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Journal Infectology

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Vol 8, No 3 (2016)
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Problem article

5-27 1542
Abstract

For the first time in a long time period the sources of actual information about anthrax in Russia and in the world are systematized. The essence of the problem, features of epidemiology and clinical manifestations of the current forms of anthrax disease are analyzed. The upgraded classification of anthrax is presented, the clinical manifestations of oro-oropharyngeal varieties of intestinal form and injectable form of anthrax are described, according to extensive literature data and international guidelines and recommendations. The recommendations for clinical management of patients and diagnosis of disease are given. The need for strict compliance to the vaccination requirements of anthrax among animals and persons from risk groups is proven.

Lectures

28-39 1092
Abstract

Infective myocarditis can be considered as a case of myocardial damage caused by different infectious agents. Traditionally discusses the questions of diagnostics and treatment infectious myocarditis. The paper has repeatedly stressed the difficulty of clinical diagnosis, and the laboriousness and economic costs of laboratory tests and additional researches. Endomyocardial biopsy findings remain the gold standard for unequivocally establishing the diagnosis. However, it is technically extremely invasive test and can be performed only in specialized cardiology centers. The paper analyzes in detail not only own materials, but also results of researches published in numerous domestic and foreign sources of literature. Publication of «Infectious myocarditis» is necessary due to the fact that patients with a diagnosis of «Myocarditis » account for 11% of all cardiovascular disease in the world. Article is timely and necessary for many professionals, senior students of medical universities.

Original Research

40-45 975
Abstract

In recent years, in Russia we found growing number of mycobacteriosis caused by nontuberculous mycobacteria in patients with HIV infection. The aim of this study was to evaluate dynamics of the detection of MAC-infection in HIVinfected patients in St. Petersburg and conduct the clinical and laboratory characteristics of them. To accomplish the task, carried out a retrospective analysis of 94 patients with HIV and mycobacteriosis treated in City TB Hospital №2 of St. Petersburg in 2004–2015 years. Mycobacteriosis cases were recorded in patients with advanced HIV disease who were not receiving HAART. High level of social adaptation of patients with mycobacteriosis (HIV infection mainly through sexual contact, low frequency of the active drug using, high level of employment, low level of imprisonment history). The clinical features was symptoms of intoxication, diarrheal syndrome. X-ray examination of chest demonstrated an increase in mediastinal lymph nodes at the scarcity of dissemination in lung tissue. In the laboratory attracted attention the presence of severe anemia and increase markers of cholestasis (GGT and alkaline phosphatase).

46-52 1875
Abstract

The aim of the study was to assess the clinical and immunological efficacy of recombinant interferon Alfa-2b. Examined 34 children aged from 1 year to 7 years carrying medium to heavy degree of measles. All patients were not vaccinated against measles. In the treatment of 18 people (Control group) were used only basic therapy (pathogenic, symptomatic). At 16 people (Study group) used a combination therapy (basic + Viferon). As an antiviral agent used and immunotropic preparation of human recombinant interferon alfa-2b in the form of rectal suppositories – Viferon (OOO «Feron», Russia). Immunological patient survey was conducted in the dynamics of the disease – during the height (in 1-6 days the rash) and in convalescence period (10-16 days rash). Indicators of cellular immunity (leukocytes, lymphocytes, CD3 +, CD3 + CD (16 + 56) +, CD3 + CD4 +, CD3 + CD8 +, CD4 + CD8 +, CD3-CD8 +, CD3-CD (16 + 56), CD19 +, CD25 +, CD3 + HLA DR +, CD (16 + 56) + HLA DR +, HLA DR +, CD95 +) were evaluated by flow cytometry. To assess the production of IFN-α and IFN-γ in the samples of peripheral blood were cultured in the CO2 incubator for 18 hours at 37 C and 4% CO2. The supernatants of cell culture were investigated with the purpose of studying spontaneous and induced production of interferon alpha and gamma. The concentrations of interferon α and γ (IFNα, IFNγ) in the blood serum, as well as levels of spontaneous and induced cytokine production data of blood cells of sick children was determined by ELISA. All the children at the peak of the disease found a dramatic inhibition of cellular immunity and the production of cytokines, which is consistent with the concept of «measles anergy» accepted in the scientific literature. The period of convalescence oppression immunity indices remained, but it was less pronounced in the group of children treated with the drug of human recombinant interferon alfa-2b -Viferon. Clinical efficacy of Viferon in the treatment of patients with measles children characterized by rapid positive dynamics of symptoms of acute period (normalization of body temperature, reducing intoxication, catarrhal symptoms and severity of the syndrome exanthema). It was also found reduction in the incidence of complications, reduction in the average bedday and smooth during the period of convalescence later.

