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1.
Nat Immunol ; 24(6): 966-978, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37248417

RESUMEN

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacuna BNT162 , COVID-19/prevención & control , Linfocitos T CD8-positivos , Australia/epidemiología , SARS-CoV-2 , Inmunoglobulina G , Anticuerpos Neutralizantes , Inmunidad , Anticuerpos Antivirales , Vacunación
2.
PLoS Pathog ; 18(3): e1010337, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35255101

RESUMEN

HLA-A*11:01 is one of the most prevalent human leukocyte antigens (HLAs), especially in East Asian and Oceanian populations. It is also highly expressed in Indigenous people who are at high risk of severe influenza disease. As CD8+ T cells can provide broadly cross-reactive immunity to distinct influenza strains and subtypes, including influenza A, B and C viruses, understanding CD8+ T cell immunity to influenza viruses across prominent HLA types is needed to rationally design a universal influenza vaccine and generate protective immunity especially for high-risk populations. As only a handful of HLA-A*11:01-restricted CD8+ T cell epitopes have been described for influenza A viruses (IAVs) and epitopes for influenza B viruses (IBVs) were still unknown, we embarked on an epitope discovery study to define a CD8+ T cell landscape for HLA-A*11:01-expressing Indigenous and non-Indigenous Australian people. Using mass-spectrometry, we identified IAV- and IBV-derived peptides presented by HLA-A*11:01 during infection. 79 IAV and 57 IBV peptides were subsequently screened for immunogenicity in vitro with peripheral blood mononuclear cells from HLA-A*11:01-expressing Indigenous and non-Indigenous Australian donors. CD8+ T cell immunogenicity screening revealed two immunogenic IAV epitopes (A11/PB2320-331 and A11/PB2323-331) and the first HLA-A*11:01-restricted IBV epitopes (A11/M41-49, A11/NS1186-195 and A11/NP511-520). The immunogenic IAV- and IBV-derived peptides were >90% conserved among their respective influenza viruses. Identification of novel immunogenic HLA-A*11:01-restricted CD8+ T cell epitopes has implications for understanding how CD8+ T cell immunity is generated towards IAVs and IBVs. These findings can inform the development of rationally designed, broadly cross-reactive influenza vaccines to ensure protection from severe influenza disease in HLA-A*11:01-expressing individuals.


Asunto(s)
Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Australia , Linfocitos T CD8-positivos , Epítopos de Linfocito T , Antígenos HLA-A , Humanos , Pueblos Indígenas , Virus de la Influenza B , Leucocitos Mononucleares , Péptidos
3.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34607957

RESUMEN

Morbidity and mortality rates from seasonal and pandemic influenza occur disproportionately in high-risk groups, including Indigenous people globally. Although vaccination against influenza is recommended for those most at risk, studies on immune responses elicited by seasonal vaccines in Indigenous populations are largely missing, with no data available for Indigenous Australians and only one report published on antibody responses in Indigenous Canadians. We recruited 78 Indigenous and 84 non-Indigenous Australians vaccinated with the quadrivalent influenza vaccine into the Looking into InFluenza T cell immunity - Vaccination cohort study and collected blood to define baseline, early (day 7), and memory (day 28) immune responses. We performed in-depth analyses of T and B cell activation, formation of memory B cells, and antibody profiles and investigated host factors that could contribute to vaccine responses. We found activation profiles of circulating T follicular helper type-1 cells at the early stage correlated strongly with the total change in antibody titers induced by vaccination. Formation of influenza-specific hemagglutinin-binding memory B cells was significantly higher in seroconverters compared with nonseroconverters. In-depth antibody characterization revealed a reduction in immunoglobulin G3 before and after vaccination in the Indigenous Australian population, potentially linked to the increased frequency of the G3m21* allotype. Overall, our data provide evidence that Indigenous populations elicit robust, broad, and prototypical immune responses following immunization with seasonal inactivated influenza vaccines. Our work strongly supports the recommendation of influenza vaccination to protect Indigenous populations from severe seasonal influenza virus infections and their subsequent complications.


