Tuberculous encephalopathy: a rare complication of pulmonary tuberculosis

A case of tuberculous encephalopathy, a rare form of neurotuberculosis, is reported in a 16-year-old girl who had pulmonary tuberculosis and extensive cerebral demyelination. The clinical, laboratory and pathological features of this entity are highlighted and the pathogenesis discussed.

Tuberculous encephalopathy. A rare complication of pulmonary tuberculosis

A case of tuberculous encephalopathy, a rare form of neurotuberculosis, is reported in a 16-year-old girl who had pulmonary tuberculosis and extensive cerebral demyelination. The clinical, laboratory and pathological features of this entity are highlighted and the pathogenesis discussed.(Au)

Clinical Utility of CERAD neuropsychological battery in elderly Jamaicans

Information on the clinical utility of neuropsychological tests in non-North-American samples is limited. We examined the diagnostic efficacy of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery in Jamaican men and women age 65 and older. A total of 72 elders were diagnosed as normal and 12 were demented based on history, physical, and neurological examination, participants were tested with the CERAD battery. Normal controls scored significantly better than dementia patients on all tests in the CERAD battery. A discriminant function found that a combination of Word List Learning Sum Recall and Boston Naming Test correctly classified a total of 81 percent of the cases (83 percent of the dements and 81 percent of the normal controls). This study is the first to demonstrate thr clinical utility of the CERAD neuropsychological battery in the differential diagnosis of memory disorders of the aged in a non-North-American sample.(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)

Antibodies to cardiolipin and beta2-glycoprotein-1 in HTLV-1-associated myelopathy/tropical spastic paraparesis

Anticardiolipin and anti-beta2GP1 antibodies were measured in 50 patients with HTLV-1-associated Myelopathy-Tropical Spastic Paraparesis (HAM-TSP) and the results were compared with those obtained for 34 HTLV-1-positive and 35 HTLV-1-negative controls, as well as 128 SLE patients. aCL but not anti-beta2GP1 was associated with HTLV-I infection. aCL was more prevalent than anti-beta2GP1 (32 percent vs. 8 percent) and was not associated with anti-beta2GP1 in HAM-TSP. IgA was the dominant isotype of aCL and anti-beta2GP1. The data suggest that tin HAM-TSP, IgA aCL are frequent and are associated with HTLV-1 infection.(Au)

Human leukocyte antigen class II alleles associated with human T cell lymphotropic virus type I infection and adult T-vell leukemia/lymphoma in a black population

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell luekemia/lymphoma (ATL) and HTLV-I associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1 percent-5 percent. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I related diseases. METHODS: We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles. RESULTS: Two antigens determined by serotyping DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42 percent versus 22 percent for DR15 [odds ratio [OR] = 2.7; 95 percent confidence interval [CI] - 1.0-7.2] and 78 percent versus 53 percent for DQ1 [OR = 3.1; 95 percent CI= 1.2-8.5]). Asymptomatic carriers were shown to have and HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP. CONCLUSIONS: These data suggest that host genetic background is an important factor in determining weather HTLV-I carriers develop either ATL or HAM/TSP.(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)

Incidence of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad

HTLV-I is sexually transmitted more efficiently from men to women than vice versa, and the majority of HTLV-I endemic areas report a female preponderance of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) cases. The objective of this study was to estimate the gender and age specific incidence rates of HAM/TSP in the general population as well as in the HTLV-I-infected population in Jamaica and Trinidad and Tobago. Incidence rates for HAM/TSP were computed based on all reported incident cases in both countries between 1990 and 1994. Population cenus reports for 1990 were used to calculate the population at risk. The age-standardized HAM/TSP incidence rate (mean +/- standard error of the mean) in Jamaica was 1.8 +/- 0.2/100,000 person years (PY). Among individuals of African descent in Trinidad and Tobago, the rate was 1.7 +/- 0.4/100,000 PY. As in HTLV-I seroprevalence, the incidence rate of HAM/TSP increased with age through the fifth decade of life and was three time as high in women than in men. The HAM/TSP incidence rate, calculated as a function of the number of HTLV-I infection persons in each age stratum, is higher in women (24.7/100,000 PY) than in men 17.3/100,000 PY). With HTLV-I infection, the lifetime risk of developing HAM/TSP was estimated to be 1.9 percent overall and is slightly higher in women (1.8 percent) than in men (1.3 percent). Thus, the higher prevalence of HTLV-I in women in endemic areas does not fully explain the preponderance of female HAM/TSP, suggesting that other cofactors must be present. The higher incidence rate in women between the ages of 40 and 59 years, as well as the increase in HAM/TSP incidence rates with age, are indicative of the importance of adult-acquired HTLV-I infection, presumably through sexual transmission(AU)

Health effects of human T-lymphotropic virus type I (HTLV-I) in a Jamaican cohort

