RESUMO
BACKGROUND: This paper discusses the ethical aspects of a large research program in virology, conducted since 1994 and which has evolved in parallel with the elaboration of bioethics laws in France. This research, which involved the collection of a considerable amount of epidemiological data in the field, focused on epidemiological determinants (mother to child transmission, genetic susceptibility/resistance) of the human oncogenic retrovirus human T cell lymphotropic virus type 1 (HTLV-1). Data were collected from a specific population (Noirs Marrons) living in remote areas in French Guiana (South America). This ethnic group of African descent is highly endemic for HTLV-1 and associated adult T cell leukemia/lymphoma. The population has lived for two centuries on either side of the Maroni river, which constitutes the frontier between French Guiana and Surinam. The low socioeconomic and education levels of a large part of this population are mainly explained by a recent housing/residence fixation on the French side of the Maroni river. It is also linked to significant immigration from Surinam due to the civil war, which lasted for five years in the late 1990s, in this country. Conducting epidemiological surveys in this peculiar context illustrates the limitations of the available current legal framework in France for such studies. Indeed, several important ethical issues arose concerning not only individual and population benefits, but also specificities of the given information and of the informed consent. Another question concerns individual information feed-back in such a context of persistent viral infection, with a very low disease incidence, in a population with a relatively low education level. The goal of this work was mainly to report several of the ethical issues encountered and to discuss possible ways of achieving better information deliver and consent procedures in such a context. Indeed, these procedures should include new ideas and regulations promoting a real partnership, in order to conduct long-term epidemiological studies in populations with a low education level.
Assuntos
Estudos Epidemiológicos , Análise Ética , Ética em Pesquisa , Infecções por HTLV-I/epidemiologia , Participação da Comunidade/legislação & jurisprudência , Escolaridade , Etnicidade/estatística & dados numéricos , França , Guiana Francesa/epidemiologia , Guiana Francesa/etnologia , Infecções por HTLV-I/etnologia , Promoção da Saúde/ética , Promoção da Saúde/legislação & jurisprudência , Humanos , Consentimento Livre e Esclarecido/ética , Consentimento Livre e Esclarecido/legislação & jurisprudência , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/etnologia , PobrezaRESUMO
Humans are exposed worldwide to a variety of environmental mycobacteria (EM) and most children are inoculated with live Bacille Calmette-Guérin (BCG) vaccine. Although rarely pathogenic, poorly virulent mycobacteria, including BCG and most EM, may cause a variety of clinical diseases. M. tuberculosis and M. leprae are more virulent, causing tuberculosis, and leprosy, respectively. Remarkably, only a minority of individuals develop clinical disease, even if infected with virulent mycobacteria. There is now accumulating evidence that the large interindividual variability of clinical outcome results in part from variability in the human genes that control host defense. We review here in current knowledge about genetic predisposition to common (leprosy and tuberculosis) and rare (BCG and EM infections) mycobacterial infections.
Assuntos
Humanos , Hanseníase/etiologia , Hanseníase/genética , Infecções por Mycobacterium/etiologia , Infecções por Mycobacterium/genética , Mycobacterium/patogenicidade , Predisposição Genética para Doença , Tuberculose Pulmonar/etiologia , Tuberculose Pulmonar/genética , Variação GenéticaRESUMO
BACKGROUND: Transmission of human herpesvirus 8 (HHV-8), the aetiological agent of Kaposi's sarcoma, is known to occur during sex among homosexual men. However, other modes of HHV-8 transmission remain to be elucidated in endemic populations. METHODS: We did a population-based seroepidemiological survey in a village in French Guiana among 1337 individuals of African origin (age 2-91 years) who had reliable genealogical data. Plasma samples were taken and tested for HHV-specific IgG by immunofluorescence assay. Risk factors and familial correlations for HHV-8 seropositivity were modelled by logistic regression analysis by use of the estimating equations approach, which expresses familial dependences in terms of odds ratios. Familial odds ratios were also acquired by use of the distribution of all possible pairs of a given familial dependence. FINDINGS: The overall HHV-8 seroprevalence was 13.2% with no difference according to sex. HHV-8 seropositivity was strongly age dependent: at 1.2% under 5 years, HHV-8 seroprevalence rose up to a plateau around 15% between 15 and 40 years, and showed a seroprevalence of more than 27% in individuals older than 40 years. Strong familial aggregation in HHV-8 seroprevalence was found with high mother-child (odd ratio 2.8 [95% CI 1.6-5.0]) and sib-sib (3.8 [1.6-9.5]) correlations. By contrast, no significant correlation between spouses (0.6 [0.2-1.9]) was seen. INTERPRETATION: This pattern of familial aggregation, together with the variation of HHV-8 seroprevalence with age, indicate that, in endemic populations, HHV-8 transmission mainly occurs from mother to child and between siblings during childhood and adolescence.
