HTLV-I infection in selected populations in Australia and the western Pacific region.

The prevalence of infection with human T lymphotropic virus type I (HTLV-I) in 19,975 blood samples from Australia and the western Pacific was determined by measuring the presence of specific antibody (anti-HTLV-I) by enzyme-linked immunosorbent assay (ELISA) with confirmation by western blot and/or radioimmunoprecipitation techniques. In Australia no evidence of HTLV-I infection was found in injecting drug users, patients with the acquired immunodeficiency syndrome (AIDS), subjects attending a sexually transmitted diseases clinic, female prostitutes, or transfusion recipients. A low prevalence of infection was detected in people with haemophilia (0.5%) and in male homosexuals (0.5%-1%). No antibody was detected in sera from Vanuatu, Kiribati, American Samoa, the Cook Islands, New Caledonia, the Federated States of Micronesia, French Polynesia and Fiji, but a low frequency of anti-HTLV-I was detected in sera from the Solomon Islands (1.2%) and Nauru (0.6%).

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.

Humoral immune responses in mice using gamma inulin preparations as adjuvants for hepatitis B vaccines.

There is an urgent need for new, powerful adjuvants suitable for use with sub-unit and peptide vaccines in humans. We have measured the humoral immune response in BALB/c mice to vaccine formulations using recombinant HBsAg antigens, and gamma inulin and alum adjuvants. Using Merck, Sharpe & Dohme (MSD) HBsAg at 10 micrograms/mL, high levels of anti-HBs were generated and geometric mean S/N ratios of 88, 133 and 107 were obtained for alum absorbed vaccine, gamma inulin, and a mixture of the two adjuvants, respectively. A dilution series produced ED50 values of 0.08, 0.15 and 0.22 micrograms/mL respectively. In a second series of experiments comparing alum and algamulin (a complex of gamma inulin and alum), MSD HBsAg induced anti-HBs levels of 81 and 52, and ED50 values of 0.3 and 0.4 when used in conjunction with alum and algamulin, respectively. SKF HBsAg induced anti-HBs levels of 126 and 111 with alum and algamulin, and ED50 values of 0.11 and 0.075. The class, subclass and level of antibody produced in mice boosted with a second dose of vaccine at 21 days was also examined. Both alum and gamma inulin induced higher levels of total antibody, IgG1 and minor IgG subclasses than algamulin, or HBsAg alone. Overall, gamma inulin appears to be an equivalent adjuvant to alum, although their mechanisms of action are different. Mixtures or complexes of the two adjuvants appear to be less effective in inducing humoral immune responses in mice than either alone.

Control of HBV and HDV infection in an isolated Pacific Island: 1. Pattern of infection.

Hepatitis B virus (HBV) and hepatitis delta virus (HDV) infections are known to be hyperendemic in Nauru. Because of the consequences of chronic HBV infection, the Nauruan Government has commenced a program that aims to reduce and eventually eliminate hepatitis B infection by immunizing susceptible adults and children on the island and every newborn baby. At the outset of this program, a national seroepidemiological survey was undertaken. Eighty-eight percent of the population were tested, of whom 69.1% had markers of HBV infection. Evidence of superinfection with HDV was found in 22.7% of HBV carriers, with the highest prevalence in adolescents and young adults. All seronegative individuals were offered three doses of plasma derived hepatitis B vaccine. A post-vaccination survey of 64% of those vaccinated showed that 98% had developed circulating antibodies.

Factors affecting the prevalence of infection with hepatitis B virus among non-pregnant women in the Alexishafen area of Papua New Guinea.

The prevalence of hepatitis B viral markers was studied in 673 women of childbearing age in 17 villages (12 indigenous and five plantation villages) on the north coast of Papua New Guinea. Some 7.9% of women were HBsAg positive and 41.3% were positive for anti-HBs. There was significant variation in prevalence between villages, ranging from 0 to 13.9% for HBsAg and 26.0 to 71.0% for all markers. The 12 indigenous villages were classified into three groups according to language (Austronesian or non-Austronesian), location (inland or coastal), and marriage patterns. The prevalence of hepatitis B was significantly higher in Austronesian than in non-Austronesian villages (P less than 0.01), and it remained significant after controlling for age differences and for possible effects on prevalence caused by women marrying into the three village groups from other areas. Interactions between malaria and hepatitis B were also investigated. Non-Austronesian villages with the highest spleen rates had the lowest prevalence of hepatitis B infection, and there was no correlation with parasitaemia. These results may reflect a lower exposure of women to hepatitis B infection in non-Austronesian villages, or may indicate different genetic or immunological responses to infection between Austronesians and non-Austronesians.

