A retrospective case series study of the seroprevalence of Human T Lymphocyte Virus 1 and 2 from the General hospital Laboratory in Grenada

OBJECTIVE: HTLV-1 is a human retrovirus that causes adult T-cell Leukemia/Lymphoma (ATL) and some other conditions – HTLV-associated myelopathy (tropical spastic paraparesis, a multiple sclerosis-like disease), uveitis, infective dermatitis and some “auto immune” diseases. While the Caribbean has been identified as an HTLV-1 endemic area, there are no published studies on HTLV-1 from Grenada. The objective of this study was to anonymously review the General Hospital laboratory records to investigate the seroprevalence of HTLV-1 and 2 in Grenada. DESIGN AND METHODS: This was a retrospective study of the records from the General Hospital Laboratory in Grenada, where ELISA serologically positive results for HTLV 1 and 2 were recorded as a percentage of the total number of tests performed between the years 1998 - 2013. The Diasoren rapid ELISA serological test was used. RESULTS: During the 16 year review period (1998-2013) a total of 2,346 (4.7%: 95% CI: 4.5% to 4.9%) out of 49,782 patients were identified as HTLV-1 and 2 positive. Females with a median age of 34 years comprised 70% of positive cases whilst the median age for males was 43 years. The rate in Grenada has been steadily declining since 1998 and appears to be leveling off at about 3.7%. CONCLUSION: The current seroprevalence of HTLV 1 and 2 in Grenada is lower than that reported in 1991 in Jamaica (5%). The rate found is still unacceptably high and additional studies are required to determine the health consequences of HTLV-1 infection. Additionally appropriate public health programs should be applied to help reduce transmission.

Ophthalmic presentation of relapsed HTLV1- associated adult T-cell leukaemia lymphoma (ATLL) in a Trinidadian man

The ophthalmic presentation of relapse in a patient with human T-lymphotropic virus type 1 (HTLV1) associated adult T-cell lymphoma leukaemia is described. Epidemiology, clinical features and therapeutic options are briefly reviewed. Antenatal screening and inclusion of HTLV1 in the differential diagnosis of inflammatory and neuromuscular eye conditions should be considered in endemic regions.

HTLV in the Americas: challenges and perspectives

The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980 followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTLV-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatological, psychiatric and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial cost on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence(AU)

Estimating the time of HTLV-I infection following mother-to-child transmission in a breast-feeding population in Jamaica

Mother-to-child transmission of human T-cell lymphotrophic virus type 1 (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the post-natal period. Most infant infections are not identifiable until 12-18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was observed in 100 percent of children at 24 months of age and 73 percent of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50 percent of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P=0.72). PCR Tests support a median time to infection that is similar to that estimated by whole virus Western blot. (AU)

Nucleotide sequence analysis of human T-cell lymphotropic virus type I pX and LTR regions from patients with sicca syndrome

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). Other inflammatory disorders may occur in HTLV-I-infected patients, such as sicca syndrome resembling Sjogren's syndrome. The sicca syndrome may be the unique clinical manifestation of HTLV-I infection, but is associated frequently with TSP/HAM, which could suggest that sicca syndrome might be an early event in disease progression to TSP/HAM in some cases. We investigated whether peculiar pX and LTR mutations could be related to sicca syndrome, or might argue the existence of clinical progression to TSP/HAM. pX, especially pX(I), pX(II), and pX(IV) ORFs corresponding to Tax cytotoxic T-lymphocyte epitopes, and LTR regions from Caribbean patients who have sicca sydrome with or without TSP/HAM, ATL patients, and healthy carriers were sequenced. The sequences were aligned and compared with ATK-1 prototype and published sequences. LTR sequences exhibited 1.5-2.4 percent of divergence with ATK-1. pX-sequenced regions showed a lower homology within p12(I) encoding sequences. Only few mutations were found within functionally important regions, but were not associated specifically with the clinical status. Finally, no existence of clinical progression to TSP/HAM were found. It would be of interest to study the clinical evolution of HTLV-I-sicca syndrome in patients and to determine HTLV-I sequences from peripheral blood and salivary glands at different stages. Copyright 1999 Wiley-Liss, Inc.(Au)

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)

