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 structure of the population morbidity with specific intestinal infections in areas with different intensities in the development of the epidemic process and an evaluation of its manifestations]

The authors analyze the morbidity structure in five enteric infections (typhoid fever, dysentery caused by Shigella flexneri and Shigella sonnei, hepatitis A, and hepatitis E (non A, non B) with the fecal/oral mechanism of the agent transmission) in three towns of Turkmenia and in the town of Novomoskovsk, Tula Province. The incidence of S. sonnei dysentery was found higher in Novomoskovsk and that of the rest enteric infections under study in Turkmenia. The incidence of typhoid fever and hepatitis E was the highest among schoolchildren and adults, whereas preschool children suffered mostly from hepatitis A and S. sonnei dysentery. The authors discuss the specific features of the epidemic process manifestation in enteric infections.     

Antigenic relationship between reactivity to hepatitis B e antigen and 19 kDa protein ofMycobacterium tuberculosis among the Tibetan settlers in Karnataka

McGlynn and her co-workers have reported that among the Vietnamese refugees in Philadelphia and among Alaskan natives who are hepatitis B carriers, there is a statistically significant association between anegative tuberculin test and the presence of hepatitis B e antigen. A repetition of this work among the population of Bangalore did not yield any significant results because of the very low incidence of hepatitis found among this population. However, on the basis of available data that hepatitis B infection is more prevalent among the Mongolian population than among people of other populations, the work was repeated among Tibetans who had settled down in Karnataka. This set of experiments showed that, contrary to the report of McGlynnet al, there is a statistically significant association between apositive tuberculin test and the presence of hepatitis B e antigen and that those individuals who showed the presence of hepatitis B e antigen exhibited less severe form of the disease than those who were negative to this antigen. These findings suggested that immunity to tuberculosis and hepatitis B infections may have a common underlying principle. Data bank search revealed a stretch of amino acid sequences which is common to hepatitis B e antigen and 19 kDa antigen ofMycobacterium tuberculosis. The significance of these results is discussed.     

Spread of hepatitis virus as a threat to national security

Information on viral hepatitis A, B and C morbidity in Russia is presented. A distinct trend to decreased viral hepatitis B and C morbidity in 2001-2002 in comparison with the 1990-ies is noted. Nevertheless, there is still unfavorable prognosis regarding high hepatitis B morbidity among the population of reproductive age, as well as among adolescents, which increases the risk for children at an early age. In addition, a new specific feature of hepatitis A spread is observed: morbidity in this infection is shifted to older age groups. The role of vaccinal prophylaxis in the decrease of hepatitis A and B morbidity, virus safety of blood and its components, the quality of the diagnostics of chronic hepatitis, especially hepatitis C, are discussed. The complex of measures for the prophylaxis of viral hepatitis is proposed.     

High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.     

Viral hepatitis A and B as a mixed infection in children

Serological examinations of 1,200 children, hospitalized at the viral hepatitis department over a year, for the presence of hepatitis A (HA) and hepatitis B (HB) markers have revealed a 7% incidence rate of mixed HA and HB infections. Three variants of mixed infection have been established (true mixed infection, HA combined with asymptomatic HBsAg carriership, cross superinfection) and the relative significance of each of them has been determined. Mixed infection took an unfavorable course with a tendency to the prolongation of the pathological process eventuating in chronic hepatitis, especially in cases of true mixed infections (15.9%).     

Outbreaks of pseudotuberculosis and intestinal yersiniosis among Soviet specialists and members of their families in the Mongolian People's Republic

In summer and winter of 1986 two outbreaks of alimentary enteric diseases occurred among Soviet specialists and members of their families in Ulan Bator. These diseases were identified as Yersinia infections registered in Mongolia for the first time. In July 114 children in a kindergarten fell ill after being fed with salad prepared from vegetables and spring onions supplied from a nearby state farm. 20 Y. pseudotuberculosis cultures, serovar 1, were isolated, and in 25 persons antibodies to the isolated microorganisms were detected; altogether 32% of cases were confirmed by laboratory methods. During the December outbreak 187 persons were affected, among them 90% of children, through the consumption of imported oranges and tangerines, simultaneous infection with Y. enterocolitica, serovars 05.27 and 09, and hepatitis A virus being observed. The fact of associated infection was registered after the simultaneous detection of the markers of viral hepatitis A and Yersinia infection in 61 patients. In the kindergarten the disease produced a typical clinical picture of Far Eastern scarlatiniform fever, and in winter the abdominal forms of the disease prevailed. In cases of combined Yersinia and viral infection a specific variant of acute hepatitis developed; as regards this variant, the authors present heretofore unknown information on its epidemiology, clinical features and outcome.     

