Expression of Complement and Toll-Like Receptor Pathway Genes is Associated with Malaria Severity in Mali: A Pilot Case Control Study

Background: The host response to infection by Plasmodium falciparum, the parasite most often responsible for severe malaria, ranges from asymptomatic parasitaemia to death. The clinical trajectory of malaria is influenced by host genetics and parasite load, but the factors determining why some infections produce uncomplicated malaria and some proceed to severe disease remain incompletely understood. Methods: To identify molecular markers of severe falciparum malaria, human gene expression patterns were compared between children aged 6 months to 5 years with severe and uncomplicated malaria who were enrolled in a case–control study in Bandiagara, Mali. Microarrays were used to obtain expression data on severe cases and uncomplicated controls at the time of acute disease presentation (five uncomplicated and five severe), 1 week after presentation (three uncomplicated and three severe) and treatment initiation, and in the subsequent dry season (late convalescence, four uncomplicated and four severe). This is a pilot study for the first use of microarray technology in Mali

Use of a pLDH-based dipstick in the diagnostic and therapeutic follow-up of malaria patients in Mali

<p>Abstract</p> <p>Background</p> <p>Malaria is a major public health problem in Mali and diagnosis is typically based on microscopy. Microscopy requires a well trained technician, a reliable power source, a functioning microscope and adequate supplies. The scarcity of resources of community health centres (CHC) does not allow for such a significant investment in only one aspect of malaria control. In this context, Rapid Diagnostic Tests (RDTs) may improve case management particularly in remote areas.</p> <p>Methods</p> <p>This multicentre study included 725 patients simultaneously screened with OptiMal-IT test and thick smears for malaria parasite detection. While evaluating the therapeutic efficacy of choroquine in 2 study sites, we compared the diagnostic values of thick smear microscopy to OptiMal-IT test applying the WHO 14 days follow-up scheme using samples collected from 344 patients.</p> <p>Results</p> <p>The sensitivity and the specificity of OptiMal-IT compared to thick smear was 97.2% and 95.4%, whereas the positive and negative predictive values were 96.7 and 96.1%, respectively. The percent agreement between the two diagnostic tests was 0.93. The two tests were comparable in detecting malaria at day 0, day 3 and day 14. The only difference was observed at day 7 due to high gametocytemia. Subjectively, health care providers found OptiMal-IT easier to use and store under field conditions.</p> <p>Conclusion</p> <p>OptiMal-IT test revealed similar results when compared to microscopy which is considered the gold standard for malaria diagnostics. The test was found to have a short processing time and was easier to use. These advantages may improve malaria case management by providing a diagnostic and drug efficacy follow-up tool to peripheral health centres with limited resources.</p

Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine

<p>Abstract</p> <p>Background</p> <p>Extensive genetic diversity in vaccine antigens may contribute to the lack of efficacy of blood stage malaria vaccines. Apical membrane antigen-1 (AMA1) is a leading blood stage malaria vaccine candidate with extreme diversity, potentially limiting its efficacy against infection and disease caused by <it>Plasmodium falciparum </it>parasites with diverse forms of AMA1.</p> <p>Methods</p> <p>Three hundred Malian children participated in a Phase 2 clinical trial of a bivalent malaria vaccine that found no protective efficacy. The vaccine consists of recombinant AMA1 based on the 3D7 and FVO strains of <it>P. falciparum </it>adjuvanted with aluminum hydroxide (AMA1-C1). The gene encoding AMA1 was sequenced from <it>P. falciparum </it>infections experienced before and after immunization with the study vaccine or a control vaccine. Sequences of <it>ama1 </it>from infections in the malaria vaccine and control groups were compared with regard to similarity to the vaccine antigens using several measures of genetic diversity. Time to infection with parasites carrying AMA1 haplotypes similar to the vaccine strains with respect to immunologically important polymorphisms and the risk of infection with vaccine strain haplotypes were compared.</p> <p>Results</p> <p>Based on 62 polymorphic AMA1 residues, 186 unique <it>ama1 </it>haplotypes were identified among 315 <it>ama1 </it>sequences that were included in the analysis. Eight infections had <it>ama1 </it>sequences identical to 3D7 while none were identical to FVO. Several measures of genetic diversity showed that <it>ama1 </it>sequences in the malaria vaccine and control groups were comparable both at baseline and during follow up period. Pre- and post-immunization <it>ama1 </it>sequences in both groups all had a similar degree of genetic distance from FVO and 3D7 <it>ama1</it>. No differences were found in the time of first clinical episode or risk of infection with an AMA1 haplotype similar to 3D7 or FVO with respect to a limited set of immunologically important polymorphisms found in the cluster 1 loop of domain I of AMA1.</p> <p>Conclusion</p> <p>This Phase 2 trial of a bivalent AMA1 malaria vaccine found no evidence of vaccine selection or strain-specific efficacy, suggesting that the extreme genetic diversity of AMA1 did not account for failure of the vaccine to provide protection.</p

Capacity building of Multi-Stakeholder Innovation Platform (PIMA) actors in members in community governance, crop calendar construction, and implementation of nature-based solutions

Conversion of dry season pasture to potato and vegetable fields in inland valleys is resulting in biodiversity loss, water resources degradation, pastoral marginalization, and increasing conflicts between herders and farmers. The AICCRA project established multi-stakeholders platforms (MSP) at three inland valleys (Finkolo Ganadougou, Blendio, and Loutana) in Mali and strengthened MSP members' capacity in community governance, crop calendar construction, and implementation of nature-based solutions, resulting in enhanced connections between the stakeholders actors, but also better access to input, information and water governance of inland valleys resources

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