The significance of immune disorder in tropical spastic paraparesis

The reports of the occurrence of HTLV-1 infection and/or HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis (TSP) in patients with certain organ-specific and nonorgan-specific autoimmune diseases prompted us to assess the relationship between TSP and humoral autoimmunity. Blood samples from 76 TSP patients, 60 asymptomatic HTLV-1 carriers and 100 HTLV-1 seronegative blood donors were examined for the presence of organ-specific and nonorgan-specific autoantibodies, reactive serological tests for syphilis, immunoglobulin and complement concentrations as well as immunecomplexes. High prevalences of autoantibodies (39/76, 51 percent), reactive serological tests for syphilis (23/76; 30 percent), hypergammaglobulinaemia (69/76, 90 percent) and the complement fixing immune complexes (44/76, 58 percent) were found in the TSP patients. These indicators of immunological disorder were found in statistically significantly lower prevalences in asymptomatic HTLV-1 carriers (12/60, 20 percent; p < 0.001; 6/60, 10 percent; p < 0.05; 32/60, 53 percent; p < 0.001 and 8/60, 13 percent; p < 0.001, respectively) and HTLV-1 seronegative blood donors (8/100, 8 percent; p < 0.001; 3/100, 3 percent; p < 0.001; 15/100, 15 percent p < 0.001 and 5/100, 5 percent; p < 0.001, respectively). The profiles of autoimmune phenomena observed in the patient and control groups revealed that they were associated with TSP rather than mere HTLV-1 infection and consequently pathogenic significance. The array of immunological features present in TSP was suggestive of autoimmune disease resulting from immune dysfunction. Studies which explore the possible existence of HTLV-1 induced autoantibodies with specificity for antigens of the spinal cord in TSP might be useful in elucidating its pathogenesis.(Au)

Direct analysis of viral-specific CD8+ T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with human T cell lymphotropic virus-associated myelopathy

Human T cell lymphotropic virus-I (HTLV-I) -associated myelopathy is a slowly progressive neurologic disease characterized by inflammatory infiltrates in the central nervous system accompanied by clonal expansion of HTLV-I-reactive CD8+ T-cells. In patients carrying the HLA-A2 allele, the immune response is primarily directed to the Tax11-19 peptide. The frequency, activation state, and TCR usage of HLA-A2/Tax11-19 binding T cells in patients with HTLV-I-associated myelopathy was determined using MHC class I tetrameters loaded with the Tax11-19 peptide. Circulating Tax11-19-reactive T cells were found at very high frequencies, approaching 1:10 circulating CD8+ T cells. T cells binding HLA-A2/Tax11-19 consisted of heterogeneous populations expressing different chemokine receptors and the IL-2R beta-chain but not the IL-2R alpha-chain. Additionally, Tax11-19-reactive CD8+ T cells used one predominant TCR beta-chain for the recognition of the HLA-A2/Tax11-19 complex. These data provide direct evidence for high frequencies of circulating Tax11-19-reactive CD8+ T cells in patients with HTLV-I-associated myelopathy.(Au)

Mother-to-child transmission of human T-cell lymphotropic virus type I associated with prolonged breast-feeding

OBJECTIVES: We assessed the risk of transmitting human T-cell lymphotropic virus type I (HTLV-I) through breastfeeding. STUDY DESIGN/METHODS: To assess the risk of mother-to-child transmission of HTLV-I, 212 HTLV-I-seropositive women and 145 HTLV-I-seronegative women were enrolled in a prospective cohort study conducted in Kingston, Jamaica. Their offspring were examined at regular intervals, and HTLV-I serostatus was determined at each visit. RESULTS: Twenty-eight of the 181 children with at least one postnatal visit born to HTLV-I-seropositive women and (none of the children born to HTLV-I-seronegative women) were persistently seropositive, compared with only 8 (9 percent) of 86 children breast-fed for less than 12 months (relative risk, 3.4; 95 percent CI, 1.7 - 6.9). Compared with children weaned at younger ages, transmission of HTLV-I was associated with continued breast-feeding of children who were 12 to 18 months of age (relative hazard, 6.4; 95 percent CI. 2.1 - 180.2) and older than 18 months (relative hazard, 18.1; 95 percent, 1.4 - 29.5). Transmission was also associated with higher maternal antibody titer (a possible marker of virus load), prolonged duration of ruptured membranes during childbirth, and lower maternal income. CONCLUSIONS: These results suggest that limiting the duration of breast-feeding to less than 12 months for children born to HTLV-I-seropositive mothers may significantly reduce mother-to-child transmission of HTLV-I.(Au)

Incidence of HIV and HTLV-1 infection among sexually transmitted disease clinic attenders in Jamaica

