An evaluation and refinement of the "Hep B Story" app, tailored to meet the community's cultural needs.

BACKGROUND: Hepatitis B is endemic amongst the Australian Aboriginal population in the Northern Territory. A participatory action research project identified the lack of culturally appropriate education tools and led to the development of the "Hep B Story" app in the Aboriginal language Yolŋu Matha. This paper describes a formal evaluation of the app's first version, which informed improvements and translation into a further ten Aboriginal languages. METHODS: The evaluation employed Participatory Action Research (PAR) principles to work within Indigenous research methodologies and prioritise Indigenous knowledge to improve the app iteratively. Semi-structured interviews and focus groups were conducted across the Northern Territory with 11 different language groups. Local Community Based Researchers and Aboriginal Research team members coordinated sessions. The recorded, translated conversations were transcribed verbatim and thematically analysed using an inductive and deductive approach. RESULTS: Between November 2018 and September 2020, 94 individuals from 11 language groups participated in 25 semi-structured interviews and 10 focus groups. All participants identified as Aboriginal. Most participants felt the app would be culturally appropriate for Aboriginal communities in the Northern Territory and improve knowledge surrounding hepatitis B. The information gathered from these interviews allowed for identifying five main themes: support for app, relationships, concept versus language, shame, and perceptions of images, along with errors that required modification. CONCLUSIONS: A "real-life" evaluation of the app was comprehensively completed using a PAR approach blended with Indigenous research methods. This evaluation allowed us to develop an updated and enhanced version of the app before creating the additional ten language versions. An iterative approach alongside strong community engagement was pivotal in ensuring the app's cultural safety and appropriateness. We recommend avoiding the use of knowledge-based evaluations in an Aboriginal setting to ensure relevant and culturally appropriate feedback is obtained.

Adapting and translating the 'Hep B Story' App the right way: A transferable toolkit to develop health resources with, and for, Aboriginal people.

ISSUE ADDRESSED: In 2014 the 'Hep B Story App', the first hepatitis B educational app in an Aboriginal language was released. Subsequently, in 2018, it was assessed and adapted before translation into an additional 10 Aboriginal languages. The translation process developed iteratively into a model that may be applied when creating any health resource in Aboriginal languages. METHODS: The adaptation and translation of the 'Hep B Story' followed a tailored participatory action research (PAR) process involving crucial steps such as extensive community consultation, adaptation of the original material, forward and back translation of the script, content accuracy verification, voiceover recording, and thorough review before the publication of the new version. RESULTS: Iterative PAR cycles shaped the translation process, leading to a refined model applicable to creating health resources in any Aboriginal language. The community-wide consultation yielded widespread chronic hepatitis B education, prompting participants to share the story within their families, advocating for hepatitis B check-ups. The project offered numerous insights and lessons, such as the significance of allocating sufficient time and resources to undertake the process. Additionally, it highlighted the importance of implementing flexible work arrangements and eliminating barriers to work for the translators. CONCLUSIONS: Through our extensive work across the Northern Territory, we produced an educational tool for Aboriginal people in their preferred languages and developed a translation model to create resources for different cultural and linguistic groups. SO WHAT?: This translation model provides a rigorous, transferable method for creating accurate health resources for culturally and linguistically diverse populations.

"Putting the power back into community": A mixed methods evaluation of a chronic hepatitis B training course for the Aboriginal health workforce of Australia's Northern Territory.

BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course. OBJECTIVES: 1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team. METHODS: We used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework. RESULTS: Eight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams. CONCLUSIONS: The "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.

Hepatitis B genotypes in Aboriginal and Torres Strait Islander Australians: correlation with clinical course and implications for management.

