Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria

Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso. Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03). MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention. ClinicalTrials.gov NCT00354380

Evaluation of the Pozzolanic Activity of Metakaolin, Glass Powder and Silica Powder for Use in Cementitious Mortars

The objective of this study is to evaluate the pozzolanic activity of metakaolin, glass powder and silica powder for use in cementitious mortars. Thus, metakaolin was produced by calcination at 700 °C of a clay soil from Burkina composed of kaolinite (62 wt.%), quartz (30 wt.%) and goethite (6 wt.%). Glass powder consists of amorphous silica and silica powder essentially contains quartz. The chemical characterization of materials showed that the metakaolin and the silica powder belong to the category of type F pozzolans while the silica powder would be type N. The lime saturation test reveals low kinetics of lime fixation by the silica powder. On the other hand, the rate of lime fixation by metakaolin and glass powder increases with treatment time. The pozzolanic index of metakaolin and glass powder at 28 and 90 days is higher than the minimum value of 75% required by the ASTM C618 standard. The presence of metakaolin and glass powder within the cement matrix improves the compressive strength of the resulting mortars due to their good pozzolanic reactivity inducing the formation of calcium silicates hydrated (CSH). Metakaolin and glass powder are therefore suitable for replacing cement in the production of mortars in the construction field

The anti-circumsporozoite antibody response to repeated, seasonal booster doses of the malaria vaccine RTS,S/AS01 E

The recently deployed RTS,S/AS01E malaria vaccine induces a strong antibody response to the circumsporozoite protein (CSP) on the surface of the Plasmodium falciparum sporozoite which is associated with protection. The anti-CSP antibody titre falls rapidly after primary vaccination, associated with a decline in efficacy, but the antibody titre and the protective response can be partially restored by a booster dose of vaccine, but this response is also transitory. In many malaria- endemic areas of Africa, children are at risk of malaria, including severe malaria, until they are five years of age or older and to sustain protection from malaria for this period by vaccination with RTS,S/AS01E, repeated booster doses of vaccine may be required. However, there is little information about the immune response to repeated booster doses of RTS,S/AS01E. In many malaria-endemic areas of Africa, the burden of malaria is largely restricted to the rainy season and, therefore, a recent trial conducted in Burkina Faso and Mali explored the impact of repeated annual booster doses of RTS,S/AS01E given immediately prior to the malaria transmission season until children reached the age of five years. Anti-CSP antibody titres were measured in sera obtained from a randomly selected subset of children enrolled in this trial collected before and one month after three priming and four annual booster doses of vaccine using the GSK ELISA developed at the University of Ghent and, in a subset of these samples, by a multiplex assay developed at the University of Oxford. Three priming doses of RTS,S/AS01E induced a strong anti-CSP antibody response (GMT 368.9 IU/mL). Subsequent annual, seasonal booster doses induced a strong, but lower, antibody response; the GMT after the fourth booster was 128.5 IU/mL. Children whose antibody response was in the upper and middle terciles post vaccination had a lower incidence of malaria during the following year than children in the lowest tercile. Results obtained with GSK ELISA and the Oxford Multiplex assay were strongly correlated (Pearson’s correlation coefficient, r = 0.94; 95% CI, 0.93–0.95). Although anti-CSP antibody titres declined after repeated booster doses of RTS,S/AS01E a high, although declining, level of efficacy was sustained suggesting that there may have been changes in the characteristics of the anti-CSP antibody following repeated booster doses. Clinical Trials Registration. NCT03143218

Safety and Efficacy of Methylene Blue Combined with Artesunate or Amodiaquine for Uncomplicated Falciparum Malaria: A Randomized Controlled Trial from Burkina Faso

Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso.Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03).MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention.ClinicalTrials.gov NCT00354380

The anti-circumsporozoite antibody response to repeated, seasonal booster doses of the malaria vaccine RTS,S/AS01E.