Innate detection of hepatitis B and C virus and viral inhibition of the response

Viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections poses a significant burden to the public health system. Although HBV and HCV differ in structure and life cycles, they share unique characteristics, such as tropism to infect hepatocytes and association with hepatic and extrahepatic disorders that are of innate immunity nature. In response to HBV and HCV infection, the liver innate immune cells eradicate pathogens by recognizing specific molecules expressed by pathogens via distinct cellular pattern recognition receptors whose triggering activates intracellular signalling pathways inducing cytokines, interferons and anti‐viral response genes that collectively function to clear infections. However, HBV and HCV evolve strategies to inactivate innate signalling factors and as such establish persistent infections without being recognized by the innate immunity. We review recent insights into how HBV and HCV are sensed and how they evade innate immunity to establish chronicity. Understanding the mechanisms of viral hepatitis is mandatory to develop effective and safe therapies for eradication of viral hepatitis.     

Hepatitis vaccines: recent advances

Despite the availability of hepatitis A vaccines that might provide protection for decades, hepatitis B vaccines that provides protection for at least 15 years and the recent introduction of a combined hepatitis A and B vaccine, these infections continue to spread in both the developed and developing world. Hepatitis A vaccine coverage has been limited to high-risk groups: such a selective immunisation policy is unlikely to have a major impact. If adequate immunogenicity in infants is confirmed, dosing schedules can be improved and the costs of vaccination reduced, universal paediatric immunisation with combined hepatitis A and B products is likely to result in the eventual eradication of these infections. In the interim, novel hepatitis A vaccines are being investigated and additional studies on hepatitis A vaccine immunogenicity in infants are in progress. Worldwide use of hepatitis B vaccines for the newborn, young children and high-risk groups should control this infection and obviate the need for a vaccine against hepatitis D. Newer hepatitis B vaccines that may reduce the likelihood of non-responsiveness and have immunotherapeutic value are under study. A recombinant hepatitis E vaccine for use in endemic regions is currently in clinical trials. The development of an effective hepatitis C vaccine has been agonisingly slow and many impediments have been recognised. These include the lack of a susceptible small animal, a high degree of hepatitis C virus (HCV) genomic diversity and failure to produce high quantities of HCV in tissue culture. The development of a novel HCV replicon system may be a major breakthrough. Nonetheless, it may still be exceedingly difficult to produce a vaccine that uniformly provides sterilising immunity; the possibility of developing a hepatitis C vaccine that can prevent chronic infection is an exciting concept that requires further investigation. Advances in recombinant technology, the use of novel genetic (DNA-based) vaccines, expression of hepatitis antigens in plants and improved adjuvants also hold considerable promise.     

Epidemiological analysis of hepatitis A morbidity

A retrospective epidemiological analysis of hepatitis A morbidity for many years among the population of two neighboring towns in the temperate climatic zone of the USSR has revealed the cyclic character of the epidemic process without a perceptible decrease in its extensiveness and has determined the high-risk groups, as well as the beginning of the seasonal rise of morbidity in these groups. The results of the study indicate that different levels of hepatitis A morbidity and risk groups can be observed in these two neighboring towns. At periods of a lower morbidity level the high-risk group embraces schoolchildren, and when morbidity is at a higher level the risk group includes schoolchildren and preschool children in organized groups. Among the latter the morbidity level is influenced by factors acting all the year round and among school children, by seasonal factors. The beginning of the seasonal rise of morbidity falls on August, while in organized groups of children of preschool age the seasonal rise of hepatitis A morbidity begins 1-1.5 months later. All prophylactic measures for controlling hepatitis A should be carried out with due regard to these features of the epidemic process.     

Etiological structure of viral hepatitis in the area about one of the cities in Gorki Province

The etiological structure of viral hepatitides (VH) in one of the towns of the Gorky region was studied with the use of specific methods for diagnosing hepatitis A (detection of IgM to hepatitis A virus) and hepatitis B (detection of HBsAg in the passive hemagglutination test). The study revealed that hepatitis A was the major nosological from in the structure of VH among children and adults in the area under survey, which was documented by the detection of IgM to hepatitis A virus. The form, second in importance among VH cases, was hepatitis B. The ratio of these two forms of VH was determined by the epidemiological situation in the area. The proportion of hepatitis B cases increased at the period between epidemics. Nondifferentiated hepatitis constituted 6.8% of all cases of sporadic hepatitis among adults. In 90% of cases clinical diagnosis coincided with the serological one.     

