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The post-Q-fever fatigue syndrome (QFS) (inappropriate fatigue, myalgia and arthralgia, night sweats, changes in mood and sleep patterns) follows about 20% of laboratory-proven, acute primary Q-fever cases. Cytokine dysregulation resulting from chronic immune stimulation and modulation by persistence of Coxiella burnetii cells or their antigens is hypothesized. We studied cytokine release patterns of peripheral blood mononuclear cells (PBMC) stimulated with various ligands in short-term culture, from 18 patients with active QFS, and 27 controls: six with resolving QFS, five who had had acute primary Q-fever without subsequent QFS, eight healthy Q-fever vaccinees and eight healthy subjects without Q-fever antibody. Conditioned media (CM) from PBMC stimulated in short-term culture with Q-fever antigens, PHA or measles antigen (as an unrelated antigen) were assayed for IL-2, IL-4, IL-5, IL-6, IL-10 and IFN gamma by AgEIA, and for IL-1 and TNF alpha/beta by bioassay. Aberrant cytokine release patterns were observed with PBMC from QFS patients when stimulated with Q-fever antigens: an accentuated release of IL-6 which was significantly [p = 0.01, non-parametric one-way analysis of variance (ANOVA)] in excess of medians for all four control groups. With IL-2, the number of responders in the active QFS group was decreased relative to control groups (Fisher's exact test, p = 0.01) whereas the number of IFN gamma responders was increased (Fisher's exact test, p = 0.0008). Significant correlations were observed between concentrations of IL-6 in CM, total symptom scores, and scores for other key symptoms.

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OBJECTIVES: To examine the efficacy of various batches of a formalin-inactivated whole cell Coxiella burnetti vaccine (Henzerling strain, Phase 1 [Q-Vax, CSL]) in the prevention of Q fever among abattoir workers. DESIGN AND SETTING: The study was a retrospective cohort survey of all employees at three South Australian abattoirs to determine the incidence of Q fever among vaccinated and unvaccinated employees during the period 1985 to 1990. RESULTS: There were two cases of Q fever among 2555 vaccinated employees of the three abattoirs, compared with 55 cases among 1365 unvaccinated employees. The two Q fever cases in vaccinated employees were within a few days of vaccination, before immunity had developed, and represented a coincidence of natural infection and vaccination. Protective efficacy was 100%, even with a batch of Q-Vax containing 20 micrograms/dose rather than the standard dose of 30 micrograms/dose. CONCLUSIONS: Vaccination was effective for at least five years, although it was uncertain whether this was due to the vaccine per se or to a combination of vaccine immunity reinforced by periodic natural exposure.

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Efforts to improve laboratory diagnostic methods for infection due to Mycoplasma pneumoniae have involved the use of a cell-sheet culture method and a modified indirect hemagglutination method for IgM antibody, while direct detection of mycoplasma has employed antigen capture-enzyme immunoassay (Ag-EIA) and polymerase chain reaction (PCR) amplification of sequences within the P1 and 16S ribosomal RNA genes and quantification of the amplified DNA by dot blot hybridization (DBH). Cell-sheet culture was slightly more sensitive and more rapid than culture with cell-free diphasic medium. Indirect hemagglutination detection of IgM antibody to M. pneumoniae was more sensitive than CF and EIA for detection of IgM antibody to mycoplasma. Ag-EIA gave a rapid and reasonably sensitive indication of infection and correlated well with a serological response of patients indicating a current infection. PCR-DBH was a highly sensitive substitute for culture of mycoplasma. Both Ag-EIA and PCR-DBH require confirmation by assessment of serological response to verify that the infection is current and that positive results of PCR-DBH, in particular, are not the result of continuing carriage of the organism from a previous infection, unrelated to the current episode under investigation.

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Direct detection assays for Mycoplasma pneumoniae were established by PCR amplification of short sequences within the foot protein/adhesin (P1) gene and the 16S ribosomal RNA gene. Specificity and sensitivity was excellent, no hybridization was observed with M. genitalium and other human Mycoplasma species. In nose and throat washings from subjects with respiratory infection a pattern of high counts (c.f.u./ml) of M. pneumoniae (deduced from the amount of amplified PCR product), and a positive antigen capture assay, was found in 83% of subjects with serological evidence of current infection with M. pneumoniae. A small proportion of subjects with serological patterns suggesting infection in the more distant past had positive PCR assays. This was considered to represent either persistence of the organism from a previous infection or perhaps transient carriage during a reinfection, without substantial change in antibody response. PCR-based assay of M. pneumoniae offers a powerful, rapid, and sensitive substitute for culture of the mycoplasma. Antigen capture, while less sensitive than PCR, offers the advantage that it is more often positive with samples from current infection and requires less stringent laboratory organization to contain false positive results. We conclude however that the laboratory diagnosis of a chosen clinical episode should not rest on the PCR or Ag-EIA assays alone, but must also include antibody assays to confirm whether infection is current or represents persistence from past exposure.