Assuntos
Transmissão de Doença Infecciosa , Infecções por Herpesviridae/transmissão , Transmissão Vertical de Doenças Infecciosas , Sarcoma de Kaposi/epidemiologia , Adolescente , Adulto , África/etnologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Estudos de Coortes , Doenças Endêmicas , Feminino , Guiana Francesa/epidemiologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Razão de Chances , Sarcoma de Kaposi/sangue , Sarcoma de Kaposi/virologia , Estudos SoroepidemiológicosRESUMO
Human T lymphotropic virus type I (HTLV-I) is a human oncoretrovirus that causes an adult T cell leukemia/lymphoma and a chronic neuromyelopathy. To investigate whether familial aggregation of HTLV-I infection (as determined by specific seropositive status) could be explained in part by genetic factors, we conducted a large genetic epidemiological survey in an HTLV-I-endemic population of African origin from French Guiana. All of the families in 2 villages were included, representing 83 pedigrees with 1638 subjects, of whom 165 (10.1%) were HTLV-I seropositive. The results of segregation analysis are consistent with the presence of a dominant major gene predisposing to HTLV-I infection, in addition to the expected familial correlations (mother-offspring, spouse-spouse) due to the virus transmission routes. Under this genetic model, approximately 1. 5% of the population is predicted to be highly predisposed to HTLV-I infection, and almost all seropositive children <10 years of age are genetic cases, whereas most HTLV-I seropositive adults are sporadic cases.
Assuntos
Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/genética , Adolescente , Adulto , África/etnologia , Fatores Etários , Criança , Pré-Escolar , Doenças Endêmicas , Feminino , Guiana Francesa/epidemiologia , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Linhagem , Penetrância , Estudos SoroepidemiológicosRESUMO
To determine the epidemiological characteristics of human T cell leukemia/lymphoma virus type I (HTLV-I) infection in the endemic village of Maripasoula, French Guiana, 1,614 persons (83.2% of the population) aged 2 to 91 years (mean age 21) were studied from November 1994 through April 1995. Plasma samples were screened by an HTLV-I ELISA and an IFA test (on MT2 cells), and positive samples were tested by an HTLV-I and -II type-specific Western blot. Overall seropositivity in the village was 6.7%, but HTLV-I infection was restricted to 3 of 6 ethnic groups, including the Noir-Marron (descendants of escaped African slaves, 8%), the Creoles (4.1%) and those of mixed Noir Marron/other ethnicity (3.6%). In the Noir-Marron population of 1,222 persons, including 606 men and 616 women and representing 76% of those tested, HTLV-I seroprevalence increased significantly with age in both sexes, reaching 40% in women older than 50 years. Univariate risk factors for HTLV-I seropositivity in women included older age, more pregnancies, more live births and a history of hospitalization. A cross-sectional analysis of sexual partners demonstrated an excess of discordant female HTLV-I+/male HTLV-I- couples, indicating preferential male-to-female sexual transmission. The demonstration of II HTLV-I-seropositive children aged less than 15 years, of whom 9 had a seropositive mother, suggested maternal-child HTLV-I transmission. Our results demonstrate a very high seroprevalence of HTLV-I in this South American population descended from African slaves, probably due to high rates of mother-to-child and sexual transmission within this rather isolated group.