This review presents the data on the spreading of all known human herpesviruses (НHVs) in female urogenital tract. According to the WHO almost 500 million people worldwide suffer from genital infection caused by НHVs. НHVs were detected in various inflammatory diseases of female upper and lower genital tract (vaginitis and cervicitis), in extrauterine pregnancy (in fallopian tubes), in infertility (cervical channel, endometrium and ovaries). Herpes simplex virus 1 (HSV‑1) was identified for the first time in oocytes after failed in vitro fertilization (IVF). НHVs produce negative effect on the entire reproductive process from conception to childbirth. It was established that HSV, cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) markedly increase the risk of spontaneous abortion, preterm birth and stillbirth. Intrauterine НHV infection is a major cause of congenital malformations. Data on humoral and cell immunity in genital herpesvirus infections (НHVI) are also reviewed. Intravaginal HSV‑2 infection changes cell composition of vaginal mucosa, i.e., together with cells mobilized from the blood, protective role is performed by resident memory T‑cells (TRM), natural killer cells (NK‑cells) and regulatory T‑cells (Treg) whose function consists in maintaining the balance of the activities of lymphocytes. Constant НHVI spreading is largely explained by transition of primary infection to potentially reactivating latent form, since latent virus is unavailable to immune recognition and medicines. The genome editing system CRISPR/Cas9 can recognize and modify not only active but also latent viruses. The promising pilot results with the use of this system offer the possibility of developing innovative technologies for НHV elimination and НHVI eradication.
Благодаря новым методам диагностики инфекционных заболеваний накопилось много данных о новых пневмотропных вирусах - метапневмовирусе и бокавирусе, вызывающих инфекции, часто с осложнениями в виде тяжелых бронхиолитов, альвеолитов и пневмоний, особенно у детей с ослабленной иммунной системой. Нередко при бокавирусной инфекции имеет место сочетанное поражение дыхательных путей и ЖКТ в форме гастроэнтерита. В настоящее время не существует разработанного этиотропного лечения метапневмо- и боковирусной инфекций. Развитию острых инфекционно-воспалительных заболеваний дыхательных путей и их осложнений, таких как пневмония, гайморит, отит и др. способствуют различные нарушения в иммунной системе, одним из важнейших компонентов которой является система интерферонов. Индуктор интерферонов Кагоцел хорошо зарекомендовал себя в ряде экспериментальных и клинических исследований: у детей, получавших терапию Кагоцелом, независимо от этиологии выделенных вирусов, достоверно быстрее купировались лихорадка и признаки интоксикации, сокращались длительность катарального и воспалительного синдромов со стороны верхних и нижних дыхательных путей.
The goal of this work was the evaluation of the frequency of human CMV infection among the women, whose pregnancy ended in miscarriage, detection of active forms of infection and treatment before pregnancy. Virological and sero-immunological techniques were used. A total of 116 women who had miscarriages before the 28 week of pregnancy were submitted to the CMV test. 109 women (94.0%) demonstrated positive results. 49 women (42.2%) had active form of the cytomegalovirus infection. 13 women (26.5%) had the recurrent form and 36 patients (73.5%) had the persistent form of CMV infection (stage of productive replication). All the women with active cMVi were treated before the next pregnancy. Immunomodulatory therapy for the treatment was used.
