High level of genomic divergence in orf-I p12 and hbz genes of HTLV-1 subtype-C in Central Australia.

BACKGROUND: Human T cell lymphotropic virus type 1 (HTLV-1) infection remains a largely neglected public health problem, particularly in resource-poor areas with high burden of communicable and non-communicable diseases, such as some remote populations in Central Australia where an estimated 37% of adults are infected with HTLV-1. Most of our understanding of HTLV-1 infection comes from studies of the globally spread subtype-A (HTLV-1a), with few molecular studies reported with the Austral-Melanesian subtype-C (HTLV-1c) predominant in the Indo-Pacific and Oceania regions. RESULTS: Using a primer walking strategy and direct sequencing, we constructed HTLV-1c genomic consensus sequences from 22 First Nations participants living with HTLV-1c in Central Australia. Phylogenetic and pairwise analysis of this subtype-C proviral gDNA showed higher levels of genomic divergence in comparison to previously published HTLV-1a genomes. While the overall genomic homology between subtypes was 92.5%, the lowest nucleotide and amino acid sequence identity occurred near the 3' end of the proviral genome coding regulatory genes, especially overlapping hbz (85.37%, 77.46%, respectively) and orf-I product p12 (82.00%, 70.30%, respectively). Strikingly, the HTLV-1c genomic consensus sequences uniformly showed a defective translation start codon for the immune regulatory proteins p12/p8 encoded by the HTLV-1A orf-I. Deletions in the proviral genome were detected in many subjects, particularly in the structural gag, pol and env genes. Similarly, using a droplet digital PCR assay measuring the copies of gag and tax per reference host genome, we quantitatively confirmed that provirus retains the tax gene region at higher levels than gag. CONCLUSIONS: Our genomic analysis of HTLV-1c in Central Australia in conjunction with earlier Melanesian HTLV-1c sequences, elucidate substantial differences with respect to the globally spread HTLV-1a. Future studies should address the impact these genomic differences have on infection and the regionally distinctive frequency of associated pulmonary disease. Understanding the host and virus subtype factors which contribute to the differential morbidity observed, is crucial for the development of much needed therapeutics and vaccine strategies against this highly endemic infection in remote First Nations communities in Central Australia.

Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection.

Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.

High Human T-Cell Leukemia Virus Type 1c Proviral Loads Are Associated With Diabetes and Chronic Kidney Disease: Results of a Cross-Sectional Community Survey in Central Australia.

BACKGROUND: A link between chronic inflammation and several noncommunicable diseases (NCDs) has been established. Although chronic infection with the human T-cell leukemia virus type 1 (HTLV-1) is the recognized cause of several inflammatory diseases and these are associated with a high number of HTLV-1-infected cells in peripheral blood (proviral load [PVL]), possible interactions between PVL and NCDs have not been studied at a community level. METHODS: Adult Aboriginal residents of 7 remote communities were invited to complete a health survey between 25 August 2014 and 30 June 2018. Blood was drawn for HTLV-1 serology and PVL, and relevant medical conditions were obtained from health records. Associations between HTLV-1 PVL and diabetes, chronic kidney disease (CKD), and coronary artery disease (CAD) were determined using logistic regression, adjusting for available confounders. RESULTS: Among 510 participants (56% of the estimated adult resident population, 922), 197 (38.6%) were HTLV-1-infected. A high HTLV-1 PVL was associated with a 2-fold increase in the odds of diabetes and CKD (diabetes, adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.61; P = .033 and CKD: aOR, 2.00; 95% CI, 1.03-3.8; P = .041). A nonsignificant association between high PVL and CAD (aOR, 7.08; 95% CI, 1.00-50.18; P = .05) was found for participants aged <50 years at the time of angiography. CONCLUSIONS: In a community-based study in central Australia, people with HTLV-1 who had high HTLV-1 PVL were more likely to have diabetes and CKD. These findings have potential clinical implications.

Pulmonary Disease Is Associated With Human T-Cell Leukemia Virus Type 1c Infection: A Cross-sectional Survey in Remote Aboriginal Communities.