Asunto(s)
Anticuerpos Antivirales/sangre , Pueblos Indígenas/estadística & datos numéricos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Activación de Linfocitos/inmunología , Australia , Linfocitos B/inmunología , Humanos , Inmunoglobulina G/sangre , Memoria Inmunológica/inmunología , Gripe Humana/inmunología , Gripe Humana/virología , Recuento de Linfocitos , Vacunación Masiva , Riesgo , Células T Auxiliares Foliculares/inmunología , Linfocitos T/inmunología
4.
Immunol Cell Biol ; 101(10): 964-974, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37725525

RESUMEN

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.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Australia , Inmunoglobulina G , Pueblos Indígenas , Inmunidad , Anticuerpos Antivirales
5.
BMC Public Health ; 23(1): 2377, 2023 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037021

RESUMEN

BACKGROUND: Recent deliberations by Australian public health researchers and practitioners produced an ethical framework of how decisions should be made to distribute pandemic influenza vaccine. The outcome of the deliberations was that the population should be considered in two categories, Level 1 and Level 2, with Level 1 groups being offered access to the pandemic influenza vaccine before other groups. However, the public health researchers and practitioners recognised the importance of making space for public opinion and sought to understand citizens values and preferences, especially First Nations peoples. METHODS: We conducted First Nations Community Panels in two Australian locations in 2019 to assess First Nations people's informed views through a deliberative process on pandemic influenza vaccination distribution strategies. Panels were asked to make decisions on priority levels, coverage and vaccine doses. RESULTS: Two panels were conducted with eighteen First Nations participants from a range of ages who were purposively recruited through local community networks. Panels heard presentations from public health experts, cross-examined expert presenters and deliberated on the issues. Both panels agreed that First Nations peoples be assigned Level 1 priority, be offered pandemic influenza vaccination before other groups, and be offered two doses of vaccine. Reasons for this decision included First Nations people's lives, culture and families are important; are at-risk of severe health outcomes; and experience barriers and challenges to accessing safe, quality and culturally appropriate healthcare. We found that communication strategies, utilising and upskilling the First Nations health workforce, and targeted vaccination strategies are important elements in pandemic preparedness and response with First Nations peoples. CONCLUSIONS: First Nations Community Panels supported prioritising First Nations peoples for pandemic influenza vaccination distribution and offering greater protection by using a two-dose full course to fewer people if there are initial supply limitations, instead of one dose to more people, during the initial phase of the vaccine roll out. The methodology and findings can help inform efforts in planning for future pandemic vaccination strategies for First Nations peoples in Australia.


Asunto(s)
Programas de Inmunización , Vacunas contra la Influenza , Gripe Humana , Humanos , Australia/epidemiología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias/prevención & control , Vacunación , Aborigenas Australianos e Isleños del Estrecho de Torres , Programas de Inmunización/organización & administración
6.
BMC Health Serv Res ; 21(1): 732, 2021 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-34301256

RESUMEN

BACKGROUND: Pandemics such as COVID-19 are a serious public health risk for Australian Aboriginal and Torres Strait Islander communities, yet primary healthcare systems are not well resourced to respond to such urgent events. At the start of the COVID-19 pandemic, a federal government advisory group recommended a rapid, tailored Indigenous response to prevent predicted high morbidity and mortality rates. This paper examines the efforts of one ACCHO, which in the absence of dedicated funding, pivoted its operations in response to COVID-19. Gurriny Yealamucka Health Service (Gurriny) is the only primary healthcare service in the discrete Indigenous community of Yarrabah, Far North Queensland. METHODS: The research was conducted at the request of the Chief Executive Officer of Gurriny. Using grounded theory methods, thirteen Gurriny staff and five Yarrabah and government leaders and community members were interviewed, transcripts of these interviews and 59 documents were imported into NVIVO-12 and coded, and key concepts were compared, organised into higher order constructs, then structured into a theoretical framework. RESULTS: Gurriny responded to COVID-19 by leading with local solutions to keep Yarrabah safe. Four key strategies were implemented: managing the health service operations, realigning services, educating and supporting community, and working across agencies. These strategies were enabled or hindered by five conditions: the governance and leadership capacity of Gurriny, relying on the health taskforce, locking the door, "copping it", and (not) having resources. A year after the first case was experienced in Australia and on the eve of vaccine rollout to Indigenous communities, there have been no COVID-19 cases in Yarrabah. DISCUSSION: The success of the locally led, holistic, comprehensive and culturally safe response of Gurriny suggests that such tailored place-based approaches to pandemics (and other health issues) are appropriate, but require dedicated resourcing. Key challenges were the fragmented and rapidly changing government processes, poorly coordinated communication and resource allocation channels, and bottlenecks in hierarchical funding approval processes. CONCLUSIONS: The COVID-19 response in Yarrabah demonstrates the need for governance reform towards greater resourcing and support for local decision making by Aboriginal community-controlled health organisations.