BACKGROUND: The prevalence of chronic hepatitis B (CHB) in Aboriginal and Torres Strait Islander Australians in Far North Queensland (FNQ) is greater than twice that of the general Australian population. CHB is common in Torres Strait Islanders diagnosed with hepatocellular carcinoma (HCC) - and in Aboriginals with HCC living in the Northern Territory - however, Aboriginals diagnosed with HCC in FNQ very rarely have CHB. The explanation for this apparent disparity is uncertain. AIMS: To determine the HBV genotypes in the FNQ Aboriginal and Torres Strait Islander population and their correlation with clinical phenotype. METHODS: We determined the HBV genotype of Aboriginal and Torres Strait Islander Australians living with CHB in FNQ and correlated this with demographic and clinical findings. RESULTS: 134/197 (68%) enrolled individuals had a sufficient viral load for genotyping. All 40 people with HBV/D genotype had Aboriginal heritage, whereas 85/93 (91%) with HBV/C had Torres Strait Islander heritage (P < 0.0001). Individuals with HBV/D were younger than those with HBV/C (median (interquartile range) age: 43 (39-48) vs 53 (42-66) years, P = 0.0002). However, they were less likely to be HBeAg positive (1/40 (3%) vs 23/93 (25%), P = 0.001). All three HCCs developed in Torres Strait Islanders; two-thirds were infected with HBV/C14; genotyping was not possible in the other individual. All 10 diagnoses of cirrhosis occurred in Torres Strait Islanders, 6/10 were infected with HBV/C14, genotyping was not possible in the other four individuals. CONCLUSIONS: HBV genotypes in Aboriginal and Torres Strait Islander Australians in FNQ differ markedly, which could explain the significant differences in the clinical phenotype in the two populations and might be used to inform cost-effective CHB care in the region.

Broad spectrum SARS-CoV-2-specific immunity in hospitalized First Nations peoples recovering from COVID-19.

Indigenous peoples globally are at increased risk of COVID-19-associated morbidity and mortality. However, data that describe immune responses to SARS-CoV-2 infection in Indigenous populations are lacking. We evaluated immune responses in Australian First Nations peoples hospitalized with COVID-19. Our work comprehensively mapped out inflammatory, humoral and adaptive immune responses following SARS-CoV-2 infection. Patients were recruited early following the lifting of strict public health measures in the Northern Territory, Australia, between November 2021 and May 2022. Australian First Nations peoples recovering from COVID-19 showed increased levels of MCP-1 and IL-8 cytokines, IgG-antibodies against Delta-RBD and memory SARS-CoV-2-specific T cell responses prior to hospital discharge in comparison with hospital admission, with resolution of hyperactivated HLA-DR+ CD38+ T cells. SARS-CoV-2 infection elicited coordinated ASC, Tfh and CD8+ T cell responses in concert with CD4+ T cell responses. Delta and Omicron RBD-IgG, as well as Ancestral N-IgG antibodies, strongly correlated with Ancestral RBD-IgG antibodies and Spike-specific memory B cells. We provide evidence of broad and robust immune responses following SARS-CoV-2 infection in Indigenous peoples, resembling those of non-Indigenous COVID-19 hospitalized patients.

"The most culturally safe training I've ever had": the co-design of a culturally safe Managing hepatitis B training course with and for the Aboriginal health workforce of the Northern Territory of Australia.

BACKGROUND: The Aboriginal health workforce provide responsive, culturally safe health care. We aimed to co-design a culturally safe course with and for the Aboriginal health workforce. We describe the factors which led to the successful co-design, delivery, and evaluation of the "Managing hepatitis B" course for the Aboriginal health workforce. METHODS: A Participatory Action Research approach was used, involving ongoing consultation to iteratively co-design and then develop course content, materials, and evaluation tools. An Aboriginal and Torres Strait Islander research and teaching team received education in chronic hepatitis B and teaching methodologies. Pilot courses were held, in remote communities of the Northern Territory, using two-way learning and teach-back methods to further develop the course and assess acceptability and learnings. Data collection involved focus group discussions, in-class observations, reflective analysis, and use of co-designed and assessed evaluation tools. RESULTS: Twenty-six participants attended the pilot courses. Aboriginal and Torres Strait Islander facilitators delivered a high proportion of the course. Evaluations demonstrated high course acceptability, cultural safety, and learnings. Key elements contributing to success and acceptability were acknowledging, respecting, and integrating cultural differences into education, delivering messaging and key concepts through an Aboriginal and Torres Strait Islander lens, using culturally appropriate approaches to learning including storytelling and visual teaching methodologies. Evaluation of culturally safe frameworks and findings from the co-design process led to the creation of a conceptual framework, underpinned by meeting people's basic needs, and offering a safe and comfortable environment to enable productive learning with attention to the following: sustenance, financial security, cultural obligations, and gender and kinship relationships. CONCLUSIONS: Co-designed education for the Aboriginal health workforce must embed principles of cultural safety and meaningful community consultation to enable an increase in knowledge and empowerment. The findings of this research can be used to guide the design of future health education for First Nations health professionals and to other non-dominant cultures. The course model has been successfully transferred to other health issues in the Northern Territory.

Preventing early childhood transmission of hepatitis B in remote aboriginal communities in Northern Australia.