BACKGROUND: The human T-cell leukemia virus type 1 (HTLV-1) subtype c is endemic to central Australia. We report the first large-scale, community-based, health survey of HTLV-1 and its disease associations in this setting. METHODS: Aboriginal community residents aged >2 years in 7 remote communities were invited to do a health survey that included a questionnaire, spirometry, and clinical examination by a physician blinded to HTLV-1 status, clinical records, and spirometry results. Blood was drawn for HTLV-1 serology and proviral load (PVL). Pulmonary disease was assessed clinically and spirometrically and, where records were available, radiologically after the clinical assessment. Associations between specific diseases and HTLV-1 status were determined using logistic regression, adjusting for available confounders. RESULTS: Overall, 579 residents (164 children aged 3-17 years; 415 adults) were examined (37.7% of the estimated resident population). HTLV-1 prevalences for children and adults were 6.1% and 39.3%, respectively. No associations were found between HTLV-1 and any assessed clinical condition among children. Chronic pulmonary disease and gait abnormalities were more common among adults with HTLV-1 infection. Adjusted odds ratios among participants with PVL ≥1000 per 105 peripheral blood leukocytes were 7.08 (95% confidence interval [CI], 2.67-18.74; P < .001), 9.81 (95% CI, 3.52-27.35; P < .001), and 14.4 (95% CI, 4.99-41.69; P < .001) for clinically defined chronic pulmonary disease, moderate-severe expiratory airflow limitation, and radiologically determined bronchiectasis/bronchiolitis, respectively, and 5.21 (95% CI, 1.50-18.07; P = .009) for gait abnormalities. CONCLUSIONS: In the first study of HTLV-1 disease associations based on community recruitment and blinded assessment, HTLV-1 infection was strongly associated with pulmonary disease and gait abnormalities.

Human T-cell leukaemia virus type 1 associated pulmonary disease: clinical and pathological features of an under-recognised complication of HTLV-1 infection.

The lung is one of several organs that can be affected by HTLV-1 mediated inflammation. Pulmonary inflammation associated with HTLV-1 infection involves the interstitium, airways and alveoli, resulting in several clinical entities including interstitial pneumonias, bronchiolitis and alveolitis, depending on which structures are most affected. Augmentation of the inflammatory effects of HTLV-1 infected lymphocytes by recruitment of other inflammatory cells in a positive feedback loop is likely to underlie the pathogenesis of HTLV-1 associated pulmonary disease, as has been proposed for HTLV-1 associated myelopathy. In contrast to the conclusions of early case series, HTLV-1 associated pulmonary disease can be associated with significant parenchymal damage, which may progress to bronchiectasis where this involves the airways. Based on our current understanding of HTLV-1 associated pulmonary disease, diagnostic criteria are proposed.

Risk factors for HTLV-1, acute kidney injury, and urinary tract infection among aboriginal adults with end stage kidney disease in central Australia.

Central Australia is a human T-cell leukemia virus type 1c (HTLV-1c) endemic region and has the highest incidence of chronic kidney disease (CKD) in Australia. The factors associated with HTLV-1 seropositivity among Aboriginal Australian adults with CKD receiving hemodialysis (HD) were determined. A retrospective observational study of Aboriginal adults (≥ 18 years) who were receiving regular HD at the two main dialysis units in Alice Springs, December 1, 2010 to December 31, 2015. Demographic and clinical data before commencing HD were extracted from hospital records from the first presentation to Alice Springs Hospital (ASH) to HD commencement and associations were determined using logistic regression. Among 373 patients receiving HD, 133 (35.9%) were HTLV-1 infected. Identifiable factors associated with HTLV-1 status included increasing age, male gender, and diabetes before HD. The odds of diabetes mellitus were significantly higher among patients with HTLV-1 (adjusted odds ratio [aOR]: 2.76, 95% confidence interval [CI]: 1.19, 6.39; p = 0.017). More than one-fifth of participants had an acute kidney injury, the risk of which was increased among those with a previous blood stream infection (aOR: 3.02, 95% CI: 1.71, 5.34, p < 0.001). Men with a high HTLV-1 proviral load (≥500 copies per 105 peripheral blood leukocytes) had an increased risk of urinary tract infection (UTI) before HD (aOR: 5.15, 95% CI: 1.62, 16.40; p = 0.006). A strong association between HTLV-1 and diabetes, and an increased risk of UTI among men with a high HTLV-1 PVL, suggest that interactions between HTLV-1 infection and conventional risk factors may increase the risk for CKD in this population.

Impact of Hepatitis B Virus Coinfection on Human T-Lymphotropic Virus Type 1 Clonality in an Indigenous Population of Central Australia.

