Risk of human T-lymphotropic virus type I-associated diseases in Jamaica with common HLA types.

Human T-lymphotropic virus-I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATL) and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We postulated a higher disease risk for people with common human leukocyte antigen (HLA) types, due to a narrower immune response against viral or neoplastic antigens, compared to people with uncommon types. HLA class-I (A,B) and class-II (DRB1, DQB1) allele and haplotype frequencies in 56 ATL patients, 59 HAM/TSP patients and 190 population-based, asymptomatic HTLV-I-infected carriers were compared by logistic regression overall (score test) and with odds ratios (ORs) for common types (prevalence >50% of asymptomatic carriers) and by prevalence quartile. HTLV-I proviral load between asymptomatic carriers with common versus uncommon types was compared by t-test. ATL differed from asymptomatic carriers in overall DQB1 allele and class-I haplotype frequencies (p

Natural history of viral markers in children infected with human T lymphotropic virus type I in Jamaica.

PURPOSE: We conducted a longitudinal analysis of human T lymphotropic virus type I (HTLV-I) viral markers in 28 Jamaican mothers and their children, who were monitored for a median of 6.2 years after the birth of the children. METHODS: The HTLV-I provirus DNA load was measured using the Taqman system (PE Applied Biosystems). The HTLV-I antibody titer was determined using the Vironstika HTLV-I/II Microelisa System (Organon Teknika). The HTLV-I Tax-specific antibody titers were measured using an enzyme-linked immunosorbent assay. Generalized estimating equations were used to describe the associations of exposure variables with sequentially measured levels of HTLV-I viral markers in children. RESULTS: The HTLV-I antibody titer increased significantly up to 1 year after infection, reaching equilibrium at a median titer of 1 : 7,786. The prevalence of Tax-specific antibody reached 80% at 2 years after infection. The provirus load increased up to 2 years after infection, reaching equilibrium at a median of 6,695 copies/100,000 peripheral blood mononuclear cells. The increase in the provirus load was significant only among children with eczema, but not among children without eczema. CONCLUSIONS: The provirus loads in children increased for an additional year after their antibody titers had stabilized, possibly as a result of the expansion of HTLV-I-infected clones. This effect was significant only for children with eczema. Among HTLV-I-infected children, eczema may be a cutaneous marker of the risk of HTLV-I-associated diseases developing in adulthood.

Human leukocyte antigen concordance and the transmission risk via breast-feeding of human T cell lymphotropic virus type I.

OBJECTIVE: We examined the association between mother-to-child human T cell lymphotropic virus type I (HTLV-I) transmission and human leukocyte antigen (HLA) class I types. METHODS: In 1989, children born to HTLV-I-infected mothers in Jamaica were enrolled and prospectively evaluated for HTLV-I infection. HLA class I types in mothers and children were determined by DNA-based polymerase chain reaction methods. Associations between HLA class I types and transmission of HTLV-I were analyzed using proportional-hazards regression models adjusted for the duration of breast-feeding. Transmission risk in children still breast-feeding at 12 months was determined using actuarial methods. RESULTS: Of 162 children, 28 (17%) became infected. After Bonferroni's adjustment for multiple comparisons, the transmission risk was not influenced by any specific HLA class type or the A2 supertype. However, compared with children who shared 3 HLA class I types with their mothers (the minimum number possible), the transmission risk increased 1.8-fold with 4 shared types and 3.0-fold with 5 or 6 shared types (Ptrend = .039; 1.75-fold increase for each additional concordant HLA type). This association was independent of maternal HTLV-I proviral level, antibody titer, and household income. CONCLUSIONS: We found a significant dose-response relationship between HTLV-I transmission via breast-feeding and mother-child HLA class I type concordance. Immunological interactions between a child's cells and maternal cells may influence the risk of HTLV-I infection by breast-feeding, perhaps because antigens on maternal cells are seen by the child as being "self."

Provirus load in breast milk and risk of mother-to-child transmission of human T lymphotropic virus type I.