Prevalence of hepatitis delta virus infection in Malaysia.

The prevalence of coinfection, superinfection and chronic infection with the hepatitis delta virus (HDV) was studied in 324 hepatitis B surface antigen (HBsAg)-positive Malaysians. Of these, 10.0% (5/50) had coinfection, 5.7% (11/194) had superinfection, but none of the 80 patients with chronic liver disease (CLD) or primary hepatocellular carcinoma (PHC) had chronic infection with HDV. The overall HDV infection was 4.9% (16/324). One of the coinfection cases acquired the HDV infection as early as 1982. HDV superinfection was detected mainly among IV drug abusers (20% or 7/35) and promiscuous males and females (13.6% or 3/22). They were all asymptomatic. Only 0.8% (1/125) apparently healthy blood donors was infected with HDV. None of the 12 multi-transfused patients examined were positive. Malaysia is the only Southeast Asian country examined so far in which HDV infection was detected. The reason could be that the IV drug abusers and the sexually promiscuous groups missed being examined in the other countries. Comparing the HDV infection rates in 4 categories of infected Malaysians (viz. acute hepatitis B patients, IV drug abusers, blood donors and CLD patients) with those of other countries, it was noted that the Malaysian rates were similar to the lowest in the range of prevalence rates of each category in the latter group. The rate of coinfection in a preliminary study in 1982-84 (9.0% or 1/11) was not very different from that obtained to date (10.0% or 5/50).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis B infection in Vanuatu: age of acquisition of infection and possible routes of transmission.

Seroepidemiological studies of hepatitis B were carried out on diverse groups of children (477) and adults (629) from the Pacific Island country of Vanuatu. In children under 14 years, prevalences of HBsAg and of all markers were 6% and 53.3% respectively; in adults greater than or equal to 20 years the prevalences were 15% and 70%. Age specific prevalence of hepatitis B infection (all markers) was low in infancy (less than 1 year) but rose sharply afterwards, suggesting that the main mechanism of transmission was horizontal spread. This finding is consistent with other developing country studies from the Pacific Islands and elsewhere. In view of the main ages and mechanisms of transmission of hepatitis B in children in developing countries and the need for simple and inexpensive immunisation strategies in this context, it is recommended that mass vaccination of all infants with hepatitis B vaccine be undertaken in hyperendemic areas.

Low dose hepatitis B vaccination in children: benefit of low dose boosters.

Fifty eight children aged 5-12 years (mean 9.3 years) who had received three x 2 micrograms of Merck Sharp and Dohme (MSD) H-B-Vax intramuscularly at time 0, 1, 6 months were given a further 2 micrograms dose 12 months after dose 3 and tested for immune response two weeks later. Fifty seven of 58 children were positive for antibody to hepatitis B surface antigen (anti-HBs) when tested by radioimmunoassay. In 56 of the 57, the response was anamnestic in nature. The geometric mean titre of anti-HBs rose from 106 IU/L before, to 15,759 IU/L after the booster dose. The latter figure was greater than that obtained in 20 adults given three x 20 micrograms of the same vaccine and also greater than that reported in children given three x 10 micrograms of MSD H-B-Vax. This study demonstrates that 8 micrograms of H-B-Vax given as four doses is at least as immunogenic in children as 30 micrograms of the same vaccine given as recommended and that the low dose strategy is appropriate for this expensive vaccine.

Immunogenicity of low doses of hepatitis B vaccine in children: a study in 650 New Zealand children.

Six hundred and fifty New Zealand children from 2-12 years of age were vaccinated three times with 2 mcg intramuscular (IM) doses of Merck Sharp and Dohme plasma-derived hepatitis B vaccine (H-B-Vax), at 0, 1, and 6 months, and tested 2-3 months later for antibody to hepatitis B surface antigen (anti-HBs) by radioimmunoassay (RIA). Overall, 96.5% of the children seroconverted for anti-HBs by RIA, having levels greater than 2.1 RIA S/N units, with 91.2% having values greater than 10 S/N units. Anti-HBs levels were also determined by enzyme immunoassay (EIA), by which method a significantly better response was demonstrated in 2-4-year-olds than in older children. This study demonstrated that a satisfactory anti-HBs response was obtained using one-fifth of the recommended doses of hepatitis B vaccine.