The prevalence of human T-cell lymphotropic virus type 1 (HTLV-1) and hepatitis B virus (HBV) coinfection is high in certain Indigenous Australian populations, but its impact on HTLV-1 has not been described. We compared 2 groups of Indigenous adults infected with HTLV-1, either alone or coinfected with HBV. The 2 groups had a similar HTLV-1 proviral load, but there was a significant increase in clonal expansion of HTLV-1-infected lymphocytes in coinfected asymptomatic individuals. The degree of clonal expansion was correlated with the titer of HBV surface antigen. We conclude that HTLV-1/HBV coinfection may predispose to HTLV-1-associated malignant disease.

Multiplex Droplet Digital PCR Assay for Quantification of Human T-Cell Leukemia Virus Type 1 Subtype c DNA Proviral Load and T Cells from Blood and Respiratory Exudates Sampled in a Remote Setting.

During human T-cell leukemia virus type 1 (HTLV-1) infection, the frequency of cells harboring an integrated copy of viral cDNA, the proviral load (PVL), is the main risk factor for progression of HTLV-1-associated diseases. Accurate quantification of provirus by droplet digital PCR (ddPCR) is a powerful diagnostic tool with emerging uses for monitoring viral expression. Current ddPCR techniques quantify HTLV-1 PVL in terms of whole genomic cellular material, while the main targets of HTLV-1 infection are CD4+ and CD8+ T cells. Our understanding of HTLV-1 proliferation and the amount of viral burden present in different compartments is limited. Recently a sensitive ddPCR assay was applied to quantifying T cells by measuring loss of germ line T-cell receptor genes as method of distinguishing non-T-cell from recombined T-cell DNA. In this study, we demonstrated and validated novel applications of the duplex ddPCR assay to quantify T cells from various sources of human genomic DNA (gDNA) extracted from frozen material (peripheral blood mononuclear cells [PBMCs], bronchoalveolar lavage fluid, and induced sputum) from a cohort of remote Indigenous Australians and then compared the T-cell measurements by ddPCR to the prevailing standard method of flow cytometry. The HTLV-1 subtype c (HTLV-1c) PVL was then calculated in terms of extracted T-cell gDNA from various compartments. Because HTLV-1c preferentially infects CD4+ T cells, and the amount of viral burden correlates with HTLV-1c disease pathogenesis, application of this ddPCR assay to accurately measure HTLV-1c-infected T cells can be of greater importance for clinical diagnostics and prognostics as well as monitoring therapeutic applications.

Higher human T-cell leukaemia virus type 1 (HTLV-1) proviral load is associated with end-stage kidney disease in Indigenous Australians: Results of a case-control study in central Australia.

Case series suggest that human T-cell leukaemia virus type 1 (HTLV-1) is associated with kidney disease; however, little is known about the impact of proviral load (PVL). The present study was commenced to determine whether higher HTLV-1 PVL is associated with end stage kidney disease (ESKD) in Indigenous Australians. A case-control study was conducted in Alice Springs Hospital (ASH), 1 July 2007 to 30 November 2015. Cases included all 80 Indigenous adults (>17 years) with HTLV-1c and ESKD, matched 1:1 by sex to controls with HTLV-1 who had no renal disease or other recognised disease associations of HTLV-1, and were recruited during the same period. The association between PVL and ESKD was assessed using logistic regression. Median (IQR) HTLV-1c PVL for subjects with ESKD (6.86, IQR (3.35, 8.23) log copies per 105 peripheral blood leukocytes (PBL) (ie, 0.95; IQR, 0.03; 3.70% PBL) was significantly higher than that of the asymptomatic group (3.47; IQR (-0.04, 6.61) log copies per 10 5 PBL (ie, 0.01; IQR, 0.00; 0.52% PBL) (asymptomatic vs ESKD, P (ranksum) < .001). Major factors associated with ESKD were diabetes (adjusted odds ratio [aOR], 21.80; 95% CI, 4.84, 98.22; P < .001), hypertension (aOR, 4.16; 1.11, 15.64; P = .03), remote residence (aOR, 5.34; 95% CI, 1.17, 27.29; P = .03) and HTLV-1c PVL greater than or equal to 100 copies per 10 5 PBL (aOR, 3.67; 95% CI, 1.36, 9.92; P = .01). Higher HTLV-1c PVL are strongly associated with inflammatory diseases. The high HTLV-1c PVL reported here may have clinical implications for people with HTLV-1 who require haemodialysis. Longitudinal studies are required to determine whether this association is causal.

