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1. Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis

Author

Pedro Rafael Dimbu, Marit De Wit, Kamala L. Thriemer, Sarah G. Staedke, Filomeno Fortes, Salim Abdulla, Julie A. Simpson, Oliver James Pratt, Bart Janssens, Andreas Mårtensson, Veronique Sinou, Steffen Borrmann, Walter R. J. Taylor, Ingrid van der Broek, Christopher J. M. Whitty, Meghna Desai, François Bompart, Zulfikarali Premji, Theonest K. Mutabingwa, Aarti Agarwal, Anupkumar R. Anvikar, Emmanuel Arinaitwe, Petra F. Mens, Piero Olliaro, François Nosten, Maman Laminou Ibrahim, Birgit Schramm, Hasifa Bukirwa, Michèle van Vugt, Jane Achan, J. Pedro Gil, Timothy M. E. Davis, Ogobara K. Doumbo, Michel Cot, Grant Dorsey, Michael Ramharter, Sue J. Lee, Sodiomon B. Sirima, Ambrose O. Talisuna, Poul-Erik Kofoed, Brian Greenwood, Catherine O. Falade, Valerie Lameyre, Mayfong Mayxay, Andre Toure Offianan, Hervé Ei Menan, Teun Bousema, Erasmus Kamugisha, Chris J. Drakeley, Elizabeth Juma, Johan Ursing, Abul Faiz, Emmanuel Temu, Carol Hopkins Sibley, Patrice Piola, Philip J. Rosenthal, Frank Smithuis, Mateusz M. Plucinski, Marco Corsi, Anastasia Grivoyannis, Richard Allan, Elizabeth A. Ashley, Harald Noedl, Jean François Faucher, Issaka Zongo, Corine Karema, Cornelis Winnips, Kamal Hamed, Umberto D'Alessandro, Venkatachalam Udhayakumar, Michael D. Edstein, Fred Kironde, Harin Karunajeewa, Philippe Deloron, Quique Bassat, Patrick Sawa, David P. Hughes, Ishag Adam, Michel Van Herp, Christopher V. Plowe, Ghulam Rahim Awab, Caterina I. Fanello, Joel Tarning, Stephan Duparc, Jean Bosco Ouedraogo, Emmanuelle Espie, Tran Tinh Hien, Jean R. Kiechel, Anders Björkman, Abdoulaye Djimde, Billy E. Ngasala, Nahla B. Gadalla, Prabin Dahal, Kasia Stepniewska, Lars Rombo, Nhien Nguyen Thuy, Philippe J Guerin, Verena I. Carrara, Babacar Faye, Christophe Rogier, Peter G. Kremsner, Oumar Gaye, Inge Sutanto, Jean-Louis A Ndiaye, Bernhards Ogutu, Mary Oguike, Vincent Jullien, Jimee Hwang, Kevin Marsh, Djibrine Djalle, Ric N. Price, Yavo William, Georgina S Humphreys, WorldWide Antimalarial Resistance Network (WWARN), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), University of Oxford-Churchill Hospital Oxford Centre for Haematology, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Infectious diseases, AII - Infectious diseases, APH - Global Health, and APH - Quality of Care

Subjects
[SDV]Life Sciences [q-bio], Network Meta-Analysis, Infektionsmedicin, Plasmodium falciparum/drug effects, Polymerase Chain Reaction, 0302 clinical medicine, Dihydroartemisinin/piperaquine, Recurrence, Cumulative incidence, 030212 general & internal medicine, Antimalarials/pharmacology, Malaria, Falciparum, biology, Malaria, Falciparum/drug therapy, food and beverages, 3. Good health, Infectious Diseases, Meta-analysis, Regression Analysis, Competing risk even, Risk, Treatment efficacy study, Infectious Medicine, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Malària, Competing risks, lcsh:Infectious and parasitic diseases, Antimalarials, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Humans, lcsh:RC109-216, business.industry, Methodology, medicine.disease, biology.organism_classification, Malaria, Competing risk event, Parasitology, Tropical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. Conclusions The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings. Electronic supplementary material The online version of this article (10.1186/s12936-019-2837-4) contains supplementary material, which is available to authorized users.

