RESUMEN
The host mechanisms responsible for protection against malaria remain poorly understood, with only a few protective genetic effects mapped in humans. Here, we characterize a host-specific genome-wide signature in whole-blood transcriptomes of Plasmodium falciparum-infected West African children and report a demonstration of genotype-by-infection interactions in vivo. Several associations involve transcripts sensitive to infection and implicate complement system, antigen processing and presentation, and T-cell activation (i.e., SLC39A8, C3AR1, FCGR3B, RAD21, RETN, LRRC25, SLC3A2, and TAPBP), including one association that validated a genome-wide association candidate gene (SCO1), implicating binding variation within a noncoding regulatory element. Gene expression profiles in mice infected with Plasmodium chabaudi revealed and validated similar responses and highlighted specific pathways and genes that are likely important responders in both hosts. These results suggest that host variation and its interplay with infection affect children's ability to cope with infection and suggest a polygenic model mounted at the transcriptional level for susceptibility.
Asunto(s)
Regulación de la Expresión Génica/inmunología , Malaria Falciparum/inmunología , Plasmodium chabaudi/inmunología , Plasmodium falciparum/inmunología , Transcriptoma/genética , África Occidental , Análisis de Varianza , Animales , Niño , Perfilación de la Expresión Génica , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Modelos Lineales , Malaria Falciparum/genética , Malaria Falciparum/parasitología , Ratones , Ratones Endogámicos C57BL , Plasmodium falciparum/genéticaRESUMEN
In an effort to explore new knowledge and to develop meaningful collaborations for improving child health, the First Pan African Workshop on Newborn Screening was convened in June 2019 in Rabat, Morocco. Participants included an informal network of newborn screening stakeholders from across Africa and global experts in newborn screening and sickle cell disease. Over 150 attendees, representing 20 countries, were present including 11 African countries. The agenda focused on newborn screening rationale, techniques, system development, implementation barriers, ongoing research, and collaborations both globally and across Africa. We provide an overview of the workshop and a description of the newborn screening activities in the 11 African countries represented at the workshop, with a focus on sickle cell disease.
RESUMEN
Human mannose- binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred forty-two healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p=0.002). This enrichment was exclusively due to an elevated proportion of heterozygotes for the p.G57E allele (47.0% vs. 35.3%,respectively; p=0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV- positive patients.
Asunto(s)
Anemia de Células Falciformes/genética , Variación Genética , Infecciones por VIH/genética , Heterocigoto , Lectina de Unión a Manosa/genética , Adolescente , Adulto , África/epidemiología , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/historia , Niño , Preescolar , Femenino , Genética de Población , Infecciones por VIH/epidemiología , Infecciones por VIH/historia , Historia del Siglo XXI , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Mutación , Prevalencia , Factores de Riesgo , Adulto JovenAsunto(s)
Anemia de Células Falciformes/genética , Bacteriemia/genética , Quimiocina CCL5/genética , Lectina de Unión a Manosa/genética , Anemia de Células Falciformes/microbiología , Bacteriemia/complicaciones , Preescolar , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Polimorfismo Genético , PronósticoRESUMEN
BACKGROUND: To study the efficacy of oral ferrous fumarate, an inexpensive, readily available preparation on iron deficiency in infants in Africa. PROCEDURE: Four months old (group 1, n = 252) and 6-18 months old (group 2, n = 360) healthy infants attending four primary health care centers (PHC) for vaccination/well-child visits in Benin were studied. Ninety-six pregnant women (PW) over 36 weeks gestational age attending the same PHC during the study period were also studied. Infants were offered 2 months supplementation with oral powdered generic ferrous fumarate (GFF), that is, 5 mg/kg/day of elemental iron, given twice and were reevaluated 2 months later for hematological indices. The prevalence of anemia and iron deficiency among pregnant women was assessed using hematological indices and transferrin saturation. RESULTS: The prevalence of anemia was 42.0%, 61.9%, and 37.5% in groups 1, 2, and PW, respectively. All anemic PW were iron deficient. Hemoglobin level shifted towards high values after supplementation. In addition, 24 infants from group 1 whose mothers interrupted the treatment, showed a significant decrease in hemoglobin level values, and similar improvement after two additional months of supplementation. CONCLUSION: Programs to prevent iron deficiency in Africa should utilize inexpensive preparations, start during pregnancy, continue in infants at 3 months of age and address problems of noncompliance.