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OBJECTIVE: To measure the prevalence of hepatitis B virus (HBV) infection in children and staff at Northern Territory schools. DESIGN: Children in Years 5-7 in 24 selected primary schools were invited, with parental consent, to provide demographic and ethnic details, and a capillary blood sample for tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs). School staff participated on a similar basis. PARTICIPANTS: 1104 children, comprising 556 from ethnic groups (originating from the United Kingdom, Ireland and northern Europe) previously reported as "low HBV prevalence", 439 Aboriginal Australians, and 109 from "other" ethnic groups (originating from Asia, the Pacific, the Middle East and southern Europe); and 209 school staff, comprising 180 from "low HBV prevalence" ethnic groups, and 29 from Aboriginal and other ethnic groups. RESULTS: Prior HBV infection (i.e. serum positive for HBsAg or anti-HBs) was detected in 28.7% of children (46.9% of 439 Aborigines; 13.7% of the 556 children from the "low prevalence" groups and 32.1% of the 109 from the "other" groups). HBsAg was detected in 8.2% of Aboriginal children, in 0.36% of those from "low prevalence" groups, and in 1.8% of those from the "other" groups. Aboriginal children in rural schools had the highest prevalence of HBV: 5.4% were positive for both HBsAg and anti-HBs, and an additional 9.8% were positive for HBsAg alone. In urban schools, the prevalence was highest in the "other" ethnic groups. For school staff, the prevalence of HBV infection was 12.8% for those from "low prevalence" ethnic groups, and 37.9% for those from all remaining groups (including Aborigines). CONCLUSION: In the Northern Territory the prevalence of past HBV infection is high in children and school staff from ethnic groups previously known to be at higher risk of HBV infection. For students and staff from ethnic backgrounds expected to be at low risk, HBV prevalence is greater than in individuals from similar backgrounds in other parts of Australia. HBV vaccination is now offered to all infants in the Northern Territory. These results also provide a rationale for the more widespread use of HBV vaccine in other situations where significant HBV transmission might occur.

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A limited, randomized, blind, placebo-controlled trial of Q fever and influenza vaccines has been conducted in three Queensland abattoirs on a sequential analysis design. Ninety-eight subjects were given Q fever vaccine and 102 influenza vaccine. Q fever cases were observed in unvaccinated workers in all three abattoirs during the period of observation. A total of seven Q fever cases in one group, one more than the number required to achieve statistical significance between the two vaccine groups, was reached after 15 months with the cases coming from two of the abattoirs. These Q fever cases were in the group which had been given influenza vaccine and none in that given Q fever vaccine. Symptomless seroconversion rates of 24% were found in the remaining influenza virus vaccinees, and those without immunity were given Q fever vaccine.

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During the period 1981-8 a clinical trial of a Q fever vaccine (Q-vax; Commonwealth Serum Laboratories, Melbourne) has been conducted in abattoir workers and other at-risk groups in South Australia. Volunteers in four abattoirs and visitors to the abattoirs were given one subcutaneous dose of 30 micrograms of a formalin-inactivated, highly-purified Coxiella burnetii cells, Henzerling strain, Phase 1 antigenic state, in a volume of 0.5 ml. During the period, over 4000 subjects have been vaccinated and the programme continues in the abattoirs and related groups. 'Common' reactions to the vaccine comprised tenderness and erythema, rarely oedema at the inoculation site and sometimes transient headache. Two more serious 'uncommon' reactions, immune abscess at the inoculation site, were observed in two subjects, and two others developed small subcutaneous lumps which gradually dispersed without intervention. Protective efficacy of the vaccine appeared to be absolute and to last for 5 years at least. Eight Q fever cases were observed in vaccinees, but all were in persons vaccinated during the incubation period of a natural attack of Q fever before vaccine-induced immunity had had time (greater than or equal to 13 days after vaccination) to develop. On the other hand, 97 Q fever cases were detected in persons working in, or visiting the same abattoir environments. Assays for antibody and cellular immunity showed an 80-82% seroconversion after vaccination, mostly IgM antibody to Phase 2 antigen, in the 3 months after vaccination. This fell to about 60%, mostly IgG antibody to Phase 1 antigen, after 20 months. On the other hand, 85-95% of vaccinees developed markers of cell mediated immunity as judged by lymphoproliferative responses with C. burnetii antigens; these rates remained elevated for at least 5 years. The Q fever vaccine, unlike other killed rickettsial vaccines, has the property of stimulating long-lasting T lymphocyte memory and this may account for its unusual protective efficacy as a killed vaccine.