Asunto(s)
COVID-19 , Servicios de Salud del Indígena , Australia , Teoría Fundamentada , Humanos , Nativos de Hawái y Otras Islas del Pacífico , Pandemias , Salud Pública , Queensland , SARS-CoV-2
7.
J Relig Health ; 60(3): 1436-1445, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33772686

RESUMEN

Faith communities are uniquely positioned for essential public health work to combat the COVID-19 pandemic and address the chronic pre-existing health disparities that have been exacerbated by COVID-19. Specifically, faith communities can (1) dialogue with public health communities, developing internal policies and meeting guidelines consistent with evidence-based recommendations and their own faith traditions, (2) bolster religious daycare and parochial school immunization policies, and (3) partner with faith-based organizations through financial support and volunteer hours. This essential work will complement governmental public health approaches and ensure faith communities can assist with future pandemics.


Asunto(s)
COVID-19 , Organizaciones Religiosas , Humanos , Pandemias , Salud Pública , SARS-CoV-2
8.
Proc Natl Acad Sci U S A ; 113(16): 4440-5, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-27036003

RESUMEN

Memory CD8(+)T lymphocytes (CTLs) specific for antigenic peptides derived from internal viral proteins confer broad protection against distinct strains of influenza A virus (IAV). However, immune efficacy can be undermined by the emergence of escape mutants. To determine how T-cell receptor (TCR) composition relates to IAV epitope variability, we used ex vivo peptide-HLA tetramer enrichment and single-cell multiplex analysis to compare TCRs targeted to the largely conserved HLA-A*0201-M158and the hypervariable HLA-B*3501-NP418antigens. The TCRαßs for HLA-B*3501-NP418 (+)CTLs varied among individuals and across IAV strains, indicating that a range of mutated peptides will prime different NP418-specific CTL sets. Conversely, a dominant public TRAV27/TRBV19(+)TCRαß was selected in HLA-A*0201(+)donors responding to M158 This public TCR cross-recognized naturally occurring M158variants complexed with HLA-A*0201. Ternary structures showed that induced-fit molecular mimicry underpins TRAV27/TRBV19(+)TCR specificity for the WT and mutant M158peptides, suggesting the possibility of universal CTL immunity in HLA-A*0201(+)individuals. Combined with the high population frequency of HLA-A*0201, these data potentially explain the relative conservation of M158 Moreover, our results suggest that vaccination strategies aimed at generating broad protection should incorporate variant peptides to elicit cross-reactive responses against other specificities, especially those that may be relatively infrequent among IAV-primed memory CTLs.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Antígeno HLA-A2 , Inmunidad Celular , Virus de la Influenza A/inmunología , Gripe Humana , Receptores de Antígenos de Linfocitos T alfa-beta , Animales , Antígenos Virales/inmunología , Perros , Femenino , Antígeno HLA-A2/genética , Antígeno HLA-A2/inmunología , Humanos , Memoria Inmunológica/genética , Virus de la Influenza A/genética , Gripe Humana/genética , Gripe Humana/inmunología , Células de Riñón Canino Madin Darby , Masculino , Péptidos/genética , Péptidos/inmunología , Péptidos/farmacología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Vacunación , Proteínas Virales/genética , Proteínas Virales/inmunología , Proteínas Virales/farmacología
10.
J Anat ; 231(6): 931-938, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28925568