The impact of VIFERON therapy on clinical, immunological, and virological characteristics was evaluated in 40 children aged 1 month to 3,5 years with acute respiratory virus infection. Study group patients (n=20) received a treatment cycle of VIFERON® in a daily dose of 1 000 000 IU. Comparison group patients (n=20) had symptomatic treatment only. The investigators revealed IgM and IgG antibodies to cytomegalovirus, Epstein—Barr virus, and human herpesvirus 6 and determined herpesvirus DNA in blood, saliva, and urine and respiratory virus DNA/RNA in nasopharyngeal swabs. Flow cytofluorometry was used to study the quantitative composition of lymphocytes with phenotypes CD3+, CD3+4+, CD3+8+, CD3-16+56+, and CD3+CD16+CD56+. The efficiency of VIFERON® therapy was evaluated comparing the results of examinations of the children before and 7 days after treatment. In the study group, the VIFERON® therapy-induced elimination rate for rhinovirus, metapneumovirus, and influenza virus A accounted for 100% and that for respiratory syncytial virus and adenovirus was 87,5 and 66,7%, respectively. In the comparison group, the elimination rate for rhinovirus accounted for 66,7% and that for respiratory syncytial virus and adenoviruses was 0%. The effiacy of VIFERON® against herpesviruses was lower than that against respiratory viruses although Epstein–Barr virus and human herpesvirus 6 eliminations were significantly more frequently noted in the study group patients. In this group, there was accelerated resolution of inflammation, a more pronounced immunotropic effect, including an antiviral effect, than in the comparison group.
The article provides an overview of the literature data about new pneumotropic viruses - metapneumovirus and bokavirus: taxonomy, structural features, pathogenesis, laboratory diagnosis, clinical symptoms of the diseases they cause and complications. The high incidence and bokavirus metapnevmovirus structure of SARS infections in preschool children, the authors have shown the example carried out at the Department of Infectious Diseases in Children Medical University (now RNIMU named after N.I. Pirogov) and on the basis of clinical Institute of Virology, multicenter, randomized, blind, placebo-controlled study on the therapeutic efficacy and safety of interferon inducer Kagocel in 120 children aged 2 to 6 years. The findings to point out on significant reduction in the rate of relief of basic clinical manifestations of SARS, regardless of etiology, in children taking Kagocel in compare with a group of children who took a placebo.
The perinatal transmission of hepatitis C virus (HCV) is the major route of infection in infants. The understanding of the risk factors of perinatal infection and the continuation of studies in this area allow one to propose immunological algorithms of prediction and to work outa follow-up strategy of infected children. The authors have made virological and Immunological studies of infants born to mothers with HCV infection.
Changes of the immune status are decisive in the pathogenesis of cytomegalovirus infection, which is a cause for the intrauterine infection. Therefore, complex immunological and virological examinations are advisable to make in pregnant women with compromised obstetrics history, pathological pregnancy course and with indirect signs of intrauterine fetus infection for the sake of choosing an optimal tactics of observation and treatment.
Acute HCV superinfection was studied in 23 patients with chronic hepatitis B virus infection. HBsAg, anti-HCV (C-100, core, NS3, NS5) were detected in patients' sera at first investigation. Predominant replication of HBV DNA was detected in the sera of 68% patients and HCV RNA in only 24% patients. The clinical course of acute hepatitis C in patients with chronic HBV infection in general corresponded to HCV monoinfection except for more pronounced biochemical shifts and shorter intoxication. The role of HBV and HCV in infectious process is discussed.
Seventy-six anti-HCV-positive patients with acute hepatitis B were observed. HBsAg, anti-HBc IgM, and anti-HCV were detected in the sera of all patients. During the acute phase of illness, HBV DNA was present in the sera of 90.8% patients, but not HCV RNA. The clinical picture of acute hepatitis B in anti-HCV-positive patients corresponded to HBV monoinfection with prolonged intoxication and a more benign biochemical course. Out of 10 patients observed during 2 years chronic mixed HBV/HCV hepatitis was diagnosed in 1 patient, in 8 patients only HCV infection was diagnosed, and in 6 cases HCV RNA was detected. Virus interference may be responsible for successive alternative dominant replication of HBV and HCV.
Clinical and biochemical features of the acute phase of icteric hepatitis C in various HCV genotypes have been studied. The HCV genotypes determine the duration of incubation period and some clinical signs in the preicteric and icteric periods of acute hepatitis C. The biochemical picture and formation of chronic hepatitis virtually did not depend on the virus genotype.
Examinations of 204 patients with acute viral hepatitis revealed HGV RNA in 65 (32%) cases. Clinical and laboratory data in HBV or HCV monoinfection virtually did not differ from these in co-infection with HBV + HGV and HCV + HGV.
