Publications

@article{Datoo2024,

title = {Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial},

author = {Mehreen S. Datoo and Alassane Dicko and Halidou Tinto and Jean Bosco Ou\'{e}draogo and Mainga Hamaluba and Ally Olotu and Emma Beaumont and Fernando Ramos Lopez and Hamtandi Magloire Natama and Sophie Weston and Mwajuma Chemba and Yves Daniel Compaore and Djibrilla Issiaka and Diallo Salou and Athanase M. Some and Sharon Omenda and Alison Lawrie and Philip Bejon and Harish Rao and Daniel Chandramohan and Rachel Roberts and Sandesh Bharati and Lisa Stockdale and Sunil Gairola and Brian M. Greenwood and Katie J. Ewer and John Bradley and Prasad S. Kulkarni and Umesh Shaligram and Adrian V. S. Hill and Almahamoudou Mahamar and Koualy Sanogo and Youssoufa Sidibe and Kalifa Diarra and Mamoudou Samassekou and Oumar Attaher and Amadou Tapily and Makonon Diallo and Oumar Mohamed Dicko and Mahamadou Kaya and Seydina Oumar Maguiraga and Yaya Sankare and Hama Yalcouye and Soumaila Diarra and Sidi Mohamed Niambele and Ismaila Thera and Issaka Sagara and Mala Sylla and Amagana Dolo and Nsajigwa Misidai and Sylvester Simando and Hania Msami and Omary Juma and Nicolaus Gutapaka and Rose Paul and Sarah Mswata and Ibrahim Sasamalo and Kasmir Johaness and Mwantumu Sultan and Annastazia Alexander and Isaac Kimaro and Kauye Lwanga and Mwajuma Mtungwe and Kassim Khamis and Lighton Rugarabam and Wilmina Kalinga and Mohammed Mohammed and Janeth Kamange and Jubilate Msangi and Batuli Mwaijande and Ivanny Mtaka and Matilda Mhapa and Tarsis Mlaganile and Thabit Mbaga and Rakiswende Serge Yerbanga and Wendkouni Samtouma and Abdoul Aziz Sienou and Zachari Kabre and Wendinpui Jedida Muriel Ouedraogo and G. Armel Bienvenu Yarbanga and Issaka Zongo and Hamade Savadogo and Joseph Sanon and Judicael Compaore and Idrissa Kere and Ferdinand Lionel Yoni and Tewende Martine Sanre and Seydou Bienvenu Ouattara and Samuel Provstgaard-Morys and Danielle Woods and Robert W. Snow and Nyaguara Amek and Caroline J. Ngetsa and Lynette Isabella Ochola-Oyier and Jennifer Musyoki and Marianne Munene and Noni Mumba and Uche Jane Adetifa and Charles Mwangi Muiruri and Jimmy Shangala Mwawaka and Mwatasa Hussein Mwaganyuma and Martha Njeri Ndichu and Joseph Ochieng Weya and Kelvin Njogu and Jane Grant and Jayne Webster and Anand Lakhkar and N. F\'{e}lix Andr\'{e} Ido and Ousmane Traore and Marc Christian Tahita and Massa Achille Bonko and Toussaint Rouamba and D. Florence Ouedraogo and Rachidatou Soma and Aida Millogo and Edouard Ouedraogo and Faizatou Sorgho and Fab\'{e} Konate and Innocent Valea},

url = {https://pubmed.ncbi.nlm.nih.gov/38310910/},

doi = {10.1016/S0140-6736(23)02511-4},

issn = {1474-547X},

year  = {2024},

date = {2024-01-01},

journal = {Lancet (London, England)},

volume = {403},

issue = {10426},

pages = {533-544},

publisher = {Lancet},

abstract = {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\textendash36 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\textendash79; p\<0·0001) at the seasonal sites and 68% (61\textendash74; 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\textendash78; p\<0·0001) at the seasonal sites and 67% (59\textendash73; 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\textendash974) cases per 1000 children-years at seasonal sites and 296 (231\textendash362) 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\textendash17 month age group compared with 18\textendash36 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\textendash84]; p\<0·001) and standard (75% [65\textendash83]; 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.},

keywords = {{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*},

pubstate = {published},

tppubtype = {article}

}

@article{Skrip2020-fq,

title = {Clinical management and mortality among COVID-19 cases in  sub-Saharan Africa: A retrospective study from Burkina Faso and  simulated case analysis},

