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Biomedical subjects

B H Robertson

Publications and source records attributed to B H Robertson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hepatitis A virus infections associated with clotting factor concentrate in the United States.

BACKGROUND: Two cases of hepatitis A among persons exposed to the same lot of solvent/detergent-treated antihemophilic factor VIII concentrate were reported to a surveillance system. An investigation was conducted to find additional cases and determine the source of infection. STUDY DESIGN AND METHODS: A seroprevalence study was conducted among persons with exposure to the suspect lot for serologic evidence of recent infection with hepatitis A virus (HAV). RESULTS: Six cases of recent HAV infection were discovered: four of the patients had been infused with material from the suspect lot of factor VIII, and two had received infusions of factor IX concentrate made from plasma pools common to the suspect factor VIII lot. HAV was identified in one of the plasma pools, in the factor VIII product, and in serum or stool from two factor VIII recipients and one factor IX recipient. The genetics sequence of the virus in the plasma pool, the factor VIII lot, and the factor VIII recipients were identical, while that of the virus in the factor IX recipient differed by a single base. CONCLUSION: These data document the transmission of HAV by a factor VIII concentrate and implicate factor IX products manufactured from a common source-plasma pool.

Adolescent↗
PubMed1998

Genomic and phylogenetic analysis of hepatitis C virus strains from Argentina.

HCV genomic characterization was performed by nucleotide sequence analysis (n=50) combined with restriction fragment length polymorphism (RFLP) of the 5' UTR region in 82 isolates corresponding to different Argentine groups. Genotype 1 was detected in 70.7% of the samples (58 out of 82), genotype 2 in 21.9% (18 of 82) and genotype 3 in the remaining 6 sera (7.3%). HCV 1b subtype contributed with 35.3% to the whole population studied (29 to 82) and was detected in 6 out of 21 sporadic cases. Besides their epidemiological significance, these results should be taken into account when future vaccines are considered on the basis of geographical HCV genotypic prevalence.

Adolescent↗
PubMed1996

Transmission of hepatitis B virus to multiple patients from a surgeon without evidence of inadequate infection control.

BACKGROUND: Although about 1 percent of surgeons are infected with hepatitis B virus (HBV), transmission from surgeons to patients is thought to be uncommon. In July 1992, a 47-year-old woman became ill with acute hepatitis B after undergoing a thymectomy in which a thoracic-surgery resident who had had acute hepatitis B six months earlier assisted. METHODS: To determine whether the surgeon transmitted HBV to this patient and others, we conducted chart reviews, interviews, and serologic testing of thoracic-surgery patients at the two hospitals where the surgeon worked from July 1991 to July 1992. Hepatitis B surface antigen (HBsAg) subtypes and DNA sequences from the surgeon and from infected patients were determined. RESULTS: Of 144 susceptible patients in whose surgery the infected surgeon participated, 19 had evidence of recent HBV infection (13 percent). One of the hospitals was selected for additional study, and none of the 124 susceptible patients of the other thoracic surgeons at this hospital had evidence of recent HBV infection (relative risk, infinity; 95 percent confidence interval, 4.7 to infinity). No evidence was found for any common source of HBV other than the infected surgeon. The HBsAg subtype and the partial HBV DNA sequences from the surgeon were identical to those in the infected patients. Transmission of the infection was associated with cardiac transplantation (relative risk, 4.9; 95 percent confidence interval, 1.5 to 15.5) but not with other surgical procedures. The surgeon was positive for hepatitis B e antigen and had a high serum HBV DNA concentration (15 ng per milliliter). Our investigations identified no deficiencies in the surgeon's infection-control practices. CONCLUSIONS: In this outbreak there was surgeon-to-patient HBV transmission despite apparent compliance with recommended infection-control practices. We could not identify any specific events that led to transmission.

Adolescent↗
PubMed1996

Effect of immune globulin on the prevention of experimental hepatitis C virus infection.

