The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study.

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.

Transfer of Bisphenol A and Trace Metals from Plastic Packaging to Mineral Water in Ouagadougou, Burkina Faso.

The consumption of packaged water is growing rapidly in both urban and rural centres in Burkina Faso. Bisphenol A (BPA) and trace metals are among the compounds used in the manufacture of plastic packaging, and their presence in water can pose a health risk to consumers due to their alleged toxicity. Therefore, this study explores the transfer of these compounds from plastic packaging to mineral water in Sudano-Sahelian climatic conditions. Ten samples of packaged sachet water commercialised in Ouagadougou were studied. An absence of BPA in the borehole water used to produce packaged water has been shown. The transfer of BPA into mineral water increases with storage temperature. The BPA that appears in packaged water degrades over time. BPA concentrations ranged from 0 to 0.38 mg/L after two weeks of storage, 0 to 0.8 mg/L after four weeks of storage and 0 to 0.35 mg/L after 8 weeks of storage. Analysis of the trace metals showed steadily increasing concentrations from the second to the sixth weeks, with concentrations ranging from 0 to 9.7 µg/L for cadmium and from 0 to 0.13 mg/L for iron in the sachet water samples.

Clinical practice recommendations for nurse-administered intramuscular injections in mental health: A modified Delphi study.

AIM: To develop clinical practice recommendations for nurse-administered intramuscular injections in mental health. BACKGROUND: Intramuscular injection is the main route of long-acting injectable antipsychotics' administration that appear to improve the long-term prognosis of mental illness. Specific guidelines related to the nurse administration of intramuscular injections need to be updated and to explore not only the technical aspects of this procedure. DESIGN: A modified RAND/University of California Los Angeles (UCLA) appropriateness method Delphi study was conducted between October 2019 and September 2020. METHODS: A multidisciplinary steering committee conducted a literature review and developed a list of 96 recommendations. These recommendations were submitted in a two-round Delphi electronic survey to a panel of 49 experienced practicing nurses from five mental health hospitals in France. Each recommendation was rated for its appropriateness and applicability in clinical practice on a 9-point Likert scale. Consensus among nurses was evaluated. The steering committee discussed the results after each round and approved the final set of recommendations. RESULTS: A final set of 79 specific recommendations were accepted for their appropriateness and applicability in clinical practice. Recommendations were classified in five domains: legal and quality assurance aspects, nurse-patient relationship, hygiene, pharmacology, and injection technique. CONCLUSION: The established recommendations placed patients at the heart of the decisions concerning the intramuscular injection and underlined the need for specific training programs. Future research should focus on the integration of these recommendations in clinical practice, by both before-and-after studies and regular assessments of professional practices with relevant indicators. IMPACT: The recommendations developed for good nursing practices explored not only the technical aspects but integrated the nurse-patient relationship. These recommendations may impact usual practices of administration of long-acting injectable antipsychotics and most of them could be applied in many countries. NO PATIENT OR PUBLIC CONTRIBUTION: Due to the study design.

Intermediate hepatitis B virus infection prevalence among 1622 pregnant women in rural Burkina Faso and implications for mother-to-child transmission.

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.

Moving from assessments to implementation: promising practices for strengthening multisectoral antimicrobial resistance containment capacity.

BACKGROUND: Antimicrobial resistance (AMR) poses a global threat to human, animal, and environmental health. AMR is a technical area in the Global Health Security Agenda initiative which uses the Joint External Evaluation tool to evaluate national AMR containment capacity. This paper describes four promising practices for strengthening national antimicrobial resistance containment capacity based on the experiences of the US Agency for International Development's Medicines, Technologies, and Pharmaceutical Services Program work with 13 countries to implement their national action plans on AMR in the areas of multisectoral coordination, infection prevention and control, and antimicrobial stewardship. METHODS: We use the World Health Organization (WHO) Benchmarks on International Health Regulations Capacities (2019) to guide national, subnational, and facility actions that advance Joint External Evaluation capacity levels from 1 (no capacity) to 5 (sustainable capacity). Our technical approach is based on scoping visits, baseline Joint External Evaluation scores, benchmarks tool guidance, and country resources and priorities. RESULTS: We gleaned four promising practices to achieve AMR containment objectives: (1) implement appropriate actions using the WHO benchmarks tool, which prioritizes actions, making it easier for countries to incrementally increase their Joint External Evaluation capacity from level 1 to 5; (2) integrate AMR into national and global agendas. Ongoing agendas and programs at international, regional, and national levels provide opportunities to mainstream and interlink AMR containment efforts; (3) improve governance through multisectoral coordination on AMR. Strengthening multisectoral bodies' and their technical working groups' governance improved functioning, which led to better engagement with animal/agricultural sectors and a more coordinated COVID-19 pandemic response; and (4) mobilize and diversify funding for AMR containment. Long-term funding from diversified funding streams is vital for advancing and sustaining countries' Joint External Evaluation capacities. CONCLUSIONS: The Global Health Security Agenda work has provided practical support to countries to frame and conduct AMR containment actions in terms of pandemic preparedness and health security. The WHO benchmarks tool that Global Health Security Agenda uses serves as a standardized organizing framework to prioritize capacity-appropriate AMR containment actions and transfer skills to help operationalize national action plans on AMR.

