Segregation of human T cell lymphotropic virus type I and II infections by antibody reactivity to unique viral epitopes

A recombinant protein of the human T cell lymphotropic virus type I (HTLV-I) gp46 outer membrane envelope, MTA-4 (residues 129-203), reacted by Western blot with sera from HTLV-I-infected individuals from the United States and Jamaica but not with 24 (10 percent) of 242 Japanese sera. A related gp46 recombinant protein, MTA-1 (residues 162-209), reacted with all 58 sera from HTLV-I-infected US and Jamaican individuals and 238 of 242 sera from infected Japanese (combined sensitivity of 99 percent). Neither recombinant showed reactivity to sera from HTLV-II-infected individuals or uninfected controls. The reactivity of recombinant proteins containing the region of HTLV-II gp46 analogous to MTA-1 was also evaluated by Western blot: GH2-K15 (residues 157-205) and GH2-K55 (residues 162-205) reacted with 88 (98 percent) and 89 (99 percent), respectively, of 90 sera from HTLV-II-infected individuals but not with sera from HTLV-I-infected individuals or uninfected controls. These recombinant proteins should permit the development of assays to unambiguously confirm and differentiate HTLV-I and HTLV-II infections. (AU)

Geographic distribution of HTLV-I and identification of a new high-risk population

Epidemiologic studies indicate that human T cell lymphotropic virus type I(HTLV-I), the causative agent of most cases of adult T-cell leukemia/lymphoma (ATLL)in Southeast Japan and the Caribbean islands and the probable cause of a progressive neurological disorder often referred to as tropical spastic paraparesis, occurs with unusual geographic clustering. The current large-scale serosurvey was undertaken to improve our understanding of HTLV-I prevalance in different parts of the world. We analyzed 43,445 serum samples collected from various geographic locales worldwide; 76 percent of these sera came from clinically healthy donors. Samples were initially screened by an enzyme-linked immunosorbent assay (ELISA) and 4,353 were further evaluated by means of competition assays. In this study, which did not include sera from endemic areas of Japan, a high prevalence of infection was observed in several countries in the Caribbean basin. A significant age-sex difference was observed between populations in the Caribbean and non-endemic regions of Japan. The reason for the male excess in non-endemic areas of Japan will require further study, while the female excess in the Caribbean basin is compatible with the previously described pattern for other HTLY-I-endemic areas. A newly recognized area of possible endemicity was southern Florida, where evidence of infection with HTLV-I or a related virus was found in a group of native Americans whose sera were collected in 1968. In certain parts of the world, particularly sub-Saharan Africa, important problems in determining specificity of reactivity occurred, probably because of cross-reacting antibodies. No pattern was detected that could explain the cross-reactivity solely on the basis of geographic areas, specific patterns of non-viral parasitic infection, or methods of handling the specimens. It is possible that these cross-reactivities are antibodies to proteins from HTLV-I-related retroviruses yet to be discovered. (AU)

Molecular epidemiology of HTLV-I-associated non-Hodgkin's lymphomas in Jamaica

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody-positive cases had onset of their disease in adulthood (age range, 21-57 years) as opposed to the broad age range of negative cases (4-66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus-positive and virus-negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV-I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV-I-positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV-I antibody-negative cases that were typed were B-cell lymphomas. (AU)

Transmission of HTLV-I and HIV among homosexual men in Trinidad

Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15 percent vs 2.4 percent in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19 percent of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation.(AU)

Non-hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma [published erratum appears in Ann Intern Med 1987 Jun;106(6):917]

Of 95 patients consecutively diagnosed with non-hodgkin lymphoma, 52(55 percent) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positively was strongly associated with skin involvement, leukemia, and hypercalcemia (p<0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinnant of adult T-cell leukemia-lymphoma.(AU)

The epidemiology of HTLV-I and HTLV-III associated diseases in Trinidad and Tobago - abstract

