Herpesvirus Infections In Children Research Articles

The influence of the Epstein-Barr virus on paraclinical indicators and cytokine levels in children with rotavirus gastroenteritis

The aim. To identify the influence of the latent form of Epstein-Barr virus infection on the clinical picture, parameters of clinical blood analysis and cytokine response of children with rotavirus gastroenteritis.
 Materials and methods. 56 children were examined. Of them, 33 children (group 1) had no background infection with herpesviruses, and 23 patients (group 2) suffered from rotavirus gastroenteritis against the background of Epstein-Barr virus (EBV) infection. The patients were comparable in terms of sex, age and disease severity. Differences at p <0.05 were considered statistically significant.
 Results. The analysis of the obtained data showed that the latent form of EBV infection affects the clinical picture, indicators of clinical blood analysis and the reaction of serum cytokines of children with rotavirus gastroenteritis.
 Сonclusions. A comparative analysis revealed that a latent form of herpesvirus infection in children with rotavirus gastroenteritis is associated with lower temperature reaction and a lower frequency of vomiting in the acute period of the disease against the background of longer persistence of fever, diarrhoea and catarrhal syndromes. On the part of the investigated laboratory indicators, the presence of EBV infection is characterized by a lower level of haemoglobin (р = 0,013) against a higher content of neutrophils (p = 0.002), eosinophils (p = 0.033) and monocytes (p < 0.001) in the acute period of RVI, and a significantly higher content of eosinophils (p = 0.001) and monocytes (p < 0.001) against the background of a lower level of the relative content of lymphocytes compared to patients of Group 1 in the period of early convalescence. Changes in the cytokine response in children with mixed infection are characterized by a significantly lower concentration of IL-1β at the onset of RVI and a higher content of IL-4 and TNF-α throughout the disease compared to children with mono-RVI

Рецидивирующие респираторные заболевания и активные герпесвирусные инфекции у детей: проблемы и варианты их решения

Background: recurrent respiratory infections (RRI) in children are a relevant medical and social issue. Reactivation of latent herpes simplex virus (HSV) infections is recognized as one of the leading causes of recurrent respiratory infections. Its rate in children is up to 40%. Therapeutic options for recurrent respiratory infections in children are discussed given the activity of HSV infections and immune disorder treatment. Aim: to assess the efficacy of inosine pranobex (Normomed®) for recurrent respiratory infections and active HSV infection in children. Patients and Methods: we examined 96 children aged 1–17 years who requested medical care in an outpatient department with complaints typical of recurrent respiratory infections and laboratory-confirmed active HSV infection. Children received inosine pranobex (50–75 mg/kg/day) in three 10-day courses (10-day breaks). 5±1 weeks after finishing therapy, control clinical and laboratory tests and virology were performed. The nature of ARI episodes during the follow-up period and HSV infection activity over time were evaluated. Results: during treatment, a reduction in the rate and severity of respiratory diseases was reported in 94% of children. Fever severity decreased twice (p=0.035), oropharynx condition improved in 66.7% (p<0.01), and the severity of lymphoproliferative syndrome reduced in 62.5% (tonsil hypertrophy in 52.1%, lymphadenopathy in 50.6%, hepatomegaly in 55.3%, splenomegaly in 66.7%). During treatment with inosine pranobex, a decrease in HSV infection activity was reported in 88.6% of children. The active HSV count also decreased. A significant (p<0.01) reduction in the percentage of patients with active HHV 6A/B (from 78.1% to 12.5%), Epstein– Barr virus (from 45.8% to 7.3%), and HSV type 1 (from 14.6% to 1.0%) was reported. Conclusion: significant improvement in the somatic and virological status of children with recurrent respiratory infections and HSV infection after a course of inosine pranobex, which is characterized by antiviral and immunomodulatory effects, was established. KEYWORDS: monthly respiratory infections, recurrent respiratory infections, Epstein–Barr virus, human herpes virus 6A/B, children, inosine pranobex, Normomed. FOR CITATION: Melekhina E.V., Preobrazhenskaia D.V., Muzyka A.D., Soldatova E.Yu., Gorelov A.V. Recurrent respiratory infections and active herpesvirus infections in children: problems and solutions. Russian Medical Inquiry. 2023;7(11):704–712 (in Russ.). DOI: 10.32364/2587- 6821-2023-7-11-2.

