SMS-based interventions for improving child and adolescent vaccine coverage and timeliness: a systematic review.

BACKGROUND: The aim of this review was to investigate the impact of short message service (SMS)-based interventions on childhood and adolescent vaccine coverage and timeliness. METHODS: A pre-defined search strategy was used to identify all relevant publications up until July 2022 from electronic databases. Reports of randomised trials written in English and involving children and adolescents less than 18 years old were included. The review was conducted in accordance with PRISMA guidelines. RESULTS: Thirty randomised trials were identified. Most trials were conducted in high-income countries. There was marked heterogeneity between studies. SMS-based interventions were associated with small to moderate improvements in vaccine coverage and timeliness compared to no SMS reminder. Reminders with embedded education or which were combined with monetary incentives performed better than simple reminders in some settings. CONCLUSION: Some SMS-based interventions appear effective for improving child vaccine coverage and timeliness in some settings. Future studies should focus on identifying which features of SMS-based strategies, including the message content and timing, are determinants of effectiveness.

Baseline incidence of adverse birth outcomes and infant influenza and pertussis hospitalisations prior to the introduction of influenza and pertussis vaccination in pregnancy: a data linkage study of 78 382 mother-infant pairs, Northern Territory, Australia, 1994-2015.

We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994-2014) formed the cohort of 78 382 births. Aboriginal mother-infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4 vs. 64.7); stillbirths 2.3 (AR 10.8 vs. 4.6); low birthweight 2.9 (AR 54 vs. 19); and SGA 1.7 (AR 187 vs. 111). Hospitalisation (2000-2015) and Immunisation Register datasets (1994-2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.

An introduction to clinical trial design.

Clinicians and other decision makers in healthcare use results from clinical trials to inform practice. Interpretation of clinical trial results can be challenging, as weaknesses in trial design, data collection, analysis or reporting, can compromise the usefulness of results. A good working knowledge of clinical trial design is essential to expertly interpret and determine the validity and generalizability of the results. This manuscript will give a brief overview of clinical trial design including the strengths and limitations of various approaches. The focus will be on confirmatory clinical trials.

High burden of RSV hospitalization in very young children: a data linkage study.

Linked administrative population data were used to estimate the burden of childhood respiratory syncytial virus (RSV) hospitalization in an Australian cohort aged <5 years. RSV-coded hospitalizations data were extracted for all children aged <5 years born in New South Wales (NSW), Australia between 2001 and 2010. Incidence was calculated as the total number of new episodes of RSV hospitalization divided by the child-years at risk. Mean cost per episode of RSV hospitalization was estimated using public hospital cost weights. The cohort comprised of 870 314 children. The population-based incidence/1000 child-years of RSV hospitalization for children aged <5 years was 4·9 with a rate of 25·6 in children aged <3 months. The incidence of RSV hospitalization (per 1000 child-years) was 11·0 for Indigenous children, 81·5 for children with bronchopulmonary dysplasia (BPD), 10·2 for preterm children with gestational age (GA) 32-36 weeks, 27·0 for children with GA 28-31 weeks, 39·0 for children with GA <28 weeks and 6·7 for term children with low birthweight. RSV hospitalization was associated with an average annual cost of more than AUD 9 million in NSW. RSV was associated with a substantial burden of childhood hospitalization specifically in children aged <3 months and in Indigenous children and children born preterm or with BPD.

Nitazoxanide for the treatment of infectious diarrhoea in the Northern Territory, Australia 2007-2012.

INTRODUCTION: Australian Indigenous children suffer a high burden of diarrhoeal disease. Nitazoxanide is an antimicrobial that has been shown to be effective against a broad range of enteropathogens. To date, its use has not been reported in the tropical Top End (northernmost part) of the Northern Territory, Australia. The objective was to describe the use of nitazoxanide at the Royal Darwin Hospital, Northern Territory, and to assess any association with the time to resolution of diarrhoea. METHODS: Eligible children (≤13 years) were identified from dispensary records as having been prescribed nitazoxanide during the audit period, 1 July 2007 to 31 March 2012. Patient demographics, symptoms, diarrheal aetiology, treatment details and clinical outcomes were obtained by chart review. RESULTS: Twenty-eight children were treated with nitazoxanide, mostly for Cryptosporidium infection associated with prolonged diarrhoea. Dehydration was evident in 27 (96%) children on admission, and 11 (41%) were underweight. Diarrhoeal duration prior to treatment was 11.5 days (6.5 days pre- and 5 days post-admission). For children ≥12 months, nitazoxanide was prescribed according to guidelines stipulated by the Centers for Disease Control and Prevention (CDC). Resolution of diarrhoea occurred a median of 2.4 days (IQR: 1.4-7.3) after starting treatment. An increase in weight for length at discharge was found for all children. CONCLUSIONS: Prompt resolution of diarrhoea without adverse outcomes suggests nitazoxanide may be an effective treatment for Cryptosporidium infection in this setting. Its role in the treatment of other causes of infectious diarrhoea needs further investigation. Randomised trials will further direct its use and determine optimal dosing regimens.

