RESUMO
Cancer causes a fifth of deaths in the Caribbean region and its incidence is increasing. Incidence and mortality patterns of cancer in the Caribbean reflect globally widespread epidemiological transitions, and show cancer profiles that are unique to the region. Providing comprehensive and locally responsive cancer care is particularly challenging in the Caribbean because of the geographical spread of the islands, the frequently under-resourced health-care systems, and the absence of a cohesive approach to cancer control. In many Caribbean countries and territories, cancer surveillance systems are poorly developed, advanced disease presentations are commonplace, and access to cancer screening, diagnostics, and treatment is often suboptimal, with many patients with cancer seeking treatment abroad. Capacity building across the cancer-control continuum in the region is urgently needed and can be accomplished through collaborative efforts and increased investment in health care and cancer control.
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Detecção Precoce de Câncer , Neoplasias/epidemiologia , Região do Caribe/epidemiologia , Causas de Morte , Humanos , Turismo Médico , Neoplasias/terapiaRESUMO
PURPOSE: To determine the histological distribution and trends in incidence of sinonasal malignancies in Jamaica. METHODS: Cases of all sinonasal malignancies diagnosed between 1973 and 2007 were extracted from the archives of the Jamaica Cancer Registry. Data recorded for each case included age at diagnosis, sex, year of diagnosis, topography, and histology. Data were used to calculate frequencies, age-specific incidence rates, and age-standardized incidence rates (ASRs). Linear regression analysis was used to determine significance of trends in incidence rates; p values of ≤0.05 were significant. RESULTS: Sinonasal malignancies were commoner in males (male: female ratio, 1.1:1), and the median ages were 62 (males) and 66 years (females). Most were located in either the maxillary sinus (61.3%) or nasal cavity (24.3%). The commonest histological types were squamous cell carcinoma (SCC) (55.9%) and non-Hodgkin's lymphoma (17.1%), which were predominantly of T-cell immunophenotype, in both the nasal cavity and sinuses. There was no documentation in registry data regarding separation into NK/T and peripheral T-subtypes. The ASRs in males and females were consistently less than 1.5 per 100,000 per year. In males, there was a significant decrease in SCC ASR (p = 0.014) over time. CONCLUSIONS: The age, gender, and anatomical and histological distribution patterns of sinonasal malignancies in Jamaica are similar to those reported internationally, and the low ASRs are in keeping with previous global reports. Broader local immunohistochemistry panels are warranted for further delineation of sinonasal T-cell lymphomas. Investigation into factors contributing to the decreasing incidence of sinonasal SCC is also required.
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Neoplasias dos Seios Paranasais/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Feminino , Humanos , Incidência , Jamaica/epidemiologia , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Adulto JovemRESUMO
We evaluated whether risk of non-Hodgkin lymphoma (NHL), particularly adult T-cell leukemia/lymphoma (ATL) related to human T-lymphotropic virus (HTLV) infection was associated with 63 single nucleotide polymorphisms (SNPs) from 38 candidate genes. The 395 NHL cases registered in Jamaica were matched by age, sex, calendar-year and HTLV serostatus to 309 controls from the same population. Interleukin 13 (IL13) Ex4+98A>G SNP (rs20541) was associated with decreased NHL risk (OR(AG/AA) = 0.62,95% CI = 0.44-0.87, p = 0.006), as was vascular cell adhesion molecule-1, VCAM1 Ex9+149G>A SNP (rs1041163) (OR(CT) = 0.77, 95% CI = 0.54-1.10, OR(CC) = 0.35, 95% CI = 0.16-0.76, p-trend = 0.007). Both results were stronger in analyses restricted to ATL cases and HTLV-positive controls, suggesting a role for these genes in ATL etiology (IL13 OR(AG/AA) = 0.54, 95% CI = 0.36-0.84, p = 0.005; VCAM1 OR(CT) = 0.65, 95% CI = 0.42-1.01, OR(CC) = 0.20, 95% CI = 0.08-0.54, p-trend = 0.001). Confirmation of these results in Caribbean and other populations is needed.