53-58 753
Abstract

Aim of our work was to evaluate the prognostic value of brainstem auditory evoked potentials (BAEPs) for the recovery period outcomes in children with acute bacterial meningitis.

Methods. 65 patients with acute bacterial meningitis (average age 3 years, range 3 months-17 years) and 20 healthy controls of comparable age were evaluated with BAEPs. I-V and III-V intervals, amplitudes of the III and V peaks were registered and analyzed. During the recovery period prolonged neurologic observation was performed for the period of 1-6 years. Severe ataxia, pareses, symptomatic epilepsy, speech disturbances and intellectual impairments were regarded as signs of psycho neurologic deficit. ROC-analysis was performed to evaluate sensitivity and specificity of BAEPs parameters in predicting the occurrence of these signs.

Results. There were statistically significant difference between the groups on the parameters of I-V interpeak interval and amplitudes of III and V peaks. ROC-analysis revealed that I-III, I-V interpeak intervals and amplitudes of III and V peaks were sensitive and specific in the predicting of the psycho neurologic deficit in the recovery period. Thus, these parameters may be used as a prognostic tool for predicting of such outcomes in acute meningitis in children.

59-65 1105
Abstract

Participation of hormones in maintaining immune homeostasis is a complicated process as the hormones can have both immunomodulatory and immunosuppressive effect. Changes in the hypothalamic-pituitary-thyroid axis in diseases may appear low triiodothyronine, and is currently being discussed the issue of the state of development, characterized by a decrease in blood levels of thyroid hormone in the absence of pathology of the thyroid gland. In the literature there is the term - (nonthyroidal illness syndrome) «netireoidnyh disease syndrome.» One of the most debated issues related to the pathogenesis of diseases netireoidnyh syndrome - this is the role of proinflammatory cytokines in violation of the secretory activity of the thyroid gland and the hypothalamus-pituitary-thyroid axis in general. However, the exact mechanisms for reducing serum triiodothyronine remain poorly studied, including thyroid status and relationship with objective criteria systemic inflammation in children, especially during viral infection. The paper presents the materials and the results of an open prospective study conducted in the city of Yekaterinburg in 2009-2012. We observed 71 children with enteroviral meningitis at the age of three to fourteen. We studied the levels of thyroid-stimulating hormone, triiodothyronine, thyroxine and intracellular cytokine synthesis in blood lymphocytes. The nature of changes in hormonal status in children with enteroviral meningitis can be treated as a syndrome netireoidnyh diseases. Low level of triiodothyronine correlates with the time of CSF readjustment and control pleocytosis indicators, more long-term liquor rehabilitation is mentioned in children with low initial level of triiodothyronine, the odds ratio (OR = 7,3, 95% CI 0,9: 6,7). This syndrome is secondary and occurs as the result of cytokine system on the thyroid gland exposure.