Studies aimed at the detection of cytomegalovirus infection (CMVI) in women of reproductive age with obstetric complications in their medical history were carried out. 230 women aged 17-44 years were examined with the use of virological and serological tests. As the result of complex examination, CMVI markers were detected in 159 (69%) of women. Three forms of CMVI were detected in the examined women: latent (30%), reactivated (14%) and persistent (25%). This investigation revealed that the most complete detection of CMVI and the evaluation of its activity in women with obstetric complications in their medical history requires the combined use of virological and serological tests.
The clinical and pathogenetic importance of a number of features characterizing cell-mediated immunity and nonspecific protective factors in acute virus hepatitis B. 124 patients with hepatitis B virus (HBV) infection were placed under observation. Of these, 115 patients had acute virus hepatitis B, 6 patients had acute virus hepatitis of mixed etiology (B + delta) and 3 patients had chronic virus hepatitis B. The study included, besides the detection of virus hepatitis markers and the biochemical analysis of blood, the determination of subpopulations of peripheral blood lymphocytes (CD3, CD4, CD8, CD57), the functional activity of natural killers, characteristics of the interferon status, serum neopterin and beta 2-microglobulin in blood serum. Considerable changes in cell-mediated immunity and the interferon system were found to occur and the optimum immune response in acute virus hepatitis B was characterized.
Leukinferon activity was studied in a controlled trial including 30 patients with acute viral hepatitis. The disease ran a moderate severity course in the majority of the patients. Leukinferon, a combined preparation of natural interferon and cytokines produced by virus-induced leukocytes, has marked immunomodulating properties at moderate antiviral activity. Leukinferon was administered intramuscularly for 10 days according to the following scheme: day 1-1 sample 3 times, day 2-1 ampule 2 times, day 3-10-1 ampule a day (overall 1 x 10(5) U of interferon). Due to leukinferon the symptoms of intoxication declined, hepatic biochemistry normalized more rapidly as well as the period of viremia and antigenemia. Positive clinical trends correlated with interferon system improvement and activation of natural killers. 6 months later complete recovery was registered in all leukinferon-treated subjects.
The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha 2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg.
The interferon response of leukocytes (IRL) alpha and gamma as well as the functional activity of natural killers (NK) were studied in patients with the verified diagnosis of acute viral hepatitis B (AVH-B) treated with leukinferon (a preparation of natural interferon-alpha and cytokines) and reaferon (recombinant alpha2 interferon). The effect of therapy with LF and RF in patients with AVH-B manifested by an increase in the functional activity of NK up to complete normalization after termination of the course of therapy. In the group of patients treated with LF as a result of therapy IRL-alpha increased by the end of the treatment and in the convalescence period. The observed activation of NK and the IF-alpha system under the effect of IF preparations in patients with AVH-B correlated with enhanced elimination of HBsAg.
The therapeutic effect of aerosol virasol was studied in young infants suffering from RS virus infection with concomitant broncho-obstructive syndrome. The study involved 60 children between 1 month and 4 years of age of whom 30 were treated with virasol and another 30 made a control group. Virasol was shown to reduce the severity of the clinical picture to a considerable degree and speed up the recovery in infants with RS virus disease. Virasol is recommended for inhalation treatment of infants with RS virus infection and concomitant broncho-obstructive syndrome. The daily dose of virasol is 10 mg per kilo of body weight. The duration of one course is 3 to 5 days.
The therapeutic effect of aerosol virasol was studied in young infants suffering from RS virus infection with concomitant bronchoobstructive syndrome. The study involved 60 children between 1 month and 4 years of age of whom 30 were treated with virasol and another 30 made a control group. Virasol was shown to reduce the severity of the clinical picture to a considerable degree and speed up the recovery in infants with RS virus disease. Virasol is recommended for inhalation treatment of infants with RS virus infection and concomitant bronchoobstructive syndrome. The daily dose of virasol is 10 mg per kilo of body weight. The duration of one course is 3 to 5 days.