Publications

@article{Gansane2023,

title = {Randomized, open-label, phase 2a study to evaluate the contribution of artefenomel to the clinical and parasiticidal activity of artefenomel plus ferroquine in African patients with uncomplicated Plasmodium falciparum malaria},

author = {Adama Gansane and Moussa Lingani and Adoke Yeka and Alain Nahum and Marielle Bouyou-Akotet and Ghyslain Mombo-Ngoma and Grace Kaguthi and Catalina Barcel\'{o} and Bart Laurijssens and Cathy Cantalloube and Fiona Macintyre and Elhadj Djeriou and Andreas Jessel and Rapha\"{e}l Bejuit and Helen Demarest and Anne Claire Marrast and Siaka Debe and Halidou Tinto and Afizi Kibuuka and Diolinda Nahum and Denise Patricia Mawili-Mboumba and Rella Zoleko-Manego and Irene Mugenya and Frederick Olewe and Stephan Duparc and Bernhards Ogutu},

url = {https://pubmed.ncbi.nlm.nih.gov/36597076/},

doi = {10.1186/S12936-022-04420-2},

issn = {1475-2875},

year  = {2023},

date = {2023-01-01},

journal = {Malaria journal},

volume = {22},

issue = {1},

publisher = {Malar J},

abstract = {Background: The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated. Methods: This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14\textendash69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated. Results: The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC0\textendash∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0\textendashd28, baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan\textendashMeier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or \> 60 ms from baseline. Conclusion: The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated. Trial registration: ClinicalTrials.gov, NCT03660839 (7 September, 2018).},

keywords = {Adama Gansane, Aminoquinolines / therapeutic use, Antimalarials* / pharmacology, Bernhards Ogutu, Clinical Trial, doi:10.1186/s12936-022-04420-2, Drug Combinations, Falciparum* / drug therapy, Falciparum* / parasitology, Humans, Malaria, MEDLINE, Moussa Lingani, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Phase II, Plasmodium falciparum, PMC9809015, pmid:36597076, PubMed Abstract, Randomized controlled trial, Treatment Outcome},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis},

author = {Anna Maria Eijk and Kasia Stepniewska and Jenny Hill and Steve M. Taylor and Stephen J. Rogerson and Gilles Cottrell and R. Matthew Chico and Julie R. Gutman and Halidou Tinto and Holger W. Unger and Stephanie K. Yanow and Steven R. Meshnick and Feiko O. Kuile and Alfredo Mayor and Steve M. Taylor and Stephen J. Rogerson and R. Matthew Chico and Julie R. Gutman and Hallidou Tinto and Holger W. Unger and Stephanie K. Yanow and Manfred Accrombessi and Ayola A. Adegnika and Rukhsana Ahmed and Eliana Mar\'{i}a Arango-Fl\'{o}rez and Myriam Arevalo-Herrera and Emmanual Arinaitwe and Paulo Arnaldo and Per Ashorn and Ulla Ashorn and Azucena Bardaji and Inoni Betuela and Praveen K. Bharti and Francis Bohissou and Camila B\^{o}tto-Menezes and Vera Braun and Valerie Briand and Jessica Briggs and Mar\'{i}a Eugenia Castellanos and Daniel Chandramohan and Enesia Banda Chaponda and Chetan Chitnis and Lauren M. Cohee and Michel Cot and Umberto d'Alessandro and Lise Denoeud-Ndam and Meghna Desai and Alassane Dicko and Xavier Ding and Grant Dorsey and Patrick E. Duffy and Maha A. Elbadry and Sonia M. Enosse and Yue Fan and Nadine Fievet and Michal Fried and Blaise Genton and Raquel Gonzalez and Brian Greenwood and Linda Kalilani and Johanna H. Kattenberg and Kassoum Kayentao and Carole Khairallah and Christopher L. King and Dhanpat Kumar Kochar and Swati Kochar and Felix Koukouikila-Koussounda and Sarah H. Landis and Miriam K. Laufer and Rose F. Leke and Eusebio Macete and Sonia Maculuve and Mwayiwawo Madanitsa and Almahamoudou Mahamar and Ken Maleta and Indu Malhotra and Rella Zoleko Manego and Flor Ernestina Martinez-Espinosa and Achille Massougbodji and Don Mathanga and Michela Menegon and Clara Menendez and Petra Mens and Martin Meremikwu and Frank P. Mockenhaupt and Ghyslain Mombo-Ngoma and Dominic Mosha and Ivo Mueller and Alain Nahum and Paul Natureeba and Nicaise Ndam and Francine Ntoumi and Olabisi A. Oduwole and Bernard A. Okech and Maria Ome-Kaius and Kephas Otieno and Norma Padilla and Michal Ramharter and Rosemary Rochford and Anna Rosanas-Urgell and Maria Ruperez and Katherine R. Sabourin and Sergi Sanz and Henk D. Schallig and Susana Scott and Esperanca Sevene and Carlo Severini and Harry Tagbor and Diane Wallace Taylor and Maminata Traore Coulibaly and Ana Vasquez and Annie Walker-Abbey and Blair J. Wylie and Djimon M. Zannou and Stephen R. Meshnick},

