Detection of HBsAg in the familial environment of children with viral hepatitis B

A total of 231 persons from the families of 62 children hospitalized in connection with viral hepatitis B were examined for the presence of HBsAg in their blood over a period of 3 years. Simultaneously with countercurrent electrophoresis (CIE) and the gel precipitation (GP) test, the passive hemagglutination (PHA) test and the GP test with sandwich treatment were used in this work. The presence of HBs-antigenemia in the members of the families of children with viral hepatitis confirmed by laboratory methods were found to occur 6.7 times more frequently than in the families of children with HBsAg-negative hepatitis. The use of the PHA test and the GP test with sandwich treatment increased the frequency of the detection of HBsAg 2.5 times in comparison with CIE and the GP test. The data indicating the possibility of children being infected through everyday contacts in families with cases of HBs-antigenemia among their members are presented, but further studies are necessary to make the final decision on this problem.     

Etiologic structure of viral hepatitis in children based on data from an comprehensive serologic study of hospitalized patients

During a year an overall serological examination of 1,200 children hospitalized with the diagnosis of viral hepatitis was carried out with a view to establish the presence of hepatitis A and hepatitis B markers (anti-HAV IgM, HBsAg, anti-HBs, anti-HBc and anti-HBe IgM) by means of the enzyme immunoassay and radioimmunoassay. The average annual proportion of cases of hepatitis A (61.4%), hepatitis B (20.4%), hepatitis non A, non B (11.2%) and mixed infection (7.0%) among children, as well as seasonal and age-group fluctuations of this proportion, were established. The etiological structure of viral hepatitides, based on commonly accepted clinico-epidemiological diagnostic criteria, was shown to differ from their true etiological structure as determined in accordance with specific serological markers detected in this investigation.     

Hepatitis A foci in children's collectives studied by using clinico-biochemical, virological and serological diagnostic methods

In 4 foci of hepatitis A (HA) at children's institutions in Moscow 218 children and 30 staff members were examined. Simultaneously with clinico-biochemical studies, specific IgM and IgG in the blood and hepatitis A virus (HAV) antigen in feces were determined by radioimmunoassay. Different forms of HA were detected in 29.1% of children in kindergartens, 19.4% of school children and 3.3% of adults, which was due to great differences in the size of the immune stratum among them (IgG to HAV was detected in 8-10% of children aged 3-6 years and in 83% of adults). In 2/3 of children with HA in the foci the disease was not accompanied by jaundice, 1/5 of them having the inapparent form of this infection. In 45% of the patients HAV antigen was detected in feces, irrespective of the form of HA, 5-14 days before the appearance of hyperfermentemia, and in 2/3 of them this antigen was also detected during the first 6 days after that. Simultaneously with an increase in aminotransferase activity, all of the HA patients showed the presence of specific IgM in their blood.     

An epidemiological assessment of the chronic carriage of the hepatitis B virus surface antigen and other markers of this infection

On the basis of prolonged (up to 10 years) observations of chronic HBsAg carriers (87 persons) slowly progressing chronic hepatitis B virus infection was detected in most of them (57.5%). In these persons up to 6 negative results of the analysis for the presence of HBsAg were periodically obtained, with the subsequent renewal of HBs-antigenemia. More profound examination of 192 persons with chronic lesions of the liver and other digestive organs helped diagnose chronic persistent hepatitis and chronic active hepatitis, accompanied by HBs-antigenemia and the circulation of other markers of this infection, in 63.5% of the examinees.     

Experience with vaccine prophylaxis of hepatitis B among different groups of children

The immunological activity of different vaccines against hepatitis B was evaluated in the Hepatological Center organized on the basis of the Infectious Hospital in Tula. Newborn infants were immunized with the use of the following vaccines: Engerix B (Belgium), Combiotech (Russia), Euvax B (Aventis Pastèur, South Korea). Altogether, after the full course of immunization anti-HBs were detected in 76 children out of 81 (in 93.8%). Vaccine Engerix B, when introduced according to the schedule 0-1-2-12 months, exhibited high immunogenic properties in a group of infants born of women with persistent HBs-antigenemia. Anti-HBs at a concentration exceeding 1000 I.U./I could be detected in 84.6%. In another group of children immunized according to the schedule 0-1-6 months first with vaccine Combiotech at the age of 0 and 1 month, then (at the age of 6 months) with vaccine Euvax, the presence of postvaccinal anti HBs at protective concentration was registered in all children. After immunization against hepatitis B with the use of all above-mentioned vaccines introduced according to both schedules high immunological activity and safety of immunization were noted.     

