Publications

@article{Koita2024,

title = {Increasing the uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) through seasonal malaria chemoprevention channel delivery: protocol of a multicenter cluster randomized implementation trial in Mali and Burkina Faso},

author = {Kadiatou Koita and Joel D. Bognini and Efundem Agboraw and Mahamadou Demb\'{e}l\'{e} and Seydou Yabr\'{e} and Bi\'{e}bo Bihoun and Oumou Coulibaly and Hamidou Niangaly and Jean Batiste N’Takp\'{e} and Maia Lesosky and Dario Scaramuzzi and Eve Worrall and Jenny Hill and Val\'{e}rie Briand and Halidou Tinto and Kassoum Kayentao},

url = {https://pubmed.ncbi.nlm.nih.gov/38166711/},

doi = {10.1186/S12889-023-17529-Z},

issn = {1471-2458},

year  = {2024},

date = {2024-01-01},

journal = {BMC public health},

volume = {24},

issue = {1},

publisher = {BMC Public Health},

abstract = {Background: The uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) remains unacceptably low, with more than two-thirds of pregnant women in sub-Saharan Africa still not accessing the three or more doses recommended by the World Health Organisation (WHO). In contrast, the coverage of Seasonal Malaria Chemoprevention (SMC), a more recent strategy recommended by the WHO for malaria prevention in children under five years living in Sahelian countries with seasonal transmission, including Mali and Burkina-Faso, is high (up to 90%). We hypothesized that IPTp-SP delivery to pregnant women through SMC alongside antenatal care (ANC) will increase IPTp-SP coverage, boost ANC attendance, and increase public health impact. This protocol describes the approach to assess acceptability, feasibility, effectiveness, and cost-effectiveness of the integrated strategy. Methods and analysis: This is a multicentre, cluster-randomized, implementation trial of IPTp-SP delivery through ANC + SMC vs ANC alone in 40 health facilities and their catchment populations (20 clusters per arm). The intervention will consist of monthly administration of IPTp-SP through four monthly rounds of SMC during the malaria transmission season (July to October), for two consecutive years. Effectiveness of the strategy to increase coverage of three or more doses of IPTp-SP (IPTp3 +) will be assessed using household surveys and ANC exit interviews. Statistical analysis of IPT3 + and four or more ANC uptake will use a generalized linear mixed model. Feasibility and acceptability will be assessed through in-depth interviews and focus group discussions with health workers, pregnant women, and women with a child \< 12 months. Discussion: This multicentre cluster randomized implementation trial powered to detect a 45% and 22% increase in IPTp-SP3 + uptake in Mali and Burkina-Faso, respectively, will generate evidence on the feasibility, acceptability, effectiveness, and cost-effectiveness of IPTp-SP delivered through the ANC + SMC channel. The intervention is designed to facilitate scalability and translation into policy by leveraging existing resources, while strengthening local capacities in research, health, and community institutions. Findings will inform the local national malaria control policies. Trial registration: Retrospectively registered on August 11th, 2022; registration # PACTR202208844472053. Protocol v4.0 dated September 04, 2023. Trail sponsor: University of Sciences Techniques and Technologies of Bamako (USTTB), Mali.},

keywords = {Antimalarials* / therapeutic use, Burkina Faso, Chemoprevention, Child, Clinical Trial Protocol, doi:10.1186/s12889-023-17529-z, Drug Combinations, Female, Humans, Joel D Bognini, Kadiatou Koita, Kassoum Kayentao, Malaria* / drug therapy, Malaria* / prevention \& control, Mali, MEDLINE, Multicenter Studies as Topic, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Parasitic* / prevention \& control, PMC10763117, pmid:38166711, Pregnancy, Pregnancy Complications, Preschool, PubMed Abstract, Pyrimethamine / therapeutic use, Randomized Controlled Trials as Topic, Research Support, Seasons, Sulfadoxine / therapeutic use},