Assuntos
Infecções por HTLV-I/genética , Leucemia-Linfoma de Células T do Adulto/genética , Linfoma não Hodgkin/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Interleucina-13/genética , Interleucina-5/genética , Jamaica/epidemiologia , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/virologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Molécula 1 de Adesão de Célula Vascular/genética , Adulto JovemRESUMO
The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive ("carriers") and 51 HTLV-I-negative individuals ("noncarriers") from each population-by age, sex and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-I noncarriers, Japanese noncarriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 vs. 71, respectively, p=0.005), soluble interleukin-2 receptor-alpha (477 vs. 623 pg/mL, p=0.0008) and soluble CD30 (34 vs. 46 U/mL, p=0.0001) and lower levels of C-reactive protein (1.1 vs. 0.43 microg/mL, p=0.0004). HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk.
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Infecções por HTLV-I/sangue , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antígenos Virais/sangue , Antígenos Virais/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Jamaica/epidemiologia , Japão/epidemiologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologiaRESUMO
OBJECTIVE: Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children. METHODS: Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR. RESULTS: The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones. CONCLUSION: The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.
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Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Provírus/classificação , Provírus/isolamento & purificação , Carga Viral , Adolescente , Criança , Pré-Escolar , Impressões Digitais de DNA , DNA Viral/genética , Feminino , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Lactente , Jamaica , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Reação em Cadeia da Polimerase/métodos , Provírus/genéticaRESUMO
Several studies suggest race-based health disparities in men with low-risk prostate cancer (PCa), with African American males having poorer oncological outcomes. We sought to determine the prevalence and predictors of pathological upgrading and upstaging in Jamaican men with low-risk PCa treated with radical prostatectomy (RP). Data on 141 men who met the National Comprehensive Cancer Network criteria for low-risk PCa and underwent RP at a single institution were reviewed. All men had a transrectal ultrasound-guided biopsy. Pre-operative clinical and final pathological data were obtained. Data were summarised as means and standard deviations or percentages as appropriate. Bivariate analyses such as independent samples t-tests and chi-square tables were conducted and logistic regression models were estimated to predict upgrading (>Gleason 6) and upstaging (p ≥ T3). The mean age was 59.5 ± 7.8 years with mean prostate specific antigen (PSA) of 6.6 ± 2 ng/mL. A total of 48.3% of men were upgraded and 11.4% were upstaged. Bivariate analyses indicated that PSA (p = 0.008) and percentage positive cores (p = 0.002) were associated with upgrading. PSA (p = 0.042) and percentage positive cores (p = 0.003) were significantly associated with upstaging. The odds of upgrading increased with increased PSA levels (OR 1.40, 95% CI 1.05-1.87, p = 0.021) or increased percentage positive cores (OR 8.27, 95% CI 2.19-31.16, p = 0.002). The odds of upstaging increased with increased PSA levels (OR 1.4, 95% CI 1.01-1.96, p = 0.046) and with increased percentages positive cores (OR 11.4; 95% CI 2.06-63.09, p = 0.005). Jamaican men with low-risk PCa are at high risk of pathological upgrading and upstaging at RP. These findings should be taken into consideration when discussing treatment options with these patients.
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OBJECTIVE: We investigated changes in hematologic and biochemical parameters associated with human T lymphotropic virus type 1 (HTLV-1) infection, antibody titer, and provirus load. Additionally, on a subset of participants, we assessed the epidemiologic relationship of HTLV-1 with Strongyloides stercoralis. METHODS: Among volunteer blood donors in Jamaica, HTLV-1 carriers (n=482) were frequency matched with HTLV-1 negative subjects (n=355) by age (+/-5 years), sex, and date of blood donation (+/-3 months). HTLV-1 antibody titer, provirus load, S. stercoralis IgG antibodies, complete blood cell count, blood chemistry, and urinalysis parameters were measured. RESULTS: HTLV-1 carriers, compared with HTLV-1-negative individuals, had elevated levels of cleaved lymphocytes (24.5% vs. 16.4%), any lymphocyte abnormalities (atypical, cleaved, and reactive lymphocytes combined, 45.7% vs. 35.4%), and gamma-glutamyl transferase levels (21.2 vs. 19.6 IU/L), as well as lower eosinophil count (2.6% vs. 3.1%). Among carriers, HTLV-1 antibody titer (n=482) was inversely correlated with mean corpuscular volume (r=-0.10) and positively correlated with levels of total protein (r=0.16), phosphorus (r=0.12), and lactate dehydrogenase (r=0.24). HTLV-1-provirus load (n=326) was higher among carriers with cleaved lymphocytes and any lymphocyte abnormalities. Provirus load was inversely correlated with hemoglobin (r=-0.11), mean corpuscular volume (r=-0.15), neutrophil (r=-0.12), and eosinophil (r=-0.19) levels and was positively correlated with lactate dehydrogenase levels (r=0.12). Provirus load was significantly higher among male than female subjects. S. stercoralis antibodies were detected in 35 (12.1%) of 288 participants but were not associated with HTLV-1 status, antibody titer, or provirus load. CONCLUSIONS: Markers of HTLV-1 infection (infection status, antibody titer, and provirus load) are associated with hematologic and biochemical alterations, such as lymphocyte abnormalities, anemia, decreased eosinophils, and elevated lactate dehydrogenase levels.
