Gene expression profiling in blood from cerebral malaria patients and mild malaria patients living in Senegal

International audienceBACKGROUND:Plasmodium falciparum malaria remains a major health problem in Africa. The mechanisms of pathogenesis are not fully understood. Transcriptomic studies may provide new insights into molecular pathways involved in the severe form of the disease.METHODS:Blood transcriptional levels were assessed in patients with cerebral malaria, non-cerebral malaria, or mild malaria by using microarray technology to look for gene expression profiles associated with clinical status. Multi-way ANOVA was used to extract differentially expressed genes. Network and pathways analyses were used to detect enrichment for biological pathways.RESULTS:We identified a set of 443 genes that were differentially expressed in the three patient groups after applying a false discovery rate of 10%. Since the cerebral patients displayed a particular transcriptional pattern, we focused our analysis on the differences between cerebral malaria patients and mild malaria patients. We further found 842 differentially expressed genes after applying a false discovery rate of 10%. Unsupervised hierarchical clustering of cerebral malaria-informative genes led to clustering of the cerebral malaria patients. The support vector machine method allowed us to correctly classify five out of six cerebral malaria patients and six of six mild malaria patients. Furthermore, the products of the differentially expressed genes were mapped onto a human protein-protein network. This led to the identification of the proteins with the highest number of interactions, including GSK3B, RELA, and APP. The enrichment analysis of the gene functional annotation indicates that genes involved in immune signalling pathways play a role in the occurrence of cerebral malaria. These include BCR-, TCR-, TLR-, cytokine-, FcεRI-, and FCGR- signalling pathways and natural killer cell cytotoxicity pathways, which are involved in the activation of immune cells. In addition, our results revealed an enrichment of genes involved in Alzheimer's disease.CONCLUSIONS:In the present study, we examine a set of genes whose expression differed in cerebral malaria patients and mild malaria patients. Moreover, our results provide new insights into the potential effect of the dysregulation of gene expression in immune pathways. Host genetic variation may partly explain such alteration of gene expression. Further studies are required to investigate this in African populations

Evaluation de l’état hydrique chez les patients hémodialysés chroniques : une étude transversale monocentrique: Assessment of the hydration status in chronic hemodialysis patients: a single-center cross-sectional study

Context and objective. For many practitioners, blood pressure is the main indicator of the hydration status of the chronic hemodialysis patient. The objective of this study was to assess the extent to which bioimpedance analysis (BIA) can assist in determining acute changes in fluid volume during the hemodialysis session. Methods. This was a 9-week longitudinal study. The total body water (TBW) was measured with a BIA analyzer, before and after 6 successive sessions. The ΔWeight was compared to the ΔTBW by calculating the P/V ratio (ΔWeight/ΔTBW) with the assumption that the dry weight is reached when P/V = 1. Results. The measurements made in 22 patients (46.6 years, 54.5% men, 92.3 months on dialysis) were reproducible. There was no statistically significant difference between ΔTBW and ΔWeight. However, at the individual level, significant differences had been observed. Using hypertension as a marker for a state of hyperhydration, a 31.8% agreement was noted between the P/V ratio and hypertension. Conclusion. Although the loss of water predicted by the BIA did not always correspond to the weight loss, BIA is a technique that can be used to assess the variations in TBW during the hemodialysis session in patients. Contexte et objectif. La pression artérielle est pour de nombreux praticiens, l’indicateur principal du statut hydrique du patient hémodialysé chronique. L’objectif de la présente étude était d’évaluer dans quelle mesure l’analyse d’impédance bioélectrique (BIA) pourrait aider à la détermination des variations aigues du volume hydrique au cours de la séance d’hémodialyse. Méthodes. Il s’agissait d’une étude de suivi longitudinal sur 9 semaines. Le volume total d’eau (VTE) a été mesuré par BIA, avant et après 6 séances. Le ΔPoids a été comparé au ΔVTE par le calcul du ratio P/V (ΔPoids / ΔVTE) dans l’hypothèse que le poids sec est atteint lorsque P/V = 1. Résultats. Les mesures faites chez 22 patients (46,6 ans, 54,5% hommes, 92,3 mois en dialyse) étaient reproductibles. Il n’y avait pas de différence statistiquement significative entre le ΔVTE et le ΔPoids. Cependant à l’échelon individuel des différences importantes étaient observées. En utilisant l’hypertension artérielle (HTA) comme marqueur d’un état d’hyperhydratation, une concordance de 31,8% était notée entre le ratio P/V et l’HTA. Conclusion. Bien que la perte d’eau prédite par la BIA ne corresponde pas toujours à celle du poids, la BIA est une technique qui peut être utilisée pour évaluer les variations du VTE au cours de la séance d’hémodialys

NCR3 polymorphism, haematological parameters, and severe malaria in Senegalese patients

