Lloyd Einsiedel

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

BackgroundInvestigations of the impact of ethnicity and socio-economic status on incidence and outcomes of Staphylococcus aureus bacteraemia are limited.MethodsWe 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.ResultsThere 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.ConclusionsIndigenous 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.

Human T-Cell Lymphotropic Virus Type 1 Subtype C Molecular Variants among Indigenous Australians: New Insights into the Molecular Epidemiology of HTLV-1 in Australo-Melanesia

Background HTLV-1 infection is endemic among people of Melanesian descent in Papua New Guinea, the Solomon Islands and Vanuatu. Molecular studies reveal that these Melanesian strains belong to the highly divergent HTLV-1c subtype. In Australia, HTLV-1 is also endemic among the Indigenous people of central Australia; however, the molecular epidemiology of HTLV-1 infection in this population remains poorly documented. Findings Studying a series of 23 HTLV-1 strains from Indigenous residents of central Australia, we analyzed coding (gag, pol, env, tax) and non-coding (LTR) genomic proviral regions. Four complete HTLV-1 proviral sequences were also characterized. Phylogenetic analyses implemented with both Neighbor-Joining and Maximum Likelihood methods revealed that all proviral strains belong to the HTLV-1c subtype with a high genetic diversity, which varied with the geographic origin of the infected individuals. Two distinct Australians clades were found, the first including strains derived from most patients whose origins are in the North, and the second comprising a majority of those from the South of central Australia. Time divergence estimation suggests that the speciation of these two Australian clades probably occurred 9,120 years ago (38,000–4,500). Conclusions The HTLV-1c subtype is endemic to central Australia where the Indigenous population is infected with diverse subtype c variants. At least two Australian clades exist, which cluster according to the geographic origin of the human hosts. These molecular variants are probably of very ancient origin. Further studies could provide new insights into the evolution and modes of dissemination of these retrovirus variants and the associated ancient migration events through which early human settlement of Australia and Melanesia was achieved.

Clinical associations of Human T-Lymphotropic Virus type 1 infection in an indigenous Australian population.

Introduction In resource-poor areas, infectious diseases may be important causes of morbidity among individuals infected with the Human T-Lymphotropic Virus type 1 (HTLV-1). We report the clinical associations of HTLV-1 infection among socially disadvantaged Indigenous adults in central Australia. Methodology and Principal Findings HTLV-1 serological results for Indigenous adults admitted 1st January 2000 to 31st December 2010 were obtained from the Alice Springs Hospital pathology database. Infections, comorbid conditions and HTLV-1 related diseases were identified using ICD-10 AM discharge morbidity codes. Relevant pathology and imaging results were reviewed. Disease associations, admission rates and risk factors for death were compared according to HTLV-1 serostatus. HTLV-1 western blots were positive for 531 (33.3%) of 1595 Indigenous adults tested. Clinical associations of HTLV-1 infection included bronchiectasis (adjusted Risk Ratio, 1.35; 95% CI, 1.14–1.60), blood stream infections (BSI) with enteric organisms (aRR, 1.36; 95% CI, 1.05–1.77) and admission with strongyloidiasis (aRR 1.38; 95% CI, 1.16–1.64). After adjusting for covariates, HTLV-1 infection remained associated with increased numbers of BSI episodes (adjusted negative binomial regression, coefficient, 0.21; 95% CI, 0.02–0.41) and increased admission numbers with strongyloidiasis (coefficient, 0.563; 95% CI, 0.17–0.95) and respiratory conditions including asthma (coefficient, 0.99; 95% CI, 0.27–1.7), lower respiratory tract infections (coefficient, 0.19; 95% CI, 0.04–0.34) and bronchiectasis (coefficient, 0.60; 95% CI, 0.02–1.18). Two patients were admitted with adult T-cell Leukemia/Lymphoma, four with probable HTLV-1 associated myelopathy and another with infective dermatitis. Independent predictors of mortality included BSI with enteric organisms (aRR 1.78; 95% CI, 1.15–2.74) and bronchiectasis (aRR 2.07; 95% CI, 1.45–2.98). Conclusion HTLV-1 infection contributes to morbidity among socially disadvantaged Indigenous adults in central Australia. This is largely due to an increased risk of other infections and respiratory disease. The spectrum of HTLV-1 related diseases may vary according to the social circumstances of the affected population.

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.

Staphylococcus aureus bacteraemia at Alice Springs Hospital, Central Australia, 2003–2006

Background:  Infectious diseases remain the leading cause of death at Alice Springs Hospital (ASH) and Staphylococcus aureus bacteraemia (SAB) is the second most common bloodstream infection. Non‐multidrug‐resistant, methicillin‐resistant S. aureus (nmMRSA) is endemic to the region.

Higher human T-lymphotropic virus type 1 subtype C proviral loads are associated with bronchiectasis in indigenous australians: results of a case-control study.

In this case-control study, HTLV-1 infection increased risk of bronchiectasis 1.84 times. HTLV-1 proviral loads for bronchiectasis patients were significantly higher than those of controls. HTLV-1 proviral loads correlated with the extent of radiologically determined pulmonary injury.

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.

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.

Human T-lymphotropic virus type 1 infective dermatitis in central Australia.

The Human T-Lymphotropic Virus type 1 (HTLV-1) is a single-stranded RNA retrovirus that preferentially infects CD4+ T cells. The spectrum of diseases that are associated with the most frequent genotype, the HTLV-1 cosmopolitan subtype A, has been well described. In contrast, very few cases of HTLV-1 related diseases have been reported for the HTLV-1 subtype C variant, which is endemic to Australia and the nearby islands of Melanesia. Here we describe the first case of infective dermatitis associated with the HTLV-1 Australo-Melanesian subtype C. This was complicated by repeated episodes of invasive infection with Staphylococcus aureus and illustrates the life-threatening nature of infective dermatitis among HTLV-1 carriers who live in conditions of social disadvantage.