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The indirect haemagglutination (IHA) test was compared with the complement-fixation (CF) test for the measurement of antibodies to Mycoplasma pneumoniae. A modification of the IHA was used to measure M. pneumoniae IgM antibodies. Sera were obtained from various groups of patients who were either culture or antigen positive for M. pneumoniae in nasopharyngeal aspirates or who had fourfold or greater increase in CF antibody or a titre greater than or equal to 320. The results of these comparisons showed that the modified IHA test was specific and more sensitive (89% as opposed to 64%) than the CF test. The modified IHA test for the detection of IgM antibody was highly effective in the recognition of recent or current infection with the mycoplasma. It was also of equal sensitivity to an indirect enzyme immunoassay for the detection of IgM antibodies to M. pneumoniae.

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A simple procedure for examining the seroconversion rates to measles vaccines in outlying communities is described; this involves the storage and transportation of dried-blood samples on filter paper, which is followed by the detection of measles-specific antibodies by means of a commercially-available immunofluorescence assay. Among 82 susceptible central Australian Aboriginal infants who were vaccinated at nine months of age, 76 (93% [95% confidence limits, 84.9%-96.6%]) children demonstrated seroconversion as a result of the vaccine, which is a figure that is similar to those that have been reported from some developing countries. The implications for a measles-vaccination policy are discussed.

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A clinical trial of Q fever vaccine in four South Australian abattoirs showed apparently complete protection against natural infection; however, only 50%-60% of vaccinees developed complement-fixing or immunofluorescent antibody after vaccination. Cell-mediated immunity to Coxiella burnetii antigens, as measured by an index of lymphoproliferative responses (LSI) of peripheral blood mononuclear cells, was therefore assessed. Eighty-five percent of 13 subjects with "low risk" of exposure to Q fever and with an initially negative LSI converted to a positive LSI after vaccination; conversion was noted nine to 13 days after vaccination, and positive values were obtained for at least 96 d. Only 35% of this group seroconverted. In a "high-risk" group (abattoir workers), higher rates of positive LSI (greater than 95%) and of antibody (50%-70%) were observed after vaccination; greater than 95% of vaccinees in this group, who had been vaccinated five years previously, had positive LSI values.

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In a double-blind evaluation of alpha 2-interferon as prophylaxis against naturally acquired respiratory infections, 120 adult members of 46 Australian families used 325 courses of intranasal spray during a six-month period, applying 5 million IU to the anterior nasal mucosa daily for seven days when respiratory symptoms developed in another member of the family. Used in this way, the alpha 2-interferon was well tolerated, and the rate of minor nasal bleeding (12 percent) did not increase with repeated courses. By comparison with the control group of 109 members of 49 families who used 319 seven-day courses of placebo spray, the users of alpha 2-interferon experienced 33 percent fewer days with nasal symptoms and 41 percent fewer episodes of "definite" respiratory illness. The users of alpha 2-interferon who were exposed to rhinovirus infections experienced 76 percent fewer days with symptoms and 86 percent fewer "definite" illnesses than their counterparts who used placebo. All of the observed clinical benefits, which suggested prevention of 6.8 "definite" respiratory illnesses per 100 courses of medication used, could be explained by a protective effect against illness associated with rhinoviruses that was not demonstrated for influenza A or B or coronavirus 229E.

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A modified haemagglutination inhibition test for rubella antibodies using prestandardized freeze-dried reagents was compared to a "standard" method. Tests of 707 serum samples showed that the modified test was sensitive and reliable by both macrotitration and microtitration techniques. The minor disadvantages of some reduction in antibody level when rubella sera were tested within one week of the rash and of spontaneous sheep erythrocyte agglutination in 0-7% of sera were out-weighed by the increased speed of the new test and the fact that it was carried out at room temperature.

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