2024 |
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Journal Articles |
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Kadiatou Koita, Joel D. Bognini, Efundem Agboraw, Mahamadou Dembélé, Seydou Yabré, Biébo Bihoun, Oumou Coulibaly, Hamidou Niangaly, Jean Batiste N’Takpé, Maia Lesosky, Dario Scaramuzzi, Eve Worrall, Jenny Hill, Valérie Briand, Halidou Tinto, Kassoum Kayentao Increasing the uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) through seasonal malaria chemoprevention channel delivery: protocol of a multicenter cluster randomized implementation trial in Mali and Burkina Faso Journal Article In: BMC public health, vol. 24, iss. 1, 2024, ISSN: 1471-2458. Abstract | BibTeX | Tags: Antimalarials* / therapeutic use, Burkina Faso, Chemoprevention, Child, Clinical Trial Protocol, doi:10.1186/s12889-023-17529-z, Drug Combinations, Female, Humans, Joel D Bognini, Kadiatou Koita, Kassoum Kayentao, Malaria* / drug therapy, Malaria* / prevention & control, Mali, MEDLINE, Multicenter Studies as Topic, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Parasitic* / prevention & control, PMC10763117, pmid:38166711, Pregnancy, Pregnancy Complications, Preschool, PubMed Abstract, Pyrimethamine / therapeutic use, Randomized Controlled Trials as Topic, Research Support, Seasons, Sulfadoxine / therapeutic use | Links: @article{Koita2024, Background: The uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) remains unacceptably low, with more than two-thirds of pregnant women in sub-Saharan Africa still not accessing the three or more doses recommended by the World Health Organisation (WHO). In contrast, the coverage of Seasonal Malaria Chemoprevention (SMC), a more recent strategy recommended by the WHO for malaria prevention in children under five years living in Sahelian countries with seasonal transmission, including Mali and Burkina-Faso, is high (up to 90%). We hypothesized that IPTp-SP delivery to pregnant women through SMC alongside antenatal care (ANC) will increase IPTp-SP coverage, boost ANC attendance, and increase public health impact. This protocol describes the approach to assess acceptability, feasibility, effectiveness, and cost-effectiveness of the integrated strategy. Methods and analysis: This is a multicentre, cluster-randomized, implementation trial of IPTp-SP delivery through ANC + SMC vs ANC alone in 40 health facilities and their catchment populations (20 clusters per arm). The intervention will consist of monthly administration of IPTp-SP through four monthly rounds of SMC during the malaria transmission season (July to October), for two consecutive years. Effectiveness of the strategy to increase coverage of three or more doses of IPTp-SP (IPTp3 +) will be assessed using household surveys and ANC exit interviews. Statistical analysis of IPT3 + and four or more ANC uptake will use a generalized linear mixed model. Feasibility and acceptability will be assessed through in-depth interviews and focus group discussions with health workers, pregnant women, and women with a child < 12 months. Discussion: This multicentre cluster randomized implementation trial powered to detect a 45% and 22% increase in IPTp-SP3 + uptake in Mali and Burkina-Faso, respectively, will generate evidence on the feasibility, acceptability, effectiveness, and cost-effectiveness of IPTp-SP delivered through the ANC + SMC channel. The intervention is designed to facilitate scalability and translation into policy by leveraging existing resources, while strengthening local capacities in research, health, and community institutions. Findings will inform the local national malaria control policies. Trial registration: Retrospectively registered on August 11th, 2022; registration # PACTR202208844472053. Protocol v4.0 dated September 04, 2023. Trail sponsor: University of Sciences Techniques and Technologies of Bamako (USTTB), Mali. | |||
