Clinical outcome and incidence of inhibitor development in severe hemophilia patients receiving low-dose prophylaxis: a 3-year follow-up study in Senegal, West Africa

ABSTRACT Introduction: In Africa, where access to diagnosis and treatment of hemophilia is the lowest in the world, prophylaxis is rarely used in preference to on-demand treatment. There are limited data of prophylaxis treatment from sub-Saharan Africa. The aim of this study was to evaluate clinical outcomes and inhibitor development in people with hemophilia receiving low-dose prophylaxis (LDP) in a sub-Saharan African setting. Methods: We conducted a three-year prospective study. A once or twice weekly prophylaxis regimen of 25 IU/kg of rFVIIIFc or 30 IU/kg of rFIXFc was given to Hemophilia A and B, respectively. We evaluated clinical outcomes and inhibitors occurrence, determined by screening and titration using the Nijmegen technique. Results: A total of 15 patients were included in the LDP regimen. The mean age was 6.3 years (1.5 - 10). A significant reduction was noted in the annualized bleeding rate, from 7.53 to 1.33 (p = 0.0001); the annualized joint bleeding rate passed from 3.6 to 1.4 (p = 0.001) and the proportion of severe bleeding, from 86.1% to 16.7% (p = 0.0001). The Hemophilia Joint Health Score (HJHS) moved from 9.6 to 3.4 (p = 0.0001) and the Functional Independence Score in Hemophilia (FISH) improved from 25.8 to 30.9 (p = 0.0001). School absenteeism decreased from 7.33% to 2.59%. Adherence to prophylaxis was 89.5% versus 60%. Consumption was 580 IU/kg/year versus 1254.6 IU/kg/year before and after prophylaxis, respectively. Incidence of inhibitors was 23% (3 /13 HA). Conclusion: The LDP in Hemophilia improves the clinical outcome without a surplus risk of inhibitor development. Using extended half-life clotting factor concentrates (CFCs) is better for prophylaxis in resource-limited countries, as they allow better compliance in treatment.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia

Abstract Objective We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. Methods In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. Results The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p= 0.0009), CD38 expression (p= 0.039), unmutated IGVH status (p= 0.0009) and presence of cytogenetic abnormalities (for del 13q, p= 0.0012, while for other cytogenetic aberrations, p= 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r= -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p= 0.41) or gender (median, 19% for males vs. 20% for females; p= 0.76). Conclusion When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Passagens adolescentes em afrodiáspora: do estado-coisa ao estado de sujeito / Pasajes adolescentes en aphrodiaspora: del estado-cosa al estado de sujeto / Adolescent passages in aphrodiaspora: from the state-thing to the state-subject / Passages adolescents en l'aphrodiaspora: de l'état-chose à l'état-sujet

Propomos uma reflexão sobre o acolhimento da urgência subjetiva e a orientação de jovens originários da África subsaariana nos serviços da rede de proteção da infância francesa. A partir do acompanhamento clínico de uma adolescente de origem senegalesa, realizado durante um ano em um centro de acolhimento de jovens menores não acompanhados da família e em situação de migração, apresentaremos os pilares de uma práxis psicanalítica realizada nestas condições. Em um segundo momento, abordaremos um caso clínico no qual a urgência subjetiva se apresenta pelo viés da perplexidade como resposta a violações sexuais, errância e exílio vividos em um percurso migratório. Finalmente, refletiremos sobre a apropriação do estrangeiro-íntimo como potencialidade de reedição narrativa e produção de ancoragens diante do trauma

Proponemos una reflexión sobre la acogida de la urgencia subjetiva y la orientación de los jóvenes del África subsahariana en los servicios de la red francesa de protección a la infancia. A partir del seguimiento clínico de una adolescente de origen senegalés, realizado durante unaño en un centro de acogida de menores no acompañados en situación migratoria, presentaremos los pilares de una práctica psicoanalítica realizada en estas condiciones. En un segundo momento, abordaremos un caso clínico en el que la urgencia subjetiva se presenta a través del sesgo de la perplejidad como respuesta a las violaciones sexuales, vagabundeos y exilios vividos en un trayecto migratorio. Finalmente, reflexionaremos sobre la apropiación del íntimo-extraño como potencial de reedición narrativa y producción de anclas ante el trauma

