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Malinin O.V.,Izhevsk State Medical Academy | Platonov A.E.,Central Research Institute of Epidemiology
Infectious Diseases | Year: 2017

Background: Intravenous ribavirin has been reported to be an effective treatment for haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus in Asia. However, its therapeutic benefits for HFRS caused by Puumala virus (PUUV) in Europe are still unknown. Methods: A randomized, open-label study of efficacy and safety of intravenous ribavirin in the treatment of HFRS was conducted in the European part of Russia. Seventy-three patients with suspected HFRS within 4 d of the onset of the disease were randomized to receive either intravenous ribavirin (33 mg/kg, followed by 16 mg/kg given every 6 h for 4 d and by 8 mg/kg given every 8 h for 3 d) plus standard therapy (n = 37) or standard therapy alone (n = 36). The primary outcome was the average change from baseline in viral load over time estimated as area under the viral load curve minus baseline (AUCMB). Fifty-five patients with HFRS confirmed by nested reverse transcriptase – polymerase chain reaction (PCR) assay were included in the assessment of the efficacy. All patients entered into the clinical trial were included in the assessment of the safety. Results: PUUV was detected in all cases of confirmed HFRS. Viral load kinetics were similar in both treatment groups. Significantly more patients receiving ribavirin than standard therapy experienced low haemoglobin level (95% vs 36%), hyperbilirubinemia (81% vs 3%), sinus bradycardia (43% vs 14%), and rash (19% vs 0%). Conclusions: Results of the study showed insufficient efficacy and safety of intravenous ribavirin in the treatment of HFRS caused by PUUV. © 2017 Society for Scandinavian Journal of Infectious Diseases


Ferenci P.,Medical University of Vienna | Lalezari J.,Quest Clinical Research | Cohen D.,AbbVie | Luo Y.,AbbVie | And 24 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. RESULTS: The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS: Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection. Copyright © 2014 Massachusetts Medical Society.


Savitskaya E.,Russian Academy of Sciences | Semenova E.,Rutgers University | Dedkov V.,Central Research Institute of Epidemiology | Metlitskaya A.,Russian Academy of Sciences | And 2 more authors.
RNA Biology | Year: 2013

In Escherichia coli, the acquisition of new CRISPR spacers is strongly stimulated by a priming interaction between a spacer in CRISPR RNA and a protospacer in foreign DNA. Priming also leads to a pronounced bias in DNA strand from which new spacers are selected. Here, ca. 200,000 spacers acquired during E. coli type I-E CRISPR/Cas-driven plasmid elimination were analyzed. Analysis of positions of plasmid protospacers from which newly acquired spacers have been derived is inconsistent with spacer acquisition machinery sliding along the target DNA as the primary mechanism responsible for strand bias during primed spacer acquisition. Most protospacers that served as donors of newly acquired spacers during primed spacer acquisition had an AAG protospacer adjacent motif, PAM. Yet, the introduction of multiple AAG sequences in the target DNA had no effect on the choice of protospacers used for adaptation, which again is inconsistent with the sliding mechanism. Despite a strong preference for an AAG PAM during CRISPR adaptation, the AAG (and CTT) triplets do not appear to be avoided in known E. coli phages. Likewise, PAM sequences are not avoided in Streptococcus thermophilus phages, indicating that CRISPR/Cas systems may not have been a strong factor in shaping host-virus interactions. © 2013 Landes Bioscience.


