Increased frequency of CD4+T cells expressing fractalkine receptor CX3CR1 in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its AIDS susceptible polymorphisms are not associated with the disease.

To investigate whether fractalkine receptor CX3CR1 polymorphisms that have been associated with rapid progression to AIDS among HIV-1 positive individuals also affects the risk of human T cell lymphotropic virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP), we compared the allele frequencies of V249I and T280M between 233 HAM/TSP patients and 213 HTLV-1 seropositive asymptomatic carriers (HCs). Although the frequency and absolute number of peripheral blood CX3CR1+CD4+T cells were significantly increased in HAM/TSP patients compared to HCs and uninfected controls independent of HTLV-1 trans-activator protein Tax, we could not observe any association between the two polymorphisms and the risk of HAM/TSP in our cohort.

Adult T-cell leukemia/lymphoma in an adolescent presenting with skin lesions.

Adult T-cell leukemia/lymphoma is a T-cell malignancy caused by the human T-cell lymphotropic virus-I. Adult T-cell leukemia/lymphoma is primarily a disease of adults due to the long latency period between initial infection and development of leukemia. We present a case of acute adult T-cell leukemia/lymphoma in an adolescent. Skin lesions had appeared 3 years earlier and were the initial sign of human T-cell lymphotropic virus-I infection and T-cell malignancy. Her disease failed to respond to both intensive chemotherapy and antiviral therapy. Cutaneous lesions are sometimes the initial sign of adult T-cell leukemia/lymphoma and early recognition is imperative.

A prospective uncontrolled trial of fermented milk drink containing viable Lactobacillus casei strain Shirota in the treatment of HTLV-1 associated myelopathy/tropical spastic paraparesis.

Ten patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were treated in an uncontrolled preliminary trial by oral administration of viable Lactobacillus casei strain Shirota (LcS) containing fermented milk. HTLV-1 provirus load, motor function, neurological findings, and immunological parameters were evaluated after 4 weeks. Although LcS did not change the frequencies or absolute numbers of all the examined cell surface phenotypes of peripheral blood mononuclear cells, NK cell activity was significantly increased after 4 weeks of oral administration of LcS preparation. Improvements in spasticity (modified Ashworth Scale scores) and urinary symptoms were also seen after LcS treatment. No adverse effect was observed in all the 10 patients throughout the study period. Our results indicated that LcS may be a safe and beneficial agent for the treatment of HAM/TSP; therefore randomized controlled studies are warranted.

Immunoglobulin prophylaxis against HTLV-I in a rabbit model.

We have investigated the protective effect of human T-cell leukemia virus I (HTLV-I) immune globulin (HTLVIG) against HTLV-I in rabbits. HTLVIG containing 77 mg/ml of IgG was prepared from pooled plasma from seropositive healthy persons. In the first experiment, four groups (A, B, C, and D) of three rabbits were transfused with 5 ml blood from an HTLV-I-infected rabbit. Groups A, B, and C were infused 24 h later with 10, 5, and 2 ml HTLVIG, respectively, while group D was infused with 10 ml HTLVIG 48 h later. Seroconversion for HTLV-I occurred in none of group A, one of group B, and all of groups C and D after 2-5 weeks. In the second experiment, four litters (E, F, G, and H) born to another virus-infected rabbit and consisting of 7, 5, 7, and 7 newborns, respectively, were used. Litters E and H were allowed to grow normally as controls, while litters F and G were given intraperitoneal inoculation of 3 ml/kg of HTLVIG weekly four times until weaning. Although three of litters E and H each seroconverted after 5-8 weeks, none of litters F, and one of litter G became antibody-positive after 10 weeks. Presence or absence of HTLV-I infection in all these animals was confirmed by transfusion assay or gene amplification. These results indicate that passive immunization protects rabbits against blood- and milk-borne transmission of HTLV-I.

High level of HTLV-I specific protein expression in a patient with adult T-cell leukemia, chronic progressive myelopathy and Kaposi's sarcoma.

