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.

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.

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.

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.

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%.

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.

Sources of pertussis infection in young infants: a review of key evidence informing targeting of the cocoon strategy.

BACKGROUND: The relative contribution of different categories of contact in transmitting pertussis to very young infants, who experience the most severe morbidity, is the most important single factor determining the likely benefit of pertussis vaccination of their close contacts (the "cocooning" strategy). OBJECTIVE: To identify, evaluate the quality of and summarise existing data on potential sources of infant pertussis infection in high income countries, focussing on infants under 6 months old. DATA SOURCES: Online databases MEDLINE and EMBASE. Additional studies were identified from the reference lists of relevant articles. Study selection and analysis: Study quality was evaluated by standardised criteria, based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Pooled estimates of the proportion of pertussis cases attributable to various contact sources were calculated using data from the highest quality studies. RESULTS: Nine studies met the inclusion criteria; seven included data on contacts of hospitalised infants less than 6 months old. Case definitions and methods of contact ascertainment were variable. Most identified sources were from the household, of which 39% (95%CI 33-45%) were mothers, 16% (95%CI 12-21%) fathers, and 5% (95%CI 2-10%) grandparents. Estimates for siblings (16-43%) and non-household contacts (4-22%) were more heterogeneous. For 32-52% of infant cases, no source was identified. Asymptomatic pertussis infection was found in 8-13% of contacts evaluated. CONCLUSIONS: These data suggest that the greatest potential impact of pertussis vaccination of adults to prevent severe disease in young infants comes from vaccinating mothers, followed by fathers, with grandparents having a minor role. Siblings varied in importance and, given recent data regarding waning immunity in vaccinated children, need further study. Non-household sources are also well documented, highlighting the potential limitations of the cocoon strategy to prevent severe infant disease.

Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia.

INTRODUCTION: In Australia, post-marketing surveillance for intussusception following vaccination commenced with funding of RotaTeq(®) and Rotarix(®) vaccines under the National Immunization Program (NIP) in July 2007. METHODS: Two active surveillance mechanisms (hospital-based case ascertainment and monthly reports from paediatricians) identified intussusception cases between 1st July 2007 and 31st December 2008 in four states. Linkage to vaccination records identified cases occurring within 1-7 and 1-21 days of rotavirus vaccination. Expected cases within the post-vaccination windows were calculated by applying rates of intussusception from national hospitalisation data over 6 years (mid-2000 to mid-2006), by age and state, to numbers vaccinated (by dose) according to the Australian Childhood Immunization Register. RESULTS: Combining exposure windows associated with all doses of rotavirus vaccine from 1 to 9 months of age, there was no evidence of an increased risk of intussusception following vaccination for either vaccine. However, in infants 1 to <3 months of age, there was suggestive evidence of excess intussusception cases 1-7 and 1-21 days following dose 1 (1-7 days: RotaTeq(®) relative risk (RR)=5.3, 95% confidence interval [CI] 1.1,15.4; Rotarix(®) RR 3.5, 95% CI 0.7,10.1; 1-21 days: RotaTeq(®) RR 3.5, 95% CI 1.3, 7.6; Rotarix(®)RR 1.5, 95% CI 0.4, 3.9). There was no evidence that clinical outcome of intussusception occurring within 21 days of rotavirus vaccination differed from that in cases occurring later post-vaccination. CONCLUSION: Although we found no overall increase in intussusception following receipt of rotavirus vaccine, there was some evidence of an elevated risk following the first dose of both vaccines. Larger population-based studies using linked databases are required to provide more definitive evidence.

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.

Lack of pneumococcal carriage in the hospitalised elderly.

UNLABELLED: There have been few surveys of Streptococcus pneumoniae and Neisseria meningitidis carriage in sick or frail elderly people who, with the very young, comprise the group who are at highest risk for pneumococcal disease. We studied pneumococcal carriage among participants in a pneumococcal immunisation study in the frail elderly. METHODS: Subjects aged >or=60 years were recruited from a large tertiary referral hospital in Sydney, Australia. Nose and throat swabs were collected at the time of enrolment and 12 months after immunisation. RESULTS: Before immunisation, only 1 of 315 participants was identified as a nasal carrier of S. pneumoniae; another was identified as throat carrier of N. meningitidis. None of the participants examined after immunisation was carrying either S. pneumoniae or N. meningitidis. CONCLUSION: The low rate of pneumococcal carriage in this population of hospitalised elderly patients was unexpected. The most likely reason is that long-term carriage is rare in this population and suggests that pneumococcal disease primarily follows recent acquisition of S. pneumoniae types not associated with carriage.

Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes.

The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100,000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

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.

Immunological responses to pneumococcal vaccine in frail older people.

UNLABELLED: Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone. AIM: To evaluate the immunogenicity of the 7-valent conjugated pneumococcal vaccine (PCV7) versus 23-valent polysaccharide vaccine (23vPPV) and compare the immune response to four serotypes (4, 6B, 18C and 19F), with respect to age or frailty in an elderly population of previously unvaccinated hospitalized patients. METHOD: 241 patients aged 60 years and over, recruited between 16 May 2005 and 20 February 2006, were randomised to 23PPV or PCV7 vaccine. We measured Frailty Index (FI), Barthel index and the MiniMental State. Serotype-specific IgG was measured by ELISA at base line and 6 months after vaccination. Antibody responses were defined by the ratio of post-vaccination to pre-vaccination IgG antibody concentration (poor < 2-fold increase, acceptable > or = 2.0 to 3.99-fold and strong > or = 4.0-fold increase). RESULTS: Pre-immunization IgG was generally low and did not differ significantly by age or frailty. Post-immunization, IgG increased to all four serotypes; acceptable or strong response ranged between 29% for (6B) and 57% for (18C). There was no significant difference between the two vaccine types (23PPV versus PCV7). At 6 months post-vaccination, the highest geometric mean IgG concentrations (GMCs) were seen for serotype 19F and the lowest for serotype 4. Although there was some variation by serotype, responses after vaccination were lowest in the most frail or aged subjects. CONCLUSIONS: Pneumococcal vaccines are perceived to offer low protection in the frail elderly, but our study showed that the proportion of this vulnerable population with acceptable responses is encouraging. Frailty, as measured by the Frailty Index, appears to be a better predictor of immune response to pneumococcal vaccines than age alone.

Factors associated with pneumococcal immunisation among hospitalised elderly persons: a survey of patient's perception, attitude, and knowledge.

AIM: To investigate attitudes, perceptions and knowledge of elderly hospital patients in regard to vaccination in general and pneumococcal vaccination in particular. SETTING: A hospital-based patient survey in Sydney, Australia. PARTICIPANTS: Patients aged 60 years and older who are admitted to selected wards in an 800-bed tertiary referral hospital in Sydney, Australia. METHODS: A face-to-face interview administered to 200 inpatients. RESULTS: Approximately half (49%) of the patients had a positive attitude to vaccination whereas 59% had less positive perception. There were 35% of the patients who were unvaccinated against influenza and pneumococcal disease. Positive perception (OR 2.9, 95% C.I.=1.3-6.5) and attitude (OR 4.4, 95% C.I.=2.0-9.4) significantly predicted vaccination with both vaccines. Similarly the odds of receiving pneumococcal vaccination for those who had a more positive attitude and more correct knowledge were significant (OR=2.3, 95% C.I.=1.0-5.4; OR=2.7, 95% C.I.=1.1-6.8). We explored reasons for non-vaccination. Physician recommendation was listed as an important factor by patients. CONCLUSIONS: Positive perception and attitude towards vaccination are significant factors associated with immunisation status. For the pneumococcal vaccination, having influenza vaccination is related to pneumococcal vaccination.

Population-based seroprevalence of Neisseria meningitidis serogroup C capsular antibody before the introduction of conjugate vaccine, in Australia.

Neisseria meningitidis serogroup C (NMC) conjugate vaccine was introduced, in Australia, in 2003. Our aims were to determine pre-immunisation IgG NMC seroprevalence and evaluate an enzyme-linked immunosorbent assay (ELISA), previously validated against the serum bactericidal assay (SBA). 2409 sera, collected in 2002, from subjects aged 2-34 years, were tested. The geometric mean concentration (GMC) of NMC anticapsular IgG was 0.38 U/mL in subjects under 19 years and it increased to 0.67 U/mL for those aged 30-34 years. Variation in GMC correlated with reported NMC disease incidence and was higher in males than females (0.52 U/mL versus 0.41 U/mL; p=0.005). The ELISA appears suitable for serosurveillance but the IgG level that correlates with protection needs further investigation. Serosurveys will be repeated to monitor the impact of vaccination.