Pertussis vaccines: acellular versus whole-cell.

Acellular pertussis vaccines containing purified Bordetella pertussis antigens have now been extensively field tested. They produce a significantly lower rate of reactions than whole-cell vaccines and their efficacy is either comparable or superior. At least three antigens appear necessary for good protection: pertussis toxoid, filamentous haemagglutinin and pertactin (an outer-membrane protein); fimbrial agglutinogens are probably not needed. It is hoped that a cellular pertussis vaccine will soon be licensed in Australia for both primary and booster vaccination.

Leprosy in Sydney: a brief account.

Individuals with leprosy and those incubating the disease continue to enter New South Wales from endemic areas. With early diagnosis and treatment, the prognosis is good. The diagnosis should be considered in any patient who has lived or worked in a leprosy endemic country and who presents with an unusual or persistent skin erpution (especially if there is associated hypoaesthesia) and/or mononeuritis or mononeuritis multiplex. Occasionally the disease presents inother guises; biopsy of the appropriate tissue and staining for acid-fact bacilli, as well as haematoxylin and eosin, will usually indicate the correct diagnosis.

Viral hepatitis and the drug cult: a brief socio-epidemiological study in Sydney.

Study of 141 individuals attending a Sydney drug referral centre revealed considerable psychosocial maladjustment in the group. Seventy-five per cent showed serological evidence of hepatitis B virus infection, past or present, as compared with 13% of control subjects. Antibody to hepatitis B core antigen was found to be twice as frequent as a serological marker of HBV infection, as antibody to hepatitis B surface antigen. Prevalence rates of antibody to hepatitis A virus were similar in the drug and control groups. Hepatitis possibly due to hepatitis non A non B virus infection, was found in 14% of those with clinical and biochemical hepatitis at the time of the study.

Viral hepatitis A and B: a seroepidemiological study of a non-hepatitic Sydney population.

The age-specific prevalence rates of hepatitis A and B virus markers in 683 patients of all ages with non-hepatitic illnesses admitted to a Sydney hospital over the period from 1971 to 1974 were determined. The pattern of prevalence rates of hepatitis A antibody (anti-HAV) appeared to be a cumulative one, with steadily increasing rates in patients up to the age of 40 years. Thereafter a large increase in prevalence occurred. In contrast, prevalence rates for hepatitis B virus (HBV) markers were fairly uniform for all age groups. Antibody to core antigen (anti-HBc) was the most frequent marker of HBV infection. Prevalence rates in subjects of non-Anglo-Saxon origin were higher for both HAV and HBV markers.

The response of institutionalized Down's syndrome subjects to enterovirus infections.

In a study comparing the responses of institutionalized Down's syndrome (DS) and non-Down's (ND) inmates to enterovirus infections, the frequency of wild enteric viruses and the excretion patterns of oral polio vaccine (OPV) viruses were similar in both groups. Antibody titres developed to poliovirus types 2 and 3 following vaccination were similar in DS and ND vaccinees, but the response to type I virus was significantly less in DS vaccinees. As judged by the development of poliovirus antibody in non-vaccinees, the spread of virus from OPV-immunized to unimmunized subjects in the institution was not noticeably different in DS and ND subjects. An unexpected finding was that the excretion patterns of all three serotypes of poliovirus were strikingly similar for each individual, although the patterns varied considerably from individual to individual. The similarity of excretion occurred despite wide differences within an individual in the titres of neutralizing serum antibodies to the three serotypes. It is suggested that the rate at which a given individual eliminates enteroviruses may be largely determined by factors, the activities of which are not reflected in serum antibody titres.

The seroepidemiology of hepatitis in Papua New Guinea. I. A long-term study of hepatitis A.

Sera from 988 subjects in four ecologic zones of the Sepik district and 219 subjects from four widely spaced altitudes of the bismarck range in Papua New Guinea were tested for antibody to the hepatitis A virus (anti-HAV) by radioimmunoassay. The Sepik district subjects, mostly children between three months and six years of age when first sampled in 1963, were re-bled on four occasions over the ensuing nine years. The Bismarck range population was sampled only in 1964. In the Sepik district, anti-HAV was detected infrequently before the age of three years and showed maximum increase in prevalence rates between 7-10 years, with little increase thereafter. Antibody acquisition rates also indicated peak transmission in this age group, with fewer conversions between three months and six years of age and in adulthood. There was a consistent, though unexplained tendency for HAV infections to occur more frequently in proximity to the Sepik river than in areas farther away, and in the lower altitudes of the Bismarck range. As determined by serial samples, anti-HAV detected in 1963-1964 was still present in 1972 in 118 out of 119 subjects.