Analysis was made of serum anti-HTLV-I antibodies, virus-specific proteins in peripheral blood lymphocytes (PBL) and proviruses in lymphocyte DNA of a patient with adult T-cell leukemia (ATL), Kaposi's sarcoma, and chronic myelopathy. Using Western blot and PCR (with HIV-1 specific primers), it was shown that Kaposi's sarcoma was not linked to HIV infection. Western blot analysis of serum revealed antibodies against p19, p24 and Pr 53 of HTLV-I. Examination of proteins in fresh PBL by Western blot revealed a high level of HTLV-I specific protein expression. Southern blot analysis of the patient's DNA revealed two different sites for HTLV-I provirus integration.

Expression and Purification of a Novel Computationally Designed Antigen for Simultaneously Detection of HTLV-1 and HBV Antibodies.

Computational tools are reliable alternatives to laborious work in chimeric protein design. In this study, a chimeric antigen was designed using computational techniques for simultaneous detection of anti-HTLV-I and anti-HBV in infected sera. Databases were searched for amino acid sequences of HBV/HLV-I diagnostic antigens. The immunodominant fragments were selected based on propensity scales. The diagnostic antigen was designed using these fragments. Secondary and tertiary structures were predicted and the B-cell epitopes were mapped on the surface of built model. The synthetic DNA coding antigen was sub-cloned into pGS21a expression vector. SDS-PAGE analysis showed that glutathione fused antigen was highly expressed in E. coli BL21 (DE3) cells. The recombinant antigen was purified by nickel affinity chromatography. ELISA results showed that soluble antigen could specifically react with the HTLV-I and HBV infected sera. This specific antigen could be used as suitable agent for antibody-antigen based screening tests and can help clinicians in order to perform quick and precise screening of the HBV and HTLV-I infections.

Human T-cell lymphotropic virus infection among blood donors in south Florida. The Transfusion Safety Study Group.

Knowledge of the epidemiologic pattern of human T-lymphotropic virus (HTLV) in the United States is being enlarged by blood donor screening. We tested stored sera from 29,937 donations made in South Florida in 1984-1985. Twenty-three donors were confirmed as seropositive, a prevalence of 0.8 per 1,000 donations. Specificity was supported by serologic retesting and virus culture of 11 donors located for follow-up. Sex- and age-specific prevalences did not differ significantly; blacks, however, accounted for 65% of seropositive donations. Within South Florida, one section of Miami had a prevalence of 4.5 per 1,000 donations, significantly above the 0.1 to 1.1 per 1,000 rates for other parts. An epidemiologic association with known HTLV-I endemic areas could account for most infections; all seven typed isolates were characterized as HTLV-I. Exposures, however, were diverse, sometimes multiple, and had no necessary relationship to personal lifestyle. This finding suggests that sources of infection were varied. Seropositive family members emphasize familial clustering of HTLV-I infection.

Multiple sclerosis or HTLV-I myelitis?

Several authors have demonstrated the presence of antibodies against the HTLV-I retrovirus in patients with MS. Considerable controversy exists regarding the etiologic significance, if any, of this finding, but the presence of these antibodies in the blood or CSF of MS patients has led to reconsideration of that diagnosis in certain cases. It is recommended that, before the diagnosis of MS is changed to that of HTLV-I-associated chronic myelitis, at least 2 of the following abnormalities be present: (1) clinical or electrophysiologic involvement of peripheral nerve or muscle; (2) the presence of oligoclonal bands in the serum; (3) the presence in blood or CSF of lymphocytes with multilobed nuclei; (4) a positive serologic test for syphilis; (5) the presence of a sicca syndrome; and (6) the presence of pulmonary lymphocytic alveolitis.

Immune function and anti-HTLV-I/II status in anti-HIV-1-negative intravenous drug users receiving methadone.

