Novartis Science’s Post

How Plasmodium falciparum genetic diversity impacts malaria drug resistance? The research explored the link between Plasmodium falciparum genetic diversity and drug resistance in Burkina Faso. Despite high genetic diversity, no significant association with drug resistance markers was found. Interestingly, infection complexity was higher in individuals with certain mutations, suggesting in-host competition affects strain survival. Full article: Moustapha Nikiema, Issiaka Soulama, Charles Quaye, Hamidou Ilboudo, Seni Nikiema, Justine Kabore, Clarisse Dah, Ali Sie, Athanase Badolo, Awa Gneme. Exploring the relationship between Plasmodium falciparum genetic diversity and antimalarial drugs resistance markers in a malaria-endemic region of Burkina Faso. Pan African Medical Journal. 2024;48:118. [doi: 10.11604/pamj.2024.48.118.43505] Authors on LinkedIn: Moustapha Nikiema | Issiaka Soulama | Charles Quaye, PhD | Ali SIE | Athanase Badolo | Awa Gneme #malaria #publichealth #plasmodium #resistance #chloroquine #africanpublichealth Interested to have your publication presented? Contact us [email protected].

📣 Our team just published a new modeling study focused on a more theoretical question concerning the spread of drug resistance appear in low-transmission settings before spreading to high-transmission setting. With the identification of more validated markers for artemisinin resistant Plasmodium falciparum malaria in Sub-Saharan Africa, this work may help guide policy makers in preparing local risk assessments. 🔬 Using a previously developed spatial, stochastic, individual-based model of malaria and drug resistance calibrated for Burkina Faso, we examined several drug resistance importation scenarios, controlling for both the time of importation and number of importation events. 📊 We found that drug-resistant genotypes imported during the low-transmission are more likely to experience stochastic extinction due to genetic drift; however, if they are able to survive this period they are more likely to lead to the establishment of drug resistance. ⭐️ The major public health implication that this work has is in the context of molecular surveillance for specific P. falciparum drug-resistance genotype. Specifically, when transmission is highly seasonally, close monitoring for known markers of drug resistance may be more important during the low transmission season and from recrudescent patients in particular. ⭐️ This work addresses an evolutionary-epidemiological gap in that our simulation highlights that seasonally changing selection pressures for drug resistance are not easily identified as such, and that the direction of change may not be clear. This has implications for modelers since it may not be clear if a relevant selection pressure is present in a model. Let me know if you have any other questions! The full open access manuscript has been published in Journal of the Royal Society Interface and is available here: https://lnkd.in/evi3bKDA #malaria #drugresistance #publichealth #mathmaticalmodeling

Happy to share that our article "Exploring the Unexplored Chemical Space: Rational identification of new Tafenoquine analogs with antimalarial properties" is finally out in Bioorganic Chemistry! This study is a practical proof of concept of our previous study published in MDPI Pharmaceuticals (doi: 10.3390/ph15091159) "Deconstructing Markush: Improving the R&D Efficiency Using Library Selection in Early Drug Discovery". We aim to show that the unveiled chemical space may contain compounds with promising potential biological activity, making them worthy of further investigation. This preliminary study on exploring the chemical space of Tafenoquine aims to provide new evidence, albeit on a small scale, that the rational selection of compounds derived from a parent drug’s Markush structure outperforms the traditional selection approach, as demonstrated by publicly available biological and chemical data. This serves as new evidence that machine learning tools are of great use, offering new opportunities in early drug discovery stages such as chemical space exploration and hit-to-lead optimization! A big "Thank you" to all the co-authors who contributed to this multidisciplinar study: Sonia Moliner, F. Javier Gamo and Benigno Crespo, from GSK and José I. Borrell, Jordi Teixidó and Roger Estrada from IQS Barcelona. Let's hope that this alternative methodology will soon lead to discovering more potent and safe hits for malaria treatment. Check it out through this 50-days free access link! https://lnkd.in/eQNu9vaq #chemicalspace #drugdiscovery #malaria #Tafenoquine #machinelearning #AI #rationalselection

