Publications

" Our main objective is to develop and maintain over time a good expertise and infrastructure ensuring high quality training and clinical research."
Prof Halidou TINTO, PharmD, Msc, PhD Head of the CRUN

2023
Journal Articles
	Adama Gansane, Moussa Lingani, Adoke Yeka, Alain Nahum, Marielle Bouyou-Akotet, Ghyslain Mombo-Ngoma, Grace Kaguthi, Catalina Barceló, Bart Laurijssens, Cathy Cantalloube, Fiona Macintyre, Elhadj Djeriou, Andreas Jessel, Raphaël Bejuit, Helen Demarest, Anne Claire Marrast, Siaka Debe, Halidou Tinto, Afizi Kibuuka, Diolinda Nahum, Denise Patricia Mawili-Mboumba, Rella Zoleko-Manego, Irene Mugenya, Frederick Olewe, Stephan Duparc, Bernhards Ogutu 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 Journal Article In: Malaria journal, vol. 22, iss. 1, 2023, ISSN: 1475-2875. Abstract \| BibTeX \| Tags: 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 \| Links: Close Close @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} } Close 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 ≥ 14–69 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–∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0–d28, 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–Meier) 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). Close
	Holger W. Unger, Anastasia Jessica Hadiprodjo, Julie R. Gutman, Valerie Briand, Nadine Fievet, Innocent Valea, Halidou Tinto, Umberto D’Alessandro, Sarah H. Landis, Feiko Ter Kuile, Peter Ouma, Martina Oneko, Victor Mwapasa, Laurence Slutsker, Dianne J. Terlouw, Simon Kariuki, John Ayisi, Bernard Nahlen, Meghna Desai, Mwayi Madanitsa, Linda Kalilani-Phiri, Per Ashorn, Kenneth Maleta, Antoinette Tshefu-Kitoto, Ivo Mueller, Danielle Stanisic, Jordan Cates, Anna Maria Van Eijk, Maria Ome-Kaius, Elizabeth H. Aitken, Stephen J. Rogerson Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis Journal Article In: Scientific reports, vol. 13, iss. 1, 2023, ISSN: 2045-2322. Abstract \| BibTeX \| Tags: Anastasia Jessica Hadiprodjo, doi:10.1038/s41598-023-37431-3, Extramural, Falciparum* / complications, Falciparum* / epidemiology, Female, Holger W Unger, Humans, Infant, Low Birth Weight, Malaria, Malaria* / complications, Malaria* / epidemiology, MEDLINE, Meta-Analysis, N.I.H., National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, Non-U.S. Gov't, placenta, Plasmodium falciparum, PMC10293221, pmid:37365258, Pregnancy, PubMed Abstract, Research Support, Stephen J Rogerson, Stillbirth \| Links: Close Close @article{Unger2023, title = {Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis}, author = {Holger W. Unger and Anastasia Jessica Hadiprodjo and Julie R. Gutman and Valerie Briand and Nadine Fievet and Innocent Valea and Halidou Tinto and Umberto D’Alessandro and Sarah H. Landis and Feiko Ter Kuile and Peter Ouma and Martina Oneko and Victor Mwapasa and Laurence Slutsker and Dianne J. Terlouw and Simon Kariuki and John Ayisi and Bernard Nahlen and Meghna Desai and Mwayi Madanitsa and Linda Kalilani-Phiri and Per Ashorn and Kenneth Maleta and Antoinette Tshefu-Kitoto and Ivo Mueller and Danielle Stanisic and Jordan Cates and Anna Maria Van Eijk and Maria Ome-Kaius and Elizabeth H. Aitken and Stephen J. Rogerson}, url = {https://pubmed.ncbi.nlm.nih.gov/37365258/}, doi = {10.1038/S41598-023-37431-3}, issn = {2045-2322}, year = {2023}, date = {2023-01-01}, journal = {Scientific reports}, volume = {13}, issue = {1}, publisher = {Sci Rep}, abstract = {In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.}, keywords = {Anastasia Jessica Hadiprodjo, doi:10.1038/s41598-023-37431-3, Extramural, Falciparum* / complications, Falciparum* / epidemiology, Female, Holger W Unger, Humans, Infant, Low Birth Weight, Malaria, Malaria* / complications, Malaria* / epidemiology, MEDLINE, Meta-Analysis, N.I.H., National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, Non-U.S. Gov't, placenta, Plasmodium falciparum, PMC10293221, pmid:37365258, Pregnancy, PubMed Abstract, Research Support, Stephen J Rogerson, Stillbirth}, pubstate = {published}, tppubtype = {article} } Close In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy. Close
	Bernhards Ogutu, Adoke Yeka, Sylvia Kusemererwa, Ricardo Thompson, Halidou Tinto, Andre Offianan Toure, Chirapong Uthaisin, Amar Verma, Afizi Kibuuka, Moussa Lingani, Carlos Lourenço, Ghyslain Mombo-Ngoma, Videlis Nduba, Tiacoh Landry N'Guessan, Guétawendé Job Wilfried Nassa, Mary Nyantaro, Lucas Otieno Tina, Piyoosh K. Singh, Myriam El Gaaloul, Anne Claire Marrast, Havana Chikoto, Katalin Csermak, Ivan Demin, Dheeraj Mehta, Rashidkhan Pathan, Celine Risterucci, Guoqin Su, Cornelis Winnips, Grace Kaguthi, Bakary Fofana, Martin Peter Grobusch Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial Journal Article In: The Lancet. Infectious diseases, vol. 23, iss. 9, pp. 1051-1061, 2023, ISSN: 1474-4457. Abstract \| BibTeX \| Tags: 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 \| Links: Close Close @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} } Close 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 (2020–003284–25) 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 81–98] with 1 day, 47 of 48 [98%, 89–100] with 2 days, and 42 of 43 [98%, 88–100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83–99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93–100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92–100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86–100] 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 83–99] vs 21 of 22 [96%, 77–100] 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. Close
	Hamtandi Magloire Natama, Gemma Moncunill, Marta Vidal, Toussaint Rouamba, Ruth Aguilar, Rebeca Santano, Eduard Rovira-Vallbona, Alfons Jiménez, M. Athanase Somé, Hermann Sorgho, Innocent Valéa, Maminata Coulibaly-Traoré, Ross L. Coppel, David Cavanagh, Chetan E. Chitnis, James G. Beeson, Evelina Angov, Sheetij Dutta, Benoit Gamain, Luis Izquierdo, Petra F. Mens, Henk D. F. H. Schallig, Halidou Tinto, Anna Rosanas-Urgell, Carlota Dobaño Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso Journal Article In: Infection and immunity, vol. 91, iss. 10, pp. 290, 2023, ISSN: 1098-5522. Abstract \| BibTeX \| Tags: Antibodies, Antigens, Burkina Faso / epidemiology, Carlota Dobaño, Child, Cohort Studies, doi:10.1128/iai.00268-23, Falciparum, Female, Gemma Moncunill, Hamtandi Magloire Natama, Humans, Immunoglobulin G, Infant, Malaria, Malaria / epidemiology, Maternal Exposure, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, placenta, Plasmodium falciparum, PMC10580994, pmid:37754682, Pregnancy, Preschool, Protozoan, PubMed Abstract \| Links: Close Close @article{Natama2023, title = {Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso}, author = {Hamtandi Magloire Natama and Gemma Moncunill and Marta Vidal and Toussaint Rouamba and Ruth Aguilar and Rebeca Santano and Eduard Rovira-Vallbona and Alfons Jim\'{e}nez and M. Athanase Som\'{e} and Hermann Sorgho and Innocent Val\'{e}a and Maminata Coulibaly-Traor\'{e} and Ross L. Coppel and David Cavanagh and Chetan E. Chitnis and James G. Beeson and Evelina Angov and Sheetij Dutta and Benoit Gamain and Luis Izquierdo and Petra F. Mens and Henk D. F. H. Schallig and Halidou Tinto and Anna Rosanas-Urgell and Carlota Doba\~{n}o}, url = {https://pubmed.ncbi.nlm.nih.gov/37754682/}, doi = {10.1128/IAI.00268-23}, issn = {1098-5522}, year = {2023}, date = {2023-01-01}, journal = {Infection and immunity}, volume = {91}, issue = {10}, pages = {290}, publisher = {Infect Immun}, abstract = {In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.}, keywords = {Antibodies, Antigens, Burkina Faso / epidemiology, Carlota Doba\~{n}o, Child, Cohort Studies, doi:10.1128/iai.00268-23, Falciparum, Female, Gemma Moncunill, Hamtandi Magloire Natama, Humans, Immunoglobulin G, Infant, Malaria, Malaria / epidemiology, Maternal Exposure, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, placenta, Plasmodium falciparum, PMC10580994, pmid:37754682, Pregnancy, Preschool, Protozoan, PubMed Abstract}, pubstate = {published}, tppubtype = {article} } Close In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood. Close