pubstate = {published},

tppubtype = {article}

}

@article{Gansane2023,

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

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

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

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

issn = {1475-2875},

year  = {2023},

date = {2023-01-01},

journal = {Malaria journal},

volume = {22},

issue = {1},

publisher = {Malar J},

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

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

pubstate = {published},

tppubtype = {article}

}

@article{Ogutu2023,

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

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

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

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

issn = {1474-4457},

year  = {2023},

date = {2023-01-01},

journal = {The Lancet. Infectious diseases},

volume = {23},

issue = {9},

pages = {1051-1061},

publisher = {Lancet Infect Dis},

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

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

pubstate = {published},

tppubtype = {article}

}

@article{Djimde2023,

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

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

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

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

issn = {2044-6055},

year  = {2023},

date = {2023-01-01},

journal = {BMJ open},

volume = {13},

issue = {10},

publisher = {BMJ Open},

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

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

pubstate = {published},

tppubtype = {article}

}

@article{Phiri2021-oy,

title = {The duration of protection from azithromycin against malaria,  acute respiratory, gastrointestinal, and skin infections when  given alongside seasonal malaria chemoprevention: Secondary  analyses of data from a clinical trial in hound\'{e}, Burkina  Faso, and bougouni, Mali},

author = {Mphatso Dennis Phiri and Matthew Cairns and Issaka Zongo and Frederic Nikiema and Modibo Diarra and Rakiswend\'{e} Serge Yerbanga and Amadou Barry and Amadou Tapily and Samba Coumare and Ismaila Thera and Irene Kuepfer and Paul Milligan and Halidou Tinto and Alassane Dicko and Jean Bosco Ou\'{e}draogo and Brian Greenwood and Daniel Chandramohan and Issaka Sagara},

doi = {10.1093/cid/ciaa1905},

issn = {1537-6591 1058-4838},

year  = {2021},

date = {2021-10-01},

urldate = {2021-10-01},

journal = {Clin. Infect. Dis.},

volume = {73},

number = {7},

pages = {e2379--e2386},

publisher = {Oxford University Press (OUP)},

abstract = {BACKGROUND: Mass drug administration (MDA) with azithromycin 

 (AZ) is being considered as a strategy to promote child survival 

 in sub-Saharan Africa, but the mechanism by which AZ reduces 

 mortality is unclear. To better understand the nature and extent 

 of protection provided by AZ, we explored the profile of 

 protection by time since administration, using data from a 

 household-randomized, placebo-controlled trial in Burkina Faso 

 and Mali. METHODS: Between 2014 and 2016, 30 977 children aged 

 3-59 months received seasonal malaria chemoprevention (SMC) with 

 sulfadoxine-pyrimethamine plus amodiaquine and either AZ or 

 placebo monthly, on 4 occasions each year. Poisson regression 

 with gamma-distributed random effects, accounting for the 

 household randomization and within-individual clustering of 

 illness episodes, was used to compare incidence of prespecified 

 outcomes between SMC+AZ versus SMC+placebo groups in fixed time 

 strata post-treatment. The likelihood ratio test was used to 

 assess evidence for a time-treatment group interaction. RESULTS: 

 Relative to SMC+placebo, there was no evidence of protection 

 from SMC+AZ against hospital admissions and deaths. Additional 

 protection from SMC+AZ against malaria was confined to the first 

 2 weeks post-administration (protective efficacy (PE): 24.2% 

 [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were 

 reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], 

 respectively, in the first 2 weeks postadministration. 

 Protection against nonmalaria fevers with a skin condition 

 persisted up to 28 days: PE: 46.3% [35.1; 55.6%]. CONCLUSIONS: 