RESUMEN

The kangaroo knee is, as in other species, a complex diarthrodial joint dependent on interacting osseous, cartilaginous and ligamentous components for its stability. While principal load bearing occurs through the femorotibial articulation, additional lateral articulations involving the fibula and lateral fabella also contribute to the functional arrangement. Several fibrocartilage and ligamentous structures in this joint remain unexplained or have been misunderstood in previous studies. In this study, we review the existing literature on the structure of the kangaroo 'knee' before providing a new description of the gross anatomical and histological structures. In particular, we present strong evidence that the previously described 'femorofibular disc' is best described as a fibular meniscus on the basis of its gross and histological anatomy. Further, we found it to be joined by a distinct tendinous tract connecting one belly of the m. gastrocnemius with the lateral meniscus, via a hyaline cartilage cornu of the enlarged lateral fabella. The complex of ligaments connecting the fibular meniscus to the surrounding connective tissues and muscles appears to provide a strong resistance to external rotation of the tibia, via the restriction of independent movement of the proximal fibula. We suggest this may be an adaptation to resist the rotational torque applied across the joint during bipedal saltatory locomotion in kangaroos.


Asunto(s)
Adaptación Biológica , Articulación de la Rodilla/anatomía & histología , Locomoción/fisiología , Macropodidae/anatomía & histología , Menisco/anatomía & histología , Animales , Peroné/anatomía & histología , Peroné/fisiología , Articulación de la Rodilla/fisiología , Macropodidae/fisiología , Menisco/fisiología , Rotación , Tibia/anatomía & histología , Tibia/fisiología
11.
BMC Endocr Disord ; 17(1): 26, 2017 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-28525998

RESUMEN

BACKGROUND: Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects. METHODS: Eleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated. RESULTS: Total testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p < 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ± 6 (p < 0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ± 5 and 29 ± 4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p < 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p < 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non-obese PCOS. CONCLUSIONS: The ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5α reductase activity increasing ADTG formation in these women.


Asunto(s)
Androsterona/análogos & derivados , Sulfato de Deshidroepiandrosterona/sangre , Obesidad/sangre , Síndrome del Ovario Poliquístico/sangre , Población Blanca , Adolescente , Adulto , Androsterona/sangre , Biomarcadores/sangre , Femenino , Humanos , Obesidad/diagnóstico , Obesidad/epidemiología , Síndrome del Ovario Poliquístico/diagnóstico , Síndrome del Ovario Poliquístico/epidemiología , Adulto Joven
12.
BMC Public Health ; 17(1): 55, 2017 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-28068977

