Neven Papić

Liver involvement during influenza infection: perspective on the 2009 influenza pandemic

Please cite this paper as: Papic et al. (2011) Liver involvement during influenza infection: perspective on the 2009 influenza pandemic. Influenza and Other Respiratory Viruses 6(3), e2–e5.

Antimicrobial susceptibility of Ureaplasma urealyticum and Mycoplasma hominis

Ureaplasma urealyticum and Mycoplasma hominis are common commensals of the lower genitourinary tract. They are causally linked to prostatitis, epydidimitis, urethral syndrome, cervicitis, urolythiasis, reactive arthritis, infertility, complications during pregnancy and serious infections in newborns and immunocompromised hosts.1 Therefore, the therapeutic use of antimicrobials and susceptibility testing is necessary because it allows adequate treatment. The aim of this study was to determine the susceptibility of U urealyticum and M hominis to tetracycline, erythromycin, clindamycin, doxycycline, ofloxacin and azithromycin. This study was conducted at the …

Influenza and hepatitis B vaccination coverage among healthcare workers in Croatian hospitals: a series of cross-sectional surveys, 2006–2011

BackgroundHealthcare workers (HCWs) are at an increased risk of exposure to and transmission of infectious diseases. Vaccination lowers morbidity and mortality of HCWs and their patients. To assess vaccination coverage for influenza and hepatitis B virus (HBV) among HCWs in Croatian hospitals, we conducted yearly nationwide surveys.MethodsFrom 2006 to 2011, all 66 Croatian public hospitals, representing 43–60% of all the HCWs in Croatia, were included. Statistical analysis was performed using the Kruskal–Wallis analysis of variance, Dunn’s multiple comparison analysis and the chi-square test, as appropriate.ResultsThe median seasonal influenza vaccination coverage rates in pre-pandemic (2006–2008) seasons were 36%, 25% and 29%, respectively. By occupation, influenza vaccination rates among physicians were 33 ± 21%, 33 ± 22% among graduate nurses, 30±34% among other HCWs, 26 ± 21% among housekeeping and the lowest, 23 ± 17%, among practical nurses (p < 0.01). In 2009–2010 season, seasonal influenza vaccination coverage was 30%, while overall vaccination coverage against pandemic influenza was fewer than 5%. Median vaccination coverage in the post-pandemic seasons of 2010–2011 and 2011–2012 decreased to 15% and 14%, respectively (reduction of 24% and 35%, respectively, p < 0.0001). Meanwhile, the median mandatory HBV vaccination coverage was 98%, albeit with considerable differences according to work setting (range 19–100%) and occupation (range 4–100%).ConclusionsWe found substantial year-on-year variations in seasonal influenza vaccination rates, with reduction in post pandemic influenza seasons. HBV vaccination is satisfactory compared to seasonal influenza vaccination coverage, although substantial variations by occupation and work setting were observed. These findings highlight the need for national strategies that optimize vaccination coverage among HCWs in Croatian hospitals. Further studies are needed to establish the potential role of mandatory vaccination for seasonal influenza.

Unresolved issue in hepatitis C: The role of liver non-parenchymal cells and semaphorins

