المؤلفون: Kentaro Kato, Yoshinori Mitsui

المصدر: Japanese Journal of Infectious Diseases. 71:382-387

مصطلحات موضوعية: 0301 basic medicine, Microbiology (medical), Neutral red, Primaquine, biology, 030231 tropical medicine, General Medicine, Amodiaquine, 030108 mycology & parasitology, Pharmacology, biology.organism_classification, Staining, Praziquantel, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Infectious Diseases, chemistry, Artesunate, parasitic diseases, medicine, Trypan blue, Schistosoma mansoni, medicine.drug

الوصف: The possible emergence of praziquantel (PZQ)-tolerant and/or -resistant schistosomes requires the study and development of new antischistosomal drugs as alternatives to PZQ. The present study investigates the capability of 3 dyes-methylene blue (MB), neutral red (NR), and trypan blue (TB)-to assess the in vitro antischistosomal effect of antimalarial drugs on Schistosoma mansoni adult worms. S. mansoni adult worms were incubated in the medium alone as the control or in the medium supplemented with 10 μg/ml primaquine (PQ), artesunate (AR), or amodiaquine (AQ) for 5 days. Viabilities of the worms were observed following staining with MB, NR, or TB. The disparity of MB and NR staining among male and female adult worms treated with PQ, AR, and AQ correlated with the various levels of damage to the male and female worms. Furthermore, the severity of the damage to the adult worms treated with the 3 drugs appeared to be reflected in the TB staining status. The results indicate that the 3 non-fluorescent dyes can serve as useful complementary tools to assess the antischistosomal effect of antimalarial drugs.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::f9a7743bc5edad638af6ecfd2954af15
https://doi.org/10.7883/yoken.jjid.2018.034

المؤلفون: Alioune Dieye, D. Gora, Ibrahim Maman Laminou, Boubacar Mahamadou, Moustapha Mahamane Lamine, Ibrahim Arzika

المصدر: Journal of Advances in Biology & Biotechnology. 18:1-8

مصطلحات موضوعية: Artemether/lumefantrine, 030231 tropical medicine, Artesunate/amodiaquine, Propeller, Plasmodium falciparum, General Medicine, Biology, medicine.disease, biology.organism_classification, Virology, Treatment failure, 03 medical and health sciences, 0302 clinical medicine, Mutation (genetic algorithm), medicine, 030212 general & internal medicine, Malaria, medicine.drug

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::d009202e6dc507f18d70838050a63379
https://doi.org/10.9734/jabb/2018/42872

المؤلفون: Michal Fried, Ahamadou Youssouf, Sidi M. Niambele, Brian Greenwood, Oumar Attaher, David L. Narum, Alassane Dicko, Almahamoudou Mahamar, Harouna M Soumare, Patrick E. Duffy, Amadou Barry, Djibrilla Issiaka

المصدر: Malaria Journal, Vol 20, Iss 1, Pp 1-7 (2021)
Malaria Journal

مصطلحات موضوعية: medicine.medical_specialty, Antibody to MSP-142, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Plasmodium falciparum, 030231 tropical medicine, Antibodies, Protozoan, Antigens, Protozoan, Amodiaquine, Mali, Chemoprevention, lcsh:Infectious and parasitic diseases, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, Antigen, CSP, Internal medicine, parasitic diseases, medicine, lcsh:RC109-216, 030212 general & internal medicine, Cumulative effect, biology, Research, biology.organism_classification, medicine.disease, Malaria, Infectious Diseases, Parasitology, AMA1, Immunology, Tropical medicine, biology.protein, Seasonal malaria chemoprevention, Antibody, medicine.drug, Seropositivity

الوصف: Background More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP. Methods In 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4–5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-142 and AMA1 by ELISA. Results The prevalence of antibodies to MSP-142 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62–1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44–6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70–5.76, p 42 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64–1.15) and 0.95 ((0.68–1.15), respectively), anti-CSP (1.30 (1.00–1.56) and 1.17 (0.87–1.47)), and anti-AMA-1 (1.45 (1.24–1.68) and 1.41 (1.17–1.64)). Conclusion In an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-142 and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period.