Published
2019
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2. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data

Author

Ouédraogo J-B., Bertrand Lell, Sanjeev Krishna, Ogobara K. Doumbo, Mbaye Pene, Emiliana Tjitra, Ric N. Price, I Van den Broek, Jennifer A. Flegg, Christian Nsanzabana, Faucher J-F., Jean-René Kiechel, Sue J. Lee, Nicholas J. White, Issaka Zongo, Adoke Yeka, Sodiomon B. Sirima, Halidou Tinto, Michel Vaillant, Etard J-F., K Sylla, Sarah G. Staedke, Andreas Mårtensson, Louis K. Penali, Meghna Desai, Martin M Meremikwu, M A Adjuik, Elizabeth A. Ashley, Peter W. Gething, Sally Hamour, Claude Rwagacondo, Clarissa Moreira, Moses R. Kamya, François Bompart, Julie Thwing, Prabin Dahal, Armedy Ronny Hasugian, Elizabeth Juma, Francesco Grandesso, Hasifa Bukirwa, Loretxu Pinoges, Vincent Jullien, Philip J. Rosenthal, Simon I. Hay, Ndiaye J-L., Raquel González, Bhawna Sharma, D Sow, Anup Anvikar, Neena Valecha, E Espié, Frank Smithuis, Didier Menard, Philippe Deloron, Carol Hopkins Sibley, Peter G. Kremsner, M S Ba, Anders Björkman, Albert Same-Ekobo, Todd D. Swarthout, G Diap, Taylor Wrj., Michael Nambozi, Georgina S Humphreys, Caterina I. Fanello, Tine Rck., Karen I. Barnes, Carolyn Nabasumba, Achille Massougbodji, Hervé Ei Menan, Jeff Smith, A Seck, Patrice Piola, Babacar Faye, Richard Allan, Philippe J Guerin, Corine Karema, Frederic Nikiema, Ambrose O. Talisuna, Véronique Sinou, E A Temu, Lyda Osorio, Gaye O, Piero Olliaro, Francine Ntoumi, Michel Cot, Grant Dorsey, Maryline Bonnet, Hubert Barennes, Birgit Schramm, Umberto D'Alessandro, Kasia Stepniewska, Elisabeth Baudin, Steffen Borrmann, Abdoulaye Djimde, Bernards Ogutu, Guthmann J-P., L M Ibrahim, Francesco Checchi, Fabrice A. Somé, Valerie Lameyre, Clara Menéndez, Quique Bassat, Philippe Brasseur, Cally Roper, Joel Tarning, WorldWide Antimalarial Resistance Network (WWARN), University of Washington [Seattle], National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Epicentre [Paris] [Médecins Sans Frontières], Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Centre Muraz [Bobo-Dioulasso, Burkina Faso], Universitat de Barcelona (UB), Karolinska Institutet [Stockholm], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM), Institut de Recherche pour le Développement (IRD), University of Oxford-Churchill Hospital Oxford Centre for Haematology, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Département d'épidémiologie des affections parasitaires (DEAP), Université de Bamako-Malaria Research and Training Center (MRTC)-Facultés de Médecine, de Pharmacie et d'Odonto-Stomatologie-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Malaria Research and Training Centre, Université de Bamako-Faculty of Medicine, Pharmacy, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Mahidol Oxford Tropical Medicine Research Unit, University of Oxford-Mahidol University [Bangkok], Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), WorldWide Antimalarial Resistance Network (WWARN) (WWARN), University of Oxford, Università degli Studi di Milano = University of Milan (UNIMI), Institut de Veille Sanitaire (INVS), Institute for Health Metrics and Evaluation [University of Washington], Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), University of Tübingen, Division of Cellular and Molecular Medicine, St George's University of London, Sanofi-Aventis R&D, SANOFI Recherche, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Department of Microbiology, Tumour and Cell biology [Stockholm, Sweden] (Malaria Research), Faculté des Sciences de la Santé de Cotonou (Faculté des Sciences de la Santé de Cotonou), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), Institut Pasteur du Cambodge, Universidad de la República [Montevideo] (UDELAR), Nuffield Department of Clinical Medicine [Oxford], Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Tropical Diseases Research Center (TDRC), Université Marien Ngouabi, Kenya Medical Research Institute (KEMRI), WHO-TDR Suisse, WHO-TDR Suisse-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Universidad del Valle [Cali] (Univalle), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), World Wide Antimalarial Resistance Network [West Africa] (WWARN-West Africa Regional Centre), University of Washington [Seattle]-University of Washington [Seattle], Institut Pasteur de Madagascar, Global Health Division, Menzies School of Health Research, 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 Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Service de Parasitologie-Mycologie Médicale, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Université de Bordeaux Ségalen [Bordeaux 2], WWARN is funded by a Bill and Melinda Gates Foundation grant., The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, We thank the patients and all the staff who participated in these clinical trials at all the sites and the WWARN team for technical and administrative support., Université de Washington Seattle, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, University of Oxford [Oxford]-University of Oxford [Oxford], Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), University of California [San Francisco] (UCSF), University of California, University of Oxford [Oxford]-Mahidol University [Bangkok], Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Università degli Studi di Milano [Milano] (UNIMI), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], University of Abomey Calavi (UAC), Universidad de la República [Montevideo] (UCUR), Université de Washington Seattle-Université de Washington Seattle, and Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Male, Artemether/lumefantrine, Artesunate, Infektionsmedicin, MESH: Africa, Pharmacology, Gastroenterology, MESH: Dose-Response Relationship, Drug, Efficacy, chemistry.chemical_compound, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Recurrence, Risk Factors, Malaria, Falciparum, MESH: Treatment Outcome, MESH: Middle Aged, MESH: Malaria, Falciparum, Artesunate/amodiaquine, Hazard ratio, General Medicine, Middle Aged, Artemisinins, 3. Good health, Drug Combinations, Dosing, Treatment Outcome, Female, medicine.drug, Research Article, medicine.medical_specialty, Infectious Medicine, Fixed-dose combination, Plasmodium falciparum, Amodiaquine, Antimalarials, Internal medicine, MESH: Artemisinins, medicine, Humans, MESH: Amodiaquine, MESH: Drug Combinations, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Antimalarials, MESH: Male, MESH: Recurrence, Malaria, chemistry, Drug resistance, Africa, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, business, MESH: Female
Abstract

