Background: In the British Isles, it is generally accepted that the Eurasian badger (Meles meles) plays a role in the maintenance of bovine tuberculosis (bTB) in cattle. Non‐selective culling is the main intervention method deployed in controlling bTB in badgers along with smaller scale Bacillus Calmette–Guérin (BCG) vaccination areas. This paper describes the use of selective badger culling combined with vaccination in a research intervention trial. Methods: In Northern Ireland, a 100 km2 area was subjected to a test and vaccinate or remove (TVR) badger intervention over a 5‐year period. Badgers were individually identified and tested on an annual basis. Physical characteristics and clinical samples were obtained from each unique badger capture event. Results: A total of 824 badgers were trapped with 1520 capture/sampling events. There were no cage‐related injuries to the majority of badgers (97%). A low level of badger removal was required (4.1%–16.4% annually), while 1412 BCG vaccinations were administered. A statistically significant downward trend in the proportion of test positive badgers was observed. Conclusion: This is the first project to clearly demonstrate the feasibility of cage side testing of badgers. The results provide valuable data on the logistics and resources required to undertake a TVR approach to control Mycobacterium bovis in badgers.
Background and aimsSustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleot(s)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We performed a meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB.MethodsStudies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older generation NA.ResultsN=37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals.ConclusionVR is common after NA discontinuation, however, CR was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by HBsAg clearance, and rates are higher with longer follow-up.
Background and Aims: Current guidelines recommend long-term nucleot(s)ide analogue (NA) therapy for patients with HBeAg-negative chronic hepatitis B (CHB). However, disease remission has been described after stopping NA therapy, as well as HBsAg loss.
Methods:We performed a prospective multi-centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg-negative CHB, the absence of cirrhosis and HBVDNA
Reactivation of hepatitis B virus (HBV) replication in patients receiving rituximab is well described. Current international guidelines recommend HBV screening prior to the commencement of immunosuppressive therapy. However, adherence to such protocols has not previously been studied. We therefore audited screening practices and clinical outcomes in patients prescribed rituximab since its introduction in a large metropolitan health service. All patients receiving rituximab over an 88-month period were identified via pharmacy records. Medical records and laboratory results were reviewed to determine the timing and type of hepatitis screening. HBV flares were identified and correlated with clinical outcomes and any screening or prophylaxis given. Rituximab was given to 355 patients over 88 months (average age, 61 years; 51% male, 48% born overseas); 83% received rituximab for treatment of a hematological malignancy. HBV screening occurred in 31% of patients and, of these, 66% had pre-emptive screening. Five patients given cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab experienced HBV flares. Four died from viral reactivation. None received antiviral prophylaxis. Hepatitis screening rates in patients receiving rituximab in this study were lower than recommended in clinical guidelines. The identification of five patients with clinically important flares and four deaths in this group highlight the critical need to identify at-risk patients and provide timely prophylactic antiviral therapy to prevent serious morbidity and mortality. Even those with evidence of HBV seroconversion are at risk for fatal flares without active prophylactic antiviral therapy. The Oncologist 2011;16:579 -584
Background and Aims We evaluated the patterns of peripheral TLR signalling activity and the expression of TLRs and NK cell activation in a cohort of patients experiencing severe hepatitis flares after stopping NA therapy. Methods Samples were collected longitudinally from CHB patients enrolled in a prospective study of NA discontinuation. Patients experiencing hepatitis flares were compared to patients with normal ALT. PBMC were stimulated with TLR ligands and cytokine secretion in the cell culture supernatant measured. Expression of TLR2/4, NKG2D, NKp46 and TREM-1 on monocytes, NK and NK-T cells was measured. Results 17 patients with severe reactivation hepatitis flares were compared to 12 non-flare patients. Hepatitis flares were associated with increased activity of TLR 2-8 and TLR 9 signalling in PBMC at the time of peak flare compared to baseline. Hepatitis flares were also associated with upregulation of TLR2, and TREM-1 receptor expression on NK. There were no differences at baseline between flare patients and non-flare patients. Conclusion Hepatitis flares off NA therapy have a significant innate inflammatory response with upregulation of TLR signalling on peripheral monocytes and TLR-2 and TREM-1 expression on NK cells. This implicates the innate immune system in the immunopathogenesis of hepatitis B flares.
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