Interferon-gamma release assays (IGRAs) in high-endemic settings: could they play a role in optimizing global TB diagnostics? Evaluating the possibilities of using IGRAs to diagnose active TB in a rural African setting

SummaryThe number of patients suffering from tuberculosis (TB) globally is increasing. Due to the HIV epidemic, most patients suffering from TB reside in sub-Saharan Africa. In order to improve TB diagnostics, new tests – interferon-gamma release assays (IGRAs) – have been developed over the last decade. In this paper we evaluate the possible use of these tests in diagnosing or excluding active TB in high HIV-burden, resource-limited settings. The inability to differentiate between active and latent TB, limited data on IGRA performance in HIV-infected patients, observed false-negative results, high costs, and logistic problems limit the potential benefit of IGRAs. We also present two theoretical study designs in order to further assess IGRAs. Setting up a study on this subject is complicated by the frequent unavailability of mycobacterial cultures, the difficulty in acquiring prospective data, and the impossibility of denying treatment to a patient suspected of having active TB. We feel that current evidence does not support the implementing of IGRAs in clinical practice in settings with high endemic latent TB infection (LTBI) and high HIV prevalence. As these settings are the ones that suffer the most from the TB epidemic, we believe that the role of IGRAs in global TB control is questionable

Origin Of The Far Off-Axis GRB171205A

We show that observed properties of the low luminosity GRB171205A and its afterglow, like those of most other low-luminosity (LL) gamma ray bursts (GRBs) associate with a supernova (SN), indicate that it is an ordinary SN-GRB, which was produced by inverse Compton scattering of glory light by a highly relativistic narrowly collimated jet ejected in a supernova explosion and viewed from a far off-axis angle. As such, VLA/VLBI follow-up radio observations of a superluminal displacement of its bright radio afterglow from its parent supernova, will be able to test clearly whether it is an ordinary SN-GRB viewed from far off-axis or it belongs to a distinct class of GRBs, which are different from ordinary GRBs, and cannot be explained by standard fireball models of GRBs as ordinary GRBsComment: 5 pages, 6 figures, updated data in Fig. 3, Corrected GRB angular distance used in Fig.

Persistence of frequently transmitted drug-resistant HIV-1 variants can be explained by high viral replication capacity

Background: In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. Results: We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. D

Asymptomatic bacteriuria may be considered a complication in women with diabetes

WSTĘP. Celem pracy jest ocena częstości występowania oraz czynników ryzyka bezobjawowej bakteriurii (ASB, asymptomatic bacteriuria) u kobiet bez cukrzycy i chorych na cukrzycę. MATERIAŁ I METODY. Do badania włączono 636 kobiet chorych na cukrzycę (typu 1 i 2) w wieku 18&#8211;75 lat, które w tym czasie nie były w ciąży i nie występowały u nich zaburzenia układu moczowego, oraz 153 kobiety bez cukrzycy, które zgłosiły się do okulisty lub do lekarza innej specjalności w celu leczenia urazów (jako grupa kontrolna). Bezobjawową bakteriurę zdefiniowano jako obecność co najmniej 105 bakterii na ml jednego lub dwóch rodzajów tworzących kolonie, wyhodowanych z czystego, środkowego strumienia moczu osoby bez objawów zakażenia dróg moczowych (UTI, urinary tract infection). WYNIKI. Bezobjawowa bakteriuria występowała u 26% kobiet chorych na cukrzycę i u 6% kobiet bez cukrzycy (p < 0,001). Częstość ASB u kobiet chorych na cukrzycę typu 1 wyniosła 21%. Czynniki ryzyka ASB w cukrzycy typu 1 to: dłuższy czas trwania choroby, neuropatia obwodowa i makroalbuminuria. U kobiet chorych na cukrzycę typu 2 ASB występowała w 29% przypadków. Czynniki ryzyka ASB w cukrzycy typu 2 to: wiek, makroalbuminuria, niższy wskaźnik BMI oraz przebyte w poprzednim roku zakażenie dróg moczowych. Nie stwierdzono związku między aktualnym poziomem HbA1c i obecnością ASB. WNIOSKI. Częstość ASB jest większa u kobiet chorych na cukrzycę niż bez cukrzycy i schorzenie to można uznać za jedno z powikłań cukrzycy u kobiet.OBJECTIVE. To study the prevalence of and risk factors for asymptomatic bacteriuria (ASB) in women with and without diabetes. RESEARCH DESIGN AND METHODS. A total of 636 nonpregnant women with diabetes (type 1 and type 2) who were 18&#150;75 years of age and had no abnormalities of the urinary tract, and 153 women without diabetes who were visiting the eye and trauma outpatient clinic (control subjects) were included. We defined ASB as the presence of at least 105 colony-forming units/ml of 1 or 2 bacterial species in a culture of clean-voided midstream urine from an individual without symptoms of a urinary tract infection (UTI). RESULTS. The prevalence of ASB was 26% in the diabetic women and 6% in the control subjects (P < 0.001). The prevalence of ASB in women with type 1 diabetes was 21%. Risk factors for ASB in type 1 diabetic women included a longer duration of diabetes, peripheral neuropathy, and macroalbuminuria. The prevalence of ASB was 29% in women with type 2 diabetes. Risk factors for ASB in type 2 diabetic women included age, macroalbuminuria, a lower BMI, and a UTI during the previous year. No association was evident between current HbA1c level and the presence of ASB. CONCLUSIONS. The prevalence of ASB is increased in women with diabetes and might be added to the list of diabetic complications in these women

Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy

Background: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4+ T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned. Methods: Study within the Dutch ATHENA HIV observational cohort. HIV-1 infected late presenters initiating cART after March 2009 were included if they had <200 CD4+ T-cells per μL and were diagnosed with an opportunistic infection. IRIS was defined either according to the criteria by French et al. (IRISFRENCH) or by a clinical IRIS diagnosis of the physician (IRISCLINICAL). The primary outcomes were the association between INI and the occurrence of IRISFRENCH and IRISFRENCH+CLINICAL in multivariable logistic regression. Findings: 672 patients with a median CD4+ T-cell count of 35 cells per μL were included. Treatment with INI was independently associated with IRISFRENCH as well as IRISFRENCH+CLINICAL (OR 2·43, 95%CI:1·45–4·07, and OR 2·17, 95%CI:1·45–3·25). When investigating INI separately, raltegravir (RAL) remained significantly associated with IRISFRENCH (OR 4·04 (95%CI:1·99-8·19) as well as IRISFRENCH+CLINICAL (OR 3·07, 95%CI:1·66-5·69), while dolutegravir (DTG) became associated with IRISFRENCH+CLINICAL after it replaced RAL as preferred INI in the cohort after 2015 (OR 4·08, 95%CI:0·99-16·82, p=0·052). Too few patients used elvitegravir to draw meaningful conclusions. Steroid initiation for IRIS was more likely in those who initiated INI versus in those who did not, but no increased hospital (re)admission or mortality rates were observed. Interpretation: In HIV late presenters from a resource rich setting, INI based treatment initiation increased the risk of IRIS. This was observed for RAL and DTG when being initiated as preferential INI in the presence of specific AIDS-conditions, indicative of channeling bias. Although we controlled for all relevant measured confounders, we cannot exclude that the observed association is partially explained by residual confounding. INI use was not associated with mortality nor hospitalization. Therefore, our observation is no reason to avoid INI in late presenters. Funding: Th