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hepatitis a and b infections in transfusion-dependent thalassaemia from endemic areas.the aim of this study was to determine the prevalence of previous hepatitis a virus (hav) and b virus (hbv) infection which is in 64 transfusion-dependent (td) patients with thalassaemia including 26 patients who were transfused before blood donors were screened for hbv. serial blood samples taken from these 64 patients and 10 non-td beta-thalassaemia intermedia patients during a 3 year period, were tested for antibody to hav (anti-hav), hepatitis b surface antigen (hbsag), antibody to hbsag (an ...19911958422
dissociation of alanine aminotransferase values in acute hepatitis a patients with and without past experience to the hepatitis b virus.serological markers and peak serum alanine aminotransferase (alt) values of 140 in-patients with acute hepatitis, either type a (n = 90), or type b (n = 50) were prospectively assessed. in 23 out of the 90 patients with acute hepatitis a, evidence of previous experience with hepatitis b virus (hbv) was found, whereas 35 out of the 50 patients with acute hepatitis b had past contact with hepatitis a virus (hav). the mean peak alt values [s.d.] were significantly higher in hepatitis a patients wit ...19912019305
age-specific prevalence of hepatitis a virus infection among teenagers in sardinia.in 1989, the prevalence of antibodies to hepatitis a virus (anti-hav) in a sample of 1350 sardinian teenagers aged 14 to 19 years was estimated by elisa method. the overall anti-hav prevalence was 20%; it increased from 12.3% among 14-16 year old subjects to 27.4% in subjects aged 17-19 years (p less than 0.01). a slight female preponderance was observed (22.1% versus 17.9) but no statistically significant difference was attained. compared with the corresponding figure (71.6% of prevalence rate) ...19911648657
effect of relative humidity and air temperature on survival of hepatitis a virus on environmental surfaces.stainless steel disks (diameter, 1 cm) were contaminated with fecally suspended hepatitis a virus (hav; strain hm-175) and held at low (25% +/- 5%), medium (55% +/- 5%), high (80% +/- 5%), or ultrahigh (95% +/- 5%) relative humidity (rh) at an air temperature of 5,20, or 35 degrees c. hav survival was inversely proportional to the level of rh and temperature, and the half-lives of the virus ranged from greater than 7 days at the low rh and 5 degrees c to about 2 h at the ultrahigh rh and 35 degr ...19911649579
parameters influencing the attachment of hepatitis a virus to a variety of continuous cell lines.we have investigated the interactions of purified radiolabelled hepatitis a virus (hav) with a variety of continuous cell lines. virus labelled either in vitro with radiolabelled iodine or in vivo with radiolabelled uridine bound to cells with similar efficiency. attachment to bs-c-1 cells was calcium ion-dependent and this correlated with infectivity assay results. the cell tropism of hav attachment was examined using cell suspensions and confluent cell monolayers at both 4 degrees c and 37 deg ...19911649900
simian hepatitis a virus (hav) strain agm-27: comparison of genome structure and growth in cell culture with other hav strains.fragments of cdna representing greater than 99% of the entire genome of wild-type hepatitis a virus (hav) strain agm-27, isolated from an african green monkey, were obtained by the polymerase chain reaction and sequenced. comparison with other hav isolates revealed differences in the predicted amino acid sequence in functionally critical parts of the genome. comparison of the biological properties of agm-27 with those of human wild-type and cell culture-adapted hm-175 strains revealed that agm-2 ...19911649901
sequence analysis of a new hepatitis a virus naturally infecting cynomolgus macaques (macaca fascicularis).a new isolate of hepatitis a virus (hav), cy-145, was isolated from stool specimens obtained from cynomolgus macaques naturally infected with this agent. sequence analysis of the capsid region of the genome indicated that this virus differed from other sequenced hav strains by about 20% at the nucleotide level and 7% at the amino acid level. two amino acid residues (residues 70 of vp3 and 102 of vp1), previously identified as constituting an immunodominant site and conserved in all sequenced hav ...19911649902
adsorption-elution with negatively and positively-charged glass powder for the concentration of hepatitis a virus from water.two methods based on virus adsorption and elution from glass powder were developed for the concentration of hepatitis a virus (hav) from large volumes of water. the cytopathogenic phm-175 strain of hav was used to test these procedures in tap water, fresh water, sea water and raw sewage. hav was quantitated by a plaque assay in the frhk-4 cell line. hav was concentrated by glass powder adsorption-elution from 20-liter samples with satisfactory efficiencies in all types of water: 100% for tap wat ...19911650787
hepatitis a outbreak in a neonatal intensive care unit: risk factors for transmission and evidence of prolonged viral excretion among preterm infants.an outbreak of hepatitis a virus (hav) infection in a neonatal intensive care unit (nicu) provided the opportunity to examine the duration of hav excretion in infants and the mechanisms by which hav epidemics are propagated in nicus. the outbreak affected 13 nicu infants (20%), 22 nicu nurses (24%), 8 other staff caring for nicu infants, and 4 household contacts; 2 seropositive infants (primary cases) received blood transfusions from a donor with hav infection. risk factors for infection among n ...19911651359
the hepatitis a virus polyprotein expressed by a recombinant vaccinia virus undergoes proteolytic processing and assembly into viruslike particles.hepatitis a virus (hav) contains a single-stranded, plus-sense rna genome with a single long open reading frame encoding a polyprotein of approximately 250 kda. viral structural proteins are generated by posttranslational proteolytic processing of this polyprotein. we constructed recombinant vaccinia viruses which expressed the hav polyprotein (rv-orf) and the p1 structural region (rv-p1). rv-orf-infected cell lysates demonstrated that the polyprotein was cleaved into immunoreactive 29- and 33-k ...19911651421
characterization of hepatitis a virus capsid proteins with antisera raised to recombinant antigens.the capsid proteins of hepatitis a virus (hav) were expressed as fusion proteins of beta-galactosidase in e. coli using the expression vector lambda gt11. four fusion proteins were stably expressed and used to immunize rabbits to obtain mono-specific antisera. the antisera were unable to neutralize viral infectivity or react with hav by radioimmunoassay. three of the antisera were able to recognize hav antigens in infected bs-c-1 cells by immunofluorescence and denatured capsid proteins by immun ...19911651950
large-scale purification of inactivated hepatitis a virus by centrifugation in non-ionic gradients.formalin-inactivated hepatitis a virus (hav) can be purified for vaccine preparation by centrifugation in renografin-76 (diatrizoate meglumine and diatrizoate sodium) gradients. both continuous-flow rate-zonal and isopycnic methods were used for the separation of a major antigen component from minor antigen and host protein. the major antigen component, which appeared to contain complete virions by electron microscopy, could be recovered from gradients and accounted for approximately one third o ...19911651954
