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1. Plasmodium ovale wallikeri and P. ovale curtisi Infections and Diagnostic Approaches to Imported Malaria, France, 2013-2018

Author

Joste, Valentin, Bailly, Justine, Hubert, Veronique, Pauc, Cecile, Gendrot, Mathieu, Guillochon, Emilie, Madamet, Marylin, Thellier, Marc, Kendjo, Eric, Argy, Nicolas, Pradines, Bruno, and Houze, Sandrine

Subjects
Genetic polymorphisms -- Identification and classification -- Health aspects, Malaria -- Diagnosis -- Care and treatment -- Genetic aspects, Molecular diagnostic techniques -- Evaluation, Health
Abstract

Malaria is a vectorborne disease caused by Plasmodium, a parasite transmitted by Anopheles mosquitoes. In 2018, malaria was responsible for [approximately equal to]228 million cases and 405,000 deaths worldwide (1). [...]

Published
2021
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2. Comparison of SD Bioline Malaria Ag Pf/Pan and Acro Malaria P.f./P.v./Pan with Microscopy and Real Time PCR for the Diagnosis of Human Plasmodium Species.

Author

Madamet, Marylin, Fonta, Isabelle, Mosnier, Joel, Benoit, Nicolas, Amalvict, Rémy, Briolant, Sébastien, and Pradines, Bruno

Subjects
*RAPID diagnostic tests, *MALARIA, *PARASITE antigens, *PLASMODIUM, *PLASMODIUM vivax
Abstract

The early diagnosis of malaria is crucial to controlling morbidity and mortality. The World Health Organization (WHO) recommends diagnosing malaria either using light microscopy or a malaria rapid diagnostic test (RDT). Most RDTs use antibodies to detect two P. falciparum histidine-rich proteins named PfHRP2 and PfHRP3. However, false-negative results are known to occur due to the poor performance of RDTs depending on the species and the deletion of the Pfhrp2 and Pfhrp3 genes. This study evaluated new malaria RDTs for the detection of the human Plasmodium species. The Acro Malaria P.f./P.v./Pan Rapid Test Cassette allows the qualitative detection of parasite antigens, such as PfHRP2 specific to Plasmodium falciparum, PvLDH specific to Plasmodium vivax, and/or panLDH Plasmodium genus lactate dehydrogenase, in the blood of infected individuals. This RDT was assessed against 229 samples collected from imported malaria cases, mainly from Africa. The samples were previously diagnosed using light microscopy and RDT (SD Malaria Ag P.f./Pan, SD Bioline Alere Abbott), then confirmed using real time PCR. The two RDTs were evaluated using a comparison with real time PCR as the reference method, and their performances were compared with each other. Compared to SD RDT, the Acro RDT showed a better sensitivity to P. falciparum (96.8% vs. 89.8%), P. vivax (78.6% vs. 64.3%), P. ovale (73.7% vs. 5.3%), and P. malariae (20.0% vs. 0%). The respective specificities of the Acro RDT and SD RDT are 90.7% vs. 95.3% to P. falciparum, 100% to P. vivax, and 100% vs. 100% to Plasmodium genus. Therefore, Acro RDT showed better performance in the identification of P. ovale and low parasitaemia of P. falciparum. In addition, Acro RDT has the advantage of detecting PvLDH-specific antigens. The Acro Malaria RDT presents the benefits of detecting a P. falciparum antigen (PfHRP2) and a P. vivax antigen (PvLDH) with high sensitivity (96.8% and 73.7%, respectively) and specificity (90.7% and 100%, respectively). Acro Malaria P.f./P.v./Pan rapid diagnostic tests could be effectively used in endemic areas, especially when microscopic examination cannot be performed. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Low polymorphisms in pfact, pfugt and pfcarl genes in African Plasmodium falciparum isolates and absence of association with susceptibility to common anti-malarial drugs

Author

Foguim, Francis Tsombeng, Robert, Marie Gladys, Gueye, Mamadou Wagué, Gendrot, Mathieu, Diawara, Silman, Mosnier, Joel, Amalvict, Rémy, Benoit, Nicolas, Bercion, Raymond, Fall, Bécaye, Madamet, Marylin, Pradines, Bruno, and The French National Reference Centre for Imported Malaria Study Group

Published
2019
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9. Copper (I)-Chloroquine Complexes: Interactions with DNA and Ferriprotoporphyrin, Inhibition of β-Hematin Formation and Relation to Antimalarial Activity

Author

W, Villarreal, Castro, William, González, Sorenlis, Madamet, Marylin, Amalvict, Rémy, Pradines, Bruno, Navarro, Maribel, Universidade Federal do Rio Grande do Sul, Grupo de Química Inorgânica Medicinal e Reações Aplicadas, Instituto de Química ((UFRGS)), Centro de Química, Instituto Venezolano de Investigaciones Cientificas (IVIC), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), and UFJF - Universidade Federal de Juiz de Fora [Minas Gerais, Brazil]

