2024 |
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Journal Articles |
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Nora Schmit, Hillary M. Topazian, H. Magloire Natama, Duncan Bellamy, Ousmane Traoré, M. Athanase Somé, Toussaint Rouamba, Marc Christian Tahita, Massa Achille Bonko, Aboubakary Sourabié, Hermann Sorgho, Lisa Stockdale, Samuel Provstgaard-Morys, Jeremy Aboagye, Danielle Woods, Katerina Rapi, Mehreen S. Datoo, Fernando Ramos Lopez, Giovanni D. Charles, Kelly McCain, Jean Bosco Ouedraogo, Mainga Hamaluba, Ally Olotu, Alassane Dicko, Halidou Tinto, Adrian V. S. Hill, Katie J. Ewer, Azra C. Ghani, Peter Winskill The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study Journal Article In: The Lancet. Infectious diseases, vol. 24, iss. 5, pp. 465-475, 2024, ISSN: 1474-4457. Abstract | BibTeX | Tags: Antibodies, Burkina Faso / epidemiology, Child, Cost-Benefit Analysis*, Falciparum* / economics, Falciparum* / epidemiology, Falciparum* / prevention & control, Female, Hillary M Topazian, Humans, Infant, Malaria, Malaria Vaccines* / administration & dosage, Malaria Vaccines* / economics, Malaria Vaccines* / immunology, Male, MEDLINE, Models, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Nora Schmit, Peter Winskill, Plasmodium falciparum / immunology, pmid:38342107, Preschool, Protozoan / blood, Protozoan Proteins / immunology, Public Health* / economics, PubMed Abstract, Research Support, Theoretical*, Vaccine Efficacy | Links: @article{Schmit2024, Background: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. Methods: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12–18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2–10 years (PfPR2–10) and ranges from 3% to 65% PfPR2–10. Findings: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815–333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868–405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4–48) in perennial settings and $6 (3–63) in seasonal settings and the incremental cost per DALY averted was $34 (29–139) in perennial settings and $30 (22–172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2–10. Interpretation: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. Funding: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy. | |||
Irene Molina–de Fuente, Marc Christian Tahita, Kabore Bérenger, Thuy Huong Ta Tang, Luz García, Vicenta González, Agustín Benito, Judith M. Hübschen, Halidou Tinto, Pedro Berzosa Malaria diagnosis challenges and pfhrp2 and pfhrp3 gene deletions using pregnant women as sentinel population in Nanoro region, Burkina Faso Journal Article In: Pathogens and global health, vol. 118, iss. 6, 2024, ISSN: 2047-7732. Abstract | BibTeX | Tags: Adolescent, Adult, Antigens, Burkina Faso / epidemiology, Diagnostic Tests, doi:10.1080/20477724.2024.2388489, Falciparum* / diagnosis, Falciparum* / epidemiology, Falciparum* / parasitology, Female, Gene Deletion*, Humans, Irene Molina-de la Fuente, Malaria, Marc Christian Tahita, MEDLINE, Microscopy, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Parasitic / diagnosis, Parasitic / epidemiology, Pedro Berzosa, Plasmodium falciparum* / genetics, Plasmodium falciparum* / isolation & purification, PMC11441055, pmid:39140699, Pregnancy, Pregnancy Complications, Protozoan Proteins* / genetics, Protozoan* / genetics, PubMed Abstract, Research Support, Routine* / methods, Sensitivity and Specificity*, Young Adult | Links: @article{nokey, Malaria in pregnancy causes adverse consequences and prompt and accurate diagnosis is essential for case management. In malaria endemic countries, diagnosis is mainly based on rapid diagnostic tests (RDT) and microscopy. However, increasing reports of false negatives caused by low parasitemia and pfhrp2/3 deletions raise concerns about HRP2-based RDT usefulness. This study aimed to assess RDT and microscopy performance and to describe pfhrp2/3 deletions in a cohort of 418 pregnant women in Burkina Faso. Malaria was diagnosed using RDT and microscopy and blood samples were collected during antenatal care visits. Diagnostic results were compared to PCR as gold standard. Pfhrp2 and pfhrp3 deletions were characterized for patients with confirmed P. falciparum infection. RDT had better sensitivity (76%) but lower specificity (83%) than microscopy (sensitivity = 57%; specificity = 98%). Low parasitemia (<150 parasites/µL), especially in multigravidae, was the principal factor causing false negatives by both methods. Moreover, pfhrp2 deletion frequency among overall false negatives by RDT was 21.43%. Higher frequency of deletions was found among all samples, independently of RDT result, for example around 2% of samples had double deletions meaning that the majority of deletions had no effect on RDT testing. Finally, it was found higher pfhrp2 deletion in women with lower uterine height during the first trimester. Wider and National surveillance study of deletions is recommended among pregnant women and in Burkina Faso. | |||
2023 |
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Journal Articles |
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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: @article{nokey, 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. | |||
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: @article{Gansane2023, 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). | |||
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: @article{Unger2023, 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. | |||
Anna Maria Eijk, Kasia Stepniewska, Jenny Hill, Steve M. Taylor, Stephen J. Rogerson, Gilles Cottrell, R. Matthew Chico, Julie R. Gutman, Halidou Tinto, Holger W. Unger, Stephanie K. Yanow, Steven R. Meshnick, Feiko O. Kuile, Alfredo Mayor, Steve M. Taylor, Stephen J. Rogerson, R. Matthew Chico, Julie R. Gutman, Hallidou Tinto, Holger W. Unger, Stephanie K. Yanow, Manfred Accrombessi, Ayola A. Adegnika, Rukhsana Ahmed, Eliana María Arango-Flórez, Myriam Arevalo-Herrera, Emmanual Arinaitwe, Paulo Arnaldo, Per Ashorn, Ulla Ashorn, Azucena Bardaji, Inoni Betuela, Praveen K. Bharti, Francis Bohissou, Camila Bôtto-Menezes, Vera Braun, Valerie Briand, Jessica Briggs, María Eugenia Castellanos, Daniel Chandramohan, Enesia Banda Chaponda, Chetan Chitnis, Lauren M. Cohee, Michel Cot, Umberto d'Alessandro, Lise Denoeud-Ndam, Meghna Desai, Alassane Dicko, Xavier Ding, Grant Dorsey, Patrick E. Duffy, Maha A. Elbadry, Sonia M. Enosse, Yue Fan, Nadine Fievet, Michal Fried, Blaise Genton, Raquel Gonzalez, Brian Greenwood, Linda Kalilani, Johanna H. Kattenberg, Kassoum Kayentao, Carole Khairallah, Christopher L. King, Dhanpat Kumar Kochar, Swati Kochar, Felix Koukouikila-Koussounda, Sarah H. Landis, Miriam K. Laufer, Rose F. Leke, Eusebio Macete, Sonia Maculuve, Mwayiwawo Madanitsa, Almahamoudou Mahamar, Ken Maleta, Indu Malhotra, Rella Zoleko Manego, Flor Ernestina Martinez-Espinosa, Achille Massougbodji, Don Mathanga, Michela Menegon, Clara Menendez, Petra Mens, Martin Meremikwu, Frank P. Mockenhaupt, Ghyslain Mombo-Ngoma, Dominic Mosha, Ivo Mueller, Alain Nahum, Paul Natureeba, Nicaise Ndam, Francine Ntoumi, Olabisi A. Oduwole, Bernard A. Okech, Maria Ome-Kaius, Kephas Otieno, Norma Padilla, Michal Ramharter, Rosemary Rochford, Anna Rosanas-Urgell, Maria Ruperez, Katherine R. Sabourin, Sergi Sanz, Henk D. Schallig, Susana Scott, Esperanca Sevene, Carlo Severini, Harry Tagbor, Diane Wallace Taylor, Maminata Traore Coulibaly, Ana Vasquez, Annie Walker-Abbey, Blair J. Wylie, Djimon M. Zannou, Stephen R. Meshnick Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis Journal Article In: The Lancet. Global health, vol. 11, iss. 7, pp. e1061-e1074, 2023, ISSN: 2214-109X. Abstract | BibTeX | Tags: {Adult, Anna Maria van Eijk, Antimalarials* / therapeutic use, Author(firstnames='Achille', Author(firstnames='Alain', Author(firstnames='Alassane', Author(firstnames='Alfredo', Author(firstnames='Almahamoudou', Author(firstnames='Ana', Author(firstnames='Anna', Author(firstnames='Annie', Author(firstnames='Ayola A', Author(firstnames='Azucena', Author(firstnames='Bernard A', Author(firstnames='Blair J', Author(firstnames='Blaise', Author(firstnames='Brian', Author(firstnames='Camila', Author(firstnames='Carlo', Author(firstnames='Carole', Author(firstnames='Chetan', Author(firstnames='Christopher L', Author(firstnames='Clara', Author(firstnames='Daniel', Author(firstnames='Dhanpat Kumar', Author(firstnames='Diane Wallace', Author(firstnames='Djimon M', Author(firstnames='Dominic', Author(firstnames='Don', Author(firstnames='Eliana María', Author(firstnames='Emmanual', Author(firstnames='Enesia Banda', Author(firstnames='Esperanca', Author(firstnames='Eusebio', Author(firstnames='Feiko O', Author(firstnames='Felix', Author(firstnames='Flor Ernestina', Author(firstnames='Francine', Author(firstnames='Francis', Author(firstnames='Frank P', Author(firstnames='Ghyslain', Author(firstnames='Gilles', Author(firstnames='Grant', Author(firstnames='Hallidou', Author(firstnames='Harry', Author(firstnames='Henk