[the chronic course of spontaneous and experimental hepatitis a in rhesus monkeys with viral persistence].the prolonged (up to 2 years) complex observation of 11 rhesus macaques (macaca mulatta) with spontaneous hepatitis a and 14 rhesus macaques with experimental hepatitis a developing after their intravenous and/or oral infection with human hepatitis a virus (hav). both natural and experimental infection took a chronic course (15-18 months). in 13 monkeys showing morphological changes in the liver during the whole period of the disease elevated enzyme levels in the blood and virus shedding in fece ...19911653510
identification and characterization of incomplete hepatitis a virus particles.the range of hepatitis a virus (hav) particles generated during persistent infection of different cell lines was studied. buoyant density and sedimentation analyses of cell extracts revealed a uniform profile of particles in all cell lines analysed except for bs-c-1 cells. the virion itself usually represented less than 50% of the total mass of virus antigen. a major portion of the antigen was associated with non-infectious, empty particles, which banded at 1.305 g/ml and 1.20 g/ml cscl, and sed ...19911654375
a recombinant vaccinia virus expressing hepatitis a virus structural polypeptides: characterization and demonstration of protective immunogenicity.a recombinant vaccinia virus containing most of the p1 region of hepatitis a virus (hav) was constructed. cell lysates of cultures infected with the virus contained hav proteins detectable by radioimmunoassay. western blot analysis revealed the presence of a single protein of mr 60k to 62k, bearing epitopes from structural polypeptides vp4, -3 and -2, and the n terminus of vp1. the size of the protein suggests that at least some of the vaccinia virus thymidine kinase is also expressed. inoculati ...19911654376
the 5' nontranslated region of hepatitis a virus rna: secondary structure and elements required for translation in vitro.although the lengthy 5' nontranslated regions (5'ntrs) of other picornaviral rnas form highly ordered structures with important functions in viral translation, little is known about the 5'ntr of hepatitis a virus (hav). we determined the nearly complete 5'ntr nucleotide sequences of two genetically divergent hav strains (pa21 and cf53) and included these data in a comparative phylogenetic analysis of the hav 5'ntr. we identified covariant nucleotide substitutions predictive of conserved secondar ...19911656072
detection of hepatitis a virus proteins in infected bs-c-1 cells.hepatitis a virus (hav) is distinguished from other picornaviruses by its tropism for the liver in infected hosts, a nonlytic infection in hepatocytes, and a slow and nonlytic growth cycle in cultured cells. although the genome structure and organization of hav appear to be similar to those of the other picornaviruses, the viral proteins synthesized in infected cells have not been previously characterized. we have utilized specific antisera raised in rabbits to recombinant hav proteins expressed ...19911656592
a simplified multiwell plate assay for the measurement of hepatitis a virus infectivity.a standardized multiwell plate assay (mwpa) was developed to provide a simple in situ measurement of hepatitis a virus (hav) infectivity titers. following attachment (4 h, 35 degrees c) of serial 10-fold dilutions of hav strain cr326 f (variant f') to confluent mrc-5 monolayers in 24-well plates, cultures were overlaid with maintenance medium and incubated for 35 days at 35 degrees c with weekly medium replacement. cells were fixed with 90% acetone and hav antigen was quantitated by reaction wit ...19911659431
hepatitis a virus attachment to cultured cell lines.identification of a hepatitis a virus (hav) receptor is important for understanding hav tissue tropism and replication sites and in the design of vaccines and antiviral therapy. the attachment of hav to cultured cell lines was evaluated: calcium-dependent specific attachment of four hav strains to permissive cells occurred, whereas binding to nonpermissive cells did not. investigation of hav antigenic variant strains (neutralization escape mutants) demonstrated identical attachment properties wi ...19911659597
concentration and detection of hepatitis a virus and rotavirus from shellfish by hybridization tests.a modified polyethylene glycol precipitation method for concentration of virus followed by a new method to recover nucleic acid was used to detect hepatitis a virus (hav) and rotavirus (sa11) in shellfish (oysters and hard-shell clams) by hybridization tests. infectious virus, seeded into relatively large quantities of shellfish, was recovered consistently, with greater than 90% efficiency as measured by either in situ hybridization (hav) or plaque assay (rotavirus sa11). viral nucleic acid for ...19911660697
a rapid method for determination of endoproteinase substrate specificity: specificity of the 3c proteinase from hepatitis a virus.the preferred amino acid residues at the p'1 and p'2 positions of peptide substrates of the 3c proteinase from hepatitis a virus (hav-3c) have been determined by a rapid screening method. the enzyme was presented with two separate mixtures of n-terminal acetylated peptides, which were identical in sequence except for the amino acids at the p'1 or p'2 positions, where a set of 15 or 16 amino acids was introduced. enzyme-catalyzed hydrolysis of the peptide mixtures generated free amino termini, wh ...19911662396
prevalence of antibodies against hepatitis a virus, hepatitis b virus, and treponema pallidum in mauritius.a seroepidemiological study on the prevalence of antibodies against hepatitis a virus (hav), hepatitis b virus (hbv) and treponema pallidum was conducted in various groups of the population of the state of mauritus (islands of mauritus and rodrigues). 618 sera were tested. the overall prevalence of anti-hav was 86.1% and yielded and age-dependent increase. serological evidence for acute or chronic hbv infection was found in 3.8%; 4.5% were positive for anti-hbc alone, and in 12.6% past hbv infec ...19911662829
immunogenicity trial of inactivated hepatitis a virus vaccine in human volunteers.an inactivated hepatitis a virus (hav) vaccine was tested on a group of human adult volunteers. the vaccine was administered subcutaneously, and a control group received a placebo (aluminium hydroxide). the vaccine was found to be relatively well tolerated and non-reactogenic, and levels of anti-hav were comparable to those in other studies.19911663301
occurrence of faecal bacteria, salmonella and antigens associated with hepatitis a virus in shellfish.an investigation was carried out over a one year period to examine jointly the occurrence of faecal bacteria, salmonella and the presence of antigens associated with the hepatitis a virus (hav) in oysters (crassostrea gigas), mussels (mytilus edulis, mytilus galloprovincialis) and cockles (cerastoderma edule), taken from 8 shellfish farming areas or natural beds along the french coast. for the faecal coliforms (fc) and faecal streptococci (fs), statistical analysis of the 176 samples examined sh ...19911663750
