Review
This review is devoted to the comparative characteristics of human herpesvirus 6A (HHV6A) and human herpesvirus 6B (HHV6B), taking into account their exogenous and endogenous (inherited chromosomally integrated) forms. The analysis of the literature data on the main interspecies differences and intraspecies features of these viruses in molecular-genetic, biological, epidemiological and clinical aspects has been consistently carried out. Modern views about HHV6A and HHV6B, including their unique inherited chromosomal-integrated form, are the basis for organizing a system of epidemiological surveillance of infections caused by these viruses, as well as developing standardized methodological approaches to differential diagnosis, treatment and specific prevention of a wide range of virus-associated diseases. The development of this direction requires a greater evidence base and intensification of joint efforts of the scientific and medical communities.
The article analyzes the clinical manifestations of the most common viral infectious diseases in children, accompanied by spotty exanthema, provides brief data on the etiology, pathogenesis and epidemiology of these infections, shows photographs for each of the described nosological forms from the authors' personal archives.
Original Research
Purpose: to investigate the level anti-pertussis IgM, IgG, IgA in pregnant women in the I — II — III trimesters. Materials and methods. A total of 288 pregnant women aged. 17 — 43 years (in the I — II — III trimesters) were examined. A serums samples tested for IgM, IgG, IgA against pertussis by ELISA of RIDASCREEN (Germany). Results. Anti-pertussis IgG concentration below the low limit of detection occurred in 75,7% of pregnant women. The majority of seropositive among pregnant women was in the age group 26 — 35 years (82,9%). The proportion of seronegative among pregnant women increased. with increasing pregnancy periods, as well as depending on age. In III trimester IgG were detected in 18,2% of pregnant women. The most seronegative among pregnant women were in the III trimester and at the age of over 36 years old. The detection of IgM, IgG and IgA made it possible to detect the active infection process in 11 (3,9%) pregnant women by elevated level of IgA. High IgA level only in combination with IgM was in serum sample from 1 pregnant woman, high IgA level in combination with IgG at negative values of IgM was in serum samples from 8 pregnant woman. Only IgA in serum sample from 2 pregnant women (I and III trimesters of pregnancy) were detected. This is probably due to the presence of whooping cough or mucosal contamination with B.pertussis (persisting IgA). Conclusion. The serological studies have shown the need to develop algorithms for protecting newborns — from, the moment pregnant women are registered, to the onset of childbirth. These algorithms will provide information about on the presence of whooping cough and will help prevent infection of the newborn.
Objective. To study the clinical and epidemiological characteristics of meningococcal disease morbidity in the Penza Region population for the period 2007-2019.
Materials and methods. The retrospective analysis carried out of archival documents of a specialized infectious diseases hospital in Penza and materials of the center of the Federal Service for Supervision of Consumer Rights Protection and Human Well-being. Methods of statistical processing were used for the analysis.
Results and discussion. As a result of the analysis, it was revealed that the incidence of meningococcal infection in the Penza region exceeds the average level in Russia for almost the entire time period under study. We revealed the predominance of the share of the child population in the structure of total morbidity throughout the entire time tranche under study was revealed. The presence of 4 peaks in the mortality rate was found — in 2009, 2012, 2014 and 2016. On the territory of the Penza region, the infection has a pronounced winter-spring seasonality, there are generalized forms of meningococcal infection and localized forms of meningococcal infection.
Conclusions. Thus, meningococci of serogroups B and C prevail in the serogroup landscape of meningococci in the Penza region. The excess of the average Russian indicators of the incidence of meningococcal infection was revealed by 2 or more times throughout the entire study period. patients under the age of 14 from unorganized groups predominate among patients with meningococcal infection. the Gender structure is dominated by males from rural areas. The infection has a pronounced winter-spring seasonality. The most common clinical forms are meningitis and mixed form.
Purpose: to improve the complex therapy of rotavirus infection in infants by including interferon and to evaluate its clinical and immunological effectiveness.