 The benefits of AZ-MDA are broad-ranging but short-lived. To 

 maximize impact, timing of AZ-MDA must address the challenge of 

 targeting asynchronous morbidity and mortality peaks from 

 different causes.},

note = {© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

PMID: 33417683 

PMCID: PMC8492219},

keywords = {Antimalarials/therapeutic use, Azithromycin, Azithromycin/therapeutic use, Burkina Faso/epidemiology, Chemoprevention, Child, child mortality, Drug Combinations, duration of protection, Humans, Infant, Malaria/drug therapy/epidemiology/prevention \& control, Mali/epidemiology, Preschool, Sahel, seasonal malaria chemoprevention, Seasons},

pubstate = {published},

tppubtype = {article}

}

@article{Chandramohan2021-qm,

title = {Seasonal malaria vaccination with or without seasonal malaria  chemoprevention},

author = {Daniel Chandramohan and Issaka Zongo and Issaka Sagara and Matthew Cairns and Rakiswend\'{e}-Serge Yerbanga and Modibo Diarra and Fr\'{e}d\'{e}ric Niki`ema and Amadou Tapily and Fr\'{e}d\'{e}ric Sompougdou and Djibrilla Issiaka and Charles Zoungrana and Koualy Sanogo and Alassane Haro and Mahamadou Kaya and Abdoul-Aziz Sienou and Seydou Traore and Almahamoudou Mahamar and Ismaila Thera and Kalifa Diarra and Amagana Dolo and Irene Kuepfer and Paul Snell and Paul Milligan and Christian Ockenhouse and Opokua Ofori-Anyinam and Halidou Tinto and Abdoulaye Djimde and Jean-Bosco Ou\'{e}draogo and Alassane Dicko and Brian Greenwood},

doi = {10.1056/NEJMoa2026330},

issn = {1533-4406 0028-4793},

year  = {2021},

date = {2021-09-09},

urldate = {2021-09-09},

journal = {N. Engl. J. Med.},

volume = {385},

number = {11},

pages = {1005--1017},

publisher = {Massachusetts Medical Society},

abstract = {BACKGROUND: Malaria control remains a challenge in many parts of 

 the Sahel and sub-Sahel regions of Africa. METHODS: We conducted 

 an individually randomized, controlled trial to assess whether 

 seasonal vaccination with RTS,S/AS01E was noninferior to 

 chemoprevention in preventing uncomplicated malaria and whether 

 the two interventions combined were superior to either one alone 

 in preventing uncomplicated malaria and severe malaria-related 

 outcomes. RESULTS: We randomly assigned 6861 children 5 to 17 

 months of age to receive sulfadoxine-pyrimethamine and 

 amodiaquine (2287 children [chemoprevention-alone group]), 

 RTS,S/AS01E (2288 children [vaccine-alone group]), or 

 chemoprevention and RTS,S/AS01E (2286 children [combination 

 group]). Of these, 1965, 1988, and 1967 children in the three 

 groups, respectively, received the first dose of the assigned 

 intervention and were followed for 3 years. Febrile seizure 

 developed in 5 children the day after receipt of the vaccine, 

 but the children recovered and had no sequelae. There were 305 

 events of uncomplicated clinical malaria per 1000 person-years 

 at risk in the chemoprevention-alone group, 278 events per 1000 

 person-years in the vaccine-alone group, and 113 events per 1000 

 person-years in the combination group. The hazard ratio for the 

 protective efficacy of RTS,S/AS01E as compared with 

 chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 

 1.01), which excluded the prespecified noninferiority margin of 

 1.20. The protective efficacy of the combination as compared 

 with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8) 

 against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against 

 hospital admission with severe malaria according to the World 

 Health Organization definition, and 72.9% (95% CI, 2.9 to 

 92.4) against death from malaria. The protective efficacy of the 

 combination as compared with the vaccine alone against these 

 outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 

 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively. 

 CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to 

 chemoprevention in preventing uncomplicated malaria. The 

 combination of these interventions resulted in a substantially 

 lower incidence of uncomplicated malaria, severe malaria, and 

 death from malaria than either intervention alone. (Funded by 

 the Joint Global Health Trials and PATH; ClinicalTrials.gov 

 number, NCT03143218.).},

note = {Copyright © 2021 Massachusetts Medical Society.

