The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone

BACKGROUND: A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS: In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS: The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS: The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION: The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218

Impact of seasonal RTS,S/AS01E vaccination plus seasonal malaria chemoprevention on the nutritional status of children in Burkina Faso and Mali.

BACKGROUND: A recent trial in Burkina Faso and Mali showed that combining seasonal RTS,S/AS01E malaria vaccination with seasonal malaria chemoprevention (SMC) substantially reduced the incidence of uncomplicated and severe malaria in young children compared to either intervention alone. Given the possible negative effect of malaria on nutrition, the study investigated whether these children also experienced lower prevalence of acute and chronic malnutrition. METHODS: In Burkina Faso and Mali 5920 children were randomized to receive either SMC alone, RTS,S/AS01E alone, or SMC combined with RTS,S/AS01E for three malaria transmission seasons (2017-2019). After each transmission season, anthropometric measurements were collected from all study children at a cross-sectional survey and used to derive nutritional status indicators, including the binary variables wasted and stunted (weight-for-height and height-for-age z-scores below - 2, respectively). Binary and continuous outcomes between treatment groups were compared by Poisson and linear regression. RESULTS: In 2017, compared to SMC alone, the combined intervention reduced the prevalence of wasting by approximately 12% [prevalence ratio (PR) = 0.88 (95% CI 0.75, 1.03)], and approximately 21% in 2018 [PR = 0.79 (95% CI 0.62, 1.01)]. Point estimates were similar for comparisons with RTS,S/AS01E, but there was stronger evidence of a difference. There was at least a 30% reduction in the point estimates for the prevalence of severe wasting in the combined group compared to the other two groups in 2017 and 2018. There was no difference in the prevalence of moderate or severe wasting between the groups in 2019. The prevalence of stunting, low-MUAC-for-age or being underweight did not differ between groups for any of the three years. The prevalence of severe stunting was higher in the combined group compared to both other groups in 2018, and compared to RTS,S/AS01E alone in 2017; this observation does not have an obvious explanation and may be a chance finding. Overall, malnutrition was very common in this cohort, but declined over the study as the children became older. CONCLUSIONS: Despite a high burden of malnutrition and malaria in the study populations, and a major reduction in the incidence of malaria in children receiving both interventions, this had only a modest impact on nutritional status. Therefore, other interventions are needed to reduce the high burden of malnutrition in these areas. TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT03143218 , registered 8th May 2017

Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention.

BACKGROUND: Malaria control remains a challenge in many parts of the Sahel and sub-Sahel regions of Africa. METHODS: We conducted an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria and whether the two interventions combined were superior to either one alone in preventing uncomplicated malaria and severe malaria-related outcomes. RESULTS: We randomly assigned 6861 children 5 to 17 months of age to receive sulfadoxine-pyrimethamine and amodiaquine (2287 children [chemoprevention-alone group]), RTS,S/AS01E (2288 children [vaccine-alone group]), or chemoprevention and RTS,S/AS01E (2286 children [combination group]). Of these, 1965, 1988, and 1967 children in the three groups, respectively, received the first dose of the assigned intervention and were followed for 3 years. Febrile seizure developed in 5 children the day after receipt of the vaccine, but the children recovered and had no sequelae. There were 305 events of uncomplicated clinical malaria per 1000 person-years at risk in the chemoprevention-alone group, 278 events per 1000 person-years in the vaccine-alone group, and 113 events per 1000 person-years in the combination group. The hazard ratio for the protective efficacy of RTS,S/AS01E as compared with chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 1.01), which excluded the prespecified noninferiority margin of 1.20. The protective efficacy of the combination as compared with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8) against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against hospital admission with severe malaria according to the World Health Organization definition, and 72.9% (95% CI, 2.9 to 92.4) against death from malaria. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively. CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. The combination of these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone. (Funded by the Joint Global Health Trials and PATH; ClinicalTrials.gov number, NCT03143218.)

Seasonal vaccination with RTS,S/AS01E vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: a double-blind, randomised, controlled, phase 3 trial.

