Ian D. Gust

The global circulation of seasonal influenza A (H3N2) viruses.

Antigenic and genetic analysis of the hemagglutinin of ∼13,000 human influenza A (H3N2) viruses from six continents during 2002–2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.

Epidemiology of hepatitis B infection in the Western Pacific and South East Asia.

The Western Pacific and South East Asia regions are the largest and most populous of the six World Health Organisation regions and include more than 40 countries. More than 75% of the worlds estimated 350 million carriers are located here. The region has therefore provided many insights into the epidemiology, natural history, and control of hepatitis B infection and has been home to the first national control programmes. Hepatitis B is hyperendemic in most countries of the region, with carrier rates ranging from 5-35% except in Australia, New Zealand, and Japan, where the mean carrier rate is less than 2%. Patterns of infection vary considerably from country to country, city to city, and even village to village, and can change with time. Most infections are acquired early in childhood or in early adult life. A variety of control measures are in place and many countries in the region have introduced widespread or universal childhood immunisation policies with significant success. While it is theoretically possible that hepatitis B infection could be eradicated by universal childhood immunisation, there are several biological and practical issues that make this extremely difficult, suggesting that, for the foreseeable future, control may be a more realisable goal.

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 of hepatitis A can be obtained by analysing hospital records and notifications to health authorities or by serological surveys. In many countries, these data are limited and seriously underestimate the true frequency of the disease. At a conservative estimate, the incidence of disease in most developed countries is probably four to five times higher than the number of notifications. HAV appears to circulate in most parts of the world and to be responsible for both epidemic and sporadic disease. Three major patterns of infection are known which reflect different epidemiological situations. These are demonstrated by different patterns of the age-specific prevalence of antibodies to HAV which reflect standards of hygiene and sanitation, the degree of crowding of the population and opportunities for the virus to survive and spread.

Immunoglobulin M antibodies against hepatitis B core antigen in patients with chronic hepatitis B infection

Summary A batch of sera obtained from subjects with acute hepatitis B virus (HBV) infection, chronic carriers of hepatitis B surface antigen (HBsAg) who were either asymptomatic or who had chronic active hepatitis, and 32 sera from patients with HBsAg negative chronic active hepatitis were examined for the presence of antibodies against hepatitis B core antigen (anti‐HBc) by radioimmunoassay (RIA). Sera containing anti‐HBc were fractionated on sucrose density gradients to separate immunoglobulin M (IgM) and the titre of anti‐HBc IgM was determined. In patients with acute HBV infection, anti‐HBc IgM was detected during the acute phase of the illness with titres ranging from 1:128 to 1:4,096 (geometric mean titre 1:709). The titre of anti‐HBc IgM fell rapidly over the following months and in most patients persisted at low levels for several years. Anti‐HBc IgM was also detected in subjects with chronic HBV infection but with significantly lower titres. In asymptomatic carriers, anti‐HBc IgM titres ranged from 1:4 to 1:32 (geometric mean titre 1:12), whilst carriers with chronic active hepatitis had titres ranging from 1:4 to 1:128 (geometric mean titre 1:35). By using a standardized assay procedure, the titre of anti‐HBc IgM in a patients serum may be of value in differentiating between acute and chronic HBV infection.

Sequence conservation and divergence of hepatitis δ virus RNA

The complete RNA sequence of the hepatitis delta virus (HDV) obtained from the Nauru Island in the Pacific was determined by cDNA cloning and amplification by polymerase chain reaction (PCR). The sequence showed 14-17% divergence from the two known HDV RNA sequences. There are three highly conserved domains: the region around the autocatalytic cleavage site of the genomic RNA (nucleotides 659 to 772), the region around the autocatalytic cleavage site of the antigenomic-sense RNA (nucleotides 847 to 966), and the region around the middle one-third domain of the open reading frame (ORF) encoding the hepatitis delta antigen on the antigenomic RNA (nucleotides 1267 to 1347). The two autocatalytic activities are required for the cleavage and ligation of HDV RNA during RNA replication. The third conserved domain codes for the RNA-binding domain of HDAg, which specifically interacts with HDV RNA. Three nucleotide changes within the genomic catalytic sequence are present but did not alter the catalytic cleavage activity of the HDV RNA. Microheterogeneity of the RNA sequences was also detected. One of these occurred within the coding region of the delta antigen, creating an amber termination codon in some of the RNA species. Thus, this HDV strain contains two different RNA species, one of which encodes a delta antigen of 214 amino acids and the other 195 amino acids. These two protein species were detected by immunoblotting of the patients plasma. In contrast to other HDV strains, only three ORFs capable of encoding more than 100 amino acids each are present in this HDV RNA. We recommend that oligonucleotides complementary to the highly conserved sequences should be used as primers for PCR in clinical detection assays of hepatitis delta virus infection.