Relationship of herpesvirus (HSV1, EBV, CMV, HHV6) seropositivity with depressive disorder and its clinical aspects: The first study in children.

Infections can lead to the onset of mood disorders in adults, partly through inflammatory mechanisms. However pediatric data are lacking. The aim of this study is to evaluate the relationship between depressive disorder and seropositivity of herpes virus infections in children. The sample group consisted of patients diagnosed with depressive disorder according to DSM-5 diagnostic criteria and healthy volunteers, being between 11 and 18 years with clinically normal mental capacity. All children completed DSM-5-Level-2 Depression Scale, DSM-5-Level-2 Irritability Scale, DSM-5-Level-2 Sleep Scale, DSM-5-Level-2 Somatic Symptoms Scale. The levels of anti-HSV1-IgG, anti-CMV-IgG, anti-EBNA, and anti-HHV6-IgG were examined in all participants. Patients with an antibody value above the cut-off values specified in the test kits were evaluated as seropositive. The mean age was 15.54 ± 1.57 years in the depression group (DG), 14.87 ± 1.76 years in the healthy control group (CG). There were 4 boys (11.2%), 32 girls (88.8%) in the DG, 9 boys (21.9%) and 32 girls (78.04%) in the CG. There was no statistically significant difference between the groups in terms of the presence of seropositivity of HSV1, CMV, EBV, and HHV6. HHV6 antibody levels were significantly higher in the DG (p = 0.000). A significant positive correlation was found between HHV6 antibodies and DSM-5 level-2 somatic symptoms scale score. HHV6 antibody levels were found to be significantly higher in patients with existing suicidal ideation in the DG (n = 13) compared to those without existing suicidal ideation in the DG(p = 0.043).HHV6 persistent infections may be responsible for somatic symptoms and etiology of suicidal ideation in childhood depressive disorder.

Сочетанное течение COVID-19 и герпесвирусных инфекций у детей

The combined course of any diseases, as a rule, is characterized by severity, a high incidence of complications, and a protracted course. The purpose is to describe the clinical and laboratory features of the combined course of COVID-19 and herpesvirus infections in children hospitalized in an Infectious Diseases Hospital. Material and methods. In the period from December 2021 to October 2022, an observational retrospective study was conducted on the basis of the RCCH in Kazan, which included monitoring 36 children hospitalized with an acute infectious disease clinic, laboratory confirmation of COVID-19 and herpes virus infection. A complete sample was used. The data were copied from the medical records of in-patients (f/003u). The observation period for each patient was limited to the period of hospitalization. Laboratory examination included standard methods and etiological interpretation of the diagnosis (PCR, ICA). Statistical data processing was performed using an online calculator https://medstatistic.ru/calculators.html. Results. Against the background of SARS-CoV-2 infection, active replication of EBV was observed in 83.3% of cases, in about half of cases in combination with HHV-6. The clinic was dominated by pyretic fever (77.7%), tonsillitis syndrome (66.7%), including with lesions of the pharyngeal tonsil (52.8%), hepato- (75%) and splenomegaly (44.4%). Diarrheal syndrome was recorded in 47.2% of the examined. Pneumonia was diagnosed only in 11.1% of hospitalized patients, hepatitis — in 36.1%. In general, the clinic was more consistent with herpesvirus infection («mononucleosis-like syndrome») than COVID-19. Leukocytosis was recorded in 94.4% of the study participants, an increase in the level of CRP — in 97.3% of the examined, and significant — in 30.6%, an increase in the level of D-dimer — in 63.9%. The average length of stay of a child in the hospital was 6 days. No lethal outcomes were registered. Conclusion. The study of the features of epidemiology, pathophysiology, clinic and long-term consequences (prognosis) will help improve our understanding of coinfection scenarios.