[the use of lanthanide immunofluorescence analysis for demonstrating the antigen of viral hepatitis a].the study dealt with the development of an express method for detection of hepatitis a virus (hav) antigen employing lantanides, especially europium. the new time-resolved fluoroimmunoassay (trfia), alongside with a significant shortening of the time for reaction, was also 8 times as sensitive as the analogous enzyme immunoassay. the trfia may be used effectively both for control of the antigen amplification in hav-infected cell culture and for early diagnosis of acute forms of viral hepatitis a ...19911664554
antiviral activity of carrageenan on hepatitis a virus replication in cell culture.sulphated polysaccharides such as iota-, lambda- and kappa-carrageenans showed a potent inhibitory effect on the replication of hepatitis a virus (hav) in the human hepatoma cell line plc/prf/5. no cytotoxic effects were detected with concentrations of carrageenans up to 200 micrograms/ml. the selectivity indices of these substances, calculated as the ratio of the dose that reduced the number of viable cells to 50% (cd50) to the effective dose that inhibited 50% of viral antigen expression (ed50 ...19911665574
genetic variability within the 5' nontranslated region of hepatitis a virus rna. implications for secondary structure and function.the rna genome of hepatitis a virus (hav) contains a lengthy and relatively well conserved 5' nontranslated region (5'ntr). in other picornaviruses, the 5'ntr has been shown to have important functions related to the initiation of viral translation and replication of viral rna, functions which are critically dependent on both primary and secondary rna structure. we have utilized a phylogenetic approach to construct a model of the secondary structure of the hav 5'ntr. by comparing the nucleotide ...19911668324
identification of hepatitis a virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals.to identify factors contributing to the pathogenesis of autoimmune chronic active hepatitis (cah) healthy relatives of 13 patients with the disorder were followed prospectively for 4 years. 58 relatives were monitored for various serological markers and for t-lymphocyte migration inhibitory activity every 2 months. 3 cases of subclinical acute hepatitis a occurred during the study. in 2 of the 3 subjects, before hepatitis a virus (hav) infection, there was a defect in suppressor-inducer t lympho ...19911673738
hepatitis a virus infection in taipei city in 1989.to evaluate the current status of hepatitis a virus (hav) infection, a seroepidemiologic study to detect the prevalence of antibodies against hav (anti-hav) has conducted in taipei city, from march to july, 1989. serum specimens were collected from 602 male and 503 female apparently healthy children age 12 and under. the prevalence rate of anti-hav was 27.5% in infants, and decreased to nearly 0% in preschool and early school children up to 10 years old. compared to a previous study in the same ...19911678406
methisoprinol-effect on the replication cycle of human hepatitis a virus.the antiviral activity of methisoprinol was investigated under different conditions using a strain of hepatitis a virus (hav), that shows a strong cytopathic effect on the frp/3 cell line 7-9 days post-infection. treatment of frp/3 at a dose range of 125-1200 micrograms/ml had no toxic effect and showed a dose dependent inhibition of the hav replication cycle. at the methisoprinol dose of 500 micrograms/ml the cytopathic effect was completely abolished and hav antigen production reduced by 50% a ...19921279362
identification of amino acids located in the antibody binding sites of human hepatitis a virus.antigenic mutants of human hepatitis a virus (human-hav) were isolated by their resistance to neutralizing monoclonal antibodies raised to human-hav. the nucleotide sequence determined for the capsid regions of 12 mutants identified amino acid changes that clustered in three non-overlapping sites; one in vp3 and two in vp1. all mutants had a change at amino acid residue 70 in vp3, indicating its primary importance for antibody binding. ten mutants had two amino acid changes occurring in the vp3 ...19921280386
the epidemiology and control of hepatitis a.hepatitis a virus (hav) infection is endemic in developing countries and remains a public health problem elsewhere. a total of 7430 cases was notified in england and wales in 1991. children and young adults were most frequently affected. risk factors include travel to countries of high endemicity, contact with an infected person and shellfish consumption. person-to-person spread is common within families, closely knit communities and schools (especially nurseries). the provision of safe water an ...19921284926
the association of infective hepatitis type a (hav) and diabetes mellitus.the cases of three patients who developed diabetes mellitus (dm) within 2-3 weeks of acute hepatitis a virus (hav) infection associated with diabetic ketoacidosis are reported. the ketoacidosis was considered an index of insulin dependent diabetes mellitus most likely precipitated by the acute virus infection.19921295148
host antibody response to viral structural and nonstructural proteins after hepatitis a virus infection.subgenomic hepatitis a virus (hav) rna sequences were translated in vitro to produce proteins representing the structural (p1) and nonstructural (p2 and p3) domains of the viral polyprotein. these proteins were used as antigens to detect the presence of antibodies in sera from acute and convalescent humans and an experimentally infected chimpanzee. all infected individuals tested had antibodies that recognized uncleaved p1 proteins as well as nonstructural proteins. antibodies in sera from infec ...19921309847
antigenic structure of human hepatitis a virus defined by analysis of escape mutants selected against murine monoclonal antibodies.we examined the antigenic structure of human hepatitis a virus (hav) by characterizing a series of 21 murine monoclonal-antibody-resistant neutralization escape mutants derived from the hm175 virus strain. the escape phenotype of each mutant was associated with reduced antibody binding in radioimmunofocus assays. neutralization escape mutations were identified at the asp-70 and gln-74 residues of the capsid protein vp3, as well as at ser-102, val-171, ala-176, and lys-221 of vp1. with the except ...19921312628
expression and characterization of recombinant hepatitis a virus 3c proteinase.the 3c proteinase from the hepatitis a virus (hav) was cloned into a multicopy expression vector in escherichia coli under control of the tac promoter. the resulting plasmid construction produced 3c proteinase as a soluble and active enzyme constituting approximately 10% of total cellular proteins. the enzyme was purified to apparent homogeneity as judged by sds gel electrophoresis and hplc reversed-phase and fplc ion-exchange chromatography. a colorimetric assay was developed, and synthetic pep ...19921313294
[inapparent infection with hepatitis a virus and glomerulonephritis in a child].a 9-year-old boy developed inapparent infection with hepatitis a virus (hav) and glomerulonephritis, simultaneously. the diagnosis was confirmed by the finding of serum anti-hav igm. we suggest that the kidney involvement was also caused by hav. recovery was uneventful.19921314215