BACKGROUND: Chronic hepatitis B is a public health concern in Aboriginal communities in the Northern Territory of Australia with prevalence almost four times the non-Aboriginal population. Infection is suspected to mainly occur in early life, however, the mode of transmission and vaccine effectiveness is not known in this population. WHO has set a target for hepatitis B elimination by 2030; elimination in this disproportionately affected population in Australia will require understanding of the modes of transmission and vaccine effectiveness. METHODS: We conducted the study at four very remote Aboriginal communities. We approached mothers who had chronic hepatitis B and had given birth between 1988 and 2013 for consent. We obtained hepatitis B serology, immunisation and birth details from the medical record. If both mother and child had hepatitis B viral DNA detected, we performed viral whole genome sequencing. RESULTS: We approached 45 women for consent, of whom 23 agreed to participate. We included 20 mothers and 38 of their children. Of the 20 included mothers, 5 (25%) had children who were hepatitis B immune by exposure and 3 (15%) had children with evidence of chronic hepatitis B infection at the time of assessment. Hepatitis B immunoglobulin (HBIg) had been given at birth in 29/38 (76.3, 95% CI 59.8-88.6) children, and 26 children (68.4, 95% CI 51.3-82.5) were fully vaccinated. Of the 3 children who had chronic hepatitis B, all had received HBIg at birth and two were fully vaccinated. Of the 5 who were immune by exposure, 4 had received HBIg at birth and one was fully vaccinated. Whole genome sequencing revealed one episode of definite mother to child transmission. There was also one definite case of horizontal transmission. CONCLUSIONS: Chronic hepatitis B in this context is a sensitive issue, with a high proportion of women refusing consent. Although uncommon, there is ongoing transmission of hepatitis B to Aboriginal children in remote northern Australia despite vaccination, and this is likely occurring by both vertical and horizontal routes. Prevention will require ongoing investment to overcome the many barriers experienced by this population in accessing care.

Hepatitis B prevalence in women giving birth in the Northern Territory, Australia, 2005-2015.

Background: Hepatitis B virus (HBV) vaccination in the Northern Territory (NT) was funded for all Aboriginal and Torres Strait Islander newborns in 1988 and for all newborns in 1990. The prevalence of HBV in the Northern Territory was found to be higher in Aboriginal and Torres Strait Islander women than in non-Indigenous women across 2005-2010. We examined more recent data to assess whether the gap remains. Methods: We linked data from two routinely collected registries, the NT Perinatal Register and the NT Notifiable Diseases System, to investigate the prevalence of HBV infection, according to eligibility for infant HBV vaccination, in women giving birth during 2005-2015. Results: There were 22,781 women recorded as giving birth in public hospitals in the Northern Territory during 2005-2015. Hepatitis B virus prevalence was highest in Aboriginal and Torres Strait Islander (1.8%) and overseas-born women (1.8%). Among Aboriginal and Torres Strait Islander women, estimated hepatitis B virus prevalence was significantly higher in those born before the implementation of the vaccination program than in those born afterwards (2.4% versus 0.3%). Prevalence was highest amongst those living in very remote areas, both overall (2.2%) and within the birth cohort eligible for HBV vaccination. Conclusions: Hepatitis B virus prevalence in Northern Territory Aboriginal and Torres Strait Islander women appears to be declining as more individuals vaccinated as part of infant vaccination programs reach adulthood. Prevalence remains highest in remote areas, highlighting the importance of ongoing monitoring and of promoting vaccination in these regions.

What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke-Korsakoff syndrome? Results of a randomized controlled trial.

BACKGROUND: The primary cause of Wernicke-Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose. METHODS: Two double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but "at-risk" alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up. RESULTS: No significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings. CONCLUSIONS: The results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.

National predictors of influenza vaccine uptake in pregnancy: the FluMum prospective cohort study, Australia, 2012-2015.

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.

A "one stop liver shop" approach improves the cascade-of-care for Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B in the Northern Territory of Australia: results of a novel care delivery model.