Clinically conditional variants of the immune response in viral hepatitis A and B in children

The immunity characteristics of the T-, B- and A-systems have been studied on the basis of the data registered in the dynamics of the acute period of the disease and several times in catamnesis during 6-12 months of the convalescence period in 217 children with viral hepatitis A and 99 children with viral hepatitis B. The clinical course of viral hepatitis A and that of viral hepatitis B have been found to have certain parallels in their development, as well as specific features of immune response, which can be subdivided into 3 main groups: (a) immunological imbalance, (b) the phase of immunodepression and (c) secondary immunodeficiency. The distinguishing of the variants of immune response and their clinical interpretation are of practical importance for the early prognostication of the course and outcome of the processes and for the differentiated approach to the treatment of viral hepatitides in children.     

Spread of viral hepatitis in organized children's collectives and the methods for its early diagnosis]

The authors present the results of observations over 407 children aged from 2 months to 16 years from the foci of viral hepatitis in children's collective bodies. During the quarantine a determination was made in children of the glutamic-pyroracemic, glutamic-oxalic transaminases (GPT and GOT, respectively) and of the hepatitis B antigen (HBAg). A necessity of using the enzymatic tests for the purpose of early diagnosis of viral hepatitis was shown, since 84% of the cases developing in the next focus coursed as an unicteric form without any markked clinical signs; HBAg was revealed in 6.1% of the children examined. A complex examination of the personnel and of the persons who came in contact with the patients with viral hepatitis showed the ways of spread of hepatitis B in a collective body; it was found that the viral hepatitis B infection took place both by parenteral and enteral routes. The expediency of active observation over the children, recipients of blood and plasma, with determination in them of the activity of the enzymes and HBAg for early diagnosis of parenteral infection was substantiated. It was also shown that the incidence of the unicteric forms of viral hepatitis in a focus of infection depended not on the periods of gamma-globulin administration but on the age of children who contracted the infection. Thus, the prevalence of the unicteric forms of the disease over the icteric ones in children under 3 years of age was more pronounced than in older children.     

Experience in the detection of the latent course of the epidemic process of viral hepatitis in children in preschool groups]

A complex study of 1273 healthy children of creches and kindergartens where no viral hepatitis occurred for a long time revealed 39 children (3.1%) with an increased activity of glutamine-pyroracemic transaminase in the blood serum. Viral hepatitis was diagnosed in 12 (0.94%) of them as a result of clinical examination (an icteric form in 1, and a nonicteric form in 11 cases). The presence of asymptomatic form of infection could be supposed in 17 other children (1.3%). The incidence of increased activity of the enzyme in the serum of "healthy" children was definitly connected with the viral hepatitis incidence registered in the town during the year as a whole, and by seasons. This permitted to prognosticate the spread of viral hepatitis in the given populated locality. By complex laboratory examination of children in collective bodies it was possible to detect the latene foci and the latently coursing epidemic process of viral hepatitis.     

Clinico-epidemiologic characteristics of infectious hepatitis in a populated area where hepatitis had not been reported for a long time

The analysis of the clinico-epidemiological characteristic of infectious hepatitis in a populated area in the Kashkadarya region of the Uzbek SSR, where the cases of infectious hepatitis were not formerly registered for a long time, is presented. The epidemic process was found to take and intensive course with the formation of a large number of foci with 2 or more patients, an in the age groups of 20-29, 40 years and older a comparatively high morbidity rate, exceeding that among the total population 2-3 times, was registered. A low proportion of patients under 14 years (21.1%) was probably due to the planned preventive gamma globulin immunization carried out in this area.     

Clinical aspects of delta infection.

The clinical features of delta infection were analysed retrospectively in 191 hepatitis B surface antigen (HBsAg) carriers and 592 cases of acute hepatitis B seen over 11 years in the Swedish town of Malmö (population 250 000). With a few exceptions delta infections occurred exclusively in drug addicts. In the chronic HBsAg-carriers the most common clinical manifestation was an episode of acute hepatitis, which in some individuals became severe with a pronounced rise in serum alanine aminotransferase activity for many months. During the period of delta infection the HBsAg titre was lowered and in three out of 26 cases the patient lost HBsAg altogether and developed hepatitis B surface antibodies (anti-HBs). In one patient the acute hepatitis due to delta infection was fulminant and fatal. In patients with acute hepatitis B the clinical picture did not distinguish between those with and without simultaneous delta infection. The frequency with which acute hepatitis B was succeeded by a chronic carrier state was the same whether or not the patient was infected simultaneously with the delta agent. The discovery of the delta agent has improved understanding of the natural history of chronic hepatitis B infection in drug addicts. Thus, instances of acute hepatitis in a chronic carrier, previously termed hepatitis non-A, non-B, may actually be episodes of delta infection.     

