movement and disease ecology. Our analysis framework offers new avenues for predicting disease spread, while providing managers tools to proactively mitigate

  19. Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. The Antibiotic Prophylaxis Study Group.

    PubMed

    Silver, A; Eichorn, A; Kral, J; Pickett, G; Barie, P; Pryor, V; Dearie, M B

    1996-06-01

    Twenty-five percent of all nosocomial infections are wound infections. Professional guidelines support the timely use of preoperative prophylaxis for prevention of postoperative wound infections. Barriers exist in implementing this practice. IPRO, the New York State peer review organization, as part of the Health Care Financing Administration's Health Care Quality Improvement Program, sought to determine the proportion of patients receiving timely antibiotic prophylaxis for aortic grafts, hip replacements and colon resections in 44 hospitals in New York State. IPRO conducted a retrospective medical record review of 44 hospitals through out New York State stratified for teaching, nonteaching status. A sample was drawn of 2651 patients, 2256 from Medicare and 395 from Medicaid, undergoing either abdominal aortic aneurysm repair, partial or total hip replacement or large bowel resection. The study determined the proportion of patients who had documentation of receiving antibiotics and those who received antibiotics timely, that is less than or equal to 2 hours preoperatively. Eighty-six percent of patients had documentation of receiving an antibiotic. Forty-six percent of aneurysm repairs and 60% of hip replacements had evidence of receiving timely antibiotic prophylaxis, that is within 2 hours prior to surgery. For colon resections, 73% of cases had either oral prophylaxis or timely parenteral therapy. An increased proportion of patients had received parenteral antibiotics prematurely as the surgical start time occurred later in the day. A total of 44 different antibiotics were recorded for prophylaxis. Antibiotic prophylaxis was performed in 81% to 94% of cases, however, anywhere from 27% to 54% of all cases did not receive antibiotics in a timely fashion. By delegating implementation of ordered antibiotic prophylaxis to the anesthesia team, timing may be improved and the incidence of postoperative wound infections may decrease.

  20. A Review of Ocular Graft-Versus-Host Disease.

    PubMed

    Munir, Saleha Z; Aylward, James

    2017-05-01

    : Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic hematopoietic stem cell transplantation, which is a potential curative therapy used in a variety of malignant or benign hematological diseases. Graft-versus-host disease primarily occurs in many organs, but most notably in the skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal system. Ocular manifestations of GVHD may precede other systemic GVHD findings, and it may be a poor prognosis for mortality. While all parts of the eye may be affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or keratoconjunctivitis sicca is the most common presenting manifestation of chronic ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability. Depending on the severity of ocular involvement and response to treatment, ocular GVHD may cause decreased quality of life. Management of GVHD begins with prevention by understanding risk factors and by implementing prophylactic treatment after allogeneic hematopoietic stem cell transplantation. A multidisciplinary approach to the prevention and treatment of GVHD is important, and there are currently no preventive therapies available for ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular surface lubrication and support, tear film stabilization, inflammation reduction, and surgical intervention. The goal of this review is to define ocular GVHD and its categorical manifestations, as well as to describe the importance of comprehensive assessment, diagnosis, and ophthalmologic treatment and management of ocular GVHD with a multidisciplinary approach.

  1. Rationale for a randomized controlled trial comparing two prophylaxis regimens in adults with severe hemophilia A: the Hemophilia Adult Prophylaxis Trial

    PubMed Central

    Ragni, Margaret V

    2011-01-01

    A major goal of comprehensive hemophilia care is to prevent occurrence of bleeds by prophylaxis or regular preventive factor, one or more times weekly. Although prophylaxis is effective in reducing bleeding and joint damage in children, whether it is necessary to continue into adulthood is not known. The purpose of this article is to describe a Phase III randomized controlled trial to evaluate prophylaxis comparing two dose regimens in adults with severe hemophilia A. I hypothesize that adults with mature cartilage and joints are less susceptible to joint bleeds and joint damage, and that once-weekly recombinant factor VIII prophylaxis, with up to two rescue doses per week, is as effective as thrice-weekly prophylaxis in reducing bleeding frequency, but less costly and more acceptable, with higher quality of life. The ultimate goal of this project is to determine whether once-weekly prophylaxis is any worse than thrice-weekly prophylaxis in reducing joint bleeding frequency, while potentially utilizing less factor, at lower cost, leading to a better quality of life. This is an innovative concept, as it challenges the current paradigm of thrice-weekly prophylaxis in adults, which is based on dosing in children. Furthermore, this trial will assess interdose thrombin generation, a novel tissue factor-based assay of hemostasis, to determine if individualized thrombin generation can predict more individualized prophylaxis dosing, which would be practice changing. PMID:21939418

  2. Host genetics of Epstein–Barr virus infection, latency and disease

    PubMed Central

    Houldcroft, Charlotte J; Kellam, Paul

    2015-01-01

    Epstein–Barr virus (EBV) infects 95% of the adult population and is the cause of infectious mononucleosis. It is also associated with 1% of cancers worldwide, such as nasopharyngeal carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma. Human and cancer genetic studies are now major forces determining gene variants associated with many cancers, including nasopharyngeal carcinoma and Hodgkin's lymphoma. Host genetics is also important in infectious disease; however, there have been no large-scale efforts towards understanding the contribution that human genetic variation plays in primary EBV infection and latency. This review covers 25 years of studies into host genetic susceptibility to EBV infection and disease, from candidate gene studies, to the first genome-wide association study of EBV antibody response, and an EBV-status stratified genome-wide association study of Hodgkin's lymphoma. Although many genes are implicated in EBV-related disease, studies are often small, not replicated or followed up in a different disease. Larger, appropriately powered genomic studies to understand the host response to EBV will be needed to move our understanding of the biology of EBV infection beyond the handful of genes currently identified. Fifty years since the discovery of EBV and its identification as a human oncogenic virus, a glimpse of the future is shown by the first whole-genome and whole-exome studies, revealing new human genes at the heart of the host–EBV interaction. © 2014 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:25430668

  3. Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact.

    PubMed

    Oh, Ding Yuan; Lowther, Sue; McCaw, James M; Sullivan, Sheena G; Leang, Sook-Kwan; Haining, Jessica; Arkinstall, Rachel; Kelso, Anne; Mcvernon, Jodie; Barr, Ian G; Middleton, Deborah; Hurt, Aeron C

    2014-09-01

    The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting. A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets. Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis. Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  4. Efficacy of palivizumab prophylaxis on the frequency of RSV-associated lower respiratory tract infections in preterm infants: determination of the ideal target population for prophylaxis.

    PubMed

    Cetinkaya, M; Oral, T K; Karatekin, S; Cebeci, B; Babayigit, A; Yesil, Y

    2017-09-01

    Respiratory syncytial virus (RSV) prophylaxis in high-risk infants is an effective intervention for the prevention of severe disease. The aim of this study was to determine the ideal target preterm population that might benefit from palivizumab prophylaxis by establishing the main risk factors for acute RSV-related infections. Former premature infants born with a gestational age ≤37 weeks and ≤1 year of age at the beginning of the RSV season and admitted with respiratory infection were included. RSV status was evaluated by RSV strip test in all infants. RSV-positive and -negative infants were compared in terms of demographic features, risk factors, requirement of hospitalisation and palivizumab administration. A total of 202 preterm infants under 1 year of age were enrolled. The RSV test was positive in 34 (16.8%) infants. Maternal age was significantly lower in RSV-positive infants compared with RSV-negative infants (p = 0.03). RSV-positive infants were found to be significantly discharged during the RSV season (p = 0.03). RSV-positive infants required significantly higher rates of hospitalisation and need for mechanical ventilation. Of the RSV-positive infants, 28 (82%) had a gestational age ≥29 weeks. Seventeen (77%) RSV-positive infants that required hospitalisation were ≥29 weeks of gestation. All infants with a gestational age ≥29 weeks and without palivizumab prophylaxis developed RSV infection. Palivizumab prophylaxis should be implemented into guidelines to cover preterm infants with a gestational age >29 weeks. Palivizumab prophylaxis should also be considered in high-risk infants ≤6 months of age during the RSV season.

  5. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis

    PubMed Central

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-01-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of > 50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with > 99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. From the Clinical Editor Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. PMID:25791815

  6. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.

    PubMed

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-07-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Human Gut Microbiota: Toward an Ecology of Disease

    PubMed Central

    Selber-Hnatiw, Susannah; Rukundo, Belise; Ahmadi, Masoumeh; Akoubi, Hayfa; Al-Bizri, Hend; Aliu, Adelekan F.; Ambeaghen, Tanyi U.; Avetisyan, Lilit; Bahar, Irmak; Baird, Alexandra; Begum, Fatema; Ben Soussan, Hélène; Blondeau-Éthier, Virginie; Bordaries, Roxane; Bramwell, Helene; Briggs, Alicia; Bui, Richard; Carnevale, Matthew; Chancharoen, Marisa; Chevassus, Talia; Choi, Jin H.; Coulombe, Karyne; Couvrette, Florence; D'Abreau, Samantha; Davies, Meghan; Desbiens, Marie-Pier; Di Maulo, Tamara; Di Paolo, Sean-Anthony; Do Ponte, Sabrina; dos Santos Ribeiro, Priscyla; Dubuc-Kanary, Laure-Anne; Duncan, Paola K.; Dupuis, Frédérique; El-Nounou, Sara; Eyangos, Christina N.; Ferguson, Natasha K.; Flores-Chinchilla, Nancy R.; Fotakis, Tanya; Gado Oumarou H D, Mariam; Georgiev, Metodi; Ghiassy, Seyedehnazanin; Glibetic, Natalija; Grégoire Bouchard, Julien; Hassan, Tazkia; Huseen, Iman; Ibuna Quilatan, Marlon-Francis; Iozzo, Tania; Islam, Safina; Jaunky, Dilan B.; Jeyasegaram, Aniththa; Johnston, Marc-André; Kahler, Matthew R.; Kaler, Kiranpreet; Kamani, Cedric; Karimian Rad, Hessam; Konidis, Elisavet; Konieczny, Filip; Kurianowicz, Sandra; Lamothe, Philippe; Legros, Karina; Leroux, Sebastien; Li, Jun; Lozano Rodriguez, Monica E.; Luponio-Yoffe, Sean; Maalouf, Yara; Mantha, Jessica; McCormick, Melissa; Mondragon, Pamela; Narayana, Thivaedee; Neretin, Elizaveta; Nguyen, Thi T. T.; Niu, Ian; Nkemazem, Romeo B.; O'Donovan, Martin; Oueis, Matthew; Paquette, Stevens; Patel, Nehal; Pecsi, Emily; Peters, Jackie; Pettorelli, Annie; Poirier, Cassandra; Pompa, Victoria R.; Rajen, Harshvardhan; Ralph, Reginald-Olivier; Rosales-Vasquez, Josué; Rubinshtein, Daria; Sakr, Surya; Sebai, Mohammad S.; Serravalle, Lisa; Sidibe, Fily; Sinnathurai, Ahnjana; Soho, Dominique; Sundarakrishnan, Adithi; Svistkova, Veronika; Ugbeye, Tsolaye E.; Vasconcelos, Megan S.; Vincelli, Michael; Voitovich, Olga; Vrabel, Pamela; Wang, Lu; Wasfi, Maryse; Zha, Cong Y.; Gamberi, Chiara

    2017-01-01

    Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

  8. [EFFECTIVENESS OF PREVENTIVE VACCINE PROPHYLAXIS OF CHICKEN POX IN MILITARY COLLECTIVES].

    PubMed

    Dubodelov, D V; Rybin, V V; Rikhter, V V; Yaroslavtsev, V V; Gritsik, A A; Kazanova, A S; Lavrov, V F; Semenenko, T A; Kuzin, S N

    2015-01-01

    Study the effectiveness of preventive vaccine prophylaxis of chicken pox in military collectives. In the focus of chicken pox, 200 servicemen of the new addition by conscription were immunized once against chicken pox; 97 servicemen by conscription of the new addition (comparison group) were not vaccinated. Epidemiologic and immunologic effectiveness of conduction of preventive vaccine prophylaxis in chicken pox focus were studied. In the group of 200 soldiers, that were present in the focus of infection and were immunized once against chicken pox, only 2 cases of this disease were registered (10 per thousand). In the comparison group, that consisted of 97 unvaccinated servicemen, chicken pox disease was registered in 7 individuals (72 per thousand). Epidemiologic effectiveness of preventive vaccine prophylaxis of chicken pox amounted to 86%. Immunologic effectiveness of vaccination 2-3 weeks after the immunization was 42%, and 2 months after--44%. Local reactions in the form of hyperemia (up to 1.5 cm) and edema were noted in 10% of the vaccinated at the location of preparation administration; in 1.7%--general reaction in the form of temperature increase to 37.8°C was observed. Post-vaccinal complications in the immunized group were not detected. Preventive vaccination of servicemen allows to minimize the spread of chicken pox, however can not serve as means of complete elimination of the infection from military collectives.

  9. Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

    PubMed

    Sanna, M; Caocci, G; Orrù, F; Ledda, A; Vacca, A; Piras, E; Fozza, C; Deias, P; Tidore, G; Dore, F; La Nasa, G

    2017-12-01

    Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia. We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses. Of these, 59 patients were with G6PD-. All patients underwent fluoroquinolone prophylaxis and were transfused according to our single-unit transfusion policy. The principal endpoint was the incidence of acute haemolytic anaemia. Secondary endpoints included the incidence of febrile neutropenia, microbiologically and clinically documented infection (MDI and CDI) and the incidence of Gram-positive or Gram-negative infections. No episode of acute haemolytic anaemia was observed in the entire cohort. The incidence of MDI and CDI was similar, but the incidence of invasive fungal disease (IFD; P<.0001, HR 11.4, 95%CI 3.5-37.05) and Candida sepsis (P=.008, HR 37, 95%CI 2.01-680.9) was higher in patients with G6PD-. Interestingly, we observed a reduced incidence of febrile neutropenia in patients with G6PD- (P=.01, HR 0.46, 95%CI 0.25-0.8). Our data suggest that fluoroquinolone prophylaxis in patients with G6PD-, treated with intensive chemotherapy, is feasible and safe. Our findings on the incidence of IFD and febrile neutropenia suggest that G6PD may be important in susceptibility to opportunistic pathogens and host response in neutropenic patients. © 2017 John Wiley & Sons Ltd.

  10. Vulvovaginal Graft-Versus-Host Disease.

    PubMed

    Kornik, Rachel I; Rustagi, Alison S

    2017-09-01

    Vulvovaginal chronic graft-versus-host disease (cGVHD) is an underrecognized complication of stem cell transplantation. Early recognition may prevent severe sequelae. Genital involvement is associated with oral, ocular, and skin manifestations. Treatment includes topical immunosuppression, dilator use, and adjuvant topical estrogen. Clinical and histologic features may mimic other inflammatory vulvar conditions. In the right clinical context, these findings are diagnostic of chronic GVHD. Female recipients of allo-hematopoietic stem cell transplantation (HCT) are at higher risk of condylomas, cervical dysplasia, and neoplasia. The National Institutes of Health publishes guidelines for the diagnosis, grading, management, and supportive care for HCT patients by organ system. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A retrospective study of antibiotic prophylaxis value in surgical treatment of lower limb fracture.

    PubMed

    Bandalović, Ante; Zindović, Antonija; Boschi, Vladimir; Bakota, Bore; Marinović, Marin; Čoklo, Miran; Rošin, Matko; Parać, Zlatko; Čukelj, Fabijan

    2015-11-01

    Surgical site infections (SSI) are nosocomial infections that cause considerable problems in orthopaedic surgery. Antibiotic prophylaxis can be used to reduce the risk for SSI. There is no universal antibiotic that can be recommended for prophylaxis in terms of coverage of all possible pathogens because of antibiotic resistance, and there are no universal recommendations for different types of patients in terms of injury type, selected operation and risk factors for development of SSI. The aim of this study was to analyse the effectiveness of antibiotic prophylaxis in surgical treatment (ORIF) of closed lower limb fractures in young, healthy patients. Patient details were collected from the patient histories. Inclusion criteria for participants were age 20-30 years, not suffering from any type of chronic disease or state that may affect postoperative infection and ISS≤9. Antibiotic prophylaxis use and outcome (SSI) were compared between two groups of patients. Data were analysed using descriptive statistics, Fisher's exact test and t-test for proportions. A total of 347 patients with closed lower limb fractures treated with ORIF met the inclusion criteria. There were 290 male and 57 female patients, with an average age of 24.47 years. Prophylactic antibiotics were given to 242 patients (69.74%); 2g ceftriaxone was administered to 88.02% of the patients who received antibiotic prophylaxis. Ten patients developed postoperative infection (eight out of 242 with antibiotic prophylaxis and two out of 105 without antibiotic prophylaxis). The difference between the two groups was not statistically significant (Fisher's exact test, P=0.749). Antibiotic prophylaxis was ineffective in preventing SSI in patients with no risk factors for SSI who were undergoing ORIF for closed lower limb fractures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Ebola virus disease: from epidemiology to prophylaxis.

    PubMed

    Liu, Wen Bin; Li, Zi Xiong; Du, Yan; Cao, Guang Wen

    2015-01-01

    The outbreak of Ebola virus disease (EVD) continues to spread through West Africa. Since the first report of EVD in March 2014, the number of cases has increased rapidly, with the fatality rate of >50%. The most prevalent Ebola virus belongs to the species of Zaire ebolavirus, with a fatality rate as high as 90%. Although there were cases introduced into other continents, Africa is the endemic area where fruit bats and apes are suspected to be Ebola virus carriers. The virus might be transmitted from the host animals to humans if humans consume raw or not fully cooked and contaminated meats. However, human-to-human transmission via close contact is the major route of current outbreaks. EVD can occur during any season and affect people of any race and age group. Direct contact with body fluids of EVD patients or living in contaminated environments greatly increases the risk of being infected. Transmission via aerosol less likely, but transmission via virus-containing droplets is possible in humans. Thus, health care providers are facing danger of getting Ebola virus infection. To date, vaccines, drugs and/or therapies to prevent Ebola virus infection or treat EVD are limited. Medical workers should follow the current standard prophylactic procedures. The military can orchestrate efficient care to mass EVD patients. Although it is necessary to speed up the pace of developing effective vaccine and therapeutics for the prevention and treatment of EVD, public health prevention and management should be important issue at present to control the spread of this disease cost-effectively.

  13. Antibiotics Prophylaxis for Operative Hysteroscopy.

    PubMed

    Muzii, Ludovico; Di Donato, Violante; Boni, Terenzio; Gaglione, Raffaele; Marana, Riccardo; Mazzon, Ivan; Imperiale, Ludovica; De Medici, Caterina; Ruggiero, Alfonso; Panici, Pierluigi Benedetti

    2017-04-01

    To evaluate the incidence of infectious complications and effect of prophylactic antibiotic administration during operative hysteroscopic procedures. A multicentric randomized controlled trial was conducted between January 2012 and December 2013. Women (n = 180) affected by endometrial hyperplasia, myomas, or endometrial polyps undergoing operative hysteroscopy were randomized to receive cefazolin 2 g intravenously 30 minutes prior to the procedure (n = 91) and no treatment (n = 89). No statistical difference in terms of postoperative fever (2.4% vs 2.3%, P = .99), endometritis (0% vs 0%), pain (6.0% vs 10.4%, P = .40), cervicitis-vaginitis (0% vs 0%), pelvic abscess (0% vs 0%), pelvic inflammatory disease (0% vs 0%), and bleeding (0% vs 0%) was noticed. No statistical difference in terms of side effects attributable to antibiotic prophylaxis such as allergy (0% vs 4.8%, P = .12), nausea (10.7% vs 17.4%, P = .27), vomiting (3.6% vs 4.6%, P = .99), diarrhea (4.8% vs 5.4%, P = .99), cephalea (9.5% vs 3.5%, P = .13), dizziness (4.8% vs 2.3%, P = .44), and meteorism (5.4% vs 3.4%, P = .99) was noticed. The results of the current study support the recommendation not to prescribe routine antibiotic prophylaxis prior to operative hysteroscopy.

  14. Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

    PubMed Central

    Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

    2012-01-01

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

  15. Sylvatic host associations of Triatominae and implications for Chagas disease reservoirs: a review and new host records based on archival specimens

    PubMed Central

    Weirauch, Christiane

    2017-01-01

    Background The 152 extant species of kissing bug include important vectors of the debilitating, chronic, and often fatal Chagas disease, which affects several million people mainly in Central and South America. An understanding of the natural hosts of this speciose group of blood-feeding insects has and will continue to aid ongoing efforts to impede the spread of Chagas disease. However, information on kissing bug biology is piecemeal and scattered, developed using methods with varying levels of accuracy over more than 100 years. Existing host records are heavily biased towards well-studied primary vector species and are derived from primarily three different types of observations, associational, immunological or DNA-based, with varying reliability. Methods We gather a comprehensive and unparalleled number of sources reporting host associations via rigorous targeted searches of publication databases to review all known natural, or sylvatic, host records including information on how each record was collected. We integrate this information with novel host records obtained via attempted amplification and sequencing of a ∼160 base pair (bp) region of the vertebrate 12S mitochondrial gene from the gastrointestinal tract of 64 archival specimens of Triatominae representing 19 species collected primarily in sylvatic habitats throughout the southern United States and Central and South America during the past 10 years. We show the utility of this method for uncovering novel and under-studied groups of Triatominae hosts, as well as detecting the presence of the Chagas disease pathogen via Polymerase Chain Reaction (PCR) of a ∼400 bp sequence of the trypanosome 18S gene. Results New host associations for several groups of arboreal mammals were determined including sloths, New World monkeys, coatis, arboreal porcupines and, for the first time as a host of any Triatominae, tayras. A thorough review of previously documented sylvatic hosts, organized by triatomine species and

  16. PrEP (Pre-Exposure Prophylaxis) 101

    MedlinePlus

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Pre-exposure prophylaxis (or PrEP) is when people at ... A Brief Intro Protect yourself. Learn about PrEP (Pre-Exposure Prophylaxis) and how it works in this ...

  17. Emerging fungal diseases: the importance of the host.

    PubMed

    Procop, Gary W; Roberts, Glenn D

    2004-09-01

    More yeasts and molds are now recognized to cause more human disease than ever before. This development is not due to a change in the virulence of these fungi, but rather to changes in the human host. These changes include immunosuppression secondary to the pandemic of HIV, the use of life-saving advances in chemotherapy and organ transplantation, and the use of corticosteroids and other immunosuppressive agents to treat a variety of diseases. Fungi that were once considered common saprophytes are now recognized as potential pathogens in these patients. This situation necessitates better communication than ever between the clinician, pathologist, and clinical mycologist to ensure the prompt and accurate determination of the cause of fungal diseases.

  18. Do Italian surgeons use antibiotic prophylaxis in thyroid surgery? Results from a national study (UEC--Italian Endocrine Surgery Units Association).

    PubMed

    Gentile, Ivan; Rosato, Lodovico; Avenia, Nicola; Testini, Mario; D'Ajello, Michele; Antonino, Antonio; De Palma, Maurizio

    2014-01-01

    Thyroid surgery is a clean procedure and therefore antibiotic prophylaxis is not routinely recommended by most international guidelines. However, antibiotics are often used in clinical practice. We enrolled 2926 patients who performed a thyroid surgical operation between the years 2009 and 2011 in the 38 centers of endocrine surgery that joined the UEC--Italian Endocrine Surgery Units Association. Antibiotic prophylaxis was used in 1132 interventions (38.7%). In case of antibiotic prophylaxis, cephalosporins or aminopenicillins ± beta lactamase inhibitors were employed. At logistic regression analysis the use of drainage or device and the presence of malignancy were independent predictors of antibiotic prophylaxis employment. In conclusion our study shows that antibiotic prophylaxis was not rarely used in clinical practice in the setting of thyroid surgery. Drainage apposition, use of device, and malignant disease were independent predictors for antibiotic prophylaxis employment. More data on everyday practice and infection rate in well-designed studies are warranted to provide definitive recommendations on the utility of antibiotic prophylaxis in this setting. According to our experience, we don't consider to be strictly necessary the antibiotic prophylaxis employment in order to reduce infection rate in thyroid surgery.

  19. The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease.

    PubMed

    Chen, Yuanyuan; Zhao, Ye; Cheng, Qiao; Wu, Depei; Liu, Haiyan

    2015-01-01

    The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed.

  20. [Respiratory syncytial virus prophylaxis among preterm infants--four seasons' experience].

    PubMed

    Klimek, Małgorzata; Kwinta, Przemko; Kruczek, Piotr; Pietrzyk, Jacek J

    2009-01-01

    Respiratory syncitial virus (RSV) is the main reason of hospitalizations due to respiratory tract infection in children within the first year of life. The course of infection is more severe in children from a risk group, which includes children who were born preterm, these with bronchopulmonary dysplasia (BPD), children with heart defects significantly influencing their hemodynamics, and immunocompromised children. Palivizumab is a humanized monoclonal antibody class IgG-1 used to prevent RSV infection. To assess the results of treatment and to evaluate factors influencing the efficacy of RSV infection prophylaxis in preterm newborns. The study included 55 preterm newborns (mean birth weight-970g, mean gestational age-27 weeks), who were given a dose of palmivizumab of 15mg per kg body weight every four weeks in autumn and winter from season 2004/ 2005 to season 2007/2008. Ten children (18%) required hospitalization between the doses and within 28 days after the last dose of palmivizumab. Among these, 2 children (3.6%) were hospitalized because of very severe RSV infection. Eight children (16%) were hospitalized due to respiratory tract infection within 12 months after completing the prophylaxis; none of them was infected with RSV. The episodes of respiratory tract infection between the doses and within 28 days after the last dose occurred in 19 children (31%), and in 26 patients included in the follow-up (51%) within 12 months after completing the prophylaxis. The effect of treatment was most beneficial in preterm neonates with extremely low birth weight and in children who did not require respiratory medications at the moment of discharge from the neonatal unit. RSV infection prophylaxis is of most benefit in children born with extremely low birth weight. In this group of children the prophylaxis should be considered both for children suffering from BPD and in children free of this disease.

  1. Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis.

    PubMed

    Nelson, Noele P

    2017-09-15

    GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.

  2. From Within Host Dynamics to the Epidemiology of Infectious Disease: Scientific Overview and Challenges

    PubMed Central

    Gutierrez, Juan B.; Galinski, Mary R.; Cantrell, Stephen; Voit, Eberhard O.

    2015-01-01

    Since their earliest days, humans have been struggling with infectious diseases. Caused by viruses, bacteria, protozoa, or even higher organisms like worms, these diseases depend critically on numerous intricate interactions between parasites and hosts, and while we have learned much about these interactions, many details are still obscure. It is evident that the combined host-parasite dynamics constitutes a complex system that involves components and processes at multiple scales of time, space, and biological organization. At one end of this hierarchy we know of individual molecules that play crucial roles for the survival of a parasite or for the response and survival of its host. At the other end, one realizes that the spread of infectious diseases by far exceeds specific locales and, due to today's easy travel of hosts carrying a multitude of organisms, can quickly reach global proportions. The community of mathematical modelers has been addressing specific aspects of infectious diseases for a long time. Most of these efforts have focused on one or two select scales of a multi-level disease and used quite different computational approaches. This restriction to a molecular, physiological, or epidemiological level was prudent, as it has produced solid pillars of a foundation from which it might eventually be possible to launch comprehensive, multi-scale modeling efforts that make full use of the recent advances in biology and, in particular, the various high-throughput methodologies accompanying the emerging –omics revolution. This special issue contains contributions from biologists and modelers, most of whom presented and discussed their work at the workshop From within Host Dynamics to the Epidemiology of Infectious Disease, which was held at the Mathematical Biosciences Institute at Ohio State University in April 2014. These contributions highlight some of the forays into a deeper understanding of the dynamics between parasites and their hosts, and the

  3. Probiotics prophylaxis in pyelonephritis infants with normal urinary tracts.

    PubMed

    Lee, Seung Joo; Cha, Jihae; Lee, Jung Won

    2016-11-01

    Pyelonephritis in infants is considered as a major factor for the formation of renal scar. To prevent recurrent pyelonephritis and renal damage, prophylaxis is extremely important. The aim of this study was to compare the effectiveness of probiotic and antibiotic prophylaxis or no-prophylaxis in infants with pyelonephritis and normal urinary tract. Altogether 191 infants, who were diagnosed with acute pyelonephritis, proven to have normal urinary tracts and followed up for 6 months on prophylaxis, were retrospectively evaluated. According to the types of prophylaxis, the infants were divided into three groups [probiotics (Lactobacillus species), antibiotics (trimethoprim/sulfamethoxazole, TMP/SMX), and noprophylaxis]. The incidence of recurrent urinary tract infection (UTI) during 6 months after the development of pyelonephritis, main causative uropathogens, and its antimicrobial sensitivities were compared. The incidence of recurrent UTI in the probiotic group was 8.2%, which was significantly lower than 20.6% in the no-prophylaxis group (P=0.035) and was not significantly different from 10.0% of the antibiotic group (P=0.532). The significant difference between the probiotic and no-prophylaxis groups was seen only in male infants (P=0.032). The main causative organism of recurrent UTI was Escherichia coli (E.coli), which was not different among the three groups (P=0.305). The resistance rate of E. coli to TMP/SMX was 100% in the antibiotic group, which was significantly higher than 25.0% in the probiotic group and 41.7% in the no-prophylaxis group (P=0.008). Probiotic prophylaxis was more effective in infants with pyelonephritis and normal urinary tract than in those with no-prophylaxis. It could be used as a natural alternative to antibiotic prophylaxis.

  4. Tinzaparin sodium: a review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease.

    PubMed

    Cheer, Susan M; Dunn, Christopher J; Foster, Rachel

    2004-01-01

    Tinzaparin sodium (tinzaparin; innohep) is a low molecular weight heparin (LMWH) formed by the enzymatic degradation of porcine unfractionated heparin (UFH). In clinical trials, once-daily subcutaneous (SC) tinzaparin was effective and generally well tolerated in the prophylaxis and treatment of thromboembolic disease. SC tinzaparin 75 anti-Xa IU/kg/day showed similar thromboprophylactic efficacy to adjusted-dosage oral warfarin in patients undergoing total hip arthroplasty; in patients undergoing knee replacement, the incidence of deep vein thrombosis (DVT) was significantly lower with tinzaparin. The drug had similar efficacy to equivalent-dosage SC enoxaparin sodium in orthopaedic surgery. In patients undergoing general surgery, SC tinzaparin 3500 anti-Xa IU/day was of equivalent thromboprophylactic efficacy to SC UFH 5000IU twice daily. Encouraging preliminary results have been obtained with tinzaparin in the prevention of DVT in patients with complete motor paralysis. In the initial treatment of acute proximal DVT and pulmonary embolism, SC tinzaparin 175 anti-Xa IU/kg/day was at least as effective as adjusted-dosage intravenous (IV) UFH. In the outpatient treatment of venous thromboembolism, tinzaparin has demonstrated similar efficacy to dalteparin sodium (dalteparin) and warfarin. Tinzaparin was effective in preventing clotting in haemodialysis circuits; the anticoagulant efficacy of tinzaparin in patients undergoing haemodialysis was similar to that of SC dalteparin and similar to or less than (although in this case the tinzaparin dose was too low for sufficient anticoagulant efficacy) that of IV UFH. Advantages of tinzaparin over UFH and warfarin include ease of administration and lack of need for laboratory monitoring. Tinzaparin is more cost effective than UFH in the treatment of established thromboembolic disease, and home-based treatment with tinzaparin may offer greater cost benefits than hospital-based therapy. Tinzaparin is well tolerated

  5. Bacterial infections and hepatic encephalopathy in liver cirrhosis-prophylaxis and treatment.

    PubMed

    Piotrowski, Damian; Boroń-Kaczmarska, Anna

    2017-09-01

    Infections are common among patients with liver cirrhosis. They occur more often in cirrhotic patient groups than in the general population and result in higher mortality. One reason for this phenomenon is bacterial translocation from the intestinal lumen that occurs as a consequence of intestinal bacterial overgrowth, increased permeability and decreased motility. The most common infections in cirrhotic patients are spontaneous bacterial peritonitis and urinary tract infections, followed by pneumonia, skin and soft tissue infections. Intestinal bacterial overgrowth is also responsible for hyperammonemia, which leads to hepatic encephalopathy. All of these complications make this group of patients at high risk for mortality. The role of antibiotics in liver cirrhosis is to treat and in some cases to prevent the development of infectious complications. Based on our current knowledge, antibiotic prophylaxis should be administered to patients with gastrointestinal hemorrhage, low ascitic fluid protein concentration combined with liver or renal failure, and spontaneous bacterial peritonitis as a secondary prophylaxis, as well as after hepatic encephalopathy episodes (also as a secondary prophylaxis). In some cases, the use of non-antibiotic prophylaxis can also be considered. Current knowledge of the treatment of infections allows the choice of a preferred antibiotic for empiric therapy depending on the infection location and whether the source of the disease is nosocomial or community-acquired. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  6. Host behaviour–parasite feedback: an essential link between animal behaviour and disease ecology

    PubMed Central

    Archie, Elizabeth A.; Craft, Meggan E.; Hawley, Dana M.; Martin, Lynn B.; Moore, Janice; White, Lauren

    2016-01-01

    Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour–disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour–parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour–parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. PMID:27053751

  7. Host behaviour-parasite feedback: an essential link between animal behaviour and disease ecology.

    PubMed

    Ezenwa, Vanessa O; Archie, Elizabeth A; Craft, Meggan E; Hawley, Dana M; Martin, Lynn B; Moore, Janice; White, Lauren

    2016-04-13

    Animal behaviour and the ecology and evolution of parasites are inextricably linked. For this reason, animal behaviourists and disease ecologists have been interested in the intersection of their respective fields for decades. Despite this interest, most research at the behaviour-disease interface focuses either on how host behaviour affects parasites or how parasites affect behaviour, with little overlap between the two. Yet, the majority of interactions between hosts and parasites are probably reciprocal, such that host behaviour feeds back on parasites and vice versa. Explicitly considering these feedbacks is essential for understanding the complex connections between animal behaviour and parasite ecology and evolution. To illustrate this point, we discuss how host behaviour-parasite feedbacks might operate and explore the consequences of feedback for studies of animal behaviour and parasites. For example, ignoring the feedback of host social structure on parasite dynamics can limit the accuracy of predictions about parasite spread. Likewise, considering feedback in studies of parasites and animal personalities may provide unique insight about the maintenance of variation in personality types. Finally, applying the feedback concept to links between host behaviour and beneficial, rather than pathogenic, microbes may shed new light on transitions between mutualism and parasitism. More generally, accounting for host behaviour-parasite feedbacks can help identify critical gaps in our understanding of how key host behaviours and parasite traits evolve and are maintained. © 2016 The Author(s).

  8. The Porphyromonas gingivalis/Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer's Disease, Diabetes and Cardiovascular Diseases

    PubMed Central

    Carter, Chris J.; France, James; Crean, StJohn; Singhrao, Sim K.

    2017-01-01

    Periodontal disease is of established etiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis. Following breakdown of the host's protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer's disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. This study analyzed the relationship between the P. gingivalis/host interactome and the genes identified in genome-wide association studies (GWAS) for the aforementioned conditions using data from GWASdb (P < 1E-03) and, in some cases, from the NCBI/EBI GWAS database (P < 1E-05). Gene expression data from periodontitis or P. gingivalis microarray was compared to microarray datasets from the AD hippocampus and/or from carotid artery plaques. The results demonstrated that the host genes of the P. gingivalis interactome were significantly enriched in genes deposited in GWASdb genes related to cognitive disorders, AD and dementia, and its co-morbid conditions T2DM, obesity, and CVD. The P. gingivalis/host interactome was also enriched in GWAS genes from the more stringent NCBI-EBI database for AD, atherosclerosis and T2DM. The misregulated genes in periodontitis tissue or P. gingivalis infected macrophages also matched those in the AD hippocampus or atherosclerotic plaques. Together, these data suggest important gene/environment interactions between P. gingivalis and susceptibility genes or gene expression changes in conditions where periodontal disease is a contributory factor. PMID:29311898

  9. The Porphyromonas gingivalis/Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer's Disease, Diabetes and Cardiovascular Diseases.

    PubMed

    Carter, Chris J; France, James; Crean, StJohn; Singhrao, Sim K

    2017-01-01

    Periodontal disease is of established etiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis . Following breakdown of the host's protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer's disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. This study analyzed the relationship between the P. gingivalis /host interactome and the genes identified in genome-wide association studies (GWAS) for the aforementioned conditions using data from GWASdb ( P < 1E-03) and, in some cases, from the NCBI/EBI GWAS database ( P < 1E-05). Gene expression data from periodontitis or P. gingivalis microarray was compared to microarray datasets from the AD hippocampus and/or from carotid artery plaques. The results demonstrated that the host genes of the P. gingivalis interactome were significantly enriched in genes deposited in GWASdb genes related to cognitive disorders, AD and dementia, and its co-morbid conditions T2DM, obesity, and CVD. The P. gingivalis /host interactome was also enriched in GWAS genes from the more stringent NCBI-EBI database for AD, atherosclerosis and T2DM. The misregulated genes in periodontitis tissue or P. gingivalis infected macrophages also matched those in the AD hippocampus or atherosclerotic plaques. Together, these data suggest important gene/environment interactions between P. gingivalis and susceptibility genes or gene expression changes in conditions where periodontal disease is a contributory factor.

  10. Survival relative to new and ancestral host plants, phytoplasma infection, and genetic constitution in host races of a polyphagous insect disease vector

    PubMed Central

    Maixner, Michael; Albert, Andreas; Johannesen, Jes

    2014-01-01

    Dissemination of vectorborne diseases depends strongly on the vector's host range and the pathogen's reservoir range. Because vectors interact with pathogens, the direction and strength of a vector's host shift is vital for understanding epidemiology and is embedded in the framework of ecological specialization. This study investigates survival in host-race evolution of a polyphagous insect disease vector, Hyalesthes obsoletus, whether survival is related to the direction of the host shift (from field bindweed to stinging nettle), the interaction with plant-specific strains of obligate vectored pathogens/symbionts (stolbur phytoplasma), and whether survival is related to genetic differentiation between the host races. We used a twice repeated, identical nested experimental design to study survival of the vector on alternative hosts and relative to infection status. Survival was tested with Kaplan–Meier analyses, while genetic differentiation between vector populations was quantified with microsatellite allele frequencies. We found significant direct effects of host plant (reduced survival on wrong hosts) and sex (males survive longer than females) in both host races and relative effects of host (nettle animals more affected than bindweed animals) and sex (males more affected than females). Survival of bindweed animals was significantly higher on symptomatic than nonsymptomatic field bindweed, but in the second experiment only. Infection potentially had a positive effect on survival in nettle animals but due to low infection rates the results remain suggestive. Genetic differentiation was not related to survival. Greater negative plant-transfer effect but no negative effect of stolbur in the derived host race suggests preadaptation to the new pathogen/symbiont strain before strong diversifying selection during the specialization process. Physiological maladaptation or failure to accept the ancestral plant will have similar consequences, namely positive assortative

  11. Survival relative to new and ancestral host plants, phytoplasma infection, and genetic constitution in host races of a polyphagous insect disease vector.

    PubMed

    Maixner, Michael; Albert, Andreas; Johannesen, Jes

    2014-08-01

    Dissemination of vectorborne diseases depends strongly on the vector's host range and the pathogen's reservoir range. Because vectors interact with pathogens, the direction and strength of a vector's host shift is vital for understanding epidemiology and is embedded in the framework of ecological specialization. This study investigates survival in host-race evolution of a polyphagous insect disease vector, Hyalesthes obsoletus, whether survival is related to the direction of the host shift (from field bindweed to stinging nettle), the interaction with plant-specific strains of obligate vectored pathogens/symbionts (stolbur phytoplasma), and whether survival is related to genetic differentiation between the host races. We used a twice repeated, identical nested experimental design to study survival of the vector on alternative hosts and relative to infection status. Survival was tested with Kaplan-Meier analyses, while genetic differentiation between vector populations was quantified with microsatellite allele frequencies. We found significant direct effects of host plant (reduced survival on wrong hosts) and sex (males survive longer than females) in both host races and relative effects of host (nettle animals more affected than bindweed animals) and sex (males more affected than females). Survival of bindweed animals was significantly higher on symptomatic than nonsymptomatic field bindweed, but in the second experiment only. Infection potentially had a positive effect on survival in nettle animals but due to low infection rates the results remain suggestive. Genetic differentiation was not related to survival. Greater negative plant-transfer effect but no negative effect of stolbur in the derived host race suggests preadaptation to the new pathogen/symbiont strain before strong diversifying selection during the specialization process. Physiological maladaptation or failure to accept the ancestral plant will have similar consequences, namely positive assortative

  12. Toxoplasmosis in the non-orthotopic heart transplant recipient population, how common is it? Any indication for prophylaxis?

    PubMed

    Dhakal, Reshika; Gajurel, Kiran; Montoya, Jose G

    2018-06-06

    Unlike in orthotopic heart transplant (OHT) setting where toxoplasma prophylaxis is a standard practice in pretransplant toxoplasma seronegative recipients who have received donor hearts from seropositive donors (D+/R-), there is no consensus regarding prophylaxis in non-OHT recipients. The incidence of toxoplasma disease in non-OHT recipients is less than 1% but its true burden is underestimated. Among 31 cases of toxoplasma disease reported from 2004 through 2017, renal and liver transplant recipients comprised of 90% of cases. A total of 94% of 18 recipients with known pretransplant serology were seronegative recipients (mostly D+/R-). Out of 16 recipients with adequate information, 10 (63%) and five (31%) were deemed to be donor derived and nondonor-derived primary toxoplasmosis respectively. Tissue invasive reactivation was uncommon. Almost all cases were described in patients not on prophylaxis at the time of presentation. Universal screening of donor/recipient toxoplasma serology for risk stratification is beneficial as illustrated by reports of fatal cases of toxoplasmosis due to unavailability of positive donor serology results. Toxoplasma disease in non-OHT predominantly occurs in pretransplant seronegative recipients- mostly in D+/R- group and is rare in seropositive recipients. Posttransplant prophylaxis should be targeted against the high-risk D+/R- group and should be considered in seropositive recipients in whom unusually high immunosuppression is implemented. Toxoplasma serologies and PCR should be used in combination for the diagnosis of toxoplasmosis in non-OHT patients.

  13. Metagenomics: A New Way to Illustrate the Crosstalk between Infectious Diseases and Host Microbiome

    PubMed Central

    Zhang, Yinfeng; Lun, Cheuk-Yin; Tsui, Stephen Kwok-Wing

    2015-01-01

    Microbes have co-evolved with human beings for millions of years. They play a very important role in maintaining the health of the host. With the advancement in next generation sequencing technology, the microbiome profiling in the host can be obtained under different circumstances. This review focuses on the current knowledge of the alteration of complex microbial communities upon the infection of different pathogens, such as human immunodeficiency virus, hepatitis B virus, influenza virus, and Mycobacterium tuberculosis, at different body sites. It is believed that the increased understanding of the correlation between infectious disease and the alteration of the microbiome can contribute to better management of disease progression in the future. However, future studies may need to be more integrative so as to establish the exact causality of diseases by analyzing the correlation between microorganisms within the human host and the pathogenesis of infectious diseases. PMID:26540050

  14. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    PubMed

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  15. The Effect of Prophylaxis on Pediatric HIV Costs

    PubMed Central

    Wilson, Leslie S.; Hensic, Lori; Paoli, Carly J.; Basu, Rituparna; Christenson, Maria; Moskowitz, Judith K.; Wara, Diane

    2011-01-01

    The objective of this study was to determine and compare the cost to treat HIV(+) and HIV(−) pediatric patients both before and after HIV prophylaxis became the standard of care. Retrospective chart review of a pediatric HIV/AIDS specialty clinic’s medical charts was conducted for clinical and healthcare utilization data on 125 children diagnosed from 1986–2007. Mean HIV-related costs were compared using bootstrapped t-tests for children born in the pre-prophylaxis (1979–1993) and prophylaxis eras (1994–2007). Patients were also stratified into two categories based on death during the follow-up period. Lastly, national cost-savings were estimated using mean costs, national number of at-risk births and national perinatal HIV transmission rates in each era. For HIV(+) children, mean annual per patient treatment cost was $15,067 (95% CI: $10,169–$19,965) in the pre-prophylaxis era (n=40) and $14,959 (95% CI: $9,140–$20,779) in the prophylaxis era (n=14), difference not statistically significant (p>0.05). For HIV(−) children, mean annual per patient treatment cost was $204 (95% CI: −$219–$627) for the pre-prophylaxis era (n=2) and $427 (95% CI: $277–$579) for the prophylaxis era (n=69), different statistically significant (p<0.05). A projected cost-savings of $16–23 million annually in the US was observed due to the adoption of prophylaxis treatment guidelines in pediatric HIV care. The prophylaxis era of pediatric HIV treatment has been successful in decreasing perinatal HIV transmission and mortality, as reflected by clinical trials and national cost-savings data, and emphasizes the value of the rapid adoption of evidence-based practice guidelines. PMID:21780991

  16. The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

    PubMed Central

    Chen, Yuanyuan; Zhao, Ye; Cheng, Qiao; Wu, Depei; Liu, Haiyan

    2015-01-01

    The mammalian intestinal microbiota is a complex ecosystem that plays an important role in host immune responses. Recent studies have demonstrated that alterations in intestinal microbiota composition are linked to multiple inflammatory diseases in humans, including acute graft-versus-host disease (aGVHD). aGVHD is one of the major obstacles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by tissue damage in the gastrointestinal (GI) tract, liver, lung, and skin. Here, we review the current understanding of the role of intestinal microbiota in the control of immune responses during aGVHD. Additionally, the possibility of using probiotic strains for potential treatment or prevention of aGVHD will be discussed. PMID:26090477

  17. Host-microbe interactions in distal airways: relevance to chronic airway diseases.

    PubMed

    Martin, Clémence; Burgel, Pierre-Régis; Lepage, Patricia; Andréjak, Claire; de Blic, Jacques; Bourdin, Arnaud; Brouard, Jacques; Chanez, Pascal; Dalphin, Jean-Charles; Deslée, Gaetan; Deschildre, Antoine; Gosset, Philippe; Touqui, Lhousseine; Dusser, Daniel

    2015-03-01

    This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways. Copyright ©ERS 2015.

  18. Neuroendocrine host factors and inflammatory disease susceptibility.

    PubMed Central

    Ligier, S; Sternberg, E M

    1999-01-01

    The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. PMID:10502534

  19. Models for the effects of host movement in vector-borne disease systems.

    PubMed

    Cosner, Chris

    2015-12-01

    Host and/or vector movement patterns have been shown to have significant effects in both empirical studies and mathematical models of vector-borne diseases. The processes of economic development and globalization seem likely to make host movement even more important in the future. This article is a brief survey of some of the approaches that have been used to study the effects of host movement in analytic mathematical models for vector-borne diseases. It describes the formulation and interpretation of various types of spatial models and describes a few of the conclusions that can be drawn from them. It is not intended to be comprehensive but rather to provide sufficient background material and references to the literature to serve as an entry point into this area of research for interested readers. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Primary response against cytomegalovirus during antiviral prophylaxis with valganciclovir, in solid organ transplant recipients

    PubMed Central

    La Rosa, Corinna; Limaye, Ajit P.; Krishnan, Aparna; Blumstein, Gideon; Longmate, Jeff; Diamond, Don J.

    2012-01-01

    Antiviral prophylaxis has proved successful for prevention of cytomegalovirus (CMV) disease in solid organ transplant (SOT) patients; though emerging data suggest that antiviral agents interfere with immunity, and may inhibit immune-priming. In this context, we investigated levels and phenotype of primary CMV-specific immune responses that developed during antiviral prophylaxis in a cohort of CMV seronegative recipients (R−) of a SOT from a seropositive donor (D+). We longitudinally monitored CMV viral load, antibodies and levels of the negative immuno-modulator IL-10. PBMC were stimulated with CMV-specific peptide libraries to measure CD137 activation marker on CMV-specific T-cells and levels of PD-1 receptor, which is overexpressed on exhausted T-cells. Unexpectedly, the majority (13/18) of D+R− patients who developed a primary CMV response showed early post-transplant CMV-specific responses, though levels of PD-1 on CMV-specific T-cells remained elevated throughout prophylaxis. A strong inverse association was found between levels of plasma IL-10 and CMV-specific cellular immune responses. Our study suggests that during prophylaxis, subclinical CMV infection might have occurred in the D+R− patients, and primary CMV-specific responses were detected early post-transplant when levels of plasma IL-10 were low. Extended prophylaxis or antiviral treatment did not appear to suppress CMV-specific antibodies or T-cells, which however showed exhaustion phenotypes. PMID:21672050

  1. [Efficacy of the treatment and secondary antifungal prophylaxis in AIDS-related histoplasmosis. Experience at the Francisco J. Muñiz Infectious Diseases Hospital in Buenos Aires].

    PubMed

    Negroni, Ricardo; Messina, Fernando; Arechavala, Alicia; Santiso, Gabriela; Bianchi, Mario

    Classic histoplasmosis is a systemic endemic mycosis due to Histoplasma capsulatum var. capsulatum. A significant reduction in the morbidity and mortality of AIDS-related histoplasmosis has been observed since the introduction of highly active antiretroviral therapy (HAART) and secondary antifungal prophylaxis. The aim of this study was to determine the current state of prognosis and treatment response of HIV-positive patients with histoplasmosis in the Francisco J. Muñiz Infectious Diseases Hospital in Buenos Aires City. A retrospective study was conducted using the demographic, clinical, immunological and treatment data of 80 patients suffering from AIDS-related histoplasmosis. Of the 80 cases studied 65 were male, the median age was 36 years, with 73.7% of the patients being drug addicts, 82.5% of the patients was not receiving HAART at diagnosis, and 58.7% of the cases had less than 50 CD4+ cells/μl at the beginning of the treatment. The initial phase of treatment consisted of intravenous amphotericin B and/or oral itraconazole for 3 months, with 78.7% of the cases showing a good clinical response. Only 26/63 patients who were discharged from hospital continued with the follow-up of the HAART, secondary prophylaxis with itraconazole or amphotericin B. Secondary prophylaxis was stopped after more than one year of HAART if the patients were asymptomatic, had two CD 4 + cell counts greater than 150cells/μl, and undetectable viral loads. No relapses were observed during a two-year follow up after prophylaxis was stopped. The treatment of histoplasmosis in HIV-positive patients was effective in 78.8% of the cases. The combination of HAART and secondary antifungal prophylaxis is safe, well tolerated, and effective. The low adherence of patients to HAART and the lack of laboratory kits for rapid histoplasmosis diagnosis should be addressed in the future. The usefulness of primary antifungal prophylaxis for cryptococcosis and histoplasmosis HIV-positive patients

  2. Helminth Infections Decrease Host Susceptibility to Immune-Mediated Diseases

    PubMed Central

    Weinstock, Joel V; Elliott, David E.

    2014-01-01

    Helminthic infection has become rare in highly industrialized nations. Concurrent with the decline in helminthic infection is an increase in prevalence of inflammatory disease. Removal of helminths from our environment and their powerful effects on host immunity may have contributed to this increase. Several different helminth species can abrogate disease in murine models of inflammatory bowel disease, type 1 diabetes, multiple sclerosis and other conditions. Helminths evoke immune regulatory pathways often involving dendritic cells, Tregs and macrophages that help control disease. Cytokines such as IL4, IL10 and TGFβ have a role. Notable is helminthic modulatory effect on innate immunity, which impedes development of aberrant adaptive immunity. Investigators are identifying key helminth-derived immune modulatory molecules that may have therapeutic utility in the control of inflammatory disease. PMID:25240019

  3. Estimating the Delay between Host Infection and Disease (Incubation Period) and Assessing Its Significance to the Epidemiology of Plant Diseases

    PubMed Central

    Leclerc, Melen; Doré, Thierry; Gilligan, Christopher A.; Lucas, Philippe; Filipe, João A. N.