D', Author(firstnames='Holger W', Author(firstnames='Indu', Author(firstnames='Inoni', Author(firstnames='Ivo', Author(firstnames='Jenny', Author(firstnames='Jessica', Author(firstnames='Johanna H', Author(firstnames='Julie R', Author(firstnames='Kasia', Author(firstnames='Kassoum', Author(firstnames='Katherine R', Author(firstnames='Ken', Author(firstnames='Kephas', Author(firstnames='Lauren M', Author(firstnames='Linda', Author(firstnames='Lise', Author(firstnames='Maha A', Author(firstnames='Maminata', Author(firstnames='Manfred', Author(firstnames='María Eugenia', Author(firstnames='Maria', Author(firstnames='Martin', Author(firstnames='Meghna', Author(firstnames='Michal', Author(firstnames='Michel', Author(firstnames='Michela', Author(firstnames='Miriam K', Author(firstnames='Mwayiwawo', Author(firstnames='Myriam', Author(firstnames='Nadine', Author(firstnames='Nicaise', Author(firstnames='Norma', Author(firstnames='Olabisi A', Author(firstnames='Patrick E', Author(firstnames='Paul', Author(firstnames='Paulo', Author(firstnames='Per', Author(firstnames='Petra', Author(firstnames='Praveen K', Author(firstnames='R Matthew', Author(firstnames='Raquel', Author(firstnames='Rella', Author(firstnames='Rose F', Author(firstnames='Rosemary', Author(firstnames='Rukhsana', Author(firstnames='Sarah H', Author(firstnames='Sergi', Author(firstnames='Sonia M', Author(firstnames='Sonia', Author(firstnames='Stephanie K', Author(firstnames='Stephen J', Author(firstnames='Stephen R', Author(firstnames='Steve M', Author(firstnames='Susana', Author(firstnames='Swati', Author(firstnames='Ulla', Author(firstnames='Umberto', Author(firstnames='Valerie', Author(firstnames='Vera', Author(firstnames='Xavier', Author(firstnames='Yue', CollabAuthor(name='Subpatent Malaria in Pregnancy Group', Falciparum* / drug therapy, Female, Humans, Kasia Stepniewska, Malaria, Malaria* / prevention & control, MEDLINE, Meta-Analysis, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, P.H.S., PMC10880462, Pregnancy, Prevalence, PubMed Abstract, Research Support, Risk Factors, Systematic review, U.S. Gov't | Links: @article{nokey, Background: Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD). Methods: For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine–pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342. Findings: The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0–55·9, 66 substudies) for submicroscopic and 8·0% (0·0–50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0–100); this proportion was highest in the Americas (73·3%, 0·0–100), followed by Asia (67·2%, 36·4–100) and Africa (56·5%, 20·5–97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02–1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45–5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection. Interpretation: During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections. Funding: Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network. | |||
Selidji T. Agnandji, Mario Recker, Benjamin Mordmüller, Stephan Glöckner, Akim A. Adegnika, Bertrand Lell, Lucas Otieno, Walter Otieno, Seth Owusu-Agyei, Kwaku P. Asante, Tsiri Agbenyega, Daniel Ansong, Eusebio Macete, Pedro Aide, Hermann Sorgho, Halidou Tinto, Neema Mturi, John P. A. Lusingu, Samwel Gesase, Irving Hoffman, Nahya Salim Masoud, Charles R. Newton, Kalifa Bojang, Gérard Krause, Peter Gottfried Kremsner Prostration and the prognosis of death in African children with severe malaria Journal Article In: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, vol. 134, pp. 240-247, 2023, ISSN: 1878-3511. Abstract | BibTeX | Tags: Anemia*, Child, Clinical Trial, Coma, doi:10.1016/j.ijid.2023.06.022, Falciparum* / drug therapy, Humans, Infant, Malaria, Malaria* / complications, Malaria* / diagnosis, Mario Recker, MEDLINE, Multicenter Study, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Peter Gottfried Kremsner, Phase III, pmid:37414210, Prognosis, PubMed Abstract, Randomized controlled trial, Selidji T Agnandji | Links: @article{Agnandji2023, Objectives: Malaria is still one of the main reasons for hospitalization in children living in sub-Saharan Africa. Rapid risk stratification at admission is essential for optimal medical care and improved prognosis. Whereas coma, deep breathing, and, to a lesser degree, severe anemia are established predictors of malaria-related death, the value of assessing prostration for risk stratification is less certain. Methods: Here we used a retrospective multi-center analysis comprising over 33,000 hospitalized children from four large studies, including two observational studies from the Severe Malaria in African Children network, a randomized controlled treatment study, and the phase-3-clinical RTS,S-malaria vaccine trial, to evaluate known risk factors of mortality and with a specific emphasis on the role of prostration. Results: Despite comparable age profiles of the participants, we found significant inter- and intra-study variation in the incidence of fatal malaria as well as in the derived risk ratios associated with the four risk factors: coma, deep breathing, anemia, and prostration. Despite pronounced variations, prostration was significantly associated with an increased risk of mortality (P <0.001) and its consideration resulted in improved predictive performance, both in a multivariate model and a univariate model based on the Lambaréné Organ Dysfunction Score. Conclusion: Prostration is an important clinical criterion to determine severe pediatric malaria with possible fatal outcomes. | |||
Peter J. Neyer, Bérenger Kaboré, Christos T. Nakas, Britta Hartmann, Annelies Post, Salou Diallo, Halidou Tinto, Angelika Hammerer-Lercher, Carlo R. Largiadèr, Andre J. Ven, Andreas R. Huber Exploring the host factors affecting asymptomatic Plasmodium falciparum infection: insights from a rural Burkina Faso study Journal Article In: Malaria journal, vol. 22, iss. 1, 2023, ISSN: 1475-2875. Abstract | BibTeX | Tags: Adolescent, Andreas R Huber, Asymptomatic Infections / epidemiology, Bérenger Kaboré, Burkina Faso / epidemiology, Child, doi:10.1186/s12936-023-04686-0, Falciparum* / epidemiology, hemoglobin, Hepcidins*, Humans, Malaria, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Peter J Neyer, Plasmodium falciparum / genetics, PMC10474782, pmid:37658365, PubMed Abstract, Sickle | Links: @article{Neyer2023, Background: Asymptomatic Plasmodium falciparum parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a P. falciparum-endemic region during the high transmission season. Methods: A sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years | |||
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: @article{Ogutu2023, 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. | |||
Moussa Djimde, Japhet Kabalu Tshiongo, Hypolite Mavoko Muhindo, Halidou Tinto, Esperanca Sevene, Maminata Traore, Anifa Vala, Salesio MacUacua, Berenger Kabore, Edgard Diniba Dabira, Annette Erhart, Hamadoun Diakite, Mohamed Keita, Mireia Piqueras, Raquel González, Clara Menendez, Thomas P. C. Dorlo, Issaka Sagara, Petra Mens, Henk Schallig, Umberto D'Alessandro, Kassoum Kayentao 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 Journal Article In: BMJ open, vol. 13, iss. 10, 2023, ISSN: 2044-6055. Abstract | BibTeX | Tags: 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 | Links: @article{Djimde2023, 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. | |||
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: @article{Natama2023, 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. | |||
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![]() | Biébo Bihoun, Serge Henri Zango, Maminata Traoré-Coulibaly, Innocent Valea, Raffaella Ravinetto, Jean Pierre Van Geertruyden, Umberto D'Alessandro, Halidou Tinto, Annie Robert Age-modified factors associated with placental malaria in rural Burkina Faso. Journal Article In: BMC pregnancy and childbirth, vol. 22, iss. 1, pp. 248, 2022, ISSN: 1471-2393. Abstract | BibTeX | Tags: *Malaria, *Malaria/epidemiology, Adult, Burkina Faso, Burkina Faso/epidemiology, Falciparum/parasitology, Female, Gravidity, Humans, Malaria, placenta, Placenta/parasitology, Pregnancy, Risk Factors | Links: @article{nokey, BACKGROUND: Malaria in pregnancy can result in placental infection with fetal implications. This study aimed at assessing placental malaria (PM) prevalence and its associated factors in a cohort of pregnant women with peripheral malaria and their offspring. METHOD: The data were collected in the framework of a clinical trial on treatments for malaria in pregnant women . Placental malaria (PM) was diagnosed by histopathological detection of parasites and/or malaria pigment on placenta biopsies taken at delivery. Factors associated with PM were assessed using logistic regression. RESULTS: Out of 745 biopsies examined, PM was diagnosed in 86.8 % of women. Acute, chronic and past PM were retrieved in 11 (1.5 %), 170 (22.8 %), and 466 (62.6 %) women, respectively. A modifying effect was observed in the association