Recombinant Human T-Cell Lymphotropic Virus Type II gp21+gp46 chimeric antigen

Author summary HTLV-1 is a life-long persistent infection with no curative treatment available. It can cause a disabling neurological disease (HAM/TSP). Public policies aiming HTLV-1 prevention are important. Cost-utility studies are essential to identify which policies should be implemented. These studies have been hampered by the lack of information about health state utility values in patients with HAM/TSP and asymptomatic carriers (AC). These values represent the quality of life (QoL) and may vary from 0 (death) to 1 (best health state). We determined these values for AC (0.7121) and HAM/TSP patients (0.2991) using a self-administered questionnaire in patients from Brazil and UK. QoL in patients with HAM/TSP is lower than that reported for more than 130 other conditions with such data, including multiple sclerosis, neuropathic pain, Parkinson's disease and HIV infection. For 12% of patients with HAM/TSP QoL was worse than death. Disease severity, rather than duration of disease, is associated with decreased QoL in HAM/TSP. HTLV-1 AC have impaired QoL compared to the general population in both countries. The data presented here will inform proper economic analysis in order to identify cost-effective policies. This is especially important for low- and middle-income countries where HTLV-1 prevalence is high and resources are limited. Background: HTLV-1 is a neglected sexually transmitted infection despite being the cause of disabling neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is no treatment for this infection and public health policies are essential to reduce its transmission. However, there are no data to support adequate cost-effective analysis in this field. The aim of this study was to obtain health state utility values for individuals with HAM/TSP and HTLV-1 asymptomatic carriers (AC). The impact of both states on quality of life (QoL) is described and compared to other diseases. Methods: A cross-sectional observational study of 141 individuals infected with HTLV-1 (79 with HAM/TSP and 62 AC) from three Brazilian states (Rio de Janeiro, Sao Paulo and Alagoas) and from the United Kingdom. Participants completed a validated general health questionnaire (EQ-5D, Euroqol) from which country specific health state utility values are generated. Clinical and epidemiological data were collated. Principal findings: Health state utility value for HAM/TSP was 0.2991. QoL for 130 reported clinical conditions ranges from 0.35 to 0.847. 12% reported their quality of life as worse as death. Low QoL was associated with severity rather than duration of disease with a moderate inverse correlation between QoL and Osame's Motor Disability Score (-0.4933) Patients who are wheelchair dependent had lowest QoL whilst those still walking unaided had the highest. AC also reported impaired QoL (0.7121) compared to general population. Conclusion: HTLV-1 and its associated neurological disease has a marked impact on QoL. This study provides robust data to support the development of cost-utility analysis of interventions for HTLV-1.

About 20% of total cancer cases are associated to infections. To date, seven human viruses have been directly linked to cancer development: high-risk human papillomaviruses (hrHPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus 1 (HTLV-1). These viruses impact on several molecular mechanisms in the host cells, often resulting in chronic inflammation, uncontrolled proliferation, and cell death inhibition, and mechanisms, which favor viral life cycle but may indirectly promote tumorigenesis. Recently, the ability of oncogenic viruses to alter autophagy, a catabolic process activated during the innate immune response to infections, is emerging as a key event for the onset of human cancers. Here, we summarize the current understanding of the molecular mechanisms by which human oncogenic viruses regulate autophagy and how this negative regulation impacts on cancer development. Finally, we highlight novel autophagy-related candidates for the treatment of virus-related cancers.