Atopic dermatitis and HTLV-1 associated-myelopathy: associated or coincidental disorders?

Reports from Jamaica have indicated that some patients with infective dermatitis or atopic dermatitis (AD) are seropositive for antibodies to human T-lymphotropic virus type 1 (HTLV-1). We describe a 32-year-old Israeli woman with long-term AD and paresthesia in the distal parts of the extremities. Neurological examination revealed a positive Babinski's sign. HLA typing demonstrated that this patient has the common HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis haplotype for DRBI* DQBI*. The presence of HTLV-1 was demonstrated with polymerase chain reaction; HTLV-1-antibodies were detected by the Western blot method and by inoculation of the patient's peripheral blood mononuclear cells into F344 rats. This study confirms the presence of HTLV-1 antibodies and proviral genome in a patient with AD which later evolved into HAM/TSP. We cannot yet conclude whether these two diseases are associated or coincidental disorders.(Au)

Ethnic composition, age and sex, together with location and standard of housing as determinants of HTLV-I infection in an urban Trinidadian community

The presence of antibody to human T-cell leukaemia virus (HTLV-I) has been assessed in 2,143 men and women who represent 83 percent of all adults aged 35 to 69 years resident in a defined urban community in Trinidad. Individuals of African descent had a higher sero-positivity rate (7.0 percent) than those originating from India (1.4 percent), Europe (0 percent) or of mixed descent (2.7 percent). Women were infected more frequently than men, and the prevalence of infection increased with age in both sexes. Sero-positivity rates were significantly increased in adults who lived in housing of poor quality (p less than 0.001) or close to water courses (p less than 0.025). These data and others raise the possibility that one route of HTLV-I transmission may be via insect vectors under particular domestic circumstances.(AU)

A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion

To evaluate the risk of transfusion-related transmisssion of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I-negative transfusion recipients at monthly intervals post-transfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44 percent) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week odds ratio (OR) = 6.34, 95 percent confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95 percent CI = 1.15 to 20.0) or use of immunosuppressive therapy at time of transfusion (OR = 12.20, 95 percent CI = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009 percent. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible (AU)

Screening for prolonged incubation of HTLV-I infection in British and Jamaican relatives of British patients with tropical spastic paraparesis [see comments]

OBJECTIVE -- To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN -- Migrant family study. Antibody state was determined by several methods and confirmed by western blotting; the polymerase chain reaction was used to detect proviral DNA. SETTING -- Britain and Jamaica. SUBJECTS -- All available first degree relatives: those born and still resident in Jamaica (group 1); those born in Jamaica who migrated to Britian (group 2); and index patients' children who were born and resident in Britian (group 3). All had been breast fed and none had had blood transfusions. RESULTS -- Of the 66 living relatives, 60 were traced. Seroprevalence among those born in Jamaica (irrespective of current residence) was 22 percent (10/46; 95 percent confidence limits 9 to 34 percent) compared with zero among British born offspring (0/14) and was higher in group 2 at 33 percent (7/21; 12 to 55 percent) than in group 1 at greatest mean age.) Proviral DNA was not detected in any subject negative for HTLV-I antibody, making prolonged viral incubation in those negative for the antibody unlikely. CONCLUSION -- In this sample factors related to place of birth and early residence were more important in transmission of HTLV-I than naternal or age effects. In areas with a low to moderate prevalence policies of preventing mothers who are carriers of the virus from breast feeding would be premature (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 cloning and complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin:Relationship to other members of the ATLV/HTLV-I subgroup

We report the first complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV) isolate from a British patient of Caribbean origin. Sequence comparisons of our proviral clone (HS-35) with other molecular clones are shown. We note the strong sequence conservation between isolates of Caribbean and Japanese origin (2.3 percent divergence), but demonstrate the higher homologies existing between isolates originating from similar geographical areas (approximately 1 percent divergence). Implications for the origin, evolution and dissemination of the ATLV/HTLV-I subgroup are discussed. Analysis of defective proviral clones isolated from the same genomic library is also reported,and suggests a pattern of proviral sequence deletions during the biogenesis of defective proviruses. (AU)

Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis

Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strenghten the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies. (AU)

The role of HTLV-I in tropical spastic paraparesis in Jamaica

We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme-linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82 percent of sera and 77 percent of cerebrospinal fluids. On Westren blot analysis, IgG antibodies detected the p19 and p24 gag-encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum . Serum-cerebrospinal fluid albumin ratios wer normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatry reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral colmns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investgations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-assiciated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent. (AU)

The neuroepidemiology of tropical spastic paraparesis

Recent neuroepidemiological studies of endemic tropical spastic paraparesis (TSP) have confirmed the existence of high-prevalence foci in several tropical islands, including Jamaica and Martinique in the Caribbean, Tumaco off the Pacific coast of Colombia, and the Seychelles in the Indian Ocean. There is a net preponderance of TSP in persons of Black African ancestry, although Caucasian, Hindu, Amerindian, and Orientals have been affected. The epidemiological, clinical, laboratory, and neuropathological features of TSP are reviewed here, as well as the evidence in favor of its retroviral origin. (AU)

HTLV-I-associated leukemia : a model for chronic retroviral diseases

Human T-lymphotropic virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, and tropical spastic paraparesis (TSP), a demyelinating neurological syndrome. This article describes the clinical and pathological features of ATL and reviews the epidemiology of this disease and of its putative etiological agent, HTLV-I. From what is known about the molecular biology and epidemiology of HTLV-I, hypotheses on the etiology of TSP are proposed, and strategies for studying the neurological syndrome are suggested. (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)