    2014-01-01

    Knowledge of the incubation period of infectious diseases (time between host infection and expression of disease symptoms) is crucial to our epidemiological understanding and the design of appropriate prevention and control policies. Plant diseases cause substantial damage to agricultural and arboricultural systems, but there is still very little information about how the incubation period varies within host populations. In this paper, we focus on the incubation period of soilborne plant pathogens, which are difficult to detect as they spread and infect the hosts underground and above-ground symptoms occur considerably later. We conducted experiments on Rhizoctonia solani in sugar beet, as an example patho-system, and used modelling approaches to estimate the incubation period distribution and demonstrate the impact of differing estimations on our epidemiological understanding of plant diseases. We present measurements of the incubation period obtained in field conditions, fit alternative probability models to the data, and show that the incubation period distribution changes with host age. By simulating spatially-explicit epidemiological models with different incubation-period distributions, we study the conditions for a significant time lag between epidemics of cryptic infection and the associated epidemics of symptomatic disease. We examine the sensitivity of this lag to differing distributional assumptions about the incubation period (i.e. exponential versus Gamma). We demonstrate that accurate information about the incubation period distribution of a pathosystem can be critical in assessing the true scale of pathogen invasion behind early disease symptoms in the field; likewise, it can be central to model-based prediction of epidemic risk and evaluation of disease management strategies. Our results highlight that reliance on observation of disease symptoms can cause significant delay in detection of soil-borne pathogen epidemics and mislead practitioners and

  4. Estimating the delay between host infection and disease (incubation period) and assessing its significance to the epidemiology of plant diseases.

    PubMed

    Leclerc, Melen; Doré, Thierry; Gilligan, Christopher A; Lucas, Philippe; Filipe, João A N

    2014-01-01

    Knowledge of the incubation period of infectious diseases (time between host infection and expression of disease symptoms) is crucial to our epidemiological understanding and the design of appropriate prevention and control policies. Plant diseases cause substantial damage to agricultural and arboricultural systems, but there is still very little information about how the incubation period varies within host populations. In this paper, we focus on the incubation period of soilborne plant pathogens, which are difficult to detect as they spread and infect the hosts underground and above-ground symptoms occur considerably later. We conducted experiments on Rhizoctonia solani in sugar beet, as an example patho-system, and used modelling approaches to estimate the incubation period distribution and demonstrate the impact of differing estimations on our epidemiological understanding of plant diseases. We present measurements of the incubation period obtained in field conditions, fit alternative probability models to the data, and show that the incubation period distribution changes with host age. By simulating spatially-explicit epidemiological models with different incubation-period distributions, we study the conditions for a significant time lag between epidemics of cryptic infection and the associated epidemics of symptomatic disease. We examine the sensitivity of this lag to differing distributional assumptions about the incubation period (i.e. exponential versus Gamma). We demonstrate that accurate information about the incubation period distribution of a pathosystem can be critical in assessing the true scale of pathogen invasion behind early disease symptoms in the field; likewise, it can be central to model-based prediction of epidemic risk and evaluation of disease management strategies. Our results highlight that reliance on observation of disease symptoms can cause significant delay in detection of soil-borne pathogen epidemics and mislead practitioners and

  5. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4).

    PubMed

    Drgona, L; Gudiol, C; Lanini, S; Salzberger, B; Ippolito, G; Mikulska, M

    2018-03-20

    The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. The risk and spectrum of infections in patients receiving CD22-targeted agents (i.e. inotuzumab ozogamicin) are similar to those observed with anti-CD20 antibodies. Anti-Pneumocystis prophylaxis and monitoring for cytomegalovirus (CMV) infection is recommended for patients receiving CD30-targeted agents (brentuximab vedotin). Due to the scarcity of data, the risk posed by CD33-targeted agents (gemtuzumab ozogamicin) cannot be assessed. Patients receiving CD38-targeted agents (i.e. daratumumab) face an increased risk of varicella-zoster virus (VZV) infection. Therapy with CD40-targeted agents (lucatumumab or dacetuzumab) is associated with opportunistic infections similar to those observed in hyper-IgM syndrome, and prevention strategies (including anti-Pneumocystis prophylaxis and pre-emptive therapy for CMV infection) are warranted. SLAMF-7 (CD319)-targeted agents (elotuzumab) induce lymphopenia and increase the risk of infection (particularly due to VZV). The impact of CCR4-targeted agents (mogamulizumab) on infection susceptibility is difficult to distinguish from the effect of underlying diseases and concomitant therapies. However, anti-Pneumocystis and anti-herpesvirus prophylaxis and screening for chronic hepatitis B virus (HBV) infection are recommended. Specific management strategies should be put in place to reduce the risk and/or the severity of infectious complications associated to the reviewed agents. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All

  6. Cost-effectiveness of rabies post exposure prophylaxis in Iran.

    PubMed

    Hatam, Nahid; Esmaelzade, Firooz; Mirahmadizadeh, Alireza; Keshavarz, Khosro; Rajabi, Abdolhalim; Afsar Kazerooni, Parvin; Ataollahi, Marzieh

    2014-01-01

    The rabies is one of the most important officially-known viral zoonotic diseases for its global distribution, outbreak, high human and veterinary costs, and high death rate and causes high economic costs in different countries of the world every year. The rabies is the deadliest disease and if the symptoms break out in a person, one will certainly die. However, the deaths resulting from rabies can be prevented by post-exposure prophylaxis. To do so, in Iran and most of the countries in the world, all the people who are exposed to animal bite receive Post-Exposure Prophylaxis (PEP) treatment. The present survey aimed to investigate the cost-effectiveness of PEP in southern Iran. The present study estimated the PEP costs from the government`s Perspective with step-down method for the people exposed to animal bite, estimated the number of DALYs prevented by PEP in the individuals using decision Tree model, and computed the Incremental cost-effectiveness Ratio. The information collected of all reported animal bite cases (n=7111) in Fars Province, who referred rabies registries in urban and rural health centers to receive active care. Performing the PEP program cost estimated 1,052,756.1 USD for one  year and the estimated cost for the treatment of each animal bite case and each prevented death was 148.04 and 5945.42 USD, respectively. Likewise 4,509.82 DALYs were prevented in southern Iran in 2011 by PEP program. The incremental cost-effectiveness ratio for each DALY was estimated to be 233.43 USD. In addition to its full effectiveness in prophylaxis from rabies, PEP program saves the financial resources of the society, as well. This study showed performing PEP to be more cost-effective.

  7. Early Gut Microbiota Perturbations Following Intrapartum Antibiotic Prophylaxis to Prevent Group B Streptococcal Disease.

    PubMed

    Mazzola, Giuseppe; Murphy, Kiera; Ross, R Paul; Di Gioia, Diana; Biavati, Bruno; Corvaglia, Luigi T; Faldella, Giacomo; Stanton, Catherine

    2016-01-01

    The faecal microbiota composition of infants born to mothers receiving intrapartum antibiotic prophylaxis with ampicillin against group B Streptococcus was compared with that of control infants, at day 7 and 30 of life. Recruited newborns were both exclusive breastfed and mixed fed, in order to also study the effect of dietary factors on the microbiota composition. Massive parallel sequencing of the V3-V4 region of the 16S rRNA gene and qPCR analysis were performed. Antibiotic prophylaxis caused the most marked changes on the microbiota in breastfed infants, mainly resulting in a higher relative abundance of Enterobacteriaceae, compared with control infants (52% vs. 14%, p = 0.044) and mixed-fed infants (52% vs. 16%, p = 0.13 NS) at day 7 and in a lower bacterial diversity compared to mixed-fed infants and controls. Bifidobacteria were also particularly vulnerable and abundances were reduced in breastfed (p = 0.001) and mixed-fed antibiotic treated groups compared to non-treated groups. Reductions in bifidobacteria in antibiotic treated infants were also confirmed by qPCR. By day 30, the bifidobacterial population recovered and abundances significantly increased in both breastfed (p = 0.025) and mixed-fed (p = 0.013) antibiotic treated groups, whereas Enterobacteriaceae abundances remained highest in the breastfed antibiotic treated group (44%), compared with control infants (16%) and mixed-fed antibiotic treated group (28%). This study has therefore demonstrated the short term consequences of maternal intrapartum antibiotic prophylaxis on the infant faecal microbial population, particularly in that of breastfed infants.

  8. Predictors for Permanent Discontinuation of Systemic Immunosuppression in Severely Affected Chronic Graft-Versus-Host Disease Patients.

    PubMed

    Curtis, Lauren M; Pirsl, Filip; Steinberg, Seth M; Mitchell, Sandra A; Baird, Kristin; Cowen, Edward W; Mays, Jacqueline; Buxbaum, Nataliya P; Pichard, Dominique C; Im, Annie; Avila, Daniele; Taylor, Tiffani; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2017-11-01

    Predicting the duration of systemic therapy in patients with chronic graft-versus-host disease (cGVHD) is of critical clinical importance when counseling patients and for treatment planning. cGVHD characteristics associated with this outcome have not been studied in severely affected patients. The National Institutes of Health (NIH) cGVHD scoring provides a standardized set of organ severity measures that could represent clinically useful and reproducible predictive characteristics. We analyzed 227 previously treated patients most with moderate (n = 54) or severe (n = 170) cGVHD defined by NIH criteria who were prospectively enrolled in a natural history protocol (NCT00092235). Patients received a median of 4 prior systemic therapy regimens and were seen at the NIH for a single time-point visit and were then monitored for survival and ability to discontinue cGVHD systemic therapy. With a median follow-up of 71.1 months, the cumulative incidence of systemic therapy discontinuation was 9.5% (95% confidence interval, 6.0% to 13.9%) at 2 years and 27.7% (95% confidence interval, 20.9% to 34.8%) by 5 years after the initial visit. Factors associated with a higher incidence of immunosuppression discontinuation included lower NIH global severity (P = .019) and lung (P = .030) scores and less extensive deep sclerosis (<37% body surface area, P = .024). Lower patient- and clinician-reported 0 to 10 severity NIH scores and noncyclosporine prophylaxis regimens were also associated with higher incidence of immunosuppression discontinuation (P <.05). In conclusion, we found low success rates for immune suppression discontinuation in previously treated patients who were severely affected with cGVHD. NIH scoring and clinical measures provide new standardized disease-specific tools to predict discontinuation of systemic therapy. Published by Elsevier Inc.

  9. Warming and fertilization alter the dilution effect of host diversity on disease severity.

    PubMed

    Liu, Xiang; Lyu, Shengman; Zhou, Shurong; Bradshaw, Corey J A

    2016-07-01

    An essential ecosystem service is the dilution effect of biodiversity on disease severity, yet we do not fully understand how this relationship might change with continued climate warming and ecosystem degradation. We designed removal experiments in natural assemblages of Tibetan alpine meadow vegetation by manipulating plot-level plant diversity to investigate the relationship between different plant biodiversity indices and foliar fungal pathogen infection, and how artificial fertilization and warming affect this relationship. Although pathogen group diversity increased with host species richness, disease severity decreased as host diversity rose (dilution effect). The dilution effect of phylogenetic diversity on disease held across different levels of host species richness (and equal abundances), meaning that the effect arises mainly in association with enhanced diversity itself rather than from shifting abundances. However, the dilution effect was weakened by fertilization. Among indices, phylogenetic diversity was the most parsimonious predictor of infection severity. Experimental warming and fertilization shifted species richness to the most supported predictor. Compared to planting experiments where artificial communities are constructed from scratch, our removal experiment in natural communities more realistically demonstrate that increasing perturbation adjusts natural community resistance to disease severity. © 2016 by the Ecological Society of America.

  10. "Leaning" the process of venous thromboembolism prophylaxis.

    PubMed

    Biffl, Walter L; Beno, Matthew; Goodman, Philip; Bahia, Amit; Sabel, Allison; Snow, Karen; Steele, Andrew W; Swartwood, Claire; Thienelt, Christiane; MacKenzie, Thomas D; Mehler, Philip S

    2011-03-01

    Lean principles have been used at Denver Health Medical Center since 2005 to streamline nonclinical processes. Despite allocation of significant resources, particularly the expense of low molecular weight heparin (LMWH), to prophylaxis of venous thromboembolism (VTE), the incidence of postoperative VTE was significantly worse than national benchmarks. VTE risk factors were not consistently assessed, and the prescribing of prophylaxis varied widely. Lean was employed to standardize and implement risk assessment and evidence-based VTE prophylaxis for the institution. In a rapid improvement event, a multidisciplinary group formulated an evidence-based risk assessment tool and clinical practice guideline for VTE prophylaxis, with plans for hospitalwide implementation and monitoring. The effects were immediate and improved steadily with feedback to clinicians. Within six months, compliance with the standard approached 100%. One year after implementation, the use of LMWH decreased more than 60% below baseline, and the use of sequential compression devices decreased by nearly 30%. With increased use of unfractionated heparin, the cost savings on VTE prophylaxis exceeded $15,000 per month, for a total of $425,000 since implementation. Moreover, the incidence of VTE decreased markedly during the same period. By reducing VTE rates, a total cost savings of $6.2 million was estimated for the past 28 months. Applying Lean to the clinical management of VTE prophylaxis improved compliance with standards and saved the hospital a significant amount of money. This was achieved without compromising clinical outcomes. This experience could be replicated at other institutions.

  11. MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDermott, Jason E.; Braun, Pascal; Bonneau, Richard A.

    Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactionsmore » is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.« less

  12. EPICO 3.0. Antifungal prophylaxis in solid organ transplant recipients.

    PubMed

    Zaragoza, Rafael; Aguado, José María; Ferrer, Ricard; Rodríguez, Alejandro H; Maseda, Emilio; Llinares, Pedro; Grau, Santiago; Muñoz, Patricia; Fortún, Jesús; Bouzada, Mercedes; Pozo, Juan Carlos Del; León, Rafael

    Although over the past decade the management of invasive fungal infection has improved, considerable controversy persists regarding antifungal prophylaxis in solid organ transplant recipients. To identify the key clinical knowledge and make by consensus the high level recommendations required for antifungal prophylaxis in solid organ transplant recipients. Spanish prospective questionnaire, which measures consensus through the Delphi technique, was conducted anonymously and by e-mail with 30 national multidisciplinary experts, specialists in invasive fungal infections from six national scientific societies, including intensivists, anesthetists, microbiologists, pharmacologists and specialists in infectious diseases that responded to 12 questions prepared by the coordination group, after an exhaustive review of the literature in the last few years. The level of agreement achieved among experts in each of the categories should be equal to or greater than 70% in order to make a clinical recommendation. In a second term, after extracting the recommendations of the selected topics, a face-to-face meeting was held with more than 60 specialists who were asked to validate the pre-selected recommendations and derived algorithm. Echinocandin antifungal prophylaxis should be considered in liver transplant with major risk factors (retransplantation, renal failure requiring dialysis after transplantation, pretransplant liver failure, not early reoperation, or MELD>30); heart transplant with hemodialysis, and surgical re-exploration after transplantation; environmental colonization by Aspergillus, or cytomegalovirus (CMV) infection; and pancreas and intestinal transplant in case of acute graft rejection, hemodialysis, initial graft dysfunction, post-perfusion pancreatitis with anastomotic problems or need for laparotomy after transplantation. Antifungal fluconazole prophylaxis should be considered in liver transplant without major risk factors and MELD 20-30, split or living

  13. Barriers to innovation in human rabies prophylaxis and treatment: A causal analysis of insights from key opinion leaders and literature.

    PubMed

    van de Burgwal, L H M; Neevel, A M G; Pittens, C A C M; Osterhaus, A D M E; Rupprecht, C E; Claassen, E

    2017-12-01

    Rabies is an essentially 100% fatal, zoonotic disease, caused by Lyssaviruses. Currently, the disease is vaccine-preventable with pre- and post-exposure prophylaxis (PrEP and PEP). Still, rabies virus is estimated to cause up to 60,000 human deaths annually, of which the vast majority occurs in rural Asia and Africa, due to the inaccessibility of prophylaxis and non-existence of treatment. Despite these unmet clinical needs, rabies control mainly focuses on the sylvatic reservoir and drug innovation receives relatively little attention compared to other neglected tropical diseases (NTDs). As such, the lag of innovation in human rabies prophylaxis and treatment cannot be explained by limited return on investment alone. Strategies countering rabies-specific innovation barriers are important for the acceleration of innovation in human rabies prophylaxis and treatment. Barriers throughout society, science, business development and market domains were identified through literature review and 23 semi-structured interviews with key opinion leaders worldwide. A subsequent root cause analysis revealed causal relations between innovation barriers and a limited set of root causes. Finally, prioritization by experts indicated their relative importance. Root causes, which are fundamental to barriers, were aggregated into four types: market and commercial, stakeholder collaboration, public health and awareness, and disease trajectory. These were found in all domains of the innovation process and thus are relevant for all stakeholders. This study identifies barriers that were not previously described in this specific context, for example the competition for funding between medical and veterinary approaches. The results stress the existence of barriers beyond the limited return on investment and thereby explain why innovation in human rabies medication is lagging behind NTDs with a lower burden of disease. A re-orientation on the full spectrum of barriers that hinder innovation in

  14. Host phylogeny determines viral persistence and replication in novel hosts.

    PubMed

    Longdon, Ben; Hadfield, Jarrod D; Webster, Claire L; Obbard, Darren J; Jiggins, Francis M

    2011-09-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

  15. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    PubMed Central

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  16. Local antimicrobial administration for prophylaxis of surgical site infections.

    PubMed

    Huiras, Paul; Logan, Jill K; Papadopoulos, Stella; Whitney, Dana

    2012-11-01

    Despite a lack of consensus guidelines, local antibiotic administration for prophylaxis of surgical site infections is used during many surgical procedures. The rationale behind this practice is to provide high antibiotic concentrations at the site of surgery while minimizing systemic exposure and adverse effects. Local antibiotic administration for surgical site prophylaxis has inherent limitations in that antibiotics are applied after the incision is made, rather than the current standard for surgical site prophylaxis that recommends providing adequate antibiotic concentrations at the site before the incision. The efficacy and safety of local application of antibiotics for surgical site prophylaxis have been assessed in different types of surgery with a variety of antibiotic agents and methods of application. We identified 22 prospective, randomized, controlled trials that evaluated local application of antibiotics for surgical site prophylaxis. These trials were subsequently divided and analyzed based on the type of surgical procedure: dermatologic, orthopedic, abdominal, colorectal, and cardiothoracic. Methods of local application analyzed included irrigations, powders, ointments, pastes, beads, sponges, and fleeces. Overall, there is a significant lack of level I evidence supporting this practice for any of the surgical genres evaluated. In addition, the literature spans several decades, and changes in surgical procedures, systemic antibiotic prophylaxis, and microbial flora make conclusions difficult to determine. Based on available data, the efficacy of local antibiotic administration for the prophylaxis of surgical site infections remains uncertain, and recommendations supporting this practice for surgical site prophylaxis cannot be made. © 2012 Pharmacotherapy Publications, Inc.

  17. Variation in seizure prophylaxis in severe pediatric traumatic brain injury.

    PubMed

    Ostahowski, Paige J; Kannan, Nithya; Wainwright, Mark S; Qiu, Qian; Mink, Richard B; Groner, Jonathan I; Bell, Michael J; Giza, Christopher C; Zatzick, Douglas F; Ellenbogen, Richard G; Boyle, Linda Ng; Mitchell, Pamela H; Vavilala, Monica S

    2016-10-01

    OBJECTIVE Posttraumatic seizure is a major complication following traumatic brain injury (TBI). The aim of this study was to determine the variation in seizure prophylaxis in select pediatric trauma centers. The authors hypothesized that there would be wide variation in seizure prophylaxis selection and use, within and between pediatric trauma centers. METHODS In this retrospective multicenter cohort study including 5 regional pediatric trauma centers affiliated with academic medical centers, the authors examined data from 236 children (age < 18 years) with severe TBI (admission Glasgow Coma Scale score ≤ 8, ICD-9 diagnosis codes of 800.0-801.9, 803.0-804.9, 850.0-854.1, 959.01, 950.1-950.3, 995.55, maximum head Abbreviated Injury Scale score ≥ 3) who received tracheal intubation for ≥ 48 hours in the ICU between 2007 and 2011. RESULTS Of 236 patients, 187 (79%) received seizure prophylaxis. In 2 of the 5 centers, 100% of the patients received seizure prophylaxis medication. Use of seizure prophylaxis was associated with younger patient age (p < 0.001), inflicted TBI (p < 0.001), subdural hematoma (p = 0.02), cerebral infarction (p < 0.001), and use of electroencephalography (p = 0.023), but not higher Injury Severity Score. In 63% cases in which seizure prophylaxis was used, the patients were given the first medication within 24 hours of injury, and 50% of the patients received the first dose in the prehospital or emergency department setting. Initial seizure prophylaxis was most commonly with fosphenytoin (47%), followed by phenytoin (40%). CONCLUSIONS While fosphenytoin was the most commonly used medication for seizure prophylaxis, there was large variation within and between trauma centers with respect to timing and choice of seizure prophylaxis in severe pediatric TBI. The heterogeneity in seizure prophylaxis use may explain the previously observed lack of relationship between seizure prophylaxis and outcomes.

  18. Metabolic Analysis Reveals Altered Long-Chain Fatty Acid Metabolism in the Host by Huanglongbing Disease.

    PubMed

    Suh, Joon Hyuk; Niu, Yue S; Wang, Zhibin; Gmitter, Frederick G; Wang, Yu

    2018-02-07

    Candidatus Liberibacter asiaticus (CLas) is the presumed causal agent of Huanglongbing, one of the most destructive diseases in citrus. However, the lipid metabolism component of host response to this pathogen has not been investigated well. Here, metabolic profiling of a variety of long-chain fatty acids and their oxidation products was first performed to elucidate altered host metabolic responses of disease. Fatty acid signals were found to decrease obviously in response to disease regardless of cultivar. Several lipid oxidation products strongly correlated with those fatty acids were also consistently reduced in the diseased group. Using a series of statistical methods and metabolic pathway mapping, we found significant markers contributing to the pathological symptoms and identified their internal relationships and metabolic network. Our findings suggest that the infection of CLas may cause the altered metabolism of long-chain fatty acids, possibly leading to manipulation of the host's defense derived from fatty acids.

  19. Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation.

    PubMed

    Scroggins, Sabrina M; Olivier, Alicia K; Meyerholz, David K; Schlueter, Annette J

    2013-01-01

    Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3-4 months) and older (14-18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died), there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice (90% survival). To investigate differences between dendritic cells (DC) in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and donor DC may

  20. Characterization of Regulatory Dendritic Cells That Mitigate Acute Graft-versus-Host Disease in Older Mice Following Allogeneic Bone Marrow Transplantation

    PubMed Central

    Scroggins, Sabrina M.; Olivier, Alicia K.; Meyerholz, David K.; Schlueter, Annette J.

    2013-01-01

    Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3–4 months) and older (14–18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died), there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice (90% survival). To investigate differences between dendritic cells (DC) in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and donor DC

  1. Angiostrongylus spp. in the Americas: geographical and chronological distribution of definitive hosts versus disease reports

    PubMed Central

    Valente, Romina; Robles, Maria del Rosario; Navone, Graciela T; Diaz, Julia I

    2018-01-01

    BACKGROUND Angiostrongyliasis is an infection caused by nematode worms of the genus Angiostrongylus. The adult worms inhabit the pulmonary arteries, heart, bronchioles of the lung, or mesenteric arteries of the caecum of definitive host. Of a total of 23 species of Angiostrongylus cited worldwide, only nine were registered in the American Continent. Two species, A. cantonensis and A. costaricensis, are considered zoonoses when the larvae accidentally parasitise man. OBJECTIVES In the present study, geographical and chronological distribution of definitive hosts of Angiostrongylus in the Americas is analysed in order to observe their relationship with disease reports. Moreover, the role of different definitive hosts as sentinels and dispersers of infective stages is discussed. METHODS The study area includes the Americas. First records of Angiostrongylus spp. in definitive or accidental hosts were compiled from the literature. Data were included in tables and figures and were matched to geographic information systems (GIS). FINDINGS Most geographical records of Angiostrongylus spp. both for definitive and accidental hosts belong to tropical areas, mainly equatorial zone. In relation to those species of human health importance, as A. cantonensis and A. costaricensis, most disease cases indicate a coincidence between the finding of definitive host and disease record. However, in some geographic site there are gaps between report of definitive host and disease record. In many areas, human populations have invaded natural environments and their socioeconomic conditions do not allow adequate medical care. MAIN CONCLUSIONS Consequently, many cases for angiostrongyliasis could have gone unreported or unrecognised throughout history and in the nowadays. Moreover, the population expansion and the climatic changes invite to make broader and more complete range of observation on the species that involve possible epidemiological risks. This paper integrates and shows the

  2. Angiostrongylus spp. in the Americas: geographical and chronological distribution of definitive hosts versus disease reports.

    PubMed

    Valente, Romina; Robles, Maria Del Rosario; Navone, Graciela T; Diaz, Julia I

    2018-03-01

    Angiostrongyliasis is an infection caused by nematode worms of the genus Angiostrongylus. The adult worms inhabit the pulmonary arteries, heart, bronchioles of the lung, or mesenteric arteries of the caecum of definitive host. Of a total of 23 species of Angiostrongylus cited worldwide, only nine were registered in the American Continent. Two species, A. cantonensis and A. costaricensis, are considered zoonoses when the larvae accidentally parasitise man. In the present study, geographical and chronological distribution of definitive hosts of Angiostrongylus in the Americas is analysed in order to observe their relationship with disease reports. Moreover, the role of different definitive hosts as sentinels and dispersers of infective stages is discussed. The study area includes the Americas. First records of Angiostrongylus spp. in definitive or accidental hosts were compiled from the literature. Data were included in tables and figures and were matched to geographic information systems (GIS). Most geographical records of Angiostrongylus spp. both for definitive and accidental hosts belong to tropical areas, mainly equatorial zone. In relation to those species of human health importance, as A. cantonensis and A. costaricensis, most disease cases indicate a coincidence between the finding of definitive host and disease record. However, in some geographic site there are gaps between report of definitive host and disease record. In many areas, human populations have invaded natural environments and their socioeconomic conditions do not allow adequate medical care. Consequently, many cases for angiostrongyliasis could have gone unreported or unrecognised throughout history and in the nowadays. Moreover, the population expansion and the climatic changes invite to make broader and more complete range of observation on the species that involve possible epidemiological risks. This paper integrates and shows the current distribution of Angiostrongylus species in America

  3. Influence of Postoperative Thrombosis Prophylaxis on the Recurrence of Chronic Subdural Hematoma After Burr-Hole Drainage.

    PubMed

    Licci, Maria; Kamenova, Maria; Guzman, Raphael; Mariani, Luigi; Soleman, Jehuda

    2018-01-01

    Chronic subdural hematoma is a commonly encountered disease in neurosurgic practice, whereas its increasing prevalence is compatible with the ageing population. Recommendations concerning postoperative thrombosis prophylaxis after burr-hole drainage of chronic subdural hematoma are lacking. The aim of this study was to analyze the correlation between recurrence of chronic subdural hematoma and postoperative application of thrombosis prophylaxis. Retrospective, consecutive sample of patients undergoing burr-hole drainage for chronic subdural hematoma over 3 years. Single, academic medical center. All patients undergoing surgical evacuation of a chronic subdural hematoma with burr-hole drainage. Exclusion: patients under the age of 18 years, who presented with an acute subdural hematoma and those who underwent a craniotomy. We compared patients receiving thrombosis prophylaxis treatment after burr-hole drainage of chronic subdural hematoma with those who were not treated. Primary outcome measure was reoperation of chronic subdural hematoma due to recurrence. Secondary outcome measures were thromboembolic and cardiovascular events, hematologic findings, morbidity, and mortality. In addition, a subanalysis comparing recurrence rate dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) was undertaken. Overall recurrence rate of chronic subdural hematoma was 12.7%. Out of the 234 analyzed patients, 135 (57.3%) received postoperative thrombosis prophylaxis (low-molecular-weight heparin) applied subcutaneously. Recurrence of chronic subdural hematoma occurred in the thrombosis prophylaxis group and control group in 12 patients (8.9%) and 17 patients (17.2%), respectively, showing no significant difference (odds ratio, 0.47 [95% CI, 0.21 - 1.04]). A subanalysis comparing recurrence rate of chronic subdural hematoma dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) showed no significant difference either (odds ratio, 2

  4. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors).

    PubMed

    Reinwald, M; Silva, J T; Mueller, N J; Fortún, J; Garzoni, C; de Fijter, J W; Fernández-Ruiz, M; Grossi, P; Aguado, J M

    2018-06-01

    The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the

  5. A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease.

    PubMed

    Biemans, Floor; de Jong, Mart C M; Bijma, Piter

    2017-06-30

    Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of (genetic) traits: host susceptibility and host infectivity. Quantitative genetic studies on infectious diseases generally connect an individual's disease status to its own genotype, and therefore capture genetic effects on susceptibility only. However, they usually ignore variation in exposure to infectious herd mates, which may limit the accuracy of estimates of genetic effects on susceptibility. Moreover, genetic effects on infectivity will exist as well. Thus, to design optimal breeding strategies, it is essential that genetic effects on infectivity are quantified. Given the potential importance of genetic effects on infectivity, we set out to develop a model to estimate the effect of single nucleotide polymorphisms (SNPs) on both host susceptibility and host infectivity. To evaluate the quality of the resulting SNP effect estimates, we simulated an endemic disease in 10 groups of 100 individuals, and recorded time-series data on individual disease status. We quantified bias and precision of the estimates for different sizes of SNP effects, and identified the optimum recording interval when the number of records is limited. We present a generalized linear mixed model to estimate the effect of SNPs on both host susceptibility and host infectivity. SNP effects were on average slightly underestimated, i.e. estimates were conservative. Estimates were less precise for infectivity than for susceptibility. Given our sample size, the power to estimate SNP effects for susceptibility was 100% for differences between genotypes of a factor 1.56 or more, and was higher than 60% for infectivity for differences between genotypes of a factor 4 or more. When disease status was recorded 11 times on each

  6. Disease in a dynamic landscape: host behavior and wildfire reduce amphibian chytrid infection

    USGS Publications Warehouse

    Hossack, Blake R.; Lowe, Winsor H.; Ware, Joy L.; Corn, Paul Stephen

    2013-01-01

    Disturbances are often expected to magnify effects of disease, but these effects may depend on the ecology, behavior, and life history of both hosts and pathogens. In many ecosystems, wildfire is the dominant natural disturbance and thus could directly or indirectly affect dynamics of many diseases. To determine how probability of infection by the aquatic fungus Batrachochytrium dendrobatidis (Bd) varies relative to habitat use by individuals, wildfire, and host characteristics, we sampled 404 boreal toads (Anaxyrus boreas boreas) across Glacier National Park, Montana (USA). Bd causes chytridiomycosis, an emerging infectious disease linked with widespread amphibian declines, including the boreal toad. Probability of infection was similar for females and the combined group of males and juveniles. However, only 9% of terrestrial toads were infected compared to >30% of aquatic toads, and toads captured in recently burned areas were half as likely to be infected as toads in unburned areas. We suspect these large differences in infection reflect habitat choices by individuals that affect pathogen exposure and persistence, especially in burned forests where warm, arid conditions could limit Bd growth. Our results show that natural disturbances such as wildfire and the resulting diverse habitats can influence infection across large landscapes, potentially maintaining local refuges and host behaviors that facilitate evolution of disease resistance.

  7. Pathogenic landscapes: Interactions between land, people, disease vectors, and their animal hosts

    PubMed Central

    2010-01-01

    Background Landscape attributes influence spatial variations in disease risk or incidence. We present a review of the key findings from eight case studies that we conducted in Europe and West Africa on the impact of land changes on emerging or re-emerging vector-borne diseases and/or zoonoses. The case studies concern West Nile virus transmission in Senegal, tick-borne encephalitis incidence in Latvia, sandfly abundance in the French Pyrenees, Rift Valley Fever in the Ferlo (Senegal), West Nile Fever and the risk of malaria re-emergence in the Camargue, and rodent-borne Puumala hantavirus and Lyme borreliosis in Belgium. Results We identified general principles governing landscape epidemiology in these diverse disease systems and geographic regions. We formulated ten propositions that are related to landscape attributes, spatial patterns and habitat connectivity, pathways of pathogen transmission between vectors and hosts, scale issues, land use and ownership, and human behaviour associated with transmission cycles. Conclusions A static view of the "pathogenecity" of landscapes overlays maps of the spatial distribution of vectors and their habitats, animal hosts carrying specific pathogens and their habitat, and susceptible human hosts and their land use. A more dynamic view emphasizing the spatial and temporal interactions between these agents at multiple scales is more appropriate. We also highlight the complementarity of the modelling approaches used in our case studies. Integrated analyses at the landscape scale allows a better understanding of interactions between changes in ecosystems and climate, land use and human behaviour, and the ecology of vectors and animal hosts of infectious agents. PMID:20979609

  8. Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials.

    PubMed

    Pasquini, Marcelo C; Logan, Brent; Jones, Richard J; Alousi, Amin M; Appelbaum, Frederick R; Bolaños-Meade, Javier; Flowers, Mary E D; Giralt, Sergio; Horowitz, Mary M; Jacobsohn, David; Koreth, John; Levine, John E; Luznik, Leo; Maziarz, Richard; Mendizabal, Adam; Pavletic, Steven; Perales, Miguel-Angel; Porter, David; Reshef, Ran; Weisdorf, Daniel; Antin, Joseph H

    2018-06-01

    Graft-versus-host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here we report a benchmark analysis to evaluate the performance of 6 GVHD prevention strategies tested at single institutions compared with a large multicenter outcomes database as a control. Each intervention was compared with the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS using the benchmark analysis further informed the design of 2 clinical trials testing GVHD prophylaxis interventions. This study demonstrates the potential benefit of using an outcomes database to select promising interventions for multicenter clinical trials and proposes novel composite endpoints for use in GVHD prevention trials. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

    PubMed

    de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria-Carmen; Chaussabel, Damien; Cohen, Daniel M; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion

    2016-11-01

    Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection. We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity. We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

  10. Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan.

    PubMed

    Cappelli, Barbara; Chiesa, Robert; Evangelio, Costanza; Biffi, Alessandra; Roccia, Tito; Frugnoli, Ilaria; Biral, Erika; Noè, Anna; Fossati, Marco; Finizio, Valentina; Miniero, Roberto; Napolitano, Sara; Ferrua, Francesca; Soliman, Clara; Ciceri, Fabio; Roncarolo, Maria G; Marktel, Sarah

    2009-11-01

    Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5-40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen-matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan-based conditioning, methotraexate + ciclosporine). All patients received a busulphan-based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day -9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high-risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low-weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.

  11. Long-term prophylaxis in severe factor VII deficiency.

    PubMed

    Siboni, S M; Biguzzi, E; Mistretta, C; Garagiola, I; Peyvandi, F

    2015-11-01

    The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three times/weeks was described to be effective. In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30 microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. © 2015 John Wiley & Sons Ltd.

  12. Diet as prophylaxis and treatment for venous thromboembolism?

    PubMed Central

    2010-01-01

    Background Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored. Methods and Findings The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment. Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using

  13. Attitudes toward infection prophylaxis in pediatric oncology: a qualitative approach.

    PubMed

    Diorio, Caroline; Tomlinson, Deborah; Boydell, Katherine M; Regier, Dean A; Ethier, Marie-Chantal; Alli, Amanda; Alexander, Sarah; Gassas, Adam; Taylor, Jonathan; Kellow, Charis; Mills, Denise; Sung, Lillian

    2012-01-01

    The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology. THE STUDY WAS COMPLETED IN THREE PHASES: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach. A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration. Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.

  14. A review of the infection pathogenesis and prophylaxis recommendations in patients with chronic lymphocytic leukemia.

    PubMed

    Tadmor, Tamar; Welslau, Manfred; Hus, Iwona

    2018-01-01

    The majority of patients with CLL will suffer from infections during their disease, accounting for approximately 60% of deaths in CLL. Patients are predisposed to infection due to immune defects related to the primary disease, and as a result of therapy. The range of infectious complications has evolved alongside therapeutic advances in the treatment of CLL. More recently several novel therapeutic compounds have been introduced in CLL, whose unique safety profiles will probably have an impact on the prophylaxis and management of infections in these patients. Areas covered: This review describes the pathogenesis of infections due to intrinsic CLL or therapy-related immunosuppression, and elightens the importance of proactive and reactive infection management as a key focus of patient care. Infections related to conventional chemotherapy, immunochemotherapy with monoclonal antibodies, target therapies with B-cell receptor pathway inhibitors and Bcl-2 antagonists are reviewed. Expert commentary: Despite the importance of infection management and prevention in high-risk patients, there are only limited infection risk-assessment guidelines that can be easily used in clinical practice to guide more appropriate infection prophylaxis and its management. Here we provide an overview of suggested prophylaxis management of infection, and include key prophylactic interventions that we feel should be performed in CLL patients routinely.

  15. Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding.

    PubMed

    Duché, Mathieu; Ducot, Béatrice; Ackermann, Oanez; Guérin, Florent; Jacquemin, Emmanuel; Bernard, Olivier

    2017-02-01

    Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known endoscopic pattern carrying a high-risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high-risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleed-free survival, overall survival and life-threatening complications of bleeding. High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis (p<0.001), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleed-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for non-cirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with non-cirrhotic causes and cirrhosis respectively. In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the child's age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can

  16. Interleukin-22 in Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation

    PubMed Central

    Lamarthée, Baptiste; Malard, Florent; Saas, Philippe; Mohty, Mohamad; Gaugler, Béatrice

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in the identification of new cellular and molecular effectors involved in GVHD pathogenesis. Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties. Its role in GVHD processes has been investigated, and the data suggest that its effect depends on the timing, the target tissue, and the origin of the producing cells (donor/host). In this review, we discuss the role of IL-22 in allo-HSCT and GVHD. PMID:27148267

  17. Interleukin-22 in Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation.

    PubMed

    Lamarthée, Baptiste; Malard, Florent; Saas, Philippe; Mohty, Mohamad; Gaugler, Béatrice

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in the identification of new cellular and molecular effectors involved in GVHD pathogenesis. Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties. Its role in GVHD processes has been investigated, and the data suggest that its effect depends on the timing, the target tissue, and the origin of the producing cells (donor/host). In this review, we discuss the role of IL-22 in allo-HSCT and GVHD.

  18. Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes.

    PubMed

    Dahlén, Torsten; Kalin, Mats; Cederlund, Kerstin; Nordlander, Anna; Björkholm, Magnus; Ljungman, Per; Blennow, Ola

    2016-02-01

    Posaconazole prophylaxis during induction chemotherapy for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) has been shown to significantly decrease the incidence of invasive fungal disease (IFD) and increase overall survival in a trial setting, but only small real-life studies have been published. This was a retrospective cohort study including consecutive patients with AML/MDS treated with intensive induction chemotherapy; 176 patients received fluconazole prophylaxis 2008-2011 and 107 patients received posaconazole prophylaxis 2011-2013. Only proven and probable IFD according to the revised EORTC/MSG criteria were included in the analysis. The two cohorts were well matched without significant differences in patient characteristics. At day 100, patients receiving posaconazole had a significantly lower incidence of total IFD (0.9% vs. 10.8%, P < 0.01), invasive aspergillosis (0% vs. 5.7%, P = 0.02) and invasive candidiasis (0% vs. 4.0%, P < 0.05). There was no significant difference in overall survival, neither at day 100 (87% in the posaconazole group vs. 85% in the fluconazole group) nor at end of follow-up (78% vs. 77%). Posaconazole prophylaxis decreased the incidence of IFD but did not improve short-term overall survival. Improved treatment efficacy of manifest IFD is likely to explain the lack of survival benefit. © 2015 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

  19. Group B Streptococcal Maternal Colonization and Neonatal Disease: Molecular Mechanisms and Preventative Approaches

    PubMed Central

    Patras, Kathryn A.; Nizet, Victor

    2018-01-01

    Group B Streptococcus (GBS) colonizes the gastrointestinal and vaginal epithelium of a significant percentage of healthy women, with potential for ascending intrauterine infection or transmission during parturition, creating a risk of serious disease in the vulnerable newborn. This review highlights new insights on the bacterial virulence determinants, host immune responses, and microbiome interactions that underpin GBS vaginal colonization, the proximal step in newborn infectious disease pathogenesis. From the pathogen perspective, the function GBS adhesins and biofilms, β-hemolysin/cytolysin toxin, immune resistance factors, sialic acid mimicry, and two-component transcriptional regulatory systems are reviewed. From the host standpoint, pathogen recognition, cytokine responses, and the vaginal mucosal and placental immunity to the pathogen are detailed. Finally, the rationale, efficacy, and potential unintended consequences of current universal recommended intrapartum antibiotic prophylaxis are considered, with updates on new developments toward a GBS vaccine or alternative approaches to reducing vaginal colonization. PMID:29520354

  20. Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients.

    PubMed

    Stern, Anat; Green, Hefziba; Paul, Mical; Vidal, Liat; Leibovici, Leonard

    2014-10-01

    Pneumocystis pneumonia (PCP) is a disease affecting immunocompromised patients. PCP among these patients is associated with significant morbidity and mortality. To assess the effectiveness of PCP prophylaxis among non-HIV immunocompromised patients; and to define the type of immunocompromised patient for whom evidence suggests a benefit for PCP prophylaxis. Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE and EMBASE (to March 2014), LILACS (to March 2014), relevant conference proceedings; and references of identified trials. Randomised controlled trials (RCTs) or quasi-RCTs comparing prophylaxis with an antibiotic effective against PCP versus placebo, no intervention, or antibiotic(s) with no activity against PCP; and trials comparing different antibiotics effective against PCP among immunocompromised non-HIV patients. We only included trials in which Pneumocystis infections were available as an outcome. Two review authors independently assessed risk of bias in each trial and extracted data from the included trials. We contacted authors of the included trials to obtain missing data. The primary outcome was documented PCP infections. Risk ratios (RR) with 95% confidence intervals (CI) were estimated and pooled using the random-effects model. Thirteen trials performed between the years 1974 and 2008 were included, involving 1412 patients. Four trials included 520 children with acute lymphoblastic leukemia and the remaining trials included adults with acute leukemia, solid organ transplantation or autologous bone marrow transplantation. Compared to no treatment or treatment with fluoroquinolones (inactive against Pneumocystis), there was an 85% reduction in the occurrence of PCP in patients receiving prophylaxis with trimethoprim/sulfamethoxazole, RR of 0.15 (95% CI 0.04 to 0.62; 10 trials, 1000 patients). The evidence was graded as moderate due to possible risk of bias. PCP

  1. Ciprofloxacin vs levofloxacin for prophylaxis during hematopoietic stem-cell transplantation.

    PubMed

    Copeland, Vanessa; McLaughlin, Milena; Trifilio, Steven

    2018-01-01

    The objective of the current retrospective study was to compare differences in rate of breakthrough infections for ciprofloxacin vs levofloxacin prophylaxis in autologous hematopoietic stem-cell transplant (HSCT) patients treated for multiple myeloma. This was a retrospective, cohort study comparing autologous HSCT recipients treated for multiple myeloma who received ciprofloxacin prophylaxis vs levofloxacin prophylaxis. A total of 297 patients, 143 levofloxacin- and 154 ciprofloxacin-treated were included. There was a significantly higher incidence of bloodstream infections in the ciprofloxacin group (24/154) compared to the levofloxacin group (10/143), P = .03, primarily caused by a statistically higher incidence of gram-positive bloodstream infections (ciprofloxacin [21/154] vs levofloxacin [8/143]; P < .01). Clinically relevant differences exist between fluoroquinolone agents used for prophylaxis. Levofloxacin prophylaxis was more effective than ciprofloxacin prophylaxis to reduce the incidence of bloodstream infections in this study. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Optimal control issues in plant disease with host demographic factor and botanical fungicides

    NASA Astrophysics Data System (ADS)

    Anggriani, N.; Mardiyah, M.; Istifadah, N.; Supriatna, A. K.

    2018-03-01

    In this paper, we discuss a mathematical model of plant disease with the effect of fungicide. We assume that the fungicide is given as a preventive treatment to infectious plants. The model is constructed based on the development of the disease in which the monomolecular is monocyclic. We show the value of the Basic Reproduction Number (BRN) ℛ0 of the plant disease transmission. The BRN is computed from the largest eigenvalue of the next generation matrix of the model. The result shows that in the region where ℛ0 greater than one there is a single stable endemic equilibrium. However, in the region where ℛ0 less than one this endemic equilibrium becomes unstable. The dynamics of the model is highly sensitive to changes in contact rate and infectious period. We also discuss the optimal control of the infected plant host by considering a preventive treatment aimed at reducing the infected host plant. The obtaining optimal control shows that it can reduce the number of infected hosts compared to that without control. Some numerical simulations are also given to illustrate our analytical results.

  3. What is the place of pre-exposure prophylaxis in HIV prevention?

    PubMed

    De Man, Jeroen; Colebunders, Robert; Florence, Eric; Laga, Marie; Kenyon, Christopher

    2013-01-01

    New tools are needed to bring down ongoing high HIV incidence. This review aims to evaluate the place of one of these new tools (pre-exposure prophylaxis) in a comprehensive prevention strategy. Several trials have demonstrated the safety and the efficacy of pre-exposure prophylaxis in HIV prevention. Two large trials have, however, failed to show such efficacy. This was likely due to poor adherence in these trials. New forms of long-acting pre-exposure prophylaxis currently in trials may deal with these problems of low adherence. Pre-exposure prophylaxis has been demonstrated to be cost-effective within certain settings. The introduction of pre-exposure prophylaxis into prevention programs needs to be carefully thought through. For example, pre-exposure prophylaxis-induced risk compensation, at both an individual and population level, could undermine other aspects of a comprehensive HIV prevention program. In conclusion, pre-exposure prophylaxis could be a useful additional tool for the prevention of HIV in specific high-risk groups. It should be implemented in a way that deals with issues such as ensuring high adherence and ensuring that pre-exposure prophylaxis does not detract from, but complements, other more fundamental elements of HIV prevention programs.

  4. HDAC Inhibition and Graft Versus Host Disease

    PubMed Central

    Choi, Sung; Reddy, Pavan

    2011-01-01

    Histone deacetylase (HDAC) inhibitors are currently used clinically as anticancer drugs. Recent data have demonstrated that some of these drugs have potent antiinflammatory or immunomodulatory effects at noncytotoxic doses. The immunomodulatory effects have shown potential for therapeutic benefit after allogeneic bone marrow transplantation in several experimental models of graft versus host disease (GVHD). These effects, at least in part, result from the ability of HDAC inhibitors (HDACi) to suppress the function of host antigen presenting cells such as dendritic cells (DC). HDACi reduce the dendritic cell (DC) responses, in part, by enhancing the expression of indoleamine 2,3-dioxygenase (IDO) in a signal transducer and activator of transcription-3 (STAT-3) dependent manner. They also alter the function of other immune cells such as T regulatory cells and natural killer (NK) cells, which also play important roles in the biology of GVHD. Based on these observations, a clinical trial has been launched to evaluate the impact of HDAC inhibitors on clinical GVHD. The experimental, mechanistic studies along with the brief preliminary observations from the ongoing clinical trial are discussed in this review. PMID:21298214

  5. Disease ecology across soil boundaries: effects of below-ground fungi on above-ground host-parasite interactions.

    PubMed

    Tao, Leiling; Gowler, Camden D; Ahmad, Aamina; Hunter, Mark D; de Roode, Jacobus C

    2015-10-22

    Host-parasite interactions are subject to strong trait-mediated indirect effects from other species. However, it remains unexplored whether such indirect effects may occur across soil boundaries and connect spatially isolated organisms. Here, we demonstrate that, by changing plant (milkweed Asclepias sp.) traits, arbuscular mycorrhizal fungi (AMF) significantly affect interactions between a herbivore (the monarch butterfly Danaus plexippus) and its protozoan parasite (Ophryocystis elektroscirrha), which represents an interaction across four biological kingdoms. In our experiment, AMF affected parasite virulence, host resistance and host tolerance to the parasite. These effects were dependent on both the density of AMF and the identity of milkweed species: AMF indirectly increased disease in monarchs reared on some species, while alleviating disease in monarchs reared on other species. The species-specificity was driven largely by the effects of AMF on both plant primary (phosphorus) and secondary (cardenolides; toxins in milkweeds) traits. Our study demonstrates that trait-mediated indirect effects in disease ecology are extensive, such that below-ground interactions between AMF and plant roots can alter host-parasite interactions above ground. In general, soil biota may play an underappreciated role in the ecology of many terrestrial host-parasite systems. © 2015 The Author(s).

  6. [Perioperative antibiotic prophylaxis in cancer surgery].

    PubMed

    Vilar-Compte, Diana; García-Pasquel, María José

    2011-01-01

    The effectiveness of perioperative antibiotic prophylaxis in reducing surgical site infections has been demonstrated. Its utility is recognized for clean-contaminated procedures and some clean surgeries. Prophylactic antibiotics are used as intended to cover the most common germs in the surgical site; first and second generation cephalosporins are the most used. For optimal prophylaxis, an antibiotic with a targeted spectrum should be administered at sufficiently high concentrations in serum, tissue, and the surgical wound during the time that the incision is open and risk of bacterial contamination. The infusion of the first dose of antimicrobial should begin within 60 min before surgical incision and should be discontinued within 24 h after the end of surgery The prolonged use of antibiotic prophylaxis leads to emergence of bacterial resistance and high costs. The principles of antimicrobial prophylaxis in cancer surgery are the same as those described for general surgery; it is recommended to follow and comply with the standard criteria. In mastectomies and clean head and neck surgery there are specific recommendations that differ from non-cancer surgery. In the case of very extensive surgeries, such as pelvic surgery or bone surgery with reconstruction, extension of antibiotics for 48-72 h should be considered.

  7. Prophylaxis for blood-borne diseases during the London 7/7 mass casualty terrorist bombing: a review and the role of bioethics.

    PubMed

    Edwards, Dafydd S; Barnett-Vanes, A; Narayan, N; Patel, H D L

    2016-10-01

    The suicide bombings in London on 7 July 2005 resulted in a mass casualty situation. Over 50% of casualties were treated at the Royal London Hospital where clinicians witnessed large numbers of severely injured patients. In some casualties human biological foreign material was found embedded in the soft tissue originating from the suicide bombers or other casualties. This had the potential of placing individuals at risk of transmission of blood-borne diseases. Advances in the fields of medicine and biology have led to increased survivorship in the context of trauma and mass casualty incidents. This has resulted in the emergence of ethical scenarios surrounding patient management. A systematic review of the literature of the 7/7 bombings, and suicide bombings reported globally, where biological implantation is noted, was performed to examine the medicolegal issues arising during such attack. Twelve casualties with human tissue implanted were recorded in the 7/7 bombings. While all patients at risk were given prophylaxis based on recommendations by the Health Protection Agency, several ethical considerations surfaced as a result. In this paper, we compare the sequence of events and the management process of the victims of the 7/7 bombings and the evidence-based research regarding blood-borne infection transmission. Furthermore, it explores the ethical dilemmas, experienced by the senior author on 7/7, surrounding prophylaxis for blood-borne diseases and protocols to avoid confusion over best practice in future bombing incidents. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Cross-talk between virus and host innate immunity in pediatric HIV-1 infection and disease progression.

    PubMed

    Freguja, Riccardo; Gianesin, Ketty; Zanchetta, Marisa; De Rossi, Anita

    2012-07-01

    Variability in the susceptibility to HIV-1 infection and disease progression depends on both virus and host determinants. Some exposed individuals remain HIV-1-uninfected and HIV-1-infected subjects develop disease at varying intervals with a small percentage remaining long-term non-progressors. As innate immunity is the earliest response to microbial entry and injury, host factors that impact innate immunity may play a role in viral infectivity and pathogenesis. In the pediatric population the interactions between the virus and the host may be of particular relevance due to the still developing adaptive immune system. Data indicate that genetic variants of defensins and Toll-Like Receptors (TLRs), key elements of innate immunity, play a role in mother-to-child transmission (MTCT) of HIV-1, and in the outcome of pediatric HIV-1 disease. Although the mechanisms by which these genetic variants influence HIV-1 interactions with the host are still largely unknown, defensins and TLRs, along with their link with regulatory T cells (Tregs), may play a critical role in the onset and persistence of immune activation, a hallmark of HIV-1 disease.

  9. Microbiome Profiles in Periodontitis in Relation to Host and Disease Characteristics

    PubMed Central

    Hong, Bo-Young; Furtado Araujo, Michel V.; Strausbaugh, Linda D.; Terzi, Evimaria; Ioannidou, Effie; Diaz, Patricia I.