Studies of Type 2 diabetes (T2D) and its pathology have mostly been performed in North America and Europe, and are thus not representative of all affected global population. In the largest such study in African population, NHGRI scientists studied metabolites (or substances made by the body breaking down food, drugs or other materials) in people with and without T2D in Nigeria. This study showed that people in this population with or without T2D had similar differences in their metabolites as previous studies. They found that T2D disrupts metabolic processes in the same way across populations, and highlighted a new metabolic signature that could help identify T2D risk and inform disease management and complications. More importantly, the study showed how metabolites can be used to characterize T2D sub-types. Studying how diseases progress in a diversity of populations is an important step to providing high-quality, equitable care to everyone. Read more about the paper, published in Genome Medicine, here: https://ow.ly/A61r50RirvJ

I am thrilled to share my most awaited research work published in the International Journal of Biological Macromolecules (Impact Factor: 8.2), titled "Development, characterization, and evaluation of withaferin-A and artesunate-loaded pH-responsive acetal-dextran polymeric nanoparticles for the management of malaria." The study introduces a novel combinatorial approach using pH-responsive nanoparticles to deliver withaferin-A and artesunate directly to infected cells, showing promising results in the fight against malaria. Key Highlights: Innovative Carrier System: Utilizing acetal-dextran nanoparticles for targeted drug delivery. Enhanced Efficacy: Improved treatment outcomes with a synergistic combination of withaferin-A and artesunate. Promising Results: Significant reduction in parasitemia and potential for lower dosing. Read the full article for an in-depth understanding of our methods and findings: https://lnkd.in/eqkjPEQw #MalariaResearch #Nanotechnology #DrugDelivery #AcetalDextran #WithaferinA #Artesunate #PublicHealth

Professor Tastan Bishop, Director of the Research Unit in Bioinformatics, Rhodes University, South Africa, is exploring the unique ways our bodies interact with medications due to genetic differences. By studying how genome variations influence protein levels, she is investigating how our bodies metabolize tuberculosis and malaria drugs. She hopes her research will bring us closer to treating patients according to their genotype – a goal of personalized medicine. Watch the video to discover how Project Africa GRADIENT, a collaboration between Novartis, GSK & the South African Medical Research Council, is supporting researchers across Africa study genetic diversity in the context of malaria and tuberculosis. #personalizedmedicine #geneticsresearch #malaria

🚨 New publication alert 🚨 I am thrilled to share our new publication titled "Apicoplast-Resident Processes: Exploiting the Chink in the Armour of Plasmodium falciparum Parasites". The apicoplast, a unique organelle in Plasmodium parasites, hosts vital metabolic processes that are absent in humans. This paper outlines the metabolic pathways of the apicoplast that are crucial for parasite survival and emphasizes its potential as a target for novel antimalarial drugs. Link: https://lnkd.in/eVJTrqwY. Many thanks to all co-authors and my supervisor Dr. Franklyn Iheagwam, Ph.D.

We are thrilled to announce the release of our latest publication in Scientific Reports! Our article, "Trio fluorophore-based phenotypic assay for the detection of artemisinin-induced growth-arrested Plasmodium falciparum in human erythrocytes," is now available online and as a PDF. Our technique uses fluorescence probe binding to DNA to specifically detect the dormant parasite in red blood cells, which resist artemisinin, the recent effective antimalarial drug. This breakthrough is especially important as the use of a light microscope is unable to accurately distinguish real and fake death of Plasmodium falciparum. Check out the full article at https://lnkd.in/gF-CJVZT. #scientificreports #malaria #sicnpd #siriraj

In Uzbekistan, TB that's resistant to many drugs is a big problem. USAID's TB Free Uzbekistan activity, is making a difference. They're teaching lab experts a new method called target genome sequencing (tNGS) to quickly identify TB types and drug resistance. This method cuts testing time from months to just a few days, helping patients start effective treatment sooner and prevent TB from spreading. Abt Global #USAID Uzbekistan. Read more here: https://lnkd.in/d69kewcp https://lnkd.in/dtsaP-QD

New Discovery on the link between APOL1 Risk Variants and the Epigenome. Apolipoprotein L1 (APOL1) coding variants increase the risk of chronic kidney disease, hypertension, and even COVID-19-associated nephropathy in individuals of African descent. However, clinical manifestation in patients could vary due to modifiers or other variants. By deploying DNA methylation quantitative locus (meQTL) analysis in African Americans, researchers have uncovered proximal DNA methylation alterations that may help explain variable disease risk and clinical manifestations seen in some people with APOL1 variants. Read more on this groundbreaking research https://lnkd.in/djX3RXHk #epigenome #genetics #kidneydisease #heartfailure #preeclampsia #COVID19