The purpose of this study is to describe and evaluate the natural history of the Human T-Lymphotropic Virus I (HTLVI) in a highly endemic population in southwestern Japan. HTLVI is a latent retrovirus which is known to produce adult T-cell leukemia/lymphoma in about 1% of all infected and is associated with spastic paraparesis or HAM). The study population consists of about 1500 persons or approximately 63% of all adults residing in two coastal villages in southeastern Miyazaki Prefecture. Of these, approximately 1 in 3 have HTLVI antibodies are presumed carriers. The population will be prospectively followed for five years with clinical, serologic, and interview information collected annually. The study will focus on four areas: 1. The prospective follow-up of subjects for the presence, level, and progression or regression of """"""""atypical' lymphocytes (virus- infected, TAC-positive T-cells). The presence and clonality of HTLVI provirus will be evaluated by southern blotting technique on all subjects with any detectable level of circulating atypical lymphoctyes, and a sample of those without. 2. The prospective follow-up of subjects for the presence, level and progression or regression of a diminished level of response to PPD skin testing, indicative of subclinical immunosuppression. 3. Clarification of the risk of infection by sexual exposure by evaluation of a variety of measures of virus status among married couples who are discordant for carrier status, in comparison to similarly aged couples who are both infected, and to those where seroconversion is observed. 4. Surveillance of the seronegative population for seroconversion and continued evaluation of the clustering of infection within families. With information on familial relationships available for almost the entire cohort, we will attempt to identify all persons who are """"""""indirectly"""""""" (non-sexual, non-perinatal) exposed to a carrier within households as a means of addressing the risk of such exposure. HTLVI antibody assays include detection of IgM, anti- gag proteins, and titration of anti p42, the trans-activating protein. The population will continue to be followed for opportunistic infections, and HAM,and the identification of additional intermediate markers of progression toward ATL will be sought.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA038450-06
Application #
3482406
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1988-12-15
Project End
1993-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Birmann, Brenda M; Breen, Elizabeth C; Stuver, Sherri et al. (2009) Population differences in immune marker profiles associated with human T-lymphotropic virus type I infection in Japan and Jamaica. Int J Cancer 124:614-21
Tanaka, Gen-ichi; Okayama, Akihiko; Watanabe, Toshiki et al. (2005) The clonal expansion of human T lymphotropic virus type 1-infected T cells: a comparison between seroconverters and long-term carriers. J Infect Dis 191:1140-7
Okayama, Akihiko; Stuver, Sherri; Matsuoka, Masao et al. (2004) Role of HTLV-1 proviral DNA load and clonality in the development of adult T-cell leukemia/lymphoma in asymptomatic carriers. Int J Cancer 110:621-5
Birmann, Brenda M; Mueller, Nancy; Okayama, Akihiko et al. (2004) Serologic assessment of type 1 and type 2 immunity in healthy Japanese adults. Cancer Epidemiol Biomarkers Prev 13:1385-91
Raker, Christina A; Tabor, Edward; Okayama, Akihiko et al. (2004) HCV core antigen as an alternative to NAT to detect HCV viremia. Transfusion 44:307-8
Iga, Mutsunori; Okayama, Akihiko; Stuver, Sherri et al. (2002) Genetic evidence of transmission of human T cell lymphotropic virus type 1 between spouses. J Infect Dis 185:691-5
Okayama, A; Stuver, S O; Tabor, E et al. (2002) Incident hepatitis C virus infection in a community-based population in Japan. J Viral Hepat 9:43-51
Ishizaki, Junzo; Okayama, Akihiko; Kuroki, Masayuki et al. (2002) Detection of human T-lymphotropic virus type I (HTLV-I) infection during coculture of HTLV-I infected and uninfected cells using inverse long PCR. Intervirology 45:164-71
Arduino, J M; Stuver, S O; Spiegelman, D et al. (2001) Assessment of markers of hepatitis C virus infection in a Japanese adult population. J Infect Dis 184:1229-35
Okayama, A; Stuver, S; Iga, M et al. (2001) Sequential change of virus markers in seroconverters with community-acquired infection of human T lymphotropic virus type I. J Infect Dis 183:1031-7

Showing the most recent 10 out of 36 publications