Background Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P

Published
2015
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3. Multicentre study evaluating the non-inferiority of the new paediatric formulation of artesunate/amodiaquine versus artemether/lumefantrine for the management of uncomplicated Plasmodium falciparum malaria in children in Cameroon, Ivory Coast and Senegal

Author

Claude A Kakpo, Koné Moussa, Thérèse Nkoa, Khadime Sylla, Babacar Faye, Albert Same-Ekobo, Jean Louis Ndiaye, Roger Tine, Christiane P Kiki-Barro, Oumar Faye, Oumar Gaye, Thomas Kuete, and Hervé Ei Menan

Subjects
Male, Pediatrics, Artemether/lumefantrine, Chemistry, Pharmaceutical, Pharmacology, Parasite Load, chemistry.chemical_compound, Artemether, Cameroon, Malaria, Falciparum, Child, Children, biology, Artesunate/amodiaquine, Artemisinins, Senegal, Drug Combinations, Infectious Diseases, Treatment Outcome, Ethanolamines, Child, Preschool, Female, medicine.drug, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Amodiaquine, Lumefantrine, lcsh:Infectious and parasitic diseases, Antimalarials, Artesunate plus Amodiaquine, parasitic diseases, West Africa, medicine, Humans, lcsh:RC109-216, Fluorenes, business.industry, Research, Artemether, Lumefantrine Drug Combination, Infant, Plasmodium falciparum, biology.organism_classification, medicine.disease, Malaria, Cote d'Ivoire, chemistry, Artesunate, Parasitology, business
Abstract

