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

Abstract

Background The human T-cell leukaemia 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 seven 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 (children aged 3-17, 164; adults, 415) 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 (aOR)(95% CI) among participants with PVL ≥ 1000 per 10 5 PBL were 7.08 (2.67, 18.74; p<0.001), 9.81 (3.52, 27.35; p<0.001) and 14.4 (4.99, 41.69; p<0.001) for clinically defined chronic pulmonary disease, moderate-severe expiratory airflow limitation and radiologically determined bronchiectasis/bronchiolitis, respectively, and 5.21 (1.50, 18.07; p=0.009) for gait abnormalities. Conclusion 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.

Very high prevalence of infection with the human T cell leukaemia virus type 1c in remote Australian Aboriginal communities: Results of a large cross-sectional community survey

“…The study also systematically measured HTLV-1 PVL in study participants, extending previously published observations from these communities [ 11 ] to reveal a wide range of inter-individual HTLV-1 proviral loads, exceeding 1000 copies per 10 5 PBL for 36% of participants with HTLV-1. An HTLV-1 PVL exceeding this level has been associated with serious adverse outcomes, including bronchiectasis and death, in hospital-based studies in this population [ 25 , 26 ].…”

“…The symptomatic group comprised predefined HTLV-1 related diseases: i) a haematological diagnosis of ATL, ii) radiologically defined bronchiectasis/bronchiolitis, iii) non-diabetic eye diseases diagnosed by an ophthalmologist, and documentation in the medical records of iv) myositis, v) infective dermatitis and vi) a diagnosis of ‘myelopathy’ or neurological symptoms associated with HTLV-1 [ 22 , 23 ] that were not explained by other causes. Clinical details for a subset of participants who were examined by a specialist in internal medicine (LE) have been published previously [ 11 ].…”

“…A minority of people with HTLV-1 develop serious HTLV-1 associated complications including a rapidly progressive haematological malignancy (adult T cell leukaemia/lymphoma, ATL) [ 7 , 8 ] and several inflammatory disorders, the best studied of which is HTLV-1 associated myelopathy (HAM) [ 9 , 10 ]. Risk of these conditions is associated with a higher number of HTLV-1 infected cells in peripheral blood (HTLV-1 proviral load, PVL) [ 1 ], which was also a risk factor for pulmonary disease and gait abnormalities in a recent clinical survey in central Australia [ 11 ].…”

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

“…HTLV‐1 is a human retrovirus that infects as many as 20 million people worldwide 14 . The virus preferentially infects CD4 + T‐cells 15 and is the recognized cause of adult T‐cell leukemia (ATL) and inflammatory diseases, including HTLV‐1 associated myelopathy/tropical spastic paraparesis (HAM), uveitis, and pulmonary disease 15–17 . The virus is also associated with intractable infective dermatitis and with complicated infections with parasites such as Strongyloides stercoralis and scabies 15 .…”

“…14 The virus preferentially infects CD4 + T-cells 15 and is the recognized cause of adult T-cell leukemia (ATL) and inflammatory diseases, including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM), uveitis, and pulmonary disease. [15][16][17] The virus is also associated with intractable infective dermatitis and with complicated infections with parasites such as Strongyloides stercoralis and scabies. 15 The risk of developing an HTLV-1 associated complication is strongly associated with the number of HTLV-1infected cells in the peripheral blood, the HTLV-1 proviral load (PVL).…”