of gravidity or anemia at the study start with pooled PM (presence of parasites and/or malaria pigment). In women under 30, gravidity ≤ 2 was associated with an increased prevalence of pooled PM but in women aged 30 years or more, gravidity was no more associated with pooled PM (OR 6.81, 95 % CI 3.18 - 14.60; and OR 0.52, 95 % CI 0.10 - 2.76, respectively). Anemia was associated with pooled PM in women under 30 (OR 1.96, 95 % CI 1.03 - 3.72) but not in women aged 30 years or more (OR 0.68, 95 % CI 0.31 - 1.49). Similarly, the association of gravidity with past-chronic PM depended also on age. A higher prevalence of active PM was observed in women under 30 presenting with symptomatic malaria (OR 3.79, 95 % CI 1.55 - 9.27), while there was no significant increase in the prevalence of active PM (presence of parasites only) in women with symptomatic malaria when aged 30 years or more (OR 0.42, 95 % CI 0.10 - 1.75). In women with chronic PM, the prevalence of low birth weight or prematurity was the highest (31.2 %) as compared with past PM or no PM. CONCLUSION: Despite the rapid diagnosis and efficacious treatment of peripheral infection, the prevalence of placental malaria remained high in women with P. falciparum peripheral infection in Nanoro, especially in younger women This underlines the importance of preventive measures in this specific group. | ||
![]() | 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: @article{Sondo2022, 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. | ||
Massa Achille Bonko, Marc Christian Tahita, Francois Kiemde, Palpouguini Lompo, Petra F. Mens, Halidou Tinto, Henk. D. F. H. Schallig Diagnostic Performance of Plasmodium falciparum Histidine-Rich Protein-2 Antigen-Specific Rapid Diagnostic Test in Children at the Peripheral Health Care Level in Nanoro (Burkina Faso) Journal Article In: Tropical Medicine and Infectious Disease, vol. 7, iss. 12, pp. 440, 2022, ISSN: 2414-6366. Abstract | BibTeX | Tags: Burkina Faso, diagnostics, febrile diseases, Malaria | Links: @article{Bonko2022, <p>(1) Background: Malaria control has strongly benefited from the implementation of rapid diagnostic tests (RDTs). The malaria RDTs used in Burkina Faso, as per the recommendation of the National Malaria Control Program, are based on the detection of histidine-rich protein-2 (PfHRP2) specific to Plasmodium falciparum, which is the principal plasmodial species causing malaria in Burkina Faso. However, there is increasing concern about the diagnostic performance of these RDTs in field situations, and so constant monitoring of their accuracy is warranted. (2) Methods: A prospective study was performed in the health district of Nanoro, where 391 febrile children under 5 years with an axillary temperature ≥37.5 °C presenting at participating health facilities were subjected to testing for malaria. The HRP2-based RDT and expert microscopy were used to determine the diagnostic performance of the former. Retrospectively, the correctness of the antimalaria prescriptions was reviewed. (3) Results: Taking expert malaria microscopy as the gold standard, the sensitivity of the employed RDT was 98.5% and the specificity 40.5%, with a moderate agreement between the RDT testing and microscopy. In total, 21.7% of cases received an inappropriate antimalarial treatment based on a retrospective assessment with expert microscopy results. (4) Conclusion: Malaria remains one of the principal causes of febrile illness in Burkina Faso. Testing with HRP2-based RDTs is inaccurate, in particular, due to the low specificity, which results in an over-prescription of antimalarials, with emerging antimalarial drug resistance as an important risk and many children not being treated for potential other causes of fever.</p> | |||
Tim Starck, Peter Dambach, Toussaint Rouamba, Halidou Tinto, Faith Osier, Catherine E. Oldenburg, Maya Adam, Till Bärnighausen, Thomas Jaenisch, Caroline A. Bulstra The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries Journal Article In: Frontiers in Public Health, vol. 10, pp. 1009865, 2022, ISSN: 2296-2565. Abstract | BibTeX | Tags: anemia-etiology, DHS, fixed-effect, hemoglobin, Malaria, multiples, Sub-Sahara Africa, twins | Links: @article{Starck2022, BACKGROUND Young children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin < 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations. METHODS We quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins. RESULTS Our analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p<0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p<0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p<0.001). CONCLUSION Even after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia. | |||
Vivi Maketa, Japhet Kabalu, Melissa Kabena, Flory Luzolo, Hypolite Muhindo-Mavoko, Henk D. F. H. Schallig, Kassoum Kayentao, Petra F. Mens, Pascal Lutumba, Halidou Tinto Comparison of intermittent screening (using ultra-sensitive malaria rapid diagnostic test) and treatment (using a newly registered antimalarial pyronaridine-artesunate—PYRAMAX®) to standard intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria in pregnant women living in endemic areas: ULTRAPYRAPREG Journal Article In: Trials, vol. 23, iss. 1, pp. 963, 2022, ISSN: 1745-6215. Abstract | BibTeX | Tags: IPTp-SP, ISTp, Malaria, Malaria indicators, Pregnancy, Ultra-sensitive RDTs | Links: @article{Maketa2022, BACKGROUND Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is an important malaria control strategy in sub-Saharan Africa. Indeed, it overcomes the risk of misdiagnosis due to low peripheral parasitemia during pregnancy by treating women with SP on predetermined schedules. However, over time, the spread of Plasmodium-resistant strains has threatened this strategy in many countries. As an alternative, the intermittent screening and treatment for pregnancy (ISTp) aims at a monthly screening of pregnant women, preferably by using very sensitive tests such as ultrasensitive rapid diagnostic tests (us-RDTs) and the treatment of positive cases with artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. Unlike IPTp-SP, ISTp prevents overuse of antimalarials limiting the drug pressure on parasites, an advantage which can be potentiated by using an ACT like pyronaridine-artesunate (Pyramax®) that is not yet used in pregnant women in the field. METHODS This study aims to compare the non-inferiority of ISTp using us-RDTs and Pyramax® versus IPTp-SP on malaria in pregnancy through a randomized clinical trial performed in Kisenso, Kinshasa, the Democratic Republic of the Congo, a malaria perennial transmission area. DISCUSSION The results will be essential for the National Malaria Control Program to update the malaria prevention policy in pregnant women in the Democratic Republic of the Congo. TRIAL REGISTRATION ClinicalTrials.gov NCT04783051. | |||
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: @article{Cairns2022, 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. | |||
Laetitia Duval, Elisa Sicuri, Susana Scott, Maminata Traoré, Bunja Daabo, Halidou Tinto, Koen Peeters Grietens, Umberto d’Alessando, Henk Schallig, Petra Mens, Lesong Conteh Household costs associated with seeking malaria treatment during pregnancy: evidence from Burkina Faso and The Gambia Journal Article In: Cost Effectiveness and Resource Allocation, vol. 20, iss. 1, pp. 42, 2022, ISSN: 1478-7547. Abstract | BibTeX | Tags: Burkina Faso, Cost, Gambia, Malaria, Pregnancy, Remittances, sub-Saharan Africa | Links: @article{Duval2022, BACKGROUND Malaria in pregnancy remains a major health threat in sub-Saharan Africa to both expectant mothers and their unborn children. To date, there have been very few studies focused on the out of pocket costs associated with seeking treatment for malaria during pregnancy. METHODS A cross-sectional survey was undertaken in Burkina Faso and The Gambia to estimate the direct and indirect costs associated with outpatient consultations (OP) and inpatient admissions (IP). Direct costs were broken down into medical (admission fees, drug charges, and laboratory fees), and non-medical (transportation and food). Indirect costs reflected time lost due to illness. In total, 220 pregnant women in Burkina Faso and 263 in The Gambia were interviewed about their treatment seeking decisions, expenditure, time use and financial support associated with each malaria episode. RESULTS In Burkina Faso 6.7% sought treatment elsewhere before their OP visits, and 27.1% before their IP visits. This compares to 1.3% for OP and 25.92% for IP in The Gambia. Once at the facility, the average direct costs (out of pocket) were 3.91US$ for an OP visit and 15.38US$ of an IP visit in Burkina Faso, and 0.80US$ for an OP visit and 9.19US$ for an IP visit in The Gambia. Inpatient direct costs were driven by drug costs (9.27US$) and transportation costs (2.72US$) in Burkina Faso and drug costs (3.44 US$) and food costs (3.44 US$) in The Gambia. Indirect costs of IP visits, valued as the opportunity cost of time lost due to the illness, were estimated at 11.85US$ in Burkina Faso and 4.07US$ in The Gambia. The difference across the two countries was mainly due to the longer time of hospitalization in Burkina Faso compared to The Gambia. In The Gambia, the vast majority of pregnant women reported receiving financial support from family members living abroad, most commonly siblings (65%). CONCLUSIONS High malaria treatment costs are incurred by pregnant women in Burkina Faso and The Gambia. Beyond the medical costs of fees and drugs, costs in terms of transport, food and time are significant drivers. The role of remittances, particularly their effect on accessing health care, needs further investigation. | |||
