Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness.

BACKGROUND: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. METHODS: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3μg/ml but 4.0μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. RESULTS: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response. CONCLUSION: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV

Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial.

INTRODUCTION: Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection. METHODS AND ANALYSES: This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM. ETHICS AND DISSEMINATION: Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals. TRIAL REGISTRATION NUMBERS: ACTRN12610000544077 and NCT01174849

Meningococcal vaccination for adolescents? An economic evaluation in Victoria

Objective: To undertake an economic evaluation of the options for vaccination of adolescents using meningococcal polysaccharide vaccine based on Victorian data. Methodology: Cost-effectiveness and cost-benefit analyses of three options for vaccination were undertaken for hypothetical populations aged 15-19 years. Baseline analyses assumed a single year of programme implementation and vaccine protection of 5 years. Sensitivity analyses of key variables were performed. Outcomes included the number of people vaccinated, cases averted, life years saved and disability adjusted life years (DALY) averted. Lost earnings avoided were included as a measure of vaccination benefit in cost-benefit analyses. Results: Vaccination of people in Years 10-12 (secondary school) and first year university within a defined population with a high rate of disease was the most cost-effective option. Excluding direct cost savings and compared with no vaccination, this resulted in a discounted cost per DALY avoided of $17 646 and benefits exceeding costs in discounted terms. The 'break-even' incidence rate for this option in the cost-benefit analysis was 11.9/100 000. Conclusions: Economic evidence favours the use of vaccination within well-defined populations with a high rate of disease

Evaluating the potential for opportunistic vaccination in a Northern Territory hospital

Objective: To evaluate the potential for opportunistic vaccination and a simple intervention aimed at improving vaccination coverage for children in hospital. Methods: Hospital records were reviewed for children under 7 years, discharged from paediatric wards (PW) and the emergency department (ED) for 4 weeks before and after an intervention (423 and 446 children, respectively). This comprised the education of staff and the introduction of prompts to record vaccination status. Results: Documentation of vaccination status increased in the PW (63-90%) and the ED (24-46%), as did the adequacy of detail recorded (51-77% and 8-36%, respectively). Opportunistic vaccination increased from zero of 84 opportunities during the first audit to six of 139 following the intervention. All but one vaccine was given in the PW. Opportunistic vaccination improved when documentation identified a need for vaccination (P = 0.02). Conclusion: There were numerous missed opportunities to vaccinate children in hospital, especially in the ED. Simple prompts improved documentation of vaccination status and the detail of information recorded. Despite improved documentation, opportunistic vaccination failed to improve in the ED. Improving documentation of vaccination status is not sufficient in itself to improve opportunistic vaccination

Should programmes for community-level meningococcal vaccination be considered in Australia? An economic evaluation

Background: Disease due to serogroup C Neisseria meningitidis is life-threatening and potentially preventable by vaccination. In 1999, the UK instigated mass vaccination after a sustained increase in serogroup C meningococcal disease. In the same year, Victoria, Australia experienced a similar change in disease epidemiology. It is timely to undertake an economic evaluation of options for community vaccination in Australia based on local data. Methods: Cost-effectiveness and cost-benefit analyses of three options for use of polysaccharide vaccine were undertaken for a hypothetical population aged 15-19 years. Baseline analyses assumed 5 years' duration of vaccine protection following a single year of programme implementation. Sensitivity analyses of key variables were performed, including vaccine coverage and effectiveness, case fatality rate and the discount rate. Outcomes included the number of people vaccinated, cases averted, life-years saved and disability-adjusted life-years (DALY) averted. Cost-benefit analysis used lost earnings avoided as a measure of vaccination benefit. Results: Vaccination of people aged 15-19 years in a defined population with a high rate of disease was the most cost-effective option. Compared with no vaccination and assuming 5 years' duration of protection and exclusion of direct cost savings, this resulted in a discounted cost per life-year saved of $23 623, a cost per DALY avoided of$21 097 and benefits exceeding costs in discounted terms. The 'break-even' incidence rate for this option with exclusion of direct cost savings was 14.0/100 000. Conclusions: Community use of polysaccharide vaccination may be cost effective in Australia under certain conditions. Economic evidence favours use of vaccination in well-defined populations with a high rate of disease. Policy decision-making also requires consideration of non-economic factors, including feasibility of implementation and risk perception by the community