BACKGROUND: Other than adult T-cell leukaemia (ATL) and HTLV-I associated myelopathy (HAM), the health effects of infection with human T-lymphotropic virus type I (HTLV-I) are not well defined. METHOD: A cohort of 201 confirmed HTLV-I seropositive Jamaican food service workers and 225 seronegative controls of similar age and sex from the same population was examined. A health questionnaire, physical examination, and laboratory tests were performed at enrollment into the cohort in 1987-1988. RESULTS: One of 201 HTLV-I seropositives, but no controls were diagnosed with HAM, for a prevalence of 0.5 percent (95 percent confidence interval) (CI) 0.01-2.7 percent); no cases of ATL were diagnosed. While there was no difference in current symptoms, the HTLV-I seropositive group was more likely to report a past medical history of hepatitis or jaundice (OR = 3.49, 95 percent CI: 0.93-13.08), malaria (OR = 2.13, 95 percent CI: 0.96-4.73), and dengue fever (OR = 1.37, 95 percent CI 0.82-2.29); however, these differences were of borderline statistical significance. Low income HTLV-I seropositive women had lower body weight (P , 0.01) and body mass index (P < 0.009) than their seronegative counterparts; similar differences were seen in the smaller male group. A trend toward higher prevalence of severe anaemia (haemoglobin < 10 g/dl) (12.6 percent verus 7.7 percent, P < 0.105) and a significantly lower prevalence of eosinophilia (1.0 percent verus 6.3 percent, P < 0.004) was seen among HTLV-I seropositives are asymptomatic, HAM may be diagnosed in approximately 0.5 percent of carriers. Chronic HTLV-I infection may also subtle effects on body mass and haematological parameters.(AU)

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectionalstudy to assess four candidate biomarkers of immune activation, beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in storedsera from asymptomatic, human T-cell leukemia virus type I (HTL V-I) seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were signigicantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- amd HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients. (AU)

Photosensitivity and antinuclear antibodies in black patients with systemic lupus erythematosus

Black patients with systemic lupus erythematosus (SLE) have a lower prevalence of photosensitivity rashes than white patients. The reasons for this are unkown, but some studies suggest a correlation between the presence of antinuclear antibodies and protection from phosensitivity. In our study, we determined serum antinuclear-antibody profiles, including anti-dsDNA, anti-Sm, anti-RNP, anti-Ro/SS-A, anti-La/SS-B antibodies, in 91 black Jamaican patients with SLE. All 91 serum samples from SLE patients (100 percent) were positive in the fluorescent antinuclear-antibody test. Using the crithidia luciliae immunofluorescence test, anti-dsDNA was found in 27.5 percent of the samples. By a double immunodiffusion method, anti-Sm antibodies were found in 15.4 percent, and anti-RNP in 18.7 percent, anti-Ro/SS-A in 9.9 percent and anti-La/SS-B in 11.0 percent. However, no statistically significant differences were observed in the seroprevalence of these antinuclear antibodies when sera from patients of the following groups were compared: only photosensitivity rashes (n = 17), photosensitivity and other rashes (n = 23), other rashes without photosensitivity (n = 27), and patients with no skin rash of any type (n = 24). These results suggest that photosensitivity in black Jamaican patients with SLE is not associated with antinuclear-antibody specificity(AU)

Risk factors and cofactors for human T-cell lymphotropic virus type 1 (HTLV-1) - associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica

Human T-cell lymphotrophic virus type 1 (HTLV-1) has been etiologically associated with a neurologic syndrome called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-1 infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-1-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-1 seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-1 seropsitive compared with two (4.0 percent) of the controls with other neurologic diseases. Given HTLV-1 seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual intercourse (odds ratio = 4.00, 95 percent confidence interval 1.29-12.46 for individuals aged ó15; odds ratio = 4.26, 95 percent confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95 percent confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse nor the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-1 infection, whereas adult T-cell leukemia/lymphoma is not. (AU)

The echocardiographic features of polymyositis - abstract

Two dimensional echocardiography with doppler studies were performed in 30 patients at the UWI with the diagnosis of dermatomyositis/polymyositis established by the usual clinical and investigative criteria. This was done in order to elucidate the echocardiographic features of this condition which had not been clearly defined before. There were 25 females and 5 males, age range 28-65 years (mean - 48 years), with the majority of patients (70 percent) being in the 41 - 70 year age group. No valvular abnormalities were observed, and left ventricular internal dimension in systole LVIDs-1.9-3.7 cm, mean-2.8cm) and contractility (ejection fraction - range 43 - 89 percent, mean - 69 percent) were normal. No regional wall motion abnormalities were observed. Only 3 patients (10 percent) had evidence of global reduction in systolic function. There was hypertrophy of the interventricular septum in 9 patients (30 percent), and in the left ventricular posterior wall in 6 patients (20 percent). The dimensions of the left atrium (2.6-3.7 cm; mean - 3.2 cm), aorta (2.5-3.6 cm; mean 3.2 cm) and right ventricle (range 1.6-2.5 cm; mean - 2.1 cm) were normal. Doppler studies did not reveal any significant valvular regurgitation, and pulmonary artery velocities documented normal mean pulmonary artery pressures (mean 18 mm Hg) in all patients. Left ventricular diastolic function as indicated by E/A ratios (0.55-1.39;mean-1.23) from mitral valve inflow studies was normal. Conclusion: Echocardiographic doppler studies in patients with dermatomyositis/polymyositis were largely normal apart from minor degrees of left ventricular hypertrophy in a minority of 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)

Identification of human T-cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the other specimens were weakly positive for gp46 in rare mononuclear cells. All controls specimens were negative for the presence of HTLV-I DNA and protein. CONClUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.(AU)

IGA antiphospholipid antibodies in HLTV-1-associated tropical spastic paraparesis

A retrovirus human T cell lymphotropic virus type I (HTLV-I), is an essential but not a sufficient aetiological factor for tropical spastic paraparesis (TSP). Because some TSP patients have biological false positive tests for trepomemal infections (BFP-STS), we used EISA to study BFP-STS and anticardiolipin antibodies in 42 Jamaican TSP patients. The data indicate that in TSP anticardiolipin antibodies accur in about 26 percent of patients, are associated with biological false positive treponemal serology, are relatively restricted to the IgA isotype and may be induced by HTLV-I or other non-treponemal infections. (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

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(AU)