Papers by Arvydas Ambrozaitis
Vilnius : [Užkrečiamųjų ligų profilaktikos ir kontrolės centras ; Vilniaus universitetas], 2006
Journal of Hepatology, Apr 1, 2012
Background and Aims: Several immunological parameters have been associated with clinical outcome ... more Background and Aims: Several immunological parameters have been associated with clinical outcome of HCV infection. We have previously found that acute HCV-infected subjects progressing to chronicity had higher serum IP-10 levels than those who spontaneously resolved the infection, which is counterintuitive given the known pro-inflammatory role of this chemokine. IP-10 is subjected to physiological cleavage of two aminoacids by DPPIV (CD26), which produces an NH 2-truncated form of the protein. The cleaved form (referred to as short IP-10) antagonizes the biologically active longer form by competitively binding to the common receptor without inducing signalling. Most IP-10 assays quantify the total IP-10 protein; however, recently developed assays also allow the distinction of the two forms. The aim of this study was to investigate the role of antagonistic short IP-10 in influencing the clinical outcome of acute HCV infection. Methods: We analysed 16 patients with acute HCV infection who met the following criteria: ALT >10× upper limit normal (ULN), exposure to HCV within previous 4 months and HCV-RNA(+). Plasma was collected from these patients longitudinally at 12 timepoints. We quantified the long and short forms of IP-10 in these samples. Results were then analysed and correlated with the clinical outcome (chronic vs resolver). The longitudinal nature of the dataset was taken into account through the use of a "mixed model" analytical strategy for repeated measures. Results: Our investigation confirmed that subjects who progressed to chronicity (n = 11) had higher serum concentrations of total IP-10 (p < 0.001) compared to patients who resolved spontaneously (n = 5). However, these higher amounts of detectable IP-10 were ascribable to increased levels of the antagonistic form (p = 0.036), whilst serum concentrations of biologically active long IP-10 form were comparable with subjects who spontaneously resolved the infection (p = 0.460). Conclusions: This study reports a novel mechanism of chemokine antagonism during acute HCV infection and may represent an additional factor in the failure of the host immune response in eradicating HCV infection. The results also reveal that the short IP-10 is a predictor of clinical outcome after acute HCV infection and may be used to aid treatment decisions during acute HCV infection.
Background. Interferon-gamma (IFN-γ) produced during influenza A virus (IAV) infection stimulates... more Background. Interferon-gamma (IFN-γ) produced during influenza A virus (IAV) infection stimulates abundant generation of the cytotoxic free radical nitric oxide (NO) in macrophages that in turn damage pulmonary cells and tissues. However, it is unknown whether IFN-γ contributes to the cytotoxicity in the IAV-infected macrophages through the stimulation of inducible nitric oxide synthase (iNOS) expression. Materials and methods. RAW 264.7 and AMJ2-C11 murine macrophages were exposed for 24 h to either IFN-γ or live IAV (A/PR/8/34), or their combination. At 24 h postexposure, cell viability was evaluated by trypan blue dye exclusion, nitrite levels in macrophage culture supernatants were measured using Griess reagent, and cells were harvested for iNOS mRNA detection by reverse transcriptase (RT)-PCR. Results. The added IFN-γ was associated with reduced viability of both cell lines only when infected with IAV, which was coincident with an elevated level of nitrite and iNOS mRNA. Furthe...
Interferon-gamma (IFN-γ) antiviral activity operates partly via inducible nitric oxide synthase (... more Interferon-gamma (IFN-γ) antiviral activity operates partly via inducible nitric oxide synthase (iNOS) induction. Whether IFN-γ affects influenza A virus (IAV) replication within macrophages through this pathway is unknown. For the investigation, RAW 264.7 and AMJ2-C11 murine macrophages were exposed to IFN-γ, live IAV (A/PR/8/34) or their combination. At 24 h post-exposure, cell viability was evaluated by trypan blue dye exclusion, nitrite levels in macrophage culture supernatants were measured using the Griess reagent, and cells were harvested for reverse transcriptase (RT)-PCR. The IFN- γ-activated macrophages incubated with live IAV demonstrated a considerably greater cytopathic effect as well as a significant viability reduction than those without IAV, or with IAV minus IFN-γ (p < 0.05). Simultaneously, iNOS gene expression and nitric oxide (NO) production were increased in both cell lines. These findings indicate that IFN-γ-induced iNOS expression and NO synthesis and IFN-γ...
