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OBJECTIVE: Recent surveys identified trachomatous inflammation - follicular (TF) at endemic levels in the Torres Strait Islands; however, local health staff do not report trachomatous trichiasis (TT) in adults. We undertook a cross-sectional survey involving eye examination and microbiological testing to better understand this disconnect. METHODS: We examined 169 of 207 (82%) residents and collected ocular swabs for polymerase chain reaction (PCR) testing for Chlamydia trachomatis. Other viral PCR tests and bacterial culture were also performed. RESULTS: TF prevalence in children aged 5-9 years was 23% (7/30). No ocular C. trachomatis was identified by PCR. For the 72 participants (43%) with follicles, bacterial culture was positive for 11 (15%) individuals. No individual had trachomatous trichiasis. CONCLUSIONS: Follicular conjunctivitis consistent with TF was prevalent but ocular C. trachomatis and cicatricial trachoma were absent. Non-chlamydial infections or environmental causes of follicular conjunctivitis may be causing TF in this community. IMPLICATIONS FOR PUBLIC HEALTH: In similar settings, reliance on simplified clinical assessment alone may lead to an overestimation of the public health problem posed by trachoma. Consideration should be given to incorporating C. trachomatis PCR, and in certain settings, a detailed clinical exam could be performed by an experienced ophthalmologist during prevalence surveys.

Background Empyema is a serious complication of pneumonia frequently caused by Streptococcus pneumoniae (SP). We assessed the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema after inclusion in the Australian National Immunisation Program. Methods For bacterial pneumonia and empyema hospitalisations, we ascertained incidence rates (IRs) using the National Hospital Morbidity Database International Statistical Classification of Disease discharge codes and relevant population denominators, and calculated incidence rate ratios (IRR) comparing the 13vPCV period (June 2012-May 2017) with the 7vPCV period (June 2007-May 2011). Blood and pleural fluid (PF) cultures and PF PCR of 401 children with empyema from 11 Australian hospitals during the 13vPCV period were compared with our previous study in the 7vPCV period. Findings Across 7vPCV and 13vPCV periods, IRs per million children (95% CIs) were 1605 (1588 to 1621) and 1272 (1259 to 1285) for bacterial pneumonia, and 14.23 (12.67 to 15.79) and 17.89 (16.37 to 19.42) for empyema hospitalisations. IRRs were 0.79 (0.78 to 0.80) for bacterial pneumonia and 1.25 (1.09 to 1.44) for empyema. Of 161 empyema cases with SP serotypes, 147 (91.3%) were vaccine types. ST3 accounted for 76.4% of identified serotypes in the 13vPCV period, more than double than the 7vPCV period (p<0.001); ST19A decreased from 36.4% to 12.4%. No cases of ST1 empyema were identified in the 13vPCV period versus 14.5% in the 7vPCV period. Interpretation 13vPCV resulted in a significant reduction in all-cause hospitalisations for bacterial pneumonia but empyema hospitalisations significantly increased, with emergence of pneumococcal ST3 as the dominant serotype in empyema. Trial registration number Australian and New Zealand Clinical Trial Registry ACTRN 12614000354684.

BACKGROUND: Following high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program. METHODS: A matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VEadj) for sex and First Nations status. RESULTS: There were 1,125 cases and 10,645 matched controls analysed. Overall VEadj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41-60). VEadj was 60% (95% CI 46-70) for children who received two doses in 2018, and 60% (95% CI 48-69) for children vaccinated appropriately according to schedule completeness. VE increased with age. CONCLUSIONS: Moderate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.

OBJECTIVE: Ascertain predictors of inactivated influenza vaccine (IIV) uptake in pregnancy in mother-infant pairs from six Australian sites over four consecutive influenza seasons (2012-2015). METHODS: Prospective observational cohort study calculating proportions of unvaccinated and vaccinated pregnancies. Multivariable logistic regression calculating adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) to determine demographic, pregnancy and birth characteristics as predictors of IIV uptake in pregnancy. RESULTS: Uptake of IIV was 36% (n=3,651/9,878) with only 3-4% during the first trimester. Validation of IIV receipt was obtained for 77% of vaccinated participants. Predictors of IIV uptake in pregnancy were: healthcare provider recommendation to have IIV during pregnancy (aOR 7.04 [95%CI 5.83-8.50]): GP (aOR 4.12 [95%CI 3.43-4.98]), obstetrician (aOR 4.41 [95%CI 3.45-5.64]), midwife (aOR 1.88 [95%CI 1.51-2.36]); previous IIV within 12 months of their current pregnancy (aOR 2.87 [95%CI 2.36-3.50]); and pertussis vaccination during the current pregnancy (aOR 4.88 [95%CI 4.08-5.83]). Conclusions and implications for public health: Healthcare provider discussions with pregnant women about the risks associated with influenza infection during pregnancy and early infancy and evidence about the safety and effectiveness of IIV are required. Recommending and offering IIV in pregnancy needs to be included in these discussions to improve uptake.

