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INTRODUCTION: Aboriginal and Torres Strait Islander Peoples (First Nations Australians) living in remote communities are hospitalised with skin and soft tissue infections (SSTIs) at three times the rate of non-First Nations Australians. The Torres Strait in tropical northern Australia has a highly dispersed population mainly comprising First Nations Australians. This study aimed to define the health service utilisation and health system costs associated with SSTIs in the Torres Strait and to improve the quality of regional healthcare delivery. METHODS: The research team conducted a retrospective, de-identified audit of health records for a 2-year period, 2018-2019. The aim was to define health service utilisation, episodes of outpatient care, emergency department care, inpatient care and aeromedical retrieval services for SSTIs. RESULTS: Across 2018 - 2019, there were 3509 outpatient episodes of care for SSTIs as well as 507 emergency department visits and 100 hospitalisations. For individuals with an SSTI, the mean outpatient clinic episode cost $240; the mean emergency department episode cost $400.85, the mean inpatient episode cost $8403.05 while an aeromedical retrieval service cost $18,670. The total costs to the health system for all services accessed for SSTI management was $6,169,881 per year, 3% of the total annual health service budget. CONCLUSION: Healthcare costs associated with SSTIs in the Torres Strait are substantial. The implementation of effective preventative and primary care interventions may enable resources to be reallocated to address other health priorities in the Torres Strait.
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Servicios de Salud del Indígena , Aceptación de la Atención de Salud , Enfermedades Cutáneas Infecciosas , Infecciones de los Tejidos Blandos , Humanos , Australia/epidemiología , Aborigenas Australianos e Isleños del Estrecho de Torres , Atención a la Salud , Estudios Retrospectivos , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
OBJECTIVE: The purpose of this article is to evaluate the COVID-19 Care in the Home (CCITH) program during the first COVID-19 omicron wave across Torres Strait and Cape York region of Far North Queensland in 2022. METHODS: A mixed-method study: An online survey and semi-structured interviews of CCITH internal and external stakeholders and participants was utilised to develop a greater understanding of perspectives of the program. RESULTS: Survey participants n=140. Most survey respondents did not attend hospital, emergency, or primary healthcare centre during isolation for medical assistance (82%, 115/140) and most strongly agreed/agreed (87%, 122/140) that the CCITH program cared for their health needs. Interview participants n=14. Thematic analysis of interviews verified survey responses and identified successes of this program including improved community relationships and primary healthcare centres and community members felt supported. Limitations included rapid changes to policies and roles and limited food availability during isolation. CONCLUSIONS: The CCITH program highlights the resilience and self-determination of First Nations communities and primary health staff across the Torres Strait and Cape York throughout the first COVID-19 outbreak in the region. IMPLICATIONS FOR PUBLIC HEALTH: This virtual model of care could be employed in similar settings to improve service provision in both primary and public health to increase community safety and achieve good health outcomes.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Queensland/epidemiología , Masculino , Femenino , Adulto , Salud Pública , Encuestas y Cuestionarios , Persona de Mediana Edad , Servicios de Atención de Salud a Domicilio , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Nativos de Hawái y Otras Islas del Pacífico/psicología , PandemiasRESUMEN
BACKGROUND: Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection. METHODS: This cohort study was done in emergency departments and intensive care units of four hospitals in Queensland, Australia, and recruited children aged 1 month to 17 years who, upon admission, underwent a diagnostic test, including blood cultures, for suspected sepsis. Whole-blood RNA sequencing of blood was performed with Illumina NovaSeq (San Diego, CA, USA). Samples with completed phenotyping, monitoring, and RNA extraction by March 31, 2020, were included in the discovery cohort; samples collected or completed thereafter and by Oct 27, 2021, constituted the Rapid Paediatric Infection Diagnosis in Sepsis (RAPIDS) internal validation cohort. An external validation cohort was assembled from RNA sequencing gene expression count data from the observational European Childhood Life-threatening Infectious Disease Study (EUCLIDS), which recruited children with severe infection in nine European countries between 2012 and 2016. Feature selection approaches were applied to derive novel gene signatures for disease class (bacterial vs viral infection) and