Asunto(s)
Anemia Ferropénica/prevención & control , Suplementos Dietéticos , Compuestos Ferrosos/administración & dosificación , Administración Oral , África del Sur del Sahara , Factores de Edad , Femenino , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Embarazo , Resultado del TratamientoRESUMEN
Human mannose-binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred forty-two healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p = 0.002). This enrichment was exclusively due to an elevated proportion of heterozygotes for the p.G57E allele (47.0% vs. 35.3%, respectively; p = 0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV-positive patients.
Asunto(s)
Anemia de Células Falciformes/genética , Genética de Población/métodos , Heterocigoto , Lectina de Unión a Manosa/genética , Adolescente , Adulto , Alelos , Anemia de Células Falciformes/epidemiología , Benin/epidemiología , Humanos , Recién Nacido , Lectina de Unión a Manosa/deficiencia , Lectina de Unión a Manosa/inmunología , Persona de Mediana EdadRESUMEN
Correlations between FimH mutations and virulence were established by studying a collection of human commensal and extraintestinal pathogenic Escherichia coli natural isolates. Pathoadaptive (A27V and, to a lesser extent, A119V) and "commensal-adaptive" (A202V) mutations were evidenced in B2 phylogenetic group strains. fimH phylogenetic analysis indicates that these pathoadaptive mutations occurred several times.
Asunto(s)
Adhesinas de Escherichia coli/genética , Escherichia coli/patogenicidad , Proteínas Fimbrias/genética , Mutación , Infecciones Urinarias/microbiología , Adhesinas de Escherichia coli/fisiología , Escherichia coli/clasificación , Proteínas Fimbrias/fisiología , Humanos , Filogenia , VirulenciaRESUMEN
Clinical severity of sickle cell anemia (SS) in Africa may not be solely determined by genetic factors. This study evaluated the effects of intensive parental education and adequate clinical care on the course of SS in children in Benin. SS children referred to the National Teaching Hospital in Cotonou were included in the study. Teaching about SS was repeated frequently, emphasizing the importance of keeping clinic appointments, improving the nutrition of the affected children, and instituting antipneumococcal and antimalarial prophylaxis. Frequency and severity of SS-related events, changes in physical growth, frequency of malarial attacks, causes of transfusion, and causes of death were the principal variables assessed. 236 young children with repeated SS-related acute complications were studied from July 1, 1993, to December 31, 1999 (983 patient-years). A marked reduction in the frequency and severity of SS-related acute events was observed. Improvement in general status and physical growth was noted in 184 patients (78%); in addition, 22 of the remaining 52 patients showed similar improvement after remotivating the parents for compliance. There were 10 deaths, primarily in this cohort of 52 patients. Intensive sociomedical intervention can produce sustained clinical improvement in many severely ill SS children in sub-Saharan Africa.
Asunto(s)
Anemia de Células Falciformes/terapia , África del Sur del Sahara , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/mortalidad , Anemia de Células Falciformes/patología , Niño , Preescolar , Manejo de la Enfermedad , Progresión de la Enfermedad , Femenino , Crecimiento , Humanos , Lactante , Masculino , Padres/educación , Educación del Paciente como Asunto , Evaluación de Programas y Proyectos de Salud , Estudios ProspectivosRESUMEN
The study of several Escherichia coli intestinal commensal isolates per individual in 265 healthy human subjects belonging to seven populations distributed worldwide showed that the E. coli population is highly structured, with major differences between the tropical and temperate populations.