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.

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.

Hepatitis C prevalence among Australian injecting drug users in the 1970s and profiles of virus genotypes in the 1970s and 1990s.

OBJECTIVES: To examine the seroprevalence of hepatitis C virus (HCV) in the Australian injecting drug-using community in the 1970s, and to compare the profile of HCV genotypes with that seen in the 1990s. DESIGN: Investigation of stored sera that were collected from injecting drug users in the 1970s and comparison with sera collected in the 1990s. SETTING: Inner Sydney, 1974-1975 and 1994-1996. PATIENTS: The 1970s group comprised 141 consecutive injecting drug users who attended the Brisbane Street Methadone Clinic. The 1990s group comprised 88 consecutive, injecting drug users of European origin who were HCV antibody-positive and attended a primary healthcare facility (the Kirketon Road Centre). MAIN OUTCOME MEASURES: HCV antibody prevalence (1970s); profile of HCV serotypes (1970s and 1990s); and serological evidence of hepatitis A and B. RESULTS: 84% of the 1970s group were HCV antibody-positive, of whom 92% were infected with HCV serotype 1 and 1% with serotype 3. In contrast, in the 1990s group, 69% were infected with HCV serotype 1 and 25% with serotype 3. The HCV-positive subjects from the early group were more likely than those from the recent group to have serological evidence of previous HBV infection. CONCLUSIONS: The high prevalence of HCV among injecting drug users in the 1970s in Australia confirms an epidemic that has been present for at least 25 years. Over this period, the proportion of HCV genotype 1 infections has decreased and genotype 3 infections have emerged.

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.

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.

Hepatitis B and C in New South Wales prisons: prevalence and risk factors.

OBJECTIVES: To determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among inmates entering the New South Wales correctional system and to examine risk factors for infection. DESIGN: Cross-sectional survey. SETTING: Reception Centre at Long Bay Correctional Centre, Sydney, New South Wales, June to December 1994. PARTICIPANTS: 408 adult male inmates received at the Reception Centre (28% of the 1450 new inmates eligible for compulsory HIV testing). OUTCOME MEASURES: Presence of HBV core and surface antibody and surface antigen; HCV antibody; risk factors; inmates' knowledge about risk factors. RESULTS: 37% of inmates tested positive for HCV antibody, 31% for HBV core antibody and 3.2% for HBV surface antigen (indicating recent infection or carrier status). Among those who reported a history of injecting illegal drugs, rates rose to 66% for HCV antibody and 43% for HBV core antibody. Prevalence of HBV and HCV antibodies was similar in Aboriginal and non-Aboriginal inmates, but HBV antigen carrier rate was significantly higher among Aboriginals (12% versus 2.2%). Knowledge about hepatitis risk factors was poor (only 20% named injecting drug use), although recidivists were significantly better informed than those new to the correctional system. Multivariate analysis identified injecting drug use, past exposure to hepatitis B virus and previous imprisonments as significant predictors for HCV infection, and age over 25 years and HCV antibodies for HBV infection. CONCLUSIONS: Results suggest that about a third of adult male prisoners entering the NSW correctional system may have been infected with HBV or HCV. Measures such as education about hepatitis risk factors and HBV vaccination are needed to reduce hepatitis transmission in this population.

Difficulties in clinical diagnosis of measles: proposal for modified clinical case definition.

OBJECTIVE: To examine the accuracy of clinical diagnosis of measles and to develop an improved measles clinical case definition. DESIGN: Case survey. SETTING: Eastern Sydney, December 1990 to August 1993. SUBJECTS: All cases of measles notified to the Eastern Sydney Public Health Unit without or before serological confirmation. OUTCOME MEASURES: Demographic and clinical details, measles- and rubella-specific IgM and measles complement fixation titres in acute and convalescent (when available) sera and epidemiological links with confirmed measles cases. RESULTS: Of 49 subjects reported and with complete follow-up, 24 were confirmed with measles, four with rubella and 21 had no definite diagnosis. Clinical diagnosis of measles had a false positive rate of 51%. Subjects with confirmed measles were significantly more likely to have a cough (23/24) than those with no definite diagnosis (15/21; P = 0.03) and to be febrile on the day of rash onset (23/24 versus 10/21; P = 0.001). The Centers for Disease Control definition had a sensitivity of 92% but specificity of only 24%. A modified case definition of rash, cough and fever present at onset of rash had equal sensitivity but greater specificity (57%). CONCLUSIONS: As measles is no longer common in Australia, clinical diagnosis is unreliable. When a public health response is needed, cases should be confirmed by serological tests or, if not available, we propose use of our modified clinical case definition.

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.

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.

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.

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.