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Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm with extremely poor prognosis caused by human T-cell leukemia virus type 1 (HTLV-1). The distribution of HTLV-1 and the incidence of ATLL in endemic areas have been well described, however, little is known about the incidences and the trends of the disease in nonendemic areas. Recently, studies have shown that the HTLV-1 carriers are increasing in nonendemic areas. Also, the incidence of ATLL seems to be significantly increasing in nonendemic areas suggesting that HTLV-1 carriers have emigrated from endemic areas. These epidemiologic studies indicate the necessity of edification of the disease caused by HTLV-1 and establishing appropriate preventive methods against infection in nonendemic areas.

The aim of this study was to assess the current human T-cell lymphotropic virus type 1 (HTLV-I) mother-to-child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow-up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short-term breast-feeding. The HTLV-I carrier rate among pregnant women in Kagoshima has declined. The current HTLV-I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT., (© 2014 Japan Pediatric Society.)

Adult T-cell leukemia-lymphoma (ATL) is a distinct peripheral T-lymphocytic malignancy associated with human T-cell lymphotropic virus type I (HTLV-1) endemics in several regions of the world including the south-west Japan. The three major routes of HTLV-1 transmission are mother-to-child infections via breast milk, sexual intercourse, and blood transfusions. A HTLV-1 infection early in life, presumably from breast feeding, is crucial to the development of ATL. The estimated cumulative risk of developing ATL among HTLV-1-positive individuals is about 3% after transmission from the mother. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into acute, lymphoma, chronic, and smoldering types defined by organ involvement, lactate dehydrogenase (LDH) and calcium values. For the acute, lymphoma and unfavorable chronic subtypes (aggressive ATL), and the favorable chronic and smoldering subtypes (indolent ATL), intensive chemotherapy followed by allogeneic stem cell transplantation and watchful waiting until disease progression has been recommended, respectively, in Japan. A retrospective analysis suggested that the combination of interferon alpha and zidovudine was promising for the treatment of ATL, especially for leukemic subtypes. There are several new trials for ATL, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody, histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor and lenalidomide., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Human T-cell leukemia virus type-1 (HTLV-1), a major source of adult T-cell leukemia and related diseases, is endemic to southwestern Japan. Mother-to-infant transmission via breast milk is an important route of infection, and establishing programs to prevent such transmission requires exact figures on the HTLV-1 prevalence rate and the number of carriers. Therefore, the seroprevalence of HTLV-1 among 1,196,321 Japanese first-time blood donors from 2006 to 2007 was investigated. A total of 3,787 of such donors were confirmed to be positive for anti-HTLV-1 antibody. By applying a fitness curve to the age ranges outside the blood donor age range, the present number of HTLV-1 carriers covering ages from 0 to 99 years was estimated to be at least 1.08 million in Japan; this value was 10% lower than that reported in 1988. The adjusted overall prevalence rates were estimated to be 0.66% and 1.02% in men and women, respectively. The peak in carrier numbers was found among individuals in their 70s, which is a shift from the previous peak observed in the 1988 database among individuals in their 50s. Carriers were distributed not only in the endemic southwestern region of Japan, but throughout the country, particularly in the greater Tokyo metropolitan area. By applying population projections, it was calculated that the carrier number will decrease by half in the next two decades; however, the carrier population will age over that interval, meaning that the age of patients with adult T-cell leukemia will also be higher., (Copyright © 2011 Wiley Periodicals, Inc.)

Japanese breast milk samples were tested for antibodies to human T-cell leukemia virus type I (HTLV-1) by particle agglutination (PA) and a line immunoassay (LIA). In the PA method, the agglutination reaction between the HTLV-1 antibody and sensitized particles occurred at a 1 : 128 dilution of some breast milk samples. The average antibody titer was one order of magnitude lower than that in the serum positive control. A total of 243 human breast milk specimens were assayed by PA, of which 21 samples from Okinawa, Hyogo, Miyagi and Hokkaido were positive or deferred. The results of the 21 positive samples were subsequently assayed by LIA (INNO-LIA™ HTLV I/II) for confirmation; and one sample was positive, and two were indeterminate. We attempted to use polymerase chain reaction (PCR) to detect HTLV-1 provirus DNA, but we did not detect PCR products for the pX1 region of the HTLV-1 genome in the LIA-positive samples. These negative PCR results are most likely due to the lower sensitivity of the PCR for amplification from milk than from HTLV-1-positive monocytes. In conclusion, the PA method to breast milk samples appears to be a suitable tool to screen for antibodies to HTLV-1 in the breast milk of carrier mothers in cases in which it would be difficult to use serum for the test. Although LIA may be able to confirm HTLV-1 infection, the presence of HTLV-1 provirus should be confirmed in the breast milk.