immunogenicity and antigenicity of chimeric picornaviruses which express hepatitis a virus (hav) peptide sequences: evidence for a neutralization domain near the amino terminus of vp1 of hav.we evaluated the antigenic characteristics of chimeric picornaviruses created by inserting peptide sequences from hepatitis a virus (hav) capsid proteins into the b-c loop of vp1 of sabin strain type 1 poliovirus (pv-1). fifteen viable chimeras were generated. each retained the ability to be neutralized by polyclonal pv-1 antisera. two chimeras (h15 and h2) stimulated production of low levels of hav neutralizing antibodies in immunized rabbits or mice, although in both cases only a small fractio ...19921314456
survival of hepatitis a virus on human hands and its transfer on contact with animate and inanimate surfaces.the survival of hepatitis a virus (hav; strain hm175) on the hands of five volunteers was determined by depositing 10 microliters of fecally suspended virus on each fingerpad and eluting the inoculum after 0, 20, 60, 120, 180, and 240 min. the amount of virus recovered from each fingerpad at 0 min was approximately 6.0 x 10(4) pfu. at the end of 4 h, 16 to 30% of the initially recoverable virus remained detectable on the fingerpads. hav inocula (10 microliters; approximately 1.0 x 10(4) pfu) pla ...19921315331
characterization of a genetic variant of human hepatitis a virus.human isolates of hepatitis a (hav) are a single serotype; however, recent genetic surveys using limited nucleotide sequencing have provided evidence that more than one genotype is responsible for hav infection in different parts of the world (jansen et al. [1990]: proc natl acad sci usa 87:2867-2871; robertson et al. [1991] j infect dis 163:286-292). one of these genotypes was originally isolated from panamanian owl monkeys (strain pa21), but has subsequently been found associated with human ca ...19921316423
genetic relatedness of hepatitis a virus strains recovered from different geographical regions.a pairwise comparison of the nucleic acid sequence of 168 bases from 152 wild-type or unique cell culture-adapted strains of hepatitis a virus (hav) revealed that hav strains can be differentiated genetically into seven unique genotypes (i to vii). in general, the nucleotide sequence of viruses in different genotypes differs at 15 to 25% of positions within this segment of the genome. viruses from four of the genotypes (i, ii, iii and vii) were recovered from cases of hepatitis a in humans, wher ...19921318940
myelopoiesis in vitro is suppressed by hepatitis a virus.perturbations of hematopoietic regulation ranging from transient granulocytopenia to rare cases of bone marrow failure are associated with infections due to hepatitis a virus (hav). in an attempt to elucidate the pathogenetic mechanisms we had previously established that hav has a direct suppressive effect on human bone marrow progenitors (cfu-gm, -gemm, bfu-e). these studies were extended to long-term bone marrow cultures (ltbmc): inoculation of bone marrow mononuclear cells with hav did not in ...19921322183
multistate outbreak of hepatitis a associated with frozen strawberries.a multistate outbreak of hepatitis a was traced to frozen strawberries processed at a single plant. among 827 students and 60 teachers at an elementary school in georgia during a 2-week period, 15 developed hepatitis a. three months later, among 174 residents and 467 staff in an institution for the developmentally disabled in montana during a 3-week period, 13 developed hepatitis a. primary attack rates were 10% in the school and 8% in the institution. cohort analysis in the school implicated co ...19921323618
intermolecular cleavage of hepatitis a virus (hav) precursor protein p1-p2 by recombinant hav proteinase 3c.active proteinase 3c of hepatitis a virus (hav) was expressed in bacteria either as a mature enzyme or as a protein fused to the entire polymerase 3d or to a part of it, and their identities were shown by immunoblot analysis. intermolecular cleavage activity was demonstrated by incubating in vitro-translated and radiolabeled hav precursor protein p1-p2 with extracts of bacteria transformed with plasmids containing recombinant hav 3c. identification of cleavage products p1, vp1, and vpo-vp3 by im ...19921328690
assessment of inactivation of hepatitis a vaccine by compound pcr.assuring the complete inactivation of hepatitis a virus (hav) vaccine commonly requires prolonged tissue culture amplification, followed by detection of virus antigen in cell lysates. a reliable, but faster, alternative procedure is highly desirable since it will permit the prescreening of experimental batches of killed hav, prior to tissue-culture amplification. we established experimental conditions for simultaneous, polymerase chain reaction (pcr)-based amplification of viral and cellular mrn ...19921331145
[family-acquired hepatitis a--prevalence of hepatitis a among the family in aichi prefecture, 1990].we studied the transmission of hepatitis a virus (hav) in 45 families, which members were diagnosed as hepatitis a in 8 hospitals in 1990. feces and sera from 50 patients and their 126 family members were tested for hav-specific antigen and igm antibody by elisa or polymerase chain reaction (pcr) technology. from the interval of the onset of hepatitis or detection of hav antigen in feces, hav transmission was recognized in 11 (24.4%) of 45 families. the transmission was found to be concerned wit ...19921331263
accumulation and persistence of hepatitis a virus in mussels.accumulation and persistence of hepatitis a virus (hav) in the mussel mytilus chilensis was evaluated. under optimal filtration activity of mussels (temperature 12 degrees c, salinity 3%, feeding twice a day with dunaliella marina), hav was concentrated 100-fold from the surrounding water. similar concentrations of hav were reached in the filtration apparatus and in the digestive system (hepatopancreas). hav persisted for about 7 days in mussels. elimination of hav from mussels was slower than e ...19921331305
identification of precursors of structural proteins vp1 and vp2 of hepatitis a virus.the morphogenetic pathway of hepatitis a virus (hav), classified as a member of the enteroviruses within the picornaviridae, still remains obscure and seems to differ considerably from that of poliovirus, the most studied representative of this genus. in order to elucidate the precursor/product relationship of hav structural proteins, subviral particles, which represent more than 50% of the viral antigen produced in infected cells, were separated from mature virions and their polypeptide pattern ...19921331311
a cis-acting element within the hepatitis a virus 5'-non-coding region required for in vitro translation.every picornavirus studied thus far has a sequence within the 5'-non-coding region that is required for internal ribosome binding and translation of the polyprotein. in an attempt to identify this region in hepatitis a virus we constructed a truncated hepatitis a virus (hav) cdna clone that contains the entire 736 bp 5' non-coding region (5'-ncr) and 754 base pairs of the viral capsid coding region (p1) under control of the sp6 promoter. in vitro transcription and translation of this transcript ...19921332279