	Japhet Kabalu Tshiongo, Flory Luzolo, Melissa Kabena, Lise Kuseke, Moussa Djimde, Patrick Mitashi, Crispin Lumbala, Kassoum Kayentao, Sandra Menting, Petra F. Mens, Henk D. F. H. Schallig, Pascal Lutumba, Halidou Tinto, Hypolite Muhindo Mavoko, Vivi Maketa Performance of ultra-sensitive malaria rapid diagnostic test to detect Plasmodium falciparum infection in pregnant women in Kinshasa, the Democratic Republic of the Congo Journal Article In: Malaria journal, vol. 22, iss. 1, 2023, ISSN: 1475-2875. Abstract \| BibTeX \| Tags: Antigens, Democratic Republic of the Congo, Diagnostic Tests, doi:10.1186/s12936-023-04749-2, Falciparum* / epidemiology, Female, Flory Luzolo, Humans, Japhet Kabalu Tshiongo, Malaria, Malaria, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Plasmodium falciparum, PMC10594769, pmid:37872634, Pregnancy, Pregnant Women, Protozoan, PubMed Abstract, Rapid diagnostic tests, Routine / methods, Sensitivity and Specificity, Vivi Maketa \| Links: Close Close @article{nokey, title = {Performance of ultra-sensitive malaria rapid diagnostic test to detect Plasmodium falciparum infection in pregnant women in Kinshasa, the Democratic Republic of the Congo}, author = {Japhet Kabalu Tshiongo and Flory Luzolo and Melissa Kabena and Lise Kuseke and Moussa Djimde and Patrick Mitashi and Crispin Lumbala and Kassoum Kayentao and Sandra Menting and Petra F. Mens and Henk D. F. H. Schallig and Pascal Lutumba and Halidou Tinto and Hypolite Muhindo Mavoko and Vivi Maketa}, url = {https://pubmed.ncbi.nlm.nih.gov/37872634/}, doi = {10.1186/S12936-023-04749-2}, issn = {1475-2875}, year = {2023}, date = {2023-01-01}, journal = {Malaria journal}, volume = {22}, issue = {1}, publisher = {Malar J}, abstract = {Background: Low peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo. Methods: To assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test. Results: The median parasite density by qPCR was 292 p/μL of blood [IQR (49.7\textendash1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6\textendash63.6)], [81.7% (95%CI 74.7\textendash87.3)] and [88% (95% CI 81.9\textendash92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6\textendash99.5), 95.2% (95% CI 92.5\textendash97.2) and 94.4% (95% CI 91.4\textendash96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1\textendash75.3) compared to 68% (95% CI 53.3\textendash80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8\textendash98.7) for RDT versus 100% (95% CI 82.3\textendash100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10\textendash33.7) and 47.3% (95% CI 24.4\textendash71.1) respectively. Conclusions: uRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity.}, keywords = {Antigens, Democratic Republic of the Congo, Diagnostic Tests, doi:10.1186/s12936-023-04749-2, Falciparum / epidemiology, Female, Flory Luzolo, Humans, Japhet Kabalu Tshiongo, Malaria, Malaria*, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Plasmodium falciparum, PMC10594769, pmid:37872634, Pregnancy, Pregnant Women, Protozoan, PubMed Abstract, Rapid diagnostic tests, Routine / methods, Sensitivity and Specificity, Vivi Maketa}, pubstate = {published}, tppubtype = {article} } Close Background: Low peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo. Methods: To assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test. Results: The median parasite density by qPCR was 292 p/μL of blood [IQR (49.7–1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6–63.6)], [81.7% (95%CI 74.7–87.3)] and [88% (95% CI 81.9–92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6–99.5), 95.2% (95% CI 92.5–97.2) and 94.4% (95% CI 91.4–96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1–75.3) compared to 68% (95% CI 53.3–80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8–98.7) for RDT versus 100% (95% CI 82.3–100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10–33.7) and 47.3% (95% CI 24.4–71.1) respectively. Conclusions: uRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity. Close
2022
Journal Articles
	Paul Sondo, Marc Christian Tahita, Hamidou Ilboudo, Toussaint Rouamba, Karim Derra, Gauthier Tougri, Florence Ouédraogo, Béatrice Marie Adélaïde Konseibo, Eli Roamba, Sabina Dahlström Otienoburu, Bérenger Kaboré, Kalynn Kennon, Kadija Ouédraogo, Wend-Timbe-Noma Arlette Raïssa Zongo, Fadima Yaya Bocoum, Kasia Stepniewska, Mehul Dhorda, Philippe J. Guérin, Halidou Tinto Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial Journal Article In: Archives of Public Health, vol. 80, iss. 1, pp. 41, 2022, ISSN: 2049-3258. Abstract \| BibTeX \| Tags: Africa, Amodiaquine, Burkina Faso, Chemoprevention, Dihydro artemisinin Piperaquine, Malaria, Plasmodium falciparum, Sulfadoxine-pyrimethamine \| Links: Close Close @article{Sondo2022, title = {Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial}, author = {Paul Sondo and Marc Christian Tahita and Hamidou Ilboudo and Toussaint Rouamba and Karim Derra and Gauthier Tougri and Florence Ou\'{e}draogo and B\'{e}atrice Marie Ad\'{e}la\"{i}de Konseibo and Eli Roamba and Sabina Dahlstr\"{o}m Otienoburu and B\'{e}renger Kabor\'{e} and Kalynn Kennon and Kadija Ou\'{e}draogo and Wend-Timbe-Noma Arlette Ra\"{i}ssa Zongo and Fadima Yaya Bocoum and Kasia Stepniewska and Mehul Dhorda and Philippe J. Gu\'{e}rin and Halidou Tinto}, url = {https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-022-00800-x}, doi = {10.1186/s13690-022-00800-x}, issn = {2049-3258}, year = {2022}, date = {2022-01-01}, urldate = {2022-01-01}, journal = {Archives of Public Health}, volume = {80}, issue = {1}, pages = {41}, abstract = {BACKGROUND Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention.}, keywords = {Africa, Amodiaquine, Burkina Faso, Chemoprevention, Dihydro artemisinin Piperaquine, Malaria, Plasmodium falciparum, Sulfadoxine-pyrimethamine}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention. Close
	Rashid Mansoor, Robert J. Commons, Nicholas M. Douglas, Benjamin Abuaku, Jane Achan, Ishag Adam, George O. Adjei, Martin Adjuik, Bereket H. Alemayehu, Richard Allan, Elizabeth N. Allen, Anupkumar R. Anvikar, Emmanuel Arinaitwe, Elizabeth A. Ashley, Hazel Ashurst, Puji B. S. Asih, Nathan Bakyaita, Hubert Barennes, Karen I. Barnes, Leonardo Basco, Quique Bassat, Elisabeth Baudin, David J Bell, Delia Bethell, Anders Bjorkman, Caroline Boulton, Teun Bousema, Philippe Brasseur, Hasifa Bukirwa, Rebekah Burrow, Verena I. Carrara, Michel Cot, Umberto D’Alessandro, Debashish Das, Sabyasachi Das, Timothy M. E. Davis, Meghna Desai, Abdoulaye A. Djimde, Arjen M. Dondorp, Grant Dorsey, Chris J. Drakeley, Stephan Duparc, Emmanuelle Espié, Jean-Francois Etard, Catherine Falade, Jean Francois Faucher, Scott Filler, Carole Fogg, Mark Fukuda, Oumar Gaye, Blaise Genton, Awab Ghulam Rahim, Julius Gilayeneh, Raquel Gonzalez, Rebecca F. Grais, Francesco Grandesso, Brian Greenwood, Anastasia Grivoyannis, Christoph Hatz, Eva Maria Hodel, Georgina S. Humphreys, Jimee Hwang, Deus Ishengoma, Elizabeth Juma, S. Patrick Kachur, Piet A. Kager, Erasmus Kamugisha, Moses R. Kamya, Corine Karema, Kassoum Kayentao, Adama Kazienga, Jean-René Kiechel, Poul-Erik Kofoed, Kwadwo Koram, Peter G. Kremsner, David G. Lalloo, Moses Laman, Sue J. Lee, Bertrand Lell, Amelia W. Maiga, Andreas Mårtensson, Mayfong Mayxay, Wilfred Mbacham, Rose McGready, Hervé Menan, Didier Ménard, Frank Mockenhaupt, Brioni R. Moore, Olaf Müller, Alain Nahum, Jean-Louis Ndiaye, Paul N. Newton, Billy E. Ngasala, Frederic Nikiema, Akindeh M. Nji, Harald Noedl, Francois Nosten, Bernhards R. Ogutu, Olusola Ojurongbe, Lyda Osorio, Jean-Bosco Ouédraogo, Seth Owusu-Agyei, Anil Pareek, Louis K. Penali, Patrice Piola, Mateusz Plucinski, Zul Premji, Michael Ramharter, Caitlin L. Richmond, Lars Rombo, Cally Roper, Philip J. Rosenthal, Sam Salman, Albert Same-Ekobo, Carol Sibley, Sodiomon B. Sirima, Frank M. Smithuis, Fabrice A. Somé, Sarah G. Staedke, Peter Starzengruber, Nathalie Strub-Wourgaft, Inge Sutanto, Todd D. Swarthout, Din Syafruddin, Ambrose O. Talisuna, Walter R. Taylor, Emmanuel A. Temu, Julie I. Thwing, Halidou Tinto, Emiliana Tjitra, Offianan A. Touré, T. Hien Tran, Johan Ursing, Innocent Valea, Giovanni Valentini, Michele Vugt, Lorenz Seidlein, Stephen A. Ward, Vincent Were, Nicholas J. White, Charles J. Woodrow, William Yavo, Adoke Yeka, Issaka Zongo, Julie A. Simpson, Philippe J. Guerin, Kasia Stepniewska, Ric N. Price Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data Journal Article In: BMC Medicine, vol. 20, iss. 1, pp. 85, 2022, ISSN: 1741-7015. Abstract \| BibTeX \| Tags: Antimalarials, Artemisinin-based therapy, Haemoglobin, Non-artemisinin-based therapy, Plasmodium falciparum, Pooled analysis of individual patient data, Severe anaemia \| Links: Close Close @article{Mansoor2022, title = {Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data}, author = {Rashid Mansoor and Robert J. Commons and Nicholas M. Douglas and Benjamin Abuaku and Jane Achan and Ishag Adam and George O. Adjei and Martin Adjuik and Bereket H. Alemayehu and Richard Allan and Elizabeth N. Allen and Anupkumar R. Anvikar and Emmanuel Arinaitwe and Elizabeth A. Ashley and Hazel Ashurst and Puji B. S. Asih and Nathan Bakyaita and Hubert Barennes and Karen I. Barnes and Leonardo Basco and Quique Bassat and Elisabeth Baudin and David J Bell and Delia Bethell and Anders Bjorkman and Caroline Boulton and Teun Bousema and Philippe Brasseur and Hasifa Bukirwa and Rebekah Burrow and Verena I. Carrara and Michel Cot and Umberto D’Alessandro and Debashish Das and Sabyasachi Das and Timothy M. E. Davis and Meghna Desai and Abdoulaye A. Djimde and Arjen M. Dondorp and Grant Dorsey and Chris J. Drakeley and Stephan Duparc and Emmanuelle Espi\'{e} and Jean-Francois Etard and Catherine Falade and Jean Francois Faucher and Scott Filler and Carole Fogg and Mark Fukuda and Oumar Gaye and Blaise Genton and Awab Ghulam Rahim and Julius Gilayeneh and Raquel Gonzalez and Rebecca F. Grais and Francesco Grandesso and Brian Greenwood and Anastasia Grivoyannis and Christoph Hatz and Eva Maria Hodel and Georgina S. Humphreys and Jimee Hwang and Deus Ishengoma and Elizabeth Juma and S. Patrick Kachur and Piet A. Kager and Erasmus Kamugisha and Moses R. Kamya and Corine Karema and Kassoum Kayentao and Adama Kazienga and Jean-Ren\'{e} Kiechel and Poul-Erik Kofoed and Kwadwo Koram and Peter G. Kremsner and David G. Lalloo and Moses Laman and Sue J. Lee and Bertrand Lell and Amelia W. Maiga and Andreas Mr{a}rtensson and Mayfong Mayxay and Wilfred Mbacham and Rose McGready and Herv\'{e} Menan and Didier M\'{e}nard and Frank Mockenhaupt and Brioni R. Moore and Olaf M\"{u}ller and Alain Nahum and Jean-Louis Ndiaye and Paul N. Newton and Billy E. Ngasala and Frederic Nikiema and Akindeh M. Nji and Harald Noedl and Francois Nosten and Bernhards