Clinical studies in Trinidad and Tobago have shown that, between May 1982 and June 1985, 24 cases of adult T-cell lymphoma/leukemia (ATL) were seen at the Port-of-Spain General Hospital. The clinical features were very similar to those reported from Japan and Jamaica. The male/female ratio was 14/10. A random survey of antibodies to HTLV-I (Elissa assay) was carried out in Trinidad and Tobago in people aged 20 years and over. In Trinidad, of 1,578 people sampled, 51 (3.3 percent) were positive. Forty-one out of 794 Trinidadians of African descent were positive (5.1 percent) while only 3 of 448 Trinidadians of Indian descent were positive (0.7 percent). In Tobago, 18 out of 151 Tobagonians were antibody positive (12.0 percent). All were Tobagonians of African descent. There were no Tobagonians of Indian descent in this survey. The first case of the Acquired Immune Deficiency Syndrome (AIDS) was diagnosed in Trinidad in February 1983, and, up to November 1985, 50 cases of this disease have been diagnosed at the Port-of-Spain General Hospital. A random survey of antibodies to HTLV-III in the general population of Trinidad showed that out of 1,578 Trinidadians studied only 6 (0.4 percent) were antibody positive. Of 151 Tobagonians, 3 were positive (1.5 percent). All positive results were confirmed by Western blotting. On the other hand, in a survey of 105 healthy homosexuals in Trinidad, 40 percent were shown to be positive for HTLV-III antibodies. Thirty-six of 81 homosexuals of African origin were antibody positive (44.4 percent) while 6 out of 16 homosexuals of Indian descent were positive (37.5 percent). All the clinical cases of ATL occurred in Trinidadians of African descent and apart from one child aged 18 months of Asian descent, all the patients with AIDS were people of African origin. These epidemiological findings suggest that a genetic factor may be proved necessary for the development of HTLV-associated diseases in Trinidad and Tobago (AU)

Skin manifestations of HTLV-associated adult T-cell lymphoma/leukaemia in Jamaica - abstract

A prospective study was conducted on 56 consecutive patients with the diagnosis of non-Hodgkins lymphoma (NHL) who presented between February 1982 and April 1984. The aims were to determine the frequency of skin involvement in patients with NHL and in particular those NHL patients who were also in HTLV-positive and satisfied the criteria for adult T-cell lymphoma-leukaemia (ATL) to characterise the types of skin lesions, to determine the relationship of skin involvements to course and prognosis and to determine whether any differences existed in the skin manifestations of HTLV positive and HTLV negative patients. Skin biopsies and skin scrapings for microscopy and culture were done where indicated, as well as HTLV antibody assays. Thirty-one patients (62 percent) were HTLV-positive, 16 males and 15 females. Their ages ranged from 20 to 63 with an average age of 41 years. Twenty (65 percent) had probable ATL and 7 (23 percent) possible ATL. Twelve of the 20 probable ATL had skin involvement. Fifty per cent (6/12) had skin lesions at initial presentation. The other 6 developed lesions during the course of their illness from 6 weeks to 1 year after diagnosis. The commonest type of skin lesion was generalized papulonodular in 50 percent of patients. Pruritus was present in 25 percent of patients. The median survival was 6 months in patients with skin involvement and 2 months in patients without - an insignificant difference statistically. Crusted scabies was found in 5/12 (42 percent) of the ATL patients and was recurrent in 3 patients. These results confirm that ATL is HTLV-associated, commonly presents with skin lesions, but is quite different from the two classical cutaneous lymphomas of the skin, mycosis fungoides and the Sezary's syndrome, in both morphology of the skin lesions and course and prognosis of the disease, the course of ATL being short and explosive with hypercalcaemia rather than skin lesions being the most important diagnostic factor (AU)

Seroepidemiologic studies of human T-cell leukemia/lymphoma virus type 1 in Jamaica

The prevalence of HTLV-1 antibodies was evaluated in Jamaica among persons with various malignant, infectious, autoimmune and hematologic disorders and in clinically normal persons. Results document that: (1) the prevalence of HTLV-I antibodies in this population increases with age; (2) overall, there is no significant difference in the antibody prevalence between females and males: (3) antibody-positive individuals are born in all major regions of the island and geographical variance in antibody prevalence by place of birth was not prominent; (4) there is further confirmation of the high prevalence of HTLV-I antibody-positive lymphomas in Jamaica; and (5) the prevalence of HTLV-I antibodies in hemophiliacs, patients with chronic lymphocytic leukemia (CLL0, myelogenous leukemias, and patients with breast cancer is higher than in age-matched populations without malignancies, although none of these differences were statistically significant. The increased prevelence in hemophiliacs is most likely related to their frequent transfusion with blood products, but it has not yet been determined whether the prevalence in patients with other diseases is related to their disease or other as yet undefined factors in common. (Au)

