Other Conditions Associated with HTLV-1

Overview

HTLV-1 infection is associated with an increase in all-cause mortality.  HTLV-1 infection may be associated with inflammatory and infective conditions resulting in either more significant disease or different disease characteristics or both. Conditions that are diagnosed more frequently in people infected with HTLV-1 include seborrheic dermatitis, tuberculosis, bronchitis, bronchiectasis and bronchiolitis, Sjogren’s syndrome, Stronglyoides hyperinfection syndrome and symptomatic Strongyloidiasis, urinary tract infection, thyroid disease and liver cancer. The strength of association of these conditions and HTLV-1 found in the meta-analysis below, was either limited or very limited except for tuberculosis where the strength was moderate. 

A full list of the possible disease associations examined by the meta-analysis is included in the table below.  

Meta-analysis of HTLV-1 Associated Conditions

In addition to diseases that are designated as HTLV-1associated conditions, that is, where HLTV-1 infection is required for the diagnosis, a number of other conditions have been investigated for their association with HTLV-1.  

The following table provided is an overall summary of a published meta-analysis of studies showing significant associations between HTLV-1 infection and either disease or death.  

HTLV-1 and Respiratory Diseases

There is very limited evidence for an association between HTLV-1 and bronchiectasis, bronchitis, bronchiolitis and asthma. International research has not found an association between respiratory diseases and HTLV-1 infection.  

One non-Australian study found an association between self-reported diagnosis of asthma and HTLV-1 infection. Two case control studies in Central Australia within the same hospital population found statistically significant associations between HTLV-1 and radiologically confirmed bronchiectasis, bronchitis and bronchiolitis, and one cross-sectional study from Central Australia found a strong association between HTLV-1 and pulmonary disease. However, an analysis of children with bronchiectasis attending Royal Darwin Hospital (a population with a similarly high prevalence of bronchiectasis to Central Australia) found no cases of HTLV-1 in the 299 children tested. 

The proposed mechanism of persistent HTLV-1 mediated airways inflammation leading to progressive bronchial wall dilatation and bronchiectasis has similarities to the mechanism of inflammation which underlies HTLV-1 associated myelopathy (HAM).  

More research is needed to understand the role that HTLV-1 plays in respiratory diseases, especially considering the high prevalence and burden of bronchiectasis and pulmonary disease in Aboriginal People living across the Northern Territory and adjacent areas of South Australia and Western Australia. It is also acknowledged that the subtype of HTLV-1 prevalent in Australia is different to subtypes prevalent internationally, so it is possible and plausible that there could be an association.

HTLV-1 and Tuberculosis

The most studied HTLV-1 related condition identified in the meta-analysis was pulmonary tuberculosis, possibly because of the strong causative association between TB and HIV, and similarities between HTLV-1 and HIV. Analysis suggests that the risk of developing tuberculosis is higher in patients with HTLV-1: the pooled odds of developing tuberculosis is 2.04 times (95% CI 1.36-3.06) higher in people with HTLV-1, thought to be secondary to the immune response increasing susceptibility. The strength of the evidence connecting these two conditions is low to moderate.

HTLV-1 and Autoimmune Diseases

There may be an increased risk of rheumatoid arthritis (RA) and Sjogren’s syndrome associated with HTLV-1 infection. Some research has suggested that there is attenuated effectiveness of TNF inhibitor medications (tumor necrosis factor) in HTLV-1-positive patients with RA. However, treatment recommendations are unchanged and at present testing for HTLV-1 prior to commencing treatment with DMARDs (disease modifying anti-rheumatic drugs) is not recommended. There is almost no data on systemic lupus erythematosus (SLE) in relation to HTLV-1. 

HTLV-1 and Strongyloidiasis

There is very limited evidence for an association between either Strongyloidiasis hyper infection syndrome or symptomatic strongyloidiasis and HTLV-1 infection. Some research showed higher rates of Strongyloidiasis treatment failure for HTLV-1 positive patients. However, this does not appear to apply to the CAPRA-recommended treatment regime of ivermectin. Due to a high prevalence of Strongyloidiasis infection in Central Australia, the risk of symptomatic strongyloidiasis or Strongyloidiasis hyper infection should be considered in patients living with HTLV-1 despite the weak evidence for an association. 

HTLV-1 and Scabies

There is some evidence that in areas that are endemic for scabies, individuals living with HTLV-1 are more susceptible for either recurrent scabies or crusted scabies. However, the strength of this evidence is low. There is significant morbidity associated with skin diseases in Central Australia, such as acute rheumatic fever and post-streptococcal glomerulonephritis. Regardless of an individual’s HTLV-1 status, early detection and treatment, and ongoing monitoring of crusted scabies is important for reduction in spread and associated morbidity.   

HTLV-1 and All-Cause Mortality

In addition to these conditions that are statistically associated with HTLV1, HTLV-1 infection is associated with an increase in all-cause mortality, with a pooled relative risk of 1.57 (95% CI 1.37-1.80).  The association appears to be slightly stronger among men. This increase is not explained by the impact that the HTLV-1 associated conditions, in particular ATLL, has on mortality. The mortality increase is consistent across different settings, in diverse geographical locations and across different subtypes, however there are no reported studies on mortality in Aboriginal people in Australia as yet.