Higher human T-lymphotropic virus type 1 subtype C proviral loads are associated with bronchiectasis in indigenous australians: results of a case-control study.
BACKGROUND
We previously suggested that infection with the human T-lymphotropic virus type 1 (HTLV-1) subtype C is associated with bronchiectasis among Indigenous Australians. Bronchiectasis might therefore result from an HTLV-1-mediated inflammatory process that is typically associated with a high HTLV-1 proviral load (PVL). Human T-lymphotropic virus type 1 PVL have not been reported for Indigenous Australians.


METHODS
Thirty-six Indigenous adults admitted with bronchiectasis from June 1, 2008, to December 31, 2009 were prospectively recruited and matched by age, sex, and ethno-geographic origin to 36 controls. Case notes and chest high-resolution computed tomographs were reviewed, and pulmonary injury scores were calculated. A PVL assay for the HTLV-1c subtype that infects Indigenous Australians was developed and applied to this study. Clinical, radiological, and virological parameters were compared between groups and according to HTLV-1 serostatus.


RESULTS
Human T-lymphotropic virus type 1 infection was the main predictor of bronchiectasis in a multivariable model (adjusted risk ratio [aRR], 1.84; 95% confidence interval [CI], 1.19-2.84; P = .006). Moreover, the median HTLV-1c PVL (interquartile range) for cases was >100-fold that of controls (cases, 0.319 [0.007, 0.749]; controls, 0.003 [0.000, 0.051] per 100 peripheral blood lymphocytes; P = .007), and HTLV-1c PVL were closely correlated with radiologically determined pulmonary injury scores (Spearman's rho = 0.7457; P = .0000). Other predictors of bronchiectasis were positive Strongyloides serology (aRR, 1.69; 95% CI, 1.13-2.53) and childhood skin infections (aRR, 1.62; 95% CI, 1.07-2.44). Bronchiectasis was the major predictor of death (aRR, 2.71; 95% CI, 1.36-5.39; P = .004).


CONCLUSIONS
These data strongly support an etiological association between HTLV-1 infection and bronchiectasis in a socially disadvantaged population at risk of recurrent lower respiratory tract infections.
Northern Territory Rural Clinical School/Flinders University , Northern Territory of Australia , Australia ; SA Pathology, Adelaide , South Australia , Australia.
Lloyd
L
Einsiedel
Institut Pasteur, Unité EPVO, Département de Virologie , F-75015 Paris , France ; CNRS, UMR 3569 , F-75015 Paris , France.
Olivier
O
Cassar
Department of Paediatrics , Alice Springs Hospital, Northern Territory of Australia , Australia.
Emma
E
Goeman
Northern Territory Rural Clinical School/Flinders University , Northern Territory of Australia , Australia.
Tim
T
Spelman
Department of Radiology , Flinders Medical Centre , Adelaide, South Australia , Australia.
Virginia
V
Au
Department of Radiology , Flinders Medical Centre , Adelaide, South Australia , Australia.
Saba
S
Hatami
Northern Territory Rural Clinical School/Flinders University , Northern Territory of Australia , Australia.
Sheela
S
Joseph
Institut Pasteur, Unité EPVO, Département de Virologie , F-75015 Paris , France ; CNRS, UMR 3569 , F-75015 Paris , France.
Antoine
A
Gessain
Australia; HTLV-1; HTLV-1 proviral load; Indigenous; Strongyloides stercoralis; bronchiectasis; pulmonary disease