Vol 88, No 11 (2016)


Acquired immunodeficiency syndrome in Russia

Pokrovsky V.V.


In 2015, the infection caused by human immunodeficiency virus (HIV) (HIV infection) dominated among life-threatening infections in Russians: it was first diagnosed in 98,177 Russians and 15,530 citizens of the Russian Federation died from HIV/AIDS, amounting to 45% of all deaths from infectious diseases in Russia. By the mid-2016, there were a total of 1,062,476 identified HIV-positive Russians, of whom 225,992 people died. The estimated number of HIV-infected patients in Russia approximated to 1% of the population, the highest prevalence of HIV being found in the age group of 30—40 years. The most active and expensive measures against HIV/AIDS in Russia are to examine the population for anti-HIV antibodies (29 million screenings per year) and to use in HIV-positive people antiretroviral therapy that was free of charge to more than 200,000 patients, i.e. nearly 25% of the registered Russians living with the HIV-infected. However, treatment coverage and quality are far from the target indicators that the international experts consider needed to reduce HIV prevalence and mortality. A wider program on HIV/AIDS, which includes a number of preventive measures with proven efficiency, as well as a program of promising researches and developments should be introduced in Russia.
Terapevticheskii arkhiv. 2016;88(11):4-11
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The sociodemographic portrait of a patient living with HIV and visiting AIDS centers in Russia

Pokrovskaya A.V., Kozyrina N.V., Gushchina Y.S., Yurin O.G., Suvorova Z.K., Pokrovsky V.V.


Aim. To study the sociodemographic data of people living with HIV who visit AIDS centers. Subjects and methods. A multicenter open-label study was conducted, which included the retrospective model “A patient’s portrait”. Outpatient records and questionnaires were analyzed in 7,000 patients older than 18 years of age who had visited AIDS centers in 27 regions of Russia from 1 April to 31 July 2014 and signed their informed consent form to participate in the study. Results. There were women accounting for 49% of the study participants, including one transgender. Their mean age was 35.6 years; the median age was 34 (18-79) years. 77.4% of the women were infected sexually; 57.4% of the men were infected parenterally; the men who had sex with men accounted for 2.5% of the whole group (4.7% among the men). Only 9.8% of the respondents reported that they had used intravenous drugs in the past 6 months. 87.8% of the respondents had secondary and higher education; 68.6% of the patients (73% were male and 64% were female) were employed; 59.3% of the respondents were married or cohabited; 66.2% of the patients reported that they had had sexual contacts with one partner, 14.2% had not had sexual intercourses. 38.3% of the women and 48.8% of the men had a permanent HIV-negative sexual partner. 46% of the study participants had dependent minor children. 30% of the women had given birth to at least one child after the diagnosis of HIV infection. Conclusion. People living with HIV in Russia and visiting AIDS centers do not differ in main social and demographic indicators from the Russian Federation citizens of the same age who do not have HIV. They represent an economically and socially active population and participate in demographic processes so one of the public health priorities is to maintain and improve their quality of life.
Terapevticheskii arkhiv. 2016;88(11):12-16
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Evaluation of the pro- and antioxidant status of women with HIV or coinfection

Kolesnikova L.I., Kolesnikov S.I., Darenskaya M.A., Grebenkina L.A., Timofeeva E.V., Leshchenko O.Y., Vanteeva O.A., Rashidova M.A.


Aim. To reveal the specific features of changes in the parameters of lipid peroxidation – antioxidant defense and the status of the reproductive system in women of fertile age with monoinfection (HIV) or coinfection (HIV and hepatitis B and/or C). Subjects and methods. 81 reproductive-aged women were examined and divided into 3 groups: 1) 28 apparently healthy women (controls); 2) 26 patients with HIV monoinfection; and 3) 27 patients with HIV coinfection (HIV + hepatitis B and/or C) who had not previously received antiretroviral therapy. Results. The HIV coinfection group showed the higher values of primary (conjugated dienes) and secondary (ketodienes and conjugated trienes) lipid peroxidation products in the presence of lower superoxide dismutase activity and obvious α-tocopherol deficiency than the control and HIV monoinfection groups. HIV coinfection in reproductive-aged women was accompanied by the high frequency of luteal phase deficiency. Conclusion. HIV coinfection is characterized by a more pronounced oxidative stress, antioxidant factor deficiency, and the high frequency of luteal phase deficiency in the patients.
Terapevticheskii arkhiv. 2016;88(11):17-21
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Causes of T lymphocyte activation in HIV-infected patients coinfected with hepatitis C virus

Shmagel K.V., Shmagel N.G., Korolevskaya L.B., Saydakova E.V., Chereshnev V.A.


Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.
Terapevticheskii arkhiv. 2016;88(11):22-28
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Insulin resistance and chronic hepatitis C

Tkachenko L.I., Maleev V.V.


Aim. To estimate the spread of insulin resistance (IR) in patients with chronic hepatitis C (CHC) and to define the role of IR in the development of hepatic steatosis (HS) and in the progression of liver fibrosis (LF), as well as the impact of IR on the results of antiviral therapy (AVT). Subjects and methods. A total of 211 patients with CHC were examined. A comparison group consisted of 75 patients with chronic hepatitis B (CHB). The patients were divided according to the presence and absence of IR and type 2 diabetes mellitus (DM). IR was analyzed in patients with CHC with a body mass index (BMI) of <25 kg/m2 and with the initial manifestations of LF. Results. In the patients with CHC, IR without DM was 1.7-fold more common and type 2 DM was 2.6 times more frequently seen than in those with CHB. The highest biochemical activity, subclinical inflammation (as evaluated from ferritin and C-reactive protein levels), and an advanced LF stage were noted in the presence of IR and type DM. IR and type 2 DM were associated with metabolic syndrome and its individual components and with no response to AVT. When the BMI was <25 kg/m2, HS, inadequate 25(OH)D provision, an advanced LF stage, and slowly progressive inflammation were related to IR. In the presence of the initial manifestations of fibrosis, IR was associated with obesity, HS, 25(OH)D deficiency, a rise in C-reactive protein greater than 3 mg/l, and no response to AVT. Conclusion. The presence of IR in CHC patients with a BMI of <25 kg/m2 and with the initial manifestations of LF and the association of IR with HS and an advanced LF stage necessitate an examination of all patients with CHC in an effort to identify IR and to perform active therapy of detected abnormalities.
Terapevticheskii arkhiv. 2016;88(11):29-36
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Assessment of awareness about the epidemiology, outcomes, and therapy of chronic hepatitis B and C in adolescents and adults

Baramzina S.V.


Aim. To estimate the level of knowledge in adults and adolescents about the issues related to viral hepatitis B and C: the transmission modes, course, and outcomes of acute and chronic hepatitis B (CHB) and C (CHC), as well as about current measures for their prevention and treatment. Subjects and methods. A total of 850 dwellers of Kirov and the Kirov Region were anomalously surveyed using an original questionnaire in 2013- 2015. The questionnaire included 24 questions on the etiology, epidemiology, outcomes, prevention, and treatment of CHB and CHC and on the sources of information. Persons younger than 16 years, people who had medical specialties, and those who were studying at a higher or secondary medical institution were excluded from the study. Results. Low levels of knowledge about the epidemiology, course, and outcomes of CHB and CHC were found in the adolescents and adults. 76.4% and 73.9% of the respondents had no clear idea as to the modes and factors of transmission of hepatitis B and C, respectively. A lack of knowledge of the issues associated with poor CHB and CHC outcomes (cirrhosis and hepatocellular carcinoma) was revealed in 84.8 and 76.2%, respectively. 81.8% of the respondents were well aware of the existence and necessity of vaccination against hepatitis B. 40.8% of the survey participants misbelieved that hepatitis C vaccine had been designed and used. Conclusion. A significant portion of the adult population is poorly aware of the problem of viral hepatitis B and C and needs to continue health education for the development and strengthening of a negative attitude towards narcotics and promiscuity; to combat false ideas about viral hepatitis; and enhance motivation for the specific and nonspecific prevention of hepatitis B and C.
Terapevticheskii arkhiv. 2016;88(11):37-42
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Follow-up of patients with Ixodes tick-borne borrelioses caused by Borrelia miyamotoi or Borrelia burgdorferi sensu lato

Bagautdinova L.I., Platonov A.E., Sarksyan D.S., Stukolova O.V., Shipulin G.A., Maleev V.V., Dudarev M.V.