Taxonomic Classification of Hepatitis A Virus

Sufficient data have accumulated to permit the ICTV Ad Hoc Study Group on the Taxonomy of Hepatitis Viruses to recognize hepatitis A virus as a picornavirus. Within the family Picornaviridae, hepatitis A virus closely resembles members of the genus Enterovirus.

The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive.

To determine whether active viral replication is associated with increased morbidity and mortality in chronic carriers of hepatitis B virus (HBV) undergoing renal transplantation, we reviewed 23 years of experience at our hospital. Over the period 1966-1989, 42 chronic carriers of hepatitis B surface antigen (HBsAg) received renal transplants, 32 of whom had functioning grafts for 12 months or longer. Stored sera were tested for markers of hepatitis B virus, hepatitis C virus (HCV), and hepatitis delta virus (HDV) infection, and the serologic findings were correlated with clinical and biochemical data. The presence of HBV DNA and/or hepatitis Be antigen (HBeAg) in serum samples collected prior to transplantation was associated with an increased probability of death from liver disease. Whereas 5 of 10 patients in this group died of chronic liver disease, only 1 of 15 patients who were HBV DNA and/or HBeAg negative prior to transplantation died of liver disease. This difference is highly significant (P less than 0.02). No difference in outcome was attributable to age at transplantation, gender, country of birth, or the presence of abnormal hepatic transaminase levels prior to transplantation.

Taxonomic classification of human hepatitis B virus

Sufficient data have accumulated to permit the ICTV Study Group on the Nomenclature of Hepatitis Viruses to recognize human hepatitis B virus as a member of a unique group of viruses and to classify it, together with a number of related animal viruses, into a new family called the Hepadnaviridae. Over the past decade, the International Committee on Taxonomy of Viruses (ICTV) has been active in the development of a classification system for viruses. The majority of viruses infecting vertebrate hosts have been classified into families and genera on the recommendations of the Vertebrate Virus Subcommittee (VVSC). In June 1980, the VVSC authorized the formation of an ad hoc Study Group on the Nomenclature of Hepatitis Viruses under the Chairmanship of Dr. Ian D. Gust. This paper represents the first report of the Study Group on the Taxonomic Classification of Human Hepatitis B Virus.

Viruses and virus-like particles in the faeces of dogs with and without diarrhoea.

SUMMARY Negative staining electron microscopy was used to identify viruses in 157 normal and 29 diarrhoeal faecal samples collected from 156 dogs admitted to an animal shelter during an 8 month period (March to October) in 1982. Seven distinct viral types were detected: 21–26 nm parvovirus‐like particles, 28–31 nm astrovirus‐like particles, a previously undescribed 34–35 nm ‘round’ virus particle, coronavirus, coronavirus‐like particles (CVLP), rotavirus and papova‐like virus. Parvovirus‐like particles alone were detected in 14 diarrhoeal and 50 normal faeces, astrovirus‐like particles in 3 normal faeces, “round” viruses in 4 normal faeces, coronavirus in 2 diarhoeal and 5 normal faeces, CVLP in one diarrhoeal and one normal faeces, rotavirus in 2 normal faeces, papova‐like virus in one normal faeces, both parvovirus‐like particles and coronavirus in 2 diarrhoeal and 2 normal faeces, parvovirus‐like particles and rotavirus in one normal faeces and parvovirus‐like and papova‐like virus in one normal faeces. The significance of these findings in canine and human disease is discussed.

The antibody response following hepatitis A infection.

A specific IgM response to hepatitis A virus was detected in sera from patients suffering acute hepatitis A infection. The presence of virus-specific IgM in 19S components of acute and early convalescent phase sera was detected by immune electron microscopy and solid-phase radioimmunoassay. The presence of virus-specific IgM in whole serum specimens was demonstrated by indirect immunoferritin labeling. Following acute infection, however, the major immunoglobulin response appears to be IgG, since titers of specific 7S and whole serum antibody were very similar.