Social and environmental malaria risk factors in urban areas of Ouagadougou, Burkina Faso

<p>Abstract</p> <p>Background</p> <p>Despite low endemicity, malaria remains a major health problem in urban areas where a high proportion of fevers are presumptively treated using anti-malarial drugs. Low acquired malaria immunity, behaviour of city-dwellers, access to health care and preventive interventions, and heterogenic suitability of urban ecosystems for malaria transmission contribute to the complexity of the malaria epidemiology in urban areas.</p> <p>Methods</p> <p>The study was designed to identify the determinants of malaria transmission estimated by the prevalence of anti-circumsporozoite (CSP) antibodies, the prevalence and density of <it>Plasmodium falciparum </it>infection, and the prevalence of malarial disease in areas of Ouagadougou, Burkina-Faso. Thick blood smears, dried blood spots and clinical status have been collected from 3,354 randomly chosen children aged 6 months to 12 years using two cross-sectional surveys (during the dry and rainy seasons) in eight areas from four ecological strata defined according to building density and land tenure (regular versus irregular). Demographic characteristics, socio-economic information, and sanitary and environmental data concerning the children or their households were simultaneously collected. Dependent variables were analysed using mixed multivariable models with random effects, taking into account the clustering of participants within compounds and areas.</p> <p>Results</p> <p>Overall prevalences of CSP-antibodies and <it>P. falciparum </it>infections were 7.7% and 16.6% during the dry season, and 12.4% and 26.1% during the rainy season, respectively, with significant differences according to ecological strata. Malaria risk was significantly higher among children who i) lived in households with lower economic or education levels, iii) near the hydrographic network, iv) in sparsely built-up areas, v) in irregularly built areas, vi) who did not use a bed net, vii) were sampled during the rainy season or ii) had traveled outside of Ouagadougou.</p> <p>Conclusion</p> <p>Malaria control should be focused in areas which are irregularly or sparsely built-up or near the hydrographic network. Furthermore, urban children would benefit from preventive interventions (e.g. anti-vectorial devices or chemoprophylaxis) aimed at reducing malaria risk during and after travel in rural areas.</p

Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial

BACKGROUND: Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at 12 months following administration of a booster vaccination. METHODS: This double-blind phase 1/2b randomised controlled trial was done in children aged 5-17 months in Nanoro, Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either 5 μg R21/25 μg Matrix-M, 5 μg R21/50 μg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity or receipt of other investigational products. A random allocation list was generated by an independent statistician by use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster vaccination. The population in which the efficacy analyses were done comprised all participants who received the primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of additional booster vaccine doses and longer-term safety. FINDINGS: Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 μg R21 adjuvanted with 25 μg Matrix-M, 137 received 5 μg R21 adjuvanted with 50 μg Matrix-M, and 140 received the control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in the high adjuvant dose (50 μg) group, similar to previous findings at 1 year after the primary series of vaccinations. Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman's ρ -0·32 [95% CI -0·45 to -0·19]; p=0·0001) and second year of follow-up (-0·20 [-0·34 to -0·06]; p=0·02). INTERPRETATION: A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these participants and the value of further booster vaccinations. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR Oxford Biomedical Research Centre. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial.

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 primary series of vaccinations after a fourth dose administered 1 year later. INTERPRETATION: R21/MM appears safe and very immunogenic in African children, and shows promising high-level efficacy. FUNDING: The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre

Household costs and time to treatment for children with severe febrile illness in rural Burkina Faso: the role of rectal artesunate

UNICEF/UNDP/World Bank/WHO Special Programme for Research & Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland [Project ID number: Burkina Faso: A80553

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Impact of a community-based intervention on Aedes aegypti and its spatial distribution in Ouagadougou, Burkina Faso

International audienceBackground: Several studies highlighted the impact of community-based interventions whose purpose was to reduce the vectors' breeding sites. These strategies are particularly interesting in low-and-middle-income countries which may find it difficult to sustainably assume the cost of insecticide-based interventions. In this case study we determine the spatial distribution of a community-based intervention for dengue vector control using different entomological indices. The objective was to evaluate locally where the intervention was most effective, using spatial analysis methods that are too often neglected in impact assessments.Methods: Two neighbourhoods, Tampouy and Juvenat in Ouagadougou, Burkina Faso, were chosen among five after a survey was conducted, as part of an assessment related to the burden of dengue. As part of the community-based intervention conducted in Tampouy between August and early October 2016, an entomological survey was implemented in two phases. The first phase consisted of a baseline entomological characterization of potential breeding sites in the neighbourhood of Tampouy as well as in Juvenat, the control area. This phase was conducted in October 2015 at the end of the rainy season. The mosquito breeding sites were screened in randomly selected houses: 206 in Tampouy and 203 in Juvenat. A second phase took place after the intervention, in October 2016. The mosquito breeding sites were investigated in the same yards as during the baseline phase. We performed several entomological analyses to measure site productivity as well as before and after analysis using multilevel linear regression. We used Local Indicators of Spatial Association (LISAs) to analyse spatial concentrations of larvae.Results: After the intervention, it is noted that LISAs at Tampouy reveal few aggregates of all types and the suppression of those existing before the intervention. The analysis therefore reveals that the intervention made it possible to reduce the number of concentration areas of high and low values of pupae.Conclusions: The contribution of spatial methods for assessing community-based intervention are relevant for monitoring at local levels as a complement to epidemiological analyses conducted within neighbourhoods. They are useful, therefore, not only for assessment but also for establishing interventions. This study shows that spatial analyses also have their place in population health intervention research

Socio-spatial disparities of obesity among adults in the urban setting of Ouagadougou, Burkina Faso

Objectives: To document the prevalence and the socio-spatial variations of obesity and to identify individual and household characteristics, lifestyles and dietary practices contributing to obesity and its socio-spatial distribution. Design: Population-based cross-sectional survey. We selected 1570 households from four strata characterised as unstructured and low building-density (ULBD), unstructured and high building-density (UHBD), structured and low building-density (SLBD) and structured and high building-density (SHBD) areas. Structured areas are those that were allotted by the township authority (cadastral services), with public services; unstructured areas refer to those developed with no cadastral organisation. Setting: Ouagadougou, the capital city of Burkina Faso. Subjects: BMI was calculated in 2022 adults aged 35 years and above who were classified as obese when their BMI was >= 30 kg/m(2). Obesity was investigated in relation to household and individual characteristics, lifestyles and dietary practices; adjusted odds ratios with 95% confidence intervals were derived from a logistic regression model. Results: The overall prevalence of obesity was 14.7% (males 5.5% and females 21.9%). Age, gender, household equipment index, usual transport with motor vehicles and micronutrient-rich food consumption were associated with obesity. After adjustment for these factors, obesity remained associated with the area of residence: residents from SHBD areas were more likely to be obese than those from ULBD areas (OR =1.41; 95% CI 2.59, 4.76). Conclusions: Obesity in Ouagadougou is a preoccupant problem that calls for more consideration. Thorough investigation is needed to assess the environmental factors that contribute to the socio-spatial disparity of obesity