Low-dose vaccination against hepatitis B in children: one-year follow-up.

Six hundred forty-three children, negative for markers of hepatitis B virus (HBV) infections, were given three X 2-micrograms doses of Merck, Sharp and Dohme (MSD) plasma derived hepatitis B vaccine (H-B-Vax) at monthly intervals. Twelve months after the first dose of vaccine, antibody to hepatitis B surface antigen (anti-HBs) was detected in 89% of children by radioimmunoassay (RIA) and in 83% by enzyme immunoassay (EIA). Seroconversion rates and anti-HBs titres were significantly greater in 1-4-year-olds than in older children (p less than 0.01). Eighteen children with no anti-HBs or other markers of HBV at this time were given 10 micrograms of vaccine and tested one month later. Seventeen developed anti-HBs, 12 at levels consistent with an anamnestic response. Forty-nine HBV-marker-negative children seroconverted for antibody to hepatitis B core antigen (anti-HBc) in the 8-month period before or the 12-month period following vaccination. Forty-six of these children were positive for anti-HBs, and one has been confirmed as a chronic carrier of hepatitis B surface antigen (HBsAg). Three cases of clinical hepatitis B in children have been seen in the community since the vaccination programme began. Two of these were amongst the estimated 5% of children who were not vaccinated. The third was in a vaccinee and occurred 4 1/2 months after the last dose of vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramuscular versus low-dose intradermal hepatitis B vaccine. Assessment by humoral and cellular immune response to hepatitis B surface antigen.

The capacity of hepatitis B surface antigen (HBsAg) vaccine (which was administered by the conventional intramuscular route or as a one-tenth dose by the intradermal route) to elicit an antibody or delayed-type hypersensitivity response to HBsAg was compared for 40 paired healthy subjects, 20 per group, of whom 38 completed the vaccination protocol. The 40 subjects were allocated at random to receive three doses of 20 micrograms of vaccine intramuscularly, or three doses of 2 micrograms of vaccine intradermally. Titres of antibody to HBsAg (anti-HBs) were expressed in a radioimmunoassay by sample ratio (signal-to-noise) units (SRU). The maximal mean levels of anti-HBs (maximal one month after the third injection) were 108 SRU for the intramuscular group and 51 SRU for the intradermal group, and the levels for the intramuscular group were significantly higher at all other time-points. The levels of anti-HBs declined equally with time over 18 months in both groups. More subjects in the intramuscular group (17 of 19 subjects) showed a response to anti-HBs than in the intradermal group (14 of 19 subjects). Non-respondents in either group responded with similar frequency to further intramuscularly-administered vaccine. The frequency of delayed-type hypersensitivity to HBsAg was similar for both groups. Thus, immunization with HBsAg, when administered intradermally in a dose that is one-tenth of that recommended for intramuscular administration, induces an immune response in healthy subjects. However, since the level of antibody is lower than that after intramuscular injection, revaccination might be needed at more frequent intervals.

An outbreak of hepatitis B and D in butchers.

This report documents an outbreak of hepatitis B (HB) and hepatitis D (HD) in a group of butcher shop employees. During the 13-month period from September 1983 to October 1984, 8 employees from 2 establishments developed acute HB. Epidemiological investigation suggested that the first case, who was also an intravenous drug user, was the source of infection for other employees. This person and 2 others were found to have concurrent HD. In November 1984 the wife of one of the infected butchers also developed HB.

Very-low-dose hepatitis B vaccine in newborn infants: an economic option for control in endemic areas.

Three 1 microgram or 2 micrograms doses of Merck, Sharp and Dohme plasma vaccine were given to 119 infants of mothers negative for antibody to hepatitis B surface antigen (anti-HBs). Anti-HBs antibodies developed in 25/29 (86%) infants given 1 microgram and in 86/90 (96%) given 2 micrograms doses. Levels of anti-HBs achieved by three 2 micrograms doses were similar to those that have been reported for conventional 10 micrograms doses. Similar levels were recorded from infants of anti-HBs-positive mothers, which suggests that maternal antibody does not interfere with the infant's immune response to low doses of vaccine. Three 2 micrograms doses of vaccine in infancy produce satisfactory immunogenicity and make possible economic control of hepatitis B in endemic areas.

Detection of IgM antibodies to delta antigen after coinfection and superinfection with the delta virus.

