Neutralization escape mutants define a dominant immunogenic neutralization site on hepatitis A virus.

Hepatitis A virus is an hepatotrophic human picornavirus which demonstrates little antigenic variability. To topologically map immunogenic sites on hepatitis A virus which elicit neutralizing antibodies, eight neutralizing monoclonal antibodies were evaluated in competition immunoassays employing radiolabeled monoclonal antibodies and HM-175 virus. Whereas two antibodies (K3-4C8 and K3-2F2) bound to intimately overlapping epitopes, the epitope bound by a third antibody (B5-B3) was distinctly different as evidenced by a lack of competition between antibodies for binding to the virus. The other five antibodies variably blocked the binding of both K3-4C8-K3-2F2 and B5-B3, suggesting that these epitopes are closely spaced and perhaps part of a single neutralization immunogenic site. Several combinations of monoclonal antibodies blocked the binding of polyclonal human convalescent antibody by greater than 96%, indicating that the neutralization epitopes bound by these antibodies are immunodominant in humans. Spontaneously arising HM-175 mutants were selected for resistance to monoclonal antibody-mediated neutralization. Fourteen clonally isolated mutants demonstrated substantial resistance to multiple monoclonal antibodies, including K3-4C8-K3-2F2 and B5-B3. In addition, 13 mutants demonstrated a 10-fold or greater reduction in neutraliztion mediated by polyclonal human antibody. Neutralization resistance was associated with reduced antibody binding. These results suggest that hepatitis A virus may differ from poliovirus in possessing a single, dominant neutralization immunogenic site and therefore may be a better candidate for synthetic peptide or antiidiotype vaccine development.     

Prevalence of GB virus C/hepatitis G virus in Hungary

In 1995 a new flavivirus, GB virus C/hepatitis G virus (GBV-C/HGV), was discovered. The aim of this study was to determine the prevalence of the virus in healthy persons and hepatitis patients in Hungary. The sera of 408 healthy persons older than 60 years were tested for the presence of GBV-C/HGV antibodies, and 113 were positive (28%). Eight of the 71 healthy persons younger than 60 years and twenty of the 51 sera (39%) taken from patients suffering from hepatitis of unknown origin proved to be positive for GBV-C/HGV antibodies. Ten of the 124 sera (8%) of healthy persons and 36 of the 247 sera (14.6%) of hepatitis patients proved to be positive for GBV-C/HGV RNA. Eleven PCR products were sequenced, and the sequences were found to be different from each other and from the previously published ones. However, three sequences taken from the same patient at different times were identical. These results show that GBV-C/HGV is present in Hungary and cannot be considered rare.     

Down's syndrome: chromosome analysis of 362 cases in Hungary.

A survey is given of the karyotypes observed in 362 children clinically diagnosed as cases of Down's syndrome from whom material was sent to 8 collaborating cytogenic laboratories in Hungary during the period 1965-1974. The sample studied cytogenetically constitutes about 20% of all children born in Hungary in this decade with Down's syndrome. The ways in which patients were selected for cytogenetic examinations could not be specified. In the sample, standard trisomy 21 was found in 91.7%, translocations in 3.9% and mosaicism in 4.4%. The mean age of the mothers of the children investigated was 29.05 years, a relatively low figure which may be explained by the decrease of the mean maternal age over the last decades.     

The load of genetic and partially genetic diseases in man. II. Some selected common multifactorial diseases: estimates of population prevalence and of detriment in terms of years of lost and impaired life