In a prospective study of 101 mother-child pairs in Jamaica, we examined the association of provirus load in breast milk and the risk of mother-to-child transmission of human T lymphotropic virus type I. The provirus load in breast milk was a strong predictor of risk of transmission to children (relative risk, 2.34/quartile), after adjustment for other known risk factors. The risk of transmission increased from 4.7/1000 person-months when the provirus load in breast milk was <0.18% to 28.7/1000 person-months when it was >1.5%. Provirus detection in maternal breast milk predicted transmission months before infection in children was detected by serologic testing.

Prediagnostic human T lymphotropic virus type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia.

In a recent clinical analysis of 308 Jamaican children, human T lymphotropic virus type I (HTLV-I) infection was found to be associated with significantly higher incidence rates of seborrheic dermatitis, eczema, and persistent hyperreflexia of the lower limbs and with nonsignificantly increased rates of severe anemia and abnormal lymphocytes. Results of examination of HTLV-I viral markers in the 28 HTLV-I-infected children provided virologic support for the epidemiologic associations of HTLV-I with seborrheic dermatitis and severe anemia in childhood.

A cohort study of health effects of human T-cell lymphotropic virus type I infection in Jamaican children.

OBJECTIVE: Human T-cell lymphotropic virus type I (HTLV-I) infection in childhood is believed to play an important role in risk for adult T-cell leukemia/lymphoma. Although HTLV-I is known to be associated with infective dermatitis in childhood, other HTLV-I-associated morbidity in children has not been well studied. We sought to determine the HTLV-I-associated health effects in Jamaican children. METHODS: We compared incidence rates of several health outcomes in 28 HTLV-I-infected and 280 uninfected children clinically followed from age 6 weeks to a maximum of 10 years. Cox proportional hazards regression analysis was used to analyze these prospectively collected data, adjusting for confounding effects of other variables as necessary. RESULTS: HTLV-I-infected children had significantly higher incidence rates of seborrheic dermatitis (rate ratio [RR] = 4.8, 95% confidence interval [CI] = 1.9-12.5), eczema (RR = 3.1, CI = 1.2-7.9) and persistent hyperreflexia (RR = 3.7, CI = 1.6-8.2). Additionally, HTLV-I infected children had increased rates of severe anemia (RR = 2.5, CI = 0.8-7.9) and abnormal lymphocytes (RR = 2.4, CI = 0.8-7.6) that were of borderline statistical significance. CONCLUSIONS: Our study suggests that HTLV-I-associated skin diseases of childhood may include seborrheic dermatitis and eczema. Additionally, these data suggest that persistent hyperreflexia of the lower limbs may be an early sign of HTLV-I-associated neurologic involvement in children. Expansion and continued clinical observation of this cohort would be valuable.

Anti-tac antibody and the diagnosis of adult T-cell leukaemia/lymphoma (ATL) - abstract

Activated T-cells express Tac antigen (defined by anti-Tac monoclonal antibody) whereas resting T-cells, B-cells and monocytes do not express this antibody. Tac-antigen is probably a T-cell growth factor receptor. As T-cells are activated in vivo by infection with Human T-cell leukaemia/lymphoma virus (HTLV), we have evaluated the usefulness of measuring Tac-antigen to detect patients with adult T-cell leukaemia/lymphoma. Tac-antigen was demonstrable in 8 of 11 patients who had clinical features typical of, or suggesting, adult T-cell leukaemia/lymphoma (ATL). Six of these patients were human T-cell leukaemia/lymphoma virus type 1 (HTLV-1) antibody positive and 2 were HTLV-1 antibody negative. One of the HTLV-1 antibody positive patients who had features of ATL but was Tac negative was immuno-suppressed at the time of the analyses. One HTLV-antibody positive who did not have features of ATL was Tac positive. Follow-up of such patients will demonstrate if they eventually develop the clinical features of ATL. We conclude that anti-Tac antibody is a useful marker for ATL (AU)