[the circulation of the hepatitis a and b viruses in the somali population].we report the results of a study carried out to evaluate the extent of hepatitis a virus (hav) and hepatitis b virus (hbv) circulation in somalia. serum samples were collected from 593 subjects (age range 0-83 years) and tested for anti-hepatitis a (hav) and anti-hav igm. serum samples taken from 1272 individuals (age range 0-83 years) were tested for hbsag, anti-hbsag, anti-hbcag, hbeag and anti-hbeag. we confirmed a very high rate of hav exposure (about 90% of the subjects tested had circulati ...19921334688
immunopotentiating reconstituted influenza virus virosome vaccine delivery system for immunization against hepatitis a.hepatitis a virus (hav) was purified from mrc-5 human diploid cell cultures, inactivated with formalin, and evaluated for safety and immunogenicity in humans. three vaccine formulations were produced: (a) a fluid preparation containing inactivated hav, (b) inactivated hav adsorbed to al(oh)3, and (c) inactivated hav coupled to novel immunopotentiating reconstituted influenza virosomes (iriv). iriv were prepared by combining phosphatidylcholine, phosphatidylethanolamine, phospholipids originating ...19921334977
prevention of viral hepatitis a: past, present and future.before hepatitis a virus (hav) was identified, spread of hepatitis a was prevented by public health measures. the first specific, preventive measure for hepatitis a was passive protection with standard, pooled human immune globulins. human immune globulin contained sufficient hav neutralizing antibodies for short-term, prophylactic passive protection and for control of the spread of local outbreaks. after many unsuccessful attempts, hav was propagated in cell cultures and the development of vacc ...19921335635
serological approaches to distinguish immune response to hepatitis a vaccine and natural infection.currently, the immune status of an individual exposed to hepatitis a virus (hav) is determined by assays which measure antibodies against the capsid proteins. these assays indicate exposure to the viral capsid that could result from either infection or from vaccination. recent data indicate that proteins from the non-structural genome region of the virus (p2 or p3), which are only produced during active virus replication, generate antibodies after clinical disease. a sub-genomic cdna segment of ...19921335637
inactivated hepatitis a vaccine: active and passive immunoprophylaxis in chimpanzees.studies of active and passive immunoprophylaxis were carried out in chimpanzees to determine whether a candidate hepatitis a virus (hav) vaccine could stimulate antibody to hav (anti-hav) that was qualitatively similar to anti-hav stimulated by natural infection. normal immune globulin (ig) was prepared from plasma obtained from human volunteers before and after vaccination with the hav vaccine, and these preparations or commercially prepared ig were administered to chimpanzees. protective effic ...19921335648
clinical manifestations and diagnosis of hepatitis a virus infection.hepatitis a is an acute, necroinflammatory disease of the liver which results from infection by the hepatitis a virus (hav). the mean incubation period is approximately 30 days. although the disease is usually self-limited, the severity of illness is age-dependent. in children, hepatitis a is usually asymptomatic, while in adults, symptomatic infection is characteristic and jaundice is common. fulminant hepatitis a is rare and is also age-dependent. the onset of hepatitis a is often abrupt and c ...19921335649
clinical assessment of the safety and efficacy of an inactivated hepatitis a vaccine: rationale and summary of findings.the objectives for the clinical testing of the inactivated hepatitis a vaccine developed by smithkline beecham biologicals are reviewed and the results obtained are summarized. the first studies were carried out in healthy young adult volunteers using pilot vaccine lots prepared from the clf and hm175 strains of hepatitis a virus (hav). it was established that the candidate vaccines were well-tolerated, caused no hypersensitivity reactions and elicited a strong antibody response. as the yield in ...19921335652
properties and classification of hepatitis a virus.hepatitis a virus (hav) is a member of the picornavirus family. it was first provisionally classified as enterovirus 72, but subsequent determinations of its nucleotide and amino acid sequences showed them to be sufficiently distinct to assign the virus to a new genus. heparna-virus (hep-a-rna-virus) has been suggested as the genus name. hav shares the key properties of the picornavirus family: an icosahedral particle 28 nm in diameter with cubic symmetry, composed of 30% rna and 70% protein. th ...19921335653
natural hosts of hepatitis a virus.the host range for hepatitis a virus (hav) is limited to man and several species of non-human primates, and involvement of vertebrates other than primates in hav circulation is unlikely. spontaneous hepatitis a infection has been reported to occur in captive non-human primates including the great apes (chimpanzee) as well as old world (cynomolgus, african vervet, stump-tailed) and new world (aotus) monkeys. the presence of anti-hav antibody in the sera of newly captured monkeys of these species ...19921335654
replication of hepatitis a virus and processing of proteins.isolation and propagation of hepatitis a virus (hav) in cell culture is routinely possible. all primary hav isolates and most established virus strains, however, show a protracted replication behaviour and tend to establish a persistent infection. rapidly replicating, cytolytic variant viruses can be selected from persistently infected cultures under distinct conditions. factors critical for the outcome of hav infection include the genetics of the virus, the physiological state of the infected c ...19921335655
genetic, antigenic and biological differences between strains of hepatitis a virus.recent studies have documented a considerable degree of genetic divergence among wild-type hepatitis a virus (hav) strains recovered from different geographical locations. human hav strains can be grouped into four genotypes (i, ii, iii and vii) and unique simian strains belong to three additional genotypes (iv, v and vi). between each of these genotypes, the nucleotide sequence varies at 15-25% of base positions in the p1 region. despite this, there is good evidence that most, if not all, human ...19921335657
passive immunization against hepatitis a.administration of human serum immune globulin (ig) is an effective means of protecting individuals against hepatitis a virus (hav) infection and disease. several large field studies have demonstrated that if given before exposure, ig will prevent infection with hav. furthermore, if ig is given during the incubation period of hepatitis a, the severity of infection may be reduced and potentially clinical infections may be converted into subclinical ones. although uncommon, infection which occurs i ...19921335658
possible approaches to develop vaccines against hepatitis a.more than a decade ago, successful replication of hepatitis a virus (hav) in cell culture opened the way to the development of live attenuated and inactivated vaccine candidates. serial passages of hav in cell culture led to attenuation as demonstrated by experiments in non-human primates. several live vaccine candidates obtained through serial passages have been evaluated in volunteers. significant improvements in the yield of viral antigen from infected cell cultures stimulated the development ...19921335659
