|Call||Senior Fellowship (SF)|
Research Capacity Building by DHA-PQ SMC Clinical Trial in school aged children in Mali
- Assess the impact of SMC on the incidence of clinical malaria and infection in school-aged children; - Evaluate the effect of SMC with DHA-PQ on malaria transmission, measured by the reduction in the prevalence of gametocytes in DHA-PQ treatment group; - Assess the impact of SMC on the genetic diversity of malaria parasites, measured by studying the dynamics of molecular markers associated with resistance to drugs used in SMC. - Evaluate the clinical tolerance of DHA-PQ compared to SP-AQ and control
Interventional study, Phase IV randomized trial with 3 treatment arms: DHA-PQ vs. SP-AQ vs. Albendazole. The trial was randomized double-blinded controlled. Efficacy and tolerability of Dihydroartemisinin-Piperaquine compared to Sulfadoxine-Pyrimethamine associated to Amodiaquine in Seasonal Malaria Chemoprevention in school aged children from 6-15 years were assessed. Participants were followed for 12 months, 4 SMC rounds and 2 cross-sectional surveys were conducted.
|MRTC- Bandiagara Malaria Project clinical center|
|Title||University||Start Date||End Date|
|Impact of Seasonal Malaria Chemoprevention on antimalarial drugs resistance markers selection||USTTB||2022-10-01|
|Type||Name||Title||University||Start Date||End Date|
|MD candidate||Mohamed Cisse||Dr||USTTB||2019||2021|
|MD candidate||Kindie Kouriba||Dr||USTTB||2020||2022|
|MD candidate||Souleymane Traore||Dr||USTTB||2020||2022|
|MD candidate||Youssouf Traore||Dr||USTTB||2020||2022|
|Master student||Bourema Guindo||Dr||USTTB||2021||2023|
|Master student||Mohamed Cisse||Dr||USTTB||2022|
|PhD student||Ali Thera||Dr||USTTB||2022|
We screened a total of 385 volunteers of which 345 were successfully enrolled. Thus, 116 were randomized to SP-AQ arm, 114 to treatment DHA-PQ arm and 115 to control arm. All randomized patients successfully completed the first two rounds of SMC. Two patients in SP-AQ arm and one patient in control arm missed the third round. In the fourth round, as in the cross-sectional visit, 113 volunteers from SP-AQ arm, 114 from DHA-PQ arm and 114 from control arm were seen. At the last cross-sectional survey, 105 volunteers from SP-AQ arm, 109 from DHA-PQ arm and 112 from control arm were seen. The total rates of lost to follow-up were 1.15% at the 4th SMC rounds, and 5.5% at the end of the study (last cross-sectional survey).
Malaria Research and Training Center
|Type||Name||Title||University||Start Date||End Date|
|Master student||Boureima Guindo||Dr||University of sciences, Technics and Technologies||2020|
|MD candidate||Kinde Kouriba||Mr||University of sciences, Technics and Technologies||2020||2022|
|MD candidate||Souleymane Traore||Mr||University of sciences, Technics and Technologies||2020||2022|
|MD Candidate||Youssouf Traore||Mr||University of sciences, Technics and Technologies||2021||2022|
|MD candidate||Mohamed Cisse||Mr||University of sciences, Technics and Technologies||2019||2021|
|Master student||Mohamed Cisse||Dr||University of sciences, Technics and Technologies||2021|
|Role||Committee/board||Start Date||End Date|
|Editorial Team||Revue Malienne d’Infectiologie et de Microbiologie||2021|
|Faculty of Medicine, Mali||MD||2002-05-22|
|Faculty of Medicine and pharmacy, Senegal||CES||2008-07-03|
|Faculty of Medicine and pharmacy, Senegal||DES||2011-06-29|
|Faculty of Medicine and pharmacy, Senegal||MSc||2012-02-02|
|University of Lyon, France||PhD||2018-02-06|
Malaria Neglected Infectious Diseases (NID)
Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host’s immunity and genes involved in controlling the parasitic infection can inform the development of blood-stage malaria vaccines. This study investigates host regulatory cytokines and immunogenomic factors associated with the clearance of Plasmodium falciparum carrying a chloroquine resistance genotype.
Biological samples from participants of previous drug efficacy trials conducted in two Malian localities were retrieved. The P. falciparum chloroquine resistance transporter (Pfcrt) gene was genotyped using parasite DNA. Children carrying parasites with the mutant allele (Pfcrt-76T) were classified based on their ability to clear their parasites. The levels of the different cytokines were measured in serum. The polymorphisms of specific human genes involved in malaria susceptibility were genotyped using human DNA.
The prevalence of the Pfcrt-76T was significantly higher in Kolle than in Bandiagara (81.6 % vs 38.6 %, p < 10−6). The prevalence of children who cleared their mutant parasites was significantly higher in Bandiagara than in Kolle (82.2 % vs 67.4 %, p < 0.05). The genotyping of host genes revealed that IFN-γ –874 T and TNF-α –308A alleles were positively associated with parasite clearance. Cytokine profiling revealed that IFN-γ level was positively associated with parasite clearance (p = 0.04).