Ixodes tick-borne borrelioses (ITBB) are caused by two different spirochetes: Borrelia from the group of Borrelia burgdorferi sensu lato, the agents of the classic Lyme borreliosis (LB), and Borrelia miyamotoi that belongs to the group of Borrelia causing tick-borne relapsing fevers. ITBB caused by B. miyamotoi (BM-ITBB) is a previously unknown infectious disease discovered in Russia. It is known that the LB sequelae may reduce the long-term life guality of convalescents. Aim. To study the follow-up of those who have recovered from new BM-ITBB infection in comparison with persons who have had LB. Subjects and methods. The investigation enrolled 41 patients with BM-ITBB and 41 patients with LB who were treated at the Republican Infectious Diseases Hospital of Udmurtia. Within a year after the disease, they were followed up through clinical and instrumental examination of cardiac performance, expanded biochemical analysis of blood and urine, which could; estimate kidney and liver functions, and psychological questioning. Results. Asthenic syndrome and complaints about and objective signs of cardiac dysfunctions persisted supraventricular extrasystoles, left ventricular diastolic dysfunction, and elevated and/or unstable systolic blood pressure were detected in 20-30% of the convalescents for a long time. Kidney dysfunctions were manifested in albuminuria and the decrease of glomerular filtration rate. A year following the disease, 10-20% patients had persistently elevated concentrations of alanine aminotransferase, aspartate aminotransferase, and C-reactive protein and had higher levels of total cholesterol and low-density lipoproteins. The pathological consequences of ITBB were polymorphic and varied in different patients; in general, only 68% of them showed health improvement. Conclusion. We assume that a significant role in the pathogenesis of BM-ITBB and LB is played by vascular endothelial damage possibly associated with the inflammatory and autoimmune aspects of an immune response in Borrelia infection. The consequences of this damage may persist and even intensify during a year, which provokes chronic dysfunction of the heart, kidney, or liver in a number of convalescents.
Terapevticheskii arkhiv. 2016;88(11):43-54
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Tick-borne neuroinfections: Clinical characteristics, immunopathogenesis, and new pharmacotherapeutic strategies

Konkova-reidman A.B.


Aim. To study the semiotics of neurological lesions in patients with tick-borne encephalitis, Ixodes tick-borne borreliosis (ITBB) and mixed infection (MI), their immunopathogenesis, and the possibilities of current pathogenetic pharmacological correction. Subjects and methods. A total of 220 patients with tick-borne encephalitis, ITBB, and MI concurrent with the syndromes of central nervous system lesions were examined. The immunological studies encompassed the examination of mononuclear cells in the cerebrospinal fluid (CSF), the population and subpopulation composition of lymphocytes, and nitroxidergic processes in the serum and CSF from the total level of final stable nitric oxide metabolites. For pharmacotherapeutic correction, the metabolic drug cytoflavin was used as newly indicated. Results. Cytofluorometric analysis of the CSF cellular composition showed the mononuclear cell predominance of CD3+ (58.6%), CD4+ (57.2%), CD8+ (16.8%) lymphocytes and monocytes (34.4%), which expressed the phenotypic marker CD14+. This reflects the nature of a local immune response: an increase in the immunoregulatory index CD4+/CD8+ from 3.4 to 5.6, respectively, while the normal proportion of these cells in the blood ranges from 1.5 to 2.2. CSF lymphocytes were found to be ready for Fas-mediated apoptosis dependent on the receptor (CD95+ was 64.3%).There was a correlation using the pair correlation coefficient between the total concentration of the metabolites of the nitroxide molecule and the percentage of CD14+ (r=0.5; p<0.05). The paired Wilcoxon test was used to analyze serum NO2, NO3, and NOx, which revealed significant differences in nitrites [2.70 (1.90, 2.95; p=0.001)] and total NO metabolites [18.00 (18.00, 22.60; p=0.006)] and statistically significant changes in nitrates [13.29 (15.70. 20.30; p=0.075)] in patients receiving cytoflavin infusions. Conclusion. The immune response of Th-1 forms between the CSF phagocytic, antigen-presenting, and immunocompetent lymphocytes in patients with tick-borne neuroinfections. The use of cytoflavin as an agent for neurotransmitter support to correct nitroxidergic processes is pathogenetically justified.
Terapevticheskii arkhiv. 2016;88(11):55-61
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Infective endocarditis: Importance of molecular biological techniques in etiological diagnosis

Kotova E.O., Domonova E.A., Karaulova Y.L., Milto A.S., Pisaryuk A.S., Silveistrova O.Y., Shipulina O.Y., Shipulin G.A., Moiseev V.S.