Materials and methods. Infants without infectious pathology and with rotavirus infection, who were on standard therapy and treatment, including standard therapy and interferon (20 in each group), were examined using general clinical methods. The diagnosis of rotavirus infection was carried out by molecular-genetic method and immunochromatography. Indicators of cellular immunity were determined by flow cytometry. Statistical processing of the results was carried out using the STATISTICA 8.0 program for related and independent samples using the nonparametric Mann-Whitney test and χ2.
Summary. In all infants with rotavirus infection, the disease occurred in a moderate form with symptoms of grade II exicosis. In the group of patients who received an additional interferon drug as part of complex therapy, the duration of intoxication symptoms was significantly less, and in the hemogram at discharge from the hospital, the relative content of neutrophils was higher and monocytes lower compared to infants who were only on standard treatment, which corresponded to the norm. In the acute period of rotavirus infection, the relative level of lymphocytes decreased, and NK cells and T-NK cells increased compared to healthy infants. The relative number of cells expressing TLR-3 at the beginning of the disease was lower than in the control group. The inclusion of interferon in the complex therapy contributes to normalization of the relative number of NK cells, while maintaining an increased content of T-NK cells in both relative and absolute terms compared to healthy infants, and a reduced content of cells expressing TLR-3.
Conclusion. Currently, rotavirus infection in infants is typical, the most pronounced and long-lasting clinical symptom of the disease is watery diarrhea. The use of interferon in complex therapy helps to reduce the duration of intoxication and normalize the hemogram. Changes in the immune status in the acute period of rotavirus infection indicate increased antigenic stimulation of the cell link and inhibition of the synthesis of pro-inflammatory cytokines, including interferons, under the influence of rotavirus, which is the justification for the use of interferon therapy.
The aim of the study was to evaluate the diagnostic markers in children with HIV —encephalopathy (HIVE) with varying degrees of severity.
Material and methods of research: The study included 260 children (153 boys — 58.85% and 107 girls —41.7%) with HIV-positive status and receiving antiretroviral therapy according to an individually selected scheme for at least 6 months. All children included in the study showed signs of HIV encephalopathy. The activity response was assessed by the concentration of IL-6, IL-10, TNF-alpha, C-reactive protein, C3, C4 components of the complement (immunofelometric analysis).
Results: The study of the activity response in children with HIV encephalopathy found that the concentration of TNF —alpha and IL-6 were increased, compared, to the reference values (12.67±0.25 PG/ml and 23.04±0.64 PG/ml, respectively, with reference values of less than 8.1 PG/ml and 7pg/ml, respectively), and the concentration of IL-10 was reduced (5.93±0.10 PG/ml with a reference value of more than 9.1 PG/ml). The study analyzed the predictor significance of various parameters response in the aspect of the development of symptomatic HIV- encephalopathy. A comparative analysis of the concentration markers was performed, and the incidence of symptomatic HIV —encephalopathy was determined depending on the diagnostic concentration of the diagnostic marker. This finding is probably explained by the effector role of systemic inflammation in the development of damage to the Central nervous system.
Conclusion. The maximum predictor significance in the aspect of the development of symptomatic HIV -encephalopathy was found in proinflammatory cytokines: an increase in IL-6 concentration above 19.6 PG / ml is associated with an increase in the risk of developing symptomatic HIV encephalopathy by 9.14 times, and an increase in TNF -alpha concentration above 12.5 PG/ml by 4.07 times (p<0.001 for both factors).
Recently, an increase in the incidence of all malignant neoplasms of the head and neck has been noted throughout the world. The most common type of head and neck cancer is squamous cell carcinoma, which originates from the epithelium of the oral mucosa, pharynx, and larynx. In Russia, cancer of the oral mucosa and cancer of the oropharynx are in 4th place in the structure of malignant neoplasms: more than 80 thousand new cases are registered every year. Human papillomavirus is the leading cause of increased incidence of squamous cell carcinoma of the head and neck in many regions of the world.
Objective: to determine the main clinical and epidemiological features of HPV-associated head and neck cancer.