Bronchiectasis in indigenous and non-indigenous residents of Australia and New Zealand.

BACKGROUND AND OBJECTIVE: Bronchiectasis not associated with cystic fibrosis is an increasingly recognized chronic lung disease. In Oceania, indigenous populations experience a disproportionately high burden of disease. We aimed to describe the natural history of bronchiectasis and identify risk factors associated with premature mortality within a cohort of Aboriginal Australians, New Zealand Maori and Pacific Islanders, and non-indigenous Australians and New Zealanders. METHODS: This was a retrospective cohort study of bronchiectasis patients aged >15 years at three hospitals: Alice Springs Hospital and Monash Medical Centre in Australia, and Middlemore Hospital in New Zealand. Data included demographics, ethnicity, sputum microbiology, radiology, spirometry, hospitalization and survival over 5 years of follow-up. RESULTS: Aboriginal Australians were significantly younger and died at a significantly younger age than other groups. Age- and sex-adjusted all-cause mortality was higher for Aboriginal Australians (hazard ratio (HR): 3.9), and respiratory-related mortality was higher for both Aboriginal Australians (HR: 4.3) and Maori and Pacific Islander people (HR: 1.7). Hospitalization was common: Aboriginal Australians had 2.9 admissions/person-year and 16.9 days in hospital/person-year. Despite Aboriginal Australians having poorer prognosis, calculation of the FACED score suggested milder disease in this group. Sputum microbiology varied with Aspergillus fumigatus more often isolated from non-indigenous patients. Airflow obstruction was common (66.9%) but not invariable. CONCLUSIONS: Bronchiectasis is not one disease. It has a significant impact on healthcare utilization and survival. Differences between populations are likely to relate to differing aetiologies and understanding the drivers of bronchiectasis in disadvantaged populations will be key.

Turning a blind eye: HTLV-1-associated uveitis in Indigenous adults from Central Australia.

PURPOSE: We describe the first two cases of HTLV-1 associated uveitis to be associated with HTLV-1c subtype infection. METHODS: Case report. RESULTS: Uveitis was demonstrated in two Indigenous Australian men, both of whom had high HTLV-1c proviral loads in peripheral blood. Visual outcomes were poor in each case. CONCLUSION: Clinicians should be aware of HTLV-1c infection as a cause of uveitis in Australia, and HTLV-1 serology should be included in the basic uveitis work-up in HTLV-1-endemic areas.

The prevalence and clinical associations of HTLV-1 infection in a remote Indigenous community.

OBJECTIVE: Hospital and laboratory data indicate that human T-lymphotropic virus type 1 (HTLV-1) is endemic to central Australia, but no community-based studies of its prevalence or disease burden have been reported. We determined the prevalence rates of HTLV-1 infection and of HTLV-1-associated diseases in a remote Indigenous community. SETTING: A remote Northern Territory community. DESIGN: All residents were asked to complete a health survey and offered a limited clinical examination, together with serological tests for HTLV-1 and Strongyloides, and HTLV-1 proviral load (PVL) assessment. MAIN OUTCOME MEASURES: HTLV-1 seropositivity rates; HTLV-1 PVL (copies/105 peripheral blood leucocytes [PBL]); presentation with HTLV-1-related clinical disease. RESULTS: HTLV-1 serostatus was determined for 97 of 138 residents (70%). The prevalence of HTLV-1 infection was significantly higher among adults (30 of 74 people tested) than children (1 of 23; P = 0.001). Nine of 30 HTLV-1-positive adults had a clinical syndrome that was potentially attributable to HTLV-1 infection (chronic lung disease, seven; symptomatic strongyloidiasis, two). The median HTLV-1 PVL was significantly higher for adults with chronic lung disease than for those who were asymptomatic (chronic lung disease, 649 copies/105 PBL [IQR, 162-2220]; asymptomatic adults, 40 copies/105 PBL [IQR, 0.9-229]; P = 0.017). Ten of 72 adults tested were seropositive for Strongyloides (six of 28 HTLV-1-positive participants and four of 44 HTLV-1-negative participants; P = 0.17), as were three of 15 children tested; the three children were HTLV-1-negative. CONCLUSION: The prevalence of HTLV-1 infection and the rate of disease potentially attributable to HTLV-1 were high among adults in this remote community.