66-74 775
Abstract

The aim of our study was the analysis of morbidity and clinical couse of tularemia in Khanty-Mansiysk autonomous District – Ugra for the period 2007–2015 timeframe. The highest incidence of tularemia in the Khanty-Mansiysk noted in the year 2013 (1036.6 о/0000), mainly urban residents (91%). The proportion of children among the sick (1005 people) accounted for 16%. Reviewed the clinical manifestations of tularemia among hospitalized children in 62 children’s infection Department for the period from 19 August to September 3, 2013 year ranging in age from 2 months to 18 years. The dominant clinical form of tularemia (98%) diagnosed ulceroglandular, easy (18%) and moderate (82%). The main clinical manifestations of tularemia in children was a triad of symptoms: ulcer of skin, fever, and lymphadenitis. Dominated femoral and inguinal lymphadenitis (55%), and in the head and neck region (29%), somewhat less frequently axillary (16%) Ultrasonography of lymph nodes with color Doppler mapping (Colour Doppler Imaging – CDI) allows you to assess the dynamics of the process and identify the presence of abscedirovania (5% of cases). 77% of cases have highlighted the febrile fever (39-40ºС), lasting an average of 4,0 ± 0,28 days. 26% of children noted chills, pain in muscles, joints and bones, weakness, loss of appetite, 24% there was a rash all over the body surface, 35% of patients have appeared anemia, 18% of patients have proteinuria was observed (up to 1 g/l), the presence of acetone and ketone bodies in the urine. At 94% of children with tularemia detected blood inflammatory changes in the form of moderate Leukocytosis, increased erythrocyte sedimentation rate, an increase in the level of c-reactive protein. Shows the high efficiency of treatment with an antibiotic in children of tularemia aminoglycoside-amikacin. Are 2 clinical observation.

75-82 951
Abstract

In prospective multicenter study were included 20 pediatriconcohematologic patients with mucormycosis. Age: 3 – 17 yy (median – 11), females – 60%. The diagnosiswas made according to EORTC/MSG 2008 criteria (post mortem – 25%). The main underlying disease was acutel eukemia (70%), risk factors – prolong severe neutropenia (median – 31 d) and lymphocytopenia (median – 33 d) after cytostatic chemotherapy or hematopoietic stem cells transplantation. Etiology agents were Lichtheimia corуmbifera, Rhizopus spp. and Rhizomucor spp. Main sites of infection were lungs (65%) and paranasal synuses (30%), dissemination – 45%. Antifungal therapy (amphotericin B lipid coplex, posaconazole, caspofungin, amphotericin B) was used in 75% patients, surgery – 30%. Overall mortality in 12 weeks was 70%.

83-91 753
Abstract

The aim. To analyse the morbidity of the enterovirus infection (EI) in Novokuznetsk – the major industrial city of Western Siberia and to determine the clinical peculiarities of enterovirus meningitis (EM) in the outbreak period in 2015.

The materials and methods. There have been analysed the official statistical data in the period of 2006–2015 and the enterovirus meningitis, clinical manifestations in 148 patients, hospitalized in 2015. Liquor was tested by the method of the polymerase chain reaction (PCR) for presence RNA of the enteroviruses. The C-reactive protein value was tested by the method of the latex test and the procalcitonin value was tested by the method of the immunoenzymatic analysis. The statistical material treatment has been done using InStat programme.

The results. There has been registered 3,2 times growth of the enterovirus infection morbidity in 2015, compared to 2014, which 6,2 times exceeds Russia, s average rate. The enteroviruses ECHO 30 have been identified in patients, biological material and in wastewater. In the structure of the clinical forms the share of the enterovirus meningitis makes 92, 91%. The children, s morbidity 4,57 times exceeds the total burden of disease. The age structure accompanying the enterovirus meningitis: children 2–6 years of age – 47,3%, 7–14 years of age – 27,7%, 15–17 years of age – 7,43%, 18–53 years of age – 17,57%. Vomiting and headache in children (under the age of 7) are registered rarely, and the full meningeal syndrome and the neutrophil pleocytosis in liquor in children (under the age of 7) are registered more frequently. The rate of children and adults has increased in 2015, compared to 2005. The alteration in clinical picture relates to degree of meningeal syndrome intensity and catarrhal manifestations. The C-reactive protein value (in 67,21%) and the procalcitonin value (in 100%) don, t exceed the threshold values in patients with leucocytosis and pleocytosis of liquor with neutrophil/mixed character, which enables to differentiate enterovirus meningitis from bacterial meningitis and to exclude antibiotic treatment.

The conclusion. The dynamics of the rate of the enterovirus infection morbidity on the territory under investigation differs from Russia, s average rate. The enterovirus meningitis has got clinical and age peculiarities in different epidemic seasons.