    2015-01-01

    Periodontitis is an inflammatory condition that affects the supporting tissues surrounding teeth. The occurrence of periodontitis is associated with shifts in the structure of the communities that inhabit the gingival sulcus. Although great inter-subject variability in the subgingival microbiome has been observed in subjects with periodontitis, it is unclear whether distinct community types exist and if differences in microbial signatures correlate with host characteristics or with the variable clinical presentations of periodontitis. Therefore, in this study we explored the existence of different community types in periodontitis and their relationship with host demographic, medical and disease-related clinical characteristics. Clustering analyses of microbial abundance profiles suggested two types of communities (A and B) existed in the 34 subjects with periodontitis evaluated. Type B communities harbored greater proportions of certain periodontitis-associated taxa, including species historically associated with the disease, such as Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola, and taxa recently linked to periodontitis. In contrast, subjects with type A communities had increased proportions of different periodontitis-associated species, and were also enriched for health-associated species and core taxa (those equally prevalent in health and periodontitis). Periodontitis subgingival clusters were not associated with demographic, medical or disease-specific clinical parameters other than periodontitis extent (proportion of sites affected), which positively correlated with the total proportion of cluster B signature taxa. In conclusion, two types of microbial communities were detected in subjects with periodontitis. Host demographics and underlying medical conditions did not correlate with these profiles, which instead appeared to be related to periodontitis extent, with type B communities present in more widespread disease cases. The two

  10. Attitudes toward Infection Prophylaxis in Pediatric Oncology: A Qualitative Approach

    PubMed Central

    Diorio, Caroline; Tomlinson, Deborah; Boydell, Katherine M.; Regier, Dean A.; Ethier, Marie-Chantal; Alli, Amanda; Alexander, Sarah; Gassas, Adam; Taylor, Jonathan; Kellow, Charis; Mills, Denise; Sung, Lillian

    2012-01-01

    Background The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology. Methods The study was completed in three phases: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach. Results A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration. Conclusion Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments. PMID:23112849

  11. Host persistence or extinction from emerging infectious disease: insights from white-nose syndrome in endemic and invading regions.

    PubMed

    Hoyt, Joseph R; Langwig, Kate E; Sun, Keping; Lu, Guanjun; Parise, Katy L; Jiang, Tinglei; Frick, Winifred F; Foster, Jeffrey T; Feng, Jiang; Kilpatrick, A Marm

    2016-03-16

    Predicting species' fates following the introduction of a novel pathogen is a significant and growing problem in conservation. Comparing disease dynamics between introduced and endemic regions can offer insight into which naive hosts will persist or go extinct, with disease acting as a filter on host communities. We examined four hypothesized mechanisms for host-pathogen persistence by comparing host infection patterns and environmental reservoirs for Pseudogymnoascus destructans (the causative agent of white-nose syndrome) in Asia, an endemic region, and North America, where the pathogen has recently invaded. Although colony sizes of bats and hibernacula temperatures were very similar, both infection prevalence and fungal loads were much lower on bats and in the environment in Asia than North America. These results indicate that transmission intensity and pathogen growth are lower in Asia, likely due to higher host resistance to pathogen growth in this endemic region, and not due to host tolerance, lower transmission due to smaller populations, or lower environmentally driven pathogen growth rate. Disease filtering also appears to be favouring initially resistant species in North America. More broadly, determining the mechanisms allowing species persistence in endemic regions can help identify species at greater risk of extinction in introduced regions, and determine the consequences for disease dynamics and host-pathogen coevolution. © 2016 The Author(s).

  12. Postpartum weight change among HIV-infected mothers by antiretroviral prophylaxis and infant feeding modality in a research setting.

    PubMed

    Cames, Cecile; Cournil, Amandine; de Vincenzi, Isabelle; Gaillard, Philippe; Meda, Nicolas; Luchters, Stanley; Nduati, Ruth; Naidu, Kevindra; Newell, Marie-Louise; Read, Jennifer S; Bork, Kirsten

    2014-01-02

    To assess the relationship between infant feeding, triple-antiretroviral prophylaxis and weight from 2 weeks (baseline) to 6 months postpartum among HIV-infected mothers in a mother-to-child transmission (MTCT) of HIV-prevention trial in five sub-Saharan African sites. HIV-infected pregnant women with CD4 cell counts of 200-500 cells/μl were counselled to choose breastfeeding to 6 months or replacement feeding from delivery. They were randomized to receive perinatal zidovudine and single-dose nevirapine or triple-antiretroviral MTCT prophylaxis until breastfeeding cessation. Mixed-effect linear models were used to compare maternal weight trajectories over time by infant feeding mode. Antiretroviral prophylaxis and BMI at baseline were examined as potential effect modifiers. Among 797 mothers, 620 (78%) initiated breastfeeding. Wasting (BMI <18.5) was rare at baseline (2%), whereas overweight/obesity (BMI ≥ 25) was common (40%). In the model including all women, breastfeeding was not associated with weight loss up to 6 months, irrespective of baseline BMI and antiretroviral prophylaxis. Triple-antiretroviral prophylaxis was associated with weight gain among replacement-feeding mothers with baseline BMI at least 25 (+0.54 kg/month; P < 0.0001). In the model including breastfeeding mothers only, triple-antiretroviral prophylaxis was associated with weight gain among mothers with baseline BMI at least 25 who ceased breastfeeding before 3 months postpartum (+0.33 kg/month; P = 0.03). The results suggest that breastfeeding up to 6 months postpartum is not detrimental for postpartum weight among well nourished HIV-infected mothers at intermediate-disease stage. In the absence of breastfeeding or after weaning, triple-antiretroviral prophylaxis is associated with weight gain among women with high BMI, even after cessation of prophylaxis.

  13. [Views of students of extension nursing studies about cancer prophylaxis].

    PubMed

    Majewski, Włodzimierz D; Majewska, Aleksandra

    2007-01-01

    Cancer prophylaxis seems nowadays to be the more and more powerful tool in fight with these serious diseases. The aim of this work is to find out opinions of students of nursing extension studies on contemporary cancer prophylaxis. The question about possibilities of practical efforts for prophylaxis and early detection of cancer was directed to 160 students of four consecutive years (2002-2006), at the end of the fourth year of lasting five and a half years extension nursing studies, during ending exam on subject: oncological nursing. There were 154 women and 6 men, predominantly at their third decade of life, with nursing experience approximately more than 5 years. Out of 160 asked students, 131 of them firstly indicated necessity of breast cancer prophylaxis, 117 mentioned lung cancer, 113 cervix cancer, 95 colorectal cancer, 33 prostate cancer. In families with cancer problems, more frequent control investigations (23 answers), and genetic tests (16) were called for. Patients should be qualified to appropriate risk groups (13) and controlled more frequently there (24). Apart from necessary wide education in media (126) personal contact with patient to discuss his or her personal problems relating to cancer is needed (91). If atypical symptoms are self-detected by patients it should alert them to not neglect and contact family physician (33). Healthy diet (62) containing fresh vegetables and fruits (73), high fibre diet (42) with less animal fat (38) and less red meat (30), containing no preservative agents (45) is recommended. Increased physical activity (84) to cease or reduce smoking (102), and alcohol intake (55), limited exposition to ultraviolet rays (49), and systematic controls of breast (105), uterus cervix (88), lungs (77), colon (55) and prostate (28) are proposed. The pollution of environment by combustion gases and smokes (34) not excluding risk factors of medical workplace (29) are mentioned as cancerogenic factors. In the time of increasing

  14. Assessment of evidence-based dental prophylaxis education in postdoctoral pediatric dentistry programs.

    PubMed

    Redford-Badwal, Deborah A; Nainar, S M Hashim

    2002-09-01

    The objective of the study was to investigate various aspects of evidence-based dental prophylaxis education in postdoctoral pediatric dentistry training programs in the United States. An anonymous nationwide postal survey of fifty-two postdoctoral pediatric dentistry program directors was conducted in September 2001. The survey had a response rate of 75 percent with all geographic regions of the nation represented and with a preponderance of university-based programs (62 percent). Most of the training programs (74 percent) routinely recommended dental prophylaxis for all recall patients. The proportion of programs that recommended dental prophylaxis for the following indications were: plaque, stain and/or calculus removal--97 percent; caries prevention--59 percent; prior to topical fluoride application--67 percent; prior to sealant application--62 percent; and for behavioral modification--77 percent. Most training programs (77 percent) defined dental prophylaxis as both rubber cup pumice prophylaxis and toothbrush prophylaxis. However, only one-half of the training programs (51 percent) had modified their teaching to substitute toothbrush prophylaxis in lieu of rubber cup pumice prophylaxis. In conclusion, only one half of postdoctoral pediatric dentistry training programs in the United States teach evidence-based practice of dental prophylaxis for recall patients.

  15. Reduction in surgical antibiotic prophylaxis expenditure and the rate of surgical site infection by means of a protocol that controls the use of prophylaxis.

    PubMed

    Gomez, Marisa I; Acosta-Gnass, Silvia I; Mosqueda-Barboza, Luisa; Basualdo, Juan A

    2006-12-01

    To evaluate the effectiveness of an intervention based on training and the use of a protocol with an automatic stop of antimicrobial prophylaxis to improve hospital compliance with surgical antibiotic prophylaxis guidelines. An interventional study with a before-after trial was conducted in 3 stages: a 3-year initial stage (January 1999 to December 2001), during which a descriptive-prospective survey was performed to evaluate surgical antimicrobial prophylaxis and surgical site infections; a 6-month second stage (January to June 2002), during which an educational intervention was performed regarding the routine use of a surgical antimicrobial prophylaxis request form that included an automatic stop of prophylaxis (the "automatic-stop prophylaxis form"); and a 3-year final stage (July 2002 to June 2005), during which a descriptive-prospective survey of surgical antimicrobial prophylaxis and surgical site infections was again performed. An 88-bed teaching hospital in Entre Ríos, Argentina. A total of 3,496 patients who underwent surgery were included in the first stage of the study and 3,982 were included in the final stage. Comparison of the first stage of the study with the final stage revealed that antimicrobial prophylaxis was given at the appropriate time to 55% and 88% of patients, respectively (relative risk [RR], 0.27 [95% confidence interval {CI}, 0.25-0.30]; P<.01); the antimicrobial regimen was adequate in 74% and 87% of patients, respectively (RR, 0.50 [95% CI, 0.45-0.55]; P<.01); duration of the prophylaxis was adequate in 44% and 55% of patients, respectively (RR, 0.80 [95% CI, 0.77-0.84]; P<.01); and the surgical site infection rates were 3.2% and 1.9%, respectively (RR, 0.59 [95% CI, 0.44-0.79]; P<.01). Antimicrobial expenditure was 10,678.66 US$ per 1,000 patient-days during the first stage and 7,686.05 US$ per 1,000 patient-days during the final stage (RR, 0.87 [95% CI, 0.86-0.89]; P<.01). The intervention based on training and application of a

  16. Secreted HSP Vaccine for Malaria Prophylaxis

    DTIC Science & Technology

    2016-10-26

    AWARD NUMBER: W81XWH-13-2-0098 TITLE: Secreted HSP Vaccine for Malaria Prophylaxis PRINCIPAL INVESTIGATOR: Dr. Natasa Strbo CONTRACTING ORGANIZATION...Secreted HSP Vaccine for Malaria Prophylaxis 4. TITLE AND SUBTITLE NATASA STRBO, M.D., D.SC NAME(S) AND E-M tzA UNIVERS]TY OF MTAMI 1600 NW 1OTH AVENUE ROOM...Here we developed malaria vaccine that relies on secreted gp96-lg chaperon-ing Plasmodium falciparum antigenic sporozoite proteins CSP and AMA1. The

  17. Hybrid stochastic framework predicts efficacy of prophylaxis against HIV: An example with different dolutegravir prophylaxis schemes.

    PubMed

    Duwal, Sulav; Dickinson, Laura; Khoo, Saye; von Kleist, Max

    2018-06-01

    To achieve the 90-90-90 goals set by UNAIDS, the number of new HIV infections needs to decrease to approximately 500,000 by 2020. One of the 'five pillars' to achieve this goal is pre-exposure prophylaxis (PrEP). Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP. Despite its advantages, Truvada is costly and requires individuals to adhere to the once-daily regimen. To improve PrEP, many next-generation regimen, including long-acting formulations, are currently investigated. However, pre-clinical testing may not guide candidate selection, since it often fails to translate into clinical efficacy. On the other hand, quantifying prophylactic efficacy in the clinic is ethically problematic and requires to conduct long (years) and large (N>1000 individuals) trials, precluding systematic evaluation of candidates and deployment strategies. To prioritize- and help design PrEP regimen, tools are urgently needed that integrate pharmacological-, viral- and host factors determining prophylactic efficacy. Integrating the aforementioned factors, we developed an efficient and exact stochastic simulation approach to predict prophylactic efficacy, as an example for dolutegravir (DTG). Combining the population pharmacokinetics of DTG with the stochastic framework, we predicted that plasma concentrations of 145.18 and 722.23nM prevent 50- and 90% sexual transmissions respectively. We then predicted the reduction in HIV infection when DTG was used in PrEP, PrEP 'on demand' and post-exposure prophylaxis (PEP) before/after virus exposure. Once daily PrEP with 50mg oral DTG prevented 99-100% infections, and 85% of infections when 50% of dosing events were missed. PrEP 'on demand' prevented 79-84% infections and PEP >80% when initiated within 6 hours after virus exposure and continued for as long as possible. While the simulation framework can easily be adapted to other PrEP candidates, our simulations indicated that oral 50mg DTG is non-inferior to

  18. Long-term, low-dose prophylaxis against urinary tract infections in young children.

    PubMed

    Brandström, Per; Hansson, Sverker

    2015-03-01

    Urinary tract infection (UTI) affects about 2 % of boys and 8 % of girls during the first 6 years of life with Escherichia coli as the predominant pathogen. Symptomatic UTI causes discomfort and distress, and carries a risk of inducing renal damage. The strong correlation between febrile UTI, dilating vesicoureteral reflux (VUR), and renal scarring led to the introduction of antibiotic prophylaxis for children with VUR to reduce the rate of UTI recurrence. It became common practice to use prophylaxis for children with VUR and other urinary tract abnormalities. This policy has been challenged because of a lack of scientific support. Now, randomized controlled studies are available that compare prophylaxis to no treatment or placebo. They show that children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. Dilating VUR may still be an indication for prophylaxis in young children. After the first year of life, boys have very few recurrences and do not benefit from prophylaxis. Girls with dilating VUR, on the other hand, are more prone to recurrences and benefit from prophylaxis. There has been a decline in the use of prophylaxis due to questioning of its efficacy, increasing bacterial resistance, and a propensity to low adherence to medication. Alternative measures to reduce UTI recurrences should be emphasized. However, in selected patients carefully followed, prophylaxis can protect from recurrent UTI and long-term sequelae. 1. There is a strong correlation between UTI, VUR, and renal scarring. 2. Children with normal urinary tracts or non-dilating VUR do not benefit from prophylaxis. 3. Young children, mainly girls, with dilating VUR are at risk of recurrent UTI and acquired renal scarring and seem to gain from antibiotic prophylaxis. 4. Increasing bacterial resistance and low adherence with prescribed medication is a major obstacle to successful antibiotic prophylaxis.

  19. TR34/L98H Mutation in CYP51A Gene in Aspergillus fumigatus Clinical Isolates During Posaconazole Prophylaxis: First Case in Korea.

    PubMed

    Lee, Hyeon-Jeong; Cho, Sung-Yeon; Lee, Dong-Gun; Park, Chulmin; Chun, Hye-Sun; Park, Yeon-Joon

    2018-06-01

    Azole resistance in Aspergillus fumigatus is an emerging problem, especially in immunocompromised patients. It has been reported worldwide, including in Asia, but has not yet been reported in Korea. Here, we report a case of invasive pulmonary aspergillosis (IPA) caused by azole-resistant A. fumigatus that developed in a hematopoietic stem cell transplantation recipient during posaconazole prophylaxis for immunosuppressive therapy of graft-versus-host diseases. We identified TR34/L98H/S297T/F495L mutation in the CYP51A gene of A. fumigatus clinical isolate obtained from bronchial washing fluid. Minimal inhibitory concentrations for itraconazole, voriconazole, and posaconazole were > 16, 1, and 4 μg/mL, respectively. While IPA improved partially under voriconazole treatment, the patient died from carbapenemase-producing Klebsiella pneumoniae bacteremia. Further epidemiological surveillance studies are warranted.

  20. Targeting the complex interactions between microbiota, host epithelial and immune cells in inflammatory bowel disease.

    PubMed

    Hirata, Yoshihiro; Ihara, Sozaburo; Koike, Kazuhiko

    2016-11-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder that includes two distinct disease categories: ulcerative colitis and Crohn's disease. Epidemiological, genetic, and experimental studies have revealed many important aspects of IBD. Genetic susceptibility, inappropriate immune responses, environmental changes, and intestinal microbiota are all associated with the development of IBD. However, the exact mechanisms of the disease and the interactions among these pathogenic factors are largely unknown. Here we introduce recent findings from experimental colitis models that investigated the interactions between host genetic susceptibility and gut microbiota. In addition, we discuss new strategies for the treatment of IBD, focusing on the complex interactions between microbiota and host epithelial and immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes

    PubMed Central

    Radolf, Justin D.; Caimano, Melissa J.; Stevenson, Brian; Hu, Linden T.

    2012-01-01

    In little more than 30 years, Lyme disease, which is caused by the spirochaete Borrelia burgdorferi, has risen from relative obscurity to become a global public health problem and a prototype of an emerging infection. During this period, there has been an extraordinary accumulation of knowledge on the phylogenetic diversity, molecular biology, genetics and host interactions of B. burgdorferi. In this Review, we integrate this large body of information into a cohesive picture of the molecular and cellular events that transpire as Lyme disease spirochaetes transit between their arthropod and vertebrate hosts during the enzootic cycle. PMID:22230951

  2. Hepatitis B reactivation and timing for prophylaxis

    PubMed Central

    Tuna, Nazan; Karabay, Oguz

    2015-01-01

    It is known that immunotherapy and cancer chemotherapy may cause hepatitis B virus (HBV) reactivation in hepatitis B surface antigen carriers and inactive chronic hepatitis B patients. Guidelines recommend antiviral prophylaxis regardless of HBV DNA levels to prevent reactivation. We read from the article written by Liu et al that Lamivudine was given inadequate time for antiviral prophylaxis. PMID:25717269

  3. GRAFT-VERSUS-HOST DISEASE PANUVEITIS AND BILATERAL SEROUS DETACHMENTS: MULTIMODAL IMAGING ANALYSIS.

    PubMed

    Jung, Jesse J; Chen, Michael H; Rofagha, Soraya; Lee, Scott S

    2017-01-01

    To report the multimodal imaging findings and follow-up of a case of graft-versus-host disease-induced bilateral panuveitis and serous retinal detachments after allogenic bone marrow transplant for acute myeloid leukemia. A 75-year-old black man presented with acute decreased vision in both eyes for 1 week. Clinical examination and multimodal imaging, including spectral domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and swept-source optical coherence tomography angiography (Investigational Device; Carl Zeiss Meditec Inc) were performed. Clinical examination of the patient revealed anterior and posterior inflammation and bilateral serous retinal detachments. Ultra-widefield fundus autofluorescence demonstrated hyperautofluorescence secondary to subretinal fluid; and fluorescein angiography revealed multiple areas of punctate hyperfluorescence, leakage, and staining of the optic discs. Spectral domain and enhanced depth imaging optical coherence tomography demonstrated subretinal fluid, a thickened, undulating retinal pigment epithelium layer, and a thickened choroid in both eyes. En-face swept-source optical coherence tomography angiography did not show any retinal vascular abnormalities but did demonstrate patchy areas of decreased choriocapillaris flow. An extensive systemic infectious and malignancy workup was negative and the patient was treated with high-dose oral prednisone immunosuppression. Subsequent 6-month follow-up demonstrated complete resolution of the inflammation and bilateral serous detachments after completion of the prednisone taper over a 3-month period. Graft-versus-host disease panuveitis and bilateral serous retinal detachments are rare complications of allogenic bone marrow transplant for acute myeloid leukemia and can be diagnosed with clinical and multimodal imaging analysis. This form of autoimmune inflammation may occur after the recovery of T-cell activity within the donor graft targeting the host

  4. Antibiotic Prophylaxis for Gynecologic Procedures prior to and during the Utilization of Assisted Reproductive Technologies: A Systematic Review.

    PubMed

    Pereira, Nigel; Hutchinson, Anne P; Lekovich, Jovana P; Hobeika, Elie; Elias, Rony T

    2016-01-01

    The use of assisted reproductive technologies (ART) has increased steadily. There has been a corresponding increase in the number of ART-related procedures such as hysterosalpingography (HSG), saline infusion sonography (SIS), hysteroscopy, laparoscopy, oocyte retrieval, and embryo transfer (ET). While performing these procedures, the abdomen, upper vagina, and endocervix are breached, leading to the possibility of seeding pelvic structures with microorganisms. Antibiotic prophylaxis is therefore important to prevent or treat any procedure-related infections. After careful review of the published literature, it is evident that routine antibiotic prophylaxis is generally not recommended for the majority of ART-related procedures. For transcervical procedures such as HSG, SIS, hysteroscopy, ET, and chromotubation, patients at risk for pelvic infections should be screened and treated prior to the procedure. Patients with a history of pelvic inflammatory disease (PID) or dilated fallopian tubes are at high risk for postprocedural infections and should be given antibiotic prophylaxis during procedures such as HSG, SIS, or chromotubation. Antibiotic prophylaxis is recommended prior to oocyte retrieval in patients with a history of endometriosis, PID, ruptured appendicitis, or multiple prior pelvic surgeries.

  5. Emerging prion disease drives host selection in a wildlife population

    USGS Publications Warehouse

    Robinson, Stacie J.; Samuel, Michael D.; Johnson, Chad J.; Adams, Marie; McKenzie, Debbie I.

    2012-01-01

    Infectious diseases are increasingly recognized as an important force driving population dynamics, conservation biology, and natural selection in wildlife populations. Infectious agents have been implicated in the decline of small or endangered populations and may act to constrain population size, distribution, growth rates, or migration patterns. Further, diseases may provide selective pressures that shape the genetic diversity of populations or species. Thus, understanding disease dynamics and selective pressures from pathogens is crucial to understanding population processes, managing wildlife diseases, and conserving biological diversity. There is ample evidence that variation in the prion protein gene (PRNP) impacts host susceptibility to prion diseases. Still, little is known about how genetic differences might influence natural selection within wildlife populations. Here we link genetic variation with differential susceptibility of white-tailed deer to chronic wasting disease (CWD), with implications for fitness and disease-driven genetic selection. We developed a single nucleotide polymorphism (SNP) assay to efficiently genotype deer at the locus of interest (in the 96th codon of the PRNP gene). Then, using a Bayesian modeling approach, we found that the more susceptible genotype had over four times greater risk of CWD infection; and, once infected, deer with the resistant genotype survived 49% longer (8.25 more months). We used these epidemiological parameters in a multi-stage population matrix model to evaluate relative fitness based on genotype-specific population growth rates. The differences in disease infection and mortality rates allowed genetically resistant deer to achieve higher population growth and obtain a long-term fitness advantage, which translated into a selection coefficient of over 1% favoring the CWD-resistant genotype. This selective pressure suggests that the resistant allele could become dominant in the population within an

  6. Antiepileptic prophylaxis following severe traumatic brain injury within a military cohort.

    PubMed

    Cranley, Mark R; Craner, M; McGilloway, E

    2016-04-01

    Traumatic brain injury increases the risk of both early and late seizures. Antiepileptic prophylaxis reduces early seizures, but their use beyond 1 week does not prevent the development of post-traumatic epilepsy. Furthermore, prolonged prophylaxis exposes patients to side effects of the drugs and has occupational implications. The American Academy of Neurology recommends that antiepileptic prophylaxis should be started for patients with severe traumatic brain injury and discontinued after 1 week. An audit is presented here that investigates the use of prophylaxis in a cohort of military patients admitted to the UK Defence Medical Rehabilitation Centre (DMRC). Data were collected and analysed retrospectively from electronic and paper records between February 2009 and August 2012. The timing and duration of antiepileptic drug use and the incidence of seizures were recorded. During the study period, 52 patients with severe traumatic brain injury were admitted to the rehabilitation centre: 25 patients (48%) were commenced on prophylaxis during the first week following injury while 27 (52%) did not receive prophylaxis. Only one patient (2%) received prophylaxis for the recommended period of 1 week, 22 patients (42%) received prophylaxis for longer than 1 week with a mean duration of 6.2 months. Two patients (4%) had post-traumatic epilepsy and started on treatment at DMRC. The use of antiepileptic prophylaxis varies widely and is generally inconsistent with evidence-based guidance. This exposes some patients to a higher risk of early seizures and others to unnecessary use of antiepileptics. Better implementation of prophylaxis is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. [From Evidence to Health Policy Making: Pre-Exposure Prophylaxis for HIV Prevention].

    PubMed

    Ko, Nai-Ying

    2016-12-01

    Pre-exposure prophylaxis (PrEP), in combination with traditional prevention strategies (such as condom use, voluntary HIV counseling and testing, and treatment for sexually transmitted infections), has been shown to effectively prevent HIV infection. As of September 2015, the World Health Organization recommends that people at substantial risk of HIV infection should be offered PrEP as an additional prevention choice, as part of comprehensive prevention. This article introduces how to apply a systematic review using the methodology of Grading of Recommendations Assessment, Development and Evaluation (GRADE) to write clinical guidelines. With support from the Taiwan Centers for Disease Control, the Taiwan AIDS Society published clinical guidelines for oral pre-exposure prophylaxis in Taiwan. Nurses are responsible to apply evidence-based knowledge and to use their professional influence to shape health policies related to HIV prevention.

  8. Graft-versus-host disease is independent of innate signaling pathways triggered by pathogens in host hematopoietic cells.

    PubMed

    Li, Hongmei; Matte-Martone, Catherine; Tan, Hung Sheng; Venkatesan, Srividhya; McNiff, Jennifer; Demetris, Anthony J; Jain, Dhanpat; Lakkis, Fadi; Rothstein, David; Shlomchik, Warren D

    2011-01-01

    Graft-versus-host disease (GVHD) is initiated by APCs that prime alloreactive donor T cells. In antipathogen responses, Ag-bearing APCs receive signals through pattern-recognition receptors, including TLRs, which induce the expression of costimulatory molecules and production of inflammatory cytokines, which in turn mold the adaptive T cell response. However, in allogeneic hematopoietic stem cell transplantation (alloSCT), there is no specific pathogen, alloantigen is ubiquitous, and signals that induce APC maturation are undefined. To investigate APC activation in GVHD, we used recipient mice with hematopoietic cells genetically deficient in pathways critical for APC maturation in models in which host APCs are absolutely required. Strikingly, CD8-mediated and CD4-mediated GVHD were similar whether host APCs were wild-type or deficient in MyD88, TRIF, or MyD88 and TRIF, which excludes essential roles for TLRs and IL-1β, the key product of inflammasome activation. Th1 differentiation was if anything augmented when APCs were MyD88/TRIF(-/-), and T cell production of IFN-γ did not require host IL-12. GVHD was also intact when APCs lacked the type I IFNR, which amplifies APC activation pathways that induce type I IFNs. Thus in GVHD, alloreactive T cells can be activated when pathways critical for antipathogen T cell responses are impaired.

  9. Non-observance of guidelines for surgical antimicrobial prophylaxis and surgical-site infections.

    PubMed

    Lallemand, S; Thouverez, M; Bailly, P; Bertrand, X; Talon, D

    2002-06-01

    A prospective multicentre study was conducted to assess major aspects of surgical prophylaxis and to determine whether inappropriate antimicrobial prophylaxis was a factor associated (risk or protective factor) with surgical site infection (SSI). Surgical prophylaxis practices were assessed by analysing four variables: indication, antimicrobial agent, timing and duration. Univariate and multivariate analyses were carried out to identify predictors of SSI among patient-specific, operation-specific and antimicrobial prophylaxis-specific factors. The frequency of SSI was 2.7% (13 SSI in 474 observations). Total compliance of the prescription with guidelines was observed in 41.1% of cases (195 prescriptions). Of the 139 patients who received an inappropriate drug, 126 (90.6%) received a drug with a broader spectrum than the recommended drug. Prophylaxis was prolonged in 71 (87.7%) of the 81 patients who received prophylaxis for inappropriate lengths of time and 43 (61.4%) of the 70 patients who did not receive prophylaxis at the optimal moment were treated too late. Multivariate analysis clearly demonstrated that SSI was associated with multiple procedures (relative risk 8.5), short duration of prophylaxis (relative risk 12.7) and long-term therapy with antimicrobial agents during the previous year (relative risk 8.8). The ecological risk of the emergence of resistance associated with the frequent use of broad-spectrum antibiotics and prophylaxis for longer periods was not offset by individual benefit to the patients who received inappropriate prophylaxis.

  10. A Missed Opportunity for U.S. Perinatal Human Immunodeficiency Virus Elimination: Pre-exposure Prophylaxis During Pregnancy.

    PubMed

    Fruhauf, Timothee; Coleman, Jenell S

    2017-10-01

    To estimate the proportion of women at increased risk of sexual human immunodeficiency virus (HIV) acquisition during pregnancy in a high HIV incidence urban setting to identify those who may be eligible for pre-exposure prophylaxis. We conducted a retrospective cohort study of women who received prenatal care at a large academic center in 2012. Univariable analyses and multiple logistic regression models were built to identify correlates for pre-exposure prophylaxis eligibility. Among 1,637 pregnant women, mean age was 27.6 years (SD 6.3), 59.7% were African American, and 56.0% were single. Based on the Centers for Disease Control and Prevention's guidelines, more than 10% of women were at increased risk for HIV acquisition during pregnancy and eligible for pre-exposure prophylaxis. Younger [adjusted odds ratio (OR) 0.9/1-year increase, 95% CI 0.8-0.9], single (adjusted OR 2.4, 95% CI 1.2-4.8), African American women (adjusted OR 3.3, 95% CI 1.6-6.7) with higher parity (adjusted OR 1.3/one-child increase, 95% CI 1.1-1.5), and who smoked regularly during pregnancy (adjusted OR 1.8, 95% CI 1.0-3.0) had greater odds of being eligible for pre-exposure prophylaxis at any time during pregnancy. Pregnancy is a vulnerable period during which some heterosexual women in urban settings have a high risk for HIV acquisition and stand to benefit from pre-exposure prophylaxis.

  11. Contentious host-microbiota relationship in inflammatory bowel disease--can foes become friends again?

    PubMed

    Satokari, Reetta

    2015-01-01

    Inflammatory bowel diseases (IBDs) are chronic debilitating disorders of unknown etiology, consisting of two main conditions, ulcerative colitis and Crohn's disease. Major advances have recently taken place in human genetic studies of IBD and over 160 risk loci for these two diseases have been uncovered. These genetic data highlight a key role for genes that code for immunological and epithelial barrier functions. Environmental factors also make substantial contributions to the pathogenesis of IBD and account for the growing incidence of the diseases around the world. Intestinal microbiota creates resistance to infection, provides nutrients, and educates the immune system and in many ways has a significant impact on human health. Aberrant microbiota composition and decreased diversity (dysbiotic microbiota) are key etiopathological events in IBD. Dysbiotic microbiota can lead to loss of normal, regulatory immune effects in the gut mucosa. This may play a central role in the development and perpetuation of chronic inflammation. Further, the expression of specific innate immune receptors that recognize microbes is altered in the IBD epithelium. Therefore, the combination of host side epithelial barrier functions and the presence of dysbiotic microbiota in the gut together promote inflammation. New therapeutic options targeting microbiota are currently considered for IBD and they may, in the future, provide means to reverse the pathogenic host-microbiota relationship into a symbiotic one. In this review, the focus is on the intestinal microbiota and host-microbe interactions in IBD.

  12. Post-Exposure Prophylaxis

    MedlinePlus

    ... gov Reason Number 87 to Get an HIV Test Veterans #DoingItMyWay – Testing for HIV June 27th is National HIV Testing Day Ryan White and HIV Testing Day 2018 Additional Resources AIDSInfo – Occupational Post-exposure Prophylaxis (PEP) Guidelines AIDSInfo – Nonoccupational Post-exposure ...

  13. Host mating system and the spread of a disease-resistant allele in a population

    USGS Publications Warehouse

    DeAngelis, D.L.; Koslow, Jennifer M.; Jiang, J.; Ruan, S.

    2008-01-01

    The model presented here modifies a susceptible-infected (SI) host-pathogen model to determine the influence of mating system on the outcome of a host-pathogen interaction. Both deterministic and stochastic (individual-based) versions of the model were used. This model considers the potential consequences of varying mating systems on the rate of spread of both the pathogen and resistance alleles within the population. We assumed that a single allele for disease resistance was sufficient to confer complete resistance in an individual, and that both homozygote and heterozygote resistant individuals had the same mean birth and death rates. When disease invaded a population with only an initial small fraction of resistant genes, inbreeding (selfing) tended to increase the probability that the disease would soon be eliminated from a small population rather than become endemic, while outcrossing greatly increased the probability that the population would become extinct due to the disease.

  14. Evaluation of immunogenicity and efficacy of anthrax vaccine adsorbed for postexposure prophylaxis.

    PubMed

    Ionin, Boris; Hopkins, Robert J; Pleune, Brett; Sivko, Gloria S; Reid, Frances M; Clement, Kristin H; Rudge, Thomas L; Stark, Gregory V; Innes, Alison; Sari, Suha; Guina, Tina; Howard, Cris; Smith, Jeffrey; Swoboda, M Lisa; Vert-Wong, Ekaterina; Johnson, Virginia; Nabors, Gary S; Skiadopoulos, Mario H

    2013-07-01

    Antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. Such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (PEP). In a rabbit PEP study, animals were subjected to lethal challenge with aerosolized Bacillus anthracis spores and then were treated with levofloxacin with or without concomitant intramuscular (i.m.) vaccination with anthrax vaccine adsorbed (AVA) (BioThrax; Emergent BioDefense Operations Lansing LLC, Lansing, MI), administered twice, 1 week apart. A significant increase in survival rates was observed among vaccinated animals compared to those treated with antibiotic alone. In preexposure prophylaxis studies in rabbits and nonhuman primates (NHPs), animals received two i.m. vaccinations 1 month apart and were challenged with aerosolized anthrax spores at day 70. Prechallenge toxin-neutralizing antibody (TNA) titers correlated with animal survival postchallenge and provided the means for deriving an antibody titer associated with a specific probability of survival in animals. In a clinical immunogenicity study, 82% of the subjects met or exceeded the prechallenge TNA value that was associated with a 70% probability of survival in rabbits and 88% probability of survival in NHPs, which was estimated based on the results of animal preexposure prophylaxis studies. The animal data provide initial information on protective antibody levels for anthrax, as well as support previous findings regarding the ability of AVA to provide added protection to B. anthracis-infected animals compared to antimicrobial treatment alone.

  15. Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney recipients on early and late post-transplantation lymphoproliferative disorder onset: a retrospective cohort study.

    PubMed

    Ville, Simon; Imbert-Marcille, Berthe-Marie; Coste-Burel, Marianne; Garandeau, Claire; Meurette, Aurélie; Cantarovitch, Diego; Giral, Magali; Hourmant, Maryvonne; Blancho, Gilles; Dantal, Jacques

    2018-05-01

    Post-transplantation lymphoproliferative disorder (PTLD) pathogenesis is related to EBV infection. Mismatch with the donor (EBV D+/R-) is the main risk factor for both early PTLD (<1 year post-transplantation) and late (>1 year). In these at-risk patients, the role of antiviral prophylaxis for preventing PTLD remains controversial. We analyzed the impact of antiviral drugs given to prevent CMV disease in a monocentric retrospective cohort of 73 adult kidney or kidney-pancreas EBV-seronegative recipients, transplanted between 01/01/2000 and 01/01/2016. Thirty-seven (50.7%, prophylaxis group) received (val-)aciclovir or (val-)ganciclovir for 3-6 months and 36 (49.3%, no-prophylaxis group) received no-prophylaxis. Mean follow-up was 69 ± 7.2 months in the prophylaxis group and 91 ± 10.3 months in the no-prophylaxis group. Monitoring of EBV PCR revealed that prophylaxis delayed primary infection at 100 days (43% vs. 84%, P = 0.02). Early PTLD incidence was not different between groups (4/37 vs. 4/36, P = 0.99). Concerning late events, EBV-related neoplasia incidence was significantly lower in treated patients among whom no cases were observed, while in the no-prophylaxis group 6 cases were reported (P = 0.02). Despite a weak level of evidence our study suggests that antiviral prophylaxis could prevent late onset PTLD. © 2017 Steunstichting ESOT.

  16. SURVIVAL OF THE RED BLOOD CELLS OF BLOOD TREATED WITH GENTIAN VIOLET. ITS IMPORTANCE IN THE PROPHYLAXIS OF CHAGAS DISEASE TRANSMITTED DURING TRANSFUSION (in Spanish)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maspes, V.; Pieroni, R.R.; Mellone, O.

    1959-01-01

    The utility of adding gentian violet to blood to be transfused for prophylaxis of Chanas disease is discussed. It is quite useful in regions where a high percentage of blood donore are infected, The survivial of the erythrocytes in blood treated with sufficient gentian violet to kill Trypanosoma Cruzi (1: 4,000) is studied. The study was made at 4 deg C with chromium as the labeling substance, Mean cell life values found varied from 66 to 91 days. It was concluded that other properties of erythrcytes are not significantly changed, Therefore, the wide use of gentian violet in the prophylaxismore » of Chagas disease is recommended. (auth)« less

  17. The lyme disease pathogen has no effect on the survival of its rodent reservoir host.

    PubMed

    Voordouw, Maarten J; Lachish, Shelly; Dolan, Marc C

    2015-01-01

    Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans but few studies have investigated whether this pathogen reduces the fitness of its reservoir hosts under natural conditions. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus. Our estimates of the probability of infection varied by an order of magnitude (0.051 to 0.535) and were consistent with our understanding of Lyme disease in the Northeastern United States. B. burgdorferi establishes a chronic avirulent infection in their rodent reservoir hosts because this pathogen depends on rodent mobility to achieve transmission to its sedentary tick vector. The estimates of B. burgdorferi infection risk will facilitate future theoretical studies on the epidemiology of Lyme disease.

  18. Oral Disease Profiles in Chronic Graft versus Host Disease

    PubMed Central

    Fassil, H.; Mays, J.W.; Edwards, D.; Baird, K.; Steinberg, S.M.; Cowen, E.W.; Naik, H.; Datiles, M.; Stratton, P.; Gress, R.E.; Pavletic, S.Z.

    2015-01-01

    At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer’s tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral c

  19. Oral disease profiles in chronic graft versus host disease.

    PubMed

    Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z

    2015-04-01

    At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral c

  20. NOD2, an Intracellular Innate Immune Sensor Involved in Host Defense and Crohn's Disease

    PubMed Central

    Strober, Warren; Watanabe, Tomohiro

    2013-01-01

    Nucleotide binding oligomerization domain 2 (NOD2) is an intracellular sensor for small peptides derived from the bacterial cell wall component, peptidoglycan. Recent studies have uncovered unexpected functions of NOD2 in innate immune responses such as induction of type I IFN and facilitation of autophagy; moreover, they have disclosed extensive cross-talk between NOD2 and Toll-like receptors which plays an indispensable role both in host defense against microbial infection and in the development of autoimmunity. Of particular interest, polymorphisms of CARD15 encoding NOD2 are associated with Crohn's disease and other autoimmune states such as graft versus host disease. In this review, we summarize recent findings regarding normal functions of NOD2 and discuss the mechanisms by which NOD2 polymorphisms associated with Crohn's disease lead to intestinal inflammation. PMID:21750585

  1. Compliance with the 2009 Royal College of Obstetricians and Gynaecologists guidelines for venous thromboembolic disease prophylaxis in pregnancy and postpartum period in Uruguay.

    PubMed

    Grille, Sofía; Vitureira, Gerardo; Morán, Rosario; Retamosa, Lucía; Alonso, Valeria; Gómez, Luis M; Quartara, Federico; Feldman, Florencia; López, Valentina; Turcatti, Paola; Castro, Viviana; Sosa, Leonardo; Guillermo, Cecilia; Díaz, Lilián; Stevenazzi, Mariana

    2018-04-01

    : Venous thromboembolism remains as one of the leading causes of maternal death. Prevention of venous thromboembolism in the obstetric population is challenging as recommendations for prophylaxis have low grade of evidence. Risk factors and prophylaxis guidelines have been highlighted by Royal College of Obstetricians and Gynaecologists. In 2014, we developed a written alert following this guidelines to guide thromboprophylaxis. The aim of this study is to assess recommendations compliance. This study was conducted at University-Hospital in Uruguay from January 2014 to December 2016. A total of 1035 women were enrolled and stratified in high, intermediate or low risk based on Royal College of Obstetricians and Gynaecologists guidelines. Thromboprophylaxis was recommended for women at intermediate and high risk. Women were followed up to assess symptomatic thromboembolism or haemorrhagic complications. A total of 309 were pregnant and 731 puerperal. Median age was 24 (19-29) years old. Of them, 3.0% (n = 31) were at high risk and 35.4% (n = 366) at intermediate risk. All high-risk women received prophylaxis with low-molecular-weight heparin. Of the 366 intermediate-risk women, 52.7% received prophylaxis. Venous thromboembolism was developed in only one woman of the intermediate group, who had received prophylaxis. Bleeding complications were not observed. Awareness of the thrombotic risk, as conferred by an easy and suitable risk assessment, has the potential to improve venous thromboembolism prophylaxis in pregnant and puerperal women. We have a good guidelines compliance with the written alert in the high-risk women group. However, we have to improve low-molecular-weight heparin indication in intermediate-risk group, especially in postcaesarean women.

  2. Missed opportunities for tetanus postexposure prophylaxis--California, January 2008-March 2014.

    PubMed

    Yen, Cynthia; Murray, Erin; Zipprich, Jennifer; Winter, Kathleen; Harriman, Kathleen

    2015-03-13

    Tetanus is an acute and sometimes fatal disease characterized by sudden muscle contractions. The number of tetanus cases reported annually in the United States has declined significantly since the 1930s and 1940s as a result of the introduction of tetanus vaccines. However, sporadic cases continue to occur in persons who are not up-to-date with tetanus toxoid-containing vaccinations (TT) and do not receive appropriate postexposure prophylaxis (PEP). To assess the extent of these cases, the California Department of Public Health reviewed all tetanus cases reported during January 2008-March 2014. A total of 21 tetanus patients were reported; five (24%) died. An average of three cases were reported each year during 2008-2013; the average annual incidence among patients aged ≥65 years (0.23 cases per 1 million population) was twice that among patients aged 21-64 years (0.10 cases per 1 million population). Of 16 patients with an acute injury before illness and diagnosis, nine (56%) sought medical care, and two (22%) of the nine received appropriate PEP. Although tetanus is rare, it is a life-threatening disease that is preventable. Health care providers should ensure that their patients are up-to-date with TT vaccination and provide appropriate postexposure prophylaxis for patients with wounds.

  3. Hydrogen, a potential safeguard for graft-versus-host disease and graft ischemia-reperfusion injury?

    PubMed Central

    Yuan, Lijuan; Shen, Jianliang

    2016-01-01

    Post-transplant complications such as graft-versus-host disease and graft ischemia-reperfusion injury are crucial challenges in transplantation. Hydrogen can act as a potential antioxidant, playing a preventive role against post-transplant complications in animal models of multiple organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on graft ischemia-reperfusion injury and graft-versus-host disease. Existing data on the effects of hydrogen on ischemia-reperfusion injury related to organ transplantation are specifically reviewed and coupled with further suggestions for future work. The reviewed studies showed that hydrogen (inhaled or dissolved in saline) improved the outcomes of organ transplantation by decreasing oxidative stress and inflammation at both the transplanted organ and the systemic levels. In conclusion, a substantial body of experimental evidence suggests that hydrogen can significantly alleviate transplantation-related ischemia-reperfusion injury and have a therapeutic effect on graft-versus-host disease, mainly via inhibition of inflammatory cytokine secretion and reduction of oxidative stress through several underlying mechanisms. Further animal experiments and preliminary human clinical trials will lay the foundation for hydrogen use as a drug in the clinic. PMID:27652837

  4. Is prophylaxis required for delivery in women with factor VII deficiency?

    PubMed Central

    Baumann Kreuziger, Lisa M.; Morton, Colleen T.; Reding, Mark T.

    2013-01-01

    Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis. PMID:23607277

  5. Is prophylaxis required for delivery in women with factor VII deficiency?

    PubMed

    Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

    2013-11-01

    Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

  6. A review of nanotechnological approaches for the prophylaxis of HIV/AIDS

    PubMed Central

    Date, Abhijit A.; Destache, Christopher J.

    2013-01-01

    Successful treatment and control of HIV/AIDS is one of the biggest challenges of 21st century. More than 33 million individuals are infected with HIV worldwide and more than 2 million new cases of HIV infection have been reported. The situation demands development of effective prevention strategies to control the pandemic of AIDS. Due to lack of availability of an effective HIV vaccine, antiretroviral drugs and nucleic acid therapeutics like siRNA have been explored for HIV prophylaxis. Clinical trials shave shown that antiretroviral drugs, tenofovir and emtricitabine can offer some degree of HIV prevention. However, complete prevention of HIV infection has not been achieved yet. Nanotechnology has brought a paradigm shift in the diagnosis, treatment and prevention of many diseases. The current review discusses potential of various nanocarriers such as dendrimers, polymeric nanoparticles, liposomes, lipid nanocarriers, drug nanocrystals, inorganic nanocarriers and nanofibers in improving efficacy of various modalities available for HIV prophylaxis. PMID:23726227

  7. Management of cytomegalovirus infection and disease in liver transplant recipients

    PubMed Central

    Bruminhent, Jackrapong; Razonable, Raymund R

    2014-01-01

    Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression

  8. Host age modulates within-host parasite competition

    PubMed Central

    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida

    2015-01-01

    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. PMID:25994010

  9. Shared and organism-specific host responses to childhood diarrheal diseases revealed by whole blood transcript profiling.

    PubMed

    DeBerg, Hannah A; Zaidi, Mussaret B; Altman, Matthew C; Khaenam, Prasong; Gersuk, Vivian H; Campos, Freddy D; Perez-Martinez, Iza; Meza-Segura, Mario; Chaussabel, Damien; Banchereau, Jacques; Estrada-Garcia, Teresa; Linsley, Peter S

    2018-01-01

    Globally, diarrheal diseases are a leading cause of death in children under five and disproportionately affect children in developing countries. Children who contract diarrheal diseases are rarely screened to identify the etiologic agent due to time and cost considerations associated with pathogen-specific screening and hence pathogen-directed therapy is uncommon. The development of biomarkers to rapidly identify underlying pathogens could improve treatment options and clinical outcomes in childhood diarrheal diseases. Here, we perform RNA sequencing on blood samples collected from children evaluated in an emergency room setting with diarrheal disease where the pathogen(s) present are known. We determine host response gene signatures specific to Salmonella, Shigella and rotavirus, but not E. coli, infections that distinguish them from each other and from healthy controls. Specifically, we observed differential expression of genes related to chemokine receptors or inflammasome signaling in Shigella cases, such as CCR3, CXCR8, and NLRC4, and interferon response genes, such as IFI44 and OASL, in rotavirus cases. Our findings add insight into the host peripheral immune response to these pathogens, and suggest strategies and limitations for the use host response transcript signatures for diagnosing the etiologic agent of childhood diarrheal diseases.

  10. No. 247-Antibiotic Prophylaxis in Obstetric Procedures.

    PubMed

    van Schalkwyk, Julie; Van Eyk, Nancy

    2017-09-01

    To review the evidence and provide recommendations on antibiotic prophylaxis for obstetrical procedures. Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in obstetrical procedures. Published literature was retrieved through searches of Medline and The Cochrane Library on the topic of antibiotic prophylaxis in obstetrical procedures. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and articles published from January 1978 to June2009 were incorporated in the guideline. Current guidelines published by the American College of Obstetrics and Gynecology were also incorporated. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of this guideline should reduce the cost and harm resulting from the administration of antibiotics when they are not required and the harm resulting from failure to administer antibiotics when they would be beneficial. RECOMMENDATIONS. Copyright © 2017. Published by Elsevier Inc.

  11. High pre-transplant serum nitrate levels predict risk of acute steroid-refractory graft-versus-host disease in the absence of statin therapy

    PubMed Central

    Dietrich, Sascha; Okun, Jürgen G.; Schmidt, Kathrin; Falk, Christine S.; Wagner, Andreas H.; Karamustafa, Suzan; Radujkovic, Aleksandar; Hegenbart, Ute; Ho, Anthony D.; Dreger, Peter; Luft, Thomas

    2014-01-01

    Steroid-refractory graft-versus-host disease is a life-threatening complication after allogeneic stem cell transplantation. Evidence is accumulating that steroid-refractory graft-versus-host disease is associated with endothelial distress. Endothelial cell homeostasis is regulated by nitric oxide, and serum nitrates are derived from nitric oxide synthase activity or dietary sources. In this retrospective study based on 417 patients allografted at our institution we investigated whether quantification of serum nitrates could predict steroid-refractory graft-versus-host disease. Elevated pre-transplant levels of serum nitrates (>26.5 μM) predicted steroid-refractory graft-versus-host disease (P=0.026) and non-relapse mortality (P=0.028), particularly in combination with high pre-transplant angiopoietin-2 levels (P=0.0007 and P=0.021, respectively). Multivariate analyses confirmed serum nitrates as independent predictors of steroid-refractory graft-versus-host disease and non-relapse mortality. Differences in serum nitrate levels did not correlate with serum levels of tumor necrosis factor or C-reactive protein or expression of inducible nitric oxide synthase in blood cells. Patients with high pre-transplant nitrate levels had significantly reduced rates of refractory graft-versus-host disease (P=0.031) when pravastatin was taken. In summary, patients at high risk of developing steroid-refractory graft-versus-host disease could be identified prior to transplantation by serum markers linked to endothelial cell function. Retrospectively, statin medication was associated with a reduced incidence of refractory graft-versus-host disease in this endothelial high-risk cohort. PMID:24142995

  12. Review of thromboembolic prophylaxis in patients attending Cork University Hospital.

    PubMed

    Byrne, Stephen; Weaver, Daniel Timothy

    2013-06-01

    Although preventable, venous thromboembolism remains a common cause of hospital acquired morbidity and mortality. Guidelines, such as the one produced by the American College of Chest Physicians (ACCP), are aimed at reducing hospital associated venous thromboemboli. Unfortunately the majority of studies have revealed inadequate adherence to these guidelines. The objective of this study was to evaluate the use of venous thromboembolism prophylaxis at Cork University Hospital. Cork University Hospital, Wilton, Cork, Ireland. Data from the patient's chart, drug kardex and laboratory results were recorded during April 2010. A Caprini score, a venous thromboembolism risk factor assessment tool, was subsequently calculated for each patient based on data collected. Appropriate prophylaxis was determined after examining data collected, Caprini score and prophylactic regime according to the ACCP 8th edition guidelines. Primary outcome was to analyse adherence to VTE prophylaxis guidelines. A total of 394 patients met the inclusion criteria and were reviewed, of which, 60% (n = 236) were medical and 37% (n = 146) were surgical patients. In total 63% of patients received some form of venous thromboembolism prophylaxis. Furthermore, 54% of medical and 76% of surgical patients received prophylaxis. However only 37% of the patients studied received appropriate thromboprophylaxis according to the ACCP 8th edition guidelines (Geerts et al. in chest 133(6 Suppl):381S-453S, 2008). Additionally 51% of surgical and 27% of medical patients received appropriate prophylaxis. Data collected from Cork University Hospital revealed poor adherence to international venous thromboembolism prophylaxis guidelines. As stated in the ACCP 8th edition guidelines, every hospital should develop a formal strategy for venous thromboembolism prevention (Geerts et al. in chest 133(6 Suppl):381S-453S, 2008). In order to improve adherence to guidelines, Cork University Hospital should develop, implement and

  13. Host persistence or extinction from emerging infectious disease: insights from white-nose syndrome in endemic and invading regions

    PubMed Central

    Hoyt, Joseph R.; Langwig, Kate E.; Sun, Keping; Lu, Guanjun; Parise, Katy L.; Jiang, Tinglei; Foster, Jeffrey T.; Feng, Jiang; Kilpatrick, A. Marm

    2016-01-01

    Predicting species' fates following the introduction of a novel pathogen is a significant and growing problem in conservation. Comparing disease dynamics between introduced and endemic regions can offer insight into which naive hosts will persist or go extinct, with disease acting as a filter on host communities. We examined four hypothesized mechanisms for host–pathogen persistence by comparing host infection patterns and environmental reservoirs for Pseudogymnoascus destructans (the causative agent of white-nose syndrome) in Asia, an endemic region, and North America, where the pathogen has recently invaded. Although colony sizes of bats and hibernacula temperatures were very similar, both infection prevalence and fungal loads were much lower on bats and in the environment in Asia than North America. These results indicate that transmission intensity and pathogen growth are lower in Asia, likely due to higher host resistance to pathogen growth in this endemic region, and not due to host tolerance, lower transmission due to smaller populations, or lower environmentally driven pathogen growth rate. Disease filtering also appears to be favouring initially resistant species in North America. More broadly, determining the mechanisms allowing species persistence in endemic regions can help identify species at greater risk of extinction in introduced regions, and determine the consequences for disease dynamics and host–pathogen coevolution. PMID:26962138

  14. Newborn vitamin K prophylaxis: an analysis of information resources for parents and professionals.

    PubMed

    Miller, Hayleigh; Wheeler, Benjamin; Kerruish, Nikki

    2016-12-02

    Vitamin K prophylaxis represents one of the first healthcare decisions families make for their newborn. Information resources are an important component of this process. This study aimed to identify and analyse written information about vitamin K. Resources concerning vitamin K prophylaxis for both parents and health professionals were accessed through tertiary hospitals in New Zealand and Australia, midwives associated with Queen Mary Maternity Centre (Dunedin, New Zealand), antenatal class providers in the Dunedin, New Zealand area, and an online search of Australian and New Zealand government and hospital websites, as well as the Centre for Disease Control (CDC) in the US. These materials were assessed with regard to coverage of information relevant to vitamin K prophylaxis, whether a statement of the recommended option was included, and information concerning parental choice. In Australia, the majority of centres use the Australian Government National Health and Medical Research Council (NHMRC) resource. In New Zealand, eight different resources are in use. There was variation between resources in all aspects, including use of different incidence rates for vitamin K deficiency bleeding (VKDB). No New Zealand resources were available in languages other than English. The resources for health professionals also varied, and the two available New Zealand consensus statements (Ministry of Health and College of Midwives) differed in terms of their main recommendation. Many different information resources are available regarding vitamin K prophylaxis in New Zealand. Standardisation of such information would be more equitable and would facilitate easier review of content and translation into multiple languages.