وصف الملف: application/pdf

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2430606c2b7eeeca74a496b60fa97f4e
https://researchonline.lshtm.ac.uk/id/eprint/4659415/1/s12936-020-03542-9.pdf

المؤلفون: Maman Laminou Ibrahim, Jean Louis Ndiaye, Jean Testa, Rafiou Adamou, A. Diallo, David Courtin, Mariama Abdoulaye Louis Padounou, Lamine Mahaman Moustapha

المصدر: Malaria Journal, Vol 20, Iss 1, Pp 1-8 (2021)
Malaria Journal

مصطلحات موضوعية: lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Plasmodium falciparum, Antibodies, Protozoan, P. falciparum, Biology, Chemoprevention, lcsh:Infectious and parasitic diseases, Antimalarials, CSP, Antigen, Immunity, Sulfadoxine, parasitic diseases, medicine, Humans, lcsh:RC109-216, Niger, Malaria, Falciparum, Antibody, Rapid diagnostic test, Research, Amodiaquine, Infant, medicine.disease, biology.organism_classification, Circumsporozoite protein, Drug Combinations, Pyrimethamine, Infectious Diseases, Parasitology, Child, Preschool, Antibody Formation, Immunology, Seasonal malaria chemoprevention, biology.protein, Seasons, GLURP-R2, Malaria

الوصف: Background In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger. Methods This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes. Results The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p Conclusion The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb37f191ec30b772af99cf93ec0e186b
https://doi.org/10.1186/s12936-020-03550-9

المؤلفون: Mateusz M. Plucinski, Eric Mukomena Sompwe, Joris Losimba Likwela, Leah F. Moriarty, Patrick Mitashi Mulopo, Aboubacar Sadou, Dieudonné Mumba Ngoyi, Gireesh Subramaniam, Gauthier Mesia Kahunu, Gerardo Chowell-Puente, Eric S. Halsey, Hypolite Muhindo Mavoko, Sarah E. Schmedes, Sam Jones, Naomi W. Lucchi, Samaly S. Svigel, Junior Matangila Rika, Albert Kutekemeni Kaputu, Nsengi Ntamabyaliro, Mame Niang, Papy Mandoko Nkoli, Jean Jacques Muyembe Tamfum

المصدر: Am J Trop Med Hyg

مصطلحات موضوعية: Male, medicine.medical_specialty, Treatment outcome, Plasmodium falciparum, Drug Resistance, Early detection, wa_395, Uncomplicated malaria, Piperazines, Article, Antimalarials, Virology, Internal medicine, parasitic diseases, medicine, Humans, Artemisinin, Malaria, Falciparum, wb_330, biology, business.industry, Artemether, Lumefantrine Drug Combination, Amodiaquine, Infant, medicine.disease, biology.organism_classification, Monitoring site, Artemisinins, wc_750, Drug Combinations, Infectious Diseases, Congo, Child, Preschool, Quinolines, Parasitology, Female, business, Malaria, medicine.drug

الوصف: Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.

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URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9af1afaf199f9dbdd806d783734e78e2

المؤلفون: Jane Achan, Mamadou Bah, John S. Bradley, Jean-Pierre Van Geertruyden, Umberto D'Alessandro, Mamadou Ousmane Ndiath, Abdullahi Ahmad, Aurelia Prom, Teun Bousema, Blessed Etoketim, Chris Drakeley

المصدر: Malaria Journal, 20
Malaria Journal
Malaria Journal, 20, 1
Malaria Journal, Vol 20, Iss 1, Pp 1-8 (2021)
Malaria journal

مصطلحات موضوعية: Male, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Plasmodium falciparum, Amodiaquine, Asymptomatic, Chemoprevention, lcsh:Infectious and parasitic diseases, Antimalarials, All institutes and research themes of the Radboud University Medical Center, Internal medicine, parasitic diseases, medicine, Gametocyte, Humans, lcsh:RC109-216, Malaria, Falciparum, Child, Asymptomatic Infections, biology, business.industry, Research, medicine.disease, biology.organism_classification, musculoskeletal system, Gametocyte carriage, Infectious Diseases, Carriage, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Parasitology, Child, Preschool, Tropical medicine, Carrier State, cardiovascular system, Seasonal malaria chemoprevention, Female, Gambia, Human medicine, Seasons, medicine.symptom, business, Malaria, medicine.drug

الوصف: Background Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children. Methods The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24–59 months old who were eligible to receive SMC (SMC group) and children 5–8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression. Results During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14–2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20–4.95; p = 1.0). Conclusion In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.