Frequency of finding hepatitis B viral markers in young children born of mothers carrying the HBs-antigen

The present communication deals with the results of investigations on the frequency of HBsAg-carriership among expectant mothers in Fergana (the Uzbek SSR) and on the risk for their children to be infected with hepatitis B virus. To detect the markers of hepatitis B virus, the passive hemagglutination test, the enzyme immunoassay, and the radioimmunoassay were used. The incidence rate of HBsAg-carriership among expectant mothers was rather high (5.1 +/- 0.52%) in comparison with the control group (3.5 +/- 0.70%). The detection of HBsAg in children 3 months after their birth, i.e. at the term corresponding to the possible incubation period of hepatitis B, suggested that the children were infected at birth. As noted in the course of this investigation, the risk for a newborn to be infected was directly related to the titer of HBsAg, as well as to the presence of HBeAg, in the blood of the carrier mother. A high detection rate of HBsAg was registered among children born to HBsAg-carrier mothers, which makes it possible to consider these children as a high risk group with respect to hepatitis B virus infection and necessitates the development of the system of antiepidemic and prophylactic measures for preventing newborns to be infected with hepatitis B.     

Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV.

OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus.     

Declining prevalence of hepatitis A virus antibodies among children from low socioeconomic groups reinforces the need for the implementation of hepatitis A vaccination in Brazil

Age-related seroprevalence studies that have been conducted in Brazil have indicated a transition from a high to a medium endemicity of hepatitis A virus (HAV) infection in the population. However, most of these studies have focused on urban populations that experience lower incidence rates of HAV infection. In the current study, the prevalence of anti-HAV antibodies was investigated in children with a low socioeconomic status (SES) that live on the periphery of three capital cities in Brazil. A total of 1,162 dried blood spot samples were collected from individuals whose ages ranged from one-18 years and tested for anti-HAV antibodies. A large number of children under five years old (74.1-90%) were identified to be susceptible to HAV infection. The anti-HAV antibody prevalence reached ≥ 50% among those that were 10-14 years of age or older. The anti-HAV prevalence rates observed were characteristics of regions with intermediate level of hepatitis A endemicity. These data indicated that a large proportion of children with a low SES that live at the periphery of urban cities might be at risk of contracting an HAV infection. The hepatitis A vaccine that is currently offered in Brazil is only available for high-risk groups or at private clinics and is unaffordable for individuals with a lower SES. The results from this study suggest that the hepatitis A vaccine should be included in the Brazilian National Program for Immunisation.     

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.     

Diarrhea,respiratory infections,protozoan gastrointestinal parasites,and child growth in Kathmandu,Nepal

The differential impact of diarrhea, respiratory infections, and protozoan parasitism on growth is investigated among children under five years of age living in periurban Kathmandu, Nepal. The children's parents are all carpet-making workers who live in an environment with crowded living conditions, poor sanitation, and contaminated water. Anthropometric data, both cross-sectional and longitudinal, were collected over a 9-month period. Morbidity data were gathered from maternal reports, and a subsample of children's stools were examined for gastrointestinal parasites. In a comparison of current growth status and growth velocity for children with and without diarrhea and respiratory infections, it is found that body weight is most affected by infections, particularly for children under 24 months of age. For a subsample of children whose stools were tested for parasites, there is a statistically significant association between stunting (low height-for-age) and the presence of a protozoan gastrointestinal parasite. It is concluded that although growth faltering is associated with diarrhea and respiratory infections, the impact of these infections is of less importance for long-term linear growth retardation than is infection by protozoan gastrointestinal parasites.     

Non-A to E hepatitis in children: Detecting a novel viral epidemic during the COVID-19 pandemic

During the COVID-19 pandemic, two further novel viral epidemics were described in 2022, monkeypox virus infections in men having sex with men and non-A to E hepatitis in children. The latter occurred in the first half of 2022 with about 1000 cases worldwide, necessitating liver transplantation in 5% and causing death in 2% of patients. It took some effort to clarify the cause of the novel hepatitis epidemic. Researchers were confronted with a polymicrobial viral infection consisting of an adenovirus-associated virus type 2 (AAV2) infection, co-occurring with either human adenovirus type 41 (HAdV41) or herpesvirus infections; most prominently human herpesvirus type 6 (HHV-6). AAV-2, a small Dependovirus of the Parvovirus family, needs these helper viruses for its replication. AAV2 is used as a vector for liver-targeting gene therapy but was not previously known to cause acute hepatitis. HAdV41 and HHV-6 are mostly known to cause diarrhoea and febrile illnesses associated with skin rashes in children, respectively. Except for a few case reports of HHV-6 hepatitis, HAdV and HHV-6 are mostly known as major pathogens in immunosuppressed transplantation patients. A potential role of SARS-CoV-2 has also been discussed but the most popular hypothesis involves an indirect role of the COVID-19 pandemic for this novel disease. Exposure to HHV-6 infections occurs nearly quantitatively during the first year of life. Social distancing measures, followed by the lifting of these measures in 2022 might have caused a delayed exposure to multiple, normally benign childhood viral infections eliciting a dysregulated immune response with pathological effects for liver cells. In the fall of 2022, when these conditions were not longer met, case numbers dwindled. The hypothesis of an unequilibrated immune response instead of intrinsic cytopathic activity of the implicated viruses is further supported by the enrichment of a particular HLA allele in cases over controls.     

