Low risk of mother-to-child transmission of human T lymphotropic virus type II in non-breast-fed infants. The NYC Perinatal HIV Transmission Collaborative Study.

The transmissibility of human T lymphotropic virus (HTLV) type II from mother to child was investigated. Of 236 women enrolled during pregnancy in a study of mother-to-child transmission of human immunodeficiency virus in 1986-1988, 21 (8.9%) were seropositive for HTLV-I/II. All 21 mothers were infected with HTLV-II by synthetic peptide testing and polymerase chain reaction (PCR). HTLV-II-infected women were older (median age, 34 vs. 28 years), more likely to be black (70% vs. 38%), and more likely to report past or current intravenous drug use (85% vs. 56%) than HTLV-II-uninfected women. Of 20 non-breast-fed infants born to 19 of these HTLV-II-infected women, none had detectable HTLV-II by PCR done on peripheral blood mononuclear cells obtained at birth to 36 months of age. Serologic testing of these infants revealed gradual disappearance of HTLV-I/II antibody. While this study does not rule out the possibility of perinatal HTLV-II transmission, the data suggest that it occurs rarely in the absence of breast-feeding.

Seroprevalence of HTLV-1 and HTLV-2 among intravenous drug users and persons in clinics for sexually transmitted diseases.

UNLABELLED: Background. The human T-cell lymphotropic virus Type I (HTLV-I) is associated with adult T-cell leukemia and myelopathy, whereas HTLV-II infection has uncertain clinical consequences. We assessed the seroprevalence of these retroviruses among intravenous drug users and among patients seen at clinics for sexually transmitted diseases (STD clinics). METHODS: We used serum samples that were collected in eight cities in 1988 and 1989 during surveys of human immunodeficiency virus infection among intravenous drug users entering treatment and persons seen in STD clinics. The serum samples were tested for antibodies to HTLV, and positive specimens were tested further by a synthetic peptide-based enzyme-linked immunosorbent assay to differentiate between HTLV-I and HTLV-II. RESULTS: Among 3217 intravenous drug users in 29-drug-treatment centers, the median seroprevalence rates of HTLV varied widely according to city (range, 0.4 percent in Atlanta to 17.6 percent in Los Angeles). Seroprevalence increased sharply with age, to 32 percent in persons over 44 years of age. HTLV infection was more common among blacks (15.5 percent) and Hispanics (10.7 percent) than among whites (4.1 percent), and it was strongly associated with a history of heroin injection (P less than or equal to 0.001). Among 5264 patients in 24 STD clinics, the median rates of HTLV infection were much lower (range, 0.1 percent in Atlanta and Newark to 2.0 percent in Los Angeles). Again, this infection was more common among intravenous drug users (7.6 percent) than among non-drug users (0.7 percent). Eighty-four percent of the seropositive samples from drug-treatment centers and 69 percent of those from STD clinics were due to HTLV-II infection (P = 0.03). CONCLUSIONS: HTLV infections are common among intravenous drug users and are primarily caused by HTLV-II. Among patients seen at STD clinics, HTLV is strongly associated with intravenous drug use, but the retrovirus is also prevalent among non-drug users.

Indeterminate HTLV serologic results in U.S. blood donors: are they due to HTLV-I or HTLV-II?

Current screening tests to detect human T-lymphotropic virus type I (HTLV-I) in volunteer blood donors commonly yield indeterminate HTLV serologic results (mostly isolated gag reactors). To assess the significance of indeterminate HTLV serologic results in U.S. blood donors, we compared 56 persons who had such serologic patterns with 30 HTLV seropositive blood donors and with HTLV seronegative controls. Polymerase chain reaction assays showed that none of the 56 individuals with indeterminate HTLV serologic results were infected with HTLV-I or HTLV-II, while all 30 HTLV seropositive blood donors were infected with either HTLV-I (in 15) or HTLV-II (in the other 15). The seroindeterminate blood donors were also different from the HTLV seropositive blood donors and more like HTLV seronegative controls in their demographic characteristics and the presence of HTLV risk factors. These results are evidence that volunteer blood donors with isolated and persistent gag seroreactivity in the United States are unlikely to be infected with HTLV-I or HTLV-II.

Synthetic peptide-based immunoassays for distinguishing between human T-cell lymphotropic virus type I and type II infections in seropositive individuals.