RESUMEN

BACKGROUND: In Australia, 'Alcohol Management Plans' (AMPs) provide the policy infrastructure for State and Commonwealth Governments to address problematic alcohol use among Aboriginal and Torres Strait Islanders. We report community residents' experiences of AMPs in 10 of Queensland's 15 remote Indigenous communities. METHODS: This cross-sectional study used a two-stage sampling strategy: N = 1211; 588 (48%) males, 623 (52%) females aged ≥18 years in 10 communities. Seven propositions about 'favourable' impacts and seven about 'unfavourable' impacts were developed from semi-structured interviews. For each proposition, one-sample tests of proportions examined participant agreement and multivariable binary logistic regressions assessed influences of gender, age (18-24, 25-44, 45-64, ≥65 years), residence (≥6 years), current drinking and Indigenous status. Confirmatory factor analyses estimated scale reliability (ρ), item loadings and covariances. RESULTS: Slim majorities agreed that: AMPs reduced violence (53%, p = 0.024); community a better place to live (54%, 0.012); and children were safer (56%, p < 0.001). More agreed that: school attendance improved (66%, p < 0.001); and awareness of alcohol's harms increased (71%, p < 0.001). Participants were equivocal about improved personal safety (53%, p = 0.097) and reduced violence against women (49%, p = 0.362). The seven 'favourable' items reliably summarized participants' experiences of reduced violence and improved community amenity (ρ = 0.90). Stronger agreement was found for six 'unfavourable' items: alcohol availability not reduced (58%, p < 0.001); drinking not reduced (56%, p < 0.001)); cannabis use increased (69%, p < 0.001); more binge drinking (73%, p < 0.001); discrimination experienced (77%, p < 0.001); increased fines, convictions and criminal records for breaching restrictions (90%, p < 0.001). Participants were equivocal (51% agreed, p = 0.365) that police could enforce restrictions effectively. 'Unfavourable' items were not reliably reflected in one group (ρ = 0.48) but in: i) alcohol availability and consumption not reduced and ii) criminalization and discrimination. In logistic regressions, longer-term (≥ 6 years) residents more likely agreed that violence against women had reduced and that personal safety had improved but also that criminalization and binge drinking had increased. Younger people disagreed that their community was a better place to live and strongly agreed about discrimination. Current drinkers' views differed little from the sample overall. CONCLUSIONS: The present Government review provides an opportunity to reinforce 'favourable' outcomes while targeting: illicit alcohol, treatment and diversion services and reconciliation of criminalization and discrimination issues.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Trastornos Relacionados con Alcohol/prevención & control , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Estudios Transversales , Análisis Factorial , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Queensland/epidemiología , Reproducibilidad de los Resultados , Violencia/prevención & control , Violencia/estadística & datos numéricos , Adulto Joven
13.
Proc Natl Acad Sci U S A ; 111(3): 1049-54, 2014 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-24395804

RESUMEN

The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus-specific CD8(+) T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16-57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701, B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Subtipo H7N9 del Virus de la Influenza A/inmunología , Gripe Humana/etnología , Gripe Humana/inmunología , Australia , Reacciones Cruzadas/inmunología , Cristalografía por Rayos X , Epítopos de Linfocito T/inmunología , Etnicidad , Antígenos HLA/inmunología , Antígenos HLA-A/inmunología , Humanos , Memoria Inmunológica , Vacunas contra la Influenza/inmunología , Leucocitos Mononucleares/citología , Funciones de Verosimilitud , Mutación , Péptidos/inmunología
14.
Immunol Cell Biol ; 94(4): 367-77, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26493179

RESUMEN

Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying mechanisms are unknown. We studied immune and genetic factors that could predicate severe influenza disease in Indigenous Australians enrolled in the LIFT study: looking into influenza T-cell immunity. To examine CD8(+) T-cell immunity, we characterised human leukocyte antigen (HLA) profiles. HLA typing confirmed previous studies showing predominant usage of HLA-A*02:01, 11:01, 24:02, 34:01 and HLA-B*13:01, 15:21, 40:01/02, 56:01/02 in Indigenous Australians. We identified two new HLA alleles (HLA-A*02:new and HLA-B*56:new). Modelling suggests that variations within HLA-A*02:new (but not HLA-B56:new) could affect peptide binding. There is a relative lack of known influenza epitopes for the majority of these HLAs, with the exception of a universal HLA-A*02:01-M158 epitope and proposed epitopes presented by HLA-A*11:01/HLA-A*24:02. To dissect universal CD8(+) T-cell responses, we analysed the magnitude, function and T-cell receptor (TCR) clonality of HLA-A*02:01-M158(+)CD8(+) T cells. We found comparable IFN-γ, TNF and CD107a and TCRαß characteristics in Indigenous and non-Indigenous Australians, suggesting that the ~15% of Indigenous people that express HLA-A*02:01 have universal influenza-specific CD8(+) T-cell immunity. Furthermore, the frequency of an influenza host risk factor, IFITM3-C/C, was comparable between Indigenous Australians and Europeans, suggesting that expression of this allele does not explain increased disease severity at a population level. Our study indicates a need to identify novel influenza-specific CD8(+) T-cell epitopes restricted by HLA-A and HLA-B alleles prevalent in Indigenous populations for the rational design of universal T-cell vaccines.