Changing Epidemiological Characteristics of Hepatitis A in Zhejiang Province,China: Increased Susceptibility in Adults

BackgroundHepatitis A is a common acute hepatitis caused by hepatitis A virus (HAV). Annually, it affects 1.4 million people worldwide. Between 1991 and 1994, HAV infections were highly endemic in Zhejiang Province (China), with 78,720 reported HAV infections per year. Hepatitis A vaccine came on the market in 1995 and was implemented for voluntary immunization. Since 2008, hepatitis A vaccine has been integrated into the national childhood routine immunization program.ObjectiveTo understand the current epidemiological profile of hepatitis A in Zhejiang Province since hepatitis A vaccine has been available for nearly two decades.MethodsThis study used the 2005–2014 National Notifiable Diseases Reporting System data to evaluate the incidence rate of notified hepatitis A cases in Zhejiang Province.ResultsThe overall trend of incidence rate of notified hepatitis A cases significantly decreased from 2005 to 2014 (P< 0.001). During the study period, the reported incidence rate in individuals aged ≤19 years declined to the historically lowest record in 2014. Compared with individuals aged ≤19 years, those aged ≥20 years showed the highest incidence rate (P< 0.001). Majority of HAV infected cases were Laborers, accounting for approximately 70% of reported cases.ConclusionsChildhood immunization strategy with hepatitis A vaccine seemed to be effective in decreasing notified hepatitis A incidence rate in individuals aged ≤19 years. Those aged ≥20 years were observed to be the most susceptible population. The vast majority of hepatitis A cases were notified among Laborers. Therefore, we strongly suggest that future preventive and control measures should focus more on adults, particularly Laborers, in addition to the current childhood hepatitis A vaccination programme.     

Update on the Mapping of Prevalence and Intensity of Infection for Soil-Transmitted Helminth Infections in Latin America and the Caribbean: A Call for Action

It is estimated that in Latin America and the Caribbean (LAC) at least 13.9 million preschool age and 35.4 million school age children are at risk of infections by soil-transmitted helminths (STH): Ascaris lumbricoides, Trichuris trichiura and hookworms (Necator americanus and Ancylostoma duodenale). Although infections caused by this group of parasites are associated with chronic deleterious effects on nutrition and growth, iron and vitamin A status and cognitive development in children, few countries in the LAC Region have implemented nationwide surveys on prevalence and intensity of infection. The aim of this study was to identify gaps on the mapping of prevalence and intensity of STH infections based on data published between 2000 and 2010 in LAC, and to call for including mapping as part of action plans against these infections. A total of 335 published data points for STH prevalence were found for 18 countries (11.9% data points for preschool age children, 56.7% for school age children and 31.3% for children from 1 to 14 years of age). We found that 62.7% of data points showed prevalence levels above 20%. Data on the intensity of infection were found for seven countries. The analysis also highlights that there is still an important lack of data on prevalence and intensity of infection to determine the burden of disease based on epidemiological surveys, particularly among preschool age children. This situation is a challenge for LAC given that adequate planning of interventions such as deworming requires information on prevalence to determine the frequency of needed anthelmintic drug administration and to conduct monitoring and evaluation of progress in drug coverage.     

Retrospective epidemiologic diagnosis of viral non-A, non-B hepatitis with a fecal-oral mechanism of transmission of the causative agent

The possibility of the retrospective epidemiological diagnosis of viral hepatitis non A, non B with the fecal-oral mechanism of the transfer of infection in three cities of Central Asia on the basis of the analysis of the dynamics of registered hepatitis A morbidity is shown. With the irregularity of morbidity levels among the total population being characteristic of all three cities, in Andizhan one rise in morbidity within a period of 3 years (1975-1978) and in Tashauz one rise within a period of 5 years (1975-1980) were registered. The analysis of the dynamics of morbidity observed in individual age and social groups showed that these rises, especially those registered in 1976 in Andizhan and in 1977 in Tashauz, were determined by morbidity levels among school children and adults. This is also true for a rise in morbidity rate registered in Tashauz in 1985. In Andizhan the highest morbidity rates among adults were registered in districts insufficiently equipped with modern amenities. Cases of infection registered as hepatitis A (HA) among persons immune to HA at territories with high intensity of the epidemic process of HA at the above-mentioned periods seem to be due to viral hepatitis non A, non B with the fecal-oral mechanism of the transmission of the infective agent.