Assuntos
Infecções por HTLV-I/complicações , Infecções por HTLV-I/patologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Estrongiloidíase/epidemiologia , Anticorpos Anti-Helmínticos/sangue , Anticorpos Antivirais/sangue , Sangue/virologia , Contagem de Células Sanguíneas , Análise Química do Sangue , Doadores de Sangue , Estudos de Casos e Controles , Humanos , Jamaica/epidemiologia , L-Lactato Desidrogenase/sangue , Linfócitos/citologia , Provírus/genética , Fatores Sexuais , Estrongiloidíase/imunologia , Urinálise , Carga ViralRESUMO
Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.
Assuntos
Pesquisa Biomédica , Vírus Linfotrópico T Tipo 1 Humano , Vírus Linfotrópico T Tipo 2 Humano , Infecções por Retroviridae , Retroviridae , Sociedades Científicas , Ensaios Clínicos como Assunto , Congressos como Assunto , Infecções por Deltaretrovirus/tratamento farmacológico , Humanos , Internacionalidade , Infecções por Retroviridae/tratamento farmacológicoRESUMO
In a prospective study involving 150 mothers and their offspring in Jamaica, we examined maternal viral factors associated with the risk of transmission of human T lymphotropic virus type 1 (HTLV-1). Overall, the incidence of HTLV-1 infection among children was 8.3 occurrences per 1000 person-months. A higher maternal provirus level (odds ratio [OR], 1.9 per quartile) and a higher HTLV-1 antibody titer (OR, 2.2 per quartile) were independently associated with transmission to children, whereas the presence of anti-Tax antibody was not. Higher maternal antibody titers also were associated with older age at infection among children who were breast-fed for =12 months, which suggests that passively transferred maternal antibodies confer protection against infection while they persist. These data imply that mothers who have high provirus loads should be encouraged not to breast-feed. Alternatively, the successful reduction of maternal provirus loads or maintenance of passive antibody levels in infants during breast-feeding may lower the risk of transmission.
Assuntos
Produtos do Gene tax/imunologia , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/transmissão , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Transmissão Vertical de Doenças Infecciosas , Adolescente , Adulto , Fatores Etários , Biomarcadores , Aleitamento Materno , Feminino , Infecções por HTLV-I/imunologia , Humanos , Jamaica/epidemiologia , Estudos Prospectivos , Provírus , Carga ViralRESUMO
AIM: To investigate pathological factors related to long term patient survival post surgical management of gastric adenocarcinoma in a Caribbean population. METHODS: This is a retrospective, observational study of all patients treated surgically for gastric adenocarcinoma from January 1(st) 2000 to December 31(st) 2010 at The University Hospital of the West Indies, an urban Jamaican hospital. Pathological reports of all gastrectomy specimens post gastric cancer resection during the specified interval were accessed. Patients with a final diagnosis other than adenocarcinoma, as well as patients having undergone surgery at an external institution were excluded. The clinical records of the selected cohort were reviewed. The following variables were analysed; patient gender, patient age, the number of gastrectomies previous performed by the lead surgeon, the gross anatomical location and appearance of the tumour, the histological appearance of the tumour, infiltration of the tumour into stomach wall and surrounding structures, presence of Helicobacter pylori and the presence of gastritis. Patient status as dead vs alive was documented for the end of the interval. The effect of the aforementioned factors on patient survival were analysed using Logrank tests, Cox regression models, Ranksum tests, Kruskal-Wallis tests and Kaplan-Meier curves. RESULTS: A total of 79 patients, 36 males and 43 females, were included. Their median age was 67 years (range 36-86 years). Median survival time from surgery was 70 mo with 40.5% of patients dying before the termination date of the study. Tumours ranged from 0.8 cm in size to encompassing the entire stomach specimen, with a median tumour size of 6 cm. The median number of nodes removed at surgery was 8 with a maximum of 28. The median number of positive lymph nodes found was 2, with a range of 0 to 22. Patients' median survival time was approximately 70 mo, with 40.5% of the patients in this cohort dying before the terminal date. An increase in the incidence of cardiac tumours was noted compared to the previous 10 year interval (7.9% to 9.1%). Patients who had serosal involvement of the tumour did have a significantly shorter survival than those who did not (P = 0.017). A significant increase in the hazard ratio (HR), 2.424, for patients with circumferential tumours was found (P = 0.044). Via Kaplan-Meier estimates, the presence of venous infiltration as well as involvement of the circumferential resection margin were found to be poor prognostic markers, decreasing survival at 50 mo by 46.2% and 36.3% respectively. The increased HR for venous infiltration, 2.424, trended toward significant (P = 0.055) Age, size of tumour, number of positive nodes found and total number of lymph nodes removed were not useful predictors of survival. It is noted that the results were mostly negative, that is many tumour characteristics did not indicate any evidence of affecting patient survival. The current sample, with 30 observed events (deaths), would have about 30% power to detect a HR of 2.5. CONCLUSION: This study mirrors pathological factors used for gastric cancer prognostication in other populations. As evaluation continues, a larger cohort will strengthen the significance of observed trends.