Aim. To investigate the specific features of conventional bacteriological methods and current molecular biological techniques for the etiological diagnosis of infective endocarditis (IE). Subjects and methods. Examinations were made in 53 patients treated at City Clinical Hospital Sixty-Four, Moscow Healthcare Department, in 2012—2015 who underwent simultaneous bacteriological and molecular biological (polymerase chain reaction (PCR) or PCR with further sequencing) examinations of blood or resected cardiac valve tissues. Results. The investigation included 53 patients (31 men; median age, 62 years) with IE (Duke 2009); its primary form was observed in 32 (60.4%) patients. Blood bacteriological tests and PCR assays were positive in 28 (52.8%) and 34 (64.2%) patients, respectively. There were concordant results in 21 of the 28 positive blood culture cases and discordant results in 7 (25%); at the same time 3 cases showed a compete discordance in the detected causative agents (the growth of Enterococcus spp. was revealed by bacteriological examination and that of Staphylococcus spp., Streptococcus spp., and Escherichia coli by DNA PCR) and a pathogen could not be identified by DNA PCR in 4 patients who had positive blood bacteriological results. The positive PCR results for cocci and fungi were obtained in 10 of the 25 (47.2%) examinees with culture-negative IE. Rare causative agents were not revealed. The tissues obtained from 8 resected damaged heart valves displayed a wider spectrum of pathogens than did blood samples, which was associated with the formation of bacterial films. Conclusion. The etiological agent of IE was revealed in venous blood by bacteriological examination in 52.8% of the examinees, by PCR in 64.2%, and by either in 71.7%. There were concordant and discordant results in 67.9 and 32.1% of the patients, respectively; among whom 18.9% were found to have pathogen DNA revealed by PCR in culture-negative IE.
Terapevticheskii arkhiv. 2016;88(11):62-67
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Treatment for acute respiratory viral infection and influenza in daily clinical practice: Results of the multicenter international observational FLU-EE study

Fazylov V.K., Sitnikov I.G., Silina E.V., Shevchenko S.B., Mozhina L.N., Zamyatina L.L., Yeganyan G.A., Groppa L.G., Korsantia B.M.


Purpose: To study the clinical aspects of influenza and acute respiratory viral infection (ARVI) in routine clinical practice, with efficacy and safety of the antiviral therapy evaluation. Subjects and methods: In the large multicenter prospective observational study were enrolled 18,946 patients aged 18 to 93 years with previously determined diagnosis of influenza or ARVI from 262 outpatient sites in Russia, Armenia, Moldova and Georgia. According to study design, 3 visits were evaluated. On each visit the detailed medical examination, determination of individual symptoms’ severity and course of disease were made. The dynamic evaluation of prescribed in routine clinical practice therapy of influenza and ARVI and cases of disease exacerbations with antibiotics concomitant therapy were assessed. Results: For the first time in outpatient practice on a large population of adult patients the objective data were obtained and analyzed. This data relating to the timing of access to medical care of patients with influenza and ARVI depending on the age and the disease severity, dynamics of clinical picture of the disease, their outcomes, timing recovery, as well as ongoing drug therapy of ARVI and influenza, allowed to identify patterns of development and course of these diseases. The effectiveness and safety of antiviral drug Kagocel for treatment of ARVI and influenza was shown. This is reflected in the improvement of the clinical picture of the disease; reducing the number of patients with exacerbations, requiring the prescription of systemic antibiotics up to 1.5 times; the acceleration of regression of symptoms and recovery periods. Conclusion: This study allows increase the level of objective assessment of the beginning and course of influenza and other ARVIs in outpatient practice, to predict their course and outcome, and to improve the treatment
Terapevticheskii arkhiv. 2016;88(11):68-75
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Acute respiratory viral infections: Topical issues of diagnosis, prevention and treatment in therapeutic practice

Trukhan D.I., Mazurov A.L., Rechapova L.A.