A sensitive microtitre radioimmunoassay was developed for detection of IgM antibodies to delta antigen. The assay was based on the selective binding of IgM from test sera to antihuman IgM (u-chain specific) fixed to wells of a microtitre plate, and utilized delta antigen extracted from the liver of an experimentally infected chimpanzee. This test proved to be useful in distinguishing between coinfection and superinfection with the hepatitis delta virus (HDV). Transient anti-delta IgM responses were observed in patients coinfected with HDV, while prolonged elevated IgM levels were found in HBsAg carriers with chronic liver disease superinfected with HDV. Two distinct serological patterns were observed in both coinfection and superinfection. In coinfection, only 50% of patients with detectable anti-delta IgM went on to develop a long-lasting antibody response. Following superinfection with HDV either stationary or fluctuating levels of IgM antibody were demonstrated. In patients with fluctuating antibody levels, the presence or absence of IgM antibody related to the level of viral replication.

Epidemiology of hepatitis D virus (delta) infection in Melbourne over a 15-year period.

The prevalence of delta infection was studied in 3986 individuals seropositive for hepatitis B surface antigen (HBsAg), who were seen in Melbourne between 1971 and 1985. The group comprised 2004 patients with acute hepatitis B, 1820 asymptomatic HBsAg carriers, 139 HBsAg carriers with evidence of chronic liver disease, and 23 carriers who had suffered more than two separate attacks of acute hepatitis. Markers of delta infection were found almost exclusively among intravenous drug abusers and their close contacts. Studies of stored sera suggest that delta infection was introduced into this group about 1970. In carriers with no evidence of chronic liver disease, the prevalence of delta infection was highest among intravenous drug abusers (19.2%). In carriers with evidence of chronic liver disease, delta markers were present in 20.1% and all 23 carriers with recurrent acute hepatitis had evidence of infection with the delta virus.

Aetiology of acute hepatitis in Malaysia.

Icteric patients with clinical and biochemical evidence of liver disease, admitted into various hospitals in Malaysia, were investigated to determine the cause of their infection. Of these patients, 11.0% (16/145) were found positive for IgM anti-HAV (EIA), 4.1% (6/145) for IgM anti-HBc (EIA), 1.0% (1/102) for IgM anti-CMV (ELISA), 17.2% (16/64) for rising titres of leptospiral agglutinin, and none for heterophile antibody of EBV. Hepatitis NANB accounted for 67.9% of cases. The mean serum transaminases (ALT and AST) values in patients with hepatitis A and B were higher (more than 500IU) than in patients with leptospirosis or non-A, non-B hepatitis, whereas serum bilirubin levels were higher in patients with hepatitis A and leptospirosis than in patients with hepatitis B.

Delta hepatitis in Malaysia.

Sera from one hundred and fifty nine Malaysian individuals were screened for the prevalence of delta markers. These included 15 HBsAg positive homosexuals, 16 acute hepatitis B cases, 9 chronic hepatitis B patients, 13 healthy HBsAg carriers and 106 intravenous (i.v.) drug abusers, of whom 27 were positive for HBsAg only and the rest were anti-HBc IgG positive but HBsAg negative. The prevalence of delta markers in the homosexuals was found to be 6.7%, in the HBsAg positive drug abusers 17.8%, in acute hepatitis B cases 12.5%. No evidence of delta infection was detected in healthy HBsAg carriers, chronic hepatitis B cases and HBsAg negative i.v. drug abusers. With reference to i.v. drug abusers, the prevalence of delta markers was higher in Malays (23%) than in Chinese (7%) although the latter had a higher HBsAg carrier rate. Although the HBsAg carrier rate in the homosexuals was high, their delta prevalence rate was low as compared to drug abusers. In Malaysia, as in other non-endemic regions, hepatitis delta virus transmission appeared to occur mainly via the parenteral and sexual routes. This is the first time in Malaysia that a reservoir of delta infection has been demonstrated in certain groups of the population at high risk for hepatitis B.

Prevalence of delta infection in the western Pacific region.

The prevalence of coinfection and superinfection with the delta agent was studied in 2,645 hepatitis B surface antigen (HBsAg)-positive subjects from six countries and nine islands in the Western Pacific region. The study group comprised 262 patients with acute hepatitis B and 2,383 chronic carriers of HBsAg, of whom 278 were suffering from chronic liver disease or primary hepatocellular carcinoma. While major foci of infection were observed in Nauru, Niue, and Western Samoa, delta infection appears to be uncommon in other parts of the region.