  15. Does the arthropod microbiota impact the establishment of vector-borne diseases in mammalian hosts?

    PubMed

    Finney, Constance A M; Kamhawi, Shaden; Wasmuth, James D

    2015-04-01

    The impact of the microbiota on the immune status of its host is a source of intense research and publicity. In comparison, the effect of arthropod microbiota on vector-borne infectious diseases has received little attention. A better understanding of the vector microbiota in relation to mammalian host immune responses is vital, as it can lead to strategies that affect transmission and improve vaccine design in a field of research where few vaccines exist and effective treatment is rare. Recent demonstrations of how microbiota decrease pathogen development in arthropods, and thus alter vector permissiveness to vector-borne diseases (VBDs), have led to renewed interest. However, hypotheses on the interactions between the arthropod-derived microbiota and the mammalian hosts have yet to be addressed. Advances in DNA sequencing technology, increased yield and falling costs, mean that these studies are now feasible for many microbiologists and entomologists. Here, we distill current knowledge and put forward key questions and experimental designs to shed light on this burgeoning research topic.

  16. Graft-versus-host disease causes failure of donor hematopoiesis and lymphopoiesis in interferon-gamma receptor-deficient hosts.

    PubMed

    Delisle, Jean-Sébastien; Gaboury, Louis; Bélanger, Marie-Pier; Tassé, Eliane; Yagita, Hideo; Perreault, Claude

    2008-09-01

    The immunopathologic condition known as graft-versus-host disease (GVHD) results from a type I T-cell process. However, a prototypical type I cytokine, interferon-gamma (IFN-gamma), can protect against several manifestations of GVHD in recipients of major histocompatibility complex (MHC)-mismatched hematopoietic cells. We transplanted hematopoietic cells from C3H.SW donors in wild-type (wt) and IFN-gamma-receptor-deficient (IFN-gammaRKO) MHC-matched C57BL/6 recipients. In IFN-gammaRKO recipients, host cells were unresponsive to IFN-gamma, whereas wt donor cells were exposed to exceptionally high levels of IFN-gamma. From an IFN-gamma perspective, we could therefore evaluate the impact of a loss-of-function on host cells and gain-of-function on donor cells. We found that lack of IFN-gammaR prevented up-regulation of MHC proteins on host cells but did not mitigate damage to most target organs. Two salient phenotypes in IFN-gammaRKO recipients involved donor cells: lymphoid hypoplasia and hematopoietic failure. Lymphopenia was due to FasL-induced apoptosis and decreased cell proliferation. Bone marrow aplasia resulted from a decreased proliferation of hematopoietic stem/progenitor cells that was associated with down-regulation of 2 genes negatively regulated by IFN-gamma: Ccnd1 and Myc. We conclude that IFN-gamma produced by alloreactive T cells may entail a severe graft-versus-graft reaction and could be responsible for cytopenias that are frequently observed in subjects with GVHD.

  17. Cost effectiveness of prophylaxis for opportunistic infections in AIDS. An overview and methodological discussion.

    PubMed

    Freedberg, K A; Paltiel, A D

    1998-08-01

    Dramatic progress has recently been made in defining the pathogenesis and treatment of HIV infection. For the first time in the history of the AIDS epidemic, clinicians have at their disposal an understanding of the replication kinetics of HIV, reliable assays to measure viral load, an increasing number of effective agents to suppress viral replication and to reverse the process of immune system destruction, and a range of options for the treatment and prophylaxis of most of the major opportunistic infections in HIV disease. These remarkable advances are not without their costs, however. New antiretroviral therapies and opportunistic infection prophylaxis regimens impose considerable financial strain on public and private budgets for HIV patient care. They force decision-makers to confront a variety of competing considerations, including issues of length and quality of life, the risks of adverse effects and toxicities, and the dangers of promoting resistance. Questions regarding the continued appropriateness and efficiency of opportunistic infection prevention have prompted increased interest in studies of the cost effectiveness of HIV patient care. In this article, we reviewed the literature on the economic evaluation of prophylaxis for HIV-related complications. Section 1 provides background on recent scientific and clinical advances. Section 2 reviews the state-of-the-art understanding of the cost effectiveness of prophylaxis against specific opportunistic infections. Section 3 broadens the discussion to consider the more general question of optimal allocation of prophylaxis resources across competing opportunistic infections. In Section 4, we briefly examined the influence of cost-effectiveness evaluations on the development and refinement of clinical guidelines for HIV-related opportunistic infection prevention in the US. Section 5 presents some of the methodological challenges that arise in applying the methods of cost-effectiveness analysis to the particular

  18. The cascading pathogenic consequences of Sarcoptes scabiei infection that manifest in host disease

    PubMed Central

    Fraser, Tamieka A.; Lesku, John A.; Simpson, Kellie; Roberts, Georgia L.; Garvey, Jillian; Polkinghorne, Adam; Burridge, Christopher P.; Carver, Scott

    2018-01-01

    Sarcoptic mange, caused by the parasitic mite Sarcoptes scabiei, causes a substantive burden of disease to humans, domestic animals and wildlife, globally. There are many effects of S. scabiei infection, culminating in the disease which hosts suffer. However, major knowledge gaps remain on the pathogenic impacts of this infection. Here, we focus on the bare-nosed wombat host (Vombatus ursinus) to investigate the effects of mange on: (i) host heat loss and thermoregulation, (ii) field metabolic rates, (iii) foraging and resting behaviour across full circadian cycles, and (iv) fatty acid composition in host adipose, bone marrow, brain and muscle tissues. Our findings indicate that mange-infected V. ursinus lose more heat to the environment from alopecia-affected body regions than healthy individuals. Additionally, mange-infected individuals have higher metabolic rates in the wild. However, these metabolic demands are difficult to meet, because infected individuals spend less time foraging and more time inactive relative to their healthy counterparts, despite being outside of the burrow for longer. Lastly, mange infection results in altered fatty acid composition in adipose tissue, with increased amounts of omega-6 acids, and decreased amounts of omega-3 acids, a consequence of chronic cutaneous inflammation and inhibition of anti-inflammatory responses. These findings highlight the interactions of mange-induced physiological and behavioural changes, and have implications for the treatment and rehabilitation of infected individuals. PMID:29765692

  19. Future therapeutic directions for factor Xa inhibition in the prophylaxis and treatment of thrombotic disorders.

    PubMed

    Turpie, Alexander G G

    2003-11-15

    The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy.

  20. Impact of High-Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients.

    PubMed

    Siodlak, Magdalena; Jorgenson, Margaret R; Descourouez, Jillian L; Leverson, Glen E; Mandelbrot, Didier A; Smith, Jeannina A; Redfield, Robert R

    2018-05-25

    To evaluate the clinical course and long-term impact of high-dose acyclovir (HD-A, 800 mg 4 times daily) cytomegalovirus (CMV) prophylaxis failure in a CMV- seropositive abdominal solid organ transplant population. Retrospective cohort study. Tertiary academic medical center. A total of 691 adults who received solid organ transplants between January 1, 2008, and June 30, 2013, without lymphocyte-depleting induction and were prescribed 3 months of HD-A prophylaxis at the time of hospital discharge; of those patients, 54 experienced prophylaxis failure, defined as CMV detected via molecular diagnostics or on biopsy while receiving HD-A (prophylaxis failure group), and 637 did not (comparator group). Mean ± SD time to failure was 64 ± 23 days; 98% (53/54 patients) was attributable to viremia diagnosed via positive polymerase chain reaction (PCR). Of these 53 patients, 34% (18 patients) were below the quantifiable range when detected. Median initial and peak CMV PCR for quantifiable readings were 1531 IU/ml (interquartile range [IQR] <250-2947) and 4442 IU/ml (IQR <250-32,500; 19 (36%) had a single detectable CMV PCR. Treatment was required in 56% (30/54 patients), with a median duration of 63 days; 40% (12 patients) were treated with valganciclovir alone, the remainder received intravenous ganciclovir. CMV disease resulted in hospitalization in 28% (15 patients). Immunosuppression was modified in 52% (28 patients). The rate of CMV recurrence after 100 days was significantly higher in the prophylaxis failure group (59% vs 13%, p<0.0001). Higher rates of rejection; higher rates of 1-, 3-, and 5-year graft failure; and higher rates of 1-, 3-, and 5-year mortality were noted in the prophylaxis failure group on univariate analysis (43% vs 30%, p=0.045; 8%, 17%, and 34% vs 4%, 12%, and 17%, p=0.006; and 6%, 17%, and 26% vs 1%, 6%, and 10%, p=0.003, respectively). Multivariate analysis demonstrated an increased risk of graft failure in the prophylaxis failure group (hazard

  1. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies.

    PubMed

    Hanagata, Nobutaka

    2017-01-01

    Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.

  2. Deep Vein Thrombosis Prophylaxis: State of the Art.

    PubMed

    Lieberman, Jay R

    2018-03-21

    The selection of a prophylaxis regimen to prevent symptomatic pulmonary embolism and deep vein thrombosis is a balance between efficacy and safety. The latest American Academy of Orthopaedic Surgeons guideline recommended that either chemoprophylaxis or mechanical prophylaxis be used after total joint arthroplasty but did not recommend specific agents. However, the latest evidence-based American College of Chest Physicians guideline recommended a variety of chemoprophylaxis and mechanical agents for a minimum of 10 to 14 days after total joint arthroplasty. Risk stratification is the key to the selection of the appropriate prophylaxis regimen for the individual patient, but the optimal risk stratification protocol still needs to be developed. Copyright © 2018. Published by Elsevier Inc.

  3. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents).

    PubMed

    Baddley, J W; Cantini, F; Goletti, D; Gómez-Reino, J J; Mylonakis, E; San-Juan, R; Fernández-Ruiz, M; Torre-Cisneros, J

    2018-06-01

    The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. To review, from an Infectious Diseases perspective, the safety profile of agents targeting tumour necrosis factor-α (TNF-α) and to suggest preventive recommendations. Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family. Preclinical and clinical evidence indicate that anti-TNF-α therapy (infliximab, adalimumab, golimumab, certolizumab pegol and etanercept) is associated with a two-to four-fold increase in the risk of active tuberculosis and other granulomatous conditions (mostly resulting from the reactivation of a latent infection). In addition, it may lead to the occurrence of other serious infections (bacterial, fungal, opportunistic and certain viral infections). These associated risks seem to be lower for etanercept than other agents. Screening for latent tuberculosis infection should be performed before starting anti-TNF-α therapy, followed by anti-tuberculosis therapy if appropriate. Screening for chronic hepatitis B virus (HBV) infection is also recommended, and antiviral prophylaxis may be warranted for hepatitis B surface antigen-positive individuals. No benefit is expected from the use of antibacterial, anti-Pneumocystis or antifungal prophylaxis. Pneumococcal and age-appropriate antiviral vaccinations (i.e. influenza) should be administered. Live-virus vaccines (i.e. varicella-zoster virus or measles-mumps-rubella) may be contraindicated in people receiving anti-TNF-α therapy, although additional data are needed before definitive recommendations can be made. Prevention measures should be implemented to reduce the risk of latent tuberculosis or HBV reactivation among individuals receiving anti-TNF-α therapy. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. How Stem Cells Speak with Host Immune Cells in Inflammatory Brain Diseases

    PubMed Central

    Pluchino, Stefano; Cossetti, Chiara

    2014-01-01

    Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases. PMID:23633288

  5. Adherence to malaria prophylaxis among Peace Corps Volunteers in the Africa region, 2013.

    PubMed

    Landman, Keren Z; Tan, Kathrine R; Arguin, Paul M

    2015-01-01

    Although malaria can be prevented with prophylaxis, it is diagnosed in over 100 Africa-region Peace Corps Volunteers annually. This suggests that prophylaxis non-adherence is a problem in these non-immune travelers. We investigated Volunteers' knowledge, attitudes, and practices regarding prophylaxis using an internet-based survey during August 19-September 30, 2013. Adherence was defined as taking doxycycline or atovaquone-proguanil daily, or taking mefloquine doses no more than 8 days apart. The survey was sent to 3248 Volunteers. Of 781 whose responses were analyzed, 514 (73%) reported adherence to prophylaxis. The most common reasons for non-adherence were forgetting (n = 530, 90%); fear of long-term adverse effects (LTAEs; n = 316, 54%); and experiencing adverse events that Volunteers attributed to prophylaxis (n = 297, 51%). Two hundred fourteen (27%) Volunteers reported not worrying about malaria. On multivariate analysis controlling for sex and experiencing adverse events Volunteers attributed to prophylaxis, the factor most strongly associated with non-adherence was being prescribed mefloquine (OR 5.4, 95% confidence interval 3.2-9.0). We found moderate adherence and a prevailing fear of LTAEs among Volunteers. Strategies to improve prophylaxis adherence may include medication reminders, increasing education about prophylaxis safety and malaria risk, and promoting prompt management of prophylaxis side effects. Published by Elsevier Ltd.

  6. Too much of a good thing: How modulating LTB4 actions restore host defense in homeostasis or disease.

    PubMed

    Brandt, Stephanie L; Serezani, C Henrique

    2017-10-01

    The ability to regulate inflammatory pathways and host defense mechanisms is critical for maintaining homeostasis and responding to infections and tissue injury. While unbalanced inflammation is detrimental to the host; inadequate inflammation might not provide effective signals required to eliminate pathogens. On the other hand, aberrant inflammation could result in organ damage and impair host defense. The lipid mediator leukotriene B 4 (LTB 4 ) is a potent neutrophil chemoattractant and recently, its role as a dominant molecule that amplifies many arms of phagocyte antimicrobial effector function has been unveiled. However, excessive LTB 4 production contributes to disease severity in chronic inflammatory diseases such as diabetes and arthritis, which could potentially be involved in poor host defense in these groups of patients. In this review we discuss the cellular and molecular programs elicited during LTB 4 production and actions on innate immunity host defense mechanisms as well as potential therapeutic strategies to improve host defense. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Antibiotic Prophylaxis for Gynecologic Procedures prior to and during the Utilization of Assisted Reproductive Technologies: A Systematic Review

    PubMed Central

    Hutchinson, Anne P.; Lekovich, Jovana P.; Hobeika, Elie; Elias, Rony T.

    2016-01-01

    The use of assisted reproductive technologies (ART) has increased steadily. There has been a corresponding increase in the number of ART-related procedures such as hysterosalpingography (HSG), saline infusion sonography (SIS), hysteroscopy, laparoscopy, oocyte retrieval, and embryo transfer (ET). While performing these procedures, the abdomen, upper vagina, and endocervix are breached, leading to the possibility of seeding pelvic structures with microorganisms. Antibiotic prophylaxis is therefore important to prevent or treat any procedure-related infections. After careful review of the published literature, it is evident that routine antibiotic prophylaxis is generally not recommended for the majority of ART-related procedures. For transcervical procedures such as HSG, SIS, hysteroscopy, ET, and chromotubation, patients at risk for pelvic infections should be screened and treated prior to the procedure. Patients with a history of pelvic inflammatory disease (PID) or dilated fallopian tubes are at high risk for postprocedural infections and should be given antibiotic prophylaxis during procedures such as HSG, SIS, or chromotubation. Antibiotic prophylaxis is recommended prior to oocyte retrieval in patients with a history of endometriosis, PID, ruptured appendicitis, or multiple prior pelvic surgeries. PMID:27047692

  8. Host age modulates within-host parasite competition.

    PubMed

    Izhar, Rony; Routtu, Jarkko; Ben-Ami, Frida

    2015-05-01

    In many host populations, one of the most striking differences among hosts is their age. While parasite prevalence differences in relation to host age are well known, little is known on how host age impacts ecological and evolutionary dynamics of diseases. Using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa, we examined how host age at exposure influences within-host parasite competition and virulence. We found that multiply-exposed hosts were more susceptible to infection and suffered higher mortality than singly-exposed hosts. Hosts oldest at exposure were least often infected and vice versa. Furthermore, we found that in young multiply-exposed hosts competition was weak, allowing coexistence and transmission of both parasite clones, whereas in older multiply-exposed hosts competitive exclusion was observed. Thus, age-dependent parasite exposure and host demography (age structure) could together play an important role in mediating parasite evolution. At the individual level, our results demonstrate a previously unnoticed interaction of the host's immune system with host age, suggesting that the specificity of immune function changes as hosts mature. Therefore, evolutionary models of parasite virulence might benefit from incorporating age-dependent epidemiological parameters. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  9. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

    PubMed

    Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

    2017-03-01

    Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Evidence for the role of synchronicity between host phenology and pathogen activity in the distribution of sudden oak death canker disease.

    PubMed

    Dodd, Richard S; Hüberli, Daniel; Mayer, Wasima; Harnik, Tamar Y; Afzal-Rafli, Zara; Garbelotto, Matteo

    2008-07-01

    Variations in synchronicity between colonization rate by the pathogen and host phenology may account for unexplained spatial distribution of canker disease. The hypothesis that synchronous pathogenicity and host development are necessary for incidence of sudden oak death disease was tested by correlating seasonal variations in host cambial phenology and response to inoculation with Phytophthora ramorum. Response to infection was estimated by inoculating branch cuttings from coast live oak (Quercus agrifolia) trees at nine dates through a full annual cycle in 2003-2004. Host phenology was estimated from measurements of bud burst and cambial activity in spring 2006. Lesions were largest in the spring soon after the cambium resumed activity. A moderate genetic component to lesion size was detected. Variation among trees in date of largest lesions correlated with variation in timing of bud burst and cambial phenology. The data support the hypothesis that active host cambial tissue is a necessary requisite for successful infection with the pathogen that causes sudden oak death canker disease. Genetic variation in host phenology will buffer coast live oak against epidemics of this disease.

  11. Host group formation decreases exposure to vector-borne disease: a field experiment in a 'hotspot' of West Nile virus transmission.

    PubMed

    Krebs, Bethany L; Anderson, Tavis K; Goldberg, Tony L; Hamer, Gabriel L; Kitron, Uriel D; Newman, Christina M; Ruiz, Marilyn O; Walker, Edward D; Brawn, Jeffrey D

    2014-12-07

    Animals can decrease their individual risk of predation by forming groups. The encounter-dilution hypothesis extends the potential benefits of gregariousness to biting insects and vector-borne disease by predicting that the per capita number of insect bites should decrease within larger host groups. Although vector-borne diseases are common and can exert strong selective pressures on hosts, there have been few tests of the encounter-dilution effect in natural systems. We conducted an experimental test of the encounter-dilution hypothesis using the American robin (Turdus migratorius), a common host species for the West Nile virus (WNV), a mosquito-borne pathogen. By using sentinel hosts (house sparrows, Passer domesticus) caged in naturally occurring communal roosts in the suburbs of Chicago, we assessed sentinel host risk of WNV exposure inside and outside of roosts. We also estimated per capita host exposure to infected vectors inside roosts and outside of roosts. Sentinel birds caged inside roosts seroconverted to WNV more slowly than those outside of roosts, suggesting that social groups decrease per capita exposure to infected mosquitoes. These results therefore support the encounter-dilution hypothesis in a vector-borne disease system. Our results suggest that disease-related selective pressures on sociality may depend on the mode of disease transmission. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  12. A national survey of antimicrobial prophylaxis in adult cardiac surgery across Canada

    PubMed Central

    Paradiso-Hardy, Fran L; Cornish, Patti; Pharand, Chantal; Fremes, Stephen E

    2002-01-01

    OBJECTIVE: To characterize national and regional patterns of antimicrobial prophylaxis in adult cardiac surgery across Canada. DESIGN: Retrospective, cross-sectional analysis. SETTING: Thirty-three adult cardiac surgical centres across Canada. INTERVENTIONS: A one-page questionnaire collecting information regarding institutional demographics and antimicrobial prophylaxis regimens for adult cardiac surgical procedures was mailed to all adult surgical centres across Canada. If a response was not received within one month, a second survey was mailed, followed by a telephone reminder within two weeks of the second mailing. MAIN RESULTS: The Overall response rate was 100%. Prophylactic antimicrobials were used in all the adult cardiac centres; single-agent prophylaxis was used in 97% (32 of 33) of centres; Single-dose antimicrobial prophylaxis was used in only 3% (one of 33) of centres. Preoperative and postoperative antimicrobial prophylaxis regimens varied both between provinces and within provinces across Canada. Cefazolin was the antimicrobial used in 88% (38 of 43) and 87% (33 of 38) of the reported pre-operative and post-operative prophylaxis regimens, respectively. Antimicrobial prophylaxis was initiated in the operating room 72% (26 of 36) of the time and intra-operative supplemental antimicrobial doses were administered for cardiac procedures longer than a median of 4 hours (range 4 to 8 hr). Overall, the median duration of antimicrobial prophylaxis was 36 hours (range 8 to 96 hr). CONCLUSIONS: Despite the availability of various published guidelines, our survey identified several areas for improvement with respect to antimicrobial prophylaxis in adult cardiac surgery across Canada. PMID:18159370

  13. Probiotics, gut microbiota, and their influence on host health and disease.

    PubMed

    Sánchez, Borja; Delgado, Susana; Blanco-Míguez, Aitor; Lourenço, Anália; Gueimonde, Miguel; Margolles, Abelardo

    2017-01-01

    The gastrointestinal tract of mammals hosts a high and diverse number of different microorganisms, known as intestinal microbiota. Many probiotics were originally isolated from the gastrointestinal tract, and they were defined by the Food and Agriculture Organization of the United Nations (FAO)/WHO as "live microorganisms which when administered in adequate amounts confer a health benefit on the host." Probiotics exert their beneficial effects on the host through four main mechanisms: interference with potential pathogens, improvement of barrier function, immunomodulation and production of neurotransmitters, and their host targets vary from the resident microbiota to cellular components of the gut-brain axis. However, in spite of the wide array of beneficial mechanisms deployed by probiotic bacteria, relatively few effects have been supported by clinical data. In this regard, different probiotic strains have been effective in antibiotic-associated diarrhea or inflammatory bowel disease for instance. The aim of this review was to compile the molecular mechanisms underlying the beneficial effects of probiotics, mainly through their interaction with the intestinal microbiota and with the intestinal mucosa. The specific benefits discussed in this paper include among others those elicited directly through dietary modulation of the human gut microbiota. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Molecules at the interface of Cryptococcus and the host that determine disease susceptibility.

    PubMed

    Wozniak, Karen L; Olszewski, Michal A; Wormley, Floyd L

    2015-05-01

    Cryptococcus neoformans and Cryptococcus gattii, the predominant etiological agents of cryptococcosis, are fungal pathogens that cause disease ranging from a mild pneumonia to life-threatening infections of the central nervous system (CNS). Resolution or exacerbation of Cryptococcus infection is determined following complex interactions of several host and pathogen derived factors. Alternatively, interactions between the host and pathogen may end in an impasse resulting in the establishment of a sub-clinical Cryptococcus infection. The current review addresses the delicate interaction between the host and Cryptococcus-derived molecules that determine resistance or susceptibility to infection. An emphasis will be placed on data highlighted at the recent 9th International Conference on Cryptococcus and Cryptococcosis (ICCC). Copyright © 2015. Published by Elsevier Inc.

  15. Antibiotic prophylaxis for operative vaginal delivery.

    PubMed

    Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

    2017-08-05

    Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2017) and reference lists of retrieved studies. All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. We assessed methodological quality of the one included trial using the GRADE approach. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. The trial compared the antibiotic intravenous cefotetan after cord clamping compared with no treatment. This trial reported only two out of the nine outcomes specified in this review. Seven women in the group

  16. Adherence to secondary antibiotic prophylaxis for patients with rheumatic heart disease diagnosed through screening in Fiji.

    PubMed

    Engelman, Daniel; Mataika, Reapi L; Kado, Joseph H; Ah Kee, Maureen; Donath, Susan; Parks, Tom; Steer, Andrew C

    2016-12-01

    Echocardiographic screening for rheumatic heart disease (RHD) can detect subclinical cases; however, adequate adherence to secondary antibiotic prophylaxis (SAP) is required to alter disease outcomes. We aimed to investigate the adherence to SAP among young people with RHD diagnosed through echocardiographic screening in Fiji and to investigate factors associated with adherence. Patients diagnosed with RHD through echocardiographic screening in Fiji from 2006 to 2014 were included. Dates of benzathine penicillin G injections were collected from 76 health clinics nationally from December 2011 to December 2014. Adherence was measured using the proportion of days covered (PDC). Multivariate logistic regression analysis was used to identify characteristics associated with any adherence (≥1 injection received) and adequate adherence (PDC ≥0.80). Of 494 patients, 268 (54%) were female and the median age was 14 years. Overall, 203 (41%) had no injections recorded and just 33 (7%) had adequate adherence. Multivariate logistic regression showed increasing age (OR 0.93 per year, 95% CI 0.87-0.99) and time since diagnosis ≥1.5 years (OR 0.53, 95% CI 0.37-0.79) to be inversely associated with any adherence. Non-iTaukei ethnicity (OR 2.58, 95%CI 1.04-6.33) and urban residence (OR 3.36, 95% CI 1.54-7.36) were associated with adequate adherence, whereas time since diagnosis ≥1.5 years (OR 0.38, 95%CI 0.17-0.83) was inversely associated with adequate adherence. Adherence to SAP after screening in Fiji is currently inadequate for individual patient protection or population disease control. Secondary prevention should be strengthened before further screening can be justified. © 2016 John Wiley & Sons Ltd.

  17. Late-onset Pneumocystis jirovecii pneumonia post-fludarabine, cyclophosphamide and rituximab: implications for prophylaxis.

    PubMed

    Haeusler, Gabrielle M; Slavin, Monica A; Seymour, John F; Lingaratnam, Senthil; Teh, Benjamin W; Tam, Constantine S; Thursky, Karin A; Worth, Leon J

    2013-08-01

    Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post-FCR in the era of highly sensitive molecular diagnostics and (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computerised tomography (CT). All patients treated with standard FCR at the Peter MacCallum Cancer Centre (March 2009 to June 2012) were identified from a medications management database. Laboratory-confirmed PJP cases during this time were identified from an electronic database. Overall, 66 patients were treated with a median of 5.5 FCR cycles. Eight PJP cases were identified, 6 of whom had received chemotherapy prior to FCR. In 5 cases, (18) F-FDG PET demonstrated bilateral ground-glass infiltrates. Median CD4(+) lymphocyte counts at time of PJP diagnosis and 9-12 months following FCR were 123 and 400 cells/μL, respectively. In patients receiving no prophylaxis, 9.1% developed PJP during FCR. The rate following FCR was 18.4%, with median onset at 6 months (2.4-24 months). Given the high rate of late-onset PJP, consideration should be given for extended PJP prophylaxis for up to 12 months post-FCR, particularly in pretreated patients. Further evaluation of the role of CD4(+) monitoring is warranted to quantify risk of disease development and to guide duration of prophylaxis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Stability of Microbiota Facilitated by Host Immune Regulation: Informing Probiotic Strategies to Manage Amphibian Disease

    PubMed Central

    Küng, Denise; Bigler, Laurent; Davis, Leyla R.; Gratwicke, Brian; Griffith, Edgardo; Woodhams, Douglas C.

    2014-01-01

    Microbial communities can augment host immune responses and probiotic therapies are under development to prevent or treat diseases of humans, crops, livestock, and wildlife including an emerging fungal disease of amphibians, chytridiomycosis. However, little is known about the stability of host-associated microbiota, or how the microbiota is structured by innate immune factors including antimicrobial peptides (AMPs) abundant in the skin secretions of many amphibians. Thus, conservation medicine including therapies targeting the skin will benefit from investigations of amphibian microbial ecology that provide a model for vertebrate host-symbiont interactions on mucosal surfaces. Here, we tested whether the cutaneous microbiota of Panamanian rocket frogs, Colostethus panamansis, was resistant to colonization or altered by treatment. Under semi-natural outdoor mesocosm conditions in Panama, we exposed frogs to one of three treatments including: (1) probiotic - the potentially beneficial bacterium Lysinibacillus fusiformis, (2) transplant – skin washes from the chytridiomycosis-resistant glass frog Espadarana prosoblepon, and (3) control – sterile water. Microbial assemblages were analyzed by a culture-independent T-RFLP analysis. We found that skin microbiota of C. panamansis was resistant to colonization and did not differ among treatments, but shifted through time in the mesocosms. We describe regulation of host AMPs that may function to maintain microbial community stability. Colonization resistance was metabolically costly and microbe-treated frogs lost 7–12% of body mass. The discovery of strong colonization resistance of skin microbiota suggests a well-regulated, rather than dynamic, host-symbiont relationship, and suggests that probiotic therapies aiming to enhance host immunity may require an approach that circumvents host mechanisms maintaining equilibrium in microbial communities. PMID:24489847

  19. Does the Arthropod Microbiota Impact the Establishment of Vector-Borne Diseases in Mammalian Hosts?

    PubMed Central

    Finney, Constance A. M.; Kamhawi, Shaden; Wasmuth, James D.

    2015-01-01

    The impact of the microbiota on the immune status of its host is a source of intense research and publicity. In comparison, the effect of arthropod microbiota on vector-borne infectious diseases has received little attention. A better understanding of the vector microbiota in relation to mammalian host immune responses is vital, as it can lead to strategies that affect transmission and improve vaccine design in a field of research where few vaccines exist and effective treatment is rare. Recent demonstrations of how microbiota decrease pathogen development in arthropods, and thus alter vector permissiveness to vector-borne diseases (VBDs), have led to renewed interest. However, hypotheses on the interactions between the arthropod-derived microbiota and the mammalian hosts have yet to be addressed. Advances in DNA sequencing technology, increased yield and falling costs, mean that these studies are now feasible for many microbiologists and entomologists. Here, we distill current knowledge and put forward key questions and experimental designs to shed light on this burgeoning research topic. PMID:25856431

  20. Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain.

    PubMed

    Villarrubia, R; Oyagüez, I; Álvarez-Román, M T; Mingot-Castellano, M E; Parra, R; Casado, M A

    2015-05-01

    A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 μg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS. © 2015 John Wiley & Sons Ltd.

  1. [Non-antibiotic prophylaxis for recurrent urinary-tract infections].

    PubMed

    Beerepoot, M A J; ter Riet, G; Verbon, A; Nys, S; de Reijke, T M; Geerlings, S E

    2006-03-11

    Urinary-tract infections (UTIs) occur frequently and hence have significant financial implications. Antibiotic prophylaxis can be considered in women with recurrent UTIs. However, frequent exposure to antibiotics can lead to antimicrobial resistance and side effects. The most important steps in the pathogenesis of UTIs are the colonisation and adherence of uropathogens. Lactobacilli impede intravaginal colonisation by competing with uropathogens. Cranberries interfere with the adherence of uropathogens to uroepithelial cells. Therefore, cranberries and lactobacilli are potential alternatives in the prophylaxis of UTIs. Randomised clinical trials comparing these compounds with long-term, low-dose antibiotics for the prevention of recurrent UTIs in women have not yet been conducted. Such a trial has recently been started in The Netherlands: the 'Non-antibiotic versus antibiotic prophylaxis for recurrent urinary-tract infections' (NAPRUTI) study.

  2. [Healthcare profile of rabies pre-exposure prophylaxis in the state of Rio Grande do Sul, Brazil, 2007-2014].

    PubMed

    Mota, Roberta Silva Silveira da; Schuch, Luiz Filipe Damé; Schuch, Dóris Gómez Marcos; Osmari, Christieli Prestes; Guimarães, Tássia Gomes

    2016-01-01

    to describe the profile of healthcare provision regarding rabies pre-exposure prophylaxis (RPrEP) in the state of Rio Grande do Sul, Brazil, as compared with the Technical Standards for Rabies Prophylaxis in Humans. this was a descriptive study using Notifiable Disease Information System data on anti-rabies healthcare provided between 2007 and 2014. only 2.4% of anti-rabies healthcare related to RPrEP (5,721/239,245), 42.5% of these were veterinary, biology and zootechnics students and 10.3% were professionals from the same areas; individuals aged 20 to 64 accounted for 71.8% of the total number of people vaccinated and the frequency of this form of prophylaxis was 53.5/100,000 inhabitants for the state as a whole, varying between 13.1 to 185.1/100,000 inhabitants in the state's different health districts. RPrEP frequency was found to be low, suggesting that this rabies prevention tool has been neglected, leaving a large number of people at occupational risk.

  3. Prophylaxis for Venous Thromboembolism.

    PubMed

    Ma, Kiet; Alhassan, Sulaiman; Sharara, Rihab; Young, Meilin; Singh, Anil C; Bihler, Eric

    Venous thromboembolisms are major risk factors for many of our hospitalized patients. These events, however, can be prevented with prophylactic measurements when administered appropriately and on a timely basis. As patients are admitted, discharged, transferred, and scheduled for procedures on an hourly basis, anticoagulation and deep vein thrombosis prophylaxis are held or discontinued in anticipation for possible procedures. This results in delay of care and intervals where patients may not be covered with any prophylactic measurements. Similarly, alterations in clinical status can quickly change such as an increase in creatinine levels or the development of a new bleed, thus requiring a revision in their deep vein thrombosis prophylaxis. Nurses, therefore, play an integral role in not only administering the medicine but also routinely assessing the patients' clinical status and, therefore, their deep vein thrombosis prophylactic regimens as well. This article will review the indications, scoring systems, common prophylactic methods, and special populations at increased risks for venous thromboembolisms.

  4. Microbiological changes associated with dental prophylaxis.

    PubMed

    Goodson, J Max; Palys, Michael D; Carpino, Elizabeth; Regan, Elizabeth O; Sweeney, Michael; Socransky, Sigmund S

    2004-11-01

    Despite the common application of dental prophylaxis as part of patient therapy, there is little reported that describes the microbiological impact of this treatment. The authors gave 20 healthy college-aged subjects three dental prophylaxes with a fluoride-containing prophylaxis paste during a two-week period and instructed them in oral hygiene. They evaluated the microbiological composition of dental plaque samples collected before and after treatment using DNA probe analysis. They analyzed 40 representative bacterial species in seven bacterial complexes by checkerboard DNA-DNA hybridization assay techniques. After three dental prophylaxes, the patients' mean Gingival Index score decreased from 0.82 to 0.77, the mean Plaque Index score decreased from 0.72 to zero, and the total number of bacteria per tooth decreased to approximately one-third of the original number. The authors computed two different measures of bacterial presence. The reduction in bacterial numbers was statistically significant and occurred in many species. Bacterial proportion (DNA percentage or percentage of the bacteria per tooth) did not change significantly. Greater reductions in bacterial count occurred in species that showed high numbers before treatment. The total bacterial count decreased by approximately 72 percent of its original level before prophylaxis was initiated. Professional dental prophylaxis did not target any particular bacteria or bacterial groups but removed bacteria nonspecifically and in proportion to their initial numbers. Repeated dental prophylaxes effect a reduction in bacterial amount that is commensurate with the initial amount, but they do does not alter composition. This suggests that mild gingivitis may be a bacterially nonspecific effect of plaque accumulation and emphasizes the need for regular plaque removal to maintain optimal gingival health.

  5. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles

    The 20th century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and water borne illnesses are frequent, multi-drug resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the 21st century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondinglymore » deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program we think that the time is at hand to redefine the pathogen-host research paradigm.« less

  6. A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

    PubMed Central

    Aderem, Alan; Adkins, Joshua N.; Ansong, Charles; Galagan, James; Kaiser, Shari; Korth, Marcus J.; Law, G. Lynn; McDermott, Jason G.; Proll, Sean C.; Rosenberger, Carrie; Schoolnik, Gary; Katze, Michael G.

    2011-01-01

    The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm. PMID:21285433

  7. Immunopathogenesis and Virus–Host Interactions of Enterovirus 71 in Patients with Hand, Foot and Mouth Disease

    PubMed Central

    Cox, Jonathan A.; Hiscox, Julian A.; Solomon, Tom; Ooi, Mong-How; Ng, Lisa F. P.

    2017-01-01

    Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans. In this review the role of the host–viral interactions of EV71 are discussed together with the various models available to examine: how EV71 utilizes its proteins to cleave host factors and proteins, aiding virus replication; how EV71 uses its own viral proteins to disrupt host immune responses and aid in its immune evasion. These discoveries along with others, such as the EV71 crystal structure, have provided possible targets for treatment and drug interventions. PMID:29238324

  8. HIV post exposure prophylaxis induced bicytopenia: a case report

    PubMed Central

    2014-01-01

    Long and short term side effects of antiretroviral drugs are not fully understood yet. Here a case of reversible blood count changes following post exposure prophylaxis with tenofovir/emtricitabin and lopinavir/ritonavir is reported. We propose that antiretroviral drugs used in post exposure prophylaxis may have a significant impact on hematopoiesis. PMID:24506969

  9. Climate change accelerates local disease extinction rates in a long-term wild host-pathogen association.

    PubMed

    Zhan, Jiasui; Ericson, Lars; Burdon, Jeremy J

    2018-02-27

    Pathogens are a significant component of all plant communities. In recent years, the potential for existing and emerging pathogens of agricultural crops to cause increased yield losses as a consequence of changing climatic patterns has raised considerable concern. In contrast, the response of naturally occurring, endemic pathogens to a warming climate has received little attention. Here, we report on the impact of a signature variable of global climate change - increasing temperature - on the long-term epidemiology of a natural host-pathogen association involving the rust pathogen Triphragmium ulmariae and its host plant Filipendula ulmaria. In a host-pathogen metapopulation involving approximately 230 host populations growing on an archipelago of islands in the Gulf of Bothnia we assessed changes in host population size and pathogen epidemiological measures over a 25-year period. We show how the incidence of disease and its severity declines over that period and most importantly demonstrate a positive association between a long-term trend of increasing extinction rates in individual pathogen populations of the metapopulation and increasing temperature. Our results are highly suggestive that changing climatic patterns, particularly mean monthly growing season (April-November) temperature, are markedly influencing the epidemiology of plant disease in this host-pathogen association. Given the important role plant pathogens have in shaping the structure of communities, changes in the epidemiology of pathogens have potentially far-reaching impacts on ecological and evolutionary processes. For these reasons, it is essential to increase understanding of pathogen epidemiology, its response to warming, and to invoke these responses in forecasts for the future. © 2018 John Wiley & Sons Ltd.

  10. Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

    PubMed Central

    McPhee, Joseph B.; Small, Cherrie L.; Reid-Yu, Sarah A.; Brannon, John R.; Le Moual, Hervé

    2014-01-01

    Host defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associated Escherichia coli commonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasive E. coli (AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6, arlA, which encodes a Mig-14 family protein implicated in defensin resistance, and arlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut. PMID:24866805

  11. The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis

    PubMed Central

    Caws, Maxine; Thwaites, Guy; Dunstan, Sarah; Hawn, Thomas R.; Thi Ngoc Lan, Nguyen; Thuong, Nguyen Thuy Thuong; Stepniewska, Kasia; Huyen, Mai Nguyet Thu; Bang, Nguyen Duc; Huu Loc, Tran; Gagneux, Sebastien; van Soolingen, Dick; Kremer, Kristin; van der Sande, Marianne; Small, Peter; Thi Hoang Anh, Phan; Chinh, Nguyen Tran; Thi Quy, Hoang; Thi Hong Duyen, Nguyen; Quang Tho, Dau; Hieu, Nguyen T.; Torok, Estee; Hien, Tran Tinh; Dung, Nguyen Huy; Thi Quynh Nhu, Nguyen; Duy, Phan Minh; van Vinh Chau, Nguyen; Farrar, Jeremy

    2008-01-01

    The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193–0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15–2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis. PMID:18369480

  12. Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus

    2015-01-01

    Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials. © 2015 S. Karger AG, Basel.

  13. Half the story: Thermal effects on within-host infectious disease progression in a warming climate.

    PubMed

    Stewart, Alexander; Hablützel, Pascal I; Brown, Martha; Watson, Hayley V; Parker-Norman, Sophie; Tober, Anya V; Thomason, Anna G; Friberg, Ida M; Cable, Joanne; Jackson, Joseph A

    2018-01-01

    Immune defense is temperature dependent in cold-blooded vertebrates (CBVs) and thus directly impacted by global warming. We examined whether immunity and within-host infectious disease progression are altered in CBVs under realistic climate warming in a seasonal mid-latitude setting. Going further, we also examined how large thermal effects are in relation to the effects of other environmental variation in such a setting (critical to our ability to project infectious disease dynamics from thermal relationships alone). We employed the three-spined stickleback and three ecologically relevant parasite infections as a "wild" model. To generate a realistic climatic warming scenario we used naturalistic outdoors mesocosms with precise temperature control. We also conducted laboratory experiments to estimate thermal effects on immunity and within-host infectious disease progression under controlled conditions. As experimental readouts we measured disease progression for the parasites and expression in 14 immune-associated genes (providing insight into immunophenotypic responses). Our mesocosm experiment demonstrated significant perturbation due to modest warming (+2°C), altering the magnitude and phenology of disease. Our laboratory experiments demonstrated substantial thermal effects. Prevailing thermal effects were more important than lagged thermal effects and disease progression increased or decreased in severity with increasing temperature in an infection-specific way. Combining laboratory-determined thermal effects with our mesocosm data, we used inverse modeling to partition seasonal variation in Saprolegnia disease progression into a thermal effect and a latent immunocompetence effect (driven by nonthermal environmental variation and correlating with immune gene expression). The immunocompetence effect was large, accounting for at least as much variation in Saprolegnia disease as the thermal effect. This suggests that managers of CBV populations in variable

  14. The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases

    PubMed Central

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-01-01

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707

  15. Effects of antimicrobial prophylaxis and blood stream infections in patients with acute liver failure: a retrospective cohort study.

    PubMed

    Karvellas, Constantine J; Cavazos, Jorge; Battenhouse, Holly; Durkalski, Valerie; Balko, Jody; Sanders, Corron; Lee, William M

    2014-11-01

    We investigated whether antimicrobial prophylaxis alters the incidence of bloodstream infection in patients with acute liver failure (ALF), and whether bloodstream infections affect overall mortality within 21 days after development of ALF. We performed a retrospective cohort analysis of 1551 patients with ALF enrolled by the US Acute Liver Failure Study Group from January 1998 through November 2009. We analyzed data on infections in the first 7 days after admission and the effects of prophylaxis with antimicrobial drugs on the development of bloodstream infections and 21-day mortality. In our study population, 600 patients (39%) received antimicrobial prophylaxis and 226 patients (14.6%) developed at least 1 bloodstream infection. Exposure to antimicrobial drugs did not affect the proportion of patients who developed bloodstream infections (12.8% in patients with prophylaxis vs 15.7% in nonprophylaxed patients; P = .12), but a greater percentage of patients who received prophylaxis received liver transplants (28% vs 22%; P = .01). After adjusting for confounding factors, overall mortality within 21 days was associated independently with age (odds ratio [OR], 1.014), Model for End-stage Liver Disease score at admission (OR, 1.078), and vasopressor administration at admission (OR, 2.499). Low grade of coma (OR, 0.47) and liver transplantation (OR, 0.101) reduced mortality. Although bloodstream infection was associated significantly with 21-day mortality (P = .004), an interaction between bloodstream infection and etiology was detected: blood stream infection affected mortality to a greater extent in nonacetaminophen ALF patients (OR, 2.03) than in acetaminophen ALF patients (OR, 1.14). Based on a large, observational study, antimicrobial prophylaxis does not reduce the incidence of bloodstream infection or mortality within 21 days of ALF. However, bloodstream infections were associated with increased 21-day mortality in patients with ALF-to a greater extent in

  16. Sea fan immunity and disease is influenced by metal pollution, host demography, and multiple stressors

    NASA Astrophysics Data System (ADS)

    Tracy, A. M.; Weil, E.; Harvell, C. D.

    2016-02-01

    Organisms in natural populations experience an onslaught of stressful conditions that may compromise their ability to fight pathogens, particularly if multiple stressors impact a host at the same time. Environmental stressors can also influence the pathogens. Despite the clear importance of environmental factors for coral host-pathogen interactions and the potential for population-level consequences, there is relatively little research to date on multiple stressors. The population of Caribbean sea fans, Gorgonia ventalina, in Parguera, Puerto Rico is a tractable system in which to study the effects of multiple stressors on two pathogens. Sea fans are dominant members of reefs that provide food and habitat for diverse reef inhabitants. In addition, there is already a foundation of research on sea fan disease and immunity. We first conducted field surveys of 15 sites to assess the effects of demographic and environmental factors on the prevalence and severity of multifocal purple spots (MFPS) and a Labyrinthulid stramenopile pathogen, as well as the host's cellular immune response to each pathogen. We complemented the field survey with a fully factorial, clonally replicated experiment on the separate and combined effects of thermal stress and copper pollution on both the host and the pathogen. Although water quality has been linked to coral disease, there are no studies investigating the role of metal or chemical pollutants, which are high at some of our study sites. Preliminary results show that the sea fan immune response to the Labyrinthulid depends on interactive effects of copper and thermal stress. The field survey identifies colony size as the main driver of MFPS. This in-depth perspective on sea fan disease speaks to the immune capabilities of cnidarians, highlights factors that modify those capabilities, and reflects the complex interaction of host, pathogens, and environment in this ecologically important coral.

  17. Lichenoid exanthema mimicking graft-versus-host disease associated with obstructive lung disease in a non-transplanted patient.

    PubMed

    Eberle, Franziska Carola; Holland, Angelique; Hörster, Stefan; Vogelmeier, Claus; Hertl, Michael

    2010-01-01

    Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis.

  18. Comparison of the efficacy and cost effectiveness of pre-emptive therapy as directed by CMV antigenemia and prophylaxis with ganciclovir in lung transplant recipients.

    PubMed

    Kelly, J; Hurley, D; Raghu, G

    2000-04-01

    CMV disease remains a major complication of lung transplantation and attempts to prevent it have met with marginal success. In a previous study we documented that universal prophylaxis did not prevent CMV disease but merely delayed it, and was very costly. We compared the efficacy and cost of pre-emptive therapy with ganciclovir, guided by CMV antigenemia, to that of historic controls that received universal prophylaxis with ganciclovir. CMV antigenemia assay was done routinely and pre-emptive therapy was initiated if greater than 25 CMV positive cells per 100,000 polymorphonuclear cells were found. Nineteen patients were enrolled; 6 of of whom received 12 courses of pre-emptive therapy. The incidence of CMV disease was 26% compared to 38% for the historical controls (p = 0.51). None of the patients that received pre-emptive therapy developed CMV disease following that therapy. Antigenemia failed to predict disease in 5 patients that developed it, and thus it is unknown if pre-emptive therapy could have prevented it. There was no mortality in either the study patients or historic controls directly related to CMV. The net savings with pre-emptive therapy was $2569 per patient. We conclude that pre-emptive therapy with ganciclovir is as safe and effective as universal prophylaxis in preventing CMV disease in lung transplant recipients, and is less expensive. The appropriate surveillance technique and timing remain to be determine to optimize the efficacy of pre-emptive therapy.

  19. Patterns of Venous Thromboembolism Prophylaxis During Treatment of Acute Leukemia: Results of a North American Web-Based Survey.

    PubMed

    Lee, Eun-Ju; Smith, B Douglas; Merrey, Jessica W; Lee, Alfred I; Podoltsev, Nikolai A; Barbarotta, Lisa; Litzow, Mark R; Prebet, Thomas; Luger, Selina M; Gore, Steven; Streiff, Michael B; Zeidan, Amer M

    2015-12-01

    Venous thromboembolism (VTE) occurs in 2% to 12% of patients with acute leukemia (AL) despite disease- and therapy-associated thrombocytopenia, and it can be associated with significant morbidity and mortality. Because of the few high-quality studies, there are no evidence-based guidelines for VTE prophylaxis in this patient population. We sought to determine the spectrum of practice regarding prevention of VTE in patients with AL during induction and consolidation therapies. We conducted a 19-question Web-based survey directed at North American providers caring for these patients. One hundred fifty-one of 215 responses received were eligible for analysis, with a response rate of 20.9% among physicians who treated leukemias. Overall, 47% and 45% of providers reported using pharmacologic VTE prophylaxis during induction and consolidation phases, respectively. Approximately 15% of providers did not provide any VTE prophylaxis, while 36% used mechanical methods and ambulation. Among providers who did not recommend pharmacologic prophylaxis, the most commonly cited reasons were the perceived high risk of bleeding (51%), absence of data supporting use (38%), and perceived low risk of VTE (11%). Large, prospective studies are needed to define the safest and most effective approach to VTE prevention in patients with AL. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Gut Microbiota and Host Reaction in Liver Diseases

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

    Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases. PMID:27682116

  1. Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy.