Subjects
[SDV]Life Sciences [q-bio]
Abstract

A new Cu(I)-chloroquine (CQ) complex [Cu(CQ)(PPh3)2]NO3 (1) was synthesized and characterized, and its mechanism of action studied concomitant with the previously reported complex [Cu(CQ)2]Cl (2). These copper (I) coordination compounds can be considered as potential antimalarial agents because they show better inhibition of the CQ-resistant strain in in vitro studies than CQ alone. In comparison with other metal-CQ complexes, only the gold complex was similar to (1), i.e., more active than CQ against both CQ-susceptible (3D7) and CQ-resistant strains (W2). These two copper (I)-compounds also demonstrated higher antiplasmodial activity against W2 than other copper complexes reported to date. This suggests that the incorporation of the copper metal center enhanced the biological activity of CQ. To better understand their significant growth inhibition of the Plasmodium falciparum parasite, the interaction with two essential molecular targets for the survival and proliferation of the malarial parasite were studied. These were the ferriprotoporphyrin group and the DNA, both important targets for current antimalarial drugs at the asexual erythrocytic stages. Both compounds (1,2) exhibited significant interactions with these targets. In particular, interactions with the DNA were dominated by the intercalator properties of the CQ ligand but may have also been affected by the presence of copper. Overall, these compounds were better parasitic inhibitors than chloroquine diphosphate (CQDP) alone or other previously reported metal-CQ complexes such as platinum, ruthenium and gold.

Published
2022

12. Plasmodium falciparum in vitro resistance to monodesethylamodiaquine, Dakar, Senegal, 2014

Author

Fall, Becaye, Madamet, Marylin, Camara, Cheikhou, Amalvict, Remy, Fall, Mansour, Nakoulima, Aminata, Diatta, Bakary, Dieme, Yaya, Wade, Boubacar, and Pradines, Bruno

Subjects
Sentinel surveillance -- Methods, Drug resistance -- Forecasts and trends, Malaria -- Drug therapy, Infection control, Market trend/market analysis, Health
Abstract

In 2004, Senegal adopted the use of sulfadoxine/pyrimethamine with amodiaquine as the first-line therapy for malaria in response to increasing chloroquine resistance. In 2006, the National Malaria Control Program of [...]

Published
2016
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15. Assessment of a Commercial Real-Time PCR Assay (Vitassay qPCR Malaria 5 Test) to Detect Human Malaria Infection in Travelers Returning to France.

Author

Madamet, Marylin, Amalvict, Rémy, Benoit, Nicolas, and Pradines, Bruno

Subjects
*MALARIA, *PARASITIC diseases, *NEUROCYSTICERCOSIS, *MIXED infections, *PLASMODIUM falciparum, *MOLECULAR diagnosis
Abstract

Malaria is the most common human parasitic disease in the world with the highest morbidity and mortality. Due to the severity of malaria caused by Plasmodium falciparum and the urgency of therapeutic management, quick and reliable diagnosis is required for early detection. Blood smear microscopy remains the gold standard for malaria diagnosis. Molecular diagnosis techniques are the most sensitive and specific in cases of low parasitaemia and in the detection of mixed infections. The purpose of this study was to evaluate a new commercial test involving the molecular diagnostic technique to detect the five human Plasmodium species. The Vitassay qPCR Malaria 5 test is based on the multiplex real-time PCR of a conserved target region of the 18S rRNA gene for the five human Plasmodium species. A total of 190 samples collected from imported cases of malaria were diagnosed using this test and compared against a homemade reference real-time PCR. The sensitivities of the Vitassay qPCR Malaria 5 test for all Plasmodium species ranged from 93.8% to 100% and specificity ranged from 97.7% to 100%. Based on these criteria, this test is recommended for the diagnosis of the human Plasmodium species. [ABSTRACT FROM AUTHOR]

Published
2022
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18. Absence of Association between Methylene Blue Reduced Susceptibility and Polymorphisms in 12 Genes Involved in Antimalarial Drug Resistance in African Plasmodium falciparum

Author

Gendrot, Mathieu, primary, Delandre, Océane, additional, Robert, Marie, additional, Foguim, Francis, additional, Benoit, Nicolas, additional, Amalvict, Rémy, additional, Fonta, Isabelle, additional, Mosnier, Joel, additional, Madamet, Marylin, additional, Pradines, Bruno, additional, and Group, on, additional

Published
2021
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19. Baseline and multinormal distribution of ex vivo susceptibilities of Plasmodium falciparum to methylene blue in Africa, 2013–18

Author

Gendrot, Mathieu, Pradines, Bruno, Brouqui, P, Drancourt, Michel, Madamet, Marylin, Mosnier, Joel, Fonta, Isabelle, Amalvict, Rémy, Benoit, Nicolas, Briolant, Sébastien, Augis, V, Bastien, P, Berry, A, Chauvin, P, Cividin, M, Courtier, F, Delaunay, P, Delhaes, L, Dubosc, N, Gaillard, T, Genin, A, Garnotel, E, Javelle, E, L’ollivier, C, Lagier, J, Ledault, E, Leveque, M, Malvy, D, Marty, P, Ménard, G, Menu, E, Millet, P, Minodier, P, Picot, S, Pomares-Estran, C, Ranque, S, Receveur, M-C, Robin, A, Sappa, E, Savini, H, Sevestre, J, Simon, F, Sterkers, Yvon, Surcouf, C, Varlet, E, Wolff, A, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Service de Santé des Armées, Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)

