A comprehensive analysis of drug resistance molecular markers and Plasmodium falciparum genetic diversity in two malaria endemic sites in Mali.

BACKGROUND: Drug resistance is one of the greatest challenges of malaria control programme in Mali. Recent advances in next-generation sequencing (NGS) technologies provide new and effective ways of tracking drug-resistant malaria parasites in Africa. The diversity and the prevalence of Plasmodium falciparum drug-resistance molecular markers were assessed in Dangassa and Nioro-du-Sahel in Mali, two sites with distinct malaria transmission patterns. Dangassa has an intense seasonal malaria transmission, whereas Nioro-du-Sahel has an unstable and short seasonal malaria transmission. METHODS: Up to 270 dried blood spot samples (214 in Dangassa and 56 in Nioro-du-Sahel) were collected from P. falciparum positive patients in 2016. Samples were analysed on the Agena MassARRAY® iPLEX platform. Specific codons were targeted in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, Pfarps10, Pfferredoxin, Pfexonuclease and Pfmdr2 genes. The Sanger's 101-SNPs-barcode method was used to assess the genetic diversity of P. falciparum and to determine the parasite species. RESULTS: The Pfcrt_76T chloroquine-resistance genotype was found at a rate of 64.4% in Dangassa and 45.2% in Nioro-du-Sahel (p = 0.025). The Pfdhfr_51I-59R-108N pyrimethamine-resistance genotype was 14.1% and 19.6%, respectively in Dangassa and Nioro-du-Sahel. Mutations in the Pfdhps_S436-A437-K540-A581-613A sulfadoxine-resistance gene was significantly more prevalent in Dangassa as compared to Nioro-du-Sahel (p = 0.035). Up to 17.8% of the isolates from Dangassa vs 7% from Nioro-du-Sahel harboured at least two codon substitutions in this haplotype. The amodiaquine-resistance Pfmdr1_N86Y mutation was identified in only three samples (two in Dangassa and one in Nioro-du-Sahel). The lumefantrine-reduced susceptibility Pfmdr1_Y184F mutation was found in 39.9% and 48.2% of samples in Dangassa and Nioro-du-Sahel, respectively. One piperaquine-resistance Exo_E415G mutation was found in Dangassa, while no artemisinin resistance genetic-background were identified. A high P. falciparum diversity was observed, but no clear genetic aggregation was found at either study sites. Higher multiplicity of infection was observed in Dangassa with both COIL (p = 0.04) and Real McCOIL (p = 0.02) methods relative to Nioro-du-Sahel. CONCLUSIONS: This study reveals high prevalence of chloroquine and pyrimethamine-resistance markers as well as high codon substitution rate in the sulfadoxine-resistance gene. High genetic diversity of P. falciparum was observed. These observations suggest that the use of artemisinins is relevant in both Dangassa and Nioro-du-Sahel

La migration féminine au Mali

Euro-Mediterranean Consortium for Applied Research on International Migration (CARIM)Les données et les recherches au sujet de la migration féminine au Mali sont rares. Cet article, qui privilégie une approche qualitative, suggère d’approfondir la question de la relation entre migration féminine et promotion de la femme, autrement dit la connaissance des conséquences de la migration féminine aux plans individuel, social, économique et culturel. Cette question renvoie, plus largement, à la question de la promotion de la femme et à la relation entre genre et développement (GeD). À travers différents exemples, cet article suggère des pistes de réflexion, afin de soutenir et de renforcer le rôle des femmes migrantes dans le développement. / Little data and research are available on gender migration in Mali. This paper, which adopts a qualitative approach, proposes, therefore, to deepen the understanding of the relationship between gender migration and the empowerment of women: in other words, the consequences of gender migration on the individual, social, economic and cultural levels. This question is related to the broader issues of women’s advancement and the relationship between gender and development (GeD). Different examples are presented in order to stimulate reflection, with the aim of supporting and strengthening women migrant’s contributions to development