The efficacy of postexposure prophylaxis for the prevention of hepatitis C virus (HCV) infection was studied in experimentally infected chimpanzees. Three chimpanzees were inoculated with HCV: Two were treated 1 h later with anti-HCV--negative intravenous immune globulin (IGIV) or hepatitis C immune globulin (HCIG), and a third animal was not treated. HCV infection was detected in all 3 animals within a few days of inoculation. Once passively transferred anti-HCV declined in the HCIG-treated animal, there was an increase of HCV antigen (Ag)--positive hepatocytes followed by reappearance of anti-HCV; HCV Ag disappeared concordant with the development of acute hepatitis. Acute hepatitis C developed in both the IGIV-treated and untreated chimpanzees, with peak liver enzyme activity on day 59, but was delayed in the HCIG-treated animal until day 146. Postexposure HCIG treatment markedly prolonged the incubation period of acute hepatitis C but did not prevent or delay HCV infection. IGIV had no effect on the course of HCV infection.

Animals↗
PubMed1995

Hepatitis A virus and polymerase chain reaction amplification: methodology and results.

Hepatitis A infection among patients receiving solvent/detergent inactivated factor VIII preparations in various locations in Europe have been documented recently. In investigations in Italy, Germany and Ireland, polymerase chain reaction (PCR) amplification was used to detect hepatitis A virus in frozen plasma pools, purified factor VIII, patient sera and samples from animal transmission studies; nucleic acid sequencing was used to clarify and identify the virus responsible based upon genotype analysis. Unique virus strains were found among the cases in Italy and Germany, and identical virus sequences were also found in some factor VIII lots. However, with the exception of the Italian investigation, lack of appropriate samples have precluded the identification of virus in these outbreaks. In addition, animal infectivity studies have not been successful in demonstrating infectivity under laboratory conditions. We discuss the limitations of PCR amplification with respect to detecting virus within these situations, and the necessity for the corresponding epidemiologic investigations.

Animals↗
PubMed1995

Direct sequencing of hepatitis A virus strains isolated during an epidemic in France.

Direct sequencing of PCR products was used to study the VP1 region of the hepatitis A virus (HAV) genome (position 2199 to 2356) of nine strains isolated from human stools collected during a hepatitis A epidemic (western France, 1992), three strains from environmental samples (1990, 1991, and 1992), and two HAV cell culture isolates (the French strain CF53/Lyon and strain CLF). These viruses differed from CF53/Lyon (genotype I) by between 1 and 10.3%, and results indicated the existence of two groups of strains belonging to two different subgenotypes (IA and IB). With this sequencing technique it was possible to monitor the epidemiology of HAV and study its relations.

Adolescent↗
PubMed1994

Effect of postexposure vaccination in a chimpanzee model of hepatitis A virus infection.

Passive transfer of antibodies to hepatitis A virus (HAV) in immune globulin (IG) effectively prevents hepatitis A when given after exposure, but does not provide lasting protection from infection. Hepatitis A vaccines have been shown to generate quickly levels of antibody equivalent to those found after IG administration. The effect of hepatitis A vaccine in preventing infection following fecal-oral exposure was evaluated in a chimpanzee model of HAV infection. Two animals were vaccinated 1 and 3 days, respectively following inoculation and two inoculated animals served as unprotected controls. Of the two immunized animals, one had no evidence of HAV infection, while the other had an attenuated infection with no evidence of virus shedding. These results suggest that while postexposure hepatitis A vaccination may be infection permissive, it attenuates disease expression and prevents virus shedding.

Alanine Transaminase↗
PubMed1994

Sequence variability of hepatitis A virus and factor VIII associated hepatitis A infections in hemophilia patients in Europe. An update.