It is 30 years since human T-cell leukemia virus type 1 (HTLV-1) was identified as the first human retrovirus. To assess the implications of the virus for human health it is very important to know the past and present prevalence. Most of the estimates of HTLV-1 prevalence are based on serological screening of blood donors, pregnant women and other selected population groups. The widely cited estimate that the number of HTLV-1 carriers in Japan is 1.2 million was calculated from data that are now more than 25 years old. Here I summarize previous reports of prevalence studies in the world and Japan. Then, a recent analysis of seroprevalence of healthy blood donors in Japan will be described in comparison with that of 1988. A decrease in the number of HTLV-1 carriers in Japan was demonstrated, however, it is still more than one million. The number has increased in the metropolitan areas, probably reflecting the migration of Japanese population. I conclude that there is a paucity of general population data in countries where HTLV-1 is endemic, and re-evaluation of HTLV-1 infection is required to understand the virus burden on the human health.

Infective dermatitis (ID) is a chronic, relapsing dermatitis associated with human T-lymphotrophic virus (HTLV)-1 which was initially described in Jamaican children. Although most cases have been reported in Jamaica, ID may be seen in other HTLV-1 endemic areas, such as Brazil, Japan, sub-Saharan Africa, and Trinidad and Tobago. Since HTLV-1 infection has been implicated in the development of adult T-cell leukemia/lymphoma, an aggressive hematologic malignancy, and HTLV-1-associated myelopathy/tropical spastic paraparesis, a neurodegenerative disease, ID may serve as an early clinical marker for either condition. Although HTLV-1-associated infective dermatitis is considered by most to be rare, it has been increasingly diagnosed over the past 20 years; some suggest ID may be underdiagnosed. One should maintain suspicion of HTLV-1 infection among individuals in or from endemic areas, recognizing the clinical features and prognostic implications of infectious dermatitis., (Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Human T-cell leukemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukemia, and the distribution of HTLV-I carriers is endemically biased, e.g. in Japan the density of carriers is high in Kyushu and Okinawa. In order to consider population dynamics over long times taking account of an increase and a decrease of a population we propose a continuous-time HTLV-I model. The model describes population dynamics of carrier numbers and that of carrier proportions, and theoretical results about an increase and a decrease of carriers are obtained. The present approach derives an explanation of the biased distribution of carriers in Japan.

Epidemiologic aspects of human T-lymphotropic virus type I (HTLV-I) infection have been thoroughly studied over the course of approximately 25 years since its first description. The geographic distribution of the virus has been defined, with Japan, Africa, Caribbean islands and South America emerging as the areas of highest prevalence. The reasons for HTLV-I clustering, such as the high ubiquity in southwestern Japan but low prevalence in neighboring regions of Korea, China and eastern Russia are still unknown. The major modes of transmission are well understood, although better quantitative data on the incidence of transmission, and on promoting/inhibiting factors, are needed. Epidemiologic proof has been obtained for HTLV-I's causative role in major disease associations: adult T-cell leukemia (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-associated uveitis and infective dermatitis. However, more and better studies are needed for other apparent disease outcomes such as rheumatologic, psychiatric and infectious diseases. Since curative treatment of ATL and HAM/TSP is lacking and a vaccine is unavailable, the social and financial cost for the individual, his/her family and the health system is immense. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of paramount importance.

Aim: Human T-lymphotropic virus type-I (HTLV-I) infection occurs via mothers' milk during feeding. However, freeze-thaw processing can eliminate the infectivity of the mother's milk of HTLV-I carriers., Methods: A long-term follow-up survey was conducted to investigate the HTLV-I infectivity of frozen-thawed mothers' milk among infants whose mothers were HTLV-I seropositive., Results: Infants fed frozen-thawed mothers' milk did not become HTLV-I antibody-positive up until 1 year old, and all children followed up until an age of 11-12 years were antibody negative., Conclusions: This study showed that freeze-thaw processing can eliminate the HTLV-I infectivity of mothers' milk, and that HTLV-I carriers can indirectly feed their infants using frozen-thawed mothers' milk as a way to prevent HTLV-I infection.