Journal of the American Medical Directors Association
The overall frequency and severity of viral respiratory infections affecting residents of long-te... more The overall frequency and severity of viral respiratory infections affecting residents of long-term care facilities (LTCFs) is not well described. This is due primarily to the cumbersome and expensive techniques required for adequate surveillance of respiratory illnesses and the associated costs and availability of a laboratory capable of the relevant and timely report of diagnostic tests. Here we describe our technique for surveillance of respiratory illness in the LTCF. Elements of it may serve as strategies for routine care. Nurses were trained to record respiratory complaints and to track them using a histogram-based calendar charting system. For the research technique, all new illnesses during the winter months, no matter how minor, were sampled for viral culture. Influenza A and B, parainfluenza types 1 through 4, herpes simplex virus types 1 and 2, rhinovirus, and respiratory syncytial virus (RSV) were detected in the nursing homes studied. Outbreaks of influenza were documen...
Antimicrobial resistance is mainly caused by inappropriate and abundant use of antibiotics. To en... more Antimicrobial resistance is mainly caused by inappropriate and abundant use of antibiotics. To enlighten the most relevant problematic areas in antibiotic use, where the decisions should be made, the different levels were analysed in this study: the self-medication with antibiotics of the population, ambulatory and also hospital antibiotic use. The results showed that wrong perception about antibiotics is characteristic to Lithuanian population, as there is lack of privity, while traditions of self-medication and also habits to apply the previous experience, when doctor prescribed antibiotics, are entrenched. As the ambulatory care covers the most of the population, the most antibiotics are consumed in this level. However often they are prescribed irrationally for non-bacterial infections just on the basis of clinical symptoms. The antibiotic prescribing for one of the most frequent infection acute pharyngitis / tonsillitis might be improved by implementation of rapid antigen detection tests. The extent of antibiotic consumption in nursing hospitals is low, but it is uncontrolled. Therefore the development of correct population approach, education of health care professionals, implementation of diagnostic tools, antibiotic sales‘ control, guidelines for diagnostics and treatment, approvement of antibiotic prescribing procedures – all those items would promote rational antibiotic use
purpose. To determine the prevalence of Staphylococcus aureus carriage and its associated potenti... more purpose. To determine the prevalence of Staphylococcus aureus carriage and its associated potential risk factors in healthy adult population in Vilnius; to estimate the presence of the Panton-Valentine leukocidin gene and to evaluate resistance patterns of isolated strains. Methods. A prevalence study involving 537 healthy adults was performed. Swabs from anterior nares and throat were taken to determine the presence of S. aureus. Antibiotic susceptibility testing was performed using the disk diffusion method according to the Clinical Laboratory Standards Institute guidelines. Polymerase chain reaction was used to detect the PVL gene in all isolated S. aureus strains. A questionnaire was obtained to identify potential risk factors for S. aureus colonization. results. The prevalence of S. aureus carriage in Vilnius adult population was 50,8 %. A total of 298 different S. aureus strains were isolated. Antimicrobial susceptibility testing revealed that 65,4 % of the isolated strains we...
Medicina
Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment f... more Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode o...
Hepatitis Monthly, 2018
Background: The current international multicentre open-label, uncontrolled, real-world retrospect... more Background: The current international multicentre open-label, uncontrolled, real-world retrospective study aimed at evaluating the effectiveness and safety of ombitasvir / paritaprevir / ritonavir + dasabuvir ± ribavirin (3D therapy) in treatment-naive and treatment-experienced hepatitis C virus (HCV) genotype 1-infected (GT1) patients. Methods: Adult patients with chronic HCV GT1 infection, scheduled for 3D therapy according to therapeutic guidelines, were eligible. Demographic and clinical data were collected retrospectively by reviewing individuals health records. The primary effectiveness endpoint was the sustained virological response at 12 weeks following the end of treatment (SVR12). Results: The participants in the current study consisted of 134 patients with HCV GT1 infection, including 10 liver transplant recipients. SVR12 was achieved in 120 (96.8%) non-transplant and all liver transplant patients (100%). Significant improvement in liver function tests were observed. Among 4 treatment failures, 2 patients were non-responders and 2 patients relapsed. OBV/PTV/r + DSV ± RBV regimen was well tolerated in most patients with treatment discontinuation due to adverse events in 3 patients. The most frequent adverse events were asthenia (25.8%), fatigue (16.1%), skin pruritus (12.9%), and dyspepsia (11.3%). Conclusions: The current real-life study demonstrated the effectiveness and safety of OBV/PTV/r + DSV ± RBV in patients with HCV GT1, including patients with cirrhosis, a liver transplant recipient and the one who failed previous antiviral therapies.