disease severity (presence vs absence of organ dysfunction 24 h post-sampling). The primary endpoint was the presence of organ dysfunction 24 h after blood sampling in the presence of confirmed bacterial versus viral infection. Gene signature performance is reported as area under the receiver operating characteristic curves (AUCs) and 95% CI. FINDINGS: Between Sept 25, 2017, and Oct 27, 2021, 907 patients were enrolled. Blood samples from 595 patients were included in the discovery cohort, and samples from 312 children were included in the RAPIDS validation cohort. We derived a ten-gene disease class signature that achieved an AUC of 94·1% (95% CI 90·6-97·7) in distinguishing bacterial from viral infections in the RAPIDS validation cohort. A ten-gene disease severity signature achieved an AUC of 82·2% (95% CI 76·3-88·1) in predicting organ dysfunction within 24 h of sampling in the RAPIDS validation cohort. Used in tandem, the disease class and disease severity signatures predicted organ dysfunction within 24 h of sampling with an AUC of 90·5% (95% CI 83·3-97·6) for patients with predicted bacterial infection and 94·7% (87·8-100·0) for patients with predicted viral infection. In the external EUCLIDS validation dataset (n=362), the disease class and disease severity predicted organ dysfunction at time of sampling with an AUC of 70·1% (95% CI 44·1-96·2) for patients with predicted bacterial infection and 69·6% (53·1-86·0) for patients with predicted viral infection. INTERPRETATION: In children evaluated for sepsis, novel host transcriptomic signatures specific for bacterial and viral infection can identify dysregulated host response leading to organ dysfunction. FUNDING: Australian Government Medical Research Future Fund Genomic Health Futures Mission, Children's Hospital Foundation Queensland, Brisbane Diamantina Health Partners, Emergency Medicine Foundation, Gold Coast Hospital Foundation, Far North Queensland Foundation, Townsville Hospital and Health Services SERTA Grant, and Australian Infectious Diseases Research Centre.
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Infecciones Bacterianas , Sepsis , Virosis , Humanos , Niño , Estudios de Cohortes , Transcriptoma , Insuficiencia Multiorgánica/diagnóstico , Insuficiencia Multiorgánica/genética , Estudios Prospectivos , Australia , Sepsis/diagnóstico , Sepsis/genéticaRESUMEN
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.
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A coronavirus disease 2019 (COVID-19) outbreak was declared in the remote Torres and Cape region of Far North Queensland soon after the Queensland border opened for quarantine-free domestic travel in December 2021, with a total of 7,784 cases notified during the first ten-month outbreak period. We report a crude attack rate among residents of 25.6% (95% confidence interval [95% CI]: 25.1-26.1%), a hospitalisation rate of 1.6% (95% CI: 1.3-1.9%) and a crude case fatality rate of 0.05% (95% CI: 0.01-0.13%). Hospitalisation and case fatality rates were similar among First Nations and non-Indigenous people, with double dose COVID-19 vaccination rates higher among First Nations than non-Indigenous people by the end of the outbreak period. We attribute the low burden of severe illness to local community leadership, community engagement, vaccination coverage and recency, and community participation in a local culturally considered COVID-19 care-in-the-home program.
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Aborigenas Australianos e Isleños del Estrecho de Torres , COVID-19 , Humanos , Australia/epidemiología , Aborigenas Australianos e Isleños del Estrecho de Torres/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/virología , Vacunas contra la COVID-19 , Brotes de Enfermedades , Queensland/epidemiología , Costo de EnfermedadRESUMEN
Toxigenic diphtheria is rare in Australia with generally fewer than 10 cases reported annually; however, since 2020, there has been an increase in toxin gene-bearing isolates of Corynebacterium diphtheriae cases in North Queensland, with an approximately 300% escalation in cases in 2022. Genomic analysis on both toxin gene-bearing and non-toxin gene-bearing C. diphtheriae isolated from this region between 2017 and 2022 demonstrated that the surge in cases was largely due to one sequence type (ST), ST381, all of which carried the toxin gene. ST381 isolates collected between 2020 and 2022 were highly genetically related to each other, and less closely related to ST381 isolates collected prior to 2020. The most common ST in non-toxin gene-bearing isolates from North Queensland was ST39, an ST that has also been increasing in numbers since 2018. Phylogenetic analysis demonstrated that ST381 isolates were not closely related to any of the non-toxin gene-bearing isolates collected from this region, suggesting that the increase in toxigenic C. diphtheriae is likely due to the expansion of a toxin gene-bearing clone that has moved into the region rather than an already endemic non-toxigenic strain acquiring the toxin gene.