PURPOSE: The study objective was to evaluate the effects of long-term methadone use and human T-cell leukemia virus (HTLV) types I and II seropositivity on the distribution of lymphocyte subsets and on lymphocyte function as measured in vitro in intravenous drug users seronegative for human immunodeficiency virus type 1 (HIV-1). PATIENTS AND METHODS: Anti-HIV-1-negative intravenous drug users receiving methadone maintenance therapy (n = 24) were studied in a Veterans Administration drug abuse treatment center. These subjects were compared to 38 age- and sex-matched control subjects who did not abuse drugs. HIV-1 and HTLV serostatus was determined by repetitive enzyme-linked immunosorbent assay and confirmed by immunoblot. Lymphocyte subsets were determined by two-color flow cytometry. Lymphocyte function was measured by proliferative response to plant mitogens and by natural killer (NK) cell-mediated cytotoxicity to a tumor cell target. RESULTS: Significant differences were seen in lymphocyte phenotype in the methadone-treated group, with elevations in the T-cell helper subset CD4+CD26+; in CD8 and CD8+I2+ cells, suppressor/cytotoxic T lymphocytes, and activated suppressor/cytotoxic T cells; and in CD2+CD26+ cells and activated total T lymphocytes. Lymphocyte function was suppressed in the methadone group, with poor responses to pokeweed mitogen and phytohemagglutinin in culture. Moreover, NK-cell cytotoxicity was significantly reduced in the methadone group. None of these immunologic differences were attributable to HTLV serostatus. CONCLUSION: The immune abnormalities seen suggest that a clinically significant degree of immune impairment exists in methadone-treated intravenous drug users. However, these abnormalities could not be explained by the presence of other retroviruses in this HIV-1-negative study group, as there was no significant difference in immune function when HTLV-seropositive patients were compared to HTLV-seronegative subjects treated with methadone.

Stable human T-lymphotropic virus type I carrier rates for 7 years among a teenaged blood donor cohort of 1986 in Kumamoto, Japan.

The human T-lymphotropic virus type I (HTLV-I) carrier rates for blood donors in Kumamoto, Kyushu, Japan for 8 years, 1986-1993, are currently available. The data show that 16-19-year-olds in 1986 and 20-29-year-olds in 1993 represent nearly the same cohort, because the median age in both groups is 24.5 years in 1993. Therefore, comparison of the HTLV-I positive rate for the two groups gives an estimate of the change in the rate over 7 years within the cohort. In males, 265 of 22,143 donors (1.20%) were seropositive for HTLV-I among 16-19-year-olds in 1986, and 214 were seropositive among 20,076 (1.07%) donors in 20-29-year-olds in 1993. In females, 203 were seropositive among 20,677 (0.98%) donors in 16-19-year-olds in 1986, and there 154 were seropositive among 18,660 (0.83%) donors in 20-29-year-olds in 1993. Thus, the seropositive rates declined in both sexes. However, the average annual rate of immigration to Kumamoto Prefecture was 2.37%. If seropositive rates for 20-29-year-olds in 1993 are adjusted for the dilution effect due to immigration (under the assumption that all immigrants were HTLV-I negative), the adjusted carrier rate for males is 1.26% and that for females is 0.98%. The adjusted carrier rates for both sexes are almost the same as those for 16-19-year-olds in 1986. This indicates that horizontal transmission was negligible for those in the cohort who were in their early reproductive period. Using all 8 year carrier rates for 16-19-year-olds and 20-29-year-olds, chronological changes of 20-29-year-olds, in the near future was estimated. The best goodness of fit model indicated that the HTLV-I carrier rate will decline exponentially, and that the rate will decrease by 50% approximately every 10 years for both sexes. It is probable that in recent years south-west Japan has lost the conditions that are favorable for HTLV-I endemicity and the virus will be virtually non-endemic within a few generations.

Antibodies in sera from Norwegian multiple sclerosis patients and the general population reacting with HTLV-1. A pilot study.

By using enzyme-linked immunosorbent assay, Western blot and passive agglutination we have performed a pilot study involving the testing of 349 sera from the general population of 3 coastal regions in southern Norway, 230 sera from multiple sclerosis patients from western Norway, 109 age- and sex-matched controls and 34 sera from patients with other neurological diseases, for antibodies to HTLV-I. About 2% and 4% of sera from the general population had antibodies reacting with HTLV-I in ELISA and Adult T-cell Leukemia Antigen by agglutination, respectively, whereas about 8% and 5% of the multiple sclerosis sera had such antibodies. In the general population antibodies were more frequent among young individuals and there appeared to be some prevalent regional differences. Western blot confirmatory tests showed that in some instances antibodies reacted with the gag proteins, in particular p19. The results obtained in this study do not indicate an association between HTLV-I and multiple sclerosis, although at this stage we cannot rule out that another retrovirus is involved.

