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

Long-Term Outcome of an HIV-Treatment Programme in Rural Africa: Viral Suppression despite Early Mortality

Objective. To define the long-term (2–4 years) clinical and virological outcome of an antiretroviral treatment (ART) programme in rural South Africa. Methods. We performed a retrospective observational cohort study, including 735 patients who initiated ART. Biannual monitoring, including HIV-RNA testing, was performed. Primary endpoint was patient retention; virological suppression (HIV-RNA < 50 copies/mL) and failure (HIV-RNA > 1000 copies/mL) were secondary endpoints. Moreover, possible predictors of treatment failure were analyzed. Results. 63% of patients (466/735) have a fully suppressed HIV-RNA, a median of three years after treatment initiation. Early mortality was high: 14% died within 3 months after treatment start. 16% of patients experienced virological failure, but only 4% was switched to second-line ART. Male gender and a low performance score were associated with treatment failure; immunological failure was a poor predictor of virological failure. Conclusions. An “all or nothing” phenomenon was observed in this rural South African ART programme: high early attrition, but good virological control in those remaining in care. Continued efforts are needed to enrol patients earlier. Furthermore, the observed viro-immunological dissociation emphasises the need to make HIV-RNA testing more widely available

Dual Antiretroviral Therapy—All Quiet Beneath the Surface?

Infection with the human immunodeficiency virus (HIV) is characterized by progressive depletion of CD4+ lymphocytes cells as a result of chronic immune activation. Next to the decreases in the number of CD4+ cells which leads to opportunistic infections, HIV-related immune activation is associated with several prevalent comorbidities in the HIV-positive population such as cardiovascular and bone disease. Traditionally, combination antiretroviral therapy (cART) consists of three drugs with activity against HIV and is highly effective in diminishing the degree of immune activation. Over the years, questions were raised whether virological suppression could also be achieved with fewer antiretroviral drugs, i.e., dual- or even monotherapy. This is an intriguing question considering the fact that antiretroviral drugs should be used lifelong and their use could also induce cardiovascular and bone disease. Therefore, the equilibrium between drug-induced toxicity and immune activation related comorbidity is delicate. Recently, two large clinical trials evaluating two-drug cART showed non-inferiority with respect to virological outcomes when compared to triple-drug regimens. This led to adoption of dual antiretroviral therapy in current HIV treatment guidelines. However, it is largely unknown whether dual therapy is also able to suppress immune activation to the same degree as triple therapy. This poses a risk for an imbalance in the delicate equilibrium. This mini review gives an overview of the current available evidence concerning immune activation in the setting of cART with less than three antiretroviral drugs

Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells

<p>Abstract</p> <p>Background</p> <p>Mannose binding lectin (MBL) is an important host defence protein against opportunistic fungal pathogens. This carbohydrate-binding protein, an opsonin and lectin pathway activator, binds through multiple lectin domains to the repeating sugar arrays displayed on the surface of a wide range of clinically relevant microbial species. We investigated the contribution of MBL to antifungal innate immunity towards <it>C. parapsilosis in vitro</it>.</p> <p>Results</p> <p>High avidity binding was observed between MBL and <it>C. albicans </it>and <it>C. parapsilosis</it>. Addition of MBL to MBL deficient serum increased the deposition of C4 and C3b and enhanced the uptake of <it>C. albicans</it>, <it>C. parapsilosis </it>and acapsular <it>C. neoformans </it>by polymorphonuclear cells (PMNs). Compared to other microorganisms, such as <it>Escherichia coli</it>, <it>Staphylococcus aureus </it>and <it>Cryptococcus neoformans</it>, <it>C. parapsilosis </it>and <it>Candida albicans </it>were potent activators of the lectin pathway.</p> <p>Conclusion</p> <p>Our results suggest that MBL plays a crucial role in the innate immunity against infections caused by yeast by increasing uptake by PMN.</p

Implementation and effect of intensified case finding on diagnosis of tuberculosis in a large urban HIV clinic in Uganda: a retrospective cohort study.