Feasibility of routine testing for hepatitis B surface antigen in hospital employees and restriction of carriers.

In 1972-73, 48 hospital staff members were tested selectively for hepatitis B surface antigen (HBsAg); 4 (8.3%) were found to be HBsAg-positive. In 1974-75, 1415 staff members were tested routinely before employment and at periodic health examination; 25 (1.8%) were found to be HBsAg-positive. Of the HBsAg-positive staff members 55.2% were Asians, this proportion being significantly (P less than 0.05) greater than that of any other ethnic group, and 31.0% were southern Europeans. Nurses and laboratory technologists were the largest professional groups among the HBsAg-positive staff, each accounting for 20.7%. Our results indicate that it is impractical to carry out routine testing of hospital staff for HBsAg. Selective testing and restriction from work in their units is proposed for staff of the renal and peritoneal dialysis units, the emergency department and the intravenous team and dietary staff who handle food directly.     

Prophylactic efficacy of reaferon in viral hepatitis A and acute respiratory infections in children

Reaferon, the analog of human alpha 2-interferon obtained by gene engineering techniques, was studied with a view to its use for the prevention of hepatitis A. The study involved children of preschool age in Tashkent. In a strictly controlled trial children aged 2-6 years received the preparation orally in a dose of 1 X 10(6) I. U. or the diluent alone used as placebo. The preparation was administered to 1,100 children and the placebo to 1,078 children. The preparation and placebo were administered twice a week for two months. On the whole, during that period hepatitis A morbidity in both test and control groups of children was the same (5.1% and 4.9% respectively), but among children of nursery age receiving Reaferon the incidence of hepatitis A and acute respiratory viral infections was lower than among those receiving the placebo, though this difference was statistically significant only for cases of acute respiratory infections.     

The prevalence and etiological structure of viral hepatitis in a climatic-geographic area at high risk for infection]

The spread of viral hepatitides on the territory of Central Asia has been analyzed, taking into account regional and territorial factors and using the Fergana Valley as an example. The analysis, based on the use of modern immunochemical, clinico-epidemiological and biochemical criteria, has made it possible to determine the etiological structure of viral hepatitides on the territory of the Fergana Valley. The epidemic outbreak on this territory has been proved to be caused by viral hepatitis E. The necessity of organizing constant epidemiological monitoring on the interstate and territorial level has been substantiated.     

Patterns in the spread and serovirological diagnosis of serous meningitis

The epidemiological and clinico-etiological study of cases of acute serous meningitis with unknown etiology in children was carried out in a large industrial city at the period of a considerable morbidity rise caused by this infection. The maximum morbidity was registered among younger children under school age attending children's institutions. In 26 closed groups of children group morbidity was revealed (4 cases and more), in 5 such groups small local outbreaks were registered. The clinico-instrumental methods of study permitted one to differentiate the groups of children having serous meningitis of supposedly enteroviral etiology, and sero virological studies carried out with the use of a wide range of diagnostic reagents revealed the etiological role of group B Coxsackie virus, mainly type 4, in 20.6% of cases, ECHO virus, serotypes 3 and 11, in 20.7% of cases, and parotitis virus in 5.3% of cases.     

The reactogenicity and safety of a multicomponent vaccine (VP-4) in the prevention of acute respiratory diseases in preschoolers

The reactogenicity and safety of poly-component vaccine (VP-4), prepared from the antigens of opportunistic bacteria, in the prophylaxis of acute respiratory diseases (ARD) in children aged 2.6-6 years. The vaccine was administered intranasally in 3 administrations and orally in 6-8 administrations at intervals of 3-4 days for a period of 24 +/- 4 days. The prophylaxis of ARD with the use of VP-4 was carried out in 168 children in 4 children's preschool institutions. The control group was made up of 120 children, attending the same institutions. The study revealed that VP-4 had low reactogenicity and induced short-time systemic and local reactions (common cold, cough). The administration of VP-4 at a period of the epidemic rise on influenza and ARD morbidity did not lead to an increase in the frequency and duration of ARD in the vaccinees, as well as to the exacerbation of chronic infection and the allergization of the body.     