BACKGROUND: Seasonal vaccination with the RTS,S/AS01E vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years. METHODS: This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso. Children who had been enrolled in the initial 3-year trial when aged 5-17 months were initially randomly assigned individually to receive SMC with sulphadoxine-pyrimethamine and amodiaquine plus control vaccines, RTS,S/AS01E plus placebo SMC, or SMC plus RTS,S/AS01E. They continued to receive the same interventions until the age of 5 years. The primary trial endpoint was the incidence of clinical malaria over the 5-year trial period in both the modified intention-to-treat and per-protocol populations. Over the 5-year period, non-inferiority was defined as a 20% increase in clinical malaria in the RTS,S/AS01E-alone group compared with the SMC alone group. Superiority was defined as a 12% difference in the incidence of clinical malaria between the combined and single intervention groups. The study is registered with ClinicalTrials.gov, NCT04319380, and is complete. FINDINGS: In April, 2020, of 6861 children originally recruited, 5098 (94%) of the 5433 children who completed the initial 3-year follow-up were re-enrolled in the extension study. Over 5 years, the incidence of clinical malaria per 1000 person-years at risk was 313 in the SMC alone group, 320 in the RTS,S/AS01E-alone group, and 133 in the combined group. The combination of RTS,S/AS01E and SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01E (protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01E was non-inferior to SMC (hazard ratio 1·03 [95% CI 0·95 to 1·12]). The protective efficacy of the combination versus SMC over the 5-year period of the study was very similar to that seen in the first 3 years with the protective efficacy of the combination versus SMC being 57·7% (53·3 to 61·7) and versus RTS/AS01E-alone being 59·0% (54·7 to 62·8). The comparable figures for the first 3 years of the study were 62·8% (58·4 to 66·8) and 59·6% (54·7 to 64·0%), respectively. Hospital admissions for WHO-defined severe malaria were reduced by 66·8% (95% CI 40·3 to 81·5), for malarial anaemia by 65·9% (34·1 to 82·4), for blood transfusion by 68·1% (32·6 to 84·9), for all-cause deaths by 44·5% (2·8 to 68·3), for deaths excluding external causes or surgery by 41·1% (-9·2 to 68·3), and for deaths from malaria by 66·8% (-2·7 to 89·3) in the combined group compared with the SMC alone group. No safety signals were detected. INTERPRETATION: Substantial protection against malaria was sustained over 5 years by combining seasonal malaria vaccination with seasonal chemoprevention, offering a potential new approach to malaria control in areas with seasonal malaria transmission. FUNDING: UK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation). TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Élimination de la matière organique des eaux de surface douces à potabiliser : effets de la reminéralisation

État des connaissances sur la matière organique des eaux naturelles -- La matière organique dans les eaux de surface -- Les substances humiques -- La matière organique biodégradable -- La demande en chlore des eaux naturelles -- La formation des sous-produits de désinfection au chlore -- Élimination de la matière organique par coagulation-floculation -- Élimination de la matière organique par traitement biologique

Quality and in vitro bioequivalence evaluation of different brands of amoxicillin + clavulanic acid (500 + 62.5) mg tablets distributed in Burkina Faso

In a previous study, we reported the evaluation of the physicochemical quality and in vitro bioequivalence of different brands of amoxicillin capsules 500 mg marketed in Burkina Faso. As our goal was to document the quality and biopharmaceutical performance of essential antibiotics marketed in resource-limited countries, we investigated here, the interchangeability with the originator of five brands of amoxicillin + clavulanic acid (500mg+62.5mg) tablets distributed in Burkina Faso. The physicochemical quality of the different brands was first verified according to the USP monograph. The comparative evaluation of the in vitro dissolution profiles was performed in three different pH environments (1.2 - 4.5 - 6.8) using statistical calculations of the difference (f1) and similarity (f2) factors. All brands of amoxicillin + clavulanic acid (500mg+62.5mg) tablets, including the originator, met USP specifications for weight uniformity, identification, content and dissolution of active ingredients. However, the similarity and difference factor values showed that two generic brands (B and E) did not have similar amoxicillin dissolution profiles to the comparator product in pH 4.5 media (f1 = 23,54 and 17.02; f2=35.96 and 46.90, respectively). Therefore, these two products cannot be used interchangeably with the originator. The other three generic brands were similar to the originator and can therefore probably be used interchangeably

C51 - Conciliation médicamenteuse à l’admission des urgences médicales du Centre Hospitalier Universitaire Pédiatrique Charles De Gaulle