Streptococcus pneumoniae antibiotic resistance in Northern Territory children in child care

Background: There is evidence that the rapid rise in Streptococcus pneumoniae (SP) antimicrobial resistance seen in other countries may have commenced in Australia. Streptococcus pneumoniae carriage and resistance levels are described for urban Northern Territory children in day care. Methods: A prospective cohort study was conducted of 250 children in nine Darwin day care centres between 24 March and 15 September 1997. Each fortnight nasopharyngeal swabs were collected from children, and parents were interviewed about medications administered. Results: Streptococcus pneumoniae was detected in 52% (1028/1974) of all nasopharyngeal swabs. Streptococcus pneumoniae was isolated from 92% (231/250) of children at some time. Penicillin resistance was found in 30% (312/1028) of isolates using a screening test. Of these, 256 (82%) had resistance confirmed by E-test. Two hundred and one (20% of all isolates) had intermediate penicillin resistance and 55 (5% of all isolates) had high level resistance. Ceftriaxone resistance was found in 19% of children's first isolates. Resistance to other antibiotics was also common: co-trimoxazole 45%, erythromycin 17%, tetracycline 17% and chloramphenicol 13%. A total of 17% (172/1028) of the isolates were multiresistant. The average fortnightly proportion of children given antibiotics was 16% (405/2476). Conclusions: Levels of intermediate and high level penicillin resistance in this day care population are consistent with previous data from the Northern Territory, and considerably higher than the rest of Australia. The national trend of increasing pencillin resistance is likely to continue

An issue of access: Delivering equitable health care for newly arrived refugee children in Australia

Newly arrived refugees and asylum seekers are faced with many difficulties in accessing effective health care when settling in Australia. Cultural, language and financial constraints, lack of awareness of available services, and lack of health provider understanding of the complex health concerns of refugees can all contribute to limiting access to health care. Understanding the complexities of a new health care system under these circumstances and finding a regular health provider may be difficult. In some cases there may be a fundamental distrust of government services. The different levels of health entitlements by visa category and (for some) detention on arrival in Australia may further complicate the provision and use of health services for providers and patients. Children are particularly at risk of suboptimal health care due to the impact of these factors combined with the effect of resettlement stresses on parents' ability to care for their children. Unaccompanied and separated children, and those in detention experience additional challenges in accessing care. This article aims to increase awareness among health professionals caring for refugee children of the challenges faced by this group in accessing and receiving effective health care in Australia. Particular consideration is given to the issues of equity, rights of asylum seekers, communication and cultural sensitivities in health care provision, and addressing barriers to health care. The aim of the paper is to alert practitioners to the complex issues surrounding the delivery of health care to refugee children and provide realistic recommendations to guide practice

Middle ear effusion: rate and risk factors in Australian children attending day care

There have been no previous longitudinal studies of otitis media conducted in non-Aboriginal Australian children. This paper describes the rate and risk factors for middle ear effusion (MEE) in children attending day care in Darwin, Australia. A prospective cohort study of 252 children under 4 years was conducted in 9 day care centres over 12 fortnights between 24 March and 15 September 1997. Tympanometry was conducted fortnightly and multivariate analysis used to determine risk factors predicting MEE. The outcome of interest was the rate of type B tympanograms per child detected in either ear at fortnightly examinations. After adjusting for clustering by child, MEE was detected on average 4.4 times in 12 fortnights (37% of all examinations conducted). Risk factors associated with presence of effusion were younger age, a family history of ear infection, previous grommets (tympanostomy tubes), ethnicity and the day care centre attended. A history of wheeze appeared protective. These effects were modest (RR 0.57-1.70). Middle ear effusion is very common in children attending day care in Darwin. This has clinical importance, since MEE during early childhood may affect optimal hearing, learning and speech development. There is little scope for modification for many of the risk factors for MEE predicted by this model. Further study of the day care environment is warranted