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A 32-year-old Afro-Caribbean woman presented with a 1-year history of slowly progressive sensory and motor symptoms initially affecting the legs and later involving the arms. Clinical examination demonstrated a mainly distal pattern of weakness with little objective sensory impairment. The clinical features suggested the possibility of chronic inflammatory demyelinating polyneuropathy. This diagnosis was supported by neurophysiological testing and examination of the cerebrospinal fluid and confirmed by sural nerve biopsy as well as by exclusion of other causes of neuropathy. Seropositivity for human T lymphotropic virus type I (HTLV-I) was demonstrated. The clinical significance of this finding in an area with a high HTLV-I endemicity, as well as its possible aetiological relevance to the diagnosis of chronic inflammatory demyelinating polyneuropathy, is discussed.
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We present a 61 year old Para 4 woman who presented with stage II Infiltrating lobular carcinoma of the breast after modified radical mastectomy. She was treated with Tamoxifen for seven years. She was diagnosed with multiple myeloma during year seven post mastectomy because of wrist pain. She was treated with melphalan, prednisone and allopurinol which she tolerated well and the pain in the wrist improved. Tamoxifen was also stopped. Ten months later she presented with vaginal bleeding and was diagnosed with a poorly differentiated endometrial adenocarcinoma at hysteroscopic suction curettage and had an abdominal hysterectomy. Two years later the patient succumbed to metastatic endometrial cancer.
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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 == 0.04). ATL risk was increased significantly with common HLA-B (OR 2.25, 95% CI 1.19-4.25) and DRB1 (OR 2.11, 95% CI 1.13-3.40) alleles. Higher prevalence HLA-B alleles were associated with higher ATL risk (OR 1.14 per quartile, p(trend) = 0.02). Asymptomatic carriers with common HLA-B alleles had marginally higher HTLV-I proviral load (p = 0.057). HAM/TSP risk did not differ consistently with common HLA types. Thus, ATL risk, but not HAM/TSP risk, was increased with higher prevalence HLA-B alleles. Perhaps breadth of cellular immunity affects risk of this viral leukemia/lymphoma.
Assuntos
Antígenos HLA/imunologia , Infecções por HTLV-I/epidemiologia , Alelos , Antígenos HLA/genética , Infecções por HTLV-I/imunologia , Humanos , Jamaica/epidemiologia , Prevalência , Fatores de RiscoRESUMO
To characterize a host polygenic profile associated with susceptibility to human T lymphotropic virus type I (HTLV-I) infection, we examined common variants in 11 immune-related genes among Jamaican children born to HTLV-I-seropositive mothers. Compared with HTLV-I seronegatives, haplotypes of IL6 (-660G/-635C/-236G) and IL10 (-6653C/-1116G) were significantly associated with HTLV-I infection in children independent of maternal provirus load and duration of breast-feeding (odds ratio [OR], 4.5 [95% confidence interval {CI}, 1.2-17.6], and OR, 3.5 [95% CI, 1.4-9.0], respectively). Our findings are the first, to our knowledge, to suggest that host variation in both proinflammatory and anti-inflammatory genes could influence susceptibility to HTLV-I infection.