Illness caused by a Kokobera-like virus in south-eastern Australia.

Three patients who lived in south-eastern Australia and who suffered acute polyarticular illnesses in the summer months of 1983-1984 and 1984-1985 are described. Two patients lived in the southwestern plains of New South Wales and one in Bairnsdale in eastern Victoria. Serological studies implicated Kokobera virus, a flavivirus, as the likely causative agent. This would appear to be the first report to indicate the pathogenicity of Kokobera virus.

The antibody response of institutionalized Down's syndrome patients to seven microbial antigens.

An earlier cross-sectional study had revealed that institutionalized Down's syndrome (DS) patients possessed much lower titres of hepatitis B surface antibodies (anti-HBs) than did their non-Down's (ND) counterparts. In an attempt to determine whether DS patients were generally deficient in humoral antibody response, the inmates of an institution for the mentally retarded (110 DS, seventy-eight ND) were immunized with tetanus, diphtheria (toxoids), influenza A, influenza B (inactivated vaccines), measles, mumps and rubella (attenuated vaccines), and tested for their antibody responses. The DS and ND groups did not respond differently to any of the seven antigens. Furthermore, there was no general relationship between the anti-HBs titres of inmates and their capacity to respond to the defined antigenic stimulus of any of the seven antigens. From these results it is apparent that a general humoral deficit in the DS group cannot explain their tendency to possess much lower anti-HBs titres than their ND counterparts upon becoming infected with the hepatitis B virus. When the antibody status and responses to immunization of the inmates who possessed anti-HBs were compared with those who had chronic HBsAg antigenaemia, there was no significant difference between the groups.

Illness caused by a Barmah Forest-like virus in New South Wales.

Barmah Forest virus, a recently-discovered arbovirus which belongs to the alphavirus genus of the family Togaviridae, has been shown to cause infections in humans in New South Wales. The present report documents three patients in whom Barmah Forest viral infection appears to have resulted in illness. Barmah Forest virus or a closely-related alphavirus may, as are several other alphaviruses, be pathogenic.

Arbovirus infection in humans in NSW: seroprevalence and pathogenicity of certain Australian bunyaviruses.

A sero epidemiological study was carried out on human sera from all regions of New South Wales for the presence of antibodies to nine bunyaviruses viz Aino, Akabane, Belmont, Gan Gan, Kowanyama, mapputta, Peaton, Tinaroo, Trubanaman and the orbivirus Corriparta. Neutralising antibodies were found in titres up to 1280 to Gan Gan and to 640 to Trubanaman viruses, prevalences 4.7% and 1.4% respectively. Neutralisation titres up to 40 were found to Belmont, Aino, Peaton and Corriparta viruses but the significance of these is uncertain since they may represent either non-specific inhibitors or cross reacting antibodies to related but currently unknown viruses. No antibodies were found to Akabane, Kowanyama, Mapputta or Tinaroo viruses in New South Wales sera. Gan Gan virus appeared to be pathogenic for man being associated with an acute epidemic polyarthritic like illness. Trubanaman virus is suspected of being pathogenic. This is the first report of the pathogenicity of these Australian bunyaviruses.

Arbovirus infections of humans in high-risk areas of south-eastern Australia: a continuing study.