Subjects
0301 basic medicine, Microbiology (medical), Veterinary medicine, Plasmodium falciparum, 030231 tropical medicine, 030106 microbiology, Drug Resistance, Context (language use), Antimalarials, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Humans, Distribution (pharmacology), Pharmacology (medical), [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria, Falciparum, ComputingMilieux_MISCELLANEOUS, EC50, Pharmacology, biology, Bayes Theorem, biology.organism_classification, 3. Good health, Methylene Blue, Infectious Diseases, Reduced susceptibility, chemistry, Africa, France, Geometric mean, Methylene blue, Ex vivo
Abstract

Background Plasmodium falciparum resistance to most antimalarial compounds has emerged in Southeast Asia and spread to Africa. In this context, the development of new antimalarial drugs is urgent. Objectives To determine the baseline in vitro activity of methylene blue (Proveblue®) on African isolates and to determine whether parasites have different phenotypes of susceptibility to methylene blue. Methods Ex vivo susceptibility to methylene blue was measured for 609 P. falciparum isolates of patients hospitalized in France for malaria imported from Africa. A Bayesian statistical analysis was designed to describe the distribution of median effective concentration (EC50) estimates. Results The EC50 ranged from 0.16 to 87.2 nM with a geometric mean of 7.17 nM (95% CI = 6.21–8.13). The 609 EC50 values were categorized into four components: A (mean = 2.5 nM; 95% CI = 2.28–2.72), B (mean = 7.44 nM; 95% CI = 7.07–7.81), C (mean = 16.29 nM; 95% CI = 15.40–17.18) and D (mean = 38.49 nM; 95% CI = 34.14–42.84). The threshold value for in vitro reduced susceptibility to methylene blue was estimated at 35 nM using the geometric mean of EC50 plus 2 SDs of the 609 isolates. This cut-off also corresponds to the lower limit of the 95% CI of the methylene blue EC50 of component D. Thirty-five isolates (5.7%) displayed EC50 values above this threshold. Conclusions Methylene blue exerts a promising efficacy against P. falciparum and is a potential partner for triple combinations.

Published
2020

20. Absence of association between polymorphisms in the pfcoronin and pfk13 genes and the presence of Plasmodium falciparum parasites after treatment with artemisinin derivatives in Senegal

Author

Delandre, Océane, primary, Daffe, Sokhna M., additional, Gendrot, Mathieu, additional, Diallo, Maguette N., additional, Madamet, Marylin, additional, Kounta, Mame B., additional, Diop, Moustapha N., additional, Bercion, Raymond, additional, Sow, Abdou, additional, Ngom, Papa M., additional, Lo, Gora, additional, Benoit, Nicolas, additional, Amalvict, Rémy, additional, Fonta, Isabelle, additional, Mosnier, Joel, additional, Diawara, Silman, additional, Wade, Khalifa A., additional, Fall, Mansour, additional, Fall, Khadidiatou B., additional, Fall, Bécaye, additional, and Pradines, Bruno, additional

Published
2020
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21. Absence of a High Level of Duplication of the Plasmepsin II Gene in Africa

Author

Robert, Marie Gladys, Tsombeng, Francis Foguim, Gendrot, Mathieu, Mosnier, Joel, Amalvict, Remy, Benoit, Nicolas, Torrentino-Madamet, Marylin, Pradines, Bruno, Imported, French Natl Reference Ctr, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Service de Biochimie, Hôpital d'instruction des armées Laveran, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)

Subjects
0301 basic medicine, DNA Copy Number Variations, 030106 microbiology, Plasmodium falciparum, Drug Resistance, Protozoan Proteins, Biology, Epidemiology and Surveillance, 03 medical and health sciences, chemistry.chemical_compound, Antimalarials, Plasmepsin II, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular marker, Piperaquine, Gene duplication, medicine, Aspartic Acid Endopeptidases, Humans, Pharmacology (medical), Malaria, Falciparum, Gene, Pharmacology, Genetics, biology.organism_classification, medicine.disease, In vitro, Artemisinins, 3. Good health, Infectious Diseases, chemistry, Africa, Quinolines, Cambodia, Malaria
Abstract

International audience; Resistance to piperaquine has been associated with the amplification of the plasmepsin II gene in Cambodia. None of the 175 African isolates that we analyzed had plasmepsin II gene amplification (piperaquine 50% inhibitory concentration ranged from 0.94 to 137.5 nM), suggesting there is a low prevalence of piperaquine reduced susceptibility in Africa. Additionally, the few isolates with reduced susceptibility to piperaquine did not harbor amplification of the plasmepsin II gene.

Published
2018

22. Prevalence of Plasmodium falciparum antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014

Author

Voumbo-Matoumona, Dominique Fatima, Kouna, Lady Charlene, Madamet, Marylin, Maghendji-Nzondo, Sydney, Pradines, Bruno, Lekana-Douki, Jean Bernard, Unité de Parasitologie et d’Entomologie [IRBA, Marseille], Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)-Département des Maladies Infectieuses, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées (IRBA)-Département des Maladies Infectieuses, and Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)

Subjects
Pfcrt, Infection and Drug Resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Plasmodium falciparum, antimalarial drug resistance, Gabon, PfK13, Pfdhfr/Pfdhps, Original Research
Abstract