BACKGROUND: Aboriginal and Torres Strait Islander Australians are disproportionately affected by Chronic Hepatitis B (CHB) with a prevalence of 6.08% in the Northern Territory (NT) and liver cancer rates 6 times higher than non-Indigenous Australians. Without appropriate care, overall 25% of those living with CHB will die from either liver failure or liver cancer, outcomes that can be minimised with regular follow up, antiviral treatment and hepatocellular carcinoma (HCC) screening. This care including antiviral treatment is publicly funded in the Australian setting however the care cascade still shows inequities in access to treatment for Aboriginal Australians. We describe the impact of a mobile care delivery model, "One Stop Liver Shop", on the cascade of care for people living with CHB in a remote Australian setting. METHODS: A retrospective analysis was performed for CHB care received between 2013 and 2018 in one very remote Northern Territory community, where the "One Stop Liver Shop" was iteratively developed with the community. Patients with positive Hepatitis B virus surface antigen (HBsAg) were identified through electronic medical records. Proportions of patients who are up-to-date with monitoring investigations and HCC screening were evaluated and compared to national guidelines and targets. RESULTS: Eighty-three HBsAg positive patients were evaluated. Eighty-eight percent were engaged in care, 16% of whom were receiving antiviral treatment. Liver function tests (LFT) were up to date in 71% of patients in 2013 and 88% in 2018. Viral load (VL) monitoring was up to date for 61 (73%) of patients. There were 44 patients in whom HCC screening was indicated. Of these, 38 (86.4%) were up to date with 6 monthly alpha-fetoprotein (AFP), 35 (79.5%) were up to date with 6 monthly liver ultrasound scan (USS), and 34 (77.3%) were up-to-date for both. CONCLUSIONS: A "One Stop Liver Shop" developed with and including Aboriginal Health Practitioners bridges gaps in the availability of services to those living with CHB in a very remote community and improves the cascade of care.

Point of care and oral fluid hepatitis B testing in remote Indigenous communities of northern Australia.

Many Indigenous Australians in northern Australia living with chronic hepatitis B are unaware of their diagnosis due to low screening rates. A venous blood point of care test (POCT) or oral fluid laboratory test could improve testing uptake in this region. The purpose of this study was to assess the field performance of venous blood POCT and laboratory performance of an oral fluid hepatitis B surface antigen (HBsAg) test in Indigenous individuals living in remote northern Australian communities. The study was conducted with four very remote communities in the tropical north of Australia's Northern Territory. Community research workers collected venous blood and oral fluid samples. We performed the venous blood POCT for HBsAg in the field. We assessed the venous blood and oral fluid specimens for the presence of HBsAg using standard laboratory assays. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the POCT and oral fluid test, using serum laboratory detection of HBsAg as the gold standard. From 215 enrolled participants, 155 POCT and 197 oral fluid tests had corresponding serum HBsAg results. The POCT had a sensitivity of 91.7% and specificity of 100%. Based on a population prevalence of 6%, the PPV was 100% and NPV was 99.5%. The oral fluid test had a sensitivity of 56.8%, specificity of 98.1%, PPV of 97.3% and NPV of 65.9%. The venous blood POCT has excellent test characteristics and could be used to identify individuals with chronic HBV infection in high prevalence communities with limited access to health care. Oral fluid performance was suboptimal.

Tracing Ancient Human Migrations into Sahul Using Hepatitis B Virus Genomes.

The entry point and timing of ancient human migration into continental Sahul (the combined landmass of Australia, New Guinea, and Tasmania) are subject to debate. Unique strains of hepatitis B virus (HBV) are endemic among modern-day Australian Aboriginals (HBV/C4) and Indigenous Melanesians (HBV/C3). We postulated that HBV genomes could be used to infer human population movements because the main HBV transmission route in endemic populations is via mother-to-child for genotypes B and C infections. Phylogenetic and phylogeographic analyses of HBV genomes inferred the origin of HBV/C4 to be >59 thousand years ago (ka) (95% HPD: 34-85 ka), and most likely to have occurred on the Sunda Shelf (southeast extension of the continental shelf of Southeast Asia). Our analysis further suggested an age of >51 ka (95% Highest Posterior Density (HPD): 36-67 ka) for the most recent common ancestor of HBV/C4 in Australia, correlating with the arrival time of anatomically modern humans into Australia, with the entry point suggested along a southern route via Timor. While we also inferred the origin of HBC/C3 to be on the Sunda Shelf, our analyses suggested that it was carried into Melanesia by Indigenous Melanesians who migrated through New Guinea north of the highlands. These findings reveal that HBV genomes can be used to infer ancient human population movements.

Towards Genotype-Specific Care for Chronic Hepatitis B: The First 6 Years Follow Up From the CHARM Cohort Study.