R. Ogutu and Olusola Ojurongbe and Lyda Osorio and Jean-Bosco Ou\'{e}draogo and Seth Owusu-Agyei and Anil Pareek and Louis K. Penali and Patrice Piola and Mateusz Plucinski and Zul Premji and Michael Ramharter and Caitlin L. Richmond and Lars Rombo and Cally Roper and Philip J. Rosenthal and Sam Salman and Albert Same-Ekobo and Carol Sibley and Sodiomon B. Sirima and Frank M. Smithuis and Fabrice A. Som\'{e} and Sarah G. Staedke and Peter Starzengruber and Nathalie Strub-Wourgaft and Inge Sutanto and Todd D. Swarthout and Din Syafruddin and Ambrose O. Talisuna and Walter R. Taylor and Emmanuel A. Temu and Julie I. Thwing and Halidou Tinto and Emiliana Tjitra and Offianan A. Tour\'{e} and T. Hien Tran and Johan Ursing and Innocent Valea and Giovanni Valentini and Michele Vugt and Lorenz Seidlein and Stephen A. Ward and Vincent Were and Nicholas J. White and Charles J. Woodrow and William Yavo and Adoke Yeka and Issaka Zongo and Julie A. Simpson and Philippe J. Guerin and Kasia Stepniewska and Ric N. Price}, url = {https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02265-9}, doi = {10.1186/s12916-022-02265-9}, issn = {1741-7015}, year = {2022}, date = {2022-01-01}, urldate = {2022-01-01}, journal = {BMC Medicine}, volume = {20}, issue = {1}, pages = {85}, abstract = {BACKGROUND Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin \< 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb \< 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age \< 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p \< 0.001). CONCLUSIONS In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.}, keywords = {Antimalarials, Artemisinin-based therapy, Haemoglobin, Non-artemisinin-based therapy, Plasmodium falciparum, Pooled analysis of individual patient data, Severe anaemia}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001). CONCLUSIONS In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery. Close
	Harvie P. Portugaliza, H. Magloire Natama, Pieter Guetens, Eduard Rovira-Vallbona, Athanase M. Somé, Aida Millogo, D. Florence Ouédraogo, Innocent Valéa, Hermann Sorgho, Halidou Tinto, Nguyen Hong, Antonio Sitoe, Rosauro Varo, Quique Bassat, Alfred Cortés, Anna Rosanas-Urgell Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients Journal Article In: eBioMedicine, vol. 83, pp. 104198, 2022, ISSN: 23523964. Abstract \| BibTeX \| Tags: Artemisinin, Malaria transmission, pfap2-g, Plasmodium falciparum, Sexual conversion \| Links: Close Close @article{Portugaliza2022, title = {Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients}, author = {Harvie P. Portugaliza and H. Magloire Natama and Pieter Guetens and Eduard Rovira-Vallbona and Athanase M. Som\'{e} and Aida Millogo and D. Florence Ou\'{e}draogo and Innocent Val\'{e}a and Hermann Sorgho and Halidou Tinto and Nguyen Hong and Antonio Sitoe and Rosauro Varo and Quique Bassat and Alfred Cort\'{e}s and Anna Rosanas-Urgell}, url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396422003802}, doi = {10.1016/j.ebiom.2022.104198}, issn = {23523964}, year = {2022}, date = {2022-01-01}, journal = {eBioMedicine}, volume = {83}, pages = {104198}, abstract = {BACKGROUND Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes. METHODS The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total}, keywords = {Artemisinin, Malaria transmission, pfap2-g, Plasmodium falciparum, Sexual conversion}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes. METHODS The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total Close
	Matthew Cairns, Amadou Barry, Issaka Zongo, Issaka Sagara, Serge R. Yerbanga, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Abdoul Aziz Sienou, Amadou Tapily, Koualy Sanogo, Mahamadou Kaya, Seydou Traore, Kalifa Diarra, Hama Yalcouye, Youssoufa Sidibe, Alassane Haro, Ismaila Thera, Paul Snell, Jane Grant, Halidou Tinto, Paul Milligan, Daniel Chandramohan, Brian Greenwood, Alassane Dicko, Jean Bosco Ouedraogo The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone Journal Article In: BMC Medicine, vol. 20, iss. 1, pp. 352, 2022, ISSN: 1741-7015. Abstract \| BibTeX \| Tags: Malaria, Malaria vaccination, Plasmodium falciparum, RTS, S/AS01E, seasonal malaria chemoprevention \| Links: Close Close @article{Cairns2022, title = {The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone}, author = {Matthew Cairns and Amadou Barry and Issaka Zongo and Issaka Sagara and Serge R. Yerbanga and Modibo Diarra and Charles Zoungrana and Djibrilla Issiaka and Abdoul Aziz Sienou and Amadou Tapily and Koualy Sanogo and Mahamadou Kaya and Seydou Traore and Kalifa Diarra and Hama Yalcouye and Youssoufa Sidibe and Alassane Haro and Ismaila Thera and Paul Snell and Jane Grant and Halidou Tinto and Paul Milligan and Daniel Chandramohan and Brian Greenwood and Alassane Dicko and Jean Bosco Ouedraogo}, url = {https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02536-5}, doi = {10.1186/s12916-022-02536-5}, issn = {1741-7015}, year = {2022}, date = {2022-01-01}, journal = {BMC Medicine}, volume = {20}, issue = {1}, pages = {352}, abstract = {BACKGROUND A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218.}, keywords = {Malaria, Malaria vaccination, Plasmodium falciparum, RTS, S/AS01E, seasonal malaria chemoprevention}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218. Close
2021
Journal Articles
	Paul Sondo, Biebo Bihoun, Bérenger Kabore, Marc Christian Tahita, Karim Derra, Toussaint Rouamba, Seydou Nakanabo Diallo, Adama Kazienga, Hamidou Ilboudo, Innocent Valea, Zekiba Tarnagda, Hermann Sorgho, Thierry Lefevre, Halidou Tinto Polymorphisms in Plasmodium falciparum parasites and mutations in the resistance genes Pfcrt and Pfmdr1 in Nanoro area, Burkina Faso. Journal Article In: Pan Afr. Med. J., vol. 39, pp. 118, 2021, ISSN: 1937-8688, (Copyright: Paul Sondo et al. PMID: 34512854 PMCID: PMC8396377). Abstract \| BibTeX \| Tags: Antimalarials/pharmacology, Burkina Faso, Drug Resistance, Falciparum/drug therapy/parasitology, GeneticRestriction Fragment Length, Genotype, Humans, Malaria, Membrane Transport Proteins/genetics, msp1, msp2, Multidrug Resistance-Associated Proteins/genetics, Mutation, Pfcrt, Pfmdr1, Plasmodium falciparum, Plasmodium falciparum/drug effects/genetics/isolation & purification, Polymerase Chain Reaction, Polymorphism, Protozoan Proteins/genetics \| Links: Close Close @article{Sondo2021-qe, title = {Polymorphisms in Plasmodium falciparum parasites and mutations in the resistance genes Pfcrt and Pfmdr1 in Nanoro area, Burkina Faso.}, author = {Paul Sondo and Biebo Bihoun and B\'{e}renger Kabore and Marc Christian Tahita and Karim Derra and Toussaint Rouamba and Seydou Nakanabo Diallo and Adama Kazienga and Hamidou Ilboudo and Innocent Valea and Zekiba Tarnagda and Hermann Sorgho and Thierry Lefevre and Halidou Tinto}, doi = {10.11604/pamj.2021.39.118.26959}, issn = {1937-8688}, year = {2021}, date = {2021-06-10}, urldate = {2021-06-10}, journal = {Pan Afr. Med. J.}, volume = {39}, pages = {118}, publisher = {Pan African Medical Journal}, abstract = {Introduction: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. Methods: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. Results: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. Conclusion: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs.}, note = {Copyright: Paul Sondo et al. PMID: 34512854 PMCID: PMC8396377}, keywords = {Antimalarials/pharmacology, Burkina Faso, Drug Resistance, Falciparum/drug therapy/parasitology, GeneticRestriction Fragment Length, Genotype, Humans, Malaria, Membrane Transport Proteins/genetics, msp1, msp2, Multidrug Resistance-Associated Proteins/genetics, Mutation, Pfcrt, Pfmdr1, Plasmodium falciparum, Plasmodium falciparum/drug effects/genetics/isolation \& purification, Polymerase Chain Reaction, Polymorphism, Protozoan Proteins/genetics}, pubstate = {published}, tppubtype = {article} } Close Introduction: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. Methods: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. Results: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. Conclusion: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs. Close
	Hamatandi Magloire Natama, Eduard Rovira-Vallbona, Meryam Krit, Pieter Guetens, Hermann Sorgho, M Athanase Somé, Maminata Traoré-Coulibaly, Innocent Valéa, Petra F Mens, Henk D F H Schallig, Dirk Berkvens, Luc Kestens, Halidou Tinto, Anna Rosanas-Urgell Genetic variation in the immune system and malaria susceptibility in infants: a nested case-control study in Nanoro, Burkina Faso Journal Article In: Malar. J., vol. 20, no. 1, pp. 94, 2021, ISSN: 1475-2875, (PMID: 33593344 PMCID: PMC7885350). Abstract \| BibTeX \| Tags: Burkina Faso, Case-Control Studies, Cytokines, Falciparum/parasitology, Female, Genetic Predisposition to Disease/genetics, Humans, Immunity, Immunogenetic variants, Infant, Innate immunity, Innate/genetics, Malaria, Male, Plasmodium falciparum, Plasmodium falciparum/physiology \| Links: Close Close @article{Natama2021-ft, title = {Genetic variation in the immune system and malaria susceptibility in infants: a nested case-control study in Nanoro, Burkina Faso}, author = {Hamatandi Magloire Natama and Eduard Rovira-Vallbona and Meryam Krit and Pieter Guetens and Hermann Sorgho and M Athanase Som\'{e} and Maminata Traor\'{e}-Coulibaly and Innocent Val\'{e}a and Petra F Mens and Henk D F H Schallig and Dirk Berkvens and Luc Kestens and Halidou Tinto and Anna Rosanas-Urgell}, doi = {10.1186/s12936-021-03628-y}, issn = {1475-2875}, year = {2021}, date = {2021-02-16}, urldate = {2021-02-01}, journal = {Malar. J.}, volume = {20}, number = {1}, pages = {94}, publisher = {Springer Science and Business Media LLC}, abstract = {BACKGROUND: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). RESULTS: Genetic variants in IL-1$beta$ (rs1143634) and Fc$gamma$RIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in Fc$gamma$RIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fc$gamma$ receptors on effector immune cells. CONCLUSIONS: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.}, note = {PMID: 33593344 PMCID: PMC7885350}, keywords = {Burkina Faso, Case-Control Studies, Cytokines, Falciparum/parasitology, Female, Genetic Predisposition to Disease/genetics, Humans, Immunity, Immunogenetic variants, Infant, Innate immunity, Innate/genetics, Malaria, Male, Plasmodium falciparum, Plasmodium falciparum/physiology}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). RESULTS: Genetic variants in IL-1$beta$ (rs1143634) and Fc$gamma$RIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in Fc$gamma$RIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fc$gamma$ receptors on effector immune cells. CONCLUSIONS: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators. Close
