Garcia H.H.,Instituto Nacional Of Ciencias Neurologicas |
Garcia H.H.,Cayetano Heredia Peruvian University |
Gonzales I.,Instituto Nacional Of Ciencias Neurologicas |
Lescano A.G.,Cayetano Heredia Peruvian University |
And 5 more authors.
Epilepsia | Year: 2014
Objective: Neurocysticercosis (NCC) is a major cause of seizures and epilepsy in endemic countries. Antiparasitic treatment of brain cysts leads to seizures due to the host's inflammatory reaction, requiring concomitant steroids. We hypothesized that increased steroid dosing will reduce treatment-associated seizures.Methods: Open-label randomized trial comparing 6 mg/day dexamethasone for 10 days (conventional) with 8 mg/day for 28 days followed by a 2-week taper (enhanced) in patients with NCC receiving albendazole. Follow-up included active seizure surveillance and brain imaging. Study outcomes were seizure days and patients with seizures, both measured in days 11-42. Additional analyses compared days 1-10, 11-21, 22-32, 33-42, 43-60, and 61-180.Results: Thirty-two individuals were randomized into each study arm; two did not complete follow-up. From days 11 to 42, 59 partial and 6 generalized seizure days occurred in 20 individuals, nonsignificantly fewer in the enhanced arm (12 vs. 49, p = 0.114). The numbers of patients with seizures in this period showed similar nonsignificant differences. In the enhanced steroid arm there were significantly fewer days and individuals with seizures during antiparasitic treatment (days 1-10: 4 vs. 17, p = 0.004, and 1 vs. 10, p = 0.003, number needed to treat [NNT] 4.6, relative risk [RR] 0.1013, 95% confidence interval [CI] 0.01-0.74) and early after dexamethasone cessation (days 11-21: 6 vs. 27, p = 0.014, and 4 vs. 12, p = 0.021, NNT 4.0, RR 0.33, 95% CI 0.12-0.92) but not after day 21. There were no significant differences in antiparasitic efficacy or relevant adverse events.Significance: Increased dexamethasone dosing results in fewer seizures for the first 21 days during and early after antiparasitic treatment for viable parenchymal NCC but not during the first 11-42 days, which was the primary predetermined time of analysis. © 2014 International League Against Epilepsy.
Andrade B.B.,Laboratory of Parasitic Diseases |
Hullsiek K.H.,University of Minnesota |
Boulware D.R.,University of Minnesota |
Rupert A.,SAIC |
And 13 more authors.
Journal of Infectious Diseases | Year: 2013
Background. Hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection with human immunodeficiency virus (HIV) has a greater risk of mortality than either HCV or HBV infection alone and is frequently associated with hepatitis flares after antiretroviral therapy (ART) initiation.Methods. We performed a retrospective cohort study of 287 HIV-positive persons coinfected with HBV and/or HCV (70 had HBV coinfection only, 207 had HCV coninfection only, and 10 had HBV and HCV coinfections) who had pre-ART plasma samples evaluated for biomarkers associated with death (within 4 years) and/or hepatitis flare (within 4 months) after ART initiation. A predictive biomarker risk score was calculated.Results. Forty-eight deaths and 50 hepatitis flares occurred. Nonsurvivors were older, had more prior AIDS-defining events, and had higher pre-ART triglycerides and aspartate transaminase levels. Detectable hyaluronic acid and higher d-dimer, interleukin 6, interleukin 8, and soluble CD14 levels were associated with death in univariate models and with a composite biomarker risk score. The risk of hepatitis flares was higher with HBV coinfection only (24.3%) and with HBV and HCV coinfection (50%) than with HCV coinfection only (13.5%). Higher levels of alanine transaminase and interleukin 10 were also associated with hepatitis flares.Conclusions. Among HIV-positive patients coinfected with HBV and/or HCV who are initiating ART, biomarkers of inflammation and coagulation are associated with an increased risk of death, whereas HBV coinfection and higher pre-ART interleukin 10 levels are associated with hepatitis flares. © 2013 The Author.
Cooper A.M.,Trudeau Institute |
Mayer-Barber K.D.,Laboratory of Parasitic Diseases |
Sher A.,Laboratory of Parasitic Diseases
Mucosal Immunology | Year: 2011
Cells of the innate immune system produce cytokines and lipid mediators that strongly influence the outcome of mycobacterial infection. In the case of Mycobacterium tuberculosis, the lung is a critical site for this interaction. Here, we review current information on the role of the major innate cytokine pathways both in controlling initial infection as well as in promoting and maintaining adaptive T-cell responses that mediate host resistance or immunopathology. Understanding this important feature of the host-pathogen interaction can provide major insights into the mechanisms of virulence and can lead to new approaches for immunological intervention in tuberculosis and other mycobacterial diseases. © 2011 Society for Mucosal Immunology.
Grainger J.R.,Laboratory of Parasitic Diseases |
Wohlfert E.A.,Laboratory of Parasitic Diseases |
Fuss I.J.,Laboratory of Host Defenses |
Bouladoux N.,Laboratory of Parasitic Diseases |
And 7 more authors.
Nature Medicine | Year: 2013
The commensal flora can promote both immunity to pathogens and mucosal inflammation. How commensal-driven inflammation is regulated in the context of infection remains poorly understood. Here, we show that during acute mucosal infection of mice with Toxoplasma gondii, inflammatory monocytes acquire a tissue-specific regulatory phenotype associated with production of the lipid mediator prostaglandin E2 (PGE2). Notably, in response to commensals, inflammatory monocytes can directly inhibit neutrophil activation in a PGE2-dependent manner. Further, in the absence of inflammatory monocytes, mice develop severe neutrophil-mediated pathology in response to pathogen challenge that can be controlled by PGE2 analog treatment. Complementing these findings, inhibition of PGE2 led to enhanced neutrophil activation and host mortality after infection. These data demonstrate a previously unappreciated dual action of inflammatory monocytes in controlling pathogen expansion while limiting commensal-mediated damage to the gut. Collectively, our results place inflammatory monocyte-derived PGE2 at the center of a commensal-driven regulatory loop required to control host-commensal dialog during pathogen-induced inflammation. © 2013 Nature America, Inc. All rights reserved.
Wynn T.A.,Laboratory of Parasitic Diseases |
Ramalingam T.R.,Laboratory of Parasitic Diseases
Nature Medicine | Year: 2012
Fibrosis is a pathological feature of most chronic inflammatory diseases. Fibrosis, or scarring, is defined by the accumulation of excess extracellular matrix components. If highly progressive, the fibrotic process eventually leads to organ malfunction and death. Fibrosis affects nearly every tissue in the body. Here we discuss how key components of the innate and adaptive immune response contribute to the pathogenesis of fibrosis. We also describe how cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. Finally, we highlight some of the key mechanisms and pathways of fibrosis that are being targeted as potential therapies for a variety of important human diseases. © 2012 Nature America, Inc. All rights reserved.