Estimating the critical immunity threshold for preventing hepatitis A outbreaks in men who have sex with men.

Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R 0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R 0 of 1·71-3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R 0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.

Anti-streptococcal antibodies in the diagnosis of acute and post-streptococcal disease: streptokinase versus streptolysin O and deoxyribonuclease B.

AIMS: To establish population normal values and compare the diagnostic value of antibodies against streptokinase (ASK), streptolysin O (ASO) and deoxyribonuclease B (ADNaseB) singularly and in combinations in acute and post-streptococcal disease. METHODS: A retrospective analysis of serological results was performed to define population norms. Subjects with acute culture-confirmed infection and post-streptococcal disease were assessed using population norms, as were matched controls. The sensitivity and specificity of each antibody assay and of combinations of the different assays were calculated. RESULTS: Age specific population normal values were derived from 2,321 specimens. None of the three antibodies alone or in combination was a reliable marker of acute streptococcal infection. The sensitivity and specificity of a single antibody titre in post-streptococcal disease ranged from 70.5 to 72.7% and 86.4 to 93.2%, respectively. The combination of ASO and ADNaseB was the most sensitive and specific combination for identifying post-streptococcal disease (sensitivity 95.5%, specificity 88.6%). CONCLUSIONS: In the diagnosis of acute and post-streptococcal disease, the addition of ASK does not increase the sensitivity or specificity of serological testing. A combination of ASO and ADNaseB is required in post-streptococcal disease to achieve maximum sensitivity and specificity.

A method for determining the cut-off value of a varicella-zoster virus IgG enzyme immunoassay for immune status.

The cut-off optical density (OD) of an enzyme immunoassay (EIA) for IgG antibody to varicella-zoster virus (VZV) was established by application of a statistical technique to OD readings on sera from known susceptible and immune populations. Children aged one to three years who lacked complement fixation (CF) antibody were considered to be known susceptible subjects. Adults whose sera contained antibody by the CF test were considered to be known immune subjects. The method provides a valid alternative to previously used techniques of establishing a cut-off OD, above which reading the EIA can be taken to indicate immunity to varicella-zoster infection.

Determination and importance of varicella immune status of nursing staff in a children's hospital.

A survey of nurses at the Prince of Wales Children's Hospital was conducted to determine the prevalence of immunity to varicella-zoster virus (VZ) as defined by enzyme immunoassay (EIA), and to establish the value of history as a predictor of immunity. Of the 209 nurses surveyed, 51% could recall suffering VZ infection, and with a single exception, all of this group were immune. However, despite a 95% prevalence of immunity among all nurses, 46% of those found to be immune by EIA could not recollect having VZ infection. In the event of a hospital VZ outbreak, the latter group, without serological testing, would thus need to be regarded as susceptible, and this would create a major logistical problem in staffing the affected areas. We suggest, to minimize this cause of disruption to services, that all paediatric staff with patient contact should be asked at the time of recruitment if they recall suffering VZ infection. Those who give a positive response may be considered immune, but all other staff should have their immune status assessed by EIA at the earliest opportunity.

Confirmation of invasive meningococcal disease by single point estimation of IgM antibody to outer membrane protein of Neisseria meningitidis.

OBJECTIVES: The sensitivity of laboratory confirmation of invasive meningococcal disease (IMD) by culture or PCR is affected by prior antibiotic treatment and decreasing use of early lumbar puncture. Serological diagnosis of IMD is not widely used because of reliance on paired serum samples. The application of single point estimations of IgM antibodies in the diagnosis of IMD was explored. DESIGN: Outer membrane proteins from a mix of commonly encountered meningococcal serotypes were partially purified and used as an antigen in an enzyme immunoassay for the detection of IgM antibody. The cut-off for the assay was derived using sera from blood bank donors and the accuracy then evaluated with sera from patients with culture-confirmed IMD, other bacterial infections and culture-proven nasopharyngeal colonisation with Neisseria meningitidis. RESULTS: The coefficient of variability of the assay was < 10% in negative, mid- and high-range positive sera and the specificity of the assay was at least 93%. In sera collected from 49 adult patients at various times after positive blood or CSF culture-confirmed IMD, the assay had a sensitivity of 100% in specimens collected between 5 and 18 days. At the time of isolation of meningococci from either blood or CSF, eight of 29 sera were IgM-positive, but beyond 70 days no positive results were detected. No differences were seen in the IgM responses in patients from whom different serogroups of N. meningitidis were recovered. CONCLUSIONS: Serological examination by single point IgM enzyme immunoassay (EIA) offers the possibility of an expanded laboratory confirmation of IMD in adults for samples taken between 5 and 18 days after onset.