    PubMed

    Gafter-Gvili, Anat; Fraser, Abigail; Paul, Mical; Vidal, Liat; Lawrie, Theresa A; van de Wetering, Marianne D; Kremer, Leontien C M; Leibovici, Leonard

    2012-01-18

    Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality. This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention. We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients. Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software. One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality).Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection (48 trials, 5758 participants; RR 0.65, 95% CI 0.56 to 0.76), microbiologically documented infection

  2. Antibiotic prophylaxis for bacterial infections in afebrile neutropenic patients following chemotherapy

    PubMed Central

    Gafter-Gvili, Anat; Fraser, Abigail; Paul, Mical; Vidal, Liat; Lawrie, Theresa A; van de Wetering, Marianne D; Kremer, Leontien CM; Leibovici, Leonard

    2014-01-01

    Background Bacterial infections are a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Trials have shown the efficacy of antibiotic prophylaxis in reducing the incidence of bacterial infections but not in reducing mortality rates. Our systematic review from 2006 also showed a reduction in mortality. Objectives This updated review aimed to evaluate whether there is still a benefit of reduction in mortality when compared to placebo or no intervention. Search methods We searched the Cochrane Cancer Network Register of Trials (2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2011), MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011), abstracts of conference proceedings and the references of identified studies. Selection criteria Randomised controlled trials (RCTs) or quasi-RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention, or another antibiotic, to prevent bacterial infections in afebrile neutropenic patients. Data collection and analysis Two authors independently appraised the quality of each trial and extracted data from the included trials. Analyses were performed using RevMan 5.1 software. Main results One-hundred and nine trials (involving 13,579 patients) that were conducted between the years 1973 to 2010 met the inclusion criteria. When compared with placebo or no intervention, antibiotic prophylaxis significantly reduced the risk of death from all causes (46 trials, 5635 participants; risk ratio (RR) 0.66, 95% CI 0.55 to 0.79) and the risk of infection-related death (43 trials, 5777 participants; RR 0.61, 95% CI 0.48 to 0.77). The estimated number needed to treat (NNT) to prevent one death was 34 (all-cause mortality) and 48 (infection-related mortality). Prophylaxis also significantly reduced the occurrence of fever (54 trials, 6658 participants; RR 0.80, 95% CI 0.74 to 0.87), clinically documented infection

  3. A decade of respiratory syncytial virus epidemiology and prophylaxis: Translating evidence into everyday clinical practice

    PubMed Central

    Paes, Bosco A; Mitchell, Ian; Banerji, Anna; Lanctôt, Krista L; Langley, Joanne M

    2011-01-01

    Respiratory syncytial virus (RSV) is a common infection in infancy, with nearly all children affected by two years of age. Approximately 0.5% to 2.0% of all children are hospitalized with lower respiratory tract disease, of which 50% to 90% have bronchiolitis and 5% to 40% have pneumonia. Morbidity and mortality are highest in children with nosocomial infection and in those with underlying medical illnesses such as cardiac and chronic lung disease. Aboriginal children residing in remote northern regions are specifically considered to be at high risk for hospitalization due to RSV infection. Thorough hand washing and health education are the principal strategies in primary prevention. In the absence of a vaccine, palivizumab prophylaxis is currently the best intervention to reduce the burden of illness and RSV-related hospitalization in high-risk children. Health care professionals should provide palivizumab prophylaxis cost effectively in accordance with recommendations issued by pediatric societies and national advisory bodies. The present article reviews the epidemiology of RSV infection and the short- and long-term impact of disease in high-risk infants and special populations. Prevention strategies and treatment are discussed based on the existing scientific evidence, and future challenges in the management of RSV infection are addressed. PMID:21499597

  4. Descriptive analysis of malaria prophylaxis for travellers from Greece visiting malaria-endemic countries.

    PubMed

    Pavli, Androula; Smeti, Paraskevi; Spilioti, Athina; Vakali, Annita; Katerelos, Panagiotis; Maltezou, Helena C

    2011-11-01

    International travel is changing the epidemiology of imported malaria. Our aim was to study malaria prophylaxis administered to travellers from Greece. The study was conducted during 2008-2009. Data were collected using a standardized form. A total of 2337 travellers were studied; prophylaxis was recommended to 60.2% of them. Of the 2337 travellers, 32.6% travelled to sub-Saharan Africa, 25.5% to South America, 11.8% to Indian subcontinent, 11.7% to Middle East, and 4.4% to Southeast Asia; prophylaxis was recommended to 77.4%, 64%, 80.6%, 4.8% and 73.5% of them, respectively. According to the purpose of travel, prophylaxis was recommended to 85.4% of those travelling for work, 75.2% of those visiting friends and relatives, and 62% of those travelling for recreation. Prophylaxis advised was provided to 68.5%, 66.2%, 61.5%, and 18.9% to those staying at a residence of local people, camping, hotels, and cruise ships, respectively. Regarding long-term travellers, malaria prophylaxis was recommended to 42.6%. Recommendation of malaria prophylaxis was significantly statistically in association with destination countries, purpose of travel, type of residence in endemic areas There is a need to improve recommendations for malaria prophylaxis for travellers from Greece, and to increase awareness and education of professionals providing travel health services in Greece. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Extracellular Vesicles Released from Human Umbilical Cord-Derived Mesenchymal Stromal Cells Prevent Life-Threatening Acute Graft-Versus-Host Disease in a Mouse Model of Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Wang, Li; Gu, Zhenyang; Zhao, Xiaoli; Yang, Nan; Wang, Feiyan; Deng, Ailing; Zhao, Shasha; Luo, Lan; Wei, Huaping; Guan, Lixun; Gao, Zhe; Li, Yonghui; Wang, Lili; Liu, Daihong; Gao, Chunji

    2016-12-15

    Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord-derived MSCs (hUC-MSC-EVs) could prevent aGVHD in a mouse model of allo-HSCT. hUC-MSC-EVs were intravenously administered to recipient mice on days 0 and 7 after allo-HSCT, and the prophylactic effects of hUC-MSC-EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival. We evaluated the effects of hUC-MSC-EVs on immune cells and inflammatory cytokines by flow cytometry and ProcartaPlex™ Multiplex Immunoassays, respectively. The in vitro effects of hUC-MSC-EVs were determined by mitogen-induced proliferation assays. hUC-MSC-EVs alleviated the in vivo manifestations of aGVHD and the associated histologic changes and significantly reduced the mortality of the recipient mice. Recipients treated with hUC-MSC-EVs had significantly lower frequencies and absolute numbers of CD3 + CD8 + T cells; reduced serum levels of IL-2, TNF-α, and IFN-γ; a higher ratio of CD3 + CD4 + and CD3 + CD8 + T cells; and higher serum levels of IL-10. An in vitro experiment demonstrated that hUC-MSC-EVs inhibited the mitogen-induced proliferation of splenocytes in a dose-dependent manner, and the cytokine changes were similar to those observed in vivo. This study indicated that hUC-MSC-EVs can prevent life-threatening aGVHD by modulating immune responses. These data provide the first evidence that hUC-MSC-EVs represent an ideal alternative in the prophylaxis of aGVHD after allo-HSCT.

  6. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia.

    PubMed

    Robien, Kim; Bigler, Jeannette; Yasui, Yutaka; Potter, John D; Martin, Paul; Storb, Rainer; Ulrich, Cornelia M

    2006-09-01

    Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) play key roles in intracellular folate metabolism. Polymorphisms in these enzymes have been shown to modify toxicity of methotrexate (MTX) after hematopoietic cell transplantation. In this study, we evaluated the risk of acute graft-versus-host disease (GVHD) associated with genetic variation in recipient and donor MTHFR and TS genotypes to assess whether genotype alters the efficacy of MTX in acute GVHD prophylaxis. Data on the transplantation course were abstracted from medical records for 304 adults who received allogeneic hematopoietic cell transplants. MTHFR (C677T and A1298C) and TS (enhancer-region 28-base pair repeat, TSER, and 1494del6) genotypes were determined using polymerase chain reaction/restriction fragment length polymorphism and TaqMan assays. Multivariable logistic regression was used to assess the associations between genotypes and risk of acute GVHD. Compared with recipients with the wild-type MTHFR 677CC genotype, those with the variant 677T allele showed a decreased risk of detectable acute GVHD (677CT: odds ratio, 0.8; 95% confidence interval, 0.4-1.6; 677TT: odds ratio, 0.4; 95% confidence interval, 0.2-0.8; P for trend = .01). The variant MTHFR 1298C allele in recipients was associated with an increased risk of acute GVHD compared with the wild-type MTHFR 1298AA genotype (1298AC: odds ratio, 2.0; 95% confidence interval, 1.1-3.9; 1298CC: odds ratio, 3.6; 95% confidence interval, 1.0-12.7; P for trend < .01). No association with risk of acute GVHD was observed for donor MTHFR genotypes or for recipient or donor TS genotypes, with the exception of an increase in acute GVHD among recipients whose donors had the TSER 3R/2R genotype (odds ratio, 3.0; 95% confidence interval, 1.3-7.2). These findings indicate that host, but not donor, MTHFR genotypes modify the risk of acute GVHD in recipients receiving MTX, in a manner consistent with our previously reported associations

  7. Pre-Exposure Prophylaxis (PrEP)

    MedlinePlus

    ... VA – HIV Pre-Exposure Prophylaxis HIV.gov on Twitter 22 hours 47 min ago. HIV.gov @HIVGov # ... routine. #HIVTestingDay Reply Retweet Favorite HIV.gov on Twitter Search Find HIV Testing Sites & Care Services Connect ...

  8. Evaluation of the duration of thromboembolic prophylaxis after high-risk orthopaedic surgery: the ETHOS observational study.

    PubMed

    Bergqvist, David; Arcelus, Juan I; Felicissimo, Paulo

    2012-02-01

    Real-life data on post-discharge venous thromboembolism (VTE) prophylaxis practices and treatments are lacking. We assessed post-operative VTE prophylaxis prescribed and received in a prospective registry, compared with the 2004 American College of Chest Physicians (ACCP) guidelines in high-risk orthopaedic surgery patients. Consecutive patients undergoing total hip arthroplasty (THA), hip fracture surgery (HFS), or knee arthroplasty (KA) were enrolled at discharge from 161 centres in 17 European countries if they had received in-hospital VTE prophylaxis that was considered in accordance with the ACCP guidelines by the treating physician. Data on prescribed and actual prophylaxis were obtained from hospital charts and patient post-discharge diaries. Post-operative prophylaxis prescribed and actual prophylaxis received were considered adherent or adequate, respectively, if recommended therapies were used for ≥28 days (HFS and THA) or ≥10 days (KA). Among 4,388 patients, 69.9% were prescribed ACCP-adherent VTE prophylaxis (THA: 1,411/2,217 [63.6%]; HFS: 701/1,112 [63.0%]; KA: 955/1,059 [90.2%]). Actual prophylaxis received was described in 3,939 patients with an available diary after discharge (non-evaluability rate of 10%). Mean actual durations of pharmacological prophylaxis from surgery were: 28.4 ± 13.7 (THA), 29.3 ± 13.9 (HFS), and 28.7 ± 14.1 days (KA). ACCP-adequate VTE prophylaxis was received by 66.5% of patients (60.9% THA, 55.4% HFS, and 88.7% KA). Prophylaxis inadequacies were mainly due to inadequate prescription, non-recommended prophylaxis prescription at discharge, or too short prophylaxis prescribed. In high-risk orthopaedic surgery patients with hospital-initiated prophylaxis, there is a gap between ACCP recommendations, prescribed and actual prophylaxis received, mainly due to inadequate prescription at discharge.

  9. Dalteparin: an update of its pharmacological properties and clinical efficacy in the prophylaxis and treatment of thromboembolic disease.

    PubMed

    Dunn, C J; Jarvis, B

    2000-07-01

    effective and well tolerated when given subcutaneously once daily in the prophylaxis and treatment of thromboembolic disease. The simplicity of the administration regimens used and the lack of necessity for laboratory monitoring facilitate home or outpatient treatment and appear to translate into cost advantages from a hospital perspective over UFH or warfarin. Dalteparin also maintains the patency of haemodialysis and haemofiltration circuits, with beneficial effects on blood lipid profiles and the potential for prophylaxis with a single bolus injection in some patients. Data are also accumulating to show dalteparin to be an effective and easily administered alternative to UFH in patients with CAD.

  10. A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis.

    PubMed

    Ellsworth, A J; Larson, E B; Strickland, D

    1987-12-01

    Forty-seven climbers participated in a double-blind, randomized trial comparing acetazolamide 250 mg, dexamethasone 4 mg, and placebo every eight hours as prophylaxis for acute mountain sickness during rapid, active ascent of Mount Rainier (elevation 4,392 m). Forty-two subjects (89.4 percent) achieved the summit in an average of 34.5 hours after leaving sea level. At the summit or high point attained above base camp, the group taking dexamethasone reported less headache, tiredness, dizziness, nausea, clumsiness, and a greater sense of feeling refreshed (p less than or equal to 0.05). In addition, they reported fewer problems of runny nose and feeling cold, symptoms unrelated to acute mountain sickness. The acetazolamide group differed significantly (p less than or equal to 0.05) from other groups at low elevations (1,300 to 1,600 m), in that they experienced more feelings of nausea and tiredness, and they were less refreshed. These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness. Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone. This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease.

  11. Transcriptome of an Armillaria root disease pathogen reveals candidate genes involved in host substrate utilization at the host­-pathogen interface

    Treesearch

    A. L. Ross-Davis; J. E. Stewart; J. W. Hanna; M.-S. Kim; B. J. Knaus; R. Cronn; H. Rai; B. A. Richardson; G. I. McDonald; N. B. Klopfenstein

    2013-01-01

    Armillaria species display diverse ecological roles ranging from beneficial saprobe to virulent pathogen. Armillaria solidipes (formerly A. ostoyae), a causal agent of Armillaria root disease, is a virulent primary pathogen with a broad host range of woody plants across the Northern Hemisphere. This white-rot pathogen grows between trees as rhizomorphs and attacks...

  12. Factors associated with short-course antiretroviral prophylaxis (dual therapy) adherence for PMTCT in Nkangala district, South Africa.

    PubMed

    Peltzer, Karl; Sikwane, Elisa; Majaja, Mmapaseka

    2011-09-01

    To identify factors that influence adherence to short-course antiretroviral (ARV) prophylaxis by pregnant women and mothers participating in the HIV prevention of mother to child (PMTCT) programme. The sample interviewed included 139 HIV-positive antenatal women (mean gestational age 32 weeks; sexually transmitted diseases [STD] = 2.8, range 4-9 months) and 607 postnatal HIV-positive women, with either having an infant aged 1-10 weeks (30.8%), 11 weeks to 6 months (36.7%) or 7-12 months (32.5%) from Nkangala district, Mpumalanga province, South Africa. A large percentage of antenatal and postnatal women in this study initiated ARV prophylaxis for PMTCT or were on ARV (85.6% and 98%, respectively). Sixty-one per cent of antenatal and 85.9% of postnatal women reported complete adherence to the appropriate medication schedule in the 4 days preceding the interview or prior to delivery. In multivariate analysis, it was found that women with higher HIV status disclosure and less discrimination were better in maternal AZT adherence, women with higher male involvement were better in maternal and infant nevirapine adherence. Adherence to maternal and infant dual therapy prophylaxis was found to be less than optimal. Community factors (discrimination, HIV disclosure, male involvement) contribute to adherence to short-course ARV prophylaxis in this largely rural setting in South Africa. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  13. Toll-like receptor cascade and gene polymorphism in host-pathogen interaction in Lyme disease.

    PubMed

    Rahman, Shusmita; Shering, Maria; Ogden, Nicholas H; Lindsay, Robbin; Badawi, Alaa

    2016-01-01

    Lyme disease (LD) risk occurs in North America and Europe where the tick vectors of the causal agent Borrelia burgdorferi sensu lato are found. It is associated with local and systemic manifestations, and has persistent posttreatment health complications in some individuals. The innate immune system likely plays a critical role in both host defense against B. burgdorferi and disease severity. Recognition of B. burgdorferi, activation of the innate immune system, production of proinflammatory cytokines, and modulation of the host adaptive responses are all initiated by Toll-like receptors (TLRs). A number of Borrelia outer-surface proteins (eg, OspA and OspB) are recognized by TLRs. Specifically, TLR1 and TLR2 were identified as the receptors most relevant to LD. Several functional single-nucleotide polymorphisms have been identified in TLR genes, and are associated with varying cytokines types and synthesis levels, altered pathogen recognition, and disruption of the downstream signaling cascade. These single-nucleotide polymorphism-related functional alterations are postulated to be linked to disease development and posttreatment persistent illness. Elucidating the role of TLRs in LD may facilitate a better understanding of disease pathogenesis and can provide an insight into novel therapeutic targets during active disease or postinfection and posttreatment stages.

  14. Prion disease tempo determined by host-dependent substrate reduction

    PubMed Central

    Mays, Charles E.; Kim, Chae; Haldiman, Tracy; van der Merwe, Jacques; Lau, Agnes; Yang, Jing; Grams, Jennifer; Di Bari, Michele A.; Nonno, Romolo; Telling, Glenn C.; Kong, Qingzhong; Langeveld, Jan; McKenzie, Debbie; Westaway, David; Safar, Jiri G.

    2014-01-01

    The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrPSc), which is derived from its cellular precursor (PrPC), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrPC and Sho, we inferred that PrPC levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrPC glycosylation and proteolytic processing, net reductions in PrPC occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrPC results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrPSc in vitro. While PrPC downregulation is not discernible in animals with unusually short incubation periods and high PrPC expression, slowly evolving prion infections exhibit downregulation of the PrPC substrate required for new PrPSc synthesis and as a receptor for pathogenic signaling. Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains. PMID:24430187

  15. Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.

    PubMed

    Hakim, James; Musiime, Victor; Szubert, Alex J; Mallewa, Jane; Siika, Abraham; Agutu, Clara; Walker, Simon; Pett, Sarah L; Bwakura-Dangarembizi, Mutsa; Lugemwa, Abbas; Kaunda, Symon; Karoney, Mercy; Musoro, Godfrey; Kabahenda, Sheila; Nathoo, Kusum; Maitland, Kathryn; Griffiths, Anna; Thomason, Margaret J; Kityo, Cissy; Mugyenyi, Peter; Prendergast, Andrew J; Walker, A Sarah; Gibb, Diana M

    2017-07-20

    In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (coformulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality. A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had

  16. Graft-versus-host disease management.

    PubMed

    Mistrik, M; Bojtarova, E; Sopko, L; Masakova, L; Roziakova, L; Martinka, J; Batorova, A

    Graft-versus-host disease (GVHD) remains a major problem of allogeneic hematopoietic-stem cell transplantation (HSCT) and an obstacle for successful outcome. Clinically significant acute GVHD (grade II or higher) developed in 20 to 65 percent of the patients. Death due to this complication accounts for approximately 50 percent of the deaths that are not due to a relapse of the neoplasm. Up to 70 % of patients who survive beyond day 100 develop chronic GVHD and it is the leading cause of nonrelapse mortality more than 2 years after allogeneic HSCT. In addition, chronic GVHD is associated with decreased quality of life, impaired functional status, and ongoing need for immunosuppressive medications. The incidence of chronic GVHD is increasing because of expansion of the donor population beyond HLA-identical siblings, older recipient age, use of peripheral blood cells as the graft source, and infusion of donor lymphocytes for treatment of recurrent malignancy after HSCT. With the current rush in new findings related to GVHD, we see a significant advancement in its management. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of GVHD, as access to the most sophisticated advances may vary depending on local circumstances (Tab. 4, Fig. 1, Ref. 51).

  17. Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases.

    PubMed

    Leone, Vanessa; Chang, Eugene B; Devkota, Suzanne

    2013-03-01

    The incidence of inflammatory bowel diseases (IBD), as well as other inflammatory conditions, has dramatically increased over the past half century. While many studies have shown that IBD exhibits a genetic component via genome-wide association studies, genetic drift alone cannot account for this increase, and other factors, such as those found in the environment must play a role, suggesting a "multiple hit" phenomenon that precipitates disease. One major environmental factor, dietary intake, has shifted to a high fat, high carbohydrate Western-type diet in developing nations, nearly in direct correlation with the increasing incidence of IBD. Recent evidence suggests that specific changes in dietary intake have led to a shift in the composite human gut microbiota, resulting in the emergence of pathobionts that can thrive under specific conditions. In the genetically susceptible host, the emerging pathobionts can lead to increasing incidence and severity of IBD and other inflammatory disorders. Since the gut microbiota is plastic and responds to dietary modulations, the use of probiotics, prebiotics, and/or dietary alterations are all intriguing complementary therapeutic approaches to alleviate IBD symptoms. However, the interactions are complex and it is unlikely that a one-size-fits all approach can be utilized across all populations affected by IBD. Exploration into and thoroughly understanding the interactions between host and microbes, primarily in the genetically susceptible host, will help define strategies that can be tailored to an individual as we move towards an era of personalized medicine to treat IBD.

  18. Parents' knowledge and perceptions regarding vitamin K prophylaxis in newborns.

    PubMed

    Eventov-Friedman, Smadar; Vinograd, Orit; Ben-Haim, Maggie; Penso, Sara; Bar-Oz, Benjamin; Zisk-Rony, Rachel Y

    2013-07-01

    There is an increasing trend of parents refusing vitamin K (VK) prophylaxis in newborns. We examined the knowledge, perceptions, cultural and religious barriers of expecting parents regarding VK prophylaxis. Questionnaires were completed by 217 participants: 151 female participants and 85% were expecting their first child. Two thirds had academic degrees, yet were ignorant regarding recommendation to provide VK (22.5%), source (15.5%), action (34%), and provision options (29%). Moreover, first-time parents had not yet decided to provide VK after birth (P<0.05). There is a need to provide expecting parents with information regarding safety, utility, and benefits of VK prophylaxis.

  19. Kinetics of disease progression and host response in a rat model of bubonic plague.

    PubMed

    Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B; Hinnebusch, B Joseph

    2005-05-01

    Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease.

  20. Kinetics of Disease Progression and Host Response in a Rat Model of Bubonic Plague

    PubMed Central

    Sebbane, Florent; Gardner, Donald; Long, Daniel; Gowen, Brian B.; Hinnebusch, B. Joseph

    2005-01-01

    Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease. PMID:15855643

  1. Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease.

    PubMed

    Cardona, Diana M; Detweiler, Claire J; Shealy, Michael J; Sung, Anthony D; Wild, Daniel M; Poleski, Martin H; Balmadrid, Bryan L; Cirrincione, Constance T; Howell, David N; Sullivan, Keith M

    2018-04-26

    - Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical record from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

  2. Columnaris disease in fish: a review with emphasis on bacterium-host interactions

    PubMed Central

    2013-01-01

    Flavobacterium columnare (F. columnare) is the causative agent of columnaris disease. This bacterium affects both cultured and wild freshwater fish including many susceptible commercially important fish species. F. columnare infections may result in skin lesions, fin erosion and gill necrosis, with a high degree of mortality, leading to severe economic losses. Especially in the last decade, various research groups have performed studies aimed at elucidating the pathogenesis of columnaris disease, leading to significant progress in defining the complex interactions between the organism and its host. Despite these efforts, the pathogenesis of columnaris disease hitherto largely remains unclear, compromising the further development of efficient curative and preventive measures to combat this disease. Besides elaborating on the agent and the disease it causes, this review aims to summarize these pathogenesis data emphasizing the areas meriting further investigation. PMID:23617544

  3. Gastro-intestinal autoimmunity: preclinical experiences and successful therapy of fistulizing bowel diseases and gut Graft versus host disease by mesenchymal stromal cells.

    PubMed

    Voswinkel, Jan; Francois, Sabine; Gorin, Norbert-Claude; Chapel, Alain

    2013-07-01

    Mesenchymal stromal cells (MSC) are multipotent adult stem cells with the potential to regenerate tissue damage and inhibit inflammation and fibrosis in parallel. As they are non-immunogenic, MSC can be safely auto- and allotransplanted and consequently represent a therapeutic option for refractory connective tissue diseases and fistulizing colitis like Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, 22 are on autoimmune diseases and 27 are actually recruiting bowel disease' patients. More than 1,500 patients with bowel diseases like Crohn's disease were treated in clinical trials by local as well as systemic MSC therapy. Phase I and II trials on fistula documented the feasibility and safety of MSC therapy, and a significant superiority compared to fibrin glue in fistulizing bowel diseases was demonstrated. Autologous as well as allogeneic use of Bone marrow as well as of adipose tissue-derived MSC are feasible. In refractory Graft versus host disease, especially in refractory gut Graft versus host diseases, encouraging results were reported using MSC. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets toward an increase in T regulatory cells and a decrease in activated effector T cells. Mesenchymal stem cells represent a safe therapy for patients with refractory inflammatory bowel diseases.

  4. Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes.

    PubMed

    Wang, Yang; Kern, Aurélie; Boatright, Naomi K; Schiller, Zachary A; Sadowski, Andrew; Ejemel, Monir; Souders, Colby A; Reimann, Keith A; Hu, Linden; Thomas, William D; Klempner, Mark S

    2016-07-15

    Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States. Mice transgenic for human immunoglobulin genes were immunized with OspA from B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays. Nearly 100 unique OspA-specific HuMabs were generated, and 4 HuMabs (221-7, 857-2, 319-44, and 212-55) were selected as lead candidates on the basis of borreliacidal activity. HuMabs 319-44, 857-2, and 212-55 were borreliacidal against 1 or 2 Borrelia genospecies, whereas 221-7 was borreliacidal (half maximal inhibitory concentration, < 1 nM) against B. burgdorferi, Borrelia afzelii, and Borrelia garinii, the 3 main genospecies endemic in the United States, Europe, and Asia. All 4 HuMabs completely protected mice from infection at 10 mg/kg in a murine model of tick-mediated transmission of B. burgdorferi  Our study indicates that OspA-specific HuMabs can prevent the transmission of Borrelia and that administration of these antibodies could be employed as preexposure prophylaxis for Lyme disease. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. Antibiotic prophylaxis adequacy in knee arthroplasty and surgical wound infection: Prospective cohort study.

    PubMed

    Del-Moral-Luque, J A; Checa-García, A; López-Hualda, Á; Villar-Del-Campo, M C; Martínez-Martín, J; Moreno-Coronas, F J; Montejo-Sancho, J; Rodríguez-Caravaca, G

    Antibiotic prophylaxis is the most suitable tool for preventing surgical wound infection. This study evaluated adequacy of antibiotic prophylaxis in surgery for knee arthroplasty and its effect on surgical site infection. Prospective cohort study. We assessed the degree of adequacy of antibiotic prophylaxis, the causes of non-adequacy, and the effect of non-adequacy on surgical site infection. Incidence of surgical site infection was studied after a maximum incubation period of a year. To assess the effect of prophylaxis non-adequacy on surgical site infection we used the relative risk adjusted with the aid of a logistic regression model. The study covered a total of 1749 patients. Antibiotic prophylaxis was indicated in all patients and administered in 99.8% of cases, with an overall protocol adequacy of 77.6%. The principal cause of non-compliance was the duration of prescription of the antibiotics (46.5%). Cumulative incidence of surgical site infection was 1.43%. No relationship was found between prophylaxis adequacy and surgical infection (RR=1.15; 95% CI: .31-2.99) (P>.05). Surveillance and infection control programs enable risk factors of infection and improvement measures to be assessed. Monitoring infection rates enables us to reduce their incidence. Adequacy of antibiotic prophylaxis was high but could be improved. We did not find a relationship between prophylaxis adequacy and surgical site infection rate. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Host genetics affect microbial ecosystems via host immunity.

    PubMed

    El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

    2016-10-01

    Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

  7. Improved survival with ursodeoxycholic acid prophylaxis in allogeneic stem cell transplantation: long-term follow-up of a randomized study.

    PubMed

    Ruutu, Tapani; Juvonen, Eeva; Remberger, Mats; Remes, Kari; Volin, Liisa; Mattsson, Jonas; Nihtinen, Anne; Hägglund, Hans; Ringdén, Olle

    2014-01-01

    We report the long-term results of a prospective randomized study on the use of ursodeoxycholic acid (UDCA) for prevention of hepatic complications after allogeneic stem cell transplantation. Two hundred forty-two patients, 232 with malignant disease, were randomized to receive (n = 123) or not to receive (n = 119) UDCA from the beginning of the conditioning until 90 days post-transplantation. The results were reported after 1-year follow-up. UDCA administration reduced significantly the proportion of patients developing high serum bilirubin levels as well as the incidence of severe acute graft-versus-host disease (GVHD), liver GVHD, and intestinal GVHD. In the UDCA prophylaxis group, nonrelapse mortality (NRM) was lower and overall survival better than in the control group. After a 10-year follow-up, the difference in the survival and NRM in favor of the UDCA-treated group, seen at 1 year, was maintained (survival 48% versus 38%, P = .037; NRM 28% versus 41%, P = .01). A landmark analysis in patients surviving at 1 year post-transplantation showed no significant differences between the study groups in the long-term follow-up in chronic GVHD, relapse rate, NRM, disease-free survival, or overall survival. These long-term results continue to support the useful role of UDCA in the prevention of transplant-related complications in allogeneic transplantation. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Butyrate Enhances Disease Resistance of Chickens by Inducing Antimicrobial Host Defense Peptide Gene Expression

    PubMed Central

    Sunkara, Lakshmi T.; Achanta, Mallika; Schreiber, Nicole B.; Bommineni, Yugendar R.; Dai, Gan; Jiang, Weiyu; Lamont, Susan; Lillehoj, Hyun S.; Beker, Ali; Teeter, Robert G.; Zhang, Guolong

    2011-01-01

    Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance. PMID:22073293

  9. Weather, host and vector — their interplay in the spread of insect-borne animal virus diseases

    PubMed Central

    Sellers, R. F.

    1980-01-01

    The spread of insect-borne animal virus diseases is influenced by a number of factors. Hosts migrate, move or are conveyed over long distances: vectors are carried on the wind for varying distances in search of hosts and breeding sites; weather and climate affect hosts and vectors through temperature, moisture and wind. As parasites of host and vector, viruses are carried by animals, birds and insects, and their spread can be correlated with the migration of hosts and the carriage of vectors on winds associated with the movements of the Intertropical Convergence Zone (ITCZ) and warm winds to the north and south of the limits of the ITCZ. The virus is often transmitted from a local cycle to a migratory cycle and back again. Examples of insect-borne virus diseases and their spread are analysed. Japanese, Murray Valley, Western equine, Eastern equine and St Louis encephalitis represent viruses transmitted by mosquito—bird or pig cycles. The areas experiencing infection with these viruses can be divided into a number of zones: A, B, C, D, E and F. In zone A there is a continuous cycle of virus in host and vector throughout the year; in zone B, there is an upsurge in the cycle during the wet season, but the cycle continues during the dry season; there is movement of infected vectors between and within zones A and B on the ITCZ and the virus is introduced to zone C by infected vectors on warm winds; persistence may occur in zone C if conditions are right. In zone D, virus is introduced each year by infected vectors on warm winds and the arrival of the virus coincides with the presence of susceptible nestling birds and susceptible piglets. The disappearance of virus occurs at the time when migrating mosquitoes and birds are returning to warmer climates. The virus is introduced to zone E only on occasions every 5-10 years when conditions are suitable. Infected hosts introduced to zone F do not lead to circulation of virus, since the climate is unsuitable for vectors

  10. Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge.

    PubMed

    Hobbs, Charlotte V; Anderson, Charles; Neal, Jillian; Sahu, Tejram; Conteh, Solomon; Voza, Tatiana; Langhorne, Jean; Borkowsky, William; Duffy, Patrick E

    2017-01-01

    Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8 + T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  11. Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice

    PubMed Central

    Nguyen, Hung; Bastian, David; Heinrichs, Jessica; Wu, Yongxia; Liu, Chen; McDonald, Daniel G.; Pidala, Joseph; Yu, Xue-Zhong

    2015-01-01

    Bruton’s Tyrosine Kinase (BTK) and IL-2 Inducible T-cell Kinase (ITK) are enzymes responsible for the phosphorylation and activation of downstream effectors in the B-cell receptor (BCR) signaling and T cell receptor (TCR) signaling pathways, respectively. Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function. CD4 T cells and B cells are essential for the induction of chronic graft-versus-host disease (cGVHD). We evaluated these targets by testing the ability of Ibrutinib to prevent or ameliorate cGVHD, which is one of the major complications for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that Ibrutinib significantly alleviated cGVHD across four different mouse models, accompanied by increased long-term survival and reduced clinical score. The clinical improvements in Ibrutinib-treated recipients were associated with decreased serum-autoantibodies, costimulatory molecule activation, B-cell proliferation, and glomerulonephritis compared to vehicle controls. Ibrutinib was also able to alleviate the clinical manifestations in acute GVHD (aGVHD), where the recipients were given grafts with or without B cells, suggesting that an inhibitory effect of Ibrutinib on T cells contributes to a reduction in both aGVHD and cGVHD pathogenesis. An effective prophylactic regimen is still lacking to both reduce the incidence and severity of human cGVHD following allo-HSCT. Our study shows that Ibrutinib is an effective prophylaxis against several mouse models of cGVHD with minimal toxicity and could be a promising strategy to combat human cGVHD clinically. PMID:26348529

  12. Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.

    PubMed

    Schutt, Steven D; Fu, Jianing; Nguyen, Hung; Bastian, David; Heinrichs, Jessica; Wu, Yongxia; Liu, Chen; McDonald, Daniel G; Pidala, Joseph; Yu, Xue-Zhong

    2015-01-01

    Bruton's Tyrosine Kinase (BTK) and IL-2 Inducible T-cell Kinase (ITK) are enzymes responsible for the phosphorylation and activation of downstream effectors in the B-cell receptor (BCR) signaling and T cell receptor (TCR) signaling pathways, respectively. Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function. CD4 T cells and B cells are essential for the induction of chronic graft-versus-host disease (cGVHD). We evaluated these targets by testing the ability of Ibrutinib to prevent or ameliorate cGVHD, which is one of the major complications for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that Ibrutinib significantly alleviated cGVHD across four different mouse models, accompanied by increased long-term survival and reduced clinical score. The clinical improvements in Ibrutinib-treated recipients were associated with decreased serum-autoantibodies, costimulatory molecule activation, B-cell proliferation, and glomerulonephritis compared to vehicle controls. Ibrutinib was also able to alleviate the clinical manifestations in acute GVHD (aGVHD), where the recipients were given grafts with or without B cells, suggesting that an inhibitory effect of Ibrutinib on T cells contributes to a reduction in both aGVHD and cGVHD pathogenesis. An effective prophylactic regimen is still lacking to both reduce the incidence and severity of human cGVHD following allo-HSCT. Our study shows that Ibrutinib is an effective prophylaxis against several mouse models of cGVHD with minimal toxicity and could be a promising strategy to combat human cGVHD clinically.

  13. Mechanical Prophylaxis after Lower Extremity Total Joint Arthroplasty: A Review.

    PubMed

    Chughtai, Morad; Newman, Jared M; Solow, Max; Davidson, Iyooh U; Sodhi, Nipun; Gaal, Benjamin; Khlopas, Anton; Sultan, Assem A; Mont, Michael A

    2017-12-22

    Venous thromboembolism (VTE) is a serious complication that can occur after total hip and knee arthroplasty, and can potentially lead to significant morbidity and even mortality. While various modalities have been used to prevent VTE development, the medications can be associated with a number of adverse events. Therefore, mechanical prophylaxis with pumps and compressive devices has been used more frequently alone, or in combination, with medications. Therefore, the purpose of this study was to review the current literature on mechanical prophylaxis for VTEs after lower extremity total joint arthroplasty. Specifically, we reviewed mechanical prophylaxis after: 1) total hip arthroplasty and 2) total knee arthroplasty.

  14. How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

    PubMed

    Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

    2016-09-01

    The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

  15. [Preoperative preparation, antibiotic prophylaxis and surgical wound infection in breast surgery].

    PubMed

    Rodríguez-Caravaca, Gil; de las Casas-Cámara, Gonzalo; Pita-López, María José; Robustillo-Rodela, Ana; Díaz-Agero, Cristina; Monge-Jodrá, Vicente; Fereres, José

    2011-01-01

    The impact of surgical wound infection on public health justifies its surveillance and prevention. Our objectives were to estimate the incidence of surgical wound infection in breast procedures and assess its protocol of antibiotic prophylaxis and preoperative preparation. Observational multicentre prospective cohort study of incidence of surgical wound infection. Incidence was evaluated, stratified by National Nosocomial Infection Surveillance (NNIS) risk index and we calculated the standardized incidence ratio (SIR). The SIR was compared with Spanish rates and U.S. rates. The compliance and performance of the antibiotic prophylaxis and preoperative preparation protocol were assessed and their influence in the incidence of infection with the relative risk. Ten hospitals from the Comunidad de Madrid were included, providing 592 procedures. The cumulative incidence of surgical wound infection was 3.89% (95% CI: 2.3-5.5). The SIR was 1.82 on the Spanish rate and 2.16 on the American. Antibiotic prophylaxis was applied in 97.81% of cases, when indicated. The overall performance of antibiotic prophylaxis was 75%, and 53% for preoperative preparation. No association was found between infection and performance of prophylaxis or preoperative preparation (P>.05). Our incidence is within those seen in the literature although it is somewhat higher than the national surveillance programs. The performance of prophylaxis antibiotic must be improved, as well as the recording of preoperative preparation data. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  16. The role of Ixodes scapularis, Borrelia burgdorferi and wildlife hosts in Lyme disease prevalence: A quantitative review.

    PubMed

    Halsey, Samniqueka J; Allan, Brian F; Miller, James R

    2018-04-16

    Due to the ongoing expansion of Ixodes scapularis (blacklegged tick) throughout the northeastern and midwestern United States, there is need to identify the role wildlife hosts play in the establishment and maintenance of tick populations. To quantify and synthesize the patterns of I. scapularis and Borrelia burgdorferi sensu stricto and sensu lato prevalence relative to wildlife hosts, we reviewed the findings of independent studies conducted throughout the United States. We performed a comprehensive literature search from 1970 to 2017 using the ISS Web of Science Core Collection and the keywords "Ixodes scapularis," "Ixodes dammini" and "Borrelia burgdorferi." We identified 116 studies for inclusion in our meta-analysis, with 187,414 individual wildlife hosts captured and examined for I. scapularis and either the host or ticks collected subsequently tested for B. burgdorferi. We found that only 13% of the wildlife mammals sampled comprised species other than Odocoileus virginianus (white-tailed deer) and Peromyscus leucopus (white-footed mouse). To examine whether there were regional differences between the Northeast, Midwest and the Southeast U.S. in I. scapularis infestation rates on wildlife hosts, we used general linear models (glm), with post hoc pairwise comparisons. In most cases, detection of I. scapularis and B. burgdorferi was significantly higher in the Northeast than the Midwest. Using data on host-specific I. scapularis infestation prevalence, B. burgdorferi prevalence in feeding larvae, and host permissiveness, we developed an epizootiological model to determine the relative contributions of individual hosts to B. burgdorferi-infected nymphs. Our model provides additional evidence that wildlife hosts other than P. leucopus may contribute more to Lyme disease risk than commonly thought. To aid in understanding the ecology of Lyme disease, we propose that additional studies sample non-Peromyscus spp. hosts to obtain more detailed tick and pathogen

  17. Comparison of the two-year outcomes and costs of prophylaxis in medical patients at risk of venous thromboembolism.

    PubMed

    Deitelzweig, Steven B; Becker, Russ; Lin, Jay; Benner, Josh

    2008-11-01

    A decision-analytic model incorporating a Markov process to assess the incremental cost and effectiveness of venous thromboembolism (VTE) prevention strategies was used. Modeling was carried out using a hypothetical cohort of medical patients at risk of VTE. The model compared clinical effectiveness (primary and recurrent VTE, death), safety (adverse events), and direct medical costs between patients receiving enoxaparin prophylaxis, unfractionated heparin (UFH) prophylaxis, and no prophylaxis (n = 10,000 for each arm). Monte Carlo simulation was performed to identify changes in inputs that would affect the results. The estimated incidence ofVTE at two years (including recurrent VTE) was 6.8% with enoxaparin prophylaxis, 7.9% with UFH prophylaxis, and 17.9% with no prophylaxis. Two-year mortality occurred in 15.7% of enoxaparin patients and 16.0% of UFH patients, with the incidences of major bleeding in these groups being 0.7% and 1.2%, respectively. However, both enoxaparin and UFH prophylaxis were associated with higher rates of major bleeds than no prophylaxis (0.6%). Total average costs per patient were (US dollars) $1,264 (for enoxaparin prophylaxis, $1,585 for UFH prophylaxis, and $2,245 for no prophylaxis). No realistic parameter changes resulted in enoxaparin prophylaxis being more costly than UFH prophylaxis. For the healthcare payer, considering all direct medical costs associated with VTE up to two years after an admission for acute illness, prophylaxis with enoxaparin was more effective and less costly than UFH. This identifies enoxaparin as a potentially favorable VTE prophylaxis regimen compared with UFH and no prophylaxis in at-risk medical patients.

  18. Resistance pattern of breakthrough urinary tract infections in children on antibiotic prophylaxis.

    PubMed

    Nateghian, Ali Reza; Robinson, Joan L; Mohandessi, Shahab; Hooman, Nakysa

    2009-01-01

    Prophylactic antibiotics are commonly used for prevention of urinary tract infections (UTIs) in children. It was postulated that the organisms and resistance patterns of breakthrough infections would differ with the choice of antimicrobial prophylaxis. This was a retrospective descriptive study of all breakthroughs UTI from 2000 to 2006 in children over 1 month of age discharged from a referral children's hospital in Tehran, Iran on continuous antibiotic prophylaxis for UTIs. Fifty-seven children discharged on prophylaxis had breakthrough UTIs of which 32 (56%) had a previously diagnosed urinary tract anomaly. Escherichia coli was responsible for the majority of infections irrespective of choice of prophylaxis. Thirty-three of 56 breakthrough UTIs (59%) were with organisms that were resistant to the prophylactic antibiotic. There was an increased incidence of resistance to prophylaxis in children on cefixime (16 of 22; 78%) when compared with children on cephalexin (7 of 19; 37%; p=0.02) and a trend toward increased resistance when compared with children on trimethoprim-sulfamethoxasole (3 of 8; 37%) (p=0.10). In conclusion, the resistance pattern of organisms causing breakthrough UTIs varies with the choice of prophylaxis which should be taken into consideration in chosing empiric therapy for such infections.

  19. Graft-versus-host disease after radiation therapy in patients who have undergone allogeneic stem cell transplantation: two case reports.

    PubMed

    Milgrom, Sarah A; Nieto, Yago; Pinnix, Chelsea C; Smith, Grace L; Wogan, Christine F; Rondon, Gabriela; Medeiros, L Jeffrey; Kebriaei, Partow; Dabaja, Bouthaina S

    2016-07-28

    Patients who undergo allogeneic stem cell transplantation and subsequent radiation therapy uncommonly develop graft-versus-host disease within the irradiated area. We quantified the incidence of this complication, which is a novel contribution to the field. From 2010 to 2014, 1849 patients underwent allogeneic stem cell transplantation, and 41 (2 %) received radiation therapy afterward. Of these, two patients (5 %) developed graft-versus-host disease within the irradiated tissues during or immediately after radiation therapy. The first patient is a 37-year-old white man who had Hodgkin lymphoma; he underwent allogeneic stem cell transplantation from a matched unrelated donor and received radiation therapy for an abdominal and pelvic nodal recurrence. After 28.8 Gy, he developed grade 4 gastrointestinal graft-versus-host disease, refractory to tacrolimus and steroids, but responsive to pentostatin and photopheresis. The other patient is a 24-year-old white man who had acute leukemia; he underwent allogeneic stem cell transplantation from a matched related donor and received craniospinal irradiation for a central nervous system relapse. After 24 cobalt Gy equivalent, he developed severe cutaneous graft-versus-host disease, sharply delineated within the radiation therapy field, which was responsive to tacrolimus and methylprednisolone. We conclude that graft-versus-host disease within irradiated tissues is an uncommon but potentially serious complication that may follow radiation therapy in patients who have undergone allogeneic stem cell transplantation. Clinicians must be aware of this complication and prepared with strategies to mitigate risk. Patients who have undergone allogeneic stem cell transplantation represent a unique population that may offer novel insight into the pathways involved in radiation-related inflammation.

  20. Cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in lymphoma patients.

    PubMed

    Lathia, Nina; Isogai, Pierre K; De Angelis, Carlo; Smith, Thomas J; Cheung, Matthew; Mittmann, Nicole; Hoch, Jeffrey S; Walker, Scott

    2013-08-07

    Febrile neutropenia is a serious toxicity of cancer chemotherapy that is usually treated in hospital. We assessed the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in diffuse large B-cell lymphoma (DLBCL) patients undergoing chemotherapy. We used a Markov model that followed patients through induction chemotherapy to compare the three prophylaxis strategies: 1) no primary prophylaxis against febrile neutropenia; 2) primary prophylaxis with 10 days of filgrastim therapy; and 3) primary prophylaxis with a single dose of pegfilgrastim. The target population was a hypothetical cohort of 64-year-old men and women with DLBCL. Data sources included published literature and current clinical practice. The analysis was conducted from a publicly funded health-care system perspective. The main outcome measures included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base-case analysis, costs associated with no primary prophylaxis, primary prophylaxis with 10 days of filgrastim, and primary prophylaxis with pegfilgrastim were CaD $7314, CaD $13947, and CaD $16290, respectively. The QALYs associated with the three strategies were 0.2004, 0.2015, and 0.2024, respectively. The ICER for the filgrastim vs no primary prophylaxis strategy was CaD $5796000 per QALY. The ICER for the pegfilgrastim vs filgrastim primary prophylaxis strategy was CaD $2611000 per QALY. All one-way sensitivity analyses yielded ICERs greater than CaD $400000 per QALY. Cost-effectiveness acceptability curves show that 20.0% of iterations are cost-effective at a willingness-to-pay threshold of CaD $1595000 for the filgrastim strategy and CaD $561000 for the pegfilgrastim strategy. Primary prophylaxis against febrile neutropenia with either filgrastim or pegfilgrastim is not cost-effective in DLBCL patients.

  1. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission.

    PubMed

    Kumwenda, Newton I; Hoover, Donald R; Mofenson, Lynne M; Thigpen, Michael C; Kafulafula, George; Li, Qing; Mipando, Linda; Nkanaunena, Kondwani; Mebrahtu, Tsedal; Bulterys, Marc; Fowler, Mary Glenn; Taha, Taha E

    2008-07-10

    Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings. Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth. Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug. Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.) 2008 Massachusetts Medical Society

  2. Clinical Prediction of Failure of Lamivudine Prophylaxis for Hepatitis B Virus-Infected Patients Undergoing Cytotoxic Chemotherapy for Malignancy

    PubMed Central

    Kim, In Kyoung; Kim, Byeong Gwan; Kim, Donghee; Kim, Yoon Jun; Yoon, Jung-Hwan; Lee, Hyo Suk

    2012-01-01

    Although lamivudine (LAM) prophylaxis is recommended for patients infected with hepatitis B virus (HBV) undergoing chemotherapy for malignant disease, HBV reactivation sometimes occurs during or after LAM administration. The aim of this study was to determine predictors of LAM prophylactic failure in patients with malignancies. Patients with malignancies were routinely screened for serum hepatitis B surface antigen (HBsAg) from June 2002 to August 2008. All consecutive, HBsAg-positive patients received LAM prophylaxis during and after completion of chemotherapy. We assessed risk factors for virologic breakthrough and withdrawal hepatitis. Death without HBV reactivation was regarded as a competing risk event, which was adjusted by Fine and Gray's model. A total of 110 patients were included in this study. They received LAM prophylaxis for a median of 9.2 months. Virologic breakthrough occurred in 15 patients at a median of 10.9 months from the initiation of LAM prophylaxis. Withdrawal hepatitis occurred in 15 patients at a median of 2.4 months after cessation of LAM prophylaxis. Multivariable analysis showed that high baseline HBV DNA titer (≥2,000 IU/ml) (hazard ratio [HR], 9.94; P = 0.0063) and the use of rituximab (HR, 3.19; P = 0.027) were significant predictors of virologic breakthrough and that high baseline HBV DNA titer (HR, 5.90; P = 0.007), liver cirrhosis (HR, 10.4; P = 0.002), and distant metastasis (HR, 5.14; P = 0.008) were independent risk factors for withdrawal hepatitis. Patients with high viremia, liver cirrhosis, rituximab treatment, and distant metastasis are at high risk of prophylactic failure and need antiviral agents with a greater barrier to resistance. PMID:22890764

  3. Alkoxycarbonate Ester Prodrugs of Preclinical Drug Candidate ELQ-300 for Prophylaxis and Treatment of Malaria.

    PubMed

    Frueh, Lisa; Li, Yuexin; Mather, Michael W; Li, Qigui; Pou, Sovitj; Nilsen, Aaron; Winter, Rolf W; Forquer, Isaac P; Pershing, April M; Xie, Lisa H; Smilkstein, Martin J; Caridha, Diana; Koop, Dennis R; Campbell, Robert F; Sciotti, Richard J; Kreishman-Deitrick, Mara; Kelly, Jane X; Vesely, Brian; Vaidya, Akhil B; Riscoe, Michael K

    2017-10-13

    ELQ-300 is a preclinical antimalarial drug candidate that is active against liver, blood, and transmission stages of Plasmodium falciparum. While ELQ-300 is highly effective when administered in a low multidose regimen, poor aqueous solubility and high crystallinity have hindered its clinical development. To overcome its challenging physiochemical properties, a number of bioreversible alkoxycarbonate ester prodrugs of ELQ-300 were synthesized. These bioreversible prodrugs are converted to ELQ-300 by host and parasite esterase action in the liver and bloodstream of the host. One such alkoxycarbonate prodrug, ELQ-331, is curative against Plasmodium yoelii with a single low dose of 3 mg/kg in a murine model of patent malaria infection. ELQ-331 is at least as fully protective as ELQ-300 in a murine malaria prophylaxis model when delivered 24 h before sporozoite inoculation at an oral dose of 1 mg/kg. Here, we show that ELQ-331 is a promising prodrug of ELQ-300 with improved physiochemical and metabolic properties and excellent potential for clinical formulation.

  4. Research Strategies to Reduce Tick Densities and the Risk of Tick-borne Disease Transmission through Host-Targeted Control

    USDA-ARS?s Scientific Manuscript database

    While white-tailed deer are not reservoir hosts for the Lyme disease agent, Borrelia burgdorferi, they are the keystone host animal on which adult female blacklegged ticks engorge on blood that is essential to production of tick eggs and completion of the life cycle. This session explores current re...

  5. Predators indirectly control vector-borne disease: linking predator-prey and host-pathogen models.

    PubMed

    Moore, Sean M; Borer, Elizabeth T; Hosseini, Parviez R

    2010-01-06

    Pathogens transmitted by arthropod vectors are common in human populations, agricultural systems and natural communities. Transmission of these vector-borne pathogens depends on the population dynamics of the vector species as well as its interactions with other species within the community. In particular, predation may be sufficient to control pathogen prevalence indirectly via the vector. To examine the indirect effect of predators on vectored-pathogen dynamics, we developed a theoretical model that integrates predator-prey and host-pathogen theory. We used this model to determine whether predation can prevent pathogen persistence or alter the stability of host-pathogen dynamics. We found that, in the absence of predation, pathogen prevalence in the host increases with vector fecundity, whereas predation on the vector causes pathogen prevalence to decline, or even become extinct, with increasing vector fecundity. We also found that predation on a vector may drastically slow the initial spread of a pathogen. The predator can increase host abundance indirectly by reducing or eliminating infection in the host population. These results highlight the importance of studying interactions that, within the greater community, may alter our predictions when studying disease dynamics. From an applied perspective, these results also suggest situations where an introduced predator or the natural enemies of a vector may slow the rate of spread of an emerging vector-borne pathogen.

  6. Graft versus host disease: what should the oculoplastic surgeon know?

    PubMed

    Tung, Cynthia I

    2017-09-01

    To provide a concise review of the oculoplastic manifestations of ocular graft versus host disease (GVHD), and to discuss their management. Ocular GVHD occurs as a common immune-mediated complication of hematopoietic stem cell transplantation that presents as a Stevens-Johnson-like syndrome in the acute phase or a Sjögren-like syndrome in the chronic phase. Cicatricial conjunctivitis may be underreported in ocular GVHD. The spectrum of oculoplastic manifestations includes GVHD of the skin, cicatricial entropion, nasolacrimal duct obstruction, and lacrimal gland dysfunction. Surgical treatment is indicated for patients with significant corneal complications from entropion. Surgical approach to repair of nasolacrimal duct obstruction is presented in this review, including modified approaches for treating patients at risk for keratitis sicca. Management of the ocular graft versus host patient may require a multidisciplinary approach involving collaboration from the oculoplastic surgeon, the corneal specialist, and the stem cell transplant physician. Oculoplastic manifestations of ocular GVHD typically present as cicatricial changes in the eyelid and lacrimal system. Careful oculoplastic and corneal evaluation are necessary when considering surgical management for the ocular GVHD patient.