This paper presents epidemiological data on the prevalence of 26 common (i.e., having a lifetime prevalence of more than 1 per 10(4) individuals in the population) multifactorial diseases in Hungary and estimates of detriment associated with them. The detriment is expressed using 3 indicators, namely years of lost life (LL), potentially impaired life (PIL) and actually impaired life (AIL). The total prevalence of these diseases in Hungary has been estimated to be about 6500 per 10(4) individuals in the population. This estimate is in agreement with published data for other parts of the world. On the basis of clinical severity, these diseases have been split into 3 groups, namely (1) very severe (schizophrenia, multiple sclerosis, epilepsy, acute myocardial infarction and related conditions, and systemic lupus erythematosus); (2) moderately severe and/or episodal or seasonal (15 entities including Graves' disease, diabetes mellitus, gout, affective psychoses, essential hypertension, peptic ulcers, asthma, etc.); and (3) less severe than those in the first 2 groups (varicose veins, allergic rhinitis, atopic dermatitis, Scheuermann disease and adolescent idiopathic scoliosis). The essential clinical and genetic aspects of these diseases are briefly discussed. With the exception of epilepsy, none of the diseases included in our list causes mortality between ages 0 and 19. However, they are among the leading causes of death between ages 20 and 69 and thereafter. A sizeable proportion of those with essential hypertension, diabetes mellitus, rheumatoid arthritis, etc. survive to 70 years and beyond, as do those with gout, glaucoma, allergic rhinitis, psoriasis, etc. Overall, about 16% of all deaths that occur in Hungary every year (all age groups) can be attributed to these diseases. The mean number of years of PIL covers a wide range (about 20-40, 12-70 and 40-60 for groups 1, 2 and 3, respectively), the overall mean being about 24 years. However, the nature and degree of impairment and the impact on the life quality of those afflicted differ for the different diseases. Likewise, the mean number of years of AIL (for which the interval between the mean age at premature retirement and mean age at death was used as a rough index) also spans a wide range from 16 to 45, and the overall mean is about 20 years. At the population level, the diseases considered in this paper cause about 2700 years of LL, 96,000 years of PIL and about 5800 years of AIL per 10(4) individuals in the population. Relative to Mendelian diseases as a whole, these multifactorial diseases are associated with much greater detriment (LL: 1.4 X; PIL: 30 X and AIL: 3.9 X).     

Studies on the epidemiology of child infections. 3. Parainfluenza viruses (types 1-4) and respiratory syncytial virus infections.

A seroepidemiological study on the rate of neutralizing antibodies for parainfluenza viruses (types 1-4) and for the respiratory syncytial virus in 2,514 infants and children between 0 and 15 years, residing in Bari and its hinterland was carried out. Positive results were very high for both the individual parainfluenza serotypes (81.7% for type 3, 78.0% for type 1, 76.6% for type 4, 71.9% for type 2) and for respiratory syncytial virus (88.5%). The pattern of infections due to respiratory syncytial virus differed from that of the parainfluenza viruses not only for the higher serologic positive rate, but also for the larger number of elevated titre responses in each age group.     

Studies on the presence of antibodies to EB virus and other herpesviruses in normal children and in infectious mononucleosis.

Children free from infectious disease have been examined by indirect immunofluorescence for the presence of antibodies to the intracellular capsid antigen of Epstein-Barr virus (EBV). In the first year of life 46%, between 2 and 6 years of age 66%, and between 7 and 14 years 91%, of the children proved positive. The corresponding percentages for the presence of antibodies to cytomegalovirus (CMV) and herpes simplex virus were about 50%, irrespective of the children's age. Serum samples from 69 patients suffering from infectious mononucleosis (IM) were tested for anti-EBV antibodies. Of the 29 Paul-Bunnell-positive patients 22 had antibodies, 11 of them in high titres (greater than 1 : 80). Of the 40 Paul-Bunnell-negative cases only 21 had antibodies, 8 in high titres. Of the Paul-Bunnell-negative cases, 73% were found to have anti-CMV antibodies, 32% in high titre. The respective percentages for the Paul-Bunnell-positive cases were 42% and 10%.     

Circadian changes in salivary constituents and conductivity in women and men.