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.

[Epidemiological and tomodensitometric aspects of post-traumatic maxillofacial fractures in Mopti, Mali]. / Profil épidémiologique et tomodensitométrique des fractures maxillo-faciales post-traumatiques à Mopti au Mali.

Introduction: facial injuries are a public health problem, both physically and psychologically, characterized by a variety of injuries and sometimes by severe esthetic or functional sequelae. The purpose of this study was to describe the epidemiological and tomodensitometric aspects of maxillofacial fractures in Mopti. Methods: we conducted a cross-sectional and descriptive study in the Department of Radiology of the Mopti Hospital from January 2019 to December 2019. All patients who had undergone maxillofacial CT scan for a trauma with fracture confirmed by CT scan during this period were included. The variables analyzed were age, sex, etiology and the types of fractures observed on CT scan. Data recording and analysis were carried out using SPSS version 20 and Excel 2013. Results: of a total of 120 patients, the mean age was 26.43 years with a standard deviation of 14.547. Men predominated (75%; n= 90). Road accidents were the leading cause of fractures (50%; n = 60). Occlusofacial fractures accounted for 38.33% (n= 46). Lefort II was the most common fracture (22.50%; n= 27). Conclusion: this study allowed us to identify the population groups most affected by maxillofacial fractures in the Mopti region: adolescents and young adults. Tomodensitometric results were dominated by occlusofacial fractures, in particular Lefort type II fractures.

Plasmidome analysis of a hospital effluent biofilm: Status of antibiotic resistance.

Plasmids are widely involved in the dissemination of characteristics within bacterial communities. Their genomic content can be assessed by high-throughput sequencing of the whole plasmid fraction of an environment, the plasmidome. In this study, we analyzed the plasmidome of a biofilm formed in the effluents of the teaching hospital of Clermont-Ferrand (France). Our analysis discovered >350 new complete plasmids, with a length ranging from 1219 to 40,193 bp. Forty-two plasmid incompatibility (Inc) groups were found among all the plasmid contigs. Ten large plasmids, described here in detail, were reconstructed from plasmid contigs, seven of which carried antibiotic resistance genes. Four plasmids potentially confer resistance to numerous families of antibiotics, including carbapenems, aminoglycosides, colistin, and chloramphenicol. Most of these plasmids were affiliated to Proteobacteria, a phylum of Gram-negative bacteria. This study therefore illustrates the composition of an environmental mixed biofilm in terms of plasmids and antibiotic resistance genes.

[Role of helical computed tomography in petrous bone trauma: about 12 cases at the University Hospital Ibn Rochd of Casablanca]. / Place du scanner hélicoïdal dans le traumatisme du rocher: à propos de 12 cas au Centre Hospitalier Universitaire Ibn Rochd de Casablanca.

Temporal bone injuries occur in 14-22% of skull fractures occurring due to head trauma. The purpose of this study is to understand the role of helical computed tomography in petrous bone trauma and to show the different types of fractures and the associated lesions. We conducted a retrospective study of 12 patients with petrous bone trauma (including 10 men and 2 women) over a period of 14 months. The average age of patients was 30, ranging from 18 to 42 years. High-resolution multi-slice computed tomography of petrous bone without contrast agent injection, with infra-millimeter slices thickness of 0.6mm every 0.3mm, allowed to detect the following fractures: 8 extralabyrinthine transverse fractures; 1 extralabyrinthine longitudinal fracture; 2 translabyrinthine fractures and 1 oblique fracture. The associated lesions were dominated by: 5 ossicular lesions; 4 cases of temporal bone involvement and 2 cases of geniculate ganglion involvement. High-resolution computed tomography can confirm the presence of a fracture, show the orientation of the fracture line and specify the different structures affected. It can be performed for emergency assessment or after a period of observation.

Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection.

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.

Households' basic needs satisfaction during the Coronavirus disease 19 (COVID-19) pandemic in Burkina Faso.

The Coronavirus disease 19 (COVID-19) pandemic has profoundly affected economic and health systems around the world. This paper aims to assess household access to basic foods and health care and food security attainment during the COVID-19 pandemic in Burkina Faso. We use the COVID-19 High-Frequency Phone Survey 2020 panel data supported by the World Bank and conducted by Institut National de la Statistique et de la Démographie (INSD). The pooled multinomial logistic, the panel logistic, and the panel ordered logistic regressions are used to analyse the access to basic foods, the access to health care and the food security of the households, respectively. The results show that during COVID-19, female-headed households, poor households and farm households remain the most vulnerable in terms of access to basic foods, health services and food insecurity. Furthermore, the results indicate that households living outside the capital, particularly in the other urbans, experience fewer difficulties obtaining basic foods than those residing in the capital and are also unlikely to experience food insecurity. For more effective policy responses to the COVID-19 or similar shocks, the interventions should focus on household socioeconomic conditions and distinguish between urban and rural areas.

Methods for testing the income-health relative hypothesis that the distribution of income in a society affects the distribution of health.

Health and income relation analysis has been the subject of controversies on the absolute income hypothesis (the higher an individual's income, the better their health status) and the relative income hypothesis (individual health is affected by the distribution of income within society). In addition, the assumed relationship has been criticised as being a statistical artefact. To overcome these issues, we formulate the hypothesis that the distribution of health in a society is correlated with the distribution of income in that society and propose the analytical method framework. The method is focused on the calculation of Foster-Greer-Thorbecke (FGT) poverty indices using health and income outcomes. Econometric time series methods, particularly the autoregressive distributed lag (ARDL) cointegration bounds test and dynamic simulation, are complementary tools used to measure the relationship between the calculated indices. Applied to the sub-sample of countries below the poverty line, the method highlights the correlation between the gaps and inequalities in health outcomes and the gaps and inequalities in income outcomes, respectively. • The Foster-Greer-Thorbecke (FGT) poverty indices are applied to income and health outcomes. • Aggregate poverty indices are measured across states. • These indices are meaningful indicators for analysing the link between the distribution of health and the distribution of income in a society.

Prevalence and identification of the determinants of influenza vaccination among French midwifery students.

INTRODUCTION: Midwifery students in France are requested to be vaccinated against influienza every year before the winter epidemic. The rationale is to protect pregnant women and newborns, the "frail" populations with whom students are in regular contact. The aims of the present study were to assess the prevalence of influenza vaccination among midwifery students and to identify the obstacles to its implementation. METHOD: This is a descriptive study carried out by questionnaire among all midwifery students enrolled in one of the 35 midwifery schools in France for the year 2018-2019. RESULTS: The 1092 questionnaires received showed that 47.9% of the students had been vaccinated during the previous winter, mainly in order to protect their patients. For those who had not been vaccinated, the main obstacles were a lack of time (64.7%), the vaccine was considered to be ineffective (57.3%) and forgetting to be vaccinated (43.4%). Most students reported that a midwifery school-based vaccination session would be effective in improving coverage. The decision to take up vaccination was influenced by the opinion of the student's entourage and information received in class. CONCLUSION: Although the objectives of vaccine protection have not yet been achieved, influenza vaccination is not compulsory and midwifery students are free to choose. Students should be provided with all the information necessary to make their decision, including education on the subject, and have easy access to vaccination.

Convergence in public health expenditure across the Sub-Saharan African countries: does club convergence matter?