Asunto(s)
Linfocitos T CD8-positivos/fisiología , Antígenos HLA/genética , Gripe Humana/inmunología , Nativos de Hawái y Otras Islas del Pacífico , Adulto , Alelos , Células Cultivadas , Epítopos de Linfocito T/metabolismo , Femenino , Prueba de Histocompatibilidad , Humanos , Vacunas contra la Influenza , Gripe Humana/genética , Interferón gamma/metabolismo , Proteína 1 de la Membrana Asociada a los Lisosomas/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas de Unión al ARN/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Riesgo , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas de la Matriz Viral/metabolismo
15.
BMC Public Health ; 15: 696, 2015 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-26202429

RESUMEN

BACKGROUND: There remains a concern that Indigenous Australians have been over-researched without corresponding improvements in their health; this trend is applicable to most Indigenous populations globally. This debate article has a dual purpose: 1) to open a frank conversation about the value of research to Indigenous Australian populations; and 2) to stimulate ways of thinking about potential resolutions to the lack of progress made in the Indigenous research benefit debate. DISCUSSION: Capturing the meaning of research benefit takes the form of ethical value-oriented methodological considerations in the decision-making processes of Indigenous research endeavours. Because research practices come from Western knowledge bases, attaining such positions in research means reconciling both Indigenous and Western knowledge systems to produce new methodologies that guide planning, evaluating and monitoring of research practices as necessary. Increasingly, more sophisticated performance measures have been implemented to ensure academic impact and benefits are captured. Assessing societal and other non-academic impacts and benefits however, has not been accorded corresponding attention. Research reform has only focussed on research translation in more recent years. The research impact debate must take account of the various standards of accountability (to whom), impact priorities (for whom), positive and negative impacts, and biases that operate in describing impact and measuring benefit. SUMMARY: A perennial question in Indigenous research discourse is whether the abundance of research conducted; purportedly to improve health, is justified and benefits Indigenous people in ways that are meaningful and valued by them. Different research stakeholders have different conceptions of the value and nature of research, its conduct, what it should achieve and the kinds of benefits expected. We need to work collaboratively and listen more closely to the voice of Indigenous Australians to better understand, demonstrate and measure health research benefits. The authors conclude that as an imperative, a systematic benefit assessment strategy that includes identification of research priorities and planning, monitoring and evaluation components needs to be developed and implemented across research projects. In Indigenous health research, this will often mean adopting a benefit-led approach by changing the way research is done and preferencing alternative research methodologies. As a point of departure to improving impact and reaching mutually beneficial outcomes for researchers and partners in Indigenous health research, we need to routinise the assessment of benefit from outset of research as one of the standards toward which we work.


Asunto(s)
Investigación sobre Servicios de Salud/organización & administración , Nativos de Hawái y Otras Islas del Pacífico , Australia , Conducta Cooperativa , Necesidades y Demandas de Servicios de Salud , Disparidades en el Estado de Salud , Humanos
17.
Rural Remote Health ; 15(3): 2923, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26223560