  7. Venous Thromboembolism Risk and Adequacy of Prophylaxis in High Risk Pregnancy in the Arabian Gulf

    PubMed Central

    Alsayegh, Faisal; Al-Jassar, Waleed; Wani, Salima; Tahlak, Muna; Al-Bahar, Awatef; Al-Kharusi, Lamya; Al-Tamimi, Halima; El-Taher, Faten; Mahmood, Naeema; Al-Zakwani, Ibrahim

    2016-01-01

    Objectives: To estimate the prevalence of venous thromboembolism (VTE) risk factors in pregnancy and the proportion of pregnancies at risk of VTE that received the recommended prophylaxis according to the American College of Chest Physicians (ACCP) 2012 published guidelines in antenatal clinics in the Arabian Gulf. Methods: The evaluation of venous thromboembolism (EVE)-Risk project was a non-interventional, cross-sectional, multi-centre, multi-national study of all eligible pregnant women (≥17 years) screened during antenatal clinics from 7 centres in the Arabian Gulf countries (United Arab Emirates, Kuwait, Bahrain, Qatar and Oman). Pregnant women were recruited during a 3-month period between September and December 2012. Results: Of 4,131 screened pregnant women, 32% (n=1,337) had ≥1 risk factors for VTE. Common VTE risk factors included obesity (76%), multiparity (33%), recurrent miscarriages (9.1%), varicose veins (6.9%), thrombophilia (2.6%), immobilization (2.0%), sickle cell disease (2.8%) and previous VTE (1.6%). Only 8.3% (n=111) of the high risk patients were on the recommended VTE prophylaxis. Enoxaparin was used in 80% (n=89) of the cases followed by tinzaparin (4%; n=4). Antiplatelet agents were prescribed in 11% (n=149) of pregnant women. Of those on anticoagulants (n=111), 59% (n=66) were also co-prescribed antiplatelet agents. Side effects (mainly local bruising at the injection site) were reported in 12% (n=13) of the cases. Conclusion: A large proportion of pregnant women in the Arabian Gulf countries have ≥1 VTE risk factor with even a smaller fraction on prophylaxis. VTE risk assessment must be adopted to identify those at risk who would need VTE prophylaxis. PMID:26517701

  8. Case Study of Intrapartum Antibiotic Prophylaxis and Subsequent Postpartum Beta-Lactam Anaphylaxis.

    PubMed

    Stark, Mary Ann; Ross, Mary Frances; Kershner, Wendy; Searing, Kimberly

    2015-01-01

    Universal screening for maternal group B Streptococcus (GBS) in the prenatal period has led to administration of intrapartum antibiotic prophylaxis (IAP). Although IAP decreased the rate of early neonatal GBS disease, exposure of childbearing women to penicillin and other beta-lactam antibiotics has increased. Beta-lactam-induced anaphylaxis in the breastfeeding woman during the postpartum period illustrates risk factors for beta-lactam allergy and anaphylaxis. Treatment and nursing implications for this adverse reaction are suggested. © 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  9. Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF)

    PubMed Central

    2013-01-01

    Background Myelosuppressive chemotherapy can lead to dose-limiting febrile neutropenia. Prophylactic use of recombinant human G-CSF such as daily filgrastim and once-per-cycle pegfilgrastim may reduce the incidence of febrile neutropenia. This comparative study examined the effect of pegfilgrastim versus daily filgrastim on the risk of hospitalization. Methods This retrospective United States claims analysis utilized 2004–2009 data for filgrastim- and pegfilgrastim-treated patients receiving chemotherapy for non-Hodgkin’s lymphoma (NHL) or breast, lung, ovarian, or colorectal cancers. Cycles in which pegfilgrastim or filgrastim was administered within 5 days from initiation of chemotherapy (considered to represent prophylaxis) were pooled for analysis. Neutropenia-related hospitalization and other healthcare encounters were defined with a “narrow” criterion for claims with an ICD-9 code for neutropenia and with a “broad” criterion for claims with an ICD-9 code for neutropenia, fever, or infection. Odds ratios (OR) for hospitalization and 95% confidence intervals (CI) were estimated by generalized estimating equation (GEE) models and adjusted for patient, tumor, and treatment characteristics. Per-cycle healthcare utilization and costs were examined for cycles with pegfilgrastim or filgrastim prophylaxis. Results We identified 3,535 patients receiving G-CSF prophylaxis, representing 12,056 chemotherapy cycles (11,683 pegfilgrastim, 373 filgrastim). The mean duration of filgrastim prophylaxis in the sample was 4.8 days. The mean duration of pegfilgrastim prophylaxis in the sample was 1.0 day, consistent with the recommended dosage of pegfilgrastim - a single injection once per chemotherapy cycle. Cycles with prophylactic pegfilgrastim were associated with a decreased risk of neutropenia-related hospitalization (narrow definition: OR = 0.43, 95% CI: 0.16–1.13; broad definition: OR = 0.38, 95% CI: 0.24–0.59) and all-cause hospitalization (OR

  10. Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses

    PubMed Central

    Hurt, Aeron C.; Oshansky, Christine M.; Oh, Ding Yuan; Reading, Patrick C.; Chua, Brendon Y.; Sun, Yilun; Tang, Li; Handel, Andreas; Jackson, David C.; Turner, Stephen J.; Thomas, Paul G.; Kedzierska, Katherine

    2015-01-01

    CD8+ T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8+ T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8+ T cell responses and the establishment of immunological CD8+ T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8+ T cell responses. Importantly, functional memory CD8+ T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4+ T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8+ T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves. PMID:26086392

  11. The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection.

    PubMed

    Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna

    2017-05-01

    People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

  12. Trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is effective against acute murine inhalational melioidosis and glanders.

    PubMed

    Barnes, Kay B; Steward, Jackie; Thwaite, Joanne E; Lever, M Stephen; Davies, Carwyn H; Armstrong, Stuart J; Laws, Thomas R; Roughley, Neil; Harding, Sarah V; Atkins, Timothy P; Simpson, Andrew J H; Atkins, Helen S

    2013-06-01

    Burkholderia pseudomallei is the causative agent of the disease melioidosis, which is prevalent in tropical countries and is intractable to a number of antibiotics. In this study, the antibiotic co-trimoxazole (trimethoprim/sulfamethoxazole) was assessed for the post-exposure prophylaxis of experimental infection in mice with B. pseudomallei and its close phylogenetic relative Burkholderia mallei, the causative agent of glanders. Co-trimoxazole was effective against an inhalational infection with B. pseudomallei or B. mallei. However, oral co-trimoxazole delivered twice daily did not eradicate infection when administered from 6h post exposure for 14 days or 21 days, since infected and antibiotic-treated mice succumbed to infection following relapse or immunosuppression. These data highlight the utility of co-trimoxazole for prophylaxis both of B. pseudomallei and B. mallei and the need for new approaches for the treatment of persistent bacterial infection. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  13. Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy.

    PubMed

    Gorski, Armin; Hamouda, Khaled; Özkur, Mehmet; Leistner, Markus; Sommer, Sebastian-Patrick; Leyh, Rainer; Schimmer, Christoph

    2015-03-01

    Ongoing debate exists concerning the optimal choice and duration of antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic therapy for hospital-acquired infections in critically ill cardiac surgery patients. A nationwide questionnaire was distributed to all German heart surgery centers concerning antibiotic prophylaxis and the calculated empiric antibiotic therapy. The response to the questionnaire was 87.3%. All clinics that responded use antibiotic prophylaxis, 79% perform it not longer than 24 h (single-shot: 23%; 2 doses: 29%; 3 doses: 27%; 4 doses: 13%; and >5 doses: 8%). Cephalosporin was used in 89% of clinics (46% second-generation, 43% first-generation cephalosporin). If sepsis is suspected, the following diagnostics are performed routinely: wound inspection 100%; white blood cell count 100%; radiography 99%; C-reactive protein 97%; microbiological testing of urine 91%, blood 81%, and bronchial secretion 81%; procalcitonin 74%; and echocardiography 75%. The calculated empiric antibiotic therapy (depending on the suspected focus) consists of a multidrug combination with broad-spectrum agents. This survey shows that existing national guidelines and recommendations concerning perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy are well applied in almost all German heart centers. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Susceptibility to Phytophthora ramorum in a key infectious host: landscape variation in host genotype, host phenotype, and environmental factors.

    PubMed

    Anacker, Brian L; Rank, Nathan E; Hüberli, Daniel; Garbelotto, Matteo; Gordon, Sarah; Harnik, Tami; Whitkus, Richard; Meentemeyer, Ross

    2008-01-01

    Sudden oak death is an emerging forest disease caused by the invasive pathogen Phytophthora ramorum. Genetic and environmental factors affecting susceptibility to P. ramorum in the key inoculum-producing host tree Umbellularia californica (bay laurel) were examined across a heterogeneous landscape in California, USA. Laboratory susceptibility trials were conducted on detached leaves and assessed field disease levels for 97 host trees from 12 225-m(2) plots. Genotype and phenotype characteristics were assessed for each tree. Effects of plot-level environmental conditions (understory microclimate, amount of solar radiation and topographic moisture potential) on disease expression were also evaluated. Susceptibility varied significantly among U. californica trees, with a fivefold difference in leaf lesion size. Lesion size was positively related to leaf area, but not to other phenotypic traits or to field disease level. Genetic diversity was structured at three spatial scales, but primarily among individuals within plots. Lesion size was significantly related to amplified fragment length polymorphism (AFLP) markers, but local environment explained most variation in field disease level. Thus, substantial genetic variation in susceptibility to P. ramorum occurs in its principal foliar host U. californica, but local environment mediates expression of susceptibility in nature.

  15. Comparative genetic diversity of Lyme disease bacteria in Northern Californian ticks and their vertebrate hosts.

    PubMed

    Swei, Andrea; Bowie, Verna C; Bowie, Rauri C K

    2015-04-01

    Vector-borne pathogens are transmitted between vertebrate hosts and arthropod vectors, two immensely different environments for the pathogen. There is further differentiation among vertebrate hosts that often have complex, species-specific immunological responses to the pathogen. All this presents a heterogeneous environmental and immunological landscape with possible consequences on the population genetic structure of the pathogen. We evaluated the differential genetic diversity of the Lyme disease pathogen, Borrelia burgdorferi, in its vector, the western black-legged tick (Ixodes pacificus), and in its mammal host community using the 5S-23S rRNA intergenic spacer region. We found differences in haplotype distribution of B. burgdorferi in tick populations from two counties in California as well as between a sympatric tick and vertebrate host community. In addition, we found that three closely related haplotypes consistently occurred in high frequency in all sample types. Lastly, our study found lower species diversity of the B. burgdorferi species complex, known as B. burgdorferi sensu lato, in small mammal hosts versus the tick populations in a sympatric study area. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Prospective multicentre PCR-based Aspergillus DNA screening in high-risk patients with and without primary antifungal mould prophylaxis.

    PubMed

    Springer, J; Lackner, M; Nachbaur, D; Girschikofsky, M; Risslegger, B; Mutschlechner, W; Fritz, J; Heinz, W J; Einsele, H; Ullmann, A J; Löffler, J; Lass-Flörl, C

    2016-01-01

    Invasive aspergillosis (IA) is associated with significant morbidity and mortality, and, among other factors, this is due to a delay in diagnosis performed with conventional techniques. A prospective, multicentre study was conducted to evaluate the efficacy of Aspergillus DNA screening in the early diagnosis of IA. Patients undergoing haematopoietic stem cell transplantation or chemotherapy for acute leukaemia were enrolled for biomarker screening. Three centres applied the same protocol for in-house PCR, which was compliant with the European Aspergillus PCR Initiative recommendations, to guarantee the highest diagnostic standards. Two thousand one hundred and twenty-eight sera from 213 patients were investigated and stratified according to the revised European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria for invasive fungal disease. The incidence rates of probable and possible IA were 18% and 38%, respectively. The sensitivity, specificity and positive predictive value (PPV) of PCR were superior in antifungal drug-naive patients, being 71.4%, 92.3%, and 62.5%, respectively. The last of these key performance indicators (PPV) was moderate in patients receiving primary prophylaxis, at 5.4%. Negative predictive values for both strategies applied were 100% with and 98.3% without antifungal mould prophylaxis. PCR has the potential to play a decisive role in the diagnosis and management of Aspergillus infections in centres not applying primary antifungal mould prophylaxis. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Host plant forensics and olfactory-based detection in Afro-tropical mosquito disease vectors.

    PubMed

    Nyasembe, Vincent O; Tchouassi, David P; Pirk, Christian W W; Sole, Catherine L; Torto, Baldwyn

    2018-02-01

    The global spread of vector-borne diseases remains a worrying public health threat, raising the need for development of new combat strategies for vector control. Knowledge of vector ecology can be exploited in this regard, including plant feeding; a critical resource that mosquitoes of both sexes rely on for survival and other metabolic processes. However, the identity of plant species mosquitoes feed on in nature remains largely unknown. By testing the hypothesis about selectivity in plant feeding, we employed a DNA-based approach targeting trnH-psbA and matK genes and identified host plants of field-collected Afro-tropical mosquito vectors of dengue, Rift Valley fever and malaria being among the most important mosquito-borne diseases in East Africa. These included three plant species for Aedes aegypti (dengue), two for both Aedes mcintoshi and Aedes ochraceus (Rift Valley fever) and five for Anopheles gambiae (malaria). Since plant feeding is mediated by olfactory cues, we further sought to identify specific odor signatures that may modulate host plant location. Using coupled gas chromatography (GC)-electroantennographic detection, GC/mass spectrometry and electroantennogram analyses, we identified a total of 21 antennally-active components variably detected by Ae. aegypti, Ae. mcintoshi and An. gambiae from their respective host plants. Whereas Ae. aegypti predominantly detected benzenoids, Ae. mcintoshi detected mainly aldehydes while An. gambiae detected sesquiterpenes and alkenes. Interestingly, the monoterpenes β-myrcene and (E)-β-ocimene were consistently detected by all the mosquito species and present in all the identified host plants, suggesting that they may serve as signature cues in plant location. This study highlights the utility of molecular approaches in identifying specific vector-plant associations, which can be exploited in maximizing control strategies such as such as attractive toxic sugar bait and odor-bait technology.

  18. Host plant forensics and olfactory-based detection in Afro-tropical mosquito disease vectors

    PubMed Central

    Nyasembe, Vincent O.; Tchouassi, David P.; Pirk, Christian W. W.; Sole, Catherine L.

    2018-01-01

    The global spread of vector-borne diseases remains a worrying public health threat, raising the need for development of new combat strategies for vector control. Knowledge of vector ecology can be exploited in this regard, including plant feeding; a critical resource that mosquitoes of both sexes rely on for survival and other metabolic processes. However, the identity of plant species mosquitoes feed on in nature remains largely unknown. By testing the hypothesis about selectivity in plant feeding, we employed a DNA-based approach targeting trnH-psbA and matK genes and identified host plants of field-collected Afro-tropical mosquito vectors of dengue, Rift Valley fever and malaria being among the most important mosquito-borne diseases in East Africa. These included three plant species for Aedes aegypti (dengue), two for both Aedes mcintoshi and Aedes ochraceus (Rift Valley fever) and five for Anopheles gambiae (malaria). Since plant feeding is mediated by olfactory cues, we further sought to identify specific odor signatures that may modulate host plant location. Using coupled gas chromatography (GC)-electroantennographic detection, GC/mass spectrometry and electroantennogram analyses, we identified a total of 21 antennally-active components variably detected by Ae. aegypti, Ae. mcintoshi and An. gambiae from their respective host plants. Whereas Ae. aegypti predominantly detected benzenoids, Ae. mcintoshi detected mainly aldehydes while An. gambiae detected sesquiterpenes and alkenes. Interestingly, the monoterpenes β-myrcene and (E)-β-ocimene were consistently detected by all the mosquito species and present in all the identified host plants, suggesting that they may serve as signature cues in plant location. This study highlights the utility of molecular approaches in identifying specific vector-plant associations, which can be exploited in maximizing control strategies such as such as attractive toxic sugar bait and odor-bait technology. PMID:29462150

  19. Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression

    USDA-ARS?s Scientific Manuscript database

    Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. I...

  20. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

    PubMed Central

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J.; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S.; Stockwell, Timothy B.; Rodriguez, Luis L.

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region. PMID:29390015

  1. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

    PubMed

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

  2. Comparative Characterization of the Sindbis Virus Proteome from Mammalian and Invertebrate Hosts Identifies nsP2 as a Component of the Virus Nucleocapsid and Sorting Nexin 5 as a Significant Host Factor for Alphavirus Replication.

    PubMed

    Schuchman, Ryan; Kilianski, Andy; Piper, Amanda; Vancini, Ricardo; Ribeiro, José M C; Sprague, Thomas R; Nasar, Farooq; Boyd, Gabrielle; Hernandez, Raquel; Glaros, Trevor

    2018-05-09

    no vaccines or prophylactics for these agents leaving one third of the world population at risk of infection. Identifying effective antivirals has been a long term goal for combating these diseases not only because of the lack of vaccines but also because they are effective during an ongoing epidemic. Mass spectrometry-based analysis of the Sindbis virus proteome can be effective in identifying host genes involved in virus replication and novel functions for virus proteins. Identification of these factors is invaluable for the prophylaxis of this group of viruses. Copyright © 2018 Schuchman et al.

  3. Estimating Coextinction Risks from Epidemic Tree Death: Affiliate Lichen Communities among Diseased Host Tree Populations of Fraxinus excelsior

    PubMed Central

    Jönsson, Mari T.; Thor, Göran

    2012-01-01

    At least 10% of the world’s tree species are threatened with extinction and pathogens are increasingly implicated in tree threats. Coextinction and threats to affiliates as a consequence of the loss or decline of their host trees is a poorly understood phenomenon. Ash dieback is an emerging infectious disease causing severe dieback of common ash Fraxinus excelsior throughout Europe. We utilized available empirical data on affiliate epiphytic lichen diversity (174 species and 17,800 observations) among 20 ash dieback infected host tree populations of F. excelsior on the island Gotland in the Baltic Sea, Sweden. From this, we used structured scenario projections scaled with empirical data of ash dieback disease to generate probabilistic models for estimating local and regional lichen coextinction risks. Average coextinction probabilities (Ā) were 0.38 (95% CI ±0.09) for lichens occurring on F. excelsior and 0.14 (95% CI ±0.03) when considering lichen persistence on all tree species. Ā was strongly linked to local disease incidence levels and generally increasing with lichen host specificity to F. excelsior and decreasing population size. Coextinctions reduced affiliate community viability, with significant local reductions in species richness and shifts in lichen species composition. Affiliates were projected to become locally extirpated before their hosts, illuminating the need to also consider host tree declines. Traditionally managed open wooded meadows had the highest incidence of ash dieback disease and significantly higher proportions of affiliate species projected to go extinct, compared with unmanaged closed forests and semi-open grazed sites. Most cothreatened species were not previously red-listed, which suggest that tree epidemics cause many unforeseen threats to species. Our analysis shows that epidemic tree deaths represent an insidious, mostly overlooked, threat to sessile affiliate communities in forested environments. Current conservation and

  4. [Acute treatment and secondary prophylaxis of ischemic stroke : An excellent example for personalized medicine].

    PubMed

    Wachter, R; Gröschel, K

    2018-03-01

    About a quarter of a million people in Germany suffer a stroke every year. Stroke is the most dreaded cardiovascular disease, even before myocardial infarction and heart failure. In the last two to three years, significant progress has been made in acute treatment, secondary prophylaxis in patients with patent foramen ovale, and the interdisciplinary evaluation of atrial fibrillation as the cause of the stroke. These new findings allow for more precise treatment.

  5. Use of antibacterial prophylaxis for patients with neutropenia. Australian Consensus Guidelines 2011 Steering Committee.

    PubMed

    Slavin, M A; Lingaratnam, S; Mileshkin, L; Booth, D L; Cain, M J; Ritchie, D S; Wei, A; Thursky, K A

    2011-01-01

    The use of oral prophylactic antibiotics in patients with neutropenia is controversial and not recommended by this group because of a lack of evidence showing a reduction in mortality and concerns that such practice promotes antimicrobial resistance. Recent evidence has demonstrated non-significant but consistent, improvement in all-cause mortality when fluoroquinolones (FQs) are used as primary prophylaxis. However, the consensus was that this evidence was not strong enough to recommend prophylaxis. The evidence base for FQ prophylaxis is presented alongside current consensus opinion to guide the appropriate and judicious use of these agents. Due consideration is given to patient risk, as it pertains to specific patient populations, as well as the net effect on selective pressure from antibiotics if FQ prophylaxis is routinely used in a target population. The potential costs and consequences of emerging FQ resistance, particularly among Escherichia coli, Clostridium difficile and Gram-positive organisms, are considered. As FQ prophylaxis has been advocated in some chemotherapy protocols, specific regard is given to whether FQ prophylaxis should be used to support these regimens. The group also provides recommendations for monitoring and surveillance of emerging resistance in those centres that have adopted FQ prophylaxis. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  6. Partial palivizumab prophylaxis and increased risk of hospitalization due to respiratory syncytial virus in a Medicaid population: a retrospective cohort analysis.

    PubMed

    Krilov, Leonard R; Masaquel, Anthony S; Weiner, Leonard B; Smith, David M; Wade, Sally W; Mahadevia, Parthiv J

    2014-10-13

    Infection with respiratory syncytial virus (RSV) is common among young children insured through Medicaid in the United States. Complete and timely dosing with palivizumab is associated with lower risk of RSV-related hospitalizations, but up to 60% of infants who receive palivizumab in Medicaid population do not receive full prophylaxis. The purpose of this study was to evaluate the association of partial palivizumab prophylaxis with the risk of RSV hospitalization among high-risk Medicaid-insured infants. Claims data from 12 states during 6 RSV seasons (October 1st to April 30th in the first year of life in 2003-2009) were analyzed. Inclusion criteria were birth hospital discharge before October 1st, continuous insurance eligibility from birth through April 30th, ≥ one palivizumab administration from August 1st to end of season, and high-risk status (≤34 weeks gestational age or chronic lung disease of prematurity [CLDP] or hemodynamically significant congenital heart disease [CHD]). Fully prophylaxed infants received the first palivizumab dose by November 30th with no gaps >35 days up to the first RSV-related hospitalization or end of follow-up. All other infants were categorized as partially prophylaxed. Of the 8,443 high-risk infants evaluated, 67% (5,615) received partial prophylaxis. Partially prophylaxed infants were more likely to have RSV-related hospitalization than fully prophylaxed infants (11.7% versus 7.9%, p< 0.001). RSV-related hospitalization rates ranged from 8.5% to 24.8% in premature, CHD, and CLDP infants with partial prophylaxis. After adjusting for potential confounders, logistic regression showed that partially prophylaxed infants had a 21% greater odds of hospitalization compared with fully prophylaxed infants (odds ratio 1.21, 95% confidence interval 1.09-1.34). RSV-related hospitalization rates were significantly higher in high-risk Medicaid infants with partial palivizumab prophylaxis compared with fully prophylaxed infants. These

  7. Extended Venous Thromboembolism Prophylaxis after Radical Cystectomy: A Call for Adherence to Current Guidelines.

    PubMed

    Klaassen, Zachary; Arora, Karan; Goldberg, Hanan; Chandrasekar, Thenappan; Wallis, Christopher J D; Sayyid, Rashid K; Fleshner, Neil E; Finelli, Antonio; Kutikov, Alexander; Violette, Philippe D; Kulkarni, Girish S

    2018-04-01

    Radical cystectomy is inherently associated with morbidity. We assess the timing and incidence of venous thromboembolism, review current guideline recommendations and provide evidence for considering extended venous thromboembolism prophylaxis in all patients undergoing radical cystectomy. We searched PubMed® for available literature on radical cystectomy and venous thromboembolism, focusing on incidence and timing, evidence supporting extended venous thromboembolism prophylaxis in patients undergoing radical cystectomy or abdominal oncologic surgery, current guideline recommendations, safety considerations and direct oral anticoagulants. Search terms included "radical cystectomy," "venous thromboembolism," "prophylaxis," and "extended oral anticoagulants" and "direct oral anticoagulants" alone and in combination. Relevant articles were reviewed, including original research, reviews and clinical guidelines. References from review articles and guidelines were also assessed to develop a narrative review. The incidence of symptomatic venous thromboembolism in short-term followup after radical cystectomy is 3% to 11.6%, of which more than 50% of cases will occur after hospital discharge. Meta-analyses of clinical trials in patients undergoing major abdominal oncologic operations suggest a decreased risk of venous thromboembolisms for patients receiving extended (4 weeks) venous thromboembolism prophylaxis. Extended prophylaxis should be considered in all radical cystectomy cases. Although the relative risk of bleeding also increases, the overall net benefit of extended prophylaxis clearly favors use for at least 28 days postoperatively. Extrarenal eliminated prophylaxis agents are preferred given the risk of renal insufficiency in radical cystectomy cases, with newer oral anticoagulants providing an alternative route of administration. Patients undergoing radical cystectomy are at high risk for venous thromboembolism after hospital discharge. There is strong evidence

  8. Oral Chronic Graft-versus-Host Disease: Current Pathogenesis, Therapy, and Research

    PubMed Central

    Mays, JW; Fassil, H; Edwards, DA; Pavletic, SZ; Bassim, CW

    2012-01-01

    Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis and treatment of oral manifestations in chronic Graft-versus-Host Disease (cGVHD) which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD, and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research, and address tools with which to accomplish the long-term goal of providing better health and quality-of-life to patients with cGVHD. PMID:23107104

  9. Graves' disease: a host defense mechanism gone awry.

    PubMed

    Kohn, L D; Napolitano, G; Singer, D S; Molteni, M; Scorza, R; Shimojo, N; Kohno, Y; Mozes, E; Nakazato, M; Ulianich, L; Chung, H K; Matoba, H; Saunier, B; Suzuki, K; Schuppert, F; Saji, M

    2000-01-01

    In this report we summarize evidence to support a model for the development of Graves' disease. The model suggests that Graves' disease is initiated by an insult to the thyrocyte in an individual with a normal immune system. The insult, infectious or otherwise, causes double strand DNA or RNA to enter the cytoplasm of the cell. This causes abnormal expression of major histocompatibility (MHC) class I as a dominant feature, but also aberrant expression of MHC class II, as well as changes in genes or gene products needed for the thyrocyte to become an antigen presenting cell (APC). These include increased expression of proteasome processing proteins (LMP2), transporters of antigen peptides (TAP), invariant chain (Ii), HLA-DM, and the co-stimulatory molecule, B7, as well as STAT and NF-kappaB activation. A critical factor in these changes is the loss of normal negative regulation of MHC class I, class II, and thyrotropin receptor (TSHR) gene expression, which is necessary to maintain self-tolerance during the normal changes in gene expression involved in hormonally-increased growth and function of the cell. Self-tolerance to the TSHR is maintained in normals because there is a population of CD8- cells which normally suppresses a population of CD4+ cells that can interact with the TSHR if thyrocytes become APCs. This is a host self-defense mechanism that we hypothesize leads to autoimmune disease in persons, for example, with a specific viral infection, a genetic predisposition, or even, possibly, a TSHR polymorphism. The model is suggested to be important to explain the development of other autoimmune diseases including systemic lupus or diabetes.

  10. Ocular manifestations of systemic disease: toxoplasmosis.

    PubMed

    Vasconcelos-Santos, Daniel V

    2012-11-01

    To provide an overview of ocular toxoplasmosis, the leading cause of infectious posterior uveitis, focusing on recent trends of disease epidemiology, pathogenesis, diagnosis, therapy and prevention. Novel aspects of epidemiology, including growing importance of water transmission are discussed. The historical controversy of congenital versus postnatally acquired toxoplasmosis is revisited. Recent insights into pathogenesis of ocular toxoplasmosis are also reviewed, tipping the delicate balance between parasite virulence and host immunity. Diagnosis of ocular toxoplasmosis is also discussed in the light of serological, molecular and imaging tools. Finally, a critical analysis of current and emerging therapies for ocular toxoplasmosis is made. Preventive aspects are also commented upon. Waterborne toxoplasmosis is increasingly recognized in outbreaks and in endemic areas. The importance of postnatally acquired toxoplasmosis is now well established, but should not lead to underestimation of congenital disease. Genetic determination of parasite virulence/individual susceptibility might correlate with disease outcomes. Serological, molecular and imaging tools may improve the diagnosis and follow-up of individuals with ocular toxoplasmosis. Despite emergence of alternative therapeutic regimens, including intravitreal antibiotics, classical therapy with sulfadiazine/pyrimethamine is still standard for toxoplasmic retinochoroiditis. Adequate prophylaxis is expected to have an effect in ocular burden of toxoplasmosis.

  11. Deep sequencing shows low-level oncogenic hepatitis B virus variants persists post-liver transplant despite potent anti-HBV prophylaxis.

    PubMed

    Lau, K C K; Osiowy, C; Giles, E; Lusina, B; van Marle, G; Burak, K W; Coffin, C S

    2018-06-01

    Recent studies suggest that withdrawal of hepatitis B immune globulin (HBIG) and nucleos(t)ide analogues (NA) prophylaxis may be considered in HBV surface antigen (HBsAg)-negative liver transplant (LT) recipients with a low risk of disease recurrence. However, the frequency of occult HBV infection (OBI) and HBV variants after LT in the current era of potent NA therapy is unknown. Twelve LT recipients on prophylaxis were tested in matched plasma and peripheral blood mononuclear cells (PBMCs) for HBV quasispecies by in-house nested PCR and next-generation sequencing of amplicons. HBV covalently closed circular DNA (cccDNA) was detected in Hirt DNA isolated from PBMCs with cccDNA-specific primers and confirmed by nucleic acid hybridization and Sanger sequencing. HBV mRNA in PBMC was detected with reverse-transcriptase nested PCR. In LT recipients on immunosuppressive therapy (10/12 male; median age 57.5 [IQR: 39.8-66.5]; median follow-up post-LT 60 months; 6 pre-LT hepatocellular carcinoma [HCC]), 9 were HBsAg-. HBV DNA was detected in all plasma and PBMC tested; cccDNA and/or mRNA was detected in the PBMC of 10/12 patients. Significant HBV quasispecies diversity (ie 143-2212 nonredundant HBV species) was noted in both sites, and single nucleotide polymorphisms associated with cirrhosis and HCC were detected at varying frequencies. In conclusion, OBI and HBV variants associated with severe liver disease persist in LT recipients on prophylaxis. Although HBV control and cccDNA transcriptional silencing may occur despite immunosuppression, complete virological eradication does not occur in LT recipients with a history of HBV-related end-stage liver disease. © 2018 John Wiley & Sons Ltd.

  12. Advantages of Reduced Prophylaxis after Tubularized Incised Plate Repair of Hypospadias.

    PubMed

    Zeiai, Said; Nordenskjöld, Agneta; Fossum, Magdalena

    2016-10-01

    Concerns about antibiotic resistance, adverse drug reactions and questionable medical benefits have led to changes in prophylactic antibiotic management in hypospadias repair at our clinic. In March 2010 our guidelines were changed from continuous prophylaxis for 14 days to 1 dose preoperatively and another at removal of the stent. We analyze the effects of this new regimen. We performed a prospective journal cohort study of all our hypospadias operations from June 2008 to December 2011. We collected data from consecutive patients undergoing primary tubularized incised plate repair and postoperative stent. Patients operated on before March 2010 were compared to those operated on later. End points were postoperative infection requiring antibiotics and any complication that required redo surgery. The study included 113 primary tubularized incised plate repairs with postoperative stents. Patient distribution was the same in both groups. Of 58 patients in the group receiving continuous antibiotic prophylaxis 17 had a complication and/or infection, compared to 9 of 55 patients receiving 2-dose prophylaxis. The infection rate was 5% in the continuous prophylaxis group and 4% in the 2-dose group. In contrast to our expectations, a lower complication rate was observed in the group with lower antibiotic dose without an increased risk of infection. There is little documented evidence concerning benefits of antibiotic prophylaxis for postoperative complications, which gives rise to large variations in clinical practice. In our study lower antibiotic dose did not increase the number of infections, but rather decreased complication rates. We advocate antibiotic prophylaxis with only a 2-dose regimen. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  13. [Prevention of circulatory system diseases in underground mining workers].

    PubMed

    Vlasova, E M; Alexeyev, M B; Shliapnikov, D M; Nosov, A E; Barannikov, V G

    2015-01-01

    The article covers results of preventive measures in workers engaged into underground mining. Those measures are aimed to prevent occupationally mediated health disorders resulting in circulatory diseases. The prophylaxis was proven effective on premorbid condition--that was demonstrated in reliable decrease of cause-effect relationship intensity for health disorders in workers subjected to prophylactic measures. Transitory disablement morbidity due to cicrulatory system diseases decreased. Situational modelling of risk changes for the studied group demonstrated changes of diseases risk under medical prophylactic measures. After the prophylaxis, the risk demonstrated 3.1 times decrease.

  14. What Is the Safety and Efficacy of Chemical Venous Thromboembolism Prophylaxis Following Vestibular Schwannoma Surgery?

    PubMed

    Casazza, Geoffrey C; Bowers, Christian A; MacDonald, Joel D; Couldwell, William T; Shelton, Clough; Gurgel, Richard K

    2018-02-01

    The benefit of routine chemical prophylaxis use for venous thromboembolism (VTE) prevention in skull base surgery is controversial. Chemical prophylaxis can prevent undue morbidity and mortality, however there are risks for hemorrhagic complications. Retrospective case-control. A retrospective chart review of patients who underwent surgery for vestibular schwannoma from 2011 to 2016 was performed. Patients were divided by receipt of chemical VTE prophylaxis. Number of VTEs and hemorrhagic complications (intracranial hemorrhage, abdominal hematoma, and postauricular hematoma) were recorded. One hundred twenty-six patients were identified, 55 received chemical prophylaxis, and 71 did not. All the patients received mechanical prophylaxis. Two patients developed a deep vein thrombosis (DVT) and one patient developed a pulmonary embolism (PE). All patients who developed a DVT or PE received chemical prophylaxis. There was no difference in DVT (p = 0.1886) or PE (p = 0.4365) between those who received chemical prophylaxis and those who did not. Five patients developed a hemorrhagic complication, two intracranial hemorrhage, three abdominal hematoma, and zero postauricular hematoma. All five patients with a complication received chemical prophylaxis (p = 0.00142). The relative risk of a hemorrhagic complication was 14.14 (95% CI = 0.7987-250.4307; p = 0.0778). There was a significant difference between the number of hemorrhagic complications but not between numbers of DVT or PE. Mechanical and chemical prophylaxis may lower the risk of VTE but in our series, hemorrhagic complications were observed. These measures should be used selectively in conjunction with early ambulation.

  15. Effectiveness of the iodine prophylaxis model adopted in Poland.

    PubMed

    Szybinski, Z; Golkowski, F; Buziak-Bereza, M; Trofimiuk, M; Przybylik-Mazurek, E; Huszno, B; Bandurska-Stankiewicz, E; Bar-Andziak, E; Dorant, B; Kinalska, I; Lewinski, A; Klencki, M; Rybakowa, M; Sowinski, J; Szewczyk, L; Szponar, L; Wasik, R

    2008-04-01

    Most of the Polish territory has been classified as an iodine-deficient and endemic goiter area according to the International Council for Control of Iodine Deficiency (ICCIDD) criteria. In 1997 the obligatory model of iodine prophylaxis was implemented. Our investigations were aimed at the effectiveness of iodine prophylaxis in Poland. We assessed urinary iodine excretion and goiter prevalence in 5663 children aged 6-12 yr. The population of children from the same 27 schools was investigated from 1992 to 1994 (1406 girls and 1244 boys) and from 1999 to 2005 (1563 girls and 1450 boys) using identical laboratory and ultrasound methods. We found significant increase in iodine urinary concentration (median 52 microg/l vs 93 microg/l, p<0.001) with accompanying drop in goiter prevalence (29.6% vs 5.2%, p<0.001) after implementation of iodine prophylaxis. Iodine excretion distribution changed significantly after 1997 with an increase in the percentage of children with iodine urinary concentration above 100 microg/l from 10.8% to 45.4%, respectively. A significantly higher iodine urinary concentration was observed in lowlands compared to uplands both before and after implementation of iodine prophylaxis (median, 50 microg/l vs 57 microg/l and 86 microg/l vs 114 microg/l, respectively, p<0.001). The goiter prevalence did not differ between girls and boys from 1992 to 1994 (28.8% vs 30.5%, p=0.35) and 1999 to 2005 (5.5% vs 4.9%, p=0.45). Implementation of the new model of iodine prophylaxis in Poland in 1997 has led to significant increase in iodine urinary concentration and decrease in goiter prevalence among Polish schoolchildren. In the youngest group of children (6-8 yr olds), prevalence of goiter decreased to 3.2%--i.e. below endemic levels.

  16. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia.

    PubMed

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-06-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m(2) in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3-4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). Copyright© Ferrata Storti Foundation.

  17. Intraoperative retinal detachment prophylaxis in vitrectomy for retained cataract fragments.

    PubMed

    Morris, Robert E; Shere, Jeffrey L; Witherspoon, C Douglas; Segal, Zachary K; Tehranchi, Linda; Kuhn, Ferenc; Sapp, Mathew

    2009-03-01

    To assess the safety and efficacy of peripheral 360-degree laser retinopexy as prophylaxis against rhegmatogenous retinal detachment (RRD) in eyes having pars plana vitrectomy (PPV) for the removal of retained cataract fragments. Private practice, Callahan Eye Foundation Hospital, University of Alabama at Birmingham, and Helen Keller Foundation for Research and Education, Birmingham, Alabama, USA. This retrospective analysis comprised a consecutive series of patients who had PPV with 360-degree laser retinopexy for retained cataract fragment removal between January 1, 1995, and December 31, 2000. All laser treatments were applied with indirect ophthalmoscope delivery. In 78 eyes of 78 patients, the mean interval between cataract surgery and PPV with 360-degree laser retinopexy prophylaxis was 14 days. One (1.3%) of 78 eyes had postoperative RRD during a mean follow-up of 6 years. No laser-related complications occurred. The incidence of RRD after PPV with 360-degree laser retinopexy prophylaxis was 1.3%, a significant reduction from the average 8.2% RRD rate in the literature (P = .024). Although future prospective trials are indicated, the results suggest that 360-degree laser retinopexy prophylaxis could significantly reduce the incidence of this visually disabling complication.

  18. Evaluation of postoperative antibiotic prophylaxis after liver resection: a randomized controlled trial.

    PubMed

    Hirokawa, Fumitoshi; Hayashi, Michihiro; Miyamoto, Yoshiharu; Asakuma, Mitsuhiro; Shimizu, Tetsunosuke; Komeda, Koji; Inoue, Yoshihiro; Uchiyama, Kazuhisa; Nishimura, Yasuichiro

    2013-07-01

    Antibiotic prophylaxis is frequently administered after liver resection to prevent postoperative infections. However, very few studies have examined the usefulness of antibiotic prophylaxis after liver resection. A randomized controlled trial was conducted to evaluate the postoperative antibiotic prophylaxis in patients after liver resection. A total of 241 patients scheduled to undergo liver resection were randomly assigned to the non-postoperative antibiotic group (n = 95) or the antibiotic group (n = 95). The antibiotic group was given flomoxef sodium every 12 hours for 3 days after the operation. The end point was signs of infection, surgical site infection, or infectious complications. There were no significant differences between the 2 groups in signs of infection (21.3% vs 25.5%, P = .606), the incidence of systemic inflammatory response syndrome (11.7% vs 17.0%, P = .406), infectious complications (7.5% vs 17.0%, P = .073), surgical site infection (10.6% vs 13.8%, P = .657), and remote site infection (2.1% vs 8.5%, P = .100). Postoperative antibiotic prophylaxis cannot prevent postoperative infections after liver resection, and it is thought that antibiotic prophylaxis is unnecessary and costly. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Antibiotic prophylaxis in dermatologic surgery: advisory statement 2008.

    PubMed

    Wright, Tina I; Baddour, Larry M; Berbari, Elie F; Roenigk, Randall K; Phillips, P Kim; Jacobs, M Amanda; Otley, Clark C

    2008-09-01

    Antibiotic prophylaxis is an important component of dermatologic surgery, and recommendations in this area should reflect the updated 2007 guidelines of the American Heart Association, the American Dental Association with the American Academy of Orthopaedic Surgeons guidelines, and recent prospective studies on surgical site infection. To provide an update on the indications for antibiotic prophylaxis in dermatologic surgery for the prevention of infective endocarditis, hematogenous total joint infection, and surgical site infection. A literature review was performed, expert consensus was obtained, and updated recommendations were created, consistent with the most current authoritative guidelines from the American Heart Association and the American Dental Association with the American Academy of Orthopaedic Surgeons. For patients with high-risk cardiac conditions, and a defined group of patients with prosthetic joints at high risk for hematogenous total joint infection, prophylactic antibiotics are recommended when the surgical site is infected or when the procedure involves breach of the oral mucosa. For the prevention of surgical site infections, antibiotics may be indicated for procedures on the lower extremities or groin, for wedge excisions of the lip and ear, skin flaps on the nose, skin grafts, and for patients with extensive inflammatory skin disease. These recommendations are not based on multiple, large-scale, prospective trials. There is a strong shift away from administration of prophylactic antibiotics in many dermatologic surgery settings, based on updated authoritative guidelines. These recommendations provide guidance to comply with the most current guidelines, modified to address dermatology-specific considerations. Managing physicians may utilize these guidelines while individualizing their approach based on all clinical considerations.

  20. A decision model to estimate a risk threshold for venous thromboembolism prophylaxis in hospitalized medical patients.

    PubMed

    Le, P; Martinez, K A; Pappas, M A; Rothberg, M B

    2017-06-01

    Essentials Low risk patients don't require venous thromboembolism (VTE) prophylaxis; low risk is unquantified. We used a Markov model to estimate the risk threshold for VTE prophylaxis in medical inpatients. Prophylaxis was cost-effective for an average medical patient with a VTE risk of ≥ 1.0%. VTE prophylaxis can be personalized based on patient risk and age/life expectancy. Background Venous thromboembolism (VTE) is a common preventable condition in medical inpatients. Thromboprophylaxis is recommended for inpatients who are not at low risk of VTE, but no specific risk threshold for prophylaxis has been defined. Objective To determine a threshold for prophylaxis based on risk of VTE. Patients/Methods We constructed a decision model with a decision-tree following patients for 3 months after hospitalization, and a lifetime Markov model with 3-month cycles. The model tracked symptomatic deep vein thromboses and pulmonary emboli, bleeding events and heparin-induced thrombocytopenia. Long-term complications included recurrent VTE, post-thrombotic syndrome and pulmonary hypertension. For the base case, we considered medical inpatients aged 66 years, having a life expectancy of 13.5 years, VTE risk of 1.4% and bleeding risk of 2.7%. Patients received enoxaparin 40 mg day -1 for prophylaxis. Results Assuming a willingness-to-pay (WTP) threshold of $100 000/ quality-adjusted life year (QALY), prophylaxis was indicated for an average medical inpatient with a VTE risk of ≥ 1.0% up to 3 months after hospitalization. For the average patient, prophylaxis was not indicated when the bleeding risk was > 8.1%, the patient's age was > 73.4 years or the cost of enoxaparin exceeded $60/dose. If VTE risk was < 0.26% or bleeding risk was > 19%, the risks of prophylaxis outweighed benefits. The prophylaxis threshold was relatively insensitive to low-molecular-weight heparin cost and bleeding risk, but very sensitive to patient age and life expectancy. Conclusions The decision to

  1. Antibiotic prophylaxis in hematopoietic stem cell transplantation. A meta-analysis of randomized controlled trials.

    PubMed

    Kimura, Shun-ichi; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Nakasone, Hideki; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Junya; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

    2014-07-01

    We performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients. We collected reports from PubMed, the Cochrane Library, EMBASE, CINAHL, and Web of Science, along with references cited therein. We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. Seventeen trials with 1453 autologous and allogeneic HSCT recipients were included. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotics in two trials. Systemic antibiotics other than fluoroquinolones were evaluated in five of these 12 trials. Four trials evaluated the effect of the addition of antibiotics for gram-positive bacteria to fluoroquinolones. One trial compared two different systemic antibiotic regimens: fluoroquinolones versus trimethoprim-sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95%CI 0.09-0.30), clinically or microbiologically documented infection (OR 0.38; 95%CI 0.22-0.63) and bacteremia (OR 0.31; 95%CI 0.16-0.59) without significantly affecting all-cause mortality or infection-related mortality. Systemic antibiotic prophylaxis successfully reduced the incidence of infection. However, there was no significant impact on mortality. The clinical benefits of prophylaxis with fluoroquinolones were inconclusive because of the small number of clinical trials evaluated. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  2. Defibrotide in the prevention and treatment of veno-occlusive disease in autologous and allogeneic stem cell transplantation in children.

    PubMed

    Qureshi, Amrana; Marshall, Lynley; Lancaster, Donna

    2008-04-01

    Hepatic veno-occlusive disease (VOD) is a common (10-50%) and serious complication of haematological stem cell transplantation (HSCT), with up to 90% mortality rates. We carried out a study to assess whether the use of prophylactic defibrotide in paediatric patients undergoing HSCT results in a lower frequency or severity of hepatic VOD. Forty-seven successive patients who underwent transplantation between April 2004 and December 2005 were given defibrotide prophylaxis and were compared with 56 historical controls transplanted between November 2001 and April 2004. No serious side effects were reported. High risk patients in the control group received ursodeoxycholic acid and tinzaparin as VOD prophylaxis. The groups were matched for sex, age, type of transplant and risk. In the defibrotide group, four patients developed clinical VOD (Seattle criteria) although two had liver biopsies which showed graft versus host disease (GvHD). Defibrotide dose was increased and symptoms resolved within 14 days. Of the control group four patients had VOD. Two of these patients had reversed hepatic vein flow and died 30 days post-transplant, partly due to VOD. VOD was associated with busulfan conditioning (P = 0.001) and not with age, sex, type of transplant, GvHD, abnormal liver function prior to transplant or type of antifungal prophylaxis. VOD incidence and severity was reduced in the defibrotide group which suggests that defibrotide might be effective in preventing and treating VOD. Sufficiently powered randomised trials are now required to definitively test the role of defibrotide in this setting. (c) 2008 Wiley-Liss, Inc.

  3. The planning, execution, and evaluation of a mass prophylaxis full-scale exercise in cook county, IL.

    PubMed

    Kilianski, Andy; O'Rourke, Amy T; Carlson, Crystal L; Parikh, Shannon M; Shipman-Amuwo, Frankie

    2014-01-01

    Increasing threats of bioterrorism and the emergence of novel disease agents, including the recent international outbreaks of H7N9 influenza and MERS-CoV, have stressed the importance and highlighted the need for public health preparedness at local, regional, and national levels. To test plans that were developed for mass prophylaxis scenarios, in April 2013 the Cook Country Department of Public Health (CCDPH) and the Triple Community (TripCom) Medical Reserve Corps (MRC) executed a full-scale mass prophylaxis exercise in response to a simulated anthrax bioterrorism attack. The exercise took place over 2 days and included the TripCom Point-of-Dispensing (POD) Management Team, volunteers from the TripCom MRC, and neighboring public health departments and MRCs. Individuals from the community volunteered as actors during the exercise, while local municipal, police, and fire personnel coordinated their responses to create the most realistic simulation possible. The exercise was designed to test the capacity of TripCom and CCDPH to implement plans for organizing municipal staff and volunteers to efficiently distribute prophylaxis to the community. Based on results from POD clinic flow, accuracy of prophylaxis distribution, and observations from evaluators, the exercise was successful in demonstrating areas that were operationally efficient as well as identifying areas that can be improved on. These include improvements to the just-in-time training for POD staff, the health screening and consent forms handed out to patients, the physical setup of the POD, and the command structure and communication for the management of POD operations. This article demonstrates the need for full-scale exercises and identifies gaps in POD planning that can be integrated into future plans, exercises, and emergency response.

  4. Antiviral stockpiles for influenza pandemics from the household perspective: treatment alone versus treatment with prophylaxis.

    PubMed

    Kwok, Kin On; Leung, Gabriel M; Mak, Peter; Riley, Steven

    2013-06-01

    Model-based studies of antiviral use to mitigate the impact of moderate and severe influenza pandemics implicitly take the viewpoint of a central public health authority. However, it seems likely that the key decision of when to use antivirals will be made at the household level. We used a stochastic compartmental model of the transmission of influenza within and between households to evaluate the expected mortality under two strategies: households saving available antivirals for treatment only and households implementing prophylaxis as well as treatment. Given that every individual in the population was allocated a single course of antivirals, we investigated the impact of these two strategies for a wide range of AVED, the efficacy of antivirals in preventing death in severe cases (AVED=1 for complete protection). We found a cross-over point for our baseline parameter values in a regime where antivirals were still highly effective in reducing the chance of death: below AVED=0.9 the optimal strategy was for households to use both treatment and prophylaxis. We also considered the possibility that a small number of households might "cheat" by choosing to follow the treatment-only strategy when other households were following treatment with prophylaxis. The cross-over point for cheating households was considerably lower, at AVED=0.6, but substantially above 0. These results suggest that unless antivirals are almost completely effective in reducing the chance of death in serious cases, households will likely be better served implementing prophylaxis as well as treatment. More generally, our study illustrates the potential value of considering viewpoints other than a central authority when conducting model-based analysis of interventions against infectious disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Comparing First- and Second-year Palivizumab Prophylaxis in Patients With Hemodynamically Significant Congenital Heart Disease in the CARESS Database (2005-2015).

    PubMed

    Li, Abby; Wang, Daniel Y; Lanctôt, Krista L; Mitchell, Ian; Paes, Bosco A

    2017-05-01

    Respiratory syncytial virus hospitalization (RSVH) rates in children <2 years of age with hemodynamically significant congenital heart disease (HSCHD) are 2- to 4-fold higher compared with healthy term infants. Pediatric recommendations differ as to whether palivizumab is beneficial beyond 1 year of age. The objective of this study was to determine whether differences exist in respiratory-related illness hospitalization (RIH) and RSVH in HSCHD infants receiving palivizumab during the first year versus second year of life in the Canadian Registry of Palivizumab. The Canadian Registry of Palivizumab is a prospective database of infants who received ≥1 dose of palivizumab in 32 hospitals from 2005 to 2015. Demographic data were collected at enrollment and RIH events recorded monthly. Infants <24 months of age with HSCHD were recruited. Of 1909 HSCHD infants, 1380 (72.3%) in the first year (mean age, 4.2 months) and 529 (27.7%) in the second year of life (mean age, 17.8 months) received prophylaxis. Baseline demographics for day-care attendance, multiple births, enrollment age and weight differed between the groups (all P < 0.05). Additionally, second year infants had a more complicated neonatal course, with significantly longer length of stay (51.2 vs. 24.9 days) compared with those in the first year. The RIH and RSVH rates in the first year were 11.2% and 2.3% and in the second year were 10.6% and 1.7%. Cox regression analysis showed similar hazard for RIH [hazard ratio, 1.9; 95% confidence interval: 0.7-4.6; P = 0.18] and RSVH [hazard ratio, 2.0; 95% confidence interval: 0.2-16.5; P = 0.52]. Infants in the first and second year of life had a similar RSVH hazard. These findings suggest that infants in the second year with HSCHD, who remain unstable, are equally at risk for RSVH and merit prophylaxis.

  6. Group B Streptococcus prophylaxis in patients who report a penicillin allergy: a follow-up study.

    PubMed

    Critchfield, Agatha S; Lievense, Stacey P; Raker, Christina A; Matteson, Kristen A

    2011-02-01

    The purpose of this study was to compare adherence to the 2002 Centers for Disease Control (CDC) guidelines for the prevention of perinatal group B Streptococcus (GBS) disease in patients who are allergic to penicillin during the years 2004-2006 and 2008. Previous data from our institution revealed suboptimal adherence to the 2002 CDC guidelines for GBS prophylaxis among women who are allergic to penicillin. These data caused the hospital to implement a series of interventions. The original cohort (2004-2006) was compared with a cohort of women who delivered between April 2008 and January 2009 (n = 74) to determine whether the proportion of women who had antimicrobial sensitivity testing and who had received an appropriate antibiotic had improved. In 2008, 76% (95% confidence interval, 66-84%) of GBS-positive women who are allergic to penicillin received an appropriate antibiotic (compared with 16.2% in 2004-2006; P < .001). Antimicrobial sensitivity testing was performed in 79.4% of cases (95% confidence interval, 68-87%), compared with 11.4% in 2004-2006 (P < .001). With directed intervention, adherence to the 2002 CDC guidelines for GBS prophylaxis in women who are allergic to penicillin improved dramatically. Copyright © 2011 Mosby, Inc. All rights reserved.

  7. Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation.

