Q fever seroprevalence in Australia suggests one in twenty people have been exposed.

Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1-79 years in 2012-2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%-6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%-6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%-8.0%). More males were seropositive (6.9%; 95% CI 5.2%-8.6%) than females (4.2%; 95% CI 2.9%-5.5%) with peak seroprevalence at 50-59 years (9.2%; 95% CI 5.2%-13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.

Tumours in white suckers from Lake Michigan tributaries: pathology and prevalence.

The prevalence and histopathology of neoplastic lesions were assessed in white sucker Catostomus commersonii captured at two Lake Michigan Areas of Concern (AOCs), the Sheboygan River and Milwaukee Estuary. Findings were compared to those observed at two non-AOC sites, the Root and Kewaunee rivers. At each site, approximately 200 adult suckers were collected during their spawning migration. Raised skin lesions were observed at all sites and included discrete white spots, mucoid plaques on the body surface and fins and large papillomatous lesions on lips and body. Microscopically, hyperplasia, papilloma and squamous cell carcinoma were documented. Liver neoplasms were also observed at all sites and included both hepatocellular and biliary tumours. Based on land use, the Kewaunee River was the site least impacted by human activities previously associated with fish tumours and had significantly fewer liver neoplasms when compared to the other sites. The proportion of white suckers with liver tumours followed the same patterns as the proportion of urban land use in the watershed: the Milwaukee Estuary had the highest prevalence, followed by the Root, Sheboygan and Kewaunee rivers. The overall skin neoplasm (papilloma and carcinoma) prevalence did not follow the same pattern, although the percentage of white suckers with squamous cell carcinoma exhibited a similar relationship to land use. Testicular tumours (seminoma) were observed at both AOC sites but not at the non-AOC sites. Both skin and liver tumours were significantly and positively associated with age but not sex.

Reconstructing larval growth and habitat use in an amphidromous goby using otolith increments and microchemistry.

High-resolution analysis of growth increments, trace element chemistry and oxygen isotope ratios (δ18 O) in otoliths were combined to assess larval and post-larval habitat use and growth of Awaous stamineus, an amphidromous goby native to Hawai'i. Otolith increment widths indicate that all individuals experience a brief period of rapid growth during early life as larvae and that the duration of this growth anomaly is negatively correlated with larval duration. A protracted high-growth period early in larval life is associated with a lower ratio of Sr:Ca, which may reflect low salinity conditions in nearshore habitats. A distinct shift in δ18 O (range: 4-5‰) is closely associated with the metamorphic mark in otoliths, indicating that larval metamorphosis occurs promptly upon return to fresh water. Strontium and other trace elements are not as tightly coupled to the metamorphosis mark, but confirm the marine-to-freshwater transition. Integration of microstructural and microchemical approaches reveals that larvae vary substantially in growth rate, possibly in association with habitat differences. Although time and financial costs make it difficult to achieve large sample sizes, present results show that examining even a small number of individuals can lead to novel inferences about early life history in diadromous fishes and illustrates the value of integrating analyses.

Colonization and demographic expansion of freshwater fauna across the Hawaiian archipelago.

It is widely accepted that insular terrestrial biodiversity progresses with island age because colonization and diversification proceed over time. Here, we assessed whether this principle extends to oceanic island streams. We examined rangewide mtDNA sequence variation in four stream-dwelling species across the Hawaiian archipelago to characterize the relationship between colonization and demographic expansion, and to determine whether either factor reflects island age. We found that colonization and demographic expansion are not related and that neither corresponds to island age. The snail Neritina granosa exhibited the oldest colonization time (~2.713 mya) and time since demographic expansion (~282 kya), likely reflecting a preference for lotic habitats most prevalent on young islands. Conversely, gobioid fishes (Awaous stamineus, Eleotris sandwicensis and Sicyopterus stimpsoni) colonized the archipelago only ~0.411-0.935 mya, suggesting ecological opportunities for colonization in this group were temporally constrained. These findings indicate that stream communities form across colonization windows, underscoring the importance of ecological opportunities in shaping island freshwater diversity.

Meningococcal disease epidemiology in Australia 10 years after implementation of a national conjugate meningococcal C immunization programme.