	Adama Gansané, Leah F Moriarty, Didier Ménard, Isidore Yerbanga, Esperance Ouedraogo, Paul Sondo, Rene Kinda, Casimir Tarama, Edwige Soulama, Madou Tapsoba, David Kangoye, Cheick Said Compaore, Ousmane Badolo, Blami Dao, Samuel Tchwenko, Halidou Tinto, Innocent Valea Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018 Journal Article In: Malar. J., vol. 20, no. 1, pp. 48, 2021, ISSN: 1475-2875. Abstract \| BibTeX \| Tags: Antimalarial, Antimalarials/pharmacology, Artemether, Artemether-lumefantrine, Artemisinins/pharmacology, Burkina Faso, Child, Dihydroartemisinin-piperaquine, Drug Resistance, Efficacy, Falciparum/drug therapy, Female, Lumefantrine Drug Combination/pharmacology, Malaria, Male, Plasmodium falciparum, Preschool, Quinolines/pharmacology \| Links: Close Close @article{Gansane2021-yh, title = {Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018}, author = {Adama Gansan\'{e} and Leah F Moriarty and Didier M\'{e}nard and Isidore Yerbanga and Esperance Ouedraogo and Paul Sondo and Rene Kinda and Casimir Tarama and Edwige Soulama and Madou Tapsoba and David Kangoye and Cheick Said Compaore and Ousmane Badolo and Blami Dao and Samuel Tchwenko and Halidou Tinto and Innocent Valea}, doi = {10.1186/s12936-021-03585-6}, issn = {1475-2875}, year = {2021}, date = {2021-01-19}, urldate = {2021-01-01}, journal = {Malar. J.}, volume = {20}, number = {1}, pages = {48}, publisher = {Springer Science and Business Media LLC}, abstract = {BACKGROUND: The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy. METHODS: This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed. RESULTS: Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92% (84-96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75-89%) in Gourcy, 89% (81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation. CONCLUSION: The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx.}, keywords = {Antimalarial, Antimalarials/pharmacology, Artemether, Artemether-lumefantrine, Artemisinins/pharmacology, Burkina Faso, Child, Dihydroartemisinin-piperaquine, Drug Resistance, Efficacy, Falciparum/drug therapy, Female, Lumefantrine Drug Combination/pharmacology, Malaria, Male, Plasmodium falciparum, Preschool, Quinolines/pharmacology}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND: The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy. METHODS: This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed. RESULTS: Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92% (84-96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75-89%) in Gourcy, 89% (81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation. CONCLUSION: The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx. Close
2015
Journal Articles
	Martin A. Adjuik, Richard Allan, Anupkumar R. Anvikar, Elizabeth A. Ashley, Mamadou S. Ba, Hubert Barennes, Karen I. Barnes, Quique Bassat, Elisabeth Baudin, Anders Björkman, François Bompart, Maryline Bonnet, Steffen Borrmann, Philippe Brasseur, Hasifa Bukirwa, Francesco Checchi, Michel Cot, Prabin Dahal, Umberto D'Alessandro, Philippe Deloron, Meghna Desai, Graciela Diap, Abdoulaye A. Djimde, Grant Dorsey, Ogobara K. Doumbo, Emmanuelle Espié, Jean Francois Etard, Caterina I. Fanello, Jean François Faucher, Babacar Faye, Jennifer A. Flegg, Oumar Gaye, Peter W. Gething, Raquel González, Francesco Grandesso, Philippe J. Guerin, Jean Paul Guthmann, Sally Hamour, Armedy Ronny Hasugian, Simon I. Hay, Georgina S. Humphreys, Vincent Jullien, Elizabeth Juma, Moses R. Kamya, Corine Karema, Jean R. Kiechel, Peter G. Kremsner, Sanjeev Krishna, Valérie Lameyre, Laminou M. Ibrahim, Sue J. Lee, Bertrand Lell, Andreas Martensson, Achille Massougbodji, Hervé Menan, Didier Ménard, Clara Menéndez, Martin Meremikwu, Clarissa Moreira, Carolyn Nabasumba, Michael Nambozi, Jean Louis Ndiaye, Frederic Nikiema, Christian Nsanzabana, Francine Ntoumi, Bernhards R. Ogutu, Piero Olliaro, Lyda Osorio, Jean Bosco Ouédraogo, Louis K. Penali, Mbaye Pene, Loretxu Pinoges, Patrice Piola, Ric N. Price, Cally Roper, Philip J. Rosenthal, Claude Emile Rwagacondo, Albert Same-Ekobo, Birgit Schramm, Amadou Seck, Bhawna Sharma, Carol Hopkins Sibley, Véronique Sinou, Sodiomon B. Sirima, Jeffery J. Smith, Frank Smithuis, Fabrice A. Somé, Doudou Sow, Sarah G. Staedke, Kasia Stepniewska, Todd D. Swarthout, Khadime Sylla, Ambrose O. Talisuna, Joel Tarning, Walter R. J. Taylor, Emmanuel A. Temu, Julie I. Thwing, Emiliana Tjitra, Roger C. K. Tine, Halidou Tinto, Michel T. Vaillant, Neena Valecha, Ingrid Van Broek, Nicholas J. White, Adoke Yeka, Issaka Zongo The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data Journal Article In: BMC Medicine, vol. 13, iss. 1, 2015, ISSN: 17417015. Abstract \| BibTeX \| Tags: Amodiaquine, Artesunate, Dosing, Drug Resistance, Efficacy, Malaria, Plasmodium falciparum \| Links: Close Close @article{Adjuik2015, title = {The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data}, author = {Martin A. Adjuik and Richard Allan and Anupkumar R. Anvikar and Elizabeth A. Ashley and Mamadou S. Ba and Hubert Barennes and Karen I. Barnes and Quique Bassat and Elisabeth Baudin and Anders Bj\"{o}rkman and Fran\c{c}ois Bompart and Maryline Bonnet and Steffen Borrmann and Philippe Brasseur and Hasifa Bukirwa and Francesco Checchi and Michel Cot and Prabin Dahal and Umberto D'Alessandro and Philippe Deloron and Meghna Desai and Graciela Diap and Abdoulaye A. Djimde and Grant Dorsey and Ogobara K. Doumbo and Emmanuelle Espi\'{e} and Jean Francois Etard and Caterina I. Fanello and Jean Fran\c{c}ois Faucher and Babacar Faye and Jennifer A. Flegg and Oumar Gaye and Peter W. Gething and Raquel Gonz\'{a}lez and Francesco Grandesso and Philippe J. Guerin and Jean Paul Guthmann and Sally Hamour and Armedy Ronny Hasugian and Simon I. Hay and Georgina S. Humphreys and Vincent Jullien and Elizabeth Juma and Moses R. Kamya and Corine Karema and Jean R. Kiechel and Peter G. Kremsner and Sanjeev Krishna and Val\'{e}rie Lameyre and Laminou M. Ibrahim and Sue J. Lee and Bertrand Lell and Andreas Martensson and Achille Massougbodji and Herv\'{e} Menan and Didier M\'{e}nard and Clara Men\'{e}ndez and Martin Meremikwu and Clarissa Moreira and Carolyn Nabasumba and Michael Nambozi and Jean Louis Ndiaye and Frederic Nikiema and Christian Nsanzabana and Francine Ntoumi and Bernhards R. Ogutu and Piero Olliaro and Lyda Osorio and Jean Bosco Ou\'{e}draogo and Louis K. Penali and Mbaye Pene and Loretxu Pinoges and Patrice Piola and Ric N. Price and Cally Roper and Philip J. Rosenthal and Claude Emile Rwagacondo and Albert Same-Ekobo and Birgit Schramm and Amadou Seck and Bhawna Sharma and Carol Hopkins Sibley and V\'{e}ronique Sinou and Sodiomon B. Sirima and Jeffery J. Smith and Frank Smithuis and Fabrice A. Som\'{e} and Doudou Sow and Sarah G. Staedke and Kasia Stepniewska and Todd D. Swarthout and Khadime Sylla and Ambrose O. Talisuna and Joel Tarning and Walter R. J. Taylor and Emmanuel A. Temu and Julie I. Thwing and Emiliana Tjitra and Roger C. K. Tine and Halidou Tinto and Michel T. Vaillant and Neena Valecha and Ingrid Van Broek and Nicholas J. White and Adoke Yeka and Issaka Zongo}, doi = {10.1186/s12916-015-0301-z}, issn = {17417015}, year = {2015}, date = {2015-01-01}, journal = {BMC Medicine}, volume = {13}, issue = {1}, publisher = {BioMed Central Ltd.}, 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 \< 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio}, keywords = {Amodiaquine, Artesunate, Dosing, Drug Resistance, Efficacy, Malaria, Plasmodium falciparum}, pubstate = {published}, tppubtype = {article} } Close 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 < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio Close

2023
Journal Articles
