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Human T-cell lymphotropic virus type 2 (HTLV-2) is endemic in injection drug users (IDU), and native American populations in the Americas. Transmission is associated with high-risk injection and sexual practices. A cohort of 2561 IDU in King County, Washington completed 2 study visits over 1 y. HTLV-2 infection was detected in 190 (7.4%) of 2561 IDU, and 13 (7.8 cases per 1000 person-y) incident infections occurred during the study. Prevalent infection was associated with female gender, non-white race, longer duration as IDU, having a tattoo, combined injection of heroin and cocaine, and with serologic evidence of hepatitis B and C infection. Seroconversion was more common in women, and was associated with African American race, heterosexual identity and longer duration as IDU. In conclusion, increased risk of HTLV-2 infection was associated with non-white race, and injection drug of choice, suggesting injection networks may play an important role in transmission of HTLV-2. The high correlation of HTLV-2 infection with HCV infection suggests the major route of transmission in IDU is via injection practices. Additional studies are needed to examine the clinical manifestations of HTLV-2 infection, as well as the clinical and virological manifestations of HTLV-2/HCV coinfection.

Purpose: A literature review was performed of the three principal subpopulations most commonly associated with human T-cell lymphotropic virus type II (HTLV-II) with the view of identifying the prevalence and transmission routes of HTLV-II. These included blood donors (BDs), intravenous drug users (IVDUs), and Amerindians (Indian populations from the Americas). We used the major criterion of serological and molecular distinction between human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II). Three questions were formulated in addressing the possibility that HTLV-II might be responsible for the reported prevalence and transmission of this virus in these groups. Question One: Which population groups have the highest HTLV-II seroprevalence rates? Question Two: Are worldwide HTLV infection rates among the three sub-populations associated predominantly with the HTLV-II retrovirus type? Question three: What are the principal modes of transmission of HTLV-II?, Methods: Since earlier epidemiologic studies did not routinely use assays capable of distinguishing between HTLV-I and HTLV-II antibodies, their findings are necessarily inaccurate. However, with the more recent development of enhanced serologic assays, using recombinant antigens that are capable of accurately making this differentiation, it is now possible to more precisely define the epidemiology of HTLV-II. We reviewed only those studies where serological and molecular methods of accurately distinguishing between the two retroviruses were utilized. Initially, we located 36 studies, which met this particular review criterion. Of the five different assays we identified, the most prevalent were the polymerase chain reaction (PCR) (n = 14) and the synthetic peptide-based enzyme-linked immunoassay (Synth EIA) (n = 13). Our BD, IVDU, and Amerindian groups were also evaluated according to this differentiation schema. We were able to locate over 100 prevalence studies where focus was on some aspect of analysis of at least one or more of these three groups. By using many search terms - such as HTLV-II endemic population, seroepidemiological, as well as case control and cohort studies - we were able to create a comprehensive bibliographic database., Results: The two groups identified with high HTLV-II prevalence rates are the IVDUs and Amerindian population. The importance of breast-feeding, IVDU, and contaminated blood products in the HTLV-II transmission process is confirmed. Sexual intercourse, however, as a mode of HTLV-II transmission remains problematic., Conclusions: By confining our evaluation to only those studies that used serological and/or molecular methods capable of distinguishing between the two retroviruses, we have been able to establish with confidence that there are consistent emerging patterns of HTLV-II infection in these populations.

To study the prevalence of HIV and infections with related transmission patterns, we interviewed and obtained blood samples from 220 injecting drug users (IDUs), sampled by snowballing, from the city of Santos in the state of São Paulo, Brazil, where the estimated number of IDUs (10,000) comprises approximately 2% of the entire population. Seroprevalence of HIV, hepatitis B and C, syphilis, and HTLV (1 and 2) was assessed and compared with that in 197 blood donors from the same city, matched for age and gender. Risk behavior related to HIV was assessed by a standard questionnaire applied to the IDU sample. Univariate and multivariate analyses of the risk factors were performed. Seroprevalences found were 62% for HIV, 75% for HCV, 75% for HBV, 34% for syphilis, and 25% for HTLV (1 and 2) among IDUs, which compare with 0.0%, 2%, 23%, 12%, and 1% for blood donors, respectively. The risk for parenterally transmitted infections in this IDU community was higher than that for sexually transmitted infections (odds ratio for syphilis, 3.57; hepatitis B, 10.0; and hepatitis C, 100). The results of the mutivariate risk analysis showed that daily rate of ID use >5 times/day (OR = 6.73), not changing behavior to avoid AIDS (OR= 3.28), ID use >15 days/month (OR = 2.72), and ID use in the last 2 months (OR = 2.23) were the risk behaviors significantly associated with HIV infection.