Moussa Lingani, Serge H. Zango, Innocent Valéa, Maïmouna Sanou, Serge Ouoba, Sékou Samadoulougou, Annie Robert, Halidou Tinto, Michèle Dramaix, Philippe Donnen Prevalence and risk factors of malaria among first antenatal care attendees in rural Burkina Faso Journal Article In: Tropical Medicine and Health, vol. 50, iss. 1, pp. 49, 2022, ISSN: 1349-4147. Abstract | BibTeX | Tags: Burkina Faso, First antenatal care visit, Malaria, Pregnancy | Links: @article{Lingani2022, BACKGROUND The WHO recommends continuous surveillance of malaria in endemic countries to identify areas and populations most in need for targeted interventions. The aim of this study was to assess the prevalence of malaria and its associated factors among first antenatal care (ANC) attendees in rural Burkina Faso. METHODS A cross-sectional survey was conducted between August 2019 and September 2020 at the Yako health district and included 1067 first ANC attendees. Sociodemographic, gyneco-obstetric, and medical characteristics were collected. Malaria was diagnosed by standard microscopy and hemoglobin level was measured by spectrophotometry. A multivariate logistic regression analysis was used to identify factors associated with malaria infection. RESULTS Overall malaria infection prevalence was 16.1% (167/1039). Among malaria-positive women, the geometric mean parasite density was 1204 [95% confidence interval (CI) 934-1552] parasites/µL and the proportion of very low (1-199 parasites/µL), low (200-999 parasites/µL), medium (1000-9999 parasites/µL) and high (≥ 10,000 parasites/µL) parasite densities were 15.0%, 35.3%, 38.3% and 11.4%, respectively. Age < 20 years (adjusted odds ratio (aOR): 2.2; 95% CI 1.4-3.5), anemia (hemoglobin < 11 g/deciliter) (aOR: 3.4; 95% CI 2.2-5.5), the non-use of bed net (aOR: 1.8; 95% CI 1.1-2.8), and the absence of intermittent preventive treatment with sulfadoxine-pyrimethamine (aOR: 5.8; 95% CI 2.1-24.5) were positively associated with malaria infection. CONCLUSIONS The study showed that one out of six pregnant women had a microscopy-detected P. falciparum malaria infection at their first ANC visit. Strengthening malaria prevention strategies during the first ANC visit is needed to prevent unfavorable birth outcomes. | |||
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![]() | Moussa Lingani, Serge H Zango, Innocent Valéa, Massa Dit A Bonko, Sékou O Samadoulougou, Toussaint Rouamba, Marc C Tahita, Ma"imouna Sanou, Annie Robert, Halidou Tinto, Philippe Donnen, Mich`ele Dramaix Malaria and curable sexually transmitted and reproductive tract coinfection among pregnant women in rural Burkina Faso Journal Article In: Trop. Med. Health, vol. 49, no. 1, pp. 90, 2021, ISSN: 1348-8945 1349-4147, (© 2021. The Author(s). PMID: 34736524 PMCID: PMC8567650). Abstract | BibTeX | Tags: Bacterial vaginosis, Burkina Faso, Chlamydia, Coinfection, Malaria, Pregnancy, Syphilis | Links: @article{Lingani2021-is, BACKGROUND: Malaria and sexually transmitted/reproductive tract infections (STI/RTI) are leading and preventable causes of low birthweight in sub-Saharan Africa. Reducing their impact on pregnancy outcomes requires efficient interventions that can be easily integrated into the antenatal care package. The paucity of data on malaria and STI/RTI coinfection, however, limits efforts to control these infections. This study aimed to determine the prevalence and associated factors of malaria and STI/RTI coinfection among pregnant women in rural Burkina Faso. METHODS: A cross-sectional survey was conducted among 402 pregnant women attending antenatal clinics at the Yako health district. Sociodemographic and behavioral data were collected, and pregnant women were tested for peripheral malaria by microscopy. Hemoglobin levels were also measured by spectrophotometry and curable bacterial STI/RTI were tested on cervico-vaginal swabs using rapid diagnostic test for chlamydia and syphilis, and Gram staining for bacterial vaginosis. A multivariate logistic regression model was used to assess the association of malaria and STI/RTI coinfection with the characteristics of included pregnant women. RESULTS: The prevalence of malaria and at least one STI/RTI coinfection was 12.9% (95% confidence interval, CI: [9.8-16.7]), malaria and bacterial vaginosis coinfection was 12.2% (95% CI: [9.3-15.9]), malaria and chlamydial coinfection was 1.6% (95% CI: [0.6-3.8]). No coinfection was reported for malaria and syphilis. The individual prevalence was 17.2%, 7.2%, 0.6%, 67.7% and 73.3%, respectively, for malaria infection, chlamydia, syphilis, bacterial vaginosis and STI/RTI combination. Only 10% of coinfections were symptomatic, and thus, 90% of women with coinfection would have been missed by the symptoms-based diagnostic approach. In the multivariate analysis, the first pregnancy (aOR = 2.4 [95% CI: 1.2-4.7]) was the only factor significantly associated with malaria and STI/RTI coinfection. Clinical symptoms were not associated with malaria and STI/RTI coinfection. CONCLUSION: The prevalence of malaria and curable STI/RTI coinfection was high among pregnant women. The poor performance of the clinical symptoms to predict coinfection suggests that alternative interventions are needed. | ||
![]() | Serge Henri Zango, Moussa Lingani, Innocent Valea, Ouindpanga Sekou Samadoulougou, Biebo Bihoun, Diagniagou Lankoande, Phillipe Donnen, Michele Dramaix, Halidou Tinto, Annie Robert Association of malaria and curable sexually transmitted infections with pregnancy outcomes in rural Burkina Faso Journal Article In: BMC Pregnancy Childbirth, vol. 21, no. 1, pp. 722, 2021, ISSN: 1471-2393, (© 2021. The Author(s). PMID: 34706705 PMCID: PMC8549350). Abstract | BibTeX | Tags: Coinfection, Impact, Malaria, Outcome, Pregnancy, STI | Links: @article{Zango2021-ti, BACKGROUND: Malaria and curable sexually transmitted infections (STIs) are severe infections associated with poor pregnancy outcomes in sub-Saharan countries. These infections are responsible for low birth weight, preterm birth, and miscarriage. In Burkina Faso, many interventions recommended by the World Health Organization were implemented to control the impact of these infections. After decades of intervention, we assessed the impact of these infections on pregnancy outcomes in rural setting of Burkina Faso. METHODS: Antenatal care and delivery data of pregnant women attending health facilities in 2016 and 2017 were collected in two rural districts namely Nanoro and Yako, in Burkina Faso. Regression models with likelihood ratio test were used to assess the association between infections and pregnancy outcomes. RESULTS: During the two years, 31639 pregnant women received antenatal care. Malaria without STI, STI without malaria, and their coinfections were reported for 7359 (23.3%), 881 (2.8 %), and 388 (1.2%) women, respectively. Low birth weight, miscarriage, and stillbirth were observed in 2754 (10.5 %), 547 (2.0 %), and 373 (1.3 %) women, respectively. Our data did not show an association between low birth weight and malaria [Adjusted OR: 0.91 (0.78 - 1.07)], STIs [Adjusted OR: 0.74 (0.51 - 1.07)] and coinfection [Adjusted OR: 1.15 (0.75 - 1.78)]. Low birth weight was strongly associated with primigravidae [Adjusted OR: 3.53 (3.12 - 4.00)]. Both miscarriage and stillbirth were associated with malaria [Adjusted OR: 1.31 (1.07 - 1.59)], curable STI [Adjusted OR: 1.65 (1.06 - 2.59)], and coinfection [Adjusted OR: 2.00 (1.13 - 3.52)]. CONCLUSION: Poor pregnancy outcomes remained frequent in rural Burkina Faso. Malaria, curable STIs, and their coinfections were associated with both miscarriage and stillbirth in rural Burkina. More effort should be done to reduce the proportion of pregnancies lost associated with these curable infections by targeting interventions in primigravidae women. | ||