Of 970 sexually transmitted disease (STD) patients enrolled at the Comprehensive Health Centre, Kingston, Jamaica, between November 1990 and January 1991, 710 (73 percent, 333 men and 377 women) were reexamined between January 1992 and July 1993 to estimated the incidence of HIV and HTLV-1 infection and to identify risk factors for infection. Of those reexamined, 20 percent were recruited passively when they returned to the clinic of their own accord, and 80 percent were recruited actively through field visits to their homes. Passively recruited persons were significantly more likely than active recruits to have had a sexually transmitted disease since enrollment or at their follow-up visit. Seven men and one women became HIV positive during the period of follow-up. The overall HIV incidence rate was 0.7 per 100 person years (95 percent confidence interval [CI] = 0.3 to 1.4 (CI = 0.6 to 2.8) for men and 0.2 (CI = 0.004 to 0.9) for women. Four of 270 men and 4 of 318 women were HTLV-1 positive, and overall incidence of 0.9 per 100 person years (CI = 0.4 to 1.7), 1.0 for men and 0.8 for women. HTLV-1 infection was associated with an age of 30 years or older (p < 0.01). The presumed lower transmission probability for HTV-1 may combine with a higher prevalence of HTLV-1 in sexual partners to produce similar overall incidence rates for the two infections. The HIV and HTLV-1 incidence rates may have been underestimated, because the study subjects who did not return to the clinic may have had a somewhat higher risk. On univariate analysis, there were significant associations between HIV infection in men and drinking alcohol before sex, cocaine use, total number of sex partners, sex with a prostitute since enrollment, ever accepting money for sex, the average number of sex partner per month, bruising during sex, and genital ulcers found on follow-up examination. This analysis needs to be interpreted with caution in view of the small number of seroconverters, which did not allow testing for independent effects in a logistic regression model(AU)

Tropical spastic paraparesis: then and now

Tropical spastic paraparesis (TSP) is a chronic myelopathy that was initially recogized in tropical countries in the nineteen century. For several decades no aetiological agent was identified until in 1985 when IgG antibodies to human T-cell lymphotropic virus Type 1 (HTLV-I) were found in serum and cerebrospinal fluid of patients from Jamaica, Columbia and Martinique. Soon after, a similar clinical syndrome named HTLV-I associated myelopathy (HAM) was described from the temperate region of Kyushu in Japan. In 988 the name TSP/HAM was introduced to include all HTLV-I positive patients with the clinical criteria of this chronic myelopathy. No major changes have been noted in the clinical features of these patients over the years but with the increased numbers of patients studied many more HTLV-I associated syndromes have been identified. Non HTLV-I positive TSP is still reported in several countries and the conclusion must be that this chronic spastic paraparesis has diverse aetiologies. (AU)

A case-control study of risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I) in Jamaica

BACKGROUND: We investigated behavioural and environmental risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I). METHODS: A nested case-control study of 201 HTLV-I seropositive subjects and 225 age and sex matched seronegative controls was performed using questionaire data from the enrollment visit of a cohort study in 1987-1988. HTLV-I serostatus was confirmed using enzyme-linked imunosorbent assay (ELISA) and Western blot. RESULTS: Among women, the number of lifetime sexual partners (P < 0.05, chi 2 trend) and the number of different men fathering a child by the woman (P < 0.06, chi 2 trend) were associated with HTLV-I seropositivity. Use by the female subject of an intrauterine device (IUD) was associated with an increased risk of seropositivity (odds ratio (OR) = 2.67, 95 percent confidence interval (CI): 1.13-6.23); condom use was rare in this population. Among male subjects, a larger number of lifetime sexual partners was also associated with HTLV-I seropositivity (P < 0.05, chi 2 trend). No association was found between HTLV-I seropositivity and educational attainment, income, or occupation. Having been breastfed as a child or receipt of a blood transfusion had elevated but imprecise OR due to very high and low prevalence of the risk factors, respectively. Several variables relating to insect or animal exposure showed no association with HTLV-I seropositivity. CONCLUSIONS: These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.(AU)

Childhood dermatitis in the tropics: with special emphasis on infective dermatitis, a marker for infection with human T-cell leukemia virus-I