	Adama Gansane, Moussa Lingani, Adoke Yeka, Alain Nahum, Marielle Bouyou-Akotet, Ghyslain Mombo-Ngoma, Grace Kaguthi, Catalina Barceló, Bart Laurijssens, Cathy Cantalloube, Fiona Macintyre, Elhadj Djeriou, Andreas Jessel, Raphaël Bejuit, Helen Demarest, Anne Claire Marrast, Siaka Debe, Halidou Tinto, Afizi Kibuuka, Diolinda Nahum, Denise Patricia Mawili-Mboumba, Rella Zoleko-Manego, Irene Mugenya, Frederick Olewe, Stephan Duparc, Bernhards Ogutu 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 Journal Article In: Malaria journal, vol. 22, iss. 1, 2023, ISSN: 1475-2875. Abstract \| BibTeX \| Tags: 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 \| Links: Close Close @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} } Close 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 ≥ 14–69 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–∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0–d28, 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–Meier) 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). Close
	Holger W. Unger, Anastasia Jessica Hadiprodjo, Julie R. Gutman, Valerie Briand, Nadine Fievet, Innocent Valea, Halidou Tinto, Umberto D’Alessandro, Sarah H. Landis, Feiko Ter Kuile, Peter Ouma, Martina Oneko, Victor Mwapasa, Laurence Slutsker, Dianne J. Terlouw, Simon Kariuki, John Ayisi, Bernard Nahlen, Meghna Desai, Mwayi Madanitsa, Linda Kalilani-Phiri, Per Ashorn, Kenneth Maleta, Antoinette Tshefu-Kitoto, Ivo Mueller, Danielle Stanisic, Jordan Cates, Anna Maria Van Eijk, Maria Ome-Kaius, Elizabeth H. Aitken, Stephen J. Rogerson Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis Journal Article In: Scientific reports, vol. 13, iss. 1, 2023, ISSN: 2045-2322. Abstract \| BibTeX \| Tags: Anastasia Jessica Hadiprodjo, doi:10.1038/s41598-023-37431-3, Extramural, Falciparum* / complications, Falciparum* / epidemiology, Female, Holger W Unger, Humans, Infant, Low Birth Weight, Malaria, Malaria* / complications, Malaria* / epidemiology, MEDLINE, Meta-Analysis, N.I.H., National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, Non-U.S. Gov't, placenta, Plasmodium falciparum, PMC10293221, pmid:37365258, Pregnancy, PubMed Abstract, Research Support, Stephen J Rogerson, Stillbirth \| Links: Close Close @article{Unger2023, title = {Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis}, author = {Holger W. Unger and Anastasia Jessica Hadiprodjo and Julie R. Gutman and Valerie Briand and Nadine Fievet and Innocent Valea and Halidou Tinto and Umberto D’Alessandro and Sarah H. Landis and Feiko Ter Kuile and Peter Ouma and Martina Oneko and Victor Mwapasa and Laurence Slutsker and Dianne J. Terlouw and Simon Kariuki and John Ayisi and Bernard Nahlen and Meghna Desai and Mwayi Madanitsa and Linda Kalilani-Phiri and Per Ashorn and Kenneth Maleta and Antoinette Tshefu-Kitoto and Ivo Mueller and Danielle Stanisic and Jordan Cates and Anna Maria Van Eijk and Maria Ome-Kaius and Elizabeth H. Aitken and Stephen J. Rogerson}, url = {https://pubmed.ncbi.nlm.nih.gov/37365258/}, doi = {10.1038/S41598-023-37431-3}, issn = {2045-2322}, year = {2023}, date = {2023-01-01}, journal = {Scientific reports}, volume = {13}, issue = {1}, publisher = {Sci Rep}, abstract = {In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy.}, keywords = {Anastasia Jessica Hadiprodjo, doi:10.1038/s41598-023-37431-3, Extramural, Falciparum* / complications, Falciparum* / epidemiology, Female, Holger W Unger, Humans, Infant, Low Birth Weight, Malaria, Malaria* / complications, Malaria* / epidemiology, MEDLINE, Meta-Analysis, N.I.H., National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, Non-U.S. Gov't, placenta, Plasmodium falciparum, PMC10293221, pmid:37365258, Pregnancy, PubMed Abstract, Research Support, Stephen J Rogerson, Stillbirth}, pubstate = {published}, tppubtype = {article} } Close In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy. Close
	Bernhards Ogutu, Adoke Yeka, Sylvia Kusemererwa, Ricardo Thompson, Halidou Tinto, Andre Offianan Toure, Chirapong Uthaisin, Amar Verma, Afizi Kibuuka, Moussa Lingani, Carlos Lourenço, Ghyslain Mombo-Ngoma, Videlis Nduba, Tiacoh Landry N'Guessan, Guétawendé Job Wilfried Nassa, Mary Nyantaro, Lucas Otieno Tina, Piyoosh K. Singh, Myriam El Gaaloul, Anne Claire Marrast, Havana Chikoto, Katalin Csermak, Ivan Demin, Dheeraj Mehta, Rashidkhan Pathan, Celine Risterucci, Guoqin Su, Cornelis Winnips, Grace Kaguthi, Bakary Fofana, Martin Peter Grobusch Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial Journal Article In: The Lancet. Infectious diseases, vol. 23, iss. 9, pp. 1051-1061, 2023, ISSN: 1474-4457. Abstract \| BibTeX \| Tags: 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 \| Links: Close Close @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} } Close 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 (2020–003284–25) 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 81–98] with 1 day, 47 of 48 [98%, 89–100] with 2 days, and 42 of 43 [98%, 88–100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83–99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93–100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92–100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86–100] 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 83–99] vs 21 of 22 [96%, 77–100] 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. Close
	Hamtandi Magloire Natama, Gemma Moncunill, Marta Vidal, Toussaint Rouamba, Ruth Aguilar, Rebeca Santano, Eduard Rovira-Vallbona, Alfons Jiménez, M. Athanase Somé, Hermann Sorgho, Innocent Valéa, Maminata Coulibaly-Traoré, Ross L. Coppel, David Cavanagh, Chetan E. Chitnis, James G. Beeson, Evelina Angov, Sheetij Dutta, Benoit Gamain, Luis Izquierdo, Petra F. Mens, Henk D. F. H. Schallig, Halidou Tinto, Anna Rosanas-Urgell, Carlota Dobaño Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso Journal Article In: Infection and immunity, vol. 91, iss. 10, pp. 290, 2023, ISSN: 1098-5522. Abstract \| BibTeX \| Tags: Antibodies, Antigens, Burkina Faso / epidemiology, Carlota Dobaño, Child, Cohort Studies, doi:10.1128/iai.00268-23, Falciparum, Female, Gemma Moncunill, Hamtandi Magloire Natama, Humans, Immunoglobulin G, Infant, Malaria, Malaria / epidemiology, Maternal Exposure, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, placenta, Plasmodium falciparum, PMC10580994, pmid:37754682, Pregnancy, Preschool, Protozoan, PubMed Abstract \| Links: Close Close @article{Natama2023, title = {Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso}, author = {Hamtandi Magloire Natama and Gemma Moncunill and Marta Vidal and Toussaint Rouamba and Ruth Aguilar and Rebeca Santano and Eduard Rovira-Vallbona and Alfons Jim\'{e}nez and M. Athanase Som\'{e} and Hermann Sorgho and Innocent Val\'{e}a and Maminata Coulibaly-Traor\'{e} and Ross L. Coppel and David Cavanagh and Chetan E. Chitnis and James G. Beeson and Evelina Angov and Sheetij Dutta and Benoit Gamain and Luis Izquierdo and Petra F. Mens and Henk D. F. H. Schallig and Halidou Tinto and Anna Rosanas-Urgell and Carlota Doba\~{n}o}, url = {https://pubmed.ncbi.nlm.nih.gov/37754682/}, doi = {10.1128/IAI.00268-23}, issn = {1098-5522}, year = {2023}, date = {2023-01-01}, journal = {Infection and immunity}, volume = {91}, issue = {10}, pages = {290}, publisher = {Infect Immun}, abstract = {In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.}, keywords = {Antibodies, Antigens, Burkina Faso / epidemiology, Carlota Doba\~{n}o, Child, Cohort Studies, doi:10.1128/iai.00268-23, Falciparum, Female, Gemma Moncunill, Hamtandi Magloire Natama, Humans, Immunoglobulin G, Infant, Malaria, Malaria / epidemiology, Maternal Exposure, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, placenta, Plasmodium falciparum, PMC10580994, pmid:37754682, Pregnancy, Preschool, Protozoan, PubMed Abstract}, pubstate = {published}, tppubtype = {article} } Close In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood. Close
	Japhet Kabalu Tshiongo, Flory Luzolo, Melissa Kabena, Lise Kuseke, Moussa Djimde, Patrick Mitashi, Crispin Lumbala, Kassoum Kayentao, Sandra Menting, Petra F. Mens, Henk D. F. H. Schallig, Pascal Lutumba, Halidou Tinto, Hypolite Muhindo Mavoko, Vivi Maketa Performance of ultra-sensitive malaria rapid diagnostic test to detect Plasmodium falciparum infection in pregnant women in Kinshasa, the Democratic Republic of the Congo Journal Article In: Malaria journal, vol. 22, iss. 1, 2023, ISSN: 1475-2875. Abstract \| BibTeX \| Tags: Antigens, Democratic Republic of the Congo, Diagnostic Tests, doi:10.1186/s12936-023-04749-2, Falciparum* / epidemiology, Female, Flory Luzolo, Humans, Japhet Kabalu Tshiongo, Malaria, Malaria, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Plasmodium falciparum, PMC10594769, pmid:37872634, Pregnancy, Pregnant Women, Protozoan, PubMed Abstract, Rapid diagnostic tests, Routine / methods, Sensitivity and Specificity, Vivi Maketa \| Links: Close Close @article{nokey, title = {Performance of ultra-sensitive malaria rapid diagnostic test to detect Plasmodium falciparum infection in pregnant women in Kinshasa, the Democratic Republic of the Congo}, author = {Japhet Kabalu Tshiongo and Flory Luzolo and Melissa Kabena and Lise Kuseke and Moussa Djimde and Patrick Mitashi and Crispin Lumbala and Kassoum Kayentao and Sandra Menting and Petra F. Mens and Henk D. F. H. Schallig and Pascal Lutumba and Halidou Tinto and Hypolite Muhindo Mavoko and Vivi Maketa}, url = {https://pubmed.ncbi.nlm.nih.gov/37872634/}, doi = {10.1186/S12936-023-04749-2}, issn = {1475-2875}, year = {2023}, date = {2023-01-01}, journal = {Malaria journal}, volume = {22}, issue = {1}, publisher = {Malar J}, abstract = {Background: Low peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo. Methods: To assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test. Results: The median parasite density by qPCR was 292 p/μL of blood [IQR (49.7\textendash1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6\textendash63.6)], [81.7% (95%CI 74.7\textendash87.3)] and [88% (95% CI 81.9\textendash92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6\textendash99.5), 95.2% (95% CI 92.5\textendash97.2) and 94.4% (95% CI 91.4\textendash96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1\textendash75.3) compared to 68% (95% CI 53.3\textendash80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8\textendash98.7) for RDT versus 100% (95% CI 82.3\textendash100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10\textendash33.7) and 47.3% (95% CI 24.4\textendash71.1) respectively. Conclusions: uRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity.}, keywords = {Antigens, Democratic Republic of the Congo, Diagnostic Tests, doi:10.1186/s12936-023-04749-2, Falciparum / epidemiology, Female, Flory Luzolo, Humans, Japhet Kabalu Tshiongo, Malaria, Malaria*, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Plasmodium falciparum, PMC10594769, pmid:37872634, Pregnancy, Pregnant Women, Protozoan, PubMed Abstract, Rapid diagnostic tests, Routine / methods, Sensitivity and Specificity, Vivi Maketa}, pubstate = {published}, tppubtype = {article} } Close Background: Low peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo. Methods: To assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test. Results: The median parasite density by qPCR was 292 p/μL of blood [IQR (49.7–1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6–63.6)], [81.7% (95%CI 74.7–87.3)] and [88% (95% CI 81.9–92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6–99.5), 95.2% (95% CI 92.5–97.2) and 94.4% (95% CI 91.4–96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1–75.3) compared to 68% (95% CI 53.3–80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8–98.7) for RDT versus 100% (95% CI 82.3–100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10–33.7) and 47.3% (95% CI 24.4–71.1) respectively. Conclusions: uRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity. Close
2022
Journal Articles
	Paul Sondo, Marc Christian Tahita, Hamidou Ilboudo, Toussaint Rouamba, Karim Derra, Gauthier Tougri, Florence Ouédraogo, Béatrice Marie Adélaïde Konseibo, Eli Roamba, Sabina Dahlström Otienoburu, Bérenger Kaboré, Kalynn Kennon, Kadija Ouédraogo, Wend-Timbe-Noma Arlette Raïssa Zongo, Fadima Yaya Bocoum, Kasia Stepniewska, Mehul Dhorda, Philippe J. Guérin, Halidou Tinto Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial Journal Article In: Archives of Public Health, vol. 80, iss. 1, pp. 41, 2022, ISSN: 2049-3258. Abstract \| BibTeX \| Tags: Africa, Amodiaquine, Burkina Faso, Chemoprevention, Dihydro artemisinin Piperaquine, Malaria, Plasmodium falciparum, Sulfadoxine-pyrimethamine \| Links: Close Close @article{Sondo2022, title = {Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial}, author = {Paul Sondo and Marc Christian Tahita and Hamidou Ilboudo and Toussaint Rouamba and Karim Derra and Gauthier Tougri and Florence Ou\'{e}draogo and B\'{e}atrice Marie Ad\'{e}la\"{i}de Konseibo and Eli Roamba and Sabina Dahlstr\"{o}m Otienoburu and B\'{e}renger Kabor\'{e} and Kalynn Kennon and Kadija Ou\'{e}draogo and Wend-Timbe-Noma Arlette Ra\"{i}ssa Zongo and Fadima Yaya Bocoum and Kasia Stepniewska and Mehul Dhorda and Philippe J. Gu\'{e}rin and Halidou Tinto}, url = {https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-022-00800-x}, doi = {10.1186/s13690-022-00800-x}, issn = {2049-3258}, year = {2022}, date = {2022-01-01}, urldate = {2022-01-01}, journal = {Archives of Public Health}, volume = {80}, issue = {1}, pages = {41}, abstract = {BACKGROUND Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention.}, keywords = {Africa, Amodiaquine, Burkina Faso, Chemoprevention, Dihydro artemisinin Piperaquine, Malaria, Plasmodium falciparum, Sulfadoxine-pyrimethamine}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention. Close
	Rashid Mansoor, Robert J. Commons, Nicholas M. Douglas, Benjamin Abuaku, Jane Achan, Ishag Adam, George O. Adjei, Martin Adjuik, Bereket H. Alemayehu, Richard Allan, Elizabeth N. Allen, Anupkumar R. Anvikar, Emmanuel Arinaitwe, Elizabeth A. Ashley, Hazel Ashurst, Puji B. S. Asih, Nathan Bakyaita, Hubert Barennes, Karen I. Barnes, Leonardo Basco, Quique Bassat, Elisabeth Baudin, David J Bell, Delia Bethell, Anders Bjorkman, Caroline Boulton, Teun Bousema, Philippe Brasseur, Hasifa Bukirwa, Rebekah Burrow, Verena I. Carrara, Michel Cot, Umberto D’Alessandro, Debashish Das, Sabyasachi Das, Timothy M. E. Davis, Meghna Desai, Abdoulaye A. Djimde, Arjen M. Dondorp, Grant Dorsey, Chris J. Drakeley, Stephan Duparc, Emmanuelle Espié, Jean-Francois Etard, Catherine Falade, Jean Francois Faucher, Scott Filler, Carole Fogg, Mark Fukuda, Oumar Gaye, Blaise Genton, Awab Ghulam Rahim, Julius Gilayeneh, Raquel Gonzalez, Rebecca F. Grais, Francesco Grandesso, Brian Greenwood, Anastasia Grivoyannis, Christoph Hatz, Eva Maria Hodel, Georgina S. Humphreys, Jimee Hwang, Deus Ishengoma, Elizabeth Juma, S. Patrick Kachur, Piet A. Kager, Erasmus Kamugisha, Moses R. Kamya, Corine Karema, Kassoum Kayentao, Adama Kazienga, Jean-René Kiechel, Poul-Erik Kofoed, Kwadwo Koram, Peter G. Kremsner, David G. Lalloo, Moses Laman, Sue J. Lee, Bertrand Lell, Amelia W. Maiga, Andreas Mårtensson, Mayfong Mayxay, Wilfred Mbacham, Rose McGready, Hervé Menan, Didier Ménard, Frank Mockenhaupt, Brioni R. Moore, Olaf Müller, Alain Nahum, Jean-Louis Ndiaye, Paul N. Newton, Billy E. Ngasala, Frederic Nikiema, Akindeh M. Nji, Harald Noedl, Francois Nosten, Bernhards R. Ogutu, Olusola Ojurongbe, Lyda Osorio, Jean-Bosco Ouédraogo, Seth Owusu-Agyei, Anil Pareek, Louis K. Penali, Patrice Piola, Mateusz Plucinski, Zul Premji, Michael Ramharter, Caitlin L. Richmond, Lars Rombo, Cally Roper, Philip J. Rosenthal, Sam Salman, Albert Same-Ekobo, Carol Sibley, Sodiomon B. Sirima, Frank M. Smithuis, Fabrice A. Somé, Sarah G. Staedke, Peter Starzengruber, Nathalie Strub-Wourgaft, Inge Sutanto, Todd D. Swarthout, Din Syafruddin, Ambrose O. Talisuna, Walter R. Taylor, Emmanuel A. Temu, Julie I. Thwing, Halidou Tinto, Emiliana Tjitra, Offianan A. Touré, T. Hien Tran, Johan Ursing, Innocent Valea, Giovanni Valentini, Michele Vugt, Lorenz Seidlein, Stephen A. Ward, Vincent Were, Nicholas J. White, Charles J. Woodrow, William Yavo, Adoke Yeka, Issaka Zongo, Julie A. Simpson, Philippe J. Guerin, Kasia Stepniewska, Ric N. Price Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data Journal Article In: BMC Medicine, vol. 20, iss. 1, pp. 85, 2022, ISSN: 1741-7015. Abstract \| BibTeX \| Tags: Antimalarials, Artemisinin-based therapy, Haemoglobin, Non-artemisinin-based therapy, Plasmodium falciparum, Pooled analysis of individual patient data, Severe anaemia \| Links: Close Close @article{Mansoor2022, title = {Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data}, author = {Rashid Mansoor and Robert J. Commons and Nicholas M. Douglas and Benjamin Abuaku and Jane Achan and Ishag Adam and George O. Adjei and Martin Adjuik and Bereket H. Alemayehu and Richard Allan and Elizabeth N. Allen and Anupkumar R. Anvikar and Emmanuel Arinaitwe and Elizabeth A. Ashley and Hazel Ashurst and Puji B. S. Asih and Nathan Bakyaita and Hubert Barennes and Karen I. Barnes and Leonardo Basco and Quique Bassat and Elisabeth Baudin and David J Bell and Delia Bethell and Anders Bjorkman and Caroline Boulton and Teun Bousema and Philippe Brasseur and Hasifa Bukirwa and Rebekah Burrow and Verena I. Carrara and Michel Cot and Umberto D’Alessandro and Debashish Das and Sabyasachi Das and Timothy M. E. Davis and Meghna Desai and Abdoulaye A. Djimde and Arjen M. Dondorp and Grant Dorsey and Chris J. Drakeley and Stephan Duparc and Emmanuelle Espi\'{e} and Jean-Francois Etard and Catherine Falade and Jean Francois Faucher and Scott Filler and Carole Fogg and Mark Fukuda and Oumar Gaye and Blaise Genton and Awab Ghulam Rahim and Julius Gilayeneh and Raquel Gonzalez and Rebecca F. Grais and Francesco Grandesso and Brian Greenwood and Anastasia Grivoyannis and Christoph Hatz and Eva Maria Hodel and Georgina S. Humphreys and Jimee Hwang and Deus Ishengoma and Elizabeth Juma and S. Patrick Kachur and Piet A. Kager and Erasmus Kamugisha and Moses R. Kamya and Corine Karema and Kassoum Kayentao and Adama Kazienga and Jean-Ren\'{e} Kiechel and Poul-Erik Kofoed and Kwadwo Koram and Peter G. Kremsner and David G. Lalloo and Moses Laman and Sue J. Lee and Bertrand Lell and Amelia W. Maiga and Andreas Mr{a}rtensson and Mayfong Mayxay and Wilfred Mbacham and Rose McGready and Herv\'{e} Menan and Didier M\'{e}nard and Frank Mockenhaupt and Brioni R. Moore and Olaf M\"{u}ller and Alain Nahum and Jean-Louis Ndiaye and Paul N. Newton and Billy E. Ngasala and Frederic Nikiema and Akindeh M. Nji and Harald Noedl and Francois Nosten and Bernhards R. Ogutu and Olusola Ojurongbe and Lyda Osorio and Jean-Bosco Ou\'{e}draogo and Seth Owusu-Agyei and Anil Pareek and Louis K. Penali and Patrice Piola and Mateusz Plucinski and Zul Premji and Michael Ramharter and Caitlin L. Richmond and Lars Rombo and Cally Roper and Philip J. Rosenthal and Sam Salman and Albert Same-Ekobo and Carol Sibley and Sodiomon B. Sirima and Frank M. Smithuis and Fabrice A. Som\'{e} and Sarah G. Staedke and Peter Starzengruber and Nathalie Strub-Wourgaft and Inge Sutanto and Todd D. Swarthout and Din Syafruddin and Ambrose O. Talisuna and Walter R. Taylor and Emmanuel A. Temu and Julie I. Thwing and Halidou Tinto and Emiliana Tjitra and Offianan A. Tour\'{e} and T. Hien Tran and Johan Ursing and Innocent Valea and Giovanni Valentini and Michele Vugt and Lorenz Seidlein and Stephen A. Ward and Vincent Were and Nicholas J. White and Charles J. Woodrow and William Yavo and Adoke Yeka and Issaka Zongo and Julie A. Simpson and Philippe J. Guerin and Kasia Stepniewska and Ric N. Price}, url = {https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02265-9}, doi = {10.1186/s12916-022-02265-9}, issn = {1741-7015}, year = {2022}, date = {2022-01-01}, urldate = {2022-01-01}, journal = {BMC Medicine}, volume = {20}, issue = {1}, pages = {85}, abstract = {BACKGROUND Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin \< 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb \< 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age \< 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p \< 0.001). CONCLUSIONS In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.}, keywords = {Antimalarials, Artemisinin-based therapy, Haemoglobin, Non-artemisinin-based therapy, Plasmodium falciparum, Pooled analysis of individual patient data, Severe anaemia}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001). CONCLUSIONS In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery. Close