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URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4a60ce99d2b1f70b7e181f58d884947
http://hdl.handle.net/2066/238220

المؤلفون: Patrick De Mol, Georges Lelo Mvumbi, Hippolyte Situakibanza, Dieudonné Makaba Mvumbi, Pius Zakayi Kabututu, Doudou Malekita Yobi, Niko Speybroeck, Nadine Kalenda Kayiba, Raphaël Boreux, Marie-Pierre Hayette, Solange E. Umesumbu

المساهمون: UCL - SSS/IRSS - Institut de recherche santé et société

المصدر: Malaria Journal, Vol. 20, no.1, p. 8p. (2021)
Malaria Journal
Malaria Journal, Vol 20, Iss 1, Pp 1-8 (2021)

مصطلحات موضوعية: Male, Resistance, Failure, Drug Resistance, Protozoan Proteins, Drug resistance, Treatment Failure, Artemisinin, Child, Rapid diagnostic test, biology, Middle Aged, Artemisinins, Drug Combinations, Infectious Diseases, Child, Preschool, Democratic Republic of the Congo, Female, Multidrug Resistance-Associated Proteins, medicine.drug, Adult, Genetic Markers, lcsh:Arctic medicine. Tropical medicine, Adolescent, lcsh:RC955-962, Plasmodium falciparum, Amodiaquine, lcsh:Infectious and parasitic diseases, Antimalarials, Young Adult, parasitic diseases, TaqMan, medicine, Humans, lcsh:RC109-216, Aged, Markers, business.industry, Research, Artemether, Lumefantrine Drug Combination, Infant, Newborn, Molecular, Infant, Membrane Transport Proteins, medicine.disease, biology.organism_classification, Democratic Republic of Congo, Virology, Treatment, Parasitology, Anti-malarial, business, Malaria

الوصف: Background The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo. Methods From November 2018 to November 2019, dried blood spots were taken from patients returning to health centres for fever within 28 days after an initial malaria treatment in six sentinel sites of the National Malaria Control Programme across Democratic Republic of Congo. The new episode of malaria was first detected by a rapid diagnostic test and then confirmed by a real-time PCR assay to define treatment failure. Fragments of interest in pfk13 and pfcrt genes were amplified by conventional PCR before sequencing and the Pfmdr1 gene copy number was determined by a TaqMan real-time PCR assay. Results Out of 474 enrolled patients, 364 (76.8%) were confirmed positive by PCR for a new episode of P. falciparum malaria, thus considered as treatment failure. Of the 325 P. falciparum isolates obtained from 364 P. falciparum-positive patients and successfully sequenced in the pfk13-propeller gene, 7 (2.2%) isolates carried non-synonymous mutations, among which 3 have been previously reported (N498I, N554K and A557S) and 4 had not yet been reported (F506L, E507V, D516E and G538S). Of the 335 isolates successfully sequenced in the pfcrt gene, 139 (41.5%) harboured the K76T mutation known to be associated with chloroquine resistance. The SVMNT haplotype associated with resistance to amodiaquine was not found. None of the isolates carried an increased copy number of the pfmdr1 gene among the 322 P. falciparum isolates successfully analysed. Conclusion No molecular markers currently known to be associated with resistance to the first-line ACT in use were detected in isolates of P. falciparum from treatment failure patients. Regular monitoring through in vivo drug efficacy and molecular studies must continue to ensure the effectiveness of malaria treatment in Democratic Republic of Congo.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::919b54dd7d01d16acaba5fc8801b2255
https://hdl.handle.net/2078.1/244409

المؤلفون: Offianan Andre Toure, Eric A. Gbessi, Tossea A Stephane Koui, Didier-Paulin Sokouri, Ronan Jambou, Albert Alloh Gnondjui, Ibrahima Sanogo, Nguessan L. Tiacoh, Berenger Aristide Ako, Serge-Brice Assi, Baba Coulibaly

المساهمون: Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Institut Pierre Richet (IPR), CHU de Youpougon, Université Félix Houphouët-Boigny (UFHB), Département de Santé Globale - Department Global Health, Institut Pasteur [Paris], We are grateful to the participants, medical staff, and all health authorities at the study sites for their collaboration. The authors would also like to acknowledge the National Malaria Control Program (PNLP-CI), WHO, Global Fund and Rotary International., Institut Pasteur [Paris] (IP)

المصدر: Parasite
Parasite, EDP Sciences, 2021, 28, pp.67. ⟨10.1051/parasite/2021063⟩
Parasite, 2021, 28, pp.67. ⟨10.1051/parasite/2021063⟩
Parasite, Vol 28, p 67 (2021)

مصطلحات موضوعية: Hemoglobins, Abnormal, Infectious and parasitic diseases, RC109-216, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Artemisinin, Malaria, Falciparum, 0303 health sciences, education.field_of_study, Artesunate/amodiaquine, Artemisinins, 3. Good health, Drug Combinations, Infectious Diseases, Hemoglobinopathy, Treatment Outcome, Ethanolamines, Artemether, Ivory Coast, medicine.drug, Research Article, medicine.medical_specialty, artemisinin containing therapy, Veterinary (miscellaneous), 030231 tropical medicine, Population, Plasmodium falciparum, malaria, Biology, 03 medical and health sciences, Antimalarials, Internal medicine, parasitic diseases, medicine, Humans, education, 030304 developmental biology, Retrospective Studies, Artemether, Lumefantrine Drug Combination, medicine.disease, biology.organism_classification, Abnormal hemoglobin, Cote d'Ivoire, Insect Science, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Animal Science and Zoology, Parasitology, Hemoglobin, Malaria