Introduction : De nombreuses erreurs médicamenteuses surviennent lors de la transition du patient de la communauté à hôpital. La conciliation médicamenteuse constitue un moyen de prévention des iatrogénies médicamenteuses et la promotion de soins de santé de qualité et sécurisés. Objectif : Cette étude avait pour but d’implémenter la conciliation des traitements médicamenteux au sein de l’unité des urgences médicales du CHUP-CDG et d’évaluer son acceptabilité par l’équipe médicale. Méthodologie : Les patients admis dans les 12 heures ont été recensés et enrôlés suivant un consentement verbal d’un des parents ou de l’accompagnant durant la période du 15 Mars au 30 Avril 2023. Une fiche de conciliation validée par une préenquête a servi à la collecte des données relatives aux traitements du patient avant et à l’admission aux urgences médicales. Les données ont été colligées grâce au logiciel Kobocollect® puis analysées grâce au logiciel Kobotoolbox® et les divergences relevées ont été caractérisées. Résultats : Au total, 135 patients enrôlés ont présenté 412 lignes de traitement sur une période de six semaines. Le temps moyen de conciliation par patient était de 57 minutes. Soixante-et-onze (71) divergences non intentionnelles ont été recueillies, dont 39 omissions, 24 erreurs de posologie et 8 erreurs de dosage. Mille cent quatre-vingt-dix-huit (1198) divergences intentionnelles ont été répertoriées, dont 1125 documentées. Quarante-et-neuf (49) divergences non intentionnelles ont été corrigées après intervention pharmaceutique soit 69,01%. Conclusion : les résultats de cette étude permettent de justifier la nécessité d’intégrer la conciliation médicamenteuse dans la pratique clinique de routine. Il convient de conduire d’autres études à l’échelle de l’hôpital en vue d’explorer les conciliations de transfert et de sortie à partir des unités d’hospitalisation

P5 Caractérisation des erreurs médicamenteuses survenues au Centre de néonatologie du Centre Hospitalier Universitaire Charles de Gaulle en avril 2023

Introduction : Les erreurs médicamenteuses sont fréquentes en néonatologie. Elles sont parfois critiques en situation de prématurité. Le but de la présente étude était de caractériser les erreurs médicamenteuses commises de la prescription à l’administration des traitements des patients admis au centre de néonatologie du CHU pédiatrique Charles de GAULLE.   Matériel et méthodes : il s’est agi d’une étude observationnelle à visée descriptive. Elle s’est déroulée durant le mois d’avril 2023 au centre de néonatologie du Centre Hospitalier Universitaire Charles de Gaulle (CHUP-CDG). La population d’étude était constituée des nouveau-nés admis pour soins au centre. Résultats : Au total 38 nouveau-nés ont été inclus dans l’étude. Deux cent quatorze (214) prescriptions, 36 préparations ou reconstitutions de médicaments, 54 administrations et 102 délivrances de traitement médicamenteux aux patients ont été analysées. Au total 179 erreurs médicamenteuses ont été identifiées. La prescription et l’administration des médicaments étaient les étapes qui comptaient le plus grand nombre d’erreur avec des proportions de 53,07 % et 40,78 %. La préparation/reconstitution des médicaments et la dispensation des traitements ont été sources d’erreurs médicamenteuses dans des proportions de 1,2% et 5,03%. Les erreurs de dose ont représenté 53,14 % des interventions pharmaceutiques. Selon le degré de réalisation, 41,90 % étaient des erreurs potentielles et la totalité des erreurs médicamenteuses n’avaient pas de conséquences significatives sur la santé des patients. Conclusion : Cette étude a permis détecter et de caractériser les erreurs survenues lors de processus du circuit clinique du médicament au centre de néonatologie du CHUP-CDG. Des renforcements de capacités des acteurs permettront de corriger les insuffisances relevées

APOL1 Renal Risk Variants and Kidney Function in HIV-1–Infected People From Sub-Saharan Africa

International audienceAPOL1 G1 and G2 alleles have been associated with kidney-related outcomes in people living with HIV (PLHIV) of Black African origin. No APOL1-related kidney risk data have yet been reported in PLHIV in West Africa, where high APOL1 allele frequencies have been observed. Methods: We collected clinical data from PLHIV followed in Burkina Faso (N = 413) and in the ANRS-12169/2LADY trial (Cameroon, Senegal, Burkina Faso, N = 369). APOL1 G1 and G2 risk variants were genotyped using TaqMan assays, and APOL1 high-risk (HR) genotype was defined by the carriage of 2 risk alleles. Results: In West Africa (Burkina Faso and Senegal), the G1 and G2 allele frequencies were 13.3% and 10.7%, respectively. In Cameroon (Central Africa), G1 and G2 frequencies were 8.7% and 8.9%, respectively. APOL1 HR prevalence was 4.9% in West Africa and 3.4% in Cameroon. We found no direct association between APOL1 HR and estimated glomerular filtration rate (eGFR) change over time. Nevertheless, among the 2LADY cohort participants, those with both APOL1 HR and high baseline viral load had a faster eGFR progression (β = −3.9[−7.7 to −0.1] ml/min per 1.73 m2 per year, P < 0.05) than those with low-risk (LR) genotype and low viral load. Conclusion: Overall, the APOL1 risk allele frequencies in PLHIV were higher in the West African countries than in Cameroon, but much lower than previously reported in some Nigeria ethnic groups, which strongly advocates for further investigation in the African continent. This study suggested that the virological status could modulate the APOL1 impact on kidney function, hence reinforcing the need for early therapeutic interventions