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HTLV-I transmission routes were found for 66 carrier pregnant women by studying sera, from the carrier pregnant women, their mothers, and their husbands, and by obtaining detailed family histories at interview. Forty-one cases (62.1%) were considered to be instances of vertical transmission, 15 (22.8%) of sexual transmission, 6 (9.1%) of blood transfusion, and 4 (6.1%) undecided. To date, most cases of adult T-cell leukemia (ATL) have been considered to result from vertical transmission. Our results therefore imply that about 30% (22.8% + 9.1%) of the carrier pregnant women are at minimal risk of ATL. Moreover, in case of presumed husband-to-wife transmission, more than half (6/11) were infected between one year and four years after marriage.

A fully automated chemiluminescence immunoassay was developed for the detection of antibodies to HTLV-I. We used partially purified viral antigens coated on small polystyrene beads together with acridinium ester-labeled anti-human immunoglobulin G mouse immunoglobulin G in this method. A good agreement was observed between our proposed method, the indirect immunofluorescence assay, the particle-agglutination test and the enzyme immunoassay. This new method, which is simple, sensitive, specific and rapid, should be useful for mass screening of anti-HTLV-I antibodies.

Breast feeding is the major route of mother-to-child transmission of human T-cell leukemia virus type I (HTLV-I). Our experiments with rabbits have shown that passive immunization is capable of blocking cell-to-cell infection of HTLV-I by blood transfusion or breast feeding. In this study, sera were collected serially from 3 infants born to seropositive mothers and were tested for the presence of neutralizing antibody to vesicular stomatitis virus (HTLV-I) pseudotype as well as antibodies to viral structural proteins. There was a good correlation between neutralizing and viral antibody titers, both of which were detectable until 3-6 months after birth. Whether maternally transmitted neutralizing antibody is protective against perinatal infection of HTLV-I remains to be studied.

We developed a polymerase chain reaction (PCR) method which has high sensitivity and simple technique in order to investigate the presence or absence of human T lymphotropic virus type I (HTLV-I) provirus in cord blood mononuclear cells of neonates born to HTLV-I carrier mothers. Out of 40, three subjects were found to contain the HTLV-I provirus genome. These three subjects remained HTLV-I sequence-positive in follow-up study. On the other hand, when examined by a conventional technique for detection of HTLV-I-associated antigen on peripheral mononuclear cells, all 40 neonates were HTLV-I-associated antigen-negative. These results suggest that PCR is more sensitive than the conventional antigen detection method and is useful in early detection of HTLV-I infection in neonates born to HTLV-I carriers.

We studied DNA sequences homologous to HTLV-1 in peripheral blood mononuclear cells (PBMC) of 30 patients with neurological disorders in Kyushu, where HTLV-1 is highly endemic. The regions of HTLV-1 amplified by means of polymerase chain reaction (PCR) included U3, U5, gag, pol, env and pX. Our system specifically detected HTLV-1 sequences only from HTLV-1-positive cells and was sufficiently sensitive to detect one proviral copy per 10(3) PBMC. All PCR-positive cases were seropositive, including 4 cases of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (4/4), and one case each of myasthenia gravis (1/7) and multiple sclerosis (1/8). The PCR-positive rate of patients, excluding 4 TSP/HAM cases, was 8% (2/26), which is similar to the seroprevalence of the adult population in the area. The data suggest that multiple sclerosis is not associated with prototype HTLV-1.

We investigated antibodies against pX gene product, p40tax, by ELISA using recombinant p40tax protein in HTLV-I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV-I healthy carriers were found to be positive for antibody against p40tax antigen and the follow-up samples at two-year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti-HTLV-I in primary infection cases. The anti-p40tax-positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti-p40tax showed a higher anti-HTLV-I-positive rate than that of children from mothers without anti-p40tax (54.5% versus 12.5%). Two men without anti-p40tax and one female with low anti-p40tax developed ATL during follow-up studies. These results suggest that HTLV-I carriers could be divided into 2 or 3 sub-populations according to antibody response to p40tax. A smaller population with anti-p40tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti-p40tax.

This study was undertaken to determine which if any pretreatment factors are statistically significant determinants of the clinical outcome in patients with non-Hodgkin's lymphoma. The pretreatment factors in 20 patients with T-cell lymphoma, including two patients with adult T-cell leukemia/lymphoma (ATLL), and 28 patients with B-cell lymphoma were evaluated. In a stepwise logistic regression analysis, a T-cell phenotype in addition to high grade histology and pleural involvement demonstrated a statistically significant correlation with decreased response rate, when the analysis did not include patients with ATLL. Analysis by means of the Cox proportional hazards model disclosed that the T-cell phenotype retained a statistically significant correlation with survival after adjustments for other prognostic factors, whether the study included the patients with ATLL or not. The decreased response rate and survival of Japanese patients with non-Hodgkin's lymphoma in comparison with those reported in Western countries seem to be due to increased intrusion of T-cell lymphomas. To permit a reliable comparison of reports on new chemotherapeutic regimens from different institutions, the tumor phenotype must be determined in the population studied.

A married couple who developed adult T-cell leukemia (ATL) is described. The husband presented with acute ATL and died soon after admission in spite of aggressive chemotherapy, and his wife, who is diagnosed as smoldering ATL, has been followed in the out-patient clinic. The couple had serum antibodies against human T-cell leukemia virus type I (HTLV-I) and the monoclonal integration of HTLV-I proviral DNA in their lymphocytes. The patients described represent the first reported example of ATL in a married couple.

In order to test the performance of particle agglutination assay (PA), 800 preselected PA-positive sera at 8 blood centers in the Kyushu area were tested in various assays. Most blood centers should improve their PA technique, since a third of the samples were PA-negative in our hands. A third of our PA high-titer sera were negative in indirect immunofluorescence and enzyme immunoassay, the results of which were consistent with each other. Western blots did not detect every positive serum. PA inhibition positivity was not consistent with PA titer. Most IgM antibody-positive sera also contained IgG antibody. PA should be used in combination with other methods before notifying the results to positive testees.

A new enzyme-linked immunosorbent assay (ELISA) for detecting the antibody to a human T-lymphotropic virus type I (HTLV-I) tax gene product, p40tax, has been developed. By this ELISA method, we have investigated the relationship between the presence of p40tax antibody in HTLV-I-infected mothers and the virus transmission rate from mothers to their children. The rate of mother-to-child transmission of HTLV-I was higher in p40tax antibody-positive mothers than in antibody-negative ones. Thus, the presence of p40tax antibody may indicate an increased risk of vertical transmission of HTLV-I.