Objective: to assess the efficacy and safety of the medication Grippferon with loratadine for the prevention of acute respiratory viral infections (ARVI) and influenza during the epidemics. Materials and methods: This study included 103 patients (67 men and 36 women) aged 18 to 52 years (mean age 35.3±3.2 years). During the first visit (september 2015), we collected patient history data on the average rate of ARVI and influenza for the past three years, the disease duration and its symptoms, presence of concomitant allergic pathologies (such as vasomotor rhinitis, hay fever and urticaria) and food allergies. Appropriate recommendations for the medication use were given to patients. During the second visit (may 2016), we collected follow-up cards and then analyzed the findings. Results: 33 percent of the patients were fully compliant with the medication dosage regimen. In the first group (68 people with a history of one-two ARVI cases in the autumn-winter period for the past three years) the average number of ARVI cases in previous years was 1,53±0,23, by comparing with 0,69±0,16 (p<0.01) during the follow-up period, when medication Grippferon with loratadine was used. No ARVI cases were noted in 21 patients. In the second group (35 people with a history of three or more ARVI cases for the past three years) the average number of ARVI cases in previous years was 3,69±0,29, by comparing with 2,49±0,22 (p<0.05) during the follow-up period, when nasal ointment Grippferon with loratadine was applied. Two people reported that they did not have ARVI. We noted a positive ARVI symptoms dynamics in patients, who received treatment with the given medication. Specifically, a reduced duration of fever and intoxication periods as well as decreased catarrhal symptoms in the nasopharynx and oropharynx were observed. Conclusion. The results of our study allow us to consider a new combined medication Grippferon with loratadine (nasal ointment) as an effective and safe medication for the prevention and treatment of influenza and acute respiratory viral infections in the complex therapy in adult patients, including patients with allergic history.
Terapevticheskii arkhiv. 2016;88(11):76-82
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Evaluation of the pharmacoeconomic efficacy of prestance in the treatment of hypertensive patients on the basis of the results of the POTENTIAL program

Dyakov I.N., Glezer M.G.


Aim. To pharmacoeconomically estimate the use of a fixed-dose combination of perindopril and amlodipine in the treatment of hypertensive patients. Materials and methods. A pharmacoeconomic study was conducted on the basis of the Russian postmarketing observational open program POTENTIAL, which included the estimation of direct and indirect costs associated with the addition of a fixed-dose combination of perindopril and amlodipine to conventional therapy for hypertension in patients who had not achieved adequate blood pressure (BP) control. Cost-difference, cost-effectiveness, and budget-impact analyses were carried out. Results. The addition of prestance to conventional therapy for hypertension can reduce total costs by 5.-5.8 times, direct costs required to achieve 1% of patients with adequate BP control by 20.5-42.1 times, and direct costs to improve a patient’s status by one visual analogue scale score by 1.03-2.11 times. Within a 5-year horizon, the administration of prestance can decrease the cost of therapy for high BP and related strokes by 1.39-1.46 times. Conclusion. Due its high efficacy, prestance (amlodipine + perindopril) is a pharmacoeconomically preferred alternative only to the conventional therapy for hypertension even if the least costly generics are used, in both the short and medium term.
Terapevticheskii arkhiv. 2016;88(11):83-90
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A case of progressive multifocal leukoencephalopathy in a HIV-infected female patient

Samotolkina E.A., Pokrovskaya A.V., Samotolkina E.S., Voznesensky S.L., Petrova E.V.


Progressive multifocal leukoencephalopathy (PML) caused by JC virus is a severe central nervous lesion developing in the presence of obvious immunodeficiency. In most cases, the disease results in a fatal outcome within a few months. Antiretroviral therapy is currently considered to be the only method for the prevention and treatment of PML in HIV-infected patients. The paper describes a positive experience in treating the HIV-infected female patient with the established diagnosis of PML.
Terapevticheskii arkhiv. 2016;88(11):91-93
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Common variable immunodeficiency in adults

Shabashova N.V., Filippova L.V., Uchevatkina A.E., Frolova E.V.