Methods: a study based on a retrospective analysis of the patient's anamnestic data was carried out. Results: Demonstrated the role of smoking OR=2.07 (CI: 1.07—4.02), hookah smoking OR=3.06 (CI: 1.06—8.80), drinking strongly hot drinks OR=3.65 (CI: 1.44—9.25), the presence of a dental prosthesis OR=7.32 (CI: 2.77—19.31), heredity OR=7.38 (CI: 3.07—17.76), “Poor” dental status OR=33.54 (CI: 15.01—74.95), positive HPV status in history OR=7.31 (CI: 2.77—19.31), 5 or more sexual partners lifetime OR=4.95 (CI: 2.47—9.93) as risk factors for HPV-associated. head, and neck cancer. Conclusion: HPV prophylaxis plays an important role in reducing the incidence of associated head and neck malignancies. The results of the study convinced of the need for preventive measures in relation to the identified risk factors for the development of HPV-associated head and neck cancer.
The purpose of the research to create a concept for diagnostics and therapy of hemostasis disorders of patients with severe leptospirosis.
Patients and Methods. The study included 474 patients with severe serologically confirmed leptospirosis with a favorable outcome of the disease and 31 patients with fatal outcome (total 505 people). Variant of coagulopathy was determined by using a set of special methods for studying hemostasis. The influence of platelet concentrate transfusion, plasma exchange and various tactics of glucocorticoid therapy on patient survival and correction of hemostasis disorders was evaluated. Survival analysis was made using Kaplan-Meyer method with a Cox proportional intensity model. Relative risk (RR) was calculated with a 95% confidence interval (CI).
Results: the use of early diagnosis of coagulopathy variants and the use of a differentiated therapy regimen in the choice of the variant of hemostasis disorder led to a decrease of mortality from 16.45% to 11.5% and decrease in the consumption of platelet concentrate and fresh frozen plasma.
Conclusion: patients with severe leptospirosis develop a multivariate hemostatic pathology: isolated thrombocytopenia (38%) with thrombotic microangiopathy (20,5%), disseminated intravascular coagulopathy (37,1%), uremic coagulopathy (4,9%), hepatic coagulopathy (3,4%). Plasma exchange in thrombotic microangiopathy is pathogenetically justified. Also, plasma exchange is pathogenetically justified in order to reduce plasma volume in DIC syndrome with consumption coagulopathy and hepatic coagulopathy. The use of GCS in isolated thrombocytopenia can be effective and safe in both “medium doses” and in the form of “pulse therapy” if the following conditions are met: acute renal injury (AKI) III stage according to AKIN and the absence of renal replacement therapy (RRT). The main indication for platelet concentrate transfusion in severe leptospirosis is extremely severe thrombocytopenia (grade 4) with active life-threatening bleeding at the time of transfusion.
Objective. To analyze the genetic structure of rotaviruses of group A, circulating on the territory of the Orenburg region in different epidemic seasons.
Materials and methods: The genetic structure of rotaviruses by G/P alleles was determined in 341 fecal samples of patients with gastroenteritis clinic under the age of 5 years in various epidemic seasons. ELISA and PCR methods were used. The typing of rotaviruses was conducted on the basis of the laboratory of molecular diagnostic and epidemiology of enteric infections of the Department molecular diagnostics Central research Institute of epidemiology.
Results: The general genetic structure of group a rotaviruses circulating in the Orenburg region in the period from 2014—2020 was determined, expressed, by the frequencies of G/P alleles. The genetic potential of group a rotaviruses for the entire study period was represented by twelve variants of genotypes for G/P alleles, the leading role in the epidemic process was played by genotypes with the highest frequency of occurrence: G4[P]8, G9[P]8, G2[P]4, Mixt. The frequency of registration of combined forms of various rotavirus genotypes (Mixed forms) was 5,9%.
Conclusion: The main and dominant genotypes, their regional diversity and inter-seasonal fluctuations are established. The spectrum of circulating rotavirus genotypes differed in different epidemic seasons, and their epidemic significance is shown.