Circadian rhythms in salivary [glucose], [Na+], [K+] and conductivity were measured in 2 age groups of men (men A, 20-45 years and men B, 46-60 years) and 8 different states of fertility in women (normally menstruating, taking oral contraceptives, pregnant, lactational amenorrhea, lactational amenorrhea and taking oral contraceptives, lactating and menstruating, menopausal, and post-menopausal). Unstimulated whole saliva (2-3 ml) was collected every 3 h over a 48 h span. Analysis of Spearman Rank Correlations indicated significant circadian rhythms (significant positive coefficients) for all groups of [Na+] (mean = 0.577 +/- 0.040) and conductivity (mean = 0.410 +/- 0.050). There was no evidence of differences in prominence of rhythm across groups for [Na+] and conductivity. [K+] showed less evidence of rhythms and much greater variability between groups (mean correlation coefficient = 0.198 +/- 0.055). Rhythms in [glucose] (mean correlation coefficient = 0.409 +/- 0.051) were evident in all groups except men B (0.016), menopausal women (0.151) and post-menopausal women (0.310). Model analysis of the data showed no discernible rhythmic trend with age for either conductivity, [Na+] or [K+], where any differences were explainable by the group characteristics. The rhythm in [glucose] showed a significant weakening with age over all groups (F-ratio = 7.46**), and was different between men A and men B (F-ratio = 6.95**). It was concluded that circadian rhythms were present in whole unstimulated saliva for conductivity and [Na+] and that these rhythms were independent of reproductive state, whereas circadian rhythms in [K+] were dependent on reproductive state. Circadian rhythms for [glucose] were dependent on age. The loss of a rhythm in [glucose] with age indicates that glucose, Na+ and K+ are not linked in their entry into saliva. The influence of entry and reabsorption on the final concentrations of glucose, Na+ and K+ in saliva is discussed.     

丙型肝炎病毒基因组部份NS5区蛋白基因在大肠杆菌中的表达

在大肠杆菌中表达了丙型肝炎病毒基因组ＮＳ５区Ａ段和部份Ｂ段蛋白。ＮＳ５Ａ蛋白溶于水,可经过ＧＳＴ亲和层析柱纯化;ＮＳ５Ｂ蛋白不溶于水,经ＰＢＳ－Ｔｒｉｔｏｎ Ｘ－１００洗涤,尿素溶解后,通过离子交换柱纯化。经ＳＤＳ－ＰＡＧＥ和Ｗｅｓｔｅｍｂｌｏｔ分析,ＮＳ５Ａ蛋白除在５７ｋＤ左右有条带外,还有不同程度的降解产物;ＮＳ５Ｂ蛋白主要在５８ｋＤ左右有条带出现。为查明表达蛋白抗体在病人血清中的分布,取９     

Viruses and the aetiology of diabetes: a study in identical twins.

Sera were collected from 49 pairs of identical twins, 27 of whom were discordant (only one twin affected) and 22 concordant (both diabetic) for insulin-dependent diabetes. All were tested for antibodies to mumps, cytomegalovirus, rubella, Coxsackie virus types B1-5, and Mycoplasma pneumoniae. The diabetic co-twins had no more antibodies to any of the viruses than the non-diabetic co-twins of the discordant pairs. Antibodies to Coxsackie B2, rubella virus, and M pneumoniae were found more often in the discordant than in the concordant twins. In 30 of the 71 diabetic twins symptoms began when they were aged 4-6 years or 10-15 years. More concordant than discordant twins were diagnosed during the months January to March. Hence there was no direct evidence of a virus aetiology of juvenile onset diabetes in these twins, and the difference in antibody titres between the concordant and discordant twins was in keeping with a genetic difference between them. The age and time of onset suggested that environmental factors may be important in causing diabetes in the twins.     

Prevalence of HTLV types I and II among drug users in King County,Washington.