The paper analyzes 7 cases of common variable immune deficiency (CVID), a primary immunodeficiency disease. All the cases were detected in outpatients over the age of 40 years. The diagnosis was based on their history data and general clinical findings with due regard for the results of previously conducted functional studies, expert opinions, and the results of immunological studies including the quantitative and functional indices of T and B cells, phagocytes and the levels of immunoglobulins. The analysis showed that the early signs of impaired immunity in all the patients were seen by physicians of various specialties in both outpatient and inpatient settings. Generalizing of all information about the patient could become the basis for a simple and accessible practical public-health study of immunoglobulins levels significantly sooner than this diagnosis being verified. This testifies that the physicians of various specialties are partially aware of the clinical signs of immunodeficiency states and that there is a need for a clinical immunologist in adult healthcare facilities. This is especially important since the early clinical manifestations of both primary immunodeficiency disorders that are increasingly frequently detected and nonhereditary – secondary ones can be very similar. The timely verification of the diagnosis is necessary for prescribing adequate therapy with intravenous immunoglobulins to prevent severe chronic pyoinflammatory lung disease and disability in patients with CVID.
Terapevticheskii arkhiv. 2016;88(11):94-98
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Intrauterine Pneumocystis infection

Samitova E.R., Ermak T.N., Koltunov I.E., Kislyakov A.N., Karazhas N.V., Rybalkina T.N., Kornienko M.Y.


Pneumocystosis is well known as an opportunistic infection that is presently most frequently registered in patients with HIV infection and in those with other immunodeficiency states. Earlier, after the Second World War, Pneumocystis pneumonia was most commonly detected in debilitated and premature children; nosocomial outbreaks of pneumocystosis were studied in detail in the 1960s and 1970s. The pathogen is transmitted through the air, but a number of references indicate that it can be transmitted through the placenta. Despite the increasing number of publications on pneumocystosis in pediatrics, physicians remain unfamiliar with this disease. The paper provides evidence that Pneumocystis jiroveci can infect the fetus in utero. If unrecognized, the disease can lead to a child’s death due to severe respiratory failure. The authors describe their case of generalized pneumocystosis that has developed in a child with evidence of intrauterine infection (detection of the pathogen in the autopsy material and placenta and identification of serological markers in his/her parents). The issues that are associated with intrafamilial infection and a risk for in utero transmission of P. jiroveci are discussed.
Terapevticheskii arkhiv. 2016;88(11):99-102
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Genetic diversity of human immunodeficiency viruses and antiretroviral therapy

Bobkova M.R.


The lecture is devoted to the analysis of the state-of-the-art of the impact of genetic diversity of human immunodeficiency (HIV) viruses on the pattern of infection and the efficiency of antiretroviral therapy (ART). It provides brief information on the origin and evolution of HIV and on the current classification of their genetic variants. The molecular epidemiological situation of HIV infection in Russia and nearby states and the major molecular HIV variants that are dominant in these countries, as well as their origin and prevalence trends are characterized. How the diversity of HIV can affect the efficiency of diagnosis, the transmission of the virus, and the pattern of HIV pathogenesis are briefly reviewed. The comparative data available in the world’s scientific literature on these topics are given. More detailed attention is given to the possible causes of varying therapeutic effects against different HIV subtypes, as well as to the specific features of the formation and phenotyping manifestation of ART drug resistance mutations. There is evidence for the necessity of forming a unified follow-up system for treated HIV-infected patients during ART scaling, including in an effort to evaluate the impact of the specific features of the HIV genome on the efficiency of treatment regimens used in Russia.
Terapevticheskii arkhiv. 2016;88(11):103-111
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The 2015-2016 epidemic season in Russia and the world: Circulation of influenza viruses, trends in incidence, clinical aspects, and treatment algorithm

Lvov D.K., Kolobukhina L.V., Burtseva E.I., Kruzhkova I.S., Malyshev N.A., Fedyakina I.T., Kirillova E.S., Trushakova S.V., Feodoritova E.L., Merkulova L.N., Krasnoslobodtsev K.G., Mukasheva Е.A., Garina E.O., Vartanyan R.V., Kisteneva L.B., Prilipov A.G., Bazarova M.V., Devyatkin A.V., Sutochnikova O.A.