OBJECTIVES: To determine the current immune status of high-risk populations of New South Wales and Victoria to the arboviral pathogens, Murray Valley encephalitis (MVE) and Kunjin (KUN) viruses, which are associated with Australian encephalitis (AE), and Ross River (RR) and Kokobera (KOK) viruses which are associated with polyarthritis. Further, to estimate seroconversion rates to these viruses in high-risk populations over the 10-year period 1981-1991. DESIGN AND STUDY POPULATION: Blood was taken from 2873 permanent residents, children and adults from previously identified high-risk areas in western NSW and northern Victoria. Samples were tested by the haemagglutination-inhibition (HI) test for antibodies to the four viruses. All sera were also tested for MVE and KUN antibodies by the more specific neutralisation test (NT). Ninety-five of the subjects had been seronegative when sampled 10 years previously. RESULTS: Age standardised prevalence rates for flavivirus HI antibodies (MVE, KUN, KOK) ranged from 66% (Bourke) to 15% (Forbes), and were similar to those observed 10 years previously. However, specific NT antibodies to MVE and KUN were uncommon in all districts except Bourke, indicating a very high level of susceptibility to Australian encephalitis, should a fresh epidemic occur. Whereas KUN virus seems enzootic in NSW and Victoria, MVE did not appear to have been present since the last outbreak in 1974, even in Bourke. Flavivirus antibody rates (as detected by the broadly reactive HI test) greatly exceeded those specifically attributable to MVE and KUN (NT test) or KOK, leading to the speculation that unidentified flaviviruses are responsible for most human infections. Ross River virus antibody prevalence rates exceeded those of flaviviruses in all districts, ranging from 72% (Bourke) to 25% (Cohuna), and were uniformly higher than those observed in 1981. Ten-year seroconversion rates in seronegative panels were 8.5% for flaviviruses and 24.2% for RR virus, and are broadly consistent with the cross-sectional study. CONCLUSIONS: Although flavivirus and alphavirus infections have occurred at a "steady rate"in western NSW and northern Victoria, there is a general lack of immunity to the agents of Australian encephalitis in all centres except Bourke. This needs to be considered in public health policy in these areas.

Use of immunoglobulin M antibody to hepatitis B core antigen in diagnosis of viral hepatitis.

To determine the diagnostic value of hepatitis B core (HBc)-specific immunoglobulin M (IgM) antibody (anti-HBc IgM), the sera of six patients with known recent acute viral hepatitis B were examined for the presence of anti-HBc periodically for up to 21 months from the onset of the attack by a sensitive radioimmunoassay technique (CORAB, Abbott Laboratories). It was found that anti-HBc IgM was detectable for approximately 17 months from the onset of the illness. Hence the finding of anti-HBc IgM suggests infection by hepatitis B virus, probably within the preceding 1 to 2 years. A high level of anti-HBc IgM in the acute-phase serum of an individual with viral hepatitis is indicative of recent hepatitis B virus etiology; one patient, however, showed a low titer of anti-HBc IgM in the acute-phase serum sample, which remained virtually unchanged 15 months from onset. The diagnostic use of this serologaical marker is illustrated in 25 patients with viral hepatitis, in whose acute-phase sera anti-HBc was found.

Hepatitis A outbreak in a residential school.

Outbreaks of hepatitis A occurred sequentially in two wards for children in a residential institution for the mentally retarded in Sydney. Twenty-six of 41 children were initially susceptible to hepatitis A. In the first ward affected, 11 of 13 susceptible children (85%), and in the second ward, four of 13 susceptibles (31%), were infected. Of the 15 showing serological evidence of infection, five (33%) were clinically jaundiced.

The seroepidemiology of hepatitis in Papua New Guinea. II. A long-term study of hepatitis B.

Sera from 862 young children and 206 older subjects, living in four zones of the Sepik district in New Guinea, and obtained in March, August, December 1963, May 1964 and again in 1972, were tested for the hepatitis B virus (HBV) markers, surface antigen and antibody (HBsAg and anti-HBs) and core antibody (anti-HBc). This population was augmented by a group of adult women living at various altitudes in the Bismarck range area, upon whose sera the same tests were performed. There was a slight tendency for males to exceed females in HBV infections and in propensity to chronic carriage of HBsAg. HBV infections increased cumulatively with age in all ecologic zones studied, with no significant increase in prevalence after early adulthood. In the Sepik district, the HBV status of the population was relatively the same in 1963 and 1972. Overall, 64% of markers of HBV infection persisted over a nine-year period; anti-HBc was more persistent than anti-HBs. Most HBsAg positive subjects detected were chronic carriers, 74% of whom retained detectable antigen for a least nine years. The study provided no evidence to support the hypothesis that mosquitoes are important vectors of HBV. The proportion of HBV infected subjects with chronic HBsAg was about 15%, similar to that found in Caucasians in other studies. This casts some doubt on the theory that tropical populations are especially predisposed to chronic HBV infection.

Arbovirus infections of humans in New South Wales. Seroepidemiology of the flavivirus group of togaviruses.

