Biomedical subjects
I D Gust
Publications and source records attributed to I D Gust.
Seroepidemiology of infection with hepatitis B virus in Fiji.
A batch of 984 sera obtained from a stratified sample of Melanesians and Indians living in rural and urban areas of Fiji in 1981 were for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) by solid phase radioimmunoassay. The prevalence of hepatitis B infection (as measured by the sum of HBsAg and anti-HBc frequencies of HBsAg negative sera in the two groups) was 81.5% and 17.9%, respectively. No major differences were detected between urban and rural populations. While hepatitis B virus is endemic in Melanesians and Indians, the epidemiology of the infection shows certain differences. Among Melanesians, infection appears to be acquired early in life and peak prevalence of serologic markers of infection occurs during the second decade. Among the Indian population, the prevalence of markers increases steadily with age, presumably as a result of continuous exposure and infection throughout life. the high prevalence of infection and carriers among Melanesians is consistent with previous observations among Pacific populations. The lower prevalence of infection among Indians is remarkable, since they constitute almost half of the total population and live under similar conditions. Since the two populations remain largely separate in terms of housing and schooling, and intermarriage is uncommon, it is no possible to determine whether these differences merely represent different degrees of exposure to the virus or are the reflection of differences in susceptibility or response to infection.
A longitudinal study of hepatitis infection in an institution for the mentally retarded.
The natural history of hepatitis A and B infections in a large institution for the mentally retarded were studied over an eight year period. Serum samples were obtained from most subjects on three occasions and tested for anti-HAV, HBsAg, anti-HBs and occasionally anti-HBc, by solid-phase radioimmunoassay. Hepatitis A was found to have been a common infection was 74.8% of subjects having detectable levels of antibody. The virus does not appear to be endemic, as the prevalence of antibody in children admitted since the last outbreak was no higher than amongst non-institutionalised children. The infection rate amongst subjects with Down's syndrome (DS) was higher than amongst subjects with other forms of mental retardation (OMR), and more than 95% of infections in both groups were unrecognised. By contrast with hepatitis A, hepatitis B virus was endemic in the institution with 81.2% of residents showing serological evidence of current or past infection. Of these, 40.8% of subjects with DS and 9.2% of those with OMR were found to be chronic carriers. The carrier rate was higher in males than females and tended to be more prolonged in subjects with DS. During the study period, the predominant subtype of HBsAg detected in the institution changed from adw to ayw.
Biophysical and biochemical characterization of hepatitis A virus.
Biophysical and biochemical analysis of hepatitis A virus has shown it to be a 27- to 32-nm icosahedral particle with 32 capsomers. The mature virion has a buoyant density of 1.33-1.34 g/cm3, a sedimentation coefficient of 156-160S, and is composed of four polypeptides with molecular weights of 30,000-33,000 (VP1), 24,000-27,000 (VP2), 21,000-23,000 (VP3), and 7,000-14,000 (VP4). The genome of hepatitis A virus consists of a single piece of single-stranded RNA which sediments at 32-35S and has a buoyant density of 1.64 g/cm3. The molecular weight of RNA is 2.25 x 10(6) when measured under nondenaturing conditions and 2.8 x 10(6) when measured under fully denaturing conditions. The genome contains a 40-80 nucleotide sequence of polyadenylic and is capable of infecting cell cultures. These findings, together with the observation that the virion is stable at pH 3.0 and resistant to ether and a temperature of 60 degrees for 1 h, indicate that hepatitis A virus should now be classified as an Enterovirus within the family Picornaviridae.
Human rotavirus infection in Efate, Vanuatu.
Serum and fecal samples collected from children with gastroenteritis and healthy children and adults living in Efate, Vanuatu (formerly the New Hebrides), were tested for the presence of human rotavirus antigen or antibody by electron microscopy and enzyme-linked immunosorbent assay. Virtually every subject was found to have detectable levels of antibody and age-specific studies showed that primary infections occur early in life. Human rotavirus was demonstrated to be the cause of an outbreak of gastroenteritis among children which occurred between August and September 1980, although it had not been detected in the population in the preceding 13 months. Epidemics of human rotavirus-associated gastroenteritis appear to occur every 2nd year in this population.
Coronavirus-like particles and other agents in the faeces of children in Efate, Vanuatu.
Between June 1979 and July 1980, faecal specimens were collected from 100 children in Efate, Vanuatu, and examined for the presence of virus-like particles by direct negative staining electron microscopy. Of the children, 40 were hospital patients 22 of whom had gastroenteritis and 18 had other illnesses. The remaining 60 children were apparently healthy controls. Coronavirus-like particles were the most common agents encountered and were detected in approximately 20% of all three groups of children. Particles with the morphological features of calicivirus, astrovirus, adenovirus and parvovirus were also detected.
Segregation of autoantibody to cytoskeletal filaments, actin and intermediate filaments with two types of chronic active hepatitis.