In the 2015—2016 epidemic season, there were dominant influenza A(H1N1)pdm09 strains (over 90%) among the circulating influenza viruses in most countries of the Northern Hemisphere and in Russia. A study of the antigenic properties of influenza A(H1N1)pdm09 strains revealed no differences in those of vaccine virus. Sequencing showed that there were amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in the genes encoding internal proteins (PA, NP, M1, and NS1). The rise in the incidence in the Russian Federation, which was etiologically associated with influenza viruses, was registered in January-February 2016 with its maximum being observed at 4—5 weeks of 2016. Within the framework of the epidemiological surveillance of circulating influenza viruses in the Russian Federation, which was conducted by the WHO European Office, the D.I. Ivanovsky Institute of Virology, Honorary Academician N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of Russia, and the Research Institute of Influenza, Ministry of Health of Russia, monitored at the Infectious Diseases Hospital One (IDH-1), Moscow Healthcare Department. Among 1491 examinees, influenza was verified in 104 (21.3%) adults, 208 (42.5%) pregnant women, and 177 (36.2%) children. Influenza A(H1N1)pdm09 was more often diagnosed in the age group of 15—40 years (63.7%); the proportion of influenza patients aged over 50 years increased (22.1%). Most adult patients had moderate influenza; pneumonia complicated the disease in 27.4%. Influenza in the pregnant women was complicated by pneumonia in 4.8% of cases. Influenza was more frequently diagnosed in infants and preschool children aged 0 to 3 years (42.9%), 4 to 6 years (41.2%), and older (15.9%), namely: 7—9 years (10%) and 10—12 years (5.9%). Influenza in the children was complicated by acute tonsillitis (19.4%) and varying degrees of laryngeal stenosis (12.4%). Bronchial obstructive syndrome developed in 2.5%, the rate of pneumonia was 6.2%. Antiviral therapy (AVT) in the early stages of the disease reduces the risk of its severity, the frequency of secondary complications, and the duration and degree of clinical symptoms of influenza. AVT with oseltamivir, zanamivir, imidazolyl ethanamide pentandioic acid (ingavirin), and interferon-a2b (viferon) has been performed in the patients hospitalized at Moscow IDH-1 in the 2015—2016 epidemic season.
Terapevticheskii arkhiv. 2016;88(11):112-120
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Use of succinate-containing agents in the treatment of infectious diseases

Tikhonova E.O., Lyapina E.P., Shul’dyakov A.A., Satarova S.A.


The review gives data that reveal the role of succinic acid in providing cells with energy and oxygen under hypoxic conditions. It presents the results of clinical and experimental studies to evaluate the efficacy of succinate-containing drugs in the combination therapy of infectious diseases. The spectrum of biological effects of these drugs, which is provided by the synergy of their active ingredients, is considered.
Terapevticheskii arkhiv. 2016;88(11):121-127
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Infective endocarditis in the elderly: The current view of the problem

Taradin G.G., Vatutin N.T., Prendergast B.D., Newton J.D., Chaus E.A., Smyrnova A.S.


The review gives the current views of the etiology and risk factors of infective endocarditis (IE) in the elderly. It reports the specific clinical picture of the disease at this age, including clinically apparent syndromes, comorbidity, and various clinical signs and peculiarities of IE. Particular emphasis is placed on the diagnosis of an endocardial infectious lesion, which is based on the use of the modified Duke criteria. The methods of IE diagnosis, particularly microbiological examination, imaging techniques, among which echocardiography in different modes plays a particular role, are listed. The treatment of the disease is based on the latest recommendations for antibiotic therapy with and without regard to a specific etiological factor. The issues of surgical intervention, as well as approaches to preventing IE in elderly people are discussed.
Terapevticheskii arkhiv. 2016;88(11):128-137
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Chronic HCV infection: An internist’s opinion (Part 2)

Zubkin M.L., Chervinko V.I., Ovchinnikov Y.V., Kryukov E.V., Kotenko O.N.


Hepatitis C virus (HCV) infection results in not only chronic hepatitis and subsequent complications as liver cirrhosis and hepatocellular carcinoma, but also in a significant number of other diseases, the so-called extrahepatic manifestations of chronic HCV infection. In addition to lymphoproliferative and autoimmune disorders discussed in Part 1 of this review, many other diseases turned to be associated with chronic HCV infection. Part 2 of this review is dedicated to the analysis of the relationship of chronic HCV-infection to the development of some endocrine diseases, such as thyroiditis and diabetes mellitus, and cardiovascular disorders. It also provides the characteristics of the currently available antiviral agents and considers whether they may be used in patents with extrahepatic manifestations of chronic HCV infection.
Terapevticheskii arkhiv. 2016;88(11):138-148
pages 138-148 views

Diagnostic possibilities of methods for the evaluation of liver fibrosis in chronic viral hepatitis

Navrotsky A.N.