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Corynebacterium diphtheriae , Difteria , Brotes de Enfermedades , Humanos , Australia/epidemiología , Corynebacterium diphtheriae/genética , Difteria/epidemiología , Toxina Diftérica/genética , Genómica , Filogenia , Queensland , Epidemiología Molecular , Salud PúblicaRESUMEN
BACKGROUND: Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B virus (HBV) infection have a significant burden of hepatocellular carcinoma (HCC). The prevalence of comorbidities that increase the risk of HCC in this population is incompletely defined. METHODS: This cross-sectional study was performed in remote tropical Queensland, Australia in January 2021. All individuals living with chronic HBV in the region were identified; the prevalence of relevant comorbidities was determined by reviewing medical records. RESULTS: All 236 individuals in the cohort identified as Aboriginal and Torres Strait Islander Australians; their median (interquartile range (IQR)) age was 48 (40-62) years; 120/236 (50.9%) were female. Of the 194/236 (82.2%) engaged in HBV care, 61 (31.4%) met criteria for HBV therapy and 38 (62.2%) were receiving it. However, 142/236 (60.2%) were obese, 73/236 (30.9%) were current smokers and 57/236 (24.2%) were drinking alcohol hazardously; 70/236 (29.7%) had ≥2 of these additional risk factors for HCC, only 43/236 (18.2%) had none. Among the 19 patients with confirmed cirrhosis, 9 (47%) were obese, 8 (42%) were currently-or had a history of-drinking alcohol hazardously and 5 (26.3%) were current smokers. Patients also had a median (IQR) of 3 (2-4) cardiovascular risk factors (cigarette smoking, hypertension, impaired glucose tolerance, dyslipidaemia, renal impairment/proteinuria). Only 9/236 (3.8%) did not have one of these 5 comorbidities. CONCLUSIONS: Aboriginal and Torres Strait Islander Australians living with chronic HBV in this region of remote Australia have a high engagement with HBV care and the majority of individuals eligible for antiviral therapy are receiving it. However, a significant comorbidity burden increases their risk of cirrhosis, HCC, and premature death. It is essential to integrate chronic HBV care with management of these comorbidities-rather than focusing on HBV alone-to achieve optimal health outcomes.
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Aborigenas Australianos e Isleños del Estrecho de Torres , Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Australia/epidemiología , Aborigenas Australianos e Isleños del Estrecho de Torres/estadística & datos numéricos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Comorbilidad , Estudios Transversales , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/terapia , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Obesidad/epidemiología , Queensland/epidemiología , Costo de Enfermedad , Prevalencia , Adulto , Factores de Riesgo , Manejo de la EnfermedadRESUMEN
BACKGROUND: There is a high burden of skin and soft tissue infections (SSTI) - including cellulitis - among Aboriginal and Torres Strait Islander peoples living in remote communities. In tropical environments, such as the Torres Strait, cellulitis accounts for 37% of potentially preventable hospitalisations. This study aimed to evaluate the safety, effectiveness and community acceptance of outpatient antibiotic treatment for the management of skin infections in the Torres Strait. CONCLUSIONS: Outpatient management of skin infection in the Torres Strait is effective, safe and appreciated by patients. METHODS: This was a 12-month prospective, observational study commencing in January 2019 involving 295 adults with a skin infection across the Torres Strait. RESULTS: Most (276/295 (94%)) participants were treated successfully in the community. Of 295 enrolled patients, 151 of 295 (51%) had cellulitis, 59 of 295 (20%) had a skin abscess and 85 of 295 (28%) had a wound infection. Of the 77 of 278 (27%) infections accompanied by systemic features, 63 of 77 (82%) were managed in the community. Staphylococcus aureus was the most frequent isolate, at 165 of 261 (63%); 56 of 165 (33%) were methicillin resistant. In the 276 community-managed cases, oral trimethoprim/sulfamethoxazole was initially used in 159 (57%), oral flucloxacillin in 75 (27%) and intravenous cefazolin plus oral probenecid in 32 (13%). The clinical course was complicated in eight of 232 (3%) patients who had complete follow-up data: seven patients required hospitalisation after initial treatment in the communityand one had an antibiotic side-effect. All 232 patients with complete follow-up data were content with the care they received.
