Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte-Binding Protein Homologue-5 in Kalifabougou, Mali

Reticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte-binding homologue-5 (PfRH5) has been found to be essential for parasite survival across strains that differ in virulence and route of host-cell invasion. Based on its essential role in invasion and early evidence of sequence conservation, PfRH5 has been prioritized for development as a vaccine candidate. However, little is known about the extent of genetic variability of RH5 in the field and the potential impact of such diversity on clinical outcomes or on vaccine evasion. Samples collected during a prospective cohort study of malaria incidence conducted in Kalifabougou, in southwestern Mali, were used to estimate genetic diversity, measure haplotype prevalence, and assess the within-host dynamics of PfRH5 variants over time and in relation to clinical malaria. A total of 10 nonsynonymous polymorphic sites were identified in the Pfrh5 gene, resulting in 13 haplotypes encoding unique protein variants. Four of these variants have not been previously observed. Plasmodium falciparum reticulocyte-binding homologue-5 had low amino acid haplotype (h = 0.58) and nucleotide (π = 0.00061) diversity. By contrast to other leading blood-stage malaria vaccine candidate antigens, amino acid differences were not associated with changes in the risk of febrile malaria in consecutive infections. Conserved B- and T-cell epitopes were identified. These results support the prioritization of PfRH5 for possible inclusion in a broadly cross-protective vaccine

Geographical and temporal distribution of human giardiasis in Ontario, Canada

BACKGROUND: Giardia is the most frequently identified intestinal parasite in North America. Although information on geographical distribution of giardiasis is critical in identifying communities at high risk, little has been done in this area. Therefore, the objective of this study was to investigate the geographical and temporal distribution of human giardiasis in Ontario in order to identify possible high risk areas and seasons. Two spatial scales of analyses and two disease measures were used with a view to identifying the best of each in assessing geographical patterns of giardiasis in Ontario. Global Moran's I and Moran Local Indicators of Spatial Associations were used to test for evidence of global and local spatial clustering, respectively. RESULTS: There were seasonal patterns with summer peaks and a significant (P < 0.001) decreasing temporal trend. Significant (P < 0.05) global spatial clustering of high rates was observed at the Census Sub-division spatial scale but not at the Census Division scale. The Census Sub-division scale was a better scale of analyses but required spatial empirical Bayesian smoothing of the rates. A number of areas with significant local clustering of giardiasis rates were identified. CONCLUSIONS: The study identified spatial and temporal patterns in giardiasis distribution. This information is important in guiding decisions on disease control strategies. The study also showed that there is benefit in performing spatial analyses at more than one spatial scale to assess geographical patterns in disease distribution and that smoothing of disease rates for mapping in small areas enhances visualization of spatial patterns

Subclinical Cardiac Dysfunction Is Associated With Extracardiac Organ Damages

Background: Several studies conducted in America or Europe have described major cardiac remodeling and diastolic dysfunction in patients with sickle cell disease (SCD). We aimed at assessing cardiac involvement in SCD in sub-Saharan Africa where SCD is the most prevalent.Methods: In Cameroon, Mali and Senegal, SCD patients and healthy controls of the CADRE study underwent transthoracic echocardiography if aged ≥10 years. The comparison of clinical and echocardiographic features between patients and controls, and the associations between echocardiographic features and the vascular complications of SCD were assessed.Results: 612 SCD patients (483 SS or Sβ0, 99 SC, and 19 Sβ+) and 149 controls were included. The prevalence of dyspnea and congestive heart failure was low and did not differ significantly between patients and controls. While left ventricular ejection fraction did not differ between controls and patients, left and right cardiac chambers were homogeneously more dilated and hypertrophic in patients compared to controls and systemic vascular resistances were lower (p &lt; 0.001 for all comparisons). Three hundred and forty nine SCD patients had extra-cardiac organ damages (stroke, leg ulcer, priapism, microalbuminuria or osteonecrosis). Increased left ventricular mass index, cardiac dilatation, cardiac output, and decreased systemic vascular resistances were associated with a history of at least one SCD-related organ damage after adjustment for confounders.Conclusions: Cardiac dilatation, cardiac output, left ventricular hypertrophy, and systemic vascular resistance are associated with extracardiac SCD complications in patients from sub-Saharan Africa despite a low prevalence of clinical heart failure. The prognostic value of cardiac subclinical involvement in SCD patients deserves further studies

Farmers’ Perceptions of the Impacts of Climate Change on Resources and Production Systems: Case of the cercle of Yélimané in Mali