Dominique Fatima Voumbo-Matoumona,1,2,3 Lady Charlène Kouna,4 Marylin Madamet,2,5,6 Sydney Maghendji-Nzondo,4 Bruno Pradines,2,5,6 Jean Bernard Lekana-Douki1,4 1Unit of Evolution, Epidemiology and Parasitic Resistances (UNEEREP), International Medical Research Center of Franceville (CIRMF), Franceville, Gabon; 2Parasitology and Entomology Unit, Department of Infectious Diseases, Biomedical Research Institute of Army, Marseille, France; 3Regional Doctoral School of Central Africa in Tropical Infectiology, Franceville, Gabon; 4Department of Parasitology, Mycology and Tropical Medicine, University of Health Sciences, Libreville, Gabon; 5Research Unit on Infectious and Tropical Emerging Diseases, Aix Marseille University, Marseille, France, 6National Malaria Reference Center, Marseille, France Purpose: The introduction of artemisinin-based combination therapies (ACTs) in treating uncomplicated malaria and sulfadoxine–pyrimethamine (SP) as intermittent preventive treatment during pregnancy drastically decreased the burden of malarial disease around the world. However, ACTs are known to select for drug resistance markers. In Gabon, artemether–­lumefantrine induced an increase in the prevalence of N86-Pfmdr1, which is associated with treatment failure. However, little data are available regarding resistance markers in Southeastern Gabon. This study aimed to evaluate the evolution of resistance haplotypes in the Pfcrt, Pfdhps, Pfdhfr, and PfK13 genes from 2011 to 2014 in Southeastern Gabon. Methods: A total of 233 Plasmodium falciparum DNA samples were collected from febrile pediatric patients in South Gabon: Franceville, an urban area; Koulamoutou, a semi-urban area; and Lastourville, a rural area. Pfcrt, Pfdhps, Pfdhfr, and the propeller domain of PfK13 were sequenced for all isolates. Results: The overall prevalence (3.7%–11.5%) of the wild-type haplotype Pfcrt 72-76 CVMNK was not significantly different between 2011 and 2014 in Southeast Gabon. For Pfdhfr (codons 51, 59, 108, 164), the IRNI triple-mutant haplotype was the most prevalent (>89.0%). The ICNI and NCNI mutant haplotypes and the NCSI wild-type haplotype showed a minor prevalence. There were no differences in the distributions of these haplotypes across the 4 years and the three study sites. For Pfdhps, the AAKAA and SGKAA mutant haplotypes and the SAKAA wild-type haplotype were similarly present in the three areas during the study period. The AGKAA double mutant was first observed in 2013 in Franceville and in 2014 in Koulamoutou and Lastourville. Interestingly, only the A578S mutation (0.4%) and two new A494V (0.4%) and V504A (0.9%) mutations were found in PfK13. Conclusion: Despite the withdrawal of chloroquine, the frequency of the resistant allele 76T remained high in the south of Gabon. Moreover, a high level of resistant haplotypes against IPTp-SP was found. Keywords: Plasmodium falciparum, antimalarial drug resistance, Pfdhfr/Pfdhps, Pfcrt, PfK13, Gabon

Published
2018

23. Modulation of in vitro antimalarial responses by polymorphisms in Plasmodium falciparum ABC transporters (pfmdr1 and pfmdr5)

Author

Gendrot, Mathieu, primary, Wague Gueye, Mamadou, additional, Tsombeng Foguim, Francis, additional, Madamet, Marylin, additional, Wade, Khalifa Ababacar, additional, Bou Kounta, Mame, additional, Fall, Mansour, additional, Diawara, Silman, additional, Benoit, Nicolas, additional, Lo, Gora, additional, Bercion, Raymond, additional, Amalvict, Rémy, additional, Mosnier, Joel, additional, Fall, Bécaye, additional, Briolant, Sébastien, additional, Diatta, Bakary, additional, and Pradines, Bruno, additional

Published
2019
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24. Baseline Ex Vivo and Molecular Responses of Plasmodium falciparum Isolates to Piperaquine before Implementation of Dihydroartemisinin-Piperaquine in Senegal

Author

Robert, Marie Gladys, primary, Foguim Tsombeng, Francis, additional, Gendrot, Mathieu, additional, Diawara, Silman, additional, Madamet, Marylin, additional, Kounta, Mame Bou, additional, Wade, Khalifa Ababacar, additional, Fall, Mansour, additional, Gueye, Mamadou Wague, additional, Benoit, Nicolas, additional, Nakoulima, Aminata, additional, Bercion, Raymond, additional, Amalvict, Rémy, additional, Fall, Bécaye, additional, Wade, Boubacar, additional, Diatta, Bakary, additional, and Pradines, Bruno, additional

Published
2019
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25. Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

Author

Jammes Yves, Fourquet Patrick, Pophillat Matthieu, Belghazi Maya, Priol Yannick, Desplans Jérôme, Alméras Lionel, Torrentino-Madamet Marylin, and Parzy Daniel

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Over its life cycle, the Plasmodium falciparum parasite is exposed to different environmental conditions, particularly to variations in O2 pressure. For example, the parasite circulates in human venous blood at 5% O2 pressure and in arterial blood, particularly in the lungs, at 13% O2 pressure. Moreover, the parasite is exposed to 21% O2 levels in the salivary glands of mosquitoes. Methods To study the metabolic adaptation of P. falciparum to different oxygen pressures during the intraerythrocytic cycle, a combined approach using transcriptomic and proteomic techniques was undertaken. Results Even though hyperoxia lengthens the parasitic cycle, significant transcriptional changes were detected in hyperoxic conditions in the late-ring stage. Using PS 6.0™ software (Ariadne Genomics) for microarray analysis, this study demonstrate up-expression of genes involved in antioxidant systems and down-expression of genes involved in the digestive vacuole metabolism and the glycolysis in favour of mitochondrial respiration. Proteomic analysis revealed increased levels of heat shock proteins, and decreased levels of glycolytic enzymes. Some of this regulation reflected post-transcriptional modifications during the hyperoxia response. Conclusions These results seem to indicate that hyperoxia activates antioxidant defence systems in parasites to preserve the integrity of its cellular structures. Moreover, environmental constraints seem to induce an energetic metabolism adaptation of P. falciparum. This study provides a better understanding of the adaptive capabilities of P. falciparum to environmental changes and may lead to the development of novel therapeutic targets.