	Harvie P. Portugaliza, H. Magloire Natama, Pieter Guetens, Eduard Rovira-Vallbona, Athanase M. Somé, Aida Millogo, D. Florence Ouédraogo, Innocent Valéa, Hermann Sorgho, Halidou Tinto, Nguyen Hong, Antonio Sitoe, Rosauro Varo, Quique Bassat, Alfred Cortés, Anna Rosanas-Urgell Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients Journal Article In: eBioMedicine, vol. 83, pp. 104198, 2022, ISSN: 23523964. Abstract \| BibTeX \| Tags: Artemisinin, Malaria transmission, pfap2-g, Plasmodium falciparum, Sexual conversion \| Links: Close Close @article{Portugaliza2022, title = {Plasmodium falciparum sexual conversion rates can be affected by artemisinin-based treatment in naturally infected malaria patients}, author = {Harvie P. Portugaliza and H. Magloire Natama and Pieter Guetens and Eduard Rovira-Vallbona and Athanase M. Som\'{e} and Aida Millogo and D. Florence Ou\'{e}draogo and Innocent Val\'{e}a and Hermann Sorgho and Halidou Tinto and Nguyen Hong and Antonio Sitoe and Rosauro Varo and Quique Bassat and Alfred Cort\'{e}s and Anna Rosanas-Urgell}, url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396422003802}, doi = {10.1016/j.ebiom.2022.104198}, issn = {23523964}, year = {2022}, date = {2022-01-01}, journal = {eBioMedicine}, volume = {83}, pages = {104198}, abstract = {BACKGROUND Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes. METHODS The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total}, keywords = {Artemisinin, Malaria transmission, pfap2-g, Plasmodium falciparum, Sexual conversion}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes. METHODS The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total Close
	Matthew Cairns, Amadou Barry, Issaka Zongo, Issaka Sagara, Serge R. Yerbanga, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Abdoul Aziz Sienou, Amadou Tapily, Koualy Sanogo, Mahamadou Kaya, Seydou Traore, Kalifa Diarra, Hama Yalcouye, Youssoufa Sidibe, Alassane Haro, Ismaila Thera, Paul Snell, Jane Grant, Halidou Tinto, Paul Milligan, Daniel Chandramohan, Brian Greenwood, Alassane Dicko, Jean Bosco Ouedraogo The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone Journal Article In: BMC Medicine, vol. 20, iss. 1, pp. 352, 2022, ISSN: 1741-7015. Abstract \| BibTeX \| Tags: Malaria, Malaria vaccination, Plasmodium falciparum, RTS, S/AS01E, seasonal malaria chemoprevention \| Links: Close Close @article{Cairns2022, title = {The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone}, author = {Matthew Cairns and Amadou Barry and Issaka Zongo and Issaka Sagara and Serge R. Yerbanga and Modibo Diarra and Charles Zoungrana and Djibrilla Issiaka and Abdoul Aziz Sienou and Amadou Tapily and Koualy Sanogo and Mahamadou Kaya and Seydou Traore and Kalifa Diarra and Hama Yalcouye and Youssoufa Sidibe and Alassane Haro and Ismaila Thera and Paul Snell and Jane Grant and Halidou Tinto and Paul Milligan and Daniel Chandramohan and Brian Greenwood and Alassane Dicko and Jean Bosco Ouedraogo}, url = {https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02536-5}, doi = {10.1186/s12916-022-02536-5}, issn = {1741-7015}, year = {2022}, date = {2022-01-01}, journal = {BMC Medicine}, volume = {20}, issue = {1}, pages = {352}, abstract = {BACKGROUND A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218.}, keywords = {Malaria, Malaria vaccination, Plasmodium falciparum, RTS, S/AS01E, seasonal malaria chemoprevention}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218. Close
2021
Journal Articles
	Paul Sondo, Biebo Bihoun, Bérenger Kabore, Marc Christian Tahita, Karim Derra, Toussaint Rouamba, Seydou Nakanabo Diallo, Adama Kazienga, Hamidou Ilboudo, Innocent Valea, Zekiba Tarnagda, Hermann Sorgho, Thierry Lefevre, Halidou Tinto Polymorphisms in Plasmodium falciparum parasites and mutations in the resistance genes Pfcrt and Pfmdr1 in Nanoro area, Burkina Faso. Journal Article In: Pan Afr. Med. J., vol. 39, pp. 118, 2021, ISSN: 1937-8688, (Copyright: Paul Sondo et al. PMID: 34512854 PMCID: PMC8396377). Abstract \| BibTeX \| Tags: Antimalarials/pharmacology, Burkina Faso, Drug Resistance, Falciparum/drug therapy/parasitology, GeneticRestriction Fragment Length, Genotype, Humans, Malaria, Membrane Transport Proteins/genetics, msp1, msp2, Multidrug Resistance-Associated Proteins/genetics, Mutation, Pfcrt, Pfmdr1, Plasmodium falciparum, Plasmodium falciparum/drug effects/genetics/isolation & purification, Polymerase Chain Reaction, Polymorphism, Protozoan Proteins/genetics \| Links: Close Close @article{Sondo2021-qe, title = {Polymorphisms in Plasmodium falciparum parasites and mutations in the resistance genes Pfcrt and Pfmdr1 in Nanoro area, Burkina Faso.}, author = {Paul Sondo and Biebo Bihoun and B\'{e}renger Kabore and Marc Christian Tahita and Karim Derra and Toussaint Rouamba and Seydou Nakanabo Diallo and Adama Kazienga and Hamidou Ilboudo and Innocent Valea and Zekiba Tarnagda and Hermann Sorgho and Thierry Lefevre and Halidou Tinto}, doi = {10.11604/pamj.2021.39.118.26959}, issn = {1937-8688}, year = {2021}, date = {2021-06-10}, urldate = {2021-06-10}, journal = {Pan Afr. Med. J.}, volume = {39}, pages = {118}, publisher = {Pan African Medical Journal}, abstract = {Introduction: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. Methods: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. Results: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. Conclusion: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs.}, note = {Copyright: Paul Sondo et al. PMID: 34512854 PMCID: PMC8396377}, keywords = {Antimalarials/pharmacology, Burkina Faso, Drug Resistance, Falciparum/drug therapy/parasitology, GeneticRestriction Fragment Length, Genotype, Humans, Malaria, Membrane Transport Proteins/genetics, msp1, msp2, Multidrug Resistance-Associated Proteins/genetics, Mutation, Pfcrt, Pfmdr1, Plasmodium falciparum, Plasmodium falciparum/drug effects/genetics/isolation \& purification, Polymerase Chain Reaction, Polymorphism, Protozoan Proteins/genetics}, pubstate = {published}, tppubtype = {article} } Close Introduction: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso. Methods: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP. Results: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections. Conclusion: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs. Close
	Hamatandi Magloire Natama, Eduard Rovira-Vallbona, Meryam Krit, Pieter Guetens, Hermann Sorgho, M Athanase Somé, Maminata Traoré-Coulibaly, Innocent Valéa, Petra F Mens, Henk D F H Schallig, Dirk Berkvens, Luc Kestens, Halidou Tinto, Anna Rosanas-Urgell Genetic variation in the immune system and malaria susceptibility in infants: a nested case-control study in Nanoro, Burkina Faso Journal Article In: Malar. J., vol. 20, no. 1, pp. 94, 2021, ISSN: 1475-2875, (PMID: 33593344 PMCID: PMC7885350). Abstract \| BibTeX \| Tags: Burkina Faso, Case-Control Studies, Cytokines, Falciparum/parasitology, Female, Genetic Predisposition to Disease/genetics, Humans, Immunity, Immunogenetic variants, Infant, Innate immunity, Innate/genetics, Malaria, Male, Plasmodium falciparum, Plasmodium falciparum/physiology \| Links: Close Close @article{Natama2021-ft, title = {Genetic variation in the immune system and malaria susceptibility in infants: a nested case-control study in Nanoro, Burkina Faso}, author = {Hamatandi Magloire Natama and Eduard Rovira-Vallbona and Meryam Krit and Pieter Guetens and Hermann Sorgho and M Athanase Som\'{e} and Maminata Traor\'{e}-Coulibaly and Innocent Val\'{e}a and Petra F Mens and Henk D F H Schallig and Dirk Berkvens and Luc Kestens and Halidou Tinto and Anna Rosanas-Urgell}, doi = {10.1186/s12936-021-03628-y}, issn = {1475-2875}, year = {2021}, date = {2021-02-16}, urldate = {2021-02-01}, journal = {Malar. J.}, volume = {20}, number = {1}, pages = {94}, publisher = {Springer Science and Business Media LLC}, abstract = {BACKGROUND: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). RESULTS: Genetic variants in IL-1$beta$ (rs1143634) and Fc$gamma$RIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in Fc$gamma$RIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fc$gamma$ receptors on effector immune cells. CONCLUSIONS: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.}, note = {PMID: 33593344 PMCID: PMC7885350}, keywords = {Burkina Faso, Case-Control Studies, Cytokines, Falciparum/parasitology, Female, Genetic Predisposition to Disease/genetics, Humans, Immunity, Immunogenetic variants, Infant, Innate immunity, Innate/genetics, Malaria, Male, Plasmodium falciparum, Plasmodium falciparum/physiology}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND: Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case-control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). RESULTS: Genetic variants in IL-1$beta$ (rs1143634) and Fc$gamma$RIIA/CD32 (rs1801274)-both in allelic, dominant and co-dominant models-were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in Fc$gamma$RIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fc$gamma$ receptors on effector immune cells. CONCLUSIONS: These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators. Close