We propose a reflection on the reception of subjective urgency and the orientation of young people from sub-Saharan Africa in the services of the French child protection network. Based on the clinical follow-up of an adolescent of Senegalese origin, carried out for one year in a reception center for young minors unaccompanied by their family and in a migration situation, we will present the pillars of a psychoanalytic practice carried out in these conditions. In a second moment, we will approach a clinical case in which the subjective urgency presents itself through the bias of perplexity as a response to sexual violations, wandering and exile experienced in a migratory path. Finally, we will reflect on the appropriation of the foreign-intimate as a potential for narrative re-editing and production of anchors in the face of trauma

Nous proposons une réflexion sur l'accueil de l'urgence subjective et l'orientation des jeunes d'Afrique subsaharienne dans les services du réseau français de protection de l'enfance. A partir du suivi clinique d'une adolescente d'origine sénégalaise, réalisé pendant un an dans un centre d'accueil pour mineurs non accompagnés en situation migratoire, nous présenterons les piliers d'une pratique psychanalytique menée dans ces conditions. Dans un second temps, nous aborderons un cas clinique dans lequel l'urgence subjective se présente à travers le biais de la perplexité comme réponse aux violations sexuelles, errances et exils vécus dans une trajectoire migratoire. Enfin, nous réfléchirons à l'appropriation de l'intime-inconnu comme potentiel de réédition narrative et de production d'ancres face au trauma

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia / Las variantes genéticas asociadas con niveles de hemoglobina fetal señalan diversos orígenes étnicos en pacientes colombianos con anemia falciforme.

Introduction: Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. Objective: We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Materials and methods: Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. Results: We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. Conclusion: These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

Introducción. La hemoglobina fetal es un importante factor modulador de la gravedad de la anemia falciforme, cuya expresión está muy condicionada por el factor genético. Los loci asociados con el incremento de la hemoglobina fetal pueden presentar frecuencias alélicas específicas para cada población. Objetivo. Investigar la presencia y el efecto de las variantes genéticas rs11886868, rs9399137, rs4895441 y rs7482144 asociadas con la persistencia de hemoglobina fetal, en 60 pacientes colombianos con anemia falciforme. Materiales y métodos. Se hizo la genotipificación de los polimorfismos de nucleótido simple ( Single Nucleotide Polymorphisms, SNP) mediante la técnica de polimorfismos de longitud de fragmentos de restricción ( Restriction Fragment Length Polymorphisms, RFLP) y el procedimiento TaqMan. La hemoglobina fetal (HbF) se cuantificó utilizando la técnica de desnaturalización alcalina de la oxihemoglobina. Las frecuencias genotípicas se compararon con las reportadas en poblaciones de referencia global. Resultados. Se observaron variantes genéticas ya reportadas para aumento de HbF en los cuatro SNP. La asociación genética entre los SNP y el incremento de la HbF no alcanzó significancia estadística. La frecuencia de estos alelos reflejó la siguiente composición específica en esta muestra de pacientes colombianos: una gran prevalencia de rs7482144-'A', lo que indica que el origen de la mutación para la anemia falciforme es África occidental, y una gran frecuencia de rs4895441-'G' y rs11886868-'C', lo que denota la influencia significativa del origen genético amerindio. Conclusión. Los resultados evidenciaron que la población con anemia falciforme de Colombia no tiene un único origen genético, sino que existen dos (africano y amerindio). Esta situación genética única ofrece la oportunidad de llevar a cabo un estudio más amplio de estos loci a nivel molecular. Se espera que el estudio de pacientes colombianos permita una visión diferente del efecto de los loci modificadores en esta enfermedad.

Taurodoncia múltiple: presentación de un caso / Multiple taurodontism: report of a case

La taurodoncia es una alteración morfológica de la anatomía dental que trae como consecuencia un cambio en la forma de la pieza dentaria, usualmente en las piezas multirradiculares. Consiste en un alargamiento de la cámara pulpar a expensas de los conductos radiculares, desplazando el piso pulpar hacia apical. El diagnóstico temprano y el seguimiento radiográfico son importantes. La mayoraía de las veces es un hallazgo radiográfico, dado que a la inspección clínica las piezas dentarias suelen verse normales. Puede presentarse aislado o asociado a otras anomalías dentarias. El propósito de este artículo es presentar un caso de taurodoncia múltiple que fue también un hallazgo radiográfico en un paciente de raza negra oriundo de Senegal y comunicar la alta incidencia de esta patología en dicho país.