الوصف: Artemisinin-based treatment in malaria patients with abnormal hemoglobin may be ineffective because of their genetic particularity, which could lead to resistance. The main purpose of this study was to assess the effect of artemisinin derivatives on in vivo parasite clearance according to erythrocyte variants. In vivo response was investigated through retrospective data obtained over a 42-day artemether-lumefantrine/artesunate amodiaquine efficacy protocol conducted from 2012 to 2016.A total of 770 patients in Côte d'Ivoire attending the hospitals of Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé and Yamoussoukro with acute uncomplicated falciparum malaria were selected for successful hemoglobin typing. HbAS, HbSS, HbAC, and HbSC genotypes were found. Parasite clearance time was obtained for 414 patients. In the population with abnormal hemoglobin, parasite densities on admission and parasite clearance rates were significantly lower in the HbSC group compared to HbAA (p = 0.02 and p = 0.007, respectively). After PCR correction on day 42, the acute treatment rate was 100% for each group. Parasite half-life and time for initial parasitaemia to decline by 50 and 99% were longer for the HbSC group (p0.05). The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups. A total of 185 and 63 samples were sequenced in the HbAA group and patients with abnormal Hb, respectively. Only two nonsynonymous mutations D559N and V510M were found in the HbAA group.Although this study proved good efficacy of artemether-lumefantrine and artesunate amodiaquine in the treatment of uncomplicated Plasmodium falciparum malaria in patients with abnormal hemoglobin, the increased delay of parasite clearance may represent a threat to health in these patients in relation with sickle cell crisis, which could support selection of parasites resistant to artemisinin.Thérapies contenant des dérivés de l’artémisinine et hémoglobine anormale : faut-il adapter le traitement ?Contexte : Le traitement à base d’artémisinine chez les patients atteints de paludisme et présentant une hémoglobine anormale peut être inefficace en raison de leur particularité génétique, ce qui pourrait entraîner une résistance. L’objectif principal de cette étude était d’évaluer in vivo l’effet des dérivés de l’artémisinine sur la clairance du parasite en fonction des variantes érythrocytaires. La réponse in vivo a été étudiée à travers des données rétrospectives obtenues au cours d’un protocole d’efficacité de 42 jours artéméther-luméfantrine/artésunate-amodiaquine mené dans les années 2012 à 2016. Résultats : Un total de 770 patients en Côte d’Ivoire fréquentant les hôpitaux d’Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé et Yamoussoukro, présentant un paludisme aigu non compliqué à falciparum ont été sélectionnés pour un typage réussi de l’hémoglobine. Les génotypes HbAS, HbSS, HbAC et HbSC ont été trouvés. Le temps de clairance du parasite a été obtenu pour 414 patients. Dans la population avec une hémoglobine anormale, les densités parasitaires à l’admission et le taux de clairance parasitaire étaient significativement plus faibles dans le groupe HbSC par rapport au groupe HbAA (respectivement, p = 0,02 et p = 0,007). Le RCPA était de 100 % pour chaque groupe après correction par PCR au jour 42. La demi-vie du parasite et le temps nécessaire pour que la parasitémie initiale diminue de 50 et 99 % étaient plus longs pour le groupe HbSC (p0,05). L’étude a également examiné la prévalence des polymorphismes du gène K13 dans différents groupes de génotype d’hémoglobine. Un total de 185 et 63 échantillons ont été séquencés respectivement dans le groupe HbAA et chez les patients présentant une Hb anormale. Seules deux mutations non synonymes D559N et V510M ont été trouvées dans le groupe HbAA. Conclusion : Bien que cette étude ait prouvé la bonne efficacité de l’artéméther-luméfantrine et de l’artésunate amodiaquine dans le traitement du paludisme simple à Plasmodium falciparum chez les patients présentant une hémoglobine anormale, le retard accru de clairance parasitaire peut représenter une menace pour la santé de ces patients en relation avec la crise drépanocytaire, et peut favoriser la sélection de parasites résistants à l’artémisinine.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5596d34b05fa4727a4ba17797c25ccb
https://hal.archives-ouvertes.fr/hal-03356316/file/parasite210034.pdf