epidemiological patterns of hepatitis a in different parts of the world.serological surveys in many communities show a high prevalence of antibodies to hepatitis a virus (hav) in people over the age of 50 years. however, few of that age can recall a previous episode of hepatitis, indicating that subclinical infections are common. the outcome of infection with hav depends on the age at which infection occurs and, perhaps, the infectious dose. fulminant disease is well recorded, with the frequency varying from one to eight per 1000 cases. information on the frequency ...19921335660
epidemiology of hepatitis a in mediterranean countries.infection with hepatitis a virus (hav) is still endemic in some mediterranean areas. in most northern mediterranean countries, the incidence of acute icteric hepatitis in adults is increasing. this is due to the shifting of hav infection to adulthood as a result of the decline of its overall prevalence due to improvements in socioeconomic, sanitary and hygienic conditions. the majority of adults remain susceptible and develop overt disease when infected, since the severity of disease is highly a ...19921335662
ecology and prevention of a shellfish-associated hepatitis a epidemic in shanghai, china.during a shellfish-borne hepatitis a outbreak in shanghai during the first quarter of 1988, 300,000 cases were reported in two months. using cell culture and experimental infection of marmosets, hepatitis a virus (hav) was isolated from clams collected from the market and the sea bed during the epidemic. a dose-response curve correlating the quantity of clams consumed to the attack rate of hepatitis a was well documented. the occurrence of the epidemic was associated with a good harvest of clams ...19921335663
hepatitis a as an occupational hazard.few studies have been carried out to evaluate the role of hepatitis a virus (hav) as an occupational hazard. our analysis of data on occupational diseases in germany showed that hepatitis a ranks as third among infectious occupational diseases. morbidity based on the frequency of compensation (15.2%) was in the same range as that observed for hepatitis b (19.7%). in another study, data were collected on anti-hav prevalence among 2293 hospital workers in southwest germany. anti-hav prevalence of ...19921335666
who should receive hepatitis a vaccine? considerations for the development of an immunization strategy.the availability of efficacious hepatitis a vaccines should greatly facilitate the prevention of hepatitis a virus (hav) infection. groups at high risk of hav infection have been identified from epidemiological studies and include both children and adults. while certain high-risk adults, such as travellers, could be a convenient target for vaccination, selective immunization of high-risk adults would not be expected to lower the overall rates of infection in most countries. because a significant ...19921335667
cost-effectiveness analysis of hepatitis a prevention in travellers.the advent of new vaccines and the changing epidemiology of hepatitis a call for an update of the economic evaluation of costs and benefits associated with the various alternative preventative strategies. a decision-tree-based model has been developed which enables the calculation of expected costs and expected numbers of hepatitis a virus hav infections based on different intervention strategies. the model is sufficiently generic to allow for the evaluation of both population-wide strategies an ...19921335668
perspectives on the control of hepatitis a by vaccination.the availability of an inactivated hepatitis a virus (hav) vaccine, and the development of live attenuated virus vaccines against hepatitis represent great advances in the effort to control an important cause of viral hepatitis. there are a number of ways hepatitis a vaccines could be used, depending on the epidemiology of hav infection in the country concerned, the cost of the product, the duration of protection that the vaccine affords and its effectiveness for postexposure prophylaxis. expert ...19921335670
[antibody titers against the hepatitis a virus in a healthy population from an urban health area].to assess the level of immunity in a healthy population to the hepatitis a virus (hav), according to age groups and in an urban health area.19921339210
the seroepidemiology of hepatitis a and b in a japanese town.sera collected from 1,118 healthy children and adults aged between four years and 90 years during the period 1989 to 1990, were tested for serological markers of hepatitis a virus (hav) [antibody to hav (anti-hav)] and hepatitis b virus (hbv) [hepatitis b surface antigen (hbsag) and antibody to hepatitis b surface antigen (anti-hbsab)]. the overall prevalence rates of anti-hav, hbsag, and anti-hbv were 20.2%, 0.36%, and 5.1%, respectively. no body was found to be positive for anti-hav below 30 y ...19921339221
primary isolation of a brazilian strain of hepatitis a virus (haf-203) and growth in a primate cell line (frhk-4).1. although hepatitis a is endemic in brazil, this is the first report describing the isolation of a brazilian strain of hepatitis a virus (hav). 2. fecal specimens obtained from patients in the acute phase of hepatitis a were inoculated into fetal rhesus kidney cell cultures (frhk-4). only one inoculum, denoted haf-203, could be propagated serially. both cell lysates and tissue culture fluids of infected cells were used as inocula and evaluated for viral antigen and rna content by enzyme immuno ...19921342600
reactogenicity and immunogenicity of inactivated hepatitis a vaccines.two inactivated hepatitis a virus (hav) candidate vaccine strain were tested, derived from strains clf and hm175. neither vaccine increased liver enzymes levels and reactogenicity was similar to that observed with other alum-absorbed products. antibody responses were dose-dependent and protection against hav can be presumed to last for at least three years. all persons receiving 720 elisa units (el.u) of the clf vaccine seroconverted after one dose. for the hm175 vaccine, anti-hav persisted unti ...19921362031
hepatitis c core antibody detection in acute hepatitis and cirrhosis patients from tunisia.the detection of anti-hepatitis c virus (hcv) core antibodies is an important addition to hcv antibody testing. in this study it appears to be more specific than the first generation hcv tests and in combination with the detection of anti-c33c antibodies, it is possibly more sensitive. in tunisia hepatitis c virus is implicated by the presence of anti-core antibodies in only 8% of the adult cases of acute hepatitis as opposed to 60% for hepatitis b virus (hbv) and 4% for hepatitis a virus (hav). ...19921383914
enteric non-a, non-b hepatitis: epidemics, animal transmission, and hepatitis e virus detection by the polymerase chain reaction.we studied epidemics of viral hepatitis occurring at three different places in india. one was a combined epidemic due to hepatitis e virus (hev) and hepatitis a virus (hav) infections. in this epidemic, hav affected children below 10 years of age, whereas hev infected the young adult population. hev was transmitted to rhesus monkeys (macaca mulata) and confirmed by the polymerase chain reaction (pcr) on bile from the animals. fecal material from acutely infected patients in one of the epidemics ...19921402825