The recently deployed RTS,S/AS01E malaria vaccine induces a strong antibody response to the circumsporozoite protein (CSP) on the surface of the Plasmodium falciparum sporozoite which is associated with protection. The anti-CSP antibody titre falls rapidly after primary vaccination, associated with a decline in efficacy, but the antibody titre and the protective response can be partially restored by a booster dose of vaccine, but this response is also transitory. In many malaria- endemic areas of Africa, children are at risk of malaria, including severe malaria, until they are five years of age or older and to sustain protection from malaria for this period by vaccination with RTS,S/AS01E, repeated booster doses of vaccine may be required. However, there is little information about the immune response to repeated booster doses of RTS,S/AS01E. In many malaria-endemic areas of Africa, the burden of malaria is largely restricted to the rainy season and, therefore, a recent trial conducted in Burkina Faso and Mali explored the impact of repeated annual booster doses of RTS,S/AS01E given immediately prior to the malaria transmission season until children reached the age of five years. Anti-CSP antibody titres were measured in sera obtained from a randomly selected subset of children enrolled in this trial collected before and one month after three priming and four annual booster doses of vaccine using the GSK ELISA developed at the University of Ghent and, in a subset of these samples, by a multiplex assay developed at the University of Oxford. Three priming doses of RTS,S/AS01E induced a strong anti-CSP antibody response (GMT 368.9 IU/mL). Subsequent annual, seasonal booster doses induced a strong, but lower, antibody response; the GMT after the fourth booster was 128.5 IU/mL. Children whose antibody response was in the upper and middle terciles post vaccination had a lower incidence of malaria during the following year than children in the lowest tercile. Results obtained with GSK ELISA and the Oxford Multiplex assay were strongly correlated (Pearson's correlation coefficient, r = 0.94; 95% CI, 0.93-0.95). Although anti-CSP antibody titres declined after repeated booster doses of RTS,S/AS01E a high, although declining, level of efficacy was sustained suggesting that there may have been changes in the characteristics of the anti-CSP antibody following repeated booster doses.Clinical Trials Registration. NCT03143218

Optimization of mycelium bio-foam packaging design through drop test simulations and environmental impact assessment

The escalating demand for packaging materials, driven by the changes in consumptions patterns and e-commerce, has placed immense pressure on the environment. Traditionally dominated by plastic materials, the packaging industry is struggling with the material's detrimental environmental impacts, including resource depletion and persistent waste. This research explores the potential of mycelium-based bio-foam (MBF) as a promising eco-friendly substitute of foam packaging such as expanded polystyrene (EPS). A comprehensive market analysis revealed a growing public consciousness regarding plastic pollution and a corresponding desire for sustainable packaging solutions. While the potential of MBF was recognized, concerns about weight, cost, and environmental performance emerged as key barriers to widespread adoption. To address these challenges, this study focused on optimizing MBF design and assessing its overall environmental profile. Through finite element analysis (FEA) simulations of drop tests on a 32-inch flat-screen TV and a porcelain vase, the study evaluated the impact of MBF properties and design configurations on shock absorption performance. Results demonstrated MBF's ability to protect both products from damage under various impact scenarios. Optimization of MBF design parameters, such as thickness and configuration, proved crucial in achieving optimal protection while minimizing material usage. To comprehensively assess the environmental implications, a life cycle assessment (LCA) was conducted comparing MBF to EPS foam packaging. While MBF exhibited higher transportation emissions due to its greater weight, the overall environmental impact was notably lower across the product lifecycle compared EPS. Factors such as biodegradability and reduced energy consumption during production contributed to MBF's superior environmental performance. This research highlights the potential of MBF as an alternative to traditional polystyrene packaging. However, to fully realize its commercial viability, continued research and development are essential to address challenges related to weight optimization, cost reduction, and large-scale production. By investing in these areas, the packaging industry can accelerate the transition towards a more sustainable future.October 202