Mehreen S. Datoo, Alassane Dicko, Halidou Tinto, Jean Bosco Ouédraogo, Mainga Hamaluba, Ally Olotu, Emma Beaumont, Fernando Ramos Lopez, Hamtandi Magloire Natama, Sophie Weston, Mwajuma Chemba, Yves Daniel Compaore, Djibrilla Issiaka, Diallo Salou, Athanase M. Some, Sharon Omenda, Alison Lawrie, Philip Bejon, Harish Rao, Daniel Chandramohan, Rachel Roberts, Sandesh Bharati, Lisa Stockdale, Sunil Gairola, Brian M. Greenwood, Katie J. Ewer, John Bradley, Prasad S. Kulkarni, Umesh Shaligram, Adrian V. S. Hill, Almahamoudou Mahamar, Koualy Sanogo, Youssoufa Sidibe, Kalifa Diarra, Mamoudou Samassekou, Oumar Attaher, Amadou Tapily, Makonon Diallo, Oumar Mohamed Dicko, Mahamadou Kaya, Seydina Oumar Maguiraga, Yaya Sankare, Hama Yalcouye, Soumaila Diarra, Sidi Mohamed Niambele, Ismaila Thera, Issaka Sagara, Mala Sylla, Amagana Dolo, Nsajigwa Misidai, Sylvester Simando, Hania Msami, Omary Juma, Nicolaus Gutapaka, Rose Paul, Sarah Mswata, Ibrahim Sasamalo, Kasmir Johaness, Mwantumu Sultan, Annastazia Alexander, Isaac Kimaro, Kauye Lwanga, Mwajuma Mtungwe, Kassim Khamis, Lighton Rugarabam, Wilmina Kalinga, Mohammed Mohammed, Janeth Kamange, Jubilate Msangi, Batuli Mwaijande, Ivanny Mtaka, Matilda Mhapa, Tarsis Mlaganile, Thabit Mbaga, Rakiswende Serge Yerbanga, Wendkouni Samtouma, Abdoul Aziz Sienou, Zachari Kabre, Wendinpui Jedida Muriel Ouedraogo, G. Armel Bienvenu Yarbanga, Issaka Zongo, Hamade Savadogo, Joseph Sanon, Judicael Compaore, Idrissa Kere, Ferdinand Lionel Yoni, Tewende Martine Sanre, Seydou Bienvenu Ouattara, Samuel Provstgaard-Morys, Danielle Woods, Robert W. Snow, Nyaguara Amek, Caroline J. Ngetsa, Lynette Isabella Ochola-Oyier, Jennifer Musyoki, Marianne Munene, Noni Mumba, Uche Jane Adetifa, Charles Mwangi Muiruri, Jimmy Shangala Mwawaka, Mwatasa Hussein Mwaganyuma, Martha Njeri Ndichu, Joseph Ochieng Weya, Kelvin Njogu, Jane Grant, Jayne Webster, Anand Lakhkar, N. Félix André Ido, Ousmane Traore, Marc Christian Tahita, Massa Achille Bonko, Toussaint Rouamba, D. Florence Ouedraogo, Rachidatou Soma, Aida Millogo, Edouard Ouedraogo, Faizatou Sorgho, Fabé Konate, Innocent Valea Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial Journal Article In: Lancet (London, England), vol. 403, iss. 10426, pp. 533-544, 2024, ISSN: 1474-547X. Abstract | BibTeX | Tags: {Alassane Dicko, Antibodies, Burkina Faso, Child, Clinical Trial, Double-Blind Method, Female, Humans, Immunization, Infant, Malaria Vaccines* / adverse effects, Malaria* / drug therapy, Male, MEDLINE, Mehreen S Datoo, Multicenter Study, Nanoparticles*, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase III, Preschool, PubMed Abstract, Randomized controlled trial, Research Support, Saponins* | Links: @article{Datoo2024, Background: Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. Methods: We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5–36 months) were enrolled and randomly assigned (2:1) to receive 5 μg R21 plus 50 μg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. Findings: From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71–79; p<0·0001) at the seasonal sites and 68% (61–74; p<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71–78; p<0·0001) at the seasonal sites and 67% (59–73; p<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762–974) cases per 1000 children-years at seasonal sites and 296 (231–362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5–17 month age group compared with 18–36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73–84]; p<0·001) and standard (75% [65–83]; p<0·001) sites. Interpretation: R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. Funding: The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy. | |||
David Twesigomwe, Britt I. Drögemöller, Galen E. B. Wright, Clement Adebamowo, Godfred Agongo, Palwendé R. Boua, Mogomotsi Matshaba, Maria Paximadis, Michèle Ramsay, Gustave Simo, Martin C. Simuunza, Caroline T. Tiemessen, Zané Lombard, Scott Hazelhurst Characterization of CYP2B6 and CYP2A6 Pharmacogenetic Variation in Sub-Saharan African Populations Journal Article In: Clinical pharmacology and therapeutics, vol. 115, iss. 3, pp. 576-594, 2024, ISSN: 1532-6535. Abstract | BibTeX | Tags: Africa South of the Sahara, Alleles, Britt I Drögemöller, Cytochrome P-450 CYP2A6 / genetics, Cytochrome P-450 CYP2B6 / genetics, David Twesigomwe, doi:10.1002/cpt.3124, Gene Frequency, Genotype, Humans, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Nicotine*, NIH, NLM, Non-U.S. Gov't, Pharmacogenetics*, pmid:38049200, PubMed Abstract, Research Support, Scott Hazelhurst | Links: @article{Twesigomwe2024, Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub-Saharan African (SSA) populations. We called star alleles from 961 high-depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high-coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21–47% and 2–19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0–6%, 3–10%, and 6–20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African-ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single-Molecule Real-Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent. | |||