RESUMEN

INTRODUCTION: This article describes the use and effectiveness of the participatory action research (PAR) framework to better understand community members' perceptions and risks of pandemic influenza. In 2009, the H1N1 influenza pandemic affected Indigenous populations more than non-Indigenous populations in Oceania and the Americas. Higher prevalence of comorbidities (diabetes, obesity, asthma and chronic obstructive pulmonary disease) as well as pregnancy in Indigenous communities may have contributed to the higher risks of severe disease. Social disparity, institutionalised racism within health services and differences in access to culturally safe health services have also been reported as contributors to disadvantage and delayed appropriate treatment. METHODS: Given these factors and the subsequent impact they had on Australian Aboriginal and Torres Strait Islander communities, the authors set out to ensure that the Australian national, state and territory pandemic plans adequately reflected the risk status of Aboriginal and Torres Strait Islander peoples and promoted meaningful engagement with communities to mitigate this risk. A national study explored the views of Aboriginal and Torres Strait Islander people and their experiences with H1N1 and used a qualitative PAR framework that was effective in gaining deep understandings from participants. Aboriginal and Torres Strait Islander community-controlled organisations and health services were involved in the implementation, interpretation and monitoring of this project. RESULTS: As a result, important features of the implementation of this PAR framework with Aboriginal and Torres Strait Islander communities and organisations emerged. These features included the importance of working in a multidisciplinary team with Aboriginal and Torres Strait Islander researchers; the complexities and importance of obtaining multi-site human research ethics approval processes; the importance and value of building the research capacity of both experienced and novice researchers in PAR; the need to use localised sampling protocols; and the process of undertaking a collective research process and enacting action research and feedback. CONCLUSIONS: The most effective responses of this project were embedded in pre-existing relationships with individuals within organisations that had been established over a long period of time between Aboriginal medical services and investigators; however, research relationships established specifically for the purposes of the project were less successful because of changes in personnel and organisational support. The participatory approach used in this study has the potential to be applied to vulnerable populations in other countries.


Asunto(s)
Investigación Participativa Basada en la Comunidad/estadística & datos numéricos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/psicología , Nativos de Hawái y Otras Islas del Pacífico/psicología , Pandemias , Australia , Creación de Capacidad , Servicios de Salud Comunitaria , Investigación Participativa Basada en la Comunidad/métodos , Relaciones Comunidad-Institución , Comorbilidad , Relaciones Familiares , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud/métodos , Humanos , Gripe Humana/prevención & control , Estilo de Vida , Pandemias/prevención & control , Grupos de Población/psicología , Investigación Cualitativa , Investigadores/ética , Factores de Riesgo , Recursos Humanos
18.
BMC Public Health ; 14: 15, 2014 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-24400846

RESUMEN

BACKGROUND: In 2002/03 the Queensland Government responded to high rates of alcohol-related harm in discrete Indigenous communities by implementing alcohol management plans (AMPs), designed to include supply and harm reduction and treatment measures. Tighter alcohol supply and carriage restrictions followed in 2008 following indications of reductions in violence and injury. Despite the plans being in place for over a decade, no comprehensive independent review has assessed to what level the designed aims were achieved and what effect the plans have had on Indigenous community residents and service providers. This study will describe the long-term impacts on important health, economic and social outcomes of Queensland's AMPs. METHODS/DESIGN: The project has two main studies, 1) outcome evaluation using de-identified epidemiological data on injury, violence and other health and social indicators for across Queensland, including de-identified databases compiled from relevant routinely-available administrative data sets, and 2) a process evaluation to map the nature, timing and content of intervention components targeting alcohol. Process evaluation will also be used to assess the fidelity with which the designed intervention components have been implemented, their uptake and community responses to them and their perceived impacts on alcohol supply and consumption, injury, violence and community health. Interviews and focus groups with Indigenous residents and service providers will be used. The study will be conducted in all 24 of Queensland's Indigenous communities affected by alcohol management plans. DISCUSSION: This evaluation will report on the impacts of the original aims for AMPs, what impact they have had on Indigenous residents and service providers. A central outcome will be the establishment of relevant databases describing the parameters of the changes seen. This will permit comprehensive and rigorous surveillance systems to be put in place and provided to communities empowering them with the best credible evidence to judge future policy and program requirements for themselves. The project will inform impending alcohol policy and program adjustments in Queensland and other Australian jurisdictions.The project has been approved by the James Cook University Human Research Ethics Committee (approval number H4967 & H5241).