Seroepidemiological survey of human T-lymphotropic retrovirus among indigenous populations in Taiwan.

The prevalence of human T-lymphotropic retrovirus (HTLV) was examined in Taiwan's indigenous populations. In all, 797 healthy subjects in Taiwan including Han Chinese and nine indigenous populations (Ami, Atayal, Bunun, Saisiat, Paiwan, Puyuma, Rukai, Tsuo, and Yami) were examined for the presence of antibodies to HTLV by particle agglutination, indirect immunofluorescence and Western blot test. Two seropositive cases were found in this screening. One Saisiat male and a Han Chinese female were seropositive for HTLV. The Western blot profile indicated the virus was type-1 HTLV.

Seroepidemiology of human T cell lymphotropic virus in the Republic of Panama.

The human T-lymphotropic virus (HTLV) and associated diseases, adult T cell leukemia and spastic paraparesis, appear to be endemic in southwestern Japan and the Caribbean. This cross-sectional population-based study was conducted to describe the seroepidemiology of HTLV in the Republic of Panama. HTLV antibody was measured by first generation and commercial ELISA tests and confirmed by competitive binding ELISA, a radioimmunoassay for anti-p 24, and Western blot. Of 3,231 subjects greater than or equal to 15 years of age, 135 (4.2%) had antibody detected in ELISA screening tests, but because only 20% were confirmed positive, HTLV seroprevalence varied from 0.2-2% throughout the Republic. Infection with HTLV clustered in Guaymi Indians living in Bocas del Toro province (9.9% prevalence rate). With the exception of Guaymi Indians, no major geographic, urban/rural, male/female or racial differences in antibody prevalence were observed; specifically, HTLV infection rates were not elevated in black Panamanians. Clustering of infection in an isolated Amerind population must be further investigated. The small proportion of screen-positive sera which confirmed positive illustrates the importance of strict uniform criteria for seropositivity.

Impairment of cell-mediated immune responses in HTLV-I-associated myelopathy.

In order to assess in vivo cell-mediated immune functions in HTLV-I-associated myelopathy (HAM), we immunized 18 HAM patients with dinitrochlorobenzene (DNCB). Of 18 patients, the skin reaction to DNCB was negative in 15. All those 15 patients also showed anergy to PPD-tuberculin and 9 of 15 patients had a persistent lymphocytopenia (less than 1500/mm3). In vitro lymphoproliferative responses to mitogens, assayed by a flow fluorocytometric method, were also significantly depressed in HAM patients when compared to normal controls. The results thus indicate that cell-mediated immune functions are significantly impaired in HAM patients.

Human T lymphotropic virus type I (HTLV-I) infection in neurological patients in Salvador, Bahia, Brazil.

HTLV-I infection represents a major health concern in endemic areas throughout the world, such as Salvador, the main city of Bahia State, with socio-demographic characteristics similar to sub-Saharan African cities, located in the Northeast of Brazil. In order to provide an estimate of the frequency distribution, and range of neurological manifestations potentially related to HTLV-I infection in this city, we conducted a cross-sectional clinical-epidemiological study to determine the prevalence of this infection in patients with neurological diseases. Patients exhibiting vascular diseases, tumoral diseases or trauma were excluded. Over a period of 16 months, we studied 322 consecutive patients with chronic neurological diseases, who attended the neurological clinics of two major hospitals in Salvador. Overall, the prevalence of HTLV-I infection among the patients was 20.9% (67/320). However, the prevalence among the 104 patients with chronic myelopathy was 50.0% (52/104). It was observed that the major prevalence of HTLV-I was between the ages of 40 and 60 years with a female predominance. Our data indicate that, in Salvador city, HTLV-I is associated with chronic myelopathies or myeloneuropathies, which seem to be the only neurological diseases associated with HTLV-I.

Laboratory diagnosis of retroviral infections.