Clinical and immunological features of activation of latent herpesvirus infection in children with rotavirus infection

The analysis of clinical parameters and indicators of immune response in rotavirus gastroenteritis in children aged 12 to 36 months infected with herpes viruses was performed. Verification of the diagnosis of RVI was carried out by isolating rotavirus antigen from the feces of patients by enzyme-linked immunosorbent assay (ELISA) and the corresponding IgM antibodies from the blood. Also, all children were examined for herpes virus infection types 1, 2, 4, 5, 6. The level of specific IgG and IgM to these herpesviruses was determined by ELISA. In the case of a positive result, the presence of DNA (qualitatively) was determined by polymerase chain reaction (PCR). PCR blood tests for the presence of herpesvirus DNA were performed twice, in the acute period of RVI and in the period of early convalescence. The first group included 71 children in whom rotavirus gastroenteritis occurred on the background of latent herpesvirus infection, in the second ¬ 15 children in whom during the early convalescence there was a reactivation of herpesvirus infection. The obtained data indicate that the activation of herpesvirus infection occurs against the background of reduced immunoregulatory index in the acute period of the disease, and in the period of early convalescence RVI is characterized by the preservation of elevated CD 16+ cells and proinflammatory cytokines (IL-1β and TNF-α). in our opinion, leads to a prolongation of clinical symptoms of rotavirus infection. Keywords: children, rotavirus infection, latent and active herpesvirus infection, cellular and humoral immunity, cytokines.

Marshall’s syndrome in the practice of infection disease doctor and pediatrician (сlinical case)

On the basis of literary sources, modern ideas about Marshall syndrome in children are given, as well as the main clinical and laboratory criteria for the diagnosis of this syndrome. A clinical case of Marshall syndrome in a boy 3 years 6 months infected with human herpes virus type 6 is described. Differential diagnostic criteria of Marshall syndrome and active herpesvirus infections in children are presented on the example of a clinical case.

Herpes virus infections in children, associated syndromes. Clinical observation

A rare variant of pathology associated, with combined, herpetic infection, involving in the joint process and the formation of reactive arthritis, is considered. A clinical case of reactive arthritis associated, with combined, herpetic infection in a child. 1 year and. 9 months is demonstrated. The indicators of the main laboratory markers of herpesvirus activity are given, the changes in the patient's complaints and. the patient's condition are tracked. The changes in the patient's complaints and. the patient's condition are monitored. Laboratory research is subject to instrumental research methods. Possible therapeutic approaches are discussed, with the use of antiviral drugs, glucocorticosteroids, nonsteroidal antiinflammatory drugs.

Herpesvirus infection in children with high grade sensoneural hearing loss

Clinical and audiological investigation of 100 children with indications for cochlear implantation was made. Indirect signs of intrauterine infection were identified, as well as the presence of predisposing factors to the development of exudative otitis media. During the investigation frequency of exudative otitis media (up to 21%) in children with high grade sensoneural hearing loss was made. The severity of lymphoproliferative syndrome and it’s combination with herpesvirus infection markers (Cytomegalovirus, Epstein-Barr virus). It was found out, that in group of patients with combination of high grade sensoneural hearing loss and exudative otitis media lymphoproliferative syndrome in more, than 77% cases had herpesvirus ethiology and significantly exceed the same data in group of patients with isolated hearing loss.

Персистенция герпесвирусной инфекции у детей и ее роль при ювенильном ревматоидном артрите (обзор литературы)

Персистенция герпесвирусной инфекции у детей и ее роль при ювенильном ревматоидном артрите (обзор литературы)

Features of diagnostics of the hepatobiliary system diffuse lesions in children with herpes viral infection caused by Epstein-Barr virus (both isolated and in the form of mixed herpesvirus infection)