Blood transfusion = Trasfusione del sangue, Jan 26, 2018
In Italy nucleic acid testing (NAT) became mandatory for hepatitis C virus (HCV) in 2002 and for ... more In Italy nucleic acid testing (NAT) became mandatory for hepatitis C virus (HCV) in 2002 and for human immunodeficiency virus (HIV) and hepatitis B virus in 2008. The aim of this study was to monitor the incidence and prevalence of HIV and HCV infections in Italian blood donors and the current residual risk of these infections after the introduction of NAT. The Italian national blood surveillance system includes data from tests used to screen for transfusion-transmissible infections. During the period of this survey (2009-2015), the NAT methods used were the transcription-mediated amplification test, for individual donor testing, and polymerase chain reaction analysis, mainly for pools of six donors. Prevalence and incidence were calculated. Three published formulae were applied to estimate the residual risk (the window period ratio model and the formulae recommended by the European Medicines Agency and the World Health Organization). Overall, 12,258,587 blood donors and 21,808,352 ...
European Journal of Neurology, 2017
Background and purpose: Lithuania is one of the countries with the highest incidence of tick-born... more Background and purpose: Lithuania is one of the countries with the highest incidence of tick-borne encephalitis (TBE) in Europe. The aim of this study was to describe the epidemiological patterns of TBE in Lithuania, and characterize clinical features in adults in the light of the high incidence in recent years. Methods: Surveillance data available on the website of the Centre for Communicable Diseases and AIDS of Lithuania were used to describe the epidemiological patterns of TBE. The retrospective study included 712 patients hospitalized in the Centre for Infectious Diseases and the Centre for Neurology of Vilnius University in the years 2005-2014. Results: Tick-borne encephalitis incidence rates have been increasing by 8.5% per year for the 45-year period from 1970 to 2014. The joinpoint model finds two joinpoints at 1991 and 1994, with a significant decrease of 8.4% per year (P < 0.05) prior to the joinpoint at 1991, and a rise of 195.2% afterwards. TBE presented with meningoencephalitis in 556 cases (81.3%). A total of 129 patients (18%) had a severe case of the disease. The most common neurological signs were ataxia (579, 81.3%), meningeal signs (474, 66.5%) and tremor (338, 47.5%). Limb paresis was observed in 6.3% of patients. Five patients (0.7%) died, and 544 patients (76.7%) were discharged with sequelae. Conclusions: Intensified efforts in promoting TBE vaccination will be needed in the light of the high incidence and expanded spatial distribution. Significant prognostic factors for severe cases of the disease were age above 61 and delayed immune response of specific immunoglobulin G.