The paper reviews the diagnostic possibilities of different methods for the evaluation of liver fibrosis in chronic viral hepatitis from the point of view of their clinical application. Histological examination retains its value as the gold standard method in evaluating the liver. Transient elastography is a rather effective tool for identifying severe liver fibrosis.
Terapevticheskii arkhiv. 2016;88(11):149-155
pages 149-155 views

Possibilities of using cepeginterferon alpha-2b in double (cepeginterferon alfa-2b and ribavirin) and triple (simeprevir, cepeginterferon alpha-2b, and ribavirin) antiviral therapy regimens for chronic hepatitis C. A review of clinical trials and experience of everyday clinical practice

Znoyko O.O., Klimova E.A., Maevskaya M.V., Shuldyakov А.A., Linkova Y.N., Morozova M.A.


Since the incidence of chronic hepatitis C (CHC) increases steadily, the priority of national health care is to provide antiviral therapy (AVT) for the maximum number of patients infected with hepatitis C virus (HCV). The regimens including pegylated interferons (PEG-IFN) are still in demand in the Russian Federation. A number of clinical trials have been conducted to evaluate the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b), an original PEG-IFN-α developed in the Russian Federation. Their results have shown that cePEG-IFN alpha-2b in the two-component AVT regimen has at least no less clinical efficacy than PEG-IFN alpha-2b and PEG-INF alpha-2a in HCV monoinfected and HCV/HIV co-infected patients. The pooled analysis of data has indicated that the use of cePEG-IFN alpha-b in combination with ribavirin allows an average of 80% of the patients with HCV genotypes 2 and 3 and 62% of those with HCV genotype 1 to achieve a sustained virological response (SVR). In clinical practice when the two-component AVT regimen (cePEG-IFN alpha-b and ribavirin) was used in patients with early-stage CHC and mild fibrosis, SVR was recorded in 90.7% of the patients with HCV genotype 2/3 and in 75% of those with HCV genotype 1. The experience in using cePEG-IFN alpha-2b as a component of the three-component AVT regimen (simeprevir, cePEG IFN alfa-2b, and ribavirin) has been published. The observational program manly covered young patients with mild or moderate fibrosis. SVR was observed in 94% of the patients. Another paper describes the experience with the triple AVT therapy (simeprevir, cePEG-IFN alfa-2b, and ribavirin) in 22 patients, the majority of whom had advanced fibrosis. SVR was recorded in 71.4% of those who had completed treatment. Thus, an individual approach and assessment of predictive response factors to two- or three-component AVT regimens including cePEG-IFN alpha 2b can achieve successful treatment outcomes in most patients with CHC, which is, in some cases, more economically sound than interferon-free regimens used as first-line therapy.
Terapevticheskii arkhiv. 2016;88(11):156-162
pages 156-162 views

Nutritional status in patients with cystic fibrosis: Possibilities of correction

Krylova N.A., Amelina E.L., Krasovsky S.A.


The major risk factor for death in cystic fibrosis (CF) is a progressive lung injury; however, low nutritional status (NS) remains an important and underestimated problem in the management of these patients. The NS of a patient with CF is impaired by many factors, such as chronic malabsorption, pancreatic failure, chronic inflammation, and recurrent pulmonary infection – they all lead to higher energy demand in the presence of lower intake of nutrients. The NS of those with CF plays an important role in maintaining lung function. The patients with higher NS have longer life expectancies. According to the Russian National Registry, both pediatric and adult patients with CF have shorter life expectancies. The article discusses various nutritional support regimens and their impact on lung function parameters.
Terapevticheskii arkhiv. 2016;88(11):163-167
pages 163-167 views

The impact of tuberculosis and chemotherapy on female reproductive health

Kayukova S.I.


The paper outlines a concise review of Russian and foreign literature on the specific features of the course of respiratory tuberculosis in reproductive-aged women. It shows the impact of active tuberculosis and massive chemotherapy on the reproductive system, analyzes clinical symptoms, immediate and long-term consequences, and prognosis of future reproductive function. The timely diagnosis and optimal correction of reproductive disorders in women with respiratory tuberculosis can improve their quality of life, fertile capacities, and birth of a successive healthy offspring
Terapevticheskii arkhiv. 2016;88(11):168-171
pages 168-171 views

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