INTRODUCTION: Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. METHODS AND ANALYSIS: 'Links2HealthierBubs' is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women's Hospital, and the West Australian Aboriginal

Chlamydia trachomatis infects the urogenital tract (UGT) and eyes. Anatomical tropism is correlated with variation in the major outer membrane protein encoded by ompA. Strains possessing the ocular ompA variants A, B, Ba and C are typically found within the phylogenetically coherent "classical ocular lineage". However, variants B, Ba and C have also been found within three distinct strains in Australia, all associated with ocular disease in children and outside the classical ocular lineage. CtGEM genotyping is a method for detecting and discriminating ocular strains and also the major phylogenetic lineages. The rationale was facilitation of surveillance to inform responses to C. trachomatis detection in UGT specimens from young children. CtGEM typing is based on high resolution melting analysis (HRMA) of two PCR amplified fragments with high combinatorial resolving power, as defined by computerised comparison of 65 whole genomes. One fragment is from the hypothetical gene defined by Jali-1891 in the C. trachomatis B_Jali20 genome, while the other is from ompA. Twenty combinatorial CtGEM types have been shown to exist, and these encompass unique genotypes for all known ocular strains, and also delineate the TI and T2 major phylogenetic lineages, identify LGV strains and provide additional resolution beyond this. CtGEM typing and Sanger sequencing were compared with 42 C. trachomatis positive clinical specimens, and there were no disjunctions. CtGEM typing is a highly efficient method designed and tested using large scale comparative genomics. It divides C. trachomatis into clinically and biologically meaningful groups, and may have broad application in surveillance.

© 2018 Giffard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chlamydia trachomatis infects the urogenital tract (UGT) and eyes. Anatomical tropism is correlated with variation in the major outer membrane protein encoded by ompA. Strains possessing the ocular ompA variants A, B, Ba and C are typically found within the phyloge-netically coherent “classical ocular lineage”. However, variants B, Ba and C have also been found within three distinct strains in Australia, all associated with ocular disease in children and outside the classical ocular lineage. CtGEM genotyping is a method for detecting and discriminating ocular strains and also the major phylogenetic lineages. The rationale was facilitation of surveillance to inform responses to C. trachomatis detection in UGT specimens from young children. CtGEM typing is based on high resolution melting analysis (HRMA) of two PCR amplified fragments with high combinatorial resolving power, as defined by computerised comparison of 65 whole genomes. One fragment is from the hypothetical gene defined by Jali-1891 in the C. trachomatis B_Jali20 genome, while the other is from ompA. Twenty combinatorial CtGEM types have been shown to exist, and these encompass unique genotypes for all known ocular strains, and also delineate the TI and T2 major phylogenetic lineages, identify LGV strains and provide additional resolution beyond this. CtGEM typing and Sanger sequencing were compared with 42 C. trachomatis positive clinical specimens, and there were no disjunctions. CtGEM typing is a highly efficient method designed and tested using large scale comparative genomics. It divides C. trachomatis into clinically and biologically meaningful groups, and may have broad application in surveillance.

© 2018 Giffard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chlamydia trachomatis infects the urogenital tract (UGT) and eyes. Anatomical tropism is correlated with variation in the major outer membrane protein encoded by ompA. Strains possessing the ocular ompA variants A, B, Ba and C are typically found within the phyloge-netically coherent “classical ocular lineage”. However, variants B, Ba and C have also been found within three distinct strains in Australia, all associated with ocular disease in children and outside the classical ocular lineage. CtGEM genotyping is a method for detecting and discriminating ocular strains and also the major phylogenetic lineages. The rationale was facilitation of surveillance to inform responses to C. trachomatis detection in UGT specimens from young children. CtGEM typing is based on high resolution melting analysis (HRMA) of two PCR amplified fragments with high combinatorial resolving power, as defined by computerised comparison of 65 whole genomes. One fragment is from the hypothetical gene defined by Jali-1891 in the C. trachomatis B_Jali20 genome, while the other is from ompA. Twenty combinatorial CtGEM types have been shown to exist, and these encompass unique genotypes for all known ocular strains, and also delineate the TI and T2 major phylogenetic lineages, identify LGV strains and provide additional resolution beyond this. CtGEM typing and Sanger sequencing were compared with 42 C. trachomatis positive clinical specimens, and there were no disjunctions. CtGEM typing is a highly efficient method designed and tested using large scale comparative genomics. It divides C. trachomatis into clinically and biologically meaningful groups, and may have broad application in surveillance.