Surface markers in lymphoproliferative disorders in Jamaica - abstract

No data have been reported on surface marker studies on haematological malignancies in the Commonwealth Caribbean. Surface marker studies were performed on 14 patients with non-Hodgkin's lymphoma (NHL) and eleven patients with chronic lymphocytic leukaemia (CLL) using rosetting and immunofluorescent techniques on lymphocytes separated by a density gradient flotation method. Twelve of the 14 NHL patients had T-cell disease, indicating that the cell origin of NHL in Jamaica differs from that reported in North America or Europe, where B-cell disease predominates. Nine of 11 were HTLV-antibody-positive, suggesting that they had adult T-cell leukaemia/lymphoma. Ten of the 11 CLL patients had B-Cll, similar to findings elsewhere. However, the frequency of HTLV-antibody-positivity was unexpectedly high in this group (35 percent) and a virus has been isolated from the T-cells of one of the B-CLL patients (AU)

The evolving natural history of infective dermatitis in Jamaica - abstract

Infective dermatitis (ID) of Jamaican children, described in 1966, has recently been shown to be associated with human T-lymphotropic virus type 1 (HTLV-1) infection. This retrospective study of patients with infective dermatitis attending the dermatology clinic since 1970 was undertaken to determine trends in the natural history of the disorder and to define any link with other established HTLV-I associated disorders such as adult T-cell leukaemia/lymphoma (ATL) and tropical spastic paraparesis (TSP). Eighty-one patients have been followed. The results indicate that scabies was the commonest associated disorder seen in 15 patients (18 percent), with crusted scabies in 2 of these patients. Corneal opacities were seen in 8 patients (10 percent). Tropical spastic paraparesis was seen in 3 patients;lymphocytic interstitial pneumonitis was seen in 2 patients both of whom were persistently negative for human immunodeficiency virus (HIV) antibodies. Chronic glomerulonephritis was seen in 2 patients which led to chronic renal failure and death in one of these. Three patients with infective dermaitis died, one of definite ATL and two of ATL-like syndromes. These results indicate that at least a proportion of patients with infective dermatitis are at risk of developing other HTLV-I associated disorders, as well as other disorders of the immune system. These patients therefore require careful long-term follow-up (AU)

Immunological studies in infective dermatitis flow cytometric analysis of lymphocyte subpopulations in 41 cases - abstract

Infective dermatitis (ID) is a newly described HTLV-I associated with chronic dermatitis that is characterized by super infection of the skin with non-virulent pathogens. In order to investigate the possible mechanisms for this associated immune dysfunction we examined, by flow cytometry, lymphocyte subpopulations in a study group of 41 patients with infective dermatitis and compared the results with an age and sex matched group of patients with atopic eczema (AE) not associated with HTLV-I. Our results show an increase in total T-cells (CD3/Leu 4 +)2 T-helper inducer cells (CD4/Leu 3+), Activated T-cells (Leu RLA - DR+) and a subpopulation of cytotoxic T-cells (CD57: CD8/Leu 7+: Leu 2+) in the study group over the controls. The results support previous observations that T-cell aberrations in asymptomatic HTLV-I seropositive individuals, patients with Tropical Spastic Paraparesis (TSP) and adult T-cell leukaemia (ATL). It would appear that HTLV-I-induced immunodeficiency may be the result of phenotypic qualitative defects in T-lymphocyte subpopulations although absolute counts may be elevated (AU)

The association of crusted scabies with T-lymphotropic virus type I and adult T-cell leukaemia/lymphoma - abstract

Crusted scabies is a hyperinfestation with the mite Sarcoptes scabei var Hominis and is characterized by hyperkeratotic plaques and crusting, especially over bony prominences. The disease is often found in association with immunosuppression, down's syndrome, mental retardation and in patients with diminished sensation. Recently a significant association with human T-lymphotropic virus type I (HTLV-I) and adult T-cell leukaemia/lymphoma (ATL) has been reported. Over a 30-month period, 18 patients with crusted scabies were admitted to the dermatology ward, University Hospital of the West Indies, Mona. Of these patients, 13 (72 percent) were found to be HTLV-I seropositive and 4 of this group on further investigation were found to have ATL. The remainder of patients had other HTLV-I associated disease (tropical spastic paraparesis, infective dermattis with lymphocytic interstitial pneumonitis and psoriasiform eczema), immunosuppression due to a carcinoma and malnutrition associated with a cerebrovascular accident, lupus erythematosus on corticosteroid, and in 4 patients no underlying cause was found. Because of this strong association of crusted scabies with HTLV-I seropositivity and HTLV-I associated diseases in our environment, the determination of HTLV-I serostatus and investigation for possible ATL are mandatory in patients with this unusual form of scabies. (AU)