Background This multicentre study was carried out in Cameroon, Ivory Coast and Senegal to evaluate the non-inferiority of the new paediatric formulation of artesunate/amodiaquine (AS+AQ)(Camoquin-Plus Paediatric®) in suspension form versus artemether/lumefantrine (AL)(Coartem®) in the management of African children with uncomplicated falciparum malaria. Methods It was an open randomized trial including children aged between 7 months and 7 years. The endpoints were Adequate Clinical and Parasitological Response (ACPR) at day 28, the clinical and biological tolerability. Statistical analyses were done in Intention To Treat (ITT) and in Per protocol (PP). Results At the end of the study 481 patients were enrolled in the three countries (249 in the AS+AQ arm and 232 in the AL arm). ACRP in ITT after PCR correction did not show any statistical difference between the two groups with 97.6% for AS+AQ versus 94.8% for AL. In the PP analysis, the corrected ACRP were respectively 98.7% and 96.9% for the two regimens. The clinical tolerance was good without significant difference. Anaemia was significantly higher at D7 in the two groups compared to D0. Conclusion This study demonstrates the non-inferiority of AS+AQ versus AL, its efficacy and tolerance in the management of uncomplicated Plasmodium falciparum malaria in African children.

Published
2012

4. Genetic Polymorphism of msp1 and msp2 in Plasmodium falciparum Isolates from Côte d'Ivoire versus Gabon.

Author

Yavo W, Konaté A, Mawili-Mboumba DP, Kassi FK, Tshibola Mbuyi ML, Angora EK, Menan EI, and Bouyou-Akotet MK

Abstract

Introduction. The characterization of genetic profile of Plasmodium isolates from different areas could help in better strategies for malaria elimination. This study aimed to compare P. falciparum diversity in two African countries. Methods. Isolates collected from 100 and 73 falciparum malaria infections in sites of Côte d'Ivoire (West Africa) and Gabon (Central Africa), respectively, were analyzed by a nested PCR amplification of msp1 and msp2 genes. Results. The K1 allelic family was widespread in Côte d'Ivoire (64.6%) and in Gabon (56.6%). For msp2, the 3D7 alleles were more prevalent (>70% in both countries) compared to FC27 alleles. In Côte d'Ivoire, the frequencies of multiple infections with msp1 (45.1%) and msp2 (40.3%) were higher than those found for isolates from Gabon, that is, 30.2% with msp1 and 31.4% with msp2. The overall complexity of infection was 1.66 (SD = 0.79) in Côte d'Ivoire and 1.58 (SD = 0.83) in Gabon. It decreased with age in Côte d'Ivoire in contrast to Gabon. Conclusion. Differences observed in some allelic families and in complexity profile may suggest an impact of epidemiological facies as well as immunological response on genetic variability of P. falciparum.

Published
2016
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5. Efficacy and Safety of Artesunate-Amodiaquine versus Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium falciparum Malaria in Sentinel Sites across Côte d'Ivoire.

Author

Yavo W, Konaté A, Kassi FK, Djohan V, Angora EK, Kiki-Barro PC, Vanga-Bosson H, and Menan EI

Abstract

Two years after the introduction of free Artesunate-Amodiaquine (ASAQ) and Artemether-Lumefantrine (AL) for the treatment of uncomplicated malaria in public health facilities in Côte d'Ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. It was a multicentre open randomised clinical trial of 3-day ASAQ treatment against AL for the treatment of 2 parallel groups of patients aged 2 years and above. The endpoints were (1) Adequate Clinical and Parasitological Response (ACPR) at day 28 and (2) the clinical and biological tolerability. Of the 300 patients who were enrolled 289, with 143 (49.5%) and 146 (50.5%) in the ASAQ and AL groups, respectively, correctly followed the WHO 2003 protocol we used. The PCR-corrected ACPR was 99.3% for each group. More than 94% of patients no longer showed signs of fever, 48 hours after treatment. Approximately 78% of the people in the ASAQ group had a parasite clearance time of 48 hours or less compared to 81% in the AL group (p = 0.496). Both drugs were found to be well tolerated by the patients. This study demonstrates the effectiveness and tolerability of ASAQ and AL supporting their continuous use for the treatment of uncomplicated P. falciparum malaria infection in Côte d'Ivoire.