Purpose: to improve the treatment quality and prognosis of herpesvirus infection in children caused by the Epstein-Barr virus (both isolated and in the form of mixed herpesvirus infection) based on the study of clinical, biochemical and immunological parameters of the hepatobiliary system. Materials and methods: We examined 95 children aged 3 to 7 years with herpesvirus infection, who were divided into three groups (the I group – children with acute Epstein-Barr infection, the II group – children with Epstein-Barr infection in combination with cytomegalovirus infection, the ІІІ group – children with Epstein-Barr infection and herpesvirus infection type 6). Age-matched healthy control group consisted of 20 children. The diagnosis was verified using a polymerase chain reaction. Biochemical studies included determination of total protein and its fractions, total bilirubin and its fractions, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, thymol index. All patients underwent echosonography of the liver. The level of cytokines (IL-1β, IL-4) and antiviral protection parameters – the content of natural killers (CD16+), T-helper (CD4 +) and/or cytotoxic lymphocytes (CD8 +) were evaluated. Results. In all examined children the disease started acutely from general intoxication syndrome, lesion of the nasopharynx and oropharynx, which were more pronounced in the children of the 1st and 2nd examined groups. Manifestations of the viral exanthema and enanthema were more commonly and pronounced in children of the III group. Most children (61.8 %) with Epstein-Barr infection in combination with herpesvirus infection type 6 had disturbances in the central nervous system. The lesions of lymphoid tissue occurred in 73 (76.7 %) children and were more prevalent in the 1st and 2nd surveyed groups. The constant symptom of the disease was hepatomegaly. Splenomegaly was observed in 82 (86.7 %) patients. We have noted an increase in the levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in the examined children. These changes were more pronounced in children of the 2nd group. Herewith, cytolysis of hepatocytes in most cases among children of all examined groups was not accompanied by hyperbilirubinemia. The jaundice of the skin and mucous membranes occurred only in 18.5% of all examined patients, who were diagnosed with moderate hyperbilirubinemia (60.0 ± 4.6 μmol/l). Proteinogram parameters in the examined patients in the acute period were characterized by a decrease in albumin content, an increase in the content of α1-, α2- and γ-globulins and a decrease in the albumin / globulin ratio. These indicators were significantly changed in the 2nd surveyed group. The majority of examined patients had coagulogram indices on average matched to the age norm. One third of patients showed moderately elevated fibrinogen levels. Immune disorders, that accompany the herpesvirus infection, are characterized by an imbalance of proinflammatory and anti-inflammatory cytokines. Indicators of portal hemodynamics in patients of the I group in the acute period of the disease were characterized by moderate changes such as a decrease in hepatic artery and portal vein blood flow without viscoelasticity and peripheral vascular resistance violations. In the II group the decrease in the diameter of the common hepatic artery and the increase in the diameter of the portal vein, the decrease in the vessels blood flow with a decrease in their viscoelasticity and peripheral vascular resistance was noted. In the III group of patients the hepatic artery and portal vein hemodynamic changes, which had a compensatory character, were identified. Conclusions: Taking into account the revealed clinical changes, it can be noted that lesions of the nasopharynx, more pronounced manifestations of intoxication and hepatolienal syndromes prevailed in infants with herpesvirus infection. Proinflammatory cytokines overactivity in patients with Epstein-Barr viral infection in combination with cytomegalovirus infection causes a longer intoxication period, pronounced liver enlargement, elevation of transaminases and inhibition of liver albumin synthesis. It could be reasonable to prescribe vasoactive therapy for patients with Epstein-Barr virus infection in combination with cytomegalovirus infection both in the acute and reconvalescence period of the disease followed by structural-functional and hemodynamic state of the liver monitoring at the stages of medical rehabilitation.

Поражение миокарда при герпесвирусных инфекциях у детей: очевидная взаимосвязь

Поражение миокарда при герпесвирусных инфекциях у детей: очевидная взаимосвязь

Mesadenitis and herpetic infections

The variants of the course of chronic herpesvirus infection in children with the involvement of several mesenteric lymph nodes in the process and the formation of inflammatory conglomerates – mesenterite (mesadenite) are considered. Possible etiological factors of mesenteritis, morphological changes in affected lymph nodes: nonspecific hyperplasia, in some cases – necrosis and suppuration, are given. Clinical cases of mesenteritis against chronic herpesvirus infections in preschool children are described with a detailed description of clinical manifestations in the form of prolonged fever, chronic intoxication, attacks of abdominal pain accompanied by an unstable stool. Dynamics of the main laboratory markers of herpesvirus activity is given, changes in the indices of instrumental methods of investigation are tracked. Possible pathogenetic mechanisms of the formation of such manifestations of the disease, the role of the systemic inflammatory response and therapeutic approaches with the use of antiviral drugs and glucocorticosteroids are discussed.

