Human TCell Lymphotrophic Virus Type

Epidemiology and Risk Factors. The human T-cell lymphotrophic virus type 1 (HTLV-1) causes a rapidly progressive adult T-cell leukemia or lymphoma (ATLL), and a slowly progressive neuromyelopathy known as HTLV- 1-associated myelopathy-tropical spastic paraparesis (HAM-TSP). y , y The distribution of HTLV-1 infection is worldwide with major foci of endemic infection in southwestern Japan, the Caribbean, Central and South America, sub-Saharan Africa, the Middle East, and Melanesia. It is estimated that between 10 and 20 million people are infected with HTLV-1. In the United States and Europe, HTLV-1 is found primarily in intravenous drug abusers. y Transmission of HTLV-1 can occur from mother to child primarily by breast milk, between intravenous drug addicts through the sharing of contaminated needles and syringes, by sexual contact, and by the transfusion of contaminated blood products. Vertical transmission of HTLV-1 from mother to child has been reported to occur in 15 to 20 percent of children born to HTLV-1 positive mothers. Breast milk appears to be the principal route because seroconversion rates are 14 to 20 percent for breast-fed infants compared to 3 to 5 percent for bottle-fed infants. [1oo] Sexual transmission of HTLV-1 is fairly inefficient compared to transmission of the human immunodeficiency virus (HIV). Blood transfusion is, however, a very efficient means of transmission of HTLV-1, and the greatest risk is incurred by recipients who receive seropositive blood stored for less than 1 week, who require multiple transfusions, or who receive immunosuppressive therapy at the time of the transfusion^]

Pathogenesis and Pathophysiology. There are presently two major theories of the pathogenesis of HAM- TSP, an autoimmune model and a cytotoxic model. In the autoimmune model, HTLV-1 activates autoreactive T cells, which then migrate to the central nervous system, penetrate the blood-brain barrier, and stimulate the production of inflammatory cytokines, leading to subsequent tissue destruction. y , W In the cytotoxic model, tissue destruction is caused by a CD8-mediated cytolytic attack against HTLV-1-infected CNS cells or infected CD4 T cells in the CNS. An early event in HAM-TSP appears to be a breakdown of the blood-brain barrier, leading to perivascular influx of mononuclear cells. CD4 T cells are the predominant cell type early in disease, but CD8 T cells are found almost exclusively in the later stages of disease. As the duration of HAM-TSP progresses, an increasing number of CD8 cells infiltrate the CNS. This infiltration is associated with an upregulation of HLA class 1 and class 2 molecules and an increased expression of cytokines. The end result is demyelination with axonal involvement that is widespread in the spinal cord, and the corticospinal tracts tend to be more affected than the more heavily myelinated posterior columns. The thoracic spinal cord is the area of maximum involvement.y , y.31

Clinical Features and Associated Findings. HTLV- 1-associated myelopathy-tropical spastic paraparesis is a slowly progressive spastic paraparesis marked by hyperreflexia, bladder dysfunction, constipation, and impotence in males. Sensory abnormalities due to demyelination of the posterior columns occur less frequently than motor abnormalities and present primarily as paresthesias of the lower extremities. y]

Differential Diagnosis. The differential diagnosis includes myelopathy due to a compressive lesion of the cord from a disk, tumor, or infection, subacute combined degeneration resulting from vitamin B12 deficiency, HIV-1 myelopathy, multiple sclerosis, and syphilis.

Serological testing should be performed to detect HTLV- 1 antibodies in serum. Magnetic resonance imaging (MRI) of the brain may demonstrate hyperintense lesions in the subcortical white matter on T2-weighted scans, resembling the lesions of multiple sclerosis. y^ Elevated antibody titers to HTLV-1 can be detected in blood and cerebrospinal fluid of patients with HAM-TSP.

Management and Prognosis. The presence of inflammatory cells including macrophages and T cells in

HAM-TSP spinal cord material, in addition to the upregulation of HLA and cytokine molecules, suggests that an increase in immunological activity in the CNS is the basis of the pathogenesis of HAM-TSP.^1 Immunosuppressive therapy is the only modality available at the present time to treat HAM-TSP. There is no specific antiviral therapy. The best means of treatment may be prevention through an HtLv-1 vaccine, and it has been suggested that the development of vaccination against the HTLV-1 retrovirus would serve as a pathfinder for the development of a vaccine against HIV. y

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