Published
2011
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26. The D113N mutation in the RING E3 ubiquitin protein ligase gene is not associated with ex vivo susceptibility to common anti-malarial drugs in African Plasmodium falciparum isolates

Author

Gendrot, Mathieu, Foguim, Francis Tsombeng, Robert, Marie Gladys, Amalvict, Remy, Mosnier, Joel, Benoit, Nicolas, Madamet, Marylin, Pradines, Bruno, Sterkers, Yvon, Group, the French National Reference Centre for Imported Malaria Study, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Service de Biochimie, Hôpital d'instruction des armées Laveran, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Centre National de Référence du Paludisme, Biologie, Génétique et Pathologie des Pathogènes Eucaryotes (MIVEGEC-BioGEPPE), Pathogènes, Environnement, Santé Humaine (EPATH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées

Subjects
0301 basic medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Ubiquitin-Protein Ligases, 030231 tropical medicine, Mutant, Plasmodium falciparum, Resistance, Drug Resistance, Context (language use), Molecular marker, Gene Expression Regulation, Enzymologic, lcsh:Infectious and parasitic diseases, Ligase Gene, 03 medical and health sciences, Antimalarials, 0302 clinical medicine, In vitro, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, RING E3 ubiquitin-protein ligase gene, lcsh:RC109-216, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Artemisinin, chemistry.chemical_classification, DNA ligase, Polymorphism, Genetic, biology, Research, biology.organism_classification, Virology, 3. Good health, Malaria, 030104 developmental biology, Infectious Diseases, Parasitology, chemistry, Africa, Mutation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ex vivo, Anti-malarial drug, medicine.drug
Abstract

International audience; Background: Plasmodium falciparum resistance to artemisinin-based combination therapy has emerged and spread in Southeast Asia. In areas where artemisinin resistance is emerging, the efficacy of combination is now based on partner drugs. In this context, the identification of novel markers of resistance is essential to monitor the emergence and spread of resistance to these partner drugs. The ubiquitylation pathway could be a possible target for anti-malarial compounds and might be involved in resistance. Polymorphisms in the E3 ubiquitin-protein ligase (PF3D7\₀627300) gene could be associated with decreased in vitro susceptibility to anti-malarial drugs.Methods: Plasmodium falciparum isolates were collected from patients hospitalized in France with imported malaria from a malaria-endemic country from January 2015 to December 2016 and, more particularly, from African French-speaking countries. In total, 215 isolates were successfully sequenced for the E3 ubiquitin-protein ligase gene and assessed for ex vivo susceptibility to anti-malarial drugs.Results: The D113N mutation in the RING E3 ubiquitin-protein ligase gene was present in 147 out of the 215 samples (68.4%). The IC50 values for the ten anti-malarial drugs were not significantly different between the wild-type and mutant parasites (p values between 0.225 and 0.933). There was no significant difference in terms of the percentage of parasites with decreased susceptibility between the D113 wild-type and the 133N mutated P. falciparum strains (p values between 0.541 and 1).Conclusion: The present data confirmed the absence of the association between polymorphisms in the RING E3 ubiquitin-protein ligase gene and the ex vivo susceptibility to common anti-malarial drugs in African P. falciparum isolates.

Published
2017

27. Prevalence of Plasmodium falciparum antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014

Author

Voumbo-Matoumona,Dominique Fatima, Kouna,Lady Charlene, Madamet,Marylin, Maghendji-Nzdondo,Sydney, Pradines,Bruno, Lekana-Douki,Jean Bernard, Voumbo-Matoumona,Dominique Fatima, Kouna,Lady Charlene, Madamet,Marylin, Maghendji-Nzdondo,Sydney, Pradines,Bruno, and Lekana-Douki,Jean Bernard