To investigate the chronologic change of mother-to-child transmission of human T lymphotropic virus type I (HTLV-I) in Okinawa, Japan, the presence of antibody to HTLV-I was tested in 4,187 healthy residents between, 4,528 nursery school children, and 3,837 pregnant women between 1968 and 2000. The chronologic change of the feeding method and the length of the breast-feeding period among 1,117 healthy mothers from 1937 to 1995 were also obtained by interview. Age-adjusted prevalence of HTLV-I among healthy residents decreased from 9.1% in 1968-1970 to 7.8% in 1981-1984 and to 6.3% in 1996-1998. The crude prevalence of antibody to HTLV-I among healthy residents less than 20 years old decreased significantly from 4.6% in 1968-1970 to 0.1% in 1996-1998 (P < 0.0001). The prevalence of antibody to HTLV-I among nursery school children decreased significantly over the study period, from a high of 1.8% in 1984 to a low of 0.2% in 1998 (P = 0.03). The prevalence among pregnant women decreased significantly from 5.6% in 1989-1992 to 3.7% in 1997-2000 (P = 0.0275). Prior to 1967, all healthy mothers breast-fed their children. After 1968, the use of bottled and mixed milk (breast milk and bottled milk) increased, with bottled milk becoming predominant after 1990 (89%). The percentage of healthy mothers breast-feeding for more than one year significantly decreased from 68.3% in 1937-1947 to 0.4% in 1990-1995 (P < 0.0001). Infection with HTLV-I in Okinawa has decreased mainly due to a reduction in the number of mothers breast-feeding and a shortening of the breast-feeding period. However, because the mother-to-child transmission rate among non-breast-feeders decreased from 12.8% in 1986-1991 to 3.2% in 1995-1999, there may be other factors involved in the decrease in mother-to-child transmission.

Clinical and laboratory findings were examined for 111 human T-cell lymphotropic virus type I (HTLV-I)-infected blood donors. HTLV-I provirus loads in subjects with a family history of adult T-cell leukemia (ATL) or HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) tended to be higher than those in subjects without a family history of these conditions. There were 3 asymptomatic patients with ATL, 4 with a history of uveitis, 7 with hyperreflexia in the lower limbs, and 3 with urinary frequency in the night. The mean CD4 cell/CD8 cell ratio +/- SD was significantly lower (p<.0001) in subjects with hyperreflexia in the lower limbs (1.3 +/- 0.2) than in subjects without any clinical abnormalities (1.7 +/- 0.6), suggesting that subjects with hyperreflexia in the lower limbs already have some immunologic abnormalities. The concordance of HTLV-I infection between husband and wife was lower in this study than in a previous study. HTLV-I-related inflammatory symptoms were more frequent (p =.021, Fisher exact test; OR = 9.5; 95% CI, 1.7-53.5) in HTLV-I tax A-infected donors (3 [50%] of 6 donors) than in HTLV-I tax B-infected donors (10 [9.5%] of 105 donors), suggesting different risks of HTLV-I-related symptoms according to the virus genotype.

To clarify the route of human T lymphotropic virus type 1 (HTLV-1) transmission, we sequenced three proviral genome regions (gag, env, int) of HTLV-1 from 18 carriers in 7 families in Okinawa, Japan and compared the strains with isolates from other countries. The nucleotide substitution frequency among sequences derived from a single carrier was low; 0-0.24% in gag, 0-0.54% in env, and 0-0.34% in int. All sequences showed the closest identity to the Cosmopolitan strain, with differences of only 0-1.91%. All 8 mother/child pairs had identical nucleotide sequences. Of 3 pairs of spouses, 2 had identical sequences, with transmission probably from husband to wife. The mothers of both wives were HTLV-1-negative. The HTLV-1 sequence of the other wife showed three nucleotide differences from the sequence of her husband, but was identical to the sequence of her mother. These results support previous seroepidemiological studies that HTLV-1 transmission occurs from mother to children and also between spouses.

Human T-cell leukaemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). HTLV-I has existed in Japanese people for thousands of years. In order to prevent an epidemic of HTLV-I, it is important to explain the infection system by a mathematical approach. By considering the main infection routes in Japan, that is: (i) mother-to-child transmission; (ii) male (husband)-to-female (wife) transmission; and (iii) female (wife)-to-male (husband) transmission, a mathematical model for describing the time-dependent change of the infection proportion can be constructed. An upper bound of the present infection rate per year in male-to-female transmission and that in female-to-male transmission is given by the model, and theoretical results related to HTLV-I infection are also deduced from the mathematical model. A simulation study based on the present model demonstrates the theoretical results relating to the HTLV-I infection., (Copyright 2001 John Wiley & Sons, Ltd.)

