Genome-wide association study of leprosy in Malawi and Mali

Leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for leprosy. There is a significant burden of leprosy in Africa, however it is uncertain whether the findings of published genetic association studies are generalizable to African populations. To address this, we conducted a genome-wide association study (GWAS) of leprosy in Malawian (327 cases, 436 controls) and Malian (247 cases, 368 controls) individuals. In that analysis, we replicated four risk loci previously reported in China, Vietnam and India; MHC Class I and II, LACC1 and SLC29A3. We further identified a novel leprosy susceptibility locus at 10q24 (rs2015583; combined p = 8.81 × 10-9; OR = 0.51 [95% CI 0.40 - 0.64]). Using publicly-available data we characterise regulatory activity at this locus, identifying ACTR1A as a candidate mediator of leprosy risk. This locus shows evidence of recent positive selection and demonstrates pleiotropy with established risk loci for inflammatory bowel disease and childhood-onset asthma. A shared genetic architecture for leprosy and inflammatory bowel disease has been previously described. We expand on this, strengthening the hypothesis that selection pressure driven by leprosy has shaped the evolution of autoimmune and atopic disease in modern populations. More broadly, our data highlights the importance of defining the genetic architecture of disease across genetically diverse populations, and that disease insights derived from GWAS in one population may not translate to all affected populations

Contribution of microbial culturomics in the study of determinants of dysbiosis in severe acute malnutrition in Mali

La malnutrition aiguë sévère demeure un problème de santé publique dans les pays en voie de développement comme le Mali. Les rechutes et le caractère réfractaire témoignent des zones d’ombre dans l’étiologie de cette maladie. Cependant, le rôle de l’altération du microbiote intestinal (dysbiose) dans la survenue de la malnutrition aiguë sévère chez les enfants a été rapporté, mais les déterminants et l’origine de cette dysbiose demeurent sous investigués. En appliquant la culturomique microbienne et de la métagénomique sur 21 échantillons de selles prélevées chez des enfants maliens repartis en 3 groupes de 7 (sains, marasme, kwashiorkor) appariés selon l’âge et le sexe, nous avons détecté une perte des bactéries commensales chez les enfants sévèrement malnutris en métagénomique et en culturomique. Par ailleurs, l’approche de culturomique nous a permis de découvrir une perte remarquable des bactéries halophiles commensales et d’origine alimentaire chez les enfants souffrant de malnutrition aiguë sévère. Parmi les 19 nouvelles espèces isolées dont 17 halophiles, une halophile pigmentée, Halobacillus ihumii était présente chez 85,7% des enfants sains et absente chez tous les enfants malnutris. La perte des bactéries halophiles commensales observée chez les enfants sévèrement malnutris pourrait traduire un retard d’acquisition du microbiote intestinal, un stress oxydatif ou une condition écologique défavorable à la survie et à la croissance de ces bactéries exigeantes dont les fonctions restent insaisissables. Une exploration plus approfondie permettrait de définir une signature du microbiote halophile africain et son implication dans la malnutrition aiguë sévère.Severe acute malnutrition (SAM) which refers mainly to marasmus or kwashiorkor remains a public health problem in low-income countries such as Mali. The high relapse rate as well the refractory cases observed despite early and adequate treatment suggest an unresolved etiology of this disease. Interestingly, the instrumental role of dysbiosis has been widely reported However, the determinants as well as the origin of the gut dysbiosis remain under- investigated whereas the health infant gut colonization way is well documented. Applying the culturomics approach as well as 16S amplicon sequencing to stool samples collected from 21 children under five years of divided into 3 groups (7 healthy children, 7 marasmus cases and 7 kwashiorkor cases) matched for age and sex, we highlighted using microbial culturomics and metagenomics a marked loss of commensal bacteria in children suffering from severe acute malnutrition. Applying the microbial culturomics approach, we discover a non-negligible loss of commensal and foodborne halophilic species in SAM children. 19 news species were isolated of which 17 halophilic species including a pigmented halophilic species, Halobacillus ihumii which is detected in 85.7% of healthy children and absent in all SAM children. Loss of commensal halophilic species in severe acute malnourished children might be due to the delay of gut microbiota establishing, the oxidative stress as well as the unfavorable conditions for halophiles growth which functions remain elusive. Deep understanding could lead to define an African halophilic microbiota signature and it involvement in severe acute malnutrition