Abstract

Dominique Fatima Voumbo-Matoumona,1,2,3 Lady Charlène Kouna,4 Marylin Madamet,2,5,6 Sydney Maghendji-Nzondo,4 Bruno Pradines,2,5,6 Jean Bernard Lekana-Douki1,4 1Unit of Evolution, Epidemiology and Parasitic Resistances (UNEEREP), International Medical Research Center of Franceville (CIRMF), Franceville, Gabon; 2Parasitology and Entomology Unit, Department of Infectious Diseases, Biomedical Research Institute of Army, Marseille, France; 3Regional Doctoral School of Central Africa in Tropical Infectiology, Franceville, Gabon; 4Department of Parasitology, Mycology and Tropical Medicine, University of Health Sciences, Libreville, Gabon; 5Research Unit on Infectious and Tropical Emerging Diseases, Aix Marseille University, Marseille, France, 6National Malaria Reference Center, Marseille, France Purpose: The introduction of artemisinin-based combination therapies (ACTs) in treating uncomplicated malaria and sulfadoxine–pyrimethamine (SP) as intermittent preventive treatment during pregnancy drastically decreased the burden of malarial disease around the world. However, ACTs are known to select for drug resistance markers. In Gabon, artemether–­lumefantrine induced an increase in the prevalence of N86-Pfmdr1, which is associated with treatment failure. However, little data are available regarding resistance markers in Southeastern Gabon. This study aimed to evaluate the evolution of resistance haplotypes in the Pfcrt, Pfdhps, Pfdhfr, and PfK13 genes from 2011 to 2014 in Southeastern Gabon. Methods: A total of 233 Plasmodium falciparum DNA samples were collected from febrile pediatric patients in South Gabon: Franceville, an urban area; Koulamoutou, a semi-urban area; and Lastourville, a rural area. Pfcrt, Pfdhps, Pfdhfr, and the propeller domain of PfK13 were sequenced for all isolates. Results: The overall prevalence (3.7%–11.5%) of the wild-type haplotype Pfcrt 72-76 CVMNK was not significantly different between 2011 and 2

Published
2018

28. PROVEBLUE, METHYLENE BLUE, AS AN ANTIMALARIAL DRUG

Author

Pradines, Bruno, Gendrot, Mathieu, Amalvict, Remy, Mosnier, Joel, Benoit, Nicolas, Madamet, Marylin, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Hôpital d'instruction des armées Laveran, Unité de Chirurgie et Physiologie Expérimentale, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Centre National de Référence du Paludisme, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées (IRBA), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), and COMBE, Isabelle

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Baltimore, MD, NOV 05-09, 2017; International audience

Published
2017

29. ABSENCE OF ASSOCIATION BETWEEN EX VIVO SUSCEPTIBILITY TO PIPERAQUINE AND POLYMORPHISMS IN EXONUCLEASE GENE AND COPY NUMBERS IN PLASMEPSIN 2 GENE IN AFRICAN PLASMODIUM FALCIPARUM ISOLATES

Author

Madamet, Marylin, Gendrot, Mathieu, Foguim, Francis, Robert, Gladys, Benoit, Nicolas, Amalvict, Remy, Mosnier, Joel, Pradines, Bruno, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Centre National de Référence du Paludisme, Service de Biochimie, Hôpital d'instruction des armées Laveran, Unité de Chirurgie et Physiologie Expérimentale, Institut de Recherche Biomédicale des Armées (IRBA), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and COMBE, Isabelle

Subjects
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Baltimore, MD, NOV 05-09, 2017; International audience

Published
2017

30. Prevalence of mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, and association with ex vivo susceptibility to common anti-malarial drugs against African Plasmodium falciparum isolates.

Author

Foguim, Francis Tsombeng, Bogreau, Hervé, Gendrot, Mathieu, Mosnier, Joel, Fonta, Isabelle, Benoit, Nicolas, Amalvict, Rémy, Madamet, Marylin, Wein, Sharon, Pradines, Bruno, The French National Reference Centre for Imported Malaria Study Group, Augis, V., Bastien, P., Benoit-Vical, F., Berry, A., Brouqui, P., Chauvin, P., Cividin, M., Courtier, F., and Delaunay, P.

Subjects
PLASMODIUM falciparum, DRUG standards, ASIAN Americans, DRUGS, QUININE
Abstract

Background: The Plasmodium falciparum chloroquine transporter gene (pfcrt) is known to be involved in chloroquine and amodiaquine resistance, and more particularly the mutations on the loci 72 to 76 localized within the second exon. Additionally, new mutations (T93S, H97Y, C101F, F145I, M343L, C350R and G353V) were recently shown to be associated with in vitro reduced susceptibility to piperaquine in Asian or South American P. falciparum strains. However, very few data are available on the prevalence of these mutations and their effect on parasite susceptibility to anti-malarial drugs, and more particularly piperaquine in Africa. Methods: A molecular investigation of these mutations was performed in 602 African P. falciparum parasites collected between 2017 and 2018 on malaria patients hospitalized in France after a travel in African countries. Associations between genotypes and in vitro susceptibilities to piperaquine and standard antimalarial drugs were assessed. Results: None of the mutations, previously described as associated with piperaquine resistance, was found in the 602 P. falciparum African isolates. The K76T mutation is associated with resistance to chloroquine (p < 0.0002) and desethylamodiaquine (p < 0.002) in Africa. The K76T mutation is not associated with in vitro reduced susceptibility to piperaquine. The mutation I356T, identified in 54.7% (n = 326) of the African isolates, was significantly associated with reduced susceptibility to quinine (p < 0.02) and increased susceptibility to mefloquine (p < 0.04). The K76T and I356T mutations were significantly associated in West African isolates (p = 0.008). Conclusion: None of the mutations in pfcrt found to be associated with piperaquine reduced susceptibility in Asia or South America (T93S, H97Y, C101F, F145I, M343L C350R and G353V) were found in the 602 African isolates including the three isolates with reduced susceptibility to piperaquine. The K76T mutation, involved in resistance to chloroquine and amodiaquine, and the I356T mutation were not associated with in vitro reduced susceptibility to piperaquine. Differences in mefloquine susceptibility between I356 and 356T isolates were, while statistically different, minimal. Further analyses are needed with a more important sample size from the same geographic area to confirm the role of the I356T mutation on quinine susceptibility. [ABSTRACT FROM AUTHOR]