La migration de haut niveau au Mali

Euro-Mediterranean Consortium for Applied Research on International Migration (CARIM)Après s’être penchée sur quelques repères historiques de migrations de haut niveau vers et à partir du Mali, l’étude met en exergue les nombreux facteurs structurels influant sur la dynamique actuelle de la migration des cadres de haut niveau dont les principaux sont : l’amélioration de l’offre d’enseignement supérieur, l’inadéquation formation – emplois, la paupérisation croissante… En outre, l’étude se penche sur les principaux acteurs–organismes étatiques et organisations de la société civile - intervenant dans la gestion des cadres supérieurs maliens de l’étranger et aboutit à la conclusion que la migration des hauts cadres va s’accentuer dans les prochaines années compte tenu de quelques facteurs dont la réalisation de l’enseignement primaire universel en 2012, l’amélioration de l’accès des femmes à l’éducation supérieure, et l’insuffisance des réformes économiques structurelles… Pour finir, quelques recommandations et bonnes pratiques susceptibles de diminuer les flux d’expatriation des hauts cadres sont formulées. After tackling some important historical junctures pertaining to highly skilled migration to and from Mali, the present study detects various structural factors impacting the migration of highly skilled nationals such as the increase in higher education opportunities, the mismatch between education and employment, and rising poverty... Furthermore, the study examines the role of various governmental and non governmental actors who play a role in managing highly skilled personnel abroad. It argues that highly skilled migration in Mali will be on the rise in years to come. This finding is corroborated by some factors such as the universal primary education plan (2012), increased female access to higher education, and insufficient structural economic reform. Finally, the study formulates some recommendations and best practices aimed at circumscribing highly skilled emigration flows from Mali

La migration irrégulière au Mali

Euro-Mediterranean Consortium for Applied Research on International Migration (CARIM)Le présent article aborde la problématique de la migration irrégulière au Mali en la plaçant dans son contexte historique, sous-régional et national. Il montre comment le concept de migration irrégulière, informelle, illégale ou clandestine est récemment apparu du fait des modifications apportées aux cadres législatifs nationaux à partir des années 1970 et 1980 afin de restreindre la mobilité internationale des personnes. Les causes qui poussent à la migration irrégulière sont esquissées et les principaux acteurs responsables de sa gestion sont passés en revue ainsi que leurs stratégies d’intervention. L’article se termine par des recommandations pertinentes pouvant contribuer à maîtriser durablement les flux migratoires provenant du Mali et de la sous-région ouest-africaine en général. Abstract This paper deals with the issue of irregular migration in Mali with an historical perspective and in the regional and national context. It shows how the concepts of irregular, informal, illegal or clandestine migration appeared because of the modification of the legal frameworks ruling migration in the 1970s and 1980s, with the aim of limiting the mobility of the persons at an international level. The push factors of irregular migration are briefly presented, as well as the main actors responsible for the management of migration and their strategies. This paper concludes with policy recommendations contributing to a sustain management of migration flows from Mali and the West African sub region

La migration circulaire au Mali : diagnostic et perspectives

Euro-Mediterranean Consortium for Applied Research on International Migration (CARIM)L’article montre que dans le domaine de la migration internationale la migration circulaire ne renvoie pas à une réalité nouvelle ni particulière. Elle représente plutôt une piste de solution pour la régulation des flux migratoires irréguliers. Si le concept en soi n’est pas nouveau, il demeure relativement flou. L’article se penche de manière critique sur sa conception et sa mise en œuvre étatique récemment introduite au Mali et qui présente des avantages, mais aussi de nombreuses faiblesses du point de vue de l’Etat de droit. Il donne une vue d’ensemble des expériences étatiques en cours et se termine avec quelques recommandations susceptibles de contribuer à une maîtrise durable des flux migratoires. Abstract The analytical note shows that in international migration, circular migration is neither a new nor characteristic phenomenon. It rather represents a potential solution for governing irregular migration flows. Then even if the concept is not new, it remains unclear. This note, therefore, critically tackles the state-led conception and implementation of circular migration that has recently been introduced into Mali and that has – notwithstanding its advantages – numerous disadvantages from the perspective of a rule-of-law state. The note provides an overview of the government’s implementation of circular migration and concludes with some recommendations for the sustainable governance of migratory flows

