Peripheral T cell lymphomas in Jamaica: relationship to HTLV-1 serostatus (abstract)

The clinico-pathologic features of 111 patients with non-Hodgkin's Lymphoma (NHL) exhibiting morphologic and immunophenotypic features of peripheral T-cell lymphoma (PTL) were analysed with respect to HTLV-I serostatus. 73 (65.8 percent) were HTLV-I seropositive (HTLV-I+) and 38 (34.2 percent) were HTLV-I seronegative (HTLV-I-). HTLV+ cases had a lower mean age (42.2 yrs) than HTLV- cases (50 yrs) and a male to female ratio of 1:1 while HTLV- cases showed a male preponderance (M:F 2:1). No significant differences in morphology were noted using the Japan Study Group classification. Both groups shared clinical features consistent with Adult T-cell leukemia/lymphoma but hypercalcemia was more likely to occur in the HTLV+ group [Hypercalcemia:- HTLV+ 50.7 percent, HTLV- 15.8 percent; Leukemia:- HTLV+ 39.7 percent, HTLV- 34.2 percent; Skin infiltration:- HTLV+ 38.3 percent, HTLV- 42.1 percent]. It would appear that some cases of HTLV- PTL could be included in the group classified as ATL given the occurrence of sentinel clinical features associated with ATL. Perhaps these will prove to be HTLV-I proviral DNA positive. Further studies to define this group are indicated. (AU)

Strongyloidiasis - the clinical enigma - abstract

The most important human parasitic infection in Jamiaca is Stronglyloidiasis, not because it is the most prevalent but because it causes significant morbidity and mortality, persists for many years, and is difficult to diagnose and treat. The parasite is capable of living in the moist ground as well as the human host and in both sites it is able to grow and multiply. Less is known about this parasite than most in Jamaica although in the past 40 years one Ph.D. thesis and many papers and abstracts have been published by University of the West Indies workers. They have shown that the parasite causes a malabsorption syndrome due to subtotal villous atrophy, that the blood flow to the small intestine is increased, often producing an audible epigastric bruit, and that the lymphatic flow from the small intestine is also increased, that the free-living cycle is dependent upon critical temperature and humidity and that a culture of the stool in charcoal may improve the diagnostic yield. There is a true association with the hyperinfection syndrome and lymphoma; hyperinfection is also likely to occur when corticosteroids are used and the use of anti-biotics in the hyperinfection syndrome is beneficial. Currently the Parasitic Research Group comprises members of the Departments of Medicine, Microbiology, Pathology, Zoology, and the Tropical Metabolism Research Unit. Recently it has been shown that the best method of diagnosis is the Harad-mori culture of fresh stool, which is better than Formolether concentration, or more invasive methods such as duodenal biopsy (either for direct microscopy for parasites or for histology) or aspirate of duodenal juice for microscopy. Anorexia and malnutrition are common, with evidenc of zinc deficiency. The cure rate with standard therapy is about 35 percent, much lower than stated in textbooks. Association of Strongyloides stercoralis with human T-cell lymphoma/leukaemia virus-1 (HTLV-I) is recognized and patients with Tropical Spastic Parapresis and Strongyloides spp., apparently stercoralis. A new method of finding out more about the parasite in the human host has been devised using the Whole Gut Irrigation technique; this allows a much better assessment of the worm burden, up to 100,000 adult parasites in an asymptomatic out-patient and also gives an assessment of the fecundity of the adult worm and what factors influence the behaviour of the parasite. Ultimately, the goal is eradication of the parasite from Jamaica (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)

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)

HTLV-I-like viral particles in spinal cord cells in Jamaican tropical spastic paraparesis

Viral-like particles morphologically identical to human T-lymphotropic virus type I or II, but distinct from human T-lymphotropic virus type III, have been seen by electron microscopy in spinal cord tissue from a Jamaican tropical spastic paraparesis patient who was known to be positive for human T-lymphotropic virus I antibody before death. This is the first electron microscopy report on a patient from an endemic tropical spastic paraparesis region. (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)

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)

Studies in healthy human T-cell-leukemia lymphoma virus (HTLV-I) carriers from the Caribbean

Six healthy relatives of 3 adult T-cell leukemia lymphoma (ATLL) patients and 6 members of a Caribbean family immigrant to the UK have been investigated for the presence of HTLV-I and expression of interleukin 2(IL-2) receptors. Serum antibodies to HTLV-I were detected in all but 4 samples. Four to 10 percent of circulating cells from 3/4 seropositive donors studied displayed IL-2 receptors (anti-Tac+) and were shown to be convoluted lymphocytes by light microscopy morphology and immunoelectromicroscopy. After 5 to 28 days in culture, cells from 4 seropositive donors reacted with monoclonal antibodies (MAbs) against the HTLV-I core proteins, p19 and p24, and released retrovirus particles. Simmilar experiments with blood from 3 seronegative donors from the same families and 4 normal controls proved negative. Our findings indicate that seropositive individuals harbour the virus in a population of T-lymphocytes which may then acquire receptors for IL-2. These individuals are at risk of developing ATLL. (AU)

Racial and other characteristics of human T cell leukemia/lymphome (HTLV-1) and AIDS (HTLV-111) in Trinidad

Adult T cell leukaemia/lymphoma was first recognised as a clinical entity in southwest Japan. Subsequently the Caribbean has been found to be another area where the disease is endemic, and sporadic cases have been identified in different parts of the world. The human T cell leukaemia/lymphoma virus (HTLV-1) is causally related to adult T cell leukaemia/lymphoma. A sub-group of HTLV, designated HTLV-111, has recently been isolated from many patients with the acquired immunodeficiency syndrome (AIDS) and preAIDS, and there is now evidence that this variant is the primary cause of AIDS. This is the first report from Trinidad to describe twelve cases of adult T cell leukaemia/lymphoma and 14 of AIDS. All were in patients of African descent. No cases were seen in subjects of East Indian descent, who, like those of African descent, comprise as much as 40 percent of the population

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)