mGem: Sepsis and antimicrobial resistance in the context of advanced HIV disease

Sepsis triggered by bloodstream infections (BSI) is a significant driver of HIV-related mortality, particularly among in-patients with advanced HIV disease (AHD). Currently, the incidence, etiology, and outcomes of BSI in this population are poorly defined. We review the existing evidence, which shows an increased risk of BSI, particularly with antimicrobial-resistant (AMR) organisms, and higher BSI-associated mortality in patients with AHD. Causative bacterial and fungal pathogens are often unknown, but when identified, limited data show etiology has shifted probably owing to increasing coverage of antiretroviral treatment, antimicrobial prophylaxis, and rising global AMR trends. Further research is crucial to design and refine interventions before, during, and after hospital admission to reduce sepsis-related mortality in patients with AHD

CASE REPORT: Disseminated fatal Talaromyces (Penicillium) marneffei infection in a returning HIV-infected traveller

We report a case of disseminated fatal Talaromyces (Penicillium) marneffei infection in an HIV-infected, antiretroviral treatmentexperienced South African woman who had travelled to mainland China. The 37-year-old woman was admitted to a private hospital in fulminant septic shock and died within 12 h of admission. Intracellular yeast-like bodies were observed on the peripheral blood smear. A serum cryptococcal antigen test was negative. Blood cultures flagged positive after 2 days; on direct microscopy, yeast-like bodies were observed and a thermally dimorphic fungus, confirmed as T. marneffei, was cultured after 5 days. The clinical features of HIV-associated disseminated penicilliosis overlap with those of tuberculosis and endemic deep fungal infections. In the southern African context, where systemic opportunistic fungal infections such as cryptococcosis are more common among HIV-infected patients with a CD4+ count of <100 cells/µL, this infection is not likely to be considered in the differential diagnosis unless a travel history is obtained

A Case of Emmonsiosis in an HIV-Infected Child

Opportunistic fungal infections can cause significant morbidity and mortality in immunocompromised patients. We describe a paediatric case of an unusual disseminated fungal infection. A three-year-old HIV-infected child with severe immunosuppression (CD4+ T-cell count 12 × 106/L) was admitted to hospital with pneumonia, gastroenteritis and herpes gingivostomatitis. Despite antibacterial and antiviral therapy, he experienced high fevers and developed an erythematous maculopapular rash and abdominal tenderness. The child’s condition progressively worsened during the admission. A thermally dimorphic fungus was cultured from bone marrow and identified as an Emmonsia species on DNA sequencing. The patient made a good recovery on amphotericin B deoxycholate and antiretroviral therapy. Itraconazole was continued for a minimum of 12 months, allowing for immune reconstitution to occur. This case is the first documented description of disseminated disease caused by a novel Emmonsia species in an HIV-infected child in South Africa

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Prior Pulmonary Tuberculosis Is a Risk Factor for Asymptomatic Cryptococcal Antigenemia in a Cohort of Adults With Advanced Human Immunodeficiency Virus Disease.

The greater mortality risk among people with advanced human immunodeficiency virus disease and cryptococcal antigenemia, despite treatment, indicates an increased susceptibility to other infections. We found that prior tuberculosis was an independent risk factor for cryptococcal antigenemia (adjusted odds ratio, 2.72; 95% confidence interval, 1.13-6.52; P = .03) among patients with CD4 counts <100 cells/µL

Microevolution of serial clinical isolates of Cryptococcus neoformans var. grubii and C. gattii

This is the final version. Available from the publisher via the DOI in this record.The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in subSaharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification of ERG11 at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution of Cryptococcus species under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis.Wellcome TrustNational Institute of Allergy and Infectious Disease

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

Measurement of the inelastic proton-proton cross section at √s=13 TeV with the ATLAS detector at the LHC

This Letter presents a measurement of the inelastic proton-proton cross section using 60  μb −1 of pp collisions at a center-of-mass energy √s of 13 TeV with the ATLAS detector at the LHC. Inelastic interactions are selected using rings of plastic scintillators in the forward region (2.0710 −6 , where M X is the larger invariant mass of the two hadronic systems separated by the largest rapidity gap in the event. In this ξ range the scintillators are highly efficient. For diffractive events this corresponds to cases where at least one proton dissociates to a system with M X >13  GeV . The measured cross section is compared with a range of theoretical predictions. When extrapolated to the full phase space, a cross section of 78.1±2.9  mb is measured, consistent with the inelastic cross section increasing with center-of-mass energy

Search for supersymmetry at √s = 13 TeV in final states with jets and two same-sign leptons or three leptons with the ATLAS detector

A search for strongly produced supersymmetric particles is conducted using signatures involving multiple energetic jets and either two isolated leptons (e or μμ ) with the same electric charge or at least three isolated leptons. The search also utilises b-tagged jets, missing transverse momentum and other observables to extend its sensitivity. The analysis uses a data sample of proton–proton collisions at s√=13s=13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015 corresponding to a total integrated luminosity of 3.2 fb −1−1. No significant excess over the Standard Model expectation is observed. The results are interpreted in several simplified supersymmetric models and extend the exclusion limits from previous searches. In the context of exclusive production and simplified decay modes, gluino masses are excluded at 95%95% confidence level up to 1.1–1.3 TeV for light neutralinos (depending on the decay channel), and bottom squark masses are also excluded up to 540 GeV. In the former scenarios, neutralino masses are also excluded up to 550–850 GeV for gluino masses around 1 TeV