url = {https://pubmed.ncbi.nlm.nih.gov/37276878/},

doi = {10.1016/S2214-109X(23)00194-8},

issn = {2214-109X},

year  = {2023},

date = {2023-01-01},

journal = {The Lancet. Global health},

volume = {11},

issue = {7},

pages = {e1061-e1074},

publisher = {Lancet Glob Health},

abstract = {Background: Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD). Methods: For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine\textendashpyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342. Findings: The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0\textendash55·9, 66 substudies) for submicroscopic and 8·0% (0·0\textendash50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0\textendash100); this proportion was highest in the Americas (73·3%, 0·0\textendash100), followed by Asia (67·2%, 36·4\textendash100) and Africa (56·5%, 20·5\textendash97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02\textendash1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45\textendash5·54; p\<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection. Interpretation: During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections. Funding: Bill \& Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.},

keywords = {{Adult, Anna Maria van Eijk, Antimalarials* / therapeutic use, Author(firstnames='Achille', Author(firstnames='Alain', Author(firstnames='Alassane', Author(firstnames='Alfredo', Author(firstnames='Almahamoudou', Author(firstnames='Ana', Author(firstnames='Anna', Author(firstnames='Annie', Author(firstnames='Ayola A', Author(firstnames='Azucena', Author(firstnames='Bernard A', Author(firstnames='Blair J', Author(firstnames='Blaise', Author(firstnames='Brian', Author(firstnames='Camila', Author(firstnames='Carlo', Author(firstnames='Carole', Author(firstnames='Chetan', Author(firstnames='Christopher L', Author(firstnames='Clara', Author(firstnames='Daniel', Author(firstnames='Dhanpat Kumar', Author(firstnames='Diane Wallace', Author(firstnames='Djimon M', Author(firstnames='Dominic', Author(firstnames='Don', Author(firstnames='Eliana Mar\'{i}a', Author(firstnames='Emmanual', Author(firstnames='Enesia Banda', Author(firstnames='Esperanca', Author(firstnames='Eusebio', Author(firstnames='Feiko O', Author(firstnames='Felix', Author(firstnames='Flor Ernestina', Author(firstnames='Francine', Author(firstnames='Francis', Author(firstnames='Frank P', Author(firstnames='Ghyslain', Author(firstnames='Gilles', Author(firstnames='Grant', Author(firstnames='Hallidou', Author(firstnames='Harry', Author(firstnames='Henk D', Author(firstnames='Holger W', Author(firstnames='Indu', Author(firstnames='Inoni', Author(firstnames='Ivo', Author(firstnames='Jenny', Author(firstnames='Jessica', Author(firstnames='Johanna H', Author(firstnames='Julie R', Author(firstnames='Kasia', Author(firstnames='Kassoum', Author(firstnames='Katherine R', Author(firstnames='Ken', Author(firstnames='Kephas', Author(firstnames='Lauren M', Author(firstnames='Linda', Author(firstnames='Lise', Author(firstnames='Maha A', Author(firstnames='Maminata', Author(firstnames='Manfred', Author(firstnames='Mar\'{i}a Eugenia', Author(firstnames='Maria', Author(firstnames='Martin', Author(firstnames='Meghna', Author(firstnames='Michal', Author(firstnames='Michel', Author(firstnames='Michela', Author(firstnames='Miriam K', Author(firstnames='Mwayiwawo', Author(firstnames='Myriam', Author(firstnames='Nadine', Author(firstnames='Nicaise', Author(firstnames='Norma', Author(firstnames='Olabisi A', Author(firstnames='Patrick