Published
2015
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6. [Intestinal helminthiasis among school children: preliminary results of a prospective study in Agboville in Southern Côte d'Ivoire].

Author

Agbaya SS, Yavo W, Menan EI, Attey MA, Kouadio LP, and Koné M

Subjects
Child, Cote d'Ivoire, Female, Helminthiasis economics, Humans, Hygiene, Intestinal Diseases, Parasitic economics, Male, Prospective Studies, Recurrence, Developing Countries, Helminthiasis etiology, Intestinal Diseases, Parasitic etiology, Social Class
Abstract

Intestinal helminthiasis affects the health and academic performance of children in developing countries. To highlight a few socio-economic factors that impact the presence and upholding of intestinal helminthiasis, a cohort study was performed from February to June 2001. This study took place in Agboville in Southern Côte d'Ivoire on 363 children, under the age of 15, regularly enrolled in school and selected by two-step clustered sampling. After the survey was completed, their stools were examined using 3 methods: direct exam, Kato's technique, and Graham's anal scotch-test. Infected students received an appropriate anti-helminthic treatment. After performing a test two weeks later, a new sample of 348 parasite-free children was made up and re-examined after three months, through the aforementioned techniques. In this sample, we assumed that students who were infested in the initial exam were "exposed", while those who were not infested in the first place were deemed to be "not exposed". The results showed that 135 students out of the 360 admitted for the first exam were infested; or a 37.5% of intestinal helminthiasis prevalence (IC95%=30.5-45). The prevalent parasite species were Necator americanus (15%), Trichuris trichiura (13.6%), Schistosoma mansoni (10%). Twenty-eight per cent of 135 infested students were infected by more than one parasite. After three months, the incidence rate of intestinal helminthiasis calculated out of the remaining 336 students was 7.7% (IC95%=4.4-13.1). The likelihood of re-infestation amounted to 3.4 (IC95%=1.5-7.3). The pattern of re-infestation rates according to socio-economic factors differed from that of infested prevalence. The prevalent parasites in re-infested patients were Trichuris trichiura (16.3%), Schistosoma mansoni (12.5%). All intestinal nematodes and Schistosoma mansoni were observed. The most frequent parasites species where those transmitted cutaneously. The high re-infestation rate suggests that intestinal helminthiasis in this region affects roughly the same children. These results show the necessity to continue our investigations in order to highlight essential hygienic factors in our long-term fight against intestinal helminthiasis.

Published
2004

7. [Antimalaria drug delivery in pharmacies in non-severe malaria treatment. A survey on the quality of the treatment: the case of Bouaké (Côte d'Ivoire)].

Author

Kiki-Barro CP, Konan FN, Yavo W, Kassi R, Menan EI, Djohan V, and Koné M

Subjects
Cote d'Ivoire, Drug Administration Schedule, Health Care Surveys, Humans, Malaria prevention & control, Quality of Health Care, Antimalarials therapeutic use, Chloroquine therapeutic use, Malaria drug therapy, Pharmaceutical Services standards
Abstract

In order to assess the action scheme of the National Program against Malaria, a study has been conducted in 25 pharmacies in Bouaké an area of high malaria transmission. The kind and quality of malaria treatments suggested by medical personnel, pharmacy sellers and used in automedication have been studied. The results proved that chloroquine is the molecule most delivered (25.7%) in private pharmacies. The parasitological diagnosis is scarcely requested by medical personnel. As in automedication, posological mistakes are relatively frequent with medical and pharmacy personnel (29.3%). The duration of the treatment is not specified in 14.2% of cases. Training and information actions must be reinforced for a better care of malaria., (Copyright John Libbey Eurotext 2003.)

Published
2004

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