We investigated the prevalence of human T-cell lymphotropic virus (HTLV) types I and II among drug users entering treatment in King County, Washington, between 1988 and 1990. Of 762 injection-drug users, 81 (10.6%) were HTLV-positive; of 89 noninjection-drug users, 2 (2%) were HTLV-positive. Most (95.8%) of those typed) were HTLV-II-positive. The relationship between HTLV and demographic and behavioral characteristics was further evaluated among injection-drug users. The prevalence rates for HTLV increased 25-fold from the youngest age group (15 to 24 years) to the oldest (older than 45 years), after adjusting for race. After adjustment for age, American Indians or Alaska Natives were 7.9 times, blacks 6.2 times, Asians or Pacific Islanders 4.7 times, and Hispanics 4.1 times as likely as whites to be HTLV-positive. The prevalence of HTLV among heroin injectors was more than double that observed among injectors of other drugs after adjusting for age, although this association was only marginally significant. The strong association between HTLV prevalence and age suggests that HTLV-II (the predominant virus) has been endemic among King County injection-drug users for some time. Its relatively high prevalence indicates that there is both an opportunity and a need to further investigate the epidemiologic and clinical implications of HTLV-II infection.     

Clinical Characteristics Are Similar across Type A and B Influenza Virus Infections

Background

Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system.

Methods

The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0–4, 5–14, 15–64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata).

Results

Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003–2004 and 2012–2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0–4 years, those aged 5–14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87–2.47) while those aged 15–64 years were less likely (OR 0.83, 95% CI 0.73–0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses.

Conclusions

Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.     

Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera

A total of 480 serum samples from donors including 384 children up to 10 years of age were examined by the hemagglutination-inhibition (HI) test for the rates of prevalence and age of acquisition of HI antibodies against JC virus and BK virus. Among 136 serum samples from various age groups, there were five (4%) with no detectable antibodies against BK or JC virus, 75 (55%) with antibodies against both viruses, 41 (30.1%) with antibodies against only BK virus and 26 (19%) with antibodies against only JC virus. The prevalence of antibodies against JC and BK viruses was 70.5% and 80.8%, respectively, and the mean HI titers (4 x 2n,n greater than or equal to 1) were 4.90 and 4.30. About 50% of the children had acquired antibodies against BK virus by 3 years of age and against JC virus by 6 years of age. These results indicate that dual latent infections with both viruses are common, although independent infections with either virus are predominant in the human population.     

Are we protected? Imported measles - on the way to eradication

In accordance with the 2015 regional goal for measles and rubella elimination of the WHO European Region, only a few imported cases have been documented of both diseases in Hungary for years.This paper presents a case of a Hungarian woman, born in 1975, who received measles vaccination at age of 12 months and later at age of 11 years, according to her certificate of vaccination. In 2009, after arriving home from a vacation in Ireland, she developed acute measles infection with clinical symptoms. It was confirmed by the detection of measles specific IgM, IgA and IgG antibodies, and by detection of viral nucleic acid from throat swab in virus transport medium.Additionally, an outbreak occurred in December of 2011 among a family emigrated from Romania to Hungary. No new measles cases were diagnosed among the contact persons of neither the young Hungarian woman returning from Ireland, nor the family emigrated from Romania. This observation refers to the effectiveness of the Hungarian vaccination program.     

Structural and functional studies of a 39,000-Mr immunodominant protein of vaccinia virus.

