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.

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.

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.

Capturing Household Structure and Mobility within and between Remote Aboriginal Communities in Northern Australia Using Longitudinal Data: A Pilot Study.

Cultural practices and development level can influence a population's household structures and mixing patterns. Within some populations, households can be organized across multiple dwellings. This likely affects the spread of infectious disease through these communities; however, current demographic data collection tools do not record these data. METHODS: Between June and October 2018, the Contact And Mobility Patterns in remote Aboriginal Australian communities (CAMP-remote) pilot study recruited Aboriginal mothers with infants in a remote northern Australian community to complete a monthly iPad-based contact survey. RESULTS: Thirteen mother-infant pairs (participants) completed 69 study visits between recruitment and the end of May 2019. Participants reported they and their other children slept in 28 dwellings during the study. The median dwelling occupancy, defined as people sleeping in the same dwelling on the previous night, was ten (range: 3.5-25). Participants who completed at least three responses (n = 8) slept in a median of three dwellings (range: 2-9). Each month, a median of 28% (range: 0-63%) of the participants travelled out of the community. Including these data in disease transmission models amplified estimates of infectious disease spread in the study community, compared to models parameterized using census data. CONCLUSIONS: The lack of data on mixing patterns in populations where households can be organized across dwellings may impact the accuracy of infectious disease models for these communities and the efficacy of public health actions they inform.

Reference exome data for Australian Aboriginal populations to support health-based research.

Whole exome sequencing (WES) is a popular and successful technology which is widely used in both research and clinical settings. However, there is a paucity of reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalogue of variants called after sequencing the exomes of 50 Aboriginal individuals from the Northern Territory (NT) of Australia and compare these to 72 previously published exomes from a Western Australian (WA) population of Martu origin. Sequence data for both NT and WA samples were processed using an 'intersect-then-combine' (ITC) approach, using GATK and SAMtools to call variants. A total of 289,829 variants were identified in at least one individual in the NT cohort and 248,374 variants in at least one individual in the WA cohort. Of these, 166,719 variants were present in both cohorts, whilst 123,110 variants were private to the NT cohort and 81,655 were private to the WA cohort. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.

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.

Genome-Wide Analysis of Genetic Risk Factors for Rheumatic Heart Disease in Aboriginal Australians Provides Support for Pathogenic Molecular Mimicry.

Background: Rheumatic heart disease (RHD) after group A streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers proinflammatory cardiac valve-reactive T cells. Methods: Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single-nucleotide polymorphisms were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region. Epitope binding affinities were mapped for human cross-reactive GAS proteins, including M5 and M6. Results: The strongest genetic association was intronic to HLA-DQA1 (rs9272622; P = 1.86 × 10-7). Conditional analyses showed rs9272622 and/or DQA1*AA16 account for the HLA signal. HLA-DQA1*0101_DQB1*0503 (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.09-1.90; P = 9.56 × 10-3) and HLA-DQA1*0103_DQB1*0601 (OR, 1.27; 95% CI, 1.07-1.52; P = 7.15 × 10-3) were risk haplotypes; HLA_DQA1*0301-DQB1*0402 (OR 0.30, 95%CI 0.14-0.65, P = 2.36 × 10-3) was protective. Human myosin cross-reactive N-terminal and B repeat epitopes of GAS M5/M6 bind with higher affinity to DQA1/DQB1 alpha/beta dimers for the 2-risk haplotypes than the protective haplotype. Conclusions: Variation at HLA_DQA1-DQB1 is the major genetic risk factor for RHD in Aboriginal Australians studied here. Cross-reactive epitopes bind with higher affinity to alpha/beta dimers formed by risk haplotypes, supporting molecular mimicry as the key mechanism of RHD pathogenesis.

Recovering streptococci from the throat, a practical alternative to direct plating in remote tropical communities.