Objective: The aim of this study was to clarify the trend of the HTLV-1 seroprevalence rate among blood donors., Methods: Samples were screened by the particle agglutination test for HTLV-1 antibodies., Materials: Serum from blood donors was screened., Results: The positive rate of HTLV-1 antibodies among blood donors decreased from 13.14 to 0.81 % over the years from 1928 to 1983., Conclusion: A decline over the years in the positive rate of HTLV-1 antibodies among blood donors was revealed.

Human T-cell lymphotropic virus type I (HTLV-I) is transmitted through infected lymphocytes mostly by breast feeding. In the present study, high prevalence of HTLV-I infection was disclosed in the family members of a patient with adult T-cell leukemia/lymphoma (ATL), all of whom were residents of Iwate, northeastern Japan. Long-term follow-up is necessary for people with HTLV-I infection because of the risk of developing ATL after a certain period of latency. New inventive treatments for the acute and lymphomatous types of ATL are needed.

To assess the relationship of anti-Tax antibody to human T-cell lymphotropic virus type-I (HTLV-I) transmission, the sero-prevalence of HTLV-I was analyzed among married couples and among mother/child (both adults) pairs. HTLV-I seroprevalence was significantly higher among wives with anti-Tax+ than those with anti-Tax- HTLV-I carrier husbands (82.4% vs. 59.5%). However, in the group of wives aged 60 years or older, there was no statistical difference in HTLV-I seropositivity based on the husbands' anti-Tax sero-status. In the group whose wives were less than 60 years old, more anti-Tax sero-positive than sero-negative husbands had high DNA levels (57.1% and 20.0%), whereas in the group of husbands whose wives were aged 60 years or older, the number of anti-Tax sero-positive and sero-negative individuals with high DNA levels was similar. HTLV-I sero-prevalence was significantly higher among the adult men with anti-Tax+ carrier mothers than those with anti-Tax- carrier mothers (52.0% vs. 14.3%). For women, HTLV-I sero-prevalence did not differ significantly according to their mothers' anti-Tax sero-status. Our results suggest that the presence of anti-Tax antibody in HTLV-I carriers is an age-dependent risk factor for male-to-female HTLV-I transmission. Furthermore, the effect of the mother's anti-Tax antibody as a risk factor for vertical HTLV-I transmission could be observed in men even after becoming adults.

The Nagasaki Prefecture, Japan (population: 1.5 million), is one of the hot endemic foci of Human T-lymphotropic virus type 1 (HTLV-1). Prevalence of HTLV-1 carriers are approximately 10% in the age group over 40 years old (40,000 individuals), approximately 10 times of the national average. Annual registry of adult T-cell leukemia (ATL) in the Prefecture is approximately 60 cases (estimated incidence: 100 cases), or a half percent of total deaths. A effective measure to control the endemic cycle of HTLV-1 has been imperative, since practical ways to prevent or control ATL are not available. A prefecture wide intervention at Nagasaki by refrain from breast-feeding blocked approximately 80% of mother-to-child transmission of HTLV-1.

The ATL prevention program (AAP) in the Nagasaki Prefecture since 1987 consists of screening of pregnant women and asking the seropositives to refrain from breast-feeding. We screened approximately 90% of gravidas in the Prefecture and > 90% of the seropositive women agreed not to breast-feed. The maternal transmission rate dropped from approximately 20% to approximately 3%. PCR of cord bloods showed that 2.5% were PCR-positive. However, among formula-fed children, none of the cord-positives seroconverted, and none of the seropositives tested had been cord-positive. Breast-feeding for less than six months decreased the transmission rate significantly, but may have a higher transmission rate than the formula feeding.

The purpose of the Miyazaki Cohort Study is to describe and analyze the natural history of human T-cell lymphotropic virus type I (HTLV-I) in a highly endemic population in southwestern Japan. As of August 1995, 1,960 individuals have been enrolled, of whom 27% were HTLV-I antibody positive at baseline. Our achievements over the past decade of following this cohort include the identification of several viral markers that characterize high-risk carriers and the documentation that carriers have subclinical evidence of impaired cellular immunity. We have begun to estimate the impact of the infection on the health of carriers and have found that men are at greater risk of HTLV-I-associated diseases than women. We have been able to identify prospectively risk factors associated with sexual transmission. Most important, by identifying subclinical markers of pathogenesis, we hope to provide the foundation for developing interventions to prevent HTLV-I-associated disease.