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Celulitis (Flemón) , Servicios de Salud del Indígena , Adulto , Humanos , Antibacterianos/uso terapéutico , Pueblos Indígenas , Estudios Prospectivos , Aborigenas Australianos e Isleños del Estrecho de TorresRESUMEN
INTRODUCTION: The first outbreak of the omicron variant of COVID-19 in the Torres and Cape region of Far North Queensland in Australia was declared in late December 2021. A COVID-19 Care at Home program was created to support the health and non-health needs of people with COVID-19 and their families throughout the mandatory isolation periods and included centralising the coordination and delivery of COVID-19 therapeutics. The therapeutics available included one intravenous monoclonal antibody (sotrovimab) and two oral antiviral therapies: nirmatrelvir and ritonavir (Paxlovid®) and molnupiravir (Lagevrio®). This article describes the uptake and delivery of this therapeutics program. METHODS: COVID-19 cases were documented in a notification database, screened to determine eligibility for COVID-19 therapies and prioritised based on case age, vaccination status, immunosuppression status and existing comorbidities, in line with Queensland clinical guidelines. Eligible cases were individually contacted by phone to discuss treatment options, and administration of therapies were coordinated in partnership with local primary healthcare centres and hospitals. RESULTS: A total of 4744 cases were notified during the outbreak period, of which 217 (4.6%) were deemed eligible for treatment after medical review. Treatment was offered to 148/217 cases (68.2%), with 90/148 cases (60.8%) declining treatment and 53/148 cases (35.8%) receiving therapeutic treatment for COVID-19. Among these 53 cases, 29 received sotrovimab (54.7%), 20 received Paxlovid (37.7%) and four received Lagevrio (7.5%). First Nations people accounted for 48/53 cases (90.6%) who received treatment, and COVID-19 therapeutics were delivered to cases in 16 remote First Nations communities during the outbreak period. CONCLUSION: The COVID-19 Care at Home program demonstrated a novel, public health led approach to delivering time-critical medications to individuals across a large, remote and logistically complex region. The application of similar models to outbreaks and chronic conditions of public health importance offers potential to address many health access inequities experienced by remote Australian First Nations communities.
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COVID-19 , Servicios de Salud del Indígena , Humanos , Nativos de Hawái y Otras Islas del Pacífico , Queensland/epidemiología , Australia/epidemiología , COVID-19/epidemiología , Ritonavir , SARS-CoV-2 , Brotes de Enfermedades , Anticuerpos Monoclonales , Antivirales , Tratamiento Farmacológico de COVID-19RESUMEN
ISSUE ADDRESSED: Skin infections such as impetigo and scabies are common in Aboriginal Australian and Torres Strait Islander children living in rural and remote settings. Effective health promotion is a key element when addressing health literacy aimed at reducing the burden of skin disease. Community-driven health promotion provides a potentially effective and sustainable model for improved health outcomes. METHODS: A one-day community-driven skin health promotional event was conducted on Waiben [Thursday Island] with the aim of improving local Torres Strait Islander children's appreciation of the importance of skin health through art, music and creation of a video. Participants completed written pre- and post-questionnaires to determine their response. RESULTS: Fifty-two children participated in the event; median (range) age was 11 (9-12) years and all identified as Torres Strait Islander. Overall, 34 of 50 children (68%) felt that participating in this workshop improved their skin health knowledge. CONCLUSIONS: Skin health promotion can be successful achieved through a locally conceived, locally driven and locally owned approach. SO WHAT?: This skin health promotional event could be a model for other health promotion activities in the Torres Strait.
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Servicios de Salud del Indígena , Nativos de Hawái y Otras Islas del Pacífico , Australia , Niño , Promoción de la Salud , Humanos , Población Rural , Encuestas y CuestionariosAsunto(s)
Investigación Participativa Basada en la Comunidad/ética , Servicios de Salud del Indígena/economía , Nativos de Hawái y Otras Islas del Pacífico/etnología , Australia/etnología , Enfermedades Transmisibles/epidemiología , Enfermedades Transmisibles/etnología , Investigación Participativa Basada en la Comunidad/métodos , Diversidad Cultural , Servicios de Salud del Indígena/estadística & datos numéricos , Humanos , Colaboración Intersectorial , Enfermedades no Transmisibles/epidemiología , Enfermedades no Transmisibles/etnologíaRESUMEN
Rheumatic heart disease (RHD) is almost entirely preventable, but its incidence in indigenous Australians remains one of the highest in the world. A community-based echocardiogram screening program of 862 Torres Strait Islander children identified 25 (2.9%) new cases of RHD. Among these 25 children, 5/7 (71%) prior acute rheumatic fever presentations had not been recognized. There was a history of microbiologically confirmed group A Streptococcus infection in 17/25 (68%) children with RHD compared with 9/25 (36%) controls (odds ratio [OR] [95% CI]: 3.78 [1.17-12.19], P = 0.03). This was more likely to be a skin swab (16/25 [64%] cases versus 6/25 [24%] controls) than a throat swab (1/25 [4%] cases versus 3/25 [12%] controls) (OR [95% CI]: 5.33 [1.51-18.90] [P = 0.01]), supporting a role for skin infection in RHD pathogenesis. Household crowding and unemployment were common in the cohort, emphasizing the need for prioritizing strategies that address the social determinants of health.