The danger of hepatitis B virus infection from transfusions of plasma in which the HBs-antigen was detected retrospectively by highly sensitive methods

The prospective dynamic laboratory and clinical study of premature children was carried out: 55 children who received plasma transfusion during the first weeks of their life and were retrospectively (i. e. after plasma transfusion) found to have HBsAg detected by the passive hemagglutination (PHA) test, the enzyme immunoassay (EIA) and the radioimmunoassay (RIA) and 127 children who received the transfusion of plasma found to be HBsAg-negative according to the results of EIA and RIA. As revealed in this study, the risk of hepatitis B virus infection in such children after the transfusion of plasma containing HBsAg at low concentrations, determined only in the PHA test or in EIA and RIA, was, respectively, 7.5 and 6.3 times greater than in children receiving plasma found to be HBsAg-negative according to the results of EIA and RIA. The results of this investigation showed the tendency towards a decrease not only in the total contamination of plasma recipients with hepatitis B virus, but also in morbidity rate in icteric forms of acute posttransfusion hepatitis B, depending on the concentration of HBsAg in plasma used for transfusion.     

Effectiveness of social hygiene and organized preventive measures in dysentery in preschool institutions]

The work presents the data on the development and realization of the complex of social and hygienic, as well as organizational and preventive measures for dysentery control at institutions for children of preschool age in one of the regions of our country. This complex comprises the improvement of "epidemiological" knowledge of the staff, preventive orientation in the work of the epidemiological section of the local Sanitary Epidemiological Station, the spread of sanitary and hygienic knowledge children and in their families, the improvement of material and technical equipment of children's institutions. The complex proved to be highly effective: at institutions for children of preschool age morbidity -ate in dysentery decrease 4--5 times, and its specific falue dropped from 40% to 5.4%, the frequency of positive results given by tests for the presence of intestinal microflora in washings from various objects decreased more than 25 times. Morbidity rate at institutions for children of preschool age decreased 4--5 times as compared with that among children not attending such institutions. The above data suggest the necessity of introducing this experience in other regions of our country.     

Association of cytomegalovirus with infantile hepatitis

Infantile hepatitis is occasionally seen in apparently healthy children. In most cases, the etiology of the infection is uncertain. However, cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), human herpesvirus-7 (HHV-7), human parvovirus B19, and TT virus (TTV) are considered to be associated with hepatitis in children. The objective of this study was to investigate the correlations between these viruses and infantile hepatitis. Twenty-six children from 1 to 24 months old (median age, 7 months) who had liver dysfunction of unknown etiology were enrolled in this study. Plasma samples were examined by a real-time PCR assay for CMV, EBV, HHV-6, HHV-7, parvovirus B19, and TTV DNA. The DNA of CMV was detected in the plasma of four patients (15.4%) and was detected significantly more often in the patient group than in the control group. The CMV-infected patients were 1 to 3 months old, which was significantly younger than the remaining patients. The serological findings did not always correlate with the results of the real-time PCR assay. The DNA of TTV was detected in four patients (15.4%), while human parvovirus B19 DNA was detected in three (11.5%). However, the detection frequencies of these viral DNAs were not significantly different from those in the control groups, and some of these patients had co-infections. These results indicate that CMV might be one of the major pathogens responsible for infantile hepatitis; however, serological tests have limited utility for the diagnosis of CMV infection in young children.     

Problems of the epidemiology of viral hepatitis in Ryazan Province

The analysis of some features of the course of the epidemic process of viral hepatitis on the territory of the Ryazan region is presented. Periodic rises and falls in viral hepatitis morbidity, varying in their regularity (4-6 years), have been registered in the region. The general level and the seasonal distribution of viral hepatitis morbidity are determined by the morbidity rate among children, the increase in the proportion of children of senior school age being observed in recent years.     

Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV

Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs) 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs) and RIG-1-like helicase receptors (RLR) in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC) following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 helicase showed the most marked expression. In hepatitis B, TLR1, 3, 9, NOD1 and NALP expression were the most conspicuous. Expression PRRs in liver from hepatitis of unknown origin was much lower. It was also the case in cytospins from human hepatoma cell line. Several correlations between PRRs expression and clinical findings in patients could be shown by statistical exploration. In conclusion, this data suggests some role for PRRs in the pathogenesis of chronic viral hepatitis.