Throat swabs are regarded as the "gold standard" for diagnosing streptococcal pharyngitis and for surveillance research. Culturing throats in remote tropical settings is logistically difficult, and these settings are commonly burdened by high rates of streptococcal disease. The survival of streptococci on swabs may depend on whether they are of "throat" or "skin" type, as determined by emm pattern typing. The aims of this study were to compare the recovery rates of beta-hemolytic streptococci (BHS) using three different transport methods and to determine whether the recovery rates correlated with the emm pattern type. Monthly duplicate throat swabs were taken from occupants of selected households in three remote Aboriginal communities. Paired swabs were separated and handled in one of three ways: (i) direct inoculation onto culture media with cold-box transport (plated), (ii) sealed in a bag with a silica gel desiccant and cold-box transport (desiccant), and (iii) transport at ambient temperature and humidity (ambient). emm pattern typing was done by standard methods. Over 23 months, 4,842 throat swabs were taken, and 4,122 were paired. BHS were recovered on 11.5% of the 4,842 occasions (group A, 4.5%; group C, 1.7%; group G, 5.4%). Results from paired swabs showed the plated method was superior to desiccant and desiccant was better than ambient. Pooled data indicated that plated and desiccant were equivalent, and both were significantly better than ambient. There was no correlation between the emm pattern type and recovery of group A streptococci by different methods. In tropical and remote settings, cold-box transport with desiccant and subsequent inoculation of culture plates in the laboratory is a practical alternative to direct plating.

Contamination of hand wash detergent linked to occupationally acquired melioidosis.

Two mechanics working at a garage in tropical northern Australia simultaneously developed upper limb melioidosis ulcers. Both patients had Burkholderia pseudomallei of identical pulsed-field gel electrophoresis (PFGE) type (Spe I). Environmental sampling identified B. pseudomallei in a container of commercial hand wash detergent as the likely source of infection, although there were multiple isolates of different PFGE types to the clinical isolates.

First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei.

Ivermectin is increasingly being used to treat scabies, especially crusted (Norwegian) scabies. However, treatment failures, recrudescence, and reinfection can occur, even after multiple doses. Ivermectin resistance has been documented for some intestinal helminths in animals with intensive ivermectin exposure. Ivermectin resistance has also been induced in arthropods in laboratory experiments but, to date, has not been documented among arthropods in nature. We report clinical and in vitro evidence of ivermectin resistance in 2 patients with multiple recurrences of crusted scabies who had previously received 30 and 58 doses of ivermectin over 4 and 4.5 years, respectively. As predicted, ivermectin resistance in scabies mites can develop after intensive ivermectin use.

Acaricidal activity of Melaleuca alternifolia (tea tree) oil: in vitro sensitivity of sarcoptes scabiei var hominis to terpinen-4-ol.

OBJECTIVE: To compare the acaricidal activity of Melaleuca alternifolia (tea tree) oil (TTO) and some of its individual active components on the itch mite Sarcoptes scabiei var hominis. DESIGN: In vitro acaricide sensitivity assessment. SETTING: The Menzies School of Health Research laboratory, located near the Infectious Diseases Ward of the Royal Darwin Hospital, Australia, where patients are admitted and treated for crusted scabies. PARTICIPANTS: Scabies mites (S scabiei var hominis) were collected from a 20-year-old Aboriginal woman admitted to the Royal Darwin Hospital with crusted scabies. Interventions Within 3 hours of collection, scabies mites were placed in continuous direct contact with the TTO products and control acaricides and were observed at regular intervals. MAIN OUTCOME MEASURES: Percentage of mites dead at regular observation intervals between 5 minutes and 24 hours during continuous exposure to the TTO products and acaricides. RESULTS: The 5% TTO and active component terpinen-4-ol were highly effective in reducing mite survival times. Statistically significant differences in mite survival curves were observed for 5% TTO, 2.1% terpinen-4-ol, 5% permethrin, and ivermectin (100 microg/g of Emulsifying Ointment British Pharmacopoeia 88). In vivo effectiveness was also observed. CONCLUSIONS: Documentation of resistance against antiectoparasitic compounds is increasing. Reported S scabiei treatment failures with lindane, crotamiton, and benzyl benzoate, as well as likely emerging resistance to 5% permethrin and oral ivermectin, are of concern and advocate for the identification and development of novel acaricidal drugs. Tea tree oil is a membrane-active biocide extracted from the tree M alternifolia. It is a principal antimicrobial in a wide range of pharmaceuticals sold in Australia, with the main active component being oxygenated terpenoids. The results suggest that TTO has a potential role as a new topical acaricide and confirm terpinen-4-ol as the primary active component.