Le cadre général de la migration au Mali

Euro-Mediterranean Consortium for Applied Research on International Migration (CARIM)La Constitution malienne garantit aux citoyens/nes maliens tous les droits humains fondamentaux (santé, éducation, emploi etc.). Mais du fait de la pauvreté grandissante, la plupart des citoyens ne jouissent pas de leurs droits et cherchent leur salut dans la migration vers les pays voisins, d’autres pays africains plus éloignés et les pays industrialisés, notamment la France, l’Espagne, l’Italie et les Etats – Unis. Environ un quart de la population malienne (quatre millions d’âmes) vivrait ainsi à l’extérieur. Le papier présente les acteurs clefs intervenant dans la gestion des flux migratoires et decrit leurs missions et strategies. Il recommande enfin de consolider certaines bonnes pratiques et esquisse des approches générales pour un contrôle durable des flux migratoires. / The Malian constitution guarantees basic human rights (health, education, employment, etc.) to Malian citizens. However, due to rising poverty, most citizens do not enjoy their rights and seek to better their lives either by emigrating to neighboring countries, to other more distant African states or to industrialized states, notably France, Spain, Italy and the United States. It is reported that almost a quarter of the Malian population (4 million) now lives abroad. This paper describes the key actors managing migratory flows and looks at the challenges they face and their methods. In its conclusion, the paper recommends consolidating certain good practices and sketches out some broad lines for managing migratory flows to, through and from Mali in a sustainable fashion

Assessment of lung injury severity using ultrasound in critically ill COVID-19 patients in resource limited settings

Abstract Background Lung ultrasound is a non-invasive tool available at the bedside for the assessment of critically ill patients. The objective of this study was to evaluate the usefulness of lung ultrasound in assessing the severity of SARS-CoV-2 infection in critically-ill patients in a low-income setting. Methods We conducted a 12-month observational study in a university hospital intensive care unit (ICU) in Mali, on patients admitted for COVID-19 as diagnosed by a positive polymerase chain reaction for SARS-CoV-2 and/or typical lung computed tomography scan findings. Results The inclusion criteria was met by 156 patients with a median age of 59 years. Almost all patients (96%) had respiratory failure at admission and many needed respiratory support (121/156, 78%). The feasibility of lung ultrasound was very good, with 1802/1872 (96%) quadrants assessed. The reproducibility was good with an intra-class correlation coefficient of elementary patterns of 0.74 (95% CI 0.65, 0.82) and a coefficient of repeatability of lung ultrasound score < 3 for an overall score of 24. Confluent B lines were the most common lesions found in patients (155/156). The overall mean ultrasound score was 23 ± 5.4, and was significantly correlated with oxygen saturation (Pearson correlation coefficient of − 0.38, p < 0.001). More than half of the patients died (86/156, 55.1%). The factors associated with mortality, as shown by multivariable analysis, were: the patients’ age; number of organ failures; therapeutic anticoagulation, and lung ultrasound score. Conclusion Lung ultrasound was feasible and contributed to characterize lung injury in critically-ill COVID-19 patients in a low income setting. Lung ultrasound score was associated with oxygenation impairment and mortality

Association of a promoter polymorphism in the gene encoding interleukin-12 P40 (IL12B) with cerebral malaria in a population living in Bamako

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A Cluster Randomized Study of The Safety of Integrated Treatment of Trachoma and Lymphatic Filariasis in Children and Adults in Sikasso, Mali