Human T-Lymphotropic Virus type 1 infection in an Indigenous Australian population: epidemiological insights from a hospital-based cohort study.

BACKGROUND: The Human T Lymphotropic Virus type 1 (HTLV-1) subtype C is endemic to central Australia where each of the major sequelae of HTLV-1 infection has been documented in the socially disadvantaged Indigenous population. Nevertheless, available epidemiological information relating to HTLV-1c infection is very limited, risk factors for transmission are unknown and no coordinated program has been implemented to reduce transmission among Indigenous Australians. Identifying risk factors for HTLV-1 infection is essential to direct strategies that could control HTLV-1 transmission. METHODS: Risk factors for HTLV-1 infection were retrospectively determined for a cohort of Indigenous Australians who were tested for HTLV-1 at Alice Springs Hospital (ASH), 1st January 2000 to 30th June 2013. Demographic details were obtained from the ASH patient management database and the results of tests for sexually transmitted infections (STI) were obtained from the ASH pathology database. RESULTS: Among 1889 Indigenous patients whose HTLV-1 serostatus was known, 635 (33.6 %) were HTLV-1 Western blot positive. Only one of 77 (1.3 %) children tested was HTLV-1 infected. Thereafter, rates progressively increased with age (15-29 years, 17.3 %; 30-49 years, 36.2 %; 50-64 years, 41.7 %) reaching 48.5 % among men aged 50-64 years. In a multivariable model, increasing age (OR, 1.04; 95 % CI, 1.03-1.04), male gender (OR, 1.41; 95 % CI, 1.08-1.85), residence in the south (OR, 10.7; 95 % CI, 7.4-15.6) or west (OR, 4.4; 95 % CI, 3.1-6.3) of central Australia and previous STI (OR, 1.42; 95 % CI, 1.04-1.95) were associated with HTLV-1 infection. Infection was acquired by three of 351 adults who were tested more than once during the study period (seroconversion rate, 0.24 (95 % CI = 0.18-2.48) per 100 person-years). CONCLUSIONS: This study confirms that HTLV-1 is highly endemic to central Australia. Although childhood infection was documented, HTLV-1 infection in adults was closely associated with increasing age, male gender and STI history. Multiple modes of transmission are therefore likely to contribute to high rates of HTLV-1 infection in the Indigenous Australian population. Future strategies to control HTLV-1 transmission in this population require careful community engagement, cultural understanding and Indigenous leadership.

Variant human T-cell lymphotropic virus type 1c and adult T-cell leukemia, Australia.

Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c.

Self-discharge by adult Aboriginal patients at Alice Springs Hospital, Central Australia: insights from a prospective cohort study.

OBJECTIVE: To determine rates and risk factors for self-discharge by Aboriginal medical inpatients at Alice Springs Hospital. METHODS: Prospective cohort study. Interviews were conducted in primary language by Aboriginal Liaison Officers, from July 2006 to August 2007. Topics included understanding of diagnosis, satisfaction with services and perceptions of staff and environment. Risk factors for self-discharge were then determined prospectively. RESULTS; During the study period 202 (14.7%) of 1380 patients admitted to general medical units at Alice Springs Hospital, were interviewed. Self-discharge rates for all admissions were significantly lower during the study period than they had been previously (pre-study, mean 22.9±standard error 0.3%; study, 17.0±0.2%) (P<0.001). Most interviewees (73.4%) did not know their reason for admission (73.4%) or estimated length of stay (82.3%). Forty interviewees (19.8%) self-discharged. Mean monthly self-discharge rates differed between the three medical units (Unit A, 13.9±0.3%; Unit B, 17.3±1.37%; Unit C, 20.0±0.4%) (P=0.005). Multivariable predictors of self-discharge included male sex (hazard ratio (HR) 2.4; 95% confidence interval (CI) 1.1, 5.2), a past history of self-discharge (HR 3.2; 95%CI 1.5, 6), planned transfer to a tertiary referral centre (HR 3.8; 95%CI 1.3-7.4) and a desire to drink alcohol (HR 4.5; 95%CI 1.8-10.2). CONCLUSIONS: Physician, institutional and patient factors all contribute to self-discharge. Improving cultural safety may be the key to lowering self-discharge rates. WHAT IS KNOWN ABOUT THE TOPIC? Rates of self-discharge by Aboriginal adults in Central Australia are the highest reported worldwide. Previous studies have been retrospective and focussed on patient demographics without addressing the environmental and cultural contexts in which self-discharge occurs. WHAT DOES THIS PAPER ADD? In this acute care setting, we found a pervasive failure to communicate effectively with Aboriginal patients. Consequently, most patients were unaware of their diagnosis or length of stay. Self-discharge was a common practice; nearly half of all previously admitted patients had self-discharged in the past. We demonstrate that physician, hospital and patient factors all contribute to this practice. Prospectively determined risk factors included the treating medical team, the need for transfer outside Central Australia, and patient factors such as male gender and alcohol dependence. Self-discharge rates fell significantly with Aboriginal Liaison involvement. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Cross-cultural communication skills must be markedly improved among medical staff caring for this marginalised population. Critical to reducing rates of self-discharge are improvements in institutional cultural safety by involving Aboriginal Liaison Officers and family members. However, persistently high self-discharge rates suggest a need to redirect medical services to a more culturally appropriate community-based model of care.