Ruzek D.,Academy of Sciences of the Czech Republic | Yakimenko V.V.,Omsk Research Institute of Natural Foci Infections | Karan L.S.,Central Research Institute of Epidemiology | Tkachev S.E.,Russian Academy of Sciences
The Lancet | Year: 2010

Omsk haemorrhagic fever is an acute viral disease prevalent in some regions of western Siberia in Russia. The symptoms of this disease include fever, headache, nausea, severe muscle pain, cough, and moderately severe haemorrhagic manifestations. A third of patients develop pneumonia, nephrosis, meningitis, or a combination of these complications. The only treatments available are for control of symptoms. No specific vaccine has been developed, although the vaccine against tick-borne encephalitis might provide a degree of protection against Omsk haemorrhagic fever virus. The virus is transmitted mainly by Dermacentor reticulatus ticks, but people are mainly infected after contact with infected muskrats (Ondatra zibethicus). Muskrats are very sensitive to Omsk haemorrhagic fever virus. The introduction of this species to Siberia in the 1930s probably led to viral emergence in this area, which had previously seemed free from the disease. Omsk haemorrhagic fever is, therefore, an example of a human disease that emerged owing to human-mediated disturbance of an ecological niche. We review the biological properties of the virus, and the epidemiological and clinical characteristics of Omsk haemorrhagic fever. © 2010 Elsevier Ltd.


Shubin V.S.,Central Research Institute of Epidemiology | Yurkiev V.A.,Central Research Institute of Epidemiology
Bulletin of Experimental Biology and Medicine | Year: 2013

Cholera toxin induced the appearance of ATPase activity in rabbit small intestinal mucosa. This enzyme significantly differed from other ATPases, including Na+,K+-ATPase and HCO3 --ATPase in the small intestinal epithelium of rabbits, by some properties, in particular, by relation to divalent and monovalent cations and anions, pH optimum, substrate specificity, and inhibitory analysis. © 2013 Springer Science+Business Media New York.


Kravchenko A.V.,Central Research Institute of Epidemiology
Terapevticheskii Arkhiv | Year: 2013

The paper gives the results of international trials of and guidelines for the use of maraviroc, the first CCR5 receptor antagonist, in treatment regimens for HIV-infected patients. The trials have convincingly shown that the maraviroc-containing antiretroviral therapy (ART) regimens are highly effective and safe for R5-tropic HIV-infected patients regardless of previous ART, baseline HIV RNA levels, and CD4+ lymphocyte count. Maraviroc can be recommended for HIV-infected patients who have previously received ART and who have been found to have a R5-tropic virus. The changes in the ART regimen and inclusion of maraviroc may be associated with both an ineffective previous treatment regimen and therapy-induced adverse events. In 2012, Russia's first reagent kit for the determination of HIV tropism was put to tests and registered at the Russian Inspectorate for the Protection of Consumer Rights and Human Welfare.


Platonov A.E.,Central Research Institute of Epidemiology | Karan L.S.,Central Research Institute of Epidemiology | Kolyasnikova N.M.,Central Research Institute of Epidemiology | Makhneva N.A.,Municipal Clinical Hospital No 33 | And 4 more authors.
Emerging Infectious Diseases | Year: 2011

Borrelia miyamotoi is distantly related to B. burgdorferi and transmitted by the same hard-body tick species. We report 46 cases of B. miyamotoi infection in humans and compare the frequency and clinical manifestations of this infection with those caused by B. garinii and B. burgdorferi infection. All 46 patients lived in Russia and had influenzalike illness with fever as high as 39.5°C; relapsing febrile illness occurred in 5 (11%) and erythema migrans in 4 (9%). In Russia, the rate of B. miyamotoi infection in Ixodes persulcatus ticks was 1%-16%, similar to rates in I. ricinus ticks in western Europe and I. scapularis ticks in the United States. B. miyamotoi infection may cause relapsing fever and Lyme disease-like symptoms throughout the Holarctic region of the world because of the widespread prevalence of this pathogen in its ixodid tick vectors.