CLINICAL AND IMMUNOLOGICAL CHARACTERISTICS OF SHIGELLOSIS ASSOCIATED WITH HERPESVIRUS INFECTIONS IN CHILDREN: A CLINIC, DIAGNOSIS AND TREATMENT

The purpose is to characterize the features of the clinical picture, interferon and immune system status in shigellosis associated with herpesvirus infections in children, and to justify the inclusion of recombinant interferon-a2b (VIFERON®) in the complex treatment program of the disease. Clinical and immunological examination of 136 patients with shigellosis at the age from 1 to 3 years was carried out. In 65 children the active form of herpesvirus infection was diagnosed, in 20 patients it was absent. Active form of herpesvirus infection developed in children with a burdened premorbid background. These patients showed a violation of the immune response regulation by cellular type (reduction of interferon-g spontaneous and stimulated production, expression of CD119 receptors), the effector stage of the adaptive immune response. Clinically associated shigellosis was characterized by a severe course, a frequent development of complications. Inclusion of recombinant interferon-a2b (VIFERON®) in the complex program of treatment promoted the modulation of the regulatory and effector stages of the immune response. There was a reduction in the duration of the main symptoms of the disease and the stay of patients in the hospital. High efficiency of recombinant interferon-a2b (VIFERON®) application make it possible to recommend the inclusion of this drug in the treatment of shigellosis associated with herpesvirus infection in children.

Current diagnosis of mixed herpesvirus infection in children with viral encephalitis

Sixty-five children aged 1 month to 15 years with a diagnosis of viral encephalitis, who had been admitted to the Clinic of the Pediatric Research and Clinical Center for Infectious Diseases, Federal Biomedical Agency, in 2013-2016 were examined. Objective: to establish the frequency of mixed herpesvirus infection in children with viral encephalitis, by using the current diagnostic methods to determine the role of reactivation of herpesvirus infection on the development of viral encephalitis. The investigators identified anti-herpesvirus antibodies and their avidity using an enzyme immunoassay and anti-cytomegalovirus antibodies specific for antigens by immunoblotting applying the kits. Herpesvirus DNA was detected in the biological material (blood, cerebrospinal fluid) by real-time polymerase chain reaction (PCR) and by electrophoresis using the PCR kits (Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Welfare (Moscow). Young children were shown to develop the disease as a result of primary infection more commonly as monoinfection in the old age groups during the persistence of one or two herpesviruses in the body. In encephalitis caused by herpes simplex virus type 1 and type 2, reactivation of cytomegalovirus that could be a cofactor in the development of brain inflammation was proven by the current diagnostic technique immunoblotting. The comprehensive laboratory approach to the etiological diagnosis of viral encephalitis, which encompassesthe determination of antibody classes, avidity, and antibodiesto individual protein determinants of viral particles, makes it possible to specify the activity of different herpesviruses in mixed infection and to determine the stage of the infectious process, which is important for the choice of therapeutic policy.

Герпесвірусна інфекція у дітей, хворих на хронічний гломерулонефрит

Герпесвірусна інфекція у дітей, хворих на хронічний гломерулонефрит

Герпесвірусна інфекція у дітей, хворих на хронічний гломерулонефрит

Герпесвірусна інфекція у дітей, хворих на хронічний гломерулонефрит

Comparative characteristic of clinical and laboratory indicators of congenital herpes virus infection in children and the course of mother’s pregnancy

