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

Abstract

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.

Keywords: Australia; HTLV-1; HTLV-1 proviral load; Indigenous; Strongyloides stercoralis; bronchiectasis; pulmonary disease.

Figure 1.

Human T-lymphotropic virus type 1 (HTLV-1) subtype C proviral loads for cases and controls. Box plot depicting median (interquartile range [IQR]) HTLV-1 proviral loads for 24 bronchiectasis cases and 15 controls. Human T-lymphotropic virus type 1 subtype C proviral load expressed as proviral copies per 100 peripheral blood lymphocytes. Data are logarithmically transformed for clarity of presentation.

Figure 2.

Pulmonary injury scores versus human T-lymphotropic virus type 1 (HTLV-1) subtype C proviral load. Correlation between HTLV-1c proviral loads (proviral copies per 100 peripheral blood lymphocytes) and pulmonary injury scores, which were calculated by applying a predetermined scoring system to chest high-resolution computed tomography for 29 HTLV-1-seropositive patients (bronchiectasis, 21; no bronchiectasis, 8). Spearman's rho = 0.7457; Prob > |t| = 0.0000.