Adult T-cell leukemia (ATL) was first reported in Japan, where it has a high incidence in the southwestern region. The retrovirus, human T-lymphotropic virus type I (HTLV-I), is the causative agent of ATL. In ATL-endemic areas, the rate of HTLV-I carriers is high. A definite diagnosis of ATL is based on the presence of HTLV-I proviral DNA in the tumor cell DNA. ATL cells originate from the CD4 subset of peripheral T cells. ATL shows diverse clinical features but can be divided into four subtypes:acute, chronic, smoldering, and lymphoma type. Chemotherapy is not effective; the acute and lymphoma types have a poor prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by transmission of live infected lymphocytes from mother to child, from man to woman, or by blood transfusion. Infection with HTLV-I can lead to other diseases, including HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I uveitis.

Adult T-cell leukaemia (ATL) was first reported in Japan, where it has a high incidence in the southwest region. The retrovirus human T-lymphotropic virus type I (HTLV-I) is the cause of ATL; and in ATL-endemic areas, the rate of carriage of antibodies to HTLV-I is high. A definite diagnosis of ATL is based on the presence of HTLV-I proviral DNA in the tumour-cell DNA. ATL cells originate from the CD4 subset of peripheral T cells. ATL shows diverse clinical features but can be divided into four subtypes--acute, chronic, smouldering, and lymphoma type. It is resistant to chemotherapy, and the acute and lymphoma types have a poor prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by transmission of live infected lymphocytes from mother to child, from man to woman, or by transfusion. Infection with HTLV-I can lead to other diseases, including HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I uveitis, possibly via induction of immunodeficiency or hyperreactivity against HTLV-I-infected cells.

Interviews and laboratory testing were conducted for 168 contacts referred by former blood donors identified as seropositive for antibody to human T-lymphotropic virus type I (HTLV-I) or type II (HTLV-II). Thirty-two (28%) of 114 heterosexual contacts of seropositive donors, including 12 women and 20 men, were found to be antibody positive. None of 40 offspring (except one adult man who reported sexual contact in Puerto Rico) or 14 other (nonspousal) family members were seropositive. Thirty-one of the seropositive contacts were typeable as having either HTLV-I (52%) or HTLV-II (48%). Assessment of couples found that the median duration of the sexual relationship was significantly longer (p = 0.03) for those in which both partners were infected than in discordant pairs. Analysis of risk history data for 22 infected couples revealed that, in three cases, risk factors (Japanese ancestry or sexual contact with an injecting drug user) could be identified in the women, but not in their male partners. Among couples in which the male had the greater risk history, the risk factor was either a history of transfusion, birth or sexual exposure in an endemic area, or injected drug use. Counseling strategies for individuals with HTLV-I or HTLV-II infection should take into account the relatively high seroprevalence in their partners and should address the potential for sexual transmission in both directions.

Six Colombian patients with adult T-cell leukemia/lymphoma (ATL) are presented. The clinical and hematological features, the familial clusters of human T lymphotropic virus type 1 (HTLV-I) carriers and the prognoses of the Colombian ATL patients were similar to those previously reported for Japanese ATL patients. The only difference was the mean age of onset, which was more than 20 years younger than in Japanese patients. Three patients with ATL were suffering from strongyloidiasis. In one patient it was suggested that ATL developed after horizontal transmission from his wife. In addition, there was a familial case of ATL and HAM/TSP. It seems that in some areas of Colombia, not only HTLV-I infection and HAM/TSP but also ATL are highly endemic.

The significant difference observed between the seroprevalence of HTLV-I in adults and in children is as yet unexplained. To evaluate a hypothetical explanation of the existence of seroconversion cases of "seronegative carriers" for this phenomenon, 21 of 55 children who had been born to seropositive mothers and who remained seronegative until the age of 18 years were further followed up at the ages of 22 and/or 24 years. None of the 21 seronegative children born to seropositive mothers seroconverted, either at 22 years or at 24 years. In addition, the polymerase-chain-reaction (PCR) technique could not prove the existence of the HTLV-I provirus genome in peripheral mononuclear cells (PBMC) of 10 of these children. Our results fail to prove the possibility of viral latency of HTLV-I in mother-to-child transmission. Therefore, the hypothetical seroconversion of "seronegative carriers" after adulthood cannot be an explanation.