The work summarizes the results of the investigations made by the researchers of Scientific Research Institute of Children’s Infections in Saint Petersburg. There are presented comparative characteristics of congenital Herpes virus infection accompanied by a course of the mother’s pregnancy. Etiologic interpretation of congenital Herpes virus infection was based on the identification of specific antibodies of M and G class immunoglobulins against CMV, HSV and EBV by fluorescence immunoassay, virus DNA by PCR in different biological environment (blood, sputum, urine). The results of the tests were filled into the created individual electronic block-cards and processed further by the methods of parametric and nonparametric statistics in the licensed version of “Windows Vista Professional” operational environment “Statistica 7.0” program (correlated, regressive, cluster, discriminant tests) with the confidence level p < 0,05. There are described two our clinical observations of those children who have survived after generalized Herpes virus infection. There are framed the risks of congenital infection revealing depending on the pregnancy course in the form of the algorithm. There are also given the practical recommendations on the interpretation of the laboratory data found. The clinical presentation of congenital Herpes infections (HSV, CMV and EBV) is extremely polymorphic and doesn’t allow definite suspecting of the disease etiology. In the case of congenital infection suspicion the method of choice is the indication of causative genome in the biological samples available. The determination of specific IgM in the first-year children is less informative in these cases. The system of laboratory follow up of the pregnancy to assess the risk of congenital infection needs further improvement (it needs monitoring, current recommendations on interpretation).

INFLAMMATORY BOWEL DISEASE AND CHRONIC ACTIVE HERPESVIRUS INFECTIONS IN CHILDREN

Еxamined 43 children with inflammatory bowel disease (IBD). IBD activity, except clinical and endoscopic manifestations of the disease was evaluated in terms of total protein, g-globulin, immunoglobulin (Ig) G, A, M, fibrinogen, soluble fibrin monomer complexes (SFMC), C-reactive protein (CRP), serum. All children per formed a serological examination of blood by ELISA for antibodies to herpes simplex virus types 1—2 (HSV1—2), Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes zoster virus (VZV). All patients underwent determination of specific DNA HSV1—2, herpes virus type 6 (HHV6), CMV and EBV in blood cells and/or intestinal biopsies using PCR. 25 children held definition of indicators of interferon (IFN). Set imbalance of IFN, characterized by increased levels of serum IFN-induced synthesis and decreased blood cells IFNa and IFNg. Active herpes virus infection in children with IBD occurred in 88.4% of cases. In 30.2% of cases were determined monogerpesvirusnye infection in 58.1% of cases — mikstgerpesvirusnye active infection. Laboratory indicators of activity in IBD were significantly higher in children with active herpes virus infection, indicating that the negative effects of chronic active herpesvirus infections on the course of IBD in children.

Neuroimaging of herpesvirus infections in children

Six members of the herpesvirus family cause well-described neurologic disease in children: herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella-zoster (VZV), Epstein-Barr (EBV), cytomegalovirus (CMV), and human herpes virus-6 (HHV-6). When herpesviruses infect the central nervous system (CNS), the clinical presentation is non-specific and often confounding. The clinical urgency is often underscored by progressive neurologic deficits, seizures, or even death, and prompt diagnosis and treatment rely heavily on neuroimaging. This review focuses on the spectrum of cerebral manifestations caused by these viruses, particularly on non-congenital presentations. Recent advances in our understanding of these viruses are discussed, including new polymerase chain reaction techniques that allow parallel detection, which has improved our recognition that the herpesviruses are neurotropic and involve the CNS more often than previously thought. Evolving knowledge has also better elucidated viral neuropathology, particularly the role of VZV vasculitis in the brain, HHV-6 in febrile seizures, and herpesvirus reactivation in immunosuppressed patients. The virology, clinical course, and CNS manifestations of each virus are reviewed, followed by descriptions of neuroimaging findings when these agents infect the brain. Characteristic but often subtle imaging findings are discussed, as well as technical pearls covering appropriate use of MRI and MRI adjuncts to help differentiate viral infection from mimics.

Advances in the antiviral therapy of herpes virus infection in children

Herpes viruses are ubiquitous, and primary infection with many of these viruses is common during childhood. In general, children tolerate primary infection well, with only mild symptoms, but in the immunocompromised, including the newborn, infection can be associated with serious morbidity and mortality. Drug treatment for many of the herpes infections is available but is often associated with serious side effects. In the pediatric age group, treatment is further hindered by a lack of information on suitable dosing regimes, unavailability of oral solutions and a lack of clinical trials specifically investigating response to treatment in this group of patients. This article will review current evidence regarding the pharmacokinetics and dosing of the most commonly used antiherpetic agents and will look specifically at the treatment of the more common herpes virus infections in children.