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Ecocardiografía/métodos , Tamizaje Masivo/métodos , Cardiopatía Reumática/diagnóstico , Cardiopatía Reumática/prevención & control , Adolescente , Australia/epidemiología , Niño , Preescolar , Estudios de Cohortes , Aglomeración , Femenino , Humanos , Islas , Masculino , Nativos de Hawái y Otras Islas del Pacífico , Estudios Retrospectivos , Cardiopatía Reumática/epidemiologíaRESUMEN
INTRODUCTION: Aboriginal and Torres Strait Islander Australians living in remote locations suffer disproportionately from chronic hepatitis B (CHB). Defining the temporospatial epidemiology of the disease-and assessing the ability of local clinicians to deliver optimal care-is crucial to improving patient outcomes in these settings. METHODS: The demographic, laboratory and radiology findings in all patients diagnosed with CHB after 1990, and presently residing in remote Far North Queensland (FNQ), tropical Australia, were correlated with their management and clinical course. RESULTS: Of the 602 patients, 514 (85%) identified as Aboriginal and Torres Strait Islander Australians, 417 (69%) of whom had Torres Strait Islander heritage. Among the 514 Aboriginal and Torres Strait Islander Australians, there were only 61 (12%) born after universal postnatal vaccination was introduced in 1985. Community CHB prevalence varied significantly across the region from 7/1707 (0.4%) in western Cape York to 55/806 (6.8%) in the Eastern Torres Strait Islands. Although 240/602 (40%) are engaged in care, with 65 (27%) meeting criteria for antiviral therapy, only 43 (66%) were receiving this treatment. Among 537 with complete data, 32 (6%) were cirrhotic, of whom 15 (47%) were engaged in care and 10 (33%) were receiving antiviral therapy. Only 64/251 (26%) in whom national guidelines would recommend hepatocellular carcinoma (HCC) surveillance are receiving screening, however, only 20 patients have been diagnosed with HCC since 1999. CONCLUSION: Vaccination has had a dramatic effect on CHB prevalence in FNQ in only a generation. However, although engagement in care is the highest in Australia, this is not translating into initiation of antiviral therapy in all those that should be receiving it, increasing their risk of developing cirrhosis and HCC. New strategies are necessary to improve the care of Indigenous Australians living with CHB to reduce the morbidity and mortality of this preventable disease.
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Hepatitis B Crónica/epidemiología , Clima Tropical , Adulto , Anciano , Femenino , Geografía , Humanos , Masculino , Persona de Mediana Edad , Queensland/epidemiologíaRESUMEN
Burkholderia pseudomallei, a bacterium that lives in the soil of the tropics, causes the disease melioidosis. This retrospective study investigated the temporospatial epidemiology of the 49 laboratory-confirmed melioidosis cases in the Torres Straits Islands of tropical Australia between 1997 and 2017. An identifiable risk factor for the disease was present in 43/49 (88%) cases and in 35/36 (97%) cases with complete clinical data. The mean incidence of melioidosis varied across the region, from 0/100,000 persons/year in the Eastern Island Cluster to 116.1/100,000 persons/year in the Near Western Island Cluster. An environmental suitability score for the growth of B. pseudomallei-constructed using the rainfall, vegetation, and soil type on each island-correlated with disease incidence (Spearman's rho 0.51; P = 0.035). Melioidosis is an opportunistic disease that occurs in patients with specific risk factors, but its incidence is also strongly influenced by environmental factors that favor the growth of the causative organism.