Background The World Health Organization (WHO) Western Pacific Region (WPR) Guidelines on verification of measles elimination were established in 2012. This article outlines Australia's approach to addressing the guideline's five lines of evidence, which led to formal verification of elimination by the WHO Regional Verification Commission (RVC) in March 2014. Methods The criteria were addressed using national measles notifications, data from selected laboratories, the national childhood immunization register, and three national serosurveys (1998/1999, 2002, 2007). Results Australia met or exceeded all indicator targets with either national or sentinel data. Laboratory and epidemiological surveillance were of high quality, with 85% of cases documented as imported/import-related (target 80%); coverage with the first dose of measles vaccine was close to 94% in 2008–2012 and second dose coverage increased to 91% in 2012 (target >95%). There is ongoing commitment by the Australian Government to increase immunization coverage, and the absence of sustained transmission of any single measles genotype was demonstrated. Conclusions This is the first documentation of the successful application of the WPR RVC guidelines. The indicators afford some flexibility but appear to provide appropriate rigor to judge achievement of measles elimination. Our experience could assist other countries seeking to verify their elimination status.

BACKGROUND: Human Parainfluenza viruses are a common cause of both upper and lower respiratory tract infections, particularly in children. Of the four Parainfluenza virus serotypes, Parainfluenza 4 is least well characterised from both the clinical, epidemiological and genetic perspectives. METHODS: Flocked nose or throat swabs from a previous study investigating viral prevalence in community-based adults suffering from influenza like illness were used as the basis for this study. Samples in which no virus was detected using a 16 viral respiratory pathogen real-time PCR panel were barcoded and pyrosequenced using the Roche 454 GS FLX Titanium chemistry. The sequences were analysed using the VirusHunter bioinformatic pipeline. Sanger sequencing was used to complete the detected Parainfluenza 4 coding region. RESULTS: A variant Parainfluenza 4 subtype b strain (QLD-01) was discovered in an otherwise healthy adult who presented with influenza like illness. Strain QLD-01 shared genomic similarities with both a and b subtypes. The extent of divergence of this genome from the 5 available whole Parainfluenza 4 genomes impacted the predicted binding efficiencies of the majority of published Parainfluenza 4 PCR assays. CONCLUSIONS: These findings further support a possible role for Parainfluenza 4 in the aetiology of adult respiratory disease within the community setting, and highlight the caution needed to be used in designing PCR assays from limited sequence information or in using proprietary commercial PCR assays.

INTRODUCTION: Influenza vaccination in pregnancy is recommended for all women in Australia, particularly those who will be in their second or third trimester during the influenza season. However, there has been no systematic monitoring of influenza vaccine uptake among pregnant women in Australia. Evidence is emerging of benefit to the infant with respect to preventing influenza infection in the first 6 months of life. The FluMum study aims to systematically monitor influenza vaccine uptake during pregnancy in Australia and determine the effectiveness of maternal vaccination in preventing laboratory-confirmed influenza in their offspring up to 6 months of age. METHODS AND ANALYSIS: A prospective cohort study of 10 106 mother-infant pairs recruited between 38 weeks gestation and 55 days postdelivery in six Australian capital cities. Detailed maternal and infant information is collected at enrolment, including influenza illness and vaccination history with a follow-up data collection time point at infant age 6 months. The primary outcome is laboratory-confirmed influenza in the infant. Case ascertainment occurs through searches of Australian notifiable diseases data sets once the infant turns 6 months of age (with parental consent). The primary analysis involves calculating vaccine effectiveness against laboratory-confirmed influenza by comparing the incidence of influenza in infants of vaccinated mothers to the incidence in infants of unvaccinated mothers. Secondary analyses include annual and pooled estimates of the proportion of mothers vaccinated during pregnancy, the effectiveness of maternal vaccination in preventing hospitalisation for acute respiratory illness and modelling to assess the determinants of vaccination. ETHICS AND DISSEMINATION: The study was approved by all institutional Human Research Ethics Committees responsible for participating sites. Study findings will be published in peer review journals and presented at national and international confere