Australia implemented conjugate meningococcal C immunization in 2003 with a single scheduled dose at age 12 months and catch-up for individuals aged 2-19 years. Several countries have recently added one or more booster doses to their programmes to maintain disease control. Australian disease surveillance and vaccine coverage data were used to assess longer term vaccine coverage and impact on invasive serogroup C disease incidence and mortality, and review vaccine failures. Coverage was 93% in 1-year-olds and 70% for catch-up cohorts. In 10 years, after adjusting for changes in diagnostic practices, population invasive serogroup C incidence declined 96% (95% confidence interval 94-98) to 0·4 and 0·6 cases/million in vaccinated and unvaccinated cohorts, respectively. Only three serogroup C deaths occurred in 2010-2012 vs. 68 in 2000-2002. Four (<1/million doses) confirmed vaccine failures were identified in 10 years with no increasing trend. Despite published evidence of waning antibody over time, an ongoing single dose of meningococcal C conjugate vaccine in the second year of life following widespread catch-up has resulted in near elimination of serogroup C disease in all age groups without evidence of vaccine failures in the first decade since introduction. Concurrently, serogroup B incidence declined independently by 55%.

Global threats to human water security and river biodiversity.

Protecting the world's freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world's population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity.

Control of varicella in the post-vaccination era in Australia: a model-based assessment of catch-up and infant vaccination strategies for the future.

In Australia, varicella vaccine was universally funded in late 2005 as a single dose at 18 months. A school-based catch-up programme for children aged 10-13 years without a history of infection or vaccination was funded until 2015, when those eligible for universal infant vaccination would have reached the age of high school entry. This study projects the impact of discontinuing catch-up vaccination on varicella and zoster incidence and morbidity using a transmission dynamic model, in comparison with alternative policy options, including two-dose strategies. At current vaccine coverage (83% at 2 years and 90% at 5 years), ceasing the adolescent catch-up programme in 2015 was projected to increase varicella-associated morbidity between 2035 and 2050 by 39%. Although two-dose infant programmes had the lowest estimated varicella morbidity, the incremental benefit from the second dose fell by 70% if first dose coverage increased from 83% to 95% by age 24 months. Overall zoster morbidity was predicted to rise after vaccination, but differences between strategies were small. Our results suggest that feasibility of one-dose coverage approaching 95% is an important consideration in estimating incremental benefit from a second dose of varicella vaccine.

The utility of seroepidemiology for tracking trends in pertussis infection.

Comparing pertussis epidemiology over time and between countries is confounded by differences in diagnostic and notification practices. Standardized serological methods applied to population-based samples enhance comparability. Population prevalence of different levels of pertussis toxin IgG (PT IgG) antibody, measured by standardized methods, were compared by age group and region of Australia between 1997/1998 and 2002. The proportion of 5- to 9-year-olds with presumptive recent pertussis infection (based on IgG levels >or=62.5 ELISA units/ml) significantly decreased in 2002, consistent with notification data for the same period and improved uptake of booster vaccines following the schedule change from whole-cell to acellular vaccine. In contrast, recent presumptive infection significantly increased in adults aged 35-49 years. Population-based serosurveillance using standardized PT IgG antibody assays has the potential to aid interpretation of trends in pertussis incidence in relation to vaccine programmes and between countries.

Effectiveness of a 3 + 0 pneumococcal conjugate vaccine schedule against invasive pneumococcal disease among a birth cohort of 1.4 million children in Australia.

BACKGROUND: Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia's national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births. METHODS: Births records for 2001-2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 - adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children. RESULTS: Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9-98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5-94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4-90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children. CONCLUSION: Our population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.

Probabilistic linkage of national immunisation and state-based health records for a cohort of 1.9 million births to evaluate Australia's childhood immunisation program.

INTRODUCTION: Several countries have developed national immunisation registers, but only the Nordic countries have linked their registers to other health data in order to comprehensively evaluate the `real world' effectiveness of vaccines. Nordic countries can link datasets deterministically using the national person identifier, but most countries, including Australia, don't have such an identifier to enable this type of linkage. OBJECTIVES: To describe the process for assembling a linked study cohort that will enable the conduct of population-based studies related to immunisation and immunisation policy. METHODS: National death and immunisation databases along with state health data (notifications of vaccine preventable diseases, perinatal data, hospital admissions and emergency department presentations) up until December 2013 were probabilistically linked (using demographic details) for children born between 1996 and 2012 in two states: Western Australia and New South Wales (42% of Australia's population, combined). RESULTS: After exclusions there were 1.95 million children in the study cohort (live born children with both a birth and perinatal record which represents 97.5% of all live births in the state perinatal data collections - our source population) and 18.0 million person years of follow up (mean: 9.2 years per child). The characteristics of children in the cohort were generally similar to those only included in state perinatal databases and outcome measures were in keeping with expected figures from unlinked data sources. However, the lack of a dynamic national population register meant immigrants could not be included. CONCLUSIONS: We have been able to develop a similarly comprehensive system to the Nordic countries based on probabilistic linkage methods. Our experience should provide encouragement to other countries with national immunisation registers looking to establish similar systems.