Effect of feeding Yucca schidigera extract and a live yeast on the rumen microbiome and performance of dairy cows fed a diet excess in rumen degradable nitrogen.

Nitrogen (N) loss from livestock agriculture via ammonia and nitrous oxide can reduce feed efficiency, production and negatively affect the environment. One option to reduce N loss is to add dietary supplements such as Yucca schidigera extract which has ammonia-binding properties and contains antimicrobial steroidal saponins, or Saccharomyces cerevisiae yeast, which can stabilise rumen pH and promote fibre degradation, increasing microbial growth and demand for degradable N. To determine the effect of Yucca schidigera extract when fed alone or in combination with a live yeast on the performance, rumen metabolism, microbiome and N balance, six rumen cannulated dairy cows were fed a mixed ration (C), mixed ration with Y. schidigera extract (De-Odorase®, Alltech®; 5 g/cow/day; D), or mixed ration with Y. schidigera extract (5 g/day) and Saccharomyces cerevisiae (Yea-Sacc®, Alltech®, 1 g/cow per day; DY), in a 3 × 3 Latin rectangle design study with three periods of 49-day duration. Digesta samples were collected via the ruminal cannula during the final week of each period and separated into liquid (LPD) and solid (SPD) phases for microbiome analysis using 16S rRNA amplicon sequencing. DM intake was 0.8 kg/d lower (P < 0.05) in cows fed DY than C or D, with milk protein concentration 1.7 g/kg higher in C than D or DY. There was a beta diversity (Bray Curtis) clustering of the LPD in cows fed D or DY compared to C (P < 0.05), driven by an increase in Prevotella ruminicola-related operational taxonomic units (OTUs), and a decrease in P. brevis and P. bryantii OTUs. A methanogen OTU, Methanobrevibacter olleyae, was decreased in cows fed D or DY and an unclassified species of Gammaproteobacteria was increased in DY (LDA > 2.0, P < 0.05) compared to C. Rumen pH, ammonia and total VFA concentration were not affected by treatment (P > 0.05) but the concentration of propionate and iso-butyrate were lower at 1700 and 2000 h in cows fed DY compared to C (P < 0.05). Measurements of N balance were unaffected by supplementation with D or DY, and there was no effect of treatment on slurry pH. In conclusion, supplementing with an extract of Yucca schidigera either alone or in combination with a live yeast had only a small effect on performance, with Yucca schidigera altering species associated with carbohydrate and protein metabolism, and reduced Methanobrevibacter olleyae which is involved in methanogenesis.

A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study).

OBJECTIVES: We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. METHODS: FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant's scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected daily for seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. RESULTS: Overall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively. CONCLUSION: Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses. CLINICAL TRIAL REGISTRATION: ACTRN12621001063808.

Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).

BACKGROUND: The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. METHODS: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer's Comirnaty, Moderna's Spikevax or Novavax's Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. DISCUSSION: PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Light microscopic observations of the ruminal papillae of cattle on diets with divergent forage to cereal ratios.