BMC Infectious Diseases, 2019
Background: HIV transmission remains a major concern in Eastern Europe, and too many people are d... more Background: HIV transmission remains a major concern in Eastern Europe, and too many people are diagnosed late. Expanded testing strategies and early and appropriate access to care are required. Infectious disease departments might be targets for expanded HIV testing owing to the intense passage of key patient populations that carry indicators of HIV disease. Our objective was to evaluate the feasibility and clinical effectiveness of a fully integrated, opt-out routine, rapid HIV testing program. Methods: A retrospective four-year study of a screening program was conducted from 2010 through 2014. The program was divided into two periods: from 2010 to 2012 (pilot study) and from 2013 to 2014. The pilot study consisted of routine HIV testing of patients aged 18-55 that were hospitalized in one department. In the second period, all inpatients aged 18-65 were eligible. Targeted testing was conducted in the other inpatient department during the pilot study and the outpatient department during both periods. Results: During the pilot study, 2203 patients were hospitalized, 1314 (59.6%) were eligible, 954 (72.6%) were tested, and 3 (0.31%) were newly diagnosed HIV-positive. In the second period, 4911 patients were hospitalized, 3727 (75.9%) were eligible, 3303 (88.6%) were tested, and 7 (0.21%) were HIV-positive. In total, 2800 targeted tests were performed, and 4 (0.14%) patients tested positive with newly discovered HIV. All 14 newly diagnosed patients were provided with care. Comparing cumulative groups of routine and targeted testing, the HIV prevalence was 0. 23% vs. 0.14% (p = 0.40) and was above the reported cost-effectiveness threshold of 0.1% (p = 0.012). A lower proportion of advanced disease and a higher proportion of heterosexually transmitted infection were found in the routine testing group. Conclusion: Routine HIV testing in admissions of infectious diseases is acceptable, feasible, sustainable and clinically effective. Compared to targeted testing, routine testing helped to discover more patients in earlier stages and those with heterosexually transmitted HIV infection.
Pharmacological Reports, 2006
The influenza virus (influenza) infection causes an intense infiltration of pulmonary tissues by ... more The influenza virus (influenza) infection causes an intense infiltration of pulmonary tissues by macrophages, which abundantly generate a free radical, nitric oxide (NO) resulting in lung damage. Neuraminidase inhibitors (NIs) restrict influenza virus replication but whether they can suppress NO production within macrophages is unknown. RAW 264.7 macrophages were exposed to interferon-gamma (IFN-gamma), live influenza (A/PR/8/34) or a combination of both and were treated with NIs (oseltamivir or zanamivir). Results revealed that the drugs reduced a synergy between influenza and IFN-gamma in NO synthesis within the cells at all of the used concentrations (0.01, 0.1, 1 microg/ml). In contrast to zanamivir, this effect occurred in a concentration-dependent manner with oseltamivir treatment. On the other hand, all concentrations of zanamivir significantly suppressed NO production in comparison to that upon the combined exposure only (p < 0.05). Both compounds also considerably decrea...
In Vivo, May 2, 2018
Background/Aim: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and e... more Background/Aim: Severe pulmonary influenza A virus (IAV) infection causes lung inflammation and expression of inducible nitric oxide synthase (iNOS), leading to overproduction of nitric oxide (NO). We studied whether zanamivir reduces pulmonary inflammation through inhibition of NO production in mice. Materials and Methods: We treated IAV-infected mice daily with intranasal zanamivir. Controls were infected and either placebo-treated or untreated, or not infected and placebo-treated. Mice were weighed daily. After euthanasia on day 3, lungs were excised and bronchoalveolar lavage was performed and fluid nitrite concentration was determined. Lungs were analyzed microscopically. iNOS and IAV RNA levels in lungs were assessed using quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results: Mice undergoing zanamivir treatment had less weight loss, viral replication, and lung damage, as well as significant reductions of local NO and iNOS mRNA synthesis (p<0.05). Conclusion: Zanamivir is associated with an anti-inflammatory effect mediated through inhibition of NO production in IAV-infected mice.
Medicina
Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infe... more Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infectious disease caused by the spirochete bacteria Borrelia. The risk of infection depends on the geographical area, ecological factors, and human behavior. Clinical manifestations of Lyme borreliosis have a wide range, but the most frequent clinical symptom, which is also a diagnostic symptom, is a skin rash called erythema migrans (EM). The disease is very common worldwide. In Lithuania, the disease frequency is 99.9 cases per 100,000 population (Centre for Communicable Diseases and AIDS, Lithuania, 2017). The main aim of this study was to obtain the baseline characteristics of the disease regarding the infected Lithuanian population. Materials and Methods: We analyzed data from the Centre for Communicable Diseases and AIDS about all Lyme disease (A69.2) diagnosed patients over a three-year period (from 2014 to 2016) in Lithuania. Results: In 2014–2016, 7424 (crude incidence rate 85.4) c...
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Papers by Arvydas Ambrozaitis