Purpose of the study. Evaluation of the efficacy, safety and tolerability of raltegravir regimens in HIV-infected patients with concomitant pathology in real clinical practice.
Materials and methods. A retrospective analysis was carried out of 277 outpatient records of HIV-infected patients who received raltegravir (RAL) as a third component both in patients without previous experience of antiretroviral therapy (ART) and in patients with experience of treatment with various somatic pathologies. The main criterion for the effectiveness of the scheme was the proportion of patients with undetectable viral load at the start of the analysis. Additional criteria for evaluating the efficacy and safety of the regimen were the dynamics of the number of CD4-lymphocytes, the frequency and nature of undesirable side reactions.
Results. On average, patients with no experience of treatment and with experience of treatment received regimens with raltegravir for about 5 years. At the time of the study in 2020, 69.8% of patients on ART for the first time continued to take a regimen containing raltegravir. In this group, the proportion of patients with virological suppression (PCR of HIV RNA less than 50 kopecks / ml) was 97.7%. 75.2% of patients in the second group in 2020 continued to take the RAL regimen. The proportion of patients with virological suppression (VL less than 50 kopecks / ml) in this group was 97.5%. During the treatment, there was no discontinuation of the regimen in both groups due to undesirable side reactions to raltegravir.
Conclusion. The results of this study confirm that RAL-based regimens provide a high level of efficacy with a good tolerance and safety profile in routine clinical practice for both naive and experienced patients with various somatic pathologies.
Epidemiology
4—5 congenital heart defect cases per 1000 newborns are diagnosed worldwide. Some malformations require surgical methods of correction. Various risk factors contribute to the development of healthcare associated infections (HAIs). The HAIs are one of the leading causes of the prolongation of hospitalization length both in intensive care unit and in the inpatient departments, and they also play a significant role in increasing the number of lethal outcomes. A number of risk factors play an important role in the development of HAIs: the duration of post-operative mechanical ventilation, neonatal age, low birth weight, co-morbidities, including malformations of other body systems.
The Tyumen Region, being the largest one in the Ural Federal District in terms of territory, has a high level of HIV prevalence, particularly among those taken into custody. This group of people involves the maximum number of injecting drug users, men having sexual encounters with other men and sex workers. All acquired diseases including the diseases aggravated during the service of sentence become the problem of the expirees as well as the entire civil society. From an epidemiological perspective it is important to search for the risk factors which are active among the prisoner population serving their sentence in the region and which cause HIV progression with fatal outcome, taking into account their unequal significance among the prisoner population and the civilians.
Object of research. 365 HIV-infected, deaths were identified, including: the study group — 222 prisoners, HlV-infected and died at the regional hospital of the Federal penitentiary service of Tyumen for the period 2008-2018; the control group - 143 civil (law-abiding) patients, HIV-infected and died at the Regional infectious diseases hospital for the period 2011-2018.
Purpose of research. Identification and assessment of priority risk factors for the expansion of the epidemic process of HIV infection with a fatal outcome in the zone of high concentration of the risk group.
Methods of research. The following methods have been used in this work: methods of epidemiological research, methods of mathematical modeling and forecasting, as well as the method, of logistic regression, of step-by-step inclusion with ROC analysis.
Results. To assess the epidemiological situation in terms of the HIV infection prevalence in the prison area a long-term and intra-annual dynamics of the epidemic process expansion in the region have been studied along with assessment of the priority risk factors, trends, forecasting of the HIV infection expansion in the penitentiary system specifying the social significance and risks to the civilian population over a long period.
Pharmacoeconomics
Varicella is a significant burden on society and the healthcare system.
Objective: to analyze the cost effectiveness of universal vaccination of children against varicella.