BACKGROUND: Sub-Saharan African (SSA) countries that currently face enormous healthcare challenges have implemented national health policies focusing on regional or international health commitments. These health commitments generally promote new healthcare financing policies (e.g., health insurance, user fee exemption and results-based financing) with the objective of providing ever-larger population cohorts with human capital and better health in particular. To achieve this, governments must involve themselves more fully in their respective healthcare sectors through the mobilisation of public funding. OBJECTIVE: This paper aims to examine convergence in health expenditure throughout SSA. The findings of club convergence will allow a robust comparison of health indicators between countries and will be suitable for the adjustment of health policies to foster the efficiency of such policies at the regional and/or country level. Such findings could also help with the conception and implementation of health policies at the regional level. METHODS: We used the methodology of convergence analysis based on dynamic factor modelling leading to the logt regression to test for full convergence, club convergence and club clustering of health expenditure on a balanced panel of 44 countries in Sub-Saharan Africa spanning the period from 2000 to 2016. RESULTS: Overall, our results do not support the hypothesis that all SSA countries converge to a single equilibrium state regarding public health expenditure. When testing for club convergence, the results highlight eight convergence clubs and one group of diverging countries. Indeed, performing the club clustering algorithm reveals the existence of three convergence clubs and the diverging group. The three clubs consist of 12, 14 and 14 members, respectively, where convergence is found to occur among different regional economic organisations. CONCLUSION: Our findings indicate that SSA governments should increase spending on healthcare in order to align their healthcare systems with a global convergence model. To foster the convergence to a single equilibrium state in public health expenditure, attention could be paid to strengthening integration within the various regional economic organisations and to the coordination and integration of healthcare policies within and across convergence clubs throughout SSA.

Altered Ex-Vivo Cytokine Responses in Children With Asymptomatic Plasmodium falciparum Infection in Burkina Faso: An Additional Argument to Treat Asymptomatic Malaria?

Introduction: Patients with clinical malaria have an increased risk for bacterial bloodstream infections. We hypothesized that asymptomatic malaria parasitemia increases susceptibility for bacterial infections through an effect on the innate immune system. We measured circulating cytokine levels and ex-vivo cytokine production capacity in asymptomatic malaria and compared with controls. Methods: Data were collected from asymptomatic participants <5 years old with and without positive malaria microscopy, as well as from hospitalized patients <5 years old with clinical malaria, bacteremia, or malaria/bacteremia co-infections in a malaria endemic region of Burkina Faso. Circulating cytokines (TNF-α, IFN-γ, IL-6, IL-10) were measured using multiplex assays. Whole blood from asymptomatic participants with and without positive malaria microscopy were ex-vivo stimulated with S. aureus, E. coli LPS and Salmonella Typhimurium; cytokine concentrations (TNF-α, IFN-γ, IL-1ß, IL-6, IL-10) were measured on supernatants using ELISA. Results: Included were children with clinical malaria (n=118), bacteremia (n=22), malaria and bacteremia co-infection (n=9), asymptomatic malaria (n=125), and asymptomatic controls (n=237). Children with either clinical or asymptomatic malaria had higher plasma cytokine concentrations than controls. Cytokine concentrations correlated positively with malaria parasite density with the strongest correlation for IL-10 in both asymptomatic (r=0.63) and clinical malaria (r=0.53). Patients with bacteremia had lower circulating IL-10, TNF-α and IFN-γ and higher IL-6 concentrations, compared to clinical malaria. Ex-vivo whole blood cytokine production to LPS and S. aureus was significantly lower in asymptomatic malaria compared to controls. Whole blood IFN-γ and IL-10 production in response to Salmonella was also lower in asymptomatic malaria. Interpretation: In children with asymptomatic malaria, cytokine responses upon ex-vivo bacterial stimulation are downregulated. Further studies are needed to explore if the suggested impaired innate immune response to bacterial pathogens also translates into impaired control of pathogens such as Salmonella spp.

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.

A prospective study on the pathogenesis of catheter-associated bacteriuria in critically ill patients.