Houreratou Barry, Edouard Lhomme, Mathieu Surénaud, Moumini Nouctara, Cynthia Robinson, Viki Bockstal, Innocent Valea, Serge Somda, Halidou Tinto, Nicolas Meda, Brian Greenwood, Rodolphe Thiébaut, Christine Lacabaratz Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen Journal Article In: PLoS neglected tropical diseases, vol. 18, iss. 4, 2024, ISSN: 1935-2735. Abstract | BibTeX | Tags: Adolescent, Adult, Africa, Aged, Animals, Antibodies, Child, Christine Lacabaratz, Cytokines / immunology, doi:10.1371/journal.pntd.0011500, Ebola Vaccines* / administration & dosage, Ebola Vaccines* / immunology, Ebola* / immunology, Ebola* / prevention & control, Ebolavirus / genetics, Ebolavirus / immunology, Edouard Lhomme, Enzyme-Linked Immunosorbent Assay, Female, Helminth / blood, Helminthiasis / immunology, Helminthiasis / prevention & control, Helminths / genetics, Helminths / immunology, Hemorrhagic Fever, Houreratou Barry, Humans, Immunoglobulin G / blood, Male, MEDLINE, Middle Aged, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, PMC11037528, pmid:38603720, Preschool, PubMed Abstract, Research Support, Viral* / blood, Young Adult | Links: @article{Barry2024, Background The exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials. Methods/Principal findings We conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d’Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p < .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline. Conclusions/Significance No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen. Trial registration NCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov. | |||
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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Zakaria Garba, Isidore O. J. Bonkoungou, Nadège O. Millogo, H. Magloire Natama, Pingdwendé A. P. Vokouma, Massa A. Bonko, Ibrahima Karama, Lagmêyesgo A. W. Tiendrebeogo, Kaisa Haukka, Halidou Tinto, Lassana Sangaré, Nicolas Barro Wastewater from healthcare centers in Burkina Faso is a source of ESBL, AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae Journal Article In: BMC microbiology, vol. 23, iss. 1, 2023, ISSN: 1471-2180. Abstract | BibTeX | Tags: Animals, Anti-Bacterial Agents / pharmacology, bacteria, Bacterial Proteins, beta-Lactamases, Burkina Faso, Carbapenem-Resistant Enterobacteriaceae*, doi:10.1186/s12866-023-03108-0, Escherichia coli, Escherichia coli Infections* / microbiology, Humans, Isidore O J Bonkoungou, Klebsiella pneumoniae, MEDLINE, Microbial Sensitivity Tests, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Nicolas Barro, NIH, NLM, Non-U.S. Gov't, PMC10655474, pmid:37978428, PubMed Abstract, Research Support, Wastewater, Zakaria Garba | Links: @article{Garba2023, Background: Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae have spread into the environment worldwide posing a potential public health threat. However, the prevalence data for low- and middle-income countries are still scarce. The aim of this study was to evaluate the presence of ESBL, AmpC-β-lactamase and carbapenemase-producing and multidrug-resistant E. coli and K. pneumoniae in wastewaters from healthcare centers in Burkina Faso. Results: Eighty-four (84) wastewater samples were collected from five healthcare centers and plated on selective ESBL ChromAgar. E. coli and Klebsiella pneumoniae isolates were identified using API20E. ESBL-producing bacteria were detected in 97.6% of the samples and their average concentration per hospital ranged from 1.10 × 105 to 5.23 × 106 CFU/mL. Out of 170 putative ESBL-producing isolates (64% of them were E. coli) and 51 putative AmpC-β-lactamase-producing isolates, 95% and 45% were confirmed, respectively. Carbapenemase production was detected in 10 isolates, of which 6 were NDM producers, 3 were OXA-48 producers and 1 was NDM and OXA-48 producer. All isolates were multidrug resistant and, moreover, all of them were resistant to all tested β-lactams. Resistance to ESBL inhibitors was also common, up to 66% in E. coli and 62% in K. pneumoniae. Amikacin, fosfomycin and nitrofurantoin were the antibiotics to which the least resistance was detected. Conclusions: This study showed that wastewater from healthcare centers constitutes a reservoir of multidrug-resistant bacteria in Burkina Faso, including carbapenemase producers. Untreated healthcare wastewater entering the environment exposes people and animals to infections caused by these multi-resistant bacteria, which are difficult to treat, especially in the resource-poor settings. | |||