OBJECTIVE: There is increasing evidence to suggest that, among those with chronic hepatitis B virus infection, the natural history and rate of progression to cirrhosis and hepatocellular carcinoma is influenced by hepatitis B virus genotype. The unique hepatitis B virus genotype C4 circulates among Indigenous Australians. The aim of this work is to describe the process of establishing this cohort and review the first 6 years of available data in an effort to understand the real-world clinical care and natural history of this subgenotype. METHOD: We followed a longitudinal cohort of Indigenous Australians from the Northern Territory of Australia with established subgenotype C4 infections. We assigned phases of disease according to Gastroenterological Society of Australia and Asian Pacific Association for the Study of the Liver criteria using clinical and laboratory information that had been collected for clinical management. RESULTS: Of 193 patients followed over a median of 38 months, 58 (30%) individuals transitioned from 1 disease phase to another, 10 (5%) cleared hepatitis B e antigen, and 6 cleared hepatitis B surface antigen (3%). In this relatively young cohort (median age 40.3 years), 26 (13%) had cirrhosis by the end of the follow up period, with the majority of these being in the immune control phase of disease. CONCLUSIONS: In this cohort of hepatitis B subgenotype C4 patients, we report an aggressive and dynamic clinical phenotype. High rates of cirrhosis at a young age appear to occur in the early phases of disease.

The Safety of Influenza and Pertussis Vaccination in Pregnancy in a Cohort of Australian Mother-Infant Pairs, 2012-2015: The FluMum Study.

Background: Inactivated influenza vaccine (IIV) and pertussis vaccination are recommended in pregnancy. Limited safety data exist for women who received IIV vaccine during the first trimester of pregnancy or received both vaccines in pregnancy. We assessed adverse birth outcomes between vaccinated and unvaccinated pregnancies. Methods: Among prospectively enrolled Australian "FluMum" participants (2012-2015), primary exposure was receipt and timing of IIV during pregnancy. Primary outcomes included preterm birth, low birthweight at term (LBWT), and small for gestational age (SGA). We compared birth outcomes for IIV in pregnancy with women unvaccinated in pregnancy using Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs). Adjusted HRs (aHRs) controlled for potential confounding variables. Sensitivity analyses were conducted in a subgroup of women who received pertussis vaccination during pregnancy to assess whether associations between IIV and adverse outcomes were maintained after adjusting for pertussis vaccination. Results: Among 8827 participants in our study, women who received IIV in pregnancy did not have an elevated risk of an adverse birth outcome compared with unvaccinated pregnant women: preterm births (HR, 1.10 [95% CI, .92-1.31]; P = .28); LBWT (HR, 1.05 [95% CI, .76-1.44]; P = .77); or SGA (HR, 0.99 [95% CI, .86-1.15]; P = .94). Adjustment for pertussis vaccination during pregnancy yielded similar results: preterm births (aHR, 1.05 [95% CI, .82-1.34]; P = .69); LBWT (aHR, 0.81 [95% CI, .50-1.29]; P = .37); SGA (aHR, 0.92 [95% CI, .74-1.14]; P = .43). There was no evidence of elevated risk by trimester of IIV. Conclusions: No significant associations were found between maternal IIV or pertussis vaccination in pregnancy and adverse birth outcomes, regardless of the trimester of pregnancy a vaccination was given compared to unvaccinated pregnancies.

Repeat pneumococcal polysaccharide vaccination does not impair functional immune responses among Indigenous Australians.

Indigenous Australians experience one of the highest rates of pneumococcal disease globally. In the Northern Territory of Australia, a unique government-funded vaccination schedule for Indigenous Australian adults comprising multiple lifetime doses of the pneumococcal polysaccharide vaccine is currently implemented. Despite this programme, rates of pneumococcal disease do not appear to be declining, with concerns raised over the potential for immune hyporesponse associated with the use of this vaccine. We undertook a study to examine the immunogenicity and immune function of a single and repeat pneumococcal polysaccharide vaccination among Indigenous adults compared to non-Indigenous adults. Our results found that immune function, as measured by opsonophagocytic and memory B-cell responses, were similar between the Indigenous groups but lower for some serotypes in comparison with the non-Indigenous group. This is the first study to document the immunogenicity following repeat 23-valent pneumococcal polysaccharide vaccine administration among Indigenous Australian adults, and reinforces the continued need for optimal pneumococcal vaccination programmes among high-risk populations.

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; or a post-vaccination antibody concentration >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.

Combination of Vancomycin and ß-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.

BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. CONCLUSIONS: Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).