Publications

@article{nokey,

title = {Malaria diagnosis challenges and pfhrp2 and pfhrp3 gene deletions using pregnant women as sentinel population in Nanoro region, Burkina Faso},

author = {Irene Molina\textendashde Fuente and Marc Christian Tahita and Kabore B\'{e}renger and Thuy Huong Ta Tang and Luz Garc\'{i}a and Vicenta Gonz\'{a}lez and Agust\'{i}n Benito and Judith M. H\"{u}bschen and Halidou Tinto and Pedro Berzosa},

url = {https://pubmed.ncbi.nlm.nih.gov/39140699/},

doi = {10.1080/20477724.2024.2388489},

issn = {2047-7732},

year  = {2024},

date = {2024-01-01},

journal = {Pathogens and global health},

volume = {118},

issue = {6},

publisher = {Pathog Glob Health},

abstract = {Malaria in pregnancy causes adverse consequences and prompt and accurate diagnosis is essential for case management. In malaria endemic countries, diagnosis is mainly based on rapid diagnostic tests (RDT) and microscopy. However, increasing reports of false negatives caused by low parasitemia and pfhrp2/3 deletions raise concerns about HRP2-based RDT usefulness. This study aimed to assess RDT and microscopy performance and to describe pfhrp2/3 deletions in a cohort of 418 pregnant women in Burkina Faso. Malaria was diagnosed using RDT and microscopy and blood samples were collected during antenatal care visits. Diagnostic results were compared to PCR as gold standard. Pfhrp2 and pfhrp3 deletions were characterized for patients with confirmed P. falciparum infection. RDT had better sensitivity (76%) but lower specificity (83%) than microscopy (sensitivity = 57%; specificity = 98%). Low parasitemia (\<150 parasites/µL), especially in multigravidae, was the principal factor causing false negatives by both methods. Moreover, pfhrp2 deletion frequency among overall false negatives by RDT was 21.43%. Higher frequency of deletions was found among all samples, independently of RDT result, for example around 2% of samples had double deletions meaning that the majority of deletions had no effect on RDT testing. Finally, it was found higher pfhrp2 deletion in women with lower uterine height during the first trimester. Wider and National surveillance study of deletions is recommended among pregnant women and in Burkina Faso.},

keywords = {Adolescent, Adult, Antigens, Burkina Faso / epidemiology, Diagnostic Tests, doi:10.1080/20477724.2024.2388489, Falciparum* / diagnosis, Falciparum* / epidemiology, Falciparum* / parasitology, Female, Gene Deletion*, Humans, Irene Molina-de la Fuente, Malaria, Marc Christian Tahita, MEDLINE, Microscopy, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Parasitic / diagnosis, Parasitic / epidemiology, Pedro Berzosa, Plasmodium falciparum* / genetics, Plasmodium falciparum* / isolation \& purification, PMC11441055, pmid:39140699, Pregnancy, Pregnancy Complications, Protozoan Proteins* / genetics, Protozoan* / genetics, PubMed Abstract, Research Support, Routine* / methods, Sensitivity and Specificity*, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@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{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}

}