Material and methods. The analysis was carried out from the perspective of the healthcare system and societal perspective, based on epidemiological data for the Russian Federation. The effect was taken into account only in the vaccinated population. The time horizon of the study is 10 years. The amount of direct medical costs for treatment of varicella was calculated based on the rates of compulsory medical insurance in St. Petersburg in 2020. The cost of drug therapy in outpatient settings was calculated based on the weighted average retail price of prescribed drugs. The analysis of direct nonmedical and indirect costs was carried out taking into account statistical data on the Russian Federation and duration of temporary disability of family members of sick children. Costs and quality-adjusted life expectancy were discounted by 3.5% per year.
Results. The average cost due to the disease in the Russian Federation is 43,139 rubles / patient, of which 8,5% is direct cost. Vaccination of 100,000 children will prevent 38,551 cases of varicella in 10 years. When analyzing from a social perspective, vaccination provides a reduction in costs compared to no vaccination, and the savings will amount to 10.1 thousand rubles per 1 vaccinated person.
If vaccination coverage is 90%, taking into account the fact that the cohort of children in the Russian Federation at the age of 1 year is about 1.9 million people, the cost of vaccination will amount to about 8.1 billion rubles annually. At the same time, already 6 years after vaccination, the volume of averted budgetary costs will exceed the costs of vaccination.
Conclusion. Universal varicella vaccination of children will reduce the incidence of the disease and reduce the budget costs associated with this disease.
Clinical Case
Hepatitis B, despite of being a controlled infection today, is one of the most common form of hepatitis in the world. According to the experts' evaluation there are about 3 million patients with chronic hepatitis B in our country. The global strategy of the World Health Organization includes the elimination of viral hepatitis by 2030.
The program used in the North-West Federal District to eliminate acute hepatitis B has reduced the incidence rate due to the widespread vaccination coverage of children and the annual increase in adult immunization coverage.
However, the relevance of HBV-infection in children still remains high which is associated with a high infection by hepatitis B virus in women of childbearing age and the possibility of the transmission of the infection from mother to her child. In case of perinatal infection the formation of chronic hepatitis B in children reaches up to 90%. The natural course of chronic hepatitis B is characterized by a change in pathogenetically determined phases, and HBsAg-negative infection, which is a latent (occult) form of hepatitis, was added to them in 2009. Occult hepatitis B is an epidemiological danger, for the child as well, if the mother suffers from this form of chronic hepatitis B. Monitoring of pregnant women is often limited to identifying only HBsAg, which is not enough to detect occult hepatitis B. Lately diagnosed occult HBV-infection can become a source of the infection for the baby, especially in cases when due to some reasons there are disorders in hepatitis B vaccination schedule after birth. The article presents an interesting clinical case of family hepatitis B.
Based on the literature sources, modern ideas about Kawasaki syndrome, its diagnostic criteria and the possible trigger role of M. pneumoniae are given. The author describes his own observation of Kawasaki syndrome, probably associated with mycoplasma infection, in a boy of 4 years and 8 months. A special feature of the case was also the presence of a combined mycoplasma-enterovirus infection, which explained the wave-like course of the disease, as well as the delayed development of the respiratory syndrome.
We have presented the first description of acute bilateral neuropathy of the abducens nerve associated with COVID-19 in a child.
A boy aged 2 years 2 months acutely developed bilateral convergent strabismus, the next day fatigue, drowsiness, and a single vomiting not associated with food intake, were joined. A differential diagnosis was performed between brainstem encephalitis, other organic (non-inflammatory) lesions of the brain stem, and idiopathic bilateral neuropathy of the abducens nerves. According to laboratory data, mild lymphocytosis, mild eosinophilia were detected, according to polymerase chain reaction DNA of the herpes virus type 1/2, cytomegalovirus, herpes virus type 6, Epstein-Barr, tick-borne encephalitis, borrelia, anaplasma, RNA ehrlichia were not detected. IgM and IgG to tick-borne encephalitis were not detected. Neurophysiological and neuroimaging examinations did not reveal any pathology. On the 6th day of the disease, SARS-CoV-2 RNA was detected by polymerase chain reaction of the nasopharynx and oropharynx discharge. The final diagnosis was formulated. — bilateral neuropathy of the abducens nerves. Bilateral convergent paralytic strabismus. Concomitant diagnosis: new coronavirus infection, subclini-cal form (positive by polymerase chain reaction in the discharge from the throat and nose of the 2019-nCoV coronavirus (SARS-CoV-2) RNA). Decrease in the severity of strabismus was noted over time against the background of the therapy.