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Burkholderia pseudomallei , Ambiente , Melioidosis/epidemiología , Adulto , Australia/epidemiología , Femenino , Promoción de la Salud , Humanos , Islas , Masculino , Melioidosis/microbiología , Vigilancia de la Población , Administración en Salud Pública , Lluvia , Factores de TiempoRESUMEN
The effects of the Pseudomonas aeruginosa virulence factor pyocyanin (PCN) on the contractile function of porcine coronary arteries was investigated in vitro. Artery rings (5 mm) were suspended in organ baths containing Krebs' solution for the measurement of isometric tension. The effect of PCN on resting and precontracted coronary arteries was initially investigated with various agents. Arteries were precontracted with prostaglandin (PG) F2α or potassium chloride and endothelium-dependent relaxations were induced by various agents in the presence of PCN. Pyocyanin (0.1-10 µmol/L) evoked small-amplitude, dose-dependent contractions in resting porcine coronary arteries. In addition, PCN amplified the contractile response to PGF2α , but did not alter responses to carbachol. Pyocyanin (0.1-10 µmol/L) significantly inhibited endothelium-dependent relaxations evoked by neurokinin A. Pyocyanin also inhibited relaxations evoked by diethylamine nitric oxide (a nitric oxide donor), forskolin (an adenylate cyclase activator), dibuytyryl-cAMP (a cAMP analogue), 8-bromo-cGMP (a cGMP analogue) and P1075 (a KATP channel activator), but not isoprenaline (ß-adrenoceceptor agonist). These results indicate that physiological concentrations of PCN interfere with multiple intracellular processes involved in vascular smooth muscle relaxation, in particular pathways downstream of nitric oxide release. Thus, PCN may alter normal vascular function in patients infected with P. aeruginosa.
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Vasos Coronarios/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Óxido Nítrico/metabolismo , Piocianina/farmacología , Vasodilatación/efectos de los fármacos , 8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , 8-Bromo Monofosfato de Adenosina Cíclica/metabolismo , Animales , Colforsina/metabolismo , Vasos Coronarios/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Dietilaminas/farmacología , Dinoprost/metabolismo , Femenino , Isoproterenol/farmacología , Masculino , Contracción Muscular/efectos de los fármacos , Pseudomonas aeruginosa/metabolismo , PorcinosRESUMEN
It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity. We here investigate the impact on HIV virulence of HIV adaptation to HLA molecules that protect against disease progression, such as HLA-B*57 and HLA-B*58:01. We analyzed cohorts in Botswana and South Africa, two countries severely affected by the HIV epidemic. In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 × 10(-82)), the protective effect of HLA-B*57/58:01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03). These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time. The potential role in this process played by increasing antiretroviral therapy (ART) access is also explored. Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation.
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Adaptación Biológica/genética , Evolución Molecular , Infecciones por VIH/epidemiología , VIH/genética , VIH/patogenicidad , Antígenos HLA-B/genética , Adulto , Secuencia de Bases , Botswana/epidemiología , Estudios de Cohortes , Infecciones por VIH/transmisión , Antígenos HLA-B/inmunología , Humanos , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Estudios Seroepidemiológicos , Sudáfrica/epidemiología , VirulenciaRESUMEN
Human immunodeficiency virus type 1 (HIV-1) genetic diversity poses a challenge to reliable viral load monitoring. Discrepancies between different testing platforms have been observed, especially for non-clade-B virus. Therefore we compare, in antiretroviral therapy (ART)-naïve South African subjects predominantly infected with HIV-1 clade-C, three commercially available assays: the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test version 2.0 by Roche (CAP/CTM v2.0), the BioMérieux NucliSens Version 2.0 Easy Q/Easy Mag (NucliSens v2.0) and the Roche COBAS Amplicor HIV-1 Monitor Test Version 1.5 (Amplicor v1.5). Strong linear correlation was observed and Bland-Altman analyses showed overall good agreement between the assays with mean viral load differences of 0.078 log cp/ml (NucliSens v2.0 - Amplicor v1.5), 0.260 log cp/ml (CAP/CTM v2.0 - Amplicor v1.5) and 0.164 log cp/ml (CAP/CTM v2.0 - NucliSens v2.0), indicating lower mean viral load results for the Amplicor v1.5 and higher mean readings for the CAP/CTM v2.0. Consistent with observations following previous comparisons of CAP/CTM v2.0 versus Amplicor v1.5, the CAP/CTM v2.0 assay detected low-level viremia (median 65 cp/ml) in more than one-third of those in whom viremia had been undetectable (<20 cp/ml) in assays using the NucliSens platform. These levels of viremia are of uncertain clinical significance but may be of importance in early detection of ART resistance in those on treatment. Overall the three assays showed good comparability of results but with consistent, albeit relatively small, discrepancies for HIV-1 clade-C samples, especially in the low-viremic range that should be taken into account when interpreting viral load data.