Background Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy.Methods In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 µg R21 plus 25 µg MM, group 2 received 5 µg R21 plus 50 µg MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724.Findings From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the pr...

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The Nanoro Health and Demographic Surveillance System (HDSS), located in the rural centre of Burkina Faso, was established in 2009 by the Clinical Research Unit of Nanoro with the aim of providing a core framework for clinical trials and also to support the Burkina Faso health authorities in generating epidemiological data that can contribute to the setup and assessment of health interventions. In the baseline of initial census, 54 781 individuals were recorded of whom 56.1% are female. After the initial census, vital events such as pregnancies, births, migrations and deaths have been monitored, and data on individuals and household characteristics are updated during regular 4-monthly household visits. The available data are categorized into demographic, cultural, socio-economic and health information, and are used for monitoring and evaluation of population development issues. As a young site, our objective has been to strengthen our skills and knowledge and share new scientific experiences with INDEPTH and HDSS sites in Burkina Faso. In addition, all data produced by the Nanoro HDSS will be made publicly available through the INDEPTH data sharing system.

Background With limited resources and spatio-temporal heterogeneity of malaria in developing countries, it is still difficult to assess the real impact of socioeconomic and environmental factors in order to set up targeted campaigns against malaria at an accurate scale. Our goal was to detect malaria hotspots in rural area and assess the extent to which household socioeconomic status and meteorological recordings may explain the occurrence and evolution of these hotspots. Methods Data on malaria cases from 2010 to 2014 and on socioeconomic and meteorological factors were acquired from four health facilities within the Nanoro demographic surveillance area. Statistical cross correlation was used to quantify the temporal association between weekly malaria incidence and meteorological factors. Local spatial autocorrelation analysis was performed and restricted to each transmission period using Kulldorff’s elliptic spatial scan statistic. Univariate and multivariable analysis were used to assess the principal socioeconomic and meteorological determinants of malaria hotspots using a Generalized Estimating Equation (GEE) approach. Results Rainfall and temperature were positively and significantly associated with malaria incidence, with a lag time of 9 and 14 weeks, respectively. Spatial analysis showed a spatial autocorrelation of malaria incidence and significant hotspots which was relatively stable throughout the study period. Furthermore, low socioeconomic status households were strongly associated with malaria hotspots (aOR = 1.21, 95% confidence interval: 1.03–1.40). Conclusion These fine-scale findings highlight a relatively stable spatio-temporal pattern of malaria risk and indicate that social and environmental factors play an important role in malaria incidence. Integrating data on these factors into existing malaria struggle tools would help in the development of sustainable bottleneck strategies adapted to the local context for malaria control. Electronic supplementary material The online version of this article (10.1186/s12889-019-6565-z) contains supplementary material, which is available to authorized users.