Clinicians dealing with the COVID-19 should also pay attention to its ophthalmological manifestations and take into account that it can debut with them, as was in our case.
Primary (hematogenic) peritonitis caused by non-tuberculosis mycobacteria is extremely rare in the clinical practice. The main number of reported episodes of primary intraabdominal infection is associated with M. tuberculosis and the development of granulomatous inflammation of the peritoneum visually similar to carcinomatosis. The vast majority of reports of peritonitis associated with non-tuberculosis mycobacteria are interlinked with chronic peritoneal dialysis or foreign bodies of the abdominal cavity, when an infection is carried out by the contact through a dialysis catheter, prosthesis or a gastric banding device. The article describes a clinical case of peritonitis and splenitis caused by M. avium with hematogenic spread of infection from the primary pulmonary focus in a young patient with immunosuppression. Diagnosis of such peritonitis at the preoperative stage is extremely difficult due to the similarity of symptoms with atypical appendicitis or infected ascites. The intraoperative picture also did not allow us to assume a mycobacterial etiology of the process, and the absence of a focal point of peritonitis made it necessary to thoroughly understand the situation. Only a peritoneal biopsy and a complete laboratory examination of exudate allowed us to verify the diagnosis, to understand the pathogenetic mechanisms of the disease and to start a timely etiotropic therapy.
The goal is to study the peculiarities of the clinical picture and the distant outcome of intestinal infection due to enteroaggregative escherichiosis and the toxigenic strain of C. difficile in a child with cystic fibrosis.
Material and methods. To verify the etiology of intestinal infection, the following studies were conducted. — fecal PCR “OKI-screen” tests to detect viral and bacterial pathogens, fecal bacteriopsy for pathogenic and opportunistic microbes; determination of C. difficile A and B toxins in feces by enzyme-linked fluorescence analysis.
Results. The combined intestinal infection caused by en-teroaggregative escherichiosis and a toxigenic strain of C. difficile, in a child with pulmonary-intestinal form of cystic fibrosis was characterized by a wavy course, a pronounced intoxication syndrome, excicosis, hemorrhagic enterocolitis, signs of systemic and local inflammation, metabolic disorders. There were no recurrences of C. difficile-infection in catamnese.
Conclusion. It is necessary to continue research on the course of intestinal infections caused by bacterial associations of pathogens.
In their medical practice doctors deal with rare diseases which present difficulties in making a clinical diagnosis, in this case additional diagnostic methods are required. One of these diseases is Caroli's disease (syndrome), characterized by cystic enlargement of the intrahepatic bile ducts with frequent formation of intrahepatic stones. Taking into account the difficulties of early diagnosis, we present our own observation.
Jubilee
2021 marks the 40th anniversary of the discovery of the hepatitis E virus by an outstanding Russian virologist, academician of the Russian Academy of Medical Sciences Mikhail Surenovich Balayan. This date is an occasion to remember this remarkable scientist and person, to analyze the current state of the problem of viral hepatitis E, to sum up the research results and to correct the prospects of scientific directions, the development of which is largely related to the basic foundations laid by M.S. Balayan.
The scientific heritage of M.S. Balayan is associated with the study of poliomyelitis, hepatitis A and hepatitis E. The main contribution of Mikhail Surenovich Balayan to world science was the discovery of the hepatitis E virus. This is, in first place, associated with the significance of the results obtained and the high moral value of the experimental selfinfection with hepatitis E.
The paper presents data on the study of virology, epidemiology, clinical course, diagnosis and prevention of hepatitis E. The main concepts and directions of studying hepatitis E are overviewed.