Little is known about the nature of poxvirus proteins involved in the host immune response. Screening a lambda gt11 expression library of genomic rabbit poxvirus DNA with hyperimmune rabbit anti-vaccinia virus serum and selection of monospecific antibodies identified a highly antigenic viral protein of about 39,000 molecular weight (39K protein). The same-size protein of vaccinia virus was also identified with a monoclonal antibody (MAb B6) obtained from hybridomas generated after fusion of hyperimmunized mouse spleen cells with mouse myeloma cells. Structural analysis revealed that the 39K protein is an acidic polypeptide, that it can exist in two molecular forms because of intramolecular disulfide linkages, and that it is part of the virus core. This protein shares antigenic determinants with a cytoplasmic component(s) from uninfected cells. Functional studies revealed that the 39K protein is synthesized at late times postinfection and appears to be required for virus assembly. This protein is highly conserved in members of the Orthopoxvirus group, but in cowpox virus, a 41K virion protein was specifically recognized by antibodies that reacted against the vaccinia virus 39K protein. Significantly, during long-term passages of Friend erythroleukemia cells persistently infected with vaccinia virus, some virus mutants were found to increase or decrease by about 2 kilodaltons the size of the 39K protein. Mapping analysis localized sequences encoding the 39K protein in a rifampin-sensitive gene cluster between the two major core-associated viral polypeptides, 4a and 4b. The fact that the 39K core protein of vaccinia virus elicits strong humoral immune response, induces antibodies that react against a host component(s), and is subjected to genetic variability suggests that this protein has important biological functions.     

TT virus in Hungary: sequence heterogeneity and mixed infections

The majority of the viral hepatitis cases is caused by five hepatitis viruses (A,B,C,D,E). In 1997, TT virus was discovered. It was supposed that a number of the unknown hepatitis cases was caused by the TT virus. The aim of this study was to characterize TT viruses carried by healthy individuals and patients suffering from hepatitis of unknown origin in Hungary. TTV DNA was detected by seminested PCR with the commonly used N22 primers. Twenty of the 108 sera (18.5%) taken from healthy persons and 115 of the 228 sera (50.4%) of patients with hepatitis of unknown origin were found to be positive. The nucleotide sequences of 26 clones derived from 17 hepatitis patients and 15 clones from nine healthy persons were determined and a phylogenetic tree was constructed. Genotype 2 (group 1) was found to be the most frequent, but other group 1 genotypes (1, 6) and genotypes 8 and 17 of group 2 were also detected. Mixed TTV infections were found in eight cases (two healthy persons and six hepatitis patients). Variants belonging to the same group were carried in seven cases, and the presence of group 1 (genotype 2) and group 2 (genotype 8) TTV sequences were found in one single hepatitis patient.     

Legal abortions among teenagers in Canada, 1974 through 1978.

Between August 1969, when the amendment to the Criminal Code went into effect, and December 1978 about 397 000 legal abortions were performed in hospitals with therapeutic abortion committees in Canada. During the 5-year period 1974-78 abortions in females under 20 years of age accounted for 30.9% of all the legal abortions performed in Canada on Canadian residents, and the abortion rate per 1000 women aged 15 to 19 years increased from 13.6 to 16.3. During 1974-77 the proportion of women in whom the gestation period was more than 12 weeks at the time of abortion was 25.3% for teenagers (females under 20 years of age) but only 14.6% for women aged 20 years or over. In 1976 the teenage abortion rate was lower in Canada (14.5) than in the United States (36.2%), Sweden (28.5), Hungary (26.4), Denmark (26.0), Norway (22.7), Finland (20.3), and England and Wales (15.4).     

Seroepidemiologic study of arbovirus infections in the north-east and south of Thailand

Blood specimens were collected from villagers in Khon-Kaen province, in the north-eastern region, and in Songkhla province, in the southern region of Thailand in the pre- and post-epidemic seasons of hemorrhagic fever. The hemagglutination inhibition antibody titers of the specimens were measured against dengue virus type 2, type 4, Japanese encephalitis virus and chikungunya virus. In general, Khon-Kaen villagers showed higher levels of HI antibodies against these arboviruses than Songkhla villagers and in both areas the antibody level against chikungunya virus, a group A arbovirus, was usually much lower than those against group B arboviruses. Specimens from Khon-Kaen province had such high antibody positive rates for group B arboviruses (80-100%) from an early age (3-4 years), in the pre-epidemic season, that scarcely any increase in the positive rate was observed in the post-epidemic season. The positive rate in specimens from Songkhla province was not so high in the pre-epidemic season and some increase was seen in the post-epidemic season, especially in lower age groups (3-4 to 7-9 years). The patterns of HI antibody titers in different age groups in the Khon-Kaen and Songkhla provinces were also compared. The patterns changed with increase of ages and were also different with different viruses. The patterns for chikungunya virus were quite different from those for dengue type 2, type 4 and Japanese encephalitis virus. These results suggest that people in Khon-Kaen are exposed to group B arbovirus infections more often in childhood and attain high antibody levels more rapidly than people in Songkhla.     