![]() | Tim Starck, Caroline A Bulstra, Halidou Tinto, Toussaint Rouamba, Ali Sie, Thomas Jaenisch, Till Bärnighausen The effect of malaria on haemoglobin concentrations: a nationally representative household fixed-effects study of 17,599 children under 5 years of age in Burkina Faso Journal Article In: Malar. J., vol. 20, no. 1, pp. 416, 2021, ISSN: 1475-2875, (© 2021. The Author(s). PMID: 34688294 PMCID: PMC8542337). Abstract | BibTeX | Tags: Anaemia, Burkina Faso, Haemoglobin, Household fixed-effects, Malaria, Microscopy, Rapid diagnostic tests | Links: @article{Starck2021-mb, BACKGROUND: Although the association between malaria and anaemia is widely studied in patient cohorts, the population-representative causal effects of malaria on anaemia remain unknown. This study estimated the malaria-induced decrease in haemoglobin levels among young children in malaria-endemic Burkina Faso. METHODS: The study was based on pooled individual-level nationally representative health survey data (2010-2011, 2014, 2017-2018) from 17 599 children under 5 years of age. This data was used to estimate the effects of malaria on haemoglobin concentration, controlling for household fixed-effects, age, and sex in a series of regression analyses. The fixed-effects controlled for observed and unobserved confounding on the household level and allowed to determine the impact of malaria infection status on haemoglobin levels and anaemia prevalence. Furthermore, the diagnostic results from microscopy and rapid diagnostic tests were leveraged to provide a quasi-longitudinal perspective of acute and prolonged effects after malaria infection. RESULTS: The prevalence of both malaria (survey prevalence ranging from 17.4% to 65.2%) and anaemia (survey prevalence ranging from 74% to 88.2%) was very high in the included surveys. Malaria was estimated to significantly reduce haemoglobin levels, with an overall effect of - 7.5 g/dL (95% CI - 8.5, - 6.5). Acute malaria resulted in a - 7.7 g/dL (95% CI - 8.8, - 6.6) decrease in haemoglobin levels. Recent malaria without current parasitaemia decreased haemoglobin concentration by - 7.1 g/dL (95% CI - 8.3, - 5.9). The in-sample predicted prevalence of severe anaemia was 9.4% among malaria positives, but only 2.2% among children without malaria. CONCLUSION: Malaria infection has a strong detrimental effect on haemoglobin levels among young children in Burkina Faso. This effect seems to carry over even after acute infection, indicating prolonged haemoglobin reductions even after successful parasite-elimination. The quasi-experimental fixed-effect approach adds a population level perspective to existing clinical evidence. | ||
![]() | Daniel Chandramohan, Issaka Zongo, Issaka Sagara, Matthew Cairns, Rakiswendé-Serge Yerbanga, Modibo Diarra, Frédéric Niki`ema, Amadou Tapily, Frédéric Sompougdou, Djibrilla Issiaka, Charles Zoungrana, Koualy Sanogo, Alassane Haro, Mahamadou Kaya, Abdoul-Aziz Sienou, Seydou Traore, Almahamoudou Mahamar, Ismaila Thera, Kalifa Diarra, Amagana Dolo, Irene Kuepfer, Paul Snell, Paul Milligan, Christian Ockenhouse, Opokua Ofori-Anyinam, Halidou Tinto, Abdoulaye Djimde, Jean-Bosco Ouédraogo, Alassane Dicko, Brian Greenwood Seasonal malaria vaccination with or without seasonal malaria chemoprevention Journal Article In: N. Engl. J. Med., vol. 385, no. 11, pp. 1005–1017, 2021, ISSN: 1533-4406 0028-4793, (Copyright © 2021 Massachusetts Medical Society. Place: United States PMID: 34432975). Abstract | BibTeX | Tags: 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 | Links: @article{Chandramohan2021-qm, 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.). | ||
![]() | Stephen A Roberts, Loretta Brabin, Halidou Tinto, Sabine Gies, Salou Diallo, Bernard Brabin Seasonal patterns of malaria, genital infection, nutritional and iron status in non-pregnant and pregnant adolescents in Burkina Faso: a secondary analysis of trial data Journal Article In: BMC Public Health, vol. 21, no. 1, pp. 1764, 2021, ISSN: 1471-2458, (© 2021. The Author(s). PMID: 34579679 PMCID: PMC8477466). Abstract | BibTeX | Tags: Abnormal vaginal flora, Adolescents, Bacterial vaginosis, Body Mass Index, Burkina Faso/epidemiology, Child, Female, Humans, Iron, iron biomarkers, Malaria, Malaria/drug therapy/epidemiology, MUAC, Pregnancy, Seasons, Vagina | Links: @article{Roberts2021-gg, BACKGROUND: Adolescents are considered at high risk of developing iron deficiency. Studies in children indicate that the prevalence of iron deficiency increased with malaria transmission, suggesting malaria seasonally may drive iron deficiency. This paper examines monthly seasonal infection patterns of malaria, abnormal vaginal flora, chorioamnionitis, antibiotic and antimalarial prescriptions, in relation to changes in iron biomarkers and nutritional indices in adolescents living in a rural area of Burkina Faso, in order to assess the requirement for seasonal infection control and nutrition interventions. METHODS: Data collected between April 2011 and January 2014 were available for an observational seasonal analysis, comprising scheduled visits for 1949 non-pregnant adolescents (≤19 years), (315 of whom subsequently became pregnant), enrolled in a randomised trial of periconceptional iron supplementation. Data from trial arms were combined. Body Iron Stores (BIS) were calculated using an internal regression for ferritin to allow for inflammation. At recruitment 11% had low BIS (< 0 mg/kg). Continuous outcomes were fitted to a mixed-effects linear model with month, age and pregnancy status as fixed effect covariates and woman as a random effect. Dichotomous infection outcomes were fitted with analogous logistic regression models. RESULTS: Seasonal variation in malaria parasitaemia prevalence ranged between 18 and 70% in non-pregnant adolescents (P < 0.001), peaking at 81% in those who became pregnant. Seasonal variation occurred in antibiotic prescription rates (0.7-1.8 prescriptions/100 weekly visits, P < 0.001) and chorioamnionitis prevalence (range 15-68%, P = 0.026). Mucosal vaginal lactoferrin concentration was lower at the end of the wet season (range 2-22 μg/ml, P < 0.016), when chorioamnionitis was least frequent. BIS fluctuated annually by up to 53.2% per year around the mean BIS (5.1 mg/kg(2), range 4.1-6.8 mg/kg), with low BIS (< 0 mg/kg) of 8.7% in the dry and 9.8% in the wet seasons (P = 0.36). Median serum transferrin receptor increased during the wet season (P < 0.001). Higher hepcidin concentration in the wet season corresponded with rising malaria prevalence and use of prescriptions, but with no change in BIS. Mean Body Mass Index and Mid-Upper-Arm-Circumference values peaked mid-dry season (both P < 0.001). CONCLUSIONS: Our analysis supports preventive treatment of malaria among adolescents 15-19 years to decrease their disease burden, especially asymptomatic malaria. As BIS were adequate in most adolescents despite seasonal malaria, a requirement for programmatic iron supplementation was not substantiated. | ||
![]() | Koudraogo Bienvenue Yaméogo, Rakiswendé Serge Yerbanga, Seydou Bienvenu Ouattara, Franck A Yao, Thierry Lef`evre, Issaka Zongo, Frederic Niki`ema, Yves Daniel Compaoré, Halidou Tinto, Daniel Chandramohan, Brian Greenwood, Adrien M G Belem, Anna Cohuet, Jean Bosco Ouédraogo Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness Journal Article In: Malar. J., vol. 20, no. 1, pp. 326, 2021, ISSN: 1475-2875, (© 2021. The Author(s). PMID: 34315475 PMCID: PMC8314489). Abstract | BibTeX | Tags: 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 | Links: @article{Yameogo2021-bb, 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. | ||
![]() | Navideh Noori, Karim Derra, Innocent Valea, Assaf P Oron, Aminata Welgo, Toussaint Rouamba, Palwende Romuald Boua, Athanase M Somé, Eli Rouamba, Edward Wenger, Hermann Sorgho, Halidou Tinto, Andre Lin Ouédraogo Patterns of child mortality in rural area of Burkina Faso: evidence from the Nanoro health and demographic surveillance system (HDSS) Journal Article In: BMC Public Health, vol. 21, no. 1, pp. 1425, 2021, ISSN: 1471-2458, (© 2021. The Author(s). PMID: 34281547 PMCID: PMC8287796). Abstract | BibTeX | Tags: Burkina Faso, Burkina Faso/epidemiology, child mortality, ChildHealth Facilities, Children under 5, Demographic surveillance, HDSS, Humans, Infant, Malaria, Nanoro, Spatial analysis, Travel | Links: @article{Noori2021-te, BACKGROUND: Half of global child deaths occur in sub-Saharan Africa. Understanding child mortality patterns and risk factors will help inform interventions to reduce this heavy toll. The Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso was described previously, but patterns and potential drivers of heterogeneity in child mortality in the district had not been studied. Similar studies in other districts indicated proximity to health facilities as a risk factor, usually without distinction between facility types. METHODS: Using Nanoro HDSS data from 2009 to 2013, we estimated the association between under-5 mortality and proximity to inpatient and outpatient health facilities, seasonality of death, age group, and standard demographic risk factors. RESULTS: Living in homes 40-60 min and > 60 min travel time from an inpatient facility was associated with 1.52 (95% CI: 1.13-2.06) and 1.74 (95% CI: 1.27-2.40) greater hazard of under-5 mortality, respectively, than living in homes < 20 min from an inpatient facility. No such association was found for outpatient facilities. The wet season (July-November) was associated with 1.28 (95% CI: 1.07, 1.53) higher under-5 mortality than the dry season (December-June), likely reflecting the malaria season. CONCLUSIONS: Our results emphasize the importance of geographical proximity to health care, distinguish between inpatient and outpatient facilities, and also show a seasonal effect, probably driven by malaria. | ||
