RESUMO
OBJECTIVES: In Guadeloupe, an island in the French West Indies, a universal newborn screening programme for sickle cell disease and other abnormal haemoglobins was initiated in 1984. In 1990, a comprehensive sickle cell centre was established to carry on the management programme. We here report the main results from the newborn screening programme from 1984 to 2010, and consider how the establishment of the sickle cell centre affected the programme. METHODS: All blood samples were screened for the haemoglobinopathies using two reference methods in a single reference diagnosis laboratory. DNA analyses were also performed for confirmatory tests and analysis of the globin gene status. RESULTS: Between 1 January 1984 and 31 December 2010, 178,428 newborns were screened at birth, and 585 children were diagnosed with major sickle cell syndromes (ie. an overall incidence of 1 in 304 births). Sickle cell anaemia (haemoglobin SS disease) was the most frequently observed (1 in 575 births), followed by haemoglobin SC disease (1 in 771 births) and haemoglobin Sß-thalassemia disease (1 in 4,243 births). Some other rare haemoglobin variants were also detected, the most common being HbD(Punjab). The establishment of a comprehensive sickle cell centre resulted in a significant improvement in the screening coverage (p < 0.001) and a significant reduction of the delay between diagnosis and the first medical visit (p < 0.001). CONCLUSION: The universal screening programme has made it possible to establish the incidence of the major sickle cell syndromes in Guadeloupe, and the management centre has improved its efficiency.
Assuntos
Hemoglobinopatias/diagnóstico , Hemoglobinopatias/genética , Triagem Neonatal/métodos , Feminino , Frequência do Gene/genética , Guadalupe/epidemiologia , Humanos , Recém-Nascido , Masculino , alfa-Globinas/genética , Globinas beta/genética , Talassemia beta/genéticaRESUMO
In this study, we have determined the frequency of beta(S) haplotypes in 163 sickle cell disease patients from Trinidad. The alpha(3.7) globin gene deletion status was also studied with an observed gene frequency of 0.17. Among the 283 beta(S) chromosomes analyzed, the Benin haplotype was the most prevalent (61.8%) followed by Bantu (17.3%), Senegal (8.5%), Cameroon (3.5%), and Arab-Indian (3.2%), while 5.7% of them were atypical. This beta(S) haplotypes distribution differed from those previously described in other Caribbean islands (Jamaica, Guadeloupe, and Cuba), in agreement with the known involvement of the major colonial powers (Spain, France, and Great Britain) in the slave trade in Trinidad and documented an Indian origin of the beta(S) gene.
Assuntos
Anemia Falciforme/epidemiologia , Globinas/genética , Família Multigênica/genética , Talassemia alfa/epidemiologia , Adulto , Anemia Falciforme/genética , Feminino , Deleção de Genes , Frequência do Gene , Marcadores Genéticos , Haplótipos , Humanos , Masculino , Mutação , Trinidad e Tobago/epidemiologia , Talassemia alfa/genéticaRESUMO
OBJECTIVE: To determine if the time courses of hemorheologic parameters are different between carriers of sickle cell trait (SCT) and subjects with normal hemoglobin in response to exercise. DESIGN: Observational and comparative study. SETTING: Testing was conducted in a laboratory of exercise physiology. PARTICIPANTS: Nine carriers of sickle cell trait (SCT group) and 7 subjects with normal hemoglobin (CONT group) performed an exercise protocol of the repetition of 3 successive maximal ramp exercise tests. INTERVENTIONS: Blood was sampled at rest (TR), at the end of each of the 3 tests (T1, T2, T3), and during the immediate (T2h) and late (T24h, T48h) recovery periods. MAIN OUTCOME MEASUREMENTS: Blood and plasma viscosity (etab and etap, respectively), hematocrit (Hct), and red blood cell (RBC) rigidity (Tk and k indexes) were determined. RESULTS: In both groups, etab significantly increased in response to exercise but the SCT group had significantly higher etab at T3 and T2h. etab then returned to baseline value at T2h in the CONT group and at T24h in the SCT group. Tk and k were not changed by exercise but significantly increased above baseline value in both groups at T24h and T48h. The increase in Tk and k during late recovery was higher in the SCT group than in the CONT group, indicating that SCT carriers had significantly higher RBC rigidity than the CONT group at that time. CONCLUSIONS: The hemorheologic changes induced by exercise in the SCT carriers could trigger microcirculatory disorders during the recovery.
Assuntos
Eritrócitos/fisiologia , Exercício Físico/fisiologia , Esforço Físico/fisiologia , Reologia , Traço Falciforme/fisiopatologia , Adulto , Teste de Esforço , Guadalupe , Humanos , Monitorização Fisiológica/métodosRESUMO
BACKGROUND: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. RESULTS: The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. CONCLUSION: Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.