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. | |||
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. | |||
Jessica Amegee Quach, Innocent Valea, Imelda Bates, Justin Pulford Factors affecting African postdoctoral researcher capacity development within 'learn-by-doing' international research partnerships: findings from the 'Partnership for Increasing the Impact of Vector Control (PIIVeC)' Journal Article In: BMJ global health, vol. 8, iss. 9, 2023, ISSN: 2059-7908. Abstract | BibTeX | Tags: doi:10.1136/bmjgh-2023-012626, Focus Groups, Health Personnel*, Humans, Innocent Valea, Jessica Amegee Quach, Justin Pulford, Leadership, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Physicians*, PMC10496693, pmid:37678937, PubMed Abstract, Qualitative research, Research Support | Links: @article{nokey, Introduction The Partnership to Increase the Impact of Vector Control sought to develop the research and leadership capacity of 10 African postdoctoral vectorborne disease scientists via a € learn-by-doing' approach. We identified factors that either supported or hindered their development and, drawing on this information, determined key lessons for future programmes with similar objectives. Methods A longitudinal qualitative study encompassing focus group discussions and semistructured interviews conducted with the cohort of African postdoctoral fellows, programme leadership, supervisory and research support staff (N=28). Data analysis was informed by a general inductive approach. Results Numerous supportive and hindering factors were identified. Supportive factors were primarily structural or attitudinal in nature, whereas hindering factors were primarily operational or contextual. None of the supporting or hindering factors were specific to vectorborne disease research. Four key lessons for future programme implementation emerged, including: the value in exposing postdoctoral fellows to a diverse work-mix and training-mix to improve understanding of the broad skillset needed for scientific career advancement; recognising and managing the potentially competing interests of different partnership members to ensure everyone benefits from participation; ensuring equity of opportunity and rewarding engagement; and ensuring flexibility in support provision. Conclusion Our study highlights numerous factors that may be readily incorporated into early career researcher capacity strengthening initiatives based on a learn-by-doing approach. Many of these factors are supported by a growing weight of evidence and would be appropriate to research capacity strengthening programmes both within and outside of a vectorborne disease context. | |||
Palwende Romuald Boua, Toussaint Rouamba, Estelle Bambara, Saidou Kaboré, Ella W. R. Compaore, Boureima Ouedraogo, Halidou Tinto, Marie Louise Newell, Kate Ward, Hermann Sorgho Undernutrition in children aged 0-59 months by region and over time: secondary analysis of the Burkina Faso 2012-2018 National Nutrition Surveys Journal Article In: BMJ open, vol. 13, iss. 9, 2023, ISSN: 2044-6055. Abstract | BibTeX | Tags: {Author(firstnames='Adélaïde', Author(firstnames='Aminata', Author(firstnames='Caroline', Author(firstnames='Cornelius', Author(firstnames='Daniella', Author(firstnames='Doreen', Author(firstnames='Edith', Author(firstnames='Engelbert', Author(firstnames='Esmond W', Author(firstnames='James', Author(firstnames='Josephine', Author(firstnames='Kadija', Author(firstnames='Karim', Author(firstnames='Keith', Author(firstnames='Marie-Louise', Author(firstnames='Mark', Author(firstnames='Mary', Author(firstnames='Maxwell', Author(firstnames='Michael', Author(firstnames='Paul', Author(firstnames='Paula', Author(firstnames='Polly', Author(firstnames='Samuel', Author(firstnames='Sarah', Author(firstnames='Shane A', Author(firstnames='Stephanie', Author(firstnames='Winfred', Burkina Faso / epidemiology, Cachexia, Child, CollabAuthor(name='INPreP