Childhood asthma diagnosis and use of asthma medication.

AIM: To determine the burden of asthma in children. METHODS: A cross sectional, randomised, computer assisted telephone survey of a community based sample of 2020 children aged 5-14 years in western Sydney (New South Wales) over a 20 day period from June 2000 to July 2000. RESULTS: Main outcome measures were carer reported history of asthma diagnosis, hospital presentation/admission for asthma, recent use of anti-asthma medications, and recent respiratory symptoms. Diagnosed asthma was reported in 31% (of whom 42% were diagnosed aged 2 years or under) and asthma medications used in the previous year by 21% of children. Factors significantly associated with a reported asthma diagnosis included: male gender (OR: 1.51), birth in Australia (OR: 1.64), living in an English speaking household (OR: 1.47), Aboriginality (OR: 2.32), possession of a health care card (OR: 1.28), previous pneumonia (OR: 2.4) or pertussis (OR: 2.0), and a recent episode of croup (OR: 1.9). Exposure to tobacco smoke and immunisation status were not significant. DISCUSSION: We confirm a high prevalence of asthma and medication use for asthma. The high proportion of children diagnosed asthmatic at 2 years or under (when asthma cannot be diagnosed reliably) suggests overdiagnosis of asthma may contribute to the apparent high prevalence.

National study of adverse reactions after vaccination with bacille Calmette-Guérin.

Few large prospective studies of adverse reactions after bacille Calmette-Guérin (BCG) vaccination are available. In a prospective national study of such adverse reactions among 918 subjects (aged 1 day to 54 years) over a 14-month period, 45 vaccinees (5%) reported 53 adverse reactions (23 injection-site abscesses, 14 severe local reactions, 10 cases of lymphadenitis, and 6 other reactions). Only 1% of vaccinees required medical attention. Reactions, particularly lymphadenitis, were significantly less common in infants <6 months old (but not in subjects aged > or =6 months) vaccinated by trained (vs. untrained) providers (relative risk [RR], 0.24; 95% confidence interval [CI], 0.09-0.68). Injection-site abscesses (RR, 2.96; 95% CI, 1.11-7.90) and severe local reactions (RR, 4.93; 95% CI, 1.11-21.90) were significantly more common in older vaccinees. Local reactions were more frequently reported by adult females than by adult males (RR, 7.18; 95% CI, 1.59-32.45). Adverse reactions were not significantly associated with any currently available vaccine batch, previous receipt of BCG vaccine, or concomitant administration of other vaccines.

Balsalazide in the maintenance treatment of patients with ulcerative colitis, a double-blind comparison with sulphasalazine.

Balsalazide (BSZ) is a pro-drug which releases 5-aminosalicylic acid (5ASA) and 4-aminobenzoyl-beta-alanine (an inert carrier) in the colon of various species including man. BSZ was compared with sulphasalazine (SASP) (both 1 g b.d. orally) in the maintenance of remission in patients with ulcerative colitis (UC). Seventy-nine patients (53 male, 26 female), mean age 49 years (range 19-79 years), with UC were randomly allocated to either treatment (41 BSZ, 38 SASP) for 6 months. The groups were similar in respect of age, sex, duration and extent of disease. Seven patients defaulted (3 BSZ, 4 SASP) leaving 38 on BSZ and 34 on SASP. Two male patients, both receiving SASP, were withdrawn because of severe side-effects. One of these patients, with an exfoliative rash, was maintained satisfactorily on open BSZ. Remission rates at 6 months (51% BSZ, 63% SASP) were not significantly different (life-table analysis P less than 0.1). Twelve patients (15%) reported troublesome side-effects (2 BSZ 5%, 10 SASP 26%, P = 0.017 Fisher Exact Test). Mean haemoglobin concentrations, similar on entry, increased after 6 months with BSZ (0.2 g/dl) but decreased with SASP (0.5 g/dl) (P less than 0.0002). BSZ was not significantly different from SASP in maintaining remission in patients with UC but had fewer side-effects.

Prednisolone absorption in inflammatory bowel disease: correlation with anatomical site and extent.