Plasma histamine levels following administration of radiographic contrast media.

The effect of two conventional high-osmolality and two new low-osmolality contrast media on plasma histamine levels has been examined. The study population included 25 patients undergoing intravenous urography with Urovison 58% (sodium and meglumine diatrizoate), 24 patients receiving intravenous Hexabrix 320 (sodium and meglumine ioxaglate) for urography, 16 patients receiving intravenous Iopamiro 370 (iopamidol) for urography and 12 patients receiving Urografin 76% (sodium and meglumine diatrizoate) for coronary angiography. Seventy-four percent of the 77 patients studied suffered adverse reactions ranging from a feeling of warmth and nausea to laryngeal oedema and bronchospasm. Hexabrix 320 and Iopamiro 370 were associated with the least patient discomfort. All contrast agents usually produced a rise in plasma histamine following injection (Iopamiro 370 causing the least change) and the histamine levels then fell towards preinjection values over a space of about 10 minutes. No relationship was observed between the magnitude of the increase in histamine and the severity of the reaction that occurred. However, a relationship was suggested between the mean peak plasma histamine level achieved and the occurrence of a Grade II reaction (i.e., dry retching/vomiting, mild urticaria or rash). These findings raise the probability that histamine contributes to the more severe grades of reaction to radiographic contrast media.

Assessment of tissue oxygenation.

A continuous supply of oxygen to all tissues is necessary for the efficient production of ATP, and this supply is considered sufficient when aerobic metabolism is maintained. Nonhealing wounds, necrotizing infections, radiation-induced necrosis, crush injury, decompression illness, and CO poisoning all exhibit impaired tissue oxygenation. The need for efficacy of HBO therapy in such conditions is in part determined by the prevailing state of tissue oxygen supply and demand. The methods currently available or under development for assessing the adequacy of tissue oxygenation include blood gas analysis, transcutaneous oxygen measurement, gastric tonometry, pulse oximetry, near-infrared spectroscopy, functional MR imaging, MR spectroscopy, electron paramagnetic resonance, positron emission tomography, and single photon emission computed tomography. The clinical and experimental applications of these methods are discussed and emphasis is placed on their role in hyperbaric medicine.

Modified fluorescent antibody technique to detect immunoglobulin M antibodies to Toxoplasma gondii in congenital infection.

Using a modified fluorescent antibody technique immunoglobulin M antibodies to Toxoplasma gondii were studied in infants' sera. The modified technique involved prolonged incubation of patients' sera with antigen at 4 C.

Pulmonary elastic recoil and diffusing capacity in subjects with intermediate concentrations of alpha-1 antitrypsin.

Serum from 224 males investigated in a prospective study of respiratory disorders in a recently established asbestos industry has been estimated for alpha-1 antitrypsin (AAT) concentration by single radial immunodiffusion. Mean AAT concentration was 213-4 mg/dl). No subject with a markedly reduced level was found. A comprehensive range of lung function tests sensitive to changes anticipated in emphysema at a preclinical stage, included measurements of diffusing capacity and pulmonary elastic recoil. The 26 subjects with AAT concentration less than 150 mg/dl, were regarded as likely to comprise a majority of genotypes MZ and SS, and the 19 subjects with AAT concentration greater than 300 mg/dl were considered to comprise mainly MM. No difference in pulmonary function could be demonstrated between these two groups. Evidence of diminished pulmonary elastic recoil was found in nine smoking subjects whose AAT concentrations were normal and also in one young non-smoking subject with moderately severe asthma, whose AAT concentration was 140 mg/dl. It is concluded that in a male working population, evidence of diminished pulmonary elastic recoil is not a function of AAT concentration.

Spontaneous pneumopericardium.

Spontaneous pneumopericardium is a relatively rare event, although cases have been recorded over the past 130 years. Many were associated with malignancy, trauma, infection or as a complication of recent surgery. Attempts at surgical resolution have been infrequent and survival extremely rare. We describe a patient in whom pneumopericardium developed spontaneously and insidiously, probably being present for some weeks before hospital investigation. Surgical exploration revealed the cause to be a benign gastric ulcer without an hiatus hernia or other diaphragmatic defect. Repair was attempted but the patient died in the early postoperative period. From an extensive review of the literature it is clear that spontaneous perforation of a gastric ulcer into the pericardium must be less rare than some authors have suggested.