92-98 828
Abstract

The objective: to analyze the experience of use of cepeginterferon
alfa-2b and ribavirin in patients with chronic hepatitis C genotypes 2 and 3 in clinical practice, to evaluate the efficacy, safety and tolerability of this treatment regimen.

Materials and methods. From 2013 to 2016 a total of 73 patients with chronic hepatitis C (CHC) received antiviral therapy with cepeginterferon alfa 2b (cePEG-IFN alfa-2b) and ribavirin in the Center for Gastroenterology and Hepatology of FSBE «Vishnevsky Third Military Clinical Hospital» of Russian Ministry of Defence. Treatment efficacy was assessed by the rate of sustained virologic response (SVR) on 24 week after completion of antiviral therapy. All cases of deterioration of the patient’s condition and laboratory abnormalities were registered throughout the treatment period and follow up. Severity of adverse events was assessed in accordance with the classification of CTCAE (Common Terminology 
Criteria for Adverse Events).

Results. 73 CHC patients genotype 2/3 received cePEGIFN alfa-2b 1.5 μg/kg/week and ribavirin 800-1400 mg/day based on body weight for 24 weeks. SVR 24 was registered in 94,7% (n=54) of patients with HCV genotype 3 and in 93,7% (n =15) patients with genotype 2. During the first 12 weeks of therapy the normalization of serum transaminase activities was registered. All adverse events were typical for interferon/ribavirin treatment regimen.

Conclusion. According to our data the use of double treatment regimen (CePEG-IFN alfa-2b and ribavirin) is reasonable in patients who don’t have negative predictive factors of response to IFN-based therapy. The SVR rate in this group of patients was 94.5%.

99-106 805
Abstract

Aim: To study the epidemiological patterns of invasive meningococcal disease in Novosibirsk region within a time 
period from 1992 to 2015.

Methods: retrospective comparative epidemiological analysis.

Results: During the analyzed period the annual incidence rate of invasive meningococcal disease was higher than average annual incidence rate in Russian Federation. Totally1690 cases were registered, average incidence rate for the period 2000–2015 was 2,2/100,000 exceeding the neighbor regions. The incidence had a tendency to continually decline and is characterized by the cyclical fluctuations with period of 4-7 years. Majority of cases occurred in children < 14 years, varying from 77,3% in 2001 to 57,8% in 2008. The highest incidence was registered in children <12 month reaching 124/100,000 of population in 2003. The increase of mortality correlated with the decrease of incidence, average mortality for period 1992–2015 was 11,4%. In etiologic structure serogroup B is predominant – 40,9%, serogrup A – 20,6%, serogrup C – 14,7%. The distinctiveness of epidemiology is cyclic dynamics with the periods of predominance of serogroup A (up to 48% in 2014). In serum analysis performed 2012 45% of probes were positive for serogroup A what demonstrates circulation of this serogoup among population.

Conclusion: High incidence among children <14 years and especially among children <12 month in emerging risk of the forthcoming rise in incidence of meningococcal disease and insufficient surveillance provide need in activation of tactics of specific immuneprophylactics. 

107-115 1493
Abstract

Objective. To study the clinical manifestations of CNS lesions caused by different factors in patients with HIV disease progression.

Materials and methods. The study involved 128 ART naïve HIV patients with CD4 cell counts <350 cells/mcL. These patients were divided into two groups: Group 1 (main group) consisted of 63 patients with clinical features of CNS involvement and Group 2 (control group) consisted with 65 patients without clinical features of CNS involvement (65). We analyzed the data of clinical, laboratory and instrumental parameters and neuropsychiatric status.

Results. In the main study group the most commonly diagnosed
CNS disorders were HIV encephalitis in 29 cases (46.0%), cerebral toxoplasmosis in 18 cases (28,6%); fungal infection of the CNS in 10 cases (17,2%), HSV infection in 14 cases (22%). In 28,6% of cases CNS lesions were caused by mixed infection. On average, the CSF HIV RNA level in the main group was 13,2 times higher than in the control group. The HIV RNA levels were higher in plasma than CSF.