Detection and genetic characterization of porcine circovirus 2 isolates from the first cases of postweaning multisystemic and wasting syndrome in wild boars in Greece

In 2002, postweaning multisystemic wasting syndrome (PMWS) was diagnosed in a European female wild boar (Sus scrofa), based on the detection of porcine circovirus 2 (PCV2) DNA in various organs, including the uterus, and on histopathologic lesions. This is the first detection of PCV2 DNA in the uterus of a wild boar. Three years later (2005), a wild boar < 6-8 mo of age was found moribund. It presented wasting and dyspnea and finally died. PCV2 DNA was detected in tissue samples, and histopathologic lesions consistent with PMWS were observed. Both wild boars were from neighboring hunting areas in central Greece. Two PCV2 strains from the wild boars were genetically characterized and compared to other reported PCV2 sequences from wild boars and domestic pigs. The PCV-2 sequences from the wild boars in this study were closely related to each other and were grouped with two isolates from wild boars from Hungary. The phylogenetic analysis revealed that the virus might be transmitted between hunting areas. In addition, PCV2 may spread from domestic pigs to wild boars and vice versa.     

Prevalence of antibodies to selected viruses in a long-term closed breeding colony of rhesus macaques (Macaca mulatta) in Brazil

The rhesus macaque breeding colony of the Oswaldo Cruz Foundation (FIOCRUZ) was established in 1932 from a founding stock of 100 animals. This population has remained closed to new animal introductions for almost 70 years. A serologic survey was performed to determine the prevalence of antibodies to selected viruses as a first approach to identifying viral pathogens endemic in this population. Banked serum samples were tested for antibodies to simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV), simian type D retrovirus (SRV), cercopithecine herpesvirus type-1 (B virus), rhesus cytomegalovirus (RhCMV), measles virus (MV), and hepatitis A virus (HAV). All samples were negative for antibodies against the simian retroviruses. The overall prevalence of antibodies was 95% for RhCMV, 45% for B virus, 35% for HAV, and 1% for MV. Prevalence was found to vary by age group.     

Impact of non-pharmaceutical interventions during the COVID-19 pandemic on common childhood respiratory viruses – An epidemiological study based on hospital data

Considering common childhood respiratory viruses and SARS-CoV-2 share similar transmission routes, non-pharmaceutical interventions (NPIs) to prevent SARS-CoV-2 may affect the epidemiology of respiratory viruses. Therefore, our study aimed to observe the epidemiologic characteristics of common childhood respiratory viruses in 2020 (after the pandemic) compared with 2019 (before the pandemic) in Hangzhou, China. The data were compared between 2019 and 2020 based on age and month, respectively. One or more viruses were detected in 3135/21452 (14.61%) specimens in 2019, which was significantly lower in 1110/8202 (13.53%) specimens in 2020. Respiratory syncytial virus (RSV) was the most commonly detected virus in 2019 and 2020. The positive rate of adenovirus (ADV), parainfluenza virus (PIV)1, PIV2, and PIV3 in 2020 was significantly decreased in 2019. In 2020, RSV replaced ADV as the most predominant virus in children aged 1–6 years, and the positive rate of influenza virus A (FluA), influenza virus B (FluB), PIV1, and PIV2 was not correlated to age. FluA, FluB, and PIV2 were not almost detected from February 2020. The positive rates of ADV and PIV1 were uncorrelated to the month in 2020. By strict NPIs, besides controlling the COVID-19 pandemic, incredible progress has been made to reduce the prevalence of common childhood respiratory viruses.