Guidelines for Counseling Persons Infected with Human T-Lymphotropic Virus Type I (HTLV-I) and Type II (HTLV-II)

Human T-lymphotropic viruses types I (HTLV-I) and II (HTLV-II) were the first human retroviruses discovered [1, 2]. Both belong to the oncovirus subfamily of retroviruses and can immortalize human lymphocytes in vitro. They are only distantly related to the human immunodeficiency viruses (HIV-1 and HIV-2), which belong to the lentivirus subfamily of retroviruses and cause the acquired immunodeficiency syndrome (AIDS). Infections with HTLV-I and HTLV-II are most easily detected serologically. The presence of antibodies to HTLV-I or HTLV-II indicates that a person is infected with the virus. In November 1988, the Food and Drug Administration issued recommendations to blood establishments to screen the U.S. blood supply for HTLV-I [3]. Since then, all whole blood and blood component donations in the United States have been screened for antibody to HTLV-I. The screening tests that were licensed, as well as the investigational supplementary tests used to confirm seroreactivity (Western immunoblot and radioimmunoprecipitation assay), do not reliably differentiate between antibodies to HTLV-I and to the closely related HTLV-II. In addition, the licensed screening tests, which use HTLV-I antigens, vary in their sensitivity to detect antibodies to HTLV-II [4, 5]. Approximately 2000 HTLV-I/II-infected volunteer blood donors were identified in the first year of screening in the United States; testing, after amplification by the polymerase chain reaction, indicated that approximately one half are infected with HTLV-I and one half with HTLV-II [6]. These donors are counseled and permanently deferred from donating blood. Because the polymerase chain reaction test is not routinely available, many donors and other individuals who tested positive by serologic assays have been told that they are infected with HTLV-I/II. The uncertainty regarding the identity of the infecting virus and the different epidemiologic and clinical correlates of HTLV-I and HTLV-II infections have made counseling of HTLV-I/II-infected persons complicated and sometimes confusing. Until recently, the only reliable way to differentiate HTLV-I from HTLV-II infection was by polymerase chain reaction [7]. Within the past 2 years, investigational peptide- and recombinant protein-based serologic assays that can more easily differentiate between antibodies to HTLV-I and HTLV-II have been developed [8, 9]. Preliminary data suggest that these investigational tests are potentially useful for typing serum samples [8, 9]. The guidelines for counseling HTLV-I-, HTLV-II-, and HTLV-I/II-infected persons included in this paper are intended for use by health care workers and public health officials in the United States. They may not be applicable in developing countries where the need for breast-feeding may outweigh concerns about transmission of these viruses. Human T-Lymphotropic Virus Type I Prevalence Human T-lymphotropic virus type I infection is endemic in southwestern Japan [10], the Caribbean basin [11], Melanesia [12], and in parts of Africa [13-15]. In some areas where HTLV-I infection is endemic, prevalence rates as high as 15% have been reported in the general population. Seroprevalence increases with age; in older age groups, rates are usually higher in women than in men. In the United States, HTLV-I/II seroprevalence rates among volunteer blood donors average 0.016% [6]. Approximately one half of HTLV-I/II-seropositive blood donors nationwide are infected with HTLV-I. Donors infected with HTLV-I most often report a history of birth in HTLV-I endemic countries or sexual contact with persons from the Caribbean or Japan. Smaller percentages report a history of either injecting drug use or blood transfusion. Clusters of HTLV-I infections have also been reported in blacks from the southeastern United States [16] and in immigrants from HTLV-I-endemic areas living in Brooklyn, New York [17]. Transmission Transmission of HTLV-I occurs from mother to child [18], by sexual contact [19], by blood transfusion [20], and by the sharing of contaminated needles. Mother-to-child transmission occurs primarily through breast-feeding [21]; in HTLV-I-endemic areas, approximately 25% of breast-fed infants born to HTLV-I-seropositive mothers acquire the infection. Recent studies suggest that transmission of HTLV-I by breast feeding may be associated with the presence of maternal antibodies to the HTLV-I transactivating protein, tax [22], or with elevated maternal titers of total antibodies to HTLV-I [23]. However, the clinical usefulness of these markers has not been established. Intrauterine or perinatal transmission of HTLV-I occurs but appears to be less frequent than transmission by breast-feeding; approximately 5% of children born to infected mothers but not breast-fed acquire infection [24]. Sexual transmission of HTLV-I appears to be more efficient from males to females than from females to