High levels of supplementation with cereal increases production rates in cattle but can increase incidence of disease, ranging from mild indigestion to acute ruminal acidosis and death. Therefore, there is motivation to determine biological markers which can be used to identify whether animals have been, or are being fed, sufficient or excessive cereals. This study aimed to describe light microscopic findings from animals being fed diverse dietary cereal proportions and to test the performance of a novel rumen epithelial scoring system. Rumen wall tissue samples were obtained from the abattoir from 195 cattle from 11 Scottish farms and processed for histological examination. Light microscopic examination was used to characterise ruminal epithelial response to dietary challenge. Secondary objectives included describing the distribution of immune-related cells in bovine ruminal epithelium and assessing the use of a modified Elastin Martius Scarlet Blue stain (EMSB) for histological examination of the rumen epithelium. Cells staining positive for cluster of differentiation 3 were distributed mainly in the lower layers of the stratum basale and were found in higher densities in animals offered lower cereal proportion diets. Cells staining positive for major histocompatibility complex class 2 (MHCII) were most common in perivascular locations and in the junction between the lower stratum basale and the propria-submucosa. The density of MHCII positive staining cells was higher in animals on lower cereal diets. The level of supplementation with cereal was also associated with the thickness of the stratum corneum (SCT) and stratum granulosum (SGT), the integrity of the stratum corneum and sloughing of cornified cells. There were no advantages in using EMSB stain over haematoxylin and eosin (H&E) in this scoring system. We concluded that a scoring system that included only SCT, SGT and a measure of the loss of appearance of intercellular space allowed differentiation of groups of animals according to the level of cereal supplementation.

Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial.

The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease) is a two-arm, multi-centre, randomised controlled trial being run in India and Australia that investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The trial was designed as a Bayesian adaptive sample size trial with regular planned analyses where pre-specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here, we describe the statistical analysis plan for the trial and define the pre-specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment.Trial registrationClinicalTrials.gov NCT04394117 . Registered on 19 May 2020Clinical Trial Registry of India CTRI/2020/07/026831Version and revisionsVersion 1.0. No revisions.

Case-control evaluation of the effectiveness of the G1P[8] human rotavirus vaccine during an outbreak of rotavirus G2P[4] infection in central Australia.

UNLABELLED: The human rotavirus vaccine was evaluated during an outbreak of rotavirus G2P[4] infection in central Australia. No overall protective effect against hospitalization was demonstrated, raising concerns over the durability of vaccine protection against heterotypic strains. BACKGROUND: Two and a half years after commencing routine vaccination with human rotavirus vaccine, an outbreak of rotavirus G2P[4] infection occurred in central Australia. Vaccine effectiveness against a P[8]-containing strain (G9P[8]) had been demonstrated previously in this setting. This subsequent outbreak provided the opportunity to evaluate vaccine effectiveness against hospitalizations for a non-vaccine-related genotype in the same population. METHODS: A case-control study was nested within a cohort of vaccine-eligible children listed on a population-based immunization register. Children with rotavirus-confirmed gastroenteritis were individually matched by date of birth and Indigenous status with 4 control subjects. RESULTS: Forty-one cases met the inclusion criteria, and 21 were severe cases among infants aged <12 months. Nineteen (46%) of 41 case patients had received 2 doses of human rotavirus vaccine, compared with 87 (53%) of 164 control subjects. Vaccine effectiveness against rotavirus-related hospitalization was 19% (odds ratio, .81; 95% confidence interval, .32-2.05) for 2 doses compared with none. On secondary analysis, there was evidence of a protective effect against disease complicated by acidosis in the subset of infants aged <12 months (odds ratio, .15; 95% confidence interval, .03-.84). CONCLUSIONS: Evidence was not found for an overall protective effect of human rotavirus vaccine against hospitalization for rotavirus disease in this setting. Post hoc analyses suggested a protective effect against severe disease in young infants.

Facing the Ethical Challenges: Consumer Involvement in COVID-19 Pandemic Research.

Consumer involvement in clinical research is an essential component of a comprehensive response during emergent health challenges. During the COVID-19 pandemic, the moderation of research policies and regulation to facilitate research may raise ethical issues. Meaningful, diverse consumer involvement can help to identify practical approaches to prioritize, design, and conduct rapidly developed clinical research amid current events. Consumer involvement might also elucidate the acceptability of flexible ethics review approaches that aim to protect participants whilst being sensitive to the challenging context in which research is taking place. This article describes the main ethical challenges arising from pandemic research and how involving consumers and the community could enable resolution of such issues.

Postmortem observations on rumen wall histology and gene expression and ruminal and caecal content of beef cattle fattened on barley-based rations.