Study Group', Growth Disorders / epidemiology, Humans, Malnutrition* / epidemiology, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Nutrition Surveys, Palwende Romuald Boua, PMC10496659, Preschool, PubMed Abstract, Research Support, Thinness* / epidemiology, Toussaint Rouamba | Links: @article{Boua2023, The global burden of undernutrition remains high, responsible for significant under-five mortality in resource-limited settings. Numerous sustainable development goals (SDGs) are linked to nutrition, and nationally representative nutrition surveillance is a key activity to track progress towards SDGs and guide efficient programmes. Objectives The aim of this study is to look at spatial and temporal trends in undernutrition in children under 5 years age in Burkina Faso. Setting We used data from annual National Nutrition Surveys using Standardised Monitoring and Assessment of Relief and Transitions methodology (anthropometry, morbidity) over 7 years (2012-2018) in Burkina Faso. Participants Children of under 5 years from households selected through systemic sampling at countrywide level. Main outcome measures Prevalence of stunting (height-for-age z-score, <-2), underweight (weight-for-age z-score, <-2) and wasting (weight-for-height z-score, <-2) at regional and national. We used general linear mixed models, adjusted by age, survey year, sex, presence of fever and/or diarrhoea, and poverty index to quantify the risk of undernutrition over time and by region of residence. Results Between 2012 and 2018, decreases were observed overall in the prevalence of growth retardation (stunting) decreased from 33.0% (95% CI 32.3 to 33.8) in 2012 to 26.7% (95% CI 26.2 to 27.3) in 2018. Underweight reduced from 24.4% (95% CI 23.7 to 25.1) to 18.7% (95% CI 18.2 to 19.2) for the same period and wasting decreased from 10.8% (95% CI 10.3 to 11.3) in 2012 to 8.4% (95% CI 8.1 to 8.8) in 2018. However, there was substantial variation across the country, with increased risk of undernutrition in the regions of Sahel, East and Cascades primarily. High-risk regions were characterised by a lower poverty index and limited access to healthcare services. Conclusions Our findings could inform national policymakers in refining and optimising resource allocation based on the identification of high-risk areas. | |||
Adelaïde Compaore, Deborah Ekusai-Sebatta, David Kaawa-Mafigiri, Vida Kukula, Selase Odopey, James Kapisi, Heidi Hopkins, François Kiemde, Halidou Tinto, Rita Baiden, Piero Olliaro, Juvenal Nkeramahame, Sabine Dittrich, Philip Horgan Viewpoint: Antimicrobial Resistance Diagnostics Use Accelerator: Qualitative Research on Adherence to Prescriptions Journal Article In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 77, iss. Suppl 2, pp. S206-S210, 2023, ISSN: 1537-6591. Abstract | BibTeX | Tags: {Adélaïde Compaoré, Anti-Bacterial Agents* / therapeutic use, Author(firstnames='Adélaïde', Author(firstnames='Alexander', Author(firstnames='Asadu', Author(firstnames='Daniel', Author(firstnames='David', Author(firstnames='Deborah', Author(firstnames='Elizeus', Author(firstnames='François', Author(firstnames='Freddy Eric', Author(firstnames='Halidou', Author(firstnames='Heidi', Author(firstnames='James', Author(firstnames='Rita', Author(firstnames='Vida', Bacterial*, Clinical Trial, CollabAuthor(name='ADIP study group', Communication, Deborah Ekusai-Sebatta, Drug Resistance, Humans, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, PMC10368411, Prescriptions, PubMed Abstract, Qualitative research, Research Support | Links: @article{Compaore2023, In this Viewpoint, the authors explore the determinants of patients' prescription adherence behaviors as part of FIND's Advancing Access to Diagnostic Innovation essential for Universal Health Coverage and AMR Prevention (ADIP) trials (ClinicalTrials.gov identifier: NCT04081051). Research findings from Burkina Faso, Ghana, and Uganda show that basic knowledge and understanding of prescription instructions are essential for adherence and can be improved through better communication. However, there are a range of other factors that influence adherence, some of which can be influenced through tailored communication messages from healthcare workers. These messages may contribute to changes in adherence behavior but may require other reinforcing interventions to be effective. Finally, there are some drivers of nonadherence centered around costs and time pressure that require other forms of intervention. | |||
