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

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/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%-5%. 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% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an 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 greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-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 whether HTLV-I carriers develop either ATL or HAM/TSP.

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-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera 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 significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the 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- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.

Viral-specific humoral immune responses following transfusion-related transmission of human T cell lymphotropic virus type-I infection.

The immunoglobulin (Ig) isotypes of antibodies to specific proteins of the human T cell lymphotropic virus type I (HTLV-I) were determined by Western blot analysis of serial specimens from six individuals who experienced HTLV-I seroconversion following blood transfusion; five remained asymptomatic carriers, while one developed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) 32 weeks posttransfusion. Analysis of Ig isotypes demonstrated that while IgM was the most frequent early response to gag (p19, p24) and env (r21e) proteins within the first 3 months following transfusion, IgG and IgA responses could also be detected within this period. HTLV-I-specific antibody responses plateaued in all Ig isotypes, including IgM, within the next 4- to 6-month period following transfusion and persisted through the entire study period (> 4 years). Comparison of antibody profiles in Ig isotypes and IgG1 and IgG3 subclass among asymptomatic carriers and one individual who developed HAM/TSP demonstrated no evidence of isotypic prominence or IgG subclass restriction in either group. These results indicate the appearance of HTLV-I-specific IgM that persists even after the primary infection and suggest that such response does not appear to provide an early marker of seroconversion. Further, we found no evidence of isotypic prominence or restriction of the antibody response in recipients who remained asymptomatic compared to one who developed HAM/TSP.

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% (95% confidence interval) (CI) 0.01-2.7%); 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% CI: 0.93-13.08), malaria (OR = 2.13, 95% CI: 0.96-4.73), and dengue fever (OR = 1.37, 95% 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% versus 7.7%, P < 0.105) and a significantly lower prevalence of eosinophilia (1.0% versus 6.3%, P < 0.004) was seen among HTLV-I seropositives compared to controls. CONCLUSIONS: Although most HTLV-I seropositives are asymptomatic, HAM may be diagnosed in approximately 0.5% of carriers. Chronic HTLV-I infection may also exert subtle effects on body mass and haematological parameters.

Seroprevalence of HTLV-1 in chronic disease patients in Jamaica.

A high seropositivity rate of human T cell lymphotropic virus type 1 (HTLV-1) infection was found in Jamaican patients with chronic diseases. However, except for tropical spastic paraparesis, polymyositis, adult T cell leukaemia/lymphoma and polyneuropathies of undetermined cause, HTLV-1 seropositivity rates in chronic disease patients were not significantly different from that found in healthy Jamaicans. These results indicate that there is no increased risk of HTLV-1 infection or HTLV-1 associated disease in patients with chronic diseases compared to the general Jamaican population. The association of unclassified polyneuropathies with HTLV-1 reported herein is a novel one which requires further studies to elucidate its nature.

Motor pathway analysis in HAM/TSP using magnetic stimulation and F-waves.

BACKGROUND: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (HAM/TSP) is a chronic, progressive myelopathy endemic to the Caribbean. In HAM/TSP, peripheral motor pathways have been assessed using electromyography and nerve conduction studies; central motor pathways have been assessed to a limited extent using electrocortical stimulation. We used magnetic cortical stimulation (a painless alternative to electrocortical stimulation) and F-wave analysis to study conduction in the central and peripheral motor pathways in 18 HTLV-I seropositive, Jamaican TSP patients (ages 29-70 years; duration of symptoms 3-20 years) and 22 normal controls. METHODS: Magnetic cortical stimulation was effected using a 9 cm diameter undamped MES10 coil. F-waves and M-responses were elicited by electrical stimulation of the ulnar nerve at the wrist, and deep peroneal stimulation at the knee. Stimulation and recording of response latencies in abductor digitii minimi (ADM) and tibialis anterior (TA) were carried out using a Cadwell Excel system. RESULTS: With cortical stimulation, response latencies (TMCTs) to ADM and TA were prolonged in the patients relative to controls. F-wave and M-response latencies were unaffected, suggesting no peripheral pathology. Latency (CMCT) between cortex and lumbar cord was significantly prolonged; that between cortex and C7/T1, also, but less markedly (P < 0.0005). Amplitudes of cortically evoked responses were significantly reduced only in the lower limbs (TA). CMCT increased as the disease progressed from mild to moderate, thereafter remaining largely unchanged. CONCLUSIONS: Meta-analysis of interlaboratory control data revealed no significant differences in TMCTs between our controls and others studied using similar techniques. The observations are consistent with pathology affecting mainly the thoracolumbar cord in HAM/TSP.

Screening for prolonged incubation of HTLV-I infection in British and Jamaican relatives of British patients with tropical spastic paraparesis.

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 had 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 Britain (group 2); and index patients' children who were born and resident in Britain (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% (10/46; 95% confidence limits 9 to 34%) compared with zero among British born offspring (0/14) and was higher in group 2 at 33% (7/21; 12 to 55%) than in group 1 at 12% (3/25; 0 to 25%). (Patients in group 1 had the 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 maternal 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.