Regional differences in serological features of chronic active hepatitis (CAH) were assessed from study of unselected patients with CAH, 53 from Zagreb, Yugoslavia and 53 from Melbourne, Australia. A group of 29 patients from Zagreb with chronic persistent hepatitis (CPH) was also included. The serological marker studied was immunofluorescence reactivity to cytoskeletal components, actin cables (AC) and intermediate filaments (IF), these being mostly responsible for the smooth muscle antibody reactivity which occurs in CAH. The Zagreb cases of CAH differed from the Melbourne cases by having a significantly lower frequency of anti-AC (8% vs 55%) and a significantly higher frequency of anti-IF (34% vs 15%), and correspondingly had a higher frequency of markers of hepatitis B virus (HBV) infection (HBsAg, 53% vs 8% and anti-HBc, 72% vs 34%), and a differing HLA profile, with HLA BW35 higher (38% vs 14%) and B8 lower (18% vs 56%). This study illustrates the differences among populations in expression of CAH, in that HBsAg is held to specify the HBV-associated type, and antibody to actin is held to specify the autoimmune type. These differences would be determined in part by environmental influences, notably HBV, and genetic influences, notably HLA, and are reflected by the differing patterns of immunofluorescence reactivity with the cellular cytoskeleton.
Serum immunoglobulin levels in acute A, B, and non-A, non-B hepatitis.
Immunoglobulin M, G, and A concentrations were determined by radial immunodiffusion in sera collected from 117 patients with acute hepatitis A, hepatitis B, or non-A, non-B hepatitis. Statistically significant differences in IgG and IgM levels were detected between the three groups. In particular, elevated IgG and almost-normal IgM levels were regularly detected in patients with non-A, non-B hepatitis while the opposite pattern was seen in patients with hepatitis A. Calculation of a serum IgG/IgM ratio enabled discrimination between most patients with non-B hepatitis. In 92% of patients with hepatitis A, the ratio was less than 6, whereas 82% of patients with non-A, non-B hepatitis had ratios of greater than 6. The IgG/IgM ratio may be of value in distinguishing between subjects with the two forms of the disease when specific serologic tests are unavailable.
Viral hepatitis.
THREE FORMS OF VIRAL HEPATITIS CAN BE RECOGNIZED: hepatitis A, hepatitis B, and hepatitis non-A, non-B. Hepatitis A is caused by a picornavirus, is transmitted by the faceal-oral route, does not become chronic, and no chronic virus carriers exist. The virus can be grown in cell cultures, and killed as well as live attenuated virus vaccines are under development. Hepatitis B is caused by an enveloped virus containing a circular, double-stranded form of DNA. The disease is transmitted parenterally through inoculation of blood or blood products containing virus or through close personal contact with a virus-positive person. Hepatitis B becomes chronic in a certain number of cases and can lead to cirrhosis and primary liver cell carcinoma. The blood and certain body secretions of individuals with a persistent or chronic infection may remain infectious for many years. The hepatitis B virus cannot be grown in cell cultures but the entire genome has been sequenced and cloned in bacterial and eukaryotic cells. An inactivated virus vaccine has been prepared from hepatitis B surface antigen present in the plasma of hepatitis B virus carriers and further vaccines are under development. The agents of hepatitis non-A, non-B have not been identified. It is possible to distinguish between a predominantly parenterally transmitted and an orally transmitted form of hepatitis non-A, non-B. The latter is reported to be caused by a picornavirus that does not, however, have any antigenic relationship with hepatitis A virus.
Detection of markers of hepatitis B infection in serum dried on to filter-paper: an application to field studies.
In an attempt to find a cheap, reliable, and convenient method for the transportation and storage of serum specimens during seroepidemiological surveys, a technique in which serum was dried on to pieces of filter paper was developed and evaluated. For the evaluation, a total of 382 sera were selected from the extensive serum collection held by the WHO Collaborating Centre for Virus Reference and Research at Fairfield Hospital, Australia. These sera were dried on to pieces of filter-paper, stored at different temperatures and then tested for the presence of the various markers of infection with hepatitis B virus by solid-phase radioimmunoassay. The results were in complete agreement with those obtained on whole serum specimens. In addition, storage at 4 degrees C, room temperature (22 degrees C), or 37 degrees C for up to 30 days did not alter the sensitivity of the test. This technique may be useful in field surveys, not only for the detection of hepatitis B infection, but also in the study of other diseases and metabolic disorders.
Maintenance dialysis of patients infected with hepatitis B virus.
Haemodialysis of patients who were acutely or chronically infected with hepatitis B virus has been undertaken at Fairfield Hospital for Communicable Diseases for the past 10 years. Over this period, only one staff member has shown serological evidence of infection. The procedures taken to prevent the spread of infection, and the results of an ongoing serological survey of all persons associated with the haemodialysis unit are presented.
Autoantibody to intermediate filaments in viral hepatitis.
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The prevalence of hepatitis B infection amongst urban and rural populations in Western Samoa.