mutations within the 5' nontranslated region of hepatitis a virus rna which enhance replication in bs-c-1 cells.passage of human hepatitis a virus (hav) in cell culture results in attenuation of the virus as well as progressive increases in the efficiency of virus replication in cell culture. because the presence of identical mutations within the 5' nontranslated regions (5'ntrs) of several independently isolated cell culture-adapted hav variants suggests that the 5'ntr may play a role in determining this change in virus host range, we constructed chimeric infectious cdna clones in which portions of the 5 ...19921404601
[complement c3 and c4 levels in serum from acute viral hepatitis].serial measurements of c3 and c4 complement components were performed in 50 patients with acute, uncomplicated viral hepatitis, in the beginning of the symptoms and in the peaks of serum transaminases. there were 17 patients diagnosed as having hepatitis a virus (hav) infection and 33 patients diagnosed as having hepatitis b virus (hbv) infection. there were 4 women and 46 men with a mean age of 22.1 years. in the sera of 50 healthy control subjects serum c3 and c4 complement components measured ...19921435361
immune pathogenesis of hepatitis a.in an effort to elucidate the mechanism of liver damage resulting from hepatitis a virus (hav) infection, we have studied infected skin fibroblasts and autologous lymphocytes from hav patients. we report here that hla-restricted virus-specific t cells play an essential role in hav-related hepatocellular injury.19921450708
relapsing hepatitis a in saimiri monkeys experimentally reinfected with a wild type hepatitis a virus (hav).saimiri monkeys were inoculated three times with hepatitis a virus and observed in a follow-up study for sixteen months. the monkeys developed recurrent hepatitis involving liver damage and cycles of hav antigen shedding in stools. the relapses were presumably due to immune response effects.19921450724
nosography and immunopathogenesis of viral hepatitis.five viruses are responsible for the vast majority of cases of viral related hepatitis. they have been named hepatitis a virus (hav), hepatitis b virus (hbv), hepatitis c virus (hcv), hepatitis d virus (hdv), hepatitis e virus (hev). the more recent literature concerning the viral structure, the epidemiology, the serological identification, the clinical course and the prevention of each type of hepatitis is reviewed. hbv is not directly cytopathic. hepatitis is a consequence of the destruction o ...19921501725
hepatitis a virus 3c proteinase substrate specificity.hepatitis a virus (hav) 3c proteinase is responsible for processing the viral precursor polyprotein into mature proteins. the substrate specificity of recombinant hepatitis a 3c proteinase was investigated using a series of synthetic peptides representing putative polyprotein junction sequences. two peptides, corresponding to the viral polyprotein 2b/2c and 2c/3a junctions, were determined to be cleaved most efficiently by the viral 3c proteinase. the kcat/km values determined for the hydrolysis ...19921510973
sociodemographic factors and the declining prevalence of anti-hepatitis a antibodies in young adults in israel: implications for the new hepatitis a vaccines.in order to examine changes in the epidemiology of hepatitis a virus (hav) infection in israel during the past decade, a sero-epidemiological study was carried out in 1989 in a random sample of 1153 members of the permanent army, aged 21-30 years. of the males 59.2%, and 54.3% of the females were anti-hav antibody positive (p = 0.22). at all ages, the highest prevalence was in those of north african origin, followed by those of asian, native israeli and western origin. there was a marked decline ...19921544745
immunoglobulin prophylaxis for hepatitis a.studies conducted over the past 45 years have shown that immunoglobulin (ig) prevents 80%-90% of cases of hepatitis a when administered before exposure or shortly thereafter. protection is short lived and requires early diagnosis and timely administration of ig to contacts. inactivated and attenuated hepatitis a virus (hav) vaccines have recently been developed and should be available for clinical use within the next few years. evaluation of antibodies to hav in ig and in ig recipients provides ...19921554845
antigenic and immunogenic properties of recombinant hepatitis a virus 14s and 70s subviral particles.hepatitis a virus (hav) has an immunodominant neutralization antigenic site. by using a panel of monoclonal antibodies targeted against the hav neutralization antigenic site, it was shown that three epitopes within this site are present on 14s subunits (pentamers of the structural unit). in contrast, two other epitopes within this site are formed upon assembly of 14s subunits into capsids. thus, the epitopes recognized by these two monoclonal antibodies are formed either by a conformational chan ...19937678298
simple method of concentrating enteroviruses and hepatitis a virus from sewage and ocean water for rapid detection by reverse transcriptase-polymerase chain reaction.a rapid and simple method was developed to detect enteroviruses and hepatitis a virus (hav) in sewage and ocean water. sewage samples were concentrated by centriprep-100 and centricon-100 at 1,000 x g. samples collected from estuary and near-shore surf zone ocean water in southern california were concentrated by vortex flow filtration and microconcentration. reverse transcriptase-polymerase chain reaction (rt-pcr), with enterovirus primers or hav capsid-specific primers, was used to detect enter ...19937504433
comparison of immunological and molecular hybridization detection methods for the detection of hepatitis a virus in sewage.immune electron microscopy (iem), radioimmunoassay (ria) and molecular hybridization with a digoxigenin-labelled cdna probe were compared for the detection of wild-type human hepatitis a virus (hav) in raw and treated sewage. in the same experiments, classic tests for culturable enteroviruses were carried out. with the hybridization probes, hav was detected in three of the 13 affluent samples (23%) and in eight out of 13 effluent samples (61%). for four of the effluent samples, positivity reveal ...19937764091
[water and viral hepatitis].the main agents responsible for acute viral hepatitis throughout the world are the hepatitis a virus (hav) and the hepatitis e virus (hev). both are transmitted by fecal-oral route and can provoke large epidemics, hav in developed countries and hev in developing countries. water is a major vehicle of spread. however, two different epidemiological patterns have to be distinguished: level of hav excretion is short but high. because of its resistance to physical and chemical agents, hav remains inf ...19937819806
propagation of hepatitis a virus in a renal cell line jtc-12.p3 of cynomolgus monkey origin.human hepatitis a virus (hav) derived from 10% hav infected marmoset liver homogenate and faeces from acute hepatitis a was successfully propagated in vitro in a new cell line, jtc-12.p3. the cell line originated from the renal cortex of cynomolgus monkey which was adapted to growth in a serum free, protein free, chemically defined synthetic medium. replication of the virus was followed by solid phase ria, immunofluorescent staining, and immunoelectron microscopy. the propagation of hav occurred ...19937905235