This study highlights the role of host’s immunity and immunogenetic factors to clear resistant parasites, suggesting further characterization of these polymorphisms may help to develop novel approaches to antiparasitic treatment strategies.
A decrease in malaria incidence following implementation of control strategies such as use of artemisinin-based combination therapies, insecticide-impregnated nets, intermittent preventive treatment during pregnancy and seasonal malaria chemoprevention (SMC) has been observed in many parts of Africa. We hypothesized that changes in malaria incidence is accompanied by a change in the predominant clinical phenotypes of severe malaria. To test our hypothesis, we used data from a severe malaria case-control study that lasted from 2014-2019 to describe clinical phenotypes of severe forms experienced by participants enrolled in Bandiagara, Bamako, and Sikasso, in Mali. We also analyzed data from hospital records of inpatient children at a national referral hospital in Bamako. Among 97 cases of severe malaria in the case-control study, there was a predominance of severe malarial anemia (49.1%). The frequency of cerebral malaria was 35.4, and 16.5% of cases had a mixed clinical phenotype (concurrent cerebral malaria and severe anemia). National referral hospital record data in 2013-15 showed 24.3% of cases had severe malarial anemia compared to 51.7% with cerebral malaria. In the years after SMC scale-up, severe malarial anemia cases increased to 30.1%, (P = 0.019), whereas cerebral malaria cases decreased to 45.5% (P = 0.025). In addition, the predominant age group for each severe malaria phenotype was the 0-1-year-olds. The decrease in malaria incidence noted with the implementation of control strategies may be associated with a change in the clinical expression patterns of severe malaria, including a potential shift in severe malaria burden to age groups not receiving seasonal malaria chemoprevention.
Plasmodium parasites caused 241 million cases of malaria and over 600,000 deaths in 2020. Both P. falciparum and P. ovale are endemic to Mali and cause clinical malaria, with P. falciparum infections typically being more severe. Here, we sequenced RNA from nine pediatric blood samples collected during infections with either P. falciparum or P. ovale, and characterized the host and parasite gene expression profiles. We found that human gene expression varies more between individuals than according to the parasite species causing the infection, while parasite gene expression profiles cluster by species. Additionally, we characterized DNA polymorphisms of the parasites directly from the RNA-seq reads and found comparable levels of genetic diversity in both species, despite dramatic differences in prevalence. Our results provide unique insights into host-pathogen interactions during malaria infections and their variations according to the infecting Plasmodium species, which will be critical to develop better elimination strategies against all human Plasmodium parasites.
The role of some nutrient-derived metabolites on the innate and adaptive immune responses is now established. Global research approach investigating the interplay between environment, lifestyle and the host's immune responses is crucial in the understanding of malaria susceptibility. Advanced Glycation end products (AGE), which are food-derived metabolites result from the link between reducing sugar and amino group of proteins, lipids or nucleic acids. The level of exposure to AGEs varies depending on the type of diet. The dysfunction of the immune system induced by AGE and the cellular receptors for AGEs (RAGE) in susceptibility to bacterial infection has been described. But no study has yet explored their role in susceptibility to malaria. Therefore, we aimed to evaluate systemic AGE and RAGE gene polymorphism in two sympatric populations with previously described difference of susceptibility to malaria. We measured by ELISA the plasma levels of AGEs, and their soluble receptors (sRAGE) from 170 volunteers (68 Fulani and 102 Dogon). We also determined by real-time quantitative PCR the expression of RAGE, and the -374 T/A, -429 T/C polymorphisms and 63 bp deletion by fragment length restriction polymorphism. The prevalence rate of Plasmodium in Fulani and Dogon were respectively 42.64% and 51.30% for P. falciparum, 5.88% and 6.5% for P. malariae, 0% and 2.6% for P. ovale. The average AGE was 12.65 μg/ml, and 496.48pg/ml for sRAGE. Highest levels of sRAGE were observed in Fulani (563,07pg/ml, 95% CI [547.81-580.13] vs 465.68pg/ml, 95% CI [331.19-467.51]) for Dogon, p = 0.00001. Fulani had the lowest mean of AGE (10.21μg/ml, 95% CI [8.02-10.92]) compared to Dogon (16.88μg/ml, 95% CI [13.92-17.96]; p = 0.00001. RAGE was more expressed in Dogon than Fulani (0.08 vs 0.04), P = 0.08. The -374A polymorphism vas more frequent in Fulani (32%) compared to Dogon (20%). The chronic exposure to dietary AGE could lead to immune responses impairment and polymorphism with implications in malaria susceptibility. More studies are necessary to better investigate this hypothesis.
|Dr Karim Traore||Mali||MRTC|
|Pr Abraham Kwabena Anang||Ghana||NMIMR|
|Dr Abdoul Habib Beavogui||Guinea||CNFR|
|Pr Emmanuele Gormally||France||Lyon Catholic University|