Piero Olliaro, Juvenal Nkeramahame, Philip Horgan, Halidou Tinto, François Kiemde, Rita Baiden, Alexander Adjei, James Kapisi, Heidi Hopkins, Olawale Salami, Catrin E. Moore, Sabine Dittrich, Stephan Weber, Stefano Ongarello Synthesis and Meta-analysis of 3 Randomized Trials Conducted in Burkina Faso, Ghana, and Uganda Comparing the Effects of Point-of-Care Tests and Diagnostic Algorithms Versus Routine Care on Antibiotic Prescriptions and Clinical Outcomes in Ambulatory Patients <18 Years of Age With Acute Febrile Illness Journal Article In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 77, iss. Suppl 2, pp. S199-S205, 2023, ISSN: 1537-6591. BibTeX | Tags: {Algorithms, Anti-Bacterial Agents* / therapeutic use, Author(firstnames='Adélaïde', Author(firstnames='Alexander', Author(firstnames='Asadu', Author(firstnames='Daniel', Author(firstnames='David', Author(firstnames='Deborah', Author(firstnames='Elizeus', Author(firstnames='François', Author(firstnames='Freddy Eric', Author(firstnames='Halidou', Author(firstnames='Heidi', Author(firstnames='James', Author(firstnames='Rita', Author(firstnames='Vida', Burkina Faso, CollabAuthor(name='ADIP study group', Diagnostic Tests, Ghana, Humans, Juvenal Nkeramahame, MEDLINE, Meta-Analysis, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Piero Olliaro, PMC10368413, Point-of-Care Testing*, Prescriptions, PubMed Abstract, Randomized Controlled Trials as Topic, Research Support | Links: @article{Olliaro2023, | |||
Francois Kiemde, Daniel Valia, Berenger Kabore, Toussaint Rouamba, Alima Nadine Kone, Seydou Sawadogo, Adelaide Compaore, Olawale Salami, Philip Horgan, Catrin E. Moore, Sabine Dittrich, Juvenal Nkeramahame, Piero Olliaro, Halidou Tinto A Randomized Trial to Assess the Impact of a Package of Diagnostic Tools and Diagnostic Algorithm on Antibiotic Prescriptions for the Management of Febrile Illnesses Among Children and Adolescents in Primary Health Facilities in Burkina Faso Journal Article In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 77, iss. Suppl 2, pp. S134-S144, 2023, ISSN: 1537-6591. Abstract | BibTeX | Tags: Adolescent, Algorithms, Anti-Bacterial Agents* / therapeutic use, Burkina Faso, Child, Daniel Valia, doi:10.1093/cid/ciad331, Francois Kiemde, Halidou Tinto, Health Facilities, Humans, Infant, Malaria* / drug therapy, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, PMC10368409, pmid:37490742, Preschool, Prescriptions, PubMed Abstract, Randomized controlled trial, Research Support | Links: @article{Kiemde2023, Background: Low- and middle-income countries face significant challenges in differentiating bacterial from viral causes of febrile illnesses, leading to inappropriate use of antibiotics. This trial aimed to evaluate the impact of an intervention package comprising diagnostic tests, a diagnostic algorithm, and a training-and-communication package on antibiotic prescriptions and clinical outcomes. Methods: Patients aged 6 months to 18 years with fever or history of fever within the past 7 days with no focus, or a suspected respiratory tract infection, arriving at 2 health facilities were randomized to either the intervention package or standard practice. The primary outcomes were the proportions of patients who recovered at day 7 (D7) and patients prescribed antibiotics at day 0. Results: Of 1718 patients randomized, 1681 (97.8%; intervention: 844; control: 837) completed follow-up: 99.5% recovered at D7 in the intervention arm versus 100% in standard practice (P =. 135). Antibiotics were prescribed to 40.6% of patients in the intervention group versus 57.5% in the control arm (risk ratio: 29.3%; 95% CI: 21.8-36.0%; risk difference [RD]: -16.8%; 95% CI: -21.7% to -12.0%; P <. 001), which translates to 1 additional antibiotic prescription saved every 6 (95% CI: 5-8) consultations. This reduction was significant regardless of test results for malaria, but was greater in patients without malaria (RD: -46.0%; -54.7% to -37.4%; P <. 001), those with a respiratory diagnosis (RD: -38.2%; -43.8% to -32.6%; P <. 001), and in children 6-59 months old (RD: -20.4%; -26.0% to -14.9%; P <. 001). Except for the period July-September, the reduction was consistent across the other quarters (P <. 001). Conclusions: The implementation of the package can reduce inappropriate antibiotic prescription without compromising clinical outcomes. Clinical Trials Registration: clinicaltrials.gov; NCT04081051. | |||