E', Author(firstnames='Paul', Author(firstnames='Paulo', Author(firstnames='Per', Author(firstnames='Petra', Author(firstnames='Praveen K', Author(firstnames='R Matthew', Author(firstnames='Raquel', Author(firstnames='Rella', Author(firstnames='Rose F', Author(firstnames='Rosemary', Author(firstnames='Rukhsana', Author(firstnames='Sarah H', Author(firstnames='Sergi', Author(firstnames='Sonia M', Author(firstnames='Sonia', Author(firstnames='Stephanie K', Author(firstnames='Stephen J', Author(firstnames='Stephen R', Author(firstnames='Steve M', Author(firstnames='Susana', Author(firstnames='Swati', Author(firstnames='Ulla', Author(firstnames='Umberto', Author(firstnames='Valerie', Author(firstnames='Vera', Author(firstnames='Xavier', Author(firstnames='Yue', CollabAuthor(name='Subpatent Malaria in Pregnancy Group', Falciparum* / drug therapy, Female, Humans, Kasia Stepniewska, Malaria, Malaria* / prevention \& control, MEDLINE, Meta-Analysis, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, P.H.S., PMC10880462, Pregnancy, Prevalence, PubMed Abstract, Research Support, Risk Factors, Systematic review, U.S. Gov't},

pubstate = {published},

tppubtype = {article}

}

@article{Agnandji2023,

title = {Prostration and the prognosis of death in African children with severe malaria},

author = {Selidji T. Agnandji and Mario Recker and Benjamin Mordm\"{u}ller and Stephan Gl\"{o}ckner and Akim A. Adegnika and Bertrand Lell and Lucas Otieno and Walter Otieno and Seth Owusu-Agyei and Kwaku P. Asante and Tsiri Agbenyega and Daniel Ansong and Eusebio Macete and Pedro Aide and Hermann Sorgho and Halidou Tinto and Neema Mturi and John P. A. Lusingu and Samwel Gesase and Irving Hoffman and Nahya Salim Masoud and Charles R. Newton and Kalifa Bojang and G\'{e}rard Krause and Peter Gottfried Kremsner},

url = {https://pubmed.ncbi.nlm.nih.gov/37414210/},

doi = {10.1016/J.IJID.2023.06.022},

issn = {1878-3511},

year  = {2023},

date = {2023-01-01},

journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},

volume = {134},

pages = {240-247},

publisher = {Int J Infect Dis},

abstract = {Objectives: Malaria is still one of the main reasons for hospitalization in children living in sub-Saharan Africa. Rapid risk stratification at admission is essential for optimal medical care and improved prognosis. Whereas coma, deep breathing, and, to a lesser degree, severe anemia are established predictors of malaria-related death, the value of assessing prostration for risk stratification is less certain. Methods: Here we used a retrospective multi-center analysis comprising over 33,000 hospitalized children from four large studies, including two observational studies from the Severe Malaria in African Children network, a randomized controlled treatment study, and the phase-3-clinical RTS,S-malaria vaccine trial, to evaluate known risk factors of mortality and with a specific emphasis on the role of prostration. Results: Despite comparable age profiles of the participants, we found significant inter- and intra-study variation in the incidence of fatal malaria as well as in the derived risk ratios associated with the four risk factors: coma, deep breathing, anemia, and prostration. Despite pronounced variations, prostration was significantly associated with an increased risk of mortality (P \<0.001) and its consideration resulted in improved predictive performance, both in a multivariate model and a univariate model based on the Lambar\'{e}n\'{e} Organ Dysfunction Score. Conclusion: Prostration is an important clinical criterion to determine severe pediatric malaria with possible fatal outcomes.},