Outbreaks and sporadic cases of hepatitis A have been observed in 4 European countries in hemophilia patients receiving factor VIII preparations. PCR amplification of potential hepatitis A virus (HAV) nucleic acid present in plasma pools, purified factor VIII and acute-phase sera from infected individuals has been performed and the nucleic acid sequence determined for those samples that resulted in a positive PCR product. HAV sequences were detected in the serum of 2 German patients, but not in the factor VIII lots administered to these individuals. Screening of plasma pools and the corresponding 5 lots of factor VIII associated with the outbreak in Ireland did not reveal any HAV sequences. In contrast, a study of samples from Italy detected HAV sequences in 5 of 12 lots and in 2 hemophilia patients who developed hepatitis A. These data suggest that implicated factor VIII preparations might have been involved in the outbreaks of HAV infection among Italian hemophiliacs. However, no molecular evidence was obtained for a similar association in Germany or Ireland. The preliminary data from these two investigations must be verified by animal inoculation studies and supported by epidemiologic analysis.

Base Sequence↗
PubMed1993

Antibody response to nonstructural proteins of hepatitis A virus following infection.

The nonstructural proteins of hepatitis A virus (HAV), produced during active virus replication, are alternative antigens that could be used to differentiate disease from inactivated vaccine-induced antibodies. An assay based on immune precipitation of proteins translated from transcripts of the P2 region of viral cDNA was used to evaluate the development of antibodies after natural infection or vaccination. Antibodies against P2 proteins were found in all sera from clinical cases of hepatitis A following the acute phase. Chimpanzees vaccinated with inactivated or cell-adapted HAV had no detectable antibodies against P2 products, either before or after wild type virus challenge. A serosurvey of sera positive for total anti-HAV (HAVAB, Abbott Laboratories, North Chicago) suggested that some individuals had no detectable antibodies to the P2 antigen by immune precipitation. These results were attributed to the lower sensitivity of the immunoprecipitation assay, since antibodies to capsid proteins, as measured by immunoprecipitation, were also not detected in most of these sera.

Adult↗
PubMed1993

Hepatitis A post-viral encephalitis.

We report a seven-year-old girl who developed a hepatitis A viral infection and encephalitis. The patient developed fever, abdominal pains and jaundice. Five days later she became delirious, combative, and did not respond to verbal commands. Laboratory studies showed elevated liver enzymes and elevated serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies to hepatitis A virus. Cerebrospinal fluid contained IgG antibodies to hepatitis A virus but not IgM antibodies. Polymerase chain reaction, which amplifies a portion of the hepatitis A virus genome, did not demonstrate viral nucleic acid in cerebrospinal fluid. These studies suggest that the patient may have suffered from a post-viral hepatitis A encephalitis from which she fully recovered.

Antibodies, Viral↗
PubMed1992

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 cases of HAV from Sweden in 1979 (H-122) and the United States of America in 1976 (GA76). The nucleic acid sequence of the exposed capsid polypeptide region of GA76 differs from other human HAV sequences by approximately 20%, yet differs by only 2.4% when compared with P1 sequence of the PA21 strain. The 20% nucleic acid variability between GA76 and other human HAV results in limited amino acid changes (3%), while a comparison with PA21 revealed only four homologous amino acid substitutions within VP2, VP3, and VP1 polypeptides. HAV infected stool specimens from Nepal and northern India during 1989 and 1990 were found to contain virus whose genetic makeup was related to the PA21 and GA76 isolates. This genotype of HAV appears to be circulating in some parts of the world where HAV is hyperendemic, and is a potential cause of hepatitis A infection within a susceptible population.

Amino Acid Sequence↗
PubMed1992

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 HAV corresponding to the P2 region was used for in vitro transcription-translation followed by immune precipitation of the translated products under non-denaturing conditions. Serial serum specimens from experimentally infected chimpanzees and humans naturally infected with hepatitis A verified the development of antibodies to P2 proteins following infection. A serosurvey of individuals positive for antibodies to the HAV capsid (HAV AB assay, Abbott Laboratories) revealed that 50-60% of children and 16-32% of adults had no detectable antibodies to the P2 antigen by immune precipitation. These results may reflect subclinical infections resulting in a lower level of antibodies against the non-structural antigens or may represent a greater sensitivity of the competitive assay (HAV AB) used to detect capsid antibodies compared to the immunoprecipitation assay used to detect non-structural antigens.