Until now, serologic tests that distinguish the closely related human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) infections have not been available. Synthetic peptide assays, employing peptides derived from the core and envelope proteins of HTLV-I and HTLV-II (SynthEIA and Select-HTLV tests), were evaluated for the ability to serologically discriminate HTLV-I and HTLV-II infections. Of 32 HTLV-I- and 57 HTLV-II-positive serum specimens from individuals whose infections were confirmed by polymerase chain reaction, the SynthEIA test categorized 29 (91%) as HTLV-I and 50 (88%) as HTLV-II, and 10 (11%) were nontypeable. In contrast, the Select-HTLV test categorized 32 (100%) as HTLV-I and 55 (96%) as HTLV-II, and 2 (2%) were nontypeable. The specificity of both the assays in seropositive serum specimens was 100% in that none of the specimens were incorrectly classified. Additional serum specimens obtained from clinically diseased patients from the United States (n = 8) and asymptomatic carriers and patients from Japan (an endemic population for HTLV-I; n = 40) were categorized as HTLV-I by at least one of the assays, while serum specimens from Guaymi Indians from Panama (an endemic population for HTLV-II; n = 13) were categorized as HTLV-II. Thus, peptide enzyme immunoassays appear to represent a simple technique employing chemically synthesized antigens for discrimination between antibodies of HTLV-I and HTLV-II.

Evaluation of a recombinant human T-cell lymphotropic virus type I (HTLV-I) p21E antibody detection enzyme immunoassay as a supplementary test in HTLV-I/II antibody testing algorithms.

To evaluate the usefulness of a human T-cell lymphotropic virus type I (HTLV-I) recombinant p21E immunoassay as a supplementary test in HTLV-I/II serologic testing algorithms, we used this assay to test 378 serum samples previously categorized as positive, indeterminant, or negative for HTLV-I/II antibody, as defined by U.S. Public Health Service guidelines. We found this test to be highly sensitive for detecting antibody to HTLV-I/II env (99.4%) but slightly less specific (96.0%), particularly among samples from intravenous drug users. Our data suggest that this test is most appropriately used to confirm the absence of env antibody in samples which are repeatably reactive in an HTLV-I/II screening assay and gag reactive only by immunoblotting. Because of the high sensitivity of this recombinant p21E test, a negative result in this context could preclude radioimmunoprecipitation testing. However, pending further evaluation of the specificity of this assay, samples testing positive for p21 env antibody may require confirmation by radioimmunoprecipitation, particularly in situations in which the results will be used for diagnostic purposes or blood donor counseling.

Human T lymphotropic virus type II (HTLV-II) infection in a cohort of New York intravenous drug users: an old infection?

To identify risk factors for human T lymphotropic virus type II (HTLV-II) infection in intravenous drug users (IVDUs), participants in a longitudinal study of human immunodeficiency virus (HIV) infection in a New York methadone maintenance program were studied. Of 270 participants tested for HTLV-I/II, 21 (8%) were seropositive. Of those, 15 (71%) had HTLV-II-specific sequences by polymerase chain reaction (PCR) and 1 (5%) had both HTLV-I- and -II-specific sequences; 3 persons with indeterminate serologic results were also PCR-positive for HTLV-II. HTLV-II infection was significantly associated with older age but was not predicted by sex, race, socioeconomic status, transfusion history, or HIV infection status. Behavioral factors since 1978, such as duration and frequency of intravenous drug use, needle sharing, visits to shooting galleries, or number of sex partners, were also not associated with HTLV-II infection. These findings are in contrast with the association of these risk factors with HIV in this group and suggest that, among IVDUs, HTLV-II is an older endemic infection that is less efficiently transmitted than HIV.

Co-infection with HIV-I and HTLV-I/II In Intravenous Drug Users in Suburban New York City, With Comparison to Other Geographic Areas.

Co-infection with human T-lymphotropic virus types I or II (HTLV-I or -II) may be a cofactor in the progression of human immunodeficiency virus (HIV) infection. We assessed the frequency of simultaneous infection with these retroviruses among intravenous drug users from Westchester County, N.Y., a suburb of New York City. Comparison was made with similar studies in the United States and Europe.

Human T cell lymphotropic virus infection in Guaymi Indians from Panama.