Amyotrophic lateral sclerosis with antecedent poliomyelitis.

Motor neurone disease may occur in patients with antecedent, sometimes remote, paralytic poliomyelitis. A Jamaican patient with this sequence is described. Research exploring the relationship between the two diseases is giving a new insight into the aetiology of motor neurone disease.

Pregnancy outcome in paraplegic women.

Six cases of paraplegia in pregnancy are reviewed. The major medical complications were urinary tract infection and anaemia. The obstetrical problems were pre-term labour and one perinatal loss due to unattended birth.

Tuberculous encephalopathy. A rare complication of pulmonary tuberculosis.

A case of tuberculous encephalopathy, a rare form of neuro-tuberculosis, 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.

Fat embolism syndrome following long bone fractures.

During the period August, 1979 to December, 1992, 14 patients with the Fat Embolism Syndrome (FES) were admitted to the University Hospital of the West Indies (UHWI). Two were females and 12 males, their ages ranging from 18 to 78 years, with a median age of 23.5 years. All had lower limb long bone fractures. Clinical features included fever, tachypnoea, confusion and drowsiness. They were all hypoxaemic; 9 required Intensive Care Unit (ICU) admission and, of these, 4 needed ventilatory support. Five patients became comatose, 4 of whom developed decerebrate posturing. There was one death from Klebsiella septicaemia, and 13 patients recovered fully. The FES is a serious life-threatening complication of long bone fractures whether simple or compound, usually occurring within 72 hours of the injury. A high index of suspicion is needed for its prompt detection, and early attempts at maintaining adequate tissue oxygenation must be instituted if serious neurological complications and death are to be avoided.

Primary antiphospholipid syndrome. A case report.

A case of the primary antiphospholipid syndrome (PAPS) in a 21-year-old Jamaican female is described. Recurrent abortions, thrombocytopenia and neurological complications as well as lupus anticoagulant positivity in the absence of features of systemic lupus erythematosus (SLE) were the main clinical findings. Diagnostic criteria, treatment and prognosis are discussed. When the antiphospholipid syndrome (APS) is present in the primary form, the diagnosis may be difficult but its recognition may prevent those vascular events which can lead to significant morbidity and foetal wastage.

Arsenic: the forgotten poison?

Chronic arsenic poisoning is an uncommon cause of peripheral neuropathy in Jamaica. A patient with this disorder is described. The insidious nature of chronic arsenic poisoning, with its disabling complications, is emphasised.

Myasthenia gravis in Jamaica. Clinical, immunological and genetic studies.

Clinical, immunological and genetic parameters were studied in 73 Jamaican patients with myasthenia gravis (MG). The reported bimodal clinical distribution of females with early onset of disease and males with late onset was not observed. The female to male ratio was 2:1. The most frequent manifestations of disease were ptosis (84.9%), general muscle weakness (68.5%), bulbar symptoms (41.1%) and diplopia (32.9%). Unusual presenting features such as unilateral ptosis, recurrent chest infection and stumbling while walking resulted in diagnosis being missed in 5.8% of cases. The sensitivity of radioimmunoassay in detecting acetylcholine receptor antibody (AchR-Ab) in sera from a subgroup of 35 MG patients was 71.4% whilst that of the ELISA was only 14.2%. There was no correlation between concentration of AchR-Ab and severity of disease. Similarly, there was no association between HLA-type, thymic pathology and course of disease. HLTV-I could not be implicated in the pathogenesis of this disease. There was a paucity of other associated autoimmune conditions among MG patients. Thymectomy was an important therapeutic modality in that improvement was observed in 22 cases and remission in 11.

Thymectomy in myasthenia gravis. The Jamaican experience.

Forty-five patients with myasthenia gravis (MG) were subjected to thymectomy by the median sternotomy technique and were followed up for 4,380 patient months. No operative deaths occurred and 93.3% of the patients benefited from surgery with 28.8% achieving remission. Forty patients (88.5%) showed improvement within one month, and 73% of those who achieved remission did so in the first 2 years. Outcome was not affected by thymic pathology except in one patient who had a thymoma removed. These results confirm the value of thymectomy in the management of MG patients with generalised disease and the efficacy of the simple median sternotomy procedure.

Thyrotoxic periodic paralysis in a Jamaican male patient.

A case of thyrotoxic periodic paralysis occurring in a Black Jamaican male patient is described. Diagnosis is based on history and confirmed by evaluation of serum electrolyte during attacks and thyroid function studies. The pathophysiology, associations, therapy and prognosis are discussed. It is important that clinicians recognise the condition as all forms of periodic paralysis are amenable to treatment, and progressive weakness can be prevented or even reversed.

Cerebral sinovenous thrombosis in a patient with paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria may be complicated by life-threatening venous thrombosis. A patient who presented with the classical clinical picture of cerebral sinus thrombosis is described. Management of the condition is discussed.