To identify factors that may modify the heterosexual transmission of human T cell leukemia/lymphoma virus type I (HTLV-I), 534 married couples enrolled in the Miyazaki Cohort Study between November 1984 and April 1989 were studied: 95 husband HTLV-I-seropositive (H+)/wife seropositive (W+), 33 H+/W-, 64 H-/W+, and 342 H-/W-. After 5 years of follow-up, seven seroconversions occurred and clustered significantly among serodiscordant pairs (relative risk [RR] = 41.2); the rate of transmission was 3.9 times higher if the carrier spouse was male (P = .19). Among H+/W- couples, husband's age > or = 60 years strongly predicted seroconversion in the wives (RR = 11.5). All 4 carrier husbands whose wives seroconverted had HTLV-I titers > or = 1:1024 (P = .04) and were anti-tax antibody positive (P = .06). In cross-sectional analysis, total parity also was independently associated with wife's serostatus but only length of marriage with husband's. Overall, sexual transmission of HTLV-I was primarily from older infected husbands to their wives, with husbands' viral status being an important factor.

Among the TORCH agents, the occurrence of rubella and human T-lymphotropic virus type 1 (HTLV-1) in Japan were studied. Rubella epidemics occurred throughout Japan from 1964 to 1969 and from 1975 to 1979. Low prevalences of CRS were observed in northeastern Japan, and high prevalences in southwestern Japan, with the highest in Okinawa. These conditions could be explained by the lower rate of rubella H1 antibody in the female population of southwestern Japan. Time of maternal rubella was in the gestational age interval from 26 to 57 days for cataract, from 25 to 62 days for heart disease and from 16 to 131 days for deafness. HTLV-1 is the causative agent of adult T-cell leukemia. Main route of transmission of this virus is mother-to-child transmission, through breast milk. Among the 311 mother-child pairs in Okinawa, 65 mothers (20.9%) and 10 children (3.2%) were seropositive for HTLV-1. Ten (15.4%) of the 65 seropositive mothers had seropositive children. These children had acquired their HTLV-1 antibodies by the age of 3 years. A significant difference existed between the prevalence rate of HTLV-1 antibodies in mothers and children.

Positivity for serum anti-HTLV-1 antibody (anti-HTLV-1) in 171 patients with various chronic liver diseases and 22 asymptomatic hepatitis B virus (HBV) carriers was compared with that of 200 healthy controls in the Chikugo district of Japan. The rate of anti-HTLV-1 positivity in patients with liver disease was 8.1% (14/171) and was higher than that (3.5%: 7/200) in healthy controls, but the difference was not significant. However, in patients with liver disease with a history of blood transfusion, the positive rate was 18.4% (7/38) which was significantly higher than that for healthy subject (P less than 0.001). On the other hand, in 133 liver disease patients without blood transfusion, anti-HTLV-1 positivity was significantly higher (P less than 0.05) in patients with hepatitis B surface antigen (11.3%: 6/53) than in those without it (1.3%: 1/80). These data suggest that the high incidence of anti-HTLV-1 in our patients with liver disease was due to the transmission of HTLV-1 by the same routes (maternal transmission and blood transfusion) and probably at the same time as the hepatitis viruses (HBV and hepatitis C virus).

The geographic distribution and clinical features of patients with HTLV-I-associated myelopathy (HAM) in Tokushima prefecture were investigated. Nine patients were found prior to December 1990. The minimal prevalence was estimated as 1.1 per 100,000 in the general population, and 1 per 1,309 in HTLV-I-seropositive persons. Seven patients were found in the southern district facing the Pacific Ocean, but only 1 patient each was found in the northern and western districts. The age at disease onset ranged from 15 to 53 yr (average 33 yr). The ratio of male to female patients was 1:8. Adult T cell leukemia was associated with HAM in 1 patient, and Hashimoto's disease in 2 patients. These cases have not been reported previously. The route of transmission of HTLV-I was concluded to be vertical in 4 patients and horizontal in 4 patients, but was uncertain in 1 patient. No evidence of transmission by blood transfusion was found in these patients.