Sub-acute ruminal acidosis (SARA) can reduce the production efficiency and impair the welfare of cattle, potentially in all production systems. The aim of this study was to characterise measurable postmortem observations from divergently managed intensive beef finishing farms with high rates of concentrate feeding. At the time of slaughter, we obtained samples from 19 to 20 animals on each of 6 beef finishing units (119 animals in total) with diverse feeding practices, which had been subjectively classified as being high risk (three farms) or low risk (three farms) for SARA on the basis of the proportions of barley, silage and straw in the ration. We measured the concentrations of histamine, lipopolysaccharide (LPS), lactate and other short-chain fatty acids (SCFAs) in ruminal fluid, LPS and SCFA in caecal fluid. We also took samples of the ventral blind sac of the rumen for histopathology, immunohistopathology and gene expression. Subjective assessments were made of the presence of lesions on the ruminal wall, the colour of the lining of the ruminal wall and the shape of the ruminal papillae. Almost all variables differed significantly and substantially among farms. Very few pathological changes were detected in any of the rumens examined. The animals on the high-risk diets had lower concentrations of SCFA and higher concentrations of lactate and LPS in the ruminal fluid. Higher LPS concentrations were found in the caecum than the rumen but were not related to the risk status of the farm. The diameters of the stratum granulosum, stratum corneum and of the vasculature of the papillae, and the expression of the gene TLR4 in the ruminal epithelium were all increased on the high-risk farms. The expression of IFN-γ and IL-1ß and the counts of cluster of differentiation 3 positive and major histocompatibility complex class two positive cells were lower on the high-risk farms. High among-farm variation and the unbalanced design inherent in this type of study in the field prevented confident assignment of variation in the dependent variables to individual dietary components; however, the CP percentage of the total mixed ration DM was the factor that was most consistently associated with the variables of interest. Despite the strong effect of farm on the measured variables, there was wide inter-animal variation.

Midwives' attitudes, beliefs and concerns about childhood vaccination: A review of the global literature.

Vaccine hesitancy in industrialised countries is an area of concern. Health professionals play a significant role in parental vaccination decisions, however, to date the role of midwives has not been widely explored. This review sought to describe the attitudes and communication practices of midwives in developed countries towards childhood vaccines. Medline, Cinahl, PsychInfo, Embase and the grey literature were searched. Inclusion criteria were qualitative and quantitative studies reporting midwives' beliefs, attitudes and communication practices toward childhood vaccination. The search returned 366 articles, of which 359 were excluded by abstract. Two additional articles were identified from the grey literature and references, resulting in nine studies from five countries included in the review. Across the studies, the majority of midwives supported vaccination, although a spectrum of beliefs and concerns emerged. A minority expressed reservations about the scientific justification for vaccination, which focussed on what is not yet known rather than mistrust of current evidence. Most midwives felt that vaccines were safe; a minority were unsure, or believed they were unsafe. The majority of midwives agreed that childhood vaccines are necessary. Among those who expressed doubt, a commonly held opinion was that vaccine preventable diseases such as measles are relatively benign and didn't warrant vaccination against them. Finally, the midwifery model of care was shown to focus on providing individualised care, with parental choice being placed at a premium. The midwifery model care appears to differ in approach from others, possibly due to a difference in the underpinning philosophies. Research is needed to understand how midwives see vaccination, and why there appears to be a spectrum of views on the subject. This information will inform the development of resources tailored to the midwifery model of care, supporting midwives in advocating for childhood vaccination.

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.

Characterisation of a G9P[8] rotavirus strain identified during a gastroenteritis outbreak in Alice Springs, Australia post Rotarix™ vaccine introduction.

A large rotavirus gastroenteritis outbreak occurred in the Alice Springs region of the Northern Territory, Australia from the 12th of March until the 11th of July 2007. The outbreak occurred five months after the introduction of the Rotarix™ vaccine. Electropherotype and sequence analysis demonstrated that a single G9P[8] strain was responsible for the outbreak and that the strain remained highly conserved during the outbreak period. The outbreak strain contained amino acid changes in regions of the VP7 and NSP4 genes, with known biological function, when compared to previously characterised G9P[8] strains from Australia and other international locations. The recent vaccine introduction was unlikely to have influenced genotype selection in this setting. Importantly, Rotarix™ vaccine was highly effective against the G9P[8] outbreak strain.

Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum.

The neural distribution and action of gastrin-releasing peptide in the extrahepatic biliary tree of the Australian brush-tailed possum was investigated. Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing peptide-containing nerves throughout the neural plexuses of the gallbladder, sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide (5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin-insensitive. Sphincter of Oddi motility and transsphincteric flow were not altered. Possible mediation of the gallbladder response by gastrin was examined. Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder motility to 64% of that produced by gastrin-releasing peptide, and did not alter sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing nerves are found in the neural plexus of the possum extrahepatic biliary tree. Gastrin-releasing peptide induces gallbladder contraction in part by a direct action on gallbladder smooth muscle and also via release of gastrin.