![]() | Mariken Wit, Matthew Cairns, Yves Daniel Compaoré, Issaka Sagara, Irene Kuepfer, Issaka Zongo, Amadou Barry, Modibo Diarra, Amadou Tapily, Samba Coumare, Ismaila Thera, Frederic Nikiema, R Serge Yerbanga, Rosemonde M Guissou, Halidou Tinto, Alassane Dicko, Daniel Chandramohan, Brian Greenwood, Jean Bosco Ouedraogo Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria Journal Article In: Malar. J., vol. 20, no. 1, pp. 274, 2021, ISSN: 1475-2875, (PMID: 34158054 PMCID: PMC8220741). Abstract | BibTeX | Tags: Acute malnutrition, Antimalarials/administration & dosage, Azithromycin/administration & dosage, Burkina Faso, Burkina Faso/epidemiology, Child, Chronic malnutrition, Female, Humans, Incidence, Infant, Malaria, Malaria/epidemiology/transmission, Male, Nutritional Status, Preschool, seasonal malaria chemoprevention, Seasons | Links: @article{De_Wit2021-yi, BACKGROUND: Malaria and malnutrition remain major problems in Sahel countries, especially in young children. The direct effect of malnutrition on malaria remains poorly understood, and may have important implications for malaria control. In this study, nutritional status and the association between malnutrition and subsequent incidence of symptomatic malaria were examined in children in Burkina Faso and Mali who received either azithromycin or placebo, alongside seasonal malaria chemoprevention. METHODS: Mid-upper arm circumference (MUAC) was measured in all 20,185 children who attended a screening visit prior to the malaria transmission season in 2015. Prior to the 2016 malaria season, weight, height and MUAC were measured among 4149 randomly selected children. Height-for-age, weight-for-age, weight-for-height, and MUAC-for-age were calculated as indicators of nutritional status. Malaria incidence was measured during the following rainy seasons. Multivariable random effects Poisson models were created for each nutritional indicator to study the effect of malnutrition on clinical malaria incidence for each country. RESULTS: In both 2015 and 2016, nutritional status prior to the malaria season was poor. The most prevalent form of malnutrition in Burkina Faso was being underweight (30.5%; 95% CI 28.6-32.6), whereas in Mali stunting was most prevalent (27.5%; 95% CI 25.6-29.5). In 2016, clinical malaria incidence was 675 per 1000 person-years (95% CI 613-744) in Burkina Faso, and 1245 per 1000 person-years (95% CI 1152-1347) in Mali. There was some evidence that severe stunting was associated with lower incidence of malaria in Mali (RR 0.81; 95% CI 0.64-1.02; p = 0.08), but this association was not seen in Burkina Faso. Being moderately underweight tended to be associated with higher incidence of clinical malaria in Burkina Faso (RR 1.27; 95% CI 0.98-1.64; p = 0.07), while this was the case in Mali for moderate wasting (RR 1.27; 95% CI 0.98-1.64; p = 0.07). However, these associations were not observed in severely affected children, nor consistent between countries. MUAC-for-age was not associated with malaria risk. CONCLUSIONS: Both malnutrition and malaria were common in the study areas, high despite high coverage of seasonal malaria chemoprevention and long-lasting insecticidal nets. However, no strong or consistent evidence was found for an association between any of the nutritional indicators and the subsequent incidence of clinical malaria. | ||
![]() | 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: @article{Sondo2021-qe, 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. | ||
![]() | Paul Sondo, Marc Christian Tahita, Toussaint Rouamba, Karim Derra, Bérenger Kaboré, Cheick Sa"id Compaoré, Florence Ouédraogo, Eli Rouamba, Hamidou Ilboudo, Estelle A"issa Bambara, Macaire Nana, Edmond Yabré Sawadogo, Hermann Sorgho, Athanase Mwinessobaonfou Somé, Innocent Valéa, Prabin Dahal, Maminata Traoré/Coulibaly, Halidou Tinto Assessment of a combined strategy of seasonal malaria chemoprevention and supplementation with vitamin A, zinc and Plumpy'Doz™ to prevent malaria and malnutrition in children under 5 years old in Burkina Faso: a randomized open-label trial (SMC-NUT) Journal Article In: Trials, vol. 22, no. 1, pp. 360, 2021, ISSN: 1745-6215, (PMID: 34030705 PMCID: PMC8142067). Abstract | BibTeX | Tags: Antimalarials/adverse effects, Burkina Faso/epidemiology, Chemoprevention, Child, Child Nutrition Disorders, Dietary Supplements, Humans, Infant, Malaria, Malaria/diagnosis/epidemiology/prevention & control, Malnutrition, Malnutrition/diagnosis/drug therapy/prevention & control, Pharmaceutical Preparations, Plumpy’Doz™, Preschool, Randomized controlled trial, Seasonal chemoprevention, Seasons, Vitamin A, Vitamin A/adverse effects, Zinc | Links: @article{Sondo2021-kc, BACKGROUND: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage. METHODS: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps. DISCUSSION: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels. TRIAL REGISTRATION: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845. | ||
![]() | Yeka Adoke, Rella Zoleko-Manego, Serge Ouoba, Alfred B Tiono, Grace Kaguthi, Juv^encio Eduardo Bonzela, Tran Thanh Duong, Alain Nahum, Marielle Bouyou-Akotet, Bernhards Ogutu, Alphonse Ouedraogo, Fiona Macintyre, Andreas Jessel, Bart Laurijssens, Mohammed H Cherkaoui-Rbati, Cathy Cantalloube, Anne Claire Marrast, Rapha"el Bejuit, David White, Timothy N C Wells, Florian Wartha, Didier Leroy, Afizi Kibuuka, Ghyslain Mombo-Ngoma, Daouda Ouattara, Ir`ene Mugenya, Bui Quang Phuc, Francis Bohissou, Denise P Mawili-Mboumba, Fredrick Olewe, Issiaka Soulama, Halidou Tinto, FALCI Study Group 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 Journal Article In: Malar. J., vol. 20, no. 1, pp. 222, 2021, ISSN: 1475-2875, (PMID: 34011358 PMCID: PMC8135182). Abstract | BibTeX | Tags: Adamantane/administration & dosage/analogs & derivatives, Adolescent, Adult, Aged, Aminoquinolines/administration & dosage, Benin, Burkina Faso, C580Y, Child, Combination treatment, Double-Blind Method, Drug Combinations, Exposure–response, 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 | Links: @article{Adoke2021-el, 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 $łeq$ 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 $łeq$ 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. | ||
![]() | Mehreen S Datoo, Magloire H Natama, Athanase Somé, Ousmane Traoré, Toussaint Rouamba, Duncan Bellamy, Prisca Yameogo, Daniel Valia, Moubarak Tegneri, Florence Ouedraogo, Rachidatou Soma, Seydou Sawadogo, Faizatou Sorgho, Karim Derra, Eli Rouamba, Benedict Orindi, Fernando Ramos Lopez, Amy Flaxman, Federica Cappuccini, Reshma Kailath, Sean Elias, Ekta Mukhopadhyay, Andres Noe, Matthew Cairns, Alison Lawrie, Rachel Roberts, Innocent Valéa, Hermann Sorgho, Nicola Williams, Gregory Glenn, Louis Fries, Jenny Reimer, Katie J Ewer, Umesh Shaligram, Adrian V S Hill, Halidou Tinto Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial Journal Article In: Lancet, vol. 397, no. 10287, pp. 1809–1818, 2021, ISSN: 1474-547X 0140-6736, (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. PMID: 33964223 PMCID: PMC8121760). Abstract | BibTeX | Tags: Adjuvants, Burkina Faso, Double-Blind Method, Falciparum/prevention & control, Female, Hepatitis B Surface Antigens, Humans, Immunogenicity, Immunologic/administration & dosage, Infant, Malaria, Malaria Vaccines/therapeutic use, Malaria/prevention & control, Male, Nanoparticles/administration & dosage, Proportional Hazards Models, Protozoan Proteins/immunology, Saponins/administration & dosage, Treatment Outcome, Vaccine, Vaccines, Virus-Like Particle/therapeutic use | Links: @article{Datoo2021-dk, BACKGROUND: Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy. METHODS: In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 $mu$g R21 plus 25 $mu$g MM, group 2 received 5 $mu$g R21 plus 50 $mu$g MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724. FINDINGS: From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered 1 year later. INTERPRETATION: R21/MM appears safe and very immunogenic in African children, and shows promising high-level efficacy. FUNDING: The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre. | ||