    PubMed

    Diri, R; Anwer, F; Yeager, A; Krishnadasan, R; McBride, A

    2016-02-01

    Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients. A single-institution retrospective review of electronic medical records was conducted for patients who underwent allo-HSCT between January 2001 and May 2013 and who had received at least 1 dose of IV PEN for PJP prophylaxis. Data collected included patient demographics, diagnosis, previous chemotherapy, pre-transplant conditioning regimen, other medications, microbiology test results, and clinical outcomes. A total of 113 patients were included in the study. The median number of PEN doses administered per patient was 3 (range 1-23). IV PEN was primary PJP prophylaxis in 74 of the patients (65%) and second-line prophylaxis in 39 (35%) post transplant, with the majority switching from oral TMP-SMX. Side effects of IV PEN administration were minimal. No patients who received IV PEN prophylaxis developed PJP infection. No case of PJP was seen in patients who received other agents for PJP prophylaxis. This retrospective study showed that IV PEN is very effective and well-tolerated prophylaxis for PJP; IV PEN can be considered a favorable alternative for PJP in situations where other agents might be contraindicated. Our findings provide strong support for prospective studies of IV PEN for PJP prophylaxis in adult HSCT recipients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Host response mechanisms in periodontal diseases

    PubMed Central

    SILVA, Nora; ABUSLEME, Loreto; BRAVO, Denisse; DUTZAN, Nicolás; GARCIA-SESNICH, Jocelyn; VERNAL, Rolando; HERNÁNDEZ, Marcela; GAMONAL, Jorge

    2015-01-01

    Periodontal diseases usually refer to common inflammatory disorders known as gingivitis and periodontitis, which are caused by a pathogenic microbiota in the subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger innate, inflammatory, and adaptive immune responses. These processes result in the destruction of the tissues surrounding and supporting the teeth, and eventually in tissue, bone and finally, tooth loss. The innate immune response constitutes a homeostatic system, which is the first line of defense, and is able to recognize invading microorganisms as non-self, triggering immune responses to eliminate them. In addition to the innate immunity, adaptive immunity cells and characteristic cytokines have been described as important players in the periodontal disease pathogenesis scenario, with a special attention to CD4+ T-cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity development is highly dependent on innate immunity-associated antigen presenting cells, which after antigen capture undergo into a maturation process and migrate towards the lymph nodes, where they produce distinct patterns of cytokines that will contribute to the subsequent polarization and activation of specific T CD4+ lymphocytes. Skeletal homeostasis depends on a dynamic balance between the activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts (OCLs). This balance is tightly controlled by various regulatory systems, such as the endocrine system, and is influenced by the immune system, an osteoimmunological regulation depending on lymphocyte- and macrophage-derived cytokines. All these cytokines and inflammatory mediators are capable of acting alone or in concert, to stimulate periodontal breakdown and collagen destruction via tissue-derived matrix metalloproteinases, a characterization of the progression of periodontitis as a stage that

  9. Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

    PubMed Central

    Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor

    2014-01-01

    SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436

  10. Macroparasite dynamics of migratory host populations.

    PubMed

    Peacock, Stephanie J; Bouhours, Juliette; Lewis, Mark A; Molnár, Péter K

    2018-03-01

    Spatial variability in host density is a key factor affecting disease dynamics of wildlife, and yet there are few spatially explicit models of host-macroparasite dynamics. This limits our understanding of parasitism in migratory hosts, whose densities change considerably in both space and time. In this paper, we develop a model for host-macroparasite dynamics that considers the directional movement of host populations and their associated parasites. We include spatiotemporal changes in the mean and variance in parasite burden per host, as well as parasite-mediated host mortality and parasite-mediated migratory ability. Reduced migratory ability with increasing parasitism results in heavily infested hosts halting their migration, and higher parasite burdens in stationary hosts than in moving hosts. Simulations reveal the potential for positive feedbacks between parasite-reduced migratory ability and increasing parasite burdens at infection hotspots, such as stopover sites, that may lead to parasite-induced migratory stalling. This framework could help understand how global change might influence wildlife disease via changes to migratory patterns and parasite demographic rates. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft-vs-host disease.

    PubMed

    Trabulo, Daniel; Ferreira, Sara; Lage, Pedro; Rego, Rafaela Lima; Teixeira, Gilda; Pereira, A Dias

    2015-08-14

    We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.

  12. Antibiotic Prophylaxis after Immediate Breast Reconstruction: The Reality of Its Efficacy.

    PubMed

    Ranganathan, Kavitha; Sears, Erika D; Zhong, Lin; Chung, Ting-Ting; Chung, Kevin C; Kozlow, Jeffrey H; Momoh, Adeyiza O; Waljee, Jennifer F

    2018-04-01

    Numerous techniques are used to prevent infection after immediate implant-based breast reconstruction. Postoperative antibiotic prophylaxis is commonly prescribed to decrease the risk of reconstructive failure, despite conflicting evidence regarding its effectiveness. The authors studied whether postoperative antibiotic prophylaxis decreases the risk of infection-related explantation in the setting of immediate prosthesis-based breast reconstruction. Using Truven MarketScan databases, the authors identified all patients who underwent immediate implant reconstruction between January of 2010 and June of 2014 with at least 6 months of follow-up. Postoperative antibiotic prophylaxis was defined as any oral antibiotic course to be taken postoperatively based on prescriptions filled within 14 days preoperatively through 24 hours after discharge. Reconstructive failure, defined as explantation because of infection, was the primary outcome. Secondary outcomes of interest included wound complications, infection, and readmission for infection. Multivariable regression analyses controlled for demographic variables/comorbidities. Of the 7443 patients, 6049 (81 percent) filled prescriptions for postoperative antibiotic prophylaxis. These patients were equally likely to develop a wound complication (OR, 0.93; 95 percent CI, 0.71 to 1.23) or infection (OR, 0.89; 95 percent CI, 0.70 to 1.14), undergo explantation because of infection (OR, 0.82; 95 percent CI, 0.57 to 1.18), or require readmission for infection (OR, 1.21; 95 percent CI, 0.82 to 1.78) compared with those who did not receive antibiotics. There was no significant difference in the risk of infection-related outcomes based on postoperative antibiotic prophylaxis duration. Postoperative antibiotic prophylaxis was not associated with a reduced risk of infection or explantation following prosthesis-based breast reconstruction. Given rising rates of antibiotic resistance, focusing instead on technical considerations and the

  13. Antibiotic prophylaxis in obstetric procedures.

    PubMed

    van Schalkwyk, Julie; Van Eyk, Nancy

    2010-09-01

    To review the evidence and provide recommendations on antibiotic prophylaxis for obstetrical procedures. Outcomes evaluated include need and effectiveness of antibiotics to prevent infections in obstetrical procedures. Published literature was retrieved through searches of Medline and The Cochrane Library on the topic of antibiotic prophylaxis in obstetrical procedures. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and articles published from January 1978 to June 2009 were incorporated in the guideline. Current guidelines published by the American College of Obstetrics and Gynecology were also incorporated. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of this guideline should reduce the cost and harm resulting from the administration of antibiotics when they are not required and the harm resulting from failure to administer antibiotics when they would be beneficial. SUMMARY STATEMENTS: 1. Available evidence does not support the use of prophylactic antibiotics to reduce infectious morbidity following operative vaginal delivery. (II-1) 2. There is insufficient evidence to argue for or against the use of prophylactic antibiotics to reduce infectious morbidity for manual removal of the placenta. (III) 3. There is insufficient evidence to argue for or against the use of

  14. Polarised press reporting about HIV prevention: Social representations of pre-exposure prophylaxis in the UK press.

    PubMed

    Jaspal, Rusi; Nerlich, Brigitte

    2017-09-01

    Pre-exposure prophylaxis is a novel biomedical HIV prevention option for individuals at high risk of HIV acquisition. Although pre-exposure prophylaxis has yielded encouraging results in various clinical trials, opponents argue that pre-exposure prophylaxis poses a number of risks to human health and to sexually transmitted infection prevention efforts. Using qualitative thematic analysis and social representation theory, this article explores coverage of pre-exposure prophylaxis in the UK print media between 2008 and 2015 in order to chart the emerging social representations of this novel HIV prevention strategy. The analysis revealed two competing social representations of pre-exposure prophylaxis: (1) as a positive development in the 'battle' against HIV (the hope representation) and (2) as a medical, social and psychological setback in this battle, particularly for gay/bisexual men (the risk representation). These social representations map onto the themes of pre-exposure prophylaxis as a superlatively positive development; pre-exposure prophylaxis as a weapon in the battle against HIV/AIDS; and risk, uncertainty and fear in relation to pre-exposure prophylaxis. The hope representation focuses on taking (individual and collective) responsibility, while the risk representation focuses on attributing (individual and collective) blame. The implications for policy and practice are discussed.

  15. Nutraceuticals in the prophylaxis of pediatric migraine: Evidence-based review and recommendations.

    PubMed

    Orr, Serena L; Venkateswaran, Sunita

    2014-07-01

    The literature on complementary and alternative medicine (CAM) is expanding. One of the most common conditions for which CAM is studied in the pediatric population is migraine. Nutraceuticals are a form of CAM that is being used for pediatric migraine prophylaxis. A literature search was carried out in order to identify both observational studies and randomized controlled trials on the use of nutraceuticals for the prophylaxis of pediatric migraine. Adult studies on included nutraceuticals were also reviewed. Thirty studies were reviewed on six different nutraceuticals: butterbur, riboflavin, ginkgolide B, magnesium, coenzyme Q10 and polyunsaturated fatty acids. Overall, the quality of the evidence for the use of nutraceuticals in pediatric migraine prophylaxis is poor. Further research needs to be done in order to study the efficacy of nutraceuticals for the prophylaxis of pediatric migraine. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection.

    PubMed

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F; Murphy, Trudy V

    2016-05-01

    In an era of antiviral treatment, reexamination of the cost-effectiveness of strategies to prevent perinatal hepatitis B virus (HBV) transmission in the United States is needed. We used a decision tree and Markov model to estimate the cost-effectiveness of the current U.S. strategy and two alternatives: (1) Universal hepatitis B vaccination (HepB) strategy: No pregnant women are screened for hepatitis B surface antigen (HBsAg). All infants receive HepB before hospital discharge; no infants receive hepatitis B immunoglobulin (HBIG). (2) Current strategy: All pregnant women are screened for HBsAg. Infants of HBsAg-positive women receive HepB and HBIG ≤12 hours of birth. All other infants receive HepB before hospital discharge. (3) Antiviral prophylaxis strategy: All pregnant women are screened for HBsAg. HBsAg-positive women have HBV-DNA load measured. Antiviral prophylaxis is offered for 4 months starting in the third trimester to women with DNA load ≥10(6) copies/mL. HepB and HBIG are administered at birth to infants of HBsAg-positive women, and HepB is administered before hospital discharge to infants of HBsAg-negative women. Effects were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICER). Compared to the universal HepB strategy, the current strategy prevented 1,006 chronic HBV infections and saved 13,600 QALYs (ICER: $6,957/QALY saved). Antiviral prophylaxis dominated the current strategy, preventing an additional 489 chronic infections, and saving 800 QALYs and $2.8 million. The results remained robust over a wide range of assumptions. The current U.S. strategy for preventing perinatal HBV remains cost-effective compared to the universal HepB strategy. An antiviral prophylaxis strategy was cost saving compared to the current strategy and should be considered to continue to decrease the burden of perinatal hepatitis B in the United States. Published 2015. This article is a U.S. Government work and is in the public

  17. Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.

    PubMed

    Longstreth, Janice; Skiadopoulos, Mario H; Hopkins, Robert J

    2016-12-01

    The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.

  18. Variation in DVT prophylaxis for adolescent trauma patients: a survey of the Society of Trauma Nurses.

    PubMed

    O'Brien, Sarah H; Haley, Kathy; Kelleher, Kelly J; Wang, Wei; McKenna, Christine; Gaines, Barbara A

    2008-01-01

    We performed a survey of the Society of Trauma Nurses to explore current practice patterns for deep venous thrombosis prophylaxis in adolescent trauma patients and analyzed responses from 133 institutions. The majority of adult prophylaxis protocols include older adolescents. Only 41% of adult programs identified patient age as "very" important in prophylaxis decision making. Pelvic fracture, spinal cord injury, and expected immobilization were rated most important. Pharmacologic prophylaxis in 11- to 15-year-olds was infrequent, with 60% of centers using never or rarely. Use was much higher but variable among older adolescents. No consensus on deep venous thrombosis prophylaxis in adolescent trauma emerged from our survey.

  19. Reduction in clinical response to empiric antimicrobial therapy of febrile granulocytopenic patients receiving TMP/SMX infection prophylaxis

    PubMed Central

    Bow, Eric J; Pater, Joseph L; Louie, Thomas J; Feld, Ronald; Mandell, Lionel; Robson, Hugh G; Chow, Anthony; Belch, Andrew; Miedzinski, Lilly; Paul, Nancy; Elliott, Catherine R; Willan, Andrew R

    1992-01-01

    In the course of a multicentre clinical trial evaluating two antibacterial regimens for the empiric treatment of suspected infection in febrile neutropenic cancer patients, a suboptimal response was noted among recipients of antibacterial prophylaxis with trimethoprim/sulphamethoxazole (TMP/SMX). Multivariate analysis identified TMP/SMX prophylaxis as a predictor of poor outcome independent of other variables such as classification of infection, marrow recovery, neutrophil count at first fever, indwelling central venous catheter use, and underlying disease. This effect appeared to be restricted to recipients of tobramycin plus ticarcillin (TT). TMP/SMX suppresses potentially pathogenic aerobic Gram-negative bacilli and allows colonization and subsequent infection by Gram-positive microorganisms against which TT-like regimens have limited activity. Recognition of this phenomenon may permit a more appropriate selection of antibacterial agents for the therapy of suspected infection in the neutropenic patient. PMID:22416197

  20. Does canine inflammatory bowel disease influence gut microbial profile and host metabolism?

    PubMed

    Xu, Jia; Verbrugghe, Adronie; Lourenço, Marta; Janssens, Geert P J; Liu, Daisy J X; Van de Wiele, Tom; Eeckhaut, Venessa; Van Immerseel, Filip; Van de Maele, Isabel; Niu, Yufeng; Bosch, Guido; Junius, Greet; Wuyts, Brigitte; Hesta, Myriam

    2016-06-16

    Inflammatory bowel disease (IBD) refers to a diverse group of chronic gastrointestinal diseases, and gut microbial dysbiosis has been proposed as a modulating factor in its pathogenesis. Several studies have investigated the gut microbial ecology of dogs with IBD but it is yet unclear if this microbial profile can alter the nutrient metabolism of the host. The aim of the present study was to characterize the faecal bacterial profile and functionality as well as to determine host metabolic changes in IBD dogs. Twenty-three dogs diagnosed with IBD and ten healthy control dogs were included. Dogs with IBD were given a clinical score using the canine chronic enteropathy clinical activity index (CCECAI). Faecal short-chain fatty acids (SCFA) and ammonia concentrations were measured and quantitative PCR was performed. The concentration of plasma amino acids, acylcarnitines, serum folate, cobalamin, and indoxyl sulfate was determined. No significant differences in the abundance of a selection of bacterial groups and fermentation metabolites were observed between the IBD and control groups. However, significant negative correlations were found between CCECAI and the faecal proportion of Lactobacillus as well as between CCECAI and total SCFA concentration. Serum folate and plasma citrulline were decreased and plasma valine was increased in IBD compared to control dogs. Increased plasma free carnitine and total acylcarnitines were observed in IBD compared with control dogs, whereas short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and, methylmalonylcarnitine) to free carnitine ratios decreased. Dogs with IBD had a higher 3-hydroxyisovalerylcarnitine + isovalerylcarnitine to leucine ratio compared to control dogs. Canine IBD induced a wide range of changes in metabolic profile, especially for the plasma concentrations of short-chain acylcarnitines and amino acids, which could have evolved from tissue damage and alteration in host metabolism. In

  1. The Johns Hopkins Venous Thromboembolism Collaborative: Multidisciplinary team approach to achieve perfect prophylaxis.

    PubMed

    Streiff, Michael B; Lau, Brandyn D; Hobson, Deborah B; Kraus, Peggy S; Shermock, Kenneth M; Shaffer, Dauryne L; Popoola, Victor O; Aboagye, Jonathan K; Farrow, Norma A; Horn, Paula J; Shihab, Hasan M; Pronovost, Peter J; Haut, Elliott R

    2016-12-01

    Venous thromboembolism (VTE) is an important cause of preventable harm in hospitalized patients. The critical steps in delivery of optimal VTE prevention care include (1) assessment of VTE and bleeding risk for each patient, (2) prescription of risk-appropriate VTE prophylaxis, (3) administration of risk-appropriate VTE prophylaxis in a patient-centered manner, and (4) continuously monitoring outcomes to identify new opportunities for learning and performance improvement. To ensure that every hospitalized patient receives VTE prophylaxis consistent with their individual risk level and personal care preferences, we organized a multidisciplinary task force, the Johns Hopkins VTE Collaborative. To achieve the goal of perfect prophylaxis for every patient, we developed evidence-based, specialty-specific computerized clinical decision support VTE prophylaxis order sets that assist providers in ordering risk-appropriate VTE prevention. We developed novel strategies to improve provider VTE prevention ordering practices including face-to-face performance reviews, pay for performance, and provider VTE scorecards. When we discovered that prescription of risk-appropriate VTE prophylaxis does not ensure its administration, our multidisciplinary research team conducted in-depth surveys of patients, nurses, and physicians to design a multidisciplinary patient-centered educational intervention to eliminate missed doses of pharmacologic VTE prophylaxis that has been funded by the Patient Centered Outcomes Research Institute. We expect that the studies currently underway will bring us closer to the goal of perfect VTE prevention care for every patient. Our learning journey to eliminate harm from VTE can be applied to other types of harm. Journal of Hospital Medicine 2016;11:S8-S14. © 2016 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.

  2. Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

    PubMed

    Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

    2015-10-28

    Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

  3. A new fetal RHD genotyping test: costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales.

    PubMed

    Szczepura, Ala; Osipenko, Leeza; Freeman, Karoline

    2011-01-18

    Postnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies. We conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications. The basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall. Currently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale introduction in England and Wales. Only

  4. Genetic assignment methods for gaining insight into the management of infectious disease by understanding pathogen, vector, and host movement.

    PubMed

    Remais, Justin V; Xiao, Ning; Akullian, Adam; Qiu, Dongchuan; Blair, David

    2011-04-01

    For many pathogens with environmental stages, or those carried by vectors or intermediate hosts, disease transmission is strongly influenced by pathogen, host, and vector movements across complex landscapes, and thus quantitative measures of movement rate and direction can reveal new opportunities for disease management and intervention. Genetic assignment methods are a set of powerful statistical approaches useful for establishing population membership of individuals. Recent theoretical improvements allow these techniques to be used to cost-effectively estimate the magnitude and direction of key movements in infectious disease systems, revealing important ecological and environmental features that facilitate or limit transmission. Here, we review the theory, statistical framework, and molecular markers that underlie assignment methods, and we critically examine recent applications of assignment tests in infectious disease epidemiology. Research directions that capitalize on use of the techniques are discussed, focusing on key parameters needing study for improved understanding of patterns of disease.

  5. Marek's disease virus immunosuppression alters host cellular responses and immune gene expression in the skin of infected chickens

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease (MD) is a highly contagious lymphoproliferative and neuropathic disease of chickens. The feather follicle epithelium (FFE) is the only anatomical site within the host where infectious enveloped cell-free MD virus (MDV) particles are produced and disseminated into the environment. MD ...

  6. A Crucial Role for Host APCs in the Induction of Donor CD4+CD25+ Regulatory T Cell-Mediated Suppression of Experimental Graft-versus-Host Disease

    PubMed Central

    Tawara, Isao; Shlomchik, Warren D.; Jones, Angela; Zou, Weiping; Nieves, Evelyn; Liu, Chen; Toubai, Tomomi; Duran-Struuck, Raimon; Sun, Yaping; Clouthier, Shawn G.; Evers, Rebecca; Lowler, Kathleen P.; Levy, Robert B.; Reddy, Pavan

    2010-01-01

    Allogeneic bone marrow transplantation is an effective treatment for a number of malignant and nonmalignant diseases (Applebaum. 2001. Nature. 411: 385–389 and Copelan. 2006. N Engl J Med. 354: 1813–1826). However, the application of this therapeutic modality has been impeded by a number of confounding side effects, the most frequent and severe of which is the development of graft-versus-host disease (GVHD) (Copelan. 2006. N Engl J Med. 354: 1813–1826 and Blazar and Murphy. 2005. Philos Trans R Soc Lond B Biol Sci. 360: 1747–1767). Alloreactive donor T cells are critical for causing GVHD (Fowler. 2006. Crit Rev Oncol Hematol. 57: 225–244 and Ferrara and Reddy. 2006. Semin Hematol. 43: 3–10), whereas recent data demonstrated a significant role for the naturally occurring thymic-derived donor CD4+CD25+Foxp3+ regulatory T cells (Tregs) (Bluestone and Abbas. 2003. Nat Rev Immunol. 3: 253–257 and Shevach. 2006. Immunity. 25: 195–201) in suppressing experimental GVHD after bone marrow transplantation (Blazar and Taylor. 2005. Biol Blood Marrow Transpl. 11: 46–49 and Joffe and van Meerwijk. 2006. Semin Immunol. 18: 128–135). Host APCs are required for induction of GVHD by the conventional donor T cells. However, it is not known whether they are also obligatory for donor Treg-mediated suppression of GVHD. Using multiple clinically relevant MHC-matched and -mismatched murine models of GVHD, we investigated the role of host APCs in the suppression of GVHD by donor Tregs. We found that alloantigen expression by the host APCs is necessary and sufficient for induction of GVHD protection by donor Tregs. This requirement was independent of their effect on the maintenance of Treg numbers and the production of IL-10 or IDO by the host APCs. PMID:20810991

  7. A simplified regimen of targeted antifungal prophylaxis in liver transplant recipients: A single-center experience.

    PubMed

    Lavezzo, B; Patrono, D; Tandoi, F; Martini, S; Fop, F; Ballerini, V; Stratta, C; Skurzak, S; Lupo, F; Strignano, P; Donadio, P P; Salizzoni, M; Romagnoli, R; De Rosa, F G

    2018-04-01

    Invasive fungal infection (IFI) is a severe complication of liver transplantation burdened by high mortality. Guidelines recommend targeted rather than universal antifungal prophylaxis based on tiers of risk. We aimed to evaluate IFI incidence, risk factors, and outcome after implementation of a simplified two-tiered targeted prophylaxis regimen based on a single broad-spectrum antifungal drug (amphotericin B). Patients presenting 1 or more risk factors according to literature were administered prophylaxis. Prospectively collected data on all adult patients transplanted in Turin from January 2011 to December 2015 were reviewed. Patients re-transplanted before postoperative day 7 were considered once, yielding a study cohort of 581 cases. Prophylaxis was administered to 299 (51.4%) patients; adherence to protocol was 94.1%. Sixteen patients developed 18 IFIs for an overall rate of 2.8%. All IFI cases were in targeted prophylaxis group; none of the non-prophylaxis group developed IFI. Most cases (81.3%) presented within 30 days after transplantation during prophylaxis; predominant pathogens were molds (94.4%). Only 1 case of candidemia was observed. One-year mortality in IFI patients was 33.3% vs 6.4% in patients without IFI (P = .001); IFI attributable mortality was 6.3%. At multivariate analysis, significant risk factors for IFI were renal replacement therapy (OR = 8.1) and re-operation (OR = 5.2). The implementation of a simplified targeted prophylaxis regimen appeared to be safe and applicable and was associated with low IFI incidence and mortality. Association of IFI with re-operation and renal replacement therapy calls for further studies to identify optimal prophylaxis in this subset of patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

    PubMed Central

    Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

    2013-01-01

    Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

  9. The Malarial Host-Targeting Signal Is Conserved in the Irish Potato Famine Pathogen

    PubMed Central

    Liolios, Konstantinos; Win, Joe; Kanneganti, Thirumala-Devi; Young, Carolyn; Kamoun, Sophien; Haldar, Kasturi

    2006-01-01

    Animal and plant eukaryotic pathogens, such as the human malaria parasite Plasmodium falciparum and the potato late blight agent Phytophthora infestans, are widely divergent eukaryotic microbes. Yet they both produce secretory virulence and pathogenic proteins that alter host cell functions. In P. falciparum, export of parasite proteins to the host erythrocyte is mediated by leader sequences shown to contain a host-targeting (HT) motif centered on an RxLx (E, D, or Q) core: this motif appears to signify a major pathogenic export pathway with hundreds of putative effectors. Here we show that a secretory protein of P. infestans, which is perceived by plant disease resistance proteins and induces hypersensitive plant cell death, contains a leader sequence that is equivalent to the Plasmodium HT-leader in its ability to export fusion of green fluorescent protein (GFP) from the P. falciparum parasite to the host erythrocyte. This export is dependent on an RxLR sequence conserved in P. infestans leaders, as well as in leaders of all ten secretory oomycete proteins shown to function inside plant cells. The RxLR motif is also detected in hundreds of secretory proteins of P. infestans, Phytophthora sojae, and Phytophthora ramorum and has high value in predicting host-targeted leaders. A consensus motif further reveals E/D residues enriched within ~25 amino acids downstream of the RxLR, which are also needed for export. Together the data suggest that in these plant pathogenic oomycetes, a consensus HT motif may reside in an extended sequence of ~25–30 amino acids, rather than in a short linear sequence. Evidence is presented that although the consensus is much shorter in P. falciparum, information sufficient for vacuolar export is contained in a region of ~30 amino acids, which includes sequences flanking the HT core. Finally, positional conservation between Phytophthora RxLR and P. falciparum RxLx (E, D, Q) is consistent with the idea that the context of their

  10. [Effect of compliance with an antibiotic prophylaxis protocol in surgical site infections in appendectomies. Prospective cohort study].

    PubMed

    Sánchez-Santana, Tomás; Del-Moral-Luque, Juan Antonio; Gil-Yonte, Pablo; Bañuelos-Andrío, Luis; Durán-Poveda, Manuel; Rodríguez-Caravaca, Gil

    Antibiotic prophylaxis is the most suitable tool for preventing surgical site infection. This study assessed compliance with antibiotic prophylaxis in surgery for acute appendicitis, and the effect of this compliance on surgical site infection. Prospective cohort study to evaluate compliance with antibiotic prophylaxis protocol in appendectomies. An assessment was made of the level of compliance with prophylaxis, as well as the causes of non-compliance. The incidence of surgical site infection was studied after a maximum incubation period of 30 days. The relative risk adjusted with a logistic regression model was used to assess the effect of non-compliance of prophylaxis on surgical site infection. The study included a total of 930 patients. Antibiotic prophylaxis was indicated in all patients, and administered in 71.3% of cases, with an overall protocol compliance of 86.1%. The principal cause of non-compliance was time of initiation. Cumulative incidence of surgical site infection was 4.6%. No relationship was found between inadequate prophylaxis compliance and infection (relative risk=0.5; 95% CI: 0.1-1.9) (P>.05). Compliance of antibiotic prophylaxis was high, but could be improved. No relationship was found between prophylaxis compliance and surgical site infection rate. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  11. Scaling up from greenhouse resistance to fitness in the field for a host of an emerging forest disease

    Treesearch

    Katherine J. Hayden; Matteo Garbelotto; Richard Dodd; Jessica W. Wright

    2013-01-01

    Forest systems are increasingly threatened by emergent, exotic diseases, yet management strategies for forest trees may be hindered by long generation times and scant background knowledge. We tested whether nursery disease resistance and growth traits have predictive value for the conservation of Notholithocarpus densiflorus, the host most...

  12. PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A.

    PubMed

    Lissitchkov, T; Rusen, L; Georgiev, P; Windyga, J; Klamroth, R; Gercheva, L; Nemes, L; Tiede, A; Bichler, J; Knaub, S; Belyanskaya, L; Walter, O; Pasi, K J

    2017-09-01

    Nuwiq ® (human-cl rhFVIII) is a 4 th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq ® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg -1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. PK-guided personalized prophylaxis with Nuwiq ® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction. © 2017 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  13. Are the Polyomaviruses BK and JC Associated with Opportunistic Infections, Graft-versus-Host Disease, or Worse Outcomes in Adult Patients Receiving Their First Allogeneic Stem Cell Transplantation with Low-Dose Alemtuzumab?

    PubMed

    Schneidewind, Laila; Neumann, Thomas; Knoll, Florian; Zimmermann, Kathrin; Smola, Sigrun; Schmidt, Christian Andreas; Krüger, William

    2017-01-01

    The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed. We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years. Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death. We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding. © 2017 S. Karger AG, Basel.

  14. Ikaros-Notch axis in host hematopoietic cells regulates experimental graft-versus-host disease

    PubMed Central

    Toubai, Tomomi; Sun, Yaping; Tawara, Isao; Friedman, Ann; Liu, Chen; Evers, Rebecca; Nieves, Evelyn; Malter, Chelsea; Chockley, Peter; Maillard, Ivan; Winandy, Susan

    2011-01-01

    Host hematopoietically derived APCs play a vital role in the initiation of GVH responses. However, the APC autonomous molecular mechanisms that are critical for the induction of GVHD are not known. We report here that the Ikaros-Notch axis in host hematopoietically derived APCs regulates the severity of acute GVHD across multiple clinically relevant murine models of experimental bone marrow transplantation. In the present study, Ikaros deficiency (Ik−/−) limited to host hematopoietically derived APCs enhanced donor T-cell expansion and intensified acute GVHD, as determined by survival and other GVHD-specific parameters. The Ik−/− conventional CD8+ and CD8−CD11c+ dendritic cells (DCs), the most potent APCs, showed no increase in the expression of activation markers or in response to TLR stimulation compared with wild-type controls. However, Ik−/− DCs demonstrated an enhanced stimulation of allogeneic T cells. Deficiency of Ikaros in the conventional CD8+ and CD8−CD11c+ DCs was associated with an increase in Notch signaling, the blockade of which mitigated the enhanced in vitro and in vivo allostimulatory capacity. Therefore, the Ikaros-Notch axis is a novel pathway that modulates DC biology in general, and targeting this pathway in host hematopoietically derived APCs may reduce GVHD. PMID:21471527

  15. Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria

    USGS Publications Warehouse

    Woodworth, B.L.; Atkinson, C.T.; Lapointe, D.A.; Hart, P.J.; Spiegel, C.S.; Tweed, E.J.; Henneman, C.; LeBrun, J.; Denette, T.; DeMots, R.; Kozar, K.L.; Triglia, D.; Lease, Dan; Gregor, A.; Smith, T.; Duffy, D.

    2005-01-01

    The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55-270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24-40% by microscopy and 55-83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on south-eastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations.

  16. Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria

    PubMed Central

    Woodworth, Bethany L.; Atkinson, Carter T.; LaPointe, Dennis A.; Hart, Patrick J.; Spiegel, Caleb S.; Tweed, Erik J.; Henneman, Carlene; LeBrun, Jaymi; Denette, Tami; DeMots, Rachel; Kozar, Kelly L.; Triglia, Dennis; Lease, Dan; Gregor, Aaron; Smith, Tom; Duffy, David

    2005-01-01

    The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55–270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24–40% by microscopy and 55–83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on southeastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations. PMID:15668377

  17. Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria.

    PubMed

    Woodworth, Bethany L; Atkinson, Carter T; Lapointe, Dennis A; Hart, Patrick J; Spiegel, Caleb S; Tweed, Erik J; Henneman, Carlene; Lebrun, Jaymi; Denette, Tami; Demots, Rachel; Kozar, Kelly L; Triglia, Dennis; Lease, Dan; Gregor, Aaron; Smith, Tom; Duffy, David

    2005-02-01

    The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55-270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24-40% by microscopy and 55-83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on southeastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations.

  18. Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma.

    PubMed

    Pérez-Losada, Marcos; Castro-Nallar, Eduardo; Bendall, Matthew L; Freishtat, Robert J; Crandall, Keith A

    2015-01-01

    High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for variation in clinical metadata. Transcriptomic (host) and metatranscriptomic (microbiota) sequences from the nasal epithelium of 8 asthmatics and 6 healthy controls were separated in silico and mapped to available human and NCBI-NR protein reference databases. Human genes differentially expressed in asthmatics and controls were then used to infer upstream regulators involved in immune and inflammatory responses. Concomitantly, microbial genes were mapped to metabolic databases (COG, SEED, and KEGG) to infer microbial functions differentially expressed in asthmatics and controls. Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation. Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested. Enrichment analysis of 499 differentially expressed host genes for inflammatory and immune responses revealed 43 upstream regulators differentially activated in asthma. Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that

  19. Prophylaxis and treatment of pregnant women for emerging infections and bioterrorism emergencies.

    PubMed

    Cono, Joanne; Cragan, Janet D; Jamieson, Denise J; Rasmussen, Sonja A

    2006-11-01

    Emerging infectious disease outbreaks and bioterrorism attacks warrant urgent public health and medical responses. Response plans for these events may include use of medications and vaccines for which the effects on pregnant women and fetuses are unknown. Healthcare providers must be able to discuss the benefits and risks of these interventions with their pregnant patients. Recent experiences with outbreaks of severe acute respiratory syndrome, monkeypox, and anthrax, as well as response planning for bioterrorism and pandemic influenza, illustrate the challenges of making recommendations about treatment and prophylaxis for pregnant women. Understanding the physiology of pregnancy, the factors that influence the teratogenic potential of medications and vaccines, and the infection control measures that may stop an outbreak will aid planners in making recommendations for care of pregnant women during large-scale infectious disease emergencies.

  20. Venous thromboembolism prophylaxis in gynecologic surgery: a systematic review.

    PubMed

    Rahn, David D; Mamik, Mamta M; Sanses, Tatiana V D; Matteson, Kristen A; Aschkenazi, Sarit O; Washington, Blair B; Steinberg, Adam C; Harvie, Heidi S; Lukban, James C; Uhlig, Katrin; Balk, Ethan M; Sung, Vivian W

    2011-11-01

    To comprehensively review and critically assess the available gynecologic surgery venous thromboembolism prophylaxis literature and provide clinical practice guidelines. MEDLINE and Cochrane databases from inception to July 2010. We included randomized controlled trials in gynecologic surgery populations. Interventions and comparators included graduated compression stockings, intermittent pneumatic compression, unfractionated heparin, and low molecular weight heparin; placebo and routine postoperative care were allowed as comparators. One thousand two hundred sixty-six articles were screened, and 14 randomized controlled trials (five benign gynecologic, nine gynecologic oncology) met eligibility criteria. In addition, nine prospective or retrospective studies with at least 150 women were identified and provided data on venous thromboembolism risk stratification, gynecologic laparoscopy, and urogynecologic populations. Two reviewers independently screened articles with discrepancies adjudicated by a third. Eligible randomized controlled trials were extracted for these characteristics: study, participant, surgery, intervention, comparator, and outcomes data, including venous thromboembolism incidence and bleeding complications. Studies were individually and collectively assessed for methodologic quality and strength of evidence. Overall incidence of clinical venous thromboembolism was 0-2% in the benign gynecologic population. With use of intermittent pneumatic compression for benign major procedures, venous thromboembolism incidence was less than 1%. No venous thromboembolisms were identified in prospective studies of benign laparoscopic procedures. Overall quality of evidence in the benign gynecologic literature was poor. Gynecologic-oncology randomized controlled trials reported venous thromboembolism incidence (including "silent" venous thromboembolisms) of 0-14.8% with prophylaxis and up to 34.6% without prophylaxis. Fair quality of evidence supports that

  1. Modulation of the host inflammatory response in periodontal disease management: exciting new directions.

    PubMed

    Bhatavadekar, Neel B; Williams, Ray C

    2009-10-01

    New strategies for periodontal disease management have been emerging as more is learned about the role of the host response. Our increasing understanding of inflammation and its resolution has opened the door to the study of new periodontal treatment strategies. This review examines periodontal disease in the light of a new understanding of the role of inflammation in disease expression thus setting the stage for the development of new prevention and treatment strategies of a widespread disease. We examined current publications and focused on articles relating to anti-inflammatory and pro-resolution mechanisms in periodontal disease. Recent research has examined the inflammatory and resolution cascade in greater detail while looking at endogenous and exogenous mediators that can be utilised to achieve therapeutic end-points. The possible introduction of 'resolution indices' for drug testing warrants a new look at pharmacologic agents that might have been overlooked for their beneficial effects in periodontal disease treatment. The emerging awareness of inflammation and its control in periodontal disease management underscores the importance of exploring inflammatory pathways and mediators, thus exploring new ways to control inflammation. This direction of research promises a new era in drug discovery and therapeutics for periodontal disease treatment.

  2. In vivo kinetics and nonradioactive imaging of rapidly proliferating cells in graft-versus-host disease

    PubMed Central

    Buxbaum, Nataliya P.; Farthing, Donald E.; Maglakelidze, Natella; Lizak, Martin; Merkle, Hellmut; Carpenter, Andrea C.; Oliver, Brittany U.; Kapoor, Veena; Castro, Ehydel; Swan, Gregory A.; dos Santos, Liliane M.; Bouladoux, Nicolas J.; Bare, Catherine V.; Flomerfelt, Francis A.; Eckhaus, Michael A.; Telford, William G.; Belkaid, Yasmine; Bosselut, Remy J.; Gress, Ronald E.

    2017-01-01

    Hematopoietic stem cell transplantation (HSCT) offers a cure for cancers that are refractory to chemotherapy and radiation. Most HSCT recipients develop chronic graft-versus-host disease (cGVHD), a systemic alloimmune attack on host organs. Diagnosis is based on clinical signs and symptoms, as biopsies are risky. T cells are central to the biology of cGVHD. We found that a low Treg/CD4+ T effector memory (Tem) ratio in circulation, lymphoid, and target organs identified early and established mouse cGVHD. Using deuterated water labeling to measure multicompartment in vivo kinetics of these subsets, we show robust Tem and Treg proliferation in lymphoid and target organs, while Tregs undergo apoptosis in target organs. Since deuterium enrichment into DNA serves as a proxy for cell proliferation, we developed a whole-body clinically relevant deuterium MRI approach to nonradioactively detect cGVHD and potentially allow imaging of other diseases characterized by rapidly proliferating cells. PMID:28614804

  3. No recurrence of Pneumocystis jirovecii Pneumonia after solid organ transplantation regardless of secondary prophylaxis.

    PubMed

    Kim, Tark; Sung, Heungsup; Lee, Yu-Mi; Hong, Hyo-Lim; Kim, Sung-Han; Choi, Sang-Ho; Woo, Jun Hee; Kim, Yang Soo; Lee, Sang-Oh

    2012-11-01

    There are no data on the efficacy of secondary prophylaxis against Pneumocystis pneumonia after solid organ transplantation. Therefore, we investigated the rate of recurrence of Pneumocystis pneumonia after solid organ transplantation in a retrospective cohort study. Between 2005 and 2011, a total of 41 recipients recovered from Pneumocystis pneumonia. Of these, 22 (53.7%) received secondary prophylaxis. None of the 41 recipients experienced recurrence of Pneumocystis pneumonia during the follow-up, regardless of secondary prophylaxis.

  4. Scaling up from greenhouse resistance to fitness in the field for a host of an emerging forest disease

    PubMed Central

    Hayden, Katherine J; Garbelotto, Matteo; Dodd, Richard; Wright, Jessica W

    2013-01-01

    Forest systems are increasingly threatened by emergent, exotic diseases, yet management strategies for forest trees may be hindered by long generation times and scant background knowledge. We tested whether nursery disease resistance and growth traits have predictive value for the conservation of Notholithocarpus densiflorus, the host most susceptible to sudden oak death. We established three experimental populations to assess nursery growth and resistance to Phytophthora ramorum, and correlations between nursery-derived breeding values with seedling survival in a field disease trial. Estimates of nursery traits’ heritability were low to moderate, with lowest estimates for resistance traits. Within the field trial, survival likelihood was increased in larger seedlings and decreased with the development of disease symptoms. The seed-parent family wide likelihood of survival was likewise correlated with family predictors for size and resistance to disease in 2nd year laboratory assays, though not resistance in 1st year leaf assays. We identified traits and seedling families with increased survivorship in planted tanoaks, and a framework to further identify seed parents favored for restoration. The additive genetic variation and seedling disease dynamics we describe hold promise to refine current disease models and expand the understanding of evolutionary dynamics of emergent infectious diseases in highly susceptible hosts. PMID:24062805

  5. Are Centers for Disease Control and Prevention Guidelines for Preexposure Prophylaxis Specific Enough? Formulation of a Personalized HIV Risk Score for Pre-Exposure Prophylaxis Initiation.

    PubMed

    Beymer, Matthew R; Weiss, Robert E; Sugar, Catherine A; Bourque, Linda B; Gee, Gilbert C; Morisky, Donald E; Shu, Suzanne B; Javanbakht, Marjan; Bolan, Robert K

    2017-01-01

    Preexposure prophylaxis (PrEP) has emerged as a human immunodeficiency virus (HIV) prevention tool for populations at highest risk for HIV infection. Current US Centers for Disease Control and Prevention (CDC) guidelines for identifying PrEP candidates may not be specific enough to identify gay, bisexual, and other men who have sex with men (MSM) at the highest risk for HIV infection. We created an HIV risk score for HIV-negative MSM based on Syndemics Theory to develop a more targeted criterion for assessing PrEP candidacy. Behavioral risk assessment and HIV testing data were analyzed for HIV-negative MSM attending the Los Angeles LGBT Center between January 2009 and June 2014 (n = 9481). Syndemics Theory informed the selection of variables for a multivariable Cox proportional hazards model. Estimated coefficients were summed to create an HIV risk score, and model fit was compared between our model and CDC guidelines using the Akaike Information Criterion and Bayesian Information Criterion. Approximately 51% of MSM were above a cutpoint that we chose as an illustrative risk score to qualify for PrEP, identifying 75% of all seroconverting MSM. Our model demonstrated a better overall fit when compared with the CDC guidelines (Akaike Information Criterion Difference = 68) in addition to identifying a greater proportion of HIV infections. Current CDC PrEP guidelines should be expanded to incorporate substance use, partner-level, and other Syndemic variables that have been shown to contribute to HIV acquisition. Deployment of such personalized algorithms may better hone PrEP criteria and allow providers and their patients to make a more informed decision prior to PrEP use.

  6. Beclomethasone in Treating Patients With Graft-Versus-Host Disease of the Esophagus, Stomach, Small Intestine, or Colon

    ClinicalTrials.gov

    2010-03-31

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Graft Versus Host Disease; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  7. Disease spread across multiple scales in a spatial hierarchy: effect of host spatial structure and of inoculum quantity and distribution.

    PubMed

    Gosme, Marie; Lucas, Philippe

    2009-07-01

    Spatial patterns of both the host and the disease influence disease spread and crop losses. Therefore, the manipulation of these patterns might help improve control strategies. Considering disease spread across multiple scales in a spatial hierarchy allows one to capture important features of epidemics developing in space without using explicitly spatialized variables. Thus, if the system under study is composed of roots, plants, and planting hills, the effect of host spatial pattern can be studied by varying the number of plants per planting hill. A simulation model based on hierarchy theory was used to simulate the effects of large versus small planting hills, low versus high level of initial infections, and aggregated versus uniform distribution of initial infections. The results showed that aggregating the initially infected plants always resulted in slower epidemics than spreading out the initial infections uniformly. Simulation results also showed that, in most cases, disease epidemics were slower in the case of large host aggregates (100 plants/hill) than with smaller aggregates (25 plants/hill), except when the initially infected plants were both numerous and spread out uniformly. The optimal strategy for disease control depends on several factors, including initial conditions. More importantly, the model offers a framework to account for the interplay between the spatial characteristics of the system, rates of infection, and aggregation of the disease.

  8. Effect of Intermediate Hosts on Emerging Zoonoses.

    PubMed

    Cui, Jing-An; Chen, Fangyuan; Fan, Shengjie

    2017-08-01

    Most emerging zoonotic pathogens originate from animals. They can directly infect humans through natural reservoirs or indirectly through intermediate hosts. As a bridge, an intermediate host plays different roles in the transmission of zoonotic pathogens. In this study, we present three types of pathogen transmission to evaluate the effect of intermediate hosts on emerging zoonotic diseases in human epidemics. These types are identified as follows: TYPE 1, pathogen transmission without an intermediate host for comparison; TYPE 2, pathogen transmission with an intermediate host as an amplifier; and TYPE 3, pathogen transmission with an intermediate host as a vessel for genetic variation. In addition, we established three mathematical models to elucidate the mechanisms underlying zoonotic disease transmission according to these three types. Stability analysis indicated that the existence of intermediate hosts increased the difficulty of controlling zoonotic diseases because of more difficult conditions to satisfy for the disease to die out. The human epidemic would die out under the following conditions: TYPE 1: [Formula: see text] and [Formula: see text]; TYPE 2: [Formula: see text], [Formula: see text], and [Formula: see text]; and TYPE 3: [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] Simulation with similar parameters demonstrated that intermediate hosts could change the peak time and number of infected humans during a human epidemic; intermediate hosts also exerted different effects on controlling the prevalence of a human epidemic with natural reservoirs in different periods, which is important in addressing problems in public health. Monitoring and controlling the number of natural reservoirs and intermediate hosts at the right time would successfully manage and prevent the prevalence of emerging zoonoses in humans.

  9. Respiratory infections in children up to two years of age on prophylaxis with palivizumab

    PubMed Central

    Monteiro, Ana Isabel M. P.; Bellei, Nancy Cristina J.; Sousa, Alessandra Ramos; dos Santos, Amélia Miyashiro N.; Weckx, Lily Yin

    2014-01-01

    OBJECTIVE: To identify the viruses involved in acute respiratory tract infections and to analyze the rates of hospitalization and death in children on palivizumab prophylaxis. METHODS: Prospective cohort of 198 infants up to one year old who were born before 29 weeks of gestational age and infants under two years old with hemodynamically unstable cardiopathy or chronic pulmonary disease who received prophylactic palivizumab against severe respiratory syncytial virus infections in 2008. During the study period, in each episode of acute respiratory tract infection, nasopharyngeal aspirate was collected to identify respiratory syncytial virus, adenovirus, parainfluenza 1, 2 and 3, influenza A and B by direct immunofluorescence, rhinovirus and metapneumovirus by polymerase chain reaction preceded by reverse transcription. Data regarding hospitalization and deaths were monitored. RESULTS: Among the 198 studied infants, 117 (59.1%) presented acute respiratory tract infections, with a total of 175 episodes. Of the 76 nasopharyngeal aspirates collected during respiratory tract infections, 37 were positive, as follow: rhinovirus (75.7%), respiratory syncytial virus (18.9%), parainfluenza (8.1%), adenovirus 2 (2.7%), metapneumovirus (2.7%) and three samples presented multiple agents. Of the 198 children, 48 (24.4%) were hospitalized: 30 (15.2%) for non-infectious etiology and 18 (9.1%) for respiratory causes. Among these 18 children, one case of respiratory syncytial virus was identified. Two deaths were reported, but respiratory syncytial virus was not identified. CONCLUSIONS: During the prophylaxis period, low frequency of respiratory syncytial virus infections and low rates of hospitalization were observed, suggesting the benefit of palivizumab prophylaxis. PMID:25119744

  10. Host control of human papillomavirus infection and disease.

    PubMed

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  11. Modelling virus- and host-limitation in vectored plant disease epidemics.

    PubMed

    Jeger, M J; van den Bosch, F; Madden, L V

    2011-08-01

    Models of plant virus epidemics have received less attention than those caused by fungal pathogens. Intuitively, the fact that virus diseases are systemic means that the individual diseased plant can be considered as the population unit which simplifies modelling. However, the fact that a vector is required in the vast majority of cases for virus transmission, means that explicit consideration must be taken of the vector, or, the involvement of the vector in the transmission process must be considered implicitly. In the latter case it is also important that within-plant processes, such as virus multiplication and systemic movement, are taken into account. In this paper we propose an approach based on the linking of transmission at the population level with virus multiplication within plants. The resulting models are parameter-sparse and hence simplistic. However, the range of model outcomes is representative of field observations relating to the apparent limitation of epidemic development in populations of healthy susceptible plants. We propose that epidemic development can be constrained by virus limitation in the early stages of an epidemic when the availability of healthy susceptible hosts is not limiting. There is an inverse relationship between levels of transmission in the population and the mean virus titre/infected plant. In the case of competition between viruses, both virus and host limitation are likely to be important in determining whether one virus can displace another or whether both viruses can co-exist in a plant population. Lotka-Volterra type equations are derived to describe density-dependent competition between two viruses multiplying within plants, embedded within a population level epidemiological model. Explicit expressions determining displacement or co-existence of the viruses are obtained. Unlike the classical Lotka-Volterra competition equations, the co-existence requirement for the competition coefficients to be both less than 1 can be

  12. Cost-Effectiveness of Antibiotic Prophylaxis Strategies for Transrectal Prostate Biopsy in an Era of Increasing Antimicrobial Resistance.

    PubMed

    Lee, Kyueun; Drekonja, Dimitri M; Enns, Eva A

    2018-03-01

    To determine the optimal antibiotic prophylaxis strategy for transrectal prostate biopsy (TRPB) as a function of the local antibiotic resistance profile. We developed a decision-analytic model to assess the cost-effectiveness of four antibiotic prophylaxis strategies: ciprofloxacin alone, ceftriaxone alone, ciprofloxacin and ceftriaxone in combination, and directed prophylaxis selection based on susceptibility testing. We used a payer's perspective and estimated the health care costs and quality-adjusted life-years (QALYs) associated with each strategy for a cohort of 66-year-old men undergoing TRPB. Costs and benefits were discounted at 3% annually. Base-case resistance prevalence was 29% to ciprofloxacin and 7% to ceftriaxone, reflecting susceptibility patterns observed at the Minneapolis Veterans Affairs Health Care System. Resistance levels were varied in sensitivity analysis. In the base case, single-agent prophylaxis strategies were dominated. Directed prophylaxis strategy was the optimal strategy at a willingness-to-pay threshold of $50,000/QALY gained. Relative to the directed prophylaxis strategy, the incremental cost-effectiveness ratio of the combination strategy was $123,333/QALY gained over the lifetime time horizon. In sensitivity analysis, single-agent prophylaxis strategies were preferred only at extreme levels of resistance. Directed or combination prophylaxis strategies were optimal for a wide range of resistance levels. Facilities using single-agent antibiotic prophylaxis strategies before TRPB should re-evaluate their strategies unless extremely low levels of antimicrobial resistance are documented. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  13. Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with Foot-and-Mouth Disease Virus.

    PubMed

    Xin, Xiu; Wang, Hailong; Han, Lingling; Wang, Mingzhen; Fang, Hui; Hao, Yao; Li, Jiadai; Zhang, Hu; Zheng, Congyi; Shen, Chao

    2018-05-01

    Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G 2 /M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell. IMPORTANCE It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells. Copyright © 2018 American Society for Microbiology.

  14. Antibiotic prophylaxis in open inguinal hernia repair: a literature review and summary of current knowledge

    PubMed Central

    Makarewicz, Wojciech; Ropel, Jerzy; Bobowicz, Maciej; Kąkol, Michał; Śmietański, Maciej

    2016-01-01

    More than 1 million inguinal hernia repairs are performed in Europe and the US annually. Although antibiotic prophylaxis is not required in clean, elective procedures, the routine use of implants (90% of inguinal hernia repairs are performed with mesh) makes the topic controversial. The European Hernia Society does not recommend routine antibiotic prophylaxis for elective inguinal hernia repairs. However, the latest randomized controlled trial, published by Mazaki et al., indicates that the use of prophylaxis is effective for the prevention of surgical site infection. Unnecessary prophylaxis contributes to the development of bacterial resistance and significantly increases healthcare costs. This review documents clinical trials on inguinal hernia repairs with mesh and summarizes the current knowledge. It also tries to solve certain problems, namely: what constitutes a real risk factor, late-onset infection, and how the “surgical environment” impacts on the need to use antibiotic prophylaxis. PMID:27829934

  15. A Cost-Benefit Analysis of Low-Dose Aspirin Prophylaxis for the Prevention of Preeclampsia in the United States.

    PubMed

    Werner, Erika F; Hauspurg, Alisse K; Rouse, Dwight J

    2015-12-01

    To develop a decision model to evaluate the risks, benefits, and costs of different approaches to aspirin prophylaxis for the approximately 4 million pregnant women in the United States annually. We created a decision model to evaluate four approaches to aspirin prophylaxis in the United States: no prophylaxis, prophylaxis per American College of Obstetricians and Gynecologists (the College) recommendations, prophylaxis per U.S. Preventive Services Task Force recommendations, and universal prophylaxis. We included the costs associated with aspirin, preeclampsia, preterm birth, and potential aspirin-associated adverse effects. TreeAge Pro 2011 was used to perform the analysis. The estimated rate of preeclampsia would be 4.18% without prophylaxis compared with 4.17% with the College approach in which 0.35% (n=14,000) of women receive aspirin, 3.83% with the U.S. Preventive Services Task Force approach in which 23.5% (n=940,800) receive aspirin, and 3.81% with universal prophylaxis. Compared with no prophylaxis, the U.S. Preventive Services Task Force approach would save $377.4 million in direct medical care costs annually, and universal prophylaxis would save $365 million assuming 4 million births each year. The U.S. Preventive Services Task Force approach is the most cost-beneficial in 79% of probabilistic simulations. Assuming a willingness to pay of $100,000 per neonatal quality-adjusted life-year gained, the universal approach is the most cost-effective in more than 99% of simulations. Both the U.S. Preventive Services Task Force approach and universal prophylaxis would reduce morbidity, save lives, and lower health care costs in the United States to a much greater degree than the approach currently recommended by the College.