A group of 240 urban and 200 rural dwellers in Western Samoa over the age of 20 years was studied for serological evidence of current or past infection with hepatitis B virus (HBV). Overall, 5.5% of subjects were found to be currently infected with HBV and a further 74.5% showed detectable levels of antibody. Antibody to the hepatitis B core antigen was found to be a better marker of past infection than antibody to the surface antigen of the virus. Both the infection rate and carrier rate were higher in males than females and subjects living in rural areas were more likely to be infected than those living in urban areas.
Hepatitis B virus infections in Melanesians and Polynesians in New Caledonia.
Hepatitis B virus infections were examined in two ethnically different Pacific Island groups, 532 Melanesians and 401 Polynesians, living under similar environmental circumstances on the island of Ouvea, New Caledonia. High hepatitis B virus infection rates (Melanesians, 89.3%, and Polynesians, 86.3%) and hepatitis B surface antigen (HBsAg) carrier rates (Melanesians, 11.7%, and Polynesians, 8.0%) were observed in both groups. The carrier rate for HBsAg was generally higher in men, particularly Melanesian men. Comparing the Ouvea Melanesians and Polynesians to 170 Melanesians living on the main island of New Caledonia, significantly lower rates for hepatitis B virus infection (47.1%) and HBsAg carrier state (0.6%) were found. The findings suggest that environmental factors may be more important than genetic factors in hepatitis B infections in these populations. Tattooing did not appear to influence the presence of hepatitis B virus infection.
Propagation of human hepatitis A virus in African green monkey kidney cell culture: primary isolation and serial passage.
Human hepatitis A virus (HAV) was propagated in primary African Green Monkey (Cercopithecus aethiops) kidney (AGMK) cell cultures. Three strains of HAV were used: MS-1, SD-11, and HM-175. Cells were inoculated with marmoset-passaged material or human clinical specimens and were stained by direct immunofluorescence to establish the identity of the virus. Both clinical samples and marmoset-passaged material produced immunofluorescence. HAV antigen was found scattered throughout the cytoplasm of inoculated cultures. The HM-175 strain produced the most intense immunofluorescence. This strain of HAV had been serially passaged in cell culture seven times. Blocking experiments with paired human sera from naturally acquired HAV infections and hyperimmune chimpanzee serum from an experimentally infected animal established that the immunofluorescence was specific. The viral antigen was found to be exclusively intracellular. The interval to maximum HAV antigen expression was decreased by serial passage. The HAV strain described herein, which was recovered directly from the stool specimen of a patient with HAV in primary AGMK cell culture, may prove useful as a source of antigen for serological tests and as a candidate vaccine strain.
Restricted replication of human hepatitis A virus in cell culture: intracellular biochemical studies.
When hepatitis A virus was inoculated into Vero cells, virus-specified protein and RNA synthesis was detected. Production of viral protein was detected by electrophoretic analysis in polyacrylamide gels by using a double-label coelectrophoresis and subtraction method which eliminated the contribution of host protein components from the profiles of virus-infected cytoplasm. Eleven virus-specified proteins were detected in the net electrophoretic profiles of hepatitis A virus-infected cells. The molecular weights of these proteins were very similar to those detected in cells infected with poliovirus type 1. Virus-specified protein synthesis could be detected at 3 to 6 h and continued for at least 48 h postinfection, but no significant effect on host-cell macromolecular synthesis was observed. Limited viral RNA replication occurred between 2 and 6 h postinfection. The genomic RNA of hepatitis A virus was extracted and shown to be capable of infecting cells and inducing the same set of proteins as intact virus, indicating that the RNA genome is positive stranded. Progeny virus was never detected in the supernatant fluids of infected cell cultures, and the cells showed no observable cytopathology, even though hepatitis A virus-specific proteins and antigens were being produced. The nature of the defect in the replicative cycle of hepatitis A virus in this system remains unknown.
Evidence that the genome of hepatitis A virus consists of single-stranded RNA.
Nucleic acid was extracted from purified hepatitis A virus, radiolabeled with 125I, and shown to consist of single-stranded RNA which sediments at 35S and contains sequences of polyadenylic acid. These findings are consistent with hepatitis A virus being a member of the genus Enterovirus within the family Picornaviridae.
Detection of antibodies to single-stranded DNA in naturally acquired and experimentally induced viral hepatitis.
A sensitive "Farr" assay, utilizing 125I-labelled DNA was developed for detecting antibody to single-stranded DNA (anti-ssDNA). The test was shown to be specific and as sensitive as assays using 14C-labelled DNA, for the detection of antibody in patients with connective tissue diseases. Groups of sera from patients with naturally acquired viral hepatitis and experimentally infected chimpanzees were tested for anti-ssDNA by the 125I assay and by counterimmunoelectrophoresis (CIEP). No consistent pattern was observed with either technique, indicating the elevated levels of this antibody are not as reliable markers of parenchymal liver damage as had been previously suggested.