Neoplasias linfoides asociadas con anticuerpos contra el virus humanos de linfomas-leucemias de células T en Colombia / Lymphoid neoplasias associated with antibodies against (HTLV) human lymphoma-leukemia T-cell virus in Colombia

Los resultados del estudio de 11 casos consecutivos de linfomas no Hodgkin que consultaron a la clínica de hematología del Hospital Universitario del Valle, muestran que en 4 había anticuerpos contra el virus de los linfomas-leucemias humanas de células T. Como 3 de los 4 eran naturales y procedentes de la costa del Pacífico, Buenaventura, se sugiere la posibilidad que tal región sea endémica para este tipo de neoplasia. Histológicamente 2 casos tuvieron linfoma difuso de células mixtas, grandes y pequeñas, un caso linfoma difuso de células intermedias y un caso linfoma difuso de células grandes, inmunoblásticas, utilizando la clasificación del grupo de trabajo para el estudio de los linfomas. Además, en los enfermos hubo compromiso visceral o mansivo ganglionar, 2 de ellos con diseminación leucémica y evolución rápidamente progresiva. Para conocer mejor la epidemiología de los linfomas-leucemias de células T sería aconsejable identificar el tipo de linfocitos (T o B) tumorales

Adult T-cell leukemia/lymphoma in Jamaica and its relationship to human T-cell leukemia/lymphoma virus type I-associated lymphoproliferative disease

We had shown previously that the prevalence of human T-cell leukemia/lymphoma virus type I (HTLV-I) antibody positivity is high in Jamaican non-Hodgkin's lymphoma (NHL) patients and that virus-positive patients have the clinical features and poor prognosis of adult T-cell leukemia/lymphoma (ATL). 62 percent of 45 NHL patients diagnosed consecutively between 2/1/82 and 1/31/84 and studied prospectively were HTLV-I-antibody positive. Skin involvement (38 percent), hypercalecemia (44 percent), and leukemia (40 percent) were unusually prevalent and there was a strong association (p < 0.05) with HTLV-I-antibody positivity. 52 percent of the patients had bone marrow infiltration, and 74 percent of these patients were HTLV-I-antibody positive (p=.06). Lymphadenopathy (96 percent), hepatomegaly (60 percent), and splenomegaly (25 percent) were detected with about the same frequency as in other series of NHL patients with advanced disease, and 61-88 percent of these patients were HTLV-I-antibody positive. Patients were classified into those with "typical ATL" (NHL associated with 2 of the 4 features) i) hypercalecemia; ii) histologically proven skin infiltration; iii) leukemia; and iv) bone marrow infiltration, providing that the morphology of infiltrating of leukemic cells was characteristic of ATL; those "consistent with ATL" (NHL associated with 1 of these 4 features); and "non-ATL" (NHL without any of these 4 additional features). Thirty-two (71 percent) of the NHL patients were ATL patients, i.e. had features typical of or consistent with ATL, and 78 percent of these were HTLV-I-antibody positive. HTLV-I provirus was detected in tumour cells of all HTLV-I-antibody positive patients tested. Three (23 percent) of the non-ATL patients were HTLV-I-antibody positive. There was no correlation between histopathological features and the clinical classification of HTLV-I-antibody positivity. Median survival of ATL and non-ATL patients was 16 and 53 weeks. Although the disease was unusually fulminant, 34 percent of the ATL patients had a subacute or chronic course. Skin involvement and leukemia were prominent in these patients. Hypercalecemia was the chief prognostic determinant. Median < 0.05). Hypercalecemia caused 10 deaths, infections 12, and death was due to tumour progression in 4 patients. Infections were usually due to pyogenic organisms and only 2 patients had systemic opportunistic infections. Six (27 percent) of 22 chronic lymphocytic leukemia (CLL) patients were HTLV-I-antibody positive. (AU)