Conclusion: We determined the most common causes of CNS involvement in HIV patients (HIV, toxoplasmosis, fungal infections, HSV). This study shows the feasibility of CSF testing for HIV RNA load and opportunistic infections in HIV patients with advanced immunosuppression.

Pharmacoeconomics

116-121 751
Abstract

The human papillomavirus (HPV) infection is one of the major risk factor of development of genital warts, a cervical dysplasia, a cervical cancer, and also some other oncologic diseases. The usage of quadrivalent HPV vaccine in girls reduces the corresponding case rate and the mortality significantly.

The objective of this study is to analyze the cost-effectiveness of quadrivalent HPV vaccination cases of 12-yearold girls in Russian Federation.

Materials and methods. A Markov model is used on the basis of epidemiological data in Russian Federation. The cost-effectiveness was estimated from societal perspective. We assumed that the effect of vaccination remains throughout all life. The analysis is performed for survival of 12-year-old girls. We considered only effect in the vaccinated population. Costs for therapy of the diseases associated with HPV infection corresponded to compulsory health insurance rates across St. Petersburg for 2016. Costs and life expectancy have been discounted for 3,5% a year.

Results. Quadrivalent HPV vaccination of 12-year-old girls in Russian Federation will allow to prevent counting on 10000 the vaccinated persons 293 cases of genital warts, 15 cases of pre invasive cervical cancer, 81 cases of invasive cervical cancer, 6 cases of vulvar cancer, 2 cases of vaginal cancer, 2 cases of anal cancer, 1 case of oropharyngeal cancer. In general, 49 cases of death caused by HPV infection on 10000 vaccinated girls would be prevented. The vaccination will provide cost reduction, caused by HPV-associated diseases, for 68% (58,38 million rubles on 10000 vaccinated), and 96% of the predicted prevented costs will be caused by decrease in incidence of cervical cancer. The quadrivalent HPV vaccination is associated with an incremental cost-effectiveness ratio (ICER) of 172 000 rubles per quality adjusted life-year (QALY) and 411 300 rubles per death caused by HPV-associated diseases.

Conclusions. Quadrivalent HPV vaccination of girls prior to the beginning of sex life could be considered in Russian Federation as an economically highly effective technology for preventing HPV-associated diseases.

122-125 664
Abstract

In the treatment of chronic hepatitis C (CHC) protease inhibitors (PI) are actively used. The aim of this analysis was to evaluate the cost-effectiveness of narlaprevir and simeprevir in the CHC (genotype 1) therapy in treatment-naïve patients and relapsers.

Material and methods. Analysis of the cost-effectiveness of simeprevir and narlaprevir was conducted from the perspective of the health care system based on QUEST-1, QUEST-2, ASPIRE and PIONEER clinical trials. The relative risk of achieving SVR 24 compared to the peg-INF + RBV therapy was used in the model. Treatment discontinuation in patients receiving narlaprevir assumed in the absence of a SVR after 12 weeks and in patients receiving simeprevir in the SVR absence after 4 weeks. The cost of narlaprevir was calculated on the basis of estimated registration price in case of EDL inclusion, including VAT. Costs of other antiviral drugs were in line with the results of 2016 average auctions prices.

Results. In the base case costs on antiviral drugs with narlaprevir as therapy are lower compared with simeprevir by 37,3 % (542,0 and 864,6 thousand rur, respectively), and the cost per patient with SVR 24 by 34,5%. In patients after relapse costs on antiviral drugs with narlaprevir as first-line therapy will decrease compared with simeprevir by 22,8% (542,0 and 702,5 thousand rur, respectively), and the cost per patient with SVR 24 by 41,3%. The sensitivity analysis demonstrated a high reliability of obtained results.

Conclusions. With comparable clinical efficacy and tolerability of narlaprevir and simeprevir both in treatment-naïve patients and patients with relapse after therapy, which included pegylated interferon and ribavirin, narlaprevir reduces the burden on the budget.

Clinical Case

Chronicle

 
130-138 450


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ISSN 2072-6732 (Print)