Adult↗
PubMed1992

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 consumption of strawberry shortcake in hepatitis A virus (HAV) infection (relative risk, 7.6; 95% confidence interval, 1.04-55.6). In the institution, such analysis implicated desserts and uncooked strawberries as the most biologically plausible vehicle of HAV transmission. Molecular analysis of HAV from patients in the two outbreaks revealed that the viral genomes were genetically identical and distinct from other known US strains. Contamination of food products before retail distribution is rare but should be considered in investigating common-source outbreaks of hepatitis A.

Adult↗
PubMed1992

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, whereas viruses from the other three genotypes (IV, V and VI) were isolated only from simian species developing a hepatitis A-like illness during captivity. Among non-epidemiologically related human HAV strains, 81 were characterized as genotype I, and 19 as genotype III. Within each of these major genotypes, there were two distinct groups (subgenotypes), which differed in sequence at approximately 7.5% of base positions. Each genotype and subgenotype has a characteristic amino acid sequence in this region of the polyprotein, with the most divergent genotypes differing at 10 of 56 residues. Strains recovered from some geographical regions belonged to a common (endemic) genotype, whereas strains from other regions belonged to several, probably imported, genotypes. Thus, HAV strains recovered in North America were for the most part closely related at the nucleotide sequence level, whereas in other regions, such as Japan and Western Europe, HAV strains were derived from multiple genotypes or sub-genotypes. These data indicate that patterns of endemic transmission can be differentiated from situations in which infections are imported due to travel.

Amino Acid Sequence↗
PubMed1991

Epidemiologic patterns of wild-type hepatitis A virus determined by genetic variation.

Hepatitis A virus (HAV) isolates from different parts of the world are a single serotype. However, genetic analysis of the VP1 genome region of published HAV sequences suggested that distinct genotypes of HAV could be defined based upon the geographic source of the original isolates. To circumvent the process of cell culture adaptation or animal passage, a 247-bp segment within the VP1 genome region of wild-type HAV was amplified by reverse transcription followed by polymerase chain reaction amplification in the presence of negative- and positive-sense primers. From the sequences obtained from 22 epidemiologically distinct HAV isolates, three genetic groups of HAV could be delineated. Two of the groups differed by 10%, while the third group differed from other isolates by approximately 20%. These investigations indicate that HAV isolates from different parts of the world can be differentiated genetically, which will facilitate studies of epidemiologic transmission.

Animals↗
PubMed1991

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 HAVs, were changed in the CY-145 virus. Sequence analysis of a second cynomolgus HAV isolate (CY-55), which came from a different geographical location, showed the same amino acid replacement at these two sites. In addition both isolates had an amino acid substitution at the VP3-VP1 cleavage site. These data suggest that the cynomolgus HAV differs genetically and antigenically from all other sequenced HAVs.

Amino Acid Sequence↗
PubMed1989

Structure of the hepatitis A virion: identification of potential surface-exposed regions.

Iodination of highly purified hepatitis A (HAV) virus results in the selective labeling of two viral polypeptides, which are identified as the the VP 1 and VP 2 capsid polypeptides. Based upon the kinetics of labeling, the exposed region of VP 1 appears to be more accessible to iodination, although the ultimate proportion of label present within VP 1 and VP 2 is approximately equal. By utilizing iodinated whole virions, isolated VP 1, VP 2, and the tryptic digest derived from VP 1 and VP 2, binding by heterologous anti-160 S antibody indicated that a significant portion of the antibodies was directed against an epitope on VP 2 that was not affected by denaturation. Identification of the regions exposed for iodination on these two polypeptides was accomplished by tryptic digestion of the isolated polypeptides followed by characterization of the iodinated tryptic peptide by gel filtration and reverse-phase chromatography. The results indicate that tyrosine 100 on VP 2 and a large tryptic peptide composed of amino acids 222 through 260 on VP 1 which contains four tyrosine residues are two regions that are surface-exposed on these molecules.

Amino Acid Sequence↗