Bronchiectasis is associated with human T-lymphotropic virus 1 infection in an Indigenous Australian population.

BACKGROUND: Recent studies suggest that infection with human T-lymphotropic virus 1 (HTLV-1) might be associated with bronchiectasis among Indigenous Australians. The present study compared the clinical characteristics and outcomes of bronchiectasis in this population, according to HTLV-1 serologic status. METHODS: We performed a retrospective cohort study of Indigenous adults with bronchiectasis and known HTLV-1 serologic status admitted to Alice Springs Hospital, central Australia, from January 2000 through December 2006. RESULTS: Among 89 Indigenous adults whose HTLV-1 serologic status was confirmed, 52 (58.4%) were HTLV-1 seropositive. Differences between HTLV-1-seropositive and HTLV-1-seronegative groups were apparent in childhood presentations and adult outcomes. Among adults, an increasing number of bronchiectatic lobes (univariable odds ratio [OR], 1.51; 95% confidence interval [CI]; 1.03-2.20; P = .033) and the presence of ground-glass opacities at chest high-resolution computed tomography (univariable OR, 8.54; 95% CI, 1.04-70.03; P = .046) predicted HTLV-1 infection. Cor pumonale (HTLV-1-positive group, 10/52; HTLV-1-negative group, 1/37; P = .023) was more frequent among HTLV-1-seropositive adults, who also experienced a higher disease-specific mortality (univariable OR, 5.78; 95% CI, 1.17-26.75; P = .028). Only HTLV-1-seropositive patients were admitted specifically for the treatment of infected skin lesions, and this finding predicted death (multivariable OR, 6.77; 95% CI, 1.46-31.34; P = .014). Overall mortality was high; 34.2% of the cohort died at a median age of 42.5 years. CONCLUSIONS: HTLV-1 infection contributes to the risk of developing bronchiectasis and worsens outcomes among Indigenous Australians.

Impact of ethnicity and socio-economic status on Staphylococcus aureus bacteremia incidence and mortality: a heavy burden in Indigenous Australians.

BACKGROUND: Investigations of the impact of ethnicity and socio-economic status on incidence and outcomes of Staphylococcus aureus bacteraemia are limited. METHODS: We prospectively identified all S. aureus bacteraemia episodes in the Australian New Zealand Cooperative on Outcomes in Staphylococcal Sepsis cohort study between 2007 and 2010. We calculated population level incidence rates using regional postcodes and stratified the analysis by ethnicity, age and socio-economic status indexes. RESULTS: There were 7539 episodes of S. aureus bacteraemia with an annual incidence of 11·2 episodes per 100,000 population. The age-adjusted incidence in the Indigenous population was 62·5 per 100,000 population with an age standardized incidence rate ratio of 5·9 compared to the non-Indigenous population and an incidence rate ratio of 29.2 for community-associated methicillin-resistant S. aureus (MRSA). Populations in the lowest socio-economic status quintile had an increased S. aureus bacteraemia incidence compared to higher quintiles. However, there was a disparity between Indigenous and non-Indigenous populations across all socio-economic status quintiles. The lower 30-day mortality for Indigenous patients (7%) compared to non-Indigenous patients (17%) was explained by differences in age. CONCLUSIONS: Indigenous Australians suffer from a higher rate of S. aureus bacteraemia than non-Indigenous Australians, particularly for community-associated MRSA. Ethnicity and socio-economic status had little impact on subsequent mortality, with other host factors contributing more significantly.