Prednisolone absorption was studied in 13 normal subjects, eight patients with ulcerative colitis and 21 patients with Crohn's disease, by measuring plasma levels after a single oral dose. Absorption of the drug was delayed in all patient groups. The peak plasma level of the drug was lower in patients with extensive small bowel Crohn's disease. Patients in this category may need higher doses of oral prednisolone than other patients with inflammatory bowel disease.

Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day.

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.

A radiological study after parenteral nutrition through silicone rubber catheters: fibrin sleeves without thrombosis.

Injection of contrast material through 38 central silicone rubber catheters at the time of withdrawal after a mean catheter life of 55 days (range 5-369) has shown no evidence of occult venous thrombosis despite the presence of a fibrin sleeve around the whole length of the intravascular portion in 37 cases. The presence of this fibrin sleeve appears to have been harmless. The absence of thrombosis suggests that silicone rubber is the material of choice for central venous feeding catheters and that the addition of heparin to the infusion fluid is unnecessary.

Pathophysiology of colonic motility disorders.

When no identifiable organic cause for colonic symptoms can be found, it is easy for the busy clinician to label the patient neurotic. It is evident that many of these "functional" disorders do reflect an underlying motility disorder, although our understanding is far from clear. However, currently, patients with severe constipation are evaluated in a much more rational manner and, as a consequence, are offered a reasonable therapeutic approach that can be predicted to have a good chance for success. We can hope that as our understanding of irritable bowel syndrome is strengthened, treatment will become more efficacious than the unproved and costly medications that are in use currently. Until dietary modification becomes commonplace, it is unlikely that the incidence of diverticular disease or its complications will change. Already, our understanding of ileus has allowed us to realize the benefits of laparoscopic surgery, and as our knowledge of the various gut hormones and the inhibitory role that some play in intestinal motility grows, ileus, and its resulting prolongation of hospital stay, may become less problematic.

A mathematical model to measure the impact of the Measles Control Campaign on the potential for measles transmission in Australia.

BACKGROUND: The aims of this study were to determine the impact of the Australian Measles Control Campaign (MCC) on the transmission dynamics of measles by calculating the reproductive number (R) before and after the MCC, and to predict measles control in Australia in the future. METHODS: A national serosurvey was conducted before and after the MCC. Sera were tested for anti-measles IgG using enzyme immunoassay (EIA). A mathematical model, using serosurvey results and vaccine coverage estimates, was used to calculate the change in R after the MCC. RESULTS: The values of R calculated before and after the MCC were 0.90 and 0.57. At vaccine coverage levels indicated by the Australian Childhood Immunisation Register (ACIR), the value of R will exceed 1 (the epidemic threshold) in 2007-2008 nationally, and sooner in some regions of Australia. Coverage of at least 84% with two doses of MMR is required to sustain measles control. CONCLUSIONS: The Australian MCC had a significant impact on the transmission dynamics of measles. However, current vaccine coverage levels may result in indigenous measles transmission by 2007. Sustained efforts are required to improve coverage with two doses of MMR and to ensure elimination of indigenous measles transmission.

Immunisation coverage reporting through the Australian Childhood Immunisation Register--an evaluation of the third-dose assumption.

OBJECTIVE: The Australian Childhood Immunisation Register (ACIR) currently classifies those children who have the third dose recorded as fully immunised at 12 months of age, even if records of earlier doses are missing. This analysis assesses the impact this "third-dose assumption" has on immunisation coverage estimates for children aged 12 months. METHODS: ACIR records from three equally spaced cohorts of children at 12 months of age, which relied on the third-dose assumption, were examined for variation in doses and vaccine types recorded by jurisdiction and Medicare registration status. RESULTS: Although the percentage reduction in coverage without application of the third-dose assumption decreased through the three cohorts examined, the proportion classified as fully immunised still decreased by 11-12% (to < 75%) if the third-dose assumption was not used in the most recent cohort. "Fully immunised" status among children with delayed Medicare registration or in jurisdictions with a high proportion of paper reporting to the ACIR was disproportionately reduced without use of the assumption. CONCLUSIONS AND IMPLICATIONS: While independent sources of data continue to show that the ACIR incorrectly classifies some children as not fully immunised even with the third-dose assumption, its use seems appropriate for reporting population trends in immunisation coverage. Earlier Medicare registration and increased electronic reporting to the ACIR, together with incentives for parents and providers to ensure complete ACIR records, should eventually eliminate the need for the third-dose assumption.