With broad usage of direct acting antivirals (DAAs) the global epidemics of hepatitis C will probably come to an end in next 20 years.1,2 The price of DAAs is still high in European countries and in USA, but it is plausible to assume that the availability of generic drugs will make the treatment possible for the majority of diagnosed patients. So we will be able to eliminate the virus without really understanding the pathophysiology of chronic infection, fibrogenesis and carcinogenesis. Substantial number of treated patients will therefore have to be followed up for cirrhosis and hepatocellular carcinoma. There is growing evidence that liver non-parenchymal cells, specifically liver sinusoidal endothelial cells (LSEC) and Kupffer cells (KC), may play key roles in regulating immune responses and facilitating tolerance induction.3,4 Previously published gene expression analyses have revealed new disease specific changes in gene expression, identified potential biomarkers of HCV infection and suggested a new mechanism of host cell-virus interaction that results in viral particle assembly, secretion and infectivity.5-9 In vitro HCV JFH-1 infection studies have shown different gene expression repertoires; unlike macrophages that demonstrated a broad increase in IL1β and NFκB-responsive proinflammatory cytokines and chemokines, transcriptome changes in hepatocytes enable the replicative infection, while LSEC favor the transcription of immunomodulators that can silence the inflammatory reaction and favor fibrogenesis.5,7-10 Multiple strategies by which HCV evades the surveillance of the host immune system are proposed and yet to be explained. These in vitro cell cultures studies suggested the connection of immune semaphorins with HCV infection. Semaphorins are a class of secreted and membrane-bound proteins that regulate key cellular functions involved in cell-cell communication. The importance of semaphorins and plexins has been emphasized by their discovery in many organ systems including the nervous, epithelial, and immune systems as well as diverse cell processes including angiogenesis, embryogenesis and cancer.11,12 Studies of plexins and semaphorins have revealed that several members of these families are involved in a series of immune cell interactions, which ultimately influence the outcome of the immune response and substantially influence the level of inflammation.11,12 Interestingly, semaphorins play the opposite roles in innate versus adaptive immune response, amplifying inflammation while dampening T-cell proliferation and activation.11,13,14 Although immune semaphorins are crucial to various phases of the immune response, so far semaphorins have not been linked with HCV infection. Previously mentioned gene expression studies have linked several semaphorins with HCV infection: SEMA3C was shown to increase the production/secretion of several extracellular matrix components (fibronectin, elastin, collagen) and promoting factors (CTGF, IL6 and TGF-β1), and the expression of SEMA3C correlated positively with the degree of fibrosis in adipose tissue;15 SEMA6B and SEMA6D might bind to and activate dendritic cells and increase type I interferon production.16 We have been able to show in our Croatian Science Foundation project Infectomics study of the human liver nonparenchymal cells in chronic hepatitis C that serum concentrations of secreted semaphorins are higher in HCV infected patients, and their serum concentration correlate with the degree of liver fibrosis.17 Immunohistochemistry in transplanted livers revealed the absence of semaphorins in healthy livers in comparison with strong positivity in LSEC and KC in explanted cirrhotic HCV positive livers (Vince A., unpublished data). Furthermore, results of that research imply the usage of semaphorins as predictive markers of liver cirrhosis, stronger then APRI score and FIB4 test.17 These results provide first evidence that semaphorins are involved in immune response to chronic HCV infection. This might have import clinical implications as well, since their concentration correlates with the extent of liver disease, they might be considered as new biomarkers of liver fibrogenesis. Although the serum concentration of semaphorins in people who develop hepatocellular carcinoma should be evaluated further, recent studies showed that semaphorins that restrict cell migration and angiogenesis are often downregulated, while those that support cancer progression and metastatic spreading are frequently upregulated in other cancers.18 It was also shown that blocking these molecules effectively reduce tumor angiogenesis and metastatic spreading in preclinical trials in mice.18-20 These data validate the identification of semaphorin signals as a potential biomarker of infection and fibrosis stage in chronic viral hepatitis and promising therapeutic targets in liver cancer.

Long Term Outcomes of Acute Aseptic Encephalitis In Adults - a Single Center Study

Abstract Background Encephalitis is a heterogeneous syndrome associated with significant mortality and neurophysiological sequelae. The etiology is identified in only 20–50% of cases, and long-term outcomes of survivors are underinvestigated, especially in patients with unknown etiology. The aim of this study was to describe long-term outcomes of patients with aseptic encephalitis of various etiologies. Methods The study population consisted of a retrospectively identified cohort of consecutive adult patients diagnosed with viral and etiologically undiagnosed encephalitis during a 24-month period (2014-2015) at the University Hospital for Infectious Diseases Zagreb, Croatia. Clinical, laboratory data and short-term outcomes were collected from medical records, and long-term outcomes were assessed by telephone interviews and quantified through modified Rankin scores (mRS). Results A total of 90 patients were identified (57.7% female; 51.5 ± 17.4 years). Viral etiology was identified in 20 (22.2%) patients: herpes simplex virus (HSV-1, 8.9%), varicella-zoster virus (VZV, 6.7%), Tick-borne encephalitis (TBE, 4.4%) and enteroviruses (2.2%). Postinfectious meningoencephalitis was suspected in 14 (15.6%) patients, and 56 (62.2%) had unknown etiology. Elevated CSF WBC was present in 77 patients (mean of 169.3 ± 279.4/mm3) and all but 6 had elevated CSF proteins (1.23 ± 0.88 g/L). Convulsions occurred more frequently in HSV-1 (37.5%) and in unknown etiology group (15.7%). GOS<3 was noted in 50% of HSV, 33% of VZV, 25% of TBE and 24% of unknown group patients during hospitalization. Mechanical ventilation was necessary in 17.1% of patients with unknown and 23.5% with viral etiology for the mean duration of 1.8 ± 6.7 and 3.2 ± 6.3 days, respectively. The mean length of stay was 23.2 ± 18.5 days. In-hospital mortality was 7.8%. Among 64 survivors who were available for follow-up interviews (mean follow-up of 28.6 ± 6.8 months), 73.1% with unknown and 90.9% with viral etiology had favorable outcomes (mRS 0–1); 4 (6.25%) had moderate (mRS 3) and 3 (4.6%) had severe neuropsychological deficits (mRS 4-5). Conclusion Although the etiology of aseptic encephalitis is often unknown, long-term outcomes are favorable in the majority of patients. Disclosures All authors: No reported disclosures.