BACKGROUND: Viral respiratory infections are associated with significant morbidity and mortality. Many new aetiological agents have been described recently. OBJECTIVES: We looked for respiratory viruses in a population-based sample of healthy adults with influenza-like illness (ILI). We investigated host and spatio-temporal associations with virus isolation and host, spatio-temporal and virus associations with self-reported symptoms. PATIENTS/METHODS: We recruited 586 participants experiencing 651 illness episodes from a population of healthy adults enrolled in an influenza vaccine effectiveness trial. At ILI assessment visits, a respiratory swab was collected and tested for viruses using a combination of polymerase chain reaction (PCR) assays. Participants also completed a questionnaire detailing their clinical course in 336 episodes. RESULTS: Of 643 samples analysed, a virus was identified in 44%. Half were picornaviruses, with influenza and coronaviruses the next most common. Individuals with influenza were significantly less likely to have been immunised than the reference (virus negative) population (OR = 0·52 (0·31, 0·87) P = 0·01). The mean symptom score (95% CI) reported by individuals with influenza was significantly higher than in all other episodes [Influenza: 10·2 (9·4, 10·9); Other: 7·4 (7·2, 7·7); Difference (95% CI): 2·5 (1·5, 3·5); P < 0·001]. In an analysis restricted to influenza-positive cases, the symptom score was not attenuated by vaccination. CONCLUSIONS: Our findings indicate that a greater number of symptoms are displayed by individuals presenting with influenza confirmed ILI compared with other agents that cause ILI. While influenza vaccination reduced the probability of influenza virus detection, symptom score for influenza-positive ILI was not attenuated.

Human rhinovirus (HRV) replication triggers exacerbation of asthma and causes most acute respiratory illnesses (ARIs), which may manifest as influenza-like illness. The recent assignment of 60 previously unknown HRV types to a third HRV species, Human rhinovirus C, raised questions about the prevalence of these picornavirus types in the community, the extent of HRV diversity at a single site, and whether the HRVs have an equally diverse clinical impact on their hosts. We quantified HRV diversity, and there was no clinical impact attributable to HRV species and genotypes among a community population of preschool-aged children with ARI who provided respiratory samples during 2003. All HRV species were represented among 138 children with ARI, and 74 distinct HRV types were cocirculating. Fever accompanied 32.8% of HRV-positive ARI cases. HRVs were less likely than DNA viruses to be codetected with another virus, suggesting virus interference at the community level, demonstrated by the inverse correlation between influenza virus detection and HRV detection.

A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.

BACKGROUND: Household transmission of influenza-like illness (ILI) may vary with viral and demographic characteristics. We examined the effect of these factors in a population-based sample of adults with ILI. METHODS: We conducted a prospective cohort study in community-dwelling Australian adults nested within an influenza vaccine effectiveness trial. On presentation with ILI, participants were swabbed for a range of respiratory viruses and asked to return a questionnaire collecting details of household members with or without similar symptoms. We used logistic and Poisson regression to assess the key characteristics of household transmission. RESULTS: 258 participants from multi-occupancy households experienced 279 ILI episodes and returned a questionnaire. Of these, 183 were the primary case in the household allowing assessment of factors associated with transmission. Transmission was significantly associated in univariate analyses with female sex (27% vs. 13%, risk ratio (RR) = 2.13 (1.08, 4.21)) and the presence of a child in the house (33% vs. 17%, RR = 1.90 (1.11, 3.26)). The secondary household attack proportion (SHAP) was 0.14, higher if influenza was isolated (RR = 2.1 (1.0, 4.5)). Vaccinated participants who nonetheless became infected with influenza had a higher SHAP (Incidence RR = 5.24 (2.17, 12.6)). CONCLUSIONS: The increased SHAP in households of vaccinated participants who nonetheless had confirmed influenza infection supports the hypothesis that in years of vaccine mismatch, not only is influenza vaccine less protective for the vaccine recipient, but that the population's immunity is also lower.

We conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (HRV)-specific PCR primer pairs, varying the oligonucleotides and annealing temperature. None of the pairs could detect all HRVs in 2 panels of genotyped clinical specimens; >1 PCR is required for accurate description of HRV epidemiology.

BACKGROUND: Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children. METHODS: We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs. RESULTS: Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95% confidence interval $263 to $354). Influenza illnesses had a mean cost of $904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories. CONCLUSION: From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.

Population-based respiratory research and vaccine efficacy studies have previously required clinic or home visits when a subject had an acute respiratory illness. This method may mean parents are unwilling to enroll their child or report an illness of interest. We conducted a community-based cohort study into respiratory illnesses in 234 pre-school aged children using parent-collected specimens. Between January 2003 and January 2004 there were 563 specimens collected from 730 identified illnesses and these were tested using a panel of respiratory virus polymerase chain reaction (PCR) assays; 409 (73%) were positive for any virus. Specimens were not more likely to be positive when collected by a healthcare worker parent, when they included a throat swab, or when a very good collection technique was reported. A delay from illness onset to specimen collection of up to 5 days did not appear to impact on sensitivity of virus identification, but a delay of six or more days with minor delays in testing saw positivity fall. Combined with daily symptom diary completion and PCR testing, parent-collected specimens are an efficient and acceptable method for the conduct of future vaccine efficacy studies and other community-based respiratory virus research.