ßS-Haplotypes in sickle cell anemia patients from Salvador, Bahia, Northeastern Brazil

ßS-Globin haplotypes were studied in 80 (160 ßS chromosomes) sickle cell disease patients from Salvador, Brazil, a city with a large population of African origin resulting from the slave trade from Western Africa, mainly from the Bay of Benin. Hematological and hemoglobin analyses were carried out by standard methods. The ßS-haplotypes were determined by PCR and dot-blot techniques. A total of 77 (48.1 percent) chromosomes were characterized as Central African Republic (CAR) haplotype, 73 (45.6 percent) as Benin (BEN), 1 (0.63 percent) as Senegal (SEN), and 9 (5.63 percent) as atypical (Atp). Genotype was CAR/CAR in 17 (21.3 percent) patients, BEN/BEN in 17 (21.3 percent), CAR/BEN in 37 (46.3 percent), BEN/SEN in 1 (1.25 percent), BEN/Atp in 1 (1.25 percent), CAR/Atp in 6 (7.5 percent), and Atp/Atp in 1 (1.25 percent). Hemoglobin concentrations and hematocrit values did not differ among genotype groups but were significantly higher in 25 patients presenting percent fetal hemoglobin ( percentHbF) > or = 10 percent (P = 0.002 and 0.003, respectively). The median HbF concentration was 7.54 ± 4.342 percent for the CAR/CAR genotype, 9.88 ± 3.558 percent for the BEN/BEN genotype, 8.146 ± 4.631 percent for the CAR/BEN genotype, and 4.180 ± 2.250 percent for the CAR/Atp genotype (P = 0.02), although 1 CAR/CAR individual presented an HbF concentration as high as 15 percent. In view of the ethnic and geographical origin of this population, we did not expect a Hardy-Weinberg equilibrium for CAR/CAR and BEN/BEN homozygous haplotypes and a high proportion of heterozygous CAR/BEN haplotypes since the State of Bahia historically received more slaves from Western Africa than from Central Africa

Studies on the biology of schistosomiasis with emphasis on the Senegal river basin

The construction of the Diama dam on the Senegal river, the Manantali dam on the Bafing river, Mali and the ensuing ecological changes have led to a massive outbreak of Schistosoma mansoni in Northern Senegal, associated with high intensity of infections, due to intense transmission, and the creation of new foci of S. haematobium. Data on the vectorial capacity of Biomphalaria pfeifferi from Ndombo, near Richard Toll, Senegal are presented with sympatric and allopatric (Cameroon) S. mansoni. Comparisons are made on infectivity, cercarial production, chronobiology of cercarial emergence and longevity of infected snails. Recent data on the intermediate host specificity of different isolates of S. haematobium from the Lower and Middle Valley of the Senegal river basin (SRB) demonstrate the existence of at least two strains of S. haematobium. The role of Bulinus truncatus in the transmission of S. haematobium in the Lower and Middle Valleys of the SRB is reviewed. Both S. haematobium and S. mansoni are transmitted in the same foci in some areas of the SRB

Age-related worm load and worm fecundity patterns in human populations, as indicated by schistosome circulating antigens

Recently, our group determined the relationship between serum CAA levels and fecal egg counts in two foci very intense Schistosoma mansoni transmission: Maniema (Zaire), an area endemic for S. mansoni since several decades, and Ndombo (Senegal), where transmission has only been established since a few years. The objetive was to study and compare age-related worm load and worm fecundity patterns in these two different endemic settings. Here, we will summarize the most important findings and conclusions of this study.

Immuno-epidemiology of Schistosoma mansoni infections in a recently exposed community in Senegal

Schistosoma mansoni was introduced in the Senegal basin around 1988, due to man-made ecological changes. Since 1991, we investigate a recent but very intense focus, Ndombo, a village near the city of Richard Toll where the outbreak was first described. Four cohorts, each a random sample (+/- 400 subjects each) from this community, were examined and followed up after treatment, starting at 8 month intervals over a 2-year period. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; followed up 6-10 weeks, one and two years after treatment; and monitored for water contact patterns and local snail densities. In the first cohort, the prevalence was 91, with a mean egg count of 663 epg. Prevalences are near 100 in all age groups, but egg counts decline strongly in adults. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens, not e.g. of worm fecundity. This is surprising, as in this focus acquired immunity in adults should not have yet developed according to current hypothesis. The antigen detection assays (CAA/CCA) showed high sensitivity and quantitative power, and promising perspectives as a research tool and possibly as a method for non-invasive diagnosis and screening in urine. Epidemiological in subsequent cohorts were highly similar, although seasonal variations were observed possibly due to transmission fluctuations. Anti-AWA and anti-SEA IgE levels increased with age, while IgG4 peaked in the age-group 10 years and correlated well with egg counts.(ABSTRACT TRUNCATED AT 250 WORDS)