<div><p>Background</p><p>Neglected tropical diseases are co-endemic in many areas of the world, including sub Saharan Africa. Currently lymphatic filariasis (albendazole/ivermectin) and trachoma (azithromycin) are treated separately. Consequently, financial and logistical benefit can be gained from integration of preventive chemotherapy programs in such areas.</p> <p>Methodology/Findings</p><p>4 villages in two co-endemic districts (Kolondièba and Bougouni) of Sikasso, Mali, were randomly assigned to coadministered treatment (ivermectin/albendazole/azithromycin) or standard therapy (ivermectin/albendazole with azithromycin 1 week later). These villages had previously undergone 4 annual MDA campaigns with ivermectin/albendazole and 2 with azithromycin. One village was randomly assigned to each treatment arm in each district. There were 7515 eligible individuals in the 4 villages, 3011(40.1%) of whom participated in the study. No serious adverse events occurred, and the majority of adverse events were mild in intensity (mainly headache, abdominal pain, diarrhoea and “other signs/symptoms”). The median time to the onset of the first event, of any type, was later (8 days) in the two standard treatment villages than in the co-administration villages. Overall the number of subjects reporting any event was similar in the co-administration group compared to the standard treatment group [18.7% (281/1501) vs. 15.8% (239/1510)]. However, the event frequency was higher in the coadministration group (30.4%) than in the standard treatment group (11.0%) in Kolondièba, while the opposite was observed in Bougouni (7.1% and 20.9% respectively). Additionally, the overall frequency of adverse events in the co-administration group (18.7%) was comparable to or lower than published frequencies for ivermectin+albendazole alone.</p> <p>Conclusions</p><p>These data suggest that co-administration of ivermectin+albendazole and azithromycin is safe; however the small number of villages studied and the large differences between them resulted in an inability to calculate a meaningful overall estimate of the difference in adverse event rates between the regimens. Further work is therefore needed before co-administration can be definitively recommended.</p> <p>Trial Registration</p><p>ClinicalTrials.gov; <a href="http://clinicaltrials.gov/ct2/show/NCT01586169" target="_blank">NCT01586169</a></p> </div

Protection of Malian children from clinical malaria is associated with recognition of multiple antigens

Contains fulltext : 153754.pdf (publisher's version ) (Open Access)BACKGROUND: Naturally acquired immunity to clinical malaria is thought to be mainly antibody-mediated, but reports on antigen targets are contradictory. Recognition of multiple antigens may be crucial for protection. In this study, the magnitude of antibody responses and their temporal stability was assessed for a panel of malaria antigens in relation to protection against clinical Plasmodium falciparum malaria. METHODS: Malian children aged two to 14 years were enrolled in a longitudinal study and followed up by passive and active case detection for seven months. Plasma was collected at enrolment and at the beginning, in the middle and after the end of the transmission season. Antibody titres to the P. falciparum-antigens apical membrane protein (AMA)-1, merozoite surface protein (MSP)-1(1)(9), MSP-3, glutamine-rich protein (GLURP-R0) and circumsporozoite antigen (CSP) were assessed by enzyme-linked immunosorbent assay (ELISA) for 99 children with plasma available at all time points. Parasite carriage was determined by microscopy and nested PCR. RESULTS: Antibody titres to all antigens, except MSP-1(1)(9), and the number of antigens recognized increased with age. After malaria exposure, antibody titres increased in children that had low titres at baseline, but decreased in those with high baseline responses. No significant differences were found between antibody titers for individual antigens between children remaining symptomatic or asymptomatic after exposure, after adjustment for age. Instead, children remaining asymptomatic following parasite exposure had a broader repertoire of antigen recognition. CONCLUSIONS: The present study provides immune-epidemiological evidence from a limited cohort of Malian children that strong recognition of multiple antigens, rather than antibody titres for individual antigens, is associated with protection from clinical malaria