Asunto(s)
Alcoholismo/etnología , Promoción de la Salud , Servicios de Salud del Indígena/organización & administración , Nativos de Hawái y Otras Islas del Pacífico , Alcoholismo/complicaciones , Alcoholismo/prevención & control , Análisis Costo-Beneficio , Servicios de Salud del Indígena/economía , Estado de Salud , Humanos , Queensland , Violencia/etnología , Violencia/estadística & datos numéricos
19.
Aust J Rural Health ; 21(2): 90-6, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23586570

RESUMEN

INTRODUCTION: Providing an emphasis on Indigenous health in medical undergraduate education is seen as a high priority by Australian medical organisations. A regional North Queensland medical school asked local Indigenous people to list personal attributes they want to see in graduate doctors who choose to practise in their remote community. METHODS: This 2011 pilot study used a participatory action research design, with 13 local Indigenous health professionals, elders and community members from Mount Isa participating as co-researchers in 'Yarning Circles' discussing desired medical graduate attributes. Medical school co-researchers inductively extracted themes from the discussions via a qualitative 'grounded theory' approach. RESULTS: Eight major subtopics were identified by the Mount Isa Indigenous community around desired skills, knowledge and attitudes for graduate doctors: provision of quality patient care; culturally appropriate communication; medical knowledge; culturally appropriate knowledge; knowing the local health system; a positive personality; a positive attitude to working with Indigenous peoples; and a desire to engage with the Indigenous community. DISCUSSION: Effective communications with Indigenous patients and working in remote Indigenous communities requires doctors to have appropriate clinical skills, medical knowledge, knowledge about how local health systems operate, familiarity with significant Indigenous health issues such as child safety and alcohol management, and positive attitudes to working with, learning about and providing an advocacy role for Indigenous peoples. CONCLUSIONS: Findings have implications for enhancing the professional behaviours and engagement of James Cook University medical students in Indigenous communities while on rural placement and after graduation, and for Australian medical and health practitioners more broadly.


Asunto(s)
Comportamiento del Consumidor , Nativos de Hawái y Otras Islas del Pacífico , Médicos/normas , Servicios de Salud Rural , Competencia Clínica , Estudios Transversales , Competencia Cultural , Humanos , Proyectos Piloto , Queensland , Servicios de Salud Rural/normas , Recursos Humanos
20.
Rural Remote Health ; 13(2): 2277, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23662942

RESUMEN

INTRODUCTION: Medical students should be equipped with the necessary knowledge, skills and attitudes to engage with local communities on placement, and later act as agents of change in addressing health system priorities and inequities. Determining what are the necessary knowledge, skills and attitudes requires the medical school to collect input from the local communities they serve. This study describes the steps taken by the James Cook University (JCU) School of Medicine & Dentistry (SMD) to develop a systematic process for collecting input from a local Indigenous community. METHODS: This 2011 study utilised a participatory action research design. An Indigenous Reference Group (IRG) consisting of 13 local Indigenous people including health professionals, Elders and community members was established by the JCU SMD in the North Queensland town of Mount Isa. 'Yarning Circle' discussions between SMD representatives and the IRG developed a Terms of Reference (ToR) to guide the engagement process, and negotiated reciprocal benefits to compensate participants for time involved in consultations and to promote sustainability. RESULTS: A framework for engaging with the Mount Isa Indigenous community was developed. Benefits for the SMD included a list of the good and bad engagement strategies with the local Indigenous community. Benefits for the IRG members included assistance with grant applications, media skills and organizing a community-wide health event. CONCLUSIONS: Successful and sustainable community partnerships between a medical school and an Indigenous community can be achieved, with Indigenous researchers and community members guiding the engagement process, and for stakeholders to follow through in providing the negotiated reciprocal benefits. Having an established IRG should increase Indigenous input and participation into the medical curriculum, and into future research and community activities to improve the health of the Indigenous people.


Asunto(s)
Relaciones Comunidad-Institución , Servicios de Salud del Indígena , Evaluación de Procesos y Resultados en Atención de Salud/métodos , Relaciones Profesional-Paciente , Facultades de Medicina , Estudiantes de Medicina/psicología , Adulto , Anciano de 80 o más Años , Investigación Participativa Basada en la Comunidad , Guías como Asunto , Conocimientos, Actitudes y Práctica en Salud , Humanos , Evaluación de Programas y Proyectos de Salud , Asociación entre el Sector Público-Privado , Queensland , Investigadores/organización & administración , Facultades de Odontología , Estudiantes de Medicina/estadística & datos numéricos
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