cytolytic activity of natural killer cells and lymphokine activated killer cells against hepatitis a virus infected fibroblasts.the role of natural killer (nk) cells, lymphokine activated killer (lak) cells and the induction of cytokines in the hepatocellular injury of hepatitis a were studied in vitro using a 51cr release assay in hepatitis a virus (hav) infected mrc-5 cells (mrc-hav). when fresh peripheral mononuclear cells (pbmc) from healthy, anti-hav antibody (-) and (+) human donors, or patients with acute hepatitis a were used as effector cells, mrc-hav were lysed more extensively than uninfected cells. similarly, ...19937932628
[the clinical picture, course and outcome of viral hepatitis a in children with chronic hbv infection].the clinical picture, course and outcomes of hepatitis a developing as a superinfection in children with chronic hepatitis b virus (hbv) infection, hospitalized in connection with acute viral hepatitis, were determined on the basis of the dynamic clinico-laboratory investigation and identification of viral hepatitides a, b and delta by the method of enzyme immunoassay. in all children hepatitis b virus surface antigen (hbsag), i.e. the serological sign of hbv infection, and anti-hav igg, the ser ...19938067100
[a system for the mass combined vaccination of the adult population against influenza, viral hepatitis, typhoid, meningitis and diphtheria].a safe, moderately reactogenic and immunologically effective scheme of complex (combined) immunization against meningitis a, diphtheria, typhoid fever, viral hepatitis a and influenza has been developed as the result of experimental and clinico-immunological studies. depending on the epidemiological situation, the newly developed scheme can be used in two variants. according to the first variant of this scheme, the following preparations are injected subcutaneously into three different sites: a ...19938067144
[the isolation and study of the characteristics of a cytopathic strain of the hepatitis a virus].a fast-growing cytopathic isolate of human hepatitis a virus (strain mb-7) was derived from fecal samples of infected patients and adapted to growth in frhk-4 cell culture. a positive serum standard against hav and electron microscopy were used to demonstrate that mb-7 belonged to human hepatitis a virus. the strain mb-7 induced plaque formation in frhk-4 under agar overlay after 10-12 days of incubation. the pcr products of gene vp1 were cloned in e. coli and its primary structure was determine ...19938073747
foodborne hepatitis a--missouri, wisconsin, and alaska, 1990-1992.person-to-person spread is the predominant mode of transmission of hepatitis a virus (hav) infection. however, based on findings for national surveillance for viral hepatitis, since 1983, 3%-8% of reported hepatitis a cases have been associated with suspected or confirmed foodborne or waterborne outbreaks (1). this report summarizes three recent foodborne outbreaks of hepatitis a and addresses the prevention of this problem.19938321179
secular trends in hepatitis a virus infection among alaska natives.to assess the epidemiologic characteristics of the population susceptible to hepatitis a virus (hav) infection and determine the natural history of infection, a retrospective survey was done using banked serum specimens. a random sample of 4030 alaska natives statewide was selected, stratified by year of birth and community of residence. overall, 1988 serum samples (49.3%) tested positive for antibody to hav (anti-hav). past hav infection was strongly age-related, increasing from 7% in persons b ...19938376812
proteins specifically binding to the 3' untranslated region of hepatitis a virus rna in persistently infected cells.establishment of persistency is the common result of hepatitis a virus (hav) infection in most hav/cell culture systems. previous studies provided evidence that shortly before or concomitantly with establishment of persistent infections synthesis of viral rna is down-regulated. this may be an effect of regulating factors. using rna/protein binding assays it was shown that, at the critical time during virus replication, proteins accumulate which interact specifically with a distinct nucleotide se ...19938380325
simple haemadherence test for the detection of class-specific immunoglobulins to hepatitis a virus.the ability of hepatitis a virus (hav) to agglutinate human erythrocytes was used to develop igm and igg antibody capture haemadherence tests (machat and gachat). haemadherence was dependent on the ph of the red cell suspension and was best in the ph range 5.4 to 5.8. the tests were applied to serum, urine, and saliva specimens from individuals susceptible to, or with recent or past infection with hav. haemadherence test reactivities were compared with results obtained with igm and igg antibody ...19938380840
search for intrafamilial transmission of hepatitis c virus in hemophilia patients.this study was performed to determine the risk of family members of anti-hepatitis c virus (hcv)-positive hemophilia patients (index patients) for infection with hcv compared with the risk of acquiring hepatitis b virus (hbv), human immunodeficiency virus (hiv), and hepatitis a virus (hav) infection. all index patients (n = 141) were found to be positive by first and second generation anti-hcv enzyme immunoassays (eias). among their household contacts (n = 228), 224 were negative and 1 positive ...19938381312
primary cleavage of the hav capsid protein precursor in the middle of the proposed 2a coding region.portions of the p1 and p2 hepatitis a virus (hav) polyprotein were generated by in vitro translation of cdna transcripts and analyzed for a primary cleavage reaction that would release the capsid protein precursor. no autocatalytic activity was observed on either side of the 2a coding sequence. incubation of these proteins with an extract containing active hav 3c protease, however, resulted in cleavage at a position approximately 40 amino acids downstream of the previously proposed p1-2a junctio ...19938382411
expression of hepatitis a virus poly(u) polymerase in the periplasmic space of escherichia coli.a cdna containing almost all of the hepatitis a virus (hav) p3 sequences was expressed as a fusion protein with protein a. a novel poly(u) polymerase activity was detected in the periplasmic space of escherichia coli cells transformed with this plasmid, and this activity showed many of the expected properties of a picornavirus 3dpol. a number of hav-specific polypeptides were detected in these cells, and it is unclear which of these was responsible for the polymerase activity.19938383186
preparation and immunogenicity of an inactivated hepatitis a vaccine.a hepatitis a vaccine was prepared by formaldehyde inactivation of purified hepatitis a virus (hav) lsh/s strain grown on human diploid mrc-5 cells. the vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. infectious hav particles were not detected in faeces and sera of the vaccinated primates by elisa or after passages in mrc-5 cells. the immunogenicity of the vaccine ...19938383387
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