Electronic excited states of planar vs bowl-shaped polycyclic aromatic hydrocarbons in interaction with water clusters: a TD-DFT study

In an astrochemical and environmental context, this work constitutes a step forward in understanding the photo-reactivity of polycyclic aromatic hydrocarbons (PAHs) with water molecules and in water ice under irradiation with low energy photons. The role of charge transfer states PAH +-H 2 O − has been proposed, motivating the study of the electronic excited states up to about 6 eV of planar and bowl-shaped PAHs, namely pyrene C 16 H 10 and corannulene C 20 H 10 , interacting with water clusters of different sizes and orientations, using a time-dependent density functional theory approach. In the case of pyrene, the systematic occurrence of low energy excitations from π orbitals to diffuse orbitals located on some water molecules, mixed with the Rydberg orbitals (R/wat), was found. Such excitations are more numerous and possess larger oscillator strengths when (i) the number of water molecules increases up to representing a first layer of hexagonal water ice and (ii) for the arrangements leading to the lower vertical ionisation potential values. In this case, the /wat orbitals are located on the most external H atoms and they ma

Candidate polymorphisms and severe malaria in a Malian population.

Malaria is a major health burden in sub-Saharan African countries, including Mali. The disease is complex, with multiple genetic determinants influencing the observed variation in response to infection, progression, and severity. We assess the influence of sixty-four candidate loci, including the sickle cell polymorphism (HbS), on severe malaria in a case-control study consisting of over 900 individuals from Bamako, Mali. We confirm the known protective effects of the blood group O and the HbS AS genotype on life-threatening malaria. In addition, our analysis revealed a marginal susceptibility effect for the CD40 ligand (CD40L)+220C allele. The lack of statistical evidence for other candidates may demonstrate the need for large-scale genome-wide association studies in malaria to discover new polymorphisms. It also demonstrates the need for establishing the region-specific repertoire of functional variation in important genes, including the glucose-6-phosphatase deficiency gene, before embarking on focused genotyping

Listeria monocytogenes in human milk in Mali: A potential health emergency

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Safety of epoietin beta-quinine drug combination in children with cerebral malaria in Mali

cerebral malaria in Mal

Clinical evidence of the role of Methanobrevibacter smithii in severe acute malnutrition

International audienceAbstract Gut microbial dysbiosis has been shown to be an instrumental factor in severe acute malnutrition (SAM) and particularly, the absence of Methanobrevibacter smithii, a key player in energy harvest. Nevertheless, it remains unknown whether this absence reflects an immaturity or a loss of the microbiota. In order to assess that, we performed a case–control study in Mali using a propensity score weighting approach. The presence of M. smithii was tested using quantitative PCR on faeces collected from SAM children at inclusion and at discharge when possible or at day 15 for controls. M. smithii was highly significantly associated with the absence of SAM, detected in 40.9% controls but only in 4.2% cases (p < 0.0001). The predictive positive value for detection of M. smithii gradually increased with age in controls while decreasing in cases. Among children providing two samples with a negative first sample, no SAM children became positive, while this proportion was 2/4 in controls (p = 0.0015). This data suggests that gut dysbiosis in SAM is not an immaturity but rather features a loss of M. smithii . The addition of M. smithii as a probiotic may thus represent an important addition to therapeutic approaches to restore gut symbiosis

Blastocystis Colonization Is Associated with Increased Diversity and Altered Gut Bacterial Communities in Healthy Malian Children

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