author = {Laura Skrip and Karim Derra and Mikaila Kabor\'{e} and Navideh Noori and Adama Gansan\'{e} and Innocent Val\'{e}a and Halidou Tinto and Bicaba W Brice and Mollie Van Gordon and Brittany Hagedorn and Herv\'{e} Hien and Benjamin M Althouse and Edward A Wenger and Andr\'{e} Lin Ou\'{e}draogo},

doi = {10.1016/j.ijid.2020.09.1432},

issn = {1878-3511 1201-9712},

year  = {2020},

date = {2020-12-01},

urldate = {2020-12-01},

journal = {Int. J. Infect. Dis.},

volume = {101},

pages = {194--200},

publisher = {Elsevier BV},

abstract = {BACKGROUND: Absolute numbers of COVID-19 cases and deaths 

 reported to date in the sub-Saharan Africa (SSA) region have 

 been significantly lower than those across the Americas, Asia 

 and Europe. As a result, there has been limited information 

 about the demographic and clinical characteristics of deceased 

 cases in the region, as well as the impacts of different case 

 management strategies. METHODS: Data from deceased cases 

 reported across SSA through 10 May 2020 and from hospitalized 

 cases in Burkina Faso through 15 April 2020 were analyzed. 

 Demographic, epidemiological and clinical information on 

 deceased cases in SSA was derived through a line-list of 

 publicly available information and, for cases in Burkina Faso, 

 from aggregate records at the Centre Hospitalier Universitaire 

 de Tengandogo in Ouagadougou. A synthetic case population was 

 probabilistically derived using distributions of age, sex and 

 underlying conditions from populations of West African countries 

 to assess individual risk factors and treatment effect sizes. 

 Logistic regression analysis was conducted to evaluate the 

 adjusted odds of survival for patients receiving oxygen therapy 

 or convalescent plasma, based on therapeutic effectiveness 

 observed for other respiratory illnesses. RESULTS: Across SSA, 

 deceased cases for which demographic data were available were 

 predominantly male (63/103, 61.2%) and aged \>50 years (59/75, 

 78.7%). In Burkina Faso, specifically, the majority of deceased 

 cases either did not seek care at all or were hospitalized for a 

 single day (59.4%, 19/32). Hypertension and diabetes were often 

 reported as underlying conditions. After adjustment for sex, age 

 and underlying conditions in the synthetic case population, the 

 odds of mortality for cases not receiving oxygen therapy were 

 significantly higher than for those receiving oxygen, such as 

 due to disruptions to standard care (OR 2.07; 95% CI 

 1.56-2.75). Cases receiving convalescent plasma had 50% reduced 

 odds of mortality than those who did not (95% CI 0.24-0.93). 

 CONCLUSIONS: Investment in sustainable production and 

 maintenance of supplies for oxygen therapy, along with messaging 

 around early and appropriate use for healthcare providers, 

 caregivers and patients could reduce COVID-19 deaths in SSA. 

 Further investigation into convalescent plasma is warranted 

 until data on its effectiveness specifically in treating 

 COVID-19 becomes available. The success of supportive or 

 curative clinical interventions will depend on earlier treatment 

 seeking, such that community engagement and risk communication 

 will be critical components of the response.},

note = {Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

PMID: 32987177 

PMCID: PMC7518969},

keywords = {Adolescent, Adult, Africa South of the Sahara, Aged, Antiviral Agents/administration \& dosage, Asia/epidemiology, Burkina Faso, Burkina Faso/epidemiology, Child, Clinical management of SARS-CoV-2 infection: convalescent plasma, COVID-19/drug therapy/epidemiology/mortality/therapy, Europe/epidemiology, Female, Health systems strengthening, Humans, Immunization, Infant, Male, Mortality, Oxygen therapy, Pandemics, Passive, Preschool, Retrospective Studies, SARS-CoV-2 infection, SARS-CoV-2/drug effects/physiology, sub-Saharan Africa, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@article{RTS2015,

title = {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},

author = {S Clinical Trials Partnership RTS},

url = {https://pubmed.ncbi.nlm.nih.gov/25913272/},

doi = {10.1016/S0140-6736(15)60721-8},

issn = {1474-547X},

year  = {2015},

date = {2015-01-01},

journal = {Lancet (London, England)},

volume = {386},

issue = {9988},

pages = {31-45},

publisher = {Lancet},

abstract = {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.},

keywords = {{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'},

pubstate = {published},

tppubtype = {article}

}