Infective dermatitis of Jamaican children: a marker for HTLV-I infection

In Jamaican children infective dermatitis is chronic eczema associated with refractory nonvirulent Staphylococcus aureus or beta haemolytic streptococcus infection of the skin and nasal vestibule. 14 children between the ages of 2 and 17 years with typical infective dermatitis, attending the dermatology clinic at the University Hospital of the West Indies in Jamaica, were tested for antibody to human T-Lymphotropic virus type 1 (HTLV-1). All were seropositive, whereas 11 children of similar age with atopic eczema were all negative. In 2 of 2 cases of infective dermatitis, the biological mother was HTLV-1 seropositive. None of the 14 patients showed signs of adult T-cell leukaemia/lymphoma, though experience with previous cases of infective dermatitis indicates the possibility of such progression. (AU)

Tropical spastic paraparesis ocurring in HLTV-1 associated infective dermatitis: report of two cases

An association between HTLV-1 infection and infective dermatitis(ID), a relapsing eczematous condition of Jamaican children, was reported in 1990. These patients are at a risk of developing other known HTLV-1 related diseases. We have observed the development of HTLV-1 associated myelopathy/tropical spastic paraparesis im two patients, ages 14 and 35 years, who were diagnosed with ID at ages 2 and 10 years, respectively. Infective dermatitis of children serves as an early marker of HTLV-1 infection and may predict later development of either the malignant outcome, adult T-cell leukaemia/lymphoma or the neurologic manifestation HAM/TSP among adult carriers of HTLV-1 infection

Sibling adult T-cell leukemia/lymphoma and clustering of human T-Cell lymphotropic virus type I infection in a Jamaican family

BACKGROUND:- Human T-cell lymphotropic virus type I (HTLV-I) infection is endemic in Jamaica, with an estimated crude seroprevalence of 5percent. Adult T-cell lymphoma/Leukemia (ATL), a disease caused by HTLV-I, has an incidence of 1-2/100,000 in the Jamiacan population. Familial ATL has not previously been reported from Jamaica. METHODS:- Hospital records and histologic specimens of the two cases were reviewed. HTLV-I infection was confirmed by antibody testing and by polymerase chain reaction on paraffin-embedded tissue,where serum was unavailable. Family members identified by the patient's parents. After giving informed consent, family members were asked to complete an interviewer-administered questionnaire and to agree to phlebotomy. RESULTS:- ATL developed 10 years apart in two siblings from a Jamaican family at age 16 and 24 years. A study of 19 members of their extended family, including both parents, 2 grandparents, and 3 siblings, revealed an overall HTLV-I seroprevalence of 17 percent. This compared with 75 percent among parents and sibling living in the same household as the patients (AU)

Patterns of HTLV-1 infection among family members of patients with adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis - abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) is strongly associated with both ATL and HAM/TSP. Only a small proportion of HTLV-1 infected individuals develop either of these diseases with lifelong risk estimates between 1 percent and 5 percent. ATL is believed to be related to early childhood infection via mother to child and HAM/TSP is thought to result from sexually or parenterally acquired infection in adulthood. Through the evaluation of HTLV-1 seroprevalence among family members of ATL and HAM/TSP patients we provide data that early life exposure is important for later development of ATL. Cases of ATV and HAM/TSP and their first degree relatives were enrolled in the study at the UWI, Jamaica, HTLV-1 seroprevalence rates were compared. We enrolled 25 ATL and 31 HAM/TSP families. All cases were HTLV-1 positive. Females accounted for 56 percent of ATL cases and 80 percent of HAM/TSP cases with mean ages of 43 and 49 respectively. The seroprevalence of HTLV-1 among mothers of ATL patients was 100 percent compared to 27 percent among mothers of HAM/TSP patients (p=0.0003). Among fathers of ATL subjects the seroprevalence was 80 percent vs 0 percent for HAM/TSP (p=0.05). The seroprevalence among all family members was 49 percent for ATL and 20 percent for HAM/TSP (p=0.0003). In contrast spouses ofHAM/TSP cases had a 86 percent seroprevalence compared to 57 percent among spouses of ATL cases. ATL and HAM/TSP evolve from distinct pathogenic pathways supported by differences in epidemiologic association. This premise is strongly supported by our observation that family members of ATL patients, particularly mothers have a significantly higher prevalence of HTLV-1 infection (AU)