Published
2020
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33. Malaria prophylaxis failure with doxycycline, central African republic, 2014

Author

Madamet, Marylin, Gaillard, Tiphaine, Velut, Guillaume, Ficko, Cecile, Houze, Pascal, Bylicki, Claire, Merat, Stephane, Houze, Sandrine, Taudon, Nicolas, Michel, Remy, Pasquier, Pierre, Rapp, Christophe, and Pradines, Bruno

Subjects
Antibiotic prophylaxis -- Methods -- Patient outcomes, Doxycycline -- Patient outcomes, Malaria -- Drug therapy, Health
Abstract

To the Editor: Doxycycline is an effective antimalarial prophylactic drug when administered as a monotherapy 1 day before, daily during, and for 4 weeks after travel to an area where [...]

Published
2015
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34. The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine

Author

Madamet, Marylin, Briolant, Sébastien, Amalvict, Rémy, Benoit, Nicolas, Bouchiba, Housem, Cren, Julien, Pradines, Bruno, Malaria, French Natl Ctr Imported, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Direction Interarmées du Service de Santé en Guyane, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Unité de Parasitologie, Centre National de Référence du Paludisme, Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées-Centre National de la Recherche Scientifique (CNRS), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Biomédicale des Armées (IRBA), and Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)

Subjects
0301 basic medicine, Plasmodium falciparum, Resistance, 030106 microbiology, Short Report, Protozoan Proteins, Antimalarial, Drug resistance, Molecular marker, Pharmacology, pfcrt, Antimalarials, Inhibitory Concentration 50, 03 medical and health sciences, In vitro, Parasitic Sensitivity Tests, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, Naphthyridines, Artemisinin, Pyronaridine, biology, Membrane transport protein, Membrane Transport Proteins, medicine.disease, biology.organism_classification, Malaria, 3. Good health, Infectious Diseases, Parasitology, biology.protein, Mutant Proteins, Ex vivo, medicine.drug
Abstract

International audience; Background: The pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (ACTs) recommended for the treatment of uncomplicated P. falciparum malaria. The emergence of P. falciparum resistance to artemisinin has recently developed in Southeast Asia. Little data are available on the association between pyronaridine susceptibility and polymorphisms in genes involved in antimalarial drug resistance. The objective of the present study was to investigate the association between ex vivo responses to pyronaridine and the K76T mutation in the pfcrt gene in P. falciparum isolates. Methods: The assessment of ex vivo susceptibility to pyronaridine was performed on 296 P. falciparum isolates using a standard 42-h 3H-hypoxanthine uptake inhibition method. The K76T mutation was also investigated. Results: The pyronaridine IC50 (inhibitory concentration 50 %) ranged from 0.55 to 80.0 nM. Ex vivo responses to pyronaridine were significantly associated with the K76T mutation (p-value = 0.020). The reduced susceptibility to pyronaridine, defined as IC50 > 60 nM, was significantly associated with the K76T mutation (p-value = 0.004). Using a Bayesian mixture modelling approach, the pyronaridine IC50 were classified into three components: component A (IC50 median 15.9 nM), component B (IC50 median 34.2 nM) and component C (IC50 median 63.3 nM). The K76T mutation was represented in 46.3 % of the isolates in component A, 47.2 % of the isolates in component B and 73.3 % of the isolates in component C (p-value = 0.021). Conclusion: These results showed the ex vivo reduced susceptibility to pyronaridine, i.e., IC50 > 60 nM, associated with the K76T mutation.

Published
2016

36. Confirmation of Plasmodium falciparum in vitro resistance to monodesethylamodiaquine and chloroquine in Dakar, Senegal, in 2015

Author

Diawara, Silman, primary, Madamet, Marylin, additional, Kounta, Mame Bou, additional, Lo, Gora, additional, Wade, Khalifa Ababacar, additional, Nakoulima, Aminata, additional, Bercion, Raymond, additional, Amalvict, Rémy, additional, Gueye, Mamadou Wague, additional, Fall, Bécaye, additional, Diatta, Bakary, additional, and Pradines, Bruno, additional

Published
2017
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37. Association between Polymorphisms in the Pf mdr6 Gene and Ex Vivo Susceptibility to Quinine in Plasmodium falciparum Parasites from Dakar, Senegal

Author

Gendrot, Mathieu, primary, Diawara, Silman, additional, Madamet, Marylin, additional, Kounta, Mame Bou, additional, Briolant, Sébastien, additional, Wade, Khalifa Ababacar, additional, Fall, Mansour, additional, Benoit, Nicolas, additional, Nakoulima, Aminata, additional, Amalvict, Rémy, additional, Diémé, Yaya, additional, Fall, Bécaye, additional, Wade, Boubacar, additional, Diatta, Bakary, additional, and Pradines, Bruno, additional

Published
2017
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40. Absence of Association between Polymorphisms in the RING E3 Ubiquitin Protein Ligase Gene and Ex Vivo Susceptibility to Conventional Antimalarial Drugs in Plasmodium falciparum Isolates from Dakar, Senegal