males. In one study of married couples in Japan, the efficiency of sexual transmission from males to females was estimated to be 60.8% during a 10-year period compared with less than 1% transmission from females to males [25]. In another study, the presence of antibody to tax in the male partner was associated with sexual transmission to the female partner [26]. In a study in Jamaica, genital ulcer disease in the male was identified as a risk for female-to-male sexual transmission [27]. In the United States, approximately 25% to 30% of sex partners of HTLV-I/II-seropositive blood donors are also seropositive [28, 29]. Transmission of HTLV-I by blood transfusion occurs with transfusion of cellular blood products (whole blood, red blood cells, and platelets) but not with the plasma fraction or plasma derivatives from HTLV-I-infected blood. Seroconversion rates of 44% to 63% have been reported in recipients of HTLV-I-infected cellular components in HTLV-I endemic areas [20, 30]. Lower rates (approximately 20%) have been reported in recipients of contaminated cellular components in the United States [31]. The probability of transmission by whole blood or packed red blood cells appears to diminish with greater duration of product storage; this finding has been ascribed to depletion of infected cells, presumably T lymphocytes [30, 32]. Sharing of blood-contaminated needles is the probable mode of transmission among injecting drug users. Human T-lymphotropic virus type I is not transmitted by casual contact. Health care workers caring for HTLV-I-infected persons need only be concerned about percutaneous exposure to HTLV-I-contaminated blood. A health care worker in Japan who accidentally inoculated himself with blood from a patient with adult T-cell leukemia/lymphoma is reported to have seroconverted [33]. However, no seroconversions occurred among 31 other laboratory and health care workers exposed to HTLV-I through puncture wounds [34]. Universal precautions, recommended for contact with all patients, are adequate to guard against HTLV-I transmission to health care workers [35]. Diseases Two diseases have been definitively associated with HTLV-I: adult T-cell leukemia/lymphoma (ATL) and a chronic degenerative neurologic disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Adult T-cell leukemia/lymphoma is a malignant condition of HTLV-I-infected CD4-positive T lymphocytes. The HTLV-I provirus is monoclonally integrated in the abnormal cell population. A spectrum of clinical and pathologic features has been described, including acute, chronic, lymphomatous, and smoldering forms [36, 37]. The acute form of ATL is characterized by infiltration of lymph nodes, viscera, and skin with malignant cells, resulting in a constellation of clinical features (Table 1). Circulating abnormal lymphocytes, called flower cells, are generally seen. Hypercalcemia, abnormal liver function values, and lytic bone lesions are common. Median survival is 11 months from diagnosis. Conventional chemotherapy is not curative and relapses often occur quickly, although prolonged survival has been reported. Adult T-cell leukemia/lymphoma has been estimated to occur in 2% to 4% of individuals infected with HTLV-I in regions where HTLV-I is endemic and where early childhood infection is common [38, 39]. It occurs most frequently among persons aged 40 to 60 years, suggesting that a latent period as long as a few decades is required for the disease to develop. One case of ATL in an immunocompromised patient has been reported in which infection appears to have been transfusion acquired [40]. Table 1. Clinical Features of Adult T-Cell Leukemia/Lymphoma Human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis is characterized by progressive and permanent lower-extremity weakness, spasticity, hyperreflexia, sensory disturbances, and urinary incontinence (Table 2). In patients with HAM/TSP, unlike in those with multiple sclerosis, the signs and symptoms do not wax and wane, cranial nerves are not involved, and cognitive function is not affected. Antibodies to HTLV-I are characteristically found in the cerebrospinal fluid [41]. Treatment with corticosteroids has been reported to be useful in some cases [42]. Danazol, a synthetic androgen, reportedly improves symptoms, including bladder dysfunction [43, 44]. Fewer than 1% of HTLV-I-infected persons develop HAM/TSP [45]; it is believed to be immunologically mediated, and it affects women more frequently than men. The latency period for HAM/TSP is shorter than that for ATL; cases of HAM/TSP have been associated with blood transfusion, with a median interval of 3.3 years between transfusion, and development of HAM/TSP [46]. Table 2. Clinical Features of HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis Recently, infective dermatitis, a chronic eczema associated with Staphylococcus aureus and -hemolytic streptococcus, has been reported in Jamaican children infected with HTLV-I [47]. The full spectrum of HTLV-I-associated disease