![]() | Sabine Gies, Stephen A Roberts, Salou Diallo, Olga M Lompo, Halidou Tinto, Bernard J Brabin Risk of malaria in young children after periconceptional iron supplementation Journal Article In: Matern. Child Nutr., vol. 17, no. 2, pp. e13106, 2021, ISSN: 1740-8709 1740-8695, (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd. PMID: 33236840 PMCID: PMC7988873). Abstract | BibTeX | Tags: Burkina Faso, child iron, Dietary Supplements/analysis, Female, Folic Acid, Humans, Infant, Malaria, Newborn, periconceptional, placenta, Pregnancy, Premature Birth, Preschool | Links: @article{Gies2021-aw, This study in Burkina Faso investigated whether offspring of young mothers who had received weekly periconceptional iron supplementation in a randomised controlled trial were at increased risk of malaria. A child safety survey was undertaken in the peak month of malaria transmission towards the end of the trial to assess child iron biomarkers, nutritional status, anaemia and malaria outcomes. Antenatal iron biomarkers, preterm birth, fetal growth restriction and placental pathology for malaria and chorioamnionitis were assessed. Data were available for 180 babies surviving to the time of the survey when their median age was 9 months. Prevalence of maternal iron deficiency in the last trimester based on low body iron stores was 16%. Prevalence of active placental malaria infection was 24.8%, past infection 59% and chorioamnionitis 55.6%. Babies of iron supplemented women had lower median gestational age. Four out of five children ≥ 6 months were iron deficient, and 98% were anaemic. At 4 months malaria prevalence was 45%. Child iron biomarkers, anaemia and malaria outcomes did not differ by trial arm. Factors associated with childhood parasitaemia were third trimester C-reactive protein level (OR 2.1; 95% CI 1.1-3.9), active placental malaria (OR 5.8; 1.0-32.5, P = 0.042) and child body iron stores (OR 1.13; 1.04-1.23, P = 0.002). Chorioamnionitis was associated with reduced risk of child parasitaemia (OR 0.4; 0.1-1.0, P = 0.038). Periconceptional iron supplementation of young women did not alter body iron stores of their children. Higher child body iron stores and placental malaria increased risk of childhood parasitaemia. | ||
![]() | Palpouguini Lompo, Marc Christian Tahita, Hermann Sorgho, William Kaboré, Adama Kazienga, Ashmed Cheick Bachirou Nana, Hamtandi Magloire Natama, Isidore Juste Ouindgueta Bonkoungou, Nicolas Barro, Halidou Tinto Pathogens associated with acute diarrhea, and comorbidity with malaria among children under five years old in rural Burkina Faso Journal Article In: Pan Afr. Med. J., vol. 38, pp. 259, 2021, ISSN: 1937-8688, (Copyright: Palpouguini Lompo et al. PMID: 34104307 PMCID: PMC8164431). Abstract | BibTeX | Tags: Abdominal Pain/epidemiology, Acute Disease, bacteria, Burkina Faso, Burkina Faso/epidemiology, Child, Comorbidity, Diarrhea, Diarrhea/epidemiology/microbiology, Female, Fever/epidemiology, Giardiasis/epidemiology, Humans, Infant, infectious, Malaria, Malaria/epidemiology, Male, parasite, pathogens, Preschool, Prevalence, Risk Factors, rotavirus, Rotavirus Infections/epidemiology, Rural Population, Seasons, Vomiting/epidemiology | Links: @article{Lompo2021-sk, INTRODUCTION: acute diarrhea in children under five years is a public health problem in developing countries and particularly in malaria-endemic areas where both diseases co-exist. The present study examined the etiology of childhood diarrhea and its comorbidity with malaria in a rural area of Burkina Faso. METHODS: conventional culture techniques, direct stools examination, and viruses´ detection by rapid tests were performed on the fresh stools and microscopy was used to diagnose malaria. Some risk factors were also assessed. RESULTS: on a total of 191 samples collected, at least one pathogen was identified in 89 cases (46.6%). The proportions of pathogens found on the 89 positive stool samples were parasites 51.69% (46 cases), viruses 39.33% (35 cases), and bacteria 14.61% (13 cases), respectively. The relationship between malaria and infectious diarrhea was significant in viral and parasites causes (p=0.005 and 0.043 respectively). Fever, vomiting and abdominal pain were the major symptoms associated with diarrhea, with 71.51%, 31.72% and 23.66% respectively. The highest viral diarrhea prevalence was reported during the dry season (OR=5.29, 95% CI: 1.74 - 16.07, p=0.001) while parasite diarrhea was more encountered during the rainy season (OR=0.41, 95% CI: 0.33 - 0.87, p=0.011). CONCLUSION: Giardia spp and rotavirus were the leading cause of acute diarrhea in Nanoro, Burkina Faso with a predominance of rotavirus in children less than 2 years. Parasite and viral diarrhea were the most pathogens associated with malaria. However, the high rate of negative stool samples suggests the need to determine other enteric microorganisms. | ||
![]() | 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: @article{Natama2021-ft, 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. | ||
![]() | 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: @article{Gansane2021-yh, 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. | ||
![]() | Paul Sondo, Biebo Bihoun, Marc Christian Tahita, Karim Derra, Toussaint Rouamba, Seydou Nakanabo Diallo, Adama Kazienga, Hamidou Ilboudo, Innocent Valea, Zekiba Tarnagda, Hermann Sorgho, Thierry Lef`evre, Halidou Tinto Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density Journal Article In: Malar. J., vol. 20, no. 1, pp. 31, 2021, ISSN: 1475-2875, (PMID: 33413393 PMCID: PMC7791700). Abstract | BibTeX | Tags: Anemia/epidemiology/parasitology, Burkina Faso/epidemiology, Falciparum/epidemiology/parasitology, Gametocyte, Humans, Malaria, msp1, msp2, Multiplicity of infection, Plasmodium falciparum, Plasmodium falciparum/physiology | Links: @article{Sondo2021-at, BACKGROUND: Multi-genotype malaria infections are frequent in endemic area, and people commonly harbour several genetically distinct Plasmodium falciparum variants. The influence of genetic multiplicity and whether some specific genetic variants are more or less likely to invest into gametocyte production is not clearly understood. This study explored host and parasite-related risk factors for gametocyte carriage, and the extent to which some specific P. falciparum genetic variants are associated with gametocyte carriage. METHODS: Gametocytes and asexual forms were detected by light microscopy on thick smears collected between 2010 and 2012 in Nanoro, Burkina Faso. Merozoite surface protein 1 and 2 were genotyped by nested PCR on clinical samples. Associations between gametocyte carriage and factors, including multiplicity of infection, parasite density, patient age, gender, haemoglobin (Hb) level, and body temperature were assessed. The relationship between the presence of a particular msp1 and msp2 genetic variants and gametocyte carriage was also explored. RESULTS: Of the 724 samples positive to P. falciparum and successfully genotyped, gametocytes were found in 48 samples (6.63%). There was no effect of patient gender, age and body temperature on gametocyte carriage. However, the probability of gametocyte carriage significantly increased with increasing values of multiplicity of infection (MOI). Furthermore, there was a negative association between parasite density and gametocyte carriage. MOI decreased with parasite density in gametocyte-negative patients, but increased in gametocyte carriers. The probability of gametocyte carriage decreased with Hb level. Finally, the genetic composition of the infection influenced gametocyte carriage. In particular, the presence of RO33 increased the odds of developing gametocytes by 2 while the other allelic families K1, MAD20, FC27, and 3D7 had no significant impact on the occurrence of gametocytes in infected patients. CONCLUSION: This study provides insight into potential factors influencing gametocyte production in symptomatic patients. The findings contribute to enhance understanding of risk factors associated with gametocyte carriage in humans. Trial registration NCT01232530. | ||
2020 |
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![]() | André Lin Ouédraogo, Julie Zhang, Halidou Tinto, Innocent Valéa, Edward A Wenger A microplanning model to improve door-to-door health service delivery: the case of Seasonal Malaria Chemoprevention in Sub-Saharan African villages Journal Article In: BMC Health Serv. Res., vol. 20, no. 1, pp. 1128, 2020, ISSN: 1472-6963, (PMID: 33287825 PMCID: PMC7720067). Abstract | BibTeX | Tags: Africa South of the Sahara/epidemiology, Antimalarials/therapeutic use, Burkina Faso, Chemoprevention, Child, CHW, Community health worker, Door-to-door, Health Services, Humans, Malaria, Malaria/drug therapy/epidemiology/prevention & control, Microplanning, Model, Satellite imagerySeasonal malaria chemoprevention, Seasons, SMC | Links: @article{Ouedraogo2020-vc, BACKGROUND: Malaria incidence has plateaued in Sub-Saharan Africa despite Seasonal Malaria Chemoprevention's (SMC) introduction. Community health workers (CHW) use a door-to-door delivery strategy to treat children with SMC drugs, but for SMC to be as effective as in clinical trials, coverage must be high over successive seasons. METHODS: We developed and used a microplanning model that utilizes population raster to estimate population size, generates optimal households visit itinerary, and quantifies SMC coverage based on CHWs' time investment for treatment and walking. CHWs' performance under current SMC deployment mode was assessed using CHWs' tracking data and compared to microplanning in villages with varying demographics and geographies. RESULTS: Estimates showed that microplanning significantly reduces CHWs' walking distance by 25%, increases the number of visited households by 36% (p < 0.001) and increases SMC coverage by 21% from 37.3% under current SMC deployment mode up to 58.3% under microplanning (p < 0.001). Optimal visit itinerary alone increased SMC coverage up to 100% in small villages whereas in larger or hard-to-reach villages, filling the gap additionally needed an optimization of the CHW ratio. CONCLUSION: We estimate that for a pair of CHWs, the daily optimal number of visited children (assuming 8.5mn spent per child) and walking distance should not exceed 45 (95% CI 27-62) and 5 km (95% CI 3.2-6.2) respectively. Our work contributes to extend SMC coverage by 21-63% and may have broader applicability for other community health programs. | ||