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. | |||
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. | |||
Daniel Valia, Juste Stéphane Kouanda, Brecht Ingelbeen, Karim Derra, Bérenger Kaboré, François Kiemdé, Toussaint Rouamba, Eli Rouamba, Franck Sovi Hien, Linda Campbell, Marie Meudec, Annie Robert, Halidou Tinto, Marianne A. B. Sande, Hector Rodriguez Villalobos Healthcare seeking outside healthcare facilities and antibiotic dispensing patterns in rural Burkina Faso: A mixed methods study Journal Article In: Tropical medicine & international health : TM & IH, vol. 28, iss. 5, pp. 391-400, 2023, ISSN: 1365-3156. Abstract | BibTeX | Tags: Anti-Bacterial Agents* / therapeutic use, Attitude of Health Personnel, Burkina Faso, Child, Daniel Valia, doi:10.1111/tmi.13868, Hector Rodriguez Villalobos, Humans, Juste Stéphane Kouanda, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Patient Acceptance of Health Care*, pmid:36871194, Preschool, PubMed Abstract, Research Support, Self Medication | Links: @article{Valia2023, Objective: Optimising antibiotic use is important to limit increasing antibiotic resistance. In rural Burkina Faso, over-the-counter dispensing of antibiotics in community pharmacies and non-licensed medicine retail outlets facilitates self-medication. We investigated its extent, reasons and dispensing patterns. Methods: In an exploratory mixed-method design conducted between October 2020 and December 2021, this study first explored illness perceptions, the range of healthcare providers in communities, antibiotics knowledge and reasons for seeking healthcare outside healthcare facilities. Second, frequencies of illness and healthcare utilisation in the last 3 months were quantitatively measured. Results: Participants distinguished between natural and magico-religious illnesses, according to origins. For illnesses considered to be ‘natural’, healthcare was mainly sought at healthcare facilities, private pharmacies and informal drug outlets. For illnesses considered as magico-religious, traditional healers were mainly visited. Antibiotics were perceived in the community as medicines similar to painkillers. Healthcare-seeking outside healthcare facilities was reported by 660/1973 (33.5%) participants reporting symptoms, including 315 (47.7%) to informal vendors. Healthcare seeking outside facilities was less common for 0–4-year-olds (58/534, 10.9% vs. 379/850, 44.1% for ≥5-year-olds) and decreased with improving socio-economic status (108/237, 45.6% in the lowest quintile; 96/418, 23.0% in the highest). Reported reasons included financial limitation, and also proximity to informal drug vendors, long waiting times at healthcare facilities, and health professionals' non-empathetic attitudes towards their patients. Conclusion: This study highlights the need to facilitate and promote access to healthcare facilities through universal health insurance and patient-centred care including reducing patients' waiting time. Furthermore, community-level antibiotic stewardship programmes should include community pharmacies and informal vendors. | |||
Serge Ouoba, Ko Ko, Moussa Lingani, Shintaro Nagashima, Alice N. Guingané, E. Bunthen, Md Razeen Ashraf Hussain, Aya Sugiyama, Tomoyuki Akita, Masayuki Ohisa, Moussa Abdel Sanou, Ousmane Traore, Job Wilfried Nassa, Maimouna Sanou, Kazuaki Takahashi, Halidou Tinto, Junko Tanaka Intermediate hepatitis B virus infection prevalence among 1622 pregnant women in rural Burkina Faso and implications for mother-to-child transmission Journal Article In: Scientific reports, vol. 13, iss. 1, 2023, ISSN: 2045-2322. Abstract | BibTeX | Tags: Burkina Faso / epidemiology, Child, DNA, doi:10.1038/s41598-023-32766-3, Female, Hepatitis B e Antigens, Hepatitis B Surface Antigens, Hepatitis B virus / genetics, Hepatitis B* / diagnosis, Humans, Infectious Disease Transmission, Infectious* / epidemiology, Junko Tanaka, Ko Ko, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, PMC10103033, pmid:37059812, Pregnancy, Pregnancy Complications, Pregnant Women, Prevalence, PubMed Abstract, Research Support, Serge Ouoba, Vertical / prevention & control, Viral / genetics | Links: @article{Ouoba2023, In highly endemic countries for hepatitis B virus (HBV) infection, childhood infection, including mother-to-child transmission (MTCT), represents the primary transmission route. High maternal DNA level (viral load ≥ 200,000 IU/mL) is a significant factor for MTCT. We investigated the prevalence of HBsAg, HBeAg, and high HBV DNA among pregnant women in three hospitals in Burkina Faso and assessed the performance of HBeAg to predict high viral load. Consenting pregnant women were interviewed on their sociodemographic characteristics and tested for HBsAg by a rapid diagnostic test, and dried blood spot (DBS) samples were collected for laboratory analyses. Of the 1622 participants, HBsAg prevalence was 6.5% (95% CI, 5.4–7.8%). Among 102 HBsAg-positive pregnant women in DBS samples, HBeAg was positive in 22.6% (95% CI, 14.9–31.9%), and viral load was quantified in 94 cases, with 19.1% having HBV DNA ≥ 200,000 IU/mL. HBV genotypes were identified in 63 samples and predominant genotypes were E (58.7%) and A (36.5%). The sensitivity of HBeAg by using DBS samples to identify high viral load in the 94 cases was 55.6%, and the specificity was 86.8%. These findings highlight the need to implement routine HBV screening and effective MTCT risk assessment for all pregnant women in Burkina Faso to enable early interventions that can effectively reduce MTCT. | |||
Lisa K. Micklesfield, Richard Munthali, Godfred Agongo, Gershim Asiki, Palwende Boua, Solomon S. R. Choma, Nigel J. Crowther, June Fabian, Francesc Xavier Gómez-Olivé, Chodziwadziwa Kabudula, Eric Maimela, Shukri F. Mohamed, Engelbert A. Nonterah, Frederick J. Raal, Hermann Sorgho, Furahini D. Tluway, Alisha N. Wade, Shane A. Norris, Michele Ramsay Identifying the prevalence and correlates of multimorbidity in middle-aged men and women: a cross-sectional population-based study in four African countries Journal Article In: BMJ open, vol. 13, iss. 3, 2023, ISSN: 2044-6055. Abstract | BibTeX | Tags: {Adult, Africa South of the Sahara / epidemiology, CollabAuthor(name='as members of AWI-Gen and the H3Africa Consortium', Cross-Sectional Studies, Dyslipidemias* / epidemiology, Extramural, Female, HIV Infections*, Humans, Hypertension* / epidemiology, Lisa K Micklesfield, Male, MEDLINE, Middle Aged, Multimorbidity, N.I.H., National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, PMC10016250, Prevalence, PubMed Abstract, Research Support, Richard Munthali, Risk Factors, Sex Factors | Links: @article{Micklesfield2023, Objectives To determine the prevalence of multimorbidity, to identify which chronic conditions cluster together and to identify factors associated with a greater risk for multimorbidity in sub-Saharan Africa (SSA). Design Cross-sectional, multicentre, population-based study. Setting Six urban and rural communities in four sub-Saharan African countries. Participants Men (n=4808) and women (n=5892) between the ages of 40 and 60 years from the AWI-Gen study. Measures Sociodemographic and anthropometric data, and multimorbidity as defined by the presence of two or more of the following conditions: HIV infection, cardiovascular disease, chronic kidney disease, asthma, diabetes, dyslipidaemia, hypertension. Results Multimorbidity prevalence was higher in women compared with men (47.2% vs 35%), and higher in South African men and women compared with their East and West African counterparts. The most common disease combination at all sites was dyslipidaemia and hypertension, with this combination being more prevalent in South African women than any single disease (25% vs 21.6%). Age and body mass index were associated with a higher risk of multimorbidity in men and women; however, lifestyle correlates such as smoking and physical activity were different between the sexes. Conclusions The high prevalence of multimorbidity in middle-aged adults in SSA is of concern, with women currently at higher risk. This prevalence is expected to increase in men, as well as in the East and West African region with the ongoing epidemiological transition. Identifying common disease clusters and correlates of multimorbidity is critical to providing effective interventions. | |||
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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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