This study examined the seroprevalence and transmission of human T cell lymphotropic virus type I (HTLV-I) in Japanese families who originated in Okinawa, an area in which HTLV-I is endemic, and who were currently residing in Hawaii, a nonendemic area. Among a cohort of Japanese men whose sera were collected in Hawaii in 1967-1975, those of Okinawan ancestry had an HTLV-I seroprevalence of 11.4%. This study, conducted in 1987-1988, sampled 142 index subjects from this male cohort and tested them along with their wives, children, and spouses of the children for HTLV-I antibodies. Seropositivity in their wives was 11.4% and 41.2% among the seronegative and seropositive index subjects, respectively; seropositivity also increased from 29.4% to 35.3% to 58.8% with the husbands' increasing antibody levels by tertiles. Elevated antibody levels may be a marker for infectivity, which is associated with more efficient sexual transmission of HTLV-I. The age-adjusted odds ratio for the association of seropositivity between husband and wife, however, was four times lower than that reported among native Okinawans. In addition, a substantially low seroprevalence (1.3%) was found among their offspring. The decline in HTLV-I transmission in this migrant population may be due to low infectivity in the parent generation who live in a nonendemic environment, increasing numbers of offspring marrying outside of the Okinawan community, and improved living circumstances.

HTLV-1 infection is endemic in Japan, black Africa, the Caribbean and several regions of South America. In these foci, the infections is very heterogeneously distributed (variations from village to village, intrafamilial clustering). The virus is transmitted from mother to child, and breast feedings seems to play a major role. Sexual transmission is usually from man to woman. The frequency of transmission by blood transfusion must not be underestimated. It justifies the systematic detection of HTLV-1 infection in areas where it is economically feasible.

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic human retrovirus of adult T-cell leukemia/lymphoma (ATLL), causes approximately 60 new cases of ATLL each year in Nagasaki Prefecture; essentially all cases are fatal, and they account for approximately 0.5% of total deaths in the area. The estimated life risk for an HTLV-I carrier to develop ATLL is approximately 5%. The major transmission pathway of HTLV-I peculiarly endemic in the Nagasaki Prefecture was studied. The prevalence of HTLV-I infection in children of carrier mothers (21%) was significantly higher than that in children in the general population in the area (1%) and more than 85% of mothers of carrier children were carriers. The breast milk of carrier mothers contained HTLV-I-infected cells and was infectious for marmoset via oral administration. A retrospective survey of children of carrier mothers showed that the prevalence of carrier children of carrier mothers was 17 (39%) of 44 and 0 (0%) of 10 when they were given breast milk only or formula only, respectively. These data provide a powerful basis for devising an intervention measure to block the endemic cycle of HTLV-I, ie, if carrier mothers refrain from breast-feeding, the incidence of ATLL will be significantly reduced some 50 years later.

Sera from 69 adult prostitutes, 139 juveniles in the reformatory for boys, and 63 juveniles in the reformatory for girls, were collected between 1986 and 1987 in Fukuoka City. These samples were tested for the presence of antibody to human T-cell leukemia virus type-I (anti-HTLV-I), for hepatitis B surface antigen (HBsAg), and for antibody to hepatitis B core antigen (anti-HBc). The juveniles in the reformatory for girls were surveyed for the incidence of venereal diseases (VD) and for a history of intravenous drug use. Anti-HTLV-I was detected in 5.8% of the prostitutes, 0.7% of the boys, and 1.6% of the girls. Prevalence of anti-HTLV-I among the prostitutes was higher than that among the controls, but no significant difference was recognized. HBsAg was detected in 7.2% of the prostitutes, but was absent in the boys and girls. Prevalence of HBsAg among the prostitutes was higher than that among the controls, but no significant difference was recognized. Anti-HBs was detected in 39.1% of the prostitutes, 10.1% of the juvenile boys, and 17.5% of the juvenile girls. In each group prevalence of anti-HBc was higher than that in the controls. Especially between the prostitutes and the controls a significant difference was recognized (p less than 0.005). In the reformatory for girls anti-HBc was detected in 40.0% of 11 girls who were exposed to VD and in 7.0% of 43 girls who were not exposed to VD. Prevalence of anti-HBc among the exposed group was significantly higher than that among the non-exposed group (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the physiologic significance of antibody to human T cell leukemia virus type 1 (HTLV-1) tax gene product (p40tax), 147 male and 243 female HTLV-1 carriers were examined for anti-p40tax, and 104 carriers were checked for anti-p40tax an average of 5.4 times during an 8-year period. Prevalence of anti-p40tax was significantly higher in female (62.6%) than in male subjects (51.0%; P less than .05). Anti-p40tax status did not change in most during the observation period. There were significantly more HTLV-1 carriers among children of anti-p40tax-positive mothers (45.3%) than among those from anti-p40tax-negative mothers (20.0%; P less than .01). However, no significant difference was observed between wives of p40tax-positive and -negative men. The p40tax antibody may be a marker of relative infectivity of HTLV-1, albeit an imperfect one.