The molecular characterization of two human T-cell lymphotropic virus type II (HTLV-II) isolates, Gu and Va, obtained from Italian injecting drug users (IDUs) has indicated that these isolates belong to the HTLV-IIb subtype. To establish whether Italian IDUs are also infected by the HTLV-IIa variant, sequencing of the gp21 env gene of proviral DNA from further patients was carried out. Two new isolates, Bo and Md, were found, which presented a divergence of 0.4-0.7% from the IIa prototype HTLV-II-Mo, thus indicating that they belong to the HTLV-IIa subtype. The results strongly support the existence of two distinct molecular subtypes of HTLV-II infecting Italian IDUs and demonstrate that, although the IIb subtype appears to be prevalent, there is the same variability for this virus in Europe as found in the United States. The Italian IIb isolates were also seen to encode an additional 25 amino acids at the C-terminal end of tax protein, as already shown for other IIb isolates. The identification of two HTLV-II molecular subtypes among Italian drug addicts will be useful in tracing the worldwide distribution of this virus and in further understanding its molecular structure and biology.

The diagnosis and confirmation of human T cell lymphotropic virus (HTLV) type II infection has proven difficult, since most assays depend on antigenic cross-reactivity between HTLV-I antigens and HTLV-II antibodies. Type-specific HTLV infection rates were evaluated in a cohort of 233 injecting drug users screened with an HTLV EIA. Of the 52 EIA-reactive specimens, 48 were indeterminate or negative by standard Western blot. Type-specific HTLV results determined by polymerase chain reaction (PCR) were 0, HTLV-I; 92%, HTLV-II; 6%, type indeterminate; and 2%, negative. Among 42 EIA-reactive, HTLV-II-PCR-positive individuals tested by a p21 envr Western blot, all were positive and 74% had antibodies to the tax protein. This study found a high rate (22.3%) of HTLV reactivity, with HTLV-II usually the sole responsible agent; shortcomings in standard HTLV-I-based diagnostics but usefulness of PCR and p21 envr Western blots for typing and confirmation of HTLV reactivity; and a high prevalence (74%) of anti-tax antibody among HTLV-II-seropositive subjects, suggesting increased potential for infectivity.

Infection with human T-cell leukemia virus type II (HTLV-II) has been associated with rare chronic T-cell malignancies and has recently been demonstrated in a significant proportion of American intravenous drug abusers (IVDA). Identification of an HTLV-II-infected cohort of IVDA has allowed analysis of the HTLV-II carrier state. We analyzed clinical, hematologic, and immunologic parameters in 21 HTLV-II-infected IVDA, two HTLV-I-infected IVDA, and 20 uninfected control IVDA identified by serologic screening and by analysis of peripheral blood mononuclear cell (PBMC) DNA by polymerase chain reaction (PCR). An elevated absolute lymphocyte count was observed in 4 of 21 HTLV-II-infected IVDA, 1 of 2 HTLV-I-infected IVDA, and 1 of 20 control IVDA. CD8+ T-cell elevation was observed in three of four HTLV-II IVDA with lymphocytosis and one of two HTLV-I-infected IVDA. Activation of CD8+ T cells in HTLV-II-infected IVDA was suggested by an overall increase in CD8+/HLA-DR+ lymphocytes. Cell fractionation and analysis by PCR of HTLV-II-infected carrier blood showed high levels of HTLV-II provirus in unfractionated PBMC and purified T cells and little or no detectable HTLV-II DNA in B cells or monocytes, indicating that T cells were the most likely target of infection in vivo. The frequency of HTLV-II-infected cells was estimated at approximately 1 in 500 cells or less using dilution analysis by PCR of PBMC DNA. Most HTLV-II-infected IVDA are asymptomatic and have no overt hematologic or immunologic abnormalities, although some manifest benign lymphocytosis.