BACKGROUND: Increased detection of tuberculosis (TB) using intensified or active case finding (ICF) is one of the cornerstones of the Stop TB Strategy, and contrasts with passive case finding (PCF) which relies on self-reported symptoms. There is no clear guidance on implementation strategies. We implemented ICF in addition to ongoing PCF in our large urban HIV clinic in July 2010 using a twice-daily announcement screen method by a trained peer educator, asking waiting patients to self-refer to a trained peer supporter for screening of TB symptoms. We sought to determine the associated effect on TB case detection. METHODS: Suspects were investigated by sputum smear, chest X-ray and ultrasound, if indicated. Routinely collected clinical and laboratory data were merged with the ICF register and TB clinic data for patients attending the clinic in 2010. We compared the yield of TB cases (defined as the prevalence of newly diagnosed TB cases in the screened population), the type of TB diagnosed and the total cost per TB case identified (in United States Dollars [USD]) for the period before and after ICF implementation. RESULTS: Of the 20,456 patients who visited the clinic in 2010, 614 were identified as TB suspects, 220 pre-ICF and 394 post-ICF (229 via PCF and 165 via ICF). The proportion diagnosed with TB dropped from 66% to 48% (60% in suspects identified through PCF and 31% through ICF). During the post-ICF period, TB suspects identified through ICF compared to PCF identification were more likely to be female, older, on ART and to have been enrolled in HIV care for a longer duration. The yield of combined PCF and ICF screening was 1.4% pre-ICF and 1.7% post-ICF with a cost per TB case identified of 12.29 USD and 21.80 USD, respectively. CONCLUSIONS: Implementation of ICF in a large HIV clinic yielded more TB suspects and cases, but substantially increased costs and was unable to capture the majority of TB suspects who were referred for diagnosis by clinicians through PCF. The overall yield of TB cases in a mature HIV clinic was low, although targeted screening of those recently enrolled in care may increase the yield

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.

Теоретичні та практичні аспекти приватизації в Україні

Цели статьи заключаются в изучении спроса покупателей на объекты приватизации и анализе финансового состояния предприятий к принятию решения об их приватизации (на основе данных за I квартал 2006 года), раскрытии основных критериев целесообразности принятия решения о приватизации объектов ведения хозяйства.Цілі статті полягають у вивченні попиту покупців на об'єкти приватизації та аналізі фінансового стану підприємств до прийняття рішення про їх приватизацію (на основі даних за I квартал 2006 року), розкритті основних критеріїв доцільності прийняття рішення про приватизацію об'єктів господарювання

Estimating regional prevalence of chronic hepatitis C with a capture-recapture analysis

Background: The hepatitis C virus (HCV) infection is a candidate disease for micro-elimination. Accurate baseline HCV prevalence estimation is essential to monitor progress to micro-elimination but can be methodologically challenging in low-endemic regions like the Netherlands due to lack of disaggregated data by age or risk-groups on the number of chronic HCV patients (i.e. HCV RNA positive). This study estimates the number of patients that has had a chronic HCV infection (ever-chronic) in the Utrecht region of the Netherlands. Methods: In the Utrecht province in the Netherlands, positive HCV tests from the period 2001–2015 from one diagnostic center and four hospital laboratories were collected. A two-source capture-recapture method was used to analyze the overlap between the two registries (with 92% HCV RNA and 8% HCV immunoblot confirmed infections) to obtain the number of ever-chronic HCV infections in the Utrecht region. The Utrecht region was defined as an area with a 25 km radius from the Utrecht city center. The current viremic HCV prevalence was calculated by taking into account the proportion of cured and deceased HCV patients from a local HCV retrieval (REACH) project. Results: The estimated number of ever-chronic HCV patients was 1245 (95% CI 1164–1326) and would indicate a prevalence of 0.10 (95% CI 0.09–0.10) in the Utrecht region. This is 30% (95% CI 21–38%) more than the number of known HCV patients in the records. The ever-chronic HCV prevalence was highest in the 1960–1969 age cohort (0.16; 95% CI 0.14–0.18). Since 50% of the HCV patients were cured or deceased in the REACH-project, the number of current viremic HCV patients was estimated at 623 individuals in the Utrecht region (prevalence 0.05%). Conclusion: The results of this study suggest a low ever-chronic and current HCV prevalence in the Utrecht area in the Netherlands, but other studies need to confirm this