Author

Gendrot, Mathieu, primary, Fall, Bécaye, additional, Madamet, Marylin, additional, Fall, Mansour, additional, Wade, Khalifa Ababacar, additional, Amalvict, Rémy, additional, Nakoulima, Aminata, additional, Benoit, Nicolas, additional, Diawara, Silman, additional, Diémé, Yaya, additional, Diatta, Bakary, additional, Wade, Boubacar, additional, and Pradines, Bruno, additional

Published
2016
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41. Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 to 2014

Author

Boussaroque, Agathe, primary, Fall, Bécaye, additional, Madamet, Marylin, additional, Wade, Khalifa Ababacar, additional, Fall, Mansour, additional, Nakoulima, Aminata, additional, Fall, Khadidiatou Ba, additional, Dionne, Pierre, additional, Benoit, Nicolas, additional, Diatta, Bakary, additional, Diemé, Yaya, additional, Wade, Boubacar, additional, and Pradines, Bruno, additional

Published
2016
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45. Emergence of Mutations in the K13 Propeller Gene of Plasmodium falciparum Isolates from Dakar, Senegal, in 2013-2014

Author

Boussaroque, Agathe, primary, Fall, Bécaye, additional, Madamet, Marylin, additional, Camara, Cheikhou, additional, Benoit, Nicolas, additional, Fall, Mansour, additional, Nakoulima, Aminata, additional, Dionne, Pierre, additional, Fall, Kadidiatou Ba, additional, Diatta, Bakary, additional, Diémé, Yaya, additional, Wade, Boubacar, additional, and Pradines, Bruno, additional

Published
2016
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48. Prevalence of <em>Plasmodium falciparum</em> antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014.

Author

Voumbo-Matoumona, Dominique Fatima, Kouna, Lady Charlène, Madamet, Marylin, Maghendji-Nzondo, Sydney, Pradines, Bruno, and Lekana-Douki, Jean Bernard

Subjects
PLASMODIUM falciparum, DRUG resistance, MALARIA, PREGNANCY
Abstract

Purpose: The introduction of artemisinin-based combination therapies (ACTs) in treating uncomplicated malaria and sulfadoxine–pyrimethamine (SP) as intermittent preventive treatment during pregnancy drastically decreased the burden of malarial disease around the world. However, ACTs are known to select for drug resistance markers. In Gabon, artemether–­lumefantrine induced an increase in the prevalence of N86-Pfmdr1, which is associated with treatment failure. However, little data are available regarding resistance markers in Southeastern Gabon. This study aimed to evaluate the evolution of resistance haplotypes in the Pfcrt, Pfdhps, Pfdhfr, and PfK13 genes from 2011 to 2014 in Southeastern Gabon. Methods: A total of 233 Plasmodium falciparum DNA samples were collected from febrile pediatric patients in South Gabon: Franceville, an urban area; Koulamoutou, a semi-urban area; and Lastourville, a rural area. Pfcrt, Pfdhps, Pfdhfr, and the propeller domain of PfK13 were sequenced for all isolates. Results: The overall prevalence (3.7%–11.5%) of the wild-type haplotype Pfcrt 72-76 CVMNK was not significantly different between 2011 and 2014 in Southeast Gabon. For Pfdhfr (codons 51, 59, 108, 164), the IRNI triple-mutant haplotype was the most prevalent (>89.0%). The ICNI and NCNI mutant haplotypes and the NCSI wild-type haplotype showed a minor prevalence. There were no differences in the distributions of these haplotypes across the 4 years and the three study sites. For Pfdhps, the AAKAA and SGKAA mutant haplotypes and the SAKAA wild-type haplotype were similarly present in the three areas during the study period. The AGKAA double mutant was first observed in 2013 in Franceville and in 2014 in Koulamoutou and Lastourville. Interestingly, only the A578S mutation (0.4%) and two new A494V (0.4%) and V504A (0.9%) mutations were found in PfK13. Conclusion: Despite the withdrawal of chloroquine, the frequency of the resistant allele 76T remained high in the south of Gabon. Moreover, a high level of resistant haplotypes against IPTp-SP was found. [ABSTRACT FROM AUTHOR]

Published
2018
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49. Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013

Author

Torrentino-Madamet, Marylin, primary, Fall, Bécaye, additional, Benoit, Nicolas, additional, Camara, Cheikhou, additional, Amalvict, Rémy, additional, Fall, Mansour, additional, Dionne, Pierre, additional, Ba Fall, Kadidiatou, additional, Nakoulima, Aminata, additional, Diatta, Bakary, additional, Diemé, Yaya, additional, Ménard, Didier, additional, Wade, Boubacar, additional, and Pradines, Bruno, additional

Published
2014
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50. High prevalence of Plasmodium falciparumantimalarial drug resistance markers in isolates from asymptomatic patients from the Republic of the Congo between 2010 and 2015

Author

Voumbo-Matoumona, Dominique Fatima, Akiana, Jean, Madamet, Marylin, Kouna, Lady Charlène, Lekana-Douki, Jean Bernard, and Pradines, Bruno

Abstract

•Impact of recommended antimalarial treatments on molecular markers of drug resistance after ACT implementation.•Pfcrtanalysis identified new haplotypes in the Congo or mixed alleles.•Pfdhfr+Pfdhpsanalysis showed high level of mutations associated with sulfadoxine–pyrimethamine resistance.•No mutations found in the PfK13propeller domain.

Published
2018
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