Immunology of non-hodgkin's lymphoma in Jamaica - abstract

This study was undertaken to determine the immunological profile of non-Hodgkin's lymphoma (NHL) patients in Jamaica. Immunoperoxidase (IP) and immunofluorescence (IF) techniques were used, employing a panel of monoclonal antibodies, to detect T and B lymphocytes and their subjects in lymph nodes and cell suspensions obtained from 22 patients diagnosed consecutively from January, 1985. Results of immunological typing were compared with results of HTLV-1 (Human T-cell lymphotropic virus type I) antibody testing, and with the histological pattern. Sixteen of the patients (73 percent) had T-cell disease and 4 had B-cell disease. Results were equivocal or unsatisfactory in 2 patients. Fourteen who had T-cell disease were further subtyped. Thirteen had the helper-inducer phenotype and 1 had the cytotoxic-suppressor phenotype. There was close agreement between the results of IP typing of lymph nodes and cell suspensions, and of IF typing of cell suspensions, 15 (12 T-cell and 3 B-cell) of the 20 patients tested showing identical results. Three patients who were typed as T-cell disease by the IP technique were typed as normal or immunosuppressed by the IF technique. However, the IP typing was done before, and the IF was done after, treatment. Discrepancies in the results for 2 patients are unexplained. Eight of the 14 patients with T-cell disease for whom results of HTLV-I antibody testing are available are HTLV-I antibody-positive. Both of the patients with B-cell disease for whom these results are available are antibody-negative. There was no correlation between lymphocyte phenotype and histological pattern (AU)

Infective dermatitis of Jamaican children 1966-1991 - abstract

Infective dermatitis of Jamaican children, first described by Sweet in 1966, is a chronic eczema associated with persistent infection of the skin or anterior nares with either staphylococcus aureus or B haemolytic streptococcus, or both. In 1990, we reported a pilot study of 14 children with infective dermatitis (ID) and 11 with atopic eczema (AE) as controls, which showed that all the ID patients were positive for antibodies to the human T-lymhotrophic virus (HTLV-1). We postulated then that there was an association between HTLV-1 infection and infective dermatitis, and suggested that this organism might be causing ID through an immune mechanism. This paper reports on findings of a case control study of 50 ID patients and 36 AE patients undertaken between December, 1990 and August, 1991, which confirms the association between HTLV-I and infective dermatitis. All 50 patients with ID were positive for HTLV-I and antibodies, while the AC controls were all negative. In addition, when compared to the atopic controls, the ID patients had lower haemoglobins, higher white cell counts, and higher ESRs. They also had lower serum albumins and serum irons. Investigations of their immune systems showed that both groups had normal responses to delayed hypersensitivity skin tests, and normal complement levels. However, there was a marked increase in the activity of both T and B-lymphocyte systems, with all immunoglobulin levels being significantly increased in ID patients. The CD4: CD 8 ratio was increased, with an increase in the CD4 counts. Monoclonal antibody tests showed increased T-cell activation. The results confirm the association between HTLV-1 infection and infective dermatitis and confirm immune dysfunction. The precise mechanism of the immunodysregulation, however, remains to be determined (AU)

Perinatal transfusion transmission of HTLV-I: risk to mother and child - abstract