المؤلفون: Manoj S. Nair, Jessica Wagoner, David A. Fidock, Pamela J. Weathers, Stephen J. Polyak, Yaoxing Huang, Melissa J. Towler

المصدر: Journal of Ethnopharmacology

مصطلحات موضوعية: medicine.medical_treatment, Artemisia annua, artemether, ASAQ, artesunate amodiaquine, Artesunate, Dihydroartemisinin, Amodiaquine, Article, Virus, DW, dry weight, dihydroartemisinin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, medicine, Deoxyartemisinin, Artemether, Artemisinin, IC50, 030304 developmental biology, ACT, artemisinin combination therapy, Pharmacology, 0303 health sciences, biology, Traditional medicine, SARS-CoV-2, EMEM, Essential Minimal Eagle’s Medium, fungi, DLA, dried leaf Artemisia, biology.organism_classification, artemisinin, chemistry, 030220 oncology & carcinogenesis, Vero cell, Covid-19, medicine.drug

الوصف: Ethnopharmacological relevance Artemisia annua L. has been used for millennia in Southeast Asia to treat “fever”. Many infectious microbial and viral diseases have been shown to respond to A. annua and communities around the world use the plant as a medicinal tea, especially for treating malaria. Aim of the Study SARS-CoV-2 (the cause of Covid-19) globally has infected and killed millions of people. Because of the broad-spectrum antiviral activity of artemisinin that includes blockade of SARS-CoV-1, we queried whether A. annua suppressed SARS-CoV-2. Materials and Methods Using Vero E6 and Calu-3 cells, we measured anti viral activity SARS-CoV-2 activity against fully infectious virusof dried leaf extracts of seven cultivars of A. annua sourced from four continents. IC50s were calculated and defined as (the concentrations that inhibited viral replication by 50%.) and CC50s (the concentrations that kill 50% of cells) were calculated. Results Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC50 values of 0.1-8.7 μM, 0.01-0.14 μg, and 23.4-57.4 μg, respectively. Antiviral efficacy did not correlate with artemisinin or total flavonoid contents of the extracts. One dried leaf sample was >12 years old, yet the hot-water extract was still found to be active. The UK and South African variants, B1.1.7 and B1.351, were similarly inhibited. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts. Artemisinin alone showed an estimated IC50 of about 70 μM, and the clinically used artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC50 = 5.8 μM. Extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude above the antiviral IC90 values. Conclusions A. annua extracts inhibit SARS-CoV-2 infection, and the active component(s) in the extracts is likely something besides artemisinin or a combination of components that block virus infection at a step downstream of virus entry. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.
Graphical abstract Image 1

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c6b252e2c8d97d88113c021995a6e8a2
https://doi.org/10.1016/j.jep.2021.114016

المؤلفون: Sachel Mok, Kathryn J. Wicht, David A. Fidock

المصدر: Annu Rev Microbiol

مصطلحات موضوعية: Plasmodium falciparum, Drug Resistance, Protozoan Proteins, ATP-binding cassette transporter, Amodiaquine, Drug resistance, Vacuole, Microbiology, Article, 03 medical and health sciences, Antimalarials, Chloroquine, Piperaquine, parasitic diseases, medicine, Humans, Artemisinin, Malaria, Falciparum, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Membrane Transport Proteins, biology.organism_classification, Artemisinins, Mutation, Quinolines, medicine.drug

الوصف: Understanding and controlling the spread of antimalarial resistance, particularly to artemisinin and its partner drugs, is a top priority. Plasmodium falciparum parasites resistant to chloroquine, amodiaquine, or piperaquine harbor mutations in the P. falciparum chloroquine resistance transporter (PfCRT), a transporter resident on the digestive vacuole membrane that in its variant forms can transport these weak-base 4-aminoquinoline drugs out of this acidic organelle, thus preventing these drugs from binding heme and inhibiting its detoxification. The structure of PfCRT, solved by cryogenic electron microscopy, shows mutations surrounding an electronegative central drug-binding cavity where they presumably interact with drugs and natural substrates to control transport. P. falciparum susceptibility to heme-binding antimalarials is also modulated by overexpression or mutations in the digestive vacuole membrane–bound ABC transporter PfMDR1 ( P. falciparum multidrug resistance 1 transporter). Artemisinin resistance is primarily mediated by mutations in P. falciparum Kelch13 protein (K13), a protein involved in multiple intracellular processes including endocytosis of hemoglobin, which is required for parasite growth and artemisinin activation. Combating drug-resistant malaria urgently requires the development of new antimalarial drugs with novel modes of action.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ccb176f9d48d154fca187657df4e10c
https://europepmc.org/articles/PMC8130186/