Citation correct de ce document / Correct citation of this document: Penda, S. et al. (2020). Perceptions paysannes des impacts du changement climatique sur les ressources et les systèmes de production : cas du cercle de Yélimané au Mali. In N'Diaye, I. et al. (eds.) Adaptation de l'Agriculture et de l'Élevage au Changement Climatique au Mali: Résultats et leçons apprises au Sahel. Bamako, Mali: Institut d'Economie Rurale. pp. 39-50.Le livre complet est accessible sur le site internet suivant / The complete book can be accessed from the following link https://hdl.handle.net/11250/2687372Le Sahel, à l’instar d’autres zones arides et semi-arides d’Afrique, est soumis aux effets néfastes du changement climatique. Les prévisions, pour ces régions, sont entre autres, une diminution des rendements des cultures, des superficies cultivées et de la durée des saisons, accompagnées d’une baisse de la production agricole. Cette étude fait une analyse de la vulnérabilité et des adaptations aux variabilités et changements climatiques des communautés de la zone de décrue dans le cercle de Yélimané, région de Kayes, en zone sahélienne. Elle a porté sur l’exploitation des données secondaires sur le milieu et sur l’analyse des perceptions des communautés. Les méthodes participatives, focus groupes villageois et entretiens semi-structurés, ont été utilisées pour la collecte des données au niveau de 301 exploitations agricoles. Les statistiques descriptives et les matrices ont été utilisées pour l’analyse des données avec l’emploi des logiciels Excel et SPSS. Les résultats ont montré que le changement climatique, perçu par les communautés de la zone résulte, selon elles, de causes naturelles et anthropiques. Les manifestations du phénomène au cours des dernières décennies ont été constatées par les populations par les sécheresses, les variabilités pluviométriques, les vents violents, les fortes températures et les inondations. Les impacts de ces phénomènes ont été observés sur les ressources et les modes d’existence des communautés à travers les faibles productions agricoles et d’élevage, des ressources halieutiques, la réduction voire la disparition de certaines espèces forestières et fauniques. Les conséquences se sont traduites par la pauvreté et l’insécurité alimentaire au niveau des exploitations agricoles. Pour l’adaptation des communautés aux risques des variabilités climatiques, des stratégies individuelles et collectives ont été développées dans la zone. Les principales portent sur l’utilisation des variétés précoces et semi précoces, l’augmentation de la pratique des cultures de décrue, le maraîchage, le stockage des résidus de culture pour l’alimentation du bétail, l’exode rural et l’immigration des populations. Les contraintes matérielles, financières et institutionnelles limitent les capacités d’adaptation des communautés.Abstract: Like other arid and semi-arid areas of Africa, the Sahel is subject to the adverse effects of climate change. Forecasts for these regions include a decrease in crop yields, cultivated areas and the length of seasons, compounded with a drop in agricultural production. This study assesses the climate vulnerability and adaptation solutions to climate variability and change of communities in the flood recession area of the cercle of Yélimané, Kayes region, in the Sahelian zone. It focused on the use of secondary environmental data as well as the analysis of the communities’ perceptions of climate change and their vulnerability to it. Participatory methods, village focus groups and semi-structured interviews were used to collect data from 301 farms. Descriptive statistics and matrices were used for data analysis with Excel and SPSS software. The results show that communities in the Yélimané floodplain area perceive climate change as resulting from natural and anthropogenic causes. In recent decades, these populations have witnessed the manifestations of the phenomenon through droughts, rainfall variability, high winds, high temperatures and floods. The impacts of these events have been observed on the resources and livelihoods of communities in the form of low agricultural and livestock production, low fish stocks, a decrease in or even disappearance of forest and wildlife species. These have resulted in poverty and farm level food insecurity. Individual and collective strategies have been developed in the area for communities’ adaptation to climate variability risks. The main ones include using early and semi-early varieties, enhancing flood recession cropping, market-gardening, the storage of crop residues for livestock, rural exodus and migration. Material, financial and institutional constraints limit the adaptive capacities of communities

Perceptions paysannes des impacts du changement climatique sur les ressources et les systèmes de production : cas du cercle de Yélimané au Mali