Eczema in the tropics is a common problem. Although it is a major cause of discomfort among children worldwide, a warm tropical climate often has important repercussions for children with dermatitis. The original description by Sweet empahasized that interest in tropical eczemas extended to the English, as children of West Indian immigrants in England were affected. Likewise, immigrants may carry these disorders with them to the United States. In Jamaica, a tropical country, the largest and most populous of the English-speaking Caribbena islands, eczema is by far the most common skin disorder seen in children attending dermatology clinics. Reports from other Caribbean islands suggest that this is true for the region as a whole. In 1981, Alabi and La Grenade reported that from 1971 to 1975 eczema accounted for 46.7 percent of skin rashes seen in children at the University Hospital of the West Indies. Review of the period 1988 to 1993 showed that 52 percent of the 601 children who attended the skin clinic for the first time had eczema, confirming the earlier finding. In this latter review, atopic eczema was the most common type of eczema (52 percent), followed by seborrheic eczema (20 percent) and infective dermatitis (10 percent). The remaining 18 percent had a variety of unclassified eczemas including pityriasis alba, discoid eczema, acute vesicular eczema of the hands and/or feet, and hyperkeratotic eczema of the feet.(AU)

De prevalentie van humaan T-Lymfotroop virus type 1 en 2 bij bloeddonors en patienten met seksueel overdraagbare aandoeningen in Suriname / The prevalence of human T-Lymphotropic virus types 1 and 2 in blood donors and patients with sexually transmitted diseases in Suriname

OBJECTIVE; To determine the prevalence of HTLV-1 and HTLV-2 infection in the population of Suriname in order to enhance the safety of blood transfusion in Suriname. DESIGN; Descriptive. SETTING; Academic Hospital, Paramaribo, Suriname. METHOD: Blood was examined of the 777 regular donors(constituting 97 procent of the total pool) who donated blood between 1 February and 1 June 1995 at the Blood Transfusion Centre of the Suriname Red Cross in Paramaribo, and also of the 140 patients with a sexually transmitted disease (STD) seen during the same period at the Dermatological centre of the Ministry of Health. All sera were sreened with particle agglutination. Sera which were not negative were subsequently tested with a western blot method which distinguishes between HTLV-1 and HTLV-2. RESUTLS. Three sera (0.4 percent) of the blood donors and 2(1.4 procent) of the STD patents were positive for HTLV-1(difference not significant). Nobody was found to be HTLV-2 positive. CONCLUSION; The HTLV-1 prevalence in the Suriname blood donors is similar to that of blood donors and general population of many regions in Brazil, but substantially lower than in several other regions in the Caribbean. Since examination of all donated blood is not a realistic option in Suriname it is recommended that all new regular blood donors should be tested for HTLV antibodies(AU)

The epidemiology of HTLV-1 and risk of disease and outcome: Jamaica

HTLV-1 is a human retrovirus endemic in the Caribbean and Japan. The crude prevalence in Jamaica is 5-6 per cent but there is a steady increase with age peaking in the 8th decade at 17 per cent among females and 9 per cent among males. The majority of persons infected with HTLV-1 do not manifest any clinical disease. However, some persons develop adult T-cell lymphoma, tropical spastic paraparesis or infective dermatitis. Associations with arthropathy, uveitis, polymyositis and panbronchiolitis have also been reported. HTLV-1 is transmitted via sexual contact, mother to child (mainly through breast milk) and by transfusion of cellular blood product. Male to female sexual transmission is far more efficient than female to male. Control of HTLV-1 requires screening blood transfusions and reducing sexual and vertical transmission. (AU)

Anterior horn cell degeneration in polymyositis associated with human T lymphotropic virus Type-1 in patients from Barbados

Anterior horn cell degeneration has only ocassionally been noted in patients with tropical spastic paraparesis associated with human T lymphotropic virus type-1 (HTLV-1) infection. We report on three adult patients with HTLV-1-associated polymyositis who had clinical evidence of anterior horn cell degeneration. One patient had moderate proximal weakness and muscle wasting in all four limbs, while two had mild upper limb weakness with more profound proximal weakness and wasting in the lower limbs. In all three patients, elctromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle cell biopsies in two patients showed features of denervation. Immunoglobulin G (IgG) antibodies to HTLV-1 were detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western immunoblot in serum and cerobrospinal fluid in all three patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen-capture technique using an anti-p19 HTLV-1 mouse monoclonal antibody. The three cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. In some cases of HTLV-1-associated polymyositis, anterior horn cell degeneration may make a significant contribution to the muscle atrophy observed. (AU)

HTLV-1 polymyositis

The case is described of an HTLV-1 seropositive Jamaican woman who presented with signs and symptoms of polymyositis and myelopathy. A muscle biopsy showed features of myositis with a mononuclear inflammatory infiltrate, variation in fibre size and evidence of regeneration. Immunocytochemistry showed the mononuclear cells were composed of macrophages and T-lymphocytes suggesting a cell-mediated response. Multiplex PCR demonstrated the presence of the HTLV-I tax gene within the muscle. (AU)