Preliminary studies found that 9% of Guaymi Indians from Bocas del Toro province have antibody to human T cell lymphotropic virus (HTLV-I/II). The present study enrolled 317 (21% of the population) Guaymi Indians from Changuinola, the capital of Bocas del Toro province and 333 (70% of the population) from Canquintu, an isolated rural village. Demographic information and family relationships were ascertained and subjects were screened for neurologic diseases. Serum specimens were screened by an enzyme-linked immunosorbent assay for HTLV-I/II antibody and positives were confirmed according to U.S. Public Health Service criteria. Twenty-five (8%) Guaymi residing in Changuinola and 7 (2.1%) from Canquintu were confirmed seropositive. In Changuinola, antibody was virtually limited to residents greater than or equal to 15 years of age (24 [16%] of 153) and rates were slightly higher in males than in females; in Canquintu, antibody rates did not increase significantly with age and appeared higher in females than in males. In Changuinola, there was no evidence for household clustering of infection. In contrast, HTLV antibody among Canquintu residents clustered significantly by household. HTLV-associated neurologic disease was not detected in either population. The atypical seroepidemiology observed in both locations might be explained if the virus endemic to the Guaymi differed from HTLV-I previously described in the Caribbean basin and Japan.

Seroprevalence of human T-lymphotropic virus type I or II in sexually transmitted disease clinic patients in the USA.

Serum specimens from patients attending sexually transmitted disease (STD) clinics in Denver and several southeastern US cities were tested for antibody to human T-lymphotropic virus type I or II (HTLV-I/II). In Denver, 8 (2.1%) of 384 patients with a history of intravenous (IV) drug use, versus none of 201 non-IV-drug users, were HTLV-I/II seropositive. Only 2 (0.18%) of 1095 STD clinic patients from the southeastern USA had antibodies to HTLV-I/II. These data document a low prevalence of HTLV-I/II in STD clinic patients from the southeastern USA and confirm that IV drug use is an important risk factor for HTLV-I/II in the USA.

Characterization of antibody reactivity to human T-cell lymphotropic virus types I and II using immunoblot and radioimmunoprecipitation assays.

We have characterized the immunoreactivity to human T-cell lymphotropic virus type I (HTLV-I) among 26,983 persons of various seroprevalence groups by using enzyme immunoassay, immunoblot (IB), and radioimmunoprecipitation assays (RIPA) in accordance with Public Health Service recommended guidelines for the interpretation of serologic test results for HTLV-I infection. IB-indeterminate serum specimens (n = 178) were reactive to HTLV-I gag proteins, and no serum contained only env reactivity. Overall, RIPA resolved 40% of IB-indeterminate serum samples; however, the probability that RIPA would confirm IB-indeterminate samples depended on the seroprevalence of the population tested. HTLV-I gag p19-only reactivity on IB was not a reliable marker of HTLV-I infection, while gag p24 reactivity on IB was clearly associated with positive seroreactive specimens. IB and RIPA tests did not clearly distinguish between HTLV-I and HTLV-II seroreactivities. These data emphasize that patterns of immunoreactivity to HTLV-I antigens are dependent upon the seroprevalence of the risk groups tested. In addition, RIPA detected antibodies to env proteins present in low titer in a substantial number of IB gag-only reactive sera and resolved the HTLV-I antibody status of these sera.

Epidemiologic assessment of screening tests for antibody to human T lymphotropic virus type I (HTLV-I).

We tested 196 sera from a human T lymphotropic virus type I (HTLV-I) risk group (prostitute women) with two commercial "research" enzyme-linked immunoabsorbent assays (EIA) for HTLV-I antibodies. All tested sera were characterized by HTLV-I Western immunoblots and by HTLV-I radioimmunoprecipitation assays. The estimated sensitivities of the EIA tests were 93.8 percent and 100 percent, and the specificities were 98.8 percent and 95.8 percent, respectively, using recommended criteria for seropositivity (requiring reactivity to both gag p24 and env gp46 or gp61/68). Calculated negative predictive values remained excellent (greater than 99.9 percent and 100 percent, respectively) at lower seroprevalence rates but the positive predictive values were only 7.3 percent and 2.3 percent when calculated for a seroprevalence rate of 0.1 percent. These results emphasize the importance and need for additional HTLV-I supplementary serologic testing when screening populations with low HTLV-I seroprevalence rates.

Seroprevalence and risk factors for HTLV-I/II infection among female prostitutes in the United States.