Fokina E.G.,Central Research Institute of Epidemiology
Terapevticheskii Arkhiv | Year: 2014

Aim: to establish the features of clinical and laboratory changes in facial erysipelas in relation to its form. Subjects and methods: Twenty-three patients (15 women and 8 men) aged 31 to 78 years who were diagnosed with moderate facial erysipelas, primary facial erysipelas being present in 91 % of cases were examined. The investigators studied the biochemical substrates and enzymes and composition of proteins in the serum by an electrophoretic method, the aggregation activity of red blood cells and platelets, plasma hemostasis (a coagulogram, levels of fibrinogen, antithrombin III, and D-dimer), and von Willebrand factor, a marker of vessel wall injury, on hospital admission at disease onset (days 1-3), over time (days A-6, 7-9), and in convalescence (days 10-12), by obligatorily using control materials. Conclusion: Bleeding disorders in facial erysipelas correspond to the vasculite purpuric type of hemorrhagic diathesis (according to the classification developed by Z.S. Barkagan) with the laboratory signs of evolving disseminated intravascular coagulation: impairments in erythrocyte hemostasis and blood vessel endothelium. The changes in the functional properties of red blood cells match with the suppression of metabolic processes. And if the neuraminidase effect of B-hemolytic streptococcus is shown at the level of the red blood cell membrane, the activity of NADase blocks processes in the entire macroenergetics. In the presence of a high fever reaction, the low levels of transaminases (aspartate aminotransferase, alanine aminotransferase) and membrane enzymes (alkaline phosphatase, creatinine phosphokinase) decrease the detoxification capacities of serum and increase a load on blood albumin and erythrocyte barriers. Rapid normalization of C-reactive protein levels enables one to use this simple and highly sensitive test to monitor the involution of erysipelatous inflammation and the efficiency of treatment. The changes in the hemostatic system and metabolic tests are less pronounced in patients with facial erysipelas than in those with lower-extremity erysipelas.


Pokrovsky V.V.,Central Research Institute of Epidemiology
Terapevticheskii Arkhiv | Year: 2014

In 2013, 80,000 new cases of infection caused by human immunodeficiency virus (HIV) (HIV infection) were registered in Russia; there have been a total of as many as 850,000 notified HIV-infected cases in this country, which suggests that the HIV/AIDS epidemic becomes generalized. Of them, 150,000 people have died, most (22,000) cases in 2013, predominantly due to the late diagnosis of HIV infection and its delayed treatment initiation. The rise of new cases denotes that counteraction against the spread of HIV is inadequately effective; in this connection a further increase in morbidity and mortality rates should be forthcoming. However, the medical community has proved to be poorly trained to fight the epidemic; there is a lower awareness i and knowledge about HIV infection among healthcare workers. To overcome the epidemic and its imminent negative implications, it is necessary to improve an epidemiological surveillance; system, to introduce proven effective methods for the prevention of the disease, to increase patient access to current treatments, which will require not only higher direct expenditures on preventive measures, the creation of an infrastructure, and the purchase of medicaments and diagnostic agents, but also on the training and retraining of a large number of healthcare workers.


Tkachenko L.I.,Stavropol State Medical University | Maleev V.V.,Central Research Institute of Epidemiology
Terapevticheskii Arkhiv | Year: 2014

Aim: To assess the relationship of different components of metabolic syndrome (MS), viral load, and HBeAg status to the risk for cirrhosis of the liver in patients with chronic hepatitis B (CHB). Subjects and methods: Fifty-three patients with CHB were examined according to the conventional criteria for patients with chronic hepatitis (the 2012 EASL guidelines). Analysis is made in relation to the degree of liver fibrosis (LF), the presence of MS, abdominal obesity, and insulin resistance (IR) Results: MS was detected in 22.6% of the patients with CHB. The duration of the latter in MS was noted to be longer; the patients with MS were accordingly older than those without MS. The patients of this category were significantly more frequently observed to have type 2 diabetes mellitus (DM2), and IR, hepatic steatosis, and >3 METAVIR scores for LF, and elevated activity of hepatic enzymes (alanine aminotransferase, aspartate aminotransferase). Marked LF was associated with a high viral load, obesity, DM2, patient age, and MS. The patients with MS showed a higher activity of hepatic enzymes than those with abdominal obesity without MS Conclusion: The percentage of CHB patients with MS increases with disease duration and patient age. High viral load, disease duration, MS, obesity, and DM2 are associated with score >3 METAVIR scores for significant LF © 2014.

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