A seroepidemiological study of 16 842 human sera, collected in 1981 and 1982 from all health regions of New South Wales, was carried out using the haemagglutination-inhibition (HI) test and eight Australasian flaviviruses: Murray Valley encephalitis (MVE); Kunjin (KUN); Alfuy (ALF); Stratford (STR); Kokobera (KOK); Edge Hill (EH); Sepik (SEP); and Saumarez Reef (SRE). A limited survey was also carried out with two recently discovered flaviviruses, Gadgets Gully and CSIRO 946. Antibody prevalence rates were low on the coast and tablelands (around 2%-8%), moderate on the western slopes (6%-11%) and high on the western plains (26%-42%). Some centres had higher prevalence rates, Bourke being the highest at 78%. The survey indicated that SEP and SRE viruses are unlikely to infect humans in New South Wales. Similarly, there was no evidence for Gadgets Gully and CSIRO 946 infection of humans. HI antibody prevalence rates were highest to STR, MVE, KUN and ALF in that order, these agents being closely related antigenetically. Reactions to KOK and EH occurred less frequently. Serological tests of greater specificity will be required to identify the flaviviruses that elicit these HI antibodies.

A major outbreak of epidemic polyarthritis in New South Wales during the summer of 1983/1984.

A large outbreak of epidemic polyarthritis (EPA) caused by Ross River virus (RRV) occurred in New South Wales in the summer of 1983/1984. The total number of cases was unknown, but 1196 cases were confirmed by laboratory tests. Most patients came from the area west of the dividing range, with especially large numbers in the Murrumbidgee irrigation area. Cases were reported from October 1983 to June 1984, with 60% of cases occurring in January and February. The seasonal pattern was similar throughout the state. Men and women were affected in approximately equal numbers, with the highest frequencies in the 30-39 years' age group. Clinical illness was uncommon in young children. Based on a detailed study of 118 patients from Griffith, arthralgia, lethargy, rash and headache were the most common symptoms. The average period of incapacity (defined as inability to resume normal duties) was about six weeks. On this basis, the cost of the epidemic was estimated at about $3 million. There were 257 cases of EPA in the Griffith Shire and it was calculated that approximately 340 RRV infections occurred in the shire. The implication is that, in this outbreak, most RRV infections resulted in clinical illness.

The epidemiology of hepatitis B in a residential institution for the mentally retarded.

A longitudinal study carried out over 43 months in a residential home for the mentally retarded confirmed the marked propensity of individuals with Down's syndrome (DS) to develop chronic HB antigenaemia. This could not be accounted for by environmental factors, and a genetic basis is postulated. In addition, DS subjects appeared innately more susceptible to hepatitis B virus (HBV) infection, requiring one-third the patient-months of exposure of non-Down's subjects (ND) before showing evidence of infection. The reciprocal geometric mean titre of anti-HBS in DS subjects was 110 compared with 705 in ND subjects, suggesting a deficiency of humoral immunity in the DS subjects. Transmission of HBV was occurring by means other than therapeutic, prophylactic, dental or diagnostic procedures, in the institution, and possible modes of transmission are discussed. These were probably both parenteral and non-parenteral. Eighty-one per cent of HBV infections in the Home were subclinical.

Acute hepatitis: significance of changes in complement components.

Serial measurements of complement components were performed in fifty-nine patients with acute, uncomplicated hepatitis and twelve with alcoholic cirrhosis. Thirty-one of the former group had detectable hepatitis B antigen. Abnormal complement profiles were observed in nine patients with hepatitis B and seven with antigen-negative hepatitis. Low levels of C4, C3 and factor B were common in the subjects with cirrhosis and confined to those cases with severe reduction in serum albumin and/or prothrombin index. By contrast, the complement changes in the patients with hepatitis occurred without significant alteration in these parameters; certain subjects also had reduction in C1q and C5 and a significant number had C3d detectable in fresh plasma. The pattern of abnormality suggests predominant involvement of the classical pathway and it is concluded that this results, at least in part, from an immune process evident only in the early clinical phase of hepatitis. Such gross changes in complement are likely to reflect immune-complex activity and it is proposed that these complexes may be important in the clearance of virus material. The data supports a previous suggestion that recovery from acute hepatitis is primarily dependent on host immune competence rather than viral cytotoxicity or generation of immune complexes.