The human T-cell leukemia virus type I (HTLV-I) is transmitted via breast milk, semen, or blood transfusion. The last route was not responsible for HTLV-I infection before the advent of modern medicine, nor will it be a major route in the future because anti HTLV-I antibody-positive blood is now screened out. Thus, the carriage rates in various areas of Japan have to be explained by the former two transmission methods. Based on the relationship between the two modes of transmission and carriage rates, several simulation experiments were performed. These experiments revealed that: (a) No population with a vertical transmission rate lower than 50% can be maintained as endemic for the virus. (b) Slight differences in horizontal transmission rates can cause a large change of the carriage rates. (c) A 1,000-fold carriage rate difference would become indistinguishable within a hundred generations if both modes of transmission were operating at nearly the same rate. (d) The probability of a formerly non-endemic population becoming endemic due to a single female carrier is not negligible. (e) Prevention of vertical transmission is much more effective in lessening the carriage rate within a short period of time than is prevention of horizontal transmission. A simulation for a real population is also presented.

The prevalence of the preleukemic state of adult T-cell leukemia (pre-ATL) was studied in Nagasaki prefecture, one of the endemic human T-lymphotropic virus type 1 (HTLV-1) areas in Japan. Pre-ATL cases have the monoclonal proliferation of abnormal lymphocytes, without signs of malignant proliferation or clinical signs and symptoms related to leukemia. HTLV-1 carriers who have monoclonal integration of HTLV-1 proviral DNA may be at high risk of developing ATL. Abnormal lymphocytes with either bilobular or large and chromatin-rich nuclei were found in 63/356 (17.7%) of HTLV-1 carriers among inhabitants. We analyzed DNA of peripheral lymphocytes from 108 carries with abnormal lymphocytes by Southern blot technique. Monoclonal integration of HTLV-1 has been detected in 12 cases (11.1%). These results lead to the conclusion that the prevalence rate of pre-ATL among all HTLV-1 carriers is about 2%. Pre-ATL is presumed to be the clinical stage which precedes ATL, although the possibility remains that the HTLV-1 carrier may develop symptoms of ATL directly, without going through the pre-ATL stage.

Mother-to-child transmission of HTLV-I as a major route in the endemic cycle of HTLV-I was established by epidemiologic evidence that (1) 22% (17/78) of children of HTLV-I carrier mothers were themselves carriers, in contrast to approximately 1% of the young age population of the same area, (2) more than 95% (23/24) of mothers of carrier children were themselves carriers, and (3) the product of the prevalence of carrier mothers and the incidence of carriers in children born to them corresponded well to the prevalence of carrier children in the same area. Intrauterine infection was not likely, since none of over 200 cord bloods of babies born to carrier mothers showed infection markers, such as IgM antibody or viral antigens. The possibility of milk-borne transmission was supported by (1) the presence of sufficient numbers of infected T-cells in the milk of carrier mothers, (2) the fact that a common marmoset was found to be a carrier after oral administration of the milk of carrier mothers, and (3) a retrospective analysis which revealed that none of nine babies fed only compound milk were carriers. An ongoing intervention study showed that none of 47 babies whose mothers refrained from breast feeding had seroconverted at 12 months of age. Compound milk feeding by carrier mothers seems to be an effective measure to reduce dramatically the infection rate of HTLV-I.

Human T-lymphotropic viruses (HTLV) are causally associated with adult T-cell leukaemia and with a progressive form of lower limb paralysis known as tropical spastic paraparesis. HTLV-1 is endemic in parts of Japan, the Caribbean, West Africa and probably South America, and is associated with disease in these areas. Horizontal transmission is probably most common through sexual intercourse which, it is postulated, must be more efficient from male to female because virus carriage is more prevalent in women in endemic areas. Vertical transmission appears to be principally through breast milk. Poor housing and hygiene may facilitate transmission.

The seroprevalence rate of human T-cell leukemia virus type I (HTLV-I) in pregnant women in the Osaka district was determined by enzyme-linked immunosorbent assay and Western blot analysis. Twenty-one (1.0%) of 2192 samples tested were positive for both assays and the seropositive parturients were found to be integrated with HTLV-I proviral DNA in their mononuclear cells by a DNA dot blot hybridization assay using HTLV-I DNA probe or by a selective DNA amplification technique using the polymerase chain reaction (PCR). On the other hand, proviral DNA was not detected in cord blood of the neonates born to the carrier mothers, indicating that transplacental infection of HTLV-I during pregnancy could be excluded. The results support the hypothesis that postpartum infection via breast milk plays a significant role among the possible perinatal transmission routes.