keywords = {Anemia*, Child, Clinical Trial, Coma, doi:10.1016/j.ijid.2023.06.022, Falciparum* / drug therapy, Humans, Infant, Malaria, Malaria* / complications, Malaria* / diagnosis, Mario Recker, MEDLINE, Multicenter Study, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Peter Gottfried Kremsner, Phase III, pmid:37414210, Prognosis, PubMed Abstract, Randomized controlled trial, Selidji T Agnandji},

pubstate = {published},

tppubtype = {article}

}

@article{Ogutu2023,

title = {Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial},

author = {Bernhards Ogutu and Adoke Yeka and Sylvia Kusemererwa and Ricardo Thompson and Halidou Tinto and Andre Offianan Toure and Chirapong Uthaisin and Amar Verma and Afizi Kibuuka and Moussa Lingani and Carlos Louren\c{c}o and Ghyslain Mombo-Ngoma and Videlis Nduba and Tiacoh Landry N'Guessan and Gu\'{e}tawend\'{e} Job Wilfried Nassa and Mary Nyantaro and Lucas Otieno Tina and Piyoosh K. Singh and Myriam El Gaaloul and Anne Claire Marrast and Havana Chikoto and Katalin Csermak and Ivan Demin and Dheeraj Mehta and Rashidkhan Pathan and Celine Risterucci and Guoqin Su and Cornelis Winnips and Grace Kaguthi and Bakary Fofana and Martin Peter Grobusch},

url = {https://pubmed.ncbi.nlm.nih.gov/37327809/},

doi = {10.1016/S1473-3099(23)00209-8},

issn = {1474-4457},

year  = {2023},

date = {2023-01-01},

journal = {The Lancet. Infectious diseases},

volume = {23},

issue = {9},

pages = {1051-1061},

publisher = {Lancet Infect Dis},

abstract = {Background: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria. Methods: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries. Patients had microscopically-confirmed uncomplicated P falciparum malaria (\>1000 and \<150 000 parasites per μL). Part A identified the optimal dose regimens in adults and adolescents (aged ≥12 years) and in part B, the selected doses were assessed in children (≥2 years and \<12 years). In part A, patients were randomly assigned to one of seven groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days; ganaplacide 800 mg plus lumefantrine-SDF 960 mg as a single dose; once a day ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; once a day ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; or twice a day artemether plus lumefantrine for 3 days [control]), with stratification by country (2:2:2:2:2:2:1) using randomisation blocks of 13. In part B, patients were randomly assigned to one of four groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days, or twice a day artemether plus lumefantrine for 3 days) with stratification by country and age (2 to \<6 years and 6 to \<12 years; 2:2:2:1) using randomisation blocks of seven. The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29, analysed in the per protocol set. The null hypothesis was that the response was 80% or lower, rejected when the lower limit of two-sided 95% CI was higher than 80%. This study is registered with EudraCT (2020\textendash003284\textendash25) and ClinicalTrials.gov (NCT03167242). Findings: Between Aug 2, 2017, and May 17, 2021, 1220 patients were screened and of those, 12 were included in the run-in cohort, 337 in part A, and 175 in part B. In part A, 337 adult or adolescent patients were randomly assigned, 326 completed the study, and 305 were included in the per protocol set. The lower limit of the 95% CI for PCR-corrected adequate clinical and parasitological response on day 29 was more than 80% for all treatment regimens in part A (46 of 50 patients [92%, 95% CI 81\textendash98] with 1 day, 47 of 48 [98%, 89\textendash100] with 2 days, and 42 of 43 [98%, 88\textendash100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83\textendash99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93\textendash100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92\textendash100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86\textendash100] with artemether plus lumefantrine). In part B, 351 children were screened, 175 randomly assigned (ganaplacide 400 mg plus lumefantrine-SDF 960 mg once a day for 1, 2, or 3 days), and 171 completed the study. Only the 3-day regimen met the prespecified primary endpoint in paediatric patients (38 of 40 patients [95%, 95% CI 83\textendash99] vs 21 of 22 [96%, 77\textendash100] with artemether plus lumefantrine). The most common adverse events were headache (in seven [14%] of 51 to 15 [28%] of 54 in the ganaplacide plus lumefantrine-SDF groups and five [19%] of 27 in the artemether plus lumefantrine group) in part A, and malaria (in 12 [27%] of 45 to 23 [44%] of 52 in the ganaplacide plus lumefantrine-SDF groups and 12 [50%] of 24 in the artemether plus lumefantrine group) in part B. No patients died during the study. Interpretation: Ganaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial (NCT04546633). Funding: Novartis and Medicines for Malaria Venture.},