The molecular biology techniques that were once the exclusive domain of the basic researcher are now becoming apparent within the diagnostic laboratory. Techniques that can detect and quantify the specific genes of retroviruses without the need for radioactive compounds are becoming a reality. In addition, they are rapidly being applied to other viral and nonviral infectious diseases. For the present, techniques that detect the presence of antiretroviral antibodies are the front-line tests for screening and detecting infected, mostly asymptomatic individuals. As vaccines and chemotherapies become the standard of care, tissue culture, PCR, in situ hybridization, and flow cytometry will become the core diagnostic technologies that will enable an accurate prognosis of disease and evaluation of therapy; however, as with any diagnostic procedures, they must be performed against a background of a strong and aggressive quality control and assurance program.

Prevalence of blood-borne viruses among intravenous drug users and alcoholics in Hiroshima, Japan.

We investigated the prevalence of human immunodeficiency viruses-1 and 2 (HIV-1 and HIV-2), human T-lymphotropic virus type I and II, hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus among intravenous drug users (IVDU) in Hiroshima, Japan, where little is known about their present levels. From June to December 1993, serum samples were collected from 47 IVDU and 98 alcoholics in Hiroshima, Japan, and examined for markers of virus infection. The prevalence of antibody to HCV (anti-HCV) and/or HCV-RNA was significantly higher in IVDU than alcoholics (74.5% vs 20.4%, 44.7% vs 10.2% respectively, P < 0.001). In contrast, the prevalence of antibody to hepatitis B surface antigen and/or core antigen (anti-HBs and/or anti-HBc) showed no significant difference between the 2 groups (57.4% vs 66.3%). HIV-1 infection was found in one (2.1%) IVDU and genome analysis indicated that it was subtype B according to Myers' classification. Thus, an extremely low level of HIV infection and a high level of HCV infection was found in IVDU. Careful follow-up of this group is thought to be needed to minimize an outbreak of HIV-1 infection in Japan.

Human T cell leukemia virus type I-associated myelopathy in a patient with systemic lupus erythematosus.

A case of human T cell leukemia virus type I (HTLV-1) associated myelopathy (HAM)/tropical spastic paraparesis (TSP) with 14-year history of systemic lupus erythematosus (SLE) is reported. For 9 years, the numbness of the feet and sacral region progressed with occasional urinary incontinence and constipation. She was admitted to hospital due to gait disturbance and aggravation of SLE and the diagnosis of HAM/TSP was confirmed, indicating that HTLV-1 infection is associated with the development of not only HAM/TSP but also SLE.

HTLV-I associated myelopathy in Brazil: a preliminary report.

In this preliminary report the authors present the finding of a high prevalence (37.5%) of seropositivity of antibodies to HTLV-I tested by Western blotting in a sample of 16 Brazilian patients with chronic myelopathies of undetermined origin.

Human T cell leukaemia/lymphoma virus infection in pregnant women in the United Kingdom: population study.

OBJECTIVE: To assess the prevalence of human T cell leukaemia/lymphoma virus (HTLV) infection in pregnant women in the United Kingdom. DESIGN: Population study. SUBJECTS: Guthrie card samples from babies born in 1997-8. Samples were linked to data on mother's age and ethnic status and parents' country of birth and then anonymised. SETTING: North Thames Regional Health Authority. MAIN OUTCOME MEASURES: Presence of antibodies against HTLV in eluates tested by gelatin particle agglutination assay and results confirmed by immunoblot. RESULTS: Of 126 010 samples tested, 67 had confirmed antibodies to HTLV (59 HTLV-I, 2 HTLV-II, 6 untyped) and six had indeterminate results. Seroprevalence was 17.0 per 1000 (95% confidence interval 9.2 to 28.3) in infants whose mothers were born in the Caribbean, 3.2/1000 (1.5 to 5.9) with mothers born in west and central Africa, and 6.8/1000 (3.1 to 12.9) in infants of black Caribbean mothers born in non-endemic regions. In infants with no known risk (both parents born in non-endemic regions and mother not black Caribbean) seroprevalence was 0.06-0.12 per 1000. Mother's country of birth, father's country of birth, and mother's ethnic status were all independently associated with neonatal seroprevalence. An estimated 223 (95% confidence interval 110 to 350) of the 720 000 pregnant women each year in the United Kingdom are infected with HTLV. CONCLUSIONS: The prevalence of HTLV and HIV infections in pregnant women in the United Kingdom are comparable. The cost effectiveness of antenatal HTLV screening should be evaluated, and screening of blood donations should be considered.