Impact of influenza on morbidity in children with cystic fibrosis.

Recommendations concerning annual influenza vaccination in children suffering from cystic fibrosis (CF) are not uniform. Previous studies have shown that influenza causes a small proportion of episodes of acute respiratory deterioration in CF patients. During the 1989 Australian winter, we studied the association between serologically proven influenza infection and acute respiratory morbidity in 20 children with CF. Six children were shown to have influenza infection, four with type A and two with type B. Four of five children requiring hospital admission were shown to have influenza, but only 2 of 15 did not need admission (P less than or equal to 0.025). As well, influenza was diagnosed in 6 of 12 children who suffered acute respiratory illness leading to school absenteeism (including hospitalization), but diagnosed in no children without this degree of illness (P less than or equal to 0.025). Influenza significantly increases the incidence of hospitalization and of less serious respiratory illness in children with CF, a finding which suggests that influenza vaccine efficacy studies are necessary in this group.

Cost effectiveness of prevaccination screening of health care workers for immunity to measles, rubella and mumps.

OBJECTIVES: To determine the value of infection and vaccination histories as predictors of immunity to measles, rubella and mumps, and to compare the costs of various screening strategies with the cost of universal vaccination of health care workers. SETTING: Staff employed by a Sydney children's hospital. METHODS: Histories of measles, rubella and mumps infection or vaccination were compared with the results of serological testing to determine which historical statements had high positive predictive values (PPV) for immunity. Using this, we devised three prevaccination screening strategies and compared their costs with the cost of universal staff vaccination. RESULTS: Of 235 participants, 98.3% were serologically immune to measles, 96.6% to rubella and 83.0% to mumps. Historical statements indicating immunity with a PPV of more than 95% were histories of measles or of rubella vaccination, and personal recollection of mumps infection. Strategies using historical screening were cheaper than universal vaccination, which in turn was cheaper than using serological screening alone. CONCLUSIONS: Among health care workers at occupational risk of measles, rubella and mumps, the need for vaccination can be reduced by combining historical and serological screening. Where screening is felt to impose an administrative burden, a universal vaccination strategy costs 30%-50% more than strategies which use historical screening.

Measles immunity and immunization status in under-5-year-old children in New South Wales: a population-based study.

OBJECTIVE: To estimate the proportion of 1-4-year-old New South Wales children immune to measles and compare the documented immunization history with serologically defined immune status. DESIGN: Population based seroprevalence survey piggybacked onto the National Survey of Lead in Children. Immune status was determined by two different enzyme immunoassays on plasma samples from subjects. SETTING: New South Wales, February-March 1995. OUTCOME MEASURES: Documented measles immunization collected by interview survey and serologically defined immunity. RESULTS: Of 689 survey subjects, 430 (62.4%) provided a blood sample. Adequate plasma remained for both assays for 347 children, of whom 279 (80.4%) were immune by both assays. Parents of 330 stated that their children were immunised, of whom 211 (63.9%) were able to produce corroborating records. Of these 211 subjects, 178 (84.4%) were immune compared to 87 (76.3%) of 114 without records (P = 0.07). CONCLUSIONS: We estimate the prevalence of true measles immunity in 1-4-year-old NSW children to be only 80%, a level inadequate to prevent outbreaks of measles in urban populations. Both long term and immediate strategies are required to increase the prevalence of immunity among NSW children; these may include lowering the age of the routine second measles dose and mounting a mass measles immunisation campaign to include preschool aged children.

Detection of early renal osteodystrophy.

Quantitative bone histology, serum biochemistry and skeletal survey were studied in 21 children aged 6-18 years with moderate renal impairment (glomerular filtration rate (GFR) 20-50 ml/min/1.73 m2) but no previous history of bone disease to try and identify early markers of the disease simpler and less invasive than histomorphometry. Ninety percent of the 20 biopsies studied exhibited abnormal quantitative bone histology. Predominant hyperparathyroidism was noted in 30%; osteomalacia in 5%, mixed picture in 55%. Parathyroid hormone (PTH) levels were elevated in all the patients. Alkaline phosphatase bone isoenzyme was elevated in 95% of the patients. X-ray was relatively insensitive showing mild changes of hyperparathyroidism in only 3 patients (14.3%), all of whom had GFR less than 30 ml/min/1.73 m2. We feel that the elevated PTH levels denote a true state of hyperparathyroidism which probably precedes histological derangement in chronic renal failure, and may justify prophylactic treatment of renal osteodystrophy in children with moderate renal impairment.