	Adama Gansané, Leah F Moriarty, Didier Ménard, Isidore Yerbanga, Esperance Ouedraogo, Paul Sondo, Rene Kinda, Casimir Tarama, Edwige Soulama, Madou Tapsoba, David Kangoye, Cheick Said Compaore, Ousmane Badolo, Blami Dao, Samuel Tchwenko, Halidou Tinto, Innocent Valea Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018 Journal Article In: Malar. J., vol. 20, no. 1, pp. 48, 2021, ISSN: 1475-2875. Abstract \| BibTeX \| Tags: Antimalarial, Antimalarials/pharmacology, Artemether, Artemether-lumefantrine, Artemisinins/pharmacology, Burkina Faso, Child, Dihydroartemisinin-piperaquine, Drug Resistance, Efficacy, Falciparum/drug therapy, Female, Lumefantrine Drug Combination/pharmacology, Malaria, Male, Plasmodium falciparum, Preschool, Quinolines/pharmacology \| Links: Close Close @article{Gansane2021-yh, title = {Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018}, author = {Adama Gansan\'{e} and Leah F Moriarty and Didier M\'{e}nard and Isidore Yerbanga and Esperance Ouedraogo and Paul Sondo and Rene Kinda and Casimir Tarama and Edwige Soulama and Madou Tapsoba and David Kangoye and Cheick Said Compaore and Ousmane Badolo and Blami Dao and Samuel Tchwenko and Halidou Tinto and Innocent Valea}, doi = {10.1186/s12936-021-03585-6}, issn = {1475-2875}, year = {2021}, date = {2021-01-19}, urldate = {2021-01-01}, journal = {Malar. J.}, volume = {20}, number = {1}, pages = {48}, publisher = {Springer Science and Business Media LLC}, abstract = {BACKGROUND: The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy. METHODS: This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed. RESULTS: Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92% (84-96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75-89%) in Gourcy, 89% (81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation. CONCLUSION: The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx.}, keywords = {Antimalarial, Antimalarials/pharmacology, Artemether, Artemether-lumefantrine, Artemisinins/pharmacology, Burkina Faso, Child, Dihydroartemisinin-piperaquine, Drug Resistance, Efficacy, Falciparum/drug therapy, Female, Lumefantrine Drug Combination/pharmacology, Malaria, Male, Plasmodium falciparum, Preschool, Quinolines/pharmacology}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND: The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy. METHODS: This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed. RESULTS: Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92% (84-96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75-89%) in Gourcy, 89% (81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation. CONCLUSION: The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx. Close
2015
Journal Articles
	Martin A. Adjuik, Richard Allan, Anupkumar R. Anvikar, Elizabeth A. Ashley, Mamadou S. Ba, Hubert Barennes, Karen I. Barnes, Quique Bassat, Elisabeth Baudin, Anders Björkman, François Bompart, Maryline Bonnet, Steffen Borrmann, Philippe Brasseur, Hasifa Bukirwa, Francesco Checchi, Michel Cot, Prabin Dahal, Umberto D'Alessandro, Philippe Deloron, Meghna Desai, Graciela Diap, Abdoulaye A. Djimde, Grant Dorsey, Ogobara K. Doumbo, Emmanuelle Espié, Jean Francois Etard, Caterina I. Fanello, Jean François Faucher, Babacar Faye, Jennifer A. Flegg, Oumar Gaye, Peter W. Gething, Raquel González, Francesco Grandesso, Philippe J. Guerin, Jean Paul Guthmann, Sally Hamour, Armedy Ronny Hasugian, Simon I. Hay, Georgina S. Humphreys, Vincent Jullien, Elizabeth Juma, Moses R. Kamya, Corine Karema, Jean R. Kiechel, Peter G. Kremsner, Sanjeev Krishna, Valérie Lameyre, Laminou M. Ibrahim, Sue J. Lee, Bertrand Lell, Andreas Martensson, Achille Massougbodji, Hervé Menan, Didier Ménard, Clara Menéndez, Martin Meremikwu, Clarissa Moreira, Carolyn Nabasumba, Michael Nambozi, Jean Louis Ndiaye, Frederic Nikiema, Christian Nsanzabana, Francine Ntoumi, Bernhards R. Ogutu, Piero Olliaro, Lyda Osorio, Jean Bosco Ouédraogo, Louis K. Penali, Mbaye Pene, Loretxu Pinoges, Patrice Piola, Ric N. Price, Cally Roper, Philip J. Rosenthal, Claude Emile Rwagacondo, Albert Same-Ekobo, Birgit Schramm, Amadou Seck, Bhawna Sharma, Carol Hopkins Sibley, Véronique Sinou, Sodiomon B. Sirima, Jeffery J. Smith, Frank Smithuis, Fabrice A. Somé, Doudou Sow, Sarah G. Staedke, Kasia Stepniewska, Todd D. Swarthout, Khadime Sylla, Ambrose O. Talisuna, Joel Tarning, Walter R. J. Taylor, Emmanuel A. Temu, Julie I. Thwing, Emiliana Tjitra, Roger C. K. Tine, Halidou Tinto, Michel T. Vaillant, Neena Valecha, Ingrid Van Broek, Nicholas J. White, Adoke Yeka, Issaka Zongo The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data Journal Article In: BMC Medicine, vol. 13, iss. 1, 2015, ISSN: 17417015. Abstract \| BibTeX \| Tags: Amodiaquine, Artesunate, Dosing, Drug Resistance, Efficacy, Malaria, Plasmodium falciparum \| Links: Close Close @article{Adjuik2015, title = {The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: A meta-analysis of individual patient data}, author = {Martin A. Adjuik and Richard Allan and Anupkumar R. Anvikar and Elizabeth A. Ashley and Mamadou S. Ba and Hubert Barennes and Karen I. Barnes and Quique Bassat and Elisabeth Baudin and Anders Bj\"{o}rkman and Fran\c{c}ois Bompart and Maryline Bonnet and Steffen Borrmann and Philippe Brasseur and Hasifa Bukirwa and Francesco Checchi and Michel Cot and Prabin Dahal and Umberto D'Alessandro and Philippe Deloron and Meghna Desai and Graciela Diap and Abdoulaye A. Djimde and Grant Dorsey and Ogobara K. Doumbo and Emmanuelle Espi\'{e} and Jean Francois Etard and Caterina I. Fanello and Jean Fran\c{c}ois Faucher and Babacar Faye and Jennifer A. Flegg and Oumar Gaye and Peter W. Gething and Raquel Gonz\'{a}lez and Francesco Grandesso and Philippe J. Guerin and Jean Paul Guthmann and Sally Hamour and Armedy Ronny Hasugian and Simon I. Hay and Georgina S. Humphreys and Vincent Jullien and Elizabeth Juma and Moses R. Kamya and Corine Karema and Jean R. Kiechel and Peter G. Kremsner and Sanjeev Krishna and Val\'{e}rie Lameyre and Laminou M. Ibrahim and Sue J. Lee and Bertrand Lell and Andreas Martensson and Achille Massougbodji and Herv\'{e} Menan and Didier M\'{e}nard and Clara Men\'{e}ndez and Martin Meremikwu and Clarissa Moreira and Carolyn Nabasumba and Michael Nambozi and Jean Louis Ndiaye and Frederic Nikiema and Christian Nsanzabana and Francine Ntoumi and Bernhards R. Ogutu and Piero Olliaro and Lyda Osorio and Jean Bosco Ou\'{e}draogo and Louis K. Penali and Mbaye Pene and Loretxu Pinoges and Patrice Piola and Ric N. Price and Cally Roper and Philip J. Rosenthal and Claude Emile Rwagacondo and Albert Same-Ekobo and Birgit Schramm and Amadou Seck and Bhawna Sharma and Carol Hopkins Sibley and V\'{e}ronique Sinou and Sodiomon B. Sirima and Jeffery J. Smith and Frank Smithuis and Fabrice A. Som\'{e} and Doudou Sow and Sarah G. Staedke and Kasia Stepniewska and Todd D. Swarthout and Khadime Sylla and Ambrose O. Talisuna and Joel Tarning and Walter R. J. Taylor and Emmanuel A. Temu and Julie I. Thwing and Emiliana Tjitra and Roger C. K. Tine and Halidou Tinto and Michel T. Vaillant and Neena Valecha and Ingrid Van Broek and Nicholas J. White and Adoke Yeka and Issaka Zongo}, doi = {10.1186/s12916-015-0301-z}, issn = {17417015}, year = {2015}, date = {2015-01-01}, journal = {BMC Medicine}, volume = {13}, issue = {1}, publisher = {BioMed Central Ltd.}, 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 \< 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio}, keywords = {Amodiaquine, Artesunate, Dosing, Drug Resistance, Efficacy, Malaria, Plasmodium falciparum}, pubstate = {published}, tppubtype = {article} } Close 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 < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio Close

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" Our main objective is to develop and maintain over time a good expertise and infrastructure ensuring high quality training and clinical research."
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" Our main objective is to develop and maintain over time a good expertise and infrastructure ensuring high quality training and clinical research." Prof Halidou TINTO, PharmD, Msc, PhD Head of the CRUN

2023

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2021

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2015

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CRUN

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" Our main objective is to develop and maintain over time a good expertise and infrastructure ensuring high quality training and clinical research."
Prof Halidou TINTO, PharmD, Msc, PhD Head of the CRUN