Evolutionary profile of patients with hemoglobin SC disease regularly followed in Côte d'Ivoire

Background: West Africa is recognized as the elective focus of hemoglobin C. The S and C combination in the same patient gives a major sickle cell syndrome. In our country, very few series dealing with the evolutionary features of this SC form have been published contrary to the homozygous SS form. The aim of this study was to describe the evolutionary profile of double heterozygous SC sickle cell patients.Methods: This was a retrospective and prospective study with descriptive and analytical purpose of 174 SC sickle cell patients.Results: The median age was 26 years with extremes of 6 years and 57 years. 96% of patients had less than 4 vaso-occlusive seizures per year. The evolutionary complications were mainly ischemic (56.30%) and infectious (39.10%). Among ischemic complications, sickle cell retinopathies and aseptic osteonecrosis are the most common with 59.20% and 31.63% respectively. Infectious complications were dominated by ENT (36.76%) and osteoarticular (35.29%) infections. Only age had an influence on the occurrence of ischemic complications (p = 0.0001). The probability of survival at 5 years was 99.38% and that at 20 years was 91.57%. The overall survival was not influenced by evolutionary complications.Conclusions: Infectious and ischemic evolutionary complications show the importance of vaccination and an early screening program

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

High-depth African genomes inform human migration and health

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals—comprising 50 ethnolinguistic groups, including previously unsampled populations—to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon—but in other genes, variants denoted as ‘likely pathogenic’ in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health

Clinical Study Characteristics and Results of the Management of Diffuse Large B-Cell Lymphomas: The Experience of Côte d'Ivoire

Diffuse large B-cell lymphomas have been little studied in black Africans. The purpose of our study was to determine the characteristics and results of the management of these lymphomas. Patients and Methods. In a descriptive and analytic retrospective study we studied the medical records of 63 patients with diffuse large B-cell lymphoma hospitalized during the period from 1991 to 2007. The diagnosis was made after lymph node or organ biopsy. Response to treatment, OS, PFS, and toxicity were studied. The complete response has been analyzed univariate and multivariate analysis. Results. The median age was 42 years. The sex ratio was 2. The HIV serology was positive in 11 cases, and 8 patients had antiretroviral therapy. In 71% the lymphoma was at stages III and IV of Ann Arbor. IPI was ≥3 in 65%. Complete remission was achieved in 43%. Only 43% of patients had had a good compliance. Progression-free survival at 3 years was 32%, and overall survival at 3 years was 50%. 13% of patients were lost to follow up, and 51% of them died. In terms of analysis the complete remission rate was influenced by the stage of Ann Arbor (P < 0.0001), biological b symptoms (P < 0.01), the IPI (P < 0.0001), and the socioeconomic standing (P = 0.001). In multivariate analysis, only IPI and stage of Ann Arbor influence the complete remission

Author Correction: High-depth African genomes inform human migration and health

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03286-9

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial

Background: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. Methods: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. Findings: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3–5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9–5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1–9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39–0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. Interpretation: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. Funding: National Research Agency on AIDS and Viral Hepatitis (ANRS)

Research capacity. Enabling the genomic revolution in Africa.

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