Le Sahel, à l’instar d’autres zones arides et semi-arides d’Afrique, est soumis aux effets néfastes du changement climatique. Les prévisions, pour ces régions, sont entre autres, une diminution des rendements des cultures, des superficies cultivées et de la durée des saisons, accompagnées d’une baisse de la production agricole. Cette étude fait une analyse de la vulnérabilité et des adaptations aux variabilités et changements climatiques des communautés de la zone de décrue dans le cercle de Yélimané, région de Kayes, en zone sahélienne. Elle a porté sur l’exploitation des données secondaires sur le milieu et sur l’analyse des perceptions des communautés. Les méthodes participatives, focus groupes villageois et entretiens semi-structurés, ont été utilisées pour la collecte des données au niveau de 301 exploitations agricoles. Les statistiques descriptives et les matrices ont été utilisées pour l’analyse des données avec l’emploi des logiciels Excel et SPSS. Les résultats ont montré que le changement climatique, perçu par les communautés de la zone résulte, selon elles, de causes naturelles et anthropiques. Les manifestations du phénomène au cours des dernières décennies ont été constatées par les populations par les sécheresses, les variabilités pluviométriques, les vents violents, les fortes températures et les inondations. Les impacts de ces phénomènes ont été observés sur les ressources et les modes d’existence des communautés à travers les faibles productions agricoles et d’élevage, des ressources halieutiques, la réduction voire la disparition de certaines espèces forestières et fauniques. Les conséquences se sont traduites par la pauvreté et l’insécurité alimentaire au niveau des exploitations agricoles. Pour l’adaptation des communautés aux risques des variabilités climatiques, des stratégies individuelles et collectives ont été développées dans la zone. Les principales portent sur l’utilisation des variétés précoces et semi précoces, l’augmentation de la pratique des cultures de décrue, le maraîchage, le stockage des résidus de culture pour l’alimentation du bétail, l’exode rural et l’immigration des populations. Les contraintes matérielles, financières et institutionnelles limitent les capacités d’adaptation des communautés

Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali

International audienceBackground: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy that was adopted in Mali as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study was designed to measure the efficacy of artemether-lumefantrine and to assess the selection of the P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genotypes that have been associated with drug resistance.Methods: A 28-day follow-up efficacy trial of artemether-lumefantrine was conducted in patients aged 6 months and older suffering from uncomplicated falciparum malaria in four different Malian areas during the 2009 malaria transmission season. The polymorphic genetic markers MSP2, MSP1, and Ca1 were used to distinguish between recrudescence and reinfection. Reinfection and recrudescence were then grouped as recurrent infections and analyzed together by PCR-restriction fragment length polymorphism (RFLP) to identify candidate markers for artemether-lumefantrine tolerance in the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multi-drug resistance 1 (pfmdr1) gene.Results: Clinical outcomes in 326 patients (96.7%) were analyzed and the 28-day uncorrected adequate clinical and parasitological response (ACPR) rate was 73.9%. The total PCR-corrected 28-day ACPR was 97.2%. The pfcrt 76T and pfmdr1 86Y population prevalence decreased from 49.3% and 11.0% at baseline (n = 337) to 38.8% and 0% in patients with recurrent infection (n = 85); p = 0.001), respectively.Conclusion: Parasite populations exposed to artemether-lumefantrine in this study were selected toward chloroquine-sensitivity and showed a promising trend that may warrant future targeted reintroduction of chloroquine or/and amodiaquine

Spatio-temporal dynamics of asymptomatic malaria : bridging the gap between annual malaria resurgences in a Sahelian environment

International audienceThese authors contributed equally to this work. Abstract. In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009–2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2–3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009–2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission

Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali.

INTRODUCTION: Interethnic differences in susceptibility to malaria provide a unique opportunity to explore immunological correlates of protection. The Fulani of Sahelian Africa are known for their reduced susceptibility to Plasmodium falciparum, compared with surrounding tribes, yet the immunology underlying this is still poorly understood. METHODS AND RESULTS: Here, we show that mononuclear cells from Fulani elicit >10-fold stronger interferon (IFN)-gamma production following a 24-h in vitro coincubation with asexual parasites than cells from sympatric Dogon. This response appears to be specific for P. falciparum among a panel of other human pathogens and is independent of the lower number of regulatory T cell counts present in Fulani. IFN-gamma responses in both tribes were inversely correlated with peripheral parasite density as quantified by nucleic acid sequenced-based amplification, but responses of Fulani remained significantly stronger than those of Dogon after adjustment for concurrent parasitemia, suggesting that hard-wired immunological differences underlie the observed protection. CONCLUSIONS: These results underscore the value of early IFN-gamma responses to P. falciparum as a correlate of anti-parasite immunity, not only in this setting but also in the wider context of malaria, and support the development of malaria vaccines aimed at inducing such responses