Background Host factors, including host genetic variation, have been shown to influence the outcome of Plasmodium falciparum infection. Genome-wide linkage studies have mapped mild malaria resistance genes on chromosome 6p21, whereas NCR3-412 polymorphism (rs2736191) lying within this region was found to be associated with mild malaria. Methods Blood samples were taken from 188 Plasmodium falciparum malaria patients (76 mild malaria patients, 85 cerebral malaria patients, and 27 severe non-cerebral malaria patients). NCR3-412 (rs2736191) was analysed by sequencing, and haematological parameters were measured. Finally, their association with clinical phenotypes was assessed. Results We evidenced an association of thrombocytopenia with both cerebral malaria and severe non-cerebral malaria, and of an association of high leukocyte count with cerebral malaria. Additionally, we found no association of NCR3-412 with either cerebral malaria, severe non-cerebral malaria, or severe malaria after grouping cerebral malaria and severe non-cerebral malaria patients. Conclusions Our results suggest that NCR3 genetic variation has no effect, or only a small effect on the occurrence of severe malaria, although it has been strongly associated with mild malaria. We discuss the biological meaning of these results. Besides, we confirmed the association of thrombocytopenia and high leukocyte count with severe malaria phenotypes

West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia.

In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites

EVALUATION COMPTABLE DU CAPITAL HUMAIN :UNE APPROCHE PAR LE TRYPTIQUE MASSE SALARIALE, CONNAISSANCES ET COMPETENCES

International audienceMany works of researchers are about human capital accounting. They especially studied its relevance in an accounting way. In accounting, it's indeed difficult to estimate the human capital. To mitigate these limits, we propose a model of accounting evaluation built on the triptych payroll, knowledge, and skills.La comptabilisation du capital humain a fait l'objet de nombreux travaux de chercheurs qui se sont interrogés sur sa pertinence dans une vision comptable stricto-sensu. En effet, la comptabilité dans une approche prudente compte tenu des difficultés d'évaluer le capital humain ne le prend en compte que de façon restrictive. Afin d'élargir cette vision, nous proposons un modèle d'évaluation comptable basé sur le triptyque masse salariale, indice de connaissances, indice de compétences

Risk factors for infection with equine influenza virus in donkeys (Equus asinus) in Senegal

In recent years, outbreaks of equine influenza are reported in several countries in the world particulary in Africa. This study is designed to assess the potential risk factors associated with equine influenza virus infection in donkeys in Senegal. The study consists in comparing, depending on the exposure to risk factors, a batch of donkeys infected with the equine influenza virus to another batch of donkeys not infected with the virus during the epizootic of March 2019 which affected the department of Foundiougne. The study reveals that the spread of the equine influenza virus in Foundiougne is associated with the lack of access to veterinary care and infected donkeys were exposed in a ratio of 2 times (95% CI: 1.38; 4.71) more than donkeys unharmed. The wandering of donkeys is also linked with the disease. The indicator reflecting the strength of the relationship, the Odds Ratio is 2.06 (95% CI: 1.10; 3.87). However, the results indicate that attendance at rural markets (Odds Ratio = 0.90; 95% CI: 0.44; 1.82), young age (Odds Ratio = 0.90; 95% CI: 0.52, 1.55) and female sex (Odds Ratio = 0.97; 95% CI: 0.57; 1, 66) do not appear to be related to the spread of the disease. At present, in Senegal, control focused on sensitizing and informing donkey owners on the sanitary management and rational use of donkeys is essential for their well-being

The use of crude Plasmodium falciparum antigens for comparison of antibody responses in patients with mild malaria vs. cerebral malaria.

analysis of Ab responses in cerebral malaria using basic tools as Ags. IgM Ab responses are of interest.International audienceBackground: Cerebral malaria (CM) is one of the major causes of death in African populations infected with Plasmodium falciparum. Only 1% of infected subjects develop CM. The reasons for these differences are not fully understood, but it is likely that the host humoral response against blood-stage antigens plays a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Objective: The purpose of this study was to distinguish between defined P. falciparum-specific Ab response patterns in patients presenting with mild malaria (MM) vs. CM. Methods: We used a panel of P. falciparum conserved antigens including crude blood-stage extracts schizont, merozoite and parasitised erythrocyte membranes and MSP-1p19, PfEB200, R23 and GST-5 recombinant antigens in a retrospective case-control study of symptomatic adults, one group presenting confirmed CM without fatal outcome and another group with MM. We further matched P. falciparum-specific Ab responses with those from individuals living in an endemic setting known to have protective immunity and considered them as "immune control" subjects (IC). Total IgG, IgM and IgG subclass Ab responses were determined using ELISA method. Results: Substantial Ab responses were found in symptomatic patients, significantly lower than the "immune control" subjects, and with a limited quantitative difference between MM versus CM. Interestingly, asynchronous IgM response was evidenced in CM contrary to MM. Conclusion: Our results suggest that the contribution of an efficient IgG response against parasite multiplication is of importance in the evolution towards CM manifestation without fatal outcome and deserves further analysis for vaccine candidates