Vancomycin Hypersensitivity Diagnosed by Lymphocyte Blast Transformation

A 15-year-old male admitted for Pott's puffy tumor developed recurrent episodes of fever, diffuse morbilliform rash, eosinophilia, and tubulointerstitial nephritis while on multiple antibiotics. Lymphocyte blast transformation (LBT), a method of detecting cellular immune response by measuring levels of interferon-γ (IFN-γ), was used to diagnose vancomycin hypersensitivity and guide antibiotic selection

The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity

The TAM receptors Tyro3, Axl, and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands, Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer leaflet of their membranes, enabling TAM receptor activation and down-regulation of antiviral responses. Accordingly, we hypothesized that a deficiency of TAM receptors would enhance antiviral responses and protect against viral infection. Unexpectedly, mice lacking Mertk and/or Axl but not Tyro3 exhibited greater vulnerability to infection with neuroinvasive West Nile and La Crosse viruses. This phenotype was associated with increased blood-brain barrier permeability, which enhanced virus entry into and infection of the brain. Activation of Mertk synergized with IFN-β to tighten cell junctions and prevent virus transit across brain microvascular endothelial cells. Because TAM receptors restrict pathogenesis of neuroinvasive viruses, these findings have implications for TAM antagonists that are currently in clinical development

Characteristics of HIV-1 Discordant Couples Enrolled in a Trial of HSV-2 Suppression to Reduce HIV-1 Transmission: The Partners Study

Background: The Partners HSV-2/HIV-1 Transmission Study (Partners Study) is a phase III, placebo-controlled trial of daily acyclovir for genital herpes (HSV-2) suppression among HIV-1/HSV-2 co-infected persons to reduce HIV-1 transmission to their HIV-1 susceptible partners, which requires recruitment of HIV-1 serodiscordant heterosexual couples. We describe the baseline characteristics of this cohort. Methods: HIV-1 serodiscordant heterosexual couples, in which the HIV-1 infected partner was HSV-2 seropositive, had a CD4 count ≥250 cells/mcL and was not on antiretroviral therapy, were enrolled at 14 sites in East and Southern Africa. Demographic, behavioral, clinical and laboratory characteristics were assessed. Results: Of the 3408 HIV-1 serodiscordant couples enrolled, 67% of the HIV-1 infected partners were women. Couples had cohabitated for a median of 5 years (range 2–9) with 28% reporting unprotected sex in the month prior to enrollment. Among HIV-1 susceptible participants, 86% of women and 59% of men were HSV-2 seropositive. Other laboratory-diagnosed sexually transmitted infections were uncommon (500 relative to <350, respectively, p<0.001). Conclusions: The Partners Study successfully enrolled a cohort of 3408 heterosexual HIV-1 serodiscordant couples in Africa at high risk for HIV-1 transmission. Follow-up of this cohort will evaluate the efficacy of acyclovir for HSV-2 suppression in preventing HIV-1 transmission and provide insights into biological and behavioral factors determining heterosexual HIV-1 transmission. Trial Registration ClinicalTrials.gov NCT0019451

Measuring the Neutrino Cross Section Using 8 years of Upgoing Muon Neutrinos Observed with IceCube

The IceCube Neutrino Observatory detects neutrinos at energies orders of magnitude higher than those available to current accelerators. Above 40 TeV, neutrinos traveling through the Earth will be absorbed as they interact via charged current interactions with nuclei, creating a deficit of Earth-crossing neutrinos detected at IceCube. The previous published results showed the cross section to be consistent with Standard Model predictions for 1 year of IceCube data. We present a new analysis that uses 8 years of IceCube data to fit the ν$_{μ}$ absorption in the Earth, with statistics an order of magnitude better than previous analyses, and with an improved treatment of systematic uncertainties. It will measure the cross section in three energy bins that span the range 1 TeV to 100 PeV. We will present Monte Carlo studies that demonstrate its sensitivity