Assuntos
Predisposição Genética para Doença , Infecções por HTLV-I/genética , Haplótipos , Interleucina-10/genética , Interleucina-6/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Jamaica , MasculinoRESUMO
Human T lymphotropic virus types I and II (HTLV-I/II) Western blot (WB) seroindeterminate status, which is defined as an incomplete banding pattern of HTLV protein Gag (p19 or p24) or Env (GD21 or rgp46), is commonly observed. To investigate the significance of this finding, we examined HTLV-I/II serostatus and HTLV-I proviral load in 2 groups of individuals with WB seroindeterminate status. Low proviral loads were detected in 42% of patients with neurologic symptoms and 44% of voluntary blood donors. These data suggest that a subset of WB seroindeterminate individuals may be infected with prototype HTLV-I. To confirm this hypothesis, we evaluated HTLV-I/II serostatus and proviral load in prospectively collected specimens from 66 WB seronegative patients who had received HTLV-I-infected blood products by transfusion. Eight individuals developed WB seroindeterminate profiles after the transfusion. In addition, using a human leukocyte antigen type A*201-restricted HTLV-I Tax11-19 tetramer, we detected virus-specific CD8(+) T cells in peripheral blood mononuclear cells from WB seroindeterminate patients. These CD8(+) T cells were effective at targeting HTLV-I-infected cells. Collectively, the results suggest that HTLV-I/II WB seroindeterminate status may reflect a history of HTLV-I exposure. Our findings warrant further investigation of the possible clinical outcomes associated with WB seroindeterminate status.
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Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/imunologia , Anticorpos Anti-HTLV-II/sangue , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 2 Humano/classificação , Doadores de Sangue , Western Blotting , DNA Viral/sangue , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/virologia , Infecções por HTLV-II/epidemiologia , Infecções por HTLV-II/imunologia , Infecções por HTLV-II/virologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Humanos , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/virologia , Provírus/isolamento & purificação , Linfócitos T Citotóxicos/imunologia , Reação Transfusional , Carga ViralRESUMO
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.
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Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/fisiopatologia , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Complicações Infecciosas na Gravidez/virologia , Aleitamento Materno , Criança , DNA Viral/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Jamaica , Masculino , Gravidez , Cuidado Pré-Natal , Carga ViralRESUMO
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."
Assuntos
Aleitamento Materno , Genes MHC Classe I , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/transmissão , Transmissão Vertical de Doenças Infecciosas , Pré-Escolar , Feminino , Anticorpos Anti-HTLV-I/sangue , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Jamaica , Provírus/isolamento & purificação , Fatores de Risco , Fatores SocioeconômicosRESUMO
BACKGROUND: Infection by Helicobacter pylori is often acquired during childhood. Recent studies suggest that inflammatory cytokines may play a role in susceptibility to, and disease phenotype caused by, H. pylori infection, but the association of host genetic variability with risk of H. pylori infection has not been studied in children. METHODS: We investigated the relationship between the risk of H. pylori antibody positivity and cytokine gene polymorphisms among 199 two-year-old Jamaicans. H. pylori seropositivity was determined by a validated research enzyme-linked immunosorbent assay. Real-time Taqman polymerase chain reaction was used to determine variants at 17 loci in 11 cytokine genes (IL1A, IL1B, IL2, TNF, TLR4, IL4, IL6, IL10, IL10RA, IL12A and IL13). We estimated the odds ratio and the 95% confidence interval for the association of genetic polymorphisms with H. pylori seropositivity, using logistic regression. RESULTS: Forty (20.1%) of 199 children were seropositive. Children's H. pylori seropositivity correlated highly with maternal H. pylori seropositivity (OR = 7.98, 95% CI = 1.05-60.60, p = .02). Children carrying IL1A-889T had a lower risk of H. pylori positivity, compared to those carrying -889C, with each T allele associated with 43% risk reduction (OR = 0.57, 95% CI = 0.33-0.99, p-trend = .05). No other loci we examined were associated with the risk of H. pylori seropositivity. CONCLUSIONS: The IL1A-889 T allele, known to express a higher level of cytokine IL-1alpha, is associated with a lower risk of H. pylori infection among Jamaican children. Our finding supports the hypothesis that an upregulation of pro-inflammatory cytokines may protect against persistent H. pylori colonization.
Assuntos
Citocinas/genética , Infecções por Helicobacter/genética , Helicobacter pylori , Interleucina-1alfa/genética , Polimorfismo Genético , Alelos , Criança , Estudos de Coortes , Variação Genética , Humanos , Jamaica , Estudos Prospectivos , Fatores de Risco , Testes SorológicosRESUMO
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.