As part of a prospective study of transfusion-transmission of HTLV-I antibody (Ab) positive blood in the perinatal period. Pretransfusion seronegative recipients of HTLV-I-positive blood components were retrospectively identified and subsequently followed up monthly for six months and then semi-annually thereafter. At each visit, a questionnaire was administered, physical examination was done and blood was drawn to assess haematological and immunological status of recipients. Mothers who were transfused during pregnancy had their pregnancy outcome noted and where possible were followed up as mother/infant pairs. The outcome of subsequent pregnancies was noted. Thirty-nine subjects in our cohort of 66 were women and 21 of them were transfused during pregnancy or in the puerperium . Nineteen of these women received cellular HTLV-I Ab-positive blood products and two received acellular products. Nine of our 21 mothers who received HTLV-I-positive blood products seroconverted, yielding a seroconversion rate of 42 percent which is consistent with the overall cohort. Fourteen of the 21 pregnancies ended in viable children but two mother/infant pairs wre lost to follow-up. Of the 12 remaining mothers, 4 received transfusion antepartum (1 day to 15 weeks prior to delivery), while 8 were transfused either interpartum or up to three weeks post partum. All of the 12 mothers breastfed their babies for periods ranging from one week to four years (median duration of six months). Six of the 12 mothers were sreoconverters and 2 of the six children of these mothers have also seroconverted between one and two years following birth. This yields a mother/infant transmission rate of 33 percent which is more than the reported 20 percent rate in previous mother/infant studies. The difference, however, is not statistically significant. One seropositive child has developed Infective Dermatitis (ID), a recently described HTLV-I associated disorder. We conclude that, HTLV-1 transmission via blood transfusion to pregnant women poses a risk to mother and child. We propose that, where widespread screening for HTLV-antibodies is not feasible, screening of blood for transfusion in to pregnant mothers should be given priority as at least two individuals are at risk of infection and disease (AU)

Lymph node pathology in infants of HTLV-I seropositive mothers - abstract

In a cohort of seronegative mother-infant pairs being studied for perinatal transmission of the human T-lymphotropic virus type (HTLV-I), it was noticed that some infants developed persistent lymphadenopathy for which no specific cause was apparent. In order to determine whether this lymphadenopathy reflected a specific lymphoreticular abnormality, the lymph node pathology was studied, using morphological and immunohistochemical methods. Of 17 infants with lymphadenopathy, 16 were from seropositive mothers. Twenty-four infants (7.0 percent) in the cohort group seroconverted. Only 4 of these were infants with lymphadenopathy. Seroconversion in these tended to occur later than in infants without lymphadenopathy (mean 12 months; range 10 - 18 months). The lymph node histology showed non-specific reactive hyperplasia with a predominance (14/15) of mixed and paracortical hyperplasia. On immunohistochemistry, CD25 staining, characteristic of neoplastic transformation by HTLV-I, was positive in 6/11 cases but without correlation with seropositivity in these infants. This pattern of hyperplasia is unusual in infancy. As in HIV-induced lymphodenopathy, although the changes are not specific, they are sufficiently distinctive, particularly in HTLV-I endemic areas, to warrant serological testing of infants and mothers. The immune reponse without seroconversion appears aberrant. (AU)

Peripheral T-cell lymphomas in Jamaica an analysis of the relationship between morphology, clinical features and HTLV-I serostatus - abstract

We analysed the clinicopathologic features of 111 patients with T-cell lymphoma in Jamaica. The lymphomas were classified histologically according to the recommendations of Rappaport, the National Cancer Institute (NCI) Working Formulation and the Lymphoma Study Group in Japan. Phenotypice classification was based on the results of immunohistochemical studies utilising a panel of monclonal antibodies directed against T and B lymphocytes. Serum samples were screened for HTLV-I antibodies using the enzyme-linked immunosorbent assay and the results were confirmed by Western Blot. The presence of clinical features of Adult T-cell leukaemia/lymphoma (ATL) were assessed and compared between HTLV-I seropositive and HTLV-I seronegative groups. Seventy-three patients (65.8 percent) were HTLV-I seropositive and 38 were HTLV-I seronegative. Marked morphologic heterogeneity was noted within both groups. As expected, within the HTLV-I seropositive group many patients showed clinical features of ATL such as hypercalcaemia (37/73), leukaemia (29/73), bone marrow involvement (18/73), skin infiltration (28/73) and lytic bone lesions (4/73). Clinical features of ATL were also seen within the HTLV-I seronegative group. Fourteen patients (36.8 percent) showed two of the clinical features of ATL. Twelve (31.6 percent) showed one of the clinical features of ATL. It is possible that these patients may be HTLV-I seronegative and proviral DNA positive and should therefore be included in the ATL group. Further studies are necessary to confirm this. The remaining seronegative patients represent cases of T-cell lymphoma that are not associated with HTLV-I infection (AU)