BACKGROUND: Updating the pathogenesis of catheter-associated bacteriuria (CA-bacteriuria) in the intensive care unit (ICU) is needed to adapt prevention strategies. Our aim was to determine whether the main pathway of CA-bacteriuria in ICU patients was endoluminal or exoluminal. In a prospective study, quantitative urine cultures were sampled from catheter sampling sites, collector bags and the catheter outer surface near the meatus from days 1 to 15 after catheterization. The endoluminal pathway was CA-bacteriuria (defined as 102 CFU/mL) first in collector bags and then in catheters. The exoluminal pathway was CA-bacteriuria first in catheters, on day 1 in early cases and after day 1 in late cases. RESULTS: Of 64 included patients, 20 had CA-bacteriuria. Means of catheterization days and incidence density were 6.81 days and 55.2/1000 catheter-days. Of 26 microorganisms identified, 12 (46.2%) were Gram positive cocci, 8 (30.8%) Gram negative bacilli and 6 yeasts. Three (11.5%) CA-bacteriuria were endoluminal and 23 (88.5%) exoluminal, of which 10 (38.5%) were early and 13 (50%) late. Molecular comparison confirmed culture findings. A quality audit showed good compliance with guidelines. CONCLUSION: The exoluminal pathway of CA-bacteriuria in ICU patients predominated and surprisingly occurred early despite good implementation of guidelines. This finding should be considered in guidelines for prevention of CA-bacteriuria.

Climate disturbance impact assessment in West Africa: evidence from field survey and satellite imagery analysis.

Extreme drought events from climate disturbances are weakening livelihood and limiting agriculture and livestock production in the Sahel region. The lack of relevant information to anticipate coping measures has exacerbated impacts leading to climate adaptation failure in most parts. In this regard, the current research paper has collected important datasets with an objective to assess the impact of extreme drought events on household's livelihoods for better understanding impacts, local people's perception, and the changes on vegetation cover in order to support a robust adaptation strategy to drought. The study conducted a household survey and collected satellite data for comparative analysis. The first survey was conducted in 2013 to collect data from 465 household heads through a structured questionnaire. Supplementary focus group discussions (FGDs) were also conducted in 2018 to collect qualitative information from targeted respondents such as village leaders and members of other key groups including women and youth. Descriptive statistics and correlation coefficient matrix were used to characterize the impact on households' main livelihoods and logistic regression to predict people's perception on pasture depletion over the last 20 years. Satellite data were used to derive spectral vegetation of land covers and unsupervised classification indexes. Both individual survey and focus group discussions identified drought as the main climate constraint which reduced crop production, water and pastures. The logistic analysis revealed that if the respondent's major occupation is livestock, the probability to perceive a depletion of pasture will increase by 28%. Concurrently, the satellite image observation in perfect agreement with the field survey showed 6.78% and 6.01% losses of water surface and vegetation cover respectively between 1986 and 2016 in the study area. These findings showed that logistic regression coupled with satellite information can inform on past and future impacts which are extremely crucial for sound adaptation planning in the Sahel region.

Long-term immunogenicity and immune memory response to the hepatitis B antigen in the RTS,S/AS01E malaria vaccine in African children: a randomized trial.

RTS,S/AS01E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01E when implemented in the Expanded Program of Immunization, infants 8-12 weeks old were randomized to receive either RTS,S/AS01E or a licensed hepatitis B control vaccine (HepB), both co-administered with various combinations of the following childhood vaccines: diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b, trivalent oral poliovirus, pneumococcal non-typeable Haemophilus influenzae protein D conjugate and human rotavirus vaccine. Long-term persistence of antibodies against the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) were assessed, together with the immune memory response to the HB antigen following a booster dose of HepB vaccine. Subgroups receiving RTS,S or the HepB control vaccine were pooled into RTS,S groups and HepB groups, respectively. One month post-HepB booster vaccination, 100% of participants in the RTS,S groups and 98.3% in the control groups had anti-HBs antibody concentrations ≥10 mIU/mL with the geometric mean concentrations (GMCs) at 46634.7 mIU/mL (95% CI: 40561.3; 53617.6) and 9258.2 mIU/mL (95% CI: 6925.3; 12377.0), respectively. Forty-eight months post-primary vaccination anti-CS antibody GMCs ranged from 2.3 EU/mL to 2.7 EU/mL in the RTS,S groups compared to 1.1 EU/mL in the control groups. Hepatitis B priming with the RTS,S/AS01E vaccine was effective and resulted in a memory response to HBsAg as shown by the robust booster response following an additional dose of HepB vaccine. RTS,S/AS01E when co-administered with PHiD-CV, HRV and other childhood vaccines, had an acceptable safety profile.