  16. New mechanisms of disease and parasite-host interactions.

    PubMed

    de Souza, Tiago Alves Jorge; de Carli, Gabriel Jose; Pereira, Tiago Campos

    2016-09-01

    An unconventional interaction between a patient and parasites was recently reported, in which parasitic cells invaded host's tissues, establishing several tumors. This finding raises various intriguing hypotheses on unpredicted forms of interplay between a patient and infecting parasites. Here we present four unusual hypothetical host-parasite scenarios with intriguing medical consequences. Relatively simple experimental designs are described in order to evaluate such hypotheses. The first one refers to the possibility of metabolic disorders in parasites intoxicating the host. The second one is on possibility of patients with inborn errors of metabolism (IEM) being more resistant to parasites (due to accumulation of toxic compounds in the bloodstream). The third one refers to a mirrored scenario: development of tumors in parasites due to ingestion of host's circulating cancer cells. The last one describes a complex relationship between parasites accumulating a metabolite and supplying it to a patient with an IEM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Antibiotic prophylaxis and complications following prostate biopsies - a systematic review.

    PubMed

    Klemann, Nina; Helgstrand, John Thomas; Brasso, Klaus; Vainer, Ben; Iversen, Peter; Røder, Martin Andreas

    2017-01-01

    Transrectal ultrasound-guided biopsies (TRUS-gb) are associated with both mild and serious complications. Prophylactic antibiotics reduce the risk of septicaemia and mortality; however, no international consensus exists on the timing and duration of antibiotics, including the optimal drug strategy. We reviewed the current evidence supporting use of prophylactic antibiotics and the risk of complications following prostate biopsies. This review was drafted in accordance with the Prisma Guidelines. The PubMed, Embase and Cochrane databases were searched. A total of 19 eligible trials were identified. One trial demonstrated a significant reduction in the risk of infection after biopsy and reported that oral ciprofloxacin as either a single-dose or a three-day regimen was superior to oral chloramphenicol and norfloxacin. Of three studies investigating the timing of the first dose of antibiotic, one study found that administration 24 h before biopsy versus administration immediately before reduced the relative risk of post-biopsy infection by 55%. Seven studies compared different durations of antibiotic prophylaxis. None showed any benefit from continuing prophylaxis beyond a single dose or a one-day regimen. Evidence supporting a specific antibiotic regimen for TRUS-gb prophylaxis is scarce. Widespread use of fluoroquinolone prophylaxis may be associated with an increase in resistant Escherichia coli strains, posing a potentially major health issue in the future.  .

  18. The 12th I. E. Melhus Graduate Student Symposium: host plant resistance and disease management, current status and future outlook

    USDA-ARS?s Scientific Manuscript database

    The 12th I. E. Melhus Graduate Student Symposium was held on 6 August 2012 during the Annual meeting of the American Phytopathological Society (APS) in Providence, RI. The theme for this symposium was “Host Plant Resistance and Disease Management: Current Status and Future Outlook”. The APS Host R...

  19. Association of mixed hematopoietic chimerism with elevated circulating autoantibodies and chronic graft-versus-host disease occurrence.

    PubMed

    Perruche, Sylvain; Marandin, Aliette; Kleinclauss, François; Angonin, Régis; Fresnay, Stéphanie; Baron, Marie Hélène; Tiberghien, Pierre; Saas, Philippe

    2006-02-27

    Use of a reduced-intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a coexistence of both host and donor hematopoietic cells may influence posttransplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced-intensity conditioning transplantation (RICT), autoantibody production, and chronic GVHD (cGVHD)-related pathology. Chimerism state, circulating anticardiolipin, and antidouble stranded DNA autoantibody (Ab) titers as well as occurrence of cGVHD-like lesions were investigated in a murine RICT model. We observed a novel association between mixed chimerism state, high levels of pathogenic IgG autoantibodies, and subsequent development of cGVHD-like lesions. Furthermore, we found that the persistence of host B cells, but not dendritic cell origin or subset, was a factor associated with the appearance of cGVHD-like lesions. The implication of host B cells was confirmed by a host origin of autoantibodies. Recipient B cell persistence may contribute to the frequency and/or severity of cGVHD after RICT.

  20. Acute graft-versus-host disease: from the bench to the bedside

    PubMed Central

    Blazar, Bruce R.

    2009-01-01

    During the past decade, progress in basic immunology has been impressive. In parallel, whereas our understanding of the pathophysiology of acute graft-versus-host disease (GVHD) has greatly improved, so has our knowledge of the complexities of the immune system. Much of the immunobiology of acute GVHD has been gleaned from preclinical models and far less from correlations with clinical observations or therapeutic interventions. In this review, we summarize some of the major advances in GVHD pathophysiology, including the translation of these from the bench to the bedside, and discuss preclinical approaches that warrant further exploration in the clinic. PMID:19713461

  1. The genetic predisposition and the interplay of host genetics and gut microbiome in Crohn disease.

    PubMed

    Jianzhong, Hu

    2014-12-01

    Extensive genetic studies have identified more than 140 loci predisposing to Crohn disease (CD). Several major CD susceptibility genes have been shown to impair biological function with regard to immune response to recognizing and clearance of bacterial infection. Recent human microbiome studies suggest that the gut microbiome composition is differentiated in carriers of many risk variants of major CD susceptibility genes. This interplay between host genetics and its associated gut microbiome may play an essential role in the pathogenesis of CD. The ongoing microbiome research is aimed to investigate the detailed host genetics-microbiome interacting mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Adherence to Antimicrobial Inhalational Anthrax Prophylaxis among Postal Workers, Washington, D.C., 2001

    PubMed Central

    Laserson, Kayla; Fry, Alicia M.; Roy, Sharon; Hayslett, James; Grummer-Strawn, Laurence; Kettel-Khan, Laura; Schuchat, Anne

    2002-01-01

    In October 2001, two envelopes containing Bacillus anthracis spores were processed at the Washington, D.C., Processing and Distribution Center of the U.S. Postal Service; inhalational anthrax developed in four workers at this facility. More than 2,000 workers were advised to complete 60 days of postexposure prophylaxis to prevent inhalational anthrax. Interventions to promote adherence were carried out to support workers, and qualitative information was collected to evaluate our interventions. A quantitative survey was administered to a convenience sample of workers to assess factors influencing adherence. No anthrax infections developed in any workers involved in the interventions or interviews. Of 245 workers, 98 (40%) reported full adherence to prophylaxis, and 45 (18%) had completely discontinued it. Experiencing adverse effects to prophylaxis, anxiety, and being <45 years old were risk factors for discontinuing prophylaxis. Interventions, especially frequent visits by public health staff, proved effective in supporting adherence. PMID:12396929

  3. Relevance of genetically determined host factors to the prognosis of meningococcal disease.

    PubMed

    Domingo, P; Muñiz-Diaz, E; Baraldès, M A; Arilla, M; Barquet, N; Pericas, R; Juárez, C; Madoz, P; Vázquez, G

    2004-08-01

    To assess the relevance of genetically determined host factors for the prognosis of meningococcal disease, Fc gamma receptor IIA (FcgammaRIIA), the tumor necrosis factor alpha (TNF-alpha) gene promoter region, and plasminogen-activator-inhibitor-1 (PAI-1) gene polymorphisms were studied in 145 patients with meningococcal disease and in 290 healthy controls matched by sex. Distribution of FcgammaRIIA, TNF-alpha, and PAI-1 alleles was not significantly different between patients and controls. Patients with the FcgammaRIIA-R/R 131 allotype scored > or =1 point in the Barcelona prognostic system more frequently than patients with other allotypes (odds ratio, 18.6; 95% confidence interval, 7.1-49.0, P<0.0001), and they had a higher risk of sequelae (odds ratio, 3.5; 95% confidence interval, 1.1-11.7; P=0.03). Fc gamma receptor IIA polymorphism was associated with markers of disease severity, but TNF-alpha and PAI-1 polymorphisms were not.

  4. Rheumatic heart disease: progress and challenges in India.

    PubMed

    Shah, Bela; Sharma, Meenakshi; Kumar, Rajesh; Brahmadathan, K N; Abraham, Vinod Joseph; Tandon, Rajan

    2013-03-01

    Rheumatic heart disease, a neglected disease, continues to be a burden in India and other developing countries. It is a result of an autoimmune sequalae in response to group A beta hemolytic streptococcus (GAS) infection of the pharynx. Acute rheumatic fever (RF), a multisystem inflammatory disease, is followed by rheumatic heart disease (RHD) and has manifestations of joints, skin and central nervous system involvement. A review of epidemiological studies indicates unchanged GAS pharyngitis and carrier rates in India. The apparent decline in RHD rates in India as indicated by the epidemiological studies has to be taken with caution as methodological differences exist among studies. Use of echocardiography increases case detection rates of RHD in population surveys. However, the significance of echo based diagnosis of carditis needs further evaluation to establish the significance. Research in this area through prospective follow up studies will have to be undertaken by the developing countries as the interest of developed countries in the disease has waned due the declined burden in their populations. Prevention of RHD is possible through treatment of GAS pharyngitis (primary prophylaxis) and continued antibiotic treatment for number of years in patients with history of RF to prevent recurrences (secondary prophylaxis). The cost effectiveness and practicality of secondary prophylaxis is well documented. The challenge to any secondary prophylaxis program for prevention of RF in India will be the availability of benzathine penicillin G and dissipation of fears of allergic reactions to penicillin among practitioners, general public and policy makers. The authors review here the progress and challenges in epidemiology, diagnosis and primary and secondary prevention of RF and RHD.

  5. Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mutter, W.; Reddehase, M.J.; Busch, F.W.

    1988-05-01

    We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation. CD8+ T lymphocytes and bone marrow cells both mediated survival, although only CD8+ T lymphocytes were able tomore » limit virus multiplication in host tissues. We concluded that not the cytopathic effect of virus replication in host tissues, but the failure in hemopoiesis, is the primary cause of death in murine CMV disease.« less

  6. A comparison of the effects of toothbrushing and handpiece prophylaxis on retention of sealants.

    PubMed

    Kolavic Gray, Shellie; Griffin, Susan O; Malvitz, Dolores M; Gooch, Barbara F

    2009-01-01

    Tooth surface cleaning before acid etching is considered to be an important step in the retention of resin-based pit-and-fissure sealants. The authors reviewed and summarized instructions for cleaning tooth surfaces from five manufacturers of 10 unfilled resin-based sealants marketed in the United States. The authors also searched electronic databases for studies that directly compared the effects of different surface-cleaning methods on sealant retention and for systematic reviews of the effectiveness of sealants. They explored the association between surface-cleaning methods and sealant retention in the studies included in the systematic reviews. They calculated the summary weighted retention rates for studies that used either a handpiece or toothbrush prophylaxis. All of the sealant manufacturers' instructions for use (IFU) recommended cleaning the tooth before acid etching. None of the IFU directly stated that a handpiece was required to perform the cleaning, but five IFU implied the use of handpiece prophylaxis. None of the IFU recommended surface-altering procedures in caries-free teeth. Direct evidence from two clinical trials showed no difference in complete sealant retention between surfaces cleaned mechanically with pumice or prophylaxis paste and those cleaned with air-water syringe or dry toothbrushing. Indirect evidence from 10 studies found that weighted summary retention by year after sealant placement in studies that used toothbrush prophylaxis was greater than or equivalent to values for studies that used handpiece prophylaxis. Levels of sealant retention after surface cleaning with toothbrush prophylaxis were at least as high as those associated with hand-piece prophylaxis. This finding may translate into lower resource costs for sealant placement.

  7. Prevention of delirium in trauma patients: Are we giving thiamine prophylaxis a fair chance?

    PubMed Central

    Blackmore, Christopher; Ouellet, Jean-Francois; Niven, Daniel; Kirkpatrick, Andrew W.; Ball, Chad G.

    2014-01-01

    Background Delirium is associated with increased morbidity and mortality in injured patients. Wernicke encephalopathy (WE) is delirium linked to malnutrition and chronic alcoholism. It is prevented with administration of thiamine. Our primary goal was to evaluate current blood alcohol level (BAL) testing and thiamine prophylaxis in severely injured patients. Methods We retrospectively reviewed the cases of 1000 consecutive severely injured patients admitted to hospital between Mar. 1, 2009, and Dec. 31, 2009. We used the patients’ medical records and the Alberta Trauma Registry. Results Among 1000 patients (mean age 48 yr, male sex 70%, mean injury severity score 23, mortality 10%), 627 underwent BAL testing at admission; 221 (35%) had a BAL greater than 0 mmol/L, and 189 (30%) had a BAL above the legal limit of 17.4 mmol/L. The mean positive BAL was 41.9 mmol/L. More than 4% had a known history of alcohol abuse. More patients were assaulted (20% v. 9%) or hit by motor vehicles (10% v. 6%) when intoxicated (both p < 0.05). Most injuries occurred after falls (37%) and motor vehicle collisions (33%). Overall, 17% of patients received thiamine prophylaxis. Of the 221 patients with elevated BAL, 44% received thiamine prophylaxis. Of those with a history of alcohol abuse, 77% received thiamine prophylaxis. Conclusion Despite the strong link between alcohol abuse, trauma and WE, more than one-third of patients were not screened for alcohol use. Furthermore, a minority of intoxicated patients received adequate prophylaxis against WE. Given the low risk and cost of BAL testing and thiamine prophylaxis and the high cost of delirium, standard protocols for prophylaxis are essential. PMID:24666443

  8. Deep Venous Thrombosis Prophylaxis in Anterior Cruciate Ligament Reconstructive Surgery: What Is the Current State of Practice?

    PubMed

    Keller, Robert A; Moutzouros, Vasilios; Dines, Joshua S; Bush-Joseph, Charles A; Limpisvasti, Orr

    Venous thromboembolism (VTE) is a significant perioperative risk with many common orthopaedic procedures. Currently, there is no standardized recommendation for the use of VTE prophylaxis during anterior cruciate ligament (ACL) reconstruction. This study sought to evaluate the current prophylactic practices of fellowship-trained sports medicine orthopaedic surgeons in the United States. Very few surgeons use perioperative VTE prophylaxis for ACL reconstructive surgery. Survey. Surveys were emailed to the alumni networks of 4 large ACGME-accredited sports medicine fellowship programs. Questions were focused on their current use of chemical and nonchemical VTE prophylaxis. Surveys were completed by 142 surgeons in the United States, yielding a response rate of 32%. Of those who responded, 50.7% stated that they routinely use chemical prophylaxis, with 95.5% of those using aspirin (acetylsalicylic acid [ASA]). There was no standardized dosing protocol, with respondents using ASA 325 mg once (46%) or twice daily (26%) or ASA 81 mg once (18%) or twice (10%) daily. The most common reason for not including chemical prophylaxis within the reconstruction procedure was that it is unnecessary given the low risk of VTE. Physicians also based their prophylaxis regimen more on their own clinical experience than concern for litigation. Half of all sports medicine fellowship-trained surgeons surveyed routinely use chemical VTE prophylaxis after ACL reconstruction, with more than 90% of those using ASA. Of those using ASA, there was no prevailing dosing protocol. For those not using chemical prophylaxis, the most important reason was that it was felt to be unnecessary due to the risks outweighing the benefits. Those who do not regularly use chemical prophylaxis would be willing to, however, if a patient had a personal or family history of clotting disorder or is currently on birth control. Additionally, clinical experience was the primary driver for a current prophylaxis protocol

  9. Antibiotic prophylaxis for operative vaginal delivery.

    PubMed

    Liabsuetrakul, Tippawan; Choobun, Thanapan; Peeyananjarassri, Krantarat; Islam, Q Monir

    2014-10-13

    Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics may be prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum or forceps deliveries, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Two review authors assessed trial eligibility and methodological quality. Two review authors extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all review authors. For this update, we assessed methodological quality of the one included trial using the standard Cochrane criteria and the GRADE approach. We calculated the risk ratio (RR) and mean difference (MD) using a fixed-effect model and all the review authors interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine outcomes specified in this review. It reported seven women with endomyometritis in the

  10. Antibiotic prophylaxis for operative vaginal delivery.

    PubMed

    Liabsuetrakul, T; Choobun, T; Peeyananjarassri, K; Islam, M

    2004-01-01

    Vacuum and forceps assisted vaginal deliveries are reported to increase the incidence of postpartum infections and maternal readmission to hospital compared to spontaneous vaginal delivery. Prophylactic antibiotics are prescribed to prevent these infections. However, the benefit of antibiotic prophylaxis for operative vaginal deliveries is still unclear. To assess the effectiveness and safety of antibiotic prophylaxis in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries including vacuum and/or forceps deliveries. We searched the Cochrane Pregnancy and Childbirth Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003) and MEDLINE (1966 to November 2003). All randomised trials comparing any prophylactic antibiotic regimens with placebo or no treatment in women undergoing vacuum or forceps deliveries were eligible. Participants were all pregnant women without evidence of infections or other indications for antibiotics of any gestational age undergoing vacuum or forceps delivery for any indications. Interventions were any antibiotic prophylaxis (any dosage regimen, any route of administration or at any time during delivery or the puerperium) compared with either placebo or no treatment. Four reviewers assessed trial eligibility and methodological quality. Two reviewers extracted the data independently using prepared data extraction forms. Any discrepancies were resolved by discussion and a consensus reached through discussion with all reviewers. We assessed methodological quality of the included trial using the standard Cochrane criteria and the CONSORT statement of randomised controlled trials. We calculated the relative risks using a fixed effect model and all the reviewers interpreted and discussed the results. One trial, involving 393 women undergoing either vacuum or forceps deliveries, was included. This trial identified only two out of the nine

  11. Factors associated with coverage of cotrimoxazole prophylaxis in HIV-exposed children in South Africa.

    PubMed

    Moodley, Dhayendre; Reddy, Leanne; Mahungo, Wisani; Masha, Rebotile

    2013-01-01

    The World Health Organisation and the Joint United Nations Programme in 2006 reaffirmed the earlier recommendation of 2000 that all HIV-exposed infants in resource-poor countries should commence cotrimoxazole (CTX) prophylaxis at 6-weeks of life. CTX prophylaxis should be continued until the child is confirmed HIV-uninfected and there is no further exposure to breastmilk transmission. We determined CTX coverage and explored factors associated with CTX administration in HIV-exposed infants at a primary health clinic in South Africa. In a cross-sectional study of HIV-exposed infants 6-18 months of age attending a child immunisation clinic, data from the current visit and previous visits related to CTX prophylaxis, feeding practice and infant HIV testing were extracted from the child's immunisation record. Further information related to the administration of CTX prophylaxis was obtained from an interview with the child's mother. One-third (33.0%) HIV-exposed infants had not initiated CTX at all and breastfed infants were more likely to have commenced CTX prophylaxis as compared to their non-breastfed counterparts (78.7% vs 63.4%) (p = 0.008). Availability of infant's HIV status was strongly associated with continuation or discontinuation of CTX after 6 months of age or after breastfeeding cessation. Maternal self-reports indicated that only 52.5% (95%CI 47.5-57.5) understood the reason for CTX prophylaxis, 126 (47%) did not dose during weekends; 55 (21%) dosed their infants 3 times a day and 70 (26%) dosed their infants twice daily. A third of HIV-exposed children attending a primary health care facility in this South African setting did not receive CTX prophylaxis. Not commencing CTX prophylaxis was strongly associated with infants not breastfeeding and unnecessary continued exposure to CTX in this paediatric population was due to limited availability of early infant diagnosis. Attendance at immunization clinics can be seen as missed opportunities for early

  12. Factors Associated with Coverage of Cotrimoxazole Prophylaxis in HIV-Exposed Children in South Africa

    PubMed Central

    Moodley, Dhayendre; Reddy, Leanne; Mahungo, Wisani; Masha, Rebotile

    2013-01-01

    Background The World Health Organisation and the Joint United Nations Programme in 2006 reaffirmed the earlier recommendation of 2000 that all HIV-exposed infants in resource-poor countries should commence cotrimoxazole (CTX) prophylaxis at 6-weeks of life. CTX prophylaxis should be continued until the child is confirmed HIV-uninfected and there is no further exposure to breastmilk transmission. We determined CTX coverage and explored factors associated with CTX administration in HIV-exposed infants at a primary health clinic in South Africa. Methods In a cross-sectional study of HIV-exposed infants 6–18 months of age attending a child immunisation clinic, data from the current visit and previous visits related to CTX prophylaxis, feeding practice and infant HIV testing were extracted from the child's immunisation record. Further information related to the administration of CTX prophylaxis was obtained from an interview with the child's mother. Results One-third (33.0%) HIV-exposed infants had not initiated CTX at all and breastfed infants were more likely to have commenced CTX prophylaxis as compared to their non-breastfed counterparts (78.7% vs 63.4%) (p = 0.008). Availability of infant's HIV status was strongly associated with continuation or discontinuation of CTX after 6 months of age or after breastfeeding cessation. Maternal self-reports indicated that only 52.5% (95%CI 47.5–57.5) understood the reason for CTX prophylaxis, 126 (47%) did not dose during weekends; 55 (21%) dosed their infants 3 times a day and 70 (26%) dosed their infants twice daily. Conclusion A third of HIV-exposed children attending a primary health care facility in this South African setting did not receive CTX prophylaxis. Not commencing CTX prophylaxis was strongly associated with infants not breastfeeding and unnecessary continued exposure to CTX in this paediatric population was due to limited availability of early infant diagnosis. Attendance at immunization clinics can be

  13. Hematology: ATG and Newton's third law of motion.

    PubMed

    Brunstein, Claudio G

    2010-01-01

    Patients with hematological malignancies have a risk of developing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem-cell transplantation. The addition of ATG to prophylaxis regimens decreases the incidence of GVHD without compromising overall survival in these patients.

  14. Bacteria causing important diseases of citrus utilise distinct modes of pathogenesis to attack a common host.

    PubMed

    Vojnov, Adrián Alberto; do Amaral, Alexandre Morais; Dow, John Maxwell; Castagnaro, Atilio Pedro; Marano, Marìa Rosa

    2010-06-01

    In this review, we summarise the current knowledge on three pathogens that exhibit distinct tissue specificity and modes of pathogenesis in citrus plants. Xanthomonas axonopodis pv. citri causes canker disease and invades the host leaf mesophyll tissue through natural openings and can also survive as an epiphyte. Xylella fastidiosa and Candidatus Liberibacter are vectored by insects and proliferate in the vascular system of the host, either in the phloem (Candidatus Liberibacter) or xylem (X. fastidiosa) causing variegated chlorosis and huanglongbing diseases, respectively. Candidatus Liberibacter can be found within host cells and is thus unique as an intracellular phytopathogenic bacterium. Genome sequence comparisons have identified groups of species-specific genes that may be associated with the particular lifestyle, mode of transmission or symptoms produced by each phytopathogen. In addition, components that are conserved amongst bacteria may have diverse regulatory actions underpinning the different bacterial lifestyles; one example is the divergent role of the Rpf/DSF cell-cell signalling system in X. citri and X. fastidiosa. Biofilm plays a key role in epiphytic fitness and canker development in X. citri and in the symptoms produced by X. fastidiosa. Bacterial aggregation may be associated with vascular occlusion of the xylem vessels and symptomatology of variegated chlorosis.

  15. The potential of targeted antibody prophylaxis in SARS outbreak control: a mathematic analysis.

    PubMed

    Bogaards, Johannes Antonie; Putter, Hein; Jan Weverling, Gerrit; Ter Meulen, Jan; Goudsmit, Jaap

    2007-03-01

    Severe acute respiratory syndrome (SARS) coronavirus-like viruses continue to circulate in animal reservoirs. If new mutants of SARS coronavirus do initiate another epidemic, administration of prophylactic antibodies to risk groups may supplement the stringent isolation procedures that contained the first SARS outbreak. We developed a mathematical model to investigate the effects of hospital admission and targeted antibody prophylaxis on the reproduction number R, defined as the number of secondary cases generated by an index case, during different SARS outbreak scenarios. Assuming a basic reproduction number R(0)=3, admission of patients to hospital within 4.3 days of symptom onset is necessary to achieve outbreak control without the need to further reduce community-based transmission. Control may be enhanced by providing pre-exposure prophylaxis to contacts of hospitalized patients, and through contact tracing and provision of post-exposure prophylaxis. Antibody prophylaxis may also be employed to reduce R below one and thereby restrict outbreak size and duration. Patient isolation alone can be sufficient to control SARS outbreaks provided that the time from onset to admission is short. Antibody prophylaxis as supplemental measure generally allows for containment of higher R(0) values and restricts both the size and duration of an outbreak.

  16. Discontinuing Pneumocystis jirovecii Pneumonia Prophylaxis in HIV-Infected Patients With a CD4 Cell Count <200 cells/mm3.

    PubMed

    Sidhu, Vaninder K; Foisy, Michelle M; Hughes, Christine A

    2015-12-01

    To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3). We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation. All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included. Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV-infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART). Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART. © The Author(s) 2015.

  17. A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

    PubMed Central

    2011-01-01

    Background Postnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies. Methods We conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications. Results The basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall. Conclusions Currently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale

  18. Molecular basis of Trypanosoma cruzi and Leishmania interaction with their host(s): exploitation of immune and defense mechanisms by the parasite leading to persistence and chronicity, features reminiscent of immune system evasion strategies in cancer diseases.

    PubMed

    Ouaissi, Ali; Ouaissi, Mehdi

    2005-01-01

    A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.

  19. Costs and clinical outcomes of primary prophylaxis of variceal bleeding in patients with hepatic cirrhosis: a decision analytic model.

    PubMed

    Saab, Sammy; DeRosa, Vincent; Nieto, Jose; Durazo, Francisco; Han, Steven; Roth, Bennett

    2003-04-01

    Current guidelines recommend upper endoscopic screening for patients with hepatic cirrhosis and primary prophylaxis with a nonselective beta-blocker for those with large varices. However, only 25% of cirrhotics develop large varices. Thus, the aim of this study is to evaluate the most cost-effective approach for primary prophylaxis of variceal hemorrhage. Using a Markov model, we compared the costs and clinical outcomes of three strategies for primary prophylaxis of variceal bleeding. In the first strategy, patients were given a beta-blocker without undergoing upper endoscopy. In the second strategy, patients underwent upper endoscopic screening; those found to have large varices were treated with a beta-blocker. In the third strategy, no prophylaxis was used. Selected sensitivity analyses were performed to validate outcomes. Our results show screening prophylaxis was associated with a cost of $37,300 and 5.72 quality-adjusted life yr (QALYs). Universal prophylaxis was associated with a cost of $34,100 and 6.65 QALYs. The no prophylaxis strategy was associated with a cost of $36,600 and 4.84 QALYs. The incremental cost-effectiveness ratio was $800/QALY for the endoscopic strategy relative to the no prophylaxis strategy. Screening endoscopy was cost saving when the compliance, bleed risk without beta-blocker, and variceal bleed costs were increased, and when the discount rate, bleed risk on beta-blockers, and cost of upper endoscopy were decreased. In contrast, the universal prophylaxis strategy was persistently cost saving relative to the no prophylaxis strategy. In comparing the strategies, sensitivity analysis on the death rates from variceal hemorrhage did not alter outcomes. Our results provide economic and clinical support for primary prophylaxis of esophageal variceal bleeding in patients with hepatic cirrhosis. Universal prophylaxis with beta-blocker is preferred because it is consistently associated with the lowest costs and highest QALYs.

  20. Antibacterial prophylaxis with ciprofloxacin for patients with multiple myeloma and lymphoma undergoing autologous haematopoietic cell transplantation: a quasi-experimental single-centre before-after study.

    PubMed

    Yeshurun, M; Vaxman, I; Shargian, L; Yahav, D; Bishara, J; Pasvolsky, O; Wolach, O; Lahav, M; Gurion, R; Magen, H; Vidal, L; Herscovici, C; Peck, A; Moshe, M; Sela-Navon, M; Naparstek, E; Raanani, P; Rozovski, U

    2018-07-01

    We aimed to study whether ciprofloxacin prophylaxis reduces infectious complications in patients undergoing autologous haematopoietic cell transplantation (AHCT). This is a quasi-experimental, retrospective, before-after study. We compared the incidence of bacterial-related complications among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154) who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a single centre. Febrile neutropaenia, bacteraemia, and pneumonia were significantly more common among patients who underwent AHCT during the second study period and did not receive antibacterial prophylaxis compared with patients who underwent AHCT during the first study period and received antibacterial prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0-14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4-16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0-12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7, respectively. Patients with ciprofloxacin prophylaxis had higher rates of ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference 44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p < 0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02). According to our single-centre experience, patients with MM and lymphoma undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Group B streptococcal immunisation of pregnant women for the prevention of early and late onset Group B streptococcal infection of the neonate as well as adult disease.

    PubMed

    Kenchington, Anna L; Lamont, Ronald F

    2017-01-01

    Early onset neonatal Group B streptococcal disease is preventable. Intrapartum antibiotic prophylaxis has resulted in a significant reduction in neonatal mortality and morbidity. National guidelines for the selection of women eligible for intrapartum antibiotic prophylaxis, whether screening-based or risk-based, differ according to the local burden of disease. Despite the introduction of intrapartum antibiotic prophylaxis, there remains a significant burden of disease, which can be resolved by better adherence to guidelines, rapid identification of maternal colonization or in the future, vaccination. Areas covered: The introduction of a vaccine to women in the third trimester is likely to further reduce the burden of disease and provide benefits beyond the prevention of early neonatal disease, including meningitis and disability following late onset disease. Development of specific polyvalent vaccines continues, but testing has challenges and may require surrogate markers or molecular-based techniques to manipulate antigenicity and immunogenicity. Expert commentary: Group B streptococcal vaccination using conjugated polyvalent vaccines against the major disease causing serotypes of Group B streptococcus, either alone, or in combination with a policy of intrapartum antibiotic prophylaxis, may decrease the burden of Group B streptococcus beyond that achieved by current use of intrapartum antibiotic prophylaxis alone.

  2. Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases.

    PubMed

    Shigemori, Suguru; Shimosato, Takeshi

    2017-01-01

    Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are chronic inflammatory diseases characterized by dysregulated immune responses of the gastrointestinal tract. In recent years, the incidence of IBDs has increased in developed nations, but their prophylaxis/treatment is not yet established. Site-directed delivery of molecules showing anti-inflammatory properties using genetically modified (gm)-probiotics shows promise as a new strategy for the prevention and treatment of IBD. Advantages of gm-probiotics include (1) the ability to use bacteria as a delivery vehicle, enabling safe and long-term use by humans, (2) decreased risks of side effects, and (3) reduced costs. The intestinal delivery of anti-inflammatory proteins such as cytokines and enzymes using Lactococcus lactis has been shown to regulate host intestinal homeostasis depending on the delivered protein-specific machinery. Additionally, clinical experience using interleukin 10-secreting Lc. lactis has been shown to be safe and to facilitate biological containment in IBD therapy. On the other hand, some preclinical studies have demonstrated that gm-strains of immunobiotics (probiotic strains able to beneficially regulate the mucosal immunity) provide beneficial effects on intestinal inflammation as a result of the synergy between the immunoregulatory effects of the bacterium itself and the anti-inflammatory effects of the delivered recombinant proteins. In this review, we discuss the rapid progression in the development of strategies for the prophylaxis and treatment of IBD using gm-probiotics that exhibit immune regulation effects (gm-immunobiotics). In particular, we discuss the type of strains used as delivery agents.

  3. Glyburide - Novel Prophylaxis and Effective Treatment for Blast-Traumatic Brain Injury

    DTIC Science & Technology

    2013-10-01

    determine the safety of the SUR1 blocker , glyburide (glibenclamide), as it might be used as prophylaxis against blast-TBI. During the 4th year of...We completed evaluation of the prophylaxis treatment with SUR1 blocker , glyburide in the neurobehavioral outcome after blast-TBI (Obj. 1d, c...APP ( Beta -amyloid precursor protein) 64 qPCR Casp 3 (caspase 3) 28 Tissue hemoglobin detection SP1 (ischemic, hypoxic marker) 7 ED1

  4. Use of Provider-Level Dashboards and Pay-for-Performance in Venous Thromboembolism Prophylaxis*

    PubMed Central

    Michtalik, Henry J.; Carolan, Howard T.; Haut, Elliott R.; Lau, Brandyn D.; Streiff, Michael B.; Finkelstein, Joseph; Pronovost, Peter J.; Durkin, Nowella; Brotman, Daniel J.

    2014-01-01

    Background Despite safe and cost-effective venous thromboembolism (VTE) prevention measures, VTE prophylaxis rates are often suboptimal. Healthcare reform efforts emphasize transparency through programs to report performance, and payment incentives through programs to pay-for-performance. Objective To sequentially examine an individualized physician dashboard and pay-for-performance program to improve VTE prophylaxis rates amongst hospitalists. Design Retrospective analysis of 3144 inpatient admissions. After a baseline observation period, VTE prophylaxis compliance was compared during both interventions. Setting 1060-bed tertiary care medical center. Participants 38 part- and full-time academic hospitalists. Interventions A Web-based hospitalist dashboard provided VTE prophylaxis feedback. After 6 months of feedback only, a pay-for-performance program was incorporated, with graduated payouts for compliance rates of 80-100%. Measurements Prescription of American College of Chest Physicians guideline-compliant VTE prophylaxis and subsequent pay-for-performance payments. Results Monthly VTE prophylaxis compliance rates were 86% (95% CI: 85, 88), 90% (95% CI: 88, 93), and 94% (95% CI: 93, 96) during the baseline, dashboard, and combined dashboard/pay-for-performance periods, respectively. Compliance significantly improved with the use of the dashboard (p=0.01) and addition of the pay-for-performance program (p=0.01). The highest rate of improvement occurred with the dashboard (1.58%/month; p=0.01). Annual individual physician performance payments ranged from $53 to $1244 (mean $633; SD ±350). Conclusions Direct feedback using dashboards was associated with significantly improved compliance, with further improvement after incorporating an individual physician pay-for-performance program. Real-time dashboards and physician-level incentives may assist hospitals in achieving higher safety and quality benchmarks. PMID:25545690

  5. Use of provider-level dashboards and pay-for-performance in venous thromboembolism prophylaxis.

    PubMed

    Michtalik, Henry J; Carolan, Howard T; Haut, Elliott R; Lau, Brandyn D; Streiff, Michael B; Finkelstein, Joseph; Pronovost, Peter J; Durkin, Nowella; Brotman, Daniel J

    2015-03-01

    Despite safe and cost-effective venous thromboembolism (VTE) prevention measures, VTE prophylaxis rates are often suboptimal. Healthcare reform efforts emphasize transparency through programs to report performance and payment incentives through pay-for-performance programs. To sequentially examine an individualized physician dashboard and pay-for-performance program to improve VTE prophylaxis rates among hospitalists. Retrospective analysis of 3144 inpatient admissions. After a baseline observation period, VTE prophylaxis compliance was compared during both interventions. A 1060-bed tertiary care medical center. Thirty-eight part-time and full-time academic hospitalists. A Web-based hospitalist dashboard provided VTE prophylaxis feedback. After 6 months of feedback only, a pay-for-performance program was incorporated, with graduated payouts for compliance rates of 80% to 100%. Prescription of American College of Chest Physicians' guideline-compliant VTE prophylaxis and subsequent pay-for-performance payments. Monthly VTE prophylaxis compliance rates were 86% (95% confidence interval [CI]: 85-88), 90% (95% CI: 88-93), and 94% (95% CI: 93-96) during the baseline, dashboard, and combined dashboard/pay-for-performance periods, respectively. Compliance significantly improved with the use of the dashboard (P = 0.01) and addition of the pay-for-performance program (P = 0.01). The highest rate of improvement occurred with the dashboard (1.58%/month; P = 0.01). Annual individual physician performance payments ranged from $53 to $1244 (mean $633; standard deviation ±$350). Direct feedback using dashboards was associated with significantly improved compliance, with further improvement after incorporating an individual physician pay-for-performance program. Real-time dashboards and physician-level incentives may assist hospitals in achieving higher safety and quality benchmarks. © 2014 Society of Hospital Medicine.

  6. Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.

    PubMed Central

    Pirruccello, S. J.; Nakamine, H.; Beisel, K. W.; Kleveland, K. L.; Okano, M.; Taguchi, Y.; Davis, J. R.; Mahloch, M. L.; Purtilo, D. T.

    1992-01-01

    In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model. Images Figure 1 Figure 3 Figure 4 PMID:1580330

  7. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

    PubMed

    Jostins, Luke; Ripke, Stephan; Weersma, Rinse K; Duerr, Richard H; McGovern, Dermot P; Hui, Ken Y; Lee, James C; Schumm, L Philip; Sharma, Yashoda; Anderson, Carl A; Essers, Jonah; Mitrovic, Mitja; Ning, Kaida; Cleynen, Isabelle; Theatre, Emilie; Spain, Sarah L; Raychaudhuri, Soumya; Goyette, Philippe; Wei, Zhi; Abraham, Clara; Achkar, Jean-Paul; Ahmad, Tariq; Amininejad, Leila; Ananthakrishnan, Ashwin N; Andersen, Vibeke; Andrews, Jane M; Baidoo, Leonard; Balschun, Tobias; Bampton, Peter A; Bitton, Alain; Boucher, Gabrielle; Brand, Stephan; Büning, Carsten; Cohain, Ariella; Cichon, Sven; D'Amato, Mauro; De Jong, Dirk; Devaney, Kathy L; Dubinsky, Marla; Edwards, Cathryn; Ellinghaus, David; Ferguson, Lynnette R; Franchimont, Denis; Fransen, Karin; Gearry, Richard; Georges, Michel; Gieger, Christian; Glas, Jürgen; Haritunians, Talin; Hart, Ailsa; Hawkey, Chris; Hedl, Matija; Hu, Xinli; Karlsen, Tom H; Kupcinskas, Limas; Kugathasan, Subra; Latiano, Anna; Laukens, Debby; Lawrance, Ian C; Lees, Charlie W; Louis, Edouard; Mahy, Gillian; Mansfield, John; Morgan, Angharad R; Mowat, Craig; Newman, William; Palmieri, Orazio; Ponsioen, Cyriel Y; Potocnik, Uros; Prescott, Natalie J; Regueiro, Miguel; Rotter, Jerome I; Russell, Richard K; Sanderson, Jeremy D; Sans, Miquel; Satsangi, Jack; Schreiber, Stefan; Simms, Lisa A; Sventoraityte, Jurgita; Targan, Stephan R; Taylor, Kent D; Tremelling, Mark; Verspaget, Hein W; De Vos, Martine; Wijmenga, Cisca; Wilson, David C; Winkelmann, Juliane; Xavier, Ramnik J; Zeissig, Sebastian; Zhang, Bin; Zhang, Clarence K; Zhao, Hongyu; Silverberg, Mark S; Annese, Vito; Hakonarson, Hakon; Brant, Steven R; Radford-Smith, Graham; Mathew, Christopher G; Rioux, John D; Schadt, Eric E; Daly, Mark J; Franke, Andre; Parkes, Miles; Vermeire, Severine; Barrett, Jeffrey C; Cho, Judy H

    2012-11-01

    Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

  8. Host susceptibility to snake fungal disease is highly dispersed across phylogenetic and functional trait space

    PubMed Central

    Burbrink, Frank T.; Lorch, Jeffrey M.; Lips, Karen R.

    2017-01-01

    Emerging infectious diseases (EIDs) reduce host population sizes, cause extinction, disassemble communities, and have indirect negative effects on human well-being. Fungal EIDs have reduced population abundances in amphibians and bats across many species over large areas. The recent emergence of snake fungal disease (SFD) may have caused declines in some snake populations in the Eastern United States (EUS), which is home to a phylogenetically and ecologically diverse assembly of 98 taxa. SFD has been documented in only 23 naturally occuring species, although this is likely an underestimate of the number of susceptible taxa. Using several novel methods, including artificial neural networks, we combine phylogenetic and trait-based community estimates from all taxa in this region to show that SFD hosts are both phylogenetically and ecologically randomly dispersed. This might indicate that other species of snakes in the EUS could be currently infected or susceptible to SFD. Our models also indicate that information about key traits that enhance susceptiblity is lacking. Surveillance should consider that all snake species and habitats likely harbor this pathogen. PMID:29291245

  9. Host susceptibility to snake fungal disease is highly dispersed across phylogenetic and functional trait space.

    PubMed

    Burbrink, Frank T; Lorch, Jeffrey M; Lips, Karen R

    2017-12-01

    Emerging infectious diseases (EIDs) reduce host population sizes, cause extinction, disassemble communities, and have indirect negative effects on human well-being. Fungal EIDs have reduced population abundances in amphibians and bats across many species over large areas. The recent emergence of snake fungal disease (SFD) may have caused declines in some snake populations in the Eastern United States (EUS), which is home to a phylogenetically and ecologically diverse assembly of 98 taxa. SFD has been documented in only 23 naturally occuring species, although this is likely an underestimate of the number of susceptible taxa. Using several novel methods, including artificial neural networks, we combine phylogenetic and trait-based community estimates from all taxa in this region to show that SFD hosts are both phylogenetically and ecologically randomly dispersed. This might indicate that other species of snakes in the EUS could be currently infected or susceptible to SFD. Our models also indicate that information about key traits that enhance susceptiblity is lacking. Surveillance should consider that all snake species and habitats likely harbor this pathogen.

  10. Host susceptibility to snake fungal disease is highly dispersed across phylogenetic and functional trait space

    USGS Publications Warehouse

    Burbrink, Frank T.; Lorch, Jeffrey M.; Lips, Karen R.

    2017-01-01

    Emerging infectious diseases (EIDs) reduce host population sizes, cause extinction, disassemble communities, and have indirect negative effects on human well-being. Fungal EIDs have reduced population abundances in amphibians and bats across many species over large areas. The recent emergence of snake fungal disease (SFD) may have caused declines in some snake populations in the Eastern United States (EUS), which is home to a phylogenetically and ecologically diverse assembly of 98 taxa. SFD has been documented in only 23 naturally occuring species, although this is likely an underestimate of the number of susceptible taxa. Using several novel methods, including artificial neural networks, we combine phylogenetic and trait-based community estimates from all taxa in this region to show that SFD hosts are both phylogenetically and ecologically randomly dispersed. This might indicate that other species of snakes in the EUS could be currently infected or susceptible to SFD. Our models also indicate that information about key traits that enhance susceptiblity is lacking. Surveillance should consider that all snake species and habitats likely harbor this pathogen.

  11. HIV Pre-exposure Prophylaxis Program Implementation Using Intervention Mapping.

    PubMed

    Flash, Charlene A; Frost, Elizabeth L T; Giordano, Thomas P; Amico, K Rivet; Cully, Jeffrey A; Markham, Christine M

    2018-04-01

    HIV pre-exposure prophylaxis has been proven to be an effective tool in HIV prevention. However, numerous barriers still exist in pre-exposure prophylaxis implementation. The framework of Intervention Mapping was used from August 2016 to October 2017 to describe the process of adoption, implementation, and maintenance of an HIV prevention program from 2012 through 2017 in Houston, Texas, that is nested within a county health system HIV clinic. Using the tasks outlined in the Intervention Mapping framework, potential program implementers were identified, outcomes and performance objectives established, matrices of change objectives created, and methods and practical applications formed. Results include the formation of three matrices that document program outcomes, change agents involved in the process, and the determinants needed to facilitate program adoption, implementation, and maintenance. Key features that facilitated successful program adoption and implementation were obtaining leadership buy-in, leveraging existing resources, systematic evaluation of operations, ongoing education for both clinical and nonclinical staff, and attention to emergent issues during launch. The utilization of Intervention Mapping to delineate the program planning steps can provide a model for pre-exposure prophylaxis implementation in other settings. Copyright © 2018. Published by Elsevier Inc.

  12. [Graft-versus-host disease, a rare complication of lung transplantation].

    PubMed

    Morisse-Pradier, H; Nove-Josserand, R; Philit, F; Senechal, A; Berger, F; Callet-Bauchu, E; Traverse-Glehen, A; Maury, J-M; Grima, R; Tronc, F; Mornex, J-F

    2016-02-01

    Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Is the working capacity of Liberian industrial workers increased by regular malaria prophylaxis?

    PubMed

    Pehrson, P O; Björkman, A; Brohult, J; Jorfeldt, L; Lundbergh, P; Rombo, L; Willcox, M; Bengtsson, E

    1984-10-01

    In a study of the impact of malaria prophylaxis upon the physical working capacity of Liberian industrial workers, two groups of men, one with and the other without malaria prophylaxis, were compared over a period of one year. At the beginning and at the end of the study, the haemoglobin concentration, haematocrit, blood volume and physical performance--measured by bicycle ergometry and expressed as work load at heart rate 170--were compared. No significant differences were found, either within or between the two groups. Routinely distributed malaria prophylaxis thus seems to be of little importance with respect to working capacity in this type of community, where malaria is meso-endemic.

  14. Association of mixed hematopoietic chimerism with elevated circulating autoantibodies and chronic graft-versus-host disease occurrence

    PubMed Central

    Perruche, Sylvain; Marandin, Aliette; Kleinclauss, François M.; Angonin, Régis; Fresnay, Stéphanie; Baron, Marie Hélène; Tiberghien, Pierre; Saas, Philippe

    2006-01-01

    Background Use of a reduced intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a co-existence of both host and donor hematopoietic cells may influence post-transplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced intensity conditioning transplantation (RICT), auto-antibody production and chronic GVHD (cGVHD)-related pathology. Methods Chimerism state, circulating anti-cardiolipin and anti-double stranded DNA auto-antibody (Ab) titers as well as occurrence of cGVHD-like lesions were investigated in a murine RICT model. Results We observed a novel association between mixed chimerism state, high levels of pathogenic IgG auto-Abs and subsequent development of cGVHD-like lesions. Furthermore, we found that the persistence of host B cells, but not dendritic cell origin or subset, was a factor associated with the appearance of cGVHD-like lesions. The implication of host B cells was confirmed by a host origin of auto-Abs. Conclusions Recipient B cell persistence may therefore contribute to the frequency and/or severity of cGVHD after RICT. PMID:16495806

  15. Constipation prophylaxis reduces length of stay in elderly hospitalized heart failure patients with home laxative use.

    PubMed

    Staller, Kyle; Khalili, Hamed; Kuo, Braden

    2015-11-01

    Elderly, hospitalized patients suffer disproportionately from constipation; however, little data suggest that constipation prophylaxis reduces length of stay (LOS). We performed a retrospective analysis of elderly patients admitted to our hospital with congestive heart failure (CHF) to determine the effects of constipation prophylaxis on LOS. Patients ≥ 65 years old admitted with the diagnosis of CHF in 2012 were evaluated for home and hospital laxative use on admission. Our primary outcome was LOS. We used linear regression modeling to independently evaluate the impact of constipation prophylaxis on LOS. Among 618 patients who were eligible for our study, 201 (32.5%) were using laxatives at home, whereas 254 (41.1%) were started on a prophylactic laxative on admission. There was no significant difference in LOS between patients receiving prophylaxis versus those who did not (P = 0.32). Patients with home laxative use had a 1 day longer LOS compared to those without laxative use (6 vs 5, P = 0.03). Among patients with home laxative use, there were 2 days longer LOS in those who were not given constipation prophylaxis on admission (8 vs 6, P = 0.002). After multivariate adjustment, failure to use constipation prophylaxis in patients with home laxative use was the only independent predictor of increased LOS (P = 0.03). Among elderly patients admitted for CHF exacerbations, failure to use constipation prophylaxis in patients with home laxative use is associated with a significantly longer LOS. Our data suggest that routine use of bowel prophylaxis for elderly CHF patients with preexisting constipation may reduce LOS. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  16. Gastrointestinal Prophylaxis in Sports Medicine.

    PubMed

    Patel, Akash R; Oheb, Daniel; Zaslow, Tracy L

    Because sports participation at all levels often requires international travel, coaches, athletic trainers, and team physicians must effectively protect athletes from gastrointestinal infections. Traveler's diarrhea is the most common travel-related illness and can significantly interfere with training and performance. A review of relevant publications was completed using PubMed and Google Scholar. Clinical review. Level 5 Results: Enterotoxigenic and enteroaggregative Escherichia coli are the most common bacterial causes of traveler's diarrhea. Traveler's diarrhea generally occurs within 4 days of arrival, and symptoms tend to resolve within 5 days of onset. There are several prophylactic agents that physicians can recommend to athletes, including antibiotics, bismuth subsalicylate, and probiotics; however, each has its own unique limitations. Decision-making should be based on the athlete's destination, length of stay, and intent of travel. Prophylaxis with antibiotics is highly effective; however, physicians should be hesitant to prescribe medication due to the side effects and risks for creating antibiotic-resistant bacterial strains. Antibiotics may be indicated for high-risk groups, such as those with a baseline disease or travelers who have little flexible time. Since most cases of traveler's diarrhea are caused by food and/or water contamination, all athletes should be educated on the appropriate food and water consumption safety measures prior to travel.

  17. Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis)

    PubMed Central

    Mian, Shahzad I.; De la Parra-Colín, Paola; De Melo-Franco, Rafael; Johnson, Christopher; Barrientos-Gutierrez, Tonatiuh

    2015-01-01

    Purpose: To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease. Methods: A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit. Results: Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis. Conclusions: Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology. PMID:27507907

  18. Long-term prophylaxis in hereditary angio-oedema: a systematic review

    PubMed Central

    Casazza, Giovanni; Bossi, Ilaria; Duca, Piergiorgio; Cicardi, Marco

    2012-01-01

    Objective To systematically review the evidence regarding long-term prophylaxis in the prevention or reduction of attacks in hereditary angio-oedema (HAE). Design Systematic review and meta-analysis. Data sources Electronic databases were searched up to April 2011. Two reviewers selected the studies and extracted the study data, patient characteristics and outcomes of interest. Eligibility criteria for selected studies Controlled trials for HAE prophylaxis. Results 7 studies were included, for a total of 73 patients and 587 HAE attacks. Due to the paucity of studies, a meta-analysis was not possible. Since two studies did not report the number of HAE attacks, five studies (52 patients) were finally included in the summary analysis. Four classes of drugs with at least one controlled trial have been proposed for HAE prophylaxis. All those drugs, except heparin, were found to be more effective than placebo. In the absence of direct comparisons, the relative efficacies of these drugs were determined by calculating a RR of attacks (drug vs placebo). The results were as follows: danazol (RR=0.023, 95% CI 0.003 to 0.162), methyltestosterone (RR=0.054, 95% CI 0.013 to 0.163), ɛ-aminocaproic acid (RR=0.095, 95% CI 0.025 to 0.356), tranexamic acid (RR=0.308, 95% CI 0.195 to 0.479) and C1-INH 0.491 (95% CI 0.395 to 0.607). Conclusions Few trials have evaluated the benefits of HAE prophylaxis, and all drugs but heparin seem to be effective in this setting. Since there are no direct comparisons of HAE drugs, it was not possible to draw definitive conclusions on the most effective one. Thus, to accumulate evidence for HAE prophylaxis, further studies are needed that consider the dose–efficacy relationship and include a head-to-head comparison between drugs, with the active group, rather than placebo, as the control. PMID:22786946

  19. Perioperative Prophylaxis for Total Artificial Heart Transplantation.

    PubMed

    Chambers, H E; Pelish, P; Qiu, F; Florescu, D F

    2017-11-01

    Practice variation regarding perioperative antimicrobial prophylaxis in total artificial heart transplantations (TAH-t) across institutions is unknown. The aim of our survey was to assess the current practices for prevention of infection in TAH-t recipients among different programs. An electronic survey was sent to programs that implant Syncardia TAH (Syncardia Systems, Tuscon, Ariz, USA). Proportions were analyzed for categorical variables; means and SDs were analyzed for continuous variables. The majority of centers (80.8%) had a formal surgical infection prophylaxis protocol. For non-penicillin-allergic patients, five (20.1%) institutions reported using a 4-drug regimen, seven (29.2%) used a 3-drug regimen, five (20.1%) used a 2-drug regimen, and seven (29.2%) used a cephalosporin alone. Similar data was seen in the penicillin-allergic patients. Infections were reported to occur postoperatively in 52.2% centers. During the first month after TAH-t, bacteremia represented 27.3%, driveline infections 27.2%, pulmonary infections 9%, and mediastinal infections 18.2%. The most common organisms seen within the first month were Candida spp., Escherichia coli, and Pseudomonas aeruginosa (21.4%). In 65% of centers, the mean rate of death post-TAH-t due to infection was 14.5% (SD, 22.3%). The mean rate of patients surviving until orthotopic heart transplantation was 58.6% (SD, 27.7%). Preventing infections post-TAH-t is key to decreasing morbidity and mortality. All institutions administered perioperative prophylaxis for TAH-t with significant variation among the centers. The majority of the centers have a formal perioperative prophylactic protocol. Copyright © 2017. Published by Elsevier Inc.

  20. Host Sexual Dimorphism and Parasite Adaptation

    PubMed Central

    Duneau, David; Ebert, Dieter

    2012-01-01

    In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host–parasite interactions, and impact epidemiological and medical science. PMID:22389630