HTLV-I TRANSMISSION DYNAMICS AND GLOBALIZATION The Effect of Increased Host Population Heterogeneity on HTLV-I Persistence J. Cole, A. Crawford, S. Palace, J. Quill Faculty Sponsor: T. Livdahl ABSTRACT HTLV-I, a human retrovirus and the causative agent of ATLL, displays highly cell-associated transmission. Consequently, HTLV-I is endemic in genetically homogenous populations in regions of Japan, Jamaica, and several South American countries. Since a degree of genetic relatedness seems to be important in effective transmission, it is possible that the disruption of isolated populations through globalization may result in lower HTLV-I prevalence rates in currently endemic areas. Several simulations were constructed using disease-modeling software to determine the effect of persistent immigration on viral prevalence in a hypothetical population prone to HTLV-I. Although this study did not find that the lower transmission rates counteracted the effects of exposing more individuals to the virus, vigorous efforts to quantify transmission rates as a function of host relatedness should be made in order to accurately assess risk of newly-exposed populations and individuals. MATERIALS / METHODS Stella 9.0 software was used to represent plausible disease dynamics in a simulated HTLV-I endemic population (Fig. 1, 2) [5, 6, 7]. Birth, death, and immigration rates were chosen to yield a stable population size. Population dynamics were graphed using Stella software until a stable state was reached. Fig. 4: HTLV-I dynamics in a population with constant immigration. DISCUSSION 鲜 INTRODUCTION The Human T-cell lymphotropic virus I (HTLV-I), a retrovirus, is the causative agent in adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis. HTLV-I is endemic in numerous areas throughout the world including southern Japan, the Caribbean, certain areas of Africa, and the southeastern United States [1, 2]. The primary target of HTLV-I is the T lymphocyte, and the virus is highly T-cell associated. HTLV-I is not easily transmissible, since cellcell contact is generally required. Two major transmission routes have been described: vertical transmission through breast milk, and horizontal transmission through sexual contact [1, 2]. The cell-associated transmission of HTLV-I requires relative genetic homogeneity in host populations. As globalization increasingly disrupts the isolation of such communities, it is possible that transmission rates of HTLV-I will fall below the minimum rate at which the virus can persist. To investigate this phenomenon, Stella disease modeling software was used to replicate the effects of constant immigration on a population in an HTLV-I endemic area. Prevalence rates were compared in this model and in a control (no immigration) model to determine potential effects of globalization on HTLV-I distribution. Fig. 1: Schematic for disease Fig. 2: Schematic for disease dynamics in dynamics in the control population. a population with constant immigration. RESULTS When the simulation populations reached a steady state, 30.8% of the control population and 34.0% of the population with immigration were infected with HTLV-I (Fig. 3, 4). Total population sizes did not change significantly, as the simulation was designed to produce populations of stable sizes. The proportion of infected individuals in the immigration-affected population was not lower than that in the control population; it appears as though the reduced transmission rates observed between members of different populations do not negatively affect HTLV-I prevalence to an extent that counteracts the risk of exposing a greater number of individuals to the disease. This conclusion is not wholly without precedence ; however, more research must be done to definitively quantify transmission differentials between unrelated populations to accurately assess the risk of disease spread. The complexity of the transmission dynamics of HTLV-I creates significant uncertainty as to the future of this disease in the face of globalization. Further research is therefore required to determine whether the global incidence of HTLV-I is likely to increase or decrease. REFERENCES  Brick, W.G., Nalamolu, Y., Jillella, A.P., Burgess, R.E., & Kallab, A.M. Adult T-Cell Leukemia/lymphoma: A Rare Case in the USA and Review of the Literature. Leukemia & Lymphoma, 43: 127-132 (2002).  Zaanen, H.C.T., & Pegels, J.G. Adult T-cell leukemia and lymphoma: report of two cases and a brief review of the literature. Van Zuiden Communications, 1-4 (2002).  Soares, B., Proietti, A., & Proietti, F. Heterogeneous geographic distribution of human T-cell lymphotropic viruses I and II (HTLV-I/II): serological screening prevalence rates in blood donors from large urban areas in Brazil. Saúde Pública, Rio de Janeiro, 21 (3): 926-931 (2005).  Stella Software 9.0. Isee Systems, Inc., 2005.  Stuver, S.O., Tachibana, N., Okayama, A., Shioiri, S., Tsunetoshi, Y., Tsuda, K., & Mueller, N.E. Heterosexual transmission of human T cell leukemia/lymphoma virus type I among married couples in Southwestern Japan : an initial report from the Miyazaki cohort study. The Journal of infectious diseases, 1 67: 1, 57-65 (1993). Fig. 3: HTLV-I dynamics in an isolated population.  Roucoux, D., Wang, B., Smith, D., Nass, C., Smith, J., Hutching, S., Newman, B., Lee, T., Chafets, D., & Murphy, E. A Prospective Study of Sexual Transmission of Human T Lymphotropic Virus (HTLV)-I and HTLV-II. The Journal of Infectious Diseases, 191: 1490-1497 (2005).  Seydel, J. & Krämer, A. Transmission and Population Dynamics of HTLV-I Infection. International Union Against Cancer, 66: 197-200 (1996).