keywords = {Adoke Yeka, Adolescent, Adult, Antimalarials*, Artemether / pharmacology, Artemether / therapeutic use, Artemisinins*, Bernhards Ogutu, Child, Clinical Trial, doi:10.1016/S1473-3099(23)00209-8, Drug Combinations, Ethanolamines / pharmacology, Ethanolamines / therapeutic use, Falciparum* / drug therapy, Falciparum* / parasitology, Fluorenes / pharmacology, Fluorenes / therapeutic use, Humans, Lumefantrine / pharmacology, Lumefantrine / therapeutic use, Malaria, Malaria* / drug therapy, Martin Peter Grobusch, MEDLINE, Multicenter Study, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase II, Plasmodium falciparum, pmid:37327809, PubMed Abstract, Randomized controlled trial, Research Support, Treatment Outcome},

pubstate = {published},

tppubtype = {article}

}

@article{Djimde2023,

title = {Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial},

author = {Moussa Djimde and Japhet Kabalu Tshiongo and Hypolite Mavoko Muhindo and Halidou Tinto and Esperanca Sevene and Maminata Traore and Anifa Vala and Salesio MacUacua and Berenger Kabore and Edgard Diniba Dabira and Annette Erhart and Hamadoun Diakite and Mohamed Keita and Mireia Piqueras and Raquel Gonz\'{a}lez and Clara Menendez and Thomas P. C. Dorlo and Issaka Sagara and Petra Mens and Henk Schallig and Umberto D'Alessandro and Kassoum Kayentao},

url = {https://pubmed.ncbi.nlm.nih.gov/37813539/},

doi = {10.1136/BMJOPEN-2022-065295},

issn = {2044-6055},

year  = {2023},

date = {2023-01-01},

journal = {BMJ open},

volume = {13},

issue = {10},

publisher = {BMJ Open},

abstract = {Introduction Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. Methods and analysis A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. Ethics and dissemination This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. Trial registration number PACTR202011812241529.},

keywords = {Antimalarials* / adverse effects, Artemether, Artemether / therapeutic use, Artemisinins* / adverse effects, Clinical Trial Protocol, Clinical Trials, doi:10.1136/bmjopen-2022-065295, Drug Combinations, Falciparum* / drug therapy, Female, Humans, Infant, Japhet Kabalu Tshiongo, Kassoum Kayentao, Lumefantrine Drug Combination / therapeutic use, Malaria, Malaria* / drug therapy, MEDLINE, Moussa Djimde, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase III as Topic, PMC10565244, pmid:37813539, Pregnancy, Pregnant Women, PubMed Abstract, Randomized Controlled Trials as Topic, Research Support, Sub-Saharan African People, Treatment Outcome},

pubstate = {published},

tppubtype = {article}

}