Place: United States

PMID: 34432975},

keywords = {Amodiaquine/therapeutic use, Antimalarials/adverse effects/therapeutic use, Burkina Faso/epidemiology, Chemoprevention, Combination, Combined Modality Therapy, Double-Blind Method, Drug Combinations, Drug Therapy, Falciparum/epidemiology/mortality/prevention \& control, Febrile/etiology, Female, Hospitalization/statistics \& numerical data, Humans, Infant, Malaria, Malaria Vaccines/administration \& dosage/adverse effects, Male, Mali/epidemiology, Pyrimethamine/therapeutic use, Seasons, Seizures, Sulfadoxine/therapeutic use},

pubstate = {published},

tppubtype = {article}

}

@article{Yameogo2021-bb,

title = {Effect of seasonal malaria chemoprevention plus azithromycin on  Plasmodium falciparum transmission: gametocyte infectivity and  mosquito fitness},

author = {Koudraogo Bienvenue Yam\'{e}ogo and Rakiswend\'{e} Serge Yerbanga and Seydou Bienvenu Ouattara and Franck A Yao and Thierry Lef`evre and Issaka Zongo and Frederic Niki`ema and Yves Daniel Compaor\'{e} and Halidou Tinto and Daniel Chandramohan and Brian Greenwood and Adrien M G Belem and Anna Cohuet and Jean Bosco Ou\'{e}draogo},

doi = {10.1186/s12936-021-03855-3},

issn = {1475-2875},

year  = {2021},

date = {2021-07-27},

urldate = {2021-07-27},

journal = {Malar. J.},

volume = {20},

number = {1},

pages = {326},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children  during the malaria transmission period. Whether the addition of azithromycin (AZ) to  SMC could potentiate the benefit of the intervention was tested through a  double-blind, randomized, placebo-controlled trial. The effect of SMC and the  addition of AZ, on malaria transmission and on the life history traits of Anopheles  gambiae mosquitoes have been investigated. METHODS: The study included 438 children  randomly selected from among participants in the SMC + AZ trial and 198 children  from the same area who did not receive chemoprevention. For each participant in the  SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the  presence of malaria sexual and asexual stages and provided as a blood meal to An.  gambiae females using a direct membrane-feeding assay. RESULTS: The SMC treatment,  with or without AZ, significantly reduced the prevalence of asexual Plasmodium  falciparum (LRT X(2)(2) = 69, P \< 0.0001) and the gametocyte prevalence (LRT  X(2)(2) = 54, P \< 0.0001). In addition, the proportion of infectious feeds (LRT  X(2)(2) = 61, P \< 0.0001) and the prevalence of oocysts among exposed mosquitoes  (LRT X(2)(2) = 22.8, P \< 0.001) was reduced when mosquitoes were fed on blood from  treated children compared to untreated controls. The addition of AZ to SPAQ was  associated with an increased proportion of infectious feeds (LRT X(2)(1) = 5.2,  P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There  was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to  mosquitoes fed with blood from control children (LRTX(2)(2) = 330, P \< 0.0001).  CONCLUSION: This study demonstrates that SMC may contribute to a reduction in human  to mosquito transmission of P. falciparum, and the reduced mosquito longevity  observed for females fed on treated blood may increase the benefit of this  intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to  enhance the infectivity of gametocytes providing further evidence that this  combination is not an appropriate intervention.},

note = {© 2021. The Author(s).

PMID: 34315475 

PMCID: PMC8314489},

keywords = {Amodiaquine/administration \& dosage, Animals, Antimalarials/administration \& dosage, Chemoprevention, Child, Culicidae/physiology, Drug Combinations, Falciparum/prevention \& control/transmission, Gametocytes, Genetic Fitness, Humans, Malaria, Plasmodium falciparum/physiology, Preschool, Pyrimethamine/administration \& dosage, seasonal malaria chemoprevention, Seasons, Sulfadoxine/administration \& dosage, Transmission},

pubstate = {published},

tppubtype = {article}

}

@article{Adoke2021-el,

title = {A randomized, double-blind, phase 2b study to investigate the  efficacy, safety, tolerability and pharmacokinetics of a  single-dose regimen of ferroquine with artefenomel in adults and  children with uncomplicated Plasmodium falciparum malaria},

author = {Yeka Adoke and Rella Zoleko-Manego and Serge Ouoba and Alfred B Tiono and Grace Kaguthi and Juv^encio Eduardo Bonzela and Tran Thanh Duong and Alain Nahum and Marielle Bouyou-Akotet and Bernhards Ogutu and Alphonse Ouedraogo and Fiona Macintyre and Andreas Jessel and Bart Laurijssens and Mohammed H Cherkaoui-Rbati and Cathy Cantalloube and Anne Claire Marrast and Rapha"el Bejuit and David White and Timothy N C Wells and Florian Wartha and Didier Leroy and Afizi Kibuuka and Ghyslain Mombo-Ngoma and Daouda Ouattara and Ir`ene Mugenya and Bui Quang Phuc and Francis Bohissou and Denise P Mawili-Mboumba and Fredrick Olewe and Issiaka Soulama and Halidou Tinto and FALCI Study Group},

doi = {10.1186/s12936-021-03749-4},

issn = {1475-2875},

year  = {2021},

date = {2021-05-19},

urldate = {2021-05-19},

journal = {Malar. J.},

volume = {20},

number = {1},

pages = {222},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: For uncomplicated Plasmodium falciparum malaria, 

 highly efficacious single-dose treatments are expected to 

 increase compliance and improve treatment outcomes, and thereby 

 may slow the development of resistance. The efficacy and safety 

 of a single-dose combination of artefenomel (800 mg) plus 

 ferroquine (400/600/900/1200 mg doses) for the treatment of 

 uncomplicated P. falciparum malaria were evaluated in Africa 

 (focusing on children $\leq$ 5 years) and Asia. METHODS: The 

 study was a randomized, double-blind, single-dose, multi-arm 

 clinical trial in patients aged \> 6 months to 5 years and 20 

 Asian patients. None of the treatment arms met the target 

 efficacy criterion for PCR-adjusted ACPR at Day 28 (lower limit 

 of 95% confidence interval [CI] \> 90%). PCR-adjusted ACPR at 

 Day 28 [95% CI] in the PP Set ranged from 78.4% [64.7; 88.7%] 

 to 91.7% [81.6; 97.2%] for the 400 mg to 1200 mg ferroquine 

 dose. Efficacy rates were low in Vietnamese patients, ranging 

 from 20 to 40%. A clear relationship was found between drug 

 exposure (artefenomel and ferroquine concentrations at Day 7) 

 and efficacy (primary endpoint), with higher concentrations of 

 both drugs resulting in higher efficacy. Six distinct kelch-13 

 mutations were detected in parasite isolates from 10/272 African 

 patients (with 2 mutations known to be associated with 

 artemisinin resistance) and 18/20 Asian patients (all C580Y 

 mutation). Vomiting within 6 h of initial artefenomel 

 administration was common (24.6%) and associated with lower 

 drug exposures. CONCLUSION: The efficacy of 

 artefenomel/ferroquine combination was suboptimal in African 

 children aged $\leq$ 5 years, the population of interest, and 

 vomiting most likely had a negative impact on efficacy. Trial 

 registration ClinicalTrials.gov, NCT02497612. Registered 14 Jul 

 2015, https://clinicaltrials.gov/ct2/show/NCT02497612?term=NCT02497612\&draw=2\&rank=1.},

note = {PMID: 34011358 

PMCID: PMC8135182},

keywords = {Adamantane/administration \& dosage/analogs \& derivatives, Adolescent, Adult, Aged, Aminoquinolines/administration \& dosage, Benin, Burkina Faso, C580Y, Child, Combination treatment, Double-Blind Method, Drug Combinations, Exposure\textendashresponse, Falciparum/prevention \& control, Female, Ferroquine, Ferrous Compounds/administration \& dosage, Gabon, Humans, Infant, Kelch-13 mutation, Kenya, Malaria, Male, Metallocenes/administration \& dosage, Middle Aged, Mozambique, Parasite clearance, Peroxides/administration \& dosage, Pharmacokinetics/pharmacodynamics, Plasmodium falciparum/drug effects, Preschool, resistance, Uganda, Vietnam, Vomiting, Young Adult},

pubstate = {published},

tppubtype = {article}

}