Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial

Background: Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25–30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. Methods: We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per μL, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 μg of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659. Findings: Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1·84, 95% CI 0·86–3·91, p=0·12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. Interpretation: Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D. Funding: The HepNet Study-House (a project of the German Liver Foundation founded by the German Liver Foundation, the German Ministry for Education and Research, and the German Center for Infectious Disease Research), Hoffmann-La Roche, and Gilead Sciences. © 2019 Elsevier Lt

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study

Objective: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. Methods: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. Results: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1–28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002–1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000–0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3–2.7, p = 0.0001) were associated with diffuse inflammation. Conclusions: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses. © 2016, Springer-Verlag Berlin Heidelberg

Temporal Trends in the Epidemiology of HIV in Turkey

Objective: The aim of this study was to analyze the temporal trends of HIV epidemiology in Turkey from 2011 to 2016.Methods: Thirty-four teams from 28 centers at 17 different cities participated in this retrospective study. Participating centers were asked to complete a structured form containing questions about epidemiologic, demographic and clinical characteristics of patients presented with new HIV diagnosis between 2011 and 2016. Demographic data from all centers (complete or partial) were included in the analyses. For the cascade of care analysis, 15 centers that provided full data from 2011 to 2016 were included. Overall and annual distributions of the data were calculated as percentages and the Chi square test was used to determine temporal changes.Results: A total of 2,953 patients between 2011 and 2016 were included. Overall male to female ratio was 5:1 with a significant increase in the number of male cases from 2011 to 2016 (p500 cells/mm(3) while 46.7% presented with a CD4 T cell count of <350 cells/mm(3). Among newly diagnosed cases, 79% were retained in care, and all such cases initiated ART with 73% achieving viral suppression after six months of antiretroviral therapy.Conclusion: The epidemiologic profile of HIV infected individuals is changing rapidly in Turkey with an increasing trend in the number of newly diagnosed people disclosing themselves as MSM. New diagnoses were mostly at a young age. The late diagnosis was found to be a challenging issue. Despite the unavailability of data for the first 90, Turkey is close to the last two steps of 90-90-90 targets.C1 [Erdinc, F. S.; Hatipoglu, C. A.] Ankara Numune Training & Res Hosp, Infect Dis & Clin Microbiol, Ankara, Turkey.[Dokuzoguz, B.; Inkaya, A. C.] Ankara Numune Training & Researh Hosp, Infect Dis & Clin Microbiol, Ankara, Turkey.[Unal, S.] Hacettepe Univ Hastaneleri, Dept Infect Dis & Clin Microbiol, Ankara, Turkey.[Komur, S.] Cukurova Univ, Dept Infect Dis & Clin Microbiol, Adana, Turkey.[Inan, D.] Akdeniz Univ, Dept Infect Dis & Clin Microbiol, Antalya, Turkey.[Karaoglan, I] Gaziantep Univ, Dept Infect Dis & Clin Microbiol, Gaziantep, Turkey.[Deveci, A.] Ondokuz Mayis Univ, Dept Infect Dis & Clin Microbiol, Samsun, Turkey.[Celen, M. K.] Dicle Univ, Dept Infect Dis & Clin Microbiol, Diyarbakir, Turkey.[Kose, S.] Izmir Tepecik Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Izmir, Turkey.[Erben, N.] Eskisehir Osmangazi Univ, Dept Infect Dis & Clin Microbiol, Fac Med, Eskisehir, Turkey.[Senturk, G. C.] Diskapi Yildirim Beyazit Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Ankara, Turkey.[Heper, Y.; Yilmaz, E.; Kazak, E.] Uludag Univ, Dept Infect Dis & Clin Microbiol, Bursa, Turkey.[Kutlu, S. S.] Pamukkale Univ, Dept Infect Dis & Clin Microbiol, Denizli, Turkey.[Sumer, S.] Selcuk Univ, Dept Infect Dis & Clin Microbiol, Konya, Turkey.[Kandemir, B.] Necmettin Erbakan Univ, Meram Med Fac Hosp, Dept Infect Dis & Clin Microbiol, Konya, Turkey.[Sirmatel, F.] Abant Izzet Baysal Univ, Dept Infect Dis & Clin Microbiol, Bolu, Turkey.[Bayindir, Y.; Ersoy, Y.; Yetkin, F.] Inonu Univ, Dept Infect Dis & Clin Microbiol, Malatya, Turkey.[Yildirmak, M. T.] Okmeydani Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Istanbul, Turkey.[Kayaaslan, B.] Yildirim Beyazit Univ, Dept Infect Dis & Clin Microbiol, Fac Med, Ankara, Turkey.[Ozden, K.] Ataturk Univ, Dept Infect Dis & Clin Microbiol, Erzurum, Turkey.[Sener, A.] Canakkale Onsekiz Mart Univ, Dept Infect Dis & Clin Microbiol, Canakkale, Turkey.[Kara, A.] Hacettepe Univ, Dept Infect Dis, Ihsan Dogramaci Childrens Hosp, Ankara, Turkey.[Gunal, O.] Samsun Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Samsun, Turkey.[Birengel, S.] Ankara Univ, Dept Infect Dis & Clin Microbiol, Fac Med, Ankara, Turkey.[Akbulut, A.] Firat Univ, Dept Infect Dis & Clin Microbiol, Elazig, Turkey.[Cuvalci, N. O.] Antalya Training & Res Hosp, Dept Infect Dis & Clin Microbiol, Antalya, Turkey.[Sargin, F.] Medeniyet Univ, Dept Infect Dis & Clin Microbiol, Goztepe Training & Res Hosp, Istanbul, Turkey.[Pullukcu, H.; Gokengin, D.] Ege Univ, Dept Infect Dis & Clin Microbiol, Izmir, Turkey

Efficacy and tolerability of antibiotic combinations in neurobrucellosis: Results of the Istanbul study

PubMed ID: 22155822No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol. Copyright © 2012, American Society for Microbiology. All Rights Reserved

Central Nervous System Infections In The Absence Of Cerebrospinal Fluid Pleocytosis

Previous multicenter/multinational studies were evaluated to determine the frequency of the absence of cerebrospinal fluid pleocytosis in patients with central nervous system infections, as well as the clinical impact of this condition. It was found that 18% of neurosyphilis, 7.9% of herpetic meningoencephalitis, 3% of tuberculous meningitis, 1.7% of Brucella meningitis, and 0.2% of pneumococcal meningitis cases did not display cerebrospinal fluid pleocytosis. Most patients were not immunosuppressed. Patients without pleocytosis had a high rate of unfavorable outcomes and thus this condition should not be underestimated.Scopu