We tested 1305 female prostitutes from eight areas of the United States for antibodies to human T-cell lymphotropic virus type I/II. Overall, 6.7% were human T-cell lymphotropic virus type I/II seropositive (with antibodies to both gag and env gene products). The seroprevalence rates ranged from 0% in southern Nevada to 25.4% in Newark, NJ. Human T-cell lymphotropic virus type I/II seropositivity was independently associated with race (odds ratio, 4.68), intravenous drug use (odds ratio, 2.94), hepatitis B seropositivity (odds ratio, 2.87), recruitment in Newark (odds ratio, 2.34), and more years of sexual activity (odds ratio, 1.08 per year of sexual activity). Groups with high rates included blacks, Hispanics, and American Indians, and the rates in these groups were significantly higher than among whites and Asian Americans for women both with and without a history of intravenous drug use. Among intravenous drug users, the only other independent associations were more years of sexual activity and recruitment in Newark; and in non-intravenous drug users, hepatitis B seropositivity. These data show that human T-cell lymphotropic virus type I/II infection is present among female prostitutes in some areas of the United States. Further studies are needed to evaluate patterns of transmission and long-term health effects.

Persistent infection of rabbits with HTLV-I: patterns of anti-viral antibody reactivity and detection of virus by gene amplification.

Two groups of rabbits were inoculated on the day of birth or at 4 weeks of age with a human T-cell leukemia virus type-I (HTLV-I)-infected and transformed rabbit cell line (Ra-I). Rabbits seroconverted to HTLV-I, as determined by indirect immunofluorescence, by 3 weeks after inoculation and remained persistently seropositive during a 22-month period of observation. Seroconversion did not occur in saline-inoculated controls. Using Western immunoblotting and radio-immunoprecipitation, persistent seroconversion occurred against viral antigens p24, p55 and gp68, while reactivity to p19 was variable between rabbits. Using the polymerase chain reaction (PCR) with HTLV-I gag and pol primer pairs, HTLV-I sequences were demonstrable in peripheral blood mononuclear cells and other tissues collected at 70 and 90 weeks after inoculation. DNA extracts from normal rabbit tissue remained negative under the same conditions. No qualitative or quantitative changes in leukocytes or erythrocytes were detected in the infected rabbits and no clinical signs could be directly attributed to infection with HTLV-I.

Absence of human T-cell lymphotropic virus type I coinfection in human immunodeficiency virus-infected hemophilic men.

Concern for transmission of human T-cell lymphotropic virus, type 1 (HTLV-1) infection to recipients of infected cellular blood products has prompted development of tests to eliminate blood units with HTLV-I antibodies. Most hemophilic men from the United States became infected with human immunodeficiency virus (HIV) before HIV donor screening and before blood products were processed to inactivate the virus. To assess whether these men might also be infected with HTLV-I, we examined the HTLV-I antibody status of 127 factor VIII (hemophilia A) recipients and 71 factor IX (hemophilia B) recipients. One HIV-seronegative and four HIV-seropositive persons were HTLV-I reactive by enzyme-linked immunosorbent assay (ELISA). Four of five ELISA-reactive serum samples were negative by HTLV-I immunoblot assay (IB); 1 reactive and 1 borderline reactive serum were indeterminate on IB (p19 reactivity), but negative by radioimmunoprecipitation assay (RIPA). Peripheral blood mononuclear cells from one patient with indeterminate HTLV-I IB were negative for HTLV-I genomic sequences by polymerase chain reaction. The other indeterminate patient's serum antibody pattern was stable over a 2-year period, suggesting this was not an instance of early HTLV-I seroconversion. These results reaffirm the safety of factor components in the United States with regard to HTLV-I but emphasize the importance and need for further testing of reactive HTLV-I ELISA results with a second more specific technique.

Seroprevalence of human T lymphotropic virus type I in Puerto Rico.

Serum specimens from Puerto Rican residents were tested for antibodies to human T lymphotropic virus type I (HTLV-I) using an enzyme immunoassay, Western immunoblot, and radioimmunoprecipitation assays. Of 1,279 specimens obtained during a dengue virus surveillance program in 1986 and 1987, 3 (0.2%) tested positive; an additional 11 were indeterminate. Of 602 specimens obtained from blood donors in Ponce in 1987, 1 (0.2%) was positive; an additional specimen was indeterminate. Of 21 persons hospitalized for problems related to intravenous drug use in 1986 and 1987, 1 (5%) tested positive for HTLV-I antibodies.