2016 |
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Francois Kiemde, René Spijker, Petra F. Mens, Halidou Tinto, Michael Boele, Henk D. F. H. Schallig Aetiologies of non-malaria febrile episodes in children under 5 years in sub-Saharan Africa. Journal Article In: Tropical medicine & international health : TM & IH, vol. 21, iss. 8, pp. 943-955, 2016. Abstract | BibTeX | Tags: aetiology, África subsahariana, Afrique subsaharienne, Children, enfants, etiología, étiologie, Fever, fiebre, fièvre, Malaria, niños, paludisme, sub-Saharan Africa @article{nokey, OBJECTIVES: To provide an overview of the most frequent aetiologies found in febrile episodes of children under 5 years from sub-Saharan Africa. METHODS: MEDLINE and EMBASE were searched for publications in English and French on non-malaria fever episodes in African children under 5 years of age, which were published between January 1990 and July 2015. Case reports and conference abstracts were excluded. RESULTS: In total, 3851 titles and abstracts were reviewed, and 153 were selected for full screening of which 18 were included in the present review. Bloodstream infection (BSI) was most commonly investigated (nine of 18) followed by urinary tract infection (UTI) (four of 18) and respiratory tract infection (RTI) (two of 18). Few studies investigated BSI and UTI in the same children (two of 18), or BSI and gastrointestinal infection (GII) (one of 18). As for BSI, the most frequently isolated bacteria were E. coli (four of 12), Streptococcus pneumonia (four of 12), Salmonella spp (three of 12) and Staphylococcus aureus (two of 12) with a positive identification rate of 19.7-33.3%, 5.2-27.6%, 11.7-65.4% and 23.5-42.0%, respectively. As for UTI, the main bacteria isolated were E. coli (six of six) and Klebsiella spp (six of six) with a positive rate of 20.0-72.3% and 10.0-28.5%, respectively. No bacterium was isolated in RTI group, but Human influenzae A and B were frequently found, with the highest positive identification rate in Tanzania (75.3%). Dengue virus (two of 12) was the most frequently reported viral infection with a positive identification rate of 16.7-30.8%. Finally, only rotavirus/adenovirus (69.2% positive identification rate) was found in GII and no bacterium was isolated in this group. CONCLUSIONS: The high prevalence of treatable causes of non-malaria fever episodes requires a proper diagnosis of the origin of fever followed by an appropriate treatment, thereby reducing the under-5 mortality in sub-Saharan Africa and preventing the overprescription of antibiotics and thus circumventing the rise of antibiotic resistance. | |||
2015 |
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Halidou Tinto, Esperança Sevene, Stephanie Dellicour, Gregory S. Calip, Umberto D'Alessandro, Eusébio Macete, Seydou Nakanabo-Diallo, Adama Kazienga, Innocent Valea, Hermann Sorgho, Anifa Valá, Orvalho Augusto, Maria Ruperez, Clara Menendez, Peter Ouma, Meghna Desai, Feiko Ter Kuile, Andy Stergachis Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): Protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique Journal Article In: Reproductive Health, vol. 12, iss. 1, pp. 161-165, 2015, ISSN: 17424755. Abstract | BibTeX | Tags: ACTs, Malaria, Pregnancy | Links: @article{Tinto2015, Background: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. Methods: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. Discussion: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. | |||
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: @article{Adjuik2015, 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 | |||
S Clinical Trials Partnership RTS Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial Journal Article In: Lancet (London, England), vol. 386, iss. 9988, pp. 31-45, 2015, ISSN: 1474-547X. Abstract | BibTeX | Tags: {Africa South of the Sahara / epidemiology, Age Factors, Clinical Trial, Double-Blind Method, Falciparum / epidemiology, Falciparum / prevention & control*, Female, Follow-Up Studies, Hospitalization / statistics & numerical data, Humans, Immunization, Immunization Schedule, Incidence, Infant, Malaria, Malaria Vaccines*, Male, 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 III, PMC5626001, PubMed Abstract, Randomized controlled trial, Research Support, S Clinical Trials Partnership' | Links: @article{RTS2015, Background The efficacy and safety of the RTS,S/AS01 candidate malaria vaccine during 18 months of follow-up have been published previously. Herein, we report the final results from the same trial, including the efficacy of a booster dose. Methods From March 27, 2009, until Jan 31, 2011, children (age 5-17 months) and young infants (age 6-12 weeks) were enrolled at 11 centres in seven countries in sub-Saharan Africa. Participants were randomly assigned (1:1:1) at first vaccination by block randomisation with minimisation by centre to receive three doses of RTS,S/AS01 at months 0, 1, and 2 and a booster dose at month 20 (R3R group); three doses of RTS,S/AS01 and a dose of comparator vaccine at month 20 (R3C group); or a comparator vaccine at months 0, 1, 2, and 20 (C3C [control group]). Participants were followed up until Jan 31, 2014. Cases of clinical and severe malaria were captured through passive case detection. Serious adverse events (SAEs) were recorded. Analyses were by modified intention to treat and per protocol. The coprimary endpoints were the occurrence of malaria over 12 months after dose 3 in each age category. In this final analysis, we present data for the efficacy of the booster on the occurrence of malaria. Vaccine efficacy (VE) against clinical malaria was analysed by negative binomial regression and against severe malaria by relative risk reduction. This trial is registered with ClinicalTrials.gov, number NCT00866619. Findings 8922 children and 6537 young infants were included in the modified intention-to-treat analyses. Children were followed up for a median of 48 months (IQR 39-50) and young infants for 38 months (34-41) after dose 1. From month 0 until study end, compared with 9585 episodes of clinical malaria that met the primary case definition in children in the C3C group, 6616 episodes occurred in the R3R group (VE 36·3%, 95% CI 31·8-40·5) and 7396 occurred in the R3C group (28·3%, 23·3-32·9); compared with 171 children who experienced at least one episode of severe malaria in the C3C group, 116 children experienced at least one episode of severe malaria in the R3R group (32·2%, 13·7 to 46·9) and 169 in the R3C group (1·1%, -23·0 to 20·5). In young infants, compared with 6170 episodes of clinical malaria that met the primary case definition in the C3C group, 4993 episodes occurred in the R3R group (VE 25·9%, 95% CI 19·9-31·5) and 5444 occurred in the R3C group (18·3%, 11·7-24·4); and compared with 116 infants who experienced at least one episode of severe malaria in the C3C group, 96 infants experienced at least one episode of severe malaria in the R3R group (17·3%, 95% CI -9·4 to 37·5) and 104 in the R3C group (10·3%, -17·9 to 31·8). In children, 1774 cases of clinical malaria were averted per 1000 children (95% CI 1387-2186) in the R3R group and 1363 per 1000 children (995-1797) in the R3C group. The numbers of cases averted per 1000 young infants were 983 (95% CI 592-1337) in the R3R group and 558 (158-926) in the R3C group. The frequency of SAEs overall was balanced between groups. However, meningitis was reported as a SAE in 22 children: 11 in the R3R group, ten in the R3C group, and one in the C3C group. The incidence of generalised convulsive seizures within 7 days of RTS,S/AS01 booster was 2·2 per 1000 doses in young infants and 2·5 per 1000 doses in children. Interpretation